TY  - JOUR
T1  - Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism
A1  - Slansky,I.
A1  - Herholz,K.
A1  - Pietrzyk,U.
A1  - Kessler,J.
A1  - Grond,M.
A1  - Mielke,R.
A1  - Heiss,W.D.
Y1  - 1995///
SP  - 270
EP  - 277
JF  - Neuroradiology
VL  - 37
IS  - 4
ER  - 

TY  - JOUR
T1  - Positron emission tomography and magnetic resonance spectroscopy of cerebral glycolysis in children with congenital lactic acidosis
A1  - Duncan,D.B.
A1  - Herholz,K.
A1  - Kugel,H.
A1  - Roth,B.
A1  - Ruitenbeek,W.
A1  - Heindel,W.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1995///
SP  - 351
EP  - 358
JF  - Annals of Neurology
VL  - 37
IS  - 3
ER  - 

TY  - JOUR
T1  - Long-term prognosis of poststroke aphasia studied with positron emission tomography
A1  - Karbe,H.
A1  - Kessler,J.
A1  - Herholz,K.
A1  - Fink,G.R.
A1  - Heiss,W.D.
Y1  - 1995///
SP  - 186
EP  - 190
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 52
IS  - 2
N2  - OBJECTIVE: To evaluate positron emission tomography with the use of fludeoxyglucose F 18 as a predictor of the long-term outcome of poststroke aphasia. BACKGROUND: Positron emission tomography shows functional deficits after stroke even in morphologically intact brain regions. The regional metabolic impairment can be related to the clinical deficit. Little is known about whether regional hypometabolism early after stroke predicts the long-term prognosis of stroke sequelae. PATIENTS AND METHODS: Twenty-two patients with language disturbance caused by a single lesion in the territory of the left middle cerebral artery were studied with fludeoxyglucose positron emission tomography and with a neuropsychological test battery that included a test of receptive language (Token Test) and a test of word fluency (/f/, /a/, /s/ test). The neuropsychological test was readministered about 2 years after the initial test. RESULTS: Regional cerebral metabolic rates of glucose measured early after stroke showed a highly significant correlation with the results of the 2-year follow-up test. The receptive language disorder best correlated with cerebral metabolic rates of glucose in the left superior temporal cortex, and word fluency correlated with cerebral metabolic rates of glucose in the left prefrontal cortex. CONCLUSION: Cerebral metabolic rates of glucose in speech-relevant brain regions measured early after stroke are a predictor of the eventual outcome of aphasia
ER  - 

TY  - JOUR
T1  - An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies
A1  - Pietrzyk,U.
A1  - Herholz,K.
A1  - Fink,G.
A1  - Jacobs,A.
A1  - Mielke,R.
A1  - Slansky,I.
A1  - Wrker,M.
A1  - Heiss,W.D.
Y1  - 1994///
SP  - 2011
EP  - 2018
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 12
ER  - 

TY  - JOUR
T1  - Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats
A1  - Heiss,W.D.
A1  - Graf,R.
A1  - Wienhard,K.
A1  - Lottgen,J.
A1  - Saito,R.
A1  - Fujita,T.
A1  - Rosner,G.
A1  - Wagner,R.
Y1  - 1994///
SP  - 892
EP  - 902
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 14
IS  - 6
ER  - 

TY  - JOUR
T1  - PET and functional testing in temporal lobe epilepsy
A1  - Pawlik,G.
A1  - Fink,G.R.
A1  - Kessler,J.
A1  - Heiss,W.D.
Y1  - 1994///
N1  - discussion 157-8
SP  - 150
EP  - 156
JF  - Acta Neurologica Scandinavica
VL  - 15 (Supplementum)
ER  - 

TY  - JOUR
T1  - Untersuchung der funktionellen Bedeutung von Stammganglienverkalkungen mit Positronenemissionstomographie
A1  - Staffen,W.
A1  - Karbe,H.
A1  - Rudolf,J.
A1  - Herholz,K.
A1  - Diederich,N.
A1  - Heiss,W.D.
Y1  - 1994///
SP  - 119
EP  - 124
JF  - Fortschritte der Neurologie-Psychiatrie
VL  - 62
IS  - 4
ER  - 

TY  - JOUR
T1  - The ECAT EXACT HR: performance of a new high resolution positron scanner
A1  - Wienhard,K.
A1  - Dahlbom,M.
A1  - Eriksson,L.
A1  - Michel,C.
A1  - Bruckbauer,T.
A1  - Pietrzyk,U.
A1  - Heiss,W.D.
Y1  - 1994///
SP  - 110
EP  - 118
JF  - Journal of Computer Assisted Tomography
VL  - 18
IS  - 1
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism as a predictor of rehabilitation after ischemic stroke
A1  - Heiss,W.D.
A1  - Emunds,H.G.
A1  - Herholz,K.
Y1  - 1993///
SP  - 1784
EP  - 1788
JF  - Stroke
VL  - 24
IS  - 12
ER  - 

TY  - JOUR
T1  - Positron emission tomography in myotonic dystrophy
A1  - Mielke,R.
A1  - Herholz,K.
A1  - Fink,G.
A1  - Ritter,D.
A1  - Heiss,W.D.
Y1  - 1993///
SP  - 93
EP  - 99
JF  - Psychiatry Research
VL  - 50
IS  - 2
ER  - 

TY  - JOUR
T1  - FDG-PET as a prognostic indicator in radiochemotherapy of glioblastoma
A1  - Hlzer,T.
A1  - Herholz,K.
A1  - Jeske,J.
A1  - Heiss,W.D.
Y1  - 1993///
SP  - 681
EP  - 687
JF  - Journal of Computer Assisted Tomography
VL  - 17
IS  - 5
N2  - OBJECTIVE: We performed a prospective cohort study in a homogeneous patient group with proven glioblastoma who received uniform therapy to determine the prognostic value and clinical correlates of [18F]fluorodeoxyglucose (FDG) PET at different stages of the disease. MATERIALS AND METHODS: Fifteen newly diagnosed patients with glioblastoma, aged 52 +/- 9 years and with Karnofsky performance score (KPS) of at least 50, were treated with surgical resection, chemotherapy (nimustine), and radiotherapy. They were followed prospectively for 2 years. Clinical data (e.g., tumor progression, performance status, and survival) were recorded and glucose metabolism was measured with PET and FDG before and during radiochemotherapy. RESULTS: Median survival of all patients was 13 months and four patients were alive 24 months after surgery. All tumors were hypermetabolic compared with normal white matter. A metabolic index was calculated as the ratio of maximum residual tumor metabolism to contralateral normal brain metabolism. It was of prognostic value for patient survival and tumor recurrence already in the first postoperative and all following PET studies and was correlated with the KPS. Reduction of contralateral brain metabolism was more closely related to prognosis than the tumor metabolism proper. CONCLUSION: These results underscore the prognostic relevance of metabolically active residual tumor tissue after surgical resection.
ER  - 

TY  - JOUR
T1  - Comparability of FDG PET studies in probable Alzheimer's disease
A1  - Herholz,K.
A1  - Perani,D.
A1  - Salmon,E.
A1  - Franck,G.
A1  - Fazio,F.
A1  - Heiss,W.D.
A1  - Comar,D.
Y1  - 1993///
SP  - 1460
EP  - 1466
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 9
ER  - 

TY  - JOUR
T1  - In vivo metabolism of childhood posterior fossa tumors and primitive neuroectodermal tumors before and after treatment
A1  - Holthoff,V.A.
A1  - Herholz,K.
A1  - Berthold,F.
A1  - Widemann,B.
A1  - Schrder,R.
A1  - Neubauer,I.
A1  - Heiss,W.D.
Y1  - 1993///
SP  - 1394
EP  - 1403
JF  - Cancer
VL  - 72
IS  - 4
ER  - 

TY  - JOUR
T1  - Experimental evidence of ischemic thresholds and functional recovery. [Review]
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 1668
EP  - 1672
JF  - Stroke
VL  - 23
IS  - 11
ER  - 

TY  - JOUR
T1  - Performance evaluation of the positron scanner ECAT EXACT
A1  - Wienhard,K.
A1  - Eriksson,L.
A1  - Grootoonk,S.
A1  - Casey,M.
A1  - Pietrzyk,U.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 804
EP  - 813
JF  - Journal of Computer Assisted Tomography
VL  - 16
IS  - 5
ER  - 

TY  - JOUR
T1  - Severity of vascular dementia is related to volume of metabolically impaired tissue
A1  - Mielke,R.
A1  - Herholz,K.
A1  - Grond,M.
A1  - Kessler,J.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 909
EP  - 913
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 49
IS  - 9
ER  - 

TY  - JOUR
T1  - Tracers for metabolic imaging of brain and heart. Radiochemistry and radiopharmacology. [Review]
A1  - Stcklin,G.
Y1  - 1992///
SP  - 527
EP  - 551
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 19
IS  - 7
ER  - 

TY  - JOUR
T1  - Positron emission tomography demonstrates frontal cortex and basal ganglia hypometabolism in dystonia
A1  - Karbe,H.
A1  - Holthoff,V.A.
A1  - Rudolf,J.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 1540
EP  - 1544
JF  - Neurology
VL  - 42
IS  - 8
ER  - 

TY  - JOUR
T1  - In vivo imaging of glucose consumption and lactate concentration in human gliomas
A1  - Herholz,K.
A1  - Heindel,W.
A1  - Luyten,P.R.
A1  - denHollander,J.A.
A1  - Pietrzyk,U.
A1  - Voges,J.
A1  - Kugel,H.
A1  - Friedmann,G.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 319
EP  - 327
JF  - Annals of Neurology
VL  - 31
IS  - 3
ER  - 

TY  - JOUR
T1  - PET correlates of normal and impaired memory functions. [Review]
A1  - Heiss,W.D.
A1  - Pawlik,G.
A1  - Holthoff,V.
A1  - Kessler,J.
A1  - Szelies,B.
Y1  - 1992///
SP  - 1
EP  - 27
JF  - Cerebrovascular & Brain Metabolism Reviews
VL  - 4
IS  - 1
N2  - To date, positron emission tomography (PET) has been the only technology for the quantitative imaging of the changes of regional cerebral glucose (rCMRGl) or oxygen metabolism and blood flow (rCBF) associated with psychophysical stimulation and with the performance of mental tasks. So far, the majority of studies performed in healthy subjects demonstrated activation patterns involving not only certain limbic structures, most of all hippocampus, amygdala, parahippocampus, and cingulate, but also temporal, parietal, and occipital association cortex, depending on the applied paradigm. Indeed, the closest correlation between regional metabolism and memory test scores was found in mesiotemporal structures during the performance of memory tasks. Metabolic or CBF studies also seem to indicate that memorizing strategies may differ among individuals. PET was repeatedly used to investigate metabolic and/or blood flow abnormalities in patients with various amnestic syndromes. In cases with uni- or bilateral lesions of mesiotemporal structures, caused by surgery, herpes simplex encephalitis, or permanent ischemic, anoxic, or toxic damage, disturbances of metabolism and blood flow typically extended far beyond the morphological defects detected by computed tomography or magnetic resonance. In acute transient global amnesia, CBF and metabolism were decreased bilaterally in the mesiotemporal lobes, where hypometabolism persisted for some time, while higher values were observed in thalamus and some cortical areas. Diencephalic lesions causing Korsakoff's syndrome were associated with decreased rCMRGl in the hippocampal formation, upper brainstem, cingulate, and thalamus. Discrete thalamic infarcts caused amnesia and metabolic depression in the morphologically intact ipsilateral thalamus and in various projection areas of the infarcted nuclei. In ischemic forebrain lesions, amnestic deficits could be related to involvement of the anterior cingulate and of basal cholinergic nuclei. A large number of pathologies are diffusely spread out in the brain and affect partially or predominantly structures in memory processing. This holds true especially in the various dementias where memory disturbances are a consistent and often leading feature. Notably, Alzheimer's disease can be distinguished from other dementias by its characteristic pattern of metabolic dysfunction, with the most prominent changes occurring in parietotemporal and frontal association cortex whose residual metabolism is related to the severity of the disease. Therefore, activation studies using paradigms involving memory functions enhance that typical pattern. Only in the activated state is metabolism of mesiotemporal structures significantly correlated with the performance in memory tests. Other dementias also affect some of the distributed memory networks, with Huntington's disease suggesting a role of the striatum in memory processing.(ABSTRACT TRUNCATED AT 400 WORDS) [References: 123] <254>
ER  - 

TY  - JOUR
T1  - Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type
A1  - Mielke,R.
A1  - Herholz,K.
A1  - Grond,M.
A1  - Kessler,J.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 93
EP  - 98
JF  - Neurobiology of Aging
VL  - 13
IS  - 1
ER  - 

TY  - JOUR
T1  - Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine
A1  - Wienhard,K.
A1  - Herholz,K.
A1  - Coenen,H.H.
A1  - Rudolf,J.
A1  - Kling,P.
A1  - Stcklin,G.
A1  - Heiss,W.D.
Y1  - 1991///
N1  -  [see comments]
SP  - 1338
EP  - 1346
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 7
ER  - 

TY  - JOUR
T1  - Plastic transformation of PET images
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Liddle,P.F.
A1  - Frackowiak,R.S.
Y1  - 1991///
SP  - 634
EP  - 639
JF  - Journal of Computer Assisted Tomography
VL  - 15
IS  - 4
ER  - 

TY  - JOUR
T1  - Impaired metabolic activation in Alzheimer's disease: a PET study during continuous visual recognition
A1  - Kessler,J.
A1  - Herholz,K.
A1  - Grond,M.
A1  - Heiss,W.D.
Y1  - 1991///
SP  - 229
EP  - 243
JF  - Neuropsychologia
VL  - 29
IS  - 3
ER  - 

TY  - JOUR
T1  - Comparing functional (PET) images: the assessment of significant change
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Liddle,P.F.
A1  - Frackowiak,R.S.
Y1  - 1991///
SP  - 690
EP  - 699
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 4
ER  - 

TY  - JOUR
T1  - Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2'-F18)fluoroethylspiperone and positron emission tomography
A1  - Jovkar,S.
A1  - Wienhard,K.
A1  - Coenen,H.H.
A1  - Pawlik,G.
A1  - Heiss,W.D.
Y1  - 1991///
SP  - 158
EP  - 163
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 18
IS  - 3
ER  - 

TY  - JOUR
T1  - Estimation of local cerebral glucose utilization by positron emission tomography: comparison of [18F]2-fluoro-2-deoxy-D- glucose and [18F]2-fluoro-2-deoxy-D-mannose in patients with focal brain lesions
A1  - Wienhard,K.
A1  - Pawlik,G.
A1  - Nebeling,B.
A1  - Rudolf,J.
A1  - Fink,G.
A1  - Hamacher,K.
A1  - Stcklin,G.
A1  - Heiss,W.D.
Y1  - 1991///
SP  - 485
EP  - 491
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 3
N2  - A comparative PET study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) and [18F]2-fluoro-2-deoxy-D-mannose (FDM) uptake was performed in 13 patients with focal brain lesions. Differences between FDG and FDM with respect to model rate constants, lumped constant, and estimated metabolic rate for glucose were determined on a regional basis. Across whole brain, the transport rate constant K1* was almost unchanged, whereas k2*, describing the transport back from tissue to plasma, was 6% higher, and the phosphorylation rate constant k3* was 9% lower for FDM compared to FDG. This implies a 20% lower lumped constant for FDM. No significant regional variability of this differential tracer behavior was observed in normal or in lesioned brain tissue. Thus, results from previous FDG studies, where the radiotracer was not 100% pure FDG but contained varying amounts of FDM, can easily be corrected by adjustment of the lumped constant employed in metabolic quantitation
ER  - 

TY  - JOUR
T1  - Widespread functional effects of discrete thalamic infarction
A1  - Szelies,B.
A1  - Herholz,K.
A1  - Pawlik,G.
A1  - Karbe,H.
A1  - Hebold,I.
A1  - Heiss,W.D.
Y1  - 1991///
SP  - 178
EP  - 182
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 48
IS  - 2
N2  - In order to investigate functional effects of various thalamic structures on metabolism in remote, morphologically intact cerebral regions, we used positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus. Patients were grouped according to computed tomographic scans showing anterior (three), medial (four), or posterior (four) lesions. Compared with a matched group of 11 healthy subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction (31.2 +/- 2.97 mumol/100 g per minute). Patients with bilateral infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute). Depending on infarct location within the thalamus, there was differential depression of rCMRGlu, with the largest effects on frontal and occipital areas in medial infarctions. Except for ipsilateral thalamic deactivation, metabolic patterns with anterior thalamic infarcts were close to normal, while posterior infarcts mostly depressed rCMRGlu in the visual and in the inferior limbic cortex. Cerebellar metabolic rates were within normal limits in most cases. These patterns of regional cerebral deactivation may be related to categories of thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse to most cortical areas, and specific to defined neocortical areas. Even small brain lesions may have widespread functional sequelae, potentially demonstrable by positron emission tomography. <265>
ER  - 

TY  - JOUR
T1  - The effect of carotid artery disease on the cerebrovascular response to physiologic stimulation
A1  - Powers,W.J.
A1  - Fox,P.T.
A1  - Raichle,M.E.
Y1  - 1988///
SP  - 1475
EP  - 1478
JF  - Neurology
VL  - 38
IS  - 9
N2  - Eight of 16 patients with severe carotid artery disease, but no evidence of functional or structural brain damage, had abnormal regional cerebral blood flow (rCBF) responses to physiologic stimulation of sensorimotor cortex (unilateral reduction in six, abnormal diffuse increase in two). Thus, in patients with cerebrovascular disease the rCBF responses during physiologic tasks may not be reliable indicators of local neuronal activity.
ER  - 

TY  - JOUR
T1  - Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects
A1  - Fox,P.T.
A1  - Raichle,M.E.
Y1  - 1986///
SP  - 1140
EP  - 1144
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 83
IS  - 4
ER  - 

TY  - JOUR
T1  - A stereotactic method of anatomical localization for positron emission tomography
A1  - Fox,P.T.
A1  - Perlmutter,J.S.
A1  - Raichle,M.E.
Y1  - 1985///
SP  - 141
EP  - 153
JF  - Journal of Computer Assisted Tomography
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - A noninvasive approach to quantitative functional brain mapping with H2 (15)O and positron emission tomography
A1  - Fox,P.T.
A1  - Mintun,M.A.
A1  - Raichle,M.E.
A1  - Herscovitch,P.
Y1  - 1984///
SP  - 329
EP  - 333
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 3
ER  - 

TY  - JOUR
T1  - Use of 18F-fluoromethane for cerebral blood flow measurement with PET
A1  - Herholz,K.
A1  - Wagner,R.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1990///
SP  - 84
EP  - 84
JF  - Nuklearmedizin
VL  - 29
IS  - 2
ER  - 

TY  - JOUR
T1  - Three-dimensional alignment of functional and morphological tomograms
A1  - Pietrzyk,U.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 1990///
SP  - 51
EP  - 59
JF  - Journal of Computer Assisted Tomography
VL  - 14
IS  - 1
ER  - 

TY  - JOUR
T1  - Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease. [Review]
A1  - Baron,J.C.
A1  - Frackowiak,R.S.
A1  - Herholz,K.
A1  - Jones,T.
A1  - Lammertsma,A.A.
A1  - Mazoyer,B.
A1  - Wienhard,K.
Y1  - 1989///
SP  - 723
EP  - 742
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 6
ER  - 

TY  - JOUR
T1  - Regional metabolic correlates of Token test results in cortical and subcortical left hemispheric infarction
A1  - Karbe,H.
A1  - Herholz,K.
A1  - Szelies,B.
A1  - Pawlik,G.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1989///
SP  - 1083
EP  - 1088
JF  - Neurology
VL  - 39
IS  - 8
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow measurement with intravenous [15O]water bolus and [18F]fluoromethane inhalation
A1  - Herholz,K.
A1  - Pietrzyk,U.
A1  - Wienhard,K.
A1  - Hebold,I.
A1  - Pawlik,G.
A1  - Wagner,R.
A1  - Holthoff,V.
A1  - Klinkhammer,P.
A1  - Heiss,W.D.
Y1  - 1989///
SP  - 1174
EP  - 1181
JF  - Stroke
VL  - 20
IS  - 9
ER  - 

TY  - JOUR
T1  - Measurement of blood-brain hexose transport with dynamic PET: comparison of [18F]2-fluoro-2-deoxyglucose and [11C]O-methylglucose
A1  - Herholz,K.
A1  - Wienhard,K.
A1  - Pietrzyk,U.
A1  - Pawlik,G.
A1  - Heiss,W.D.
Y1  - 1989///
SP  - 104
EP  - 110
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - Effect of piracetam on cerebral glucose metabolism in Alzheimer's disease as measured by positron emission tomography
A1  - Heiss,W.D.
A1  - Hebold,I.
A1  - Klinkhammer,P.
A1  - Ziffling,P.
A1  - Szelies,B.
A1  - Pawlik,G.
A1  - Herholz,K.
Y1  - 1988///
SP  - 613
EP  - 617
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 8
IS  - 4
N2  - The effect of piracetam (a putative enhancer of cerebral metabolism) on regional CMRGlu was studied by positron emission tomography of 2and 2 over black square]; [1 and 2 over black square]8F]-fluoro-2-deoxy-D-glucose in nine patients with Alzheimer's disease, and in seven cases with multiinfarct dementia or unclassified dementia. In Alzheimer's disease, i.v. administration of piracetam, 6 g b.i.d. for 2 weeks, significantly improved rCMRGlu in most cortical areas, whereas no effect on CMRGlu of the drug was observed in the multiinfarct dementia/unclassified dementia groups. These results lend further support to the notion that adjuvant piracetam treatment is of benefit in Alzheimer's disease. They may also indicate that the typical metabolic depression in Alzheimer's disease is caused by complex interaction of disturbed transmitter and cellular function rather than by a specific deficit in the cholinergic system alone. <286>
ER  - 

TY  - JOUR
T1  - The influence of tissue heterogeneity on results of fitting nonlinear model equations to regional tracer uptake curves: with an application to compartmental models used in positron emission tomography
A1  - Herholz,K.
A1  - Patlak,C.S.
Y1  - 1987///
SP  - 214
EP  - 229
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 2
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming
A1  - Heiss,W.D.
A1  - Pawlik,G.
A1  - Herholz,K.
A1  - Wagner,R.
A1  - Wienhard,K.
Y1  - 1985///
SP  - 362
EP  - 366
JF  - Brain Research
VL  - 327
IS  - 1-2
ER  - 

TY  - JOUR
T1  - Estimation of local cerebral glucose utilization by positron emission tomography of [18F]2-fluoro-2-deoxy-D-glucose: a critical appraisal of optimization procedures
A1  - Wienhard,K.
A1  - Pawlik,G.
A1  - Herholz,K.
A1  - Wagner,R.
A1  - Heiss,W.D.
Y1  - 1985///
SP  - 115
EP  - 125
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 1
N2  - Various approaches estimating local cerebral glucose utilization by positron emission tomography of labeled deoxyglucose are compared. Autoradiographic methods that predict the glucose utilization rate from a single scan are unreliable in pathologic tissue because of abnormal values of the model rate constants. A normalization procedure using the ratio of measured tissue activity to activity calculated with standard rate constants is proposed to readjust the values of the rate constants. Reliable estimates of metabolic rates can be obtained from dynamic recordings of tracer uptake. In the graphic approach, metabolic rate can be derived from the slope of a segment of a transformed uptake curve, which becomes linear at 15-20 min after intravenous tracer injection, with an accuracy comparable with that in complete dynamic studies. However, by recording and analyzing full-length uptake curves, in addition to metabolic rate, the model rate constants can be determined regionally. The physiological significance of those parameters is demonstrated in crossed cerebellar deactivation in 30 patients with supratentorial infarcts. Mild hypometabolism both within the ischemic lesion and in the morphologically intact cerebellum is accompanied by a reduction of the phosphorylation rate only. Severe metabolic depression, by contrast, affects both cerebellar transport and phosphorylation processes, whereas in the cerebrum, only the rate constant k1 is significantly correlated with the degree of metabolic disturbance. <315>
ER  - 

TY  - JOUR
T1  - Computer assisted mapping in quantitative analysis of cerebral positron emission tomograms
A1  - Herholz,K.
A1  - Pawlik,G.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1985///
SP  - 154
EP  - 161
JF  - Journal of Computer Assisted Tomography
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of regional glucose metabolism in cerebral ischemia--topographic and kinetic aspects
A1  - Pawlik,G.
A1  - Wienhard,K.
A1  - Herholz,K.
A1  - Wagner,R.
A1  - Heiss,W.D.
Y1  - 1984///
SP  - 253
EP  - 262
JF  - Progress in Brain Research
VL  - 62
ER  - 

TY  - JOUR
T1  - Computerized transverse axial scanning (tomography): Part. I. Description of system
A1  - Hounsfield,G.N.
Y1  - 1973///
SP  - 1016
EP  - 1022
JF  - British Journal of Radiology
VL  - 46
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow measurement in man
A1  - Lassen,N.A.
A1  - Ingvar,D.H.
Y1  - 1963///
SP  - 615
EP  - 622
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 9
ER  - 

TY  - JOUR
T1  - Fully 3-dimensional reconstruction for a PET camera with retractable septa
A1  - Townsend,D.W.
A1  - Geissbuhler,A.
A1  - Defrise,M.
A1  - Hoffman,E.J.
A1  - Spinks,T.J.
A1  - Bailey,D.L.
A1  - Gilardi,M.C.
A1  - Jones,T.
Y1  - 1991///
SP  - 505
EP  - 512
JF  - IEEE Transactions on Medical Imaging
VL  - 10
IS  - 4
ER  - 

TY  - JOUR
T1  - Oral administration of NNC 756--a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man
A1  - Karlsson,P.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Sedvall,G.
A1  - Ynddal,L.
A1  - Sloth-Nielsen,M.
Y1  - 1995///
SP  - 1
EP  - 8
JF  - Psychopharmacology
VL  - 119
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of human narcolepsy: no increase in striatal dopamine D2 receptors
A1  - Rinne,J.O.
A1  - Hublin,C.
A1  - Partinen,M.
A1  - Ruottinen,H.
A1  - Ruotsalainen,U.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Laihinen,A.
Y1  - 1995///
SP  - 1735
EP  - 1738
JF  - Neurology
VL  - 45
IS  - 9
ER  - 

TY  - JOUR
T1  - Decreased cerebral glucose metabolism in patients with brain tumors: an effect of corticosteroids
A1  - Fulham,M.J.
A1  - Brunetti,A.
A1  - Aloj,L.
A1  - Raman,R.
A1  - Dwyer,A.J.
A1  - Di Chiro,G.
Y1  - 1995///
N1  - Approx. 30% reduction of CMRGlu in contralateral hemispere due to dexamethasone
SP  - 657
EP  - 664
JF  - Journal of Neurosurgery
VL  - 83
IS  - 4
N2  - The authors measured cerebral glucose metabolism (CMR(glc)) using [F-18]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMR(glc) compared to normal volunteers and other brain tumor patients (Kruskal-Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMR The authors conclude that there is a generalized reduction in CMR in brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication: acid transhemispheric functional disconnection (transhemispheric diaschisis).
ER  - 

TY  - JOUR
T1  - Positron emission tomography of 5-HT transporter sites in the baboon brain with [11C]McN5652
A1  - Szabo,Z.
A1  - Scheffel,U.
A1  - Suehiro,M.
A1  - Dannals,R.F.
A1  - Kim,S.E.
A1  - Ravert,H.T.
A1  - Ricaurte,G.A.
A1  - Wagner,H.N.,Jr.
Y1  - 1995///
SP  - 798
EP  - 805
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 15
IS  - 5
ER  - 

TY  - JOUR
T1  - Principal component analysis and the scaled subprofile model compared to intersubject averaging and statistical parametric mapping: I. "Functional connectivity" of the human motor system studied with [15O]water PET
A1  - Strother,S.C.
A1  - Anderson,J.R.
A1  - Schaper,K.A.
A1  - Sidtis,J.J.
A1  - Liow,J.S.
A1  - Woods,R.P.
A1  - Rottenberg,D.A.
Y1  - 1995///
SP  - 738
EP  - 753
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 15
IS  - 5
ER  - 

TY  - JOUR
T1  - Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenics, and controls
A1  - Siegel,B.V.,Jr.
A1  - Nuechterlein,K.H.
A1  - Abel,L.
A1  - Wu,J.C.
A1  - Buchsbaum,M.S.
Y1  - 1995/09//
N1  - UI - 96117982
SP  - 85
EP  - 94
JA  - Schizophr.Res
VL  - 17
IS  - 1
N2  - Twenty-five schizophrenic patients, fourteen adults with a history of infantile autism, and twenty normal controls performed a test of sustained attention, the degraded stimulus continuous performance test (CPT), during the 35 minute 18-fluoro-2-deoxyglucose uptake period preceding positron emission tomographic (PET) scan acquisition. This is the first analysis comparing correlations between glucose metabolic rate (GMR) for selected regions and CPT performance. CPT performance differed in controls and schizophrenics, but autistics did not differ from either group. In controls and schizophrenic patients, task performance correlated with GMR in medial superior frontal gyrus and lateral inferior temporal gyrus, suggesting that activation of those regions is important in the normal performance of the task and that damage to those regions, which also showed low GMR in schizophrenics, contributes to the attentional dysfunction in schizophrenia. Also, schizophrenics showed negative correlations of task performance with anterior cingulate activity suggesting that overactivity of that region, which is involved in mental effort and whose GMR was low in our larger study of schizophrenia, impairs task performance in schizophrenics. Autistic patients showed negative correlations of medial frontal cortical GMR with attentional performance, suggesting that neuronal inefficiency in that region may contribute to poor performance
AD  - Department of Psychiatry, Mount Sinai School of Medicine, Bronx Veteran's Administration Medical Center, Bronx, NY 10468, USA
UR  - PM:8541254
ER  - 

TY  - JOUR
T1  - Striatal opioid receptor binding in Parkinson's disease, striatonigral degeneration and Steele-Richardson-Olszewski syndrome, A [11C]diprenorphine PET study
A1  - Burn,D.J.
A1  - Rinne,J.O.
A1  - Quinn,N.P.
A1  - Lees,A.J.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1995///
SP  - 951
EP  - 958
JF  - Brain
VL  - 118
IS  - Pt 4
N2  - The clinical differentiation of Parkinson's disease from the striatonigral degeneration (SND) type of multiple system atrophy (MSA) and Steele-Richardson-Olszewski syndrome (SRO) may be difficult. This is reflected by a 20-25% misdiagnosis rate in clinicopathological series of cases labelled as Parkinson's disease in life. The caudate and putamen contain a high density of opioidergic neurons and receptors which have a close anatomical and physiological relationship with the dopaminergic system. We used [11C]diprenorphine with PET to investigate striatal opioid receptor binding in groups of patients with clinically defined Parkinson's disease (n = 8), SND (n = 7) and SRO (n = 6), compared with normal controls (n = 8). There was no significant difference between mean ligand binding in the putamen and caudate of Parkinson's disease cases when compared with normals. Mean putamen, but not caudate, opioid receptor binding was significantly reduced in the SND group, when compared with normals. By contrast, in the SRO group, both mean caudate and putamen opioid receptor binding was significantly reduced when compared with both normal and Parkinson's disease groups. When considering the individual patients, none of the eight Parkinson's disease cases (0%), none of the seven SND cases (0%), but four of the six SRO cases (67%) had caudate opioid receptor binding that was > 2.5 SDs below the normal mean. Corresponding figures for putamen opioid receptor binding were: none of the Parkinson's disease cases (0%); three of the SND cases (43%); and all of the SRO cases (100%). We conclude that there are differences in the pattern of opioid receptor binding in the striatum of Parkinson's disease, SND and SRO patients, as determined by [11C]diprenorphine PET. The different binding patterns may help to differentiate these akinetic-rigid syndromes in life
ER  - 

TY  - JOUR
T1  - Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects
A1  - Jahanshahi,M.
A1  - Jenkins,I.H.
A1  - Brown,R.G.
A1  - Marsden,C.D.
A1  - Passingham,R.E.
A1  - Brooks,D.J.
Y1  - 1995///
SP  - 913
EP  - 933
JF  - Brain
VL  - 118
IS  - Pt 4
ER  - 

TY  - JOUR
T1  - Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology
A1  - Wolkin,A.
A1  - Sanfilipo,M.
A1  - Angrist,B.
A1  - Duncan,E.
A1  - Wieland,S.
A1  - Wolf,A.P.
A1  - Brodie,J.D.
A1  - Cooper,T.B.
A1  - Laska,E.
A1  - Rotrosen,J.P.
Y1  - 1994/09/01/
N1  - UI - 95086130
SP  - 317
EP  - 325
JA  - Biol.Psychiatry
VL  - 36
IS  - 5
N2  - The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however
AD  - Psychiatry Service, New York Veterans Administration Medical Center, NY
UR  - PM:7993958
ER  - 

TY  - JOUR
T1  - Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652
A1  - Szabo,Z.
A1  - Kao,P.F.
A1  - Scheffel,U.
A1  - Suehiro,M.
A1  - Mathews,W.BXXA.U.
A1  - Musachio,J.L.
A1  - Marenco,S.
A1  - Kim,S.E.
A1  - Ricaurte,G.A.
A1  - et al.
Y1  - 1995///
SP  - 37
EP  - 43
JF  - Synapse
VL  - 20
IS  - 1
ER  - 

TY  - JOUR
T1  - Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis
A1  - Minoshima,S.
A1  - Frey,K.A.
A1  - Foster,N.L.
A1  - Kuhl,D.E.
Y1  - 1995///
SP  - 541
EP  - 547
JF  - Journal of Computer Assisted Tomography
VL  - 19
IS  - 4
ER  - 

TY  - JOUR
T1  - Developmental changes in brain metabolism in sedated rhesus macaques and vervet monkeys revealed by positron emission tomography
A1  - Jacobs,B.
A1  - Chugani,H.T.
A1  - Allada,V.
A1  - Chen,S.
A1  - Phelps,M.E.
A1  - Pollack,D.B.
A1  - Raleigh,M.J.
Y1  - 1995///
SP  - 222
EP  - 233
JF  - Cerebral Cortex
VL  - 5
IS  - 3
ER  - 

TY  - JOUR
T1  - Serial positron emission tomography with fludeoxyglucose F 18 in Creutzfeldt-Jakob disease
A1  - Ogawa,T.
A1  - Inugami,A.
A1  - Fujita,H.
A1  - Hatazawa,J.
A1  - Shimosegawa,E.
A1  - Kanno,I.
A1  - Okudera,T.
A1  - Uemura,K.
A1  - Nagata,K.
Y1  - 1995///
SP  - 978
EP  - 981
JF  - Ajnr: American Journal of Neuroradiology
VL  - 16
IS  - 4 Suppl
ER  - 

TY  - JOUR
T1  - Improved sensitivity of 18FDG-positron emission tomography scans in frontal and "frontal plus" epilepsy
A1  - Swartz,B.W.
A1  - Khonsari,A.
A1  - Vrown,C.
A1  - Mandelkern,M.
A1  - Simpkins,F.
A1  - Krisdakumtorn,T.
Y1  - 1995///
SP  - 388
EP  - 395
JF  - Epilepsia
VL  - 36
IS  - 4
N2  - We evaluated three techniques of analyzing 18FDG-positron emission tomography-(PET) scans in 23 cases of presumed frontal lobe epilepsy (FLE): routine visual or "qualitative linear," "qualitative normalized," and quantitative normalized approaches. Patients were then classified as having pure frontal, probable frontal, frontoparietal and frontotemporal epilepsy based on prolonged surface EEG monitoring with video, magnetic resonance imaging (MRI), chronic intracranial recording (CIR), and results of surgical excision. Overall sensitivity and accuracy of the scans was 52 and 48%for qualitative linear analysis, which was equivalent to that of MRI, and 69 and 43% for qualitative normalized analysis. Quantitative normalized analysis had 96% sensitivity and 74 - 78% accuracy and also detected 9 of 11 (81%) abnormalities in nonlesional cases, improving routine sensitivity from 1 of 11 (9%). We conclude that qualitative linear (routine) analysis is inadequate for diagnosis of FLE lobe or "frontal-plus" epilepsies and does not add to the MRI scan. Because qualitative normalized images improve on routine analysis only slightly, quantitative techniques should be applied for preoperaive evaluations.
ER  - 

TY  - JOUR
T1  - Large-scale plasticity of the human motor cortex
A1  - Seitz,R.J.
A1  - Huang,Y.
A1  - Knorr,U.
A1  - Tellmann,L.
A1  - Herzog,H.
A1  - Freund,H.J.
Y1  - 1995///
N1  - O-15-butanol PET in 6 patients with tumors in precentral gyrus, displacement of activations
SP  - 742
EP  - 744
JF  - Neuroreport
VL  - 6
IS  - 5
ER  - 

TY  - JOUR
T1  - Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography
A1  - Nordberg,A.
A1  - Lundqvist,H.
A1  - Hartvig,P.
A1  - Lilja,A.
A1  - Langstrom,B.
Y1  - 1995///
SP  - 21
EP  - 27
JF  - Alzheimer Disease & Associated Disorders
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - Striatal D1 and D2 receptor binding in patients with Huntington's disease and other choreas. A PET study
A1  - Turjanski,N.
A1  - Weeks,R.
A1  - Dolan,R.
A1  - Harding,A.E.
A1  - Brooks,D.J.
Y1  - 1995///
SP  - 689
EP  - 696
JF  - Brain
VL  - 118
IS  - Pt 3
ER  - 

TY  - JOUR
T1  - Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11- deprenyl-D2 for MAO B mapping
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Xie,S.
A1  - Volkow,N.D.
A1  - MacGregor,R.R.
A1  - Schlyer,D.J.
A1  - Pappas,N.
A1  - Alexoff,D.L.
A1  - Patlak,C.
A1  - et al.
Y1  - 1995///
SP  - 1255
EP  - 1262
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 36
IS  - 7
N2  - Recent human PET studies with the monoamine oxidase B (MAO B) tracer [11C]L-deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl ([11C]L-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity. METHODS: Five normal subjects (43-64 yr) were studied with [11C]L-deprenyl and [11C]L-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems. RESULTS: For both tracers, maximum radioactivity accumulation occurred at about 5 min. For [11C]L-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With [11C]L-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for [11C]L-deprenyl was higher than the plateau for [11C]L-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity. CONCLUSION: This study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration.
ER  - 

TY  - JOUR
T1  - Aging effect on neutral amino acid transport at the blood-brain barrier measured with L-[2-18F]-fluorophenylalanine and PET
A1  - Ito,H.
A1  - Hatazawa,J.
A1  - Murakami,M.
A1  - Miura,S.
A1  - Iida,H.
A1  - Bloomfield,P.M.
A1  - Kanno,I.
A1  - Fukuda,H.
A1  - Uemura,K.
Y1  - 1995///
SP  - 1232
EP  - 1237
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 36
IS  - 7
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in autopsy-confirmed Creutzfeldt-Jakob disease
A1  - Matochik,J.A.
A1  - Molchan,S.E.
A1  - Zametkin,A.J.
A1  - Warden,D.L.
A1  - Sunderland,T.
A1  - Cohen,R.M.
Y1  - 1995///
SP  - 153
EP  - 157
JF  - Acta Neurologica Scandinavica
VL  - 91
IS  - 2
ER  - 

TY  - JOUR
T1  - Landau-Kleffner syndrome with continuous spikes and waves during slow-wave sleep
A1  - Rintahaka,P.J.
A1  - Chugani,H.T.
A1  - Sankar,R.
Y1  - 1995///
SP  - 127
EP  - 133
JF  - Journal of Child Neurology
VL  - 10
IS  - 2
ER  - 

TY  - JOUR
T1  - Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia
A1  - Cleghorn,J.M.
A1  - Garnett,E.S.
A1  - Nahmias,C.
A1  - Firnau,G.
A1  - Brown,G.M.
A1  - Kaplan,R.
A1  - Szechtman,H.
A1  - Szechtman,B.
Y1  - 1989/05//
N1  - UI - 89316143
SP  - 119
EP  - 133
JA  - Psychiatry Res
VL  - 28
IS  - 2
N2  - Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls
AD  - Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada
UR  - PM:2787515
ER  - 

TY  - JOUR
T1  - Recovery from Wernicke's aphasia: a positron emission tomographic study
A1  - Weiller,C.
A1  - Isensee,C.
A1  - Rijntjes,M.
A1  - Huber,W.
A1  - Muller,S.
A1  - Bier,D.
A1  - Dutschka,K.
A1  - Woods,R.P.
A1  - Noth,J.
A1  - Diener,H.C.
Y1  - 1995///
SP  - 723
EP  - 732
JF  - Annals of Neurology
VL  - 37
IS  - 6
N2  - Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke
ER  - 

TY  - JOUR
T1  - Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain
A1  - Volkow,N.D.
A1  - Ding,Y.S.
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Gatley,J.S.
A1  - Dewey,S.
A1  - Ashby,C.
A1  - Liebermann,J.
A1  - Hitzemann,R.
A1  - et al.
Y1  - 1995///
SP  - 456
EP  - 463
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 52
IS  - 6
ER  - 

TY  - JOUR
T1  - Sustained withdrawal allows normalization of in vivo [11C]N-methylspiperone dopamine D2 receptor binding after chronic binge cocaine: a positron emission tomography study in rats
A1  - Maggos,C.E.
A1  - Tsukada,H.
A1  - Kakiuchi,T.
A1  - Nishiyama,S.
A1  - Myers,J.E.
A1  - Kreuter,J.
A1  - Schlussman,S.D.
A1  - Unterwald,E.M.
A1  - Ho,A.
A1  - Kreek,M.J.
Y1  - 1998/08//
N1  - UI - 98293213
SP  - 146
EP  - 153
JF  - Neuropsychopharmacology
VL  - 19
IS  - 2
N2  - In our previous positron emission tomography studies striatal binding for both [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain on the last day of chronic (14 days) binge cocaine administration. We have found that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control levels within ten days withdrawal from chronic binge cocaine and remains at control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to dopamine D2 receptors was observed after ten days withdrawal. However, importantly, after 21 days withdrawal [11C]NMSP binding was at saline control levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine D2 receptors after prolonged abstinence from chronic cocaine and the different rates of normalization for dopamine D1 versus D2 receptors may be critical information for development of pharmacotherapies for cocaine dependent patients
AD  - Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA
UR  - PM:9629568
ER  - 

TY  - JOUR
T1  - [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment
A1  - Perani,D.
A1  - Colombo,C.
A1  - Bressi,S.
A1  - Bonfanti,A.
A1  - Grassi,F.
A1  - Scarone,S.
A1  - Bellodi,L.
A1  - Smeraldi,E.
A1  - Fazio,F.
Y1  - 1995///
SP  - 244
EP  - 250
JF  - British Journal of Psychiatry
VL  - 166
IS  - 2
N2  - BACKGROUND. We used [18F]FDG and PET in patients with obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement before and after treatment with serotonin-specific reuptake inhibitors. METHOD. In 11 untreated, drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was compared with that of 15 age-matched normal controls. RESULTS. rCMRglu values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen complex. After treatment a significant improvement in obsessive-compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P < 0.01). CONCLUSIONS. These findings indicate that OCD is associated with functional hyperactivity of a selected neuronal network and that treatment to reduce symptoms may have a selective neuromodulatory effect on cingulate cortex.
ER  - 

TY  - JOUR
T1  - Brain hypometabolism of glucose in anorexia nervosa: a PET scan study
A1  - Delvenne,V.
A1  - Lotstra,F.
A1  - Goldman,S.
A1  - Biver,F.
A1  - De Maertelaer,V.
A1  - Appelboom-Fondu,J.
A1  - Schoutens,A.
A1  - Bidaut,L.M.
A1  - Luxen,A.
A1  - Mendelwicz,J.
Y1  - 1995///
N1  - Reduced cortical metabolism
SP  - 161
EP  - 169
JF  - Biological Psychiatry
VL  - 37
IS  - 3
N2  - Cerebral glucose metabolism was studied in 20 underweight anorectic girls and in 10 age- and sex-matched healthy volunteers using positron emission tomography with (18-F)-fluorodeoxy-glucose. Both groups were scanned during rest, with eye closed and with low ambient noise. Compared to controls, the underweight anorectic group showed a global hypometabolism (p = .002) and an absolute (p < .001) as well as relative (p < .01) hypometabolism of glucose in cortical regions, with the most significant differences found in the frontal and the parietal cortices. Within the underweight anorectic and the control groups, no correlations were found between absolute or relative rCMRGlu and BMI, anxiety scores, or Hamilton scores of depression. Different factors might explain this reduction of glucose metabolism in anorexia nervosa. It might be the consequence of neurophysiological or morphological aspects of anorexia nervosa and/or the result of some associated symptoms such as anxiety or depressed feelings. Supported by cognitive studies, we can also hypothesize a primary corticocerebral dysfunctioning in anorexia nervosa
ER  - 

TY  - JOUR
T1  - N-omega-fluoroalkyl analogs of (1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-tropane (beta-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters
A1  - Neumeyer,J.L.
A1  - Wang,S.
A1  - Gao,Y.
A1  - Milius,R.A.
A1  - Kula,N.S.
A1  - Campbell,A.
A1  - Baldessarini,R.J.
A1  - Zea-Ponce,Y.
A1  - Baldwin,R.M.
A1  - Innis,R.B.
Y1  - 1994/05/27/
N1  - UI - 94260512
SP  - 1558
EP  - 1561
JA  - J Med Chem.
VL  - 37
IS  - 11
AD  - Research Biochemicals International, Natick, Massachusetts 01760
UR  - PM:8201589
ER  - 

TY  - JOUR
T1  - Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET
A1  - Delbeke,D.
A1  - Meyerowitz,C.
A1  - Lapidus,R.L.
A1  - Maciunas,R.J.
A1  - Jennings,M.T.
A1  - Moots,P.L.
A1  - Kessler,R.M.
Y1  - 1995///
SP  - 47
EP  - 52
JF  - Radiology
VL  - 195
IS  - 1
ER  - 

TY  - JOUR
T1  - Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease
A1  - Small,G.W.
A1  - Mazziotta,J.C.
A1  - Collins,M.T.
A1  - Baxter,L.R.
A1  - Phelps,M.E.
A1  - Mandelkern,M.A.
A1  - Kaplan,A.
A1  - La Rue,A.
A1  - Adamson,C.F.
A1  - Chang,L.
A1  - et al.
Y1  - 1995///
N1  - Reduced parietal CMRGlu
SP  - 942
EP  - 947
JF  - JAMA
VL  - 273
IS  - 12
N2  - Objective.-Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familiar AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. Design.-After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. Setting.-University medical center. Patients.-At-risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). Main Outcome Measures.-Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. Results.-Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4, Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. Conclusions.-These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in nondemented relatives at risk for probable AD, Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder. [References: 60]
ER  - 

TY  - JOUR
T1  - In vivo protein synthesis rate determination in primary or recurrent brain tumors using L-[1-11C]-tyrosine and PET
A1  - Willemsen,A.T.
A1  - van Waarde,A.
A1  - Paans,A.M.
A1  - Pruim,J.
A1  - Luurtsema,G.
A1  - Go,K.G.
A1  - Vaalburg,W.
Y1  - 1995///
SP  - 411
EP  - 419
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 36
IS  - 3
ER  - 

TY  - JOUR
T1  - Assessment of disease severity in parkinsonism with fluorine-18- fluorodeoxyglucose and PET
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Ishikawa,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Chaly,T.
A1  - Robeson,W.
A1  - Dahl,J.R.
A1  - Margouleff,D.
Y1  - 1995///
SP  - 378
EP  - 383
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 36
IS  - 3
ER  - 

TY  - JOUR
T1  - Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease
A1  - Meyer,M.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Foster,N.L.
A1  - Kuhl,D.E.
Y1  - 1995///
SP  - 314
EP  - 317
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 52
IS  - 3
ER  - 

TY  - JOUR
T1  - Diagnostic yield of stereotactic brain biopsy guided by positron emission tomography with [18F]fluorodeoxyglucose
A1  - Levivier,M.
A1  - Goldman,S.
A1  - Pirotte,B.
A1  - Brucher,J.M.
A1  - Baleriaux,D.
A1  - Luxen,A.
A1  - Hildebrand,J.
A1  - Brotchi,J.
Y1  - 1995///
SP  - 445
EP  - 452
JF  - Journal of Neurosurgery
VL  - 82
IS  - 3
ER  - 

TY  - JOUR
T1  - Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol
A1  - Delforge,J.
A1  - Pappata,S.
A1  - Millet,P.
A1  - Samson,Y.
A1  - Bendriem,B.
A1  - Jobert,A.
A1  - Crouzel,C.
A1  - Syrota,A.
Y1  - 1995///
SP  - 284
EP  - 300
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 15
IS  - 2
ER  - 

TY  - JOUR
T1  - Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography
A1  - Alkire,M.T.
A1  - Haier,R.J.
A1  - Barker,S.J.
A1  - Shah,N.K.
A1  - Wu,J.C.
A1  - Kao,Y.J.
Y1  - 1995///discussion 27A
SP  - 393
EP  - 403
JF  - Anesthesiology
VL  - 82
IS  - 2
N2  - BACKGROUND: Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia. METHODS: Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg-1.h-1). Scans were obtained using the 18fluorodeoxyglucose technique. RESULTS: Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mumoles.100 g-1.min-1 (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mumoles.100 g-1.min-1 (paired t test, P < or = 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < or = 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. CONCLUSION: Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans. <204>
ER  - 

TY  - JOUR
T1  - Sex differences in regional cerebral glucose metabolism during a resting state
A1  - Gur,R.C.
A1  - Mozley,L.H.
A1  - Mozley,P.D.
A1  - Resnick,S.M.
A1  - Karp,J.S.
A1  - Alavi,A.
A1  - Arnold,S.E.
A1  - Gur,R.E.
Y1  - 1995///
SP  - 528
EP  - 531
JF  - Science
VL  - 267
IS  - 5197
ER  - 

TY  - JOUR
T1  - Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle
A1  - Lassen,N.A.
A1  - Bartenstein,P.A.
A1  - Lammertsma,A.A.
A1  - Prevett,M.C.
A1  - Turton,D.R.
A1  - Luthra,S.K.
A1  - Osman,S.
A1  - Bloomfield,P.M.
A1  - Jones,T.
A1  - Patsalos,P.N.
A1  - et al.
Y1  - 1995///
SP  - 152
EP  - 165
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 15
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomographic studies of cerebral benzodiazepine-receptor binding in chronic alcoholics
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Adams,K.
A1  - Johnson-Greene,D.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Brunberg,J.
A1  - Martorello,S.
A1  - Lohman,M.
Y1  - 1996/08//
N1  - UI - 96369657
SP  - 163
EP  - 171
JA  - Ann.Neurol
VL  - 40
IS  - 2
N2  - Positron emission tomography was used with [11C]flumazenil (FMZ) and [18F]fluorodeoxyglucose to study GABA type A/benzodiazepine (GA-BA-A/BDZ) receptors and cerebral metabolic rates for glucose (1CMRg1c) in 17 male patients with severe chronic alcoholism (ALC), 8 with (ACD) and 9 without alcoholic cerebellar degeneration (non-ACD). In comparison with male normal controls of similar ages, the ALC group had significantly reduced FMZ ligand influx (K1), FMZ distribution volume (DV), and lCMRglc bilaterally in the medial frontal lobes, including superior frontal gyrus and rostral cingulate gyrus; the ACD group had significant reductions of K1, DV, and 1CMRg1c bilaterally in the same distribution, and also in the superior cerebellar vermis; and the non-ACD group had significant reductions of K1, DV, and 1CMRg1c bilaterally in the same regions of the frontal lobes but not in the superior cerebellar vermis. When compared with the non-ACD group, the ACD group had significant reductions of K1, and DV bilaterally in the superior cerebellar vermis. The results suggest that severe chronic alcoholism damages neurons containing GA-BA-A/BDZ receptors in the superior medial aspects of the frontal lobes, and in patients with clinical signs of ACD, neurons containing GABA-A/BDZ receptors in the superior cerebellar vermis
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0316, USA
UR  - PM:8773597
ER  - 

TY  - JOUR
T1  - Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomography studies of older alcoholic patients
A1  - Adams,K.M.
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Kluin,K.J.
A1  - Brunberg,J.A.
A1  - Dede,D.
A1  - Berent,S.
A1  - Kroll,P.D.
Y1  - 1993/04//
N1  - UI - 93256205
SP  - 205
EP  - 210
JA  - Alcohol Clin.Exp.Res
VL  - 17
IS  - 2
N2  - In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Psychology Service, Veteran's Affairs Medical Center, Ann Arbor, MI
UR  - PM:8488956
ER  - 

TY  - JOUR
T1  - Effects of hyperglycemia on FDG uptake in human brain and glioma [see comments]
A1  - Ishizu,K.
A1  - Nishizawa,S.
A1  - Yonekura,Y.
A1  - Sadato,N.
A1  - Magata,Y.
A1  - Tamaki,N.
A1  - Tsuchida,T.
A1  - Okazawa,H.
A1  - Miyatake,S.
A1  - Ishikawa,M.
A1  - et al.
Y1  - 1994///
SP  - 1104
EP  - 1109
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 7
N2  - This study evaluates the effects of hyperglycemia on fluorodeoxyglucose (FDG) uptake in the human brain and in brain tumors. METHODS: We performed glucose loading during FDG PET studies in nine patients with brain tumors (eight gliomas and one brain metastasis) and one with resected glioma. Two FDG PET scans were obtained in all cases within 1 wk in a control state and with glucose loading by intravenous infusion of 10% glucose solution. Serial arterial blood sampling was performed in all cases to obtain fractional uptake of FDG normalized by the plasma integral uptake of radioactivity (FU). RESULTS: In all nine patients with brain tumors, the tumor was depicted more clearly with glucose loading than in the control state. Glucose loading decreased FU in the cerebral cortex (54.2% +/- 13.8%) nearly in inverse proportion to the plasma glucose level, while the tumors showed a decrease (42.5% +/- 15.6%), resulting in an increased tumor-to-cortex ratio by 26.0% +/- 5.7%. Fractional uptake in the cerebellum, white matter and the edematous area also decreased by glucose loading (53.9% +/- 13.2%, 49.6% +/- 10.3% and 34.9% +/- 9.6%, respectively). CONCLUSION: These results demonstrate the different effects of hyperglycemia on normal brain tissue and on tumor, suggesting that glucose loading may be a valuable adjunct to FDG PET to enhance detection of recurrent or residual brain tumors.
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography [see comments]
A1  - Rauch,S.L.
A1  - Jenike,M.A.
A1  - Alpert,N.M.
A1  - Baer,L.
A1  - Breiter,H.C.
A1  - Savage,C.R.
A1  - Fischman,A.J.
Y1  - 1994///
SP  - 62
EP  - 70
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 51
IS  - 1
N2  - BACKGROUND: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. RESULTS: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008); increases in the left thalamus approached but did not reach statistical significance (P = .07). CONCLUSIONS: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms
ER  - 

TY  - JOUR
T1  - Brain glucose utilization in band heterotopia: synaptic activity of "double cortex"
A1  - De Volder,A.G.
A1  - Gadisseux,J.F.
A1  - Michel,C.J.
A1  - Maloteaux,J.M.
A1  - Bol,A.C.
A1  - Grandin,C.B.
A1  - Duprez,T.P.
A1  - Evrard,P.
Y1  - 1994///
SP  - 290
EP  - 294
JF  - Pediatric Neurology
VL  - 11
IS  - 4
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism as a predictor of recovery from aphasia in ischemic stroke
A1  - Heiss,W.D.
A1  - Kessler,J.
A1  - Karbe,H.
A1  - Fink,G.R.
A1  - Pawlik,G.
Y1  - 1993/09//
N1  - UI - 93371208
SP  - 958
EP  - 964
JA  - Arch Neurol
VL  - 50
IS  - 9
N2  - OBJECTIVE--The recovery of language function seen in poststroke aphasia is significantly related to the severity of the initial neurologic deficit. However, a great deal of variability still remains in the improvement that is actually achieved. To detect predictors that will help in explaining this variability, positron emission tomography (PET) and fluorodeoxyglucose F 18 (18-F-fluorodeoxyglucose) were used and the results were analyzed by stepwise regression. DESIGN--Using PET imaging after injection of fluorodeoxyglucose F 18, the regional changes in glucose metabolism in 26 patients at a period of 12 to 18 days following an ischemic stroke involving the left middle cerebral artery were examined. A second PET examination was performed on 17 of our 26 patients who were able to perform speech activation exercises. All patients received an initial and a 4-month follow-up evaluation of language performance. SETTING--During the two PET studies and the first language assessment, the patients were hospitalized in a neurologic clinic. The follow-up evaluation of language performance was performed when the patients were ambulatory. PATIENTS--Twenty-six patients (10 women, 16 men; aged 38 to 77 years; mean +/- SD, 60 +/- 9.2 years) were selected in the study. Their aphasias were of various types and of varying severity ranging from mild impairment to severe global aphasia. MAIN OUTCOME MEASURES--For the stepwise regression analysis of variables, the following variables were analyzed in resting and activation PET to explain residual variance from the first to the second Token Test: regional cerebral metabolic rate for glucose of infarct and mirror region, left and right cerebral and cerebellar hemispheres, left and right Broca's area, left and right Wernicke's area, and left and right temporoparietal cortex. RESULTS--As was expected, early and late Token Tests exhibit a high correlation (.85). The stepwise regression analysis shows that only the left cerebral hemisphere glucose value of the resting PET had significant effect on the residual variance of the Token Test regression. Regional metabolic rates during speech activation had the largest contribution to a significant recovery from aphasia. The infarct area and its corresponding mirror region, the left Broca's area, and the entire left cerebral hemisphere accounted for 80% of the residual variance. CONCLUSIONS--These results emphasize not only the application of PET activation studies in the prediction of a tissue's potential reserve capacity but also the importance of left hemisphere integrity in the recovery of functional language
AD  - Max-Planck-Institut fur Neurologische Forschung and Neurologische Universitatsklinik Koln, Germany
UR  - PM:8363450
ER  - 

TY  - JOUR
T1  - Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow
A1  - Dolan,R.J.
A1  - Bench,C.J.
A1  - Brown,R.G.
A1  - Scott,L.C.
A1  - Frackowiak,R.S.
Y1  - 1994///
SP  - 849
EP  - 857
JF  - Psychological Medicine
VL  - 24
IS  - 4
N2  - The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex. <206>
ER  - 

TY  - JOUR
T1  - Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE
A1  - Peyron,R.
A1  - Cinotti,L.
A1  - Le Bars,D.
A1  - Garcia-Larrea,L.
A1  - Galy,G.
A1  - Landais,P.
A1  - Millet,P.
A1  - Lavenne,F.
A1  - Froment,J.C.
A1  - Krogsgaard-Larsen,P.
A1  - et al.
Y1  - 1994///
SP  - 55
EP  - 62
JF  - Epilepsy Research
VL  - 19
IS  - 1
ER  - 

TY  - JOUR
T1  - Functional and morphological imaging of small striato-capsular infarction by CT, MRI and multitracer PET
A1  - Fink,G.R.
A1  - Pietrzyk,U.
A1  - Herholz,K.
A1  - Huber,M.
A1  - Heiss,W.D.
Y1  - 1992///
N1  - UI - 92396316
SP  - 139
EP  - 142
JA  - Neurol Res
VL  - 14
IS  - 2 Suppl
N2  - Regional cerebral blood flow, oxygen consumption, blood volume and glucose metabolism were studied by positron emission tomography (PET) in 16 patients with striato-capsular infarction during the acute phase. Visual evaluation of tomograms and quantitative analysis of PET data detected in all patients severe flow disturbances and metabolic derangement within the territory of the penetrating branches of the middle cerebral artery. Additionally remote effects were observed. The correspondence of early PET changes with the diagnosis of striato-capsular infarction was verified later on by computerized three-dimensional alignment of PET scans and MRI. These results demonstrate that PET allows localization of small striato-capsular infarction with high accuracy in the acute phase by demonstrating both severe local flow disturbances and metabolic derangement, as well as remote effects
AD  - Max-Planck-Institut fur Neurologische Forschung Koln, Germany
UR  - PM:1355871
ER  - 

TY  - JOUR
T1  - Predictors of outcome after anterior temporal lobectomy: positron emission tomography
A1  - Manno,E.M.
A1  - Sperling,M.R.
A1  - Ding,X.
A1  - Jaggi,J.
A1  - Alavi,A.
A1  - O'Connor,M.J.
A1  - Reivich,M.
Y1  - 1994///
SP  - 2331
EP  - 2336
JF  - Neurology
VL  - 44
IS  - 12
N2  - We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fisher's exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.
ER  - 

TY  - JOUR
T1  - PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756
A1  - Laihinen,A.O.
A1  - Rinne,J.O.
A1  - Ruottinen,H.M.
A1  - Nagren,K.A.
A1  - Lehikoinen,P.K.
A1  - Oikonen,V.J.
A1  - Ruotsalainen,U.H.
A1  - Rinne,U.K.
Y1  - 1994///
SP  - 1916
EP  - 1920
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 12
ER  - 

TY  - JOUR
T1  - Altered cerebral energy metabolism in Alzheimer's disease: a PET study
A1  - Fukuyama,H.
A1  - Ogawa,M.
A1  - Yamauchi,H.
A1  - Yamaguchi,S.
A1  - Kimura,J.
A1  - Yonekura,Y.
A1  - Konishi,J.
Y1  - 1994///
SP  - 1
EP  - 6
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 1
N2  - In an effort to better understand the metabolic basis for the reported decreases in regional cerebral cortex glucose metabolism in patients with Alzheimer's disease, glucose
ER  - 

TY  - JOUR
T1  - Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy
A1  - Chugani,H.T.
A1  - Jacobs,B.
Y1  - 1994///
SP  - 794
EP  - 797
JF  - Annals of Neurology
VL  - 36
IS  - 5
ER  - 

TY  - JOUR
T1  - Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride
A1  - Khan,N.
A1  - Antonini,A.
A1  - Parkes,D.
A1  - Dahlitz,M.J.
A1  - Meier-Ewert,K.
A1  - Weindl,A.
A1  - Leenders,K.L.
Y1  - 1994///
SP  - 2102
EP  - 2104
JF  - Neurology
VL  - 44
IS  - 11
N2  - We investigated in vivo D2 receptor binding using 11C-raclopride and PET in the striatum of 17 subjects with the narcoleptic syndrome. Putamen and caudate nucleus 11C-raclopride uptake was comparable in the total patient group and controls, and the tracer uptake was similar in the HLA-DR2-positive (n = 12) and HLA-DR2-negative (n = 5) narcoleptic subjects. There was a significant increase in 11C-raclopride uptake in the putamen of narcoleptic subjects older than 31 years (n = 11) when compared with age-matched controls (n = 15). There was no evidence of involvement of the striatal D2 dopaminergic neurotransmitter system in the basic pathophysiology of the narcoleptic syndrome despite an age-related increase in putaminal 11C-raclopride uptake
ER  - 

TY  - JOUR
T1  - Cerebral network underlying unilateral motor neglect: evidence from positron emission tomography
A1  - von Giesen,H.J.
A1  - Schlaug,G.
A1  - Steinmetz,H.
A1  - Benecke,R.
A1  - Freund,H.J.
A1  - Seitz,R.J.
Y1  - 1994///
SP  - 29
EP  - 38
JF  - Journal of the Neurological Sciences
VL  - 125
IS  - 1
N2  - In 4 male patients (age range 50-73 years) with unilateral motor hemineglect as a sequelae of circumscribed cerebral infarction, depressions of the regional cerebral glucose metabolism (rCMRGlu) were mapped to identify the metabolically affected cerebral structures. Motor neglect was defined according to Castaigne by lack of spontaneous and pain-induced motor activity on one side of the body in the absence of paresis, pyramidal signs, and sensory loss. The depressions of the rCMRGlu as determined by positron emission tomography (PET) were found to exceed the areas of structural damage but to be restricted to the affected cerebral hemisphere. Significant mean rCMRGlu depressions followed a focal pattern involving the premotor, prefrontal, parietal and cingulate cortex, as well as the thalamus. In correspondence to the lack of significant mean rCMRGlu depressions in primary sensorimotor cortex, basal ganglia, and cerebellum the cortico-spinal pathway was spared as indicated by preserved magnetic evoked motor potentials. Our data provide evidence suggesting that motor hemineglect is a disturbance in a cerebral network of higher order cortical areas subserving motor activity in the presence of an intact motor cortical output system
ER  - 

TY  - JOUR
T1  - A double FDG/PET study of the effects of scopolamine in older adults
A1  - Molchan,S.E.
A1  - Matochik,J.A.
A1  - Zametkin,A.J.
A1  - Szymanski,H.V.
A1  - Cantillon,M.
A1  - Cohen,R.M.
A1  - Sunderland,T.
Y1  - 1994///
SP  - 191
EP  - 198
JF  - Neuropsychopharmacology
VL  - 10
IS  - 3
N2  - Two consecutive positron emission scans were done in one session using a double injection method of [18F]2-fluoro-2-deoxyglucose administration to examine the effects of the antimuscarinic drug scopolamine on cerebral glucose metabolism in ten older adults. Scopolamine causes temporary memory impairment, and its effects have been used to model aspects of the cognitive impairment that occur in Alzheimer's disease (AD). Cortical metabolic rates of patients with AD have been reported to be depressed, especially in parietal, temporal, and frontal association areas. After scopolamine administration to the elderly volunteers, absolute and normalized glucose metabolic rates were depressed in prefrontal and occipital regions and increased in parietal-occipital cortical regions and a left middle temporal region. These changes in the older volunteers are generally not consistent with changes seen in AD. We conclude that deficits in muscarinic system function may contribute to some but not all of the hypometabolic changes seen in AD patients
ER  - 

TY  - JOUR
T1  - Buprenorphine reduces cerebral glucose metabolism in polydrug abusers
A1  - Walsh,S.L.
A1  - Gilson,S.F.
A1  - Jasinski,D.R.
A1  - Stapleton,J.M.
A1  - Phillips,R.L.
A1  - Dannals,R.F.
A1  - Schmidt,J.
A1  - Preston,K.L.
A1  - Grayson,R.
A1  - Bigelow,G.E.
A1  - et al.
Y1  - 1994///
SP  - 157
EP  - 170
JF  - Neuropsychopharmacology
VL  - 10
IS  - 3
N2  - Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs. <213>
ER  - 

TY  - JOUR
T1  - Striatal D2 dopamine receptor characteristics in neuroleptic- naive schizophrenic patients studied with positron emission tomography
A1  - Hietala,J.
A1  - Syvalahti,E.
A1  - Vuorio,K.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Ruotsalainen,U.
A1  - Rakkolainen,V.
A1  - Lehtinen,V.
A1  - Wegelius,U.
Y1  - 1994///
SP  - 116
EP  - 123
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 51
IS  - 2
ER  - 

TY  - JOUR
T1  - The dynamics of metabolic change following seizures as measured by positron emission tomography with fludeoxyglucose F 18
A1  - Leiderman,D.B.
A1  - Albert,P.
A1  - Balish,M.
A1  - Bromfield,E.
A1  - Theodore,W.H.
Y1  - 1994///
SP  - 932
EP  - 936
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 51
IS  - 9
ER  - 

TY  - JOUR
T1  - Anatomic standardization: linear scaling and nonlinear warping of functional brain images
A1  - Minoshima,S.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Kuhl,D.E.
Y1  - 1994///
SP  - 1528
EP  - 1537
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 9
ER  - 

TY  - JOUR
T1  - Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography
A1  - Blin,J.
A1  - Piercey,M.F.
A1  - Giuffra,M.E.
A1  - Mouradian,M.M.
A1  - Chase,T.N.
Y1  - 1994///
SP  - 44
EP  - 51
JF  - Journal of the Neurological Sciences
VL  - 123
IS  - 1-2
N2  - Two of the more consistent findings in Alzheimer's disease are depressions in frontal and temporoparietal glucose metabolism and a loss of cholinergic neurons in the nucleus basalis of Meynert. Nonetheless, cholinergic replacement strategies have had only minimal therapeutic successes. Whether this situation reflects the limited contribution of cholinergic deafferentation to the intellectual decline or the meager ability of the pharmaceuticals tested to exert their intended pharmacologic action remains unclear. To address this question, the distribution of cerebral abnormalities found in untreated Alzheimer patients, as revealed by positron emission tomography following 18F-fluorodeoxyglucose, were compared with the pattern of functional changes produced by drugs that block or stimulate cholinergic function. Physostigmine was administered to 6 Alzheimer patients to increase brain cholinergic neurotransmission. The anticholinergic scopolamine, given to normal volunteers, was administered to 6 age-matched controls. These data were compared to those obtained from the same subjects while receiving placebo. Amnestic doses of the anticholinergic, scopolamine increased glucose metabolism by up to 20% (p < 0.001) in all brain regions studied, except thalamus. This response contrasted with the metabolic reductions of up to 17% (p < 0.01), especially in parietal and frontal association cortices, occurring in unmedicated Alzheimer patients. Maximum tolerated doses of the anti-cholinesterase, physostigmine, rather than tending to normalize abnormalities in these patients, further reduced cerebral metabolism (p < 0.01) and increased metabolism in thalamus in a pattern inversely correlated (p < 0.001) with that produced by scopolamine. These results fail to support a cholinergic basis for the abnormal metabolic pattern in Alzheimer's disease
ER  - 

TY  - JOUR
T1  - Imaging endogenous dopamine competition with [11C]raclopride in the human brain
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Schlyer,D.
A1  - Hitzemann,R.
A1  - Lieberman,J.
A1  - Angrist,B.
A1  - Pappas,N.
A1  - MacGregor,R.
A1  - et al.
Y1  - 1994///
SP  - 255
EP  - 262
JF  - Synapse
VL  - 16
IS  - 4
ER  - 

TY  - JOUR
T1  - Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography
A1  - Schlaug,G.
A1  - Knorr,U.
A1  - Seitz,R.
Y1  - 1994///
SP  - 523
EP  - 534
JF  - Experimental Brain Research
VL  - 98
IS  - 3
N2  - Cerebral structures activated during sequential right-hand finger movements were mapped with regional cerebral blood flow (rCBF) measurements by positron emission tomography (PET) in individual subjects. Nine healthy volunteers were examined twice; after initial learning and after practicing the finger movement sequence for more than 1 h. Task-specific activation sites were identified by statistical distributions of maximal activity and region size in rCBF subtraction images. A consistent task-specific activation in all nine subjects was detected in the contralateral sensorimotor cortex at an average movement rate of 3.2 Hz reached after practice. This corresponded to a significant increase of the mean rCBF in the left primary sensorimotor cortex in spatially standardised and averaged PET images. Additional task-specific activation sites detected by individual analysis were found in the lateral and medial premotor, parietal, and cingulate areas, and in subcortical structures including the basal ganglia of both cerebral hemispheres. These activations showed no or little spatial overlap from subject to subject, thus being obscured in the analysis of pooled data. The observed activity patterns were related to movement rate and accuracy in individual subjects. It is suggested that the rCBF changes associated with acquisition of a motor skill in individual humans may correspond to plasticity of sensorimotor representations reported in monkeys.
ER  - 

TY  - JOUR
T1  - Positron emission tomographic measurement of cerebral blood flow and temporal lobectomy
A1  - Theodore,W.H.
A1  - Gaillard,W.D.
A1  - Sato,S.
A1  - Kufta,C.
A1  - Leiderman,D.
Y1  - 1994///
SP  - 241
EP  - 244
JF  - Annals of Neurology
VL  - 36
IS  - 2
ER  - 

TY  - JOUR
T1  - Performance characteristics of a whole-body PET scanner
A1  - DeGrado,T.R.
A1  - Turkington,T.G.
A1  - Williams,J.J.
A1  - Stearns,C.W.
A1  - Hoffman,J.M.
A1  - Coleman,R.E.
Y1  - 1994///
SP  - 1398
EP  - 1406
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 8
ER  - 

TY  - JOUR
T1  - Detection of an Alzheimer disease pattern of cerebral metabolism in Down syndrome
A1  - Azari,N.P.
A1  - Pettigrew,K.D.
A1  - Pietrini,P.
A1  - Horwitz,B.
A1  - Schapiro,M.B.
Y1  - 1994///
SP  - 69
EP  - 78
JF  - Dementia
VL  - 5
IS  - 2
ER  - 

TY  - JOUR
T1  - [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors
A1  - Antonini,A.
A1  - Schwarz,J.
A1  - Oertel,W.H.
A1  - Beer,H.F.
A1  - Madeja,U.D.
A1  - Leenders,K.L.
Y1  - 1994///
SP  - 1325
EP  - 1329
JF  - Neurology
VL  - 44
IS  - 7
ER  - 

TY  - JOUR
T1  - The effect of entacapone (OR-611) on brain [18F]-6-L-fluorodopa metabolism: implications for levodopa therapy of Parkinson's disease
A1  - Sawle,G.V.
A1  - Burn,D.J.
A1  - Morrish,P.K.
A1  - Lammertsma,A.A.
A1  - Snow,B.J.
A1  - Luthra,S.
A1  - Osman,S.
A1  - Brooks,D.J.
Y1  - 1994///
SP  - 1292
EP  - 1297
JF  - Neurology
VL  - 44
IS  - 7
N2  - We used PET and [18F]-6-L-fluorodopa ([18F]dopa) to measure the effect of a peripheral COMT inhibitor, entacapone, on the extracerebral metabolism and subsequent striatal uptake of [18F]dopa. Four parkinsonian patients and six age-matched normal controls were each scanned twice, once after carbidopa (150 mg) plus placebo and once after carbidopa (150 mg) plus entacapone (400 mg or 800 mg). Without entacapone premedication, by 90 minutes from injection, only 22% of the [18F] signal in plasma represented unmetabolized [18F]dopa (the balance being 3-O-methyl[18F]dopa). After entacapone medication, this fraction increased to 56% of the [18F] signal (p < 0.0001). We did not find any significant differences between the changes observed in patients versus controls or between those subjects who received 400 mg entacapone versus 800 mg in either this or any of the other reported measures. PET image contrast increased in all cases, reflecting an increase in the specific striatal signal ([striatum-occipital]:occipital ratio increased 38% [p < 0.0001]). Entacapone did not alter the rate of striatal uptake and decarboxylation of [18F]dopa as estimated using a graphic approach with metabolite-corrected plasma as input function to calculate the influx constant, Ki(p) (p = NS). This confirms that such an analytic approach adequately corrects for the effect of extracerebral [18F]dopa methylation. In contrast, the influx constant Ki(o) (calculated using occipital counts as the input function) increased 45% after entacapone (p < 0.0001). This demonstrates the sensitivity of this analytic approach to the presence of peripheral 3-O-methyl[18F]dopa and provides an estimate of the percentage increase in brain free [18F]dopa resulting from entacapone premedication.
ER  - 

TY  - JOUR
T1  - Tactile exploration of shape after subcortical ischaemic infarction studied with PET
A1  - Weder,B.
A1  - Knorr,U.
A1  - Herzog,H.
A1  - Nebeling,B.
A1  - Kleinschmidt,A.
A1  - Huang,Y.
A1  - Steinmetz,H.
A1  - Freund,H.J.
A1  - Seitz,R.J.
Y1  - 1994///
SP  - 593
EP  - 605
JF  - Brain
VL  - 117
IS  - Pt 3
ER  - 

TY  - JOUR
T1  - Non-stationary spatial filtering and accelerated curve fitting for parametric imaging with dynamic PET
A1  - Herholz,K.
Y1  - 1988///
N1  - UI - 89107243
SP  - 477
EP  - 484
JA  - Eur.J Nucl Med
VL  - 14
IS  - 9-10
N2  - A non-stationary spatial low pass filter was developed and implemented in combination with an accelerated non-linear curve fitting routine to create low noise-high contrast images of physiological parameters with dynamic positron emission tomography. The method was applied to 18F-2-fluoro-2-deoxyglucose (FDG) studies, and images of local blood volume, kinetic rate constants, precursor pool volume and glucose metabolism were generated. Noise reduction and contrast preservation was demonstrated in a simulated pie phantom and a study of a patient with a recent brain infarct. Considerably improvement in quantitative accuracy of pixel parameter values was observed in the phantom study in comparison with unprocessed or conventionally smoothed images
AD  - Max-Planck-Institut fur neurologische Forschung, Koln, Federal Republic of Germany
UR  - PM:3265103
ER  - 

TY  - JOUR
T1  - In vivo demonstration of altered benzodiazepine receptor density in patients with generalised epilepsy
A1  - Savic,I.
A1  - Pauli,S.
A1  - Thorell,J.O.
A1  - Blomqvist,G.
Y1  - 1994///
SP  - 797
EP  - 804
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 57
IS  - 7
N2  - Electrophysiological data suggest that an abnormal oscillatory pattern of discharge in cortical and thalamic neurons may be the major mechanism underlying primary generalised epilepsy. No neurochemical or anatomical substrate for this theory has hitherto been demonstrated in humans and the pathophysiology of primary generalised epilepsy remains unknown. By means of PET and the benzodiazepine (BZ) ligand [11C]flumazenil it has been previously shown that the BZ receptor density is reduced in the epileptic foci of patients with partial epilepsy. In the present study the method was further developed and used in a comparative analysis of cortical, cerebellar, and subcortical BZ receptor binding in patients with primary generalised tonic and clonic seizures (n = 8), and healthy controls (n = 8). Patients with generalised seizures had an increased BZ receptor density in the cerebellar nuclei (p = 0.006) and decreased density in the thalamus (p = 0.003). No significant changes were seen in the cerebral and cerebellar cortex or in the basal ganglia. The observed alterations suggest that the gamma-amino-butyric acid (GABA)-BZ system may be affected in the cerebello-thalamocortical loop of patients with generalised epilepsy and indicate possible targets for selective pharmacological treatment.
ER  - 

TY  - JOUR
T1  - A clinically practical method to acquire parametric images of unidirectional metabolic rates and blood spaces
A1  - Wong,W.H.
A1  - Hicks,K.
Y1  - 1994///
SP  - 1206
EP  - 1212
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 7
ER  - 

TY  - JOUR
T1  - Carbon-11-methionine and fluorine-18-FDG PET study in brain hematoma
A1  - Dethy,S.
A1  - Goldman,S.
A1  - Blecic,S.
A1  - Luxen,A.
A1  - Levivier,M.
A1  - Hildebrand,J.
Y1  - 1994///
SP  - 1162
EP  - 1166
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 7
N2  - Three patients were examined using PET with L-methyl-11C-methionine (11C-methionine) and 2-18F-fluoro-2-deoxy-D-glucose (FDG) 20 to 32 days after the occurrence of nontumoral brain hematomas. PET revealed high uptake of 11C-methionine in the area surrounding the hematoma in all three patients. In two patients, discrete spots of moderate uptake of FDG were found at the periphery of a hypometabolic area. PET studies were repeated in two patients 76 and 103 days after the bleeding, respectively, and showed a dramatic decrease in 11C-methionine uptake around the hematoma. The spots of FDG uptake disappeared on the repeated late scans. We hypothesize that the subacute gliotic reaction surrounding brain hematomas is responsible for increased uptake of 11C-methionine and for the presence of spots of FDG uptake. PET studies with 11C-methionine and FDG performed 20 to 32 days after the initial symptom are not helpful in the differentiation between neoplastic and non-neoplastic origins of an intracerebral hemorrhage since tracer uptake at the periphery of the lesion may be increased in both
ER  - 

TY  - JOUR
T1  - Methodological aspects of brain activation studies: cerebral blood flow determined with [15O]butanol and positron emission tomography
A1  - Ingvar,M.
A1  - Eriksson,L.
A1  - Greitz,T.
A1  - Stone-Elander,S.
A1  - Dahlbom,M.
A1  - Rosenqvist,G.
A1  - af Trampe,P.
A1  - von Euler,C.
Y1  - 1994///
SP  - 628
EP  - 638
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 14
IS  - 4
ER  - 

TY  - JOUR
T1  - Deficient cerebral activation pattern in stroke recovery
A1  - Weder,B.
A1  - Seitz,R.J.
Y1  - 1994///
SP  - 457
EP  - 460
JF  - Neuroreport
VL  - 5
IS  - 4
ER  - 

TY  - JOUR
T1  - The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts
A1  - Hakim,A.M.
A1  - Pokrupa,R.P.
A1  - Villanueva,J.
A1  - Diksic,M.
A1  - Evans,A.C.
A1  - Thompson,C.J.
A1  - Meyer,E.
A1  - Yamamoto,Y.L.
A1  - Feindel,W.H.
Y1  - 1987/03//
N1  - UI - 87269413
SP  - 279
EP  - 289
JA  - Ann.Neurol
VL  - 21
IS  - 3
N2  - Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 +/- 2.5 ml/100 gm/min (mean +/- SEM) and was in every patient lower than that in C (33.1 +/- 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 +/- 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 +/- 1.5). In Group I, region I showed a CMRGlc(N)/CMRO2 ratio of 0.22 +/- 0.06 and a CpH of 6.83 +/- 0.06. In Group 2, the same ratio in the region I was 0.58 +/- 0.09 and the CpH was 7.12 +/- 0.05. The CMRGlc (N)/CMRO2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRO2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed
UR  - PM:3496844
ER  - 

TY  - JOUR
T1  - Cerebral haemodynamic changes after extracranial-intracranial bypass surgery
A1  - Gibbs,J.M.
A1  - Wise,R.J.
A1  - Thomas,D.J.
A1  - Mansfield,A.O.
A1  - Russell,R.W.
Y1  - 1987/02//
N1  - UI - 87197362
SP  - 140
EP  - 150
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 50
IS  - 2
N2  - Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in twelve patients with carotid artery occlusion. Follow-up studies were carried out at a mean interval of eleven weeks after extracranial-intracranial bypass surgery. Clinical improvement was observed in three patients who had presented with frequent transient ischaemic attacks. One patient with multiple vascular occlusions suffered a stroke at the time of surgery. Follow-up studies showed an increase of regional cerebral blood flow in only two of the twelve patients. In the group as a whole, there was no significant change of cerebral blood flow, oxygen consumption or fractional oxygen extraction after bypass surgery. The most consistent post-operative change, observed in eleven of the twelve patients, was a fall of cerebral blood volume in the cortical territory of the bypassed carotid artery (p less than 0.01). This effect was most marked in patients with bilateral carotid occlusion, in whom there was often an accompanying fall of blood volume in the contralateral hemisphere. The post-operative findings were consistent with an increase of regional cerebral perfusion pressure as a result of the bypass procedure. Although this effect is potentially of value, those patients with most to gain from bypass surgery may also run the highest risk of peri-operative cerebral ischaemia
UR  - PM:3494814
ER  - 

TY  - JOUR
T1  - Cortical function in progressive lower motor neuron disorders and amyotrophic lateral sclerosis: a comparative PET study
A1  - Kew,J.J.
A1  - Brooks,D.J.
A1  - Passingham,R.E.
A1  - Rothwell,J.C.
A1  - Frackowiak,R.S.
A1  - Leigh,P.N.
Y1  - 1994///
SP  - 1101
EP  - 1110
JF  - Neurology
VL  - 44
IS  - 6
N2  - OBJECTIVE: To compare cortical function at rest and during limb movement in patients with progressive lower motor neuron degeneration (LMND) and amyotrophic lateral sclerosis (ALS). METHODS: PET was used to measure regional cerebral blood flow (rCBF) in five patients with progressive LMND, six patients with classic ALS with a similar degree of motor impairment, and six age-matched control subjects; measurements were taken in the resting state and while subjects moved a joystick with their right hand. RESULTS: rCBF at rest in the primary sensorimotor cortex (SMC) was significantly (p < 0.001) lower in ALS patients than in control subjects or LMND patients. rCBF at rest did not differ significantly between LMND patients and controls. During joystick movement, ALS patients showed significantly (p < 0.001) greater rCBF increases than controls or LMND patients in the hand/arm area of the SMC bilaterally, the face area of the contralateral SMC, the second somatic sensory (SII) cortex bilaterally, and the contralateral premotor and supplementary motor cortices. LMND patients showed significantly (p < 0.001) greater rCBF increases than controls and ALS patients only in the anterior insular cortex bilaterally. CONCLUSIONS: The finding of reduced rCBF at rest, together with abnormal bilateral activation and altered somatotopy during movement, in the sensorimotor cortex of ALS but not LMND patients suggests that these abnormalities reflect loss of pyramidal neurons. Abnormal activation of perisylvian areas (insular and SII cortices) during limb movement in both LMND and ALS patients suggests that these may be accessory sensorimotor areas that are recruited nonspecifically in response to limb weakness.
ER  - 

TY  - JOUR
T1  - Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease
A1  - Schwarz,J.
A1  - Antonini,A.
A1  - Kraft,E.
A1  - Tatsch,K.
A1  - Vogl,T.
A1  - Kirsch,C.M.
A1  - Leenders,K.L.
A1  - Oertel,W.H.
Y1  - 1994///
SP  - 1079
EP  - 1082
JF  - Neurology
VL  - 44
IS  - 6
ER  - 

TY  - JOUR
T1  - Motor sequence learning: a study with positron emission tomography
A1  - Jenkins,I.H.
A1  - Brooks,D.J.
A1  - Nixon,P.D.
A1  - Frackowiak,R.S.
A1  - Passingham,R.E.
Y1  - 1994///
SP  - 3775
EP  - 3790
JF  - Journal of Neuroscience
VL  - 14
IS  - 6
N2  - We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using
ER  - 

TY  - JOUR
T1  - Stereotactic PET atlas of the human brain: aid for visual interpretation of functional brain images
A1  - Minoshima,S.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Ishihara,M.
A1  - Kuhl,D.E.
Y1  - 1994///
SP  - 949
EP  - 954
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 6
ER  - 

TY  - JOUR
T1  - Differential diagnosis of Parkinson's disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data
A1  - Burn,D.J.
A1  - Sawle,G.V.
A1  - Brooks,D.J.
Y1  - 1994///
SP  - 278
EP  - 284
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 57
IS  - 3
N2  - Clinicopathological series indicate that the clinical diagnosis of Parkinson's disease is correct in only 80% of cases. Multiple system atrophy (MSA) and Steele-Richardson-Olszewski syndrome (SRO) comprise most of the misdiagnoses. By means of 18F-dopa PET the pattern of nigrostriatal dopaminergic dysfunction in 28 patients with clinically probable Parkinson's disease, 25 with MSA, and 10 patients with SRO, was assessed and compared with the pattern in 27 normal subjects. Discriminant function analysis was used to assess the ability of 18F-dopa PET to categorize individual parkinsonian patients on the basis of their caudate and putamen tracer uptake. Discriminant function analysis assigned all control subjects a normal category. One Parkinsonian patient out of 63 was classified as "normal" on the basis of PET findings, although this patient had significantly reduced putamen 18F-dopa uptake. Discriminant function analysis was less effective at distinguishing different categories of akinetic-rigid syndrome on the basis of their striatal 18F-dopa uptake, as judged against clinical criteria. Patients clinically labelled as having typical or atypical Parkinsonian syndromes were assigned the same category on PET criteria 64% and 69% of the time, respectively. When all three categories of Parkinson's disease, MSA, and SRO were considered together, clinical and 18F-dopa PET findings correlated in 64% of patients assigned a diagnosis of Parkinson's disease and 70% of those given a diagnosis of SRO; MSA was less readily discriminated, patients with MSA being assigned to MSA, Parkinson's disease, and SRO groups with equal frequency
ER  - 

TY  - JOUR
T1  - Differential diagnosis of Alzheimer's disease with PET
A1  - Salmon,E.
A1  - Sadzot,B.
A1  - Maquet,P.
A1  - Degueldre,C.
A1  - Lemaire,C.
A1  - Rigo,P.
A1  - Comar,D.
A1  - Franck,G.
Y1  - 1994///
SP  - 391
EP  - 398
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 3
ER  - 

TY  - JOUR
T1  - Saturation analysis in PET--analysis of errors due to imperfect reference regions
A1  - Litton,J.E.
A1  - Hall,H.
A1  - Pauli,S.
Y1  - 1994///
SP  - 358
EP  - 361
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 14
IS  - 2
ER  - 

TY  - JOUR
T1  - Asymmetric interictal glucose hypometabolism and cognitive performance in epileptic patients
A1  - Rausch,R.
A1  - Henry,T.R.
A1  - Ary,C.M.
A1  - Engel,J.,Jr.
A1  - Mazziotta,J.
Y1  - 1994///
SP  - 139
EP  - 144
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 51
IS  - 2
ER  - 

TY  - JOUR
T1  - [11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology and kinetic modeling alternatives
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Mulholland,G.K.
A1  - Kilbourn,M.R.
A1  - Buck,A.
A1  - Lee,K.S.
A1  - Kuhl,D.E.
Y1  - 1994///
SP  - 85
EP  - 99
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 14
IS  - 1
ER  - 

TY  - JOUR
T1  - Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride
A1  - Bench,C.J.
A1  - Lammertsma,A.A.
A1  - Dolan,R.J.
A1  - Grasby,P.M.
A1  - Warrington,S.J.
A1  - Gunn,K.
A1  - Cuddigan,M.
A1  - Turton,D.J.
A1  - Osman,S.
A1  - Frackowiak,R.S.
Y1  - 1993///
SP  - 308
EP  - 314
JF  - Psychopharmacology
VL  - 112
IS  - 2-3
ER  - 

TY  - JOUR
T1  - PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor
A1  - Karlsson,P.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Swahn,C.G.
A1  - Sedvall,G.
A1  - Foged,C.
A1  - Hansen,K.T.
A1  - Skrumsager,B.
Y1  - 1993///
SP  - 149
EP  - 156
JF  - Psychopharmacology
VL  - 113
IS  - 2
ER  - 

TY  - JOUR
T1  - 5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone
A1  - Nyberg,S.
A1  - Farde,L.
A1  - Eriksson,L.
A1  - Halldin,C.
A1  - Eriksson,B.
Y1  - 1993///
SP  - 265
EP  - 272
JF  - Psychopharmacology
VL  - 110
IS  - 3
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions.
A1  - Bench,C.J.
A1  - Friston,K.J.
A1  - Brown,R.G.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 1993///
N1  - Steady-state resting CBF, 3 symptom factors: anxiety corr. with posterior cingulate, depressed mood with left dorsolat. prefrontal and angular cortex, cognitive performance with left mesial prefrontal cortex
SP  - 579
EP  - 590
JF  - Psychological Medicine
VL  - 23
IS  - 3
ER  - 

TY  - JOUR
T1  - Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Hitzemann,R.
A1  - Logan,J.
A1  - Schlyer,D.J.
A1  - Dewey,S.L.
A1  - Wolf,A.P.
Y1  - 1993///
SP  - 169
EP  - 177
JF  - Synapse
VL  - 14
IS  - 2
ER  - 

TY  - JOUR
T1  - Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients
A1  - Nordstrom,A.L.
A1  - Farde,L.
A1  - Wiesel,F.A.
A1  - Forslund,K.
A1  - Pauli,S.
A1  - Halldin,C.
A1  - Uppfeldt,G.
Y1  - 1993///
SP  - 227
EP  - 235
JF  - Biological Psychiatry
VL  - 33
IS  - 4
ER  - 

TY  - JOUR
T1  - The cortical topography of temporal lobe hypometabolism in early Alzheimer's disease
A1  - Jagust,W.J.
A1  - Eberling,J.L.
A1  - Richardson,B.C.
A1  - Reed,B.R.
A1  - Baker,M.G.
A1  - Nordahl,T.E.
A1  - Budinger,T.F.
Y1  - 1993///
N1  - Single slice tomograph, FWHM in-plane 2.6 mm, 6 mm thick, mesial to lateral ratio, mesial CMRGlu reduced in early AD (MMSE > 23), correlated with memory deficit, and reduced at higher age
SP  - 189
EP  - 198
JF  - Brain Research
VL  - 629
IS  - 2
ER  - 

TY  - JOUR
T1  - The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls
A1  - Braun,A.R.
A1  - Stoetter,B.
A1  - Randolph,C.
A1  - Hsiao,J.K.
A1  - Vladar,K.
A1  - Gernert,J.
A1  - Carson,R.E.
A1  - Herscovitch,P.
A1  - Chase,T.N.
Y1  - 1993///
SP  - 277
EP  - 291
JF  - Neuropsychopharmacology
VL  - 9
IS  - 4
N2  - Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.
ER  - 

TY  - JOUR
T1  - A comparative study on protein incorporation of L-[methyl- 3H]methionine, L-[1-14C]leucine and L-2-[18F]fluorotyrosine in tumor bearing mice
A1  - Ishiwata,K.
A1  - Kubota,K.
A1  - Murakami,M.
A1  - Kubota,R.
A1  - Senda,M.
Y1  - 1993///
SP  - 895
EP  - 899
JF  - Nuclear Medicine & Biology
VL  - 20
IS  - 8
ER  - 

TY  - JOUR
T1  - The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study
A1  - Kew,J.J.
A1  - Goldstein,L.H.
A1  - Leigh,P.N.
A1  - Abrahams,S.
A1  - Cosgrave,N.
A1  - Passingham,R.E.
A1  - Frackowiak,R.S.
A1  - Brooks,D.J.
Y1  - 1993///
SP  - 1399
EP  - 1423
JF  - Brain
VL  - 116
IS  - Pt 6
N2  - Positron emission tomography was used to measure regional cerebral blood flow (rCBF) in 12 patients with amyotrophic lateral sclerosis (ALS) and six age-matched controls. Scans were performed at rest, and while subjects performed stereotyped and freely selected movements of a joystick with their right hand. Statistical parametric mapping was used to determine significant differences in rCBF between the two groups at rest and during activation. The ALS group showed no significant difference in global cerebral blood flow at rest compared with controls. However, rCBF at rest was significantly (P < 0.01) reduced in the ALS group in the primary sensorimotor cortex, the lateral premotor cortex, the supplementary motor area, the anterior cingulate cortex, the paracentral lobule and the superior and inferior parietal cortex. Comparison of the increase in rCBF caused by freely selected joystick movements over the resting state between the two groups of subjects showed significantly (P < 0.001) greater activation in ALS patients in the ventral third (face area) of the contralateral primary sensorimotor cortex and in the adjacent contralateral ventral premotor and parietal association cortices; significantly (P < 0.01) greater activation of the contralateral anterior insula and the ipsilateral anterior cingulate cortex (dorso-caudal area 24) was also present in ALS patients. When a comparison of the rCBF response to the free selection task with that to the stereotyped task was performed between the two groups of subjects, ALS patients showed significantly impaired (P < 0.01) activation of the rostral anterior cingulate cortex (area 32), medial prefrontal cortex (area 10), left parahippocampal gyrus and retrosplenial cortex. The pattern of reduced rCBF at rest in ALS patients probably reflects a combination of neuronal loss in all areas of cortex projecting through the pyramidal tract together with loss of projections from the sensorimotor cortex to the motor association areas. The expansion of the upper limb output zone of the sensorimotor cortex in ALS patients during contralateral upper limb movement may represent cortical reorganization in response to Betz cell loss or corticospinal tract disruption. Abnormal . Focally impaired activation of the medial prefrontal cortex and parahippocampal gyrus in ALS patients during the process of internal generation of movement could underlie the frontal lobe cognitive deficits reported in previous neuropsychological studies of ALS.
ER  - 

TY  - JOUR
T1  - Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity?
A1  - Dolan,R.J.
A1  - Bench,C.J.
A1  - Liddle,P.F.
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Grasby,P.M.
A1  - Frackowiak,R.S.
Y1  - 1993///
SP  - 1290
EP  - 1294
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 56
IS  - 12
N2  - Neurophysiological deficits in the left dorsolateral prefrontal cortex (DLPFC) have been described in positron emission tomography studies of schizophrenia and depression. In schizophrenia and depression this deficit has been associated with the syndromes of psychomotor poverty and psychomotor retardation, respectively. Such findings lead to a prediction that DLPFC dysfunction is symptom rather than disease related. This prediction was empirically tested in a retrospective study that pooled data from 40 patients meeting research diagnostic criteria for depression and 30 patients meeting DSM-III R criteria for schizophrenia. The patients were categorised into those with and without poverty of speech, a symptom that is an observable manifestation of psychomotor impairment. The profile of regional cerebral blood flow (rCBF), measured in all subjects under resting conditions, was subsequently compared in these two groups. Patients with poverty of speech had significantly lower rCBF in the left DLFPC. This reduction of rCBF was independent of diagnosis. The findings support the view that the study of symptoms, or symptom clusters, can provide information additional to that of traditional diagnostic systems in the study of the major psychoses. <219>
ER  - 

TY  - JOUR
T1  - PET studies on the early and differential diagnosis of Parkinson's disease
A1  - Brooks,D.J.
Y1  - 1993///
SP  - S6
EP  - 16
JF  - Neurology
VL  - 43
IS  - 12 Suppl 6
ER  - 

TY  - JOUR
T1  - In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428
A1  - Wong,D.F.
A1  - Yung,B.
A1  - Dannals,R.F.
A1  - Shaya,E.K.
A1  - Ravert,H.T.
A1  - Chen,C.A.
A1  - Chan,B.
A1  - Folio,T.
A1  - Scheffel,U.
A1  - Ricaurte,G.A.
A1  - et al.
Y1  - 1993///
SP  - 130
EP  - 142
JF  - Synapse
VL  - 15
IS  - 2
ER  - 

TY  - JOUR
T1  - [18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions
A1  - Perani,D.
A1  - Cortelli,P.
A1  - Lucignani,G.
A1  - Montagna,P.
A1  - Tinuper,P.
A1  - Gallassi,R.
A1  - Gambetti,P.
A1  - Lenzi,G.L.
A1  - Lugaresi,E.
A1  - Fazio,F.
Y1  - 1993///
SP  - 2565
EP  - 2569
JF  - Neurology
VL  - 43
IS  - 12
ER  - 

TY  - JOUR
T1  - Magnetic resonance imaging and positron emission tomography of band heterotopia
A1  - Miura,K.
A1  - Watanabe,K.
A1  - Maeda,N.
A1  - Matsumoto,A.
A1  - Kumagai,T.
A1  - Ito,K.
A1  - Kato,T.
Y1  - 1993///
N1  - normal CMRGlc
SP  - 288
EP  - 290
JF  - Brain & Development
VL  - 15
IS  - 4
ER  - 

TY  - JOUR
T1  - Human brain measures of clinical pain: a review. II. Tomographic imagings. [Review]
A1  - Chen,A.C.
Y1  - 1993///
SP  - 133
EP  - 144
JF  - Pain
VL  - 54
IS  - 2
ER  - 

TY  - JOUR
T1  - Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo?
A1  - Ishiwata,K.
A1  - Kubota,K.
A1  - Murakami,M.
A1  - Kubota,R.
A1  - Sasaki,T.
A1  - Ishii,S.
A1  - Senda,M.
Y1  - 1993///
SP  - 1936
EP  - 1943
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 11
ER  - 

TY  - JOUR
T1  - Positron emission tomography and histopathology in Creutzfeldt- Jakob disease
A1  - Goldman,S.
A1  - Laird,A.
A1  - Flament-Durand,J.
A1  - Luxen,A.
A1  - Bidaut,L.M.
A1  - Stanus,E.
A1  - Hildebrand,J.
A1  - Przedborski,S.
Y1  - 1993///
SP  - 1828
EP  - 1830
JF  - Neurology
VL  - 43
IS  - 9
ER  - 

TY  - JOUR
T1  - Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators
A1  - Alavi,A.
A1  - Newberg,A.B.
A1  - Souder,E.
A1  - Berlin,J.A.
Y1  - 1993///
SP  - 1681
EP  - 1687
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 10
ER  - 

TY  - JOUR
T1  - Functional imaging, the frontal lobes, and dementia
A1  - Friedland,R.P.
A1  - Koss,E.
A1  - Lerner,A.
A1  - Hedera,P.
A1  - Ellis,W.
A1  - Dronkers,N.
A1  - Ober,B.A.
A1  - Jagust,W.J.
Y1  - 1993///
N1  - Case report: Picks disease, with autopsy
SP  - 192
EP  - 203
JF  - Dementia
VL  - 4
IS  - 3-4
ER  - 

TY  - JOUR
T1  - Phosphoinositide turnover imaging linked to muscarinic cholinergic receptor in the central nervous system by positron emission tomography
A1  - Imahori,Y.
A1  - Fujii,R.
A1  - Ueda,S.
A1  - Ohmori,Y.
A1  - Wakita,K.
A1  - Matsumoto,K.
Y1  - 1993///
SP  - 1543
EP  - 1551
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 9
N2  - Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to assess in vivo signal transduction. Using in vivo autoradiography and positron emission tomography (PET), we attempted to visualize the PI response to muscarinic cholinergic receptor (mAChR)-stimulation in rats and monkeys, which were administered [11C]diacylglycerol (DAG) intravenously. Enhancement of 1,2-and 2 over black square]; [1 and 2 over black square]1C]DAG incorporation was observed in the rat ipsilateral hippocampus and cortex in which mAChR-agonist was administered by local injection, but this was in contrast to spreading cortical depression in the ipsilateral cortex using KCl. In monkey PET studies, dynamic brain scanning revealed increase in activity over time for about 15 min after a bolus injection of 1,2-and 2 over black square]; [1 and 2 over black square]1C]DAG in an awake state. The activity then remained at a constant level. This finding documented the theoretical "membrane-trapping" mechanism. The systemic mAChR-stimulation accelerated incorporation in the cerebral cortices of the same monkey brain. Radioactivity uptake did not differ significantly between the mAChR-stimulated and nonstimulated early scan images. This suggested that cerebral blood flow does not greatly affect DAG incorporation. In sequential membrane processes of PI turnover, diacylglycerol kinase rapidly metabolizes DAG, included in PI turnover. In conclusion 1,2-and 2 over black square]; [1 and 2 over black square]1C]DAG incorporation was limited by receptor-mediated PI turnover, which can represent real synaptic transmission in neural networks.
ER  - 

TY  - JOUR
T1  - Parametric imaging of the rate constant Ki using [18Fluoro]-L- dopa positron emission tomography in progressive supranuclear palsy
A1  - Cordes,M.
A1  - Snow,B.J.
A1  - Morrison,S.
A1  - Sossi,V.
A1  - Ruth,T.J.
A1  - Calne,D.B.
Y1  - 1993///
SP  - 404
EP  - 409
JF  - Neuroradiology
VL  - 35
IS  - 6
ER  - 

TY  - JOUR
T1  - Correlation of striatal fluorodopa uptake in the MPTP monkey with dopaminergic indices
A1  - Pate,B.D.
A1  - Kawamata,T.
A1  - Yamada,T.
A1  - McGeer,E.G.
A1  - Hewitt,K.A.
A1  - Snow,B.J.
A1  - Ruth,T.J.
A1  - Calne,D.B.
Y1  - 1993///
SP  - 331
EP  - 338
JF  - Annals of Neurology
VL  - 34
IS  - 3
ER  - 

TY  - JOUR
T1  - Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels
A1  - Snow,B.J.
A1  - Tooyama,I.
A1  - McGeer,E.G.
A1  - Yamada,T.
A1  - Calne,D.B.
A1  - Takahashi,H.
A1  - Kimura,H.
Y1  - 1993///
SP  - 324
EP  - 330
JF  - Annals of Neurology
VL  - 34
IS  - 3
ER  - 

TY  - JOUR
T1  - Evidence of multiple memory systems in the human brain. A [18F]FDG PET metabolic study
A1  - Perani,D.
A1  - Bressi,S.
A1  - Cappa,S.F.
A1  - Vallar,G.
A1  - Alberoni,M.
A1  - Grassi,F.
A1  - Caltagirone,C.
A1  - Cipolotti,L.
A1  - Franceschi,M.
A1  - Lenzi,G.L.
A1  - et al.
Y1  - 1993///
N1  - Neocortical association cortex impaired only in AD, hippocampus, cingulate, and basal frontal cortex in all memory deficits, thalamic hypomet. in global amnesia only
SP  - 903
EP  - 919
JF  - Brain
VL  - 116
IS  - Pt 4
ER  - 

TY  - JOUR
T1  - Comparison of striatal 18F-dopa uptake in adult-onset dystonia- parkinsonism, Parkinson's disease, and dopa-responsive dystonia
A1  - Turjanski,N.
A1  - Bhatia,K.
A1  - Burn,D.J.
A1  - Sawle,G.V.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1993///
SP  - 1563
EP  - 1568
JF  - Neurology
VL  - 43
IS  - 8
ER  - 

TY  - JOUR
T1  - Identification of task-specific rCBF changes in individual subjects: validation and application for PET
A1  - Knorr,U.
A1  - Weder,B.
A1  - Kleinschmidt,A.
A1  - Wirrwar,A.
A1  - Huang,Y.
A1  - Herzog,H.
A1  - Seitz,R.J.
Y1  - 1993///
SP  - 517
EP  - 528
JF  - Journal of Computer Assisted Tomography
VL  - 17
IS  - 4
ER  - 

TY  - JOUR
T1  - Improved detection of focal cerebral blood flow changes using three-dimensional positron emission tomography
A1  - Cherry,S.R.
A1  - Woods,R.P.
A1  - Hoffman,E.J.
A1  - Mazziotta,J.C.
Y1  - 1993///
SP  - 630
EP  - 638
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 4
ER  - 

TY  - JOUR
T1  - In vivo visualization of acetylcholinesterase with positron emission tomography
A1  - Tavitian,B.
A1  - Pappata,S.
A1  - Planas,A.M.
A1  - Jobert,A.
A1  - Bonnot-Lours,S.
A1  - Crouzel,C.
A1  - DiGiamberardino,L.
Y1  - 1993///
SP  - 535
EP  - 538
JF  - Neuroreport
VL  - 4
IS  - 5
ER  - 

TY  - JOUR
T1  - Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve
A1  - Takikawa,S.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Robeson,W.
A1  - Chaly,T.
A1  - Dahl,R.
A1  - Margouleff,D.
A1  - Eidelberg,D.
Y1  - 1993///
SP  - 131
EP  - 136
JF  - Radiology
VL  - 188
IS  - 1
N2  - The authors have developed a technique to estimate input functions from a population-based arterial blood curve in positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose (FDG). A standardized pump injection was used in 34 subjects. A population-based blood curve was generated based on the first 10 subjects. In the remaining 24 subjects, an estimated input function (EIFa) was obtained by scaling the population-based curve with two arterial blood samples, one obtained at 10 minutes and the other at 45. Time integrals for EIFa and the real arterial input function (RIF) were in excellent agreement (r = .998, P < .0001). Cerebral metabolic rates for glucose calculated with EIFa and RIF and the autoradiographic method also correlated excellently (r = .992, P < .0001). Analogous correlations were achieved with arterialized venous samples as scaling factors. These results suggest that individually scaled, population-derived input functions may serve as an adequate alternative to continuous arterial blood sampling in quantitative FDG-PET imaging.
ER  - 

TY  - JOUR
T1  - Noninvasive arterial monitor for quantitative oxygen-15-water blood flow studies [see comments]
A1  - Nelson,A.D.
A1  - Miraldi,F.
A1  - Muzic,R.F.,Jr.
A1  - Leisure,G.P.
A1  - Semple,W.E.
Y1  - 1993///
SP  - 1000
EP  - 1006
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 6
ER  - 

TY  - JOUR
T1  - Interictal metabolic anatomy of mesial temporal lobe epilepsy
A1  - Henry,T.R.
A1  - Mazziotta,J.C.
A1  - Engel,J.,Jr.
Y1  - 1993///
SP  - 582
EP  - 589
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 50
IS  - 6
ER  - 

TY  - JOUR
T1  - Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease
A1  - Eidelberg,D.
A1  - Takikawa,S.
A1  - Moeller,J.R.
A1  - Dhawan,V.
A1  - Redington,K.
A1  - Chaly,T.
A1  - Robeson,W.
A1  - Dahl,J.R.
A1  - Margouleff,D.
A1  - Fazzini,E.
A1  - et al.
Y1  - 1993///
N1  - FDG PET: Reduced CMRGlu in caudate and putamen
SP  - 518
EP  - 527
JF  - Annals of Neurology
VL  - 33
IS  - 5
N2  - Regional and global metabolic rates for glucose were estimated using 18F-fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 +/- 6.9 years; mean disease duration, 4.7 +/- 2.2 years; mean Hoehn and Yahr score, 3.5 +/- 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age-matched normal volunteers, 10 disease severity-matched patients with Parkinson's disease (PD), and 10 disease duration-matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate (p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitative ratings of motor disability (p < 0.02). These results suggest that quantitative 18F-fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions
ER  - 

TY  - JOUR
T1  - Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride
A1  - Antonini,A.
A1  - Leenders,K.L.
A1  - Reist,H.
A1  - Thomann,R.
A1  - Beer,H.F.
A1  - Locher,J.
Y1  - 1993///
N1  - Steep decline of binding capacity until age 30, then slower decline
SP  - 474
EP  - 480
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 50
IS  - 5
ER  - 

TY  - JOUR
T1  - Striatal binding of the PET ligand 11C-raclopride is altered by drugs that modify synaptic dopamine levels
A1  - Dewey,S.L.
A1  - Smith,G.S.
A1  - Logan,J.
A1  - Brodie,J.D.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
Y1  - 1993///
SP  - 350
EP  - 356
JF  - Synapse
VL  - 13
IS  - 4
ER  - 

TY  - JOUR
T1  - Modeling analysis of [11C]flumazenil kinetics studied by PET: application to a critical study of the equilibrium approaches
A1  - Delforge,J.
A1  - Syrota,A.
A1  - Bottlaender,M.
A1  - Varastet,M.
A1  - Loc'h,C.
A1  - Bendriem,B.
A1  - Crouzel,C.
A1  - Brouillet,E.
A1  - Maziere,M.
Y1  - 1993///
SP  - 454
EP  - 468
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 3
ER  - 

TY  - JOUR
T1  - Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data
A1  - Azari,N.P.
A1  - Pettigrew,K.D.
A1  - Schapiro,M.B.
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Pietrini,P.
A1  - Salerno,J.A.
A1  - Heston,L.L.
A1  - Rapoport,S.I.
A1  - Horwitz,B.
Y1  - 1993///
SP  - 438
EP  - 447
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 3
ER  - 

TY  - JOUR
T1  - Correction and characterization of scattered events in three- dimensional PET using scanners with retractable septa
A1  - Cherry,S.R.
A1  - Meikle,S.R.
A1  - Hoffman,E.J.
Y1  - 1993///
SP  - 671
EP  - 678
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 4
ER  - 

TY  - JOUR
T1  - FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS
A1  - Hoffman,J.M.
A1  - Waskin,H.A.
A1  - Schifter,T.
A1  - Hanson,M.W.
A1  - Gray,L.
A1  - Rosenfeld,S.
A1  - Coleman,R.E.
Y1  - 1993///
SP  - 567
EP  - 575
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 4
ER  - 

TY  - JOUR
T1  - Activation of cerebral blood flow during a visuoperceptual task in patients with Alzheimer-type dementia
A1  - Grady,C.L.
A1  - Haxby,J.V.
A1  - Horwitz,B.
A1  - Gillette,J.
A1  - Salerno,J.A.
A1  - Gonzalez-Aviles,A.
A1  - Carson,R.E.
A1  - Herscovitch,P.
A1  - Schapiro,M.B.
A1  - Rapoport,S.I.
Y1  - 1993///
SP  - 35
EP  - 44
JF  - Neurobiology of Aging
VL  - 14
IS  - 1
ER  - 

TY  - JOUR
T1  - Measurement of regional cerebral glucose utilization with fluorine-18-FDG and PET in heterogeneous tissues: theoretical considerations and practical procedure
A1  - Lucignani,G.
A1  - Schmidt,K.C.
A1  - Moresco,R.M.
A1  - Striano,G.
A1  - Colombo,F.
A1  - Sokoloff,L.
A1  - Fazio,F.
Y1  - 1993///
SP  - 360
EP  - 369
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 3
ER  - 

TY  - JOUR
T1  - Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride
A1  - Rinne,J.O.
A1  - Hietala,J.
A1  - Ruotsalainen,U.
A1  - Sako,E.
A1  - Laihinen,A.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Oikonen,V.
A1  - Syvalahti,E.
Y1  - 1993///
SP  - 310
EP  - 314
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 2
ER  - 

TY  - JOUR
T1  - Automated detection of the intercommissural line for stereotactic localization of functional brain images
A1  - Minoshima,S.
A1  - Koeppe,R.A.
A1  - Mintun,M.A.
A1  - Berger,K.L.
A1  - Taylor,S.F.
A1  - Frey,K.A.
A1  - Kuhl,D.E.
Y1  - 1993///
SP  - 322
EP  - 329
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 2
ER  - 

TY  - JOUR
T1  - Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study [see comments]
A1  - Brooks,D.J.
A1  - Playford,E.D.
A1  - Ibanez,V.
A1  - Sawle,G.V.
A1  - Thompson,P.D.
A1  - Findley,L.J.
A1  - Marsden,C.D.
Y1  - 1992///
SP  - 1554
EP  - 1560
JF  - Neurology
VL  - 42
IS  - 8
ER  - 

TY  - JOUR
T1  - Negative symptoms and hypofrontality in chronic schizophrenia
A1  - Wolkin,A.
A1  - Sanfilipo,M.
A1  - Wolf,A.P.
A1  - Angrist,B.
A1  - Brodie,J.D.
A1  - Rotrosen,J.
Y1  - 1992///
SP  - 959
EP  - 965
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 49
IS  - 12
ER  - 

TY  - JOUR
T1  - Measuring the neuromodulatory effects of drugs in man with positron emission tomography
A1  - Friston,K.J.
A1  - Grasby,P.M.
A1  - Bench,C.J.
A1  - Frith,C.D.
A1  - Cowen,P.J.
A1  - Liddle,P.F.
A1  - Frackowiak,R.S.
A1  - Dolan,R.
Y1  - 1992///
SP  - 106
EP  - 110
JF  - Neuroscience Letters
VL  - 141
IS  - 1
N2  - Cognitive activation in conjunction with pharmacological challenge was used to demonstrate neuromodulation in man. Using positron emission tomography (PET), measurements of regional cerebral blood flow were made during the performance of memory tasks, before and after the administration of apomorphine (dopamine agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory-induced increases in regional cerebral blood flow were assessed, on a voxel-by-voxel basis, using statistical parametric mapping. Increases of regional cerebral blood flow in response to the memory challenge were attenuated by apomorphine in the dorsolateral prefrontal cortex and augmented in the retrosplenial region of the posterior cingulate. Conversely, buspirone attenuated blood flow increases in the retrosplenial region. These interactions between drugs and a cognitive challenge can best be interpreted as neuromodulatory effects
ER  - 

TY  - JOUR
T1  - Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects
A1  - Farde,L.
A1  - Nordstrom,A.L.
A1  - Wiesel,F.A.
A1  - Pauli,S.
A1  - Halldin,C.
A1  - Sedvall,G.
Y1  - 1992///
SP  - 538
EP  - 544
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 49
IS  - 7
ER  - 

TY  - JOUR
T1  - PET analysis of alcohol interaction with the brain disposition of [11C]flumazenil
A1  - Pauli,S.
A1  - Liljequist,S.
A1  - Farde,L.
A1  - Swahn,C.G.
A1  - Halldin,C.
A1  - Litton,J.E.
A1  - Sedvall,G.
Y1  - 1992///
SP  - 180
EP  - 185
JF  - Psychopharmacology
VL  - 107
IS  - 2-3
ER  - 

TY  - JOUR
T1  - Individual somatotopy of primary sensorimotor cortex revealed by intermodal matching of MEG, PET, and MRI
A1  - Walter,H.
A1  - Kristeva,R.
A1  - Knorr,U.
A1  - Schlaug,G.
A1  - Huang,Y.
A1  - Steinmetz,H.
A1  - Nebeling,B.
A1  - Herzog,H.
A1  - Seitz,R.J.
Y1  - 1992///
SP  - 183
EP  - 187
JF  - Brain Topography
VL  - 5
IS  - 2
ER  - 

TY  - JOUR
T1  - Corticobasal degeneration: decreased and asymmetrical glucose consumption as studied with PET
A1  - Blin,J.
A1  - Vidailhet,M.J.
A1  - Pillon,B.
A1  - Dubois,B.
A1  - Feve,J.R.
A1  - Agid,Y.
Y1  - 1992///
SP  - 348
EP  - 354
JF  - Movement Disorders
VL  - 7
IS  - 4
N2  - Cerebral energy metabolism was studied by positron emission tomography and [18F]fluorodeoxyglucose in five patients with clinical diagnoses of probable corticobasal degeneration. A reduction in glucose consumption was observed in most cortical and subcortical structures compared to age-matched controls. The reduction was greatest on the side of the brain contralateral to the most affected limbs, as shown by the significantly lower ratios of contralateral to homolateral metabolic rates, in the temporal and sensorimotor cortex of patients compared to controls. A distinct asymmetry between the two hemispheres could be observed in a patient who was examined twice in the course of his illness. Detection of this asymmetrical decrease in brain cortical and subcortical glucose metabolism may prove useful as additional evidence supporting clinical diagnoses of the disease
ER  - 

TY  - JOUR
T1  - Comparative PET studies of the kinetics and distribution of cocaine and cocaethylene in baboon brain
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - MacGregor,R.R.
A1  - Logan,J.
A1  - Dewey,S.L.
A1  - Gatley,S.J.
A1  - Wolf,A.P.
Y1  - 1992///
SP  - 220
EP  - 227
JF  - Synapse
VL  - 12
IS  - 3
ER  - 

TY  - JOUR
T1  - Temporal lobectomy for uncontrolled seizures: the role of positron emission tomography
A1  - Theodore,W.H.
A1  - Sato,S.
A1  - Kufta,C.
A1  - Balish,M.B.
A1  - Bromfield,E.B.
A1  - Leiderman,D.B.
Y1  - 1992///
SP  - 789
EP  - 794
JF  - Annals of Neurology
VL  - 32
IS  - 6
ER  - 

TY  - JOUR
T1  - Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing
A1  - Fulham,M.J.
A1  - Brooks,R.A.
A1  - Hallett,M.
A1  - Di Chiro,G.
Y1  - 1992///
SP  - 2267
EP  - 2273
JF  - Neurology
VL  - 42
IS  - 12
ER  - 

TY  - JOUR
T1  - Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging
A1  - Eriksson,H.
A1  - Tedroff,J.
A1  - Thuomas,K.A.
A1  - Aquilonius,S.M.
A1  - Hartvig,P.
A1  - Fasth,K.J.
A1  - Bjurling,P.
A1  - Langstrom,B.
A1  - Hedstrom,K.G.
A1  - Heilbronn,E.
Y1  - 1992///
SP  - 403
EP  - 407
JF  - Archives of Toxicology
VL  - 66
IS  - 6
N2  - A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-L-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-L-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-L-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i.e. before a reversal of the manganese accumulation.
ER  - 

TY  - JOUR
T1  - PET in relation to intracranial electrode evaluations. [Review]
A1  - Engel,J.,Jr.
A1  - Henry,T.R.
A1  - Risinger,M.W.
A1  - Sutherling,W.W.
A1  - Chugani,H.T.
Y1  - 1992///
SP  - 111
EP  - 120
JF  - Epilepsy Research - Supplement
VL  - 5
ER  - 

TY  - JOUR
T1  - Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration
A1  - Wszolek,Z.K.
A1  - Pfeiffer,R.F.
A1  - Bhatt,M.H.
A1  - Schelper,R.L.
A1  - Cordes,M.
A1  - Snow,B.J.
A1  - Rodnitzky,R.L.
A1  - Wolters,E.C.
A1  - Arwert,F.
A1  - Calne,D.B.
Y1  - 1992///
SP  - 312
EP  - 320
JF  - Annals of Neurology
VL  - 32
IS  - 3
N2  - We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6-fluoro-L-dopa (6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD (p less than 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.
ER  - 

TY  - JOUR
T1  - The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression
A1  - Bench,C.J.
A1  - Friston,K.J.
A1  - Brown,R.G.
A1  - Scott,L.C.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 1992///
SP  - 607
EP  - 615
JF  - Psychological Medicine
VL  - 22
IS  - 3
N2  - Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder. <241>
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow abnormalities in depressed patients with cognitive impairment
A1  - Dolan,R.J.
A1  - Bench,C.J.
A1  - Brown,R.G.
A1  - Scott,L.C.
A1  - Friston,K.J.
A1  - Frackowiak,R.S.
Y1  - 1992///
SP  - 768
EP  - 773
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 55
IS  - 9
N2  - Depression with cognitive impairment, so called depressive pseudodementia, is commonly mistaken for a neurodegenerative dementia. Using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort of 33 patients with major depression was studied. Ten patients displayed significant and reversible cognitive impairment. The patterns of rCBF of these patients were compared with a cohort of equally depressed non-cognitively impaired depressed patients. In the depressed cognitively impaired patients a profile of rCBF abnormalities was identified consisting of decreases in the left anterior medial prefrontal cortex and increases in the cerebellar vermis. These changes were additional to those seen in depression alone and are distinct from those described in neurodegenerative dementia. The cognitive impairment seen in a proportion of depressed patients would seem to be associated with dysfunction of neural systems distinct from those implicated in depression alone or the neurodegenerative dementias. <243>
ER  - 

TY  - JOUR
T1  - Individual integration of positron emission tomography and high- resolution magnetic resonance imaging
A1  - Steinmetz,H.
A1  - Huang,Y.
A1  - Seitz,R.J.
A1  - Knorr,U.
A1  - Schlaug,G.
A1  - Herzog,H.
A1  - Hacklander,T.
A1  - Freund,H.J.
Y1  - 1992///
SP  - 919
EP  - 926
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 12
IS  - 6
ER  - 

TY  - JOUR
T1  - Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol
A1  - Nordstrom,A.L.
A1  - Farde,L.
A1  - Halldin,C.
Y1  - 1992///
SP  - 433
EP  - 438
JF  - Psychopharmacology
VL  - 106
IS  - 4
ER  - 

TY  - JOUR
T1  - D1 dopamine receptor binding in mood disorders measured by positron emission tomography
A1  - Suhara,T.
A1  - Nakayama,K.
A1  - Inoue,O.
A1  - Fukuda,H.
A1  - Shimizu,M.
A1  - Mori,A.
A1  - Tateno,Y.
Y1  - 1992///
SP  - 14
EP  - 18
JF  - Psychopharmacology
VL  - 106
IS  - 1
ER  - 

TY  - JOUR
T1  - Cortical glucose metabolism in Huntington's disease
A1  - Martin,W.R.
A1  - Clark,C.
A1  - Ammann,W.
A1  - Stoessl,A.J.
A1  - Shtybel,W.
A1  - Hayden,M.R.
Y1  - 1992///
SP  - 223
EP  - 229
JF  - Neurology
VL  - 42
IS  - 1
ER  - 

TY  - JOUR
T1  - A functional anatomical study of unipolar depression
A1  - Drevets,W.C.
A1  - Videen,T.O.
A1  - Price,J.L.
A1  - Preskorn,S.H.
A1  - Carmichael,S.T.
A1  - Raichle,M.E.
Y1  - 1992///
SP  - 3628
EP  - 3641
JF  - Journal of Neuroscience
VL  - 12
IS  - 9
N2  - The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression. <245>
ER  - 

TY  - JOUR
T1  - In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons
A1  - Varastet,M.
A1  - Brouillet,E.
A1  - Chavoix,C.
A1  - Prenant,C.
A1  - Crouzel,C.
A1  - Stulzaft,O.
A1  - Bottlaender,M.
A1  - Cayla,J.
A1  - Maziere,B.
A1  - Maziere,M.
Y1  - 1992///
SP  - 275
EP  - 284
JF  - European Journal of Pharmacology
VL  - 213
IS  - 2
ER  - 

TY  - JOUR
T1  - Physical performance of a positron tomograph for brain imaging with retractable septa
A1  - Spinks,T.J.
A1  - Jones,T.
A1  - Bailey,D.L.
A1  - Townsend,D.W.
A1  - Grootoonk,S.
A1  - Bloomfield,P.M.
A1  - Gilardi,M.C.
A1  - Casey,M.E.
A1  - Sipe,B.
A1  - Reed,J.
Y1  - 1992///
SP  - 1637
EP  - 1655
JF  - Physics in Medicine & Biology
VL  - 37
IS  - 8
ER  - 

TY  - JOUR
T1  - Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder
A1  - Baxter,L.R.,Jr.
A1  - Schwartz,J.M.
A1  - Bergman,K.S.
A1  - Szuba,M.P.
A1  - Guze,B.H.
A1  - Mazziotta,J.C.
A1  - Alazraki,A.
A1  - Selin,C.E.
A1  - Ferng,H.K.
A1  - Munford,P.
A1  - et al.
Y1  - 1992///
SP  - 681
EP  - 689
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 49
IS  - 9
ER  - 

TY  - JOUR
T1  - Language localization with activation positron emission tomography scanning
A1  - Leblanc,R.
A1  - Meyer,E.
A1  - Bub,D.
A1  - Zatorre,R.J.
A1  - Evans,A.C.
Y1  - 1992///
SP  - 369
EP  - 373
JF  - Neurosurgery
VL  - 31
IS  - 2
ER  - 

TY  - JOUR
T1  - Brain energy metabolism in bilateral paramedian thalamic infarcts. A positron emission tomography study
A1  - Levasseur,M.
A1  - Baron,J.C.
A1  - Sette,G.
A1  - Legault-Demare,F.
A1  - Pappata,S.
A1  - Mauguiere,F.
A1  - Benoit,N.
A1  - Tran Dinh,S.
A1  - Degos,J.D.
A1  - Laplane,D.
A1  - et al.
Y1  - 1992///
SP  - 795
EP  - 807
JF  - Brain
VL  - 115
IS  - Pt 3
ER  - 

TY  - JOUR
T1  - Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects
A1  - Muller-Gartner,H.W.
A1  - Links,J.M.
A1  - Prince,J.L.
A1  - Bryan,R.N.
A1  - McVeigh,E.
A1  - Leal,J.P.
A1  - Davatzikos,C.
A1  - Frost,J.J.
Y1  - 1992///
SP  - 571
EP  - 583
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 12
IS  - 4
ER  - 

TY  - JOUR
T1  - Functional reorganization of the brain in recovery from striatocapsular infarction in man
A1  - Weiller,C.
A1  - Chollet,F.
A1  - Friston,K.J.
A1  - Wise,R.J.
A1  - Frackowiak,R.S.
Y1  - 1992///
SP  - 463
EP  - 472
JF  - Annals of Neurology
VL  - 31
IS  - 5
N2  - We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex
ER  - 

TY  - JOUR
T1  - Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L- tryptophan in the rhesus monkey. A study using positron emission tomography
A1  - Hartvig,P.
A1  - Lindner,K.J.
A1  - Tedroff,J.
A1  - Andersson,Y.
A1  - Bjurling,P.
A1  - Langstrom,B.
Y1  - 1992///
SP  - 1
EP  - 10
JF  - Journal of Neural Transmission - General Section
VL  - 88
IS  - 1
ER  - 

TY  - JOUR
T1  - Metabolic impairment in human amnesia: a PET study of memory networks
A1  - Fazio,F.
A1  - Perani,D.
A1  - Gilardi,M.C.
A1  - Colombo,F.
A1  - Cappa,S.F.
A1  - Vallar,G.
A1  - Bettinardi,V.
A1  - Paulesu,E.
A1  - Alberoni,M.
A1  - Bressi,S.
A1  - et al.
Y1  - 1992///
SP  - 353
EP  - 358
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 12
IS  - 3
ER  - 

TY  - JOUR
T1  - Blinded clinical evaluation of positron emission tomography for diagnosis of probable Alzheimer's disease
A1  - Powers,W.J.
A1  - Perlmutter,J.S.
A1  - Videen,T.O.
A1  - Herscovitch,P.
A1  - Griffeth,L.K.
A1  - Royal,H.D.
A1  - Siegel,B.A.
A1  - Morris,J.C.
A1  - Berg,L.
Y1  - 1992///
SP  - 765
EP  - 770
JF  - Neurology
VL  - 42
IS  - 4
ER  - 

TY  - JOUR
T1  - Effect of sleep deprivation on brain metabolism of depressed patients
A1  - Wu,J.C.
A1  - Gillin,J.C.
A1  - Buchsbaum,M.S.
A1  - Hershey,T.
A1  - Johnson,J.C.
A1  - Bunney,W.E.,Jr.
Y1  - 1992///
SP  - 538
EP  - 543
JF  - American Journal of Psychiatry
VL  - 149
IS  - 4
N2  - OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with and 2 over black square]; [1 and 2 over black square]8F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression. <255>
ER  - 

TY  - JOUR
T1  - Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen
A1  - Ohta,S.
A1  - Meyer,E.
A1  - Thompson,C.J.
A1  - Gjedde,A.
Y1  - 1992///
SP  - 179
EP  - 192
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 12
IS  - 2
ER  - 

TY  - JOUR
T1  - Contribution of positron emission tomography to the investigation of epilepsies of frontal lobe origin
A1  - Franck,G.
A1  - Maquet,P.
A1  - Sadzot,B.
A1  - Salmon,E.
A1  - Debets,R.
A1  - Dive,D.
A1  - Grisar,T.
A1  - Guillaume,D.
A1  - Van Veelen,C.
A1  - Van Huffelen,A.
A1  - et al.
Y1  - 1992///
SP  - 471
EP  - 485
JF  - Advances in Neurology
VL  - 57
ER  - 

TY  - JOUR
T1  - Synthesis, rodent biodistribution, dosimetry, metabolism, and monkey images of carbon-11-labeled (+)-2 alpha-tropanyl benzilate: a central muscarinic receptor imaging agent [published erratum appears in J Nucl Med 1992 May;33(5):667]
A1  - Mulholland,G.K.
A1  - Otto,C.A.
A1  - Jewett,D.M.
A1  - Kilbourn,M.R.
A1  - Koeppe,R.A.
A1  - Sherman,P.S.
A1  - Petry,N.A.
A1  - Carey,J.E.
A1  - Atkinson,E.R.
A1  - Archer,S.
A1  - et al.
Y1  - 1992///
SP  - 423
EP  - 430
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 3
ER  - 

TY  - JOUR
T1  - Decreased cerebral glucose utilization in myotonic dystrophy
A1  - Fiorelli,M.
A1  - Duboc,D.
A1  - Mazoyer,B.M.
A1  - Blin,J.
A1  - Eymard,B.
A1  - Fardeau,M.
A1  - Samson,Y.
Y1  - 1992///
SP  - 91
EP  - 94
JF  - Neurology
VL  - 42
IS  - 1
N2  - To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease.
ER  - 

TY  - JOUR
T1  - PET studies in the primate brain and biodistribution in mice using (-)-5'-18F-delta 8-THC
A1  - Charalambous,A.
A1  - Marciniak,G.
A1  - Shiue,C.Y.
A1  - Dewey,S.L.
A1  - Schlyer,D.J.
A1  - Wolf,A.P.
A1  - Makriyannis,A.
Y1  - 1991///
SP  - 503
EP  - 507
JF  - Pharmacology, Biochemistry & Behavior
VL  - 40
IS  - 3
N2  - Cannabinoids, the active constituents of marijuana, are known to have many therapeutic properties; however, their exact mechanism of action is not well understood. In an effort to obtain more information concerning the pharmacokinetics and biodistribution of psychoactive THC analogs we synthesized (-)-18F-delta 8-THC and studied its biodistribution in mice and baboon brains. The analog was obtained by nucleophilic fluorination of the ditriflate ester of (-)-5'-OH-delta 8-THC with K18F/Kryptofix followed by deprotection with LiAIH4 and purification with HPLC in 8% yield in a 90-min synthesis from EOB. The uptake of (-)-5'-18F-delta 8-THC in mouse tissue was high at 5 min, but radioactivity declined rapidly in almost all the tissues studied. Following IV administration, (-)-5'-18F-delta 8-THC uptake in baboon brain was similar in the basal ganglia, thalamus and cerebellum, and the clearance from these regions was relatively rapid. Also, a study from baboon plasma clearance of (-)-5'-18F-delta 8-THC showed rapid metabolism of the analog
ER  - 

TY  - JOUR
T1  - Parametric in vivo imaging of benzodiazepine receptor distribution in human brain
A1  - Frey,K.A.
A1  - Holthoff,V.A.
A1  - Koeppe,R.A.
A1  - Jewett,D.M.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
Y1  - 1991///
SP  - 663
EP  - 672
JF  - Annals of Neurology
VL  - 30
IS  - 5
ER  - 

TY  - JOUR
T1  - Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography
A1  - Mayberg,H.S.
A1  - Sadzot,B.
A1  - Meltzer,C.C.
A1  - Fisher,R.S.
A1  - Lesser,R.P.
A1  - Dannals,R.F.
A1  - Lever,J.R.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Wagner,H.N.,Jr.
A1  - et al.
Y1  - 1991///
SP  - 3
EP  - 11
JF  - Annals of Neurology
VL  - 30
IS  - 1
N2  - Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy
ER  - 

TY  - JOUR
T1  - Compartmental analysis of [11C]flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography
A1  - Koeppe,R.A.
A1  - Holthoff,V.A.
A1  - Frey,K.A.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
Y1  - 1991///
SP  - 735
EP  - 744
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 5
ER  - 

TY  - JOUR
T1  - The on-line monitoring of continuously withdrawn arterial blood during PET studies using a single BGO/photomultiplier assembly and non-stick tubing
A1  - Ranicar,A.S.
A1  - Williams,C.W.
A1  - Schnorr,L.
A1  - Clark,J.C.
A1  - Rhodes,C.G.
A1  - Bloomfield,P.M.
A1  - Jones,T.
Y1  - 1991///
SP  - 259
EP  - 264
JF  - Medical Progress through Technology
VL  - 17
IS  - 3-4
ER  - 

TY  - JOUR
T1  - User-friendly image processing software tools: general purpose features and application to the correlation of PET-CT brain images
A1  - Pisani,P.
A1  - Guzzardi,R.
A1  - Bellina,C.R.
A1  - Sorace,O.
Y1  - 1991///
SP  - 205
EP  - 209
JF  - Medical Progress through Technology
VL  - 17
IS  - 3-4
ER  - 

TY  - JOUR
T1  - Interictal cerebral metabolism in partial epilepsies of neocortical origin
A1  - Henry,T.R.
A1  - Sutherling,W.W.
A1  - Engel,J.,Jr.
A1  - Risinger,M.W.
A1  - Levesque,M.F.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1991///
SP  - 174
EP  - 182
JF  - Epilepsy Research
VL  - 10
IS  - 2-3
ER  - 

TY  - JOUR
T1  - Brain kinetics and specific binding of [11C]PK 11195 to omega 3 sites in baboons: positron emission tomography study
A1  - Petit-Taboue,M.C.
A1  - Baron,J.C.
A1  - Barre,L.
A1  - Travere,J.M.
A1  - Speckel,D.
A1  - Camsonne,R.
A1  - MacKenzie,E.T.
Y1  - 1991///
SP  - 347
EP  - 351
JF  - European Journal of Pharmacology
VL  - 200
IS  - 2-3
ER  - 

TY  - JOUR
T1  - The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography
A1  - Eidelberg,D.
A1  - Dhawan,V.
A1  - Moeller,J.R.
A1  - Sidtis,J.J.
A1  - Ginos,J.Z.
A1  - Strother,S.C.
A1  - Cederbaum,J.
A1  - Greene,P.
A1  - Fahn,S.
A1  - Powers,J.M.
A1  - et al.
Y1  - 1991///
SP  - 856
EP  - 862
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 54
IS  - 10
N2  - Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.
ER  - 

TY  - JOUR
T1  - The transport of tyrosine into the human brain as determined with L-[1-11C]tyrosine and PET
A1  - Wiesel,F.A.
A1  - Blomqvist,G.
A1  - Halldin,C.
A1  - Sjogren,I.
A1  - Bjerkenstedt,L.
A1  - Venizelos,N.
A1  - Hagenfeldt,L.
Y1  - 1991///
SP  - 2043
EP  - 2049
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 11
ER  - 

TY  - JOUR
T1  - Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies
A1  - Buchsbaum,M.S.
A1  - Kesslak,J.P.
A1  - Lynch,G.
A1  - Chui,H.
A1  - Wu,J.
A1  - Sicotte,N.
A1  - Hazlett,E.
A1  - Teng,E.
A1  - Cotman,C.W.
Y1  - 1991///
SP  - 840
EP  - 847
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 48
IS  - 9
N2  - Positron emission tomography with fludeoxyglucose F 18 was used to assess cortical metabolic rate during an olfactory memory task in six patients with dementia of the Alzheimer type. Metabolic activity was compared with that of both age-matched controls performing the olfactory task and controls resting with their eyes closed. Patients had lower metabolic rates in the anterior portion of the medial-temporal cortex than did controls, and the difference was greatest between patients and the controls performing the memory task. This region is known to receive a large olfactory input and has been implicated in the encoding of human memory. Normal controls resting with their eyes closed had significantly lower metabolic rates in this area when compared with normal controls performing the task. Our results are consistent with those of earlier reports of temporal lobe decreases in metabolic rate and extend them through the examination of areas salient to the behavioral loss.
ER  - 

TY  - JOUR
T1  - Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow [see comments]
A1  - Kanno,I.
A1  - Iida,H.
A1  - Miura,S.
A1  - Murakami,M.
Y1  - 1991///
SP  - 1931
EP  - 1934
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 10
ER  - 

TY  - JOUR
T1  - Epilepsia partialis continua studied by PET
A1  - Hajek,M.
A1  - Antonini,A.
A1  - Leenders,K.L.
A1  - Wieser,H.G.
Y1  - 1991///
SP  - 44
EP  - 48
JF  - Epilepsy Research
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - The neocortico to mesio-basal limbic propagation of focal epileptic activity during the spike-wave complex
A1  - Stefan,H.
A1  - Schneider,S.
A1  - Abraham-Fuchs,K.
A1  - Pawlik,G.
A1  - Feistel,H.
A1  - Bauer,J.
A1  - Neubauer,U.
A1  - Huk,W.J.
A1  - Holthoff,V.
Y1  - 1991///
SP  - 1
EP  - 10
JF  - Electroencephalography & Clinical Neurophysiology
VL  - 79
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomography in progressive supranuclear palsy
A1  - Bhatt,M.H.
A1  - Snow,B.J.
A1  - Martin,W.R.
A1  - Peppard,R.
A1  - Calne,D.B.
Y1  - 1991///
SP  - 389
EP  - 391
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 48
IS  - 4
N2  - Positron emission tomography with 6-[18F]fluoro-L-dopa (6-FD) provides in vivo information on the function of nigrostriatal dopaminergic neurons. We used 6-FD and positron emission tomography to investigate the integrity of the nigrostriatal system in seven patients with progressive supranuclear palsy. All patients had axial hypertonia, vertical gaze palsy, and parkinsonian features. Dementia, pyramidal signs, and ataxia were seen in varying proportions. We analyzed the scans with a graphic method to calculate a steady-state 6-FD uptake rate constant for the whole striatum. Results were compared with those obtained in seven age-matched controls. As a group, the patients with progressive supranuclear palsy had reduced 6-FD uptake constants. The 6-FD uptake constant correlated inversely with the duration of the disease. Normal positron emission tographic findings in one patient with the shortest duration of symptoms suggests that in early progressive supranuclear palsy, parkinsonism may relate to dysfunction distal to the dopaminergic neurons.
ER  - 

TY  - JOUR
T1  - Corticobasal degeneration. A unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography
A1  - Sawle,G.V.
A1  - Brooks,D.J.
A1  - Marsden,C.D.
A1  - Frackowiak,R.S.
Y1  - 1991///
SP  - 541
EP  - 556
JF  - Brain
VL  - 114
IS  - Pt 1B
ER  - 

TY  - JOUR
T1  - Cerebral activation during speech discrimination in temporal lobe epilepsy
A1  - Bromfield,E.B.
A1  - Ludlow,C.L.
A1  - Sedory,S.
A1  - Leiderman,D.B.
A1  - Theodore,W.H.
Y1  - 1991///
SP  - 49
EP  - 58
JF  - Epilepsy Research
VL  - 9
IS  - 1
ER  - 

TY  - JOUR
T1  - Differentiation of radioligand delivery and binding in the brain: validation of a two-compartment model for [11C]flumazenil
A1  - Holthoff,V.A.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Paradise,A.H.
A1  - Kuhl,D.E.
Y1  - 1991///
SP  - 745
EP  - 752
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 5
ER  - 

TY  - JOUR
T1  - A comparison of the brain uptake of N- (cyclopropyl[11C]methyl)norbuprenorphine ([11C]buprenorphine) and N-(cyclopropyl[11C]methyl)nordiprenorphine ([11C]diprenorphine) in baboon using PET
A1  - Shiue,C.Y.
A1  - Bai,L.Q.
A1  - Teng,R.R.
A1  - Arnett,C.D.
A1  - Dewey,S.L.
A1  - Wolf,A.P.
A1  - McPherson,D.W.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Holland,M.J.
A1  - et al.
Y1  - 1991///
SP  - 281
EP  - 288
JF  - International Journal of Radiation Applications & Instrumentation - Part B, Nuclear Medicine & Biology
VL  - 18
IS  - 3
N2  - Buprenorphine and diprenorphine were radiolabeled with 11C and their distributions in the baboon brain were studied using positron emission tomography (PET). Specific binding was demonstrated in the striatum (but not in the cerebellum) by pretreating the baboon with (-)naloxone. The absolute striatal uptakes and time courses were similar for these two radioligands but the ratio of radioactivity in the striatum to cerebellum in the baboon was higher for [11C]diprenorphine than for [11C]buprenorphine. Analysis of baboon plasma indicated that both [11C]diprenorphine and [11C]buprenorphine are rapidly metabolized. Analysis of radioactivity in mouse brain indicated that these two radioligands are stable to metabolic transformation. At 30 min after injection, 86-90% of extracted radioactivity was due to unchanged 11C-labeled radioligands. These results suggest that both [11C]diprenorphine and [11C]buprenorphine may be useful radioligands for studying opioid receptors in humans, although [11C]diprenorphine may be a better radioligand than [11C]buprenorphine for this purpose because of its more rapid clearance from the cerebellum.
ER  - 

TY  - JOUR
T1  - Clinical value of PET with 18F-fluorodeoxyglucose and L-methyl- 11C-methionine for diagnosis of recurrent brain tumor and radiation injury
A1  - Ogawa,T.
A1  - Kanno,I.
A1  - Shishido,F.
A1  - Inugami,A.
A1  - Higano,S.
A1  - Fujita,H.
A1  - Murakami,M.
A1  - Uemura,K.
A1  - Yasui,N.
A1  - Mineura,K.
A1  - Kowada,M.
Y1  - 1991///
SP  - 197
EP  - 202
JF  - Acta Radiologica
VL  - 32
IS  - 3
ER  - 

TY  - JOUR
T1  - 3D PET using a conventional multislice tomograph without septa
A1  - Cherry,S.R.
A1  - Dahlbom,M.
A1  - Hoffman,E.J.
Y1  - 1991///
SP  - 655
EP  - 668
JF  - Journal of Computer Assisted Tomography
VL  - 15
IS  - 4
ER  - 

TY  - JOUR
T1  - Decreases in regional cerebral blood flow with normal aging
A1  - Martin,A.J.
A1  - Friston,K.J.
A1  - Colebatch,J.G.
A1  - Frackowiak,R.S.
Y1  - 1991///
SP  - 684
EP  - 689
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 4
ER  - 

TY  - JOUR
T1  - Effect of valproate on human cerebral glucose metabolism
A1  - Leiderman,D.B.
A1  - Balish,M.
A1  - Bromfield,E.B.
A1  - Theodore,W.H.
Y1  - 1991///
SP  - 417
EP  - 422
JF  - Epilepsia
VL  - 32
IS  - 3
ER  - 

TY  - JOUR
T1  - Abnormal cerebral glucose metabolism in long-term survivors of childhood acute lymphocytic leukemia
A1  - Phillips,P.C.
A1  - Moeller,J.R.
A1  - Sidtis,J.J.
A1  - Dhawan,V.
A1  - Steinherz,P.G.
A1  - Strother,S.C.
A1  - Ginos,J.Z.
A1  - Rottenberg,D.A.
Y1  - 1991///
SP  - 263
EP  - 271
JF  - Annals of Neurology
VL  - 29
IS  - 3
ER  - 

TY  - JOUR
T1  - Amphetamine induced decreases in (18F)-N-methylspiroperidol binding in the baboon brain using positron emission tomography (PET)
A1  - Dewey,S.L.
A1  - Logan,J.
A1  - Wolf,A.P.
A1  - Brodie,J.D.
A1  - Angrist,B.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
Y1  - 1991///
SP  - 324
EP  - 327
JF  - Synapse
VL  - 7
IS  - 4
ER  - 

TY  - JOUR
T1  - Multiple representations of pain in human cerebral cortex [see comments]
A1  - Talbot,J.D.
A1  - Marrett,S.
A1  - Evans,A.C.
A1  - Meyer,E.
A1  - Bushnell,M.C.
A1  - Duncan,G.H.
Y1  - 1991///
SP  - 1355
EP  - 1358
JF  - Science
VL  - 251
IS  - 4999
N2  - The representation of pain in the cerebral cortex is less well understood than that of any other sensory system. However, with the use of magnetic resonance imaging and positron emission tomography in humans, it has now been demonstrated that painful heat causes significant activation of the contralateral anterior cingulate, secondary somatosensory, and primary somatosensory cortices. This contrasts with the predominant activation of primary somatosensory cortex caused by vibrotactile stimuli in similar experiments. Furthermore, the unilateral cingulate activation indicates that this forebrain area, thought to regulate emotions, contains an unexpectedly specific representation of pain
ER  - 

TY  - JOUR
T1  - Diminished glucose transport in Alzheimer's disease: dynamic PET studies
A1  - Jagust,W.J.
A1  - Seab,J.P.
A1  - Huesman,R.H.
A1  - Valk,P.E.
A1  - Mathis,C.A.
A1  - Reed,B.R.
A1  - Coxson,P.G.
A1  - Budinger,T.F.
Y1  - 1991///
SP  - 323
EP  - 330
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 2
ER  - 

TY  - JOUR
T1  - MRI-PET correlation in three dimensions using a volume-of- interest (VOI) atlas
A1  - Evans,A.C.
A1  - Marrett,S.
A1  - Torrescorzo,J.
A1  - Ku,S.
A1  - Collins,L.
Y1  - 1991///
SP  - A69
EP  - 78
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 2
ER  - 

TY  - JOUR
T1  - Statistical analysis of functional neuroimaging data: exploratory versus inferential methods. [Review]
A1  - Pawlik,G.
Y1  - 1991///
SP  - A136
EP  - 9
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 2
ER  - 

TY  - JOUR
T1  - The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography
A1  - Chollet,F.
A1  - DiPiero,V.
A1  - Wise,R.J.
A1  - Brooks,D.J.
A1  - Dolan,R.J.
A1  - Frackowiak,R.S.
Y1  - 1991///
SP  - 63
EP  - 71
JF  - Annals of Neurology
VL  - 29
IS  - 1
ER  - 

TY  - JOUR
T1  - Sensitivity of measurements of regional brain activation with oxygen-15-water and PET to time of stimulation and period of image reconstruction
A1  - Volkow,N.D.
A1  - Mullani,N.
A1  - Gould,L.K.
A1  - Adler,S.S.
A1  - Gatley,S.J.
Y1  - 1991///
SP  - 58
EP  - 61
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 1
N2  - Measurement of oxygen-15- (15O) water uptake with positron emission tomography (PET) is a sensitive technique to monitor regional brain activation secondary to stimulation paradigms. In order to investigate data acquisition times that show maximal changes in regional activation and to assess the optimal time for stimulus presentation, we investigated 10 controls with 15O-water and PET during baseline and stroboscopic light stimulation. Sequential scans were done varying the time of stimulus presentation. The images were reconstructed using three different periods of data acquisition: uptake phase (initial 30-35 sec), washout phase (40 sec following peak activity in brain), and total activity (3 min). The images reconstructed during the uptake phase showed the largest changes in occipital cortex from stimulation. Maximal changes in occipital cortex were obtained when the visual stimulus was maintained during the uptake phase only.
ER  - 

TY  - JOUR
T1  - L-methionine uptake by human cerebral cortex: maturation from infancy to old age [see comments]
A1  - O'Tuama,L.A.
A1  - Phillips,P.C.
A1  - Smith,Q.R.
A1  - Uno,Y.
A1  - Dannals,R.F.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Loats,S.
A1  - Loats,H.A.
A1  - Wagner,H.N.,Jr.
Y1  - 1991///
SP  - 16
EP  - 22
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 1
ER  - 

TY  - JOUR
T1  - A computerized brain atlas: construction, anatomical content, and some applications
A1  - Greitz,T.
A1  - Bohm,C.
A1  - Holte,S.
A1  - Eriksson,L.
Y1  - 1991///
SP  - 26
EP  - 38
JF  - Journal of Computer Assisted Tomography
VL  - 15
IS  - 1
ER  - 

TY  - JOUR
T1  - Changes in regional cerebral blood flow on recovery from depression
A1  - Bench,C.J.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 1995///
SP  - 247
EP  - 261
JF  - Psychological Medicine
VL  - 25
IS  - 2
ER  - 

TY  - JOUR
T1  - Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates
A1  - Dettmers,C.
A1  - Hartmann,A.
A1  - Rommel,T.
A1  - Hartmann,S.
A1  - Pappata,S.
A1  - Baron,J.C.
Y1  - 1995///
SP  - 109
EP  - 112
JF  - Neurological Research
VL  - 17
IS  - 2
ER  - 

TY  - JOUR
T1  - In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon
A1  - Sette,G.
A1  - Baron,J.C.
A1  - Young,A.R.
A1  - Miyazawa,H.
A1  - Tillet,I.
A1  - Barre,L.
A1  - Travere,J.M.
A1  - Derlon,J.M.
A1  - MacKenzie,E.T.
Y1  - 1993///discussion 2057-8
SP  - 2046
EP  - 2057
JF  - Stroke
VL  - 24
IS  - 12
ER  - 

TY  - JOUR
T1  - Measurement of regional cerebral blood flow with positron emission tomography: a comparison of [15O]water to [11C]butanol with distributed-parameter and compartmental models
A1  - Quarles,R.P.
A1  - Mintun,M.A.
A1  - Larson,K.B.
A1  - Markham,J.
A1  - MacLeod,A.M.
A1  - Raichle,M.E.
Y1  - 1993///
SP  - 733
EP  - 747
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 5
N2  - To further our understanding of the best way to measure regional CBF with positron emission tomography (PET), we directly compared two candidate tracers ([15O]water and [11C]butanol, administered intravenously) and two popular implementations of the one-compartment (1C) model: the autoradiographic implementation representing a single PET measurement of tissue radioactivity over 1 min and a dynamic implementation representing a sequence of measurements of tissue radioactivity over 200 s. We also examined the feasibility of implementing a more realistic, and thus more complex, distributed-parameter (DP) model by assigning fixed values for all of its parameters other than CBF and tracer volume of distribution (Vd), a requirement imposed by the low temporal resolution and statistical quality of PET data. The studies were performed in three normal adult human subjects during paired rest and visual stimulation. In each subject seven regions of interest (ROIs) were selected, one of which was the primary visual cortex. The corresponding ROI were anatomically equivalent in the three subjects. Regional CBF, Vd, tracer arrival delay, and dispersion were estimated for the dynamic data curves. A total of 252 parameter sets were estimated. With [11C]butanol both implementations of the 1C model provided similar results (r = 0.97). Flows estimated using the 1C models were lower (p < 0.01) with [15O]water than with [11C]butanol. In comparison with the 1C model, the constrained version of the DP used in these studies performed inadequately, overestimating high flow and underestimating low flow with both tracers, possibly as the result of the necessity of assigning fixed values for all of its parameters other than CBF and Vd.
ER  - 

TY  - JOUR
T1  - Functional connectivity: the principal-component analysis of large (PET) data sets
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Liddle,P.F.
A1  - Frackowiak,R.S.
Y1  - 1993///
SP  - 5
EP  - 14
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 1
ER  - 

TY  - JOUR
T1  - Plasma pharmacokinetics and metabolism of the benzodiazepine antagonist [11C] Ro 15-1788 (flumazenil) in baboon and human during positron emission tomography studies
A1  - Debruyne,D.
A1  - Abadie,P.
A1  - Barre,L.
A1  - Albessard,F.
A1  - Moulin,M.
A1  - Zarifian,E.
A1  - Baron,J.C.
Y1  - 1991///
SP  - 141
EP  - 152
JF  - European Journal of Drug Metabolism & Pharmacokinetics
VL  - 16
IS  - 2
ER  - 

TY  - JOUR
T1  - PET studies of cortical diaschisis in patients with motor hemi- neglect
A1  - Fiorelli,M.
A1  - Blin,J.
A1  - Bakchine,S.
A1  - Laplane,D.
A1  - Baron,J.C.
Y1  - 1991///
SP  - 135
EP  - 142
JF  - Journal of the Neurological Sciences
VL  - 104
IS  - 2
ER  - 

TY  - JOUR
T1  - The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis
A1  - Okada,J.
A1  - Yoshikawa,K.
A1  - Imazeki,K.
A1  - Minoshima,S.
A1  - Uno,K.
A1  - Itami,J.
A1  - Kuyama,J.
A1  - Maruno,H.
A1  - Arimizu,N.
Y1  - 1991///
SP  - 686
EP  - 691
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 4
ER  - 

TY  - JOUR
T1  - Striatal function in normal aging: implications for Parkinson's disease
A1  - Sawle,G.V.
A1  - Colebatch,J.G.
A1  - Shah,A.
A1  - Brooks,D.J.
A1  - Marsden,C.D.
A1  - Frackowiak,R.S.
Y1  - 1990///
N1  - no age effect in Ki
SP  - 799
EP  - 804
JF  - Annals of Neurology
VL  - 28
IS  - 6
ER  - 

TY  - JOUR
T1  - The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET
A1  - Brooks,D.J.
A1  - Salmon,E.P.
A1  - Mathias,C.J.
A1  - Quinn,N.
A1  - Leenders,K.L.
A1  - Bannister,R.
A1  - Marsden,C.D.
A1  - Frackowiak,R.S.
Y1  - 1990///
SP  - 1539
EP  - 1552
JF  - Brain
VL  - 113
IS  - Pt 5
N2  - 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.
ER  - 

TY  - JOUR
T1  - Progressive degeneration of the right temporal lobe studied with positron emission tomography
A1  - Tyrrell,P.J.
A1  - Warrington,E.K.
A1  - Frackowiak,R.S.
A1  - Rossor,M.N.
Y1  - 1990///
SP  - 1046
EP  - 1050
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 53
IS  - 12
ER  - 

TY  - JOUR
T1  - The lumped constant of the deoxyglucose method in hypoglycemia: effects of moderate hypoglycemia on local cerebral glucose utilization in the rat
A1  - Suda,S.
A1  - Shinohara,M.
A1  - Miyaoka,M.
A1  - Lucignani,G.
A1  - Kennedy,C.
A1  - Sokoloff,L.
Y1  - 1990///
SP  - 499
EP  - 509
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 4
N2  - The applicability of the [14C]deoxyglucose method for measuring local cerebral glucose utilization (lCMRglc) has been extended for use in hypoglycemia by determination of the values of the lumped constant to be used in rats with plasma glucose concentrations ranging from approximately 2 to 6 mM. Lumped constant values were higher in hypoglycemia and declined from a value of 1.2 at the lowest arterial plasma glucose level (1.9 mM) to about 0.48 in normoglycemia. The distribution of glucose, and therefore also of the lumped constant, was found to remain relatively uniform throughout the brain at the lowest plasma glucose levels studied. lCMRglc in moderate, insulin-induced hypoglycemia (mean arterial plasma glucose concentration +/- SD of 2.4 +/- 0.3 mM) was determined with the appropriate lumped constant corresponding to the animal's plasma glucose concentration and compared with the results obtained in six normoglycemic rats. The weighted average rate of glucose utilization for the brain as a whole was significantly depressed by 14% in the hypoglycemic animals, i.e., 61 mumols/100 g/min in hypoglycemia compared to 71 mumols/100 g/min in the normoglycemic controls (p less than 0.05). lCMRglc was lower in 47 of 49 structures examined but statistically significantly below the rate in normoglycemic rats in only six structures (p less than 0.05) by multiple comparison statistics. Regions within the brainstem were most prominently affected. The greatest reductions, statistically significant or not, occurred in structures in which glucose utilization is normally high, suggesting that glucose delivery and transport to the tissue became rate-limiting first in those structures with the greatest metabolic demands for glucose.
ER  - 

TY  - JOUR
T1  - The relationship between global and local changes in PET scans
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Liddle,P.F.
A1  - Dolan,R.J.
A1  - Lammertsma,A.A.
A1  - Frackowiak,R.S.
Y1  - 1990///
SP  - 458
EP  - 466
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 4
ER  - 

TY  - JOUR
T1  - Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study
A1  - Pappata,S.
A1  - Mazoyer,B.
A1  - Tran Dinh,S.
A1  - Cambon,H.
A1  - Levasseur,M.
A1  - Baron,J.C.
Y1  - 1990///
SP  - 519
EP  - 524
JF  - Stroke
VL  - 21
IS  - 4
ER  - 

TY  - JOUR
T1  - Localisation in PET images: direct fitting of the intercommissural (AC-PC) line
A1  - Friston,K.J.
A1  - Passingham,R.E.
A1  - Nutt,J.G.
A1  - Heather,J.D.
A1  - Sawle,G.V.
A1  - Frackowiak,R.S.
Y1  - 1989///
SP  - 690
EP  - 695
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 5
ER  - 

TY  - JOUR
T1  - Steele-Richardson-Olszewski syndrome. Brain energy metabolism, blood flow and fluorodopa uptake measured by positron emission tomography
A1  - Leenders,K.L.
A1  - Frackowiak,R.S.
A1  - Lees,A.J.
Y1  - 1988///
SP  - 615
EP  - 630
JF  - Brain
VL  - 111
IS  - Pt 3
N2  - Brain function was measured in 5 patients with clinically diagnosed Steele-Richardson-Olszewski syndrome using positron emission tomography and tracers of dopamine metabolism, blood flow and oxygen metabolism. A global decrease in blood flow and oxygen utilization compared with normal values was found but the decrease was more marked in the frontal regions. The degree of impairment in oxygen utilization in the frontal region paralleled roughly the duration of the disease. Blood flow was impaired to a greater extent than oxygen utilization, resulting in raised oxygen extraction. This can partially be explained by a lower pCO2 in the patients. Alternatively it may imply involvement of brain vasculature in the pathophysiology of the disease in addition to neuronal degeneration. Striatal dopamine formation and storage, as indicated by L-(18F)fluorodopa uptake, was significantly decreased compared with control values. The severity of this decrease paralleled the degree of reduction in frontal cerebral blood flow. The results suggest that the impairment of cerebral function in Steele-Richardson-Olszewski syndrome is determined to a large extent by brainstem pathology.
ER  - 

TY  - JOUR
T1  - Measurement of local cerebral protein synthesis in vivo: influence of recycling of amino acids derived from protein degradation
A1  - Smith,C.B.
A1  - Deibler,G.E.
A1  - Eng,N.
A1  - Schmidt,K.
A1  - Sokoloff,L.
Y1  - 1988///
SP  - 9341
EP  - 9345
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 85
IS  - 23
ER  - 

TY  - JOUR
T1  - [18F]setoperone: a new high-affinity ligand for positron emission tomography study of the serotonin-2 receptors in baboon brain in vivo
A1  - Blin,J.
A1  - Pappata,S.
A1  - Kiyosawa,M.
A1  - Crouzel,C.
A1  - Baron,J.C.
Y1  - 1988///
SP  - 73
EP  - 82
JF  - European Journal of Pharmacology
VL  - 147
IS  - 1
ER  - 

TY  - JOUR
T1  - Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin
A1  - Mintun,M.A.
A1  - Dennis,D.R.
A1  - Welch,M.J.
A1  - Mathias,C.J.
A1  - Schuster,D.P.
Y1  - 1987///
SP  - 1704
EP  - 1716
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 28
IS  - 11
ER  - 

TY  - JOUR
T1  - Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]3-O-methyl-D-glucose and positron emission tomography
A1  - Brooks,D.J.
A1  - Beaney,R.P.
A1  - Lammertsma,A.A.
A1  - Herold,S.
A1  - Turton,D.R.
A1  - Luthra,S.K.
A1  - Frackowiak,R.S.
A1  - Thomas,D.G.
A1  - Marshall,J.
A1  - Jones,T.
Y1  - 1986///
SP  - 230
EP  - 239
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography
A1  - Brooks,D.J.
A1  - Frackowiak,R.S.
A1  - Lammertsma,A.A.
A1  - Herold,S.
A1  - Leenders,K.L.
A1  - Selwyn,A.P.
A1  - Turton,D.R.
A1  - Brady,F.
A1  - Jones,T.
Y1  - 1986///
SP  - 415
EP  - 422
JF  - Acta Neurologica Scandinavica
VL  - 73
IS  - 4
ER  - 

TY  - JOUR
T1  - Diaschisis. [Review]
A1  - Feeney,D.M.
A1  - Baron,J.C.
Y1  - 1986///
SP  - 817
EP  - 830
JF  - Stroke
VL  - 17
IS  - 5
ER  - 

TY  - JOUR
T1  - Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man
A1  - Baron,J.C.
A1  - D'Antona,R.
A1  - Pantano,P.
A1  - Serdaru,M.
A1  - Samson,Y.
A1  - Bousser,M.G.
Y1  - 1986///
SP  - 1243
EP  - 1259
JF  - Brain
VL  - 109
IS  - Pt 6
ER  - 

TY  - JOUR
T1  - Crossed cerebellar diaschisis. Further studies
A1  - Pantano,P.
A1  - Baron,J.C.
A1  - Samson,Y.
A1  - Bousser,M.G.
A1  - Derouesne,C.
A1  - Comar,D.
Y1  - 1986///
SP  - 677
EP  - 694
JF  - Brain
VL  - 109
IS  - Pt 4
ER  - 

TY  - JOUR
T1  - Loss of striatal [76Br]bromospiperone binding sites demonstrated by positron tomography in progressive supranuclear palsy
A1  - Baron,J.C.
A1  - Maziere,B.
A1  - Loc'h,C.
A1  - Cambon,H.
A1  - Sgouropoulos,P.
A1  - Bonnet,A.M.
A1  - Agid,Y.
Y1  - 1986///
SP  - 131
EP  - 136
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - The 15O continuous-inhalation method: correction for intravascular signal using C15O
A1  - Pantano,P.
A1  - Baron,J.C.
A1  - Crouzel,C.
A1  - Collard,P.
A1  - Sirou,P.
A1  - Samson,Y.
Y1  - 1985///
SP  - 387
EP  - 391
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 10
IS  - 9-10
ER  - 

TY  - JOUR
T1  - Kinetics and displacement of [11C]RO 15-1788, a benzodiazepine antagonist, studied in human brain in vivo by positron tomography
A1  - Samson,Y.
A1  - Hantraye,P.
A1  - Baron,J.C.
A1  - Soussaline,F.
A1  - Comar,D.
A1  - Maziere,M.
Y1  - 1985///
SP  - 247
EP  - 251
JF  - European Journal of Pharmacology
VL  - 110
IS  - 2
ER  - 

TY  - JOUR
T1  - Effects of extra-intracranial arterial bypass on cerebral blood flow and oxygen metabolism in humans
A1  - Samson,Y.
A1  - Baron,J.C.
A1  - Bousser,M.G.
A1  - Rey,A.
A1  - Derlon,J.M.
A1  - David,P.
A1  - Comoy,J.
Y1  - 1985///
SP  - 609
EP  - 616
JF  - Stroke
VL  - 16
IS  - 4
ER  - 

TY  - JOUR
T1  - Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy
A1  - D'Antona,R.
A1  - Baron,J.C.
A1  - Samson,Y.
A1  - Serdaru,M.
A1  - Viader,F.
A1  - Agid,Y.
A1  - Cambier,J.
Y1  - 1985///
SP  - 785
EP  - 799
JF  - Brain
VL  - 108
IS  - Pt 3
ER  - 

TY  - JOUR
T1  - Brain oxygen utilization measured with oxygen-15 radiotracers and positron emission tomography: generation of metabolic images
A1  - Herscovitch,P.
A1  - Mintun,M.A.
A1  - Raichle,M.E.
Y1  - 1985///
SP  - 416
EP  - 417
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 26
IS  - 4
ER  - 

TY  - JOUR
T1  - A method to quantitate the fractional extraction of rubidium-82 across the blood-brain barrier using positron emission tomography
A1  - Lammertsma,A.A.
A1  - Brooks,D.J.
A1  - Frackowiak,R.S.
A1  - Heather,J.D.
A1  - Jones,T.
Y1  - 1984///
SP  - 523
EP  - 534
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - Human brain glucose utilization and cognitive function in relation to age
A1  - Duara,R.
A1  - Grady,C.
A1  - Haxby,J.
A1  - Ingvar,D.
A1  - Sokoloff,L.
A1  - Margolin,R.A.
A1  - Manning,R.G.
A1  - Cutler,N.R.
A1  - Rapoport,S.I.
Y1  - 1984///
SP  - 703
EP  - 713
JF  - Annals of Neurology
VL  - 16
IS  - 6
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow and oxygen consumption in human aging
A1  - Pantano,P.
A1  - Baron,J.C.
A1  - Lebrun-Grandie,P.
A1  - Duquesnoy,N.
A1  - Bousser,M.G.
A1  - Comar,D.
Y1  - 1984///
SP  - 635
EP  - 641
JF  - Stroke
VL  - 15
IS  - 4
ER  - 

TY  - JOUR
T1  - Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography
A1  - Mintun,M.A.
A1  - Raichle,M.E.
A1  - Martin,W.R.
A1  - Herscovitch,P.
Y1  - 1984///
SP  - 177
EP  - 187
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 25
IS  - 2
ER  - 

TY  - JOUR
T1  - Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: a positron tomography study
A1  - Baron,J.C.
A1  - Rougemont,D.
A1  - Soussaline,F.
A1  - Bustany,P.
A1  - Crouzel,C.
A1  - Bousser,M.G.
A1  - Comar,D.
Y1  - 1984///
SP  - 140
EP  - 149
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 2
ER  - 

TY  - JOUR
T1  - A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography
A1  - Mintun,M.A.
A1  - Raichle,M.E.
A1  - Kilbourn,M.R.
A1  - Wooten,G.F.
A1  - Welch,M.J.
Y1  - 1984///
N1  - introduces binding potential (Bmax/KD)
SP  - 217
EP  - 227
JF  - Annals of Neurology
VL  - 15
IS  - 3
ER  - 

TY  - JOUR
T1  - Comparison study of CT and positron emission tomographic data in recent cerebral infarction
A1  - Baron,J.C.
A1  - Delattre,J.Y.
A1  - Bories,J.
A1  - Chiras,J.
A1  - Cabanis,E.A.
A1  - Blas,C.
A1  - Bousser,M.G.
A1  - Comar,D.
Y1  - 1983///
SP  - 536
EP  - 540
JF  - Ajnr: American Journal of Neuroradiology
VL  - 4
IS  - 3
ER  - 

TY  - JOUR
T1  - Brain uptake and organ distribution of 11C from 11C-labeled glucose
A1  - Jones,S.C.
A1  - Ackerman,R.H.
A1  - Hoop,B.,Jr.
A1  - Baron,J.C.
A1  - Brownell,G.L.
A1  - Taveras,J.M.
Y1  - 1983///
SP  - 173
EP  - 180
JF  - International Journal of Nuclear Medicine & Biology
VL  - 10
IS  - 4
ER  - 

TY  - JOUR
T1  - In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas
A1  - Rhodes,C.G.
A1  - Wise,R.J.
A1  - Gibbs,J.M.
A1  - Frackowiak,R.S.
A1  - Hatazawa,J.
A1  - Palmer,A.J.
A1  - Thomas,D.G.
A1  - Jones,T.
Y1  - 1983///
SP  - 614
EP  - 626
JF  - Annals of Neurology
VL  - 14
IS  - 6
N2  - Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18-labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 +/- 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 +/- 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.
ER  - 

TY  - JOUR
T1  - Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients
A1  - Lammertsma,A.A.
A1  - Wise,R.J.
A1  - Heather,J.D.
A1  - Gibbs,J.M.
A1  - Leenders,K.L.
A1  - Frackowiak,R.S.
A1  - Rhodes,C.G.
A1  - Jones,T.
Y1  - 1983///
SP  - 425
EP  - 431
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 3
IS  - 4
ER  - 

TY  - JOUR
T1  - Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation
A1  - Raichle,M.E.
A1  - Martin,W.R.
A1  - Herscovitch,P.
A1  - Mintun,M.A.
A1  - Markham,J.
Y1  - 1983///
SP  - 790
EP  - 798
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 24
IS  - 9
ER  - 

TY  - JOUR
T1  - Brain regional pharmacokinetics of 11C-labeled diphenylhydantoin: positron emission tomography in humans
A1  - Baron,J.C.
A1  - Roeda,D.
A1  - Munari,C.
A1  - Crouzel,C.
A1  - Chodkiewicz,J.P.
A1  - Comar,D.
Y1  - 1983///
SP  - 580
EP  - 585
JF  - Neurology
VL  - 33
IS  - 5
ER  - 

TY  - JOUR
T1  - Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction
A1  - Wise,R.J.
A1  - Bernardi,S.
A1  - Frackowiak,R.S.
A1  - Legg,N.J.
A1  - Jones,T.
Y1  - 1983///
SP  - 197
EP  - 222
JF  - Brain
VL  - 106
IS  - Pt 1
ER  - 

TY  - JOUR
T1  - A theoretical study of the steady-state model for measuring regional cerebral blood flow and oxygen utilisation using oxygen-15
A1  - Lammertsma,A.A.
A1  - Jones,T.
A1  - Frackowiak,R.S.
A1  - Lenzi,G.L.
Y1  - 1981///
SP  - 544
EP  - 550
JF  - Journal of Computer Assisted Tomography
VL  - 5
IS  - 4
ER  - 

TY  - JOUR
T1  - Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography
A1  - Di Chiro,G.
A1  - DeLaPaz,R.L.
A1  - Brooks,R.A.
A1  - Sokoloff,L.
A1  - Kornblith,P.L.
A1  - Smith,B.H.
A1  - Patronas,N.J.
A1  - Kufta,C.V.
A1  - Kessler,R.M.
A1  - Johnston,G.S.
A1  - Manning,R.G.
A1  - Wolf,A.P.
Y1  - 1982///
SP  - 1323
EP  - 1329
JF  - Neurology
VL  - 32
IS  - 12
ER  - 

TY  - JOUR
T1  - Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography
A1  - Frackowiak,R.S.
A1  - Pozzilli,C.
A1  - Legg,N.J.
A1  - Du Boulay,G.H.
A1  - Marshall,J.
A1  - Lenzi,G.L.
A1  - Jones,T.
Y1  - 1981///
SP  - 753
EP  - 778
JF  - Brain
VL  - 104
IS  - Pt 4
N2  - The cerebral blood flow, oxygen extraction and oxygen utilization has been measured regionally in 22 dements, and 14 aged normal volunteers. Ten demented patients were studied twice at a six-month interval from initial measurements. The use of a steady-state 15O technique and positron tomography for measuring regional cerebral blood flow, regional oxygen extraction fraction and mean cerebral oxygen utilization is discussed. The limitations of measurements are reviewed in the light of the present results and the current state of technological development in positron emission tomography is discussed. A decline in cerebral blood flow and mean cerebral oxygen utilization was correlated with increasing severity of dementia in both degenerative and vascular dements. The decline was coupled, both for the cerebral hemisphere as a whole and regionally. There was no increase in oxygen extraction ratio globally, and therefore no evidence to support the existence of a chronic ischaemic brain syndrome. Focal abnormalities in oxygen utilization were observed for both vascular and degenerative groups. In the vascular group, parietal defects were the most pronounced. Individual derangements of the regional pattern varied, reflecting the different unique patterns of ischaemic damage in these patients. In the degenerative group, parietal and temporal defects were seen in the less severe group, but a profound depression in the frontal regions with relative sparing of occipital area characterized the severe degenerative dements. <337>
ER  - 

TY  - JOUR
T1  - Reversal of focal "misery-perfusion syndrome" by extra- intracranial arterial bypass in hemodynamic cerebral ischemia. A case study with 15O positron emission tomography
A1  - Baron,J.C.
A1  - Bousser,M.G.
A1  - Rey,A.
A1  - Guillard,A.
A1  - Comar,D.
A1  - Castaigne,P.
Y1  - 1981///
SP  - 454
EP  - 459
JF  - Stroke
VL  - 12
IS  - 4
ER  - 

TY  - JOUR
T1  - Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values
A1  - Frackowiak,R.S.
A1  - Lenzi,G.L.
A1  - Jones,T.
A1  - Heather,J.D.
Y1  - 1980///
SP  - 727
EP  - 736
JF  - Journal of Computer Assisted Tomography
VL  - 4
IS  - 6
ER  - 

TY  - JOUR
T1  - Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity
A1  - Mata,M.
A1  - Fink,D.J.
A1  - Gainer,H.
A1  - Smith,C.B.
A1  - Davidsen,L.
A1  - Savaki,H.
A1  - Schwartz,W.J.
A1  - Sokoloff,L.
Y1  - 1980///
SP  - 213
EP  - 215
JF  - Journal of Neurochemistry
VL  - 34
IS  - 1
ER  - 

TY  - JOUR
T1  - Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method
A1  - Phelps,M.E.
A1  - Huang,S.C.
A1  - Hoffman,E.J.
A1  - Selin,C.
A1  - Sokoloff,L.
A1  - Kuhl,D.E.
Y1  - 1979///
SP  - 371
EP  - 388
JF  - Annals of Neurology
VL  - 6
IS  - 5
ER  - 

TY  - JOUR
T1  - The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man
A1  - Reivich,M.
A1  - Kuhl,D.
A1  - Wolf,A.
A1  - Greenberg,J.
A1  - Phelps,M.
A1  - Ido,T.
A1  - Casella,V.
A1  - Fowler,J.
A1  - Hoffman,E.
A1  - Alavi,A.
A1  - Som,P.
A1  - Sokoloff,L.
Y1  - 1979///
SP  - 127
EP  - 137
JF  - Circulation Research
VL  - 44
IS  - 1
ER  - 

TY  - JOUR
T1  - The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat
A1  - Sokoloff,L.
A1  - Reivich,M.
A1  - Kennedy,C.
A1  - Des Rosiers,M.H.
A1  - Patlak,C.S.
A1  - Pettigrew,K.D.
A1  - Sakurada,O.
A1  - Shinohara,M.
Y1  - 1977///
SP  - 897
EP  - 916
JF  - Journal of Neurochemistry
VL  - 28
IS  - 5
ER  - 

TY  - JOUR
T1  - PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system
A1  - Wienhard,K.
A1  - Coenen,H.H.
A1  - Pawlik,G.
A1  - Rudolf,J.
A1  - Laufer,P.
A1  - Jovkar,S.
A1  - Stcklin,G.
A1  - Heiss,W.D.
Y1  - 1990///
SP  - 195
EP  - 213
JF  - Journal of Neural Transmission - General Section
VL  - 81
IS  - 3
ER  - 

TY  - JOUR
T1  - Positron emission tomography findings relevant to neurosurgery for epilepsy
A1  - Pawlik,G.
A1  - Holthoff,V.A.
A1  - Kessler,J.
A1  - Rudolf,J.
A1  - Hebold,I.R.
A1  - Lottgen,J.
A1  - Heiss,W.D.
Y1  - 1990///
SP  - 84
EP  - 87
JF  - Acta Neurochirurgica
VL  - 50 (Suppl.)
N2  - Using the 2-[F-18]fluorodeoxyglucose method, 213 positron emission tomographic (PET) studies of local brain glucose metabolism (CMRglu) were performed in 124 patients with various forms of epilepsy. Interictal PET scans of primary epileptics typically showed some global metabolic depression and decreased functional activity of insular, basal and anterior temporal cortex. Epilepsia partialis continua Kozevnikov was characterized by hypo- or hyper-metabolism of perirolandic cortex. Tuberous sclerosis was distinguished by neocortical foci of significantly decreased glucose consumption. Even in the interictal resting state, with regard to sensitivity (greater than 90%) and accuracy of focus localization. PET was superior to other diagnostic methods in typical temporal lobe epilepsy. Averaging 23% below normal CMRglu, the majority of hypometabolic foci were found in mesial temporal structures. Improved distinction between the epileptogenic area and the surrounding tissue showing comparatively normal functional responsiveness, was achieved by psychophysical activation using emotional speech or continuous visual recognition during PET scanning. In patients who had undergone total cerebral hemispherectomy because of uncontrolled epilepsy, remarkable recruitment of association areas was observed on both motor and speech activation. <266>
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism in Parkinson's disease
A1  - Metter,E.J.
A1  - Kuhl,D.E.
A1  - Riege,W.H.
Y1  - 1990///
SP  - 135
EP  - 139
JF  - Advances in Neurology
VL  - 53
ER  - 

TY  - JOUR
T1  - Positron emission tomography in Creutzfeldt-Jakob disease
A1  - Holthoff,V.A.
A1  - Sandmann,J.
A1  - Pawlik,G.
A1  - Schrder,R.
A1  - Heiss,W.D.
Y1  - 1990///
SP  - 1035
EP  - 1038
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 47
IS  - 9
ER  - 

TY  - JOUR
T1  - Correlation methods for the centering, rotation, and alignment of functional brain images
A1  - Junck,L.
A1  - Moen,J.G.
A1  - Hutchins,G.D.
A1  - Brown,M.B.
A1  - Kuhl,D.E.
Y1  - 1990///
SP  - 1220
EP  - 1226
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 31
IS  - 7
ER  - 

TY  - JOUR
T1  - Positron emission tomographic evaluation of cerebral blood flow during state anxiety in simple phobia
A1  - Mountz,J.M.
A1  - Modell,J.G.
A1  - Wilson,M.W.
A1  - Curtis,G.C.
A1  - Lee,M.A.
A1  - Schmaltz,S.
A1  - Kuhl,D.E.
Y1  - 1989///
SP  - 501
EP  - 504
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 46
IS  - 6
N2  - The present study was undertaken to clarify some of the conflicting findings of previous reports on the effect of state anxiety on cerebral blood flow (CBF). Seven subjects with simple phobia of small animals were studied to permit the generation of wide ranges of anxiety. Each subject received five positron emission tomography (PET) scans in a rest-fear-rest-fear-rest, repeated-measures paradigm. A population of eight normal controls was employed. The phobic stimuli produced significant increases in state anxiety during fear and significant differences in physiologic measurements between the fear and rest scans. Absolute global and regional CBF was significantly lower during fear scans than during rest scans; however, when hypocapnia resulting from anxiety-induced hyperventilation was taken into account, the pattern vanished, and all global and regional CBF differences among scans became not significant. Resting global and regional CBF values in the phobic subjects did not significantly differ from those of the normal controls. That a relationship between anxiety and CBF was not found in 35 scans among seven subjects strongly suggests that CBF changes induced by state anxiety are either not presently measurable by PET techniques or that such a relationship may not exist. These findings should also reduce concerns that subject anxiety may confound CBF measurements during routine PET scanning.
ER  - 

TY  - JOUR
T1  - PET measurement of D2 and S2 receptor binding of 3-N-[( 2'- 18F]fluoroethyl)spiperone in baboon brain
A1  - Coenen,H.H.
A1  - Wienhard,K.
A1  - Stcklin,G.
A1  - Laufer,P.
A1  - Hebold,I.
A1  - Pawlik,G.
A1  - Heiss,W.D.
Y1  - 1988///
SP  - 80
EP  - 87
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 14
IS  - 2
ER  - 

TY  - JOUR
T1  - 3-N-(2-[18F]-fluoroethyl)-spiperone: a novel ligand for cerebral dopamine receptor studies with pet
A1  - Coenen,H.H.
A1  - Laufer,P.
A1  - Stcklin,G.
A1  - Wienhard,K.
A1  - Pawlik,G.
A1  - Bocher-Schwarz,H.G.
A1  - Heiss,W.D.
Y1  - 1987///
SP  - 81
EP  - 88
JF  - Life Sciences
VL  - 40
IS  - 1
ER  - 

TY  - JOUR
T1  - Functional and morphological abnormalities in temporal lobe epilepsy: a comparison of interictal and ictal EEG, CT, MRI, SPECT and PET
A1  - Stefan,H.
A1  - Pawlik,G.
A1  - Bocher-Schwarz,H.G.
A1  - Biersack,H.J.
A1  - Burr,W.
A1  - Penin,H.
A1  - Heiss,W.D.
Y1  - 1987///
SP  - 377
EP  - 384
JF  - Journal of Neurology
JA  - J.Neurol.
VL  - 234
IS  - 6
ER  - 

TY  - JOUR
T1  - Estimation of cerebral oxygen utilization rate by single-bolus 15O2 inhalation and dynamic positron emission tomography
A1  - Meyer,E.
A1  - Tyler,J.L.
A1  - Thompson,C.J.
A1  - Redies,C.
A1  - Diksic,M.
A1  - Hakim,A.M.
Y1  - 1987///
SP  - 403
EP  - 414
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 4
ER  - 

TY  - JOUR
T1  - Local cerebral metabolic rate for glucose during petit mal absences
A1  - Engel,J.,Jr.
A1  - Lubens,P.
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
Y1  - 1985///
SP  - 121
EP  - 128
JF  - Annals of Neurology
VL  - 17
IS  - 2
N2  - Four patients with primary generalized or true petit mal epilepsy were studied with positron emission tomography using and 2 over black square]; [1 and 2 over black square]8F]fluorodeoxyglucose (FDG). FDG studies were carried out during 10 minutes of hyperventilation before and again after medical control of spontaneous absences. Before seizures were controlled all 4 patients demonstrated frequent bilaterally synchronous three-per-second spike-and-wave discharges associated with altered consciousness. After spontaneous seizures were controlled, hyperventilation produced only electroencephalographic slowing without clinical symptoms in 3; the fourth patient had absences less frequently. Patterns of local cerebral metabolic rate for glucose (CMRGlc) were normal and identical for ictal and interictal scans; there was, however, a 2.5- to 3.5-fold diffuse ictal increase in global CMRGlc evident when ictal studies were compared with hyperventilation control studies in which no seizures occurred. The CMRGlc was similar in the two scans obtained from the patient who had absences during both studies. No anatomical substrate of petit mal epilepsy was identified. The CMRGlc in these patients during petit mal absences was higher than that recorded in other patients during partial or generalized convulsive seizures. This difference may reflect the fact that petit mal absences are not associated with postictal depression. <314>
ER  - 

TY  - JOUR
T1  - Patterns of local cerebral glucose utilization determined in Parkinson's disease by the [18F]fluorodeoxyglucose method
A1  - Kuhl,D.E.
A1  - Metter,E.J.
A1  - Riege,W.H.
Y1  - 1984///
SP  - 419
EP  - 424
JF  - Annals of Neurology
VL  - 15
IS  - 5
ER  - 

TY  - JOUR
T1  - Hypometabolic cortical lesions in tuberous sclerosis with epilepsy: demonstration by positron emission tomography
A1  - Szelies,B.
A1  - Herholz,K.
A1  - Heiss,W.D.
A1  - Rackl,A.
A1  - Pawlik,G.
A1  - Wagner,R.
A1  - Ilsen,H.W.
A1  - Wienhard,K.
Y1  - 1983///
SP  - 946
EP  - 953
JF  - Journal of Computer Assisted Tomography
VL  - 7
IS  - 6
ER  - 

TY  - JOUR
T1  - Local cerebral metabolism during partial seizures
A1  - Engel,J.,Jr.
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
A1  - Rausch,R.
A1  - Nuwer,M.
Y1  - 1983///
SP  - 400
EP  - 413
JF  - Neurology
VL  - 33
IS  - 4
N2  - Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated. <333>
ER  - 

TY  - JOUR
T1  - The fluorodeoxyglucose 18F scan in Alzheimer's disease and multi- infarct dementia
A1  - Benson,D.F.
A1  - Kuhl,D.E.
A1  - Hawkins,R.A.
A1  - Phelps,M.E.
A1  - Cummings,J.L.
A1  - Tsai,S.Y.
Y1  - 1983///
SP  - 711
EP  - 714
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 40
IS  - 12
ER  - 

TY  - JOUR
T1  - Flow and neuronal density in tissue surrounding chronic infarction
A1  - Mies,G.
A1  - Auer,L.M.
A1  - Ebhardt,G.
A1  - Traupe,H.
A1  - Heiss,W.D.
Y1  - 1983///
SP  - 22
EP  - 27
JF  - Stroke
VL  - 14
IS  - 1
ER  - 

TY  - JOUR
T1  - Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3
A1  - Kuhl,D.E.
A1  - Engel,J.,Jr.
A1  - Phelps,M.E.
A1  - Selin,C.
Y1  - 1980///
SP  - 348
EP  - 360
JF  - Annals of Neurology
VL  - 8
IS  - 4
N2  - Seventeen patients with partial epilepsy had electroencephalographic (EEG) monitoring concurrent with cerebral positron emission computed tomography (PECT) after 18F-fluorodeoxyglucose (18FDG) and 13N-ammonia (13NH3) were given intravenously as indicators of local cerebral glucose utilization (LCMRglc) and relative perfusion, respectively. In 12 of 15 patients who had unilateral or focal electrical abnormalities, interictal 18FDG scan patterns clearly showed localized regions of decreased (14 to 58%) LCMRglc that correlated anatomically with the eventual EEG localization. These hypometabolic zones appeared normal on x-ray computed tomography in all but 3 patients and were unchanged on 18FDG scans repeated on different days. In 5 of 6 patients who underwent anterior temporal lobectomy the interictal 18FDG scan correctly detected the pathologically confirmed lesion as a hypometabolic zone, and removal of the lesion site resulted in marked clinical improvement. In contrast, the ictal 18FDG scan patterns clearly showed foci of increased (82 to 130%) LCMRglc that correlated temporally and anatomically with ictal EEG spike foci and were within the zones of interictal hypometabolism (three studies in 2 patients). 13NH3 distributions paralleled 18FDG increases and decreases in abnormal zones, but 13NH3 differences were of lesser magnitude. When the relationship of 13NH3 uptake to local blood flow found in dog brain was applied as a correction to the patients' 13NH3 scan data, local alterations in perfusion and glucose utilization were usually matched in both the interictal and the ictal state. We conclude that the interictal 18FDG-PECT scan is useful in aiding localization of the dysfunctional cerebral zone most likely to be responsible for seizures in patients being considered for anterior temporal lobectomy. With further development, emission computed tomography may help in better categorizing the various forms of the disorder and in elucidating the basic mechanisms of epilepsy in humans.
ER  - 

TY  - JOUR
T1  - Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy
A1  - Engel,J.,Jr.
A1  - Brown,W.J.
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
A1  - Mazziotta,J.C.
A1  - Crandall,P.H.
Y1  - 1982///
SP  - 518
EP  - 528
JF  - Annals of Neurology
VL  - 12
IS  - 6
N2  - Histopathological studies were carried out on temporal lobe tissue from 25 patients with partial complex seizures who were studied by interictal positron computed tomography (PCT) with 18F-fluorodeoxyglucose and subsequently underwent anterior temporal lobe resection. Abnormalities were identified on x-ray computed tomographic scans in 7 patients, but none indicated the site of a pathologically confirmed structural lesion. Hypometabolic zones were observed on PCT scans of 22 patients and corresponded to focal pathological abnormalities in 19 (15 mesial temporal sclerosis, 2 small neoplasms, 1 angioma, 1 heterotopia). In 1 patient with a focally abnormal PCT scan and no pathological changes, the lesion may have been located posterior to the resection. In the remaining 2 patients, the hypometabolic zones later disappeared and may have represented a transient response induced by depth electrode implantation. Three patients with normal PCT scans had no pathological abnormalities in their resected tissue. The degree of relative hypometabolism measured by PCT correlated well with the severity of the pathological lesion, but the size of the hypometabolic zone was generally much larger than the area of pathological involvement. This discrepancy could not be considered an artifact of technique and must represent either structural abnormalities below the resolution of routine histopathological studies (e.g., loss of synapses) or functional inactivation of neuronal elements associated with the epileptogenic lesion.
ER  - 

TY  - JOUR
T1  - Tomographic mapping of human cerebral metabolism: sensory deprivation
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Carson,R.E.
A1  - Kuhl,D.E.
Y1  - 1982///
SP  - 435
EP  - 444
JF  - Annals of Neurology
VL  - 12
IS  - 5
ER  - 

TY  - JOUR
T1  - Patterns of human local cerebral glucose metabolism during epileptic seizures
A1  - Engel,J.,Jr.
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
Y1  - 1982///
SP  - 64
EP  - 66
JF  - Science
VL  - 218
IS  - 4567
N2  - Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with 18F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.
ER  - 

TY  - JOUR
T1  - Tomographic mapping of human cerebral metabolism: auditory stimulation
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Carson,R.E.
A1  - Kuhl,D.E.
Y1  - 1982///
SP  - 921
EP  - 937
JF  - Neurology
VL  - 32
IS  - 9
ER  - 

TY  - JOUR
T1  - Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method
A1  - Kuhl,D.E.
A1  - Metter,E.J.
A1  - Riege,W.H.
A1  - Phelps,M.E.
Y1  - 1982///
SP  - 163
EP  - 171
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 2
IS  - 2
ER  - 

TY  - JOUR
T1  - Quantitation in positron emission computed tomography: 5. Physical--anatomical effects
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Plummer,D.
A1  - Kuhl,D.E.
Y1  - 1981///
SP  - 734
EP  - 743
JF  - Journal of Computer Assisted Tomography
VL  - 5
IS  - 5
ER  - 

TY  - JOUR
T1  - Metabolic mapping of the brain's response to visual stimulation: studies in humans
A1  - Phelps,M.E.
A1  - Kuhl,D.E.
A1  - Mazziotta,J.C.
Y1  - 1981///
SP  - 1445
EP  - 1448
JF  - Science
VL  - 211
IS  - 4489
ER  - 

TY  - JOUR
T1  - Noninvasive determination of local cerebral metabolic rate of glucose in man
A1  - Huang,S.C.
A1  - Phelps,M.E.
A1  - Hoffman,E.J.
A1  - Sideris,K.
A1  - Selin,C.J.
A1  - Kuhl,D.E.
Y1  - 1980///
SP  - E69
EP  - 82
JF  - American Journal of Physiology
VL  - 238
IS  - 1
ER  - 

TY  - JOUR
T1  - Assessment of pharmacological effects on cerebral blood flow
A1  - Heiss,W.D.
A1  - Podreka,I.
Y1  - 1978///
SP  - 135
EP  - 143
JF  - European Neurology
VL  - 17 Suppl 1
ER  - 

TY  - JOUR
T1  - Crossed cerebellar diaschisis in human supratentorial brain infarction
A1  - Baron,J.C.
A1  - Bousser,M.G.
A1  - Comar,D.
A1  - Duquesnoy,N.
A1  - Sastre,J.
A1  - Castaigne,P.
Y1  - 1980///
SP  - 459
EP  - 461
JF  - Transactions of the American Neurological Association
VL  - 105
ER  - 

TY  - BOOK
T1  - Principles and procedures of statistics. A biometrical approach
A1  - Steel,R.D.G.
A1  - Torrie,J.H.
Y1  - 1980///
VL  - 2nd
CY  - New York
PB  - McGraw-Hill
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - (4-[18F]fluoro-3-iodobenzyl)guanidine, a potential MIBG analogue for positron emission tomography
A1  - Vaidyanathan,G.
A1  - Affleck,D.J.
A1  - Zalutsky,M.R.
Y1  - 1994///
SP  - 3655
EP  - 3662
JF  - Journal of Medicinal Chemistry
VL  - 37
IS  - 21
N2  - The aims of this investigation were to develop a no-carrier-added (nca) synthesis of (4-[18F]-fluoro-3-iodobenzyl)guanidine ([18F]FIBG) and to evaluate its potential as an MIBG analogue useful for positron emission tomography. [18F]FIBG was prepared in four steps starting from 4-cyano-2-iodo-N,N,N-trimethylanilinium trifluoromethanesulfonate in 5% decay-corrected radiochemical yield in a total synthesis time of 130 min. The specific activity was more than 1500 Ci per mmol. In vitro binding studies showed that the percent binding of [18F]FIBG to SK-N-SH human neuroblastoma cells remained constant over a 3-log activity range and was similar to that of nca [131I]MIBG. Specific and high uptake of FIBG was also seen in mouse heart and adrenals. The in vitro and in vivo properties of [18F]FIBG suggest that this compound may be a useful positron-emitting analogue of MIBG
ER  - 

TY  - JOUR
T1  - Gallium-67/gallium-68-[DFO]-octreotide--a potential radiopharmaceutical for PET imaging of somatostatin receptor- positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies
A1  - Smith-Jones,P.M.
A1  - Stolz,B.
A1  - Bruns,C.
A1  - Albert,R.
A1  - Reist,H.W.
A1  - Fridrich,R.
A1  - Macke,H.R.
Y1  - 1994///
SP  - 317
EP  - 325
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 2
ER  - 

TY  - JOUR
T1  - Neuroimaging of juvenile pilocytic astrocytomas: an enigma [see comments]
A1  - Fulham,M.J.
A1  - Melisi,J.W.
A1  - Nishimiya,J.
A1  - Dwyer,A.J.
A1  - Di Chiro,G.
Y1  - 1993///
SP  - 221
EP  - 225
JF  - Radiology
VL  - 189
IS  - 1
ER  - 

TY  - JOUR
T1  - Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy [see comments]
A1  - Radtke,R.A.
A1  - Hanson,M.W.
A1  - Hoffman,J.M.
A1  - Crain,B.J.
A1  - Walczak,T.S.
A1  - Lewis,D.V.
A1  - Beam,C.
A1  - Coleman,R.E.
A1  - Friedman,A.H.
Y1  - 1993///
SP  - 1088
EP  - 1092
JF  - Neurology
VL  - 43
IS  - 6
ER  - 

TY  - JOUR
T1  - Cerebral glioma: evaluation with methionine PET
A1  - Ogawa,T.
A1  - Shishido,F.
A1  - Kanno,I.
A1  - Inugami,A.
A1  - Fujita,H.
A1  - Murakami,M.
A1  - Shimosegawa,E.
A1  - Ito,H.
A1  - Hatazawa,J.
A1  - Okudera,T.
A1  - Uemura,K.
A1  - Yasui,N.
A1  - Mineura,K.
Y1  - 1993///
N1  - Comparison with CT and surgical specimens: delineation better than with CT
SP  - 45
EP  - 53
JF  - Radiology
VL  - 186
IS  - 1
ER  - 

TY  - JOUR
T1  - Quantification of glucose utilization in liver metastases: parametric imaging of FDG uptake with PET
A1  - Messa,C.
A1  - Choi,Y.
A1  - Hoh,C.K.
A1  - Jacobs,E.L.
A1  - Glaspy,J.A.
A1  - Rege,S.
A1  - Nitzsche,E.
A1  - Huang,S.C.
A1  - Phelps,M.E.
A1  - Hawkins,R.A.
Y1  - 1992///
SP  - 684
EP  - 689
JF  - Journal of Computer Assisted Tomography
VL  - 16
IS  - 5
ER  - 

TY  - JOUR
T1  - PET-fluorodeoxyglucose of cranial and spinal neuromas
A1  - Borbely,K.
A1  - Fulham,M.J.
A1  - Brooks,R.A.
A1  - Di Chiro,G.
Y1  - 1992///
SP  - 1931
EP  - 1934
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 11
N2  - Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.
ER  - 

TY  - JOUR
T1  - Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L- deprenyl
A1  - Bergstrom,M.
A1  - Muhr,C.
A1  - Jossan,S.
A1  - Lilja,A.
A1  - Nyberg,G.
A1  - Langstrom,B.
Y1  - 1992///
SP  - 855
EP  - 861
JF  - Neurosurgery
VL  - 30
IS  - 6
N2  - Seven patients with clinically nonsecreting pituitary adenoma and 5 patients with meningioma were examined with positron emission tomography using [11C]-LL-deprenyl and [11C]-LL-methionine. The dynamics of the uptake of [11C]-L-deprenyl in the pituitary adenomas demonstrated a rapid and high uptake immediately after the injection, and, later, an almost constant level was observed that was equal to or higher than that observed in normal brain tissue. In the meningiomas, however, the initially high uptake was followed by a marked decrease with time, reaching a level that was approximately half that observed in brain tissue. The study demonstrated high binding of [11C]-L-deprenyl to monoamine oxidase B in pituitary adenomas, whereas the binding in meningiomas was very low. This fact can be used in the differential diagnosis of pituitary adenoma and parasellar meningioma. Operative samples from 10 patients with meningioma and from 5 patients with pituitary adenoma were analyzed biochemically for activity of monoamine oxidase B, using [14C]-phenyl-ethylamine as substrate. The nonsecreting pituitary adenomas demonstrated high enzyme activity, the secreting adenomas about one-tenth of that of the nonsecreting, and the meningiomas one-thirtieth of that of nonsecreting adenomas.
ER  - 

TY  - JOUR
T1  - PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma
A1  - Shulkin,B.L.
A1  - Wieland,D.M.
A1  - Schwaiger,M.
A1  - Thompson,N.W.
A1  - Francis,I.R.
A1  - Haka,M.S.
A1  - Rosenspire,K.C.
A1  - Shapiro,B.
A1  - Sisson,J.C.
A1  - Kuhl,D.E.
Y1  - 1992///
SP  - 1125
EP  - 1131
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 6
ER  - 

TY  - JOUR
T1  - Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole
A1  - Valk,P.E.
A1  - Mathis,C.A.
A1  - Prados,M.D.
A1  - Gilbert,J.C.
A1  - Budinger,T.F.
Y1  - 1992///
SP  - 2133
EP  - 2137
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 12
N2  - Positron emission tomography (PET) with the hypoxic-cell tracer [18F]fluoromisonidazole presents a possible means of noninvasively demonstrating tumor hypoxia. PET studies using this tracer were performed in three patients with malignant glioma, and in all patients the tumor was clearly seen at 5 min postinjection and initial tumor activity exceeded cortical activity. In one patient, there was no tumor retention of [18F] fluoromisonidazole and tumor activity fell while cortical activity increased, with the two tissues reaching equality at 40-50 min. The tumor-to-plasma ratio was 0.71 at 3 hr. The other two patients showed variable tumor retention of [18F]fluoromisonidazole, with tumor-to-plasma ratios of 1.10 and 1.49 at 2 and 3 hr. These results demonstrate the feasibility of using [18F]fluoromisonidazole PET to detect hypoxia in human gliomas in vivo. Clinical trials are needed to determine whether a relationship exists between [18F]fluoromisonidazole uptake and tumor radiation response.
ER  - 

TY  - JOUR
T1  - Dynamic study of methionine uptake in glioma using positron emission tomography
A1  - Sato,K.
A1  - Kameyama,M.
A1  - Ishiwata,K.
A1  - Hatazawa,J.
A1  - Katakura,R.
A1  - Yoshimoto,T.
Y1  - 1992///
SP  - 426
EP  - 430
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 19
IS  - 6
ER  - 

TY  - JOUR
T1  - New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose
A1  - Kim,C.K.
A1  - Alavi,J.B.
A1  - Alavi,A.
A1  - Reivich,M.
Y1  - 1991///
SP  - 85
EP  - 91
JF  - Journal of Neuro-Oncology
VL  - 10
IS  - 1
N2  - Positron emission tomography (PET) using fluorine-18 (18F)-fluorodeoxyglucose (FDG) has been reported to be a powerful diagnostic and prognostic tool in patients with primary brain tumors. This study was undertaken to compare the prognostic value of: (1) visual grading of [18]FDG uptake in the tumor, (2) the absolute glucose metabolic rate of the tumor (TMRglc), (3) the ratio of glucose metabolism between the tumor and whole brain (T/WB) and (4) between the tumor and contralateral cerebellum (T/CBL). Each of these four parameters was correlated with the survival time in 20 patients with malignant cerebral gliomas. Excellent correlation was obtained with visual grading and reasonably good correlation was obtained with T/WB or T/CBL, but TMRglc alone was only a fair prognostic indicator. Thus, visual grading provides a qualitative analysis and T/WB provides a semi-quantitative analysis neither of which requires arterial blood sampling for quantification of absolute metabolic rates for glucose.
ER  - 

TY  - JOUR
T1  - Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography
A1  - Mineura,K.
A1  - Sasajima,T.
A1  - Kowada,M.
A1  - Uesaka,Y.
A1  - Shishido,F.
Y1  - 1991///
SP  - 726
EP  - 728
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 32
IS  - 4
N2  - A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR.
ER  - 

TY  - JOUR
T1  - Clinical evaluation of a high-resolution (2.6-mm) positron emission tomography
A1  - Valk,P.E.
A1  - Jagust,W.J.
A1  - Derenzo,S.E.
A1  - Huesman,R.H.
A1  - Geyer,A.B.
A1  - Budinger,T.F.
Y1  - 1990///
SP  - 783
EP  - 790
JF  - Radiology
VL  - 176
IS  - 3
N2  - The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.
ER  - 

TY  - JOUR
T1  - PET evaluation of spinal cord tumor using 11C-methionine
A1  - Higano,S.
A1  - Shishido,F.
A1  - Nagashima,M.
A1  - Tomura,N.
A1  - Murakami,M.
A1  - Inugami,A.
A1  - Fujita,H.
A1  - Tabata,K.
A1  - Yasui,N.
A1  - Uemura,K.
Y1  - 1990///
SP  - 297
EP  - 299
JF  - Journal of Computer Assisted Tomography
VL  - 14
IS  - 2
ER  - 

TY  - JOUR
T1  - Positron emission tomography in the detection of malignant degeneration of low-grade gliomas
A1  - Francavilla,T.L.
A1  - Miletich,R.S.
A1  - Di Chiro,G.
A1  - Patronas,N.J.
A1  - Rizzoli,H.V.
A1  - Wright,D.C.
Y1  - 1989///
SP  - 1
EP  - 5
JF  - Neurosurgery
VL  - 24
IS  - 1
ER  - 

TY  - JOUR
T1  - Glucose uptake by gliomas after treatment. A positron emission tomographic study
A1  - Rozental,J.M.
A1  - Levine,R.L.
A1  - Nickles,R.J.
A1  - Dobkin,J.A.
Y1  - 1989///
N1  - 8-drugs-in-1-day
SP  - 1302
EP  - 1307
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 46
IS  - 12
ER  - 

TY  - JOUR
T1  - In defense of quantitative PET techniques [letter]
A1  - Rottenberg,D.A.
A1  - Strother,S.C.
A1  - Moeller,J.R.
Y1  - 1989///
SP  - 564
EP  - 564
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 30
IS  - 4
ER  - 

TY  - JOUR
T1  - Positron emission tomography in patients with glioma. A predictor of prognosis
A1  - Alavi,J.B.
A1  - Alavi,A.
A1  - Chawluk,J.
A1  - Kushner,M.
A1  - Powe,J.
A1  - Hickey,W.
A1  - Reivich,M.
Y1  - 1988///
SP  - 1074
EP  - 1078
JF  - Cancer
VL  - 62
IS  - 6
ER  - 

TY  - JOUR
T1  - PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids
A1  - Bergstrom,M.
A1  - Ericson,K.
A1  - Hagenfeldt,L.
A1  - Mosskin,M.
A1  - von Holst,H.
A1  - Noren,G.
A1  - Eriksson,L.
A1  - Ehrin,E.
A1  - Johnstrom,P.
Y1  - 1987///
SP  - 208
EP  - 213
JF  - Journal of Computer Assisted Tomography
VL  - 11
IS  - 2
ER  - 

TY  - JOUR
T1  - Metabolic and hemodynamic evaluation of gliomas using positron emission tomography
A1  - Tyler,J.L.
A1  - Diksic,M.
A1  - Villemure,J.G.
A1  - Evans,A.C.
A1  - Meyer,E.
A1  - Yamamoto,Y.L.
A1  - Feindel,W.
Y1  - 1987///
SP  - 1123
EP  - 1133
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 28
IS  - 7
N2  - Positron emission tomography (PET) was used on 16 patients with untreated cerebral gliomas to measure cerebral glucose and oxygen metabolism, oxygen extraction, blood flow, and blood volume. In addition, pH values were obtained for seven cases. Gliomas were later proven by biopsy; two patients had tumors with degrees of malignancy of grade II, two patients had grade III, and 12 patients had grade IV tumors. Compared with homologous gray matter regions in the opposite hemisphere, tumor tissue showed increased blood volume, but decreased oxygen extraction and oxygen metabolism. Compared with grade II tumors, grade IV tumors demonstrated higher blood volumes, but lower relative oxygen extraction and utilization. Tumor blood flow was variable, but was lower in the higher grade tumors. Rates of glucose utilization in tumor, calculated by using individually determined rate constants, were variable, and did not correlate with tumor size or tumor grade. Parietal tumors (n = 6) tended to have higher relative glucose utilization and blood flow, and lower relative oxygen extraction, when compared with frontal tumors (n = 4). Tumor pH differed significantly from the pH in contralateral brain (p less than 0.005); alkalotic pH values were consistently seen. These findings in and around cerebral gliomas studied before intervention differ from the results found in gliomas after exposure to radiation or chemotherapy.
ER  - 

TY  - JOUR
T1  - Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study
A1  - Di Chiro,G.
A1  - Hatazawa,J.
A1  - Katz,D.A.
A1  - Rizzoli,H.V.
A1  - De Michele,D.J.
Y1  - 1987///
SP  - 521
EP  - 526
JF  - Radiology
VL  - 164
IS  - 2
ER  - 

TY  - JOUR
T1  - The normal pituitary examined with positron emission tomography and (methyl-11C)-L-methionine and (methyl-11C)-D-methionine
A1  - Bergstrom,M.
A1  - Muhr,C.
A1  - Ericson,K.
A1  - Lundqvist,H.
A1  - Lilja,A.
A1  - Eriksson,L.
A1  - Blomquist,G.
A1  - Langstrom,B.
A1  - Johnstrom,P.
Y1  - 1987///
SP  - 221
EP  - 225
JF  - Neuroradiology
VL  - 29
IS  - 3
N2  - Four patients with radiologically normal pituitary gland were examined with positron emission tomography after the administration of (methyl-11C)-L-methionine. On a following day the examination was repeated with (methyl-11C)-D-methionine. The accumulation rate of L-methionine in the pituitary was measured, giving a value that was about twice that of normal brain tissue. The accumulation rate of D-methionine in the pituitary was almost a factor of 10 lower than that of L-methionine. In the normal brain tissue that ratio was 2.3. The study clearly indicates that the methionine uptake in the pituitary is stereospecific. 11C-D-methionine is freely distributed in the tissue without entrapment, whereas 11C-L-methionine is irreversibly bound. It is concluded that PET with 11C-L-methionine can be used to study amino acid utilization in the pituitary.
ER  - 

TY  - JOUR
T1  - Non selective transport of [11C-methyl]-L-and D-methionine into a malignant glioma
A1  - Schober,O.
A1  - Duden,C.
A1  - Meyer,G.J.
A1  - Muller,J.A.
A1  - Hundeshagen,H.
Y1  - 1987///
SP  - 103
EP  - 105
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 13
IS  - 2
ER  - 

TY  - JOUR
T1  - Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET
A1  - Tyler,J.L.
A1  - Yamamoto,Y.L.
A1  - Diksic,M.
A1  - Theron,J.
A1  - Villemure,J.G.
A1  - Worthington,C.
A1  - Evans,A.C.
A1  - Feindel,W.
Y1  - 1986///
SP  - 775
EP  - 780
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 27
IS  - 6
ER  - 

TY  - JOUR
T1  - Brain tumor protein synthesis and histological grades: a study by positron emission tomography (PET) with C11-L-Methionine
A1  - Bustany,P.
A1  - Chatel,M.
A1  - Derlon,J.M.
A1  - Darcel,F.
A1  - Sgouropoulos,P.
A1  - Soussaline,F.
A1  - Syrota,A.
Y1  - 1986///
SP  - 397
EP  - 404
JF  - Journal of Neuro-Oncology
VL  - 3
IS  - 4
N2  - Brain protein synthesis may be evaluated in vivo by a PET three compartment methionine model. 14 human brain tumor patients were studied. Protein synthesis rate (PSR) was increased in any glial tumor even in low grades, but this increase was statistically more important in anaplastic tumor. Radiotherapy action was evaluated in two patients. Local tumoral PSR was reduced to normal brain PSR after treatment. No difference was seen in normal cortex contralateral to the lesion between pre and post radiotherapy examination. 11 C-L-Methionine incorporation measured by PET looks as a very sensitive method for studying tumor metabolism and treatment effects.
ER  - 

TY  - JOUR
T1  - Prediction of survival in glioma patients by means of positron emission tomography
A1  - Patronas,N.J.
A1  - Di Chiro,G.
A1  - Kufta,C.
A1  - Bairamian,D.
A1  - Kornblith,P.L.
A1  - Simon,R.
A1  - Larson,S.M.
Y1  - 1985///
SP  - 816
EP  - 822
JF  - Journal of Neurosurgery
VL  - 62
IS  - 6
ER  - 

TY  - JOUR
T1  - Measurement of cerebral blood flow using bolus inhalation of C15O2 and positron emission tomography: description of the method and its comparison with the C15O2 continuous inhalation method
A1  - Kanno,I.
A1  - Lammertsma,A.A.
A1  - Heather,J.D.
A1  - Gibbs,J.M.
A1  - Rhodes,C.G.
A1  - Clark,J.C.
A1  - Jones,T.
Y1  - 1984///
SP  - 224
EP  - 234
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 2
N2  - This article describes a rapid method for the regional measurement of cerebral blood flow using a single breath of C15O2 and positron emission tomography. The technique is based on the bolus distribution principle and utilises a reference table for the calculation of flow. Seven subjects were studied using both this method and the C15O2 continuous inhalation steady-state technique. The single-breath method gave flow values 20% higher than those obtained using the steady-state method. A simulation study was performed in an attempt to define the reasons for the difference between the two techniques. Estimations were made of identified sources of error in the measurement of regional cerebral blood flow using the single-breath technique and compared with results from a similar study previously described for the steady-state technique. However, further comparative studies will be necessary to satisfactorily explain the difference between both techniques
ER  - 

TY  - JOUR
T1  - Positron emission tomographic study of suppression of gray-matter glucose utilization by brain tumors
A1  - DeLaPaz,R.L.
A1  - Patronas,N.J.
A1  - Brooks,R.A.
A1  - Smith,B.H.
A1  - Kornblith,P.L.
A1  - Milam,H.
A1  - Di Chiro,G.
Y1  - 1983///
SP  - 826
EP  - 829
JF  - Ajnr: American Journal of Neuroradiology
VL  - 4
IS  - 3
ER  - 

TY  - JOUR
T1  - Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain
A1  - Patronas,N.J.
A1  - Di Chiro,G.
A1  - Brooks,R.A.
A1  - DeLaPaz,R.L.
A1  - Kornblith,P.L.
A1  - Smith,B.H.
A1  - Rizzoli,H.V.
A1  - Kessler,R.M.
A1  - Manning,R.G.
A1  - Channing,M.
A1  - Wolf,A.P.
A1  - O'Connor,C.M.
Y1  - 1982///
SP  - 885
EP  - 889
JF  - Radiology
VL  - 144
IS  - 4
ER  - 

TY  - JOUR
T1  - Brain tumor evaluation using Rb-82 and positron emission tomography
A1  - Yen,C.K.
A1  - Yano,Y.
A1  - Budinger,T.F.
A1  - Friedland,R.P.
A1  - Derenzo,S.E.
A1  - Huesman,R.H.
A1  - O'Brien,H.A.
Y1  - 1982///
SP  - 532
EP  - 537
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 23
IS  - 6
N2  - Positron emission tomography of the brain with 75-sec rubidium-82 obtained from a portable generator (25-day Sr-82 leads to Rb-82) was used to evaluate the integrity of the blood-brain barrier (BBB) in patients with brain tumors. Rubidium is normally excluded from the central nervous system by the intact BBB, but when the BBB is disrupted by a tumor. Rb enters and pools in the extravascular spaces of the central nervous system. Since Rb is also rapidly cleared from the blood, a high tissue-to-blood ratio of the Rb-82 tracer is achieved in regions of BBB disruption after intravenous injection. With dynamic positron emission tomographic imaging, the extravasation of the Rb tracer can be evaluated independent of the intravascular Rb concentration, and very small changes in the BBB permeability can be detected. The results of our studies in eight patients show that this technique is a promising method for evaluation of the BBB integrity in brain-tumor patients
ER  - 

TY  - JOUR
T1  - Comparison of PET measurements of cerebral blood flow and glucose metabolism for the localization of human epileptic foci
A1  - Leiderman,D.B.
A1  - Balish,M.
A1  - Sato,S.
A1  - Kufta,C.
A1  - Reeves,P.
A1  - Gaillard,W.D.
A1  - Theodore,W.H.
Y1  - 1992///
SP  - 153
EP  - 157
JF  - Epilepsy Research
VL  - 13
IS  - 2
ER  - 

TY  - JOUR
T1  - PET imaging of opiate receptor binding in human epilepsy using [18F]cyclofoxy
A1  - Theodore,W.H.
A1  - Carson,R.E.
A1  - Andreasen,P.
A1  - Zametkin,A.
A1  - Blasberg,R.
A1  - Leiderman,D.B.
A1  - Rice,K.
A1  - Newman,A.
A1  - Channing,M.
A1  - Dunn,B.
A1  - et al.
Y1  - 1992///
SP  - 129
EP  - 139
JF  - Epilepsy Research
VL  - 13
IS  - 2
ER  - 

TY  - BOOK
T1  - Co-planar stereotaxic atlas of the human brain
A1  - Talairach,J.
A1  - Tournoux,P.
Y1  - 1988///
CY  - Stuttgart
PB  - Georg Thieme Verlag
Y2  - -32676///
ER  - 

TY  - CHAP
T1  - Integrated quantitative analysis of functional and morphological 3D data by volumes of interest
A1  - Herholz,K.
A1  - Dickhoven,S.
A1  - Karbe,H.
A1  - Halber,M.
A1  - Pietrzyk,U.
A1  - Heiss,W.D.
Y1  - 1996///
SP  - 175
EP  - 180
T2  - Quantification of brain function using PET
A2  - Myers,R.
A2  - Cunningham,V.J.
A2  - Bailey,D.L.
A2  - Jones,T.
IS  - 34
CY  - San Diego
PB  - Academic Press
SN  - 0-12-389760-2
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Topographical variation of the human primary cortices: implications for neuroimaging, brain mapping, and neurobiology
A1  - Rademacher,J.
A1  - Caviness,V.S.,Jr.
A1  - Steinmetz,H.
A1  - Galaburda,A.M.
Y1  - 1993///
SP  - 313
EP  - 329
JF  - Cerebral Cortex
VL  - 3
IS  - 4
ER  - 

TY  - JOUR
T1  - Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci
A1  - Savic,I.
A1  - Ingvar,M.
A1  - Stone-Elander,S.
Y1  - 1993///
SP  - 615
EP  - 621
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 56
IS  - 6
N2  - Recent PET results indicate that the benzodiazepine (BZ) receptor density measured with the BZ receptor antagonist [11C]flumazenil is reduced in human epileptic foci. The present study examines the applicability of this finding in the presurgical investigation of patients with intractable partial epilepsy. In eight patients, the PET measurements were performed after injection of the BZ receptor antagonist [11C]flumazenil and [2-18F]2-deoxy-2-fluoro-D-glucose ([18F]FDG)--a tracer for measurements of the rate of regional glucose metabolism. The focus localising ability of the two PET tracers was examined using extra--and intracranial EEG recordings as reference. The focus was first determined visually on the PET images obtained after a bolus injection of each of the PET tracers. Its anatomical localisation and spatial delimitation was then evaluated for each patient with a computerised anatomical brain atlas. [11C]flumazenil was found to be a more sensitive and accurate focus localiser than [18F]FDG. This observation was valid both for quantified and non-quantified images. In the preoperative diagnosis of epileptic foci, the PET measurements of BZ receptors may be a suitable and, in some cases, superior method to the generally used "[18F]FDG-PET" method.
ER  - 

TY  - JOUR
T1  - Methionine PET for follow-up of radiation therapy of primary lymphoma of the brain
A1  - Ogawa,T.
A1  - Kanno,I.
A1  - Hatazawa,J.
A1  - Inugami,A.
A1  - Fujita,H.
A1  - Shimosegawa,E.
A1  - Murakami,M.
A1  - Okudera,T.
A1  - Uemura,K.
A1  - Yasui,N.
A1  - et al.
Y1  - 1994///
SP  - 101
EP  - 110
JF  - Radiographics
VL  - 14
IS  - 1
ER  - 

TY  - JOUR
T1  - Effects of radiotherapy determined by 11C-methyl-L-methionine positron emission tomography in patients with primary cerebral malignant lymphoma
A1  - Sawataishi,J.
A1  - Mineura,K.
A1  - Sasajima,T.
A1  - Kowada,M.
A1  - Sugawara,A.
A1  - Shishido,F.
Y1  - 1992///
SP  - 517
EP  - 519
JF  - Neuroradiology
VL  - 34
IS  - 6
N2  - Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using 11C-methyl-L-methionine (11C Met). Lesions delineated by 11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of 11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma.
ER  - 

TY  - JOUR
T1  - Brain tumors - L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate
A1  - Pruim,J.
A1  - Willemsen,A.T.M.
A1  - Molenaar,W.M.
A1  - Vanwaarde,A.
A1  - Paans,A.M.J.
A1  - Heesters,M.A.A.M.
A1  - Go,K.G.
A1  - Visser,G.M.
A1  - Franssen,E.J.F.
A1  - Vaalburg,W.
Y1  - 1995///
SP  - 221
EP  - 226
JF  - Radiology
VL  - 197
IS  - 1
ER  - 

TY  - JOUR
T1  - Cortical language localization in left, dominant hemisphere
A1  - Ojemann,G.
A1  - Ojemann,J.
A1  - Lettich,E.
A1  - Berger,M.
Y1  - 1989///
SP  - 316
EP  - 326
JF  - Journal of Neurosurgery
VL  - 71
ER  - 

TY  - JOUR
T1  - Antiepileptic drugs and cerebral glucose metabolism
A1  - Theodore,W.H.
Y1  - 1988///
SP  - S48
EP  - 55
JF  - Epilepsia
VL  - 29
IS  - Supplement 2
ER  - 

TY  - JOUR
T1  - High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET
A1  - Messa,C.
A1  - Perani,D.
A1  - Lucignani,G.
A1  - Zenorini,A.
A1  - Zito,F.
A1  - Rizzo,G.
A1  - Grassi,F.
A1  - Del Sole,A.
A1  - Franceschi,M.
A1  - Gilardi,M.C.
A1  - et al.
Y1  - 1994///
SP  - 210
EP  - 216
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 35
IS  - 2
ER  - 

TY  - JOUR
T1  - The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Dhawan,V.
A1  - Sidtis,J.J.
A1  - Ginos,J.Z.
A1  - Strother,S.C.
A1  - Cedarbaum,J.
A1  - Greene,P.
A1  - Fahn,S.
A1  - Rottenberg,D.A.
Y1  - 1990///
SP  - 203
EP  - 213
JF  - Movement Disorders
VL  - 5
IS  - 3
N2  - We studied the metabolic anatomy of typical Parkinson's disease (PD) using [18F]fluorodeoxyglucose (FDG) and [18F]fluorodopa (FDOPA) and positron emission tomography (PET). Fourteen PD patients (mean age 49 years) had FDG/PET scans, of which 11 were scanned with both FDOPA and FDG. After the injection of FDOPA, brain uptake and arterial plasma radioactivity were monitored for 2 h. Striatal FDOPA uptake was analyzed with regard to a two-compartment model, and target-to-background ratios (TBRs) and TBR-versus-time slopes were also calculated. Regional patterns of metabolic covariation were extracted from FDG/PET data using the Scaled Subprofile Model (SSM). SSM pattern weights, FDOPA uptake constants (Ki), TBRs, and TBR slopes were correlated with clinical measures for bradykinesia, rigidity, tremor, gait disturbance, left-right asymmetry, dementia, and overall disease severity. In PD patients, rate constants for FDOPA uptake correlated with individual measures of bradykinesia (p = 0.001) and gait disability (p less than 0.05). SSM analysis revealed a distinct pattern of regional metabolic asymmetries, which correlated with motor asymmetries (p less than 0.001) and left-right differences in Ki (p less than 0.01). Our data suggest that in PD patients, FDG/PET and FDOPA/PET may provide unique and complementary information about underlying disease processes.
ER  - 

TY  - JOUR
T1  - Effect of selecting a fixed dephosphorylation rate on the estimation of rate constants and rCMRGlu from dynamic [18F] fluorodeoxyglucose/PET data
A1  - Dhawan,V.
A1  - Moeller,J.R.
A1  - Strother,S.C.
A1  - Evans,A.C.
A1  - Rottenberg,D.A.
Y1  - 1989///
SP  - 1483
EP  - 1488
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 30
IS  - 9
ER  - 

TY  - JOUR
T1  - Effect of blood curve smearing on the accuracy of parameter estimates obtained for 82Rb/PET studies of blood-brain barrier permeability
A1  - Dhawan,V.
A1  - Jarden,J.O.
A1  - Strother,S.
A1  - Rottenberg,D.A.
Y1  - 1988///
SP  - 61
EP  - 74
JF  - Physics in Medicine & Biology
VL  - 33
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomographic measurement of blood-to-brain and blood-to-tumor transport of 82Rb: the effect of dexamethasone and whole-brain radiation therapy
A1  - Jarden,J.O.
A1  - Dhawan,V.
A1  - Poltorak,A.
A1  - Posner,J.B.
A1  - Rottenberg,D.A.
Y1  - 1985///
SP  - 636
EP  - 646
JF  - Annals of Neurology
VL  - 18
IS  - 6
ER  - 

TY  - JOUR
T1  - In vivo measurement of brain tumor pH using [11C]DMO and positron emission tomography
A1  - Rottenberg,D.A.
A1  - Ginos,J.Z.
A1  - Kearfott,K.J.
A1  - Junck,L.
A1  - Dhawan,V.
A1  - Jarden,J.O.
Y1  - 1985///
SP  - 70
EP  - 79
JF  - Annals of Neurology
VL  - 17
IS  - 1
N2  - In vivo measurements of regional brain tissue/tumor pH (rpH) have been accomplished in 9 patients with primary or metastatic brain tumors using [11C]dimethyloxazolidinedione [( 11C]DMO) and positron emission tomography. Tumor rpH values ranged from 6.88 to 7.26, whereas gray matter and white matter rpH values ranged from 6.74 to 7.09 and from 6.77 to 7.03, respectively. Our results, which are consistent with reported [14C]DMO autoradiographic measurements of brain and tumor pH, suggest that the pH microenvironment of brain tumors is not more "acidic" than that of normal gray or white matter.
ER  - 

TY  - JOUR
T1  - C-11 dimethyloxazolidinedione (DMO): biodistribution, radiation absorbed dose, and potential for PET measurement of regional brain pH: concise communication
A1  - Kearfott,K.J.
A1  - Junck,L.
A1  - Rottenberg,D.A.
Y1  - 1983///
SP  - 805
EP  - 811
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 24
IS  - 9
ER  - 

TY  - JOUR
T1  - A convenient method for regional monoamine oxidase-A determination by [14C]clorgyline autoradiography
A1  - Murakami,M.
A1  - Kondoh,Y.
A1  - Weimin,Y.
A1  - Mizusawa,S.
A1  - Nakamichi,H.
A1  - Takahashi,K.
A1  - Sasaki,H.
A1  - Iida,H.
A1  - Miura,S.
A1  - Kanno,I.
A1  - et al.
Y1  - 1992///
SP  - 619
EP  - 626
JF  - International Journal of Radiation Applications & Instrumentation - Part B, Nuclear Medicine & Biology
VL  - 19
IS  - 6
ER  - 

TY  - JOUR
T1  - Blood sampling devices and measurements
A1  - Eriksson,L.
A1  - Kanno,I.
Y1  - 1991///
SP  - 249
EP  - 257
JF  - Medical Progress through Technology
VL  - 17
IS  - 3-4
ER  - 

TY  - JOUR
T1  - A new approach of weighted integration technique based on accumulated images using dynamic PET and H2(15)O
A1  - Yokoi,T.
A1  - Kanno,I.
A1  - Iida,H.
A1  - Miura,S.
A1  - Uemura,K.
Y1  - 1991///
SP  - 492
EP  - 501
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 3
ER  - 

TY  - JOUR
T1  - Error analysis of a quantitative cerebral blood flow measurement using H2(15)O autoradiography and positron emission tomography, with respect to the dispersion of the input function
A1  - Iida,H.
A1  - Kanno,I.
A1  - Miura,S.
A1  - Murakami,M.
A1  - Takahashi,K.
A1  - Uemura,K.
Y1  - 1986///
SP  - 536
EP  - 545
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 5
ER  - 

TY  - JOUR
T1  - Analysis of covariance in statistical parametric mapping [letter]
A1  - Clark,C.
A1  - Carson,R.
Y1  - 1993///
SP  - 1038
EP  - 1040
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 6
ER  - 

TY  - JOUR
T1  - Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil
A1  - Price,J.C.
A1  - Mayberg,H.S.
A1  - Dannals,R.F.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Sadzot,B.
A1  - Rattner,Z.
A1  - Kimball,A.
A1  - Feldman,M.A.
A1  - Frost,J.J.
Y1  - 1993///
SP  - 656
EP  - 667
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 13
IS  - 4
ER  - 

TY  - JOUR
T1  - Functional interactions in the brain: use of correlations between regional metabolic rates
A1  - Horwitz,B.
Y1  - 1991///
SP  - A114
EP  - 20
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 2
N2  - Correlation coefficients between pairs of regional metabolic rates have been used to study patterns of functional associations among brain regions in humans and animals. An overview is provided concerning the additional information about brain functioning this type of analysis yields. A computer simulation model is presented for the purpose of giving a partial validation for correlational analysis. The model generates a set of simulated metabolic data upon which correlational analysis is performed. Because the underlying pattern of functional couplings in the model is known, these simulations demonstrate that the correlation coefficient between normalized metabolic rates is proportional to the strength of the functional coupling constant and that correlational analysis yields information on regional involvement in neural systems not evident in the pattern of absolute metabolic values
ER  - 

TY  - JOUR
T1  - In vivo binding of spiperone and N-methylspiperone to dopaminergic and serotonergic sites in the rat brain: multiple modeling and implications for PET scanning
A1  - Swart,J.A.
A1  - van der Werf,J.F.
A1  - Wiegman,T.
A1  - Paans,A.M.
A1  - Vaalburg,W.
A1  - Korf,J.
Y1  - 1990///
SP  - 297
EP  - 306
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 3
ER  - 

TY  - JOUR
T1  - Positron emission tomographic measurements of cerebral glucose utilization using [1-11C]D-glucose
A1  - Blomqvist,G.
A1  - Stone-Elander,S.
A1  - Halldin,C.
A1  - Roland,P.E.
A1  - Widen,L.
A1  - Lindqvist,M.
A1  - Swahn,C.G.
A1  - Langstrom,B.
A1  - Wiesel,F.A.
Y1  - 1990///
SP  - 467
EP  - 483
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 4
N2  - Regional CMRglc was measured in seven healthy volunteers with positron emission tomography using [1-11C]D-glucose. Regional CBF was measured using [11C]fluoromethane. The arteriovenous differences of unlabeled glucose and oxygen together with 11C metabolites were also measured. In addition to the loss of [11C]CO2, a loss of acidic 11C metabolites was also detected. A three-compartment model was applied to the tracer data in the time interval 0-24 min. After correction for the loss of 11C metabolites, the tracer method gave an average CMRglc of 26.4 +/- 1.9 (SD) mumol/100 g/min, close to the value obtained with the Fick principle. After correction for the loss of [11C]CO2 only, the tracer method gave 23.6 +/- 2.1 mumol/100 g/min, compatible with (1/6) CMRO2, obtained with the Fick principle. These results and the time course of the loss of acidic 11C metabolites are consistent with the presence of nonoxidative metabolism of glucose that causes an early loss of mainly [11C]lactate after a bolus injection of the tracer. This implies that [1-11C]D-glucose measures the rate of glucose oxidation rather than the total CMRglc. The experiments using [1-11C]D-glucose were compared to five analogous experiments using [U-11C]D-glucose together with [15O]H2O as a flow tracer. After correction for the loss of [11C]CO2, the two glucose tracers gave similar global values of CMRglc and other parameters associated with glucose utilization, but with labeling in the carbon-1 position, the loss of [11C]CO2 was substantially delayed and the contrast between gray and white matter was improved.(ABSTRACT TRUNCATED AT 250 WORDS)
ER  - 

TY  - JOUR
T1  - Graphical analysis of reversible radioligand binding from time- activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wolf,A.P.
A1  - Dewey,S.L.
A1  - Schlyer,D.J.
A1  - MacGregor,R.R.
A1  - Hitzemann,R.
A1  - Bendriem,B.
A1  - Gatley,S.J.
A1  - et al.
Y1  - 1990///
SP  - 740
EP  - 747
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 5
ER  - 

TY  - JOUR
T1  - Michaelis-Menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F]fluorodeoxyglucose
A1  - Kuwabara,H.
A1  - Evans,A.C.
A1  - Gjedde,A.
Y1  - 1990///
SP  - 180
EP  - 189
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 10
IS  - 2
ER  - 

TY  - JOUR
T1  - A double-injection technique for in vivo measurement of dopamine D2-receptor density in monkeys with 3-(2'- [18F]fluoroethyl)spiperone and dynamic positron emission tomography
A1  - Huang,S.C.
A1  - Bahn,M.M.
A1  - Barrio,J.R.
A1  - Hoffman,J.M.
A1  - Satyamurthy,N.
A1  - Hawkins,R.A.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1989///
SP  - 850
EP  - 858
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 6
ER  - 

TY  - JOUR
T1  - Models for in vivo kinetic interactions of dopamine D2- neuroreceptors and 3-(2'-[18F]fluoroethyl)spiperone examined with positron emission tomography
A1  - Bahn,M.M.
A1  - Huang,S.C.
A1  - Hawkins,R.A.
A1  - Satyamurthy,N.
A1  - Hoffman,J.M.
A1  - Barrio,J.R.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1989///
SP  - 840
EP  - 849
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 6
ER  - 

TY  - JOUR
T1  - 3-(2'-[18F]fluoroethyl)spiperone: in vivo biochemical and kinetic characterization in rodents, nonhuman primates, and humans
A1  - Barrio,J.R.
A1  - Satyamurthy,N.
A1  - Huang,S.C.
A1  - Keen,R.E.
A1  - Nissenson,C.H.
A1  - Hoffman,J.M.
A1  - Ackermann,R.F.
A1  - Bahn,M.M.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1989///
SP  - 830
EP  - 839
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 6
ER  - 

TY  - JOUR
T1  - Kinetic analysis of central [11C]raclopride binding to D2- dopamine receptors studied by PET--a comparison to the equilibrium analysis
A1  - Farde,L.
A1  - Eriksson,L.
A1  - Blomquist,G.
A1  - Halldin,C.
Y1  - 1989///
SP  - 696
EP  - 708
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 5
ER  - 

TY  - JOUR
T1  - Estimation of local cerebral protein synthesis rates with L-[1- 11C]leucine and PET: methods, model, and results in animals and humans
A1  - Hawkins,R.A.
A1  - Huang,S.C.
A1  - Barrio,J.R.
A1  - Keen,R.E.
A1  - Feng,D.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1989///
SP  - 446
EP  - 460
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 4
ER  - 

TY  - JOUR
T1  - In vivo cerebral protein synthesis rates with leucyl-transfer RNA used as a precursor pool: determination of biochemical parameters to structure tracer kinetic models for positron emission tomography
A1  - Keen,R.E.
A1  - Barrio,J.R.
A1  - Huang,S.C.
A1  - Hawkins,R.A.
A1  - Phelps,M.E.
Y1  - 1989///
SP  - 429
EP  - 445
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 9
IS  - 4
ER  - 

TY  - JOUR
T1  - Measurement of end-capillary PO2 with positron emission tomography
A1  - Alpert,N.M.
A1  - Buxton,R.B.
A1  - Correia,J.A.
A1  - Katz,P.M.
A1  - Ackerman,R.H.
Y1  - 1988///
SP  - 403
EP  - 410
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 8
IS  - 3
N2  - The analysis of positron emission tomography measurements of oxygen metabolism has been extended to provide a quantitative estimate of end-capillary PO2. The principle of this extension rests on the idea that the oxygen extraction fraction can be used to calculate the end-capillary oxygen saturation of the blood. The relation between oxygen saturation and PO2 is obtained through the oxygen dissociation curve. Our studies show that in addition to the local oxygen extraction fraction, arterial PO2 and pH values are needed in the calculation, whereas fairly large variations in factors such as PCO2, hematocrit, hemoglobin, and plasma protein levels have little or no effect. Rough estimates of end-capillary PO2 can be made using standard O2 dissociation nomograms. Blood gas and acid-base properties of blood have been known for decades, making it possible to account accurately for individual differences that may be encountered when studying patients. Measurements in nine normal subjects yielded a mean end-capillary PO2 value of 31.2 mm Hg. The ability to make a quantitative visualization of altered patterns of end-capillary PO2 provides an additional dimension to the investigation of stroke disease and tumor metabolism
ER  - 

TY  - JOUR
T1  - Assessment of [11C]-L-methionine transport into the human brain
A1  - O'Tuama,L.A.
A1  - Guilarte,T.R.
A1  - Douglass,K.H.
A1  - Wagner,H.N.,Jr.
A1  - Wong,D.F.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Wilson,A.A.
A1  - LaFrance,N.D.
A1  - Bice,A.N.
A1  - et al.
Y1  - 1988///
SP  - 341
EP  - 345
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 8
IS  - 3
ER  - 

TY  - JOUR
T1  - Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. I. pH changes measured in states of altered PCO2
A1  - Buxton,R.B.
A1  - Alpert,N.M.
A1  - Babikian,V.
A1  - Weise,S.
A1  - Correia,J.A.
A1  - Ackerman,R.H.
Y1  - 1987///
SP  - 709
EP  - 719
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 6
N2  - The 11CO2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11CO2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO2 (range 21-67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO2). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO2. The interpretation of these pH values in normal and pathological states is discussed.
ER  - 

TY  - JOUR
T1  - Effect of adenosine on human cerebral blood flow as determined by positron emission tomography
A1  - Sollevi,A.
A1  - Ericson,K.
A1  - Eriksson,L.
A1  - Lindqvist,C.
A1  - Lagerkranser,M.
A1  - Stone-Elander,S.
Y1  - 1987///
SP  - 673
EP  - 678
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 6
N2  - The effect of intravenous infusion of adenosine on CBF was studied in seven patients with cerebral arteriovenous malformation. The patients were examined with positron emission tomography with controlled ventilation using [15O] water and [11C] fluoromethane as tracers. Total and regional CBF were determined before and during infusion of adenosine at rates producing a reduction of the MABP by approximately 10-40%. Six patients were normoventilated, and one was hyperventilated. Mean CBF in areas with normal brain tissue was 54 ml/100 g/min before adenosine infusion under normoventilation. Adenosine infusion increased mean CBF with 23-85%. Mean CVR was decreased with 43-65% and exceeded the percentage reduction of MABP in all normoventilated subjects. In the hyperventilated patient, the reduction of CVR was similar to the reduction of MABP, and CBF was unaffected, except for the 30% increase in the thalamus. It is concluded that intravenous administration of adenosine produces marked cerebral vasodilation in normoventilated subjects and that this response can be counteracted by hyperventilation.
ER  - 

TY  - JOUR
T1  - Positron emission tomographic measurement of cerebral blood flow and permeability-surface area product of water using [15O]water and [11C]butanol
A1  - Herscovitch,P.
A1  - Raichle,M.E.
A1  - Kilbourn,M.R.
A1  - Welch,M.J.
Y1  - 1987///
SP  - 527
EP  - 542
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 5
N2  - We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H2(15)O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H2(15)O, may lead to an underestimation of CBF. We therefore validated the use of [11C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H2(15)O, and thereby were able to calculate the extraction Ew and permeability-surface area product PSw of H2(15)O. Measurements of the permeability of rhesus monkey brain to [11C]butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and [11C]butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H2(15)O and [11C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [11C]butanol (53.1 ml/min-100 g) than with H2(15)O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain-blood partition coefficient for [11C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.
ER  - 

TY  - JOUR
T1  - Cerebral blood volume measured with inhaled C15O and positron emission tomography
A1  - Martin,W.R.
A1  - Powers,W.J.
A1  - Raichle,M.E.
Y1  - 1987///
SP  - 421
EP  - 426
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 4
ER  - 

TY  - JOUR
T1  - Behavioral activation and the variability of cerebral glucose metabolic measurements
A1  - Duara,R.
A1  - Gross-Glenn,K.
A1  - Barker,W.W.
A1  - Chang,J.Y.
A1  - Apicella,A.
A1  - Loewenstein,D.
A1  - Boothe,T.
Y1  - 1987///
SP  - 266
EP  - 271
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 3
N2  - Variability in cerebral glucose metabolism was examined between and within subjects when paired studies were performed in the resting state or in a behaviorally activated state. Both normal and demented subjects were studied twice each, from 1 to 6 weeks apart, under near-identical conditions, using positron emission tomography (PET) and [18F]fluorodeoxyglucose. Resting state studies were repeated in nine normal and four demented subjects. A picture-viewing test, used for activation during PET, was used repeatedly in seven normal and five demented subjects. Within-subject variability, as assessed by the percent difference in metabolic rates in paired studies, was reduced by 60-70% for activation state compared to resting state studies in normals. It is concluded that PET studies of brain metabolism, which are designed to study the active brain, should indeed be performed in functionally activated states, as in addition to demonstrating metabolism during a defined functional state, activation studies show reduced variability of cerebral metabolic measures.
ER  - 

TY  - JOUR
T1  - The effect of anxiety on cortical cerebral blood flow and metabolism
A1  - Gur,R.C.
A1  - Gur,R.E.
A1  - Resnick,S.M.
A1  - Skolnick,B.E.
A1  - Alavi,A.
A1  - Reivich,M.
Y1  - 1987///
SP  - 173
EP  - 177
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 7
IS  - 2
N2  - The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using 18Flurodeoxyglucose (18FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between anxiety and performance
ER  - 

TY  - JOUR
T1  - Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity
A1  - Wong,D.F.
A1  - Gjedde,A.
A1  - Wagner,H.N.,Jr.
A1  - Dannals,R.F.
A1  - Douglass,K.H.
A1  - Links,J.M.
A1  - Kuhar,M.J.
Y1  - 1986///
SP  - 147
EP  - 153
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands
A1  - Wong,D.F.
A1  - Gjedde,A.
A1  - Wagner,H.N.,Jr.
Y1  - 1986///
SP  - 137
EP  - 146
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - Studies on regional cerebral pH in patients with cerebral tumours using continuous inhalation of 11CO2 and positron emission tomography
A1  - Brooks,D.J.
A1  - Beaney,R.P.
A1  - Thomas,D.G.
A1  - Marshall,J.
A1  - Jones,T.
Y1  - 1986///
SP  - 529
EP  - 535
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 5
N2  - Regional cerebral pH (rpH) was measured in 12 patients with cerebral tumours and in 5 normal subjects using continuous inhalation of 11CO2 and positron emission tomography (PET). Cerebral tumours with a disrupted blood-brain barrier (BBB) on computed tomography scanning had a similar rpH to that of equivalent regions of contralateral brain tissue (mean tumour rpH, 6.98; mean contralateral brain pH, 6.99). Cerebral tumours with an intact BBB were consistently found to be more alkaline than contralateral brain tissue (mean tumour rpH, 7.09). There was no significant difference between the mean rpH values obtained for peripheral cortical gray and central white matter in normal subjects (7.02 and 6.98, respectively). It is concluded that in spite of reports of raised levels of aerobic glycolysis in neoplastic tissue, there is no evidence that cerebral tumour rpH values are depressed.
ER  - 

TY  - JOUR
T1  - Neuroreceptor assay with positron emission tomography: equilibrium versus dynamic approaches
A1  - Huang,S.C.
A1  - Barrio,J.R.
A1  - Phelps,M.E.
Y1  - 1986///
N1  - Basics of PET receptor study
SP  - 515
EP  - 521
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 5
ER  - 

TY  - JOUR
T1  - Effect of phenytoin on human cerebral glucose metabolism
A1  - Theodore,W.H.
A1  - Bairamian,D.
A1  - Newmark,M.E.
A1  - Di Chiro,G.
A1  - Porter,R.J.
A1  - Larson,S.
A1  - Fishbein,D.
Y1  - 1986///
SP  - 315
EP  - 320
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 3
ER  - 

TY  - JOUR
T1  - Weighted integration method for local cerebral blood flow measurements with positron emission tomography
A1  - Carson,R.E.
A1  - Huang,S.C.
A1  - Green,M.V.
Y1  - 1986///
SP  - 245
EP  - 258
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - Effects of temporal sampling, glucose metabolic rates, and disruptions of the blood-brain barrier on the FDG model with and without a vascular compartment: studies in human brain tumors with PET
A1  - Hawkins,R.A.
A1  - Phelps,M.E.
A1  - Huang,S.C.
Y1  - 1986///
SP  - 170
EP  - 183
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 2
ER  - 

TY  - JOUR
T1  - Model dependency and estimation reliability in measurement of cerebral oxygen utilization rate with oxygen-15 and dynamic positron emission tomography
A1  - Huang,S.C.
A1  - Feng,D.G.
A1  - Phelps,M.E.
Y1  - 1986///
SP  - 105
EP  - 119
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 6
IS  - 1
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans
A1  - Powers,W.J.
A1  - Grubb,R.L.,Jr.
A1  - Darriet,D.
A1  - Raichle,M.E.
Y1  - 1985///
SP  - 600
EP  - 608
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 4
N2  - This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100 g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia
ER  - 

TY  - JOUR
T1  - Performance comparison of parameter estimation techniques for the quantitation of local cerebral blood flow by dynamic positron computed tomography
A1  - Koeppe,R.A.
A1  - Holden,J.E.
A1  - Ip,W.R.
Y1  - 1985///
SP  - 224
EP  - 234
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 2
ER  - 

TY  - JOUR
T1  - What is the correct value for the brain--blood partition coefficient for water?
A1  - Herscovitch,P.
A1  - Raichle,M.E.
Y1  - 1985///
SP  - 65
EP  - 69
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 1
N2  - A knowledge of the brain-blood partition coefficient (lambda) for water is usually required for the measurement of CBF with [15O]water. The currently accepted value for whole-brain lambda, 0.95-0.96 ml/g, calculated from brain and blood water content data, is incorrect because in the calculation, the blood water content was not adjusted for the density of blood. The correct value is 0.90 ml/g. Variations in brain or blood water content affect lambda. Thus, lambda changes during development of the brain and varies regionally in it, even among different gray matter structures, owing to variation in brain water content. In addition, lambda would be expected to vary with the hematocrit, owing to changes in blood water content. The impact of using an incorrect value for lambda will depend on the sensitivity of the CBF measurement technique used to errors in lambda.
ER  - 

TY  - JOUR
T1  - A kinetic evaluation of blood-brain barrier permeability in human brain tumors with [68Ga]EDTA and positron computed tomography
A1  - Hawkins,R.A.
A1  - Phelps,M.E.
A1  - Huang,S.C.
A1  - Wapenski,J.A.
A1  - Grimm,P.D.
A1  - Parker,R.G.
A1  - Juillard,G.
A1  - Greenberg,P.
Y1  - 1984///
SP  - 507
EP  - 515
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - Measurement of brain pH using 11CO2 and positron emission tomography
A1  - Buxton,R.B.
A1  - Wechsler,L.R.
A1  - Alpert,N.M.
A1  - Ackerman,R.H.
A1  - Elmaleh,D.R.
A1  - Correia,J.A.
Y1  - 1984///
SP  - 8
EP  - 16
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 1
N2  - We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue PCO2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue PCO2. Assuming that the blood--brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation
ER  - 

TY  - JOUR
T1  - On the construction of functional maps in positron emission tomography
A1  - Blomqvist,G.
Y1  - 1984///
SP  - 629
EP  - 632
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - In vivo measurement of regional cerebral haematocrit using positron emission tomography
A1  - Lammertsma,A.A.
A1  - Brooks,D.J.
A1  - Beaney,R.P.
A1  - Turton,D.R.
A1  - Kensett,M.J.
A1  - Heather,J.D.
A1  - Marshall,J.
A1  - Jones,T.
Y1  - 1984///
SP  - 317
EP  - 322
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 3
N2  - A method is described for measuring the regional cerebral-to-large vessel haematocrit ratio using inhalation of carbon-11-labelled carbon monoxide and the intravenous injection of carbon-11-labelled methyl-albumin in combination with positron emission tomography. The mean value in a series of nine subjects was 0.69. This is approximately 20% lower than the value of 0.85 previously reported. It is concluded that previous measurements of regional cerebral blood volume using a haematocrit ratio of 0.85 will have underestimated the value of regional cerebral blood volume by 20%.
ER  - 

TY  - JOUR
T1  - Alternative approach to single-scan estimation of cerebral glucose metabolic rate using glucose analogs, with particular application to ischemia
A1  - Hutchins,G.D.
A1  - Holden,J.E.
A1  - Koeppe,R.A.
A1  - Halama,J.R.
A1  - Gatley,S.J.
A1  - Nickles,R.J.
Y1  - 1984///
SP  - 35
EP  - 40
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 1
ER  - 

TY  - JOUR
T1  - Strategy for the measurement of regional cerebral blood flow using short-lived tracers and emission tomography
A1  - Alpert,N.M.
A1  - Eriksson,L.
A1  - Chang,J.Y.
A1  - Bergstrom,M.
A1  - Litton,J.E.
A1  - Correia,J.A.
A1  - Bohm,C.
A1  - Ackerman,R.H.
A1  - Taveras,J.M.
Y1  - 1984///
SP  - 28
EP  - 34
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 4
IS  - 1
ER  - 

TY  - JOUR
T1  - Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer's disease
A1  - DeLeon,M.J.
A1  - Ferris,S.H.
A1  - George,A.E.
A1  - Reisberg,B.
A1  - Christman,D.R.
A1  - Kricheff,I.I.
A1  - Wolf,A.P.
Y1  - 1983///
SP  - 391
EP  - 394
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 3
IS  - 3
ER  - 

TY  - JOUR
T1  - Measurement of local blood flow and distribution volume with short-lived isotopes: a general input technique
A1  - Huang,S.C.
A1  - Carson,R.E.
A1  - Phelps,M.E.
Y1  - 1982///
N1  - Double integration technique
SP  - 99
EP  - 108
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 2
IS  - 1
ER  - 

TY  - JOUR
T1  - Cerebral transport and metabolism of 1-11C-D-glucose during stepped hypoglycemia
A1  - Powers,W.J.
A1  - Dagogo-Jack,S.
A1  - Markham,J.
A1  - Larson,K.B.
A1  - Dence,C.S.
Y1  - 1995///
SP  - 599
EP  - 609
JF  - Annals of Neurology
VL  - 38
IS  - 4
ER  - 

TY  - JOUR
T1  - Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography
A1  - Gilman,S.
A1  - Adams,K.
A1  - Koeppe,R.A.
A1  - Berent,S.
A1  - Kluin,K.J.
A1  - Modell,J.G.
A1  - Kroll,P.
A1  - Brunberg,J.A.
Y1  - 1990///
SP  - 775
EP  - 785
JF  - Annals of Neurology
VL  - 28
IS  - 6
ER  - 

TY  - JOUR
T1  - Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography
A1  - Gilman,S.
A1  - Junck,L.
A1  - Markel,D.S.
A1  - Koeppe,R.A.
A1  - Kluin,K.J.
Y1  - 1990///
SP  - 750
EP  - 757
JF  - Annals of Neurology
VL  - 28
IS  - 6
ER  - 

TY  - JOUR
T1  - Nigrostriatal function in humans studied with positron emission tomography
A1  - Martin,W.R.
A1  - Palmer,M.R.
A1  - Patlak,C.S.
A1  - Calne,D.B.
Y1  - 1989///
N1  - decline of FDOPA Ki with age
SP  - 535
EP  - 542
JF  - Annals of Neurology
VL  - 26
IS  - 4
ER  - 

TY  - JOUR
T1  - Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration
A1  - De Volder,A.G.
A1  - Francart,J.
A1  - Laterre,C.
A1  - Dooms,G.
A1  - Bol,A.
A1  - Michel,C.
A1  - Goffinet,A.M.
Y1  - 1989///
SP  - 239
EP  - 247
JF  - Annals of Neurology
VL  - 26
IS  - 2
ER  - 

TY  - JOUR
T1  - Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy
A1  - Frost,J.J.
A1  - Mayberg,H.S.
A1  - Fisher,R.S.
A1  - Douglass,K.H.
A1  - Dannals,R.F.
A1  - Links,J.M.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Rosenbaum,A.E.
A1  - Snyder,S.H.
A1  - et al.
Y1  - 1988///
SP  - 231
EP  - 237
JF  - Annals of Neurology
VL  - 23
IS  - 3
N2  - Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures
ER  - 

TY  - JOUR
T1  - The Lennox-Gastaut syndrome: metabolic subtypes determined by 2- deoxy-2[18F]fluoro-D-glucose positron emission tomography
A1  - Chugani,H.T.
A1  - Mazziotta,J.C.
A1  - Engel,J.,Jr.
A1  - Phelps,M.E.
Y1  - 1987///
SP  - 4
EP  - 13
JF  - Annals of Neurology
VL  - 21
IS  - 1
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in the Lennox-Gastaut syndrome
A1  - Theodore,W.H.
A1  - Rose,D.
A1  - Patronas,N.
A1  - Sato,S.
A1  - Holmes,M.
A1  - Bairamian,D.
A1  - Porter,R.J.
A1  - Di Chiro,G.
A1  - Larson,S.
A1  - Fishbein,D.
Y1  - 1987///
SP  - 14
EP  - 21
JF  - Annals of Neurology
VL  - 21
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of human brain functional development
A1  - Chugani,H.T.
A1  - Phelps,M.E.
A1  - Mazziotta,J.C.
Y1  - 1987///
SP  - 487
EP  - 497
JF  - Annals of Neurology
VL  - 22
IS  - 4
ER  - 

TY  - JOUR
T1  - Slowly progressive aphasia without generalized dementia: studies with positron emission tomography
A1  - Chawluk,J.B.
A1  - Mesulam,M.M.
A1  - Hurtig,H.
A1  - Kushner,M.
A1  - Weintraub,S.
A1  - Saykin,A.
A1  - Rubin,N.
A1  - Alavi,A.
A1  - Reivich,M.
Y1  - 1986///
SP  - 68
EP  - 74
JF  - Annals of Neurology
VL  - 19
IS  - 1
ER  - 

TY  - JOUR
T1  - Assessment of dopamine receptor densities in the human brain with carbon-11-labeled N-methylspiperone
A1  - Wagner,H.N.,Jr.
A1  - Burns,H.D.
A1  - Dannals,R.F.
A1  - Wong,D.F.
A1  - Langstrom,B.
A1  - Duelfer,T.
A1  - Frost,J.J.
A1  - Ravert,H.T.
A1  - Links,J.M.
A1  - Rosenbloom,S.B.
A1  - et al.
Y1  - 1984///
SP  - S79
EP  - 84
JF  - Annals of Neurology
VL  - 15 Suppl
ER  - 

TY  - JOUR
T1  - Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography
A1  - Phelps,M.E.
A1  - Barrio,J.R.
A1  - Huang,S.C.
A1  - Keen,R.E.
A1  - Chugani,H.
A1  - Mazziotta,J.C.
Y1  - 1984///
SP  - S192
EP  - 202
JF  - Annals of Neurology
VL  - 15 Suppl
ER  - 

TY  - JOUR
T1  - Cyclotrons, radionuclides, precursors, and demands for routine versus research compounds
A1  - Wolf,A.P.
Y1  - 1984///
SP  - S19
EP  - 24
JF  - Annals of Neurology
VL  - 15 Suppl
ER  - 

TY  - JOUR
T1  - Regional cortical dysfunction in Alzheimer's disease as determined by positron emission tomography
A1  - Chase,T.N.
A1  - Foster,N.L.
A1  - Fedio,P.
A1  - Brooks,R.
A1  - Mansi,L.
A1  - Di Chiro,G.
Y1  - 1984///
SP  - S170
EP  - 4
JF  - Annals of Neurology
VL  - 15 Suppl
ER  - 

TY  - JOUR
T1  - Technology assessment revisited: does positron emission tomography have proven clinical efficacy? [see comments]
A1  - Powers,W.J.
A1  - Berg,L.
A1  - Perlmutter,J.S.
A1  - Raichle,M.E.
Y1  - 1991///
SP  - 1339
EP  - 1340
JF  - Neurology
VL  - 41
IS  - 9
ER  - 

TY  - JOUR
T1  - Positron emission tomography in neuropsychiatric lupus erythematosus [see comments]
A1  - Stoppe,G.
A1  - Wildhagen,K.
A1  - Seidel,J.W.
A1  - Meyer,G.J.
A1  - Schober,O.
A1  - Heintz,P.
A1  - Kunkel,H.
A1  - Deicher,H.
A1  - Hundeshagen,H.
Y1  - 1990///
SP  - 304
EP  - 308
JF  - Neurology
VL  - 40
IS  - 2
ER  - 

TY  - JOUR
T1  - Differences between lateral and mesial temporal metabolism interictally in epilepsy of mesial temporal origin
A1  - Sackellares,J.C.
A1  - Siegel,G.J.
A1  - Abou-Khalil,B.W.
A1  - Hood,T.W.
A1  - Gilman,S.
A1  - McKeever,P.E.
A1  - Hichwa,R.D.
A1  - Hutchins,G.D.
Y1  - 1990///
SP  - 1420
EP  - 1426
JF  - Neurology
VL  - 40
IS  - 9
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose transport and utilization in Alzheimer's disease
A1  - Friedland,R.P.
A1  - Jagust,W.J.
A1  - Huesman,R.H.
A1  - Koss,E.
A1  - Knittel,B.
A1  - Mathis,C.A.
A1  - Ober,B.A.
A1  - Mazoyer,B.M.
A1  - Budinger,T.F.
Y1  - 1989///
SP  - 1427
EP  - 1434
JF  - Neurology
VL  - 39
IS  - 11
ER  - 

TY  - JOUR
T1  - Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease
A1  - Akiyama,H.
A1  - Harrop,R.
A1  - McGeer,P.L.
A1  - Peppard,R.
A1  - McGeer,E.G.
Y1  - 1989///
SP  - 541
EP  - 548
JF  - Neurology
VL  - 39
IS  - 4
ER  - 

TY  - JOUR
T1  - Longitudinal studies of regional cerebral metabolism in Alzheimer's disease
A1  - Jagust,W.J.
A1  - Friedland,R.P.
A1  - Budinger,T.F.
A1  - Koss,E.
A1  - Ober,B.
Y1  - 1988///
SP  - 909
EP  - 912
JF  - Neurology
VL  - 38
IS  - 6
ER  - 

TY  - JOUR
T1  - The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease
A1  - Hayden,M.R.
A1  - Hewitt,J.
A1  - Stoessl,A.J.
A1  - Clark,C.
A1  - Ammann,W.
A1  - Martin,W.R.
Y1  - 1987///
SP  - 1441
EP  - 1447
JF  - Neurology
VL  - 37
IS  - 9
ER  - 

TY  - JOUR
T1  - Wilson's disease studied with FDG and positron emission tomography
A1  - Hawkins,R.A.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1987///
SP  - 1707
EP  - 1711
JF  - Neurology
VL  - 37
IS  - 11
ER  - 

TY  - JOUR
T1  - Metabolic and clinical correlates of acute ischemic infarction
A1  - Kushner,M.
A1  - Reivich,M.
A1  - Fieschi,C.
A1  - Silver,F.
A1  - Chawluk,J.
A1  - Rosen,M.
A1  - Greenberg,J.
A1  - Burke,A.
A1  - Alavi,A.
Y1  - 1987///
SP  - 1103
EP  - 1110
JF  - Neurology
VL  - 37
IS  - 7
ER  - 

TY  - JOUR
T1  - Positron emission tomography and histopathology in Pick's disease
A1  - Kamo,H.
A1  - McGeer,P.L.
A1  - Harrop,R.
A1  - McGeer,E.G.
A1  - Calne,D.B.
A1  - Martin,W.R.
A1  - Pate,B.D.
Y1  - 1987///
SP  - 439
EP  - 445
JF  - Neurology
VL  - 37
IS  - 3
ER  - 

TY  - JOUR
T1  - Positron emission tomography in the early diagnosis of Huntington's disease
A1  - Hayden,M.R.
A1  - Martin,W.R.
A1  - Stoessl,A.J.
A1  - Clark,C.
A1  - Hollenberg,S.
A1  - Adam,M.J.
A1  - Ammann,W.
A1  - Harrop,R.
A1  - Rogers,J.
A1  - Ruth,T.
A1  - et al.
Y1  - 1986///
SP  - 888
EP  - 894
JF  - Neurology
VL  - 36
IS  - 7
ER  - 

TY  - JOUR
T1  - Barbiturates reduce human cerebral glucose metabolism
A1  - Theodore,W.H.
A1  - Di Chiro,G.
A1  - Margolin,R.
A1  - Fishbein,D.
A1  - Porter,R.J.
A1  - Brooks,R.A.
Y1  - 1986///
SP  - 60
EP  - 64
JF  - Neurology
VL  - 36
IS  - 1
N2  - We studied the effect of barbiturates on local cerebral glucose metabolism by performing positron emission scans before and after withdrawal of phenobarbital or primidone. The postwithdrawal scan showed a significant increase (mean, 37%) in seven of eight cortical regions tested. Patients who had serial scans without a drug change showed a nonsignificant tendency for metabolic rates to go down on the second scan (mean decrease, 7%). Addition or deletion of a single drug other than barbiturate did not change metabolic rates on repeat scans. The depression in cerebral glucose metabolic rate due to phenobarbital, if confirmed, may have bearing on the adverse neuropsychological effects of the drug.
ER  - 

TY  - JOUR
T1  - Alzheimer's disease: focal cortical changes shown by positron emission tomography
A1  - Foster,N.L.
A1  - Chase,T.N.
A1  - Fedio,P.
A1  - Patronas,N.J.
A1  - Brooks,R.A.
A1  - Di Chiro,G.
Y1  - 1983///
SP  - 961
EP  - 965
JF  - Neurology
VL  - 33
IS  - 8
ER  - 

TY  - JOUR
T1  - Positron emission tomography in two cases of childhood epileptic encephalopathy (Lennox-Gastaut syndrome)
A1  - Gur,R.C.
A1  - Sussman,N.M.
A1  - Alavi,A.
A1  - Gur,R.E.
A1  - Rosen,A.D.
A1  - O'Connor,M.
A1  - Goldberg,H.I.
A1  - Greenberg,J.H.
A1  - Reivich,M.
Y1  - 1982///
SP  - 1191
EP  - 1194
JF  - Neurology
VL  - 32
IS  - 10
N2  - Two patients with childhood epileptic encephalopathy were studied by positron emission tomography before and after corpus callosotomy. Preoperatively, both patients showed in the temporal lobe unilateral hypometabolism that is characteristic of interictal epileptic foci. Postoperatively, the first patient had no seizures by the time of scanning, and his temporal lobe metabolism was bilaterally symmetric. Seizure control in the second patient did not improve by the time of scanning, and unilateral temporal hypometabolism persisted. This finding suggests a temporal lobe focus in two patients with Lennox-Gastaut syndrome.
ER  - 

TY  - JOUR
T1  - Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose
A1  - London,E.D.
A1  - Broussolle,E.P.
A1  - Links,J.M.
A1  - Wong,D.F.
A1  - Cascella,N.G.
A1  - Dannals,R.F.
A1  - Sano,M.
A1  - Herning,R.
A1  - Snyder,F.R.
A1  - Rippetoe,L.R.
A1  - et al.
Y1  - 1990///
SP  - 73
EP  - 81
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 47
IS  - 1
ER  - 

TY  - JOUR
T1  - Reduction of prefrontal cortex glucose metabolism common to three types of depression
A1  - Baxter,L.R.,Jr.
A1  - Schwartz,J.M.
A1  - Phelps,M.E.
A1  - Mazziotta,J.C.
A1  - Guze,B.H.
A1  - Selin,C.E.
A1  - Gerner,R.H.
A1  - Sumida,R.M.
Y1  - 1989///
SP  - 243
EP  - 250
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 46
IS  - 3
N2  - Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non-sex-matched patients with mania. Mean (+/- SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 +/- 0.05; bipolar depression = 1.04 +/- 0.05), and were significantly lower than those in normal controls (1.12 +/- 0.06) or OCD without depression (1.15 +/- 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 +/- 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 +/- 0.03) on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n = 12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem.(ABSTRACT TRUNCATED AT 250 WORDS) <284>
ER  - 

TY  - JOUR
T1  - PET images of blood flow changes during anxiety: correction [letter]
A1  - Drevets,W.C.
A1  - Videen,T.Q.
A1  - MacLeod,A.K.
A1  - Haller,J.W.
A1  - Raichle,M.E.
Y1  - 1992///
SP  - 1696
EP  - 1696
JF  - Science
VL  - 256
IS  - 5064
ER  - 

TY  - JOUR
T1  - Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET
A1  - Fowler,J.S.
A1  - MacGregor,R.R.
A1  - Wolf,A.P.
A1  - Arnett,C.D.
A1  - Dewey,S.L.
A1  - Schlyer,D.
A1  - Christman,D.
A1  - Logan,J.
A1  - Smith,M.
A1  - Sachs,H.
A1  - et al.
Y1  - 1987///
SP  - 481
EP  - 485
JF  - Science
VL  - 235
IS  - 4787
N2  - The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.
ER  - 

TY  - JOUR
T1  - Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET
A1  - Farde,L.
A1  - Hall,H.
A1  - Ehrin,E.
A1  - Sedvall,G.
Y1  - 1986///
SP  - 258
EP  - 261
JF  - Science
VL  - 231
IS  - 4735
ER  - 

TY  - JOUR
T1  - Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease
A1  - Calne,D.B.
A1  - Langston,J.W.
A1  - Martin,W.R.
A1  - Stoessl,A.J.
A1  - Ruth,T.J.
A1  - Adam,M.J.
A1  - Pate,B.D.
A1  - Schulzer,M.
Y1  - 1985///
SP  - 246
EP  - 248
JF  - Nature
VL  - 317
IS  - 6034
ER  - 

TY  - JOUR
T1  - Dopamine visualized in the basal ganglia of living man
A1  - Garnett,E.S.
A1  - Firnau,G.
A1  - Nahmias,C.
Y1  - 1983///
SP  - 137
EP  - 138
JF  - Nature
VL  - 305
IS  - 5930
ER  - 

TY  - JOUR
T1  - Visualization of dopamine nerve terminals by positron tomography using [18F]fluoro-beta-fluoromethylene-m-tyrosine
A1  - DeJesus,O.T.
A1  - Holden,J.E.
A1  - Endres,C.
A1  - Murali,D.
A1  - Oakes,T.R.
A1  - Shelton,S.
A1  - Uno,H.
A1  - Houser,D.
A1  - Freund,L.
A1  - Perlman,S.B.
A1  - et al.
Y1  - 1992///
SP  - 151
EP  - 154
JF  - Brain Research
VL  - 597
IS  - 1
ER  - 

TY  - JOUR
T1  - Mapping cocaine binding sites in human and baboon brain in vivo
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wolf,A.P.
A1  - Dewey,S.L.
A1  - Schlyer,D.J.
A1  - MacGregor,R.R.
A1  - Hitzemann,R.
A1  - Logan,J.
A1  - Bendriem,B.
A1  - Gatley,S.J.
A1  - et al.
Y1  - 1989///
SP  - 371
EP  - 377
JF  - Synapse
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - Huntington's disease: studies with structural imaging techniques and positron emission tomography
A1  - Mazziotta,J.C.
Y1  - 1989///
SP  - 360
EP  - 369
JF  - Seminars in Neurology
VL  - 9
IS  - 4
ER  - 

TY  - JOUR
T1  - Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography
A1  - Leenders,K.L.
A1  - Palmer,A.J.
A1  - Quinn,N.
A1  - Clark,J.C.
A1  - Firnau,G.
A1  - Garnett,E.S.
A1  - Nahmias,C.
A1  - Jones,T.
A1  - Marsden,C.D.
Y1  - 1986///
SP  - 853
EP  - 860
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 49
IS  - 8
N2  - L-[18F] fluorodopa was administered in trace amounts intravenously to healthy control subjects and to patients with Parkinson's disease. Striatal uptake of radioactivity was measured using positron emission tomography. The capacity of the striatum to retain tracer was severely impaired in patients compared to controls. This may reflect a reduction of striatal dopamine storage in Parkinson's disease. Patients showing the "on/off" phenomenon had an even greater decrease of striatal storage capacity
ER  - 

TY  - JOUR
T1  - Striatal dopamine distribution in parkinsonian patients during life
A1  - Nahmias,C.
A1  - Garnett,E.S.
A1  - Firnau,G.
A1  - Lang,A.
Y1  - 1985///
SP  - 223
EP  - 230
JF  - Journal of the Neurological Sciences
VL  - 69
IS  - 3
N2  - Eleven neuropsychologically normal Parkinsonian patients were studied with [18F]6-fluoro-L-dopa and positron tomography. In all of the patients dopaminergic activity was reduced in the putamen on the side opposite to the major motor signs. The reduction was similar in tremulous and rigid patients. In contrast dopaminergic activity was normal in the caudate nuclei. It is argued that the putamen is mainly involved in the regulation of movement while the caudate nuclei assume a role in cognitive processes.
ER  - 

TY  - JOUR
T1  - Temporoparietal cortex in aphasia. Evidence from positron emission tomography
A1  - Metter,E.J.
A1  - Hanson,W.R.
A1  - Jackson,C.A.
A1  - Kempler,D.
A1  - van Lancker,D.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
Y1  - 1990///
SP  - 1235
EP  - 1238
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 47
IS  - 11
N2  - Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas.
ER  - 

TY  - JOUR
T1  - Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Koss,E.
A1  - Horwitz,B.
A1  - Heston,L.
A1  - Schapiro,M.
A1  - Friedland,R.P.
A1  - Rapoport,S.I.
Y1  - 1990///
SP  - 753
EP  - 760
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 47
IS  - 7
ER  - 

TY  - JOUR
T1  - Subcortical structures in aphasia. An analysis based on (F-18)- fluorodeoxyglucose, positron emission tomography, and computed tomography
A1  - Metter,E.J.
A1  - Riege,W.H.
A1  - Hanson,W.R.
A1  - Jackson,C.A.
A1  - Kempler,D.
A1  - van Lancker,D.
Y1  - 1988///
SP  - 1229
EP  - 1234
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 45
IS  - 11
N2  - Subcortical structural damage that includes the anterior and posterior internal capsule, caudate, thalamus, lenticular nuclei, and insula has been shown to cause aphasias. A critical question that has not been resolved is whether the role of these structures on behavior is a direct one or whether it is indirect through the cortex. We have used pathway analysis to evaluate computed tomography, glucose metabolic, and language data from 47 aphasic patients to answer this question. For fluency (from the Western Aphasia Battery), subcortical structural damage had direct and indirect (through frontal lobe) effects on the behavior. For a comprehension task (sequential commands), subcortical damage had no direct effect and only a slight indirect effect through the temporal lobe. Thus, both direct and indirect effects of subcortical damage can be demonstrated for specific behavioral measures.
ER  - 

TY  - JOUR
T1  - Cerebral perfusion imaging in Alzheimer's disease. Use of single photon emission computed tomography and iofetamine hydrochloride I 123
A1  - Johnson,K.A.
A1  - Mueller,S.T.
A1  - Walshe,T.M.
A1  - English,R.J.
A1  - Holman,B.L.
Y1  - 1987///
SP  - 165
EP  - 168
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 44
IS  - 2
N2  - We used single photon emission computed tomography (SPECT) to study 15 patients with Alzheimer's disease and nine controls. Iofetamine hydrochloride I 123 uptake data
ER  - 

TY  - JOUR
T1  - Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Duara,R.
A1  - Schlageter,N.
A1  - Test,T.
A1  - Rapoport,S.I.
Y1  - 1986///
SP  - 882
EP  - 885
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 43
IS  - 9
ER  - 

TY  - JOUR
T1  - In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci
A1  - Savic,I.
A1  - Persson,A.
A1  - Roland,P.
A1  - Pauli,S.
A1  - Sedvall,G.
A1  - Widen,L.
Y1  - 1988///
SP  - 863
EP  - 866
JF  - Lancet
VL  - 2
IS  - 8616
N2  - Ten patients with partial epilepsy and five healthy controls had positron emission tomography (PET) of the brain after intravenous administration of the 11C-labelled benzodiazepine (BZ) receptor ligand 'Ro-15 1788'. In all ten patients BZ receptor binding was significantly lower in the epileptic focus than in the contralateral homotopic reference region and the remaining neocortex. No asymmetries in BZ receptor binding were observed between homotopic reference regions in the controls or the non-epileptic regions of patients. These results demonstrate the potential of the BZ receptor as a biochemical marker for display of epileptic foci by PET, and also strengthen the hypothesis that inhibitory mechanisms are disturbed in the epileptic focus.
ER  - 

TY  - JOUR
T1  - C-11-labeled glucose and its utilization in positron-emission tomography
A1  - Ehrin,E.
A1  - Stone-Elander,S.
A1  - Nilsson,J.L.
A1  - Bergstrom,M.
A1  - Blomqvist,G.
A1  - Brismar,T.
A1  - Eriksson,L.
A1  - Greitz,T.
A1  - Jansson,P.E.
A1  - Litton,J.E.
A1  - Malmborg,P.
A1  - Ugglas,M.,af
A1  - Widen,L.
Y1  - 1983///
SP  - 326
EP  - 331
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 24
IS  - 4
N2  - Carbon-11-labeled glucose was prepared photosynthetically using the green alga Scenedesmus obtusiusculus Chod. The carbohydrates were extracted from the cells with dilute HCI and the glucose was isolated and purified using high-performance liquid chromatography. The manipulations in the hot cell are described. Analysis of the material (gas liquid chromatography and HPLC) showed that the glucose obtained was radiochemically pure. The total incorporation of the 11CO2 added to the algae was 60-80%. The radiochemical yield of pure carrier-added glucose was approximately 25%, at 40 min after E.O.B. including the HPLC purification and sterile filtration. The C-11 glucose uptake in rat brain was compared with that of commercial D[U-14C]glucose, and preliminary PET studies with D-[11C]glucose in a patient with a brain infarct are presented.
ER  - 

TY  - JOUR
T1  - NONPARAMETRIC ANALYSIS OF STATISTIC IMAGES FROM FUNCTIONAL MAPPING EXPERIMENTS
A1  - Holmes,A.P.
A1  - Blair,R.C.
A1  - Watson,J.D.G.
A1  - Ford,I.
Y1  - 1996///
SP  - 7
EP  - 22
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 1
ER  - 

TY  - JOUR
T1  - A FUNCTIONAL NEUROANATOMY OF HALLUCINATIONS IN SCHIZOPHRENIA
A1  - Silbersweig,D.A.
A1  - Stern,E.
A1  - Frith,C.
A1  - Cahill,C.
A1  - Holmes,A.
A1  - Grootoonk,S.
A1  - Seaward,J.
A1  - Mckenna,P.
A1  - Chua,S.E.
A1  - Schnorr,L.
A1  - Jones,T.
A1  - Frackowiak,R.S.J.
Y1  - 1995///
SP  - 176
EP  - 179
JF  - Nature
VL  - 378
IS  - 6553
ER  - 

TY  - JOUR
T1  - Inhibition of monoamine oxidase B in the brains of smokers
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Pappas,N.
A1  - Logan,J.
A1  - MacGregor,R.
A1  - Alexoff,D.
A1  - Shea,C.
A1  - Shlyer,D.
A1  - Wolf,A.P.
A1  - Warner,D.
A1  - Zezulkova,I.
A1  - Cilento,R.
Y1  - 1996///
N1  - 11C-Deprenyl PET study
SP  - 733
EP  - 736
JF  - Nature
VL  - 379
N2  - The massive health problem associated with cigarette smoking is exacerbated by the addictive properties of tobacco smoke and the limited success of current approaches to cessation of smoking. Yet little is known about the neuropharmacological actions of cigarette smoke that contribute to smoking behaviour, or why smoking is so prevalent in psychiatric disorders and is associated with a decreased risk of Parkinson's disease. Here we report that brains of living smokers show a 40% decrease in the level of monoamine oxidase B (MAO B; EC 1.4.3.4) relative to non-smokers or former smokers. MAO B is involved in the breakdown of dopamine, a neurotransmitter implicated in reinforcing and motivating behaviours as well as movement. MAO B inhibition is therefore associated with enhanced activity of dopamine, as well as with decreased production of hydrogen peroxide, a source of reactive oxygen species. We propose that reduction of MAO B activity may synergize with nicotine to produce the diverse behavioural and epidemiological effects of smoking
ER  - 

TY  - JOUR
T1  - Clinical diagnosis of Alzheimer's disease
A1  - McKhann,G.
A1  - Drachman,D.
A1  - Folstein,M.F.
A1  - Katzman,R.
A1  - Price,D.
A1  - Stadlan,E.M.
Y1  - 1984///
SP  - 939
EP  - 944
JF  - Neurology
VL  - 34
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism and postmortem pathology in Alzheimer's disease
A1  - Mielke,R.
A1  - Schrder,R.
A1  - Fink,G.R.
A1  - Kessler,J.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 1996///
SP  - 174
EP  - 179
JF  - Acta Neuropathologica
VL  - 91
IS  - 2
ER  - 

TY  - JOUR
T1  - In vivo studies of acetylcholinesterase activity using a labeled substrate, n-[C-11]methylpiperdin-4-yl propionate ([C-11]PMP)
A1  - Kilbourn,M.R.
A1  - Snyder,S.E.
A1  - Sherman,P.S.
A1  - Kuhl,D.E.
Y1  - 1996///
N1  - Same tracers as Irie, no kinetic analysis, favor propionate instead of the acetate (too intense binding, question of flow limitation)
SP  - 123
EP  - 131
JF  - Synapse
VL  - 22
IS  - 2
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in children with deterioration of one or more cognitive functions and continuous spike-and-wave discharges during sleep
A1  - Maquet,P.
A1  - Hirsch,E.
A1  - Metzlutz,M.N.
A1  - Motte,J.
A1  - Dive,D.
A1  - Marescaux,C.
A1  - Franck,G.
Y1  - 1995///
SP  - 1497
EP  - 1520
JF  - Brain
VL  - 118
IS  - Part 6
N2  - The Landau-Kleffner syndrome (LKS) and the syndrome of continuous spike-and-wave discharges during slow sleep (CSWS) were originally described, and are still considered, separately. The former combines an acquired aphasia with spike-and-wave discharges that are activated by slow wave sleep, behavioural disturbances, and sometimes epileptic seizures. The latter is characterized by continuous spike-and-wave discharges during slow wave sleep, usually combined with global intellectual deterioration and epileptic seizures. These two syndromes share many common features: (i) onset during childhood; (ii) deterioration of cognitive functions that were previously normally acquired; (iii) seizure type; (iv) EEG pattern; (v) pharmacological reactivity; (vi) regression of the neuropsychological symptoms, of the EEG abnormalities and of the seizures before the end of adolescence; (vii) absence of obvious structural lesion detected by CT or MRI scan. Therefore, we postulated that these patients might, in fact, be presenting several facets of a single process associating the deterioration of cognitive functions and continuous spike-and-wave discharges during slow wave sleep. The pathogenesis of this syndrome remains unknown. Seven patients, presenting CSWS associated with neuropsychological deterioration (isolated aphasia, three cases; language disturbances with more widespread cognitive deterioration, three cases; isolated apraxia, one case) were studied using PET with [18F]fluorodeoxyglucose (FDG). We hoped to find metabolic arguments in favour of a unifying hypothesis, and to reveal clues as to pathogenesis. We present the retrospective analysis of 21 studies performed between 1986 and 1993, 12 of which were done during sleep. For three of these patients, follow-up studies were obtained until recovery. The metabolic patterns were very variable from one patient to another and in the same patient over time. Among the six patients studied during the active phase of the affection, our results showed unilateral, focal or regional increase in glucose metabolism of the cortex in five patients. This hypermetabolism was observed during sleep with continuous spike-and-wave discharges, but also persisted during wakefulness. In the last patient, the metabolic pattern was different: decreased regional glucose metabolism was observed during wakefulness, whereas during sleep, the metabolic pattern in the temporal areas varied during the course of the affection. After recovery, the metabolic pattern in four children (including the seventh patient) was either normal or showed focal or regional, uni- or bilateral decrease in cortical glucose metabolism. Despite this apparent disparity, four basic metabolic characteristics formed a common pattern in all patients, in line with our unifying postulate: (i) the metabolism of the cortical mantle was higher than in the subcortical structures, especially in the thalamic nuclei. This metabolic pattern is characteristic of an immature brain. (ii) The metabolic abnormalities involved focal or regional areas of the cortex. This finding is in good agreement with recent neurophysiological data suggesting a focal origin of the spike-and-wave discharges. (iii) The metabolic disturbances predominantly involved associative cortices. The pattern of neuropsychological deterioration is in good agreement with the topography of the disturbances of cortical glucose metabolism. (iv) The thalamic nuclei remained symmetrical despite significant cortical asymmetries, suggesting either that cortico-thalamic neurons do not participate in the generation of spike-and-wave discharges or that they are inhibited by the pathologic mechanisms. We hypothesize that the acquired deterioration of cognitive function with CSWS is caused by an alteration of the maturation of one or several associative cortices, primarily involving local interneurons and cortico-cortical associative neurons
ER  - 

TY  - JOUR
T1  - QUANTITATION OF BENZODIAZEPINE RECEPTORS IN HUMAN BRAIN USING THE PARTIAL SATURATION METHOD
A1  - Delforge,J.
A1  - Spelle,L.
A1  - Bendriem,B.
A1  - Samson,Y.
A1  - Bottlaender,M.
A1  - Papageorgiou,S.
A1  - Syrota,A.
Y1  - 1996///
SP  - 5
EP  - 11
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 1
ER  - 

TY  - JOUR
T1  - AUTOMATED INTERSTUDY IMAGE REGISTRATION TECHNIQUE FOR SPECT AND PET
A1  - Eberl,S.
A1  - Kanno,I.
A1  - Fulton,R.R.
A1  - Ryan,A.
A1  - Hutton,B.F.
A1  - Fulham,M.J.
Y1  - 1996///
SP  - 137
EP  - 145
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 1
ER  - 

TY  - JOUR
T1  - Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease
A1  - Ruottinen,H.M.
A1  - Rinne,J.O.
A1  - Ruotsalainen,U.H.
A1  - Bergman,J.R.
A1  - Oikonen,V.J.
A1  - Haaparanta,M.T.
A1  - Solin,O.H.
A1  - Laihinen,A.O.
A1  - Rinne,U.K.
Y1  - 1995///
SP  - 91
EP  - 106
JF  - Journal of Neural Transmission - Parkinsons Disease & Dementia Section
VL  - 10
IS  - 2-3
N2  - The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.
ER  - 

TY  - JOUR
T1  - Amino acids for the measurement of protein synthesis in vivo by PET. [Review]
A1  - Vaalburg,W.
A1  - Coenen,H.H.
A1  - Crouzel,C.
A1  - Elsinga,P.H.
A1  - Langstrom,B.
A1  - Lemaire,C.
A1  - Meyer,G.J.
Y1  - 1992///
SP  - 227
EP  - 237
JF  - International Journal of Radiation Applications & Instrumentation - Part B, Nuclear Medicine & Biology
VL  - 19
IS  - 2
ER  - 

TY  - JOUR
T1  - Radiation-induced inhibition of tumor growth as monitored by PET using L-[1-11C]tyrosine and fluorine-18-fluorodeoxyglucose
A1  - Daemen,B.J.
A1  - Elsinga,P.H.
A1  - Paans,A.M.
A1  - Wieringa,A.R.
A1  - Konings,A.W.
A1  - Vaalburg,W.
Y1  - 1992///
SP  - 373
EP  - 379
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 3
ER  - 

TY  - JOUR
T1  - The metabolic topography of normal aging
A1  - Moeller,J.R.
A1  - Ishikawa,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Mandel,F.
A1  - Alexander,G.E.
A1  - Grady,C.
A1  - Pietrini,P.
A1  - Eidelberg,D.
Y1  - 1996///
N1  - FDG PET with SSM, 130 + 20 normals, relative frontal hypometabolism, comparison with Parkinson patients: more basal ganglia hypermetabolism
SP  - 385
EP  - 398
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 3
N2  - Normal aging is associated with the degeneration of specific neural systems. We used [18F] fluorodeoxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMRglc) in two groups of normal subjects studied independently on different tomographs: Group 1--130 normal subjects (62 men and 68 women; range 21-90 years); Group 2--20 normal subjects (10 men and 10 women; range 24-78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMRglc data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R2 = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R2 = 0.30, p < 0.00001; group 2: R2 = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal aging process
ER  - 

TY  - JOUR
T1  - Statistical parametric maps in functional imaging: a general linear approach
A1  - Friston,K.J.
A1  - Holmes,A.P.
A1  - Worsley,K.J.
A1  - Poline,J.B.
A1  - Frith,C.D.
A1  - Frackowiak,R.S.J.
Y1  - 1995///
SP  - 189
EP  - 210
JF  - Human Brain Mapping
VL  - 2
IS  - 4
ER  - 

TY  - JOUR
T1  - Network analysis of brain cognitive function using metabolic and blood flow data. [Review]
A1  - Horwitz,B.
A1  - McIntosh,A.R.
A1  - Haxby,J.V.
A1  - Grady,C.L.
Y1  - 1995///
SP  - 187
EP  - 193
JF  - Behavioural Brain Research
VL  - 66
IS  - 1-2
ER  - 

TY  - JOUR
T1  - Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease patients
A1  - Bancher,C.
A1  - Braak,H.
A1  - Fischer,P.
A1  - Jellinger,K.A.
Y1  - 1993///
SP  - 179
EP  - 182
JF  - Neuroscience Letters
VL  - 162
IS  - 1-2
ER  - 

TY  - JOUR
T1  - Evaluation of a neural-network classifier for PET scans of normal and Alzheimer's disease subjects
A1  - Kippenhan,J.S.
A1  - Barker,W.W.
A1  - Pascal,S.
A1  - Nagel,J.
A1  - Duara,R.
Y1  - 1992///
N1  - mainly senile AD, MMSE 15 to 19
SP  - 1459
EP  - 1467
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 33
IS  - 8
ER  - 

TY  - JOUR
T1  - Neuropathological stageing of Alzheimer-related changes. [Review]
A1  - Braak,H.
A1  - Braak,E.
Y1  - 1991///
SP  - 239
EP  - 259
JF  - Acta Neuropathologica
VL  - 82
IS  - 4
ER  - 

TY  - JOUR
T1  - Subgroups in dementia of the Alzheimer type identified using positron emission tomography
A1  - Grady,C.L.
A1  - Haxby,J.V.
A1  - Schapiro,M.B.
A1  - Gonzalez-Aviles,A.
A1  - Kumar,A.
A1  - Ball,M.J.
A1  - Heston,L.
A1  - Rapoport,S.I.
Y1  - 1990///
SP  - 373
EP  - 384
JF  - Journal of Neuropsychiatry & Clinical Neurosciences
VL  - 2
IS  - 4
N2  - We examined patterns of cerebral glucose metabolism in 33 patients with dementia of the Alzheimer type by applying principal component analysis to identify subgroups. Four subgroups were identified: one with predominant parietotemporal hypometabolism (15 patients); one with paralimbic metabolic deficits (8 patients); one with left hemisphere neocortical abnormality (5 patients); and one with frontal and parietotemporal deficit (5 patients). Differences among the subgroups were found in neuropsychological impairments and prevalence of psychiatric symptoms. These metabolic subgroups could not be explained on the basis of dementia severity, illness duration, or age, but were most likely related to an underlying pathology with a variable regional distribution.
ER  - 

TY  - JOUR
T1  - Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioral features
A1  - Kumar,A.
A1  - Schapiro,M.B.
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Friedland,R.P.
Y1  - 1990///
SP  - 97
EP  - 109
JF  - Journal of Psychiatric Research
JA  - J.Psychiatr.Res.
VL  - 24
IS  - 2
N2  - Three subjects with dementia of the Alzheimer type (DAT) with frontal lobe features of behavioral disinhibition were studied using positron emission tomography with [18F]2-fluoro-2-deoxy-D-glucose (18 FDG) and standardized neuropsychological tests. The three subjects showed significant decrements (p less than .05) in relative glucose metabolism (regional/mean gray metabolism) in the orbitofrontal, prefrontal and anterior cingulate regions when compared to healthy controls. Severity-matched subjects with DAT without the associated frontal lobe features did not show the relative reductions in glucose metabolism in these regions when compared to controls. However, on neuropsychological testing of frontal lobe cognitive functions the three subjects did not show decrements that were more severe than those shown by severity-matched DAT patients without the behavioral features. These data demonstrate physiologic dysfunction in specific cortical regions in subjects with behavioral aberrations attributed to these regions and an apparent dissociation between behavioral and cognitive functions of the frontal lobe.
ER  - 

TY  - JOUR
T1  - Dementia in Down's syndrome: cerebral glucose utilization, neuropsychological assessment, and neuropathology
A1  - Schapiro,M.B.
A1  - Ball,M.J.
A1  - Grady,C.L.
A1  - Haxby,J.V.
A1  - Kaye,J.A.
A1  - Rapoport,S.I.
Y1  - 1988///
SP  - 938
EP  - 942
JF  - Neurology
VL  - 38
IS  - 6
ER  - 

TY  - JOUR
T1  - Heterogeneous anterior-posterior metabolic patterns in dementia of the Alzheimer type
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Koss,E.
A1  - Horwitz,B.
A1  - Schapiro,M.
A1  - Friedland,R.P.
A1  - Rapoport,S.I.
Y1  - 1988///
SP  - 1853
EP  - 1863
JF  - Neurology
VL  - 38
IS  - 12
ER  - 

TY  - JOUR
T1  - Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type
A1  - Grady,C.L.
A1  - Haxby,J.V.
A1  - Horwitz,B.
A1  - Berg,G.
A1  - Rapoport,S.I.
Y1  - 1987///
SP  - 807
EP  - 816
JF  - Neuropsychologia
VL  - 25
IS  - 5
N2  - Differences in age at onset of dementia of the Alzheimer type (DAT) have been associated with differences in cognitive impairments and course of the disease. To investigate this, we examined cerebral metabolism and cognitive performance in early and late onset DAT patients, who had equivalent duration and severity of illness. Regional cerebral metabolic rates for glucose were measured in the resting state by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. A cross-sectional analysis showed no significant differences between the two groups in performance on neuropsychological tests, but the early onset patients showed significantly more parietal metabolic dysfunction than did the late onset patients. Longitudinal analysis showed no significant differences between early and late onset patients in rate of cognitive decline over a mean interval of 19 months. Thus, our results do not support the hypothesis of different subgroups in DAT based on age at onset, nor suggest a faster rate of cognitive decline in younger patients.
ER  - 

TY  - JOUR
T1  - Neocortical metabolic abnormalities precede nonmemory cognitive impairments in early dementia of the Alzheimer type: longitudinal confirmation
A1  - Haxby,J.V.
A1  - Grady,C.L.
A1  - Friedland,R.P.
A1  - Rapoport,S.I.
Y1  - 1994///
SP  - 49
EP  - 53
JF  - Journal of Neural Transmission
VL  - Supplementum 1987;24
ER  - 

TY  - JOUR
T1  - Stability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type
A1  - Grady,C.L.
A1  - Haxby,J.V.
A1  - Schlageter,N.L.
A1  - Berg,G.
A1  - Rapoport,S.I.
Y1  - 1986///
SP  - 1390
EP  - 1392
JF  - Neurology
VL  - 36
IS  - 10
ER  - 

TY  - JOUR
T1  - Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease
A1  - Haxby,J.V.
A1  - Duara,R.
A1  - Grady,C.L.
A1  - Cutler,N.R.
A1  - Rapoport,S.I.
Y1  - 1985///
SP  - 193
EP  - 200
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 2
ER  - 

TY  - JOUR
T1  - Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer's disease
A1  - Perry,E.K.
A1  - Haroutunian,V.
A1  - Davis,K.L.
A1  - Levy,R.
A1  - Lantos,P.
A1  - Eagger,S.
A1  - Honavar,M.
A1  - Dean,A.
A1  - Griffiths,M.
A1  - McKeith,I.G.
A1  - et al.
Y1  - 1994///
SP  - 747
EP  - 749
JF  - Neuroreport
VL  - 5
IS  - 7
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset
A1  - Small,G.W.
A1  - Kuhl,D.E.
A1  - Riege,W.H.
A1  - Fujikawa,D.G.
A1  - Ashford,J.W.
A1  - Metter,E.J.
A1  - Mazziotta,J.C.
Y1  - 1989///
SP  - 527
EP  - 532
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 46
IS  - 6
N2  - No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.
ER  - 

TY  - JOUR
T1  - Post-mortem neurofibrillary tangle densities but not senile plaque densities are related regional metabolic rates for glucose during life in Alzheimer's disease patients
A1  - DeCarli,C.
A1  - Atack,J.R.
A1  - Ball,M.J.
A1  - Kay,J.A.
A1  - Grady,C.L.
A1  - Fewster,P.
A1  - Pettigrew,K.D.
A1  - Rapoport,S.I.
A1  - Schapiro,M.B.
Y1  - 1992///
N1  - 6 patients, in 5 significant corr. of CMRGlu with tangle density
SP  - 113
EP  - 121
JF  - Neurodegeneration
VL  - 1
ER  - 

TY  - JOUR
T1  - Clinical applications of registration and fusion of multimodality brain images from PET, SPECT, CT, and MRI
A1  - Pietrzyk,U.
A1  - Herholz,K.
A1  - Schuster,A.
A1  - von Stockhausen,H.M.
A1  - Lucht,H.
A1  - Heiss,W.D.
Y1  - 1996///
SP  - 174
EP  - 182
JF  - European Journal of Radiology
VL  - 21
ER  - 

TY  - JOUR
T1  - Preserved speech abilities and compensation following prefrontal damage
A1  - Buckner,R.L.
A1  - Corbetta,M.
A1  - Schatz,J.
A1  - Raichle,M.E.
A1  - Petersen,S.E.
Y1  - 1996///
N1  - O-15-water PET. Compensatory activation of right frontal ctx and SMA during word stem completion task
SP  - 1249
EP  - 1253
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 93
IS  - 3
N2  - Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study
ER  - 

TY  - JOUR
T1  - Bilateral fetal grafts for Parkinson's disease: 22 months results
A1  - Iacono,R.P.
A1  - Tang,Z.S.
A1  - Mazziotta,J.C.
A1  - Grafton,S.
A1  - Hoehn,M.
Y1  - 1992///
SP  - 84
EP  - 87
JF  - Stereotactic & Functional Neurosurgery
VL  - 58
ER  - 

TY  - JOUR
T1  - Carbon-11-methionine PET evaluation of intracerebral hematoma: distinguishing neoplastic from non-neoplastic hematoma
A1  - Ogawa,T.
A1  - Hatazawa,J.
A1  - Inugami,A.
A1  - Murakami,M.
A1  - Fujita,H.
A1  - Shimosegawa,E.
A1  - Noguchi,K.
A1  - Okudera,T.
A1  - Kanno,I.
A1  - Uemura,K.
A1  - et al.
Y1  - 1995///
N1  - Higher uptake in malignant gliomas with bleeding than in non-tumorous hematomas, the latter with unspecific uptake (lesion/cortex = 1.36)
SP  - 2175
EP  - 2179
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 36
IS  - 12
ER  - 

TY  - JOUR
T1  - Cerebral blood flow in the newborn infant: measurement and role in the pathogenesis of periventricular and intraventricular hemorrhage. [Review]
A1  - Altman,D.I.
A1  - Volpe,J.J.
Y1  - 1987///
SP  - 111
EP  - 138
JF  - Advances in Pediatrics
VL  - 34
ER  - 

TY  - JOUR
T1  - Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy
A1  - Wrker,M.
A1  - Herholz,K.
A1  - Voges,J.
A1  - Pietrzyk,U.
A1  - Treuer,H.
A1  - Bauer,B.
A1  - Sturm,V.
A1  - Heiss,W.D.
Y1  - 1996///
SP  - 583
EP  - 586
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 23
IS  - 5
ER  - 

TY  - JOUR
T1  - Alteration of blood-brain barrier in human brain tumors: comparison of [18F]fluorodeoxyglucose, [11C]methionine and rubidium-82 using PET
A1  - Roelcke,U.
A1  - Radu,E.W.
A1  - von Ammon,K.
A1  - Hausmann,O.
A1  - Maguire,R.P.
A1  - Leenders,K.L.
Y1  - 1995///
SP  - 20
EP  - 27
JF  - Journal of the Neurological Sciences
VL  - 132
IS  - 1
ER  - 

TY  - JOUR
T1  - Individual functional anatomy of verb generation
A1  - Herholz,K.
A1  - Thiel,A.
A1  - Wienhard,K.
A1  - Pietrzyk,U.
A1  - von Stockhausen,H.M.
A1  - Karbe,H.
A1  - Kessler,J.
A1  - Bruckbauer,T.
A1  - Halber,M.
A1  - Heiss,W.D.
Y1  - 1996///
SP  - 185
EP  - 194
JF  - Neuroimage
VL  - 3
IS  - 3
ER  - 

TY  - JOUR
T1  - Evaluation of SCH 39166 as PET ligand for central D1 dopamine receptor binding and occupancy in man
A1  - Karlsson,P.
A1  - Sedvall,G.
A1  - Halldin,C.
A1  - Swahn,C.G.
A1  - Farde,L.
Y1  - 1995///
SP  - 300
EP  - 308
JF  - Psychopharmacology
VL  - 121
IS  - 3
ER  - 

TY  - JOUR
T1  - Variability in D2-dopamine receptor density and affinity: a PET study with [11C]raclopride in man
A1  - Farde,L.
A1  - Hall,H.
A1  - Pauli,S.
A1  - Halldin,C.
Y1  - 1995///
SP  - 200
EP  - 208
JF  - Synapse
VL  - 20
IS  - 3
ER  - 

TY  - JOUR
T1  - [O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations
A1  - Lundkvist,C.
A1  - Halldin,C.
A1  - Swahn,C.G.
A1  - Hall,H.
A1  - Karlsson,P.
A1  - Nakashima,Y.
A1  - Wang,S.
A1  - Milius,R.A.
A1  - Neumeyer,J.L.
A1  - Farde,L.
Y1  - 1995///
SP  - 905
EP  - 913
JF  - Nuclear Medicine & Biology
VL  - 22
IS  - 7
N2  - The cocaine congener 2beta-carbomethoxy-3beta-(4'-iodophenyl)tropane (beta-CIT) has a chemical structure that enables labelling with carbon-11 either by N-methylation or by O-methylation. The regional brain uptake of [N-methyl-11C]beta-CIT and [O-methyl-11C]beta-CIT was compared in cynomolgus monkeys using positron emission tomography (PET). The striatal uptake of radioactivity after intravenous injection of [O-methyl-11C]beta-CIT reached a plateau at 30-40 min, whereas the uptake of [N-methyl-11C]beta-CIT increased continuously during the time of the PET measurement. Two of the putative labelled metabolites, [N-methyl-11C]beta-CIT-acid and [O-methyl-11C]nor-beta-CIT were prepared and examined with PET to investigate if they may enter the brain and thus add to the radioactivity uptake obtained with [11C]beta-CIT. Less than 0.4% of injected [N-methyl-11C]beta-CIT-acid entered the brain whereas 5-6% of [O-methyl-11C]nor-beta-CIT entered the brain and accumulated in the striatum and in the thalamus. The fraction of [O-methyl-11C]nor-beta-CIT obtained in plasma after intravenous injection of [O-methyl-11C]nor-beta-CIT, however, never exceeded 3%. Consequently, the formation of [N-methyl-11C]beta-CIT-acid and [O-methyl-11C]nor-beta-CIT cannot be the explanation for the different time-activity curves in the monkey brain demonstrated with [11C]beta-CIT labelled in two different positions. An unidentified labelled lipophilic metabolite, detected in monkey plasma after injection of [O-methyl-11C]beta-CIT, remains as the only possible explanation for the differences between [N-methyl-11C]beta-CIT and [O-methyl-11C]beta-CIT
ER  - 

TY  - JOUR
T1  - HYPEROSMOLAR BLOOD-BRAIN BARRIER DISRUPTION IN BABOONS - AN IN VIVO STUDY USING POSITRON EMISSION TOMOGRAPHY AND RUBIDIUM-82
A1  - Zunkeler,B.
A1  - Carson,R.E.
A1  - Olson,J.
A1  - Blasberg,R.G.
A1  - Girton,M.
A1  - Bacher,J.
A1  - Herscovitch,P.
A1  - Oldfield,E.H.
Y1  - 1996///
SP  - 494
EP  - 502
JF  - Journal of Neurosurgery
VL  - 84
IS  - 3
ER  - 

TY  - JOUR
T1  - Levodopa-induced changes in synaptic dopamine in patients with Parkinsons's disease as measured by [11C]raclopride displacement and PET
A1  - Tedroff,J.
A1  - Pedersen,M.
A1  - Aquilonius,S.M.
A1  - Hartvig,P.
A1  - Jacobsson,G.
A1  - Langstrom,B.
Y1  - 1996///
N1  - More displacement in more severly affected patients, indicating more rapid Dopa turnover
SP  - 1430
EP  - 1436
JF  - Neurology
VL  - 46
N2  - Changes in striatal binding of [11C]raclopride, a dopamine D2 receptor antagonist, induced by acute levodopa administration, were evaluated with PET in 10 patients with idiopathic Parkinson's disease (PD). The patients were scanned on two occasions: drug-free and 15 minutes after a 5-minute intravenous infusion of 3 mg/kg levodopa. Levodopa administration produced reductions in striatal [11C]raclopride uptake index with a rostrocaudal gradient. The most pronounced reduction was found in the posterior putamen (to 82% of baseline), followed by the anterior putamen (to 88% of baseline) and the caudate nucleus (to 94% of baseline). The magnitude of [11C]raclopride uptake index reduction correlated with drug-free disability. Moreover, in four hemiparkinsonian patients, a reduction in [11C]raclopride uptake index was measured in the putamen contralateral to the parkinsonian symptoms. The present results demonstrate a positive correlation between striatal dopaminergic nerve-terminal deficiency and the capacity for levodopa to increase synaptic dopamine and displace [11C]raclopride binding, which corresponds to an accelerated amine turnover in dopamine-depleted striatal tissue. We therefore suggest that dopaminergic degeneration in PD is paralleled by a progressive acceleration of amine turnover. This mechanistic consequence of nigrostriatal degeneration, the selective restoration of synaptic dopaminergic neurotransmission in denervated striatal subregions, may explain the effectiveness of levodopa in producing symptomatic benefits in early PD. However, we also suggest that in the vastly denervated striatum, as in advanced PD, an excessive acceleration of amine turnover results in swings in levodopa-induced synaptic dopamine levels that are far beyond normal. This phenomenon most likely plays a key role in the pathogenesis underlying the development of motor-response complications in PD.
ER  - 

TY  - JOUR
T1  - PET findings in a brain abscess associated with a silent atrial septal defect
A1  - Dethy,S.
A1  - Manto,M.
A1  - Kentos,A.
A1  - Konopnicki,D.
A1  - Pirotte,B.
A1  - Goldman,S.
A1  - Hildebrand,J.
Y1  - 1995///
N1  - Ring-structure, C-11-methionine: 1.6 of contralateral, FDG: 1.2 o.c.
SP  - 349
EP  - 353
JF  - Clinical Neurology & Neurosurgery
VL  - 97
IS  - 4
ER  - 

TY  - JOUR
T1  - Acute effect of carmustine on glucose metabolism in brain and glioblastoma
A1  - De Witte,O.
A1  - Hildebrand,J.
A1  - Luxen,A.
A1  - Goldman,S.
Y1  - 1994///
N1  - Corr. between increase 24 hrs after treatment and survival
SP  - 2836
EP  - 2842
JF  - Cancer
VL  - 74
IS  - 10
ER  - 

TY  - JOUR
T1  - Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans
A1  - Herzog,H.
A1  - Seitz,R.J.
A1  - Tellmann,L.
A1  - Rota Kops,E.
A1  - Julicher,F.
A1  - Schlaug,G.
A1  - Kleinschmidt,A.
A1  - Muller-Gartner,H.W.
Y1  - 1996///
N1  - list mode, fitted with time shift and dispersion, gray matter CBF 83, white 16
SP  - 645
EP  - 649
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 4
ER  - 

TY  - JOUR
T1  - Radiofluorinated L-m-tyrosines: New in-vivo probes for central dopamine biochemistry
A1  - Barrio,J.R.
A1  - et al.
Y1  - 1996///
N1  - higher signal to background ratio than F-DOPA, resistant to peripheral 3-O methylation, monkey data
SP  - 667
EP  - 678
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 4
ER  - 

TY  - JOUR
T1  - F-Dopa as an amino acid tracer to detect brain tumors
A1  - Heiss,W.D.
A1  - Wienhard,K.
A1  - Wagner,R.
A1  - Lanfermann,H.
A1  - Thiel,A.
A1  - Herholz,K.
A1  - Pietrzyk,U.
Y1  - 1996///
SP  - 1180
EP  - 1182
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
ER  - 

TY  - JOUR
T1  - Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive- compulsive disorder
A1  - Schwartz,J.M.
A1  - Stoessel,P.W.
A1  - Baxter,L.R.,Jr.
A1  - Martin,K.M.
A1  - Phelps,M.E.
Y1  - 1996///
SP  - 109
EP  - 113
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 53
IS  - 2
N2  - BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder
ER  - 

TY  - JOUR
T1  - Alzheimer disease: improved visual interpretation of PET images by using three-dimensional stereotaxic surface projections
A1  - Burdette,J.H.
A1  - Minoshima,S.
A1  - Vander Borght,T.
A1  - Tran,D.D.
A1  - Kuhl,D.E.
Y1  - 1996///
SP  - 837
EP  - 843
JF  - Radiology
VL  - 198
IS  - 3
ER  - 

TY  - JOUR
T1  - Central representation of chronic ongoing neuropathic pain studied by positron emission tomography
A1  - Hsieh,J.C.
A1  - Belfrage,M.
A1  - Stone-Elander,S.
A1  - Hansson,P.
A1  - Ingvar,M.
Y1  - 1995///
N1  - O-15-butanol, pain vs. pain-free (local lidocain): bilateral prefrontal, parietal, post. cingulate; right anterior cingulate (BA24)
SP  - 225
EP  - 236
JF  - Pain
VL  - 63
IS  - 2
N2  - This study was undertaken to explore whether the neural substrates demonstrated in brain imaging studies on experimentally induced pain are involved in the perception of chronic neuropathic pain. We investigated the cerebral representation of chronic lateralised ongoing pain in patients with painful mononeuropathy (PMN, i.e., pain in the distribution of a nerve, neuralgia) with positron emission tomography (PET), using regional cerebral blood flow (rCBF) as an index for neuronal activity. Eight patients (29-53 years) with PMN in the lower extremity (4 in the right, 4 in the left) were recruited. Paired comparisons of rCBF were made between the patient's habitual pain (HP) state and the pain alleviated (PA) state following a successful regional nerve block (RNB) with lidocaine. The ongoing neuropathic pain resulted in activation of bilateral anterior insula, posterior parietal, lateral inferior prefrontal, and posterior cingulate cortices as well as the posterior sector of the right anterior cingulate cortex (ACC), Brodmann area (BA) 24, regardless of the side of PMN. In addition, a reduction in rCBF was noted in the contralateral posterior thalamus. No significant change of rCBF was detected in the somatosensory areas, i.e., SI and SII. The cerebral activation pattern, while addressing the differences between the HP and PA states, emphasises the affective-motivational dimension in chronic ongoing neuropathic pain. The striking preferential activation of the right ACC (BA 24), regardless of the side of the PMN, not only confirms that the ACC participates in the sensorial/affectional aspect of the pain experience but also suggests a possible right hemispheric lateralisation of the ACC for affective processing in chronic ongoing neuropathic pain. Our data suggests that the brain employs different central mechanisms for chronic neuropathic pain and experimentally induced acute pain, respectively.
ER  - 

TY  - JOUR
T1  - Role of the nondominant hemisphere and undamaged area during word repetition in poststroke aphasics. A PET activation study
A1  - Ohyama,M.
A1  - Senda,M.
A1  - Kitamura,S.
A1  - Ishii,K.
A1  - Mishina,M.
A1  - Terashi,A.
Y1  - 1996///
SP  - 897
EP  - 903
JF  - Stroke
VL  - 27
IS  - 5
N2  - BACKGROUND AND PURPOSE: Although the resting regional cerebral blood flow (rCBF) in aphasic patients has been thoroughly investigated with positron emission tomography (PET) and single-photon emission CT, and PET studies in normal subjects have elucidated the functional localization of language processing, little is known about the activation pattern of language processing in aphasic patients. METHODS: We measured the changes in rCBF during a repetition task (hearing a single word and repeating it aloud) and the resting state using the H2(15)O PET activation technique in 6 normal subjects (mean +/- SD age, 58.3 +/- 8.1 years) and 16 aphasic patients: 10 fluent aphasics (age, 60.3 +/- 12.5 years) and 6 nonfluent aphasics (age, 50.5 +/- 8.3 years). RESULTS: In normal subjects, the posteroinferofrontal area (PIF) including Broca's area, the posterosuperotemporal area (PST) including Wernicke's area, the rolandic areas, and a few other areas were activated with left side dominance by the repetition task. In the resting state, the rCBF in the left PIF and the left posterotemporal area was reduced in both fluent and nonfluent aphasics. In aphasic patients, the magnitude of activation in the right PIF and PST by the repetition task was greater than in normal subjects. The increase in rCBF during the repetition task in the left PIF correlated with the Western Aphasia Battery score of spontaneous speech in the nonfluent aphasics with a left inferofrontal lesion. CONCLUSIONS: This study shows the importance in aphasic patients of the mirror regions of the left PIF and PST in the nondominant (right) hemisphere for performing the word repetition task. The results also show the importance for nonfluent aphasic patients of the recruitment of the undamaged PIF for spontaneous speech.
ER  - 

TY  - JOUR
T1  - Thalamic metabolism and corticospinal tract integrity determine motor recovery in stroke
A1  - Binkofski,F.
A1  - Seitz,R.J.
A1  - Arnold,S.
A1  - Classen,J.
A1  - Benecke,R.
A1  - Freund,H.J.
Y1  - 1996///
SP  - 460
EP  - 470
JF  - Annals of Neurology
VL  - 39
IS  - 4
N2  - We studied the role of remote metabolic depressions and pyramidal tract involvement regarding motor recovery following a first hemiparetic ischemic stroke. In 23 patients the regional cerebral glucose metabolism (rCMRGlu) was measured with positron emission tomography and the location and spatial extent of the stroke lesions were assessed by magnetic resonance imaging. Motor impairment during the acute and chronic stages (4 weeks after stroke) was determined by a motor score and recordings of magnetic evoked motor potentials. Twelve patients recovered significantly, whereas 11 patients retained a disabling hemiparesis. In contrast to patients with good motor recovery, rCMRGlu was severely depressed in the thalamus on the lesion side in patients with poor motor recovery. This patient group also showed more severe damage to the pyramidal tract on magnetic resonance images and a more pronounced reduction of the magnetic evoked motor potential amplitude. Neither the size of the stroke lesions nor the spatial extent of the lesional and remote rCMRGlu depressions outside the thalamus correlated with the thalamic hypometabolism and the improvement of the motor score. We conclude that preservation both of parts of the pyramidal tract and of the thalamic circuitry is a major determinant for the quality of hand motor recovery following acute brain ischemia in the adult
ER  - 

TY  - JOUR
T1  - Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson's disease
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Ishikawa,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Silbersweig,D.
A1  - Stern,E.
A1  - Woods,R.P.
A1  - Fazzini,E.
A1  - Dogali,M.
A1  - Beric,A.
Y1  - 1996///
N1  - Increase of CMRGlu in frontal and motor cortex, reduction in thalamus -> reduced overactivation of pallidothalamic projections
SP  - 450
EP  - 459
JF  - Annals of Neurology
VL  - 39
IS  - 4
N2  - Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site
ER  - 

TY  - JOUR
T1  - Neurophysiology of the human supplementary motor area. Positron emission tomography. [Review]
A1  - Seitz,R.J.
A1  - Schlaug,G.
A1  - Knorr,U.
A1  - Steinmetz,H.
A1  - Tellmann,L.
A1  - Herzog,H.
Y1  - 1996///
SP  - 167
EP  - 175
JF  - Advances in Neurology
VL  - 70
ER  - 

TY  - JOUR
T1  - Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis
A1  - Marchal,G.
A1  - Beaudouin,V.
A1  - Rioux,P.
A1  - de la Sayette,V.
A1  - Le Doze,F.
A1  - Viader,F.
A1  - Derlon,J.M.
A1  - Baron,J.C.
Y1  - 1996///
SP  - 599
EP  - 606
JF  - Stroke
VL  - 27
IS  - 4
ER  - 

TY  - JOUR
T1  - Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms
A1  - Wolkin,A.
A1  - Sanfilipo,M.
A1  - Duncan,E.
A1  - Angrist,B.
A1  - Wolf,A.P.
A1  - Cooper,T.B.
A1  - Brodie,J.D.
A1  - Laska,E.
A1  - Rotrosen,J.P.
Y1  - 1996///
SP  - 346
EP  - 354
JF  - American Journal of Psychiatry
VL  - 153
IS  - 3
ER  - 

TY  - JOUR
T1  - [11C]MDL 100907, a radioligland for selective imaging of 5- HT(2A) receptors with positron emission tomography
A1  - Lundkvist,C.
A1  - Halldin,C.
A1  - Ginovart,N.
A1  - Nyberg,S.
A1  - Swahn,C.G.
A1  - Carr,A.A.
A1  - Brunner,F.
A1  - Farde,L.
Y1  - 1996///
SP  - PL 187
EP  - 92
JF  - Life Sciences
VL  - 58
IS  - 10
N2  - The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occurred within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [11C]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [11C]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.
ER  - 

TY  - JOUR
T1  - Cortical benzodiazepine receptor changes are related to frequency of partial seizures: a positron emission tomography study
A1  - Savic,I.
A1  - Svanborg,E.
A1  - Thorell,J.O.
Y1  - 1996///
SP  - 236
EP  - 244
JF  - Epilepsia
VL  - 37
IS  - 3
N2  - Measurements of benzodiazepine (BZD) receptor density with positron emission tomography (PET) are a promising method of identifying and localizing epileptogenic regions. We investigated whether the pattern of BZD receptor changes depends on seizure frequency, studying 19 patients with matching seizure semiology but different rates of seizure occurrence, using [11C]flumazenil as the ligand. All patients had partial epilepsy and normal magnetic resonance imaging (MRI) of the brain. The visually determined PET focus, characterized by reduced BZD receptor density, corresponded to the epileptogenic focus/seizure onset region in all patients. The degree of BZD receptor reduction showed a positive correlation with seizure frequency. Patients with daily seizures differed from those with fewer seizures in two aspects: (a) the degree and extent of BZD receptor reduction was more pronounced, and (b) BZD receptors were also reduced in the primary projection areas of the focus. Flumazenil-PET reliably identifies epileptogenic brain regions in patients with partial seizures. In addition, flumazenil-PET can distinguish patients with frequent seizures. The method therefore is not only suitable for noninvasive localization of the seizure focus, but also may provide a biochemical marker of epileptogenicity
ER  - 

TY  - JOUR
T1  - The functional neuroanatomy of Tourette's syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness
A1  - Braun,A.R.
A1  - Randolph,C.
A1  - Stoetter,B.
A1  - Mohr,E.
A1  - Cox,C.
A1  - Vladar,K.
A1  - Sexton,R.
A1  - Carson,R.E.
A1  - Herscovitch,P.
A1  - Chase,T.N.
Y1  - 1995///
SP  - 151
EP  - 168
JF  - Neuropsychopharmacology
VL  - 13
IS  - 2
N2  - We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex
ER  - 

TY  - JOUR
T1  - The metabolic topography of idiopathic torsion dystonia
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Ishikawa,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Przedborski,S.
A1  - Fahn,S.
Y1  - 1995///
SP  - 1473
EP  - 1484
JF  - Brain
VL  - 118
IS  - Pt 6
N2  - We used [18F]fluorodeoxyglucose (FDG) and PET with a statistical model of regional metabolic covariation to study brain topographic organization in idiopathic torsion dystonia (ITD). We studied 11 patients with predominantly right-sided ITD and 11 age-matched controls, and measured global, regional cerebral and normalized metabolic rates for glucose (GMR, rCMRGlc, rCMRGlc/GMR). The Scaled Subprofile Model was applied to the combined rCMRGlc dataset to identify topographic covariance profiles associated with ITD. We found that global and regional metabolic rates were normal in ITD. The SSM analysis of the combined groups of ITD patients and normals revealed a significant topographic profile characterized by relative bilateral increases in the metabolic activity of the lateral frontal and paracentral cortices, associated with relative covariate hypermetabolism of the contralateral lentiform nucleus, pons and midbrain. Subject scores for this profile correlated significantly with Fahn-Marsden disease severity ratings (r = 0.67, P < 0.02). In contrast to parkinsonism, lentiform and thalamic metabolism were dissociated in dystonia. We conclude that ITD is characterized by relative metabolic overactivity of the lentiform nucleus and premotor cortices. The presence of lentiform thalamic metabolic dissociation suggests that in this disorder hyperkinetic movements may arise through excessive activity of the direct putameno-pallidal inhibitory pathway.
ER  - 

TY  - JOUR
T1  - In vivo quantification of cerebral muscarinic receptors in normal human aging using positron emission tomography and [11C]tropanyl benzilate
A1  - Lee,K.S.
A1  - Frey,K.A.
A1  - Koeppe,R.A.
A1  - Buck,A.
A1  - Mulholland,G.K.
A1  - Kuhl,D.E.
Y1  - 1996///
SP  - 303
EP  - 310
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 2
ER  - 

TY  - JOUR
T1  - Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E
A1  - Reiman,E.M.
A1  - Caselli,R.J.
A1  - Yun,L.S.
A1  - Chen,K.
A1  - Bandy,D.
A1  - Minoshima,S.
A1  - Thibodeau,S.N.
A1  - Osborne,D.
Y1  - 1996///
SP  - 752
EP  - 758
JF  - New England Journal of Medicine
VL  - 334
IS  - 12
ER  - 

TY  - JOUR
T1  - An elastic computerized brain atlas for the analysis of clinical PET/SPET data
A1  - Rizzo,G.
A1  - Gilardi,M.C.
A1  - Prinster,A.
A1  - Grassi,F.
A1  - Scotti,G.
A1  - Cerutti,S.
A1  - Fazio,F.
Y1  - 1995///
SP  - 1313
EP  - 1318
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 22
IS  - 11
ER  - 

TY  - JOUR
T1  - Sites and mechanisms of function-related changes in energy metabolism in the nervous system. [Review]
A1  - Sokoloff,L.
Y1  - 1993///
SP  - 194
EP  - 206
JF  - Developmental Neuroscience
VL  - 15
IS  - 3-5
ER  - 

TY  - JOUR
T1  - Comparison of rates of local cerebral glucose utilization determined with deoxy[1-14C]glucose and deoxy[6-14C]glucose
A1  - Dienel,G.A.
A1  - Cruz,N.F.
A1  - Nakanishi,H.
A1  - Melzer,P.
A1  - Moulis,P.
A1  - Sokoloff,L.
Y1  - 1992///
SP  - 1430
EP  - 1436
JF  - Journal of Neurochemistry
VL  - 59
IS  - 4
N2  - The activity of the pentose phosphate shunt pathway in brain is thought to be linked to neurotransmitter metabolism, glutathione reduction, and synthetic pathways requiring NADPH. There is currently no method available to assess flux of glucose through the pentose phosphate pathway in localized regions of the brain of conscious animals in vivo. Because metabolites of deoxy[1-14C]glucose are lost from brain when the experimental period of the deoxy[14C]glucose method exceeds 45 min, the possibility was considered that the loss reflected activity of this shunt pathway and that this hexose might be used to assay regional pentose phosphate shunt pathway activity in brain. Decarboxylation of deoxy[1-14C]glucose by brain extracts was detected in vitro, and small quantities of 14C were recovered in the 6-phosphodeoxygluconate fraction when deoxy[14C]glucose metabolites were isolated from freeze-blown brains and separated by HPLC. Local rates of glucose utilization determined with deoxy[1-14C]glucose and deoxy[6-14C]glucose were, however, similar in 20 brain structures at 45, 60, 90, and 120 min after the pulse, indicating that the rate of loss of 14CO2 from deoxy[1-14C]glucose-6-phosphate in normal adult rat brain is too low to permit assay pentose phosphate shunt activity in vivo. Further metabolism of deoxy[1-14]glucose-6-phosphate via this pathway does not interfere during routine use of the deoxyglucose method or explain the progressive decrease in calculated metabolic rate when the experimental period exceeds 45 min.
ER  - 

TY  - JOUR
T1  - Determination of regional rates of cerebral protein synthesis adjusted for regional differences in recycling of leucine derived from protein degradation into the precursor pool in conscious adult rats
A1  - Sun,Y.
A1  - Deibler,G.E.
A1  - Sokoloff,L.
A1  - Smith,C.B.
Y1  - 1992///
SP  - 863
EP  - 873
JF  - Journal of Neurochemistry
VL  - 59
IS  - 3
ER  - 

TY  - JOUR
T1  - Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging
A1  - Meltzer,C.C.
A1  - Zubieta,J.K.
A1  - Brandt,J.
A1  - Tune,L.E.
A1  - Mayberg,H.S.
A1  - Frost,J.J.
Y1  - 1996///
N1  - Still reduced CMRGlu, corr. with neuropsychology
SP  - 454
EP  - 461
JF  - Neurology
VL  - 47
ER  - 

TY  - JOUR
T1  - Estimation of neocortical serotonin-2 receptor binding potential by single-dose fluorine-18-setoperone kinetic PET data analysis
A1  - Petit-Taboue,M.C.
A1  - Landeau,B.
A1  - Osmont,A.
A1  - Tillet,I.
A1  - Barre,L.
A1  - Baron,J.C.
Y1  - 1996///
SP  - 95
EP  - 104
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 1
ER  - 

TY  - JOUR
T1  - Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra
A1  - Furlan,M.
A1  - Marchal,G.
A1  - Viader,F.
A1  - Derlon,J.M.
A1  - Baron,J.C.
Y1  - 1996///
N1  - 26 patients with MCA infarct, within 18 hours, recovery of CBF in penumbra correlated with clinical outcome in 11 patients with increased OEF
SP  - 216
EP  - 226
JF  - Annals of Neurology
VL  - 40
N2  - We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., "penumbral") tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm x min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p < 0.04 to p < 0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials
ER  - 

TY  - JOUR
T1  - The luxury perfusion syndrome and its possible relation to acute metabolic acidosis localised within the brain
A1  - Lassen,N.A.
Y1  - 1966///
SP  - 1113
EP  - 1115
JF  - Lancet
VL  - II
ER  - 

TY  - JOUR
T1  - Peri-infarct perfusion in human ischemia: its relation to tissue metabolism, morphology, and clinical outcome
A1  - Fink,G.R.
A1  - Herholz,K.
A1  - Pietrzyk,U.
A1  - Huber,M.
A1  - Heiss,W.D.
Y1  - 1993///
SP  - 123
EP  - 131
JF  - Journal of Stroke and Cerebrovascular Disease
VL  - 3
ER  - 

TY  - JOUR
T1  - PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome
A1  - Marchal,G.
A1  - Serrati,C.
A1  - Rioux,P.
A1  - Petit-Taboue,M.C.
A1  - Viader,F.
A1  - de la Sayette,V.
A1  - Le Doze,F.
A1  - Lochon,P.
A1  - Derlon,J.M.
A1  - Orgogozo,J.M.
A1  - Baron,J.C.
Y1  - 1993///
SP  - 925
EP  - 927
JF  - Lancet
VL  - 341
ER  - 

TY  - CHAP
T1  - Remote effects of focal lesions on cerebral blood flow and metabolism
A1  - Pawlik,G.
A1  - Herholz,K.
A1  - Beil,C.
A1  - Wagner,R.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1985///
SP  - 59
EP  - 84
T2  - Functional mapping of the brain in vascular disorders
A2  - Heiss,W.D.
CY  - Berlin
PB  - Springer
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Prolonged muscular flaccidity in stroke patients is associated with crossed cerebellar diaschisis
A1  - Pantano,P.
A1  - Formisano,R.
A1  - Ricci,M.
A1  - Barbanti,P.
A1  - Fiorelli,M.
A1  - Sabatini,U.
A1  - Di Piero,V.
A1  - Lenzi,G.L.
Y1  - 1993///
N1  - SPECT study
SP  - 80
EP  - 85
JF  - Cerebrovascular Diseases
VL  - 3
IS  - 2
ER  - 

TY  - JOUR
T1  - Crossed cerebellar diaschisis - Occurence and resolution demonstrated with PET during carotid temporary occlusion
A1  - Brunberg,J.A.
A1  - Frey,K.A.
A1  - Horton,J.A.
A1  - Kuhl,D.E.
Y1  - 1992///
SP  - 58
EP  - 61
JF  - Ajnr: American Journal of Neuroradiology
VL  - 13
ER  - 

TY  - JOUR
T1  - Time dependency of the acetazolamide effect on cerebral hemodynamics in patients with chronic occlusive cerebral arteries. Early steal phenomenon demonstrated by [15O]H2O positron emission tomography
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Sasaki,M.
A1  - Yoshida,T.
A1  - Masuda,K.
Y1  - 1995///
SP  - 1825
EP  - 1829
JF  - Stroke
VL  - 26
IS  - 10
ER  - 

TY  - JOUR
T1  - Evaluation of cerebral perfusion reserve in patients with carotid artery occlusion
A1  - Gibbs,J.M.
A1  - Wise,R.J.S.
A1  - Leenders,K.L.
A1  - Jones,T.
Y1  - 1984///
N1  - O-15 PET
SP  - 310
EP  - 314
JF  - Lancet
VL  - I
ER  - 

TY  - JOUR
T1  - Functional neuroanatomy of human rapid-eye-movement sleep and dreaming
A1  - Maquet,P.
A1  - Peters,J.M.
A1  - Aerts,J.
A1  - Delfiore,G.
A1  - Degueldre,C.
A1  - Luxen,A.
A1  - Franck,G.
Y1  - 1996///
N1  - PET: activation of amygdala, anterior cingulate cortex and other brain areas
SP  - 163
EP  - 166
JF  - Nature
VL  - 382
N2  - Rapid-eye-movement (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming. The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.
ER  - 

TY  - JOUR
T1  - Do changes in oxygen metabolism in the unaffected cerebral hemisphere underlie early neurological recovery after stroke? - A positron emission tomography study
A1  - Iglesias,S.
A1  - Marchal,G.
A1  - Rioux,P.
A1  - Beaudouin,V.
A1  - Hauttement,J.L.
A1  - Delasayette,V.
A1  - Ledoze,F.
A1  - Derlon,J.M.
A1  - Viader,F.
A1  - Baron,J.C.
Y1  - 1996///
SP  - 1192
EP  - 1199
JF  - Stroke
VL  - 27
IS  - 7
N2  - BACKGROUND AND PURPOSE: Whether an initial depression of function in the unaffected hemisphere ("transcallosal diaschisis") plays a role in early neurological recovery after acute stroke remains controversial. Previous studies were confounded by lack of acute-stage assessment with follow-up and by the problem of defining a suitable control group, since preexisting stroke risk factors may influence prestroke cerebral metabolism. We evaluated with positron emission tomography (PET) the relationships between unaffected-hemisphere (ie, contralateral) oxygen consumption (cCMRO2) and quantitative neurological assessments (and their respective evolution over time) after ischemic stroke. METHODS: Among 30 consecutive patients with first-ever middle cerebral artery ischemic stroke studied with the (15)O equilibrium method, we selected all survivors (n=19; mean age, 74.6 years) who were investigated both within the first 18 hours after stroke onset (PET1; mean, 11 +/- 4 hours) and 15 to 30 days later (PET2; mean, 24 +/- 10 days), with each patient serving as his/her own control. Neurological deficits were quantified using Orgogozo's middle cerebral artery scale (N score) at each PET session. Neurological changes were calculated as changes in the N score. A late CT scan coregistered with PET provided infarct topography and volume index. RESULTS: At PET2, we observed the overall expected neurological recovery. There was a nearly significant trend for a decrease in cCMRO2 from PET1 to PET2, especially for the neocortex (P=.08, F test); in a subgroup of eight patients with large infarcts, this CMRO2 decline was significant (P<.05) in the mirror region to the infarct. There was no significant correlation (Spearman's tests) between acute-stage cCMRO2 and same-day N scores or between changes in cCMRO2 versus changes in N score from PET1 to PET2 (any region). There was a nearly significant trend for lower PET2 cCMRO2 in the subgroup of eight patients with large compared with small infarcts (P=.06). CONCLUSIONS: We found no evidence for an influence of cCMRO2 on acute-stage neurological deficit or for a role of the unaffected hemisphere in early recovery after acute MCA ischemic stroke. The decline in unaffected-hemisphere metabolism from the acute to the subacute stage in the face of overall clinical recovery appears clinically irrelevant. The fact that the neocortical cCMRO2 at PET2 tended to be lower, and declined significantly from PET1 to PET2 in the mirror region in the subgroup of patients with large infarcts, suggests that this delayed effect represents transcallosal fiber degeneration. <193>
ER  - 

TY  - JOUR
T1  - Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions
A1  - Gilman,S.
A1  - Sima,A.A.F.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Koeppe,R.A.
A1  - Lohman,M.E.
A1  - Little,R.
Y1  - 1996///
SP  - 241
EP  - 255
JF  - Annals of Neurology
VL  - 39
IS  - 2
N2  - Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological disorder characterized by neuronal degeneration and reactive gliosis in the cerebellum, brainstem, spinocerebellar tracts, and dorsal columns. Multiple system atrophy is a sporadic progressive neurological disorder with degeneration and gliosis in the basal ganglia, cerebellum, brainstem, and spinal autonomic nuclei, and with argyrophilic glial cytoplasmic inclusions. We describe 4 members of a family with the SCA1 mutation and a dominantly inherited progressive ataxia in which autopsy examination of 1 member showed neuropathological changes typical of multiple system atrophy, including glial cytoplasmic inclusions. In this patient, magnetic resonance imaging revealed marked brainstem and cerebellar volume loss and mild supratentorial generalized volume loss. Positron emission tomography with [18F]fluorodeoxyglucose revealed widespread hypometabolism in a pattern found in sporadic multiple system atrophy and not in dominantly inherited olivopontocerebellar atrophy. Positron emission tomography with [11C]flumazenil revealed normal benzodiazepine receptor distribution volumes, similar to those seen in sporadic multiple system atrophy. Two other family members still living had similar changes in the imaging studies. The findings in this family suggest that the SCA1 gene mutation can result in a disorder similar to multiple system atrophy, both clinically and neuropathologically.
ER  - 

TY  - JOUR
T1  - Brain acetylcholinesterase activity - validation of a PET tracer in a rat model of Alzheimers disease
A1  - Irie,T.
A1  - Fukushi,K.
A1  - Namba,H.
A1  - Iyo,M.
A1  - Tamagami,H.
A1  - Nagatsuka,S.
A1  - Ikota,N.
Y1  - 1996///
SP  - 649
EP  - 655
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 4
ER  - 

TY  - JOUR
T1  - In vivo measurement of acetylcholinesterase activity in the brain with a radioactive acetylcholine analog
A1  - Namba,H.
A1  - Irie,T.
A1  - Fukushi,K.
A1  - Iyo,M.
Y1  - 1994///
SP  - 278
EP  - 282
JF  - Brain Research
VL  - 667
IS  - 2
ER  - 

TY  - JOUR
T1  - Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia
A1  - Mielke,R.
A1  - Kittner,B.
A1  - Ghaemi,M.
A1  - Kessler,J.
A1  - Szelies,B.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 1996///
N1  - Decline of frontal cortex resting MRGlu in placebo group, improvement in motor cortex in verum group
SP  - 59
EP  - 64
JF  - Journal of the Neurological Sciences
VL  - 141
N2  - In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy
ER  - 

TY  - JOUR
T1  - Structural brain abnormalities in patients with bulimia nervosa
A1  - Krieg,J.C.
A1  - Lauer,C.
A1  - Pirke,K.M.
Y1  - 1989///
SP  - 39
EP  - 48
JF  - Psychiatry Research
VL  - 27
IS  - 1
ER  - 

TY  - JOUR
T1  - SEX DIFFERENCES IN HUMAN BRAIN MORPHOMETRY AND METABOLISM - AN IN VIVO QUANTITATIVE MAGNETIC RESONANCE IMAGING AND POSITRON EMISSION TOMOGRAPHY STUDY ON THE EFFECT OF AGING
A1  - Murphy,D.G.M.
A1  - DeCarli,C.
A1  - McIntosh,A.R.
A1  - Daly,E.
A1  - Mentis,M.J.
A1  - Pietrini,P.
A1  - Szczepanik,J.
A1  - Schapiro,M.B.
A1  - Grady,C.L.
A1  - Horwitz,B.
A1  - Rapoport,S.I.
Y1  - 1996///
N1  - More volume loss in men: frontal and temporal lobes, mor in women: hippocampus and parietal, significant metabolic asymmetries in FDG PET
SP  - 585
EP  - 594
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 53
IS  - 7
ER  - 

TY  - JOUR
T1  - Estimating smoothness in statistical parametric maps: variability of p values
A1  - Poline,J.B.
A1  - Worsley,K.J.
A1  - Holmes,A.P.
A1  - Frackowiak,R.S.
A1  - Friston,K.J.
Y1  - 1995///
SP  - 788
EP  - 796
JF  - Journal of Computer Assisted Tomography
VL  - 19
IS  - 5
ER  - 

TY  - JOUR
T1  - Diminished glucose transport and phosphorylation in Alzheimer's disease determined by dynamic FDG-PET
A1  - Piert,M.
A1  - Koeppe,R.A.
A1  - Giordani,B.
A1  - Berent,S.
A1  - Kuhl,D.E.
Y1  - 1996///
SP  - 201
EP  - 208
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 2
ER  - 

TY  - JOUR
T1  - Synthesis, in vivo biodistribution and dosimetry of [11C]N- methylpiperidyl benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist
A1  - Mulholland,G.K.
A1  - Kilbourn,M.R.
A1  - Sherman,P.
A1  - Carey,J.E.
A1  - Frey,K.A.
A1  - Koeppe,R.A.
A1  - Kuhl,D.E.
Y1  - 1995///
SP  - 13
EP  - 17
JF  - Nuclear Medicine & Biology
VL  - 22
IS  - 1
ER  - 

TY  - JOUR
T1  - Neuropathologic overlap of progressive supranuclear palsy, Pick's disease and corticobasal degeneration
A1  - Feany,M.B.
A1  - Mattiace,L.A.
A1  - Dickson,D.W.
Y1  - 1996///
SP  - 53
EP  - 67
JF  - Journal of Neuropathology & Experimental Neurology
VL  - 55
IS  - 1
ER  - 

TY  - JOUR
T1  - Effect of seizures on cerebral blood flow measured with 15O-H2O and positron emission tomography
A1  - Theodore,W.H.
A1  - Balish,M.
A1  - Leiderman,D.
A1  - Bromfield,E.
A1  - Sato,S.
A1  - Herscovitch,P.
Y1  - 1996///
SP  - 796
EP  - 802
JF  - Epilepsia
VL  - 37
IS  - 8
ER  - 

TY  - JOUR
T1  - Low-grade gliomas: when to treat? [editorial; comment]
A1  - Shapiro,W.R.
Y1  - 1992///
SP  - 437
EP  - 438
JF  - Annals of Neurology
VL  - 31
IS  - 4
ER  - 

TY  - CHAP
T1  - Protein synthesis studies in rats with methionine
A1  - Planas,A.M.
A1  - Prenant,C.
A1  - Mazoyer,B.M.
A1  - Chadan,S.
A1  - Comar,D.
A1  - DiGiamberardino,L.
Y1  - 1993///
SP  - 53
EP  - 68
T2  - PET studies on amino acid metabolism and protein synthesis
A2  - Mazoyer,B.
A2  - Heiss,W.D.
A2  - Comar,D.
IS  - 4
CY  - Dordrecht
PB  - Kluwer Academic Publishers
A3  - Cox,P.H.
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F- fluorodeoxyglucose PET
A1  - Kahn,D.
A1  - Follett,K.A.
A1  - Bushnell,D.L.
A1  - Nathan,M.A.
A1  - Piper,J.G.
A1  - Madsen,M.
A1  - Kirchner,P.T.
Y1  - 1994///Dec
N1  - 95084909 Department of Radiology, University of Iowa College of Medicine, Iowa City 52242 OBJECTIVE.  0 (Thallium Radioisotopes). 154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18)
SP  - 1459
EP  - 1465
JF  - AJR
VL  - 163
IS  - 6
N2  - This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same. SUBJECTS AND METHODS. Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed. RESULTS. The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false- negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times. CONCLUSION. We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations
ER  - 

TY  - JOUR
T1  - Pathophysiological aspects of malignant brain tumors studied with positron emission tomography
A1  - Jarden,J.O.
Y1  - 1994///
SP  - 1
EP  - 35
JF  - Acta Neurologica Scandinavica
VL  - Supplementum.  156
N2  - To further understand the control of brain tumor fluid balance and pH, the following studies were undertaken. The transport of a water soluble molecule across the brain and tumor capillary endothelium was studied during glucocorticoid and radiation treatment. The brain and brain-tumor acidity (pH) was evaluated as a single measurement in patients receiving a low maintenance dose of glucocorticoid. Transport changes and pH were measured in 61 patients with cerebral tumors using 82Rubidium (82Rb) and 11C- Dimethyloxa-zolidindione (11C-DMO), respectively, and Positron Emission Tomography (PET). Supplementary studies of tumor and contralateral brain blood flow and blood volume using the C15O2/PET and C15O/PET technique, respectively, were included to validate the 82Rb/PET model and obtain further information. A total of 125 PET scans were performed. Supplementary studies were undertaken to estimate delay of blood registration and form distribution of arterial blood isotope activity curves. Blood-to- tumor barrier transport was outlined at baseline and at 6 and 24 hours after the start of glucocorticoid treatment, finding a significant decrease in the transport. Radiation treatment (2-6 gray) did not alter the blood-to-tumor barrier transport when restudied within one hour in patients receiving glucocorticoid. In accordance with others, we observed pH values in gray and white matter in the range of 6.74-7.09 and 6.77-7.03 respectively. The pH in brain tumors was as high as 6.88-7.26, suggesting that tumors are more alkalotic than the normal brain. The permeability surface area product and the permeability coefficient were determined from the 82Rb/PET transport and C15O2/PET flow studies. Baseline permeability values were comparable to the literature values both for 82Rb and potassium. No difference in tissue blood volume was seen between 82Rb/PET and C15O/PET models and was of the same magnitude in the tumor and the contralateral tissue. The pH and fluid control in human brain tumors are perceived as metabolically controlled rather than, as previously believed, a result of simple passive exchange of alkalotic or osmotic active molecules between plasma and tumor interstitial space. Aspects of tumor alkalosis, tumor edema production, glucocorticoid edema clearance, and relationship between the anti-edema effect of glucocorticoid and the shown transport changes to 82Rb will be reviewed in the light of metabolic control mechanisms
ER  - 

TY  - JOUR
T1  - Analysis of 2-carbon-11-thymidine blood metabolites in PET imaging
A1  - Shields,A.F.
A1  - Mankoff,D.
A1  - Graham,M.M.
A1  - Zheng,M.
A1  - Kozawa,S.M.
A1  - Link,J.M.
A1  - Krohn,K.A.
Y1  - 1996///Feb
N1  - 96223817 Department of Medicine, University of Washington, Seattle, USA Carbon-11-thymidine labeled in the ring-2 position was used with PET to image tumor and tissue proliferation. Since thymidine is rapidly degraded in the body, one must consider the generation of metabolites to fully interpret the PET data. METHODS: We have measured the blood time-activity curves of thymidine and its metabolites in arterial blood samples. Blood was processed to obtain three input curves, including the total activity, the activity with CO2 removed and the fraction of CO2-free activity in intact thymidine (% Tdr). RESULTS: We found that CO2 reached a plateau of 65% (+/- 12%) of total blood activity by 11 min after injection. When a 1-min infusion of labeled thymidine is used, the time to 50% degradation to thymine and metabolites other than CO2 (measured in acidified samples by HPLC) was 2.9 +/- 0.6 min. We fit the results of the blood metabolism with a compartmental model. We found that we could accurately determine the % Tdr curve with as few as three measured points with an root mean square (RMS) error of 2% in the integrated curve, compared to the curve using all blood samples (mean of seven samples per patient). The integral of thymidine blood activity serves as the input to thymidine models, so similar errors could be expected in calculations of DNA synthetic rates. We found that the determination of CO2 could be accomplished with as few as five samples, with an RMS error of 4% in plateau %CO2 value. CONCLUSION: While it is essential to take metabolites into account when interpreting results obtained with 11C-thymidine, the reproducibility of these degradation curves may allow the use of a limited number of samples to measure the catabolic products of thymidine. These data from the blood, along with tissue kinetic models, are needed to calculate DNA synthetic rates 0 (Carbon Radioisotopes). 124-38-9 (Carbon Dioxide). 50-89-5 (Thymidine). 65-71-4 (Thymine)
SP  - 290
EP  - 296
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 2
ER  - 

TY  - JOUR
T1  - Determination of the deoxyglucose and glucose phosphorylation ratio and the lumped constant in rat brain and a transplantable rat glioma
A1  - Kapoor,R.
A1  - Spence,A.M.
A1  - Muzi,M.
A1  - Graham,M.M.
A1  - Abbott,G.L.
A1  - Krohn,K.A.
Y1  - 1989///Jul
N1  - 89257420 Department of Radiology, University of Washington, Seattle 98195 Mitochondrially bound hexokinase (ATP-D-hexose-6- phosphotransferase; EC 2.7.1.1) was dissociatively extracted from normal rat brains and intracerebral and subcutaneous implants of the 36B-10 glioma. At least 70% of the total hexokinase enzyme activity in normal and glioma tissue was associated with the mitochondrial fraction. Purification of the crude tissue extracts by ion-exchange and affinity chromatography followed by analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a successive purification of the enzyme to homogeneity with a molecular size of 98 kilodaltons. Enzyme kinetics with glucose or 2-deoxyglucose (2-DG) as the substrate were measured spectrophotometrically by coupling the appropriate reactions to either NADPH or NAD+ formation. The Km of hexokinase with glucose as the substrate in the intracerebral glioma (0.138 mM) and subcutaneous glioma (0.183 mM) tissues was 2.1-2.7-fold higher than that observed in normal brain tissue (0.067 mM) (p less than 0.001). No significant differences were observed in the Km for hexokinase with 2-DG as the substrate in the glioma and normal brain tissue. The phosphorylation ratio for normal brain was 0.320 and was increased in the intracerebral glioma to 0.694 and in the subcutaneous glioma to 0.519. The ratios of deoxyglucose and glucose volumes of distribution in normal brain and intracerebral glioma tissues were 1.70 and 1.85, respectively. The lumped constants calculated directly from the phosphorylation ratios and the volumes of distribution of deoxyglucose and glucose were 0.517 in normal brain and 1.168 in intracerebral glioma. Our results indicate the lumped constant is increased 2.26-fold in intracerebral glioma compared with normal brain EC 2-7-1-1 (Hexokinase). 0 (Deoxy Sugars). 154-17-6 (Deoxyglucose). 50-99-7 (Glucose)
SP  - 37
EP  - 44
JF  - Journal of Neurochemistry
VL  - 53
IS  - 1
ER  - 

TY  - JOUR
T1  - Recovery from nonfluent aphasia after melodic intonation therapy - a PET study
A1  - Belin,P.
A1  - Vaneeckhout,P.
A1  - Zilbovicius,M.
A1  - Remy,P.
A1  - Francois,C.
A1  - Guillaume,S.
A1  - Chain,F.
A1  - Rancurel,G.
A1  - Samson,Y.
Y1  - 1996///Dec
N1  - VX507-0027  [References: 45] Reprint available from: Belin P CEA SERV HOSP FREDERIC JOLIOT DRM 4 PL GEN LECLERC F-91401 ORSAY FRANCE CHU BRETONNEAU INSERM U316 F-37044 TOURS FRANCE CHU PITIE SALPETRIERE SERV URGENCES CEREBROVASC PARIS FRANCE CHU PITIE SALPETRIERE CTR LANGAGE PARIS FRANCE
SP  - 1504
EP  - 1511
JF  - Neurology
VL  - 47
IS  - 6
N2  - We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.
ER  - 

TY  - JOUR
T1  - NIGROSTRIATAL DOPAMINERGIC FUNCTION IN FAMILIAL AMYOTROPHIC LATERAL SCLEROSIS PATIENTS WITH AND WITHOUT COPPER/ZINC SUPEROXIDE DISMUTASE MUTATIONS
A1  - Przedborski,S.
A1  - Dhawan,V.
A1  - Donaldson,D.M.
A1  - Murphy,P.L.
A1  - Mckennayasek,D.
A1  - Mandel,F.S.
A1  - Brown,R.H.
A1  - Eidelberg,D.
Y1  - 1996///Dec
N1  - VX507-0035 . [References: 41] Reprint available from: Przedborski S COLUMBIA UNIV COLL PHYS & SURG DEPT NEUROL BB-307 650 W 168TH ST NEW YORK, NY 10032 USA N SHORE UNIV HOSP DEPT NEUROL MANHASSET, NY USA N SHORE UNIV HOSP DEPT RES MANHASSET, NY USA CORNELL UNIV MED COLL MANHASSET, NY 11030 USA HARVARD UNIV SCH MED MASSACHUSETTS GEN HOSP CECIL B DAY LAB NEUROMUSCULAR RES BOSTON, MA 02115 USA
SP  - 1546
EP  - 1551
JF  - Neurology
VL  - 47
IS  - 6
N2  - Some cases of familial amyotrophic lateral sclerosis (FALS) are associated with copper/zinc superoxide dismutase (Cu/Zn-SOD) mutations, which are implicated in the death of motor neurons. Because Cu/ZnSOD is present in high amounts in nigrostriatal dopaminergic neurons, we considered the possibility that FALS may be associated with subclinical nigrostriatal dopaminergic dysfunction. We used [F-18]fluorodopa (FDOPA) and PET to study 14 FALS patients (50+/-11 years [mean+/-SD]): seven with (FALS-1) and seven without (FALS-0) Cu/Zn-SOD mutations. Fourteen age- matched normal volunteers (48+/-18 years) served as controls. Striato-occipital ratios (SORs) for the caudate and the putamen were calculated. Five of the 14 FALS patients had reduced striatal FDOPA uptake in the caudate nucleus, putamen, or both. Mean caudate SOR did not differ among FALS-1, FALS-0, and control subjects. Mean putamen SOR was significantly abnormal in FALS-0 but not in FALS-1 patients. These findings indicate that subclinical nigrostriatal dopaminergic dysfunction is present in some FALS patients and that FDOPA/PET abnormalities are more likely to be associated with FALS-0 status. This suggests that SOD mutations are less cytotoxic to dopaminergic than to motor neurons
ER  - 

TY  - JOUR
T1  - Alpha-methyl-L-tryptophan as a tracer to study brain serotonergic system. [Review]
A1  - Diksic,M.
A1  - Grdisa,M.
Y1  - 1995///Nov
N1  - 96242281 Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada 0 (Radioactive Tracers). 13510-08-2 (alpha-methyltryptophan). 50- 67-9 (Serotonin). 6912-86-3 (Tryptophan)
SP  - 1353
EP  - 1360
JF  - Neurochemical Research
VL  - 20
IS  - 11
ER  - 

TY  - JOUR
T1  - The sequential changes in DNA synthesis, glucose utilization, protein synthesis, and peripheral benzodiazepine receptor density in C6 brain tumors after chemotherapy to predict the response of tumors to chemotherapy
A1  - Takeda,N.
A1  - Diksic,M.
A1  - Yamamoto,Y.L.
Y1  - 1996///Mar 15
N1  - 96232472 Cone Laboratory for Neurosurgical Research, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada  0 (Antineoplastic Agents, Alkylating). 0 (Proteins). 0 (Receptors, GABA-A). 154-93-8 (Carmustine). 50-99-7 (Glucose). 59- 14-3 (Bromodeoxyuridine). 9007-49-2 (DNA)
SP  - 1167
EP  - 1179
JF  - Cancer
VL  - 77
IS  - 6
N2  - BACKGROUND: Monitoring therapy in patients with brain tumors is very difficult and unreliable. It has been shown that there is no good correlation between tumor sensitivity measured in vitro and in situ tumor response to therapies. METHODS: Sequential changes in tumor size, number of DNA synthesizing cells (labelling index [LI]), glucose utilization (LCGU), protein synthesis (LCPS), and peripheral benzodiazepine receptor (PBR) density were examined after chemotherapy for seven days. This was done using antibromodeoxyuridine immunohistochemical stain and multiple tracer quantitative autoradiography in a C6 rat brain with an implanted glioma. On Day 10 after inoculation, the rats were divided into 5 experimental groups: (1) a nontreatment group (control Group 1); (2) a group received 5% dextrose intraarterial (IA) administration (control Group 2); (3) a group received 1,3- bis-(2-chloroethyl) nitrosourea (BCNU) intravenous (i.v.) administration (Group 3) (5% dextrose was solvent); (4) a group received BCNU IA administration (Group 4) (5% dextrose was solvent); and (5) a group received sarcosinamide chloroethyl nitrosourea (SarCNU) IA administration (Group 5) (solvent as for the BCNU group). RESULTS: Three treatments showed a significant decrease (P < 0.003) in tumor growth. The most effective treatment was BCNU IA and SarCNU IA was moderately effective. BCNU i.v. showed no effect on tumor growth when compared with the two control groups. The change in the peak LI correlated well with the peak LCGU. These parameters decreased markedly and significantly in both Group 4 and Group 5 from Day 1 after treatment. The rates of the decrease in these biologic factors also correlated well with a decrease in the tumor growth. The LCPS did not correlate with a decrease in the LI or LCGU. The dissociation constant (Kd) and densities of the receptors PBR (B max) did not change significantly in any of the treatment groups during the observation period. CONCLUSIONS: From the results presented, we concluded that changes in the LI and LCGU represent the most reliable parameters with which to predict the response or sensitivity of this glial tumor to the treatments applied. These data suggest that if changes in peak LCGU were measured in tumors using positron emission tomography, they might be instrumental in providing in vivo information about the sensitivity of a tumor to a given treatment without the need for repeated tumor biopsy
ER  - 

TY  - JOUR
T1  - Elevated dopa decarboxylase activity in living brain of patients with psychosis
A1  - Reith,J.
A1  - Benkelfat,C.
A1  - Sherwin,A.
A1  - Yasuhara,Y.
A1  - Kuwabara,H.
A1  - Andermann,F.
A1  - Bachneff,S.
A1  - Cumming,P.
A1  - Diksic,M.
A1  - Dyve,S.E.
A1  - et al.
Y1  - 1994///Nov 22
N1  - 95062326 McConnell Brain Imaging Center, Montreal Neurological Institute, PQ Canada  EC 4-1-1 (Dopa Decarboxylase). 63-84-3 (Dopa)
SP  - 11651
EP  - 11654
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 91
IS  - 24
N2  - The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission
ER  - 

TY  - JOUR
T1  - Generalized decrease in brain glucose metabolism during fasting in humans studied by PET
A1  - Redies,C.
A1  - Hoffer,L.J.
A1  - Beil,C.
A1  - Marliss,E.B.
A1  - Evans,A.C.
A1  - Lariviere,F.
A1  - Marrett,S.
A1  - Meyer,E.
A1  - Diksic,M.
A1  - Gjedde,A.
A1  - et al.
Y1  - 1989///Jun
N1  - 89285395 McConnell Brain Imaging Unit, Montreal Neurological Institute, Quebec, Canada  0 (Deoxy Sugars). 0 (Fluorine Radioisotopes). 154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18)
SP  - E805
EP  - 10
JF  - American Journal of Physiology
VL  - 256
IS  - 6 Pt 1
N2  - In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D- glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged
ER  - 

TY  - JOUR
T1  - Pharmacokinetics of positron-labeled 1,3-bis(2- chloroethyl)nitrosourea in human brain tumors using positron emission tomography
A1  - Diksic,M.
A1  - Sako,K.
A1  - Feindel,W.
A1  - Kato,A.
A1  - Yamamoto,Y.L.
A1  - Farrokhzad,S.
A1  - Thompson,C.
Y1  - 1984///Jul
N1  - 84205496  154-93-8 (Carmustine)
SP  - 3120
EP  - 3124
JF  - Cancer Research
JA  - Cancer Res
VL  - 44
IS  - 7
N2  - The nitrosoureas are widely used in the chemotherapy of brain tumors, two of the most common being 1,3-bis(2-chloroethyl)nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. However, we do not understand how these compounds work, nor do we know which part of the molecule has antitumor activity. In six patients with brain tumor, we measured the kinetic behavior of positron-labeled 1,3-bis(2- chloroethyl)nitrosourea in both the tumor and the normal brain with the aid of positron emission tomography; we also analyzed the distribution of radioactivity in plasma. We found the clearance of total radioactivity from the tumor to be significantly slower than from the contralateral brain and plasma, indicating a different rate of 1,3-bis(2-chloroethyl)nitrosourea decomposition in the tumor than in normal brain
ER  - 

TY  - JOUR
T1  - Evidence of misery perfusion and risk for recurrent stroke in major cerebral arterial occlusive diseases from PET
A1  - Yamauchi,H.
A1  - Fukuyama,H.
A1  - Nagahama,Y.
A1  - Nabatame,H.
A1  - Nakamura,K.
A1  - Yamamoto,Y.
A1  - Yonekura,Y.
A1  - Konishi,J.
A1  - Kimura,J.
Y1  - 1996///Jul
N1  - 96276359 Department of Neurology, Faculty of Medicine, Kyoto University, Japan OBJECTIVES--
SP  - 18
EP  - 25
JF  - Journal of Neurology, Neurosurgery & Psychiatry
VL  - 61
IS  - 1
N2  - In major cerebral arterial occlusive diseases, patients with inadequate blood supply relative to metabolic demand (misery perfusion) may be at increased risk for cerebral ischaemia. This study investigated whether patients showing misery perfusion on PET have a high risk of recurrent ischaemic stroke. METHODS--The relation between the regional haemodynamic status of cerebral circulation and the subsequent risk of recurrent stroke was prospectively evaluated in 40 patients with symptomatic internal carotid or middle cerebral arterial occlusive diseases who underwent PET. Patients were divided into two haemodynamic categories according to the mean hemispheric value of oxygen extraction fraction in the hemisphere supplied by the artery with symptomatic disease: patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction (misery perfusion). All patients were followed up for at least 12 months. RESULTS--The one year incidence of ipsilateral ischaemic strokes for patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction were two of 33 and four of seven patients respectively. A significantly higher incidence of ipsilateral strokes was found in patients with increased oxygen extraction fraction (Fisher's exact test; P = 0.005). In patients with increased oxygen extraction fraction, three of four strokes were watershed infarctions and the location of the infarction corresponded with the area of increased oxygen extraction fraction. CONCLUSION-- These findings contradict conclusions of a previous study and suggest that patients with major cerebral arterial occlusive diseases and misery perfusion have a high risk for recurrent ischaemic stroke
ER  - 

TY  - JOUR
T1  - ANALYSIS OF DYNAMIC RADIOLIGAND DISPLACEMENT OR ACTIVATION STUDIES
A1  - Friston,K.J.
A1  - Malizia,A.L.
A1  - Wilson,S.
A1  - Cunningham,V.J.
A1  - Jones,T.
A1  - Nutt,D.J.
Y1  - 1997///Jan
N1  - VZ028-0011  [References: 18] Reprint available from: Friston KJ NATL HOSP WELLCOME DEPT COGNIT NEUROL NEUROL INST QUEEN SQ LONDON WC1N 3BG ENGLAND HAMMERSMITH HOSP MRC CYCLOTRON UNIT LONDON W12 0HS ENGLAND UNIV BRISTOL PSYCHOPHARMACOL UNIT BRISTOL AVON ENGLAND
SP  - 80
EP  - 93
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 17
IS  - 1
N2  - We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission tomography (PET) activation studies. The approach is designed to facilitate dynamic activation studies using selective radioligands. These studies are, in principle, capable of characterising functional neurochemistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent compartmental models of tracer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive, voxel-based and data-led assessment of regionally specific effects. The statistical model proposed in this paper is predicated on a single-compartment model extended to allow for time-dependent changes in kinetics. We have addressed the sensitivity and specificity of the analysis, as it would be used operationally, by applying the analysis to C-11-Flumazenil dynamic displacement studies. The activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge, 30 min after administration of the tracer. We were able to demonstrate, and make statistical inferences about, regional increases in k(2) (or decreases in the volume of distribution) in prefrontal and other cortical areas.
ER  - 

TY  - BOOK
T1  - Brain mapping. The methods
Y1  - 2002///
VL  - 2
A2  - Toga,A.W.
A2  - Mazziotta,J.C.
CY  - San Diego
PB  - Academic Press
AV  - ZB: 1996A3808 (1st ed.)
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - On the origin of cancer cells
A1  - Warburg,O.
Y1  - 1956///
SP  - 309
EP  - 314
JF  - Science
VL  - 123
ER  - 

TY  - BOOK
T1  - Histological typing of tumors of the central nervous system.
A1  - Kleihues,P.
A1  - Burger,P.C.
A1  - Scheithauer,B.W.
Y1  - 1993///
VL  - 2
IS  - 21
CY  - Berlin
PB  - Springer
T3  - WHO international histological classification of tumors
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Simple, fast preparation of gallium-68-labelled human serum albumin microspheres
A1  - Yvert,J.P.
A1  - Maziere,B.
A1  - Verhas,M.
A1  - Comar,D.
Y1  - 1979///Apr 1
N1  - 80046756
SP  - 95
EP  - 99
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 4
IS  - 2
N2  - Following a study of the main factors involved in the 68-Ga labelling of human serum albumin microspheres (H.S.A.M.), especially methods of production and preparation of active solution and conditions of radioelement fixation on the protein support, the practical details of a fast technique (60 min) based on the process described by Hnatowich are presented. This method gives high labelling yields (93 +/- 3%), and after washing of the microspheres leads to a radiopharmaceutical product almost without free 68Ga (less than 2%). The spheres ready for use carry a total radioactivity corresponding to about 35%, including decay, of the activity originally recovered in the generator eluate and to more than 98% of that, found in the final suspension. The labelled product is sterile, non-pyrogenic and non-toxic. When it is injected in animals by left ventrical catheterization the uptake rates in the heart, lungs, spleen, left kidney and right kidney are similar to those observed with reference 85Sr-labelled carbonized microspheres. This radiopharmaceutical, easy to prepare and having excellent biological and nuclear properties, seems ideally suited for the scanning of organs by position emission tomoscintigraphy
ER  - 

TY  - JOUR
T1  - Gender differences in cerebellar metabolism: test-retest reproducibility
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Hitzemann,R.
A1  - Pappas,N.
A1  - Pascani,K.
A1  - Wong,C.
Y1  - 1997///Jan
N1  - 97142961 Department of Psychiatry, State University of New York at Stony Brook, USA. volkow:brain.med.bnl.gov  154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18). 50- 99-7 (Glucose)
SP  - 119
EP  - 121
JF  - American Journal of Psychiatry
VL  - 154
IS  - 1
N2  - OBJECTIVE: The purpose of this study was to evaluate gender differences in baseline measures of regional brain metabolism and to assess their reproducibility. METHOD: Fifteen male and 13 female healthy subjects, whose mean age was 44 years, were tested with positron emission tomography and [18F]fluorodeoxyglucose (FDG) under resting conditions; eight of the men and 11 of the women underwent a second FDG scan under the same conditions 4-6 weeks later to assess the reproducibility of the previous results. RESULTS: There were no differences in whole brain metabolism between the women and the men. In the first evaluation the female subjects showed significantly higher metabolism in the temporal poles and cerebellum than the male subjects. During the second evaluation the female subjects had significantly higher metabolism only in the cerebellum. CONCLUSIONS: This study documents significant and reproducible gender differences in cerebellar metabolism; their functional significance merits further evaluation
ER  - 

TY  - JOUR
T1  - Global aphasia due to thalamic hemorrhage: a case report and review of the literature. [Review] [16 refs]
A1  - Kumar,R.
A1  - Masih,A.K.
A1  - Pardo,J.
Y1  - 1996///Dec
N1  - 97130555 Department of Physical Medicine and Rehabilitation, Veterans Affairs Medical Center, West Los Angeles, CA, USA  [References: 16]
SP  - 1312
EP  - 1315
JF  - Archives of Physical Medicine & Rehabilitation
VL  - 77
IS  - 12
N2  - A 55-year-old patient was admitted with weakness in the right extremities and with significant language deficits. Both computed tomography (CT) and positron-emission tomography (PET) using 2- fluoro-2-deoxy-D-glucose were done within 1 month and repeated at 10 months after onset. Language evaluation was done using parts of the Western Aphasia Battery (WAB) and the Boston Diagnostic Aphasia Examination (BDAE) at 1 month after admission, at 3 months, and at 10 months. The initial CT scan revealed hemorrhage in the left thalamus with edema surrounding the hemorrhage. A follow-up CT scan after 10 months showed an old hemorrhage in the left thalamus with no new lesions. The initial PET scan revealed hypometabolism in the left thalamus, and a repeat PET scan at 10 months showed reduced uptake in the left frontal, left parietal, and left temporal cortex. An initial language evaluation showed impaired auditory and reading comprehension, poor verbal expression, impaired repetition, and difficulty with naming and with sentence completion. The patient was diagnosed with global aphasia. Follow-up language evaluation at 3 months and 10 months showed only minimal improvement in his communication. Global aphasia due to lesions in the thalamic region is rare and the prognosis is poor.
ER  - 

TY  - JOUR
T1  - Brain monoamine oxidase A inhibition in cigarette smokers
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Pappas,N.
A1  - Logan,J.
A1  - Shea,C.
A1  - Alexoff,D.
A1  - MacGregor,R.R.
A1  - Schlyer,D.J.
A1  - Zezulkova,I.
A1  - Wolf,A.P.
Y1  - 1996///Nov 26
N1  - 97098521 Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. fowler:simbrain.chm.bnl.gov  EC 1-4-3-4 (Monoamine Oxidase). 0 (Carbon Radioisotopes). 0 (Isoenzymes). 0 (Monoamine Oxidase Inhibitors). 155-09-9 (Tranylcypromine). 17780-72-2 (Clorgyline)
SP  - 14065
EP  - 14069
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 93
IS  - 24
N2  - Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [11C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [11C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term lambda k3 which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean lambda k3 values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 ccbrain (mlplasma)-1 min-1 for nonsmokers and smokers, respectively; P < 0.0003). Tranyl-cypromine treatment reduced lambda k3 by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation
ER  - 

TY  - JOUR
T1  - PET study of cerebral glucose metabolism and fluorodopa uptake in patients with corticobasal degeneration
A1  - Nagasawa,H.
A1  - Tanji,H.
A1  - Nomura,H.
A1  - Saito,H.
A1  - Itoyama,Y.
A1  - Kimura,I.
A1  - Tuji,S.
A1  - Fujiwara,T.
A1  - Iwata,R.
A1  - Itoh,M.
A1  - Ido,T.
Y1  - 1996///Aug
N1  - 97009550 Department of Neurology, Miyagi National Hospital, Sendai, Japan  107597-46-6 (2-fluorodopa). 154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18). 50-99-7 (Glucose). 63-84-3 (Dopa)
SP  - 210
EP  - 217
JF  - Journal of the Neurological Sciences
VL  - 139
IS  - 2
N2  - We measured cerebral glucose utilization and fluorodopa metabolism in the brain of patients with corticobasal degeneration using position emission tomography. The clinical pictures are distinctive, comprising features referable to both cerebral cortical and basal ganglionic dysfunctions. Brain images of glucose metabolism can demonstrate specific abnormalities with a marked asymmetry in the parietal cortex (the primary motor and sensory cortex and the lateral parietal cortex), the thalamus, the caudate nucleus and the putamen of the dominantly affected hemisphere related to clinical symptoms in six patients. [18F]dopa uptake also reduced in an asymmetric pattern, both the caudate nucleus and the putamen in four patients. This unique combination study measuring both cerebral glucose utilization and fluorodopa metabolism in the nigrostriatal system can provide efficient information about the dysfunctions which are correlated with individual clinical symptoms
ER  - 

TY  - JOUR
T1  - Neurotransmitter positron emission tomographic-studies in adults with phenylketonuria, a pilot study
A1  - Paans,A.M.
A1  - Pruim,J.
A1  - Smit,G.P.
A1  - Visser,G.
A1  - Willemsen,A.T.
A1  - Ullrich,K.
Y1  - 1996///Jul
N1  - 96426322 PET Centre, Groningen University Hospital, The Netherlands Patients with phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of catecholamines. The function of phenylalanine (Phe) as an inhibitor of the uptake of the precursor amino acid tyrosine (Tyr) through the blood-brain barrier as well as an inhibitor of the expression of dopamine receptors in the brain is under investigation. Positron emission tomography (PET) is a method for quantitatively determining biochemical and physiological processes in vivo. In the current pilot study, L-[1-11C]-Tyr and 18F-fluoro-ethyl-spiperone (FESP) have been used. The metabolic pathway of carboxylic labelled Tyr is mainly incorporation into protein. From the measured tissue and plasma activity as a function of time in combination with a compartimental model the Protein Synthesis Rate (PSR) for Tyr can be calculated. FESP is a ligand which binds irreversibly to the dopamine D2-receptor and has also a low non specific binding, although affinity to the serotonin receptor has been described. The ratio of FESP concentration in striatum and in cerebellum is a measure of the receptor status in vivo. In patients with plasma Phe levels above the maximum therapeutic concentration (> 700 mumol/l) the PSR for Tyr was decreased as compared to controls and patients with plasma Phe concentrations within the therapeutic range, indicating a decreased availability of Tyr for neurotransmitter synthesis, and hence explaining the reduced cerebral concentration of catecholamines 0 (Carbon Radioisotopes). 106114-42-5 (3-N-(2- fluoroethyl)spiperone). 3617-44-5 (Phenylalanine). 55520-40-6 (Tyrosine). 749-02-0 (Spiperone)
SP  - S78
EP  - 81
JF  - European Journal of Pediatrics
VL  - 155 Suppl 1
N2  - Patients with phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of catecholamines. The function of phenylalanine (Phe) as an inhibitor of the uptake of the precursor amino acid tyrosine (Tyr) through the blood-brain barrier as well as an inhibitor of the expression of dopamine receptors in the brain is under investigation. Positron emission tomography (PET) is a method for quantitatively determining biochemical and physiological processes in vivo. In the current pilot study, L-[1-11C]-Tyr and 18F-fluoro-ethyl-spiperone (FESP) have been used. The metabolic pathway of carboxylic labelled Tyr is mainly incorporation into protein. From the measured tissue and plasma activity as a function of time in combination with a compartimental model the Protein Synthesis Rate (PSR) for Tyr can be calculated. FESP is a ligand which binds irreversibly to the dopamine D2-receptor and has also a low non specific binding, although affinity to the serotonin receptor has been described. The ratio of FESP concentration in striatum and in cerebellum is a measure of the receptor status in vivo. In patients with plasma Phe levels above the maximum therapeutic concentration (> 700 mumol/l) the PSR for Tyr was decreased as compared to controls and patients with plasma Phe concentrations within the therapeutic range, indicating a decreased availability of Tyr for neurotransmitter synthesis, and hence explaining the reduced cerebral concentration of catecholamines
ER  - 

TY  - JOUR
T1  - Effects of zolpidem on local cerebral glucose metabolism during non-REM sleep in normal volunteers: a positron emission tomography study
A1  - Gillin,J.C.
A1  - Buchsbaum,M.S.
A1  - Valladares-Neto,D.C.
A1  - Hong,C.C.
A1  - Hazlett,E.
A1  - Langer,S.Z.
A1  - Wu,J.
Y1  - 1996///Sep
N1  - 97026945 Department of Psychiatry, University of California, San Diego, USA  0 (Hypnotics and Sedatives). 0 (Pyridines). 50-99-7 (Glucose). 82626-48-0 (zolpidem)
SP  - 302
EP  - 313
JF  - Neuropsychopharmacology
VL  - 15
IS  - 3
N2  - Using positron emission tomography with fluorodeoxyglucose (18FDG or FDG), we compared the effects of zolpidem (10 mg), an imidazopyridine hypnotic, which is relatively selective for the BZ1 or omega receptor and placebo on cerebral glucose metabolism during the first non-REM sleep period of 12 young normal volunteers. Plasma zolpidem pharmacokinetics varied considerably among subjects, and plasma concentrations were lower than usually reported. In general, the effects of zolpidem on local cerebral glucose metabolism varied directly with plasma concentrations of zolpidem. Zolpidem induced changes in local cerebral glucose metabolism were unevenly distributed throughout the brain and were greater in subcortical areas than lateral cortical areas. Significant negative correlations were found between change in local absolute glucose metabolic rate (calculated by subtracting individual data on placebo nights from that on zolpidem nights) and plasma concentration of zolpidem for the following areas: medial frontal cortex, cingulate gyrus, putamen, thalamus, and hippocampus. The effects of zolpidem on local cerebral glucose metabolism were partially but not closely related to the reported density of BZ1 receptors
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of the alterations in brain distribution of [11C]methamphetamine in methamphetamine- sensitized dog
A1  - Nakamura,H.
A1  - Hishinuma,T.
A1  - Tomioka,Y.
A1  - Ido,T.
A1  - Iwata,R.
A1  - Funaki,Y.
A1  - Itoh,M.
A1  - ujiwara,T.;
A1  - anai,K.;
A1  - ato,M.;
A1  - umachi,Y.;
A1  - oshida,S.;
A1  - izugaki,M.;
Y1  - 1996///Oct 31
N1  - 97118171 Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan  0 (Carbon Radioisotopes). 537-46-2 (Methamphetamine)
SP  - 401
EP  - 408
JF  - Annals of the New York Academy of Sciences
VL  - 801
N2  - We newly prepared a MAP-sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP-sensitized dog using PET. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP-sensitized brain indicates that subchronic MAP administration causes some functional change in the uptake site of MAP. The pharmacokinetic change may, in part, account for behavioral sensitization
ER  - 

TY  - JOUR
T1  - Individual variation in D2 dopamine receptor occupancy in clozapine-treated patients
A1  - Pickar,D.
A1  - Su,T.P.
A1  - Weinberger,D.R.
A1  - Coppola,R.
A1  - Malhotra,A.K.
A1  - Knable,M.B.
A1  - Lee,K.S.
A1  - Gorey,J.
A1  - Bartko,J.J.
A1  - Breier,A.
A1  - Hsiao,J.
Y1  - 1996///Dec
N1  - 97097912 Experimental Therapeutics Branch, NIMH, Bethesda, MD 20892-1380, USA OBJECTIVE: The objectives of this study were 1) to pursue the question of clozapine's striatal D2 occupancy in relation to its clinical effectiveness; 2) to investigate the relation between schizophrenic symptoms, clozapine blood levels, and estimated D2 occupancy during clinically stable and unstable conditions; and 3) to examine long-term stability in D2 occupancy. METHOD: Specific binding of the D2 radioligand [123I]benzamide ([123I]IBZM) was studied with single photon emission computed tomography in 13 patients with schizophrenia when they were clinically stable during chronic clozapine treatment, after clozapine dose reduction of > or = 50%, and in a subgroup (N = 7) after restabilization on clozapine regimens. Clozapine's estimated D2 occupancy was based on comparison with values from drug-free normal subjects. RESULTS: A wide range of estimated D2 occupancies (18% to > or = 80%) were associated with sustained, favorable response to clozapine without correlation with residual symptoms. Clozapine blood levels were negatively related to [123I]IBZM specific binding. Acute dose reduction was associated with predicted worsening in positive and negative symptoms and increases in [123I]IBZM specific binding. Independent of clozapine blood level, patients with more symptoms showed lower [123I]IBZM specific binding, consistent with competition of endogenous dopamine for D2 binding sites in patients with greater symptoms. Restabilization on clozapine regimens produced D2 occupancies closely correlated with baseline values. CONCLUSIONS: There was no evidence for a critical degree of D2 occupancy required to sustain clozapine's therapeutic effects across subjects. Simple linear regression was the best-fit model for clozapine's D2 occupancy. Longitudinal follow-up suggests stability over time of D2 occupancy in relation to dose and clinical response within individual patients 0 (Benzamides). 0 (Pyrrolidines). 0 (Receptors, Dopamine D2). 5786-21-0 (Clozapine). 84226-06-2 (3-iodo-2-hydroxy-6-methoxy-N- ((1-ethyl-2-pyrrolidinyl)methyl)benzamide)
SP  - 1571
EP  - 1578
JF  - American Journal of Psychiatry
VL  - 153
IS  - 12
ER  - 

TY  - JOUR
T1  - [18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: biodistribution in rats
A1  - Haaparanta,M.
A1  - Bergman,J.
A1  - Laakso,A.
A1  - Hietala,J.
A1  - Solin,O.
Y1  - 1996///Aug
N1  - 97008373 Medical Cyclotron/PET Center, University of Turku, Finland  0 (dopamine-binding protein). 0 (Carrier Proteins). 0 (Dopamine Uptake Inhibitors). 0 (Fluorine Radioisotopes). 50-36-2 (Cocaine). 50370-56-4 (Win 35428)
SP  - 321
EP  - 327
JF  - Synapse
VL  - 23
IS  - 4
N2  - We describe the 18F-radiolabelling synthesis (18F; T(1/2) = 109.8 min) of 2-beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (also known as CFT or WIN 35,428) and the biodistribution of this compound in rats. 18F-labelled CFT has high chemical and radiochemical purity and relatively high specific radioactivity [specific radioactivity up to 14.8 GBq/mumol (400 mCi/mumol) at end of synthesis]. Striatum to cerebellum radioactivity uptake ratios were calculated from digitised images of rat brain slices recorded with a phosphoimaging device, the maximum ratio of about 10 was obtained at 2 h postinjection. Pretreatment of the rats with a specific dopamine transport inhibitor, GBR 12909, showed that CFT binding is specific in striatum. The highest accumulation of 18F-radioactivity was found in the liver, urine, striatum, and kidney of the rat. Clearance from blood was rapid. The uptake in bone was low, indicating that [18F]CFT is not defluorinated. The relatively long half-life of 18F makes it possible to study the uptake of [18F]CFT in the brain, as equilibrium between specific and non-specific binding is reached. This will improve the signal to noise ratio as compared to positron emission tomography (PET) studies with [11C]CFT (11C; T(1/2) = 20.4 min). CFT labelled with 18F is clearly a promising radioligand for PET studies of the dopamine transporter system in humans
ER  - 

TY  - JOUR
T1  - Modeling of fluorine-18-6-fluoro-L-Dopa in humans
A1  - Wahl,L.
A1  - Nahmias,C.
Y1  - 1996///Mar
N1  - 96368631 Department of Nuclear Medicine, McMaster University Medical Centre Hamilton, Ontario, Canada  0 (Fluorine Radioisotopes). 107257-16-9 (3-O-methyl-6-fluoro- dopa). 51-61-6 (Dopamine). 63-84-3 (Dopa). 75290-51-6 (fluorodopa F 18)
SP  - 432
EP  - 437
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 3
N2  - Fluorine-18-6-fluoro-L-Dopa (F-Dopa) has been used successfully to evaluate striatal dopaminergic function in humans. The kinetic analysis of F-Dopa studies, however, is confounded by the presence of [18F]6-fluoro-3-O-methyl-L-Dopa (OMFD), the major metabolite of F-Dopa formed in the periphery that crosses the blood-brain barrier. We present results of compartmental analysis in subjects in whom we independently measured the kinetics of OMFD in the blood and striatum, and used this knowledge to solve for the kinetics of F-Dopa. METHODS: The kinetics of F-Dopa in striatum were measured with PET from 0 to 150 min after an intravenous bolus injection of tracer in four normal subjects and two patients suffering from Parkinson's disease. On a separate occasion, the kinetics of OMFD were determined in the plasma and striatum of the same individuals. The measured OMFD kinetics of each individual allowed us to reduce the number of compartments and rate constants which have to be solved for any compartmental analysis of the kinetics of F-Dopa. RESULTS: A two-compartmental, three rate-constant model was sufficient to describe the time course of F-Dopa and its metabolites in the striatum. The rate constant (k21) representing the decarboxylation rate of F-Dopa was 0.0124 min-1 in the normal subjects, and 0.0043 min-1 in the parkinsonian patients. CONCLUSION: The data do not support the need to include a fourth rate constant representing the egress of F-Dopamine and its metabolites. The forward transport rates for F- Dopa and OMFD from plasma to striatum are very similar in humans
ER  - 

TY  - JOUR
T1  - Reproducibility and discriminating ability of fluorine-18-6- fluoro-L-Dopa PET in Parkinson's disease
A1  - Vingerhoets,F.J.
A1  - Schulzer,M.
A1  - Ruth,T.J.
A1  - Holden,J.E.
A1  - Snow,B.J.
Y1  - 1996///Mar
N1  - 96368628 Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada  0 (Fluorine Radioisotopes). 63-84-3 (Dopa). 75290-51-6 (fluorodopa F 18)
SP  - 421
EP  - 426
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 3
N2  - Fluorine-18-fluorodopa (F-Dopa) PET assesses the integrity of the nigrostriatal dopaminergic neurons in Parkinson's disease. It has been used in longitudinal studies to measure the progression of Parkinson's disease and the effects of medications and intracerebral transplants. The significance of changes in PET indices in such studies depends largely on the reproducibility of the F-Dopa PET measurements. METHODS: We performed repeated F- Dopa PET scans in 12 subjects with Parkinson's disease (between Hoehn and Yahr stages I and III) to measure scan-to-scan variations. Data were analyzed using five methods comprising two sets of regions of interest (ROIs) (total striatum and substriatal), the striatum-to-cortex ratio and two graphical methods (one using plasma radioactivity, the other using cortical radioactivity as the input function). We also studied the effectiveness of each method in discriminating between patients with Parkinson's disease and normal subjects using data obtained from a similar study in 10 normal subjects. RESULTS: We found reliability coefficients between 66% and 93%; the scan-to-scan intrasubject standard deviation ranged from 2% to 16% of the mean value depending on the method of analysis and the size of the ROIs. All methods discriminated significantly between patients with Parkinson's disease and normal subjects. The ability to discriminate, as reflected by the intergroup/intragroup ratio of variance, ranged from 2 to 18. CONCLUSION: These results permit selection of the best method of analysis for studies of nigrostriatal dopaminergic function
ER  - 

TY  - JOUR
T1  - TEST-RETEST RELIABILITY OF CENTRAL [C-11]RACLOPRIDE BINDING AT HIGH D-2 RECEPTOR OCCUPANCY - A PET STUDY IN HALOPERIDOL-TREATED PATIENTS
A1  - Nyberg,S.
A1  - Farde,L.
A1  - Halldin,C.
Y1  - 1996///Oct 7
N1  - VQ760-0001 Central D-2 dopamine receptor occupancy may be a useful measure to establish clinical guidelines for optimal antipsychotic drug treatment. The use of positron emission tomography (PET) to explore quantitative relationships among D-2 receptor occupancy and clinical effects depends on the reliability of such measurements. The calculation of D-2 receptor occupancy using [C- 11]raclopride is routinely based on a ratio-equilibrium analysis, in which the ratio of radioactivity concentration in the striatum to that in the cerebellum is determined. To examine the reliability of such ratios, a test-retest analysis was performed in four schizophrenic patients treated with haloperidol decanoate. PET experiments with [C-11]raclopride were repeated in each subject during the same day. The putamen to cerebellum ratio (P/C ratio) ranged from 1.44 to 1.07 among the four patients, corresponding to a D, receptor occupancy of 62 to 71%. In each subject, the P/C ratios remained highly similar, with quotients 0.98, 1.01, 1.04 and 1.06 between the two experiments. The high test-retest reproducibility of the P/C ratios indicates that measurements of D-2 receptor occupancy with the present methods are highly reliable, and support the further use of PET to optimize the drug treatment of schizophrenia. [References: 28] Reprint available from: Nyberg S KAROLINSKA INST KAROLINSKA HOSP DEPT CLIN NEUROSCI PSYCHIAT SECT S-17176 STOCKHOLM SWEDEN
SP  - 163
EP  - 171
JF  - Psychiatry Research: Neuroimaging
VL  - 67
IS  - 3
ER  - 

TY  - JOUR
T1  - DEVELOPMENT OF RADIOLIGANDS FOR THE DOPAMINE TRANSPORTER
A1  - Muller,L.
A1  - Halldin,C.
A1  - Lundkvist,C.
A1  - Swahn,C.G.
A1  - Foged,C.
A1  - Hall,H.
A1  - Karlsson,P.
A1  - Ginovart,N.
A1  - Nakashima,Y.
A1  - Suhara,T.
A1  - Farde,L.
Y1  - 1996///May
N1  - VD125-0015 The use of benzhydryl substituted piperazine derivatives and 3- substituted cocaine analogues as radioligands are compared for in vivo visualization of dopamine transporter by PET. [References: 48] Reprint available from: Muller L KAROLINSKA INST KAROLINSKA HOSP DEPT CLIN NEUROSCI PSYCHIAT SECT S-17176 STOCKHOLM SWEDEN NOVO NORDISK AS PHARMACEUT DEV DK-2760 MALOV DENMARK
SP  - 133
EP  - 144
JF  - Journal of Radioanalytical & Nuclear Chemistry
VL  - 206
IS  - 1
ER  - 

TY  - JOUR
T1  - Positron emission tomography using [F-18]-fluorodeoxyglucose in brain tumors - a powerful diagnostic and prognostic tool
A1  - Di Chiro,G.
Y1  - 1987///
SP  - 360
EP  - 371
JF  - Investigative Radiology
VL  - 22
ER  - 

TY  - JOUR
T1  - Radiation necrosis or recurrence
A1  - Levivier,M.
A1  - Becerra,A.
A1  - De Witte,O.
A1  - Brotchi,J.
A1  - Goldman,S.
Y1  - 1996///Jan
N1  - Recurrent tumor vs necrosis by FDG PET
SP  - 148
EP  - 149
JF  - Journal of Neurosurgery
VL  - 84
IS  - 1
ER  - 

TY  - JOUR
T1  - Pituitary microadenomas: a PET study
A1  - De Souza,B.
A1  - Brunetti,A.
A1  - Fulham,M.J.
A1  - Brooks,R.A.
A1  - DeMichele,D.
A1  - Cook,P.
A1  - Nieman,L.
A1  - Doppman,J.L.
A1  - Oldfield,E.H.
A1  - Di Chiro,G.
Y1  - 1990///Oct
N1  - 90378097 Neuroimaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
SP  - 39
EP  - 44
JF  - Radiology
VL  - 177
IS  - 1
N2  - Twenty cases of surgically verified pituitary microadenoma (17 with Cushing disease and three with acromegaly) were studied with positron emission tomography (PET) with use of fluorine-18-2- fluorodeoxyglucose (FDG). The diagnostic results were compared with those of other modalities, namely, computed tomography (CT), magnetic resonance (MR) imaging, and, in the cases of Cushing disease, simultaneous bilateral inferior petrosal sinus sampling (SIPS). The PET results showed 12 positive readings and one questionable reading, compared with seven positive readings and one questionable reading for CT (18 cases studied) and 13 positive and two questionable MR imaging readings. PET complemented MR imaging, in the sense that five of the positive PET readings were negative or questionable at MR imaging. PET studies of 20 healthy control subjects showed no false-positive cases, whereas other studies of healthy subjects with contrast material-enhanced CT and MR imaging have yielded, respectively, 20% and 15% positive readings, with findings suggestive of silent or occult adenomas
ER  - 

TY  - JOUR
T1  - Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography
A1  - Doyle,W.K.
A1  - Budinger,T.F.
A1  - Valk,P.E.
A1  - Levin,V.A.
A1  - Gutin,P.H.
Y1  - 1987///Jul-Aug
N1  - 87251538  0 (Radioisotopes). 154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18). 7440-17-7 (Rubidium). 7782-41-4 (Fluorine)
SP  - 563
EP  - 570
JF  - Journal of Computer Assisted Tomography
VL  - 11
IS  - 4
N2  - Nine radiation-treated brain tumor patients were studied by positron emission tomography (PET) in an attempt to differentiate tumor recurrence from radiation necrosis. Rubidium-82 was used to define the region of absent or disturbed blood-brain barrier and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) was used to evaluate the metabolic state of the brain. By comparing glucose utilization in the pathologic region with utilization in the adjacent tissue, a diagnosis of recurrent tumor (increased [18F]FDG accumulation) or necrosis (decreased FDG accumulation) was made. In the seven patients who underwent surgery the PET diagnosis was confirmed by histologic examination of resected tissue. The two patients who did not undergo surgery have had a clinical course consistent with the PET diagnosis of necrosis. Dynamic 82Rb imaging showed that the rate of 82Rb accumulation was greater in tumor than in normal brain. However, this finding alone did not differentiate tumor from necrosis, as some necrotic tissue also showed high rates of 82Rb accumulation, and washout kinetics were similarly nonspecific. The differentiation of radiation necrosis from tumor recurrence is reliably achieved by [18F]FDG PET examination and is aided by information obtained from a 82Rb PET study done immediately prior to the [18F]FDG injection
ER  - 

TY  - JOUR
T1  - The in vivo metabolic pattern of low-grade brain gliomas: A positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine
A1  - Derlon,J.M.
A1  - Petit-Taboue,M.C.
A1  - Chapon,F.
A1  - Beaudouin,V.
A1  - Noel,M.H.
A1  - Creveuil,C.
A1  - Courtheoux,P.
A1  - Houtteville,J.P.
Y1  - 1997///
SP  - 276
EP  - 288
JF  - Neurosurgery
VL  - 40
IS  - 2
N2  - OBJECTIVE: The object of the present study was to identify metabolic differences between low-grade astrocytomas and oligodendrogliomas and to improve their diagnosis and noninvasive assessment, because both types of tumors look very similar from the point of view of clinical and radiological data (as assessed by computed tomography and magnetic resonance imaging). METHODS: Before any aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in 12 patients and oligodendrogliomas in 10) were investigated with positron emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and amino acid uptake (11C-L-methylmethionine). An original software that allows a full metabolic analysis of the tumor region of interest (defined from the T1-weighted magnetic resonance image) and compares tumor tissue uptake tracer concentrations with average healthy tissue values has been implemented for data processing. Heterogeneity of each individual tumor has been taken into account and was expressed in histograms, which provided data about the mean and also extreme and intermediate values of tracer concentrations and the way these values are distributed among the full tumor mass. RESULTS: It has been shown that both tumor types exhibit a glucose hypometabolism (slightly more pronounced with astrocytomas), whereas they strongly differ in methionine uptake, which is high in all oligodendrogliomas and either decreased, normal, or moderately increased in astrocytomas. This latter metabolic difference between both tumor populations may be partially explained by their different cell densities. CONCLUSION: This study suggests that despite similar radiological and clinical presentations, these two kinds of low-grade gliomas are metabolically different and could therefore have specific responses to different therapies. Moreover, their in vivo metabolic follow-up with positron emission tomography should rely on different parameters, depending on their histological type; methionine uptake may be more relevant than glucose metabolism in the follow-up of oligodendrogliomas.
ER  - 

TY  - JOUR
T1  - THE ANATOMY OF MOOD DISORDERS - REVIEW OF STRUCTURAL NEUROIMAGING STUDIES [Review]
A1  - Soares,J.C.
A1  - Mann,J.J.
Y1  - 1997///Jan 1
N1  - WA835-0010 The structural neuroimaging findings in mood disorders were reviewed, to evaluate evidence for a neuroanatomic model of pathophysiology, involving the prefrontal cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and connections among these structures. Global atrophy is not consistently found. The best replicated finding is an increased rate of white matter and periventricular hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear present in unipolar depression, A larger third ventricle, anal smaller cerebellum and perhaps temporal lobe appear present in bipolar disorder. These localized structural changes involve regions that may be critical in the pathogenesis of mood disorders. Generalized and localized anatomic alterations may be related to age or vascular disease. The clinical and biological correlates of these changes need to be investigated to allow development of a more complete model of pathophysiology of mood disorders. (C) 1997 J.C. Soares and J.J. Mann. [References: 218] Reprint available from: Mann JJ NEW YORK STATE PSYCHIAT INST & HOSP DEPT NEUROSCI 722 W 168TH ST BOX 28 NEW YORK, NY 10032 USA UNIV PITTSBURGH WESTERN PSYCHIAT INST & CLIN MED CTR LABS NEUROPHARMACOL PITTSBURGH, PA 15213 USA
SP  - 86
EP  - 106
JF  - Biological Psychiatry
VL  - 41
IS  - 1
ER  - 

TY  - JOUR
T1  - Cerebral hemodynamics and metabolism of severe diffuse brain injury measured by PET [see comments]
A1  - Yamaki,T.
A1  - Imahori,Y.
A1  - Ohmori,Y.
A1  - Yoshino,E.
A1  - Hohri,T.
A1  - Ebisu,T.
A1  - Ueda,S.
Y1  - 1996///Jul
N1  - 96268145 Department of Neurosurgery, Kyoto Prefectural University of Medicine, Japan  0 (Fluorine Radioisotopes). 0 (Oxygen Radioisotopes). 154-17-6 (Deoxyglucose). 29702-43-0 (fludeoxyglucose F 18). 50-99-7 (Glucose)
SP  - 1166
EP  - 1170
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 7
N2  - Cerebral hemodynamics and metabolism in three patients with severe diffuse brain injury were measured 10 days after onset using PET. In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood volume (rCBV), cerebral metabolic rate for oxygen (rCMRO2), cerebral metabolic rate for glucose (rCMRglc) and cerebral metabolic ratio (rCMRO2/rCMRglc) were measured. The Glasgow Coma Scale scores on admission were 4, 5 and 5, respectively, and CT on admission showed typical findings of diffuse brain injury. As a result, PET revealed misery perfusion and hyperglycolysis in Patient 1 and matching low perfusion and low glucose metabolism in Patients 2 and 3. Although Patient 1 died, Patients 2 and 3 had good recoveries. We speculate that a long-lasting anaerobic state, indicated by a high OEF value and low metabolic ratio, is an important undesirable factor related to the outcome
ER  - 

TY  - JOUR
T1  - IMPROVED METHODS FOR IMAGE REGISTRATION
A1  - Alpert,N.M.
A1  - Berdichevsky,D.
A1  - Levin,Z.
A1  - Morris,E.D.
A1  - Fischman,A.J.
Y1  - 1996///Feb
N1  - TY638-0002  (C) 1996 Academic Press, Inc. [References: 16] Reprint available from: Alpert NM MASSACHUSETTS GEN HOSP DIV NUCL MED PET IMAGING LAB FRUIT ST BOSTON, MA 02114 USA
SP  - 10
EP  - 18
JF  - Neuroimage
VL  - 3
IS  - 1
N2  - We report a system for PET-MRI registration that is improved or optimized in several areas: (1) Automatic scalp/brain segmentation replaces manual drawing operations, (2) a new fast and accurate method of image registration, (3) visual assessment of registration quality is enhanced by composite imaging methods (i.e., fusion) and (4) the entire procedure is embedded in a commercially available scientific visualization package, thereby providing a consistent graphical user interface. The segmentation algorithm was tested on 17 MRI data sets and was successful in all cases. Accuracy of image registration was equal to that of the Woods algorithm, but 10 times faster for PET-PET and 4 times faster for PET-MRI. The image fusion method allows detection of misalignments on the order of 2-3 mm. These results demonstrate an integrated system for intermodality image registration, which is important because the procedure can be performed by technicians with no anatomic knowledge and reduces the required time from hours to about 15 min on a modern computer workstation.
ER  - 

TY  - JOUR
T1  - A PROBABILISTIC ATLAS OF THE HUMAN BRAIN - THEORY AND RATIONALE FOR ITS DEVELOPMENT
A1  - Mazziotta,J.C.
A1  - Toga,A.W.
A1  - Evans,A.
A1  - Fox,P.
A1  - Lancaster,J.
Y1  - 1995///Jun
N1  - RE540-0001 Reprint available from: Mazziotta JC UNIV CALIF LOS ANGELES SCH MED INST NEUROPSYCHIAT DIV BRAIN MAPPING LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED DEPT NEUROL LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED DEPT RADIOL LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED DEPT PHARMACOL LOS ANGELES, CA 90024 USA MCGILL UNIV MONTREAL NEUROL INST DEPT NEUROL MONTREAL PQ CANADA MCGILL UNIV MONTREAL NEUROL INST DEPT NEUROSURG MONTREAL PQ CANADA MCGILL UNIV MONTREAL NEUROL INST DEPT BIOMED ENGN MONTREAL PQ CANADA UNIV TEXAS CTR RES IMAGING DEPT RADIOL SAN ANTONIO, TX 78285 USA UNIV TEXAS CTR RES IMAGING DEPT NEUROL SAN ANTONIO, TX 78285 USA UNIV TEXAS CTR RES IMAGING DEPT PSYCHIAT SAN ANTONIO, TX 78285 USA
SP  - 89
EP  - 101
JF  - Neuroimage
VL  - 2
IS  - 2 Part 1
ER  - 

TY  - JOUR
T1  - Enhanced regional cerebral metabolic interactions in thalamic circuitry predicts motor recovery in hemiparetic stroke
A1  - Azari,N.P.
A1  - Binkofski,F.
A1  - Pettigrew,K.D.
A1  - Freund,H.J.
A1  - Seitz,R.J.
Y1  - 1996///
N1  - WK786-0002 We applied a multiple regression/discriminant analysis to resting metabolic data from patients with first hemiparetic suprathalamic infarctions to determine if metabolic interdependencies, which may separate recovered (N = 12) from nonrecovered (N = 9) patients, suggest important motor-recovery pathways. Recovered, vs. nonrecovered, patients showed an enhanced ipsileisonal thalamic-contralesional cerebellar metabolic interdependency. This pattern correctly classified 91% of recovered and 88% of nonrecovered patients. Metabolic interactions involving bilateral supplementary motor area, ipsilesional thalamus, and contralesional cerebellum distinguished all recovered patients from age/sex-matched controls (N = 12). These results suggest that altered functional interactions in thalamic circuitry may reflect plastic reorganization associated with motor recovery from hemiparesis. (C) 1997 Wiley-Liss, Inc., Inc. [References: 66] Reprint available from: Seitz RJ UNIV DUSSELDORF DEPT NEUROL UNIV STR 1 D-40225 DUSSELDORF GERMANY UNIV DUSSELDORF DEPT NEUROL D-40225 DUSSELDORF GERMANY NIMH DIV EPIDEMIOL APPL & SERV RES NIH BETHESDA, MD 20892 USA
SP  - 240
EP  - 253
JF  - Human Brain Mapping
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - A UNIFIED STATISTICAL APPROACH FOR DETERMINING SIGNIFICANT SIGNALS IN IMAGES OF CEREBRAL ACTIVATION
A1  - Worsley,K.J.
A1  - Marrett,S.
A1  - Neelin,P.
A1  - Vandal,A.C.
A1  - Friston,K.J.
A1  - Evans,A.C.
Y1  - 1996///
N1  - UR301-0004 We present a unified statistical theory for assessing the significance of apparent signal observed in noisy difference images. The results are usable in a wide range of applications, including fMRI, but are discussed with particular reference to PET images which represent changes in cerebral blood flow elicited by a specific cognitive or sensorimotor task. Our main result is an estimate of the P-value for local maxima of Gaussian, t, chi(2) and F fields over search regions of any shape or size in any number of dimensions. This unifies the P-values for large search areas in 2-D (Friston et al. [1991]: J Cereb Blood Flow Metab 11:690-699) large search regions in 3-D (Worsley et al. [1992]: J Cereb Blood Flow Metab 12:900-918) and the usual uncorrected P-value at a single pixel or voxel. (C) 1996 Wiley- Liss, Inc. [References: 19] Reprint available from: Worsley KJ MCGILL UNIV DEPT MATH & STAT 805 SHERBROOKE ST W MONTREAL PQ H3A 2K6 CANADA MONTREAL NEUROL INST MCCONNELL BRAIN IMAGING CTR MONTREAL PQ H3A 2B4 CANADA WELLCOME DEPT COGNIT NEUROL LONDON WC1N 3BG ENGLAND
SP  - 58
EP  - 73
JF  - Human Brain Mapping
VL  - 4
IS  - 1
ER  - 

TY  - JOUR
T1  - A PET investigation of implicit and explicit sequence learning
A1  - Rauch,S.L.
A1  - Savage,C.R.
A1  - Brown,H.D.
A1  - Curran,T.
A1  - Alpert,N.M.
A1  - Kendrick,A.
A1  - Fischman,A.J.
A1  - Kosslyn,S.M.
Y1  - 1995///
N1  - UE953-0002 The purpose of this study was to determine the mediating neuroanatomy of implicit and explicit sequence learning using a modified version of the serial reaction time (SRT) paradigm. Subjects were seven healthy, right-handed adults (three male, four female, mean age 26.7, range 18-43 yr). PET data were acquired via the oxygen-15-labeled-carbon dioxide inhalation method while subjects performed the SRT. Subjects were scanned during two blocks each of 1) no sequence (Random), 2) single- blind, 12-item sequence (Implicit), and 3) unblinded, same sequence (Explicit). Whole-brain-normalized images reflecting relative regional cerebral blood flow (rCBF) were transformed to Talairach space, and statistical parametric maps (SPMs) of z- scores were generated for comparisons of interest. The threshold for significant activation was defined as z-score greater than or equal to 3.00. Behavioral data demonstrated significant learning (P <.05) for Implicit and Explicit conditions. Tests of explicit knowledge reflected non-significant explicit contamination during the Implicit condition. Foci of significant activation in the Implicit condition were found in right ventral premotor cortex, right ventral caudate/nucleus accumbens, right thalamus, and bilateral area 19; activation in the Explicit condition included primary visual cortex, peri-sylvian cortex, and cerebellar vermis. Activations in visual and language areas during the Explicit condition may reflect conscious learning strategies including covert verbal rehearsal and visual imagery. Right-sided premotor, striatal, and thalamic activations support the notion that implicit sequence learning is mediated by cortico-striatal pathways, preferentially within the right hemisphere. (C) 1996 Wiley-Liss, Inc. [References: 69] Reprint available from: Rauch SL MASSACHUSETTS GEN HOSP EAST CNY- 9130 BLDG 149 13TH ST BOSTON, MA 02129 USA MASSACHUSETTS GEN HOSP DEPT PSYCHIAT BOSTON, MA 02114 USA MASSACHUSETTS GEN HOSP DEPT RADIOL BOSTON, MA 02114 USA MASSACHUSETTS GEN HOSP DEPT NEUROL BOSTON, MA 02114 USA HARVARD UNIV SCH MED DEPT PSYCHIAT BOSTON, MA 02115 USA HARVARD UNIV SCH MED DEPT PSYCHOL BOSTON, MA 02115 USA
SP  - 271
EP  - 286
JF  - Human Brain Mapping
VL  - 3
IS  - 4
ER  - 

TY  - JOUR
T1  - TOPOGRAPHY OF DIPRENORPHINE BINDING IN HUMAN CINGULATE GYRUS AND ADJACENT CORTEX DERIVED FROM COREGISTERED PET AND MR IMAGES
A1  - Vogt,B.A.
A1  - Watanabe,H.
A1  - Grootoonk,S.
A1  - Jones,A.K.P.
Y1  - 1995///
N1  - TU287-0001  (C) 1995 Wiley-Liss, Inc. [References: 55] Reprint available from: Vogt BA WAKE FOREST UNIV BOWMAN GRAY SCH MED DEPT PHYSIOL & PHARMACOL MED CTR BLVD WINSTON SALEM, NC 27157 USA NATL CARDIOVASC CTR RES INST DEPT INVESTIGAT RADIOL OSAKA JAPAN HAMMERSMITH HOSP ROYAL POSTGRAD MED SCH MRC CTR CLIN SCI LONDON W12 0HS ENGLAND HOPE HOSP CTR RHEUMAT DIS SALFORD M6 8HD LANCS ENGLAND UNIV MANCHESTER SALFORD LANCS ENGLAND
SP  - 1
EP  - 12
JF  - Human Brain Mapping
VL  - 3
IS  - 1
N2  - Positron emission tomography (PET) studies of ligand binding lack sufficient anatomical detail to evaluate topographical variations in binding within each of the lobes of the human cerebral cortex. This study employed PET to localize [C- 11]diprenorphine binding to opioid receptors and magnetic resonance (MR) imaging for defining medial surface structures. Continuous arterial sampling for metabolite corrected [C- 11]diprenorphine levels and CNS blood flow were used to model the volume of distribution (VDtot) of binding for three subjects. The PET images of VDtot were coregistered to the MR images for each case and 37 regions of interest were used to calculate VDtot. The VDtot was averaged for the three cases and coregistered with an MR reconstruction of the medial surface and plotted onto a flat map of this region. The average VDtot showed that binding was highest in anterior cingulate, rostral cingulofrontal transition, and prefrontal cortices, while binding in caudal parts of anterior cingulate and superior frontal cortices, and posterior cingulate cortex varied from high to low. Three statistical levels of binding were defined in relation to the high binding in perigenual area 24: high and equal to area 24, moderate and significantly lower than area 24 (P < 0.01), or low (P < 0.001). These levels of binding were plotted onto an unfolded map of the medial cortex. The VDtot was high in rostral cortex, and a strip of high binding continued caudally on the dorsal lip of the cingulate gyrus. There were patches of high binding in cinguloparietal transition, posterior parietal, and supplementary motor cortices. Four regions had low binding: 1) areas 29 and 30 in the callosal sulcus, 2) fundus of the cingulate sulcus likely involving the cingulate motor areas, 3) fundus of the superior cingulate sulcus involving two divisions of supplementary motor cortex, and 4) sensorimotor cortex on the paracentral lobule. Variations in binding may reflect functional specializations such as low binding in the cingulate motor and visuospatial areas and high levels in areas involved in processing information with affective content. The higher sensitivity of three-dimensional scanning and coregistration of PET and MR images makes it feasible to analyze single individuals and, by performing pixel- by-pixel spectral analysis and generation of parametric maps, statistical analyses are possible.
ER  - 

TY  - JOUR
T1  - Preoperative assessment of the cerebral hemisphere dominance for language with CBF PET
A1  - Pardo,J.V.
A1  - Fox,P.T.
Y1  - 1993///
N1  - Correspondence with Wada test in 8/9 subjects, reading and verb generation task, 11 patients in total
SP  - 57
EP  - 68
JF  - Human Brain Mapping
VL  - 1
ER  - 

TY  - JOUR
T1  - Assessing the significance of focal activations using their spatial extent
A1  - Friston,K.J.
A1  - Worsley,K.J.
A1  - Frackowiak,R.S.J.
A1  - Mazziotta,J.C.
A1  - Evans,A.C.
Y1  - 1994///
SP  - 210
EP  - 220
JF  - Human Brain Mapping
VL  - 1
ER  - 

TY  - JOUR
T1  - Functional effects of striatal dysfunction in Parkinson disease
A1  - Holthoff-Detto,V.A.
A1  - Kessler,J.
A1  - Herholz,K.
A1  - Bnner,H.
A1  - Pietrzyk,U.
A1  - Wrker,M.
A1  - Ghaemi,M.
A1  - Wienhard,K.
A1  - Wagner,R.
A1  - Heiss,W.-D.
Y1  - 1997///
N1  - Memory deficit correlated with caudate FDOPA reduction, motor deficit with putamen
SP  - 145
EP  - 150
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 54
N2  - BACKGROUND: Concepts of basal ganglia organization suggest structually and functionally segregated pathways that link putamen and caudate function to motor and cognitive performance, respectively. OBJECTIVE: To investigate whether motor and cognitive impairment in Parkinson disease is attributable to selective disturbance in nigrostriatal, dopaminergic function and regional cerebral glucose metabolism. DESIGN: Twenty patients with probable Parkinson disease underwent positron emission tomographic measurements of dopaminergic, nigrostriatal function (positron emission tomography with fluorodopa F 18), regional glucose metabolism (positron emission tomography with fludeoxyglucose F 18), memory testing, and evaluation of locomotor disability. RESULTS: Memory performance in the patient cohort strongly correlated with the individual disease duration and degree of locomotor disability (P < .05). Striatal uptake rates of fluorodopa F 18 were significantly reduced in all patients (P < .05) compared with those in normal control subjects, and putaminal rates correlated significantly with the patients' degree of locomotor disability (P < .01) but not with memory performance. In the patients with an advanced stage of disease, there was a significant correlation between reduced caudate uptake rates of fluorodopa F 18 and the patients' impairment in delayed recall performance of the memory task (P < .05) but not with the individual degree of locomotor disability. No changes were found for regional glucose metabolic rates in the patients compared with the controls. CONCLUSIONS: The present study provides evidence for the hypothesis that on the level of the striatum, motor impairment in Parkinson disease may be assigned to altered dopamine neuronal integrity in the putamen but not in the caudate, whereas memory impairment in the more advanced cases may be attributed to caudate but not putaminal dysfunction
ER  - 

TY  - JOUR
T1  - PARAMETRIC IMAGES OF BENZODIAZEPINE RECEPTOR CONCENTRATION USING A PARTIAL-SATURATION INJECTION
A1  - Delforge,J.
A1  - Spelle,L.
A1  - Bendriem,B.
A1  - Samson,Y.
A1  - Syrota,A.
Y1  - 1997///Mar
N1  - WQ178-0011 The in vivo quantification of the benzodiazepine receptor concentration in human brain using positron emission tomography (PET) and C-11-flumazenil (C-11-FMZ), is usually based on a three- compartment model and on PET curves measured in a small number of large regions of interest; however, it should be interesting to estimate the receptor concentration for each pixel and to build quantified images of the receptor concentration. The main advantage is to allow screening of the receptor site localization and visual observation of the possible abnormalities. Up to now, all the methods described include complex experimental protocols, difficult to use in routine examinations. In this paper, we propose the partial-saturation approach to obtain parametric images of benzodiazepine receptor concentration and FMZ affinity. It consists of a single FMZ injection with a low specific activity, followed by Scatchard analysis. Like other parametric imaging methods, this partial-saturation approach can lead to a small percentage (<1%) of unrealistic values in receptor-poor regions; how ever, it is the only method that allows receptor concentration and affinity images to be obtained from a single- injection 40-min experiment without blood sampling. We also propose a second method in which the receptor concentration map is directly deduced from the PET image acquired 5 to 10 min after a partial-saturation injection. This method assumes a known and constant FMZ affinity value but requires only very simple corrections of this PET image. It is robust (negative values are never found) and quite simple to use in routine examination of patients (no blood sampling, single injection, only 10-min experiment). [References: 19] Reprint available from: Delforge J CEA SERV HOSP FREDERIC JOLIOT HOP ORSAY COMMISSARIAT ENERGIE ATOM 4 PL G LECLERC F-91400 ORSAY FRANCE
SP  - 343
EP  - 355
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 17
IS  - 3
ER  - 

TY  - JOUR
T1  - THE IPSILATERAL CEREBELLAR HEMISPHERE IS OVERACTIVE DURING HAND MOVEMENTS IN AKINETIC PARKINSONIAN PATIENTS
A1  - Rascol,O.
A1  - Sabatini,U.
A1  - Fabre,N.
A1  - Brefel,C.
A1  - Loubinoux,I.
A1  - Celsis,P.
A1  - Senard,J.M.
A1  - Montastruc,J.L.
A1  - Chollet,F.
Y1  - 1997///Jan
N1  - WJ826-0009 We compared the rCBF changes induced by the execution of a finger-to-thumb opposition motor task in the cerebellar hemispheres of 12 normal subjects, 12 parkinsonian patients whose medication had been withheld for at least 18 h and 16 parkinsonian patients on medication using single photon emission tomography and i.v. Xe-133. The normal subjects and parkinsonian patients on medication exhibited the same pattern of response, with a significant increase in rCBF in the contralateral primary motor cortex and in the supplementary motor areas. No significant rCBF change was detected in the cerebellum of these two groups; this finding was expected since our technique cannot detect cerebellar activation when the motor task is executed at a relatively low rate and small amplitude as it was in this study The parkinsonian patients off medication exhibited a markedly different pattern of activation characterized by a significant over-activation in the ipsilateral cerebellar hemisphere and a significant underactivation in the supplementary motor areas. These results suggest that parkinsonian patients off medication may try to compensate for their basal ganglia-cortical loop's dysfunction using other motor pathways involving cerebellar relays. [References: 49] Reprint available from: Rascol O FAC MED TOULOUSE INSERM U455 LAB PHARMACOL MED & CLIN 37 ALLEES JULES GUESDE F-31073 TOULOUSE FRANCE UNIV HOSP DEPT NEUROL TOULOUSE FRANCE IST MEDITERRANEO NEUROSCI SANATRIX DEPT NEUROL POZZILI ITALY UNIV HOSP DEPT MED & CLIN PHARMACOL TOULOUSE FRANCE UNIV HOSP INSERM U317 TOULOUSE FRANCE UNIV HOSP INSERM U455 TOULOUSE FRANCE
SP  - 103
EP  - 110
JF  - Brain
VL  - 120
IS  - Part 1
ER  - 

TY  - JOUR
T1  - EFFECT OF RESERPINE-INDUCED DEPLETION OF SYNAPTIC DOPAMINE ON [C- 11]RACLOPRIDE BINDING TO D-2-DOPAMINE RECEPTORS IN THE MONKEY BRAIN
A1  - Ginovart,N.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Swahn,C.G.
Y1  - 1997///Apr
N1  - WQ983-0002 Positron emission tomography was used to examine the in vivo binding of [C-11]raclopride to D-2-dopamine (DA) receptors in the striatum of two Cynomolgus monkeys after a single dose of reserpine (1 mg/kg, i.v.). A Scatchard procedure was repeated five times to follow D-2 receptor density and apparent affinity for 7 weeks after reserpine. Reserpine-induced depletion of DA lead to a marked increase in [C-11]raclopride binding, which was still detectable 20 days after treatment. Scatchard analyses indicated that the measured increase in [C-11]raclopride binding reflected an increase in receptor affinity but no evident change in receptor density (B-max). Thus, the increase in [C- 11]raclopride binding after reserpine should correspond to a reduced competition with endogenous DA for binding to D-2 receptors. The results were used to estimate the DA-induced D-2 occupancy to be about 40% at physiological conditions. (C) 1997 Wiley-Liss, Inc. [References: 27] Reprint available from: Ginovart N KAROLINSKA INST SECT PSYCHIAT DEPT CLIN NEUROSCI KAROLINSKA HOSP S-17176 STOCKHOLM SWEDEN
SP  - 321
EP  - 325
JF  - Synapse
VL  - 25
IS  - 4
ER  - 

TY  - JOUR
T1  - Occupational and evironmental causes of parkinsonism
A1  - Tanner,C.M.
Y1  - 1992///
N1  - from Dr. Jansen
SP  - 503
EP  - 513
JF  - Occupational Medicine
VL  - 7
IS  - 3
ER  - 

TY  - JOUR
T1  - PET STUDY OF THE PRE- AND POST-SYNAPTIC DOPAMINERGIC MARKERS FOR THE NEURODEGENERATIVE PROCESS IN HUNTINGTONS-DISEASE
A1  - Ginovart,N.
A1  - Lundin,A.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Bckman,L.
A1  - Swahn,C.G.
A1  - Pauli,S.
A1  - Sedvall,G.
Y1  - 1997///Mar
N1  - WV142-0011 [References: 64] Reprint available from: Ginovart N KAROLINSKA INST KAROLINSKA HOSP DEPT CLIN NEUROSCI SECT PSYCHIAT S-17176 STOCKHOLM SWEDEN KAROLINSKA INST CTR GERONTOL RES STOCKHOLM SWEDEN KAROLINSKA INST DEPT CLIN NEUROSCI & FAMILY MED SECT GERIATR STOCKHOLM SWEDEN GOTHENBURG UNIV DEPT PSYCHOL GOTHENBURG SWEDEN
SP  - 503
EP  - 514
JF  - Brain
VL  - 120
IS  - Part 3
N2  - PET and markers for the pre- and postsynaptic neurons were used to study the dopamine system in vivo in Huntington's disease. The radioligands used were [C-11]SCH 23390 for D1-receptors, [C- 11]raclopride for D2-receptors and [C-11]beta-CIT for dopamine transporters. Five patients with Huntington's disease and five matched controls were recruited. Brain anatomy was examined by MRI. The findings in patients were as follows. Postsynaptic D1- and D2-receptor densities were similarly reduced in the striatum. A reduction in D1-receptor density was shown in the temporal cortex; it draws attention to the cortical degeneration in relation to the cognitive deficits observed in Huntington's disease. The reduction of D1- and D2-receptor binding potentials in the striatum correlated significantly with increasing duration of illness. The correlation between the duration of illness and decline of D1- and D2-receptors make these receptors valuable as quantitative markers for the Huntington's disease degenerative process. Besides postsynaptic changes, a significant 50% decrease of [C-11]beta-CIT binding to the dopamine transporter was found in the striatum. A reduced striatal bloodflow in Huntington's disease cannot be excluded and could account for a small part of the decrease in [C-11]beta-CIT binding. We suggest that the finding reflects a loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease.
ER  - 

TY  - JOUR
T1  - RELATIONSHIP BETWEEN SUBJECTIVE EFFECTS OF COCAINE AND DOPAMINE TRANSPORTER OCCUPANCY
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fischman,M.W.
A1  - Foltin,R.W.
A1  - Fowler,J.S.
A1  - Abumrad,N.N.
A1  - Vitkun,S.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - Pappas,N.
A1  - Hitzemann,R.
A1  - Shea,C.E.
Y1  - 1997///Apr 24
N1  - WV706-0053  [References: 24] Reprint available from: Volkow ND BROOKHAVEN NATL LAB DEPT MED UPTON, NY 11973 USA BROOKHAVEN NATL LAB DEPT CHEM UPTON, NY 11973 USA SUNY STONY BROOK DEPT PSYCHIAT STONY BROOK, NY 11794 USA SUNY STONY BROOK DEPT ANESTHESIOL STONY BROOK, NY 11794 USA COLUMBIA UNIV DEPT PSYCHIAT NEW YORK, NY 10032 USA N SHORE UNIV HOSP DEPT SURG MANHASSET, NY 11030 USA
SP  - 827
EP  - 830
JF  - Nature
VL  - 386
IS  - 6627
N2  - Cocaine is believed to work by blocking the dopamine transporter (DAT) and thereby increasing the availability of free dopamine within the brain(1-4). Although this concept is central to current cocaine research and to treatment development, a direct relationship between DAT blockade and the subjective effects of cocaine has not been demonstrated in humans. We have used positron emission tomography to determine what level of DAT occupancy is required to produce a subjective 'high' in human volunteers who regularly abuse cocaine. We report here that intravenous cocaine at doses commonly abused by humans (0.3-0.6 mg kg(-1)) blocked between 60 and 77% of DAT sites in these subjects. The magnitude of the self-reported high was correlated with the degree of DAT occupancy, and at least 47% of the transporters had to be blocked for subjects to perceive cocaine's effects. Furthermore, the time course for the high paralleled that of cocaine concentration within the striatum, a brain region implicated in the control of motivation and reward. This is the first demonstration in humans that the doses used by cocaine abusers lead to significant blockade of DAT, and that this blockade is associated with the subjective effects of cocaine. Although these findings provide justification to target the DAT for medication development they suggest that for drugs to be effective in blocking cocaine's effects they would have to be given at doses that achieve almost complete DAT occupancy.
ER  - 

TY  - JOUR
T1  - DECREASED STRIATAL DOPAMINERGIC RESPONSIVENESS IN DETOXIFIED COCAINE-DEPENDENT SUBJECTS
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - Hitzemann,R.
A1  - Chen
A1  - Dewey,S.L.
A1  - Pappas,N.
Y1  - 1997///Apr 24
N1  - WV706-0054
SP  - 830
EP  - 833
JF  - Nature
VL  - 386
IS  - 6627
N2  - Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens(1,2). But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine(3). Addicts showed reduced dopamine release in the striatum, the brain region where tile nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.
ER  - 

TY  - JOUR
T1  - THE METABOLIC ANATOMY OF TOURETTES-SYNDROME
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Antonini,A.
A1  - Kazumata,K.
A1  - Dhawan,V.
A1  - Budman,C.
A1  - Feigin,A.
Y1  - 1997///Apr
N1  - WU327-0024  [References: 44] Reprint available from: Eidelberg D N SHORE UNIV HOSP MOVEMENT DISORDERS CTR DEPT NEUROL 444 COMMUNITY DR MANHASSET, NY 11030 USA COLUMBIA UNIV COLL PHYS & SURG NEW YORK STATE PSYCHIAT INST DEPT PSYCHIAT MANHASSET, NY USA N SHORE UNIV HOSP DEPT PSYCHIAT MANHASSET, NY 11030 USA
SP  - 927
EP  - 934
JF  - Neurology
VL  - 48
IS  - 4
N2  - The functional brain networks underlying the clinical manifestations of Gilles de la Tourette's syndrome (TS) are currently unknown. To identify these networks, we studied TS patients and normal subjects with F-18-fluorodeoxyglucose (FDG) and PET employing a statistical model of regional metabolic covariation. We studied 10 TS patients (mean age, 41.5 +/- 12.7 years) who were either drug naive or medication free for at least 2 years. Ten normal volunteers (mean age, 42.5 +/- 11.5) served as controls. We used quantitative FDG/PET to calculate global, regional, and normalized rates of glucose metabolism (GMR, rCMRGlc, and rCMRGlc/GMR) in all subjects. The Scaled Subprofile Model (SSM) was used to identify specific patterns of regional metabolic covariation associated with TS. We found that global and regional metabolic rates were normal in TS. SSM analysis identified two TS-related brain networks. One pattern (15.8% variance accounted for, VAF) was characterized by covariate bilateral metabolic increases in lateral premotor and supplementary motor association cortices and in the midbrain. Individual patient expression of this pattern (subject score) was abnormally increased in the TS group (p < 0.01). A second pattern (10.5% VAF) was characterized by covariate decreases in caudate and thalamic metabolism associated with smaller reductions in lentiform and hippocampal metabolic activity. Subject scores for this pattern correlated with Tourette Syndrome Global Scale (TSGS) global ratings (r = 0.85, p < 0.005). We conclude that the metabolic landscape of TS is characterized by a nonspecific pattern of increased motor cortical activity identified in other hyperkinetic disorders. TS is also associated with a specific brain network characterized by a reduction in the activity of limbic basal ganglia-thalamocortical projection systems.
ER  - 

TY  - JOUR
T1  - EFFECTS OF DURATION OF EPILEPSY ON THE UNCOUPLING OF METABOLISM AND BLOOD FLOW IN COMPLEX PARTIAL SEIZURES
A1  - Breier,J.I.
A1  - Mullani,N.A.
A1  - Thomas,A.B.
A1  - Wheless,J.W.
A1  - Plenger,P.M.
A1  - Gould,K.L.
A1  - Papanicolaou,A.
A1  - Willmore,L.J.
Y1  - 1997///Apr
N1  - WU327-0043  [References: 36] Reprint available from: Breier JI UNIV TEXAS HLTH SCI CTR SCH MED TEXAS COMPREHENS EPILEPSY PROGRAM DEPT NEUROSURG HOUSTON, TX 77030 USA UNIV TEXAS HLTH SCI CTR TEXAS COMPREHENS EPILEPSY PROGRAM DEPT NEUROL HOUSTON, TX 77030 USA UNIV TEXAS HLTH SCI CTR TEXAS COMPREHENS EPILEPSY PROGRAM DEPT PEDIAT HOUSTON, TX 77030 USA UNIV TEXAS HLTH SCI CTR TEXAS COMPREHENS EPILEPSY PROGRAM DEPT INTERNAL MED HOUSTON, TX 77030 USA
SP  - 1047
EP  - 1053
JF  - Neurology
VL  - 48
IS  - 4
N2  - We derived interhemispheric asymmetry indices (AIs) in interictal glucose uptake and blood flow in the temporal lobes of patients with intractable complex partial seizures from F-18 and O-15 positron emission tomograms. All patients subsequently underwent either left (n = 16) and right (n = 18) temporal lobectomy. We determined the effects on AIs of clinical seizure variables, including duration of seizure disorder, age at seizure onset, frequency of complex partial seizures, history of secondary generalization, history of febrile seizures, and magnetic resonance imaging evidence for mesial temporal sclerosis. Duration of seizure disorder produced the only significant effects. Degree of interhemispheric asymmetry in both glucose uptake and blood flow increased with duration of seizure disorder. However, the rate of increase in asymmetry was significantly greater for glucose uptake than for blood flow. These results indicate that uncoupling of metabolism and blood flow is a progressive process that results from the differential response of glucose metabolism and blood flow to chronic seizure activity. The results also suggest that duration of seizure disorder may be an important variable to consider in the interpretation of PET studies for evaluation of seizure surgery candidates.
ER  - 

TY  - JOUR
T1  - PRESYNAPTIC AND POSTSYNAPTIC STRIATAL DOPAMINERGIC FUNCTION IN PATIENTS WITH MANGANESE INTOXICATION - A POSITRON EMISSION TOMOGRAPHY STUDY
A1  - Shinotoh,H.
A1  - Snow,B.J.
A1  - Chu,N.S.
A1  - Huang,C.C.
A1  - Lu,C.S.
A1  - Lee,C.
A1  - Takahashi,H.
A1  - Calne,D.B.
Y1  - 1997///Apr
N1  - WU327-0044  [References: 17] Reprint available from: Caine DB VANCOUVER HOSP & HLTH SCI CTR CTR NEURODEGENERAT DISORDERS PURDY PAVIL 2211 WESBROOK MALL VANCOUVER BC V6T 2B5 CANADA UNIV BRITISH COLUMBIA CTR NEURODEGENERAT DISORDERS VANCOUVER BC V5Z 1M9 CANADA CHANG GUNG MED COLL DEPT NEUROL TAIPEI TAIWAN MEM HOSP TAIPEI TAIWAN
SP  - 1053
EP  - 1056
JF  - Neurology
VL  - 48
IS  - 4
N2  - We performed PET on four patients with chronic industrial Mn intoxication; presynaptic and postsyn aptic dopaminergic function were measured with [F-18]6-fluoro-L-dopa (6FD) and [C- 11]raclopride (RAC). All patients had a rigid-akinetic syndrome; they had no sustained benefit from L-dopa. Influx constants (Ki) of 6FD were normal in the caudate and putamen. RAC binding was mildly reduced in the caudate and normal in the putamen. We conclude that nigrostriatal dopaminergic dysfunction is not responsible for the parkinsonism caused by chronic Mn intoxication. The pathology is likely to be downstream of the dopaminergic projection.
ER  - 

TY  - JOUR
T1  - A DIRECT COMPARISON OF PET ACTIVATION AND ELECTROCORTICAL STIMULATION MAPPING FOR LANGUAGE LOCALIZATION
A1  - Bookheimer,S.Y.
A1  - Zeffiro,T.A.
A1  - Blaxton,T.
A1  - Malow,B.A.
A1  - Gaillard,W.D.
A1  - Sato,S.
A1  - Kufta,C.
A1  - Fedio,P.
A1  - Theodore,W.H.
Y1  - 1997///Apr
SP  - 1056
EP  - 1065
JF  - Neurology
VL  - 48
IS  - 4
N2  - Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET, We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation, Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.
ER  - 

TY  - JOUR
T1  - Human cortical plasticity - Functional recovery with mirror movements
A1  - Nirkko,A.C.
A1  - Rosler,K.M.
A1  - Ozdoba,C.
A1  - Heid,O.
A1  - Schroth,G.
A1  - Hess,C.W.
Y1  - 1997///Apr
N1  - WU327-0051 Cortical plasticity of the human brain permits functional recovery after brain injury even in the absence of neuronal recovery. We report the combined evaluation, including electrophysiology and functional magnetic resonance imaging, of the pattern of cortical and cerebellar reorganization, in a patient with mirror movements as a sequel of perinatal unilateral brain injury. Recovery resulted in motor control by the healthy hemisphere using direct ipsilateral corticospinal projections and the contralateral cerebellum. [References: 15] Reprint available from: Nirkko AC UNIV HOSP BERN DEPT NEUROL CH- 3010 BERN SWITZERLAND UNIV HOSP BERN DEPT NEURORADIOL CH-3010 BERN SWITZERLAND UNIV HOSP BERN ENMC STN CH-3010 BERN SWITZERLAND
SP  - 1090
EP  - 1093
JF  - Neurology
VL  - 48
IS  - 4
ER  - 

TY  - JOUR
T1  - Retrospective fusion of radiographic and MR data for localization of subdural electrodes
A1  - Grzeszczuk,R.
A1  - Tan,K.K.
A1  - Levin,D.N.
A1  - Pelizzari,C.A.
A1  - Hu,X.
A1  - Chen,G.T.
A1  - Beck,R.N.
A1  - Chen,C.T.
A1  - Cooper,M.
A1  - Milton,J.
A1  - et al.
Y1  - 1992///Sep-Oct
N1  - 92395219 Department of Radiology, University of Chicago Hospitals, IL 60637
SP  - 764
EP  - 773
JF  - Journal of Computer Assisted Tomography
VL  - 16
IS  - 5
N2  - Prior to epilepsy surgery, subdural electrodes are often implanted and monitored for a few days to identify the focus of abnormal electrical activity. During the implantation and subsequent brain resection, there may be uncertainty about the exact location of the electrodes with respect to features of brain anatomy such as specific gyral convolutions or lesions. In experiments with a phantom and patients, implanted electrodes were imaged with multiplanar skull radiographs (or CT scans). After retrospective registration with preimplantation MR data, the electrodes were mapped from these studies onto an MR-derived three-dimensional brain model. The resulting multimodality displays showed the relationship of the electrodes to brain anatomy. In one patient the position of each electrode with respect to a metabolic lesion was also displayed by mapping preimplantation PET data onto the same brain model. This new display of electrode positions may strengthen the interpretation of subdural electrical recordings and thereby reduce uncertainty in planning the resection of epileptic tissue
ER  - 

TY  - JOUR
T1  - Retrospective geometric correlation of MR, CT, and PET images
A1  - Levin,D.N.
A1  - Pelizzari,C.A.
A1  - Chen,G.T.
A1  - Chen,C.T.
A1  - Cooper,M.D.
Y1  - 1988///Dec
N1  - 89042832 Department of Radiology, University of Chicago Hospitals, IL 60637
SP  - 817
EP  - 823
JF  - Radiology
VL  - 169
IS  - 3
N2  - Magnetic resonance imaging, computed tomographic, and positron emission tomographic studies of the brain provide complementary information, and many patients undergo more than one of these studies during the course of their diagnostic workup and treatment. A new technique for quantitative geometric correlation of such studies makes it possible to create integrated multimodality images by mapping features from one image onto an image obtained with another modality. The coordinate transformation between any pair of images is found by a semiautomatic algorithm for matching models of the patient's external surface as depicted in the two data sets. The resultant hybrid images, which combine complementary features of different studies, are often more useful for diagnosis and treatment planning than are the original single-modality images. The algorithm can also be used for spatial registration of baseline studies with follow-up images created with the same modality, which allows tracking of a lesion to detect subtle interval changes in size and shape. This technique can be applied to images acquired in routine clinical practice, since it is completely retrospective and does not necessitate special positioning or landmarking of the patient
ER  - 

TY  - JOUR
T1  - PET WITH 1-[1-CARBON-11]-TYROSINE TO VISUALIZE TUMORS AND MEASURE PROTEIN SYNTHESIS RATES
A1  - Kole,A.C.
A1  - Pruim,J.
A1  - Nieweg,O.E.
A1  - Vanginkel,R.J.
A1  - Hoekstra,H.J.
A1  - Koops,H.S.
A1  - Vaalburg,W.
Y1  - 1997///Feb
N1  - WF888-0014 [References: 28] Reprint available from: Kole AC UNIV GRONINGEN HOSP PET CTR POB 30001 NL-9700 RB GRONINGEN NETHERLANDS UNIV GRONINGEN HOSP DEPT SURG ONCOL NL-9700 RB GRONINGEN NETHERLANDS NETHERLANDS CANC INST DEPT SURG AMSTERDAM NETHERLANDS
SP  - 191
EP  - 195
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 2
N2  - We studied the potential of PET with L-[1-C-11]-tyrosine (TYR) to visualize tumors outside the central nervous system and to quantify their protein synthesis rates (PSRs). Methods: Twenty- two patients suspected of having a malignant tumor underwent a PET study with TYR before biopsy, The PSR in nanomoles per milliliter tumor tissue per minute as well as the PSR in contralateral normal tissue, standardized uptake values (SUVs) and tumor-to-nontumor-ratios (T/N ratios) were calculated. Results: Fifteen of the 16 malignancies (94%) were correctly visualized as a hot spot. A chondrosarcoma of the sacrum was not visualized. Of the six patients with benign lesions, cold spots were correctly identified in four (67%), A benign schwannoma and an intramuscular hemangioma of the forearm were visualized as hot spots. PSR in tumor tissue was higher than in the corresponding contralateral normal tissues. PSR and SUV in malignant tumors were higher than in benign tumors. Conclusion: TYR appears to be a good tracer for imaging malignancies. The PSR, which was higher in malignant tumors than in normal tissue and the studied benign lesions, could be quantified and correlated with the SUV.
ER  - 

TY  - JOUR
T1  - INTRACRANIAL ADMINISTRATION OF ADENOVIRUS EXPRESSING HSV-TK IN COMBINATION WITH GANCICLOVIR PRODUCES A DOSE-DEPENDENT, SELF- LIMITING INFLAMMATORY RESPONSE
A1  - Smith,J.G.
A1  - Raper,S.E.
A1  - Wheeldon,E.B.
A1  - Hackney,D.
A1  - Judy,K.
A1  - Wilson,J.M.
A1  - Eck,S.L.
Y1  - 1997///May 20
N1  - XC072-0007 Replication-defective adenovirus expressing the herpes simplex thymidine kinase gene (H5.010RSVtk) may be useful in treating human gliomas. To determine the toxicity of this therapeutic strategy, we injected H5.010RSVtk stereotactically into the normal brain of Wistar rats, cotton rats, and rhesus monkeys in conjunction with systemic ganciclovir (GCV) at 10 mg/kg per day. In the Wistar rat, 5.7 x 10(9) pfu resulted in histopathologic injury consisting of localized necrosis, mild gliosis, marked malacia, and focal astrocytosis; however, 1.0 x 10(8) pfu resulted in only mild gliosis and trace meningitis and approximates a ''no toxic effect'' dose. A dose of 1.0 x 10(9) pfu in both adenoviral immune and adenoviral naive cotton rats resulted in similar findings. In the rhesus monkey, doses ranging from 1.4 x 10(8) pfn to 1.5 x 10(11) pfu resulted in localized gliosis, necrosis, perivascular cuffing, meningitis, and roughly correlated in severity with increasing dose. No histologic evidence of toxicity was found in non-central nervous system (CNS) tissues, and no virus could be cultured from cerebrospinal fluid (CSF), blood, urine, and stool samples. All animals survived to prescribed end points without signs of general toxicity or neurologic symptoms, except for 2 of the rhesus monkeys, one of which became febrile and the other of which developed a grand mal seizure (both subsequently resolved). These toxicology studies define the parameters for developing a phase I clinical trial. [References: 37] Reprint available from: Eck SL UNIV PENN STELLAR CHANCE LABS ROOM 409 422 CURIE BLVD PHILADELPHIA, PA 19104 USA UNIV PENN MED CTR DEPT MED DIV HEMATOL ONCOL PHILADELPHIA, PA 19104 USA UNIV PENN MED CTR INST HUMAN GENE THERAPY PHILADELPHIA, PA 19104 USA HOFFMANN LA ROCHE INC NUTLEY, NJ 07110 USA UNIV PENN MED CTR DEPT RADIOL PHILADELPHIA, PA 19104 USA UNIV PENN MED CTR DEPT SURG DIV NEUROSURG PHILADELPHIA, PA 19104 USA
SP  - 943
EP  - 954
JF  - Human Gene Therapy
VL  - 8
IS  - 8
ER  - 

TY  - JOUR
T1  - HYPOFRONTALITY IN SCHIZOPHRENIA - DISTRIBUTED DYSFUNCTIONAL CIRCUITS IN NEUROLEPTIC-NAIVE PATIENTS
A1  - Andreasen,N.C.
A1  - Oleary,D.S.
A1  - Flaum,M.
A1  - Nopoulos,P.
A1  - Watkins,G.L.
A1  - Ponto,L.L.B.
A1  - Hichwa,R.D.
Y1  - 1997///Jun 14
N1  - XE065-0010  [References: 30] Reprint available from: Andreasen NC UNIV IOWA COLL MED MENTAL HLTH CLIN RES CTR IOWA CITY, IA 52242 USA UNIV IOWA COLL MED PET IMAGING CTR IOWA CITY, IA 52242 USA UNIV IOWA HOSP & CLIN IOWA CITY, IA 52242 USA
SP  - 1730
EP  - 1734
JF  - Lancet
VL  - 349
IS  - 9067
N2  - Background There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). Methods We studied 17 neuroleptic-native patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. Findings An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. Interpretation These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.
ER  - 

TY  - JOUR
T1  - FUNCTIONAL NEUROANATOMY OF HUMAN SLOW WAVE SLEEP
A1  - Maquet,P.
A1  - Degueldre,C.
A1  - Delfiore,G.
A1  - Aerts,J.
A1  - Peters,J.M.
A1  - Luxen,A.
A1  - Franck,G.
Y1  - 1997///Apr 15
N1  - WX903-0017  [References: 74] Reprint available from: Maquet P UNIV LIEGE CYCLOTRON RES CTR B 30 B-4000 LIEGE BELGIUM CTR HOSP UNIV LIEGE DEPT NEUROL LIEGE BELGIUM
SP  - 2807
EP  - 2812
JF  - Journal of Neuroscience
VL  - 17
IS  - 8
N2  - The distribution of regional cerebral blood flow (rCBF) was estimated during sleep and wakefulness by using (H2O)-O-15 positron emission tomography (PET) and statistical parametric mapping. A group analysis on 11 good sleepers (8 with steady slow wave sleep, SWS) showed a significant negative correlation between the occurrence of SWS and rCBF in dorsal pens and mesencephalon, thalami, basal ganglia, basal forebrain/hypothalamus, orbitofrontal cortex, anterior cingulate cortex, precuneus, and, on the right side, in a region that follows the medial aspect of the temporal lobe. Given the known decrease in global cerebral blood flow levels during SWS, these negative correlations suggest that rCBF is decreased significantly more in these cerebral areas than in the rest of the brain. The marked rCBF decreases in the pens, mesencephalon, thalamic nuclei, and basal forebrain reflect their close implication in the generation of SWS rhythms. The influence of these rhythms on the telencephalon usually are thought to be global and homogeneous. In contrast, our results show that rCBF is decreased more in some cortical areas (especially in orbitofrontal cortex) than in the rest of the cortex. We hypothesize that cellular processes taking place during SWS might be modulated differently in these regions. Given the functions of the ventromedial frontal areas, we surmise that SWS might be particularly critical for the adaptation of behavior to environmental pressures. This hypothesis is supported indirectly by results of sleep deprivation experiments.
ER  - 

TY  - JOUR
T1  - FUNCTIONAL NEUROIMAGING OF CORTICAL DYSFUNCTION IN ALCOHOLIC KORSAKOFFS SYNDROME
A1  - Paller,K.A.
A1  - Acharya,A.
A1  - Richardson,B.C.
A1  - Plaisant,O.
A1  - Shimamura,A.P.
A1  - Reed,B.R.
A1  - Jagust,W.J.;
Y1  - 1997///Mar
N1  - WW374-0008 [References: 78] Reprint available from: Paller KA NORTHWESTERN UNIV DEPT PSYCHOL 2029 SHERIDAN RD EVANSTON, IL 60208 USA LAWRENCE BERKELEY LAB BERKELEY, CA USA UNIV CALIF DAVIS DAVIS, CA 95616 USA UNIV CALIF BERKELEY BERKELEY, CA 94720 USA
SP  - 277
EP  - 293
JF  - Journal of Cognitive Neuroscience
VL  - 9
IS  - 2
N2  - Many neuropsychological investigations of human memory have focused on the amnesic deficits of alcoholic Korsakoff's syndrome. Structural neuroimaging suggests that the syndrome results from midline diencephalic damage, but functional neuroimaging has the potential to reveal additional neuropathology that may be responsible for cognitive dysfunction. Accordingly, high-resolution positron emission tomography (PET) was used to measure regional cerebral metabolic rates for glucose utilization in five alcoholic Korsakoff patients and nine alcoholic control subjects. Results from a continuous recognition test administered during the radiotracer uptake period indicated that all subjects performed normally with respect to immediate memory, whereas Korsakoff patients demonstrated a marked memory impairment in delayed recognition. PET results from the Korsakoff group showed a widespread decline in glucose metabolism in frontal, parietal, and cingulate regions, suggesting that these functional abnormalities in the cerebral cortex contribute to the memory impairment. Hippocampal glucose metabolism did not differ between the groups. Thus, the evidence did not support the hypothesis that parallel brain dysfunctions are responsible for the similar amnesic symptomatology after hippocampal and diencephalic damage. We hypothesize that the amnesic dysfunction of Korsakoff's syndrome depends on a disruption of thalamocortical interactions that mediate a function critical for normal memory storage.
ER  - 

TY  - JOUR
T1  - Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimers disease
A1  - Iyo,M.
A1  - Namba,H.
A1  - Fukushi,K.
A1  - Shinotoh,H.
A1  - Nagatsuka,S.
A1  - Suhara,T.
A1  - Sudo,Y.
A1  - Suzuki,K.
A1  - Irie,T.
Y1  - 1997///Jun 21
N1  - XF735-0012 Background [References: 28] Reprint available from: Irie T NATL INST RADIOL SCI DIV CLIN RES INAGE KU 4-9-1 ANAGAWA CHIBA 263 JAPAN NATL INST RADIOL SCI DIV CLIN RES INAGE KU CHIBA 263 JAPAN NATL CTR NEUROL & PSYCHIAT NATL INST MENTAL HLTH CHIBA JAPAN CHIBA CANC CTR HOSP DIV NEUROL SURG CHIBA JAPAN CHIBA UNIV SCH MED DEPT NEUROL CHIBA 280 JAPAN DAIICHI PURE CHEM CO LTD TOKAI RES LABS IBARAKI OSAKA JAPAN
SP  - 1805
EP  - 1809
JF  - Lancet
VL  - 349
IS  - 9068
N2  - Acetylcholinesterase activity, a marker for degeneration of the central cholinergic system, has consistently been reported, in necropsy brain studies, to be reduced in the cerebral cortex of patients with Alzheimer's disease. We have shown regional acetylcholinesterase activity in vivo in rodent and primate brains with radioactive acetylcholine analogues. In the present study, we used one of the analogues to map acetylcholinesterase activity in the brains of living people. Methods Positron emission tomography (PET) and a radiolabelled acetylcholine analogue with high hydrolytic specificity to acetylcholinesterase [C-11]N-methyl-4-piperidyl acetate (MP4A), was used in eight elderly healthy controls and five patients with Alzheimer's disease who had mild dementia. All participants were given an intravenous injection of [C-11]MP4A and then sequential patterns of radioactivity in various brain regions were obtained by PET. Time courses of [C-11]MP4A concentration in arterial blood were also measured to obtain an input function. A three- compartment model was used to estimate regional acetylcholinesterase activity in the brain. Findings The estimated acetylcholinesterase distribution in the brain of the control participants agreed with the acetylcholinesterase distribution at necropsy. All patients with Alzheimer's disease had multiple cortical regions with a reduced estimated acetylcholinesterase activity in comparison with control participants. The reduction was more pronounced in the parietotemporal cortex, with an average reduction rate of 31% in temporal and 38% in parietal cortex, and less pronounced in other cortical lesions (19% in frontal, 24% in occipital, and 20% in sensorimotor cortex), Each patient was found to have at least two cortical regions with significantly reduced acetylcholinesterase activity. Interpretation The method we describe for non-invasive in-vivo detection of regional acetylcholinesterase changes in the living human brain that is feasible for biochemical assessment of Alzheimer's disease.
ER  - 

TY  - JOUR
T1  - Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET
A1  - Okubo,Y.
A1  - Suhara,T.
A1  - Suzuki,K.
A1  - Kobayashi,K.
A1  - Inoue,O.
A1  - Terasaki,O.
A1  - Someya,Y.
A1  - Sassa,T.
A1  - Sudo,Y.
A1  - Matsushima,E.
A1  - Iyo,M.
A1  - Tateno,Y.
A1  - Toru,M.
Y1  - 1997///Feb 13
N1  - WH294-0050  [References: 24] Reprint available from: Okubo Y TOKYO MED & DENT UNIV SCH MED DEPT NEUROPSYCHIAT BUNKYO KU 1-5-45 YUSHIMA TOKYO 113 JAPAN NATL INST RADIOL SCI DIV ADV TECHNOL MED IMAGING INAGE KU CHIBA 263 JAPAN
SP  - 634
EP  - 636
JF  - Nature
VL  - 385
IS  - 6617
N2  - Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R)(1). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics(2-5), raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex(6), has been implicated in the control of working memory(7, 8), and working memory dysfunction is a prominent feature of schizophrenia(9). We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test(10). We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.
ER  - 

TY  - JOUR
T1  - INTRAVENOUS THROMBOLYSIS FOR ACUTE STROKE [Review]
A1  - Lyden,P.D.
A1  - Grotta,J.C.
A1  - Levine,S.R.
A1  - Marler,J.R.
A1  - Frankel,M.R.
A1  - Brott,T.G.
Y1  - 1997///Jul
N1  - XK353-0004 Reprint available from: Lyden PD 3350 LA JOLLA VILLAGE DR SAN DIEGO, CA 92161 USA UNIV CALIF SAN DIEGO SCH MED DEPT NEUROSCI SAN DIEGO, CA 92103 USA VET ADM MED CTR DEPT NEUROL SAN DIEGO, CA 92161 USA UNIV TEXAS DEPT NEUROL HOUSTON, TX USA HENRY FORD HOSP & HLTH SCI CTR DEPT NEUROL CTR STROKE RES DETROIT, MI USA NINCDS BETHESDA, MD 20892 USA EMORY UNIV SCH MED DEPT NEUROL ATLANTA, GA 30322 USA UNIV CINCINNATI MED CTR CINCINNATI, OH 45267 USA
SP  - 14
EP  - 20
JF  - Neurology
VL  - 49
IS  - 1
ER  - 

TY  - JOUR
T1  - CEREBRAL METABOLISM IN FATAL FAMILIAL INSOMNIA - RELATION TO DURATION, NEUROPATHOLOGY, AND DISTRIBUTION OF PROTEASE-RESISTENT PRION PROTEIN
A1  - Cortelli,P.
A1  - Perani,D.
A1  - Parchi,P.
A1  - Grassi,F.
A1  - Montagna,P.
A1  - Demartin,M.
A1  - Castellani,R.
A1  - Tinuper,P.
A1  - Gambetti,P.
A1  - Lugaresi,E.
A1  - Fazio,F.
Y1  - 1997///Jul
N1  - XK353-0020 We used [F-18]-2-fluoro-2-deoxy-D-glucose (FDG) and PET to study regional cerebral glucose utilization in seven patients with fatal familial insomnia (FFI), an inherited prion disease with a mutation at codon 178 of the prion protein gene. Four patients were methionine/methionine homozygotes at codon 129 (symptom duration, 8.5 +/- 1 months) and three were methionine/valine (MET/VAL(129)) heterozygotes (symptom duration, 35 +/- 11 months). A severely reduced glucose utilization of the thalamus and a mild hypometabolism of the cingulate cortex were found in all FFI patients. In six subjects the brain hypometabolism also affected the basal and lateral frontal cortex, the caudate nucleus, and the middle and inferior temporal cortex. Comparison between homozygous or heterozygous patients at codon 129 showed that the hypometabolism was more widespread in the MET/VAL(129) group, which had a significantly longer symptom duration at the time of [F-18] FDG PET study. Comparison between neuropathologic and [F-18] FDG PET findings in six patients showed that areas with neuronal loss were also hypometabolic. However, cerebral hypometabolism was more widespread than the histopathologic changes and significantly correlated with the presence of protease-resistent prion protein (PrPres). Our findings indicate that hypometabolism of the thalamus and cingulate cortex is the hallmark of FFI, while the involvement of other brain regions depends on the duration of symptoms and some unknown factors specific to each patient. The present data also support the notion that PrPres formation is the cause of neuronal dysfunction in prion diseases. [References: 36] Reprint available from: Cortelli P NEUROL CLIN VIA U FOSCOLO 7 I- 40123 BOLOGNA ITALY UNIV BOLOGNA NEUROL INST I-40126 BOLOGNA ITALY UNIV MILAN SAN RAFFAELE SCI INST CNR INB I-20122 MILAN ITALY CASE WESTERN RESERVE UNIV INST PATHOL DIV NEUROPATHOL CLEVELAND, OH 44106 USA
SP  - 126
EP  - 133
JF  - Neurology
VL  - 49
IS  - 1
ER  - 

TY  - JOUR
T1  - REDUCED GLUCOSE METABOLISM IN THE FRONTAL CORTEX AND BASAL GANGLIA OF MULTIPLE SCLEROSIS PATIENTS WITH FATIGUE - A F-18- FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY STUDY
A1  - Roelcke,U.
A1  - Kappos,L.
A1  - Lechnerscott,J.
A1  - Brunnschweiler,H.
A1  - Huber,S.
A1  - Ammann,W.
A1  - Plohmann,A.
A1  - Dellas,S.
A1  - Maguire,R.P.
A1  - Missimer,J.
A1  - Radu,E.W.
A1  - Steck,A.
A1  - Leenders,K.L.
Y1  - 1997///Jun
N1  - XE091-0017  [References: 43] Reprint available from: Leenders KL PAUL SCHERRER INST PET PROGRAM CH-5232 VILLIGEN SWITZERLAND PAUL SCHERRER INST PET PROGRAM CH-5232 VILLIGEN SWITZERLAND UNIV BASEL HOSP DEPT NEUROL CH-4031 BASEL SWITZERLAND UNIV BASEL HOSP DEPT NEURORADIOL CH- 4031 BASEL SWITZERLAND UNIV ZURICH HOSP DEPT NEUROL CH-8091 ZURICH SWITZERLAND
SP  - 1566
EP  - 1571
JF  - Neurology
VL  - 48
IS  - 6
N2  - To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMRGlu) in 47 MS patients using PET and F-18-fluorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mu mol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the light prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.
ER  - 

TY  - JOUR
T1  - [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold
A1  - Guttman,M.
A1  - Burkholder,J.
A1  - Kish,S.J.
A1  - Hussey,D.
A1  - Wilson,A.
A1  - Dasilva,J.
A1  - Houle,S.
Y1  - 1997///Jun
N1  - XE091-0019  [References: 21] Reprint available from: Guttman M CLARKE INST PSYCHIAT HUMAN NEUROCHEM PATHOL LAB DIV NEUROL 250 COLL ST TORONTO ON M5T 1R8 CANADA CLARKE INST PSYCHIAT PET CTR TORONTO ON M5T 1R8 CANADA UNIV TORONTO FAC MED TORONTO ON CANADA
SP  - 1578
EP  - 1583
JF  - Neurology
VL  - 48
IS  - 6
N2  - To estimate the threshold of nigrostriatal dysfunction required for symptomatic Parkinson's disease (PD), we employed [C-11]RTI- 32 and PET to study the dopamine transporter in striatal subdivisions of 11 L-dopa-naive patients with very early parkinsonism. As compared with the controls (N = 10), the PD group had on the side contralateral to the maximal clinical symptoms, significantly reduced binding in the posterior putamen (-56%) and anterior putamen (-28%), with the reduction in caudate (-12%) not significantly different. To the extent that dopamine transporter binding accurately reflects the number of nigrostriatal dopamine nerve terminals, these findings suggest that the clinical threshold for PD in the middle-age human is approximately 50% loss of dopaminergic innervation to the posterior putamen. Our data also suggest that damage to the putamen component of the striatum is sufficient far the clinical expression of PD.
ER  - 

TY  - JOUR
T1  - EVIDENCE FOR LATERAL PREMOTOR AND PARIETAL OVERACTIVITY IN PARKINSONS-DISEASE DURING SEQUENTIAL AND BIMANUAL MOVEMENTS - A PET STUDY
A1  - Samuel,M.
A1  - Ceballos-Baumann,A.O.
A1  - Blin,J.
A1  - Uema,T.
A1  - Boecker,H.
A1  - Passingham,R.E.
A1  - Brooks,D.J.
Y1  - 1997///Jun
N1  - XK255-0005  [References: 54] Reprint available from: Samuel M HAMMERSMITH HOSP MRC CYCLOTRON UNIT DU CANE RD LONDON W12 0NN ENGLAND INST NEUROL WELLCOME DEPT COGNIT NEUROL LONDON WC1N 3BG ENGLAND TECH UNIV MUNICH NEUROL KLIN D-8000 MUNICH GERMANY NATL HOSP MENTAL NERVOUS & MUSCULAR DISORDERS TOKYO JAPAN
SP  - 963
EP  - 976
JF  - Brain
VL  - 120
IS  - Part 6
N2  - Patients with Parkinson's disease have great difficulty in performing sequential and bimanual movements. We used (H2O)-O-15 PET to study the regional cerebral blood flow associated with performance of sequential finger movements made unimanually and bimanually in a group of Parkinson's disease patients and a group of control volunteers. In controls, sequential finger movements led to activation of the contralateral motor cortex and inferior parietal cortex (Brodmann area 40), the lateral premotor cortex and bilateral supplementary motor area. No prefrontal activation was seen. Sequential finger movements in the Parkinson's disease group were associated with a similar pattern of activation but there was relative impairment of activation in the mesial frontal and prefrontal areas. A novel finding was the presence of relative overactivity in the lateral premotor and inferolateral parietal regions. We conclude that in Parkinson's disease there is a switch from the use of striato-mesial frontal to parietal- lateral premotor circuits in order to facilitate performance of complex finger movements.
ER  - 

TY  - JOUR
T1  - ANTERIOR CINGULATE AND MOTOR NETWORK METABOLIC IMPAIRMENT IN PROGRESSIVE SUPRANUCLEAR PALSY
A1  - Salmon,E.
A1  - Vanderlinden,M.
A1  - Franck,G.
Y1  - 1997///Apr
N1  - WX697-0001  (C) 1997 Academic Press. [References: 52] Reprint available from: Salmon E UNIV LIEGE CYCLOTRON RES CTR B- 4000 LIEGE BELGIUM UNIV LIEGE DEPT NEUROL B-4000 LIEGE BELGIUM UNIV LIEGE DEPT NEUROPSYCHOL B-4000 LIEGE BELGIUM
SP  - 173
EP  - 178
JF  - Neuroimage
VL  - 5
IS  - 3
N2  - Progressive supranuclear palsy is the prototype of subcortical dementia. Using positron emission tomography and statistical parametric mapping, we compared the glucose metabolic pattern obtained in this subcortical dementia to that observed in elderly healthy controls and in Alzheimer's disease, the prototype of cortical dementia. Progressive supranuclear palsy was characterized by a relative decrease of metabolism in anterior cingulate, adjacent supplementary motor area, precentral cortex, middle prefrontal cortex, midbrain tegmentum, globus pallidus, and ventrolateral and dorsomedial nuclei of thalamus. The data in progressive supranuclear palsy highlight predominant metabolic impairment in brain structures engaged in response selection, in attention for action, and in motor networks.
ER  - 

TY  - JOUR
T1  - Combining spatial extent and peak intensity to test for activations in functional imaging
A1  - Poline,J.B.
A1  - Worsley,K.J.
A1  - Evans,A.C.
A1  - Friston,K.J.
Y1  - 1997///Feb
N1  - WT243-0001 Within the framework of statistical mapping, there are up to now only two tests used to assess the regional significance in functional images. One is based on the magnitude of the foci and tends to detect high intensity signals, while the second is based on the spatial extent of regions defined by a simple thresholding of the statistical map, a test that is more sensitive to extended signals, The aim of this paper is to combine the two tests into a single test that is more sensitive to a wider range of signals, This combined test is based on an analytical approximation of the distribution of these two parameters (size and height) and is applied in the context of statistical maps. The risk of error in noise-only 2D or 3D volumes is assessed under a wide range of experimental conditions obtained by varying both the resolution of the map and the threshold at which clusters are defined, In addition, we have investigated this new test on simulated signals, and applied it to an experimental PET dataset. The experimental risk of error is close to the predicted one, and the overall sensitivity increases when analyzing a volume containing different types of signals. (C) 1997 Academic Press. [References: 15] Reprint available from: Poline JB INST NEUROL WELLCOME DEPT COGNIT NEUROL QUEEN SQ LONDON WC1N 3BG ENGLAND MCGILL UNIV DEPT MATH & STAT MONTREAL PQ CANADA MCGILL UNIV MONTREAL NEUROL INST MONTREAL PQ CANADA
SP  - 83
EP  - 96
JF  - Neuroimage
VL  - 5
IS  - 2
ER  - 

TY  - JOUR
T1  - MAPPING HISTOLOGY TO METABOLISM - COREGISTRATION OF STAINED WHOLE-BRAIN SECTIONS TO PREMORTEM PET IN ALZHEIMERS DISEASE
A1  - Mega,M.S.
A1  - Chen,S.S.
A1  - Thompson,P.M.
A1  - Woods,R.P.
A1  - Karaca,T.J.
A1  - Tiwari,A.
A1  - Vinters,H.V.
A1  - Small,G.W.
A1  - Toga,A.W.
Y1  - 1997///Feb
N1  - WT243-0005  (C) 1997 Academic Press. [References: 32] Reprint available from: Mega MS UNIV CALIF LOS ANGELES SCH MED DEPT NEUROL LAB NEUROIMAGING DIV BRAIN MAPPING LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED DEPT PATHOL & LAB MED SECT NEUROPATHOL LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED DEPT PSYCHIAT & BIOBEHAV SCI LOS ANGELES, CA 90024 USA UNIV CALIF LOS ANGELES SCH MED ALZHEIMERS DIS CTR LOS ANGELES, CA 90024 USA
SP  - 147
EP  - 153
JF  - Neuroimage
VL  - 5
IS  - 2
N2  - The association between [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) counts obtained 8 h before death and neurofibrillary tangle (NFT) staining density in a patient with Alzheimer's disease (AD) was evaluated. In our patient FDG- PET counts were globally decreased with a greater focal deficit in the left medial temporal region independent of volume loss. After death, whole-brain sections derived from cryomacrotome sectioning were stained for NFTs by the Gallyas method and elastically warped into their native space enabling registration with premortem FDG-PET data. Gallyas staining density was localized to the paralimbic cortex of the basal forebrain, medial temporal, and orbital frontal regions. The poor correlation between NFT staining density and hypometabolism on FDG-PET implicates alternate mechanisms underlying the metabolic defect in AD.
ER  - 

TY  - JOUR
T1  - A PET follow-up study of recovery after stroke in acute aphasics
A1  - Cappa,S.F.
A1  - Perani,D.
A1  - Grassi,F.
A1  - Bressi,S.
A1  - Alberoni,M.
A1  - Franceschi,M.
A1  - Bettinardi,V.
A1  - Todde,S.
A1  - Fazio,F.
Y1  - 1997///Jan
N1  - 97148066 Department of Neurology, University of Brescia, Italy  50-99-7 (Glucose)
SP  - 55
EP  - 67
JF  - Brain & Language
VL  - 56
IS  - 1
N2  - The neural correlates of recovery from aphasia are largely unknown. Several different sources of evidence, from clinical studies to neurophysiological investigations, have suggested a contribution of the contralateral, undamaged hemisphere in recovery from aphasia. Eight patients with unilateral left hemispheric stroke were submitted to a standard language examination and to a [18F]FDG PET study in the recent phase after stroke (within 2 weeks) and 6 months later. All patients had a substantial recovery of specific aspects of language functions at the follow-up. Analysis of regional glucose metabolism showed hypometabolism in structurally unaffected regions both in the left and in the right hemisphere (diaschisis), in the acute stage. Glucose metabolism increased significantly on both sides in all patients at the second PET study. Regional analysis showed significant positive correlations between changes in metabolic values in several cortical and subcortical regions in the right hemisphere and changes in language performance at follow-up. The present findings show that an extensive, bihemispheric depression of metabolism is found in the acute stage after stroke in aphasic patients. Language recovery in the first months after aphasia onset is associated with regression of functional depression (diaschisis) in structurally unaffected regions, in particular in the right hemisphere
ER  - 

TY  - JOUR
T1  - Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers
A1  - Breier,A.
A1  - Malhotra,A.K.
A1  - Pinals,D.A.
A1  - Weisenfeld,N.I.
A1  - Pickar,D.
Y1  - 1997///Jun
N1  - XA587-0013 Objective:  [References: 45] Reprint available from: Breier A NIMH EXPT THERAPEUT BRANCH BLDG 10 RM 4N212 9000 ROCKVILLE PIKE ROCKVILLE, MD 20892 USA
SP  - 805
EP  - 811
JF  - American Journal of Psychiatry
VL  - 154
IS  - 6
N2  - Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor, such as phencyclidine and ketamine, produce an acute psychotic state in normal individuals that resembles some symptoms of schizophrenia. The aim of this study was to determine which brain regions are involved in NMA receptor-mediated psychosis. Method: Positron emission tomography with [F- 18]fluorodeoxyglucose was used to determine cerebral metabolic activity in 17 healthy volunteers while an acute psychotic state was induced simultaneously by the administration of subanesthetic doses of ketamine. Results: Ketamine produced focal increases in metabolic activity in the prefrontal cortex and an acute psychotic state. A change in one psychotic symptom, conceptual disorganization, was significantly related to prefrontal activation. Conclusions: These data suggest that the prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis.
ER  - 

TY  - JOUR
T1  - Preoperative activation and intraoperative stimulation of language-related areas in glioma patients
A1  - Herholz,K.
A1  - Reulen,H.J.
A1  - von Stockhausen,H.M.
A1  - Thiel,A.
A1  - Ilmberger,J.
A1  - Kessler,J.
A1  - Eisner,W.
A1  - Yousry,T.A.
A1  - Heiss,W.-D.
Y1  - 1997///
SP  - 1253
EP  - 1262
JF  - Neurosurgery
VL  - 41
ER  - 

TY  - JOUR
T1  - Performance of a randomization test for single-subject 15O-water PET activation studies
A1  - Halber,M.
A1  - Herholz,K.
A1  - Wienhard,K.
A1  - Pawlik,G.
A1  - Heiss,W.-D.
Y1  - 1997///in
SP  - 1033
EP  - 1039
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 17
IS  - 10
ER  - 

TY  - JOUR
T1  - Cerebral networks and functional brain asymmetry. Evidence from regional metabolic changes during word repetition
A1  - Karbe,H.
A1  - Herholz,K.
A1  - Weber-Luxenburger,G.
A1  - Ghaemi,M.
A1  - Heiss,W.-D.
Y1  - 1998///in press
SP  - 108
EP  - 121
JF  - Brain & Language
VL  - 63
ER  - 

TY  - JOUR
T1  - LOW GLUCOSE METABOLISM DURING BRAIN STIMULATION IN OLDER DOWNS SYNDROME SUBJECTS AT RISK FOR ALZHEIMERS DISEASE PRIOR TO DEMENTIA
A1  - Pietrini,P.
A1  - Dani,A.
A1  - Furey,M.L.
A1  - Alexander,G.E.
A1  - Freo,U.
A1  - Grady,C.L.
A1  - Mentis
A1  - MJ
A1  - Mangot,D.
A1  - Simon,E.W.
A1  - Horwitz,B.
A1  - Haxby,J.V.
A1  - Schapiro,M.B.
Y1  - 1997/08//
N1  - XN537-0006
SP  - 1063
EP  - 1069
JF  - American Journal of Psychiatry
VL  - 154
IS  - 8
N2  - Objective: Down's syndrome is characterized by the genetically programmed accumulation of substantial Alzheimer's disease neuropathology after age 40 and the development of early dementia years later, providing a unique human model to investigate the preclinical phases of Alzheimer's disease. Older nondemented adults with Down's syndrome show normal rates of regional cerebral glucose metabolism at rest before the onset of dementia, indicating that their neurons maintain function at rest. The authors hypothesized that an audiovisual stimulation paradigm, acting as a stress test, would reveal abnormalities in cerebral glucose metabolism before dementia in the neocortical parietal and temporal areas most vulnerable to Alzheimer's disease. Method: Regional cerebral glucose metabolism was assessed by means of positron emission tomography (PET) with [F-18]fluorodeoxyglucose in eight younger (mean age=35 years, SD=2) and eight older (mean age=50, SD=7) healthy, nondemented adults with trisomy 21 Down's syndrome. PET scans were performed at rest and during audiovisual stimulation [watching a movie] in the same scanning session [double injection]. Levels of general intellectual functioning and compliance were similar in the two groups. Results: At rest the two groups showed no difference in glucose metabolism in any cerebral region. In contrast, during audiovisual stimulation the older subjects with Down's syndrome had significantly lower glucose metabolic rates in the parietal and temporal cortical areas. Conclusions: Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. These results indicate that a stress test paradigm can detect metabolic abnormalities in the preclinical stages of Alzheimer's disease despite normal cerebral metabolism at rest. [References: 31]
AD  - Reprint available from: Pietrini P NIA NEUROSCI LAB NIH RM 6C414 BLDG 10 9000 ROCKVILLE PIKE BETHESDA, MD 20892 USA ELWYN INST ELWYN, PA USA
ER  - 

TY  - JOUR
T1  - Pain affect encoded in human anterior cingulate but not somatosensory cortex
A1  - Rainville,P.
A1  - Duncan,G.H.
A1  - Price,D.D.
A1  - Carrier,B.
A1  - Bushnell,M.C.
Y1  - 1997/08/15/
N1  - XQ985-0045
SP  - 968
EP  - 971
JF  - Science
VL  - 277
IS  - 5328
N2  - Recent evidence demonstrating multiple regions of human cerebral cortex activated by pain has prompted speculation about their individual contributions to this complex experience. To differentiate cortical areas involved in pain affect, hypnotic suggestions were used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity. Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived unpleasantness, whereas primary somatosensory cortex activation was unaltered. These findings provide direct experimental evidence in humans linking frontal-lobe limbic activity with pain affect, as originally suggested by early clinical lesion studies. [References: 38]
AD  - Reprint available from: Bushnell MC UNIV MONTREAL CTR RECH SCI NEUROL MONTREAL PQ H3C 3J7 CANADA UNIV MONTREAL CTR RECH SCI NEUROL MONTREAL PQ H3C 3J7 CANADA MONTREAL NEUROL INST MCCONNELL BRAIN IMAGING CTR MONTREAL PQ CANADA MCGILL UNIV DEPT ANESTHESIOL MONTREAL PQ H3A 1A1 CANADA
ER  - 

TY  - JOUR
T1  - Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain.
A1  - Doudet,D.J.
A1  - McLellan,C.A.
A1  - Carson,R.
A1  - Adams,H.R.
A1  - Miyake,H.
A1  - Aigner,T.G.
A1  - Finn,R.T.
A1  - Cohen,R.M.
Y1  - 1991/09//
N1  - 91340860
SP  - 726
EP  - 734
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 11
IS  - 5
N2  - Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes.
AD  - Section on Clinical Brain Imaging, LCM, NIMH, IRP, Bethesda, Maryland.
ER  - 

TY  - JOUR
T1  - Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine.
A1  - Benkelfat,C.
A1  - Nordahl,T.E.
A1  - Semple,W.E.
A1  - King,A.C.
A1  - Murphy,D.L.
A1  - Cohen,R.M.
Y1  - 1990/09//
N1  - 90365596
SP  - 840
EP  - 848
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 47
IS  - 9
N2  - In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive-compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus.
AD  - Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, Md.
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic rates in obsessive compulsive disorder.
A1  - Nordahl,T.E.
A1  - Benkelfat,C.
A1  - Semple,W.E.
A1  - Gross,M.
A1  - King,A.C.
A1  - Cohen,R.M.
Y1  - 1989/03//
N1  - 90026744
SP  - 23
EP  - 28
JF  - Neuropsychopharmacology
VL  - 2
IS  - 1
N2  - Brain metabolism was measured with positron emission tomography and [18F] 2-fluoro-2-deoxyglucose in normal subjects and in patients with obsessive compulsive disorder (OCD) while they performed a continuous auditory discrimination task designed to evaluate the functional localization of sustained attention. Data on 8 nondepressed patients with OCD were compared with 30 normal volunteers. We observed significantly higher normalized regional metabolism both in the right orbital frontal cortex (p = 0.002, two-tailed t test) and in the left anterior orbital frontal cortex (p = 0.017, one-tailed t test) and in patients with OCD as compared to normal controls. We observed no normalized glucose metabolic differences in basal ganglia structures in patients with OCD as compared to our normal controls. There were no statistical differences in global glucose metabolic values between the OCD and the control group. Our findings are consistent with the findings of Baxter et al. (Arch Gen Psychiatry 44:211-218, 1987). Regions in the parietal cortex also appear to show differences in this preliminary study.
AD  - Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892.
ER  - 

TY  - JOUR
T1  - Regional [14C]misonidazole distribution in experimental RT-9 brain tumors.
A1  - Horowitz,M.
A1  - Blasberg,R.
A1  - Molnar,P.
A1  - Strong,J.
A1  - Kornblith,P.
A1  - Pleasants,R.
A1  - Fenstermacher,J.
Y1  - 1983/08//
N1  - 83232759
SP  - 3800
EP  - 3807
JF  - Cancer Research
JA  - Cancer Res
VL  - 43
IS  - 8
N2  - Regional [14C]misonidazole-derived radioactivity (MISO) was measured by quantitative autoradiography in experimental RT-9 brain tumors 0.5, 2, and 4 hr after an i.v. bolus (25 mg) and constant infusion (10 mg/hr). Misonidazole (MISO) concentration in plasma and brain was also measured by high-pressure liquid chromatography; the brain/plasma MISO ratio ranged between 0.5 and 0.7. MISO equivalents were calculated from tissue or plasma 14C radioactivity and [14C]MISO specific activity data. The MISO/MISO equivalents ratio, which represents the nonmetabolized fraction of [14C]MISO, fell gradually in plasma (0.89 at 4 hr) and more rapidly in brain (0.67 at 4 hr) and tumor (0.30 at 4 hr). MISO distributed uniformly throughout the brain at all three time periods. In contrast, MISO distribution in tumor was variable, and tumor concentrations relative to that in brain increased with time. The average tumor/brain MISO ratio was 1.3, 1.7, and 2.6 at 0.5, 2, and 4 hr, respectively, which suggests tumor uptake and binding of MISO or, more likely, MISO-derived 14C-labeled metabolites. In addition, MISO distribution in tumor tissue was strikingly heterogeneous at 4 hr, resulting in an average high/low tumor activity ratio of 4/1 and an average high tumor/brain ratio of 5/1. Tumor regions with high MISO activity correlated in part to viable-appearing cells around necrotic foci.
ER  - 

TY  - JOUR
T1  - Gallium-transferrin as a macromolecular tracer of vascular permeability.
A1  - Brunetti,A.
A1  - Blasberg,R.G.
A1  - Finn,R.D.
A1  - Larson,S.M.
Y1  - 1988///
N1  - 89291450
SP  - 665
EP  - 672
JF  - International Journal of Radiation Applications & Instrumentation - Part B, Nuclear Medicine & Biology
VL  - 15
IS  - 6
N2  - Labeling of plasma transferrin with gallium was investigated to determine whether the gallium-transferrin complex could be effectively used as a macromolecular tracer in studies of capillary permeability using Positron Emission Tomography (PET). Three gallium-plasma preparations were tested and 2 h biodistribution studies were performed in rats. The three preparations gave similar blood clearance and tissue distribution data, but the methods used for evaluating gallium-transferrin binding were found to be suboptimal. Gallium clearance from blood was biexpoential with both components faster than that of 125I-albumin. Gallium distribution spaces in all tissues including intracerebral Walker-256 tumors were larger than those of albumin. These results indicate a relative instability of the gallium-transferrin complex in vivo, which appears to preclude its use as an acceptable radiolabeled protein for vascular permeability studies using PET.
AD  - Department of Nuclear Medicine, N.I.H., Bethesda, MD 20892.
ER  - 

TY  - JOUR
T1  - Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations.
A1  - Patlak,C.S.
A1  - Blasberg,R.G.
Y1  - 1985/12//
N1  - 86034229
SP  - 584
EP  - 590
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 4
N2  - The method of graphical analysis for the evaluation of sequential data (e.g., tissue and blood concentrations over time) in which the test substance is irreversibly trapped in the system has been expanded. A simpler derivation of the original analysis is presented. General equations are derived that can be used to analyze tissue uptake data when the blood-plasma concentration of the test substance cannot be easily measured. In addition, general equations are derived for situations when trapping of the test substance is incomplete and for a combination of these two conditions. These derivations are independent of the actual configuration of the compartmental system being analyzed and show what information can be obtained for the period when the reversible compartments are in effective steady state with the blood. This approach is also shown to result in equations with at least one less nonlinear term than those derived from direct compartmental analysis. Specific applications of these equations are illustrated for a compartmental system with one reversible region (with or without reversible binding) and one irreversible region.
ER  - 

TY  - JOUR
T1  - Regional blood flow in ethylnitrosourea-induced brain tumors.
A1  - Blasberg,R.G.
A1  - Kobayashi,T.
A1  - Horowitz,M.
A1  - Rice,J.M.
A1  - Groothuis,D.
A1  - Molnar,P.
A1  - Fenstermacher,J.D.
Y1  - 1983/08//
N1  - 84022399
SP  - 189
EP  - 201
JF  - Annals of Neurology
VL  - 14
IS  - 2
N2  - Regional blood flow was measured in experimental brain tumors using iodoantipyrine labeled with carbon 14 and quantitative autoradiography. A total of fifteen oligodendrogliomas, sixteen mixed gliomas, one astrocytoma, one ependymoma, and three malignant schwannomas were studied in 9 rats. The mean tumor blood flows for all glioma classifications were similar, averaging 45 +/- 3 (standard error of the mean) ml . hg-1 . min-1. Flow was fairly uniform within individual oligodendrogliomas and there was no apparent correlation between blood flow and tumor size or location. The mixed gliomas were larger than the oligodendrogliomas and had a wider range of blood flow. Small focal areas of necrosis were observed in 7 mixed gliomas, and low flows were usually measured in these regions; these flows were not always the lowest regional values measured within the mixed gliomas or total group of tumors, however. Small tumor regions with increased vascularity, frequently with endothelial cell proliferation, were observed in oligodendrogliomas and to a greater extent in mixed gliomas; these regions were correlated with small elevations in blood flow (10 to 15 ml . hg-1 . min-1) in comparison with surrounding tumor tissue. Brain adjacent to tumor usually had higher blood flows than that in tumor periphery. Hemispheric differences in blood flow related to the site of primary tumor growth were not observed.
ER  - 

TY  - JOUR
T1  - Transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes.
A1  - Blasberg,R.G.
A1  - Fenstermacher,J.D.
A1  - Patlak,C.S.
Y1  - 1983/03//
N1  - 83109351
SP  - 8
EP  - 32
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 3
IS  - 1
N2  - The transport of alpha-aminoisobutyric acid (AIB), N-methyl-AIB (MeAIB), and diethylenetriaminepentaacetic acid (DTPA) from blood to brain was measured over different experimental periods in eight regions of the rat brain. Unidirectional transfer rate constants were determined from multiple-time/graphical and single-time analysis of the experimental data; values of 0.0018, 0.00057, and 0.000021 ml g-1 min-1, respectively, were obtained for the thalamus by graphical analysis. The initial distribution volume of AIB and MeAIB in brain tissue was several-fold greater than that of DTPA and the tissue plasma volume, and this difference was not accounted for by red blood cell uptake. This discrepancy could be due to rapid transport of AIB and MeAIB into brain endothelial cells in addition to the relatively rapid uptake by choroidal, meningeal, and ependymal associated tissues that was demonstrated by autoradiography. Thus, it may be misleading and erroneous to consider the blood-brain barrier (BBB) to be a simple, single-membrane structure when analyzing the blood-brain transfer data of solutes such as amino acids. The data from the ventriculocisternal perfusion experiments and previously published AIB uptake data in mouse brain slices were used to estimate the transfer rate constants across brain cell membranes. These studies indicated that the transport of AIB into brain cells was approximately 110 to 265 times greater than that across normal brain capillaries per unit mass of brain tissue, and that the BBB limits blood-to-brain cell transport of this amino acid. These observations (low rate of transport across normal brain capillaries and rapid concentrative uptake by brain cells) indicate that AIB is a good marker for measuring moderate to large increases in BBB permeability by experiments that require unidirectional flux of the tracer.
ER  - 

TY  - JOUR
T1  - Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data.
A1  - Patlak,C.S.
A1  - Blasberg,R.G.
A1  - Fenstermacher,J.D.
Y1  - 1983/03//
N1  - 83109336
SP  - 1
EP  - 7
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 3
IS  - 1
N2  - A theoretical model of blood-brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period. If the graph indicates unidirectionality of uptake, then an influx constant (Ki) can be calculated. The model is general, assumes linear transfer kinetics, and consists of a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The solution of the equations for this model shows that a graph of the ratio of the total tissue solute concentration at the times of sampling to the plasma concentration at the respective times (Cp) versus the ratio of the arterial plasma concentration-time integral to Cp should be drawn. If the data are consistent with this model, then this graph will yield a curve that eventually becomes linear, with a slope of Ki and an ordinate intercept less than or equal to the vascular plus steady-state space of the reversible tissue region.
ER  - 

TY  - JOUR
T1  - PALLIDOTOMY IN PARKINSONS-DISEASE INCREASES SUPPLEMENTARY MOTOR AREA AND PREFRONTAL ACTIVATION DURING PERFORMANCE OF VOLITIONAL MOVEMENTS - AN (H2O)-O-15 PET STUDY
A1  - Samuel,M.
A1  - Ceballos-Baumann,A.O.
A1  - Turjanski,N.
A1  - Boecker,H.
A1  - Gorospe,A.
A1  - Linazasoro,G.
A1  - Holmes,A.P.
A1  - Delong,M.R.
A1  - Vitek,J.L.
A1  - Thomas,DG T.
A1  - Quinn,N.P.
A1  - Obeso,J.A.
A1  - Brooks,D.J.
Y1  - 1997/08//
N1  - XT039-0002
SP  - 1301
EP  - 1313
JF  - Brain
VL  - 120
IS  - Part 8
N2  - Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinsons's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had (H2O)-O-15 PET when 'off' medication before and 3-4 months after surgery Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre-and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7 % (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease. [References: 48]
AD  - Reprint available from: Samuel M HAMMERSMITH HOSP MRC CYCLOTRON UNIT DU CANE RD LONDON W12 0NN ENGLAND NEUROL INST WELLCOME DEPT COGNIT NEUROL LONDON ENGLAND TECH UNIV MUNICH NEUROL KLIN D-8000 MUNICH GERMANY CLIN QUIRON CTR NEUROL & NEUROCIRUGIA FUNCT SAN SEBASTIAN SPAIN EMORY UNIV DEPT NEUROL ATLANTA, GA 30322 USA
ER  - 

TY  - JOUR
T1  - DRUG DELIVERY TO THE BRAIN [Review]
A1  - Pardridge,W.M.
Y1  - 1997/07//
N1  - XR345-0001
SP  - 713
EP  - 731
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 17
IS  - 7
AD  - Reprint available from: Pardridge WM UNIV CALIF LOS ANGELES SCH MED DEPT MED LOS ANGELES, CA 90095 USA
ER  - 

TY  - JOUR
T1  - INDICATIONS FOR DIFFERENTIAL DIAGNOSIS OF NONTUMOR CENTRAL NERVOUS SYSTEM DISEASES FROM TUMORS - A POSITRON EMISSION TOMOGRAPHY STUDY
A1  - Mineura,K.
A1  - Ogawa,T.
A1  - Sasajima,T.
A1  - Hatazawa,J.
A1  - Kowada,M.
A1  - Uemura,K.
Y1  - 1997/01//
N1  - WN534-0002
SP  - 8
EP  - 15
JF  - Journal of Neuroimaging
VL  - 7
IS  - 1
N2  - To accurately differentiate nontumor central nervous system (CNS) diseases from brain tumors, we retrospectively evaluated the cerebral circulation and metabolism in patients with nontumor CNS diseases using positron emission tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen (rCMRO(2)), and of glucose (rCMRGI), and the uptake of C-11-methyl-L-methionine (C-11-Met) were visually evaluated in lesions and compared with values for the contralateral white matter regions. PET findings were correlated with those of x-ray computed tomography (CT) and magnetic resonance imaging (MRI), and were analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were changeable from disease to disease or from stage to stage of disease progression. rOEF and rCMRO, remained low in 5 and 6, respectively, of 9 nontumor CNS diseases examined, whereas these parameters were increased in CNS infections such as brain abscess. Overall, noteworthy was the locally increased rOEF and rCMRO(2) in the patients with a brain abscess in contrast to the values for patients with gliomas, rCMRGI reflected biological characteristics of each disease, and correlated with cell density, whether reactive glial cells or inflammatory cells. C-11-Met was accumulated at a certain stage of nontumor CNS diseases, which implied uptake of the tracer as a result of disruption of the blood-brain barrier as well as metabolic incorporation. [References: 51] Qualitative evaluation only.
AD  - Reprint available from: Mineura K AKITA UNIV HOSP NEUROL SERV 1-1-1 HONDO AKITA 010 JAPAN RES INST BRAIN & BLOOD VESSELS DEPT RADIOL & NUCL MED AKITA JAPAN
ER  - 

TY  - JOUR
T1  - CLINICAL POSITRON EMISSION TOMOGRAPHY FOR BRAIN TUMORS - COMPARISON OF FLUDEOXYGLUCOSE F 18 AND L-METHYL-C-11-METHIONINE
A1  - Ogawa,T.
A1  - Inugami,A.
A1  - Hatazawa,J.
A1  - Kanno,I.
A1  - Murakami,M.
A1  - Yasui,N.
A1  - Mineura,K.
A1  - Uemura,K.
Y1  - 1996/02//
N1  - TW234-0030
SP  - 345
EP  - 353
JF  - Ajnr: American Journal of Neuroradiology
VL  - 17
IS  - 2
N2  - PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-C-11-methionine (C-11-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, C-11-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and C-11-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with C-11-methionine outlined [not actually demonstrated] the tumors as areas of increased accumulation of C-11-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with C-11-methionine can play complementary roles in the evaluation of brain tumors. [References: 39]
AD  - Reprint available from: Ogawa T RES INST BRAIN & BLOOD VESSELS DEPT RADIOL & NUCL MED 6-10 SENSHU KUBOTA MACHI AKITA 010 JAPAN RES INST BRAIN & BLOOD VESSELS DEPT NEUROL SURG AKITA 010 JAPAN AKITA UNIV SCH MED DEPT NEUROL SERV AKITA 010 JAPAN
ER  - 

TY  - JOUR
T1  - In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease.
A1  - Kuhl,D.E.
A1  - Minoshima,S.
A1  - Fessler,J.A.
A1  - Frey,K.A.
A1  - Foster,N.L.
A1  - Ficaro,E.P.
A1  - Wieland,D.M.
A1  - Koeppe,R.A.
Y1  - 1996/09//
N1  - 96390543
SP  - 399
EP  - 410
JF  - Annals of Neurology
VL  - 40
IS  - 3
N2  - To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [123I]iodobenzovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18F]fluorodeoxyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22-91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocampus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetyltransferase activity (50-80%).
AD  - University of Michigan Hospitals, Division of Nuclear Medicine, Ann Arbor 48109-0028, USA.
ER  - 

TY  - JOUR
T1  - C-11-methionine PET for low-grade gliomas
A1  - Herholz,K.
A1  - Hlzer,T.
A1  - Bauer,B.
A1  - Schrder,R.
A1  - Voges,J.
A1  - Ernestus,R.I.
A1  - Mendoza,G.
A1  - Heiss,W.-D.
Y1  - 1997///
SP  - S20
EP  - S20
JF  - Journal of Neuro-Oncology
VL  - 35 (Suppl.1)
ER  - 

TY  - JOUR
T1  - Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography.
A1  - al-Mousawi,A.H.
A1  - Evans,N.
A1  - Ebmeier,K.P.
A1  - Roeda,D.
A1  - Chaloner,F.
A1  - Ashcroft,G.W.
Y1  - 1996/10//
N1  - 97049474
SP  - 509
EP  - 516
JF  - British Journal of Psychiatry
VL  - 169
IS  - 4
N2  - BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.
AD  - Department of Psychological Medicine, University of Wales College of Medicine, Wrexham.
ER  - 

TY  - JOUR
T1  - EQUILIBRIUM VERSUS COMPARTMENTAL ANALYSIS FOR ASSESSMENT OF THE VESICULAR MONOAMINE TRANSPORTER USING (+)-ALPHA-[C-11]DIHYDROTETRABENAZINE (DTBZ) AND POSITRON EMISSION TOMOGRAPHY
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Kume,A.
A1  - Albin,R.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
Y1  - 1997/09//
N1  - XX163-0001
SP  - 919
EP  - 931
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 17
IS  - 9
N2  - This work compares equilibrium to kinetic analysis of positron emission tomography data for the assessment of vesicular monoamine transporter (VMAT2) binding density using (+)-alpha-[C-11]dihydrotetrabenazine ((+)-alpha-[C-11]DTBZ). Studies were performed for 80 minutes after intravenous administration of 18 +/- 1 mCi (+)-alpha-[C-11]DTBZ on 9 young control subjects, 20 to 45 years of age. A 9-mCi bolus was injected over the first minute of the study, whereas the remaining 9 mCi were infused at a constant rate over the following 79 minutes. Steady-state was reached in both blood and brain by approximately 30 minutes after initiation of the study. Nonlinear least-squares analysis using two-and three-compartment models, weighted integral analysis using a two-compartment configuration, and Logan plot analysis all yielded kinetic estimates of the total tissue distribution volume, DVtot(kin). These results were compared with equilibrium distribution volume estimates, DVtot(eq), calculated from the tissue to metabolite corrected arterial plasma concentration ratio after 30 minutes. Kinetic modeling results from this study were in close agreement with prior bolus-injection (+)-alpha-[C-11]DTBZ studies. In the current study, coefficients of variation in DVtot(kin) (19% to 23% across regions) and DVtot(eq) (18% to 22%) were nearly identical. Equilibrium estimates of DVtot(eq) were slightly lower than kinetic estimates, averaging 5% +/- 9% lower (P = 0.04, paired t test) in regions of high binding density (caudate and putamen), but only 2% +/- 6% (P = 0.09) in lower binding density regions (cortex, thalamus, cerebellum). DVtot(eq) estimates, however, still correlated highly with DVtot(kin) estimates (r = 0.977 - 0.989). Steady-state conditions can be achieved in both tissue and blood by 30 minutes, and the tissue-to-blood ratios of (+)-alpha-[C-11]DTBZ at equilibrium yield DVtot(eq) measures that are in close agreement with DVtot(kin) estimates. Thus, a simple, easily tolerated protocol using a loading bolus followed by continuous infusion can provide excellent measures of VMAT2 binding. [References: 32]
AD  - Reprint available from: Koeppe RA UNIV MICHIGAN SCH MED DIV NUCL MED DEPT INTERNAL MED 3480 KRESGE 3 BOX 0552 ANN ARBOR, MI 48109 USA UNIV MICHIGAN DEPT NEUROL ANN ARBOR, MI 48109 USA ANN ARBOR VET ADM MED CTR CTR GERIATR RES EDUC & CLIN ANN ARBOR, MI USA
ER  - 

TY  - JOUR
T1  - C-11-FLUMAZENIL PET, VOLUMETRIC MRI, AND QUANTITATIVE PATHOLOGY IN MESIAL TEMPORAL LOBE EPILEPSY
A1  - Koepp,M.J.
A1  - Richardson,M.P.
A1  - Labbe,C.
A1  - Brooks,D.J.
A1  - Cunningham,V.J.
A1  - Ashburner,J.
A1  - Vanpaesschen,W.
A1  - Revesz,T.
A1  - Duncan,J.S.
Y1  - 1997/09//
N1  - XX774-0023
SP  - 764
EP  - 773
JF  - Neurology
VL  - 49
IS  - 3
N2  - Background: Using statistical parametric mapping and C-11-flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) due to hippocampal sclerosis (HS). The limited spatial resolution of PET, however, results in partial-volume averaging that affects quantitative analysis of cBZR density. Method: We determined hippocampal volume loss and reduction in cBZR binding using an MRI-based method for partial-volume effect: correction of C-11-FMZ volume of distribution (FMZ-Vd) in 17 patients with refractory mTLE and an MRI diagnosis of HS that was subsequently histologically verified in all cases. Quantitative neuropathology was performed with assessment of neuron density in 14 of the 17 patients. Absolute FMZ-Vd and asymmetry indices (FMZ-AI) were compared before and after partial-volume effect correction with MRI-determined hippocampal volumes (HCV), hippocampal T-2 measurements, and, if available, neuronal cell densities. Results: Compared with 15 age-matched healthy volunteers, significant reductions of absolute hippocampal FMZ-Vd were found before correction for partial-volume effects in 11 of 17 patients (65%) and only abnormal FMZ-AI in the other six patients. After partial-volume effect correction all 17 patients (100%) showed both significant unilateral reduction of absolute FMZ-Vd and abnormal FMZ-AI. There was no correlation between corrected absolute FMZ-Vd and HCV or neuronal cell density. After correction for partial-volume effect we found a mean 38% reduction of FMZ-Vd in the sclerosed hippocampus, over and above the reduction of HCV. Conclusion: Correction for partial-volume effect allows absolute quantitation of FMZ-PET and increases its sensitivity for detecting abnormalities in TLE due to HS, The lack of correlation between cBZR binding and neuronal density implies that atrophy with neuron loss is not the sole determinant of reduced cBZR binding in patients with mTLE and hippocampal sclerosis. [References: 49]
AD  - Reprint available from: Duncan JS INST NEUROL EPILEPSY RES GRP QUEEN SQ LONDON WC1N 3BG ENGLAND INST NEUROL EPILEPSY RES GRP LONDON WC1N 3BG ENGLAND HAMMERSMITH HOSP MRC CYCLOTRON UNIT LONDON W12 0HS ENGLAND INST NEUROL DEPT PATHOL LONDON WC1N 3BG ENGLAND
ER  - 

TY  - JOUR
T1  - REGIONAL BRAIN DISTRIBUTION AND BINDING OF THE MUSCARINIC RECEPTOR AGONIST CI-979 STUDIED BY POSITRON EMISSION TOMOGRAPHY IN THE MONKEY
A1  - Hartvig,P.
A1  - Torstenson,R.
A1  - Bjurling,P.
A1  - Fasth,K.J.
A1  - Langstrom,B.
A1  - Nordberg,A.
Y1  - 1997/09//
N1  - XT590-0001
SP  - 259
EP  - 266
JF  - Dementia & Geriatric Cognitive Disorders
VL  - 8
IS  - 5
N2  - The regional brain distribution and selective binding of the cholinergic muscarinic receptor agonist CI-979 labelled with C-11 was studied in rhesus monkeys by means of positron emission tomography, The selective binding was measured as displacement of [C-11]CI-979-derived radioactivity following constant-rate infusion of CI-979 at doses of 0.5-10 mu g/kg/h. An extensive and rapid distribution of [C-11]CI-979 was observed to the basal ganglia and temporal occipital cortices, i.e., regions of the brain with a high density of muscarinic receptors. The radioactivity was dose-dependently decreased in cortical regions following infusions of unlabelled CI-979 (0.5-10 mu g/kg/h), indicating selective receptor binding of [C-11]CI-979 in these brain regions, The binding of [C-11]CI-979 was unaltered or even higher in the striatum following unlabelled CI-979 infusion. The high densities of autoreceptors in the striatum may explain the inhibitory feedback mechanism on endogenous acetylcholine induced by the muscarinic receptor agonist. Since muscarinic receptor agonists release acetylcholine, the higher releasable pool of acetylcholine in the striatum will induce feedback inhibition of acetylcholine release and less competition between acetylcholine and CI-979 at the muscarinic receptors. This may explain the differences between cortex and striatum in [C-11]CI-979 binding, The cerebral blood flow was not changed by the infusion of unlabelled CI-979, supporting the assumption that effects of CI-979 in brain may be due to the interaction with brain muscarinic receptors. Despite a relative rapid clearance of [C-11]CI-979 radioactivity from binding in the brain characteristic of a receptor agonist, the radioligand might be useful in positron emission tomography studies to reveal changes in cholinergic receptors and functional activity in Alzheimer patients treated with muscarinic agonists. [References: 31]
AD  - Reprint available from: Nordberg A HUDDINGE UNIV HOSP DEPT CLIN NEUROSCI & FAMILY MED DIV NICOTINE RES KAROLINSKA INST B84 S-14186 HUDDINGE SWEDEN HUDDINGE UNIV HOSP DEPT CLIN NEUROSCI & FAMILY MED DIV NICOTINE RES KAROLINSKA INST S-14186 HUDDINGE SWEDEN UNIV UPPSALA HOSP PET CTR UPPSALA SWEDEN HOSP PHARM UPPSALA SWEDEN UNIV UPPSALA UPPSALA SWEDEN RES DEV CORP JAPAN SUBFEMTOMOLE BIORECOGNIT PROJECT OSAKA JAPAN
ER  - 

TY  - JOUR
T1  - Brain monoamines in progressive supranuclear palsy--comparison with idiopathic Parkinson's disease. [Review] [33 refs]
A1  - Hornykiewicz,O.
A1  - Shannak,K.
Y1  - 1994///
N1  - 95053978
SP  - 219
EP  - 227
JF  - Journal of Neural Transmission
VL  - Supplementum. 42
N2  - Like idiopathic Parkinson's disease (iPD), Progressive Supranuclear Palsy (PSP) is characterized, inter alia, by a pronounced non-overlapping loss of dopamine (DA) in caudate, putamen and substantia nigra. Unlike iPD, in PSP the striatal DA loss is more severe in the caudate than in the putamen; this may contribute to the higher frequency of cognitive deficits in PSP. In contrast to iPD, in patients with PSP the serotonin (5-HT) levels in the basal ganglia are not significantly reduced, thus resulting in a relative predominance of the inhibitory serotonergic influences on the motor behaviour in these patients. It is suggested that combination of levodopa with a 5-HT receptor blocker may substantially improve the (poor) responsiveness of patients with PSP to DA substitution therapy. [References: 33]
AD  - Institute of Biochemical Pharmacology, University of Vienna, Austria.
ER  - 

TY  - JOUR
T1  - Three-dimensional imaging of cortical structure, function and glioma for tumor resection
A1  - Nariai,T.
A1  - Senda,M.
A1  - Ishii,K.
A1  - Maehara,T.
A1  - Wakabayashi,S.
A1  - Toyama,H.
A1  - Ishiwata,K.
A1  - Hirakawa,K.
Y1  - 1997/10//
N1  - XZ766-0019
SP  - 1563
EP  - 1568
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 10
N2  - A three-dimensional brain imaging protocol with PET and MRI was used to visualize the cortical structure in relation to brain function and glioma infiltration to determine tumor resectability. Methods: Sixteen patients with glioma had a PET scan with C-11-methionine to visualize tumor infiltration. The PET images were cc-registered to the patients' own MRI reconstructed to the three-dimensional brain surface images to indicate the gyral structure and the extent of tumor infiltration. Thirteen patients, who bore tumors adjacent to the language or motor cortex, had (H2O)-O-15 activation study to locate the eloquent cortex. The area of tumor infiltration was superimposed on the brain surface images together with the language and/or motor cortex, Results: When a tumor was located within a single gyrus without influencing surface cortical gyrus pattern, the motor and language areas were identified morphologically by three-dimensional surface image alone. However, when the tumor caused swelling and deformation of cortical structure, functional mapping with (H2O)-O-15 activation technique was essential in locating them correctly. In such cases, the combined mapping of the facial motor area with oral movement and the language area with word repetition was the most useful method to identify the parasylvian structure in the dominant hemisphere. Total or near total resection of low-grade glioma in eight patients and the effective decompression of the active part of the malignant glioma in four patients was completed without causing functional neurological deterioration. Conclusion: The three-dimensional expression of cortical structure and function combined with PET glioma imaging with C-11-methionine is useful for radical resection of cerebral glioma. [References: 39]
AD  - Reprint available from: Nariai T TOKYO MED & DENT UNIV DEPT NEUROSURG SCH MED BUNKYO KU 1-5-45 YUSHIMA TOKYO 113 JAPAN TOKYO METROPOLITAN INST GERONTOL POSITRON MED CTR TOKYO JAPAN
ER  - 

TY  - JOUR
T1  - Persistent post-traumatic retrograde amnesia: a neuropsychological and (18F)FDG PET study.
A1  - Mattioli,F.
A1  - Grassi,F.
A1  - Perani,D.
A1  - Cappa,S.F.
A1  - Miozzo,A.
A1  - Fazio,F.
Y1  - 1996/03//
N1  - 96268906
SP  - 121
EP  - 129
JF  - Cortex
VL  - 32
IS  - 1
N2  - We report the case of a 48-year old woman who, after a severe closed head injury, developed a severe and persistent disruption of retrograde memory, associated with a mild impairment of learning abilities. The patient's dense amnesia spared only the childhood period and included both explicit memory (autobiographical and semantic) and procedural skills. Because of her partially spared learning ability and intact language, intensive training by family members resulted in the reacquisition and retention of many autobiographical events and of some skills she had lost after the accident. Brain CT scan and MRI were normal; a PET study with (18F)FDG revealed a significant bilateral reduction of metabolism in the hippocampus and anterior cingulate cortex, suggesting a role for these structures in memory for past events.
AD  - Clinica Neurologica, Universita di Brescia.
ER  - 

TY  - JOUR
T1  - Varieties of progressive non-fluent aphasia.
A1  - Cappa,S.F.
A1  - Perani,D.
A1  - Messa,C.
A1  - Miozzo,A.
A1  - Fazio,F.
Y1  - 1996/01/17/
N1  - 96187025
SP  - 243
EP  - 248
JF  - Annals of the New York Academy of Sciences
VL  - 777
N2  - We report four patients with progressive aphasia of the non-fluent type as the presenting clinical manifestation. The patients were included in a longitudinal study of focal progressive neuropsychological syndromes, and were periodically submitted to neuropsychological evaluations and neuroimaging studies (TC, MRI, SPET or PET). The pattern of neuropsychological impairment was in good agreement with the results of functional imaging studies, which indicated involvement of the anterior regions of the left hemisphere. The evolution of the clinical picture was extremely heterogeneous in the four patients, ranging from a relatively stable picture of transcortical motor aphasia to a severe progressive frontal lobe syndrome. Progressive non-fluent aphasia appears to be a reliable clinical marker of the localization of the pathological process; whether this is related to specific neuropathological conditions, such as Pick's disease, remains for the moment a matter of speculation.
AD  - Laboratorio di Neuropsicologia, Clinica Neurologica, University of Brescia, Italy. cappa:master.cci.unibs.it
ER  - 

TY  - JOUR
T1  - Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.
A1  - Shin,L.M.
A1  - Kosslyn,S.M.
A1  - McNally,R.J.
A1  - Alpert,N.M.
A1  - Thompson,W.L.
A1  - Rauch,S.L.
A1  - Macklin,M.L.
A1  - Pitman,R.K.
Y1  - 1997/03//
N1  - 97229901
SP  - 233
EP  - 241
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 54
IS  - 3
N2  - BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.
AD  - Department of Psychology, Harvard University, Cambridge, Mass, USA.
ER  - 

TY  - JOUR
T1  - EFFECT OF ANTIPSYCHOTICS ON REGIONAL CEREBRAL BLOOD FLOW MEASURED WITH POSITRON EMISSION TOMOGRAPHY
A1  - Miller,D.D.
A1  - Andreasen,N.C.
A1  - Oleary,D.S.
A1  - Rezai,K.
A1  - Watkins,L.
A1  - Ponto,LL B.
A1  - Hichwa,R.D.
Y1  - 1997/10//
N1  - XY691-0002
SP  - 230
EP  - 240
JF  - Neuropsychopharmacology
VL  - 17
IS  - 4
N2  - Positron Emission Tomography (PET) imaging of regional cerebral blood flow (rCBF) provides an in vivo method for studying brain function. We used [O-15]H2O PET to assess the effect of antipsychotic medications on rCBF in 17 subjects with schizophrenia. Each subject was scanned whlle receiving antipsychotic medication, and after having been withdrawn from antipsychotic medication for a 3-week period. The two scans were subtracted from one another, using a within subjects design, and the areas of difference were identified using the Montreal method. Subjects treated with antipsychotic medication had significantly higher rCBF in the left basal ganglia and Ieft fusiform gyrus compared with the ''off-medication'' condition. Significantly higher relative rCBF in the anterior cingulate, left dorsolateral and inferior frontal cortex, and left and right cerebellum was observed when off antipsychotic medication. Upregulation of dopamine D-2 receptors may lead to a regional increase of blood flow and metabolism in the basal ganglia, which may explain recently reported anatomical enlargement in these regions. (C) 1997 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. [References: 49]
AD  - Reprint available from: Miller DD UNIV IOWA HOSP & CLIN DEPT PSYCHIAT ADMIN POSITRON EMISS TOMOG IMAGING CTR IOWA CITY, IA 52242 USA UNIV IOWA COLL MED MENTAL HLTH CLIN RES CTR MAJOR PSYCHOSES IOWA CITY, IA USA UNIV IOWA COLL MED DEPT PSYCHIAT IOWA CITY, IA 52242 USA UNIV IOWA COLL MED DEPT RADIOL IOWA CITY, IA 52242 USA
ER  - 

TY  - JOUR
T1  - TIME COURSE OF 5-HT2A RECEPTOR OCCUPANCY IN THE HUMAN BRAIN AFTER A SINGLE ORAL DOSE OF THE PUTATIVE ANTIPSYCHOTIC DRUG MDL 100,907 MEASURED BY POSITRON EMISSION TOMOGRAPHY
A1  - Grunder,G.
A1  - Yokoi,F.
A1  - Offord,S.J.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
A1  - Salzmann,J.K.
A1  - Szymanski,S.
A1  - Wilson,P.D.
A1  - Howard,D.R.
A1  - Wong,D.F.
Y1  - 1997/09//
N1  - XR375-0006
SP  - 175
EP  - 185
JF  - Neuropsychopharmacology
VL  - 17
IS  - 3
N2  - MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animal studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [C-11]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 Hours compared to the timepoint at 8 hours, when only 10 mg are administered (p < 0.05). Our results should allow determination of the appropriate dosing regimen for future trials in schizophrenic patients. (C) 1997 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. [References: 31]
AD  - Reprint available from: Wong DF JOHNS HOPKINS MED INST JHOC DEPT RADIOL DIV NUCL MED ROOM 3245 601 N CAROLINE ST BALTIMORE, MD 21287 USA JOHNS HOPKINS MED INST JHOC DEPT RADIOL DIV NUCL MED BALTIMORE, MD 21287 USA UNIV MARYLAND SCH MED DEPT EPIDEMIOL & PREVENT MED BALTIMORE, MD 21201 USA HOECHST MAR ROUSSEL CINCINNATI, OH USA
ER  - 

TY  - JOUR
T1  - PREOPERATIVE INDICATORS OF CLINICAL OUTCOME FOLLOWING STEREOTAXIC PALLIDOTOMY
A1  - Kazumata,K.
A1  - Antonini,A.
A1  - Dhawan,V.
A1  - Moeller,J.R.
A1  - Alterman,R.L.
A1  - Kelly,P.
A1  - Sterio,D.
A1  - Fazzini,E.
A1  - Beric,A.
A1  - Eidelberg,D.
Y1  - 1997/10//
N1  - YC431-0030
SP  - 1083
EP  - 1090
JF  - Neurology
VL  - 49
IS  - 4
N2  - We assessed the utility of preoperative clinical assessment and functional brain imaging with F-18-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in predicting the clinical outcome of stereotaxic pallidotomy for the treatment of advanced Parkinson's disease (PD). Twenty-two PD patients undergoing posteroventral pallidotomy were assessed preoperatively with the Core Assessment Program for Intracerebral Transplantation (CAPIT) ratings measured on and off levodopa; quantitative FDG/PET was also performed before surgery. Preoperative clinical and metabolic measurements were correlated with changes in off-state CAPIT ratings determined 3 months after surgery. Clinical outcome following pallidotomy was also correlated with intraoperative measures of spontaneous pallidal single-unit activity as well as postoperative MRI measurements of lesion volume and location. We found that unilateral pallidotomy resulted in variable clinical improvement in off-state CAPIT scores for the contralateral limbs (mean change 30.9 +/- 15.5%). Postoperative MRI revealed that pallidotomy lesions were comparable in location and volume across the patients. Clinical outcome following surgery correlated significantly with preoperative measures of CAPIT score change with levodopa administration (r = 0.60, p < 0.005) and with preoperative FDG/PET measurements of lentiform glucose metabolism (r = 0.71, p < 0.0005). Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. We conclude that preoperative measurements of lentiform glucose metabolism and levodopa responsiveness may be useful indicators of motor improvement following pallidotomy. Both preoperative quantitative measures, either singly or in combination, may be helpful in selecting optimal candidates for surgery. [References: 35]
AD  - Reprint available from: Eidelberg D N SHORE UNIV HOSP DEPT NEUROL 350 COMMUNITY DR MANHASSET, NY 11030 USA N SHORE UNIV HOSP DEPT NEUROL MANHASSET, NY 11030 USA COLUMBIA UNIV COLL PHYS & SURG NEW YORK STATE PSYCHIAT INST DEPT PSYCHIAT NEW YORK, NY USA NYU SCH MED DEPT NEUROSURG NEW YORK, NY 10003 USA NYU SCH MED DEPT NEUROL NEW YORK, NY 10003 USA HOSP JOINT DIS & MED CTR NEW YORK, NY USA
ER  - 

TY  - JOUR
T1  - FLUORODOPA AND RACLOPRIDE PET ANALYSIS OF PATIENTS WITH MACHADO-JOSEPH-DISEASE
A1  - Shinotoh,H.
A1  - Thiessen,B.
A1  - Snow,B.J.
A1  - Hashimoto,S.
A1  - Macleod,P.
A1  - Silveira,I.
A1  - Rouleau,G.A.
A1  - Schulzer,M.
A1  - Calne,D.B.
Y1  - 1997/10//
N1  - YC431-0038
SP  - 1133
EP  - 1136
JF  - Neurology
VL  - 49
IS  - 4
N2  - We performed [F-18]G-fluoro-L-dopa (6-FD) and [C-11]raclopride (RAG) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAG-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD. [References: 11]
AD  - Reprint available from: Calne DB VANCOUVER HOSP & HLTH SCI CTR CTR NEURODEGENERAT DISORDERS PURDY PAVILL 2221 WESBROOK MALL VANCOUVER BC V6T 2B5 CANADA UNIV BRITISH COLUMBIA CTR NEURODEGENERAT DISORDERS VANCOUVER BC V5Z 1M9 CANADA VICTORIA HOSP DEPT LAB MED GENET SECT LONDON BC CANADA MCGILL UNIV CTR RES NEUROSCI QUEBEC CITY PQ CANADA MONTREAL GEN HOSP RES INST QUEBEC CITY PQ CANADA
ER  - 

TY  - JOUR
T1  - PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia.
A1  - Ganguli,R.
A1  - Carter,C.
A1  - Mintun,M.
A1  - Brar,J.
A1  - Becker,J.
A1  - Sarma,R.
A1  - Nichols,T.
A1  - Bennington,E.
Y1  - 1997/01/01/
N1  - 97142771
SP  - 33
EP  - 42
JF  - Biological Psychiatry
VL  - 41
IS  - 1
N2  - Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.
AD  - Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pennsylvania 15213-2593, USA.
ER  - 

TY  - JOUR
T1  - 11C-Methionine PET for differential diagnosis of low-grade gliomas
A1  - Herholz,K.
A1  - Hlzer,T.
A1  - Bauer,B.
A1  - Schrder,R.
A1  - Voges,J.
A1  - Ernestus,R.I.
A1  - Mendoza,G.
A1  - Weber-Luxenburger,G.
A1  - Lttgen,J.
A1  - Thiel,A.
A1  - Wienhard,K.
A1  - Heiss,W.-D.
Y1  - 1998///
SP  - 1316
EP  - 1322
JF  - Neurology
VL  - 50
IS  - 5
ER  - 

TY  - JOUR
T1  - Combined FDOPA and 3OMFD PET studies in Parkinson's disease [see comments].
A1  - Dhawan,V.
A1  - Ishikawa,T.
A1  - Patlak,C.
A1  - Chaly,T.
A1  - Robeson,W.
A1  - Belakhlef,A.
A1  - Margouleff,C.
A1  - Mandel,F.
A1  - Eidelberg,D.
Y1  - 1996/02//
N1  - 96223800
SP  - 209
EP  - 216
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 37
IS  - 2
N2  - PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. It has been suggested that the estimation of dopa-decarboxylation (DDC) rate, kD3, using a compartmental approach to dynamic FDOPA/PET data, can provide a better objective marker of parkinsonism. This modeling process, however, requires many assumptions to estimate DDC activity with acceptable errors. METHODS: We combined FDOPA 3-O-methyl-fluorodopa PET studies on three normal subjects and five Parkinson's disease patients. RESULTS: The contradicted modeling assumptions are: (a) the rate constants across the blood-brain barrier, KD1 and kD2, for 3OMFD and FDOPA were in similar range (ratio approximately equal to 1) and thus not equal to assumed values of KM1/KD1 of 2.3 derived from rat studies and applied to human FDOPA studies and (b) the KD1/kD2 ratio for frontal cortex was not equal to that for the striatum (0.70 +/- 0.15 versus 1.07 +/- 0.3; p < 0.002). Discriminant analyses indicate that simple estimates like the striatum-to-occipital ratio, or the graphically derived unidirectional transport rate constant (KiFD) separate normals from Parkinson's disease patients at least as accurately as estimates of striatal DDC activity (kD3). CONCLUSION: Measurements of striatal DDC activity with dynamic FDOPA/PET and compartmental modeling may be based on incorrect assumptions. Even though such complex models yield microparameters that may be applicable to certain clinical research demands, they may produce misleading results in other experimental settings.
AD  - Department of Neurology, North Shore University Hospital/Cornell University Medical College, Manhasset, New York 11030, USA.
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study.
A1  - Braun,A.R.
A1  - Balkin,T.J.
A1  - Wesenten,N.J.
A1  - Carson,R.E.
A1  - Varga,M.
A1  - Baldwin,P.
A1  - Selbie,S.
A1  - Belenky,G.
A1  - Herscovitch,P.
Y1  - 1997/07//
N1  - 97379831
SP  - 1173
EP  - 1197
JF  - Brain
VL  - 120
IS  - Pt 7
N2  - To assess dynamic changes in brain function throughout the sleep-wake cycle, CBF was measured with H2(15)O and PET in 37 normal male volunteers: (i) while awake prior to sleep onset; (ii) during Stage 3-4 sleep, i.e. slow wave sleep (SWS); (iii) during rapid eye movement (REM) sleep; and (iv) upon waking following recovery sleep. Subjects were monitored polysomnographically and PET images were acquired throughout the course of a single night. Stage-specific contrasts were performed using statistical parametric mapping. Data were analysed in repeated measures fashion, examining within-subject differences between stages [pre-sleep wakefulness-SWS (n = 20 subjects); SWS-post-sleep wakefulness (n = 14); SWS-REM sleep (n = 7); pre-sleep wakefulness-REM sleep (n = 8); REM sleep-post-sleep wakefulness (n = 7); pre-sleep wakefulness-post-sleep wakefulness (n = 20)]. State dependent changes in the activity of centrencephalic regions, including the brainstem, thalamus and basal forebrain (profound deactivations during SWS and reactivations during REM sleep) are consistent with the idea that these areas are constituents of brain systems which mediate arousal. Shifts in the level of activity of the striatum suggested that the basal ganglia might be more integrally involved in the orchestration of the sleep-wake cycle than previously thought. State-dependent changes in the activity of limbic and paralimbic areas, including the insula, cingulate and mesial temporal cortices, paralleled those observed in centrencephalic structures during both REM sleep and SWS. A functional dissociation between activity in higher order, heteromodal association cortices in the frontal and parietal lobes and unimodal sensory areas of the occipital and temporal lobes appeared to be characteristic of both SWS and REM sleep. SWS was associated with selective deactivation of the heteromodal association areas, while activity in primary and secondary sensory cortices was preserved. SWS may not, as previously thought, represent a generalized decrease in neuronal activity. On the other hand, REM sleep was characterized by selective activation of certain post-rolandic sensory cortices, while activity in the frontoparietal association cortices remained depressed. REM sleep may be characterized by activation of widespread areas of the brain, including the centrencephalic, paralimbic and unimodal sensory regions, with the specific exclusion of areas which normally participate in the highest order analysis and integration of neural information. Deactivation of the heteromodal association areas (the orbital, dorsolateral prefrontal and inferior parietal cortices) constitutes the single feature common to both non-REM and REM sleep states, and may be a defining characteristic of sleep itself. The stages of sleep could also be distinguished by characteristic differences in the relationships between the basal ganglia, thalamic nuclei and neocortical regions of interest.
AD  - Language Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
ER  - 

TY  - JOUR
T1  - Quantification and pharmacokinetics of blood-brain barrier disruption in humans.
A1  - Zunkeler,B.
A1  - Carson,R.E.
A1  - Olson,J.
A1  - Blasberg,R.G.
A1  - DeVroom,H.
A1  - Lutz,R.J.
A1  - Saris,S.C.
A1  - Wright,D.C.
A1  - Kammerer,W.
A1  - Patronas,N.J.
A1  - Dedrick,R.L.
A1  - Herscovitch,P.
A1  - Oldfield,E.H.
Y1  - 1996/12//
N1  - 97083537
SP  - 1056
EP  - 1065
JF  - Journal of Neurosurgery
VL  - 85
IS  - 6
N2  - Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 microl/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 microl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 microM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
ER  - 

TY  - JOUR
T1  - 18F-desmethoxyfallypride: a fluorine-18 labeled radiotracer with properties similar to carbon-11 raclopride for PET imaging studies of dopamine D2 receptors.
A1  - Mukherjee,J.
A1  - Yang,Z.Y.
A1  - Brown,T.
A1  - Roemer,J.
A1  - Cooper,M.
Y1  - 1996///
N1  - Franklin McLean Institute, Department of Radiology, University of Chicago, Il 60637, USA jogm@fciad3bsduchicagoeduPMID- 0008761017
SP  - 669
EP  - 678
JA  - Life Sci.
VL  - 59
IS  - 8
N2  - We have developed (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-18F- fluoropropyl)-2- methoxybenzamide (18F-desmethoxyfallypride) as a fluorine-18 radiotracer with properties analogous to that of 11C- raclopride. In vitro experiments in rat brain homogenates showed an association rate constant of 2.16 x 10(8) M(-1)min(-1) and a dissociation rate constant of 0.073 min(-1). High striatal uptake (up to 0.08% injected dose/cc) of 18F-desmethoxyfallypride in rhesus monkeys was observed in PET experiments. The radiotracer cleared from the striata with a dissociation rate of 1.80 x 10(-2) min(-1). Striatum to cerebellum ratios peaked at 3.0 in 30 min after which they decreased steadily. Intravenously administered haloperidol displaced specifically bound 18F-desmethoxyfallypride with a koff of 0.058 min(-1). Synaptic dopamine released by the treatment of the monkeys with d-amphetamine increased the dissociation rate of 18F-desmethoxyfallypride to 0.83 min(-1) thus reducing specifically bound 18F-desmethoxyfallypride by 56% over a period of 42 mins compared to a reduction of only 20% in controls during this time period. The sensitivity of 18F- desmethoxyfallypride towards competition with dopamine should make this radiotracer useful in PET studies to evaluate in vivo pharmacological effects of various agents that alter levels of endogenous dopamine.
ER  - 

TY  - JOUR
T1  - Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography.
A1  - Hartvig,P.
A1  - Torstenson,R.
A1  - Tedroff,J.
A1  - Watanabe,Y.
A1  - Fasth,K.J.
A1  - Bjurling,P.
A1  - Langstrom,B.
Y1  - 1997///
N1  - Uppsala University PET Centre, University Hospital, University of Uppsala, SwedenPMID- 0009295169
SP  - 329
EP  - 339
JA  - J.Neural Transm.
VL  - 104
IS  - 4-5
N2  - Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys. L-[beta-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 +/- 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant for L-[beta-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors. L-[beta-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.
ER  - 

TY  - JOUR
T1  - Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.
A1  - Smith,G.S.
A1  - Dewey,S.L.
A1  - Brodie,J.D.
A1  - Logan,J.
A1  - Vitkun,S.A.
A1  - Simkowitz,P.
A1  - Schloesser,R.
A1  - Alexoff,D.A.
A1  - Hurley,A.
A1  - Cooper,T.
A1  - Volkow,N.D.
Y1  - 1997/04//
N1  - Department of Psychiatry, New York University, School of Medicine, New York, USAPMID- 0009090335
SP  - 490
EP  - 496
JA  - Am.J.Psychiatry
VL  - 154
IS  - 4
N2  - OBJECTIVE: This study was undertaken to measure serotonergic modulation of dopamine in vivo by using positron emission tomography (PET), a radiotracer for the striatal dopamine D2 receptor ([11C]raclopride), and a pharmacologic challenge of the serotonin system (d,l- fenfluramine). METHOD: Two PET studies using [11C]raclopride were performed in 11 normal male subjects before administration of the serotonin-releasing agent and reuptake inhibitor fenfluramine (60 mg p.o.) and 3 hours afterward. A graphical analysis method was used with the [11C]raclopride data to derive the distribution volume of D2 receptors. Plasma levels of fenfluramine, norfenfluramine, homovanillic acid (HVA), cortisol, and prolactin were determined. RESULTS: Levels of fenfluramine and prolactin were elevated 2 hours after fenfluramine administration and remained significantly elevated during the second scan, while levels of HVA and cortisol were not altered significantly during the time of scanning. A significant decrease in the specific binding (striatum) and the nonspecific binding subtracted from the specific binding (striatum minus cerebellum) of [11C]raclopride was observed. The rate of metabolism of [11C]raclopride and the nonspecific binding (cerebellum) were not significantly altered by the fenfluramine intervention. CONCLUSIONS: The observed decrease in [11C]raclopride binding is consistent with an increase in dopamine concentrations and with the ability of serotonin to stimulate dopamine activity. The ability to measure serotonergic modulation of dopamine in vivo may have implications for the study of etiologic and therapeutic mechanisms in schizophrenia, major depressive disorder, obsessive-compulsive disorder, and substance abuse.
ER  - 

TY  - JOUR
T1  - Parametric imaging of ligand-receptor binding in PET using a simplified reference region model
A1  - Gunn,R.N.
A1  - Lammertsma,A.A.
A1  - Hume,S.P.
A1  - Cunningham,V.J.
Y1  - 1997/11//
N1  - PET Methodology Group, MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
SP  - 279
EP  - 287
JA  - Neuroimage.
VL  - 6
IS  - 4
N2  - A method is presented for the generation of parametric images of radioligand-receptor binding using PET. The method is based on a simplified reference region compartmental model, which requires no arterial blood sampling, and gives parametric images of both the binding potential of the radioligand and its local rate of delivery relative to the reference region. The technique presented for the estimation of parameters in the model employs a set of basis functions which enables the incorporation of parameter bounds. This basis function method (BFM) is compared with conventional nonlinear least squares estimation of parameters (NLM), using both simulated and real data. BFM is shown to be more stable than NLM at the voxel level and is computationally much faster. Application of the technique is illustrated for three radiotracers: [11C]raclopride (a marker of the D2 receptor), [11C]SCH 23390 (a marker of the D1 receptor) in human studies, and [11C]CFT (a marker of the dopamine transporter) in rats. The assumptions implicit in the model and its implementation using BFM are discussed. Copyright 1997 Academic Press. Copyright 1997 Academic Press
ER  - 

TY  - JOUR
T1  - In vivo saturation kinetics of two dopamine transporter probes measured using a small animal positron emission tomography scanner.
A1  - Hume,S.P.
A1  - Brown,D.J.
A1  - Ashworth,S.
A1  - Hirani,E.
A1  - Luthra,S.K.
A1  - Lammertsma,A.A.
Y1  - 1997/09/05/
N1  - PET Methodology Group, Hammersmith Hospital, London, UKPMID- 0009334938
SP  - 45
EP  - 51
JA  - J.Neurosci.Methods
VL  - 76
IS  - 1
N2  - When estimated in vitro, the parameters which describe the binding of radiolabelled analogues of cocaine to sites on the dopamine transporter are very much influenced by the methodology used. In the present study, a small animal positron emission tomography (PET) scanner was used to estimate in vivo saturation kinetics for two carbon-11 labelled compounds presently used to monitor dopamine terminal function. The binding of [11C]CFT (WIN 35,428) in rat striatum was adequately described by a single-site model, giving an apparent dissociation constant corresponding to an intravenous dose of 242 nmol/kg. In contrast, the binding of [11C]RTI-121 was better described by a two- site model with the 'high-affinity' site or state (dissociation constant = 1 nmol/kg) being significantly occupied at doses routinely used in PET scanning. Such findings cannot readily be predicted from in vitro work, but could aid in both the choice of ligand and the model used in quantification of scan data. While multi-dose in vivo PET studies are difficult in man, rat PET can easily be employed either pre- clinically for putative radioligands, or experimentally, to study drug interactions and receptor occupancy related to functional efficacy.
ER  - 

TY  - JOUR
T1  - Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635.
A1  - Pike,V.W.
A1  - McCarron,J.A.
A1  - Lammertsma,A.A.
A1  - Osman,S.
A1  - Hume,S.P.
A1  - Sargent,P.A.
A1  - Bench,C.J.
A1  - Cliffe,I.A.
A1  - Fletcher,A.
A1  - Grasby,P.M.
Y1  - 1996/04/22/
N1  - MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK vpike@rpmsacukPMID- 0008773468
SP  - R5
EP  - R7
JA  - Eur.J.Pharmacol.
VL  - 301
IS  - 1-3
N2  - The 5-HT1A receptor antagonist, WAY-100635 [N-(2-(4-(2-methoxyphenyl)- 1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide], was labelled in its carbonyl group with carbon-11 (t1/2 = 20.4 min), injected intravenously into healthy male volunteers and studied with positron emission tomography (PET). The acquired data provide exquisite delineation of 5-HT1A receptors in brain, with the ratio of radioactivity uptake in receptor-rich regions, such as medial temporal cortex, to that in receptor-devoid cerebellum reaching 25 by 60 min after radioligand injection. Application of biomathematical modelling to the data revealed high values (7.8) for binding potential, a measure of Bmax/Kp, in receptor-rich regions. Only very polar radioactive metabolites were present in plasma, a finding consistent with the low level of nonspecific binding seen in cerebellum. [carbonyl-11C]WAY- 100635 is concluded to be far superior to the previously reported [0- methyl-11C]WAY-100635 as a radioligand for PET studies of 5-HT1A receptors in human brain.
ER  - 

TY  - JOUR
T1  - Evaluation of [11C]RTI-121 as a selective radioligand for PET studies of the dopamine transporter.
A1  - Hume,S.P.
A1  - Luthra,S.K.
A1  - Brown,D.J.
A1  - Opacka-Juffry,J.
A1  - Osman,S.
A1  - Ashworth,S.
A1  - Myers,R.
A1  - Brady,F.
A1  - Carroll,F.I.
A1  - Kuhar,M.J.
A1  - Brooks,D.J.
Y1  - 1996/04//
N1  - Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UKPMID- 0008782251
SP  - 377
EP  - 384
JA  - Nucl.Med.Biol.
VL  - 23
IS  - 3
N2  - The cocaine analogue RTI-121 (3 beta-(4-iodophenyl)tropane-2 beta- carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [11C]RTI-55 (2 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5- HT uptake site. The results indicate that [11C]RTI-121 could be used in preference to [11C]RTI-55 in man. Experimentally, [11C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography.
ER  - 

TY  - JOUR
T1  - Comparison of methods for analysis of clinical [11C]raclopride studies.
A1  - Lammertsma,A.A.
A1  - Bench,C.J.
A1  - Hume,S.P.
A1  - Osman,S.
A1  - Gunn,K.
A1  - Brooks,D.J.
A1  - Frackowiak,R.S.
Y1  - 1996/01//
N1  - Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, LondonPMID- 0008530554
SP  - 42
EP  - 52
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 16
IS  - 1
N2  - Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two- tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.
ER  - 

TY  - JOUR
T1  - Effect of L-dopa and 6-hydroxydopamine lesioning on [11C]raclopride binding in rat striatum, quantified using PET.
A1  - Hume,S.P.
A1  - Opacka-Juffry,J.
A1  - Myers,R.
A1  - Ahier,R.G.
A1  - Ashworth,S.
A1  - Brooks,D.J.
A1  - Lammertsma,A.A.
Y1  - 1995/09//
N1  - PET Methodology and Neurosciences Groups, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, United KingdomPMID- 0008525461
SP  - 45
EP  - 53
JF  - Synapse
VL  - 21
IS  - 1
N2  - A positron emission tomograph (PET) was used to image D2 dopamine receptor function in rat striata and to obtain regional time- radioactivity curves from individual rat brains following i.v. injection of carbon-11-labelled raclopride. Despite the limited resolution of the camera, together with associated spillover and partial volume effects, the kinetic data obtained from striata were such that specific binding of the radioligand could be quantified unilaterally, using a reference tissue compartmental model, with cerebellum data as an indirect input function. With the exception that the rat is anaesthetised, the experimental system is analogous to the acquisition and collection of clinical PET data and, by using animal models of disease, can be used to aid the interpretation of clinical studies. Using 6-hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta to produce a rat hemiparkinsonian model, the present results confirm that deafferentation causes a supersensitivity of post-synaptic D2 dopamine receptors. Saturation studies indicated that the measured 23% increase in [11C]raclopride binding potential reflected a change in receptor affinity. Modulation of extracellular dopamine concentration, monitored by in vivo microdialysis, demonstrated that the increased binding was unlikely to be due to a reduction in receptor occupancy by endogenous dopamine. Acute administration of L-3,4-dihydroxyphenylalanine (L-dopa) also caused an increase in [11C]raclopride binding potential, confirming the suggestion that L-dopa plays a more complex role than that of dopamine precursor in the nigrostriatal pathway.
ER  - 

TY  - JOUR
T1  - Functional neuroanatomy of robbery re-experience: affective memories studied with PET.
A1  - Fischer,H.
A1  - Wik,G.
A1  - Fredrikson,M.
Y1  - 1996/09/02/
N1  - Department of Clinical Psychology, Uppsala University, SwedenPMID- 0008930963
SP  - 2081
EP  - 2086
JF  - Neuroreport
VL  - 7
IS  - 13
N2  - Using positron emission tomography (PET) and [15O]butanol, regional cerebral blood flow (rCBF) was determined in six bank officials during exposure to a video of a jointly experienced armed bank robbery, and a control video. Besides elevating subjective and physiological indices of anxiety, traumatic stimulation increased rCBF bilaterally in the primary and secondary visual cortex, the posterior gyrus cinguli and in the left orbitofrontal cortex compared with that during the control stimulation. Decreased rCBF was found in Broca's area, the left angular gyrus, the left operculum and the secondary somatosensory cortex. Thus, the stress induced by visual re-experience of a robbery is associated with altered activity in paralimbic and cortical brain regions of relevance for cognition and affect.
ER  - 

TY  - JOUR
T1  - Expectation maximization reconstruction of positron emission tomography images using anatomical magnetic resonance information.
A1  - Lipinski,B.
A1  - Herzog,H.
A1  - Kops,E.R.
A1  - Oberschelp,W.
A1  - Muller-Gartner,H.W.
Y1  - 1997/04//
N1  - Institute of Medicine, Research Centre Julich GmbH, GermanyPMID- 0009101322
SP  - 129
EP  - 136
JA  - IEEE Trans.Med.Imaging
VL  - 16
IS  - 2
N2  - Using statistical methods the reconstruction of positron emission tomography (PET) images can be improved by high-resolution anatomical information obtained from magnetic resonance (MR) images. We implemented two approaches that utilize MR data for PET reconstruction. The anatomical MR information is modeled as a priori distribution of the PET image and combined with the distribution of the measured PET data to generate the a posteriori function from which the expectation maximization (EM)-type algorithm with a maximum a posteriori (MAP) estimator is derived. One algorithm (Markov-GEM) uses a Gibbs function to model interactions between neighboring pixels within the anatomical regions. The other (Gauss-EM) applies a Gauss function with the same mean for all pixels in a given anatomical region. A basic assumption of these methods is that the radioactivity is homogeneously distributed inside anatomical regions. Simulated and phantom data are investigated under the following aspects: count density, object size, missing anatomical information, and misregistration of the anatomical information. Compared with the maximum likelihood-expectation maximization (ML-EM) algorithm the results of both algorithms show a large reduction of noise with a better delineation of borders. Of the two algorithms tested, the Gauss-EM method is superior in noise reduction (up to 50%). Regarding incorrect a priori information the Gauss-EM algorithm is very sensitive, whereas the Markov-GEM algorithm proved to be stable with a small change of recovery coefficients between 0.5 and 3%.
ER  - 

TY  - JOUR
T1  - A methodology for specifying PET VOI's using multimodality techniques.
A1  - Klein,G.J.
A1  - Teng,X.
A1  - Jagust,W.J.
A1  - Eberling,J.L.
A1  - Acharya,A.
A1  - Reutter,B.W.
A1  - Huesman,R.H.
Y1  - 1997/08//
N1  - Center for Functional Imaging, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA gjklein@iblgovPMID- 0009262998
SP  - 405
EP  - 415
JA  - IEEE Trans.Med.Imaging
VL  - 16
IS  - 4
N2  - Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements requires correct identification and delineation of the anatomical feature being studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's on a multislice positron emission tomography (PET) dataset. The software is particularly suited for specifying cerebral cortex VOI's which represent a particular gyrus or deep brain structure. A registered 3-D magnetic resonance image (MRI) dataset is used to provide high-resolution anatomical information, both as oblique two-dimensional (2-D) sections and as volume renderings of a segmented cortical surface. VOI's are specified indirectly in two dimensions by drawing a stack of 2-D regions on the MRI data. The regions are tiled together to form closed triangular mesh surface models, which are subsequently transformed into the observation space of the PET scanner. Quantification by this method allows calculation of radionuclide activity in the VOI's, as well as their statistical uncertainties and correlations. The methodology for this type of analysis and validation results are presented.
ER  - 

TY  - JOUR
T1  - Localization of language-related cortex with O-15-water in patients with gliomas
A1  - Thiel,A.
A1  - Herholz,K.
A1  - von Stockhausen,H.M.
A1  - van Leyen-Pilgram,K.
A1  - Pietrzyk,U.
A1  - Kessler,J.
A1  - Wienhard,K.
A1  - Klug,N.
A1  - Heiss,W.-D.
Y1  - 1998///
SP  - 284
EP  - 295
JF  - Neuroimage
VL  - 7
ER  - 

TY  - THES
T1  - 3D-Visualisierung der Funktion und der Morphologie des menschlichen Gehirns aus tomographischen Daten
A1  - von Stockhausen,H.M.
Y1  - 1998///
PB  - Universitt zu Kln
ER  - 

TY  - JOUR
T1  - Multimodality image registration by maximization of mutual information.
A1  - Maes,F.
A1  - Collignon,A.
A1  - Vandermeulen,D.
A1  - Marchal,G.
A1  - Suetens,P.
Y1  - 1997/04//
N1  - Laboratory for Medical Imaging Research, Katholieke Universiteit Leuven, Universitair Ziekenhuis Gasthuisberg, Belgium FrederikMaes@uzkuleuvenacbePMID- 0009101328
SP  - 187
EP  - 198
JA  - IEEE Trans.Med.Imaging
VL  - 16
IS  - 2
N2  - A new approach to the problem of multimodality medical image registration is proposed, using a basic concept from information theory, mutual information (MI), or relative entropy, as a new matching criterion. The method presented in this paper applies MI to measure the statistical dependence or information redundancy between the image intensities of corresponding voxels in both images, which is assumed to be maximal if the images are geometrically aligned. Maximization of MI is a very general and powerful criterion, because no assumptions are made regarding the nature of this dependence and no limiting constraints are imposed on the image content of the modalities involved. The accuracy of the MI criterion is validated for rigid body registration of computed tomography (CT), magnetic resonance (MR), and photon emission tomography (PET) images by comparison with the stereotactic registration solution, while robustness is evaluated with respect to implementation issues, such as interpolation and optimization, and image content, including partial overlap and image degradation. Our results demonstrate that subvoxel accuracy with respect to the stereotactic reference solution can be achieved completely automatically and without any prior segmentation, feature extraction, or other preprocessing steps which makes this method very well suited for clinical applications.
ER  - 

TY  - JOUR
T1  - Alignment of volume MR images and high resolution [18F]fluorodeoxyglucose PET images for the evaluation of patients with brain tumors.
A1  - Nelson,S.J.
A1  - Day,M.R.
A1  - Buffone,P.J.
A1  - Wald,L.L.
A1  - Budinger,T.F.
A1  - Hawkins,R.
A1  - Dillon,W.P.
A1  - Huhn,S.
A1  - Prados,M.D.
A1  - Chang,S.
A1  - Vigneron,D.B.
Y1  - 1997/03//
N1  - Department of Radiology, University of California, San Francisco 94143, USAPMID- 0009071283
SP  - 183
EP  - 191
JA  - J.Comput.Assist.Tomogr.
VL  - 21
IS  - 2
N2  - PURPOSE: The goal of the study was to investigate the use of automated registration techniques for interpretation of volume MR and high resolution FDG-PET images that were obtained from patients with brain tumors. METHOD: Twenty-one patients with brain tumors were studied on one or more occasions using MRI and high resolution FDG-PET. The data were aligned using automated volume- and surface-matching algorithms. Composite images comprising the resliced pre- and postgadolinium spoiled GRE, T2-weighted SE, and PET data were constructed to correlate intensities of regions on the PET images with regions that corresponded to normal gray matter, white matter, and gadolinium enhancement. RESULTS: The accuracy of registration between the MR and PET images was estimated to be within 1-2 mm based upon the distance between surfaces of the outside of the head. In 12 of the 24 examinations, there were diagnoses of recurrent tumor, with only 5 of these exhibiting regions of higher FDG uptake than normal gray matter. For 19 of the 24 studies, the anatomic context provided by the registered MR images was found to be important in distinguishing recurrent tumor from necrosis based upon FDG uptake. CONCLUSION: The automated alignment was found to be an important factor in interpreting the high resolution PET images. This was particularly true for small lesions close to the cortex and for situations where FDG uptake had been reduced by prior treatment with radiation therapy.
ER  - 

TY  - JOUR
T1  - D2-like dopamine receptor density in Tourette syndrome measured by PET.
A1  - Wong,D.F.
A1  - Singer,H.S.
A1  - Brandt,J.
A1  - Shaya,E.
A1  - Chen,C.
A1  - Brown,J.
A1  - Kimball,A.W.
A1  - Gjedde,A.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Wilson,P.D.
A1  - Wagner,H.N.,Jr
Y1  - 1997/08//
N1  - Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAPMID- 0009255158
SP  - 1243
EP  - 1247
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 8
N2  - Tourette syndrome (TS) is a chronic neurologic disorder characterized by the presence of involuntary motor and phonic tics. There is evidence that TS is associated with an abnormality of the dopaminergic system, involving postsynaptic D2 receptors. We tested the hypothesis that D2- like dopamine receptors are elevated in TS. METHODS: Twenty-nine adult patients with TS were studied by PET imaging with [11C]3-N- methylspiperone ([11C]NMSP). Two methods of data analysis were used. The first was a caudate-to-cerebellar ratio, measured at 45 min. The second method, applied in 20 subjects, was a two-PET scan procedure. Both used high specific activity [11C]NMSP, but the second scan was preceded by a dose of unlabeled haloperidol, which partially occupied the D2-like dopamine receptors. This was done to provide an absolute measure of receptor density (Bmax). All patients were compared to age- and sex-matched controls. RESULTS: Neither group showed significant differences from their control group in caudate-to-cerebellar ratio. However, the two-PET scan Bmax measurement demonstrated that 4 of the 20 patients had significantly elevated D2-like receptors. In this group of 20 patients, multiple linear regression analysis revealed a trend between the severity of vocal tics and Bmax values. This Bmax measure also revealed a significant (p < 0.05) association with performance on the Wisconsin Card Sorting Test. CONCLUSION: These findings suggest that not all patients with TS have an abnormality of D2-like receptors, but a subgroup of TS subjects has a significant D2-like dopamine receptor elevation. These findings also support the importance of applying a more quantitative method for Bmax determination to PET imaging analysis. The Bmax findings in the subgroup do not exclude an effect of intrasynaptic dopamine competition, but this effect may be less likely due to the high affinity of [11C]NMSP.
ER  - 

TY  - JOUR
T1  - Changes of blood flow and oxygen consumption in visual cortex of living humans.
A1  - Marrett,S.
A1  - Gjedde,A.
Y1  - 1997///
N1  - McConnell Brain Imaging Center, Montreal Neurological Institute, Canada
SP  - 205
EP  - 208
JA  - Adv.Exp.Med.Biol.
VL  - 413:205-8
ER  - 

TY  - JOUR
T1  - Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.
A1  - Duara,R.
A1  - Barker,W.W.
A1  - Chang,J.
A1  - Yoshii,F.
A1  - Loewenstein,D.A.
A1  - Pascal,S.
Y1  - 1992/11//
N1  - Wien Center, Mount Sinai Medical Center, Miami Beach, FL 33140PMID- 0001400646
SP  - 927
EP  - 934
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 12
IS  - 6
N2  - Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.
ER  - 

TY  - CHAP
T1  - Magnetic resonance imaging-guided language activation PET in patients: Technical aspects and clinical results
A1  - Herholz,K.
A1  - Thiel,A.
A1  - Pietrzyk,U.
A1  - Karbe,H.
A1  - von Stockhausen,H.M.
A1  - Ghaemi,M.
A1  - Berzdorf,A.
A1  - Sobesky,J.
A1  - Heiss,W.-D.
Y1  - 1998///
SP  - 159
EP  - 163
T2  - Quantitative functional brain imaging with positron emission tomography
A2  - Carson,R.E.
A2  - Daube-Witherspoon,M.E.
A2  - Herscovitch,P.
IS  - 23
CY  - San Diego, CA
PB  - Academic Press
ER  - 

TY  - JOUR
T1  - Calculation of the FDG lumped constant by simultaneous measurements of global glucose and FDG metabolism in humans.
A1  - Hasselbalch,S.G.
A1  - Madsen,P.L.
A1  - Knudsen,G.M.
A1  - Holm,S.
A1  - Paulson,O.B.
Y1  - 1998/02//
N1  - Department of Neurology, National University Hospital, Rigshospitalet, Copenhagen, DenmarkPMID- 0009469157
SP  - 154
EP  - 160
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 2
N2  - The lumped constant defined as the conversion factor between the net uptake of fluoro-2-deoxy-D-glucose (FDG) and glucose was calculated from global CMRglc and from positron emission tomography (PET) using FDG as tracer (CMRFDG). Fifteen healthy, normal volunteers (mean age 24 +/- 4 years) were studied. Global CBF and CMRglc were measured with the Kety-Schmidt technique using 133Xe as tracer, and values were corrected for errors from incomplete diffusion equilibrium for inert gas tracer between brain tissue and cerebral venous blood. Measurements of CMRFDG were obtained with PET using the dynamic and single-scan methods and the K1-k3 model. Measurements with the Kety-Schmidt technique and PET- FDG were performed simultaneously. Global CBF was 47.1 +/- 8.0 mL.100 g- 1.min-1, and CMRglc was 22.8 +/- 4.1 mumol.100 g-1.min-1. No difference in CMRFDG was found with the two methods (17.8 +/- 1.6 and 18.2 +/- 1.3 mumol .100 g-1.min-1, dynamic and single scan methods, respectively). Accordingly, the lumped constant ranged from 0.80 +/- 0.16 to 0.82 +/- 0.15, with a mean value of 0.81 +/- 0.15. The mean ratio between phosphorylation of FDG and glucose (k3*/k3) was 0.39 +/- 0.25. The discrepancy between the lumped constant determined in this study and previously obtained values can be explained partly by methodologic problems, and we conclude that most of the discrepancy results from previous overestimation of global CBF.
ER  - 

TY  - JOUR
T1  - Increased functional vascular response in the region of a glioma.
A1  - Ojemann,J.G.
A1  - Neil,J.M.
A1  - MacLeod,A.M.
A1  - Silbergeld,D.L.
A1  - Dacey,R.G.,Jr
A1  - Petersen,S.E.
A1  - Raichle,M.E.
Y1  - 1998/02//
N1  - Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USAPMID- 0009469156
SP  - 148
EP  - 153
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 2
N2  - Functional imaging of a language task using positron emission tomography was performed as part of the preoperative assessment of a patient with a left supplementary motor area (SMA) tumor. Positron emission tomography scans were obtained during language tasks (verb generation and word reading of visually presented nouns) that normally lead to increased blood flow in the SMA relative to a control condition (visual fixation). In the patient, the normal SMA response was an order of magnitude larger in the region of the tumor. Other regions, such as left inferior frontal cortex and right cerebellum, showed equivalent activation in the patient and normal subjects. Histopathologic study revealed an anaplastic astrocytoma. Thus, this exaggerated vascular response to local neuronal activation occurred in the setting of a proliferation of glial cells. This is consistent with models of coupling of regional CBF and neuronal activity that implicate glia as the mediator between neurons and vasculature. The concept that tumoral disruption of normal vascular responses could, in some cases, potentially enhance rather than dampen the response is proposed.
ER  - 

TY  - JOUR
T1  - Global cerebral blood flow decreases during pain.
A1  - Coghill,R.C.
A1  - Sang,C.N.
A1  - Berman,K.F.
A1  - Bennett,G.J.
A1  - Iadarola,M.J.
Y1  - 1998/02//
N1  - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, Bethesda, Maryland, USAPMID- 0009469155
SP  - 141
EP  - 147
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 2
N2  - Positron emission tomography studies have identified a common set of brain regions activated by pain. No studies, however, have quantitatively examined pain-induced CBF changes. To better characterize CBF during pain, 14 subjects received positron emission tomography scans during rest, during capsaicin-evoked pain (250 micrograms, intradermal injection), and during innocuous vibration. Using the H215O intravenous bolus method with arterial blood sampling, global CBF changes were assessed quantitatively. Painful stimulation produced a 22.8% decrease in global CBF from resting levels (P < 0.0005). This decrease was not accounted for by arterial PCO2 or heart rate changes. Although the exact mechanism remains to be determined, this pain-induced global decrease represents a previously unidentified response of CBF.
ER  - 

TY  - JOUR
T1  - Interictal seizure resections show two configurations of endothelial Glut1 glucose transporter in the human blood-brain barrier.
A1  - Cornford,E.M.
A1  - Hyman,S.
A1  - Cornford,M.E.
A1  - Landaw,E.M.
A1  - Delgado-Escueta,A.V.
Y1  - 1998/01//
N1  - Department of Neurology, UCLA School of Medicine, USAPMID- 0009428303
SP  - 26
EP  - 42
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 1
N2  - Immunogold electron microscopy was used to analyze and quantify the Glut1 glucose transporter in brain tissue from five patients undergoing surgery for treatment of seizures. Samples were prepared from two different regions of each resection: (1) the most actively spiking epileptogenic site, and (2) the least actively spiking region, as indicated by intraoperative EEG monitoring. Two configurations of endothelial cell Glut1 were observed. About one half of the capillary profiles examined displayed abundant Glut1 immunoreactivity on both luminal and abluminal endothelial membranes. In the remainder of the profiles, reduced Glut1 labeling was seen, but adjacent erythrocyte membranes remained highly Glut1 immunoreactive, suggesting that reduced endothelial Glut1 reactivity was not attributable to method artifacts. Immunogold studies using antisera to human glial fibrillary acidic protein and human serum albumin demonstrated increased quantities of these two epitopes in the extravascular regions in which more EEG spiking activity had been demonstrated. These observations were consistent with the hypotheses that capillary integrity was more compromised, and gliosis was quantitatively increased, in the more actively spiking region of the resection. Altered glucose transporter activity in the blood-brain barrier was characterized by a bimodal Glut1 distribution in which the smaller (type B) endothelial cells displayed low Glut1 immunoreactivity, whereas adjacent (and even contiguous) larger (type A) endothelial cells showed 5- to 10-fold greater expression of membrane Glut1 transporter protein. Because this transporter facilitates glucose entry to the brain, small pericapillary volumes of brain tissue may have quite different concentrations of glucose. We hypothesize that in complex partial seizures and other forms of brain insult, an alteration of blood-brain barrier Glut1 glucose transporter activity is indicated by the appearance of these two subpopulations of endothelial cells. In comparison with previous studies of human brain capillaries in hemangioblastoma and brain injury, endothelial Glut1 density was apparently reduced (interictally) in affected temporal lobes of patients with complex partial seizures.
ER  - 

TY  - JOUR
T1  - Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke
A1  - Heiss,W.D.
A1  - Grond,M.
A1  - Thiel,A.
A1  - Ghaemi,M.
A1  - Sobesky,J.
A1  - Rudolf,J.
A1  - Bauer,B.
A1  - Wienhard,K.
Y1  - 1998/02//
N1  - Max-Planck-Institut fur neurologische Forschung and Neurologische Universitatsklinik Koln, GermanyPMID- 0009472889
SP  - 454
EP  - 461
JF  - Stroke
VL  - 29
IS  - 2
N2  - BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.
ER  - 

TY  - JOUR
T1  - Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats.
A1  - Heiss,W.D.
A1  - Graf,R.
A1  - Fujita,T.
A1  - Ohta,K.
A1  - Bauer,B.
A1  - Lottgen,J.
A1  - Wienhard,K.
Y1  - 1997/10//
N1  - Max-Planck-Institut fur neurologische Forschung, Koln, GermanyPMID- 0009341717
SP  - 2045
EP  - 2051
JF  - Stroke
VL  - 28
IS  - 10
N2  - BACKGROUND AND PURPOSE: Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [11C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia. METHODS: In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined approximately 15 hours after MCAO). RESULTS: Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images. CONCLUSIONS: The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.
ER  - 

TY  - JOUR
T1  - Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep.
A1  - Braun,A.R.
A1  - Balkin,T.J.
A1  - Wesensten,N.J.
A1  - Gwadry,F.
A1  - Carson,R.E.
A1  - Varga,M.
A1  - Baldwin,P.
A1  - Belenky,G.
A1  - Herscovitch,P.
Y1  - 1998/01/02/
N1  - Language Section, Voice Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA abraun@popnidcdnihgovPMID- 0009417032
SP  - 91
EP  - 95
JF  - Science
VL  - 279
IS  - 5347
N2  - Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the ventral processing stream, and an unexpected attenuation of activity in the primary visual cortex; increases in regional cerebral blood flow in extrastriate areas were significantly correlated with decreases in the striate cortex. Extrastriate activity was also associated with concomitant activation of limbic and paralimbic regions, but with a marked reduction of activity in frontal association areas including lateral orbital and dorsolateral prefrontal cortices. This pattern suggests a model for brain mechanisms subserving REM sleep where visual association cortices and their paralimbic projections may operate as a closed system dissociated from the regions at either end of the visual hierarchy that mediate interactions with the external world.
ER  - 

TY  - JOUR
T1  - Forebrain activation in REM sleep: an FDG PET study.
A1  - Nofzinger,E.A.
A1  - Mintun,M.A.
A1  - Wiseman,M.
A1  - Kupfer,D.J.
A1  - Moore,R.Y.
Y1  - 1997/10/03/
N1  - Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, PA 15213, USA nofzingerea@msxupmceduPMID- 0009372219
SP  - 192
EP  - 201
JA  - Brain Res.
VL  - 770
IS  - 1-2
N2  - Rapid eye movement (REM) sleep is a behavioral state characterized by cerebral cortical activation with dreaming as an associated behavior. The brainstem mechanisms involved in the generation of REM sleep are well-known, but the forebrain mechanisms that might distinguish it from waking are not well understood. We report here a positron emission tomography (PET) study of regional cerebral glucose utilization in the human forebrain during REM sleep in comparison to waking in six healthy adult females using the 18F-deoxyglucose method. In REM sleep, there is relative activation, shown by increased glucose utilization, in phylogenetically old limbic and paralimbic regions which include the lateral hypothalamic area, amygdaloid complex, septal-ventral striatal areas, and infralimbic, prelimbic, orbitofrontal, cingulate, entorhinal and insular cortices. The largest area of activation is a bilateral, confluent paramedian zone which extends from the septal area into ventral striatum, infralimbic, prelimbic, orbitofrontal and anterior cingulate cortex. There are only small and scattered areas of apparent deactivation. These data suggest that an important function of REM sleep is the integration of neocortical function with basal forebrain- hypothalamic motivational and reward mechanisms. This is in accordance with views that alterations in REM sleep in psychiatric disorders, such as depression, may reflect dysregulation in limbic and paralimbic structures.
ER  - 

TY  - JOUR
T1  - Localized and lateralized cerebral glucose metabolism associated with eye movements during REM sleep and wakefulness: a positron emission tomography (PET) study.
A1  - Hong,C.C.
A1  - Gillin,J.C.
A1  - Dow,B.M.
A1  - Wu,J.
A1  - Buchsbaum,M.S.
Y1  - 1995/09//
N1  - Department of Psychiatry, University of California, San Diego, La Jolla 92093-0603, USA
SP  - 570
EP  - 580
JA  - Sleep.
VL  - 18
IS  - 7
N2  - In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, we analyzed the positron emission tomography (18Fluorodeoxyglucose positron emission tomography) scan data obtained from normal subjects. Eye movement data were available on nine subjects studied during nighttime REM sleep and six control subjects studied during waking as they periodically moved their eyes. The number of eye movements during REM sleep was positively correlated with glucose metabolic rate in the areas corresponding to (a) the saccadic eye movement system (frontal eye field and dorsolateral prefrontal cortex, statistically significant only on the right side), (b) the midline attentional system (cingulate and medial frontal cortex, precuneus) and (c) the parietal visual spatial attentional system (bilateral superior parietal lobules, right inferior parietal lobule); and negatively correlated with relative metabolic rate in the left inferior parietal lobule. Positive correlations between waking eye movements and metabolic rate were observed in the same areas except inferior parietal lobule. Our results show that the same cortical areas are involved in eye movements in both REM sleep and wakefulness and suggest that REM sleep eye movements are saccadic scans of targets in the dream scene. Our data also suggest right hemispheric specialization in saccadic eye movement control and reciprocal inhibition in the contralateral homologous area during higher cortical functioning.
ER  - 

TY  - JOUR
T1  - A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain.
A1  - Murphy,D.G.
A1  - Mentis,M.J.
A1  - Pietrini,P.
A1  - Grady,C.
A1  - Daly,E.
A1  - Haxby,J.V.
A1  - De,La Granja
A1  - Allen,G.
A1  - Largay,K.
A1  - White,B.J.
A1  - Powell,C.M.
A1  - Horwitz,B.
A1  - Rapoport,S.I.
A1  - Schapiro,M.B.
Y1  - 1997/02/01/
N1  - Department of Psychological Medicine, Institute of Psychiatry, London, UKPMID- 0009024951
SP  - 285
EP  - 298
JA  - Biol.Psychiatry
VL  - 41
IS  - 3
N2  - Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.
ER  - 

TY  - JOUR
T1  - Brain organization of motor and language functions following hemispherectomy: a [(15)O]-water positron emission tomography study
A1  - Mller,R.A.
A1  - Chugani,H.T.
A1  - Muzik,O.
A1  - Mangner,T.J.
Y1  - 1998/01//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit 48201-2196, USA
SP  - 16
EP  - 22
JA  - J.Child Neurol.
VL  - 13
IS  - 1
N2  - The capacity of the developing brain for compensatory reorganization after early hemispherectomy has been previously shown in neurobehavioral studies, above all with regard to language recovery. The present study examines the organization of motor and language areas by means of [(15)O]-water positron emission tomography (PET) in a 6- year-old boy who underwent right functional hemispherectomy at age 3 years. The results suggest that compensatory allocation for movement of the weak hand primarily involves the premotor, inferior frontal, and insular cortices, and the supplementary motor area in the retained hemisphere, as well as the bilateral cerebellum. Receptive language and prosodic functions primarily activated the left perisylvian cortices. However, language and motor activations were also seen in cortical and subcortical remains on the hemispherectomized side suggesting incomplete disconnection by functional hemispherectomy.
ER  - 

TY  - JOUR
T1  - Landau-Kleffner syndrome: metabolic abnormalities in temporal lobe are a common feature.
A1  - Da Silva,E.A.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Chugani,H.T.
Y1  - 1997/11//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USAPMID- 0009430313
SP  - 489
EP  - 495
JA  - J.Child Neurol.
VL  - 12
IS  - 8
N2  - Landau-Kleffner syndrome (acquired epileptic aphasia) is characterized by language regression following normal acquisition of language skills, accompanied by epileptiform abnormalities on the electroencephalogram (EEG) with or without clinical seizures. Continuous spikes and waves during slow wave sleep may be seen on the EEG, but are not required to make the diagnosis. Structural neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI) is typically normal. We have evaluated 17 children (aged 2.4 to 10.6 yr) with Landau-Kleffner syndrome using positron emission tomography (PET) with 2-deoxy-2- [18F]fluoro-D-glucose (FDG) in order to determine whether there are metabolic abnormalities common to this syndrome. Patients were awake for the uptake period of FDG, and the EEG was monitored. On a visual analysis of the PET images, patients showed metabolic abnormalities in the temporal lobes. Two children had focal hypermetabolism in the left temporal cortex, one of whom also showed right temporal cortex hypometabolism. The remaining patients (n = 15) showed bilateral temporal hypometabolism, and comparison of these patients with a neurologically normal age-matched control group (n = 8) demonstrated significantly reduced glucose metabolism bilaterally in middle temporal gyrus (P < .02). In addition, other cortical regions displayed hypometabolism, although these regions were not consistently abnormal in all patients. The finding of temporal lobe abnormalities in all Landau-Kleffner syndrome patients suggests that temporal lobe structures are important in the pathophysiology of this syndrome, whereas the presence of additional cortical abnormalities in many patients indicates that extensive brain functional disturbances are common.
ER  - 

TY  - JOUR
T1  - Human brain serotonin synthesis capacity measured in vivo with alpha-[C- 11]methyl-L-tryptophan.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Chakraborty,P.
A1  - Mangner,T.
A1  - Chugani,H.T.
Y1  - 1998/01//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USAPMID- 0009414016
SP  - 33
EP  - 43
JF  - Synapse
VL  - 28
IS  - 1
N2  - Local cerebral serotonin synthesis capacity was measured with alpha-[C- 11]methyl-L-tryptophan ([C-11]AMT) in normal adult human brain (n = 10; five males, five females; age range, 18-38 years, mean 28.3 years) by using positron emission tomography (PET). [C-11]AMT is an analog of tryptophan, the precursor for serotonin synthesis, and is converted to alpha-[C-11]methyl-serotonin ([C-11]AM-5HT), which is trapped in serotonergic neurons because [C-11]AM-5HT is not degraded by monoamine oxidase. Kinetic analysis of [C-11] activity in brain after injection of [C-11]AMT confirmed the presence of a compartment with unidirectional uptake that represented approximately 40% of the activity in the brain at 50 min after tracer administration. The undirectional rate constant K, which represents the uptake of [C-11]AMT from the plasma to brain tissue followed by the synthesis and physiologic trapping of [C-11]AM-5HT, was calculated using the Patlak graphic approach on a pixel-by-pixel basis, thus creating parametric images. The rank order of K values for different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < .0001). High serotonin synthesis capacity values were measured in putamen, caudate, thalamus, and hippocampus. Among cortical regions, the highest values were measured in the rectal gyrus of the inferior frontal lobe, followed by transverse temporal gyrus; anterior and posterior cingulate gyrus; middle, superior, and inferior temporal gyri; parietal cortex; occipital cortex, in descending order. Values in women were 10-20% higher (P < .05, MANOVA) throughout the brain than those measured in men. Differences in the serotonin synthesis capacity between men and women measured in this study may reflect gender differences of importance to both normal and pathologic behavior. This study demonstrates the suitability of [C-11]AMT as a tracer for PET scanning of serotonin synthesis capacity in human brain and provides normal adult values for future comparison with patient groups.
ER  - 

TY  - JOUR
T1  - Glucose metabolism in the human cerebellum: an analysis of crossed cerebellar diaschisis in children with unilateral cerebral injury.
A1  - Shamoto,H.
A1  - Chugani,H.T.
Y1  - 1997/10//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, USAPMID- 0009373796
SP  - 407
EP  - 414
JA  - J.Child Neurol.
VL  - 12
IS  - 7
N2  - Using high-resolution positron emission tomography (PET), we have recently described the normal pattern of glucose utilization in 11 anatomical regions of the human cerebellum. In the present study, we evaluated the phenomenon of crossed cerebellar diaschisis in 40 patients (mostly children) with unilateral cerebral injury sustained at various periods of brain development. Diaschisis refers to a functional impairment at a remote site following injury to an anatomically connected area of brain and, presumably due to a loss of afferent input to the remote site. Of the 40 patients, 11 had sustained their cerebral injury prenatally, 7 in the perinatal period (+/- 24 hours of birth), and 22 postnatally (1 day to 15 years). Crossed cerebellar hypometabolism was seen in 22 patients; symmetric cerebellar metabolism was found in 16 subjects. The presence of crossed cerebellar hypometabolism was typically associated (75% of cases) with a postnatal injury, while symmetric cerebellar metabolism was seen only in patients with injury occurring prior to 4 weeks of age (13 of the 16 had prenatal or perinatal insults). A third pattern of cerebellar metabolism, consisting of paradoxical crossed cerebellar hypermetabolism, was seen in two patients; both had sustained their cerebral injury at 4 months of age. These findings suggest the presence of considerable plasticity, which is dependent on age at injury, in the cerebrocerebellar pathway of developing brain.
ER  - 

TY  - JOUR
T1  - Plasticity of motor organization in children and adults.
A1  - Mller,R.A.
A1  - Rothermel,R.D.
A1  - Behen,M.E.
A1  - Muzik,O.
A1  - Chakraborty,P.K.
A1  - Chugani,H.T.
Y1  - 1997/09/29/
N1  - Children's Hospital of Michigan, Department of Pediatrics, Detroit, USAPMID- 0009331922
SP  - 3103
EP  - 3108
JF  - Neuroreport
VL  - 8
IS  - 14
N2  - We explored the effects of maturational plasticity on motor activations for the affected hand in patients with unilateral lesion involving the rolandic cortex. Ten patients with early lesion (onset < 4 years), seven patients with late lesion (onset > or = 10 years) and eight normal adults underwent [15O]-water positron emission tomography (PET). Rolandic activations in the contralesional hemisphere were enhanced in both patient groups when compared to normal adults. Secondary motor and frontoparietal nonmotor cortices were more activated in the early than in the late lesion group, suggesting a greater potential for reorganization during early development than later in life. Cerebellar activations were similar in late lesion patients and normal adults, but significantly weaker in early lesion patients.
ER  - 

TY  - JOUR
T1  - Pediatric Rasmussen encephalitis: social communication, language, PET and pathology before and after hemispherectomy.
A1  - Caplan,R.
A1  - Curtiss,S.
A1  - Chugani,H.T.
A1  - Vinters,H.V.
Y1  - 1996/10//
N1  - Department of Psychiatry, University of California, Los Angeles, USAPMID- 0008899214
SP  - 45
EP  - 66
JA  - Brain Cogn.
VL  - 32
IS  - 1
N2  - This prospective case study examined social communication (i.e., formal thought disorder, cohesion), language, positron emission tomography glucose utilization, and neuropathology in four children with Rasmussen encephalitis who achieved seizure control following right hemispherectomy. Prior to hemispherectomy, all four children had illogical thinking, loose associations, cohesive deficits, and impaired performance on formal language tests. Their postoperative improvement in social communication and language appeared to be related to age of onset, duration of illness, and postsurgical reversibility of hypometabolism in the nonresected prefrontal cortex. These changes were not associated with increase in IQ scores. The variability in the type and extent of pathologic change across subjects reflected the severity and duration of the illness. The study's findings imply that early surgical intervention might have mitigated certain aspects of the social communication and linguistic deficits found in these children.
ER  - 

TY  - JOUR
T1  - Psychic trauma causing grossly reduced brain metabolism and cognitive deterioration
A1  - Markowitsch,H.J.
A1  - Kessler,J.
A1  - Van Der Ven,C.
A1  - Weber-Luxenburger,G.
A1  - Albers,M.
A1  - Heiss,W.D.
Y1  - 1998/01//
N1  - Physiological Psychology, University of Bielefeld, Germany hjmarkowitsch@postuni-bielefeldde
SP  - 77
EP  - 82
JF  - Neuropsychologia
VL  - 36
IS  - 1
N2  - While amnesia and other cognitive disturbances are usually caused by structural brain damage, there are a few instances in which environmental stress may induce neuronal death in memory-sensitive brain regions such as the hippocampus. Here we report on a patient who, after a single brief exposure to an event reminding him of a similar stressful event from his childhood, deteriorated immediately and persistently without manifesting structural, but manifesting functional, brain damage as measured by position emission tomography. This patient probably represents the first case in which a direct relation between a single psychic event and the occurrence of brain malfunctioning in cognition is documented by dynamic neuroimaging methods. Psychic shock may cause lasting reductions in brain metabolism with the consequence of severe intellectual malfunctioning.
ER  - 

TY  - JOUR
T1  - Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma. A PET study
A1  - Roelcke,U.
A1  - Radu,E.W.
A1  - Hausmann,O.
A1  - Vontobel,P.
A1  - Maguire,R.P.
A1  - Leenders,K.L.
Y1  - 1998/02//
N1  - PET Program, Paul Scherrer Institut, Villigen, Switzerland
SP  - 279
EP  - 283
JA  - J.Neurooncol.
VL  - 36
IS  - 3
N2  - We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), 18F-fluorodeoxyglucose (FDG), 11C- methionine (MET), and 82Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor.
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in patients with spasmodic torticollis.
A1  - Magyar-Lehmann,S.
A1  - Antonini,A.
A1  - Roelcke,U.
A1  - Maguire,R.P.
A1  - Missimer,J.
A1  - Meyer,M.
A1  - Leenders,K.L.
Y1  - 1997/09//
N1  - Paul Scherrer Institute, PET Program, Villigen, SwitzerlandPMID- 0009380052
SP  - 704
EP  - 708
JA  - Mov.Disord.
VL  - 12
IS  - 5
N2  - The pathophysiology of spasmodic torticollis is not clear. Basal ganglia dysfunction has been suggested to underlie this clinical syndrome. We studied resting cerebral glucose metabolism in 10 spasmodic torticollis patients and 10 healthy controls by using positron-emission tomography and [18F]2-fluoro-2-deoxy-D-glucose. Statistical parametric mapping (SPM95) was used to compare both groups on a pixel-by-pixel basis. Torticollis patients showed a significantly higher glucose metabolism bilaterally in the lentiform nucleus (p < 0.005). Analyses performed using normalization of regional to global glucose metabolism confirmed this finding (controls, 1.26 +/- 0.06, and patients, 1.35 +/- 0.06; p < 0.01). The torticollis score did not correlate with glucose metabolism, nor did disease duration or side of chin direction. Our results indicate that the lentiform nucleus plays a predominant role in the pathophysiology of idiopathic spasmodic torticollis.
ER  - 

TY  - JOUR
T1  - The effect of different diagnostic criteria on the prevalence of dementia.
A1  - Erkinjuntti,T.
A1  - Ostbye,T.
A1  - Steenhuis,R.
A1  - Hachinski,V.
Y1  - 1997/12/04/
N1  - Department of Neurology, University of Helsinki, FinlandPMID- 0009385127
SP  - 1667
EP  - 1674
JA  - N.Engl.J.Med.
VL  - 337
IS  - 23
N2  - BACKGROUND: There are several widely used sets of criteria for the diagnosis of dementia, but little is known about their degree of agreement and their effects on estimates of the prevalence of dementia. METHODS: We examined 1879 men and women 65 years of age or older who were enrolled in the Canadian Study of Health and Aging and calculated the proportion given a diagnosis of dementia according to six commonly used classification systems: the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition (DSM-III), the third edition, revised of the DSM (DSM-III-R), the fourth edition of the DSM (DSM-IV), the World Health Organization's International Classification of Diseases (ICD), 9th revision (ICD-9) and 10th revision (ICD-10), and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). The degree of concordance among classification schemes and the importance of various factors in determining diagnostic agreement or disagreement were examined. RESULTS: The proportion of subjects with dementia varied from 3.1 percent when we used the criteria of the ICD-10 to 29.1 percent when the DSM-III criteria were used. The six classification systems identified different groups of subjects as having dementia; only 20 subjects were given a diagnosis of dementia according to all six systems. The classifications based on the various systems differed little according to the patients' age, sex, educational level, or status with respect to institutionalization. The factors that most often caused disagreement in diagnosis between DSM-III and ICD-10 were long-term memory, executive function, social activities, and duration of symptoms. CONCLUSIONS: The commonly used criteria for diagnosis can differ by a factor of 10 in the number of subjects classified as having dementia. Such disagreement has serious implications for research and treatment, as well as for the right of many older persons to drive, make a will, and handle financial affairs.
ER  - 

TY  - JOUR
T1  - Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.
A1  - Spence,A.M.
A1  - Muzi,M.
A1  - Graham,M.M.
A1  - O'Sullivan,F.
A1  - Krohn,K.A.
A1  - Link,J.M.
A1  - Lewellen,T.K.
A1  - Lewellen,B.
A1  - Freeman,S.D.
A1  - Berger,M.S.
A1  - Ojemann,G.A.
Y1  - 1998/03//
N1  - Department of Neurology, University of Washington School of Medicine, Seattle 98195, USAPMID- 0009529289
SP  - 440
EP  - 448
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 3
N2  - Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three- compartment, four-rate constant models for the two hexoses. RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). CONCLUSION: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2- Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.
ER  - 

TY  - JOUR
T1  - Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive dystonia measured with [11C]-raclopride and positron-emission tomography
A1  - Kishore,A.
A1  - Nygaard,T.G.
A1  - de,la Fuente
A1  - Naini,A.B.
A1  - Schulzer,M.
A1  - Mak,E.
A1  - Ruth,T.J.
A1  - Calne,D.B.
A1  - Snow,B.J.
A1  - Stoessl,A.J.
Y1  - 1998/04//
N1  - Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada
SP  - 1028
EP  - 1032
JF  - Neurology
VL  - 50
IS  - 4
N2  - We tested the hypothesis that asymptomatic carriers of dopa-responsive dystonia (DRD) have increased dopamine D2 receptors in the striatum that protect them from the clinical manifestations of dopaminergic deficiency. We examined striatal D2-receptor binding in (1) symptomatic subjects (treated and untreated) and (2) asymptomatic gene carriers. Using [11C]-raclopride PET, we found elevated striatal D2-receptor binding in both groups. In one of our drug-naive symptomatic subjects, 7 months of treatment with levodopa/carbidopa did not affect the receptor binding as measured on a second scan. We conclude that increased D2-receptor binding in DRD may be a homeostatic response to the dopaminergic deficit in subjects carrying the DRD gene, but is not the sole factor determining the clinical state of these individuals.
ER  - 

TY  - JOUR
T1  - "Facilitated" amino acid transport is upregulated in brain tumors
A1  - Miyagawa,T.
A1  - Oku,T.
A1  - Uehara,H.
A1  - Desai,R.
A1  - Beattie,B.
A1  - Tjuvajev,J.
A1  - Blasberg,R.
Y1  - 1998/05//
N1  - Department of Neurosurgery, Chiba University School of Medicine, Japan
SP  - 500
EP  - 509
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 5
N2  - The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]- labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga- DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2- fold difference in facilitated transport is obtained after normalization for differences in capillary surface area between RG2 tumors and contralateral cortex. K1ACPC, deltaK1ACPC, and K DTPA were directly related to tumor cell density, were higher in regions of "impending" necrosis, and the tumor/contralateral brain ACPC radio- activity ratios (0 to 10 minutes) were very similar to that obtained with 0 to 60 minutes experiments. These results indicate that facilitated transport of ACPC is upregulated across C6 and RG2 glioma capillaries, and that tumors can induce upregulation of amino acid transporter expression in their supporting vasculature. They also suggest that early imaging (e.g., 0 to 20 minutes) with radiolabeled amino acids in a clinical setting may be optimal for defining brain tumors.
ER  - 

TY  - JOUR
T1  - Preoperative evaluation of 54 gliomas by PET with fluorine-18- fluorodeoxyglucose and/or carbon-11-methionine
A1  - Kaschten,B.
A1  - Stevenaert,A.
A1  - Sadzot,B.
A1  - Deprez,M.
A1  - Degueldre,C.
A1  - Del,Fiore G.
A1  - Luxen,A.
A1  - Reznik,M.
Y1  - 1998/05//
N1  - Department of Neurosurgery, University Hospital of Liege and Cyclotron Research Center, University of Liege, Belgium
SP  - 778
EP  - 785
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 5
N2  - This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.
ER  - 

TY  - JOUR
T1  - Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET.
A1  - Yamaguchi,S.
A1  - Meguro,K.
A1  - Itoh,M.
A1  - Hayasaka,C.
A1  - Shimada,M.
A1  - Yamazaki,H.
A1  - Yamadori,A.
Y1  - 1997/06//
N1  - Division of Disability Science, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanPMID- 0009219745
SP  - 596
EP  - 600
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 62
IS  - 6
N2  - OBJECTIVE: To investigate the relation between atrophy of the hippocampus and parahippocampal gyrus (the % hippocampal area) and cerebral metabolic rate for glucose (CMRGlc) in Alzheimer's disease. METHODS: 13 patients with probable Alzheimer's disease by NINCDS-ADRDA criteria (six men; seven women, mean age 71 years, mini mental state 13.8 (SD 4.6)) and age matched controls were studied. T1 weighted MRI (0.5T) images were used for evaluation of the hippocampal area. With a digitiser system, a percentage of the hippocampal area to the brain (the % hippocampal area) was calculated. Eight patients received another T1 weighted MRI (1.5T) for further evaluation of the minimum thickness of the hippocampus. Regional CMRGlc (rCMRGlc) was measured using PET and the FDG technique. RESULTS: The hippocampal area in patients with Alzheimer's disease was significantly lower than that of controls (P < 0.01). All the cortical rCMRGlc values in patients with Alzheimer's disease were lower than those of controls (P < 0.01). A significant correlation (P < 0.05) was found between the % hippocampal area and rCMRGlc in the temporal lobe, temporoparieto-occipital (TPO) region, and frontal lobe in Alzheimer's disease. There was a significant correlation between minimal hippocampal thickness and ipsilateral TPO metabolism on both sides. CONCLUSION: The ipsilateral correlation between hippocampal atrophy and decreased TPO metabolism in Alzheimer's disease suggests a functional relation and the asymmetries show that Alzheimer's disease is an asymmetric disease in its early stages.
ER  - 

TY  - JOUR
T1  - Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.
A1  - Sibson,N.R.
A1  - Dhankhar,A.
A1  - Mason,G.F.
A1  - Rothman,D.L.
A1  - Behar,K.L.
A1  - Shulman,R.G.
Y1  - 1998/01/06/
N1  - Department of Molecular Biophysics, Yale University School of Medicine, New Haven, CT 06520, USA sibson@mrcbsmedyaleeduPMID- 0009419373
SP  - 316
EP  - 321
JF  - Proceedings of the National Academy of Sciences of the United States of America
JA  - Proc.Natl.Acad.Sci.USA
VL  - 95
IS  - 1
N2  - To determine the relationship between cerebral Glc metabolism and glutamatergic neuronal function, we used 13C NMR spectroscopy to measure, simultaneously, the rates of the tricarboxylic acid cycle and Gln synthesis in the rat cortex in vivo. From these measurements, we calculated the rates of oxidative Glc metabolism and glutamate- neurotransmitter cycling between neurons and astrocytes (a quantitative measure of glutamatergic neuronal activity). By measuring the rates of the tricarboxylic acid cycle and Gln synthesis over a range of synaptic activity, we have determined the stoichiometry between oxidative Glc metabolism and glutamate-neurotransmitter cycling in the cortex to be close to 1:1. This finding indicates that the majority of cortical energy production supports functional (synaptic) glutamatergic neuronal activity. Another implication of this result is that brain activation studies, which map cortical oxidative Glc metabolism, provide a quantitative measure of synaptic glutamate release.
ER  - 

TY  - JOUR
T1  - Evidence for striatal dopamine release during a video game
A1  - Koepp,M.J.
A1  - Gunn,R.N.
A1  - Lawrence,A.D.
A1  - Cunningham,V.J.
A1  - Dagher,A.
A1  - Jones,T.
A1  - Brooks,D.J.
A1  - Bench,C.J.
A1  - Grasby,P.M.
Y1  - 1998/05/21/
N1  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
SP  - 266
EP  - 268
JF  - Nature
VL  - 393
IS  - 6682
N2  - Dopaminergic neurotransmission may be involved in learning, reinforcement of behaviour, attention, and sensorimotor integration. Binding of the radioligand 11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of endogenous dopamine, which can be released by pharmacological challenge. Here we use 11C-labelled raclopride and positron emission tomography scans to provide evidence that endogenous dopamine is released in the human striatum during a goal-directed motor task, namely a video game. Binding of raclopride to dopamine receptors in the striatum was significantly reduced during the video game compared with baseline levels of binding, consistent with increased release and binding of dopamine to its receptors. The reduction in binding of raclopride in the striatum positively correlated with the performance level during the task and was greatest in the ventral striatum. These results show, to our knowledge for the first time, behavioural conditions under which dopamine is released in humans, and illustrate the ability of positron emission tomography to detect neurotransmitter fluxes in vivo during manipulations of behaviour.
ER  - 

TY  - JOUR
T1  - GABAergic inhibition of endogenous dopamine release measured in vivo with 11C-raclopride and positron emission tomography.
A1  - Dewey,S.L.
A1  - Smith,G.S.
A1  - Logan,J.
A1  - Brodie,J.D.
A1  - Yu,D.W.
A1  - Ferrieri,R.A.
A1  - King,P.T.
A1  - MacGregor,R.R.
A1  - Martin,T.P.
A1  - Wolf,A.P.
Y1  - 1992/10//
N1  - Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973PMID- 0001357114
SP  - 3773
EP  - 3780
JA  - J.Neurosci.
VL  - 12
IS  - 10
N2  - Extensive neuroanatomical, neurophysiological, and behavioral evidence demonstrates that GABAergic neurons inhibit endogenous dopamine release in the mammalian corpus striatum. Positron emission tomography (PET) studies in adult female baboons, using the dopamine D2-specific radiotracer 11C-raclopride, were undertaken to assess the utility of this imaging technique for measuring these dynamic interactions in vivo. 11C-raclopride binding was imaged prior to and following the administration of either gamma-vinyl-GABA (GVG), a specific suicide inhibitor of the GABA-catabolizing enzyme GABA transaminase, or lorazepam, a clinically prescribed benzodiazepine agonist. Striatal 11C- raclopride binding increased following both GVG and lorazepam administration. This increase exceeded the test/retest variability of 11C-raclopride binding observed in the same animals. These findings confirm that changes in endogenous dopamine concentrations resulting from drug-induced potentiation of GABAergic transmission can be measured with PET and 11C-raclopride. Finally, this new strategy for noninvasively evaluating the functional integrity of neurophysiologically linked transmitter systems with PET supports its use as an approach for assessing the multiple mechanisms of drug action and their consequences in the human brain.
ER  - 

TY  - JOUR
T1  - Dexamethasone treatment and plasma glucose levels: relevance for fluorine-18-fluorodeoxyglucose uptake measurements in gliomas.
A1  - Roelcke,U.
A1  - Blasberg,R.G.
A1  - von,Ammon K.
A1  - Hofer,S.
A1  - Vontobel,P.
A1  - Maguire,R.P.
A1  - Radu,E.W.
A1  - Herrmann,R.
A1  - Leenders,K.L.
Y1  - 1998/05//
N1  - PET Program, Paul Scherrer Institute, Villigen, SwitzerlandPMID- 0009591593
SP  - 879
EP  - 884
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 5
N2  - Dexamethasone (DEX) is frequently used in brain tumor management. This study investigated the effect of DEX treatment and plasma glucose levels on 18F-fluorodeoxyglucose (FDG) uptake in patients with malignant gliomas (16 glioblastoma, 3 anaplastic astrocytoma). METHODS: Fifteen DEX-treated patients (mean relative dose 0.23 +/- 0.15 mg(-1) x kg(-1) x day(-1), range 0.07-0.53), four patients not treated with DEX and nine healthy subjects were studied using PET and FDG. PET data obtained from tumors and the contralateral cortex were fitted to a standard two-tissue compartment model. The FDG transport and phosphorylation rates, distribution volume (DV), steady-state accumulation (Ki), deoxyglucose metabolism (R), plasma volume as well as standardized uptake values (SUVs) and tumor-to-brain ratios were determined. In addition, the tumor size was estimated from the maximal area of contrast-enhancing tumor on computed cranial tomography (CCT) scans or MRI. RESULTS: FDG uptake was depressed in the contralateral cortex of patients and was related to tumor size. With increasing relative DEX dose, a decrease in the DV of tumors (linear regression p = 0.021) and in the DV (p = 0.109) and plasma volume (p = 0.010) of contralateral cortex was found. R, Ki and SUVs in tumors and contralateral cortex were not related to the relative DEX dose. With increasing plasma glucose levels, differential decreases in Ki and SUVs in tumors (p = 0.057 and p = 0.733, respectively) and contralateral cortex (p = 0.001 and p = 0.029, respectively) were observed. CONCLUSION: The data suggest that DEX affects FDG uptake in malignant gliomas through interaction with cerebral blood vessels and extracellular space, whereas FDG metabolism in tumors is not influenced substantially. This is of practical importance for patients having serial brain tumor imaging for treatment evaluation because patients may receive different DEX doses at different time points in the course of their disease. By contrast, the plasma glucose level must be considered a confounding variable when SUVs, tumor-to-brain ratios or Ki are used for treatment evaluation.
ER  - 

TY  - JOUR
T1  - Cortical and subcortical glucose metabolism in childhood epileptic encephalopathies.
A1  - Ferrie,C.D.
A1  - Marsden,P.K.
A1  - Maisey,M.N.
A1  - Robinson,R.O.
Y1  - 1997/08//
N1  - Department of Paediatric Neurology, The General Infirmary at Leeds, UKPMID- 0009285456
SP  - 181
EP  - 187
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 63
IS  - 2
N2  - OBJECTIVES: Nearly one third of children with cryptogenic epileptic encephalopathies have been reported to have focal cortical defects on 18fluorodeoxyglucose (FDG) PET. As diffuse cortical dysfunction and involvement of subcortical structures, particularly the thalami, is postulated to underlie the propensity to seizures in these conditions, the aim was to determine the frequency of bilateral and diffuse cortical metabolic defects and of subcortical metabolic abnormalities in the same patients. METHODS: The interictal uptake of FDG was studied in 32 children with epileptic encephalopathies. Using a semiquantitative technique, the ratio of uptake in cortical regions and subcortical structures to that in the cerebellum was compared with that of age matched historical controls. Uptake more than 2 SD above ("hypermetabolic") or below ("hypometabolic") that of age matched controls was considered abnormal. RESULTS: Diffusely abnormal cortical up-take (nearly always hypometabolic) occurred in almost two thirds of patients; in all but two of the remaining patients at least one cortical region showed significantly decreased uptake bilaterally. When analysed as age cohorts, the mean cortical:cerebellar FDG uptake was significantly lower than that of controls in all cortical regions (P<0.005). Ninety per cent of patients had evidence of relative thalamic hypometabolism and in each age group there was a significant reduction in relative thalamic FDG uptake compared with that of controls (P<0.005). In nine out of 11 patients with unilateral cortical hypometabolic defects thalamic FDG up-take was lower ipsilateral to the cortical abnormality. CONCLUSIONS: Diffuse cortical dysfunction is common in the epileptic encephalopathies and may reflect the underlying cause of the condition or arise as a consequence of uncontrolled seizures. Altered thalamic glucose metabolism is further evidence of subcortical involvement in these conditions.
ER  - 

TY  - JOUR
T1  - Dopamine and the mechanisms of cognition: Part II. D-amphetamine effects in human subjects performing a selective attention task [In Process Citation]
A1  - Servan-Schreiber,D.
A1  - Carter,C.S.
A1  - Bruno,R.M.
A1  - Cohen,J.D.
Y1  - 1998/05/15/
N1  - Department of Psychiatry, University of Pittsburgh, Pennsylvania, USA
SP  - 723
EP  - 729
JA  - Biol.Psychiatry
VL  - 43
IS  - 10
N2  - BACKGROUND: A neural network computer model described in a companion paper predicted the effects of increased dopamine transmission on selective attention under two different hypotheses. METHODS: To evaluate these predictions we conducted an empirical study in human subjects of D-amphetamine effects on performance of the Eriksen response competition task. Ten healthy volunteers were tested before and after placebo or D-amphetamine in a double-blind cross-over design. RESULTS: D-amphetamine induced a speeding of reaction time overall and an improvement of accuracy at fast reaction times but only in the task condition requiring selective attention. CONCLUSIONS: This pattern of results conforms to the prediction of the model under the hypothesis that D-amphetamine primarily affects dopamine transmission in cognitive rather than motor networks. This suggests that the principles embodied in parallel distributed processing models of task performance may be sufficient to predict and explain specific behavioral effects of some drug actions in the central nervous system.
ER  - 

TY  - JOUR
T1  - In vivo imaging of oligonucleotides with positron emission tomography.
A1  - Tavitian,B.
A1  - Terrazzino,S.
A1  - Kuhnast,B.
A1  - Marzabal,S.
A1  - Stettler,O.
A1  - Dolle,F.
A1  - Deverre,J.R.
A1  - Jobert,A.
A1  - Hinnen,F.
A1  - Bendriem,B.
A1  - Crouzel,C.
A1  - Di Giamberardino,L.
Y1  - 1998/04//
N1  - INSERM U334, CEA-SHFJ, Orsay, FrancePMID- 0009546795
SP  - 467
EP  - 471
JA  - Nat.Med.
VL  - 4
IS  - 4
ER  - 

TY  - JOUR
T1  - A hybrid image registration method employing interactive and automated techniques
A1  - Pietrzyk,U.
A1  - Thiel,A.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 1998///
SP  - S789
JF  - Neuroimage
VL  - 7 (Suppl.)
IS  - 4
ER  - 

TY  - JOUR
T1  - "3D-Tool" - A software system for visualization and analysis of coregistered multimodality volume datasets of individual subjects
A1  - von Stockhausen,H.M.
A1  - Pietrzyk,U.
A1  - Herholz,K.
Y1  - 1998///
SP  - S799
JF  - Neuroimage
VL  - 7 (Suppl.)
IS  - 4
ER  - 

TY  - JOUR
T1  - Noninvasive quantification of the cerebral metabolic rate for glucose using positron emission tomography, 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function
A1  - Chen,K.
A1  - Bandy,D.
A1  - Reiman,E.
A1  - Huang,S.C.
A1  - Lawson,M.
A1  - Feng,D.
A1  - Yun,L.S.
A1  - Palant,A.
Y1  - 1998/07//
N1  - PET Center, Good Samaritan Regional Medical Center, Phoenix, Arizona 85006, USA
SP  - 716
EP  - 723
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 7
N2  - The authors developed and tested a method for the noninvasive quantification of the cerebral metabolic rate for glucose (CMRglc) using positron emission tomography (PET), 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function. Dynamic PET data acquired 12 to 48 seconds after rapid tracer injection were summed to identify carotid artery regions of interest (ROIs). The input function then was generated from the carotid artery ROIs. To correct spillover, the early summed image was superimposed over the last PET frame, a tissue ROI was drawn around the carotid arteries, and a tissue time activity curve (TAC) was generated. Three venous samples were drawn from the tracer injection site at a later time and used for the spillover and partial volume correction by non-negative least squares method. Twenty-six patient data sets were studied. It was found that the image-derived input function was comparable in shape and magnitude to the one obtained by arterial blood sampling. Moreover, no significant difference was found between CMRglc estimated by the Patlak method using either the arterial blood sampling data or the image- derived input function.
ER  - 

TY  - JOUR
T1  - Brain networks affected by synchronized sleep visualized by positron emission tomography
A1  - Andersson,J.L.R.
A1  - Onoe,H.
A1  - Hetta,J.
A1  - Lidstrom,K.
A1  - Valind,S.
A1  - Lilja,A.
A1  - Sundin,A.
A1  - Fasth,K.J.
A1  - Westerberg,G.
A1  - Broman,J.E.
A1  - Watanabe,Y.
A1  - Langstrom,B.
Y1  - 1998/07//
N1  - Uppsala University PET-Centre, Subfemtomole Biorecognition Project, Sweden
SP  - 701
EP  - 715
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 7
N2  - Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and positron emission tomography (PET). Scanning was performed during wakefulness and after the subjects had fallen asleep. Sleep stage was graded retrospectively from electroencephalogram (EEG) recordings, and scans were divided into two groups: wakefulness or synchronized sleep. Global flow was quantified, revealing no difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way analysis of variance (ANOVA) was performed after correcting for differences in anatomy and global flow. The sum of squares of the z- score distribution showed a highly significant (P < 0.00001) omnibus difference between sleep and wakefulness. The z-score images indicated decreased flow in the thalamus and the frontal and parietal association cortices and increased flow in the cerebellum during sleep. A principal component (PC) analysis was performed on data after correction for global flow and block effects, and a multivariate analysis of variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep and revealed distinct networks consisting of PC 2, cerebellum and frontal and parietal association cortices, and PC 5, thalamus.
ER  - 

TY  - JOUR
T1  - Quantification of muscarinic cholinergic receptors with [11C]NMPB and positron emission tomography: method development and differentiation of tracer delivery from receptor binding.
A1  - Zubieta,J.K.
A1  - Koeppe,R.A.
A1  - Mulholland,G.K.
A1  - Kuhl,D.E.
A1  - Frey,K.A.
Y1  - 1998/06//
N1  - Department of Internal Medicine (Division of Nuclear Medicine), University of Michigan, Ann Arbor, USAPMID- 0009626186
SP  - 619
EP  - 631
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 6
N2  - Quantification of human brain muscarinic cholinergic receptors was investigated with the use of [11C]N-methyl-4-piperidyl benzylate (NMPB) and positron emission tomography (PET). Whole-brain uptake of NMPB at 90 to 110 minutes after intravenous injection was approximately 10% of the administered dose. The initial cerebral distribution of NMPB corresponded to the pattern of cerebral perfusion; however, at progressively longer postinjection intervals, regional distinctions consistent with muscarinic receptor binding were evident: activity at 90 to 110 minutes postinjection was highest in the striatum and cerebral cortex, intermediate in the thalamus and pons, and lowest in the cerebellum. After the development of a chromatographic system for isolation of authentic [11C]NMPB in plasma, tracer kinetic modeling was used to estimate receptor binding from the cerebral and arterial plasma tracer time-courses. Ligand transport rate and receptor-binding estimates were obtained with the use of compartmental models and analytical methods of varying complexity, including a two-parameter pixel-by-pixel-weighted integral approach and regional least-squares curve-fitting analyses employing both two- and three-compartment model configurations. In test-retest experiments, precision of the methods and their abilities to distinguish altered ligand delivery from binding in occipital cortex during an audiovisual presentation were evaluated. Visual stimulation increased the occipital blood-to-brain NMPB transport rate by 25% to 46% in estimates arising from the various approaches. Weighted integral analyses resulted in lowest apparent transport changes and in a concomitant trend toward apparent binding increases during visual activation. The regional least-squares procedures were superior to the pixel-by-pixel method in isolating the effects of altered tracer delivery from receptor-binding estimates, indicating larger transport effects and unaltered binding. Precision was best (less than 10% test-retest differences) for the weighted integral analyses and was somewhat lower in the least-squares analyses (10-25% differences). The authors conclude that pixel-by-pixel-weighted integral analyses of NMPB distribution introduce transport biases into receptor-binding estimates. Similar confounding effects also are predicted in noncompartmental analyses of delayed radiotracer distribution. The use of regional nonlinear least-squares fitting to two- and three-compartment models, although more labor intensive, provides accurate distinction of receptor-binding estimates from tracer delivery with acceptable precision in both intra- and intersubject comparisons.
ER  - 

TY  - JOUR
T1  - Klinische Wertigkeit der Positronen-Emissions-Tomographie in der Neuromedizin: Positionspapier zu den Ergebnissen einer interdisziplinren Konsensuskonferenz
A1  - Kuwert,T.
A1  - Bartenstein,P.
A1  - Grnwald,F.
A1  - Herholz,K.
A1  - Larisch,R.
A1  - Sabri,O.
A1  - Biersack,H.J.
A1  - Moser,E.
A1  - Mller-Grtner,H.-W.
A1  - Schober,O.
A1  - Schwaiger,M.
A1  - Bll,U.
A1  - Heiss,W.-D.
Y1  - 1998///in press
SP  - 1045
EP  - 1060
JF  - Nervenarzt
VL  - 69
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease.
A1  - Ishii,K.
A1  - Imamura,T.
A1  - Sasaki,M.
A1  - Yamaji,S.
A1  - Sakamoto,S.
A1  - Kitagaki,H.
A1  - Hashimoto,M.
A1  - Hirono,N.
A1  - Shimomura,T.
A1  - Mori,E.
Y1  - 1998/07//
N1  - Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, JapanPMID- 0009674790
SP  - 125
EP  - 130
JF  - Neurology
VL  - 51
IS  - 1
N2  - OBJECTIVE: To delineate the features of regional cerebral metabolic rate of glucose (CMRglc) in dementia with Lewy bodies (DLB). METHODS: We compared absolute CMRglc in 12 patients with a clinical diagnosis of DLB, 12 patients with a clinical diagnosis of Alzheimer's disease (AD), and 12 normal volunteers (NC), using 18F-fluorodeoxyglucose (FDG) and PET. The three groups were matched for age and sex, and there were no differences in disease duration or severity of cognitive disturbances between the DLB and AD groups. RESULTS: CMRglc was significantly lower in patients with DLB than in that of NC in most parts of the brain, except the sensorimotor cortices, basal ganglia, thalamus, and pons. Between the DLB and AD groups, there were significant regional CMRglc differences in the medial and lateral occipital lobes. In DLB and AD, the CMRglc reduction patterns were similar, though the global metabolic reduction was larger in DLB, and the occipital CMRglc reduction in DLB could differentiate DLB from AD. The relative occipital CMRglc (normalized to the sensorimotor CMRglc) was a useful measure for the differential diagnosis of DLB from AD. The sensitivity and the specificity were 92% when using the minimal value of the normalized occipital CMRglc in the NC group as the cut-off point. CONCLUSION: These different regional CMRglc reductions substantiate the pathologic, neurochemical, and clinical differences between DLB and AD.
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and oxygen metabolism before and after a stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)
A1  - Takahashi,S.
A1  - Tohgi,H.
A1  - Yonezawa,H.
A1  - Obara,S.
A1  - Nagane,Y.
Y1  - 1998/06/11/
N1  - Department of Neurology, Iwate Medical University, Morioka, Japan
SP  - 58
EP  - 64
JA  - J.Neurol.Sci.
VL  - 158
IS  - 1
N2  - Cerebral blood flow and oxygen metabolism were examined in two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke- like episodes (MELAS) using positron emission tomography (PET). Regional cerebral blood flow (rCBF), regional cerebral oxygen metabolic rate (rCMRO2) and regional oxygen extraction fraction (rOEF) were determined with the steady-state technique using oxygen-15-labeled tracers (15O2, C15O2 and C15O). Case 1, a 45-year-old woman, presented with abrupt onset of fluent aphasia. T2-weighted magnetic resonance imaging (MRI) showed a high signal intensity lesion in the left temporoparietal region. The first PET study on day 16 showed increased rCBF and decreased rCMRO2 in the temporal region. In the second PET study, on day 35, rCBF in the temporal region had decreased. Case 2 was a 19-year-old male; the second son of Case 1. He complained of transient blurring of vision, and then generalized tonic-clonic convulsion occurred. A PET study six days before this stroke-like episode demonstrated increased rCBF in both frontal lobes and putamen, where MRI showed lesions after the episode. Focal hyperemia of the lesion antedated and lasted for at least sixteen days after the stroke- like episode in these MELAS patients. These stroke-like episodes appear to be the result of metabolic dysfunction in neural tissue, although the role of an ischemic vascular event cannot be ruled out.
ER  - 

TY  - JOUR
T1  - Cerebral metabolism of oxygen and glucose in a patient with MELAS syndrome.
A1  - Sano,M.
A1  - Ishii,K.
A1  - Momose,Y.
A1  - Uchigata,M.
A1  - Senda,M.
Y1  - 1995/12//
N1  - Department of Neurology, Showa General Hospital, JapanPMID- 0008750117
SP  - 497
EP  - 502
JA  - Acta Neurol.Scand.
VL  - 92
IS  - 6
N2  - We studied cerebral oxygen and glucose metabolism as well as cerebral blood flow using positron emission tomography (PET) in a case with MELAS showing dementia, diabetes mellitus, ataxia and lactic acidosis without any signs of stroke. This case, confirmed to have a point mutation at position 3243 in the transfer RNA gene of mitochondrial DNA, developed a stroke-like episode 8 months after the PET study. Uncoupling was observed between cerebral oxygen metabolism and cerebral blood flow with reduced fractional oxygen extraction ratio, indicating "hyperemia", not ischemia. The "hyperemia" may be closely related to the malfunction of mitochondria in aerobic energy production. A drastic decrease in cerebral oxygen metabolism (CMRO2) was found globally in contrast to preserved cerebral glucose metabolism (CMRglu), resulting in a remarkable decrease in the metabolic ratio (CMRO2/CMRglu). The dissociation between cerebral glucose and oxygen metabolism may be characteristic of MELAS.
ER  - 

TY  - JOUR
T1  - Cerebral blood flow in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.
A1  - Ooiwa,Y.
A1  - Uematsu,Y.
A1  - Terada,T.
A1  - Nakai,K.
A1  - Itakura,T.
A1  - Komai,N.
A1  - Moriwaki,H.
Y1  - 1993/02//
N1  - Department of Neurological Surgery, Wakayama Medical College, JapanPMID- 0008421833
SP  - 304
EP  - 309
JF  - Stroke
VL  - 24
IS  - 2
N2  - BACKGROUND AND PURPOSE: The precise mechanism of neurological symptoms with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is still controversial. We investigated the correlation between strokelike episodes and cerebral blood flow in two patients with MELAS and discuss the pathogenesis of strokelike episodes with MELAS. SUMMARY OF REPORT: Cerebral dynamic computed tomography and cerebral angiography were used to measure cerebral circulation in the first case, that of a 20-year-old woman with MELAS. The second subject was a 13-year-old female who was studied with xenon-enhanced computed tomography. The cerebral blood flow studies were performed 3-72 hours after the onset of strokelike episodes. Serial cerebral angiography, dynamic computed tomography, and xenon-enhanced computed tomography showed vasodilation localized in the affected cerebral cortexes during strokelike episodes, without any reduction in regional cerebral blood flow. CONCLUSIONS: Our study suggests that the strokelike episodes associated with MELAS are different in origin from ischemic stroke.
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow and oxygen metabolism in a patient with Korsakoff syndrome.
A1  - Matsuda,K.
A1  - Yamaji,S.
A1  - Ishii,K.
A1  - Sasaki,M.
A1  - Sakamoto,S.
A1  - Kitagaki,H.
A1  - Imamura,T.
A1  - Mori,E.
Y1  - 1997/02//
N1  - Divisions of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), JapanPMID- 0009095320
SP  - 33
EP  - 35
JA  - Ann.Nucl.Med.
VL  - 11
IS  - 1
N2  - We report a functional neuroimaging study of a patient clinically diagnosed with Korsakoff syndrome. Positron emission tomography (PET) with the 15O inhalation method showed decreased regional cerebral blood flow (rCBF) and decreased regional cerebral metabolic ratio for oxygen (rCMRO2) in the bilateral fronto-temporal areas and in the left thalamus. These results suggest that dysfunction of the frontal- thalamic neural network plays a role in the disturbance of Korsakoff syndrome.
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and oxygen metabolism in hemiparetic patients with chronic subdural hematoma. Quantitative evaluation using positron emission tomography.
A1  - Ishikawa,T.
A1  - Kawamura,S.
A1  - Hadeishi,H.
A1  - Suzuki,A.
A1  - Yasui,N.
A1  - Uemura,K.
Y1  - 1995/02//
N1  - Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-Akita, JapanPMID- 0007892656
SP  - 130
EP  - 136
JA  - Surg.Neurol.
VL  - 43
IS  - 2
N2  - BACKGROUND: It remains unclear why chronic subdural hematoma (CSH) can cause hemiparesis, although the contribution of impaired cerebral blood flow and metabolism has been suggested. METHODS: We studied six hemiparetic patients (five men, one woman; mean age 60.5 +/- 7.5 years) with unilateral CSH using positron emission tomography. The 15O2 steady state technique was used to measure regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), and regional cerebral metabolic rate of oxygen (rCMRO2), followed by the 1-minute inhalation of C15O to measure regional cerebral blood volume (rCBV). RESULTS: On the hematoma side, rCBF and rCMRO2 were significantly reduced in the caudate nucleus and the cingulate gyrus. We observed a tendency toward reduced levels of rCBF and rCMRO2 in the lentiform nucleus. rCBV was not elevated. rOEF was significantly elevated in the lentiform nucleus, the cingulate gyrus, the frontal gray matters under the hematoma and the semioval center. On the nonhematoma side, rCBF and rCMRO2 were normal except for the significant reduction in the cingulate gyrus. rCBV was elevated in the lentiform nucleus, the middle temporal gyrus and the inferior frontal gyrus. rOEF was elevated significantly in the cingulate gyrus, the precentral gyrus and the semioval center. CONCLUSIONS: Our hemiparetic patients with CSH were observed to have a circulatory disturbance of blood; it was manifested by an elevation of rOEF, specifically in the hemisphere adjacent to the hematoma. This circulatory disturbance was highly pronounced and resulted in a consistent reduction in rCBF and rCMRO2 in the anterior central cerebral area such as the caudate nucleus, the lentiform nucleus and the cingulate gyrus.
ER  - 

TY  - JOUR
T1  - The significance of family history status in relation to neuropsychological test performance and cerebral glucose metabolism studied with positron emission tomography in older alcoholic patients
A1  - Adams,K.M.
A1  - Gilman,S.
A1  - Johnson-Greene,D.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Martorello,S.
A1  - Johnson,M.J.
A1  - Heumann,M.
A1  - Hill,E.
Y1  - 1998/02//
N1  - Ann Arbor Veteran's Affairs Medical Center, Department of Psychiatry, University of Michigan, USAPMID- 0009514291
SP  - 105
EP  - 110
JA  - Alcohol Clin.Exp.Res.
VL  - 22
IS  - 1
N2  - Patients with severe chronic alcoholism have decreased rates of glucose metabolism in the medial frontal lobe and correlated abnormalities of neuropsychological functioning. The potential influence of family history of alcoholism has not been examined in these patients. In a retrospective study, we used neuropsychological tests and neuroimaging employing [18F]fluorodeoxyglucose with positron emission tomography to study 48 older subjects who had histories of severe, chronic alcohol dependence. These patients were divided into two groups: 27 with a first-degree relative with chronic alcoholism and 21 patients without first-degree relative with chronic alcoholism. No differences were found between groups on either neuropsychological or neuroimaging tests. These results suggest that a family history of alcoholism does not moderate the damaging effects of severe chronic alcoholism on the functioning of the medial frontal lobe
ER  - 

TY  - JOUR
T1  - Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism
A1  - Johnson-Greene,D.
A1  - Adams,K.M.
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Martorello,S.
A1  - Heumann,M.
Y1  - 1997/06//
N1  - University of Michigan Alcohol Research Center, USAPMID- 0009268812
SP  - 378
EP  - 385
JA  - J.Clin.Exp.Neuropsychol.
VL  - 19
IS  - 3
N2  - Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of lCMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol
ER  - 

TY  - JOUR
T1  - Effects of disulfiram on positron emission tomography and neuropsychological studies in severe chronic alcoholism
A1  - Gilman,S.
A1  - Adams,K.M.
A1  - Johnson-Greene,D.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Martorello,S.
A1  - Heumann,M.
A1  - Hill,E.
Y1  - 1996/11//
N1  - Department of Neurology, University of Michigan, Ann Arbor 48109-0316, USAPMID- 0008947325
SP  - 1456
EP  - 1461
JA  - Alcohol Clin.Exp.Res.
VL  - 20
IS  - 8
N2  - Disulfiram is an aldehyde dehydrogenase inhibitor that is widely used as an adjunctive agent in the treatment of patients with severe chronic alcoholism. Recent positron emission tomography (PET) studies of local cerebral metabolic rates for glucose (ICMRglc) and benzodiazepine receptor binding in alcoholic patients have shown regional cerebral abnormalities; however, some of the patients were studied while receiving disulfiram, which could influence the biochemical processes under investigation. In a retrospective investigation, we examined the influence of disulfiram administration on the results of PET studies of ICMRglc and benzodiazepine receptor binding and neuropsychological tests of cognition and executive function in patients with severe chronic alcoholism. [18F]Fluorodeoxyglucose was used to measure ICMRglc in 48 male patients, including 11 receiving and 37 not receiving disulfiram in therapeutic doses. [11C]Flumazenil was used to measure benzodiazepine receptor binding in 17 male patients, including 3 receiving and 14 not receiving disulfiram. All patients studied with FMZ were also examined with fluorodeoxyglucose. PET studies of ICMRglc revealed significantly decreased global values in the patients receiving disulfiram compared with those not receiving disulfiram. PET studies of benzodiazepine receptor binding revealed decreased flumazenil influx and distribution volume in patients receiving disulfiram. The neuropsychological tests demonstrated no differences between the two groups of subjects. The findings suggest that disulfiram may influence the results of PET studies of glucose metabolism and benzodiazepine receptor binding
ER  - 

TY  - JOUR
T1  - Differentiating recurrent tumor from radiation necrosis: time for re- evaluation of positron emission tomography? [see comments]
A1  - Ricci,P.E.
A1  - Karis,J.P.
A1  - Heiserman,J.E.
A1  - Fram,E.K.
A1  - Bice,A.N.
A1  - Drayer,B.P.
Y1  - 1998/03//
N1  - Department of Neuroradiology, Barrow Neurological Institute, Phoenix, AZ 85001, USA
SP  - 407
EP  - 413
JA  - AJNR.Am.J.Neuroradiol.
VL  - 19
IS  - 3
N2  - Our purpose was to evaluate the ability of FDG PET to differentiate recurrent tumor from posttherapy radiation necrosis. METHODS: MR images, PET scans, and medical records of 84 consecutive patients with a history of a treated intracranial neoplasm were evaluated retrospectively. In all patients, recurrent tumor or radiation necrosis was suggested by clinical or MR findings. Metabolic activity of the PET abnormality was compared qualitatively with normal contralateral gray and white matter. RESULTS: PET findings were confirmed histologically in 31 patients. With contralateral white matter as the standard of comparison, the PET scan sensitivity and specificity were found to be 86% and 22%, respectively. With contralateral gray matter as the reference standard, the sensitivity and specificity became 73% and 56%, respectively. Overall, nearly one third of the patients would have been treated inappropriately in either scheme had the PET scan been the sole determinant of therapy. CONCLUSION: Our data suggest that the ability of FDG PET to differentiate recurrent tumor from radiation necrosis is limited. Both false-positive and false-negative PET scan results contributed to unacceptably low sensitivity and specificity values
ER  - 

TY  - JOUR
T1  - Precentral glioma location determines the displacement of cortical hand representation
A1  - Wunderlich,G.
A1  - Knorr,U.
A1  - Herzog,H.
A1  - Kiwit,J.C.
A1  - Freund,H.J.
A1  - Seitz,R.J.
Y1  - 1998/01//
N1  - Department of Neurology, Heinrich-Heine-Universitat Dusseldorf, GermanyPMID- 0009442499
SP  - 18
EP  - 26
JF  - Neurosurgery
VL  - 42
IS  - 1
N2  - OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas
ER  - 

TY  - JOUR
T1  - Use of positron emission tomography for presurgical localization of eloquent brain areas in children with seizures
A1  - Duncan,J.D.
A1  - Moss,S.D.
A1  - Bandy,D.J.
A1  - Manwaring,K.
A1  - Kaplan,A.M.
A1  - Reiman,E.M.
A1  - Chen,K.
A1  - Lawson,M.A.
A1  - Wodrich,D.L.
Y1  - 1997/03//
N1  - Division of Neurosurgery, University of Arizona College of Medicine, Tucson, USAPMID- 0009419031
SP  - 144
EP  - 156
JA  - Pediatr.Neurosurg.
VL  - 26
IS  - 3
N2  - Successful surgical management of a neoplastic or nonneoplastic seizure focus in close proximity to or within eloquent brain areas relies on precise delineation of the relationship between the lesion and functional brain areas. The aim of this series was to validate the usefulness and test the efficacy of noninvasive presurgical PET mapping of eloquent brain areas to predict surgical morbidity and outcome in children with seizures. To identify eloquent brain areas in 15 children (6 female and 9 male; mean age 11 years) with epileptogenic lesions PET images of regional cerebral blood flow were performed following the administration of [(15)O]water during motor, visual, articulation, and receptive language tasks. These images with coregistered magnetic resonance (MR) images were then used to delineate the anatomic relationship of a seizure focus to eloquent brain areas. Additional PET images using [18F]fluoro-2-deoxy-D-glucose (FDG) and [11C]methionine (CMET) were acquired to help localize the seizure focus, as well as characterize the lesion. Patient surgical management decisions were based on PET mapping in combination with coregistered MR images, PET- FDG findings, and the anatomic characteristics of the lesion. At follow- up 1-26 months after surgery, all patients that underwent temporal lobectomy (9 patients) and extratemporal resection (4 patients) for a neoplastic or nonneoplastic seizure focus are seizure-free with minimal postoperative morbidity. Of prime importance, no child sustained a postoperative speech or language deficit. PET imaging was also well tolerated without procedural complications. Based on PET mapping, a nonoperative approach was used for 2 children and a biopsy only was used in one child. When cortical injury involved prenatally determined eloquent cortex, PET demonstrated reorganization of language areas to new adjacent areas or even to the contralateral hemisphere. Integration of anatomical and functional data enhanced the surgical safety, defined optimal surgical approach, delineated the seizure focus from eloquent brain areas, facilitated maximum resection and optimized the timing of surgery, thereby minimizing surgical morbidity while maximizing surgical goals. PET measurements of FDG and CMET uptake were also helpful in localizing the seizure focus and grading the tumors. PET used for brain mapping in children provides the surgeon with strategic preoperative information not readily attainable with traditional invasive Wada testing or intraoperative cortical stimulation. PET mapping may also improve the outcome of extratemporal resections by allowing aggressive seizure focus resection. In addition, serial brain maps may optimize timing for surgical intervention by demonstrating reorganization of eloquent cortex often seen in younger children after cortical injury. Our results suggest that noninvasive presurgical brain mapping has the potential to reduce risk and improve neurologic outcome
ER  - 

TY  - JOUR
T1  - MRI and PET coregistration--a cross validation of statistical parametric mapping and automated image registration
A1  - Kiebel,S.J.
A1  - Ashburner,J.
A1  - Poline,J.B.
A1  - Friston,K.J.
Y1  - 1997/05//
N1  - Department of Neurology, Friedrich-Schiller University, Jena, GermanyPMID- 0009345556
SP  - 271
EP  - 279
JA  - Neuroimage.
VL  - 5
IS  - 4 Pt 1
N2  - Coregistration of functional PET and T1-weighted MR images is a necessary step for combining functional information from PET images with anatomical information in MR images. Several coregistration algorithms have been published and are used in functional brain imaging studies. In this paper, we present a comparison and cross validation of the two most widely used coregistration routines (Friston et al., 1995, Hum. Brain Map. 2: 165-189; Woods et al., 1993, J. Comput. Assisted Tomogr: 17: 536-546). Several transformations were applied to high- resolution anatomical MR images to generate simulated PET images so that the exact (rigid body) transformations between each MR image and its associated simulated PET images were known. The estimation error of a coregistration in relation to the known transformation allows a comparison of the performance of different coregistration routines. Under the assumption that the simulated PET images embody the salient features of real PET images with respect to coregistration, this study shows that the routines examined reliably solve the MRI to PET coregistration problem
ER  - 

TY  - JOUR
T1  - Mapping voxel-based statistical power on parametric images
A1  - Van Horn,J.D.
A1  - Ellmore,T.M.
A1  - Esposito,G.
A1  - Berman,K.F.
Y1  - 1998/02//
N1  - Unit on PET, CBDB/NIMH, National Institutes of Health, Bethesda, Maryland 20892, USAPMID- 0009558642
SP  - 97
EP  - 107
JA  - Neuroimage.
VL  - 7
IS  - 2
N2  - Using a classic technique based on the noncentral F-distribution method for computing statistical power, we developed a general approach to the estimation of voxel-based power in functional brain image data analysis. We applied this method to PET data from a large sample (N = 40) of subjects performing the Wisconsin Card Sorting (WCST) paradigm analyzed with SPM95, produced statistical power maps for a range of samples sizes and smoothing filter widths, and examined the effects of sample size and image smoothing on the expected reliability of activation findings. At an uncorrected alpha of 0.01, a fixed filter size of 10 mm3, and a range of power thresholds, maps revealed that the power to reject the null hypothesis in brain regions implicated in the task at Ns of 5 and 10 may not be sufficient to ensure reliable replication of significant findings and so should be interpreted with caution. At sample sizes approaching 20 subjects, sufficient power was found in the right dorsolateral prefrontal cortex (BA 46/9), right and left inferior parietal lobule (BA 40), and left inferior temporal lobe (BA 37), comprising the cortical network typically observed during the WCST. Filter size needed to maximize power varied widely, but systematically, across the brain, tending to follow known neuroanatomical landmarks. Statistical power considerations in brain imaging studies are critical for controlling the rate of false negatives and assuring reliable detection of cognitive activation. The variation of filter size for maximizing power across the brain suggests that the underlying neuroanatomy of functional units is an important consideration in the a priori selection of filter size
ER  - 

TY  - JOUR
T1  - 11C-flumazenil PET in neocortical epilepsy
A1  - Richardson,M.P.
A1  - Koepp,M.J.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 1998/08//
N1  - Epilepsy Research Group, Institute of Neurology, Hammersmith Hospital, London, UK
SP  - 485
EP  - 492
JF  - Neurology
VL  - 51
IS  - 2
N2  - OBJECTIVE: To investigate focal cortical abnormalities of gamma- aminobutyric acid type A-central benzodiazepine receptors (GABA(A)- cBZRs) in patients with extratemporal partial seizures with acquired lesions and in patients with normal high-resolution MRI. METHODS: Six patients with acquired lesions and 18 patients with normal high- resolution MRI and extratemporal partial seizures, as well as 24 normal controls, were studied with 11C-flumazenil (FMZ) PET to produce voxel- by-voxel images of FMZ volume of distribution (FMZVD), which reflects density of GABA(A)-cBZRs. These images were analyzed using Statistical Parametric Mapping (SPM). Each patient was compared with the control group to reveal regions with abnormal FMZVD at p < 0.001 uncorrected, corrected to p < 0.05 for the whole brain volume. Each normal control was compared with the remaining controls in the same manner. RESULTS: All six patients with acquired lesions had a single region of reduced FMZVD. Thirteen of 18 patients with normal MRI had regions of abnormal cortical FMZVD: 10 had regions of increased FMZVD, 6 had regions of decreased FMZVD, and 3 had both regions of increased and decreased FMZVD. Seven patients had an abnormality in the lobe and 12 in the hemisphere of presumed seizure origin. CONCLUSIONS: FMZ PET analyzed with SPM is an automated, objective, sensitive, and specific means for detecting regional cortical abnormalities of GABA(A)-cBZRs in patients with partial seizures. This technique may be useful in the evaluation of patients with refractory partial seizures for surgical treatment, particularly in those patients with normal MRI
ER  - 

TY  - JOUR
T1  - PET with 18fluorodeoxyglucose and hexamethylpropylene amine oxime SPECT in late whiplash syndrome
A1  - Bicik,I.
A1  - Radanov,B.P.
A1  - Schafer,N.
A1  - Dvorak,J.
A1  - Blum,B.
A1  - Weber,B.
A1  - Burger,C.
A1  - von Schulthess,G.K.
A1  - Buck,A.
Y1  - 1998/08//
N1  - Department of Medical Radiology, University of Zurich, Switzerland
SP  - 345
EP  - 350
JF  - Neurology
VL  - 51
IS  - 2
N2  - BACKGROUND: Many patients have cognitive abnormalities and psychological problems after whiplash injury to the cervical spine. To our knowledge, neuroradiologic imaging has not depicted brain damage that explains the symptoms. Parietotemporo-occipital perfusion deficits on hexamethylpropylene amine oxime (HMPAO) SPECT studies have been described among patients who have sustained whiplash injury. METHODS: We examined 13 patients with typical late whiplash syndrome (study group) using HMPAO SPECT, 18fluorodeoxyglucose (FDG) PET, and MRI of the brain and compared the findings with those for 16 control subjects who underwent FDG PET. RESULTS: In the study group, statistical parametric mapping revealed significantly decreased FDG uptake in the frontopolar and lateral temporal cortex and in the putamen. The frontopolar hypometabolism correlated significantly with scores of the Beck Depression Inventory. However, in individual cases, reliability in the depiction of hypometabolic areas was relatively low. No alterations were found in the parietotemporo-occipital area. In these areas, decreased uptake of HMPAO and FDG correlated with cortical mass. CONCLUSION: FDG PET did not allow reliable diagnosis of metabolic disturbances for individual patients. Therefore, we do not recommend FDG PET or HMPAO SPECT as a diagnostic tool in routine examinations of patients with late whiplash syndrome
ER  - 

TY  - JOUR
T1  - PET study and neuropsychological assessment of a long-lasting post- encephalitic parkinsonism
A1  - Caparros-Lefebvre,D.
A1  - Cabaret,M.
A1  - Godefroy,O.
A1  - Steinling,M.
A1  - Remy,P.
A1  - Samson,Y.
A1  - Petit,H.
Y1  - 1998///
N1  - Department of Neurology, CHU Pointe a Pitre, French West Indies
SP  - 489
EP  - 495
JA  - J.Neural Transm.
VL  - 105
IS  - 4-5
N2  - A 76-year old woman was affected by lethargic encephalitis in 1918, at the age of 3 months. Long-term clinical follow-up with late neuropsychological evaluation revealed post-encephalitic parkinsonism, which worsened very slowly and was improved by levodopa. Obsessive and compulsive disorders (OCD) were associated to nosophobia. Neuropsychological evaluation showed mild visuocontructional memory deficit, which was isolated. 18 Fluoro-Dopa PET demonstrated a severe bilateral and symmetrical reduction in fluoro-dopa uptake, which was more marked in the putamen than in the caudate. Thus, the pattern of dopaminergic denervation was similar to the one observed in idiopathic Parkinson's disease
ER  - 

TY  - JOUR
T1  - Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy?
A1  - Debets,R.M.
A1  - Sadzot,B.
A1  - van Isselt,J.W.
A1  - Brekelmans,G.J.
A1  - Meiners,L.C.
A1  - van Huffelen,A.O.
A1  - Franck,G.
A1  - van Veelen,C.W.
Y1  - 1997/02//
N1  - Instituut veor Epilepsiebestrijding, Meer en Bosch-de Cruquiushoeve, Heemstede, The NetherlandsPMID- 0009048714
SP  - 141
EP  - 150
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 62
IS  - 2
N2  - OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C- flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C- flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non- lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery
ER  - 

TY  - JOUR
T1  - Hypothalamic activation in cluster headache attacks
A1  - May,A.
A1  - Bahra,A.
A1  - Buchel,C.
A1  - Frackowiak,R.S.
A1  - Goadsby,P.J.
Y1  - 1998/07/25/
N1  - University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK amay@ionuclacuk
SP  - 275
EP  - 278
JF  - Lancet
VL  - 352
IS  - 9124
N2  - BACKGROUND: Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache. METHODS: We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group. FINDINGS: In the acute pain state, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout. INTERPRETATION: Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work
ER  - 

TY  - JOUR
T1  - [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET
A1  - Suehiro,M.
A1  - Scheffel,U.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
A1  - Wagner,H.N.,Jr
Y1  - 1993///
N1  - Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179PMID- 0008366755
SP  - 883
EP  - 892
JA  - Life Sci.
VL  - 53
IS  - 11
N2  - The in vivo behavior of the stereoisomers of [11C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [11C](+)McN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [11C]-labeled racemic mixture, while [11C](-)McN5652 washed out rapidly. With the [11C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [11C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [11C](-)McN5652 showed no specific binding in any of the regions. The [11C]-labeled cis isomer, [11C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [11C](+)McN5652 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo
ER  - 

TY  - JOUR
T1  - In vivo detection of short- and long-term MDMA neurotoxicity--a positron emission tomography study in the living baboon brain
A1  - Scheffel,U.
A1  - Szabo,Z.
A1  - Mathews,W.B.
A1  - Finley,P.A.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Szabo,K.
A1  - Yuan,J.
A1  - Ricaurte,G.A.
Y1  - 1998/06//
N1  - Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USAPMID- 0009593108
SP  - 183
EP  - 192
JF  - Synapse
VL  - 29
IS  - 2
N2  - The present study evaluated short- and long-term effects of MDMA (3,4- methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI- 55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](- )McN5652 (the inactive enantiomer of the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the difference in radioactivity concentrations between (+) and (-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and 13 months showed regional differences in the apparent recovery of 5-HT transporters, with increases in some brain regions (e.g., hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained from PET studies correlated well with regional 5-HT axonal marker concentrations in the CNS measured after sacrifice of the animal. The results of these studies indicate that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can detect changes in regional 5-HT transporter density secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to determine whether human MDMA users are also susceptible to MDMA's neurotoxic effects
ER  - 

TY  - JOUR
T1  - Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
A1  - Minoshima,S.
A1  - Giordani,B.
A1  - Berent,S.
A1  - Frey,K.A.
A1  - Foster,N.L.
A1  - Kuhl,D.E.
Y1  - 1997/07//
N1  - Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0028, USAPMID- 0009225689
SP  - 85
EP  - 94
JA  - Ann.Neurol.
VL  - 42
IS  - 1
N2  - This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [18F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0-23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 +/- 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age- similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21-22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease
ER  - 

TY  - JOUR
T1  - Metabolic impairment of association cortex predicts progression in Alzheimer's disease: a prospective multicenter positron emission tomography (PET) study
A1  - Herholz,K.
A1  - Nordberg,A.
A1  - Salmon,E.
A1  - Perani,D.
A1  - Kessler,J.
A1  - Mielke,R.
A1  - Halber,M.
A1  - Jelic,V.
A1  - Almkvist,O.
A1  - Collette,F.
A1  - Alberoni,M.
A1  - Kennedy,A.
A1  - Hasselbalch,S.
A1  - Fazio,F.
A1  - Heiss,W.-D.
Y1  - 1998///
N1  - Similar abstract: Eur J Clin Invest 29, Suppl. 1, 73, 1999
SP  - S24
JF  - European Journal of Neurology
JA  - Eur J Neurol
VL  - 5
IS  - Suppl. 3
ER  - 

TY  - JOUR
T1  - Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies
A1  - Di Chiro,G.
A1  - Oldfield,E.
A1  - Wright,D.C.
A1  - De Michele,D.
A1  - Katz,D.A.
A1  - Patronas,N.J.
A1  - Doppman,J.L.
A1  - Larson,S.M.
A1  - Ito,M.
A1  - Kufta,C.V.
Y1  - 1988/01//
N1  - Neuroimaging Section, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892PMID- 0003257119
SP  - 189
EP  - 197
JA  - AJR.Am.J.Roentgenol.
VL  - 150
IS  - 1
N2  - Cerebral necrosis after radiotherapy for brain tumors is being recognized as a problem more common than previously estimated. Distinction between this iatrogenic complication and tumor recurrence cannot be made by either CT or MR imaging. By using positron emission tomography (PET) with 18F-deoxyglucose (FDG) we were able to reach a diagnosis of radiation necrosis, later verified, in 10 of 95 patients referred for the purpose of differentiating tumor recurrence from necrosis. The critical PET-FDG feature was focal hypometabolism in the area of necrosis, which contrasted with the hypermetabolism associated with the residual/recurrent tumor. In addition, four cases of cerebral necrosis after supraophthalmic, intraarterial chemotherapy (BCNU) were studied with the PET-FDG method. The area of chemotherapy damage was also characterized by marked hypometabolism. Histology revealed both similarities and differences between radio- and chemonecrosis
ER  - 

TY  - JOUR
T1  - Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy
A1  - Goldman,S.
A1  - Levivier,M.
A1  - Pirotte,B.
A1  - Brucher,J.M.
A1  - Wikler,D.
A1  - Damhaut,P.
A1  - Dethy,S.
A1  - Brotchi,J.
A1  - Hildebrand,J.
Y1  - 1997/09//
N1  - PET/Biomedical Cyclotron Unit, Service de Neurologie, ULB-Hopital Erasme, Brussels, Belgium
SP  - 1459
EP  - 1462
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 9
N2  - Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. METHODS: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. RESULTS: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C- MET. CONCLUSION: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures
ER  - 

TY  - JOUR
T1  - Assessment of cancer recurrence in residual tumors after fractionated radiotherapy: a comparison of fluorodeoxyglucose, L-methionine and thymidine
A1  - Reinhardt,M.J.
A1  - Kubota,K.
A1  - Yamada,S.
A1  - Iwata,R.
A1  - Yaegashi,H.
Y1  - 1997/02//
N1  - Department of Nuclear Medicine and Radiology, Tohoku University, Sendai, JapanPMID- 0009025756
SP  - 280
EP  - 287
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 2
N2  - This study evaluates the midterm follow-up of tumor and normal tissue uptake of deoxyglucose, thymidine and methionine after fractionated radiotherapy to assess cancer recurrence in residual tumors. METHODS: AH109A tumor-burdened rats were treated with one to eight doses of 5Gy 60Co radiation. Tissue distribution study with 18F-FDG, 3H-thymidine and 14C-methionine, double-tracer autoradiography with 18F-FDG and 14C- methionine, and single-tracer autoradiography with 14C-labeled deoxyglucose, thymidine and methionine were performed 6 days after the end of therapy. RESULTS: Dose response study shows a significant decrease of tumor uptake of all tracers after two and more doses, even in the case of later recurrence. Whereas 3H-Thd and 14C-Met tumor uptake was similar to that of normal muscle, 18F-FDG tumor uptake remains higher than that of muscle, even in the case of complete tumor cure. The irradiated muscle shows a higher 18F-FDG uptake than the nonirradiated muscle. Autoradiography after eight doses (100% tumor cure) reveals elevated 14C-DG tumor uptake to be ascribable to nonmalignant cellular elements, in particular to a macrophage layer at the rim of necrotic areas. Autoradiography after four and six doses (33% and 57% tumor cure) shows the highest methionine and thymidine uptake in viable cancer cells, whereas deoxyglucose uptake did not differ between viable cancer cells and macrophages. CONCLUSION: To detect and differentiate viable cancer cells in a residual tumor mass after radiotherapy, PET using 11C-methionine or 11C-thymidine may have some advantages over 18F-FDG, especially if the residual tumor includes larger areas of necrosis
ER  - 

TY  - JOUR
T1  - Comparison of the transient equilibrium and continuous infusion method for quantitative PET analysis of [11C]raclopride binding [In Process Citation]
A1  - Ito,H.
A1  - Hietala,J.
A1  - Blomqvist,G.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 1998/09//
N1  - Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
SP  - 941
EP  - 950
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 9
N2  - Several approaches have been applied for quantification of D2 dopamine receptors in positron emission tomography studies using [11C]raclopride. Initial approaches were based on analyses of data obtained after rapid bolus injection of [11C]raclopride. A continuous infusion paradigm has more recently been applied. The current study compares these approaches in healthy men. Two positron emission tomography measurements were performed in each of six healthy men, the first with rapid bolus injection and the second with continuous infusion of [11C]raclopride. In rapid bolus injection, the binding potential was calculated by the following methods. One approach is the kinetic analysis using the standard three-compartment model. Another is to define a transient equilibrium at the moment when the specific binding reaches its maximum. In continuous infusion, binding potential was calculated by using time-activity data at equilibrium condition. All methods gave almost identical binding potential, representing cross- validation of these methods. The continuous infusion method can provide "true" equilibrium condition. The kinetic analysis is a sophisticated approach but requires determination of an arterial input function. The transient equilibrium method thus is suitable for routine clinical research, since it does not require determination of an arterial input function
ER  - 

TY  - JOUR
T1  - Cerebral activation in malformations of cortical development
A1  - Richardson,M.P.
A1  - Koepp,M.J.
A1  - Brooks,D.J.
A1  - Coull,J.T.
A1  - Grasby,P.
A1  - Fish,D.R.
A1  - Duncan,J.S.
Y1  - 1998/07//
N1  - Epilepsy Research Group, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UKPMID- 0009679781
SP  - 1295
EP  - 1304
JF  - Brain
VL  - 121
IS  - Pt 7
N2  - Malformations of cortical development (MCD) are an important aetiology of localization-related epilepsy. Previous MRI and [11C]flumazenil PET studies have demonstrated widespread structural and neuroreceptor abnormalities beyond the region of MCD that is visually apparent on MRI. We investigated the ability of brain regions affected by MCD to participate in normal cognitive and motor tasks and compared the responses seen in such patients with those in normal subjects. We studied five patients known to have MCD affecting the occipital region and seven normal subjects using H2 (15)O PET whilst they were performing a visual attention task. We also studied five right-handed patients known to have MCD affecting the left frontal lobe and seven right-handed normal subjects, using H2 (15)O PET whilst they were performing a motor learning task with the right hand. The patient and normal control data were examined using statistical parametric mapping to determine the ability of the brain region affected by MCD to participate in the task and also to detect evidence for atypical organization of cortical function in association with the MCD. Eight of the ten patients with MCD showed significant alteration of relative regional cerebral blood flow during the task compared with 'rest' in the affected brain region. These regions included focally dysgenetic cortex, the cortex lining schizencephalic clefts, heterotopic bands, subependymal grey matter heterotopia, and the cortex overlying band and subependymal heterotopia. In addition there was a significant alteration in the overall activation pattern in five patients compared with the normal control groups; in all five patients this atypical organization involved regions of cortex that appeared entirely normal on MRI. We conclude that regions of MCD may participate in normal cognitive functions but widespread cortical atypical organization may be seen. These findings have implications for surgical planning in any such patients
ER  - 

TY  - JOUR
T1  - The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies
A1  - Magistretti,P.J.
A1  - Pellerin,L.
Y1  - 1996/12//
N1  - Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Faculte de Medecine, Universite de Lausanne, Switzerland pmagistr@ulysunilch
SP  - 445
EP  - 452
JA  - Mol.Psychiatry
VL  - 1
IS  - 6
N2  - With the development of functional brain imaging techniques such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) it has become possible to visualize brain areas that are activated by a variety of sensory, motor or cognitive tasks. This technological progress has permitted a kind of in vivo functional neuroanatomy which has led to the identification of neural circuits subserving specific brain functions. Metabolic processes linked to neuronal activity--such as blood flow, glucose utilization and oxygen consumption--provide the signals detected with most functional brain- imaging techniques. These metabolic indices have been examined in a variety of psychiatric and neurological disorders. This article focuses on the use of (18F)fluoro-2-deoxyglucose (FDG)-PET in the study of psychiatric disorders; it is mainly intended to bring a novel perspective, based on recent experimental data, on the cellular and molecular mechanisms that underlie the FDG-based PET imaging. These new observations point to a critical role of a particular glial cell type, the astrocyte, in coupling neuronal activity to glucose utilization. Indeed it appears that in response to glutamate released by active neurons, glucose is predominantly taken up by specialized astrocytic processes, the end-feet, which surround brain capillaries; glucose is then metabolized to lactate, which provides a preferred energy substrate for neurons. These data support the notion that astrocytes markedly contribute to the FDG-PET signal. This perspective may also provide renewed insights for the interpretation of FDG-PET studies in psychiatric disorders
ER  - 

TY  - JOUR
T1  - Alcohol activates the cerebral reward system in man
A1  - Ingvar,M.
A1  - Ghatan,P.H.
A1  - Wirsen-Meurling,A.
A1  - Risberg,J.
A1  - Von Heijne,G.
A1  - Stone-Elander,S.
A1  - Ingvar,D.H.
Y1  - 1998/05//
N1  - PET-Cognitive Neurophysiology R2-01, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, SwedenPMID- 0009598706
SP  - 258
EP  - 269
JA  - J.Stud.Alcohol
VL  - 59
IS  - 3
N2  - OBJECTIVE: We investigated the effect of 0.07% alcohol on regional brain activity at rest and during cognitive performance in order to elucidate the anatomical substrate for the effects of alcohol in man as well as to clarify the interaction between changes in cerebral activity induced by cognitive performance and alcohol inebriation. METHOD: Regional cerebral blood flow (3D-PET, 15O Butanol) was measured in 13 male, nonalcoholic volunteers. Each subject was scanned 12 times, three scans in each of the following four situations: sober/rest, sober/test and inebriated/rest, inebriated/test. We used statistical parametric mapping and a computerized brain atlas for localization. RESULTS: Alcohol induced a sense of inebriation and elation as well as a relative increase of the cerebral blood flow in medial parts of the temporal lobes, in the anterobasal parts of the anterior cingulate cortex including the septal region. In addition, there was an increase of blood flow in midline parts of the lower brain stem. Relative decreases of flow were observed in the cerebellum and in the occipital cortex bilaterally. In the sober state, a computerized perceptual maze test and a (silent) serial seven test induced two distinct neocortical activation patterns that were specific to the tasks. Alcohol did not change these patterns and the test performance was also uninfluenced. CONCLUSIONS: A moderate dose of alcohol selectively activates target structures that pertain to the so-called cerebral reward system and the ascending reticular activating system. Alcohol (approximately 0.07%) appears to have only minor effects in the neocortical systems that are involved in on-line cognitive activity. This apparent independence between the subcortical alcohol target and the neocortical cognitive mechanisms is a new finding that appears to be of importance for an understanding of the effect of moderate doses of alcohol on the brain
ER  - 

TY  - JOUR
T1  - [15O]-water PET and intraoperative brain mapping: a comparison in the localization of eloquent cortex
A1  - Vinas,F.C.
A1  - Zamorano,L.
A1  - Mueller,R.A.
A1  - Jiang,Z.
A1  - Chugani,H.
A1  - Fuerst,D.
A1  - Muzik,O.
A1  - Mangner,T.J.
A1  - Diaz,F.G.
Y1  - 1997/12//
N1  - Department of Neurosurgery, Children's Hospital, Wayne State University, Detroit, MI 48201, USAPMID- 0009427960
SP  - 601
EP  - 608
JA  - Neurol.Res.
VL  - 19
IS  - 6
N2  - [15O]-water PET was performed on 12 patients with structural lesions for localization of the motor (n = 5), language (receptive and expressive; n = 6), and visual cortex (n = 1). All these patients underwent interactive image-guided surgery using an infrared digitizer and intraoperative electrical stimulation mapping for motor, sensory, language, and visual cortex location. MRI-PET coregistration was performed using a surface matching approach that integrated functional information with interactive image guidance during the surgical procedure. An awake craniotomy with motor and sensory intraoperative stimulation was performed using a registered bipolar electrode that was tracked on real-time during the surgical procedure. Intraoperative functional findings were displayed and saved on the registered MRI images. The sites of functional PET activation during the performance of motor, visual and language tasks were then compared to the results of intraoperative cortical stimulation in 11 patients and visual evoked potentials in one. The results of the PET activation studies were concordant with the findings of intraoperative stimulation in all cases. During resection of the structural lesions, intraoperative stimulation was continued in the subcortical pathways, and five patients had positive responses on areas not identified by the functional PET. Furthermore, 3 patients showed transitory changes in function (speech arrest 1, naming difficulty 1, and motor weakness 1) that were reversible after changing the dissection technique or a brain retractor. [15O]-water PET was reliable in identifying the motor, visual, and language cortex. Language-related rCBF increases were highly distributive, although only part of these activations were subjected to intraoperative stimulation. We conclude that [15O]-water PET can be used for preoperative noninvasive identification of functional cortex and may be useful in neurosurgical preplanning. Intraoperative mapping still remains the main means to avoid neurological damage as it can be performed during the entire surgical procedure to avoid damage to cortex, pathways, and damage secondary to ischemia or edema (brain retraction)
ER  - 

TY  - JOUR
T1  - Hemispheric language dominance studied with functional MR: preliminary study in healthy volunteers and patients with epilepsy
A1  - van der Kallen,B.F.
A1  - Morris,G.L.
A1  - Yetkin,F.Z.
A1  - van Erning,L.J.
A1  - Thijssen,H.O.
A1  - Haughton,V.M.
Y1  - 1998/01//
N1  - Department of Radiology, University Hospital Nijmegen, The NetherlandsPMID- 0009432160
SP  - 73
EP  - 77
JA  - AJNR.Am.J.Neuroradiol.
VL  - 19
IS  - 1
N2  - PURPOSE: We used functional MR imaging to compare hemispheric language dominance in healthy volunteers and in patients with epilepsy. METHODS: We retrospectively reviewed the functional MR images of 23 healthy volunteers and 16 patients with epilepsy obtained by using an echo- planar technique designed for whole-brain imaging. The activation paradigm used was a silent word generation task. Hemispheric language dominance was assessed as the percentage of activated pixels in the left hemisphere minus the percentage of activated pixels in the right hemisphere x 100. RESULTS: We found no significant difference in language lateralization between right-handed male and right-handed female volunteers. However, a statistically significant difference in language distribution was found between left- and right-handed female volunteers. The left-handed female volunteers showed a more bilateral hemispheric language lateralization. Language lateralization in right- handed male epilepsy patients with early age at seizure onset and seizure locus in the left temporal lobe was not significantly different from that of healthy right-handed male volunteers. Similarly, we found no difference in language lateralization between right-handed female volunteers and right-handed female epilepsy patients with late age at seizure onset and seizures in the left temporal lobe. CONCLUSION: Handedness has a significant influence on hemispheric language dominance in healthy volunteers. Sex has no influence on hemispheric language dominance, regardless of the task used to assess such dominance, nor does age at seizure onset influence language lateralization in patients with left temporal lobe epilepsy. Therefore, hemispheric language dominance can be assessed and compared effectively with functional MR imaging
ER  - 

TY  - JOUR
T1  - Functional anatomy of dominance for speech comprehension in left handers vs right handers
A1  - Tzourio,N.
A1  - Crivello,F.
A1  - Mellet,E.
A1  - Nkanga-Ngila,B.
A1  - Mazoyer,B.
Y1  - 1998/07//
N1  - Groupe d'Imagerie Neurofonctionnelle, UPRES EA 2127 Universite de Caen and CEA LRC 13, Caen, France
SP  - 1
EP  - 16
JA  - Neuroimage.
VL  - 8
IS  - 1
N2  - In order to study the functional anatomy of hemispheric dominance for language comprehension we compared the patterns of activations and deactivations with PET and H(2)15O during a story-listening task in two groups of normal volunteers selected on the basis of their handedness. The reference task was a silent rest. The results showed asymmetrical temporal activations favoring the left hemisphere in right handers (RH) together with Broca's area and medial frontal activations. A rightward lateralization of deactivations located in the parietal and inferior temporal gyrus was also observed. In left handers (LH) the temporal activations were more symmetrical as were the parietal and inferior frontal deactivations. Broca's area and medial frontal gyrus activations were present in LH. The direct comparison of RH and LH activations revealed larger activations in the left superior temporal, in particular in the left planum temporale and temporal pole of RH, while LH activated an additional right middle temporal region. Individual analysis of LH differences images superimposed on individual MRI planes demonstrated an important variability of functional dominance, with two LH leftward lateralized, two symmetrical, and one showing a rightward lateralization of temporal activations. There was no relationship between functional dominance and handedness scores. These results are in accordance with data from aphasiology that suggest a greater participation of the right hemisphere in language processing in LH. In addition, the presence of bilateral deactivations of the dorsal route could support the assumption that LH ambilaterality concerns, in addition to language, other cognitive functions such as visuospatial processing
ER  - 

TY  - JOUR
T1  - Clinical usefulness of 11C-MET PET and 201T1 SPECT for differentiation of recurrent glioma from radiation necrosis
A1  - Sonoda,Y.
A1  - Kumabe,T.
A1  - Takahashi,T.
A1  - Shirane,R.
A1  - Yoshimoto,T.
Y1  - 1998/06//
N1  - Department of Neurosurgery, Tohoku University School of Medicine, SendaiPMID- 0009689817
SP  - 342
EP  - 347
JA  - Neurol.Med.Chir.(Tokyo.)
VL  - 38
IS  - 6
N2  - The clinical usefulness of L-methyl-11C-methionine positron emission tomography (11C-MET PET) and thallium-201 single photon emission computed tomography (201T1 SPECT) for distinguishing glioma recurrence from radiation-induced changes was evaluated. Ten patients with lesions highly suggestive of recurrent glioma on magnetic resonance imaging underwent 11C-MET PET and 201T1 SPECT studies. Two patients were examined twice, so a total of 12 studies were performed. The clinical diagnoses were five recurrent gliomas and seven radiation necrosis. The five recurrent gliomas appeared as increased uptakes on both 11C-MET PET and 201T1 SPECT scans. Four of the seven radiation necrosis lesions also appeared as increased uptakes on the 201T1 SPECT scans. In contrast, only one radiation necrosis appeared as increased uptake on the 11C-MET PET scans. There was no significant difference in 201T1 SPECT indices between radiation necrosis and tumor recurrence, but the ratio of the differential absorption ratio of tumor tissue to that of the homologous contralateral gray matter in PET of recurrent glioma was significantly higher than that of radiation necrosis. 11C-MET PET is superior to 201T1 SPECT for the differentiation of tumor recurrence from radiation necrosis and delineation of the extent of the tumor
ER  - 

TY  - JOUR
T1  - Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography [In Process Citation]
A1  - Tjuvajev,J.G.
A1  - Avril,N.
A1  - Oku,T.
A1  - Sasajima,T.
A1  - Miyagawa,T.
A1  - Joshi,R.
A1  - Safer,M.
A1  - Beattie,B.
A1  - DiResta,G.
A1  - Daghighian,F.
A1  - Augensen,F.
A1  - Koutcher,J.
A1  - Zweit,J.
A1  - Humm,J.
A1  - Larson,S.M.
A1  - Finn,R.
A1  - Blasberg,R.
Y1  - 1998/10/01/
N1  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
SP  - 4333
EP  - 4341
JA  - Cancer Res.
VL  - 58
IS  - 19
N2  - We report a series of studies that assess the feasibility and sensitivity of imaging of herpes virus type one thymidine kinase (HSV1- tk) gene transfer and expression with [124I]-5-iodo-2'-fluoro-1-beta-D- arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV1-tk gene expression. Studies were performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral-mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild-type W256 tumor in each animal was accomplished by direct intratumoral injection of retroviral vector- producer cells (W256-->W256TK* tumors). Tumors produced from W256 and W256TK+ cells served as the negative and positive control in each animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in nontransduced wild-type W256 tumors. The level of "specific" incorporated radioactivity in transduced portions of both W256TK* and W256TK+ tumors was relatively constant between 4 and 50 h. In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate between different levels of HSV1- tk gene expression. Multiple s.c. tumors were produced from wild-type RG2 cells and stably transduced RG2TK cell lines that express different levels of HSV1-tk. A highly significant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation constant (Ki)] and an independent measure of HSV1-tk expression (sensitivity of the transduced tumor cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship was defined as a sensitivity index. We have demonstrated for the first time that highly specific noninvasive images of HSV1-tk expression in experimental animal tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system. The ability to image the location (distribution) of gene expression and the level of expression over time provides new and useful information for monitoring clinical gene therapy protocols in the future
ER  - 

TY  - JOUR
T1  - Muscarinic cholinergic receptor measurements with [18F]FP-TZTP: control and competition studies
A1  - Carson,R.E.
A1  - Kiesewetter,D.O.
A1  - Jagoda,E.
A1  - Der,M.G.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
Y1  - 1998/10//
N1  - Positron Emission Tomography Department, National Institutes of Health, Bethesda, Maryland 20892-1180, USA
SP  - 1130
EP  - 1142
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 18
IS  - 10
N2  - [18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane- anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 microg x kg(-1) x h(-1)) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL x min(-1) x mL(-1) in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution (V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower (P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller (P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography
ER  - 

TY  - JOUR
T1  - N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic [In Process Citation]
A1  - Hagberg,G.
A1  - Gefvert,O.
A1  - Bergstrom,M.
A1  - Wieselgren,I.M.
A1  - Lindstrom,L.
A1  - Wiesel,F.A.
A1  - Langstrom,B.
Y1  - 1998/06/30/
N1  - Uppsala University PET Centre, University Hospital, Sweden giselahagberg@petuuse
SP  - 147
EP  - 160
JA  - Psychiatry Res.
VL  - 82
IS  - 3
N2  - The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D2 dopamine receptor was investigated using the PET tracers [11C]raclopride and N-[11C]methylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51% +/- 10% occupancy at the 750 mg dose) was detected with [11C]raclopride (P < 0.01), no such trend was apparent for N-[11C]methylspiperone (P > 0.09, maximal occupancy values were 2% +/- 3%, measured for the group of three patients on 450 mg). The study suggests that N-[11C]methylspiperone cannot be used for the assessment of D2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants
ER  - 

TY  - JOUR
T1  - Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Gatley,S.J.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Hitzemann,R.
A1  - Pappas,N.
Y1  - 1998/10//
N1  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA volkow@bnlgovPMID- 0009766762
SP  - 1325
EP  - 1331
JA  - Am.J.Psychiatry
VL  - 155
IS  - 10
N2  - OBJECTIVE: The therapeutic effects of methylphenidate in the treatment of attention deficit disorder have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters. However, the levels of dopamine transporter blockade achieved by therapeutic doses of methylphenidate are not known. This study measured, for the first time, dopamine transporter occupancy by orally administered methylphenidate in the human brain and its rate of uptake in the brain. METHOD: Positron emission tomography (PET) and [11C]cocaine were used to estimate dopamine transporter occupancies after different doses of oral methylphenidate in seven normal subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral methylphenidate were measured in the baboon brain through use of PET and [11C]methylphenidate administered through an orogastric tube. RESULTS: At 120 minutes after administration, oral methylphenidate produced a dose-dependent blockade of dopamine transporter; means=12% (SD= 4%) for 5 mg, 40% (SD=12%) for 10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg. The estimated dose of oral methylphenidate required to block 50% of the dopamine transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak concentration in brain until 60 minutes after its administration. CONCLUSIONS: Oral methylphenidate is very effective in blocking dopamine transporters, and at the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely to occupy more than 50% of the dopamine transporters. The time to reach peak brain uptake for oral methylphenidate in brain corresponds well with the reported time course to reach peak behavioral effects
ER  - 

TY  - JOUR
T1  - In vitro and ex vivo autoradiographic studies of nicotinic acetylcholine receptors using [18F]fluoronochloroepibatidine in rodent and human brain [In Process Citation]
A1  - Gatley,S.J.
A1  - Ding,Y.S.
A1  - Brady,D.
A1  - Gifford,A.N.
A1  - Dewey,S.L.
A1  - Carroll,F.I.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
Y1  - 1998/07//
N1  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA gatley@bnlgov
SP  - 449
EP  - 454
JA  - Nucl.Med.Biol.
VL  - 25
IS  - 5
N2  - A fluorine-18-labeled analog of the potent nicotinic agonist epibatidine is a candidate radioligand for positron emission tomographic (PET) studies of nicotinic acetylcholine receptors (nAcChR). Following intravenous administration of [18F]exo-2-(2'-fluoro- 5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (NFEP), high uptake in thalamus was visualized in sections of mouse and rat brain by autoradiography using a phosphor imaging device. Binding of [18F]NFEP to rat thalamic homogenate was consistent with a single class of binding site with a Kd value of 71 pM. In vitro autoradiography of thaw- mounted sections of human thalamus revealed a heterogeneous pattern of binding; Bmax values for ventrolateral nucleus, insular cortex and dorsomedial nucleus, and internal capsule were 20, 8, and 3 pmol/cc of tissue, respectively. However, similar Kd values close to 50 pM were calculated for all regions. These studies support the suitability of [18F]NFEP as a radioligand for PET studies of nAcChR in the living human brain
ER  - 

TY  - JOUR
T1  - An acute dose of nicotine does not inhibit MAO B in baboon brain in vivo
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - Pappas,N.
A1  - King,P.
A1  - MacGregor,R.
A1  - Shea,C.
A1  - Garza,V.
A1  - Gatley,S.J.
Y1  - 1998///
N1  - Brookhaven National Laboratory, Upton, NY 11973-5000, USAPMID- 0009674950
SP  - L19
EP  - L23
JA  - Life Sci.
VL  - 63
IS  - 2
N2  - Tobacco smoke exposure has been shown to inhibit brain and platelet MAO B in animals and in humans. Though the mechanism(s) responsible for MAO B inhibition are not known, studies in rodents have shown that nicotine administration does not inhibit brain MAO B. In this study we investigated whether brain MAO B is also unaffected by nicotine in the living primate. Brain MAO B was measured with positron emission tomography (PET) and deuterium substituted [11C]L-deprenyl ([11C]L- deprenyl-D2) in three baboons at baseline and 5 minutes after the injection of (-)-nicotine (0.3 mg administered intravenously). A three- compartment model was used to calculate the plasma to brain transfer constant K1 which is related to blood flow, and lambda k3, which is a function of the concentration of catalytically active MAO B molecules. Nicotine administration did not produce significant changes in either of these parameters. This study in living baboons confirms previous studies in rodents and solidifies the notion that other mechanisms for MAO B inhibition observed in smokers need to be considered
ER  - 

TY  - JOUR
T1  - Evaluation of gender difference in regional brain metabolic responses to lorazepam
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Hitzemann,R.J.
A1  - Pappas,N.R.
A1  - Netusil,N.
Y1  - 1998/04/10/
N1  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA gjwang@bnlgovPMID- 0009645549
SP  - 37
EP  - 46
JA  - Psychiatry Res.
VL  - 82
IS  - 1
N2  - Women are prescribed benzodiazepines twice as frequently as men and there is evidence of differences in therapeutic responsiveness to benzodiazepines between genders. In this study we compared the regional brain metabolic response to benzodiazepines between male and female subjects. Sixteen healthy men and 12 healthy women were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30 microg/kg) on separate days. Lorazepam significantly and consistently decreased whole brain metabolism and the magnitude as well as the regional pattern of the changes was comparable for both genders (M = -4.7+/- 3 and F = -3.9 +/- 3.8 micromol/100 g/min). Lorazepam effects were largest in thalamus (- 12.5 +/- 6.2 and -8.6 +/- 7.1 micromol/100 g/min) and occipital cortex (-10.5 +/- 5.5 and -10.1 +/- 6.6 micromol/100 g/min). Lorazepam- induced changes in 'relative' metabolism were also similar for both genders except for trend differences (0.01 < P < 0.05) in rectal gyrus, where lorazepam increased relative metabolism in women (+4.4 +/- 9.9%) whereas it decreased in men (-3.2 +/- 8.8%, P < 0.04) and in cerebellum, where lorazepam-induced decrements were larger in women (- 5.9 +/- 6%) than in men (-1.1% +/- 6.6%, P < 0.05). There were no differences between genders for any of the behavioral effects of lorazepam. In summary, this study does not show differences in the response to lorazepam between the genders as assessed by its behavioral effects and the changes in absolute metabolism; the trend toward a difference in the relative changes in rectal gyrus and cerebellum merits further investigation
ER  - 

TY  - JOUR
T1  - Enhanced sensitivity to benzodiazepines in active cocaine-abusing subjects: a PET study
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Hitzemann,R.
A1  - Gatley,S.J.
A1  - Dewey,S.S.
A1  - Pappas,N.
Y1  - 1998/02//
N1  - Medical Department, Brookhaven National Laboratory, NY 11973, USA volkow@bnlgovPMID- 0009464198
SP  - 200
EP  - 206
JA  - Am.J.Psychiatry
VL  - 155
IS  - 2
N2  - OBJECTIVE: Because cocaine enhances dopamine brain activity and dopamine signals are transferred through gamma-aminobutyric acid pathways, the authors hypothesized GABA-ergic disruption in cocaine- abusing subjects. This study tests this hypothesis. METHOD: GABA brain function was assessed indirectly by measuring the brain metabolic responses to lorazepam, a drug that facilitates GABA neurotransmission. Thirteen current cocaine-abusing subjects and 14 comparison subjects were scanned twice with positron emission tomography and [18F]fluorodeoxyglucose; the first scan was obtained after placebo administration and the second after lorazepam administration (30 micrograms/kg). RESULTS: Despite significantly higher plasma lorazepam concentrations in comparison subjects than in cocaine-abusing subjects, lorazepam-induced decrements in whole brain metabolism were significantly greater in cocaine-abusing (mean = 21%, SD = 13%) than in comparison (mean = 13%, SD = 7%) subjects. These differences were largest in striatum, thalamus, and parietal cortex. Lorazepam-induced sleepiness in cocaine-abusing subjects was intense and was significantly greater than in comparison subjects, and it was correlated with lorazepam-induced changes in thalamic metabolism. Whereas regional metabolic measures during placebo administration were significantly higher in cocaine-abusing subjects than in comparison subjects, the measures during lorazepam administration were equivalent for both groups. CONCLUSIONS: The enhanced sensitivity to lorazepam in cocaine-abusing subjects suggests disruption of GABA pathways that may reflect, in part, cocaine withdrawal. The intense sleepiness induced by lorazepam in some of the abusers, despite their significantly lower plasma concentrations, should alert clinicians of the potential toxicity from accentuated responses to sedative hypnotics in active cocaine-abusing subjects
ER  - 

TY  - JOUR
T1  - Evaluation of the importance of rebinding to receptors in slowing the approach to equilibrium of high-affinity PET and SPECT radiotracers
A1  - Gifford,A.N.
A1  - Gatley,S.J.
A1  - Volkow,N.D.
Y1  - 1998/02//
N1  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USAPMID- 0009450517
SP  - 167
EP  - 175
JF  - Synapse
VL  - 28
IS  - 2
N2  - The importance of rebinding to receptors in influencing the kinetics of in vivo binding of PET and SPECT radiotracers was evaluated by examining the binding of a high-affinity D1 receptor radiotracer, [3H]SCH 23390, in tissue homogenates, living brain slices, and in vivo. In rat striatal homogenates, [3H]SCH 23390 binding reached equilibrium with a half-time of 6 min. By contrast, in striatal brain slices incubated in [3H] SCH 23390, the radioactivity levels in the slice increased in a linear fashion over the 4-h incubation, with no indication of an approach to equilibrium at the termination of the experiment. In in vivo experiments, [3H]SCH 23390 was given as a slow intravenous infusion to mice, using a paradigm that kept the plasma concentration at a constant level. Under these conditions, striatal [3H] SCH 23390 levels increased in a linear fashion over the 4-h infusion period, similar to what was observed in the brain slices, and as in the slices there was no indication of approach to a steady state. However, when given instead as a single-bolus intravenous dose, the striatal [3H]SCH 23390 levels reached a peak only 15 min after injection. Calculations based on the slice experiments, in which the blood-brain barrier is absent, suggested that the rate-limiting step accounting for the failure of [3H]SCH 23390 levels to reach equilibrium was its hindered diffusion as a result of repeated rebinding to receptors. This phenomenon may also be important in vivo and should be considered as a factor in determining the time-course of binding of radiotracers in PET and SPECT experiments where either the receptor density or radiotracer affinity is high
ER  - 

TY  - JOUR
T1  - Measuring dopamine transporter occupancy by cocaine in vivo: radiotracer considerations
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - Pappas,N.
A1  - King,P.
A1  - Ding,Y.S.
A1  - Wang,G.J.
Y1  - 1998/02//
N1  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA fowler@simbrainchmbnlgovPMID- 0009450511
SP  - 111
EP  - 116
JF  - Synapse
VL  - 28
IS  - 2
N2  - Several recent neuroimaging studies in humans and in monkeys using different radiotracers have reported widely differing values of dopamine transporter (DAT) occupancy by doses of cocaine which are perceived as reinforcing by humans. Here we tested the hypothesis that the measurement of DAT occupancies by drugs with fast pharmacokinetics such as cocaine requires a radioligand with similar kinetics in order to effectively compete with the drug. We measured DAT occupancy by four different doses of cocaine (1.0, 0.5, 0.25, and 0.1 mg/kg) using [11C]d- threo-methylphenidate (a radiotracer which binds rapidly to the DAT in vivo) and compared them to estimates reported previously using [11C]cocaine in the same two baboons and with the same four doses of cocaine [Volkow et al. (1996b) Synapse 24:399-402). Cocaine reduced [11C]d-threo-methylphenidate binding in striatum in a dose-dependent manner, and values were significantly correlated with those obtained previously with [11C]cocaine (r = 0.9, F = 37, P < 0.001). The ED50s (50% occupancy of DAT by cocaine) were 0.27 and 0.17 mg/kg for [11C]d- threo-methylphenidate and [11C]cocaine, respectively. This is significantly lower than values obtained with labeled beta-CIT and other similar radiotracers with a slow uptake and clearance (ED50s: 3-7 mg/kg). We conclude that in vivo measurements of DAT occupancy by rapidly clearing drugs like cocaine requires the use of radiotracers having similar kinetics to the drug itself
ER  - 

TY  - JOUR
T1  - Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects
A1  - Smith,G.S.
A1  - Schloesser,R.
A1  - Brodie,J.D.
A1  - Dewey,S.L.
A1  - Logan,J.
A1  - Vitkun,S.A.
A1  - Simkowitz,P.
A1  - Hurley,A.
A1  - Cooper,T.
A1  - Volkow,N.D.
A1  - Cancro,R.
Y1  - 1998/01//
N1  - Department of Psychiatry, New York University School of Medicine, New York, USAPMID- 0009408915
SP  - 18
EP  - 25
JA  - Neuropsychopharmacology.
VL  - 18
IS  - 1
N2  - Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C- raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, i.v. infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function
ER  - 

TY  - JOUR
T1  - Brain serotonin synthesis rates in rhesus monkeys determined by [11C]alpha-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations [In Process Citation]
A1  - Shoaf,S.E.
A1  - Carson,R.
A1  - Hommer,D.
A1  - Williams,W.
A1  - Higley,J.D.
A1  - Schmall,B.
A1  - Herscovitch,P.
A1  - Eckelman,W.
A1  - Linnoila,M.
Y1  - 1998/11//
N1  - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
SP  - 345
EP  - 353
JA  - Neuropsychopharmacology.
VL  - 19
IS  - 5
N2  - Twelve male, fasted, anesthetized rhesus monkeys were studied with positron emission tomography (PET) and [11C]alpha-methyl-L-tryptophan (alpha MTP) to determine serotonin synthesis rates as described by Diksic et al. (1991). It was expected that the serotonin synthesis rates determined for the whole brain would be correlated with CSF 5- hydroxyindole-3-acetic acid concentrations, a measure of central serotonin turnover, because both measures were obtained at steady state. However, no significant correlation was found. During data analysis, it was noticed that the calculated serotonin synthesis rates were significantly correlated to free plasma tryptophan (TP) concentrations (r = 0.88, p < .001). From repeat scans conducted in six monkeys, it was determined that day-to-day variability in free plasma TP and the percentage of protein binding (average percent difference was 48 and 37%, respectively) produced most of the variability in the calculated sertonin synthesis rates (50%); repeat K images, obtained from the PET data alone, differed by only 11%. Calculated serotonin synthesis rates reported for [11C]alpha MTP PET studies of humans (Nishizawa et al. 1997) and dogs (Diksic et al. 1991) were also highly correlated to reported differences in plasma free TP concentrations. It seems that the [11C]alpha MTP model for the computation of serotonin synthesis rates is very dependent on plasma free TP concentration and that it may not accurately determine actual serotonin synthesis rates
ER  - 

TY  - JOUR
T1  - Focal cortical release of endogenous opioids during reading-induced seizures
A1  - Koepp,M.J.
A1  - Richardson,M.P.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 1998/09/19/
N1  - MRC Cyclotron Unit Hammersmith Hospital, London, UKPMID- 0009752818
SP  - 952
EP  - 955
JF  - Lancet
VL  - 352
IS  - 9132
N2  - BACKGROUND: Studies in animals implicate endogenous release of opioid peptides as a mechanism for terminating partial and generalised seizures. To localise dynamic changes in opioid neurotransmission associated with partial seizures and higher cognitive function, we investigated the release of endogenous opioids in patients with reading-induced seizures compared with healthy controls. METHODS: Five patients who had reading epilepsy and six controls had 11C-diprenorphine (DPN) positron-emission-tomography (PET) scans while reading a string of symbols (baseline) or a scientific paper (activation). Statistical parametric mapping was used to find areas with differences in opioid- receptor binding. FINDINGS: On activation scans mean 11C-DPN binding to opioid receptors was significantly lower (p<0.05 corrected for multiple non-independent comparisons) in the left parieto-temporo-occipital cortex (Brodmann area 37) in reading-epilepsy patients compared with controls. INTERPRETATION: These findings suggest that opioid-like substances are involved in the termination of reading-induced seizures
ER  - 

TY  - JOUR
T1  - Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet- size dependent phenomenon
A1  - Annane,D.
A1  - Fiorelli,M.
A1  - Mazoyer,B.
A1  - Pappata,S.
A1  - Eymard,B.
A1  - Radvanyi,H.
A1  - Junien,C.
A1  - Fardeau,M.
A1  - Merlet,P.
A1  - Gajdos,P.
A1  - Syrota,A.
A1  - Sansom,Y.
A1  - Duboc,D.
Y1  - 1998/02//
N1  - Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, Commissariat a L'Energie Atomique, Orsay, FrancePMID- 0009565989
SP  - 39
EP  - 45
JA  - Neuromuscul.Disord.
VL  - 8
IS  - 1
N2  - Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat sequence in the 3'-noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. Impaired glucose penetration into brain tissues has been described in DM patients and is a phenomenon that remains unexplained. The present study shows that altered brain glucose metabolism is triplet repeat dependent. We studied brain glucose metabolism (CMRGlu, mumol/100 g/min) by the use of positron emission tomography and 18F-fluoro-2-deoxy-D-glucose in 11 ambulatory non-obese DM patients and in 11 age and sex matched healthy subjects. All subjects underwent a glucose tolerance test with plasma insulin determinations. The expansion of CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. As compared to controls, in DM patients, the CMRGlu was significantly decreased (26.26 +/- 5.05 vs. 33.43 +/- 2.18, mumol/100 g/min, P = 0.004), and after oral glucose loading, plasma insulin levels were significantly higher and plasma glucose levels remained unchanged (respectively, F = 11.21, P = 0.004 and F = 0.20, P = 0.66). Subsequently, the glucose/insulin ratio was significantly lower in DM patients (F = 6.25, P = 0.02). The length of the expansion of the CTG repeats correlated negatively with the CMRGlu (r2 = 0.63, P = 0.003) and positively with the area under the curve for insulin changes over time after oral glucose (r2 = 0.49, P = 0.016). We conclude that, in DM patients, the brain metabolism of glucose is impaired in a repeat dependent manner
ER  - 

TY  - JOUR
T1  - Functional anatomy of calorie fear in anorexia nervosa
A1  - Ellison,Z.
A1  - Foong,J.
A1  - Howard,R.
A1  - Bullmore,E.
A1  - Williams,S.
A1  - Treasure,J.
Y1  - 1998/10/10/
N1  -  [letter] [In Process Citation]
SP  - 1192
JF  - Lancet
VL  - 352
IS  - 9135
ER  - 

TY  - JOUR
T1  - Positron emission tomography in a case of intracranial hemangiopericytoma
A1  - Kracht,L.-W.
A1  - Bauer,A.
A1  - Herholz,K.
A1  - Terstegge,K.
A1  - Friese,M.
A1  - Schrder,R.
A1  - Heiss,W.-D.
Y1  - 1999///
SP  - 365
EP  - 368
JF  - Journal of Computer Assisted Tomography
VL  - 23
ER  - 

TY  - JOUR
T1  - Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole
A1  - Read,S.J.
A1  - Hirano,T.
A1  - Abbott,D.F.
A1  - Sachinidis,J.I.
A1  - Tochon-Danguy,H.J.
A1  - Chan,J.G.
A1  - Egan,G.F.
A1  - Scott,A.M.
A1  - Bladin,C.F.
A1  - McKay,W.J.
A1  - Donnan,G.A.
Y1  - 1998/12//
N1  - Department of Neurology, Austin & Repatriation Medical Centre, Heidelberg, Vic, AustraliaPMID- 0009855512
SP  - 1617
EP  - 1621
JF  - Neurology
VL  - 51
IS  - 6
N2  - OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days)
ER  - 

TY  - JOUR
T1  - Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria
A1  - Neary,D.
A1  - Snowden,J.S.
A1  - Gustafson,L.
A1  - Passant,U.
A1  - Stuss,D.
A1  - Black,S.
A1  - Freedman,M.
A1  - Kertesz,A.
A1  - Robert,P.H.
A1  - Albert,M.
A1  - Boone,K.
A1  - Miller,B.L.
A1  - Cummings,J.
A1  - Benson,D.F.
Y1  - 1998/12//
N1  - Manchester Royal Infirmary, UK
SP  - 1546
EP  - 1554
JF  - Neurology
VL  - 51
IS  - 6
N2  - OBJECTIVE: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. METHODS: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. RESULTS: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. CONCLUSIONS: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years
ER  - 

TY  - JOUR
T1  - Overlap between acetylcholinesterase-rich and choline acetyltransferase- positive (cholinergic) axons in human cerebral cortex
A1  - Mesulam,M.M.
A1  - Geula,C.
Y1  - 1992/04/10/
N1  - Bullard and Denny-Brown Laboratories, Harvard Neurology Department, Beth Israel Hospital, Boston, MA 02215PMID- 0001521137
SP  - 112
EP  - 120
JA  - Brain Res.
VL  - 577
IS  - 1
N2  - The distribution of acetylcholinesterase-rich axons was compared to that of choline acetyltransferase-positive (cholinergic) axons in 28 major cytoarchitectonic divisions of the adult human cerebral cortex. Acetylcholinesterase-rich as well as choline acetyltransferase-positive cortical axons contained multiple varicosities. Each type of axon was more densely distributed in limbic-paralimbic regions of the brain. In all the cortical areas that were examined, the two markers displayed laminar and regional distribution patterns that were indistinguishable from each other. A method that allowed the concurrent visualization of both reaction products demonstrated that acetylcholinesterase and choline acetyltransferase were colocalized in the same axon. These observations show that there is probably a complete correspondence between choline acetyltransferase-positive and acetylcholinesterase- rich axons and that the acetylcholinesterase reaction can be used as a specific marker for cortical cholinergic axons in the adult human brain
ER  - 

TY  - JOUR
T1  - Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients
A1  - Ryvlin,P.
A1  - Bouvard,S.
A1  - Le Bars,D.
A1  - De Lamerie,G.
A1  - Gregoire,M.C.
A1  - Kahane,P.
A1  - Froment,J.C.
A1  - Mauguiere,F.
Y1  - 1998/11//
N1  - Epilepsy Surgery Unit, and CERMEP, Neurological Hospital, Lyon, France ryvlin@cermepfrPMID- 0009827767
SP  - 2067
EP  - 2081
JF  - Brain
VL  - 121
IS  - Pt 11
N2  - We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery
ER  - 

TY  - JOUR
T1  - [18F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses
A1  - Mulholland,G.K.
A1  - Wieland,D.M.
A1  - Kilbourn,M.R.
A1  - Frey,K.A.
A1  - Sherman,P.S.
A1  - Carey,J.E.
A1  - Kuhl,D.E.
Y1  - 1998/11//
N1  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA kmulholl@xrayindyradiupuieduPMID- 0009776130
SP  - 263
EP  - 274
JF  - Synapse
VL  - 30
IS  - 3
N2  - Loss of cholinergic transmission in the cortex and hippocampus is a characteristic feature of Alzheimer's disease, and visualization of functional cholinergic synapses in the brain with PET could be a useful method for studying this degenerative condition in living humans. We investigated [18F]fluoroethoxybenzovesamicol, (-)-[18F] FEOBV,(-)- (2R,3R)-trans-2-hydroxy-3-(4-phenylpiperidino)-5-(2-[18F ]fluoroethoxy)- 1,2,3,4-tetralin, a high affinity positron emitting ligand for the vesicular acetylcholine transporter, as a potential in vivo cholinergic synapse mapping agent. Rodent biodistribution, dosimetry, stereospecificity of biological effects, pharmacologic blocking studies, in vivo rodent brain autoradiography and metabolites were examined. (-)-[18F]FEOBV brain uptake following intravenous injection was robust, with 2.65% dose/brain in mice at 5 min, and the regional localization matched the known distributions of presynaptic cholinergic markers at later times. Both the cholinergic localization and curare- like effects of FEOBV were associated with the "(-)"-enantiomer exclusively. (-)-[18F]FEOBV regional brain distribution in rodents was changed little by pretreatment with haloperidol, (+)-3-PPP, or E-2020, indicating FEOBV, unlike other vesamicol analogs, did not interact in vivo with dopamine or sigma receptor systems. Autoradiography of rat brain 3 h following i.v. injection of (-)-[18F]FEOBV showed high localization in brain areas rich in presynaptic cholinergic elements. Metabolic defluorination in rodents was modest, and analysis of brain tissue following tracer administration found FEOBV as the only extractable radioactive species. (-)-[18F]FEOBV dosimetry calculated from rat data estimate 10 mCi doses can be given to humans. These studies show FEOBV maps cholinergic areas with high specificity in vivo, and may provide a noninvasive means to safely and accurately gauge the functional integrity of cholinergic synapses in man using PET
ER  - 

TY  - BOOK
T1  - Human brain function
A1  - Frackowiak,R.S.J.
A1  - Friston,K.J.
A1  - Frith,C.D.
A1  - Dolan,R.J.
A1  - Mazziotta,J.C.
Y1  - 1997///
CY  - San Diego
PB  - Academic Press
ER  - 

TY  - JOUR
T1  - Developmental changes of cortical and cerebellar motor control: a clinical positron emission tomography study with children and adults [In Process Citation]
A1  - Mller,R.A.
A1  - Rothermel,R.D.
A1  - Behen,M.E.
A1  - Muzik,O.
A1  - Mangner,T.J.
A1  - Chugani,H.T.
Y1  - 1998/11//
N1  - Department of Pediatrics, Wayne State University Medical School, Detroit, MI, USA
SP  - 550
EP  - 556
JA  - J.Child Neurol.
VL  - 13
IS  - 11
N2  - Functional neuroimaging data regarding the development of motor organization in normal children and adolescents are virtually unavailable because of ethical concerns. As an alternative approach, we studied child and adult lesion patients, focusing on movement of the hand ipsilateral to the lesion and on brain activations in the contralesional hemisphere. [15O]-water positron emission tomography was performed during rest and sequential finger-thumb tapping in 10 children (aged 6 to 14 years) and 15 adults (aged 18 to 74 years) with unilateral lesion. We expected more distinct activation/deactivation patterns during movement in adults than in children. While there were no group differences in activation of primary and secondary motor cortices, deactivations in nonmotor cortex were significantly more pronounced in adults than in children. This indirectly supports our hypothesis of developmental focalization of cerebral motor control. Activations in the cerebellum and vermis were significantly stronger in the adults than in the children, possibly reflecting normal developmental patterns
ER  - 

TY  - JOUR
T1  - A Method for Assessing the Accuracy of Intersubject Registration of the Human Brain Using Anatomic Landmarks
A1  - Grachev,I.D.
A1  - Berdichevsky,D.
A1  - Rauch,S.L.
A1  - Heckers,S.
A1  - Kennedy,D.N.
A1  - Caviness,V.S.
A1  - Alpert,N.M.
Y1  - 1999///
SP  - 250
EP  - 268
JF  - Neuroimage
VL  - 9
N2  - Several groups have developed methods for registering an individual's 3D MRI by deforming a standard template. This achievement leads to many possibilities for segmentation and morphology that will impact nuclear medical research in areas such as activation and receptor studies. Accordingly, there is a need for methods that can assess the accuracy of intersubject registration. We have developed a method based on a set of 128 anatomic landmarks per hemisphere, both cortical and subcortical, that allows assessment of both global and local transformation accuracy. We applied our method to compare the accuracy of two standard methods of intersubject registration, AIR 3.0 with fifth-order polynomial warping and the Talairach stereotaxic transformation (Talairach and Tournoux, 1988). SPGR MRI's (256 x 256 x 160) of six normal subjects (age 18-24 years) were derformed to match a standard template volume. To assess registration accuracy the landmarks were located on both the template volume and the transformed volumes by an experienced neuroanatomist. The resulting list of coordinates was analyzed graphically and by ANOVA to compare the accuracy of the two methods and the results of the manual analysis. ANOVA performed over all 128 landmarks showed that the Woods method was more accurate than Talairach (left hemisphere F = 2.8, P < 0.001 and right hemisphere F =2.4, P < 0.006). The Woods method provided a better brain surface transformation than did Talairach (F = 18.0, P < 0.0001), but as expected there was a smaller difference for subcortical structures and both had an accuracy <1 mm for the majority of subcortical landmarks. Overall, both the Woods and Talairach method located about 70% of landmarks with an error of 3 mm or less. More striking differences were noted for landmark accuracy
ER  - 

TY  - JOUR
T1  - 1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging studies
A1  - Graham,M.M.
A1  - Peterson,L.M.
A1  - Muzi,M.
A1  - Graham,B.B.
A1  - Spence,A.M.
A1  - Link,J.M.
A1  - Krohn,K.A.
Y1  - 1998/10//
N1  - Department of Radiology, University of Washington School of Medicine, Seattle 98195, USAPMID- 0009776292
SP  - 1805
EP  - 1810
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 10
N2  - 1-[Carbon-11]-D-glucose ([11C]-glucose) is an important imaging agent for PET studies that have been used to study the normal brain, encephalitis, epilepsy, manic-depressive disorder, schizophrenia and brain tumors. METHODS: Dosimetry estimates were calculated in subjects undergoing imaging studies to help define the radiation risk of [11C]- glucose PET imaging. Time-dependent radioactivity concentrations in normal tissues in 33 subjects after intravenous injection of [11C]- glucose were obtained by PET imaging. Radiation absorbed doses were calculated according to the procedures of the Medical Internal Radiation Dose (MIRD) committee along with the variation in dose based on the calculated standard deviation of activity distribution seen in the individual patients. RESULTS: Total body exposure was a median of 3.0 microGy/MBq in men and 3.8 microGy/MBq in women. The effective dose equivalent was 3.8 microGy/ MBq in men and 4.8 microGy/MBq in women. The critical organs were those that typically take up the most glucose (brain, heart wall and liver). CONCLUSION: The organ doses reported here are small and comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this radiotracer are within generally accepted limits
ER  - 

TY  - JOUR
T1  - Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain
A1  - Galynker,I.
A1  - Schlyer,D.J.
A1  - Dewey,S.L.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - MacGregor,R.R.
A1  - Ferrieri,R.A.
A1  - Holland,M.J.
A1  - Brodie,J.
A1  - Simon,E.
A1  - Wolf,A.P.
Y1  - 1996/04//
N1  - Beth Israel Hospital, New York, NY 10003, USAPMID- 0008782244
SP  - 325
EP  - 331
JA  - Nucl.Med.Biol.
VL  - 23
IS  - 3
N2  - Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O- [11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% +/- 2.2% and 43% +/- 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi
ER  - 

TY  - JOUR
T1  - 11C-labelling of Ro 15-1788 in two different positions, and also 11C- labelling of its main metabolite Ro 15-3890, for PET studies of benzodiazepine receptors
A1  - Halldin,C.
A1  - Stone-Elander,S.
A1  - Thorell,J.O.
A1  - Persson,A.
A1  - Sedvall,G.
Y1  - 1988///
N1  - Karolinska Pharmacy, Stockholm, SwedenPMID- 0002848785
SP  - 993
EP  - 997
JA  - Int.J.Rad.Appl.Instrum.[A.]
VL  - 39
IS  - 9
N2  - The benzodiazepine receptor antagonist Ro 15-1788 has been labelled with 11C in two different positions [( methyl-11C]Ro 15-1788 (I) and [ethyl-11C]Ro 15-1788 (II]. Product I was prepared by N-alkylation of the desmethyl compound (Ro 15-5528) with [11C]methyl iodide and product II was prepared by esterification of the desethyl compound (Ro 15-3890) with [11C]ethyl iodide. Ro 15-3890, the main metabolic product of Ro 15- 1788, was labelled by two synthetic routes. In route A, [methyl-11C]Ro 15-3890 (III) was prepared by N-alkylation of the corresponding desmethyl compound (Ro 15-6877) with [11C]methyl iodide. In route B, III was prepared by a subsequent hydrolysis of I. The radiochemical yields were on the order of 15-60% (EOB) with an overall synthesis time of 40-50 min. Compounds I, II and III were isolated by semi-preparative HPLC and the radiochemical purity was in all cases greater than 99%
ER  - 

TY  - JOUR
T1  - Regional specific binding of [11C]RO 15 1788 to central type benzodiazepine receptors in human brain: quantitative evaluation by PET
A1  - Pappata,S.
A1  - Samson,Y.
A1  - Chavoix,C.
A1  - Prenant,C.
A1  - Maziere,M.
A1  - Baron,J.C.
Y1  - 1988/06//
N1  - Commissariat a l'Energie Atomique, Service Hospitalier Frederic Joliot, Departement de Biologie, Orsay, FrancePMID- 0002835381
SP  - 304
EP  - 313
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 8
IS  - 3
N2  - The central type benzodiazepine receptors were studied in 17 healthy human subjects with 11C-RO 15 1788 and positron emission tomography (PET). The brain regional distribution of the tracer in eight control studies performed after injection of trace doses of 11C-RO 15 1788 was consistent with that of benzodiazepine receptors. Saturation studies with co-injected cold RO 15 1788 in the remaining subjects showed a dose-dependent decrease of brain radiotracer until full inhibition of specific binding was achieved with doses above 0.1 mg/kg (four studies). Based on the results, a simple method to estimate the specifically bound 11C-RO 15 1788 regionally in a single PET study is proposed, using the data from the full-saturation studies as a stable estimate of the nondisplaceable radioligand concentration. Using this method, it was found that quasiequilibrium between the estimated specifically bound and nondisplaceable components was achieved at times equal to or longer than 20 min after tracer administration. The validity of this method was partly supported by further results, showing a good agreement between the regional specific binding so calculated and postmortem data of receptor density
ER  - 

TY  - JOUR
T1  - Imaging of [11C]-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography
A1  - Persson,A.
A1  - Ehrin,E.
A1  - Eriksson,L.
A1  - Farde,L.
A1  - Hedstrom,C.G.
A1  - Litton,J.E.
A1  - Mindus,P.
A1  - Sedvall,G.
Y1  - 1985///
SP  - 609
EP  - 622
JF  - Journal of Psychiatric Research
JA  - J.Psychiatr.Res.
VL  - 19
IS  - 4
N2  - The benzodiazepine antagonist Ro 15-1788 was labelled with [11C] and examined for possible use as ligand for PET scan studies on benzodiazepine receptors in the brain of cynomolgus monkeys and human subjects. [11C] Ro 15-1788 allowed the in vivo visualization of benzodiazepine receptor binding in cerebral and cerebellar cortical areas as well as in basal brain nuclei in PET scan images. [11C] Ro 15- 1788 exhibited a high ratio of specific benzodiazepine receptor binding (cerebral cortex) to non-specific binding (pons) and the kinetics of binding should be satisfactory for quantitative clinical PET scan studies using [11C]. The in vivo binding of [11C] Ro 15-1788 in the cerebral cortex of cynomolgus monkeys and healthy human subjects was reduced by approximately 90% within 10 min after the intravenous injection of a high dose of unlabelled Ro 15-1788 (0.5 mg/kg i.v.). Different areas of the healthy human brain showed an approximately 10- fold variation in maximal [11C] Ro 15-1788 binding that corresponded to the previously known distribution of benzodiazepine receptors in these regions. The highest degree of binding was obtained in the medial occipital cerebral cortex followed by frontal cortex, cerebellum, thalamus, striatum and pons. Two psychiatric patients with anxiety syndromes who had been treated for a long time with high doses of benzodiazepines had roughly the same degree of maximal [11C] Ro 15-1788 binding in brain regions as the healthy subjects but the rate of decline of [11C] Ro 15-1788 in the brain was higher. This indicates that there is measurable competition between [11C] Ro 15-1788 binding and clinical benzodiazepine concentrations in the body fluids of psychiatric patients. The results demonstrate that [11C] Ro 15-1788 should be a valuable tool for quantitative analyses of benzodiazepine receptor characteristics and receptor occupancy in the brain of patients with neuropsychiatric disorders
ER  - 

TY  - JOUR
T1  - Estimation of upper limits on human radiation absorbed doses from carbon-11-labeled compounds
A1  - Gatley,S.J.
Y1  - 1993/12//
N1  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973PMID- 0008254413
SP  - 2208
EP  - 2215
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 12
N2  - Radiation absorbed dose estimates for short-lived PET tracers are commonly based on biodistributions in rodents which (because of more rapid distribution and other species differences) may have limited relevance to humans. The initial purpose of this study was to estimate an intravenously injectable quantity of 11C which could not, on a priori grounds, exceed regulatory limits on radiation absorbed doses for individual organs. Upper limits on organ cumulative activities were estimated by assuming that 11C-labeled compounds are instantaneously distributed in the blood plasma, and then transferred solely and irreversibly to a single organ. The rate-constant (min-1) for each organ was taken to be its fractional cardiac output, since the plasma volume of 3 liters is recirculated each minute. The method was extended by using measured time courses of radioactivity in human arterial plasma available from previous PET studies with several 11C compounds in place of the assumption that the injected radioactivity was initially instantaneously distributed throughout the plasma. Calculations for 11C L-deprenyl, cogentin, cocaine, N-methylspiperone, putrescine and 2-deoxy-D-glucose, assuming transfer limited to a single organ, gave the kidneys rather than the thyroid as critical organ in each case. The upper-limit self-doses were 140, 210, 320, 360, 450 and 750 mrad/mCi, respectively, indicating that 34, 24, 15, 14 and 6.5 mCi, respectively, could be administered in a single PET study. These results suggest a strategy for human studies with 11C-labeled compounds: a preliminary study at the 3.5-mCi level would yield 11C arterial plasma data which could in turn be used to give a refined upper limit on radiation absorbed doses. For many 11C compounds, this strategy would demonstrate that sufficient radioactivity could be injected to give acceptable human PET images and would avoid the death of animals for biodistribution studies
ER  - 

TY  - JOUR
T1  - Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age
A1  - Namba,H.
A1  - Iyo,M.
A1  - Fukushi,K.
A1  - Shinotoh,H.
A1  - Nagatsuka,S.
A1  - Suhara,T.
A1  - Sudo,Y.
A1  - Suzuki,K.
A1  - Irie,T.
Y1  - 1999/02/05/
N1  - Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, JapanPMID- 0009933347PID - 90260135259
SP  - 135
EP  - 143
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 26
IS  - 2
N2  - The regional cerebral metabolic rate of [11C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24-89 years). Quantitative measurement was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch the rapid metabolism of the tracer in the blood. The distribution of the rate constant k3, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067- 0.097 min-1) and thalamus (0.268 min-1), where AChE activity was low to moderate. The k3 values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement of the input function. The method should be applicable to patients with Alzheimer's disease and those with other kinds of dementia whose central cholinergic system has been reported to be disturbed
ER  - 

TY  - JOUR
T1  - Motor correlates of occipital glucose hypometabolism in Parkinson's disease without dementia
A1  - Bohnen,N.I.
A1  - Minoshima,S.
A1  - Giordani,B.
A1  - Frey,K.A.
A1  - Kuhl,D.E.
Y1  - 1999/02//
N1  - Department of Internal Medicine, The University of Michigan, Ann Arbor 48109-0028, USA
SP  - 541
EP  - 546
JF  - Neurology
VL  - 52
IS  - 3
N2  - OBJECTIVE: To determine whether occipital reduction in regional cerebral glucose metabolism in PD reflects retinal versus nigrostriatal dopaminergic degeneration. We hypothesized that occipital glucose metabolic reduction should be symmetric if parkinsonian retinopathy is responsible for the reduction. METHODS: PD patients without dementia (n = 29; age 63 +/- 10 years) and normal controls (n = 27; age 60 +/- 12 years) underwent [18F]fluorodeoxyglucose PET imaging. Regional cerebral glucose metabolic rates were assessed quantitatively. RESULTS: When compared with normal controls, PD patients showed most severe glucose metabolic reduction in the primary visual cortex (mean -15%, p < 0.001). Occipital glucose metabolic reduction was greater in the hemisphere contralateral to the side of the body affected initially or more severely in PD. There was an inverse correlation between side-to- side asymmetries in finger-tapping performance and occipital glucose metabolic reduction (r = -0.45, p < 0.05; n = 28). The correlation was strongest in patients with a relatively early stage of PD with more unilateral motor impairment (Hoehn and Yahr stage I, r = -0.74, p < 0.01; n = 10). CONCLUSION: The results indicate a pathophysiologic association between nigrostriatal dysfunction and occipital glucose metabolic reduction in PD
ER  - 

TY  - JOUR
T1  - Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping
A1  - Signorini,M.
A1  - Paulesu,E.
A1  - Friston,K.
A1  - Perani,D.
A1  - Colleluori,A.
A1  - Lucignani,G.
A1  - Grassi,F.
A1  - Bettinardi,V.
A1  - Frackowiak,R.S.J.
A1  - Fazio,F.
Y1  - 1999/01//
N1  - Istituto Scientifico H San Raffaele, Universita' di Milano via Olgeltina 60, 20132, Milano, Italia
SP  - 63
EP  - 80
JF  - Neuroimage
VL  - 9
IS  - 1
N2  - The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies. Copyright 1999 Academic Press
ER  - 

TY  - JOUR
T1  - Pharmacokinetic assessment of novel anti-cancer drugs using spectral analysis and positron emission tomography: a feasibility study
A1  - Meikle,S.R.
A1  - Matthews,J.C.
A1  - Brock,C.S.
A1  - Wells,P.
A1  - Harte,R.J.
A1  - Cunningham,V.J.
A1  - Jones,T.
A1  - Price,P.
Y1  - 1998///
N1  - PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Camperdown, NSW, Australia steve@nucmedrpacsnswgovauPMID- 0009685053
SP  - 183
EP  - 193
JA  - Cancer Chemother.Pharmacol.
VL  - 42
IS  - 3
N2  - PURPOSE: The aim of this study was to investigate the feasibility of evaluating the pharmacokinetics of radiolabeled anti-cancer drugs using spectral analysis, a non-compartmental tracer kinetic modeling technique, and positron emission tomography (PET). METHODS: Dynamic PET studies were performed on patients receiving tracer doses of 5- fluorouracil (5-[18F]-FU) and two developmental drugs [11C]- temozolomide and [11C]-acridine carboxamide. Spectral analysis was then used to (a) determine individual and group average pharmacokinetics, (b) predict tumour handling in response to different drug administration regimens, and (c) produce functional parametric images describing regional pharmacokinetics. RESULTS: Spectral analysis could distinguish tumour kinetics from normal tissue kinetics in an individual [11C]-temozolomide study and demonstrated a markedly greater volume of distribution (VD) in glioma than in normal brain, although there was no appreciable difference in mean residence time. Analysis of pooled acridine carboxamide data (n = 22) revealed a relatively large VD (and prolonged retention) in the liver and spleen and a markedly lower VD (and initial uptake) in the brain. Continuous infusion of 5- [18F]-FU was predicted to achieve a concentration in colorectal metastases in liver approximately 10 times that achieved in plasma at 10 h after commencement of the infusion. CONCLUSIONS: We conclude that spectral analysis provides important pharmacokinetic information about radiolabeled anti-cancer drugs with relatively few model assumptions
ER  - 

TY  - JOUR
T1  - In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease
A1  - Kuhl,D.E.
A1  - Koeppe,R.A.
A1  - Minoshima,S.
A1  - Snyder,S.E.
A1  - Ficaro,E.P.
A1  - Foster,N.L.
A1  - Frey,K.A.
A1  - Kilbourn,M.R.
Y1  - 1999/03/10/
N1  - Division of Nuclear Medicine, University of Michigan, Ann Arbor, USA dkuhl@umichedu
SP  - 691
EP  - 699
JF  - Neurology
VL  - 52
IS  - 4
N2  - OBJECTIVE: To validate an in vivo method for mapping acetylcholinesterase (AChE) activity in human brain, preparatory to monitoring inhibitor therapy in AD. BACKGROUND: AChE activity is decreased in postmortem AD brain. Lacking a reliable in vivo measure, little is known about central activity in early AD, when the disease is commonly targeted by AChE inhibitor drug therapy. METHODS: Intravenous N-[11C]methylpiperidin-4-yl propionate ([11C]PMP) served as an in vivo AChE substrate. AChE activity was defined using cerebral PET for tracer kinetic estimates of the local rate of [11C]PMP hydrolysis in 26 normal controls and 14 patients with AD. Eleven AD patients also had concomitant in vivo cerebral measures of vesicular acetylcholine transporter (cholinergic terminal) density and glucose metabolism. RESULTS: Cerebral AChE activity measures 1) were independent of changes in tracer delivery to cerebral cortex; 2) agreed with reported postmortem data concerning normal relative cerebral distributions, absence of large age-effect in normal aging, and deficits in AD; 3) correlated in AD cerebral cortex with concomitant in vivo measures of cholinergic terminal deficits, but not with metabolic deficits; and 4) agreed quantitatively with predicted level of cerebral AChE inhibition induced by physostimine. CONCLUSIONS: This in vivo PET method provided valid measures of central AChE activity in normal subjects and AD patients. Applied in early AD, it should facilitate inhibitor treatment by confirming central inhibition, optimizing drug dosage, identifying likely responders, and testing surrogate markers of therapeutic response
ER  - 

TY  - JOUR
T1  - Evolution of brain glucose metabolism with age in epileptic infants, children and adolescents
A1  - Bentourkia,M.
A1  - Michel,C.
A1  - Ferriere,G.
A1  - Bol,A.
A1  - Coppens,A.
A1  - Sibomana,M.
A1  - Bausart,R.
A1  - Labar,D.
A1  - De Volder,A.G.
Y1  - 1998/10//
N1  - Positron Tomography Laboratory, University of Louvain, School of Medicine, Louvain-La-Neuve, BelgiumPMID- 0009840673
SP  - 524
EP  - 529
JA  - Brain Dev.
VL  - 20
IS  - 7
N2  - During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo- parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain
ER  - 

TY  - JOUR
T1  - Physostigmine results in an increased decrement in brain glucose consumption in Alzheimer's disease
A1  - Blin,J.
A1  - Ivanoiu,A.
A1  - De Volder,A.
A1  - Michel,C.
A1  - Bol,A.
A1  - Verellen,C.
A1  - Seron,X.
A1  - Duprez,T.
A1  - Laterre,E.C.
Y1  - 1998/04//
N1  - Laboratory of Positron Emission Tomography, Universityof Louvain, Louvain-La-Neuve, Belguim jb@arcadisbePMID- 0009566811
SP  - 256
EP  - 263
JA  - Psychopharmacology (Berl.)
VL  - 136
IS  - 3
N2  - The responsibility of cerebral cholinergic lesions for the weak clinical response to cholinergic neurotransmission enhancement of Alzheimer's disease (AD) was studied by measuring the effects of physostigmine on glucose consumption and neuropsychological tests. Ten AD and ten aged normals (AN) were examined twice, under placebo and under maximal tolerated dose of physostigmine, in randomized order and blind fashion. Under physostigmine, both groups showed better performances in tests measuring attention (P < 0.05-0.001) but not long- term memory, and cerebral glucose consumption was regionally modified (P < 0.0001). We observed a regional decrease in AD and in AN which was larger in AD, where each patient exhibited a mean metabolic decrease. With normalized values, AD and AN showed a similar decrease in the metabolic values of prefrontal cortex and striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission enhancement depresses glucose consumption and increases selective attention in similar ways in both groups, but to a larger extent in AD. This suggests that brain metabolism in AD over-responds to enhancement of cholinergic neurotransmission. The observed weak response of clinical symptomatology to anticholinesterase agents does not appear to be due to the failure to enhance the activity of the cholinergic system in AD
ER  - 

TY  - JOUR
T1  - No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET
A1  - Trichard,C.
A1  - Paillere-Martinot,M.L.
A1  - Attar-Levy,D.
A1  - Blin,J.
A1  - Feline,A.
A1  - Martinot,J.L.
Y1  - 1998/05/04/
N1  - INSERM U334, SHFJ, DRM, DSV, CEA, Orsay, FrancePMID- 0009633832
SP  - 13
EP  - 17
JA  - Schizophr.Res.
VL  - 31
IS  - 1
N2  - To investigate putative abnormalities of cortical 5-HT2A receptor density in schizophrenia, we used positron emission tomography and [18F]setoperone, a high-affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive schizophrenic patients and in 15 normal controls. No significant difference between the groups was observed in the whole or regional cortical binding potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor cortical density abnormalities in schizophrenics
ER  - 

TY  - JOUR
T1  - Does the enhancement of cholinergic neurotransmission influence brain glucose kinetics and clinical symptomatology in progressive supranuclear palsy?
A1  - Blin,J.
A1  - Mazetti,P.
A1  - Mazoyer,B.
A1  - Rivaud,S.
A1  - Ben Ayed,S.
A1  - Malapani,C.
A1  - Pillon,B.
A1  - Agid,Y.
Y1  - 1995/12//
N1  - INSERM U289, Nouvelle pharmacie, Hopital de la Salpetriere, FrancePMID- 0008595479
SP  - 1485
EP  - 1495
JF  - Brain
VL  - 118
IS  - Pt 6
N2  - Cholinergic systems are markedly affected both in cortical and subcortical cerebral areas of patients with progressive supranuclear palsy (PSP). To determine whether it is possible to modify the clinical picture of PSP through the enhancement of brain cholinergic neurotransmission, we studied the effects of physostigmine, an anticholinesterase reference drug, on symptoms and brain glucose metabolism using [18F]fluorodeoxyglucose (FDG) and PET. Patients were evaluated blind in a randomized order with both placebo and physostigmine infusions after an individual determination of maximal tolerated dose. Under steady-state physostigmine infusions, although glucose consumption was not significantly modified, the entry of glucose from blood to brain was regionally increased from 8 to 32% of placebo values suggesting an increase in cerebral blood flow (CBF) or an increase in the activity of brain glucose transporter. Following physostigmine administration in the same patients: the errors in antisaccades during ocular movement testing were significantly reduced, a significant reduction in errors or performance was found in four out of seven neuropsychological tests, and motor disability was not significantly altered. Although the precise pathophysiology of these physostigmine-induced effects needs further investigations, our study suggests that part of the clinical symptomatology in PSP could be relieved by the enhancement of brain cholinergic neurotransmission
ER  - 

TY  - JOUR
T1  - Mechanisms of recovery from aphasia: evidence from positron emission tomography studies [see comments]
A1  - Warburton,E.
A1  - Price,C.J.
A1  - Swinburn,K.
A1  - Wise,R.J.
Y1  - 1999/02//
N1  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK
SP  - 155
EP  - 161
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 66
IS  - 2
N2  - OBJECTIVES: Language functions comprise a distributed neural system, largely lateralised to the left cerebral hemisphere. Late recovery from aphasia after a focal lesion, other than by behavioural strategies, has been attributed to one of two changes at a systems level: a laterality shift, with mirror region cortex in the contralateral cortex assuming the function(s) of the damaged region; or a partial lesion effect, with recovery of perilesional tissue to support impaired language functions. Functional neuroimaging with PET allows direct observations of brain functions at systems level. This study used PET to compare regional brain activations in response to a word retrieval task in normal subjects and in aphasic patients who had shown at least some recovery and were able to attempt the task. Emphasis has been placed on single subject analysis of the results as there is no reason to assume that the mechanisms of recovery are necessarily uniform among aphasic patients. METHODS: Six right handed aphasic patients, each with a left cerebral hemispheric lesion (five strokes and one glioma), were studied. Criteria for inclusion were symptomatic or formal test evidence of at least some recovery and an ability to attempt word retrieval in response to heard word cues. Each patient underwent 12 PET scans using oxygen-15 labelled water (H2(15)O) as tracer to index regional cerebral blood flow (rCBF). The task, repeated six times, required the patient to think of verbs appropriate to different lists of heard noun cues. The six scans obtained during word retrieval were contrasted with six made while the subject was "at rest". The patients' individual results were compared with those of nine right handed normal volunteers undergoing the same activation study. The data were analysed using statistical parametric mapping (SPM96, Wellcome Department of Cognitive Neurology, London, UK). RESULTS: Perception of the noun cues would be expected to result in bilateral dorsolateral temporal cortical activations, but as the rate of presentation was only four per minute the auditory perceptual activations were not evident in all people. Anterior cingulate, medial premotor (supplementary speech area) and dorsolateral frontal activations were evident in all normal subjects and patients. There were limited right dorsolateral frontal activations in three of the six patients, but a similar pattern was also found in four of the nine normal subjects. In the left inferolateral temporal cortex, activation was found for the normal subjects and five of the six patients, including two of the three subjects with lesions involving the left temporal lobe. The only patient who showed subthreshold activation in the left inferolateral temporal activation had a very high error rate when performing the verb retrieval task. CONCLUSIONS: The normal subjects showed a left lateralised inferolateral temporal activation, reflecting retrieval of words appropriate in meaning to the cue from the semantic system. Lateralisation of frontal activations to the left was only relative, with right prefrontal involvement in half of the normal subjects. Frontal activations are associated with parallel psychological processes involved in word retrieval, including task initiation, short term (working) memory for the cue and responses, and prearticulatory processes (even though no overt articulation was required). There was little evidence of a laterality shift of word retrieval functions to the right temporal lobe after a left hemispheric lesion. In particular, left inferolateral temporal activation was seen in all patients except one, and he proved to be very inefficient at the task. The results provide indirect evidence that even limited salvage of peri-infarct tissue with acute stroke treatments will have an important impact on the rehabilitation of cognitive functions
ER  - 

TY  - JOUR
T1  - Disrupted temporal lobe connections in semantic dementia
A1  - Mummery,C.J.
A1  - Patterson,K.
A1  - Wise,R.J.
A1  - Vandenbergh,R.
A1  - Price,C.J.
A1  - Hodges,J.R.
Y1  - 1999/01//
N1  - Wellcome Department of Cognitive Neurology, Institute of Neurology, London, UK cmummery@filionuclacukPMID- 0010050895
SP  - 61
EP  - 73
JF  - Brain
VL  - 122
IS  - Pt 1
N2  - Semantic dementia refers to the variant of frontotemporal dementia in which there is progressive semantic deterioration and anomia in the face of relative preservation of other language and cognitive functions. Structural imaging and SPECT studies of such patients have suggested that the site of damage, and by inference the region critical to semantic processing, is the anterolateral temporal lobe, especially on the left. Recent functional imaging studies of normal participants have revealed a network of areas involved in semantic tasks. The present study used PET to examine the consequences of focal damage to the anterolateral temporal cortex for the operation of this semantic network. We measured PET activation associated with a semantic decision task relative to a visual decision task in four patients with semantic dementia compared with six age-matched normal controls. Normals activated a network of regions consistent with previous studies. The patients activated some areas consistently with the normals, including some regions of significant atrophy, but showed substantially reduced activity particularly in the left posterior inferior temporal gyrus (iTG) (Brodmann area 37/19). Voxel-based morphometry, used to identify the regions of structural deficit, revealed significant anterolateral temporal atrophy (especially on the left), but no significant structural damage to the posterior inferior temporal lobe. Other evidence suggests that the left posterior iTG is critically involved in lexical-phonological retrieval: the lack of activation here is consistent with the observation that these patients are all anomic. We conclude that changes in activity in regions distant from the patients' structural damage support the argument that their prominent anomia is due to disrupted temporal lobe connections
ER  - 

TY  - JOUR
T1  - Kinetic analysis of 2-[11C]thymidine PET imaging studies: validation studies
A1  - Mankoff,D.A.
A1  - Shields,A.F.
A1  - Link,J.M.
A1  - Graham,M.M.
A1  - Muzi,M.
A1  - Peterson,L.M.
A1  - Eary,J.F.
A1  - Krohn,K.A.
Y1  - 1999/04//
N1  - Division of Nuclear Medicine, University of Washington, Seattle, USA
SP  - 614
EP  - 624
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 4
N2  - 2-[11C]thymidine has been tested as a PET tracer of cellular proliferation. We have previously described a model of thymidine and labeled metabolite kinetics for use in quantifying the flux of thymidine into DNA as a measure of tumor proliferation. We describe here the results of studies to validate some of the model's assumptions and to test the model's ability to predict the time course of tracer incorporation into DNA in tumors. METHODS: Three sets of studies were conducted: (a) The uptake of tracers in proliferative tissues of normal mice was measured early after injection to assess the relative delivery of thymidine and metabolites of thymidine catabolism (thymine and CO2) and calculate relative blood-tissue transfer rates (relative K1s). (b) By using sequential injections of [11C]thymidine and [11C]thymine in normal human volunteers, the kinetics of the first labeled metabolite were measured to determine whether it was trapped in proliferating tissue such as the bone marrow. (c) In a multitumor rat model, 2- [14C]thymidine injection, tumor sampling and quantitative DNA extraction were performed to measure the time course of label uptake into DNA for comparison with model predictions. RESULTS: Studies in mice showed consistent relative delivery of thymidine and metabolites in somatic tissue but, as expected, showed reduced delivery of thymidine and thymine in the normal brain compared to CO2. Thymine studies in volunteers showed only minimal trapping of label in bone marrow in comparison to thymidine. This quantity of trapping could be explained by a small amount of fixation of labeled CO2 in tissue, a process that is included as part of the model. Uptake experiments in rats showed early incorporation of label into DNA, and the model was able to fit the time course of uptake. CONCLUSION: These initial studies support the assumptions of the compartmental model and demonstrate its ability to quantify thymidine flux into DNA by using 2- [11C]thymidine and PET. Results suggest that further work will be necessary to investigate the effects of tumor heterogeneity and to compare PET measures of tumor proliferation to in vitro measures of proliferation and to clinical tumor behavior in patients undergoing therapy
ER  - 

TY  - JOUR
T1  - 2-[C-11]thymidine imaging of malignant brain tumors
A1  - Eary,J.F.
A1  - Mankoff,D.A.
A1  - Spence,A.M.
A1  - Berger,M.S.
A1  - Olshen,A.
A1  - Link,J.M.
A1  - O'Sullivan,F.
A1  - Krohn,K.A.
Y1  - 1999/02/01/
N1  - Division of Nuclear Medicine, University of Washington Medical Center, Seattle 98195-6113, USAPMID- 0009973209
SP  - 615
EP  - 621
JA  - Cancer Res.
VL  - 59
IS  - 3
N2  - Malignant brain tumors pose diagnostic and therapeutic problems. Despite the advent of new brain imaging modalities, including magnetic resonance imaging (MRI) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), determination of tumor viability and response to treatment is often difficult. Blood-brain barrier disruption can be caused by tumor or nonspecific reactions to treatment, making MRI interpretation ambiguous. The high metabolic background of the normal brain and its regional variability makes it difficult to identify small or less active tumors by FDG imaging of cellular energetics. We have investigated 2-[C-11]thymidine (dThd) and PET to image the rate of brain tumor cellular proliferation. A series of 13 patients underwent closely spaced dThd PET, FDG PET, and MRI procedures, and the image results were compared by standardized visual analysis. The resulting dThd scans were qualitatively different from the other two scans in approximately 50% of the cases, which suggests that dThd provided information distinct from FDG PET and MRI. In two cases, recurrent tumor was more apparent on the dThd study than on FDG; in two other patients, tumor dThd uptake was less than FDG uptake, and these patients had slower tumor progression than the three patients with both high dThd and FDG uptake. To better characterize tumor proliferation, kinetic modeling was applied to dynamic dThd PET uptake data and metabolite-analyzed blood data in a subset of patients. Kinetic analysis was able to remove the confounding influence of [C- 11]CO2, the principal labeled metabolite of 2-[C-11]dThd, and to estimate the flux of dThd incorporation into DNA. Sequential, same-day [C-11]CO2 and [C-11]dThd imaging demonstrated the ability of kinetic analysis to model both dThd and CO2 simultaneously. Images of dThd flux obtained using the model along with the mixture analysis method for pixel-by-pixel parametric imaging significantly enhanced the contrast of tumor compared with normal brain. Comparison of model estimates of dThd transport versus dThd flux was able to discern increased dThd uptake simply on the basis of blood-brain barrier disruption retention on the basis of increased cellular proliferation. This preliminary study demonstrates the potential for imaging brain tumor cellular proliferation to provide unique information for guiding patient treatment
ER  - 

TY  - JOUR
T1  - Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease
A1  - Berent,S.
A1  - Giordani,B.
A1  - Foster,N.
A1  - Minoshima,S.
A1  - Lajiness-O'Neill,R.
A1  - Koeppe,R.
A1  - Kuhl,D.E.
Y1  - 1999/01//
N1  - Department of Psychiatry, University of Michigan, Ann Arbor, USA
SP  - 7
EP  - 16
JF  - Journal of Psychiatric Research
JA  - J.Psychiatr.Res.
VL  - 33
IS  - 1
N2  - We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development
ER  - 

TY  - JOUR
T1  - Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Behen,M.
A1  - Rothermel,R.
A1  - Janisse,J.J.
A1  - Lee,J.
A1  - Chugani,H.T.
Y1  - 1999/03//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201, USAPMID- 0010072042
SP  - 287
EP  - 295
JA  - Ann.Neurol.
VL  - 45
IS  - 3
N2  - Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children
ER  - 

TY  - JOUR
T1  - Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis
A1  - Tlle,T.R.
A1  - Kaufmann,T.
A1  - Siessmeier,T.
A1  - Lautenbacher,S.
A1  - Berthele,A.
A1  - Munz,F.
A1  - Zieglgansberger,W.
A1  - Willoch,F.
A1  - Schwaiger,M.
A1  - Conrad,B.
A1  - Bartenstein,P.
Y1  - 1999/01//
N1  - Department of Neurology, Technical University, Munich, GermanyPMID- 0009894875
SP  - 40
EP  - 47
JA  - Ann.Neurol.
VL  - 45
IS  - 1
N2  - Brain imaging with positron emission tomography has identified some of the principal cerebral structures of a central network activated by pain. To discover whether the different cortical and subcortical areas process different components of the multidimensional nature of pain, we performed a regression analysis between noxious heat-related regional blood flow increases and experimental pain parameters reflecting detection of pain, encoding of pain intensity, as well as pain unpleasantness. The results of our activation study indicate that different functions in pain processing can be attributed to different brain regions; ie, the gating function reflected by the pain threshold appeared to be related to anterior cingulate cortex, the frontal inferior cortex, and the thalamus, the coding of pain intensity to the periventricular gray as well as to the posterior cingulate cortex, and the encoding of pain unpleasantness to the posterior sector of the anterior cingulate cortex
ER  - 

TY  - JOUR
T1  - (15)O water positron emission tomography in language localization: a study comparing positron emission tomography visual and computerized region of interest analysis with the Wada test
A1  - Hunter,K.E.
A1  - Blaxton,T.A.
A1  - Bookheimer,S.Y.
A1  - Figlozzi,C.
A1  - Gaillard,W.D.
A1  - Grandin,C.
A1  - Anyanwu,A.
A1  - Theodore,W.H.
Y1  - 1999/05//
N1  - Clinical Epilepsy Section, National Institutes of Health, National Institute of Neurological and Communicative Disorders and Stroke, Epilepsy Research Branch, Bethesda, MD 20892, USA
SP  - 662
EP  - 665
JA  - Ann.Neurol.
VL  - 45
IS  - 5
N2  - We compared (15)O water positron emission tomography (PET) auditory and visual confrontational naming activation with an intracarotid amobarbital (Amytal) injection procedure (IAP) for language lateralization in 12 patients with intractable epilepsy. PET scans were evaluated by three raters experienced in functional imaging as well as by a region of interest (ROI) approach. Compared with IAP, raters' positive predictive value for language lateralization ranged from 88 to 91%. ROI analysis had a positive predictive value of 80%. Six patients had surgery; 1 with right-sided IAP language dominance but left-sided PET activation had dysphasia for 6 months after left temporal lobectomy
ER  - 

TY  - JOUR
T1  - Cerebellar reorganization following cortical injury in humans: effects of lesion size and age
A1  - Niimura,K.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Chugani,H.T.
Y1  - 1999/03/10/
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USAPMID- 0010078730
SP  - 792
EP  - 797
JF  - Neurology
VL  - 52
IS  - 4
N2  - OBJECTIVE: The authors investigated chronic cerebellar reorganization following unilateral cortical lesions in children and adults using PET to measure benzodiazepine receptor (BZR) binding with [11C]flumazenil (FMZ) and glucose metabolism with 2-deoxy-2[18F]fluoro-D-glucose (FDG). BACKGROUND: Crossed cerebellar diaschisis (CCD) is defined as decreased metabolism or blood flow in the cerebellum contralateral to a cortical insult measured by functional neuroimaging, and is typically seen in adults with large frontal or parietal lesions. The authors previously reported that CCD of glucose metabolism was not as prominent in children as in adults, and that some children showed a paradoxical pattern of increased glucose utilization in cerebellar cortex contralateral to the cortical lesion. The current study investigated whether CCD is associated with alterations in the gamma-aminobutyric acid (GABA(A))/BZR complex. METHODS: Patients with frontal lesions alone or with parietal lesions were compared with patients with temporal lesions, which are typically not associated with CCD. RESULTS: Children with lesion onset before 1 year of age showed significantly higher glucose utilization in contralateral posterior quadrangular and superior semilunar lobules of cerebellar cortex than did adults. Two patterns of change in cerebellar BZR binding were seen in children: 1) Five of 10 children showed increased BZR binding in the dentate nucleus contralateral to the lesion, and 2) the remaining five children showed no increase in dentate nucleus BZR binding but showed increased binding in the lateral lobules of the cerebellar cortex contralateral to the lesion. Adults showed increased binding only in contralateral dentate nucleus and not in cerebellar cortex. The size and severity of the supratentorial lesion, as well as age at the time of injury, were important factors in these findings. CONCLUSIONS: Reorganization of GABA-mediated mechanisms and glucose metabolism in cerebellum following cortical injury differs with size of lesion and age at the time of injury
ER  - 

TY  - JOUR
T1  - Hippocampal cell density and subcortical metabolism in temporal lobe epilepsy
A1  - Dlugos,D.J.
A1  - Jaggi,J.
A1  - O'Connor,W.M.
A1  - Ding,X.S.
A1  - Reivich,M.
A1  - O'Connor,M.J.
A1  - Sperling,M.R.
Y1  - 1999/04//
N1  - Division of Neurology, Children's Hospital of Philadelphia, PA 19104, USAPMID- 0010219265
SP  - 408
EP  - 413
JF  - Epilepsia
VL  - 40
IS  - 4
N2  - PURPOSE: Correlations between hippocampal cell density and subcortical metabolism in patients with temporal lobe epilepsy (TLE) were studied to explore possible links between subcortical function and the regulation of hippocampal excitability. METHODS: Resected hippocampal cell densities were correlated with cortical and subcortical regional cerebral metabolic rate for glucose (CMRglu), as measured by [18F]- fluorodeoxyglucose positron emission tomography (18-FDG-PET), in 39 patients with intractable TLE who underwent anterior temporal lobectomy (ATL). CMRglu was measured ipsilateral and contralateral to the resected temporal lobe. Linear regression techniques were used for statistical analysis. RESULTS: Hilar cell densities correlated positively and significantly with CMRglu in the bilateral thalamus, putamen and globus pallidus, and the ipsilateral caudate. Dentate granule cell densities correlated positively and significantly with CMRglu in the bilateral thalamus and putamen. There was no significant correlation between cell densities and CMRglu in any cortical region, including the hippocampus. CONCLUSIONS: We postulate that hippocampal cell loss results in decreased efferent synaptic activity to the thalamus and basal ganglia, causing decreased neuronal activity in these structures with consequent hypometabolism. This synaptic activity has a significant bilateral component. Subcortical hypometabolism in patients with TLE may reinforce the epileptogenic potential of mesial temporal lobe discharges
ER  - 

TY  - JOUR
T1  - Interictal spikes increase cerebral glucose metabolism and blood flow: a PET study
A1  - Bittar,R.G.
A1  - Andermann,F.
A1  - Olivier,A.
A1  - Dubeau,F.
A1  - Dumoulin,S.O.
A1  - Pike,G.B.
A1  - Reutens,D.C.
Y1  - 1999/02//
N1  - Montreal Neurological Institute and Hospital, and Department of Neurology and Neurosurgery, McGill University, Quebec, CanadaPMID- 0009952263
SP  - 170
EP  - 178
JF  - Epilepsia
VL  - 40
IS  - 2
N2  - PURPOSE: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges. METHODS: To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer [15O]H20 and with [18F]fluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively. RESULTS: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: - 71, z: 39; t = 4.5; p<0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 micromol/100 g/min with eyes open and 44.1 micromol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone. CONCLUSIONS: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism
ER  - 

TY  - JOUR
T1  - NMDA-receptor activity visualized with (S)-[N-methyl-11C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy
A1  - Kumlien,E.
A1  - Hartvig,P.
A1  - Valind,S.
A1  - Oye,I.
A1  - Tedroff,J.
A1  - Langstrom,B.
Y1  - 1999/01//
N1  - Department of Neurology, University Hospital, Uppsala University, SwedenPMID- 0009924899
SP  - 30
EP  - 37
JF  - Epilepsia
VL  - 40
IS  - 1
N2  - PURPOSE: To determine whether neurochemical activation of the N-methyl- D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 11C-labeled (S)-[N-methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE). METHODS: Eight patients with MTLE who were evaluated regarding epilepsy surgery underwent positron emission tomography (PET) with (S)-[N-methyl- 11C]ketamine. The presurgical investigations included magnetic resonance imaging (MRI), PET with 18F-fluoro-deoxyglucose (18FDG), and seizure monitoring by using video-EEG. The uptake of (S)-[N-methyl- 11C]ketamine in the temporal lobe of ictal onset was compared with the contralateral side and correlated to changes in regional glucose metabolism measured by PET with 18FDG. RESULTS: (S)-[N-methyl- 11C]ketamine rapidly reached the brain, and high radioactivities were measured in the striatum, thalamic nuclei, and cortical regions. Overall the brain uptake and regional binding potentials of (S)-[N- methyl-11C]ketamine were similar to measurements observed previously in healthy controls. However, 20 min after administration, when blood flow influence was negligible, a side-to-side comparison revealed a 9-34% reduction of tracer radioactivity in the temporal lobes of ictal onset. At earlier times, the differences in binding potentials were less pronounced, 9-21%. The magnitude and distribution of the reduction were similar to the metabolic pattern seen on PET scans with 18FDG. CONCLUSIONS: Radioactivity uptake of intravenously administered (S)-[N- methyl-11C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion, focal atrophy, or other factors
ER  - 

TY  - JOUR
T1  - Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy
A1  - Foldvary,N.
A1  - Lee,N.
A1  - Hanson,M.W.
A1  - Coleman,R.E.
A1  - Hulette,C.M.
A1  - Friedman,A.H.
A1  - Bej,M.D.
A1  - Radtke,R.A.
Y1  - 1999/01//
N1  - Division of Neurology, Duke University Medical Center, Durham, North Carolina, USAPMID- 0009924898
SP  - 26
EP  - 29
JF  - Epilepsia
VL  - 40
IS  - 1
N2  - PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60-80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE. METHODS: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA). RESULTS: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies. CONCLUSIONS: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE
ER  - 

TY  - JOUR
T1  - Clinical value of "ictal" FDG-positron emission tomography and the routine use of simultaneous scalp EEG studies in patients with intractable partial epilepsies
A1  - Barrington,S.F.
A1  - Koutroumanidis,M.
A1  - Agathonikou,A.
A1  - Marsden,P.K.
A1  - Binnie,C.D.
A1  - Polkey,C.E.
A1  - Maisey,M.N.
A1  - Panayiotopoulos,C.P.
Y1  - 1998/07//
N1  - The Guys and St Thomas' Clinical PET Centre, London, UKPMID- 0009670905
SP  - 753
EP  - 766
JF  - Epilepsia
VL  - 39
IS  - 7
N2  - PURPOSE: EEG is widely used during positron emission tomography (PET) to confirm the interictal state of the patient and assist in scan interpretation when a seizure occurs. Ictal scans usually reflect mixed interictal-ictal-postictal metabolic activity as seizures are brief in comparison to the 30-min uptake period of the tracer. We wished to determine whether routine EEG is justified and if seizures commonly affect the diagnostic information of the PET scan. METHODS: We examined the PET scans of 6 of 236 outpatients with intractable epilepsy with clinical and electrical evidence of a seizure during tracer uptake. We performed semi-quantitative analysis in 2 patients who had "ictal" and control interictal scans. RESULTS: Patients with single seizures lasting 23 s to 4 min [four complex partial seizures (CPS) and one absence seizure (AS)] had focal hypometabolism concordant with results of other investigations. One patient with complex partial status had irregular cortical uptake and focal hypometabolism, but the site of the ictal focus could not be confirmed. CONCLUSIONS: In this group of patients, seizures occurred infrequently during tracer uptake. The interpretation of the PET scan when single seizures occurred did not appear to be influenced by the continuous scalp EEG (CSEEG) recordings. The value of routine CSEEG in outpatients treated with medication should be reappraised, with potential cost savings. In rare circumstances in which a true ictal study occurs (complex partial status, epilepsia partialis continua, and repetitive CPS), PET scanning may be inconclusive and repeat interictal scanning should be pursued
ER  - 

TY  - JOUR
T1  - Bilateral temporal hypometabolism in epilepsy
A1  - Blum,D.E.
A1  - Ehsan,T.
A1  - Dungan,D.
A1  - Karis,J.P.
A1  - Fisher,R.S.
Y1  - 1998/06//
N1  - Barrow Neurological Institute, Phoenix, Arizona 85013, USAPMID- 0009637608
SP  - 651
EP  - 659
JF  - Epilepsia
VL  - 39
IS  - 6
N2  - PURPOSE: Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known. METHODS: We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH. RESULTS: BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age- matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MRI. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH. CONCLUSIONS: Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery
ER  - 

TY  - JOUR
T1  - A Functional Anatomy of Anticipatory Anxiety
A1  - Chua,P.
A1  - Krams,M.
A1  - Toni,I.
A1  - Passingham,R.
A1  - Dolan,R.
Y1  - 1999/06//
N1  - Wellcome Department of Cognitive Neurology, Institute of Neurology, Queen Square, London, WC1N 3BG, United KingdomPMID- 0010334900PID - nimg199904074101- 101006/nimg19990407
SP  - 563
EP  - 571
JF  - Neuroimage
VL  - 9
IS  - 6
N2  - Anticipatory anxiety is a complex combination of a future-oriented cognitive state, negative affect, and autonomic arousal. A dual-task paradigm of anticipation of electric shocks and a motor-learning task was used to examine the changes in neural patterns of activation associated with modulation of the cognitive state in anxiety by a distracting motor task. We used positron emission tomography (PET) and 15O-water to measure regional cerebral blood flow (rcbf) in 10 healthy male volunteers. A 2 x 2 factorial design-(shock vs no shock) x (low vs high distraction) was used with three scans per condition. Twelve PET scans were performed on each subject. In six of these scans, subjects were given electric shocks. In all scans, subjects also simultaneously performed a motor repetition (low distraction) or learning (high distraction) task. Galvanic skin conductance (GSR), Spielberger State and Trait Anxiety Inventory (STAI), and self-report data were also collected. In comparisons between the shock and no-shock conditions, the main finding was of increased rcbf in the left insula (-38,8,8) (z = 4.85, P < 0.05 corrected) and a homologous area in the right insula at a lower threshold (z =3.20, P = 0.001 uncorrected). Other areas activated were the right superior temporal sulcus, left fusiform, and left anterior cingulate. Using the STAI-state scores as a covariate of interest, significant correlations with rCBF were seen in the left orbitofrontal cortex, left insula, and left anterior cingulate cortex. There was no significant distraction effect as measured by the STAI, self-report, GSR response or interactional analysis of the PET data. These findings support the role of paralimbic structures as neural substrates of anticipatory anxiety. The failure to demonstrate behavioral and neurophysiological changes with the distractor task may reflect the modest increases in anxiety with the shock, the relatively simple distractor task, and small sample size. Copyright 1999 Academic Press
ER  - 

TY  - JOUR
T1  - Language organization in patients with early and late left-hemisphere lesion: a PET study [In Process Citation]
A1  - Mller,R.A.
A1  - Rothermel,R.D.
A1  - Behen,M.E.
A1  - Muzik,O.
A1  - Chakraborty,P.K.
A1  - Chugani,H.T.
Y1  - 1999/05//
N1  - Department of Pediatrics, Wayne State University Medical Center, Detroit, MI, USA amueller@cogsciucsdedu
SP  - 545
EP  - 557
JA  - Neuropsychologia.
VL  - 37
IS  - 5
N2  - Functional neuroimaging studies have shown enhanced right-hemisphere language activations in adults with left-hemisphere damage. We hypothesized that this effect would be stronger in patients with lesion occurring early in development. Using [15O]-water PET, we studied eight normal adults and 23 patients with unilateral left lesion during rest, listening to sentences, and sentence repetition. Thirteen patients had lesions with early onset (< 5 years) and ten had lesions with late onset (> 20 years). For listening to sentences, frontotemporal blood flow increases were significantly stronger in the left than in the right hemisphere in normal adults. This normal asymmetry was reduced in patients with late lesion and reversed in those with early lesion. For sentence repetition, analogous group differences were significant for the basal ganglia, but failed to reach significance for the (pre)motor and insular regions. We conclude that left lesion leads to alterations in the asymmetry of language activations (in and beyond the perisylvian areas). In addition, rightward shifts of language activation tend to be stronger as a consequence of early (as compared to late) lesion. Finally, postlesional reorganization appears to reflect a coexistence of 'additive' and 'subtractive' effects, i.e., activation in some regions that are not normally involved in language processing and lack of activation in other (undamaged) regions that are normally activated by language tasks
ER  - 

TY  - JOUR
T1  - Two instances of excessive blood flow increase in brain tumors during functional brain activation
A1  - Herholz,K.
A1  - Thiel,A.
A1  - Kracht,L.
A1  - Heiss,W.-D.
Y1  - 1999///
SP  - S569
JF  - Neuroimage
VL  - 9 (Supplement)
ER  - 

TY  - JOUR
T1  - Midbrain 18F-DOPA uptake differs in Parkinson's disease and in striatonigral degeneration
A1  - Ghaemi,M.
A1  - Hilker,R.
A1  - Herholz,K.
A1  - Wrker,M.
A1  - Heiss,W.-D.
Y1  - 1999///
SP  - X
JA  - J.Neural Transm.
VL  - 106
ER  - 

TY  - JOUR
T1  - An in vivo microdialysis study of striatal 6-[18F]fluoro-L-m-tyrosine metabolism
A1  - Jordan,S.
A1  - Bankiewicz,K.S.
A1  - Eberling,J.L.
A1  - VanBrocklin,H.F.
A1  - O'Neil,J.P.
A1  - Jagust,W.J.
Y1  - 1998/04//
N1  - Center for Functional Imaging, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA jorda02@aawlcomPMID- 0009566585
SP  - 513
EP  - 517
JA  - Neurochem.Res.
VL  - 23
IS  - 4
N2  - In vivo brain microdialysis was used to monitor 6-[18F]fluoro-L-m- tyrosine (FMT) uptake and metabolism in the striatum of conscious freely moving rats for 3 hours after FMT injection (25 mg/kg, i.v.). Microdialysate collected 20 to 120 min post-dose, contained FMT at a concentration (0.2 to 0.3 nM) approximately ten-fold below that of its metabolite [18F]fluoro-3-hydroxyphenylacetic acid (FPAC; 3.2 to 3.3 nM). D-amphetamine (2.5 mg/kg, i.p.) injected 120 min after significantly increased microdialysate FPAC (3.27 +/- 0.31 nM to 4.51 +/- 0.45 nM) in control but not reserpinized rats. Taken together these data demonstrate FMT is heavily metabolized following its entry into the striatum yielding FPAC which appears to be stored, at least in part, in reserpine sensitive cytoplasmic vesicles. Presynaptic retention of FPAC may contribute to the preferential accumulation of FMT positron emission tomography (PET) signaling in dopaminergic brain areas
ER  - 

TY  - JOUR
T1  - Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease
A1  - Bckman,L.
A1  - Andersson,J.L.
A1  - Nyberg,L.
A1  - Winblad,B.
A1  - Nordberg,A.
A1  - Almkvist,O.
Y1  - 1999/06/10/
N1  - Department of Psychology, Uppsala University, Sweden
SP  - 1861
EP  - 1870
JF  - Neurology
VL  - 52
IS  - 9
N2  - OBJECTIVE: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. BACKGROUND: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD; and 2) some of the earliest brain changes in this disease occur in regions critical to episodic memory, such as the hippocampus and neighboring regions. Yet, it remains largely unknown whether the episodic memory deficit seen in AD is paralleled by concomitant alterations in brain activity during actual task performance in these or other brain areas. METHODS: Using PET, blood flow was assessed in normal elderly subjects and patients with early AD during two retrieval conditions involving completion of word stems: baseline and cued recall. RESULTS: The patients with AD showed a marked performance deficit in cued recall, although the two groups were indistinguishable in the baseline task condition. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, as well as decreased activity in distinct left temporal regions during cued recall. The normal elderly alone activated the left parietal cortex and the left hippocampal formation during episodic retrieval. By contrast, AD- related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. CONCLUSIONS: The similar patterns of activations in the two groups suggest that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Those retrieval activations seen in the normal elderly, as opposed to the patients, may reflect AD-related failures in semantic processing and successful recollection of the target information, respectively. Finally, the AD-related increases in activity were interpreted in terms of compensatory reactions to the difficulties in performing the episodic memory task
ER  - 

TY  - JOUR
T1  - Primary progressive aphasia: a case report
A1  - Nagy,T.G.
A1  - Jelencsik,I.
A1  - Szirmai,I.
Y1  - 1999/07//
N1  - Department of Neurology, Semmelweis Medical University, Balassa u 6, 1083, Budapest, HungaryPMID- 0010362910PID - NE060419
SP  - 515
EP  - 519
JA  - Eur.J.Neurol.
VL  - 6
IS  - 4
N2  - We report a 69-year-old male patient whose motor aphasia started at the age of 61. The language disability remained isolated and progressed over a period of eight years without any additional cognitive deficits. Computed tomography (CT) and magnetic resonance imaging (MRI) showed moderate cortical atrophy with frontal dominance. Single photon emission tomography (SPECT) showed hypoperfusion in the frontotemporoparietal region, positron emission tomography (PET) demonstrated a global cortical reduction of glucose utilization with a lesser decrement in the occipital lobes. The clinical symptoms and the neuropsychological findings fit the diagnosis of primary progressive aphasia. Copyright 1999 Lippincott Williams & Wilkins
ER  - 

TY  - JOUR
T1  - Crossed aphasia. Functional brain imaging with PET or SPECT
A1  - Bakar,M.
A1  - Kirshner,H.S.
A1  - Wertz,R.T.
Y1  - 1996/10//
N1  - Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tenn, USA
SP  - 1026
EP  - 1032
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 53
IS  - 10
N2  - OBJECTIVES: To study patients with crossed aphasia (aphasia secondary to lesions in the right hemisphere in right-handed patients) with functional brain imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT); to see whether left hemisphere structures were metabolically depressed during the acute phase and, in 1 patient, during recovery; and to review the modern literature on crossed aphasia, with special reference to left hemisphere involvement. DESIGN: Case studies of 3 patients with crossed aphasia, including language testing, computed tomographic scanning, and functional imaging with PET or SPECT. SETTING: Hospital case studies. PATIENTS: Three right-handed patients with crossed aphasia secondary to acute infarctions in the right hemisphere and left hemiparesis. METHODS: All 3 patients were studied by means of bedside language testing, computed tomographic scanning, and functional brain imaging with PET or SPECT. Patient 1 also underwent serial testing with the Boston Diagnostic Aphasia Examination and follow-up PET scanning after 2 months of recovery. OUTCOME MEASURES: Clinical examination in all 3 patients and follow-up Boston Diagnostic Aphasia Examination and PET scanning in patient 1. RESULTS: Two patients had severe global aphasia and 1 had Broca aphasia. In all cases, computed tomographic scans failed to reveal any left hemispheric lesions. Functional imaging with PET or SPECT showed extensive hypometabolism or hypoperfusion in the right hemisphere, with initial reductions in the left hemisphere as well. In patient I, a follow-up PET image showed only persistent hypometabolism in the right hemisphere. CONCLUSIONS: These findings suggest that abnormal dominance for at least some language functions in the right hemisphere underlies the syndrome of crossed aphasia. Diaschisis, or functional depression of the anatomically normal left hemisphere, was seen in all 3 patients during the acute phase, but not in patient 1 after recovery had begun
ER  - 

TY  - JOUR
T1  - Slowly progressive aphasia: three cases with language, memory, CT and PET data
A1  - Kempler,D.
A1  - Metter,E.J.
A1  - Riege,W.H.
A1  - Jackson,C.A.
A1  - Benson,D.F.
A1  - Hanson,W.R.
Y1  - 1990/11//
N1  - School of Medicine, University of Southern California, Los AngelesPMID- 0001704428
SP  - 987
EP  - 993
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 53
IS  - 11
N2  - Three cases of slowly progressive speech and language disturbance were studied at various points post onset (three, five and 15 years respectively). Language, neuropsychological and brain imaging (computer tomography and positron emission tomography) evaluations were completed on all three patients. The data suggest that the syndrome of "progressive aphasia": 1) does not involve a uniform symptom complex; 2) does not necessarily develop into a full blown dementia syndrome; 3) varies greatly in rate of progression from case to case; 4) is associated with normal brain structure (on computer tomography); and 5) is associated with abnormal left temporal lobe metabolism as measured by fluorodeoxyglucose (FDG) positron emission tomography (PET). One patient had histological findings consistent with Alzheimer's disease at necropsy
ER  - 

TY  - JOUR
T1  - High-speed automated discrete blood sampling for positron emission tomography
A1  - Graham,M.M.
A1  - Lewellen,B.L.
Y1  - 1993/08//
N1  - Department of Radiology, University of Washington, Seattle 98195PMID- 0008326399
SP  - 1357
EP  - 1360
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 8
N2  - A computer controlled blood sampling system was designed specifically for rapid blood sampling for quantitative PET studies and uses solenoids that pinch silastic tubing, a roller pump and an inexpensive fraction collector. The controlling computer is an Apple II plus. The maximum sampling rate is one sample per 2 sec. Typical sample size is 0.90 +/- 0.02 g s.d. The loss of blood per sample is 2.6 ml. Tubing dead space is 1.2 ml. The response to a step change in activity between samples is 91% of the expected activity during high-speed sampling and 99% in the slower sampling mode. The major advantage of this device over flow-through detectors is that the blood is available for further processing to measure plasma or metabolite activities. This device has become a useful tool for quantitative PET studies, resulting in reliable sampling, lower radiation dose to personnel and fewer personnel necessary to conduct a study
ER  - 

TY  - JOUR
T1  - Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose
A1  - Reivich,M.
A1  - Alavi,A.
A1  - Wolf,A.
A1  - Fowler,J.
A1  - Russell,J.
A1  - Arnett,C.
A1  - MacGregor,R.R.
A1  - Shiue,C.Y.
A1  - Atkins,H.
A1  - Anand,A.
Y1  - 1985/06//
SP  - 179
EP  - 192
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 5
IS  - 2
N2  - The rate constants and lumped constants (LCs) for [18F]fluorodeoxyglucose ([18F]FDG) and [11C]deoxyglucose ([11C]DG) were determined in humans for the glucose metabolic rate kinetic model used to measure local cerebral glucose consumption. The mean values (+/- SE) of the LCs for [18F]FDG and [11C]DG are 0.52 +/- 0.028 (n = 9) and 0.56 +/- 0.043 (n = 6), respectively. The mean values (+/- SE) of the rate constants k*1, k*2, k*3, and k*4 for [18F]FDG for gray matter are 0.095 +/- 0.005, 0.125 +/- 0.002, 0.069 +/- 0.002, and 0.0055 +/- 0.0003, respectively. The corresponding values for white matter are 0.065 +/- 0.005, 0.126 +/- 0.003, 0.066 +/- 0.002, and 0.0054 +/- 0.0006, respectively. Using these values and previously published values for the rate constants for [11C]DG, the average whole-brain metabolic rates for glucose in normal subjects measured with [18F]FDG and [11C]DG are 5.66 +/- 0.37 (n = 6) and 4.99 +/- 0.23 (n = 6) mg/100 g/min, respectively. These values are not significantly different (t = 1.56, p greater than 0.10) and agree well with reported values in the literature determined by means of the Kety-Schmidt technique
ER  - 

TY  - JOUR
T1  - Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP) for in vivo measurements of acetylcholinesterase activity
A1  - Snyder,S.E.
A1  - Tluczek,L.
A1  - Jewett,D.M.
A1  - Nguyen,T.B.
A1  - Kuhl,D.E.
A1  - Kilbourn,M.R.
Y1  - 1998/11//
N1  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028, USA snyderse@umicheduPMID- 0009863562
SP  - 751
EP  - 754
JA  - Nucl.Med.Biol.
VL  - 25
IS  - 8
N2  - Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4- hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [11C]methyl trifluoromethanesulfonate at room temperature in N,N- dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [11C]PMP in 57% radiochemical yield, > 99% radiochemical purity, and > 1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [11C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography
ER  - 

TY  - JOUR
T1  - Measuring reproducibility of regional brain metabolic responses to lorazepam using statistical parametric maps
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Levy,A.V.
A1  - Felder,C.A.
A1  - Fowler,J.S.
A1  - Pappas,N.R.
A1  - Hitzemann,R.J.
A1  - Wong,C.T.
Y1  - 1999/05//
N1  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USAPMID- 0010319741
SP  - 715
EP  - 720
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 5
N2  - Statistical parametric mapping (SPM) is a method for localizing differences in brain activation patterns without the need for anatomic predefined constraints. The purpose of this study was to assess the reproducibility of the patterns of activation obtained with SPM for baseline measures and for metabolic changes in response to lorazepam on a test-retest design. The results were compared with those we previously published using region-of-interest (ROI) methods. METHODS: Sixteen healthy right-handed men were scanned twice with PET and [18F]fluorodeoxyglucose (FDG): before placebo and before lorazepam (30 microg/kg). The same double FDG procedure was repeated 6-8 wk later to assess test-retest reproducibility. Image datasets were analyzed by using SPM95 software. Difference images between baseline and lorazepam were compared for the first and second evaluations, both for relative decreases as well as increases in metabolism. Significance level was systematically varied to P < 0.001, P < 0.01 and P < 0.05. RESULTS: There were no differences in the baseline SPM maps obtained for the first and second evaluations. SPM showed similar, although not identical, differences in response to lorazepam between the two evaluations. Both evaluations showed significant decreases in occipital cortex (9.7% and 10%) and significant relative increases in left temporal pole (6.8% and 10.4%). However, the second evaluation showed a decrease in the left frontal cortex (areas 6 and 8), which was not present in the first evaluation. The results were very similar to those we had obtained with ROI methods, except for the activation in the left temporal pole, which we had not observed with ROI analyses. CONCLUSION: Although the overall pattern of lorazepam-induced activation depicted by SPM was reproducible in pattern and magnitude, there were some differences that included a left frontal area of deactivation during the second but not the first evaluation. Results with SPM are similar to those with the ROI method, and, because it systematically analyses the whole brain, SPM can uncover patterns not seen with the ROI method
ER  - 

TY  - JOUR
T1  - Regional brain metabolic response to lorazepam in alcoholics during early and late alcohol detoxification
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Overall,J.E.
A1  - Hitzemann,R.
A1  - Fowler,J.S.
A1  - Pappas,N.
A1  - Frecska,E.
A1  - Piscani,K.
Y1  - 1997/10//
N1  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USAPMID- 0009347090
SP  - 1278
EP  - 1284
JA  - Alcohol Clin.Exp.Res.
VL  - 21
IS  - 7
N2  - Changes in GABA function have been postulated to be involved in alcohol tolerance, withdrawal and addiction. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission), in alcoholics during early and late withdrawal. Brain metabolism was measured using PET and 2-deoxy-2[18F]fluoro-D-glucose after placebo (baseline) and after lorazepam (30 micrograms/kg intravenously) in 10 alcoholics and 16 controls. In the alcoholics evaluations were performed 2 to 3 weeks after detoxification and were repeated 6 to 8 weeks later. Controls were also evaluated twice at a 6 to 8 weeks interval. While during the initial evaluation metabolism was significantly lower for most brain regions in the alcoholics than in controls in the repeated evaluation the only significant differences were in cingulate and orbitofrontal cortex. Lorazepam-induced decrements in metabolism did not change with protracted alcohol withdrawal and the magnitude of these changes were similar in controls and alcoholics except for a trend towards a blunted response to lorazepam in orbitofrontal cortex in alcoholics during the second evaluation. Abnormalities in orbitofrontal cortex and cingulate gyrus in alcoholics are unlikely to be due to withdrawal since they persist 8 to 11 weeks after detoxification. The fact that there was only a trend of significance for an abnormal response to lorazepam in orbitofrontal cortex indicates that mechanisms other than GABA are involved in the brain metabolic abnormalities observed in alcoholic subjects
ER  - 

TY  - JOUR
T1  - Brain organization for language in children, adolescents, and adults with left hemisphere lesion: a PET study [In Process Citation]
A1  - Mller,R.A.
A1  - Behen,M.E.
A1  - Rothermel,R.D.
A1  - Muzik,O.
A1  - Chakraborty,P.K.
A1  - Chugani,H.T.
Y1  - 1999/05//
N1  - Department of Pediatrics, Wayne State University Medical School, Detroit, MI, USA
SP  - 657
EP  - 668
JA  - Prog.Neuropsychopharmacol.Biol.Psychiatry
VL  - 23
IS  - 4
N2  - 1. There is evidence for pronounced brain plasticity during postnatal maturation. The authors hypothesized that left-hemisphere lesion would be associated with greater than normal language participation of the right hemisphere and that atypical asymmetry of perisylvian language activations would be enhanced after lesion occurring in early childhood as compared to lesion occurring later in life. 2. Eleven patients with left-hemisphere lesion (aged 8-33 yrs.) and 9 normal adult comparison subjects were studied, using [15O]-water positron emission tomography. One patient group (N = 6) had early lesion onset (< or = 6 years of age), a second group (N = 5) had lesion onset later in life (> or = 10 years of age). Regional cerebral blood flow (rCBF) changes during listening to sentences (minus rest) and sentence generation (minus repetition) were compared between groups in predefined regions of interest. 3. Variance of regional activations within early and late lesion onset groups was considerable and qualitative inspection revealed only few robust group differences. However, when 4 patient pairs were approximately matched for chronological age, lesion site and VIQ, significantly reduced leftward asymmetry of activations in early lesion patients was found in the prefrontal, inferior frontal, and inferior parietal regions for expressive language, with concordant and marginally significant trends in the inferior frontal and superior temporal regions for receptive language. 4. The results suggest enhanced postlesional plasticity in childhood, while also reflecting strong individual variability probably due to clinical and demographic factors beside lesion onset
ER  - 

TY  - JOUR
T1  - [11C]Flumazenil PET in patients with epilepsy with dual pathology
A1  - Juhasz,C.
A1  - Nagy,F.
A1  - Muzik,O.
A1  - Watson,C.
A1  - Shah,J.
A1  - Chugani,H.T.
Y1  - 1999/05//
N1  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, USAPMID- 0010386525
SP  - 566
EP  - 574
JF  - Epilepsia
VL  - 40
IS  - 5
N2  - PURPOSE: Coexistence of hippocampal sclerosis and a potentially epileptogenic cortical lesion is referred to as dual pathology and can be responsible for poor surgical outcome in patients with medically intractable partial epilepsy. [11C]Flumazenil (FMZ) positron emission tomography (PET) is a sensitive method for visualizing epileptogenic foci. In this study of 12 patients with dual pathology, we addressed the sensitivity of FMZ PET to detect hippocampal abnormalities and compared magnetic resonance imaging (MRI) with visual as well as quantitative FMZ PET findings. METHODS: All patients underwent volumetric MRI, prolonged video-EEG monitoring, and glucose metabolism PET before the FMZ PET. MRI-coregistered partial volume-corrected PET images were used to measure FMZ-binding asymmetries by using asymmetry indices (AIs) in the whole hippocampus and in three (anterior, middle, and posterior) hippocampal subregions. Cortical sites of decreased FMZ binding also were evaluated by using AIs for regions with MRI-verified cortical lesions as well as for non-lesional areas with visually detected asymmetry. RESULTS: Abnormally decreased FMZ binding could be detected by quantitative analysis in the atrophic hippocampus of all 12 patients, including three patients with discordant or inconclusive EEG findings. Decreased FMZ binding was restricted to only one subregion of the hippocampus in three patients. Areas of decreased cortical FMZ binding were obvious visually in all patients. Decreased FMZ binding was detected visually in nonlesional cortical areas in four patients. The AIs for these nonlesional regions with visual asymmetry were significantly lower than those for regions showing MRI lesions (paired t test, p = 0.0075). CONCLUSIONS: Visual as well as quantitative analyses of FMZ-binding asymmetry are sensitive methods to detect decreased benzodiazepine-receptor binding in the hippocampus and neocortex of patients with dual pathology. MRI-defined hippocampal atrophy is always associated with decreased FMZ binding, although the latter may be localized to only one sub-region within the hippocampus. FMZ PET abnormalities can occur in areas with normal appearance on MRI, but FMZ-binding asymmetry of these regions is lower when compared with that of lesional areas. FMZ PET can be especially helpful when MRI and EEG findings of patients with intractable epilepsy are discordant
ER  - 

TY  - JOUR
T1  - Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
A1  - Hagell,P.
A1  - Schrag,A.
A1  - Piccini,P.
A1  - Jahanshahi,M.
A1  - Brown,R.
A1  - Rehncrona,S.
A1  - Widner,H.
A1  - Brundin,P.
A1  - Rothwell,J.C.
A1  - Odin,P.
A1  - Wenning,G.K.
A1  - Morrish,P.
A1  - Gustavii,B.
A1  - Bjorklund,A.
A1  - Brooks,D.J.
A1  - Marsden,C.D.
A1  - Quinn,N.P.
A1  - Lindvall,O.
Y1  - 1999/06//
N1  - Division of Neurology, Department of Clinical Neuroscience, University of Lund, SwedenPMID- 00103560644099- http://brainoupjournalsorg/cgi/content/full/122/6/11214100- http://brainoupjournalsorg/cgi/content/abstract/122/6/1121
SP  - 1121
EP  - 1132
JF  - Brain
VL  - 122
IS  - Pt 6
N2  - Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on- off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value
ER  - 

TY  - JOUR
T1  - Intracranial EEG vs. flumazenil and glucose PET in children with extratemporal lobe epilepsy
A1  - Muzik,O.
A1  - Da Silva,E.A.
A1  - Juhasz,C.
A1  - Chugani,D.C.
A1  - Shah,J.
A1  - Nagy,F.
A1  - Canady,A.
A1  - von Stockhausen,H.M.
A1  - Herholz,K.
A1  - Gates,J.
A1  - Frost,M.
A1  - Ritter,F.
A1  - Watson,C.
A1  - Chugani,H.T.
Y1  - 2000///
SP  - 171
EP  - 179
JF  - Neurology
VL  - 54
N2  - OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.
ER  - 

TY  - JOUR
T1  - Comparison of Impaired Subcortico-Frontal Metabolic Networks in Normal Aging, Subcortico-Frontal Dementia, and Cortical Frontal Dementia
A1  - Garraux,G.
A1  - Salmon,E.
A1  - Degueldre,C.
A1  - Lemaire,C.
A1  - Laureys,S.
A1  - Franck,G.
Y1  - 1999/08//
N1  - Cyclotron Research Centre, University of Li#ge, Li#ge, B-4000, BelgiumPMID- 0010417247PID - nimg199904634101- 101006/nimg19990463
SP  - 149
EP  - 162
JF  - Neuroimage
VL  - 10
IS  - 2
N2  - Normal aging, progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD) are characterized by different degrees of decline in frontal lobe functions. We used (18)FDG-PET and statistical parametric mapping (SPM96) to compare relative subcorticofrontal metabolic impairment at rest in 21 healthy elderly subjects (HES), 20 PSP patients, and 6 FTD patients. When HES were compared to 22 healthy young subjects, widespread decrease in metabolism was observed in bilateral medial prefrontal areas including anterior cingulate cortices, in dorsolateral prefrontal areas, in left lateral premotor area, in Broca's area, and in left insula. In PSP compared to the 43 healthy subjects (HS), we observed subcorticofrontal metabolic impairment including both motor and cognitive neural networks. Impairment of functional connections between midbrain tegmentum and cerebellar, temporal and pallidal regions was demonstrated in PSP as compared to HS. When comparing FTD to HS, glucose uptake was primarily reduced in dorsolateral and ventrolateral prefrontal cortices and in frontopolar and anterior cingulate regions. There was also bilateral anterior temporal, right inferior parietal, and bilateral striatal hypometabolism. Finally, FTD showed more severe striatofrontal metabolic impairment than PSP, while mesencephalothalamic involvement was only observed in PSP. Our data suggest that subcorticofrontal metabolic impairment is distributed in distinct subcorticocortical networks in normal aging, PSP, and FTD. Subcorticofrontal dementia in PSP is related to hypometabolism in discrete frontal areas, which are probably disconnected from certain subcortical structures. The concept of subcortical dementia is reinforced by our data, which show disrupted functional connections between mesencephalon and cerebellar cortex, inferior and medial temporal regions, and pallidum. Copyright 1999 Academic Press
ER  - 

TY  - JOUR
T1  - Preoperative PET activation for assessment of motor cortex area in precentral chondroma
A1  - Schreckenberger,M.
A1  - Spetzger,U.
A1  - Sabri,O.
A1  - Meyer,P.
A1  - Schulz,G.
A1  - Hermanns,B.
A1  - Krombach,G.
A1  - Gilsbach,J.
A1  - Buell,U.
Y1  - 1999/07//
N1  - Department of Nuclear Medicine, Aachen University of Technology, GermanyPMID- 0010390168
SP  - 24
EP  - 29
JA  - Surg.Neurol.
VL  - 52
IS  - 1
N2  - BACKGROUND: A main problem in the preoperative planning for precentral tumors is the exact assessment of the spatial relationship between the tumor and the functionally relevant brain areas, which may be difficult using only morphologically oriented imaging (CT, MRI). Therefore, we applied motor activation PET and PET/MRI overlay in a patient with a precentral tumor. DESCRIPTION: We report the case of a 21-year-old woman suffering from progressive right-sided headache and intermittent dysesthesia of the left leg. MRI showed a hypointense tumor with inhomogenous contrast enhancement in the right precentral area. For preoperative assessment of the spatial relationship between the tumor and the motor cortex area, the patient underwent two F-18- fluorodeoxyglucose positron emission tomography (PET) scans (1. resting condition and 2. motor activation of the left leg) and subsequent calculation of subtraction images of activation minus rest. Fusion of PET and MRI data (PET/MRI overlay) was performed for bimodal function and morphology presentation. PET revealed an activation pattern behind and below the tumor, indicating that the motor cortex area was shifted to the back. PET findings were confirmed by intraoperative electrophysiology. Cortical stimulation combined with intraoperative neuronavigation localized the motor area of the left foot and leg exactly at the dorsal border, below and lateral to the lesion. After complete resection of the solid tumor, histopathological examination revealed a chondroma. The postoperative course was uneventful, and the patient was discharged without neurological deficits. CONCLUSIONS: This case shows that biomodal imaging (PET/MRI) provides a noninvasive exact assessment of functionally important cortex areas for preoperative planning in patients with cerebral lesions
ER  - 

TY  - JOUR
T1  - Neurometabolic effects of psilocybin, 3,4- methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG
A1  - Gouzoulis-Mayfrank,E.
A1  - Schreckenberger,M.
A1  - Sabri,O.
A1  - Arning,C.
A1  - Thelen,B.
A1  - Spitzer,M.
A1  - Kovar,K.A.
A1  - Hermle,L.
A1  - Bull,U.
A1  - Sass,H.
Y1  - 1999/06//
N1  - Department of Psychiatry and Psychotherapy, University of Technology, Aachen, GermanyPMID- 0010327426
SP  - 565
EP  - 581
JA  - Neuropsychopharmacology.
VL  - 20
IS  - 6
N2  - The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F- 18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens
ER  - 

TY  - JOUR
T1  - Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness
A1  - Mayberg,H.S.
A1  - Liotti,M.
A1  - Brannan,S.K.
A1  - McGinnis,S.
A1  - Mahurin,R.K.
A1  - Jerabek,P.A.
A1  - Silva,J.A.
A1  - Tekell,J.L.
A1  - Martin,C.C.
A1  - Lancaster,J.L.
A1  - Fox,P.T.
Y1  - 1999/05//
N1  - Research Imaging Center, University of Texas Health Science Center at San Antonio, USA hmayberg@rotman-baycrestoncaPMID- 0010327898
SP  - 675
EP  - 682
JA  - Am J Psychiatry
VL  - 156
IS  - 5
N2  - OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic- cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression
ER  - 

TY  - JOUR
T1  - Reorganization of Sensory and Motor Systems in Hemiplegic Stroke Patients : A Positron Emission Tomography Study
A1  - Nelles,G.
A1  - Spiekermann,G.
A1  - Jueptner,M.
A1  - Leonhardt,G.
A1  - ller,S.
A1  - Gerhard,H.
A1  - Diener,H.C.
Y1  - 1999/08//
N1  - Department of Neurology, University of Essen (GN, GS, GL, CD)PMID- 00104360924099- http://wwwstrokeahaorg/cgi/content/full/30/8/15104100- http://wwwstrokeahaorg/cgi/content/abstract/30/8/1510
SP  - 1510
EP  - 1516
JF  - Stroke
VL  - 30
IS  - 8
N2  - Background and Purpose--Cortical reorganization of motor systems has been found in recovered stroke patients. Reorganization in nonrecovered hemiplegic stroke patients early after stroke, however, is less well described. We used positron emission tomography to study the functional reorganization of motor and sensory systems in hemiplegic stroke patients before motor recovery. Methods--Regional cerebral blood flow (rCBF) was measured in 6 hemiplegic stroke patients with a single, subcortical infarct and 3 normal subjects with the [(15)O]H(2)O injection technique. Brain activation was achieved by passive elbow movements driven by a torque motor. Increases of rCBF comparing passive movements and rest were assessed with statistical parametric mapping. Significant differences were defined at P<0.01. Results--In normal subjects, significant increases of rCBF were found in the contralateral sensorimotor cortex, supplementary motor area, cingulate cortex, and bilaterally in the inferior parietal cortex. In stroke patients, significant activation was observed bilaterally in the inferior parietal cortex and in the contralateral sensorimotor cortex, ipsilateral prefrontal cortex, supplementary motor area, and cingulate cortex. Significantly larger increases of rCBF in patients compared with normal subjects were found bilaterally in the sensorimotor cortex, stronger in the ipsilateral, unaffected hemisphere, and in both parietal lobes, including the ipsilateral precuneus. Conclusions-- Passive movements in hemiplegic stroke patients before clinical recovery elicit some of the brain activation patterns that have been described during active movements after substantial motor recovery. Changes of cerebral activation in sensory and motor systems occur early after stroke and may be a first step toward restoration of motor function after stroke
ER  - 

TY  - JOUR
T1  - Cerebral 6-[(18)F]fluoro-L-DOPA (FDOPA) metabolism in pig studied by positron emission tomography [In Process Citation]
A1  - Danielsen,E.H.
A1  - Smith,D.F.
A1  - Gee,A.D.
A1  - Venkatachalam,T.K.
A1  - Hansen,S.B.
A1  - Hermansen,F.
A1  - Gjedde,A.
A1  - Cumming,P.
Y1  - 1999/09/15/
N1  - PET-Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
SP  - 247
EP  - 258
JF  - Synapse
VL  - 33
IS  - 4
N2  - We measured 6-[(18)F]fluoro-L-DOPA (FDOPA) uptake and metabolism in the brain of 4-month-old female pigs (n = 8) using a high-resolution positron emission tomograph (PET) in 3D mode. The mean net blood-brain clearance of FDOPA (K(i)(D)) to striatum was 0.011 ml g(-1) min(-1). Correcting for the elimination of decarboxylated metabolites from striatum (k(loss) = 0.004 min(-1)) increased the apparent magnitude of the estimate of K(i)(D) by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k(3)(s)) was 0.008 min(-1). For multicompartmental analyses, the FDOPA partition volume (V(e)(D)) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g(-1)), with correction for the presence in brain of the plasma metabolite 3-O-methyl-FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k(3)(D)) was estimated to be 0.037 min(-1 )in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame-sequence (120 min) increased the variance of the estimate of k(3)(D) in striatum. The magnitude of k(3)(D) in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI-based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k(3)(D) in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Copyright 1999 Wiley-Liss, Inc
ER  - 

TY  - JOUR
T1  - [18F]Fluoro-beta-fluoromethylene-m-tyrosine derivatives show stereo, geometrical, and regio specificities as in vivo central dopaminergic probes in monkeys
A1  - Huang,S.C.
A1  - Quintana,J.
A1  - Satyamurthy,N.
A1  - Lacan,G.
A1  - Yu,D.C.
A1  - Phelps,M.E.
A1  - Barrio,J.R.
Y1  - 1999/05//
N1  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095, USAPMID- 0010382838
SP  - 365
EP  - 370
JA  - Nucl.Med.Biol.
VL  - 26
IS  - 4
N2  - Stereo (D and L), geometrical (E and Z), and regiospecific (2-, 4-, and 6-[18F]fluoro) analogs of beta-fluoromethylene-m-tyrosine (FMMT) have been investigated in adult vervet monkeys (Cercopithecus aethiops sabaeus, n = 12) in vivo with positron emission tomography (PET). Brain transport through the blood-brain barrier and central aromatic amino acid decarboxylase (AAAD)-mediated decarboxylation rates were established. Results show strict structural dependency of the kinetic behavior of radiofluorinated FMMT analogs, with the E-isomer exhibiting a higher specificity over the (Z) geometrical counterpart for central dopaminergic structures. The 6-[18F]fluoro substituted L-(E)-FMMT was also favored over the 2- and 4-[18F]fluorosubstituted isomers in terms of their ability to localize in the same brain areas. The role of PET in drug development is also exemplified in this work
ER  - 

TY  - JOUR
T1  - Recovery of neglect after right hemispheric damage: H2(15)O positron emission tomographic activation study
A1  - Pizzamiglio,L.
A1  - Perani,D.
A1  - Cappa,S.F.
A1  - Vallar,G.
A1  - Paolucci,S.
A1  - Grassi,F.
A1  - Paulesu,E.
A1  - Fazio,F.
Y1  - 1998/04//
N1  - Faculty of Psychology, Universita' di Roma La Sapienza, Center for Research of Neuropsychology-Istituto di Ricovero e Cura a Carattere Scientifico Clinica S Lucia, Rome, Italy PIZZAMIGLIO@UNIROMA1ITPMID- 0009561986
SP  - 561
EP  - 568
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 55
IS  - 4
N2  - BACKGROUND: The neural correlates of recovery of unilateral neglect (ULN), as well as of other consequences of focal brain damage, are largely unknown. Functional neuroimaging methods (in particular, positron emission tomography [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic patients. OBJECTIVE: To evaluate the functional cerebral correlates of recovery from ULN in patients with right-sided lesions, with the use of a PET activation paradigm. METHODS: Study of 3 patients with cerebrovascular lesions that involved corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the right hemisphere. Unilateral neglect was tested twice, before and after completion of a 2-month rehabilitation program, after which all 3 patients showed considerable improvement. Similarly, 2 PET examinations were performed, before and after recovery, during the performance of a visuospatial task requiring the patients to detect and respond to visual targets moving on a computer screen from the right to the left visual hemifield (experimental condition). The cerebral activation was compared with a baseline task in which subjects responded to a black dot flashing in a fixed position of the right hemifield. RESULTS: The brain areas activated by the performance of the visuospatial task before and after recovery were compared. In all 3 patients, the regions notably more active after recovery were almost exclusively found in right-sided cortical areas and largely overlapped with those observed in a group of 4 normal subjects performing the same task. Other areas, which have been shown to be involved in attentional and oculomotor tasks in other PET studies, were also activated in patients with ULN. CONCLUSIONS: The behavioral recovery of ULN in these patients with predominantly subcortical lesions is mainly associated with cerebral activations in cortical regions similar to those observed in normal subjects. There is some evidence of functional reorganization in individual subjects, which involves other areas related to space representation and exploration
ER  - 

TY  - JOUR
T1  - Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited
A1  - Simpson,I.A.
A1  - Appel,N.M.
A1  - Hokari,M.
A1  - Oki,J.
A1  - Holman,G.D.
A1  - Maher,F.
A1  - Koehler-Stec,E.M.
A1  - Vannucci,S.J.
A1  - Smith,Q.R.
Y1  - 1999/01//
N1  - Experimental Diabetes, Metabolism, and Nutrition Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USAPMID- 0009886075
SP  - 238
EP  - 247
JA  - J.Neurochem.
VL  - 72
IS  - 1
N2  - The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1 -azi-2,2,2-trifluoroethyl)[2- 3H]propyl]-1,3-bis(D-mannose-4-ylo xy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB. We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous- release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p.) for a 14- to 21- day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[14C]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarly, there was a 23+/-4% increase in total GLUT1/mg of microvessel protein and a 52+/-13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization. In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface
ER  - 

TY  - JOUR
T1  - Glucose transporter expression in brain: relationship to cerebral glucose utilization
A1  - Vannucci,S.J.
A1  - Clark,R.R.
A1  - Koehler-Stec,E.
A1  - Li,K.
A1  - Smith,C.B.
A1  - Davies,P.
A1  - Maher,F.
A1  - Simpson,I.A.
Y1  - 1998///
N1  - Department of Pediatrics, Milton S Hershey Medical Center-Pennsylvania State University, Hershey, PA, USAPMID- 0009778574
SP  - 369
EP  - 379
JA  - Dev.Neurosci.
VL  - 20
IS  - 4-5
N2  - Glucose is the principle energy source for mammalian brain. Delivery of glucose from the blood to the brain requires its transport across the endothelial cells of the blood-brain barrier and across the plasma membranes of neurons and glia, which is mediated by the facilitative glucose transporter proteins. The two primary glucose transporter isoforms which function in cerebral glucose metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood-brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose transporter. The levels of expression of both transporters are regulated in concert with metabolic demand and regional rates of cerebral glucose utilization. We present several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. These include normal cerebral development in the rat, Alzheimer's disease, neuronal differentiation in vitro, and dehydration in the rat
ER  - 

TY  - JOUR
T1  - Reduced glucose transporter concentrations in brains of patients with Alzheimer's disease [letter; comment]
A1  - Simpson,I.A.
A1  - Davies,P.
Y1  - 1994/11//
SP  - 800
EP  - 801
JA  - Ann.Neurol.
VL  - 36
IS  - 5
ER  - 

TY  - JOUR
T1  - Determination of language dominance by 15O-water PET in children and adolescents: a comparison with the Wada test
A1  - Mller,R.A.
A1  - Rothermel,R.D.
A1  - Muzik,O.
A1  - Becker,C.
A1  - Fuerst,D.R.
A1  - Behen,M.E.
A1  - Mangner,T.J.
A1  - Chugani,H.T.
Y1  - 1998///
SP  - 152
EP  - 161
JF  - Journal of Epilepsy
VL  - 11
ER  - 

TY  - JOUR
T1  - Selective cerebral hematocrit decrease in the centrum semiovale after carotid artery occlusion: a PET study
A1  - Yamauchi,H.
A1  - Fukuyama,H.
A1  - Nagahama,Y.
A1  - Katsumi,Y.
A1  - Hayashi,T.
A1  - Okazawa,H.
A1  - Yonekura,Y.
Y1  - 1999/01//
N1  - Department of Neurology, Faculty of Medicine, Kyoto University, JapanPMID- 0009886361
SP  - 109
EP  - 114
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 1
N2  - The centrum semiovale may be susceptible to hypoperfusion as a result of carotid artery occlusion. Recent studies suggest that the cerebral hematocrit decreases with diminished cerebral perfusion pressure. To investigate whether the effect of carotid artery occlusion on the hematocrit in the centrum semiovale is different from that in the cerebral cortex, seven patients with unilateral carotid artery occlusion were studied with positron emission tomography. The distributions of the red blood cell and plasma volumes were assessed using carbon monoxide labeled with oxygen 15 and human serum albumin- dithiosemicarbazone tracers labeled with copper 62, respectively. The CBF and CMRO2 were also measured with the (15)O steady-state technique. The calculated values for the hematocrit in the centrum semiovale ipsilateral to the arterial occlusion were significantly decreased compared with those in any of the other regions examined (the overlying cortical region and the contralateral cortex and centrum semiovale). This decrease in hematocrit, which resulted from a more pronounced increase in plasma volume than in red blood cell volume, was associated with a decrease in CBF and an increase in the oxygen extraction fraction. Hemodynamic disturbance caused by carotid artery occlusion may induce selective decrease of hematocrit limited to the centrum semiovale
ER  - 

TY  - JOUR
T1  - The substantia nigra of the human brain: II. Patterns Of loss of dopamine-containing neurons in Parkinson's disease
A1  - Damier,P.
A1  - Hirsch,E.C.
A1  - Agid,Y.
A1  - Graybiel,A.M.
Y1  - 1999/08//
N1  - INSERM U289, Hopital de la Salpetriere, Paris, France and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
SP  - 1437
EP  - 1448
JF  - Brain
VL  - 122
IS  - Pt 8
N2  - To achieve accuracy in studying the patterns of loss of midbrain dopamine-containing neurons in Parkinson's disease, we used compartmental patterns of calbindin D(28K) immunostaining to subdivide the substantia nigra with landmarks independent of the degenerative process. Within the substantia nigra pars compacta, we identified dopamine-containing neurons in the calbindin-rich regions ('matrix') and in five calbindin-poor pockets ('nigrosomes') defined by analysis of the three-dimensional networks formed by the calbindin-poor zones. These zones were recognizable in all of the brains, despite severe loss of dopamine-containing neurons. The degree of loss of dopamine- containing neurons in the substantia nigra pars compacta was related to the duration of the disease, and the cell loss followed a strict order. The degree of neuronal loss was significantly higher in the nigrosomes than in the matrix. Depletion was maximum (98%) in the main pocket (nigrosome 1), located in the caudal and mediolateral part of the substantia nigra pars compacta. Progressively less cell loss was detectable in more medial and more rostral nigrosomes, following the stereotyped order of nigrosome 1 > nigrosome 2 > nigrosome 4 > nigrosome 3 > nigrosome 5. A parallel, but lesser, caudorostral gradient of cell loss was observed for dopamine-containing neurons included in the matrix. This pattern of neuronal loss was consistent from one parkinsonian substantia nigra pars compacta to another. The spatiotemporal progression of neuronal loss related to disease duration can thus be drawn in the substantia nigra pars compacta for each Parkinson's disease patient: depletion begins in the main pocket (nigrosome 1) and then spreads to other nigrosomes and the matrix along rostral, medial and dorsal axes of progression
ER  - 

TY  - JOUR
T1  - Early postischemic hyperperfusion: pathophysiologic insights from positron emission tomography
A1  - Marchal,G.
A1  - Young,A.R.
A1  - Baron,J.C.
Y1  - 1999/05//
N1  - Cyceron INSERM U320 and University of Caen, France
SP  - 467
EP  - 482
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 5
N2  - Early postischemic hyperperfusion (EPIH) has long been documented in animal stroke models and is the hallmark of efficient recanalization of the occluded artery with subsequent reperfusion of the tissue (although occasionally it may be seen in areas bordering the hypoperfused area during arterial occlusion). In experimental stroke, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called "reperfusion injury"). In humans, focal hyperperfusion in the subacute stage (i.e., more than 48 hours after onset) has been associated with tissue necrosis in most instances, but regarding the acute stage, its occurrence, its relations with tissue metabolism and viability, and its clinical prognostic value were poorly understood before the advent of positron emission tomography (PET), in part because of methodologic issues. By measuring both CBF and metabolism, PET is an ideal imaging modality to study the pathophysiologic mechanism of EPIH. Although only a few PET studies have been performed in the acute stage that have systematically assessed tissue and clinical outcome in relation to EPIH, they have provided important insights. In one study, about one third of the patients with first-ever middle cerebral artery (MCA) territory stroke studied within 5 to 18 hours after symptom onset exhibited EPIH. In most cases, EPIH affected large parts of the cortical MCA territory in a patchy fashion, together with abnormal vasodilation (increased cerebral blood volume), "luxury perfusion" (decreased oxygen extraction fraction), and mildly increased CMRO2, which was interpreted as postischemic rebound of cellular metabolism in structurally preserved tissue. In that study, the spontaneous outcome of the tissue exhibiting EPIH was good, with late structural imaging not showing infarction. This observation was supported by another PET study, which showed, in a few patients, that previously hypoperfused tissue that later exhibited hyperperfusion after thrombolysis did not undergo frank infarction at follow-up. In both studies, clinical outcome was excellent in all patients showing EPIH except one, but in this case the hyperperfused area coexisted with an extensive area of severe hypoperfusion and hypometabolism. These findings from human studies therefore suggest that EPIH is not detrimental for the tissue, which contradicts the experimental concept of "reperfusion injury" but is consistent with the apparent clinical benefit from thrombolysis. However, PET studies performed in the cat have shown that although hyperperfusion was associated with prolonged survival and lack of histologic infarction when following brief (30-minute) MCA occlusion, it often was associated with poor outcome and extensive infarction when associated with longer (60-minute) MCA occlusion. It is unclear whether this discrepancy with human studies reflects a shorter window for tissue survival after stroke in cats, points to the cat being more prone to reperfusion injury, or indicates that EPIH tends not to develop in humans after severe or prolonged ischemia because of a greater tendency for the no- reflow phenomenon, for example. Nevertheless, the fact that the degree of hyperperfusion in these cat studies was related to the severity of prior flow reduction suggests that hyperperfusion is not detrimental per se. Preliminary observations in temporary MCA occlusion in baboons suggest that hyperperfusion developing even after 6 hours of occlusion is mainly cortical and associated with no frank infarction, as in humans. Overall, therefore, PET studies in both humans and the experimental animal, including the baboon, suggest that hyperperfusion is not a key factor in the development of tissue infarction and that it may be a harmless phenomenon
ER  - 

TY  - JOUR
T1  - Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study
A1  - Abadie,P.
A1  - Boulenger,J.P.
A1  - Benali,K.
A1  - Barre,L.
A1  - Zarifian,E.
A1  - Baron,J.C.
Y1  - 1999/04//
N1  - INSERM U 320, Caen, FrancePMID- 0010103141
SP  - 1470
EP  - 1478
JA  - Eur.J.Neurosci.
VL  - 11
IS  - 4
N2  - The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III-R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C-flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger's and Covi's scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F-values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety-score-PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety
ER  - 

TY  - JOUR
T1  - Parametric PET imaging of 5HT2A receptor distribution with 18F-setoperone in the normal human neocortex
A1  - Petit-Taboue,M.C.
A1  - Landeau,B.
A1  - Barre,L.
A1  - Onfroy,M.C.
A1  - Noel,M.H.
A1  - Baron,J.C.
Y1  - 1999/01//
N1  - INSERM U320, Cyceron, University of Caen, CEA DSV/DRM, FrancePMID- 0009935052
SP  - 25
EP  - 32
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 1
N2  - Because of 5HT2A receptor's (5HT2AR) putative role in several neuropsychiatric diseases, studying it in vivo is an important goal. 18F-setoperone is a well-validated and widely used PET radioligand for the study of neocortical 5HT2AR. We have previously developed and validated in baboons a method to generate parametric maps of the binding potential (i.e., the k3-to-k4 ratio) on a pixel-by-pixel basis, based on a single-dose tracer amount dynamic 18F-setoperone PET paradigm, and with the receptor-poor cerebellum as reference structure. However, previous semiquantitative PET human studies suggested that nonspecific (NS) binding in the neocortex might not be identical to that in the cerebellum. MEHODS: As a first step in the development of k3:k4 parametric mapping in humans, we therefore estimated directly the NS binding of 18F-setoperone in the neocortex of four young healthy volunteers who were studied with PET both before and after 2 wk of daily therapeutic oral doses of sertindole, an atypical neuroleptic possessing strong 5HT2AR antagonistic activity. RESULTS: Visual analysis of the dynamic PET data obtained over 120 min confirmed that virtually full receptor saturation had indeed been achieved; however, the late neocortical time-activity curves (TACs) progressively fell to lower uptake values than corresponding cerebellar TACs and could not be fitted according to a four-compartment (four-Cpt) nonlinear model, indicating lack of specific binding. The cerebellum TACs for both the control and the challenge conditions, as well as the challenge neocortical TACs, were fitted according to three-Cpt modeling, providing the k/k6 ratio and in turn the f2 fraction for both structures. Despite the small sample of only four subjects, the f2 fraction for the neocortex was significantly larger (i.e., NS binding was smaller) than that estimated for the cerebellum. This allowed us to determine the k3-to-k4 ratio for the control neocortex using the challenge neocortex as reference structure, that is, without using the cerebellum at all. This "assumption-free" approach was also successfully used to generate k3:k4 maps for these four subjects, which showed highest values for the temporal cortex. CONCLUSION: This study shows that, for every new PET or SPECT radioligand and when estimation of specific binding is based on a reference structure, it is important to determine the uniformity of nonspecific binding before proceeding with human investigations
ER  - 

TY  - JOUR
T1  - Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors
A1  - Massou,J.M.
A1  - Trichard,C.
A1  - Attar-Levy,D.
A1  - Feline,A.
A1  - Corruble,E.
A1  - Beaufils,B.
A1  - Martinot,J.L.
Y1  - 1997/09//
N1  - INSERM U 334, CEA, Service Hospitalier Frederic Joliot, Orsay, FrancePMID- 0009335087
SP  - 99
EP  - 101
JA  - Psychopharmacology (Berl.)
VL  - 133
IS  - 1
N2  - To investigate adaptative changes of 5-HT2A receptors induced by SSRIs, six patients chronically treated for a depressive episode (four with fluoxetine, two with fluvoxamine) were studied with PET and [18F]setoperone. They were compared to eight untreated depressive patients. The mean frontal to cerebellum radioactivity concentration ratio, an index of the [18F]setoperone specific binding to 5-HT2A receptors, was higher in treated than in untreated patients, when age was taken into account. This suggests that chronic treatment by SSRIs could induce an up-regulation of the 5-HT2A receptors, and that 5-HT2A receptor down-regulation is not a common mechanism for the therapeutic effects of all serotoninergic antidepressive drugs
ER  - 

TY  - JOUR
T1  - Reliability of a simple non-invasive method for the evaluation of 5-HT2 receptors using [18F]-setoperone PET imaging
A1  - Kapur,S.
A1  - Jones,C.
A1  - Dasilva,J.
A1  - Wilson,A.
A1  - Houle,S.
Y1  - 1997/05//
N1  - Schizophrenia Division, Clarke Institute of Psychiatry, University of Toronto, Ontario, CanadaPMID- 0009194079
SP  - 395
EP  - 399
JA  - Nucl.Med.Commun.
VL  - 18
IS  - 5
N2  - Position emission tomography (PET) imaging of 5-HT2 receptors can be potentially very useful in investigating neuropsychiatric disorders and their pharmacological treatments. [18F]-setoperone, a PET radio-ligand, has been shown to be useful for the delineation of 5-HT2 receptors in the cortex. However, there is no available data regarding the scan- rescan reliability of this technique. The purpose of this study was to assess the reliability of the [18F]-setoperone PET technique for assessing the binding potential (Bmax/ Kd) for 5-HT2 receptors. Ten healthy subjects had two [18F]-setoperone PET scans on two separate occasions 6-21 days apart. The average difference in the 5-HT2 binding potential (BP) as measured on the two occasions in the prefrontal, temporal, parietal and occipital region was between 5 and 7%. Thus 5- HT2 BP can be measured with a high reliability using a non-invasive technique that uses the cerebellum as a reference region. A power analysis based on the reliability data suggests that this technique can be used to detect within-subject differences of 10% or more, and between-group differences of 25% or more, with a reasonable number of subjects. It is concluded that [18F]-setoperone can be routinely produced and reliably used for the PET imaging of 5-HT2 receptors in clinical situations
ER  - 

TY  - JOUR
T1  - Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study
A1  - Rakshi,J.S.
A1  - Uema,T.
A1  - Ito,K.
A1  - Bailey,D.L.
A1  - Morrish,P.K.
A1  - Ashburner,J.
A1  - Dagher,A.
A1  - Jenkins,I.H.
A1  - Friston,K.J.
A1  - Brooks,D.J.
Y1  - 1999/09//
N1  - UI - 0
SP  - 1637
EP  - 1650
JF  - Brain
VL  - 122
IS  - Pt 9
N2  - We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [(18)F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [(18)F]dopa influx rate constant (K(i)(o)) were generated for each subject from dynamic 3D [(18)F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [(18)F]dopa K(i)(o) values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [(18)F]dopa K(i)(o) were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [(18)F]dopa K(i)(o). In advanced Parkinson's disease, significant extrastriatal decreases in [(18)F]dopa K(i)(o) were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [(18)F]dopa K(i)(o) were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [(18)F]dopa K(i)(o) reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [(18)F]dopa K(i)(o) reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [(18)F]dopa K(i)(o) increase seen in early Parkinson's disease. In conclusion, using SPM with [(18)F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [(18)F]dopa signal in dorsal midbrain and pontine regions suggests that [(18)F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder
AD  - MRC Cyclotron Unit, Hammersmith Hospital, The Wellcome Department of Cognitive Neurology and Department of Clinical Neurology, Institute of Neurology, London, UK and Department of Biofunctional Research, National Institute for Longevity Sciences, Obu, Japan
UR  - PM:0010468504;http://brain.oupjournals.org/cgi/content/full/122/9/1637;http://brain.oupjournals.org/cgi/content/abstract/122/9/1637
ER  - 

TY  - JOUR
T1  - Cortical control of movement in Huntington's disease. A PET activation study
A1  - Weeks,R.A.
A1  - Ceballos-Baumann,A.
A1  - Piccini,P.
A1  - Boecker,H.
A1  - Harding,A.E.
A1  - Brooks,D.J.
Y1  - 1997/09//
N1  - UI - 97458865
SP  - 1569
EP  - 1578
JF  - Brain
VL  - 120 ( Pt 9)
N2  - Regional cerebral blood flow was measured with H2(15)O PET in seven patients with choreic Huntington's disease and seven age-matched control subjects. Subjects were scanned at rest and when performing paced joystick movements, in freely chosen directions, with the dominant arm. During movement, the patients showed impaired activation of contralateral primary motor, medial premotor, bilateral parietal and bilateral prefrontal areas along with increased activation of bilateral insular areas. The underactivity of frontal areas in Huntington's disease is similar to the pattern of impaired activation in Parkinson's disease and is likely to result from degeneration of basal ganglia to frontal projections. Primary motor underactivity may explain the bradykinesia that these patients exhibit and, if inhibitory neurons are involved, also their chorea
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:0009313640
ER  - 

TY  - JOUR
T1  - Haemodynamic brain responses to acute pain in humans: Sensory and attentional networks
A1  - Peyron,R.
A1  - Larrea,L.
A1  - Gregoire,M.C.
A1  - Costes,N.
A1  - Convers,P.
A1  - Lavenne,F.
A1  - Mauguiere,F.
A1  - Michel,D.
A1  - Laurent,B.
Y1  - 1999/09//
SP  - 1765
EP  - 1780
JF  - Brain
VL  - 122
IS  - Pt 9
N2  - Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6 degrees C) or low (mean 39 degrees C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. Only the insular/second somatosensory cortices were found to respond whatever the attentional context and might, therefore, subserve the sensory-discriminative dimension of pain (intensity coding). In parallel, other rCBF changes previously described as 'pain-related' appeared to depend essentially on the attentional context. Attention to the thermal stimulus involved a large network which was primarily right- sided, including prefrontal, posterior parietal, anterior cingulate cortices and thalamus. Anterior cingulate activity was not found to pertain to the intensity coding network but rather to the attentional neural activity triggered by pain. The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain
AD  - Departement de Neurologie and Centre de la douleur, H#pital de Bellevue, Saint-Etienne, CERMEP, H#pital Neuro-cardiologique and UPRES EA 1880, Universit# Claude Bernard, Lyon, France
UR  - PM:0010468515;http://brain.oupjournals.org/cgi/content/full/122/9/1765;http://brain.oupjournals.org/cgi/content/abstract/122/9/1765
ER  - 

TY  - JOUR
T1  - Positron emission tomography during motor cortex stimulation for pain control
A1  - Garcia-Larrea,L.
A1  - Peyron,R.
A1  - Mertens,P.
A1  - Gregoire,M.C.
A1  - Lavenne,F.
A1  - Bonnefoi,F.
A1  - Mauguiere,F.
A1  - Laurent,B.
A1  - Sindou,M.
Y1  - 1997///
N1  - UI - 98377586
SP  - 141
EP  - 148
JA  - Stereotact.Funct.Neurosurg.
VL  - 68
IS  - 1-4 Pt 1
N2  - We studied regional changes in cerebral flood flow (rCBF) in 9 patients undergoing motor cortex stimulation (MCS) for pain control. Significant increase in rCBF was observed in the lateral thalamus ipsilateral to MCS probably reflecting corticothalamic connections from motor/premotor areas. Subsignificant increases were observed in the anterior cingulate, left insula and upper brainstem. Mean rCBF in the anterior cingulate increased during MCS in patients with good analgesic efficacy, while it decreased in those with poor clinical outcome; conversely, thalamic rCBF increased in the two groups, albeit to a greater extent in patients with good clinical results. Our results support a model of MCS action whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in other pain-related structures, including the anterior cingulate and the periaqueductal gray. MCS could influence the affective-emotional component of chronic pain by way of cingulate activation, and lead to descending inhibition of pain impulses by activation of the brainstem. Such effects may be obtained only if thalamic activation reaches a 'threshold' level, below which the analgesic cascade would not be successfully triggered
AD  - CERMEP (Positron Emission Tomography Center), Lyon, France
UR  - PM:0009711707
ER  - 

TY  - JOUR
T1  - Training-induced brain plasticity in aphasia
A1  - Musso,M.
A1  - Weiller,C.
A1  - Kiebel,S.
A1  - ller,S.P.
A1  - lau,P.
A1  - Rijntjes,M.
Y1  - 1999/09//
N1  - UI - 0
SP  - 1781
EP  - 1790
JF  - Brain
VL  - 122
IS  - Pt 9
N2  - It has long been a matter of debate whether recovery from aphasia after left perisylvian lesions is mediated by the preserved left hemispheric language zones or by the homologous right hemisphere regions. Using PET, we investigated the short-term changes in the cortical network involved in language comprehension during recovery from aphasia. In 12 consecutive measurements of regional cerebral blood flow (rCBF), four patients with Wernicke's aphasia, caused by a posterior left middle cerebral artery infarction, were tested with a language comprehension task. Comprehension was estimated directly after each scan with a modified version of the Token Test. In the interval between the scans, the patients participated in brief, intense language comprehension training. A significant improvement in performance was observed in all patients. We correlated changes in blood flow measured during the language comprehension task with the scores achieved in the Token Test. The regions which best correlated with the training-induced improvement in verbal comprehension were the posterior part of the right superior temporal gyrus and the left precuneus. This study supports the role of the right hemisphere in recovery from aphasia and demonstrates that the improvement in auditory comprehension induced by specific training is associated with functional brain reorganization
AD  - Department of Neurology, Friedrich-Schiller-Universit#t Jena, Department of Nuclear Medicine, Universit#t Essen and Neurorehabilitationsklinik, Waldbreitbach, Germany
UR  - PM:0010468516;http://brain.oupjournals.org/cgi/content/full/122/9/1781;http://brain.oupjournals.org/cgi/content/abstract/122/9/1781
ER  - 

TY  - JOUR
T1  - Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease
A1  - Dierks,T.
A1  - Linden,D.E.
A1  - Hertel,A.
A1  - Gunther,T.
A1  - Lanfermann,H.
A1  - Niesen,A.
A1  - Frolich,L.
A1  - Zanella,F.E.
A1  - Hor,G.
A1  - Goebel,R.
A1  - Maurer,K.
Y1  - 1999/02/22/
N1  -  [corrected and republished article originally printed in Psychiatry Res 1998 Nov 9;84(1):27-35]
SP  - 67
EP  - 75
JA  - Psychiatry Res.
VL  - 90
IS  - 1
N2  - In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level- dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders
AD  - Department of Psychiatry and Psychotherapy I, University of Frankfurt/Main, Frankfurt, Germany dierks@emuni-frankfurtde
UR  - PM:0010320212
ER  - 

TY  - JOUR
T1  - Imaging proliferation in vivo with [F-18]FLT and positron emission tomography
A1  - Shields,A.F.
A1  - Grierson,J.R.
A1  - Dohmen,B.M.
A1  - Machulla,H.J.
A1  - Stayanoff,J.C.
A1  - Lawhorn-Crews,J.M.
A1  - Obradovich,J.E.
A1  - Muzik,O.
A1  - Mangner,T.J.
Y1  - 1998/11//
N1  - UI - 99025415
SP  - 1334
EP  - 1336
JA  - Nat.Med.
VL  - 4
IS  - 11
N2  - Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects
AD  - Karmanos Cancer Institute, Department of Medicine, Wayne State University, Detroit Medical Center, MI 48301, USA shieldsA@karmanosorg
UR  - PM:0009809561
ER  - 

TY  - JOUR
T1  - Kinetic analysis of 2-[carbon-11]thymidine PET imaging studies: compartmental model and mathematical analysis
A1  - Mankoff,D.A.
A1  - Shields,A.F.
A1  - Graham,M.M.
A1  - Link,J.M.
A1  - Eary,J.F.
A1  - Krohn,K.A.
Y1  - 1998/06//
SP  - 1043
EP  - 1055
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 6
N2  - Carbon-11-thymidine is a PET tracer of DNA synthesis and cellular proliferation. Quantitative analysis of [11C]thymidine images is complicated by the presence of significant quantities of labeled metabolites. Estimation of the rate of thymidine incorporation into DNA using [11C]thymidine requires a kinetic model that is capable of describing the behavior of thymidine and labeled metabolites. METHODS: Based on previous studies with labeled thymidine, we constructed a five- compartment model describing the kinetic behavior of 2-[11C]thymidine and its labeled metabolites. In addition, we have performed a series of calculations and simulations to calculate the sensitivity and identifiability of model parameters to estimate the extent to which individual parameters can be estimated; to determine appropriate model constraints necessary for reproducible estimates of the constant describing flux of thymidine from the blood into DNA, i.e., thymidine flux constant; and to determine the potential accuracy of model parameter and thymidine flux constant estimates from PET imaging data. RESULTS: The underlying assumptions in the thymidine compartmental model lead to a description of the thymidine flux constant for DNA incorporation in terms of model parameters. Sensitivity and identifiability analyses suggest that the model parameters pertaining to labeled metabolites will be difficult to estimate independently of the thymidine parameters. Exact evaluation of the kinetic parameters of the labeled metabolites is not the principal goal of this model. Simulations were performed that suggest that it is preferable to tightly constrain these parameters to preset values near the center of their expected ranges. Although it is difficult to estimate individual thymidine model parameters, the flux constant for incorporation into DNA can be accurately estimated (r > 0.9 for estimated versus true simulated flux constant). Flux constant estimates are not affected by modest levels of local degradation of thymidine that may occur in proliferating tissue. CONCLUSION: By using a kinetic model for thymidine and labeled metabolites, it is possible to estimate the flux of thymidine uptake and incorporation into DNA and, thereby, noninvasively estimate regional cellular proliferation using [11C]thymidine and PET
AD  - Division of Nuclear Medicine, University of Washington, Seattle 98195, USA
UR  - PM:0009627342
ER  - 

TY  - JOUR
T1  - Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events
A1  - Jacobs,A.
A1  - Neveling,M.
A1  - Horst,M.
A1  - Ghaemi,M.
A1  - Kessler,J.
A1  - Eichstaedt,H.
A1  - Rudolf,J.
A1  - Model,P.
A1  - Bonner,H.
A1  - de Vivie,E.R.
A1  - Heiss,W.D.
Y1  - 1998/03//
N1  - UI - 98165453
SP  - 660
EP  - 667
JF  - Stroke
VL  - 29
IS  - 3
N2  - BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated. METHODS: Eighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with 18F-2-fluoro- 2-deoxy-D-glucose (FDG-PET), respectively. RESULTS: Intraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (P<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMR Glc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (r= -0.46, P<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc. CONCLUSIONS: HITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage
AD  - Department of Neurology, University of Cologne, and the Max-Planck Institute for Neurological Research, Germany jacobs@helixmghharvardedu
UR  - PM:0009506609
ER  - 

TY  - JOUR
T1  - Automated image registration: II. Intersubject validation of linear and nonlinear models
A1  - Woods,R.P.
A1  - Grafton,S.T.
A1  - Watson,J.D.
A1  - Sicotte,N.L.
A1  - Mazziotta,J.C.
Y1  - 1998/01//
N1  - Department of Neurology, UCLA School of Medicine, USAPMID- 0009448780
SP  - 153
EP  - 165
JA  - J.Comput.Assist.Tomogr.
VL  - 22
IS  - 1
N2  - PURPOSE: Our goal was to validate linear and nonlinear intersubject image registration using an automated method (AIR 3.0) based on voxel intensity. METHOD: PET and MRI data from 22 normal subjects were registered to corresponding averaged PET or MRI brain atlases using several specific linear and nonlinear spatial transformation models with an automated algorithm. Validation was based on anatomically defined landmarks. RESULTS: Automated registration produced results that were superior to a manual nine parameter variant of the Talairach registration method. Increasing the degrees of freedom in the spatial transformation model improved the accuracy of automated intersubject registration. CONCLUSION: Linear or nonlinear automated intersubject registration based on voxel intensities is computationally practical and produces more accurate alignment of homologous landmarks than manual nine parameter Talairach registration. Nonlinear models provide better registration than linear models but are slower
ER  - 

TY  - JOUR
T1  - Automated image registration: I. General methods and intrasubject, intramodality validation
A1  - Woods,R.P.
A1  - Grafton,S.T.
A1  - Holmes,C.J.
A1  - Cherry,S.R.
A1  - Mazziotta,J.C.
Y1  - 1998/01//
N1  - Division of Brain Mapping, UCLA School of Medicine, USAPMID- 0009448779
SP  - 139
EP  - 152
JA  - J.Comput.Assist.Tomogr.
VL  - 22
IS  - 1
N2  - PURPOSE: We sought to describe and validate an automated image registration method (AIR 3.0) based on matching of voxel intensities. METHOD: Different cost functions, different minimization methods, and various sampling, smoothing, and editing strategies were compared. Internal consistency measures were used to place limits on registration accuracy for MRI data, and absolute accuracy was measured using a brain phantom for PET data. RESULTS: All strategies were consistent with subvoxel accuracy for intrasubject, intramodality registration. Estimated accuracy of registration of structural MRI images was in the 75 to 150 microns range. Sparse data sampling strategies reduced registration times to minutes with only modest loss of accuracy. CONCLUSION: The registration algorithm described is a robust and flexible tool that can be used to address a variety of image registration problems. Registration strategies can be tailored to meet different needs by optimizing tradeoffs between speed and accuracy
ER  - 

TY  - JOUR
T1  - Generalizable patterns in neuroimaging: how many principal components?
A1  - Hansen,L.K.
A1  - Larsen,J.
A1  - Nielsen,F.A.
A1  - Strother,S.C.
A1  - Rostrup,E.
A1  - Savoy,R.
A1  - Lange,N.
A1  - Sidtis,J.
A1  - Svarer,C.
A1  - Paulson,O.B.
Y1  - 1999/05//
N1  - Department of Mathematical Modeling, Technical University of Denmark, Building 321, Lyngby, DK-2800, Denmark lkhansen@immdtudkPMID- 0010329293
SP  - 534
EP  - 544
JA  - Neuroimage.
VL  - 9
IS  - 5
N2  - Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets. Copyright 1999 Academic Press
ER  - 

TY  - JOUR
T1  - Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging
A1  - Wester,H.J.
A1  - Herz,M.
A1  - Weber,W.
A1  - Heiss,P.
A1  - Senekowitsch-Schmidtke,R.
A1  - Schwaiger,M.
A1  - Stocklin,G.
Y1  - 1999/01//
N1  - Department of Nuclear Medicine, Klinikum Rechts der Isar, Technischer Universitat Munchen, Munich, GermanyPMID- 0009935078
SP  - 205
EP  - 212
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 1
N2  - The aim of the study was to develop a simple 18F-labeled amino acid as a PET tracer for cerebral and peripheral tumors. O-(2-[18F]fluoroethyl)- L-tyrosine (L-[18F]FET) was synthesized and biologically evaluated. Results of the first human PET study are reported. METHODS: No carrier added (n.c.a.) and D-[18F]FET were prepared by 18F-fluoroethylation of L- and D-tyrosine in a two-step procedure. Biodistribution studies were performed in mice. The metabolic fate of L-[18F]FET was investigated in plasma, brain, tumor and pancreatic tissue samples using chromatographic procedures. Tumor uptake studies were performed in mammary carcinoma-bearing mice and in mice with the colon carcinoma SW 707. In a human PET study, a 59-y-old man with a recurrent astrocytoma was imaged using n.c.a. L-[18F]FET. RESULTS: Synthesis of [18F]FET was accomplished in about 50 min with an overall radiochemical yield of 40%. The uptake of L-[18F]FET in the brain of mice reached a level >2% ID/g between 30 and 60 min postinjection. The brain uptake of the D- isomer was negligible, indicating blood-brain barrier penetration by a specific amino acid transport system. L-[18F]FET is not incorporated into proteins. High-performance liquid chromatography (HPLC) analysis of brain, pancreas and tumor homogenates as well as plasma samples of mice at 10, 40 or 60 min postinjection showed only unchanged L- [18F]FET. Activity uptake in the bone did not exceed 2% ID/g at 40 min postinjection. The brain uptake of L-[18F]FET in mice bearing mammary carcinomas and colon carcinomas reached 7.1%+/-1.2% ID/g and 6.4%+/- 1.7% ID/g 1h postinjection, respectively. In the first human study, L- [18F]FET-PET allowed a clear delineation of a recurrent astrocytoma. Thirty-five minutes postinjection, the tumor-to-cortex ratio was >2.7. A tumor-to-blood ratio >1.5 was reached at 30 min postinjection and continued to increase. No significant activity accumulation was observed in peripheral organs after approximately 40 min postinjection. CONCLUSION: The high in vivo stability of L-[18F]FET, its fast brain and tumor uptake kinetics, its low accumulation in nontumor tissue and its ease of synthesis strongly support further evaluation of L-[18F]FET as an amino acid tracer for cerebral and peripheral tumors
ER  - 

TY  - JOUR
T1  - PET-pharmacokinetics of 18F-octreotide: a comparison with 67Ga-DFO- and 86Y-DTPA-octreotide
A1  - Wester,H.J.
A1  - Brockmann,J.
A1  - Rosch,F.
A1  - Wutz,W.
A1  - Herzog,H.
A1  - Smith-Jones,P.
A1  - Stolz,B.
A1  - Bruns,C.
A1  - Stocklin,G.
Y1  - 1997/05//
N1  - Institute fur Nuklearchemie, KFA Julich, GermanyPMID- 0009257325
SP  - 275
EP  - 286
JA  - Nucl.Med.Biol.
VL  - 24
IS  - 4
N2  - The quantitative uptake kinetics of (2-[18F]fluoropropionyl-(D)phe1)- octreotide (I), a somatostatin (SRIF) receptor-specific tracer, was measured by PET. Conventional organ biodistribution and in vivo stabilities of the tracer as well as in vivo displacement and SRIF receptor blocking were determined. The 18F-fluorinated octreotide was compared with ([67Ga]-DFO-B-succinyl-(D)phe1)-octreotide (II) and ([86Y]-DTPA-(D)phe1)-octreotide (III). Initially, 2-10 MBq of the labeled tracers were injected into male Lewis rats bearing an exocrine pancreatic islet cell tumor. PET measurements were performed dynamically between 0 and 120 min postinjection. Organ distributions were determined 5, 15, 30, 60, and 120 min postinjection. The extent of metabolic degradation was analyzed in serial blood and urine samples as well as in homogenized samples of tumor, liver, and kidney. The uptake of (I) by the tumor was rapid (maximum accumulation at 1-2 min postinjection) and high (about 0.5 +/- 0.2% ID/g), followed by a fast and continuous release with koff = 10 +/- 2. 10(-5) s-1. The tracer was found to remain intact in vivo up to 120 min postinjection. Specific binding of (I) to SRIF receptors in the adrenals, the pancreas, and the pituitary gland was demonstrated in vivo by pretreatment and displacement experiments. Compound (II) also showed a fast uptake by the tumor. Its tumor residence half-life was longer (koff = 3.0 +/- 0.5 . 10(-5) s-1). Compound (II) was also predominantly excreted intact. One hour postinjection, the remaining activity in the blood pool was found to be bound to serum proteins. Early uptake kinetics for compound (III) were also rapid but reached only half the tumor uptake of (II). Compared to (I), the release of 86Y-activity from the tumor was slower (koff = 3.1 +/- 1.3 . 10(-5) s-1). Compared to (II), compound (III) was considerably less stable in vivo. The main critical organs for (II) and (III) are kidneys and bones, whereas (I) is predominantly accumulated in the liver. The in vivo behavior of (I) closely resembles 14C-labeled octreotide. Thus, 18F-labeled octreotide may be of interest in the quantitation and investigation of in vivo properties of somatostatin receptors by PET. However, the short residence of (2- [18F]fluoropropionyl-(D)phe1)-octreotide in tumors and its hepatobiliary excretion may complicate the interpretation of abdominal tumors
ER  - 

TY  - JOUR
T1  - (2-[18F]fluoropropionyl-(D)phe1)-octreotide, a potential radiopharmaceutical for quantitative somatostatin receptor imaging with PET: synthesis, radiolabeling, in vitro validation and biodistribution in mice
A1  - Guhlke,S.
A1  - Wester,H.J.
A1  - Bruns,C.
A1  - Stocklin,G.
Y1  - 1994/08//
N1  - Institut fur Nuklearchemie, Forschungszentrum Julich GmbH, GermanyPMID- 0009234331
SP  - 819
EP  - 825
JA  - Nucl.Med.Biol.
VL  - 21
IS  - 6
N2  - Octreotide is labeled with fluorine-18 as a potential radiopharmaceutical for quantitative in vivo mapping of somatostatin receptors. [18F]-fluoroacylation is achieved with n.c.a. 2- [18F]fluoropropionic acid 4-nitrophenylester which is reacted with epsilon-Boc-Lys5-octreotide. After deprotection the desired N alpha- [18F]fluoropropionylated octreotide ([18F]SDZ 223-228) is obtained. Final HPLC purification gives rise to radiochemical yields of 65 +/- 5% based on the fluoroacylation agent. Binding experiments using rat cortex membranes indicate an affinity for somatostatin receptors of pKi = 8.6 +/- 0.2. The biological activity of this SRIF analog is demonstrated by the inhibition of growth hormone release from cultured pituitary cells. The pIC50 in this test system is 8.75, indicating full biological activity. Biodistribution studies with NMRI mice show predominantly renal excretion, rapid blood clearance and only negligible bone activity, i.e. formation of free fluoride
ER  - 

TY  - JOUR
T1  - Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates
A1  - Subramanian,T.
A1  - Emerich,D.F.
A1  - Bakay,R.A.
A1  - Hoffman,J.M.
A1  - Goodman,M.M.
A1  - Shoup,T.M.
A1  - Miller,G.W.
A1  - Levey,A.I.
A1  - Hubert,G.W.
A1  - Batchelor,S.
A1  - Winn,S.R.
A1  - Saydoff,J.A.
A1  - Watts,R.L.
Y1  - 1997/09//
N1  - Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USAPMID- 0009331498
SP  - 469
EP  - 477
JA  - Cell Transplant.
VL  - 6
IS  - 5
N2  - Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer- encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP- treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer- encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease
ER  - 

TY  - JOUR
T1  - An H(2)(15)O-PET study of cerebral blood flow changes during focal epileptic discharges induced by intracerebral electrical stimulation
A1  - Kahane,P.
A1  - Merlet,I.
A1  - Gregoire,M.C.
A1  - Munari,C.
A1  - Perret,J.
A1  - Maguire,F.
Y1  - 1999/10//
N1  - Department of Neurosciences and INSERM 318 Research Unit, Grenoble Hospital, CERMEP and Functional Neurology and Epilepsy Department, Neurological Hospital, Lyon, FrancePMID- 00105060884099- http://brainoupjournalsorg/cgi/content/full/122/10/18514100- http://brainoupjournalsorg/cgi/content/abstract/122/10/1851
SP  - 1851
EP  - 1865
JF  - Brain
VL  - 122
IS  - Pt 10
N2  - Partial epileptic seizures are known to cause a focal increase in cerebral blood flow (CBF). However, quantified studies of ictal CBF changes under intracranial EEG control are still needed to assess the relationships in time and space between CBF changes and electrical discharges. Ten patients undergoing an intracerebral stereotaxic EEG (stereo-EEG) investigation for epilepsy surgery were prospectively studied for local perfusion changes. These were measured by H(2)(15)O- PET during 12 subclinical or mild symptomatic focal epileptic discharges induced by intracerebral electrical stimulation of the hippocampus (eight), amygdala (two), temporal pole (one) and fusiform gyrus (one). This study aimed to assess whether a significant focal blood flow change reflected the geographical extent of the underlying coincident epileptic discharge, as measured by this method at seizure onset. No significant CBF change was observed on test-retest at rest or during ineffective electrical stimulations outside the epileptogenic area. Compared with the resting condition, a significant focal perfusion increase of 16-55% occurred during eight discharges, there was no CBF change in three and a significant CBF decrease in one. Ictal CBF increases were mostly associated with low-voltage fast activity, but their magnitude had no obvious link with the duration of the discharge (range 8-106 s). Regional analysis of ictal PET was performed in 10 anatomical areas during each of the 12 discharges. Of all the 120 regions, 59 were not explored by intracerebral electrodes and 14 (24%) of these demonstrated ictal CBF changes. In 43 of the 61 regions explored by stereo-EEG (70.5%), PET and depth EEG findings converged, showing either a CBF change in a discharging area or no CBF change in a region unaffected by the discharge. Areas of increased CBF indicated an underlying epileptic discharge in almost 100% of the cases. Conversely, of the 18 regions showing discrepancies between intracerebral recordings and PET data, 17 were discharging regions showing no ictal CBF changes. Thus, a focal CBF increase, when detected at the seizure onset concomitantly with the initial low-voltage fast activity, was a reliable marker of an underlying epileptic discharge. It emphasizes the importance of injecting blood-flow tracers as soon as possible after detection of the discharge in routine clinical studies, even at a subclinical stage of the seizure. However, the extent of significant ictal CBF changes can be more restricted than that of the electrical discharge, thus limiting the reliability of ictal CBF images for outlining the contours of a tailored cortectomy
ER  - 

TY  - JOUR
T1  - Striatal presynaptic monoaminergic vesicles are not increased in Tourette's syndrome
A1  - Meyer,P.
A1  - Bohnen,N.I.
A1  - Minoshima,S.
A1  - Koeppe,R.A.
A1  - Wernette,K.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
A1  - Frey,K.A.
A1  - Albin,R.L.
Y1  - 1999/07/22/
SP  - 371
EP  - 374
JF  - Neurology
VL  - 53
IS  - 2
N2  - BACKGROUND: Abnormal function of striatal dopaminergic synapses is suggested to underlie Tourette's syndrome (TS). OBJECTIVE: To determine dorsal striatal dopaminergic innervation in TS. Prior in vitro and in vivo studies of dopamine reuptake transporter binding sites suggest increased striatal dopaminergic innervation in TS. METHODS: We used in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding to quantify striatal dopaminergic innervation in TS. Eight TS patients (mean age 30+/-9 years) and 22 age-comparable normal controls (age 34+/-8 years) underwent PET imaging with the VMAT2 ligand (+)-alpha-[11C]dihydrotetrabenazine (DTBZ). Compartmental modeling was used to quantify blood-to-brain ligand transport and VMAT2 binding site density from the tissue-to-plasma distribution volume (DV) during continuous (+)-alpha-[11C]DTBZ infusion. DTBZ DV in dorsal striatal regions was expressed relative to the occipital cortex to estimate relative specific VMAT2 binding (binding potential). RESULTS: We found no significant differences in VMAT2 binding potential between patients and controls in the caudate nucleus, anterior putamen, or posterior putamen. There were no significant differences in striatal VMAT2 binding between patients with (n = 5) or without (n = 3) features of obsessive-compulsive disorder. CONCLUSIONS: There is no evidence for increased binding to the VMAT2 in TS striatum and that dorsal striatal dopaminergic innervation density is normal in TS. The previously reported changes in dopamine transporter binding sites may reflect medication effect and/or altered synaptic activity or regulation of dopamine transporter expression in nigrostriatal neurons
AD  - Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, USA
UR  - PM:0010430428
ER  - 

TY  - JOUR
T1  - Imaging central nicotinic acetylcholine receptors in baboons with [18F]fluoro-A-85380
A1  - Valette,H.
A1  - Bottlaender,M.
A1  - Dolle,F.
A1  - Guenther,I.
A1  - Fuseau,C.
A1  - Coulon,C.
A1  - Ottaviani,M.
A1  - Crouzel,C.
Y1  - 1999/08//
N1  - Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, Commissariat a l'Energie Atomique, Orsay, FrancePMID- 0010450691
SP  - 1374
EP  - 1380
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 8
N2  - Central nicotinic acetylcholine receptors (nAChRs) have been implicated in learning-memory processes. Postmortem brain tissue of patients who suffered senile dementia or Parkinson's disease shows low density of nAChRs. In this study, we used PET to evaluate the distribution and kinetics of the fluoro derivative of the high-affinity and alpha4beta2- subtype-selective, nicotinic ligand 3-[2(S)-2- azetidinylmethoxy]pyridine (A-85380) in baboons. METHODS: After intravenous injection of 37 MBq (1 mCi, 1-1.5 nmol) [18F]fluoro-A-85380 into isoflurane-anesthetized baboons, dynamic PET data were acquired for 180 min. Time-activity curves were generated from regions of interest. Displacement experiments (80 min after injection of the radiotracer) were performed using cytisine (1 mg/kg subcutaneously) and unlabeled fluoro-A-85380 (0.1 and 0.3 mg/kg intravenously). Toxicological studies were performed in mice. RESULTS: Brain radioactivity reached a plateau within 40-50 min of injection of the tracer. In the thalamic area, radioactivity remained constant for 180 min, while clearance from the cerebellum was slow (t1/2 = 145-190 min). Cytisine and unlabeled fluoro-A-85380 reduced brain radioactivity at 180 min by 50%-60%, 30%-35% and 20%-35% of control values in the thalamus, cerebellum and frontal cortex, respectively. A slight, transient increase (20 mm Hg) in blood pressure was observed with the highest displacing dose of unlabeled fluoro-A-85380. Lethal dose in mice was found to be 2.2 mg/kg intravenously. CONCLUSION: These results demonstrate the feasibility and the safety of imaging nAChRs in vivo using labeled or unlabeled fluoro-A-85380
ER  - 

TY  - JOUR
T1  - Comparative evaluation of multiresolution optimization strategies for multimodality image registration by maximization of mutual information
A1  - Maes,F.
A1  - Vandermeulen,D.
A1  - Suetens,P.
Y1  - 1999///
SP  - 373
EP  - 368
JF  - Medical Image Analysis
VL  - 3
N2  - Maximization of mutual information of voxel intensities has been demonstrated to be a very powerful criterion for three-dimensional
ER  - 

TY  - JOUR
T1  - Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset
A1  - Baumgartner,C.
A1  - Serles,W.
A1  - Leutmezer,F.
A1  - Pataraia,E.
A1  - Aull,S.
A1  - Czech,T.
A1  - Pietrzyk,U.
A1  - Relic,A.
A1  - Podreka,I.
Y1  - 1998/06//
N1  - Universitatsklinik fur Neurologie, Vienna, AustriaPMID- 0009627329
SP  - 978
EP  - 982
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 6
N2  - Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m- hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state
ER  - 

TY  - JOUR
T1  - Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy
A1  - Shinotoh,H.
A1  - Namba,H.
A1  - Yamaguchi,M.
A1  - Fukushi,K.
A1  - Nagatsuka,S.
A1  - Iyo,M.
A1  - Asahina,M.
A1  - Hattori,T.
A1  - Tanada,S.
A1  - Irie,T.
Y1  - 1999/07//
N1  - Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, JapanPMID- 0010401781
SP  - 62
EP  - 69
JA  - Ann.Neurol.
VL  - 46
IS  - 1
N2  - We measured brain acetylcholinesterase activity in 16 patients with Parkinson's disease (PD), 12 patients with progressive supranuclear palsy (PSP), and 13 age-matched controls, using N-methyl-4- [11C]piperidyl acetate and positron emission tomography. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. In PD patients, there was a significant reduction (-17%) of cerebral cortical k3 compared with normal controls, whereas there was only a nonsignificant reduction (-10%) of cortical k3 in PSP patients. However, there was a prominent reduction (-38%) of thalamic k3 in PSP patients compared with normal controls, whereas there was only a nonsignificant reduction (-13%) of thalamic k3 in PD patients. The results suggest that there is a loss of cholinergic innervation to the cerebral cortex in association with cholinergic innervation to the thalamus in PD, whereas there is a preferential loss of cholinergic innervation to the thalamus in PSP. When the thalamic to cerebral cortical k3 ratio was taken for each subject, PD and PSP were separated, suggesting that positron emission tomography measurement of acetylcholinesterase activity may be useful for differentiating the two similar disorders
ER  - 

TY  - JOUR
T1  - A comparison of 11C-labeled L-DOPA and L-fluorodopa as positron emission tomography tracers for the presynaptic dopaminergic system [In Process Citation]
A1  - Torstenson,R.
A1  - Tedroff,J.
A1  - Hartvig,P.
A1  - Fasth,K.J.
A1  - Langstrom,B.
Y1  - 1999/10//
N1  - The Subfemtomole Biorecognition Project, Uppsala University and Japanese Research and Development Council, Sweden
SP  - 1142
EP  - 1149
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 10
N2  - 11C-labeled 3,4-Dihydroxy-phenyl-L-alanine (L-DOPA) and L-fluorodopa were used as tracers for the functional state of the presynaptic dopamine system in anesthetized monkeys with positron emission tomography. The radiotracer disposition in brain tissue and plasma were studied and effects induced by pharmacologic challenges were evaluated. 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) increased the striatal influx rate constant, e.g., striatal K(i) for L-[beta- 11C]DOPA, but it induced no effect on the K(i)-value using L-[beta-11C]- 6-fluorodopa. Studies of radiolabeled tracer and metabolites in plasma showed substantial differences between the two tracers. At baseline conditions, 60% unchanged L-[beta-11C]DOPA was detected in plasma 50 minutes after tracer injection and the 3-O-methylated fraction accounted for 25% of total radioactivity. For L-[beta-11C]-6- fluorodopa, the relation was inverse; about 25% unchanged tracer and 60% 3-O-methyl metabolite were present in plasma after 50 minutes. A site-specific 11C-labeling in the carboxylic position in the molecules revealed a significant specific retention of radioactivity in striatum with L-[car-boxy-11C]-6-fluorodopa but not with L-[carboxy-11C]DOPA. The 3-O-methyl metabolite of L-DOPA is known to pass the blood-brain barrier and may interfere with the calculation of the K(i)value using a brain reference region. Thus, extensive 3-O-methylation in circulation of the fluorinated analog could obscure the detectability of potential functional change in striatal K(i) of the tracer when using a reference tissue model for calculation
ER  - 

TY  - JOUR
T1  - Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study
A1  - McAllister,T.W.
A1  - Saykin,A.J.
A1  - Flashman,L.A.
A1  - Sparling,M.B.
A1  - Johnson,S.C.
A1  - Guerin,S.J.
A1  - Mamourian,A.C.
A1  - Weaver,J.B.
A1  - Yanofsky,N.
Y1  - 1999/10/12/
N1  - Department of Psychiatry, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA thomaswmcallister@dartmouthedu
SP  - 1300
EP  - 1308
JF  - Neurology
VL  - 53
IS  - 6
N2  - OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI
ER  - 

TY  - JOUR
T1  - A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS
A1  - Blinkenberg,M.
A1  - Jensen,C.V.
A1  - Holm,S.
A1  - Paulson,O.B.
A1  - Sorensen,P.S.
Y1  - 1999/07/13/
N1  - MS Research Unit, Rigshospitalet, Copenhagen University Hospital, Denmark blink@petrhdkPMID- 0010408551
SP  - 149
EP  - 153
JF  - Neurology
VL  - 53
IS  - 1
N2  - OBJECTIVE: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. BACKGROUND: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function. METHODS: The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18- fluorodeoxyglucose (FDG). RESULTS: The global cortical CMRglc decreased with time (p<0.001) and the most pronounced reductions of CMRglc were detected in frontal and parietal cortical areas. There was a statistically significant increase of disability (p<0.01) and TLA (p<0.05) measurements during the study, but changes in CMRglc were not correlated to changes in TLA and EDSS. CONCLUSIONS: Global cortical cerebral metabolism in MS is decreased significantly during a 2-year observation period, suggesting a deterioration of cortical activity with disease progression. The time-related changes of cortical CMRglc are statistically stronger than changes in TLA measurements and neurologic disability, and might be a useful secondary measure of treatment efficacy
ER  - 

TY  - JOUR
T1  - Depressive illness, depressive symptomatology and regional cerebral blood flow in elderly people with sub-clinical cognitive impairment
A1  - Ritchie,K.
A1  - Gilham,C.
A1  - Ledesert,B.
A1  - Touchon,J.
A1  - Kotzki,P.O.
Y1  - 1999/07//
N1  - Institut National de la Sante et de la Recherche Medicale, CJF 97-2 Epidemiology of Neurodegenerative Pathologies of the CNS, Montpellier, FrancePMID- 0010459793
SP  - 385
EP  - 391
JF  - Age and Ageing
JA  - Age Ageing
VL  - 28
IS  - 4
N2  - BACKGROUND: Depressive illness in dementia is often assumed to be a unitary clinical phenomenon. AIM: To describe changes in patterns of depressive symptomatology with time, and associated changes in cerebral blood flow to the frontal and temporal regions. METHOD AND RESULTS: 397 elderly people with sub-clinical cognitive dysfunction were observed over 3 years. Sixteen percent of them developed dementia during the study The prevalence of depressive symptomatology was higher in this group than in the general population, especially in women, who also had higher recovery rates. A changing profile of depressive symptoms was found in depressed elderly people progressing to dementia, with fewer affective symptoms and increases in agitation and motor slowing. These changes were paralleled by greater reductions in left temporal regional cerebral blood flow than in non-depressed subjects with Alzheimer's disease. CONCLUSION: In dementia, there may be two separate and interacting depressive syndromes whose differentiation may be clinically important
ER  - 

TY  - JOUR
T1  - Depression, cerebral atrophy, cognitive performance and incidence of dementia. Population study of 85-year-olds
A1  - Palsson,S.
A1  - Aevarsson,O.
A1  - Skoog,I.
Y1  - 1999/03//
N1  - Department of Psychiatry, Sahlgrenska University Hospital, Goteborg, Sweden sigpp@rspisPMID- 0010448451
SP  - 249
EP  - 253
JA  - Br.J.Psychiatry
VL  - 174
N2  - BACKGROUND: Hospital-based studies suggest that depression in old age relates to organic brain changes. AIMS: To determine whether these findings are confirmed in a population-based sample. METHOD: A population sample of non-demented 85-year-olds (227 mentally healthy and 62 with DSM-III-R depression were given a neuropsychiatric examination and computerised tomographic scans of the brain, and followed for three years. RESULTS: On the Mini-Mental State Examination, those with a low educational level with major depression performed worse than the mentally healthy; this distinction was not evident among those who had received higher education. Measures of brain atrophy were similar in depressed and mentally healthy individuals. The three-year incidence of dementia was increased in those with early-onset major depression. CONCLUSIONS: Higher education may protect against cognitive symptoms in depressed individuals. The association between depression and cerebral atrophy in the elderly is not very strong. The higher incidence of dementia in those with early- onset major depression may be due to a longer lifetime duration of depression, emphasising the importance of detecting and treating depression in the community
ER  - 

TY  - JOUR
T1  - Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study
A1  - Bremner,J.D.
A1  - Staib,L.H.
A1  - Kaloupek,D.
A1  - Southwick,S.M.
A1  - Soufer,R.
A1  - Charney,D.S.
Y1  - 1999/04/01/
N1  - Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USAPMID- 0010202567
SP  - 806
EP  - 816
JA  - Biol.Psychiatry
VL  - 45
IS  - 7
N2  - BACKGROUND: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. METHODS: Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat- related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. RESULTS: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non- PTSD subjects in these areas. CONCLUSIONS: The findings suggest that functional alternations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD
ER  - 

TY  - JOUR
T1  - Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: alternatives for analysis of an irreversible positron emission tomography trace for measurement of acetylcholinesterase activity in human brain
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Snyder,S.E.
A1  - Meyer,P.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
Y1  - 1999/10//
N1  - Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA
SP  - 1150
EP  - 1163
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 10
N2  - N-[11C]Methylpiperidin-4-yl propionate ([11C]PMP) is a substrate for hydrolysis by acetylcholinesterase (AChE). This work evaluates kinetic analysis alternatives for estimation of relative AChE activity using dynamic positron emission tomography (PET) studies of [11C]PMP. The PET studies were performed on three groups of subjects: (1) 12 normal volunteer subjects, aged 20 to 45 years, who received a single intravenous injection of 16 to 32 mCi of [11C]PMP; (2) six subjects, aged 21 to 44 years, who received two 16-mCi injections of [11C]PMP (baseline and visual stimulation, respectively); and (3) five subjects, aged 24 to 40 years, who received two 16-mCi injections separated by 200 minutes (baseline and after a 1-hour constant infusion of 1.5 mg of physostigmine, respectively). Dynamic acquisition consisted of a 17- frame sequence over 80 minutes. All analysis methods were based on a first-order kinetic model consisting of two tissue compartments with the parameter k3, representing PMP hydrolysis, being the index of AChE activity. Four different schemes were used to estimate k3: (1) an unconstrained non-linear least-squares fit estimating blood-brain barrier transport parameters, K1 and k2, in addition to the hydrolysis rate constant k3; (2) and (3), two methods of constraining the fit by fixing the volume of distribution of free tracer (DVfree); and (4), a direct estimation of k3 without use of an arterial input function based on the shape of the tissue time-activity curve alone. Results showed that k3 values from the unconstrained fitting and no input methods were estimated with similar accuracy, whereas the two methods using DVfree constraints yielded similar results. The authors conclude that the optimal analysis method for [11C]PMP differs as a function of AChE activity. All four methods gave precise measures of k3 in regions with low AChE activity (approximately 10% coefficient of variation in cortex), but surprisingly, with unconstrained methods yielding estimates with lower variability than constrained methods. In regions with moderate to high AChE activity, constrained methods were required to yield meaningful estimates and were superior to the unconstrained methods
ER  - 

TY  - JOUR
T1  - Discrepancy between regional cerebral blood flow and glucose metabolism of the brain in systemic lupus erythematosus patients with normal brain magnetic resonance imaging findings
A1  - Kao,C.H.
A1  - Ho,Y.J.
A1  - Lan,J.L.
A1  - Changlai,S.P.
A1  - Liao,K.K.
A1  - Chieng,P.U.
Y1  - 1999/01//
N1  - Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan, Republic of ChinaPMID- 0009920015
SP  - 61
EP  - 68
JA  - Arthritis Rheum.
VL  - 42
IS  - 1
N2  - OBJECTIVE: In this study, 2 updated brain-imaging modalities, technetium-99m hexamethylpropylene amine oxime-single-photon-emission computed tomography (HMPAO-SPECT) and fluorine-18 2-fluoro-2-deoxy-D- glucose-positron emission tomography (FDG-PET), were used to simultaneously detect regional cerebral blood flow (rCBF) and glucose metabolism of the brain in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-five female SLE patients, ages 25-40 years, were enrolled in this study and assigned to 1 of 2 groups. Group 1 consisted of 13 patients with neuropsychiatric manifestations (7 had major and 6 had minor manifestations). Group 2 consisted of 12 patients without neuropsychiatric manifestations. Serum levels of anticardiolipin antibodies (aCL) and anti-ribosomal P antibodies (anti-P) were measured. All patients had normal brain magnetic resonance imaging (MRI) findings. Ten healthy female volunteers also underwent brain MRI, HMPAO-SPECT, and FDG-PET for comparison. RESULTS: 99mTc-HMPAO-SPECT revealed hypoperfusion lesions in 11 (44%) of 25 SLE patients, including 9 (69%) of the 13 patients in group 1, 7 (100%) of the 7 patients with major manifestations, 2 (33%) of the 6 patients with minor manifestations, and 2 (17%) of the 12 patients in group 2. Parietal lobes were the areas most commonly involved. FDG-PET revealed hypometabolism in 7 (54%) of the group 1 patients, 6 (86%) of the 7 patients with major manifestations, and 1 (17%) of the 6 patients with minor manifestations. Temporal lobes were the most commonly involved areas. However, no significant hypometabolism brain lesions were found in group 2 patients. All of the 4 patients with headaches and dizziness or headaches alone had normal findings on HMPAO-SPECT and FDG-PET. Nine (36%) of the 25 patients were positive for aCL. However, the presence of aCL was not related to neuropsychiatric manifestations or to HMPAO- SPECT or FDG-PET findings. Five (20%) of the 25 patients had anti-P antibodies and psychosis/depression. CONCLUSION: In patients with normal brain MRI findings, decreases in glucose metabolism coupled with decreases in rCBF are associated with serious neuropsychiatric SLE (NPSLE) presentations, while normal glucose metabolism with decreases in rCBF may be found in SLE patients with or without NPSLE
ER  - 

TY  - JOUR
T1  - Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study
A1  - Ouchi,Y.
A1  - Kanno,T.
A1  - Okada,H.
A1  - Yoshikawa,E.
A1  - Futatsubashi,M.
A1  - Nobezawa,S.
A1  - Torizuka,T.
A1  - Sakamoto,M.
Y1  - 1999/11//
N1  - Positron Medical Center and Department of Neurology, Hamamatsu Medical Center, Hirakuchi, Japan
SP  - 723
EP  - 731
JA  - Ann.Neurol.
VL  - 46
IS  - 5
N2  - To investigate changes in the relation between presynaptic and postsynaptic dopaminergic functions in vivo in both nigrostriatal and mesocortical systems in Parkinson's disease (PD), 10 drug-naive early PD patients were studied twice using positron emission tomography with [11C]CFT (dopamine transporter probe) followed by [11C]SCH 23390 (D1 receptor probe). Regional binding potentials (k3/k4) of [11C]CFT and [11C]SCH 23390 in the striatum (nigrostriatal system) and the orbitofrontal cortex (mesocortical system) were estimated by compartment analyses. Levels of [11C]CFT k3/k4 in the two projection areas were shown to be significantly lower in PD, whereas [11C]SCH 23390 levels remained unchanged. Regression analysis showed that estimates of CFT k3/k4 were positively correlated with those of SCH 23390 k3/k4 in the striatum in normal control, whereas the two binding estimates were less positively correlated in the caudate and inversely correlated in the putamen in PD. No significant correlation was observed in the orbitofrontal cortex in both groups. These results indicated that dopamine transporters and D1 receptors change in parallel in the normal striatal synapses, but the association becomes asymmetrical because of reduction in presynaptic and relative elevation in postsynaptic markers in PD. Alterations in synaptic parallel regulation in the nigrostriatal system might reflect early pathophysiology in the parkinsonian brain
ER  - 

TY  - JOUR
T1  - Statistical limitations in functional neuroimaging. II. Signal detection and statistical inference
A1  - Petersson,K.M.
A1  - Nichols,T.E.
A1  - Poline,J.B.
A1  - Holmes,A.P.
Y1  - 1999/07/29/
N1  - Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden karlmp@neuroksse
SP  - 1261
EP  - 1281
JA  - Philos.Trans.R.Soc.Lond B Biol.Sci.
VL  - 354
IS  - 1387
N2  - The field of functional neuroimaging (FNI) methodology has developed into a mature but evolving area of knowledge and its applications have been extensive. A general problem in the analysis of FNI data is finding a signal embedded in noise. This is sometimes called signal detection. Signal detection theory focuses in general on issues relating to the optimization of conditions for separating the signal from noise. When methods from probability theory and mathematical statistics are directly applied in this procedure it is also called statistical inference. In this paper we briefly discuss some aspects of signal detection theory relevant to FNI and, in addition, some common approaches to statistical inference used in FNI. Low-pass filtering in relation to functional-anatomical variability and some effects of filtering on signal detection of interest to FNI are discussed. Also, some general aspects of hypothesis testing and statistical inference are discussed. This includes the need for characterizing the signal in data when the null hypothesis is rejected, the problem of multiple comparisons that is central to FNI data analysis, omnibus tests and some issues related to statistical power in the context of FNI. In turn, random field, scale space, non-parametric and Monte Carlo approaches are reviewed, representing the most common approaches to statistical inference used in FNI. Complementary to these issues an overview and discussion of non-inferential descriptive methods, common statistical models and the problem of model selection is given in a companion paper. In general, model selection is an important prelude to subsequent statistical inference. The emphasis in both papers is on the assumptions and inherent limitations of the methods presented. Most of the methods described here generally serve their purposes well when the inherent assumptions and limitations are taken into account. Significant differences in results between different methods are most apparent in extreme parameter ranges, for example at low effective degrees of freedom or at small spatial autocorrelation. In such situations or in situations when assumptions and approximations are seriously violated it is of central importance to choose the most suitable method in order to obtain valid results
ER  - 

TY  - JOUR
T1  - Statistical limitations in functional neuroimaging. I. Non-inferential methods and statistical models
A1  - Petersson,K.M.
A1  - Nichols,T.E.
A1  - Poline,J.B.
A1  - Holmes,A.P.
Y1  - 1999/07/29/
N1  - Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden karlmp@neuroksse
SP  - 1239
EP  - 1260
JA  - Philos.Trans.R.Soc.Lond B Biol.Sci.
VL  - 354
IS  - 1387
N2  - Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference
ER  - 

TY  - JOUR
T1  - Correlation between rCBF and speech perception in cochlear implant users
A1  - Fujiki,N.
A1  - Naito,Y.
A1  - Hirano,S.
A1  - Kojima,H.
A1  - Shiomi,Y.
A1  - Nishizawa,S.
A1  - Konishi,J.
A1  - Honjo,I.
Y1  - 1999/07//
N1  - Department of Hearing and Speech Science, Kyoto University Graduate School of Medicine, Japan fujiki@entkuhpkyoto-uacjpPMID- 0010419029
SP  - 229
EP  - 236
JA  - Auris Nasus Larynx
VL  - 26
IS  - 3
N2  - OBJECTIVE: Although cochlear implants (CIs) have provided the opportunity for bilaterally deaf individuals to recover their hearing abilities, the speech perception performances of the CI users varies considerably. To elucidate the cortical mechanisms of processing speech signals coded by CIs, we evaluated the correlation between the brain activity during speech activation and speech perception in CI users by PET. METHODS: Fourteen postlingually deaf CI users were examined. CI used in the patients was a 22-channel system and its speech-coding strategy was the Nucleus spectral peak (SPEAK) strategy. To evaluate the speech perception performances, we examined vowel perception, consonant perception and speech tracking performances in the Japanese language. Regional cerebral blood flow (rCBF) was measured during no sound stimulation and speech sound stimulation. PET data of the silent condition was subtracted from that of speech stimulation to determine changes in rCBF. In the search for changes in rCBF in the areas for auditory processing, three regions of interest (ROI) were selected; primary auditory area, auditory association area and Broca's area. The correlation between the rCBF changes in the ROIs and the speech perception performances was analyzed using Pearson's correlation coefficient. RESULTS: The patient's speech perception performances ranged widely. Although there were no significant correlations between the speech perception and the rCBF increases in the primary auditory area and Broca's area, there were positive correlations in the auditory association area. In the left auditory association area, the correlation coefficient of the vowel perception performance was 0.546 (P <0.05) and that of the speech-tracking test was 0.657 (P < 0.05). Regarding the consonant perception performance, the correlation coefficient was 0.743 (P < 0.01). There was a positive correlation only between the consonant perception performance and the rCBF increase (R = 0.576, P < 0.05) in the right auditory association area. These correlations are stronger in the left hemisphere than in the right hemisphere. CONCLUSIONS: It is suggested that the improvement of the auditory processing of speech in CI users with SPEAK strategy is accompanied by the recruitment of more neurons in the auditory association areas. The adult auditory cortices may still have plasticity or
ER  - 

TY  - JOUR
T1  - Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction
A1  - Ruottinen,H.M.
A1  - Rinne,J.O.
A1  - Oikonen,V.J.
A1  - Bergman,J.R.
A1  - Haaparanta,M.T.
A1  - Solin,O.H.
A1  - Ruotsalainen,U.H.
A1  - Rinne,U.K.
Y1  - 1997/12//
N1  - Department of Neurology, University of Turku, Finland hannaruottinen@utufiPMID- 0009372556
SP  - 336
EP  - 346
JF  - Synapse
VL  - 27
IS  - 4
N2  - The aim was to investigate the effects of inhibition of monoamine oxidase type B (MAO-B) with selegiline alone and the combined inhibition of peripheral catechol-O-methyltransferase (COMT) with entacapone and MAO-B with selegiline on striatal 6-[18F]fluorodopa (FDOPA) accumulation, and whether the effect of entacapone + selegiline on FDOPA uptake differed depending on the severity of the presynaptic dopaminergic dysfunction. Thus, eight healthy controls, eight de novo patients with Parkinson's disease (PD), and 18 levodopa-treated PD patients were investigated with positron emission tomography (PET). Half of the subjects in each population belonged to the selegiline group and half to the entacapone + selegiline group. Both groups were studied twice with PET using FDOPA. After the first (baseline) FDOPA PET investigation, both groups were on 2 weeks of selegiline treatment, 10 mg daily. Thereafter, the second FDOPA PET was performed for all subjects with a premedication administered 60 min before the PET imaging; one group received 10 mg of selegiline, and the other group received a single 400 mg dose of entacapone coadministered with 10 mg of selegiline. Selegiline treatment alone had no significant influence on striatal FDOPA metabolism. The FDOPA accumulation, expressed as striatal-to-occipital ratios and modified decarboxylation coefficients (k3R0), increased significantly after entacapone + selegiline administration in all subject populations. The FDOPA uptake rate constant (Ki) remained virtually unchanged in controls and in de novo patients but decreased significantly in levodopa-treated PD patients after entacapone + selegiline intake. Entacapone + selegiline administration did not influence significantly the unidirectional blood- to-brain clearance for FDOPA (K1D) or the relative dopadecarboxylase activity (k3D). The changes in the studied parameters after entacapone + selegiline administration probably reflect the effects of entacapone, since entacapone alone has caused similar changes in previous PET studies. Response in FDOPA accumulation to entacapone + selegiline was higher in controls and de novo patients compared with levodopa-treated PD patients. The milder response in levodopa-treated patients might reflect the reduced ability of the degenerated dopaminergic neurons to utilize the prolonged FDOPA availability, produced by entacapone
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in type I alpha-N-acetylgalactosaminidase deficiency: an infantile neuroaxonal dystrophy
A1  - Rudolf,J.
A1  - Grond,M.
A1  - Schindler,D.
A1  - Heiss,W.D.
A1  - Desnick,R.J.
Y1  - 1999/08//
N1  - Max Planck Institute for Neurologic Research, Cologne, GermanyPMID- 0010456768
SP  - 543
EP  - 547
JA  - J.Child Neurol.
VL  - 14
IS  - 8
N2  - Cerebral glucose metabolism was investigated in a 4.8-year-old boy with alpha-N-acetylgalactosaminidase deficiency using 2-[18F]fluoro-2-deoxy- D-glucose and positron emission tomography (PET). In comparison to normal values for age, the overall cerebral glucose metabolism was reduced and the regional cerebral glucose metabolism was decreased in proportion to the degree of atrophy. In the supratentorial cortical regions, the hypometabolism was asymmetric. However, the level of regional cerebral glucose metabolism in all cortical regions excluded a persistent vegetative state. In the lentiform nucleus and the head of the caudate, comparatively increased regional cerebral glucose metabolism was documented, similar to findings in neurodegenerative disorders with active epilepsy. In contrast, the infratentorial structures (cerebellar hemispheres, brain stem, mesencephalon, and hypothalamus), which are predominantly affected by the atrophic process, showed distinct and symmetric hypometabolism. Thus, the 2- [18F]-fluoro-2-deoxy-D-glucose PET scans provided additional insight into and correlation of the functional and structural disturbances in type I alpha-N-acetylgalactosaminidase deficiency, in addition to documenting the hypometabolism due to brain atrophy
ER  - 

TY  - JOUR
T1  - Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Pappas,N.R.
A1  - Wong,C.T.
A1  - Hitzemann,R.J.
A1  - Netusil,N.
Y1  - 1999/08//
N1  - Eng
SP  - 1285
EP  - 1291
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 8
N2  - The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. METHODS: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. RESULTS: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DVstr) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77+/-0.44; E2: 2.97+/-0.44). MP administration did not change K1, but it significantly decreased DVstr (E1: -25.9%+/-8.7%, P < or = 0.0002; E2: -20.7%+/- 11.7%, P < or = 0.007) and Bmax/Kd (E1: -18.4%+/-8.7%, P < or = 0.002; E2: -13.4%+/-9.2%, P < or = 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate (E1: +64%+/-43%, P < or = 0.002; E2: +69%+/-33%, P < or = 0.001), systolic pressure (E1: +37%+/-19%, P < or = 0.0006; E2: +29%+/-15%, P < or = 0.0009), self reports for drug effects (0: nothing to 10: extreme) of "rush" (E1: +8+/-3, P < or = 0.0004; E2: +6+/-4, P < or = 0.01) and "high" (E1: +8+/-3, P < or = 0.0001, E2: +8+/-3, P < or = 0.0003), anxiety (E1: +5+/-4, P < or = 0.02; E2: +4+/-4, P = 0.1) and restlessness (E1: +4+/-4, P < or = 0.04; E2: +4+/-5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. CONCLUSION: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. PMID- 0010450679
ER  - 

TY  - JOUR
T1  - Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Fischman,M.
A1  - Foltin,R.
A1  - Abumrad,N.N.
A1  - Gatley,S.J.
A1  - Logan,J.
A1  - Wong,C.
A1  - Gifford,A.
A1  - Ding,Y.S.
A1  - Hitzemann,R.
A1  - Pappas,N.
Y1  - 1999///
N1  - Eng
SP  - L7
EP  - 12
JA  - Life Sci.
VL  - 65
IS  - 1
N2  - The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability we compared the levels of DAT occupancies that we had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [11C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd +1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose- dependent blockade of DAT with an estimated ED50 (dose required to block 50% of the DAT) for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine. The similar in vivo potencies at the DAT for methylphenidate than for cocaine are in agreement with their reported relative in vitro affinities (Ki 390 nM and 640 nM respectively), which is likely to reflect the similar degree of uptake (8-10% of the injected dose) and regional distribution of these two drugs in the human brain. Thus, differences in the in vivo potency of these two drugs at the DAT cannot be responsible for the differences in their rate of abuse in humans. Other variables i.e. longer duration of methylphenidate's side effects may counterbalance its reinforcing effects
AD  - Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov PMID- 0010403500
ER  - 

TY  - JOUR
T1  - Regional brain metabolic activation during craving elicited by recall of previous drug experiences
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Cervany,P.
A1  - Hitzemann,R.J.
A1  - Pappas,N.R.
A1  - Wong,C.T.
A1  - Felder,C.
Y1  - 1999///
N1  - Eng
SP  - 775
EP  - 784
JA  - Life Sci.
VL  - 64
IS  - 9
N2  - Cocaine cues elicit craving and physiological responses. The cerebral circuits involved in these are poorly understood. The purpose of this study was to assess the relation between regional brain activation and cocaine cue elicited responses. Thirteen right-handed cocaine abusers were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice; during an interactive interview about neutral themes and during an interactive interview about cocaine themes designed to elicit cocaine craving. In parallel the behavioral (rated from 0: felt nothing to 10: felt extreme) and cardiovascular responses were recorded. During the cocaine theme interview subjects reported higher self reports for cocaine craving (+2.5+/-3.3, p < or = 0.02) and had higher heart rates (+4.7+/-7.2%, p < or = 0.001), systolic (+4+/- 4%, p < or = 0.0001), and diastolic blood pressures (+2.6+/-3.8%, p < or = 0.003) than during the neutral interview. Absolute and relative metabolic values in the orbitofrontal (+16.4+/-17.1%, p < or = 0.005; +11.3+/-14.3%, p < or = 0.008) and left insular cortex (+21.6+/-19.6%, p < or = 0.002; +16.7+/-19.7%, p < or = 0.01) and relative values in cerebellum (+17.9+/-14.8%, p < or = 0.0008) were higher during the cocaine theme than during the neutral theme interview. Relative metabolic values in the right insular region (p < or = 0.0008) were significantly correlated with self reports of cocaine craving. Activation of the temporal insula, a brain region involved with autonomic control, and of the orbitofrontal cortex, a brain region involved with expectancy and reinforcing salience of stimuli, during the cocaine theme support their involvement with craving in cocaine addicted subjects
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gjwang@bnl.gov PMID- 0010075110
ER  - 

TY  - JOUR
T1  - Distribution of tracer levels of cocaine in the human brain as assessed with averaged [11C]cocaine images
A1  - Telang,F.W.
A1  - Volkow,N.D.
A1  - Levy,A.
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Felder,C.
A1  - Wong,C.
A1  - Wang,G.J.
Y1  - 1999/03/15/
N1  - Eng
SP  - 290
EP  - 296
JF  - Synapse
VL  - 31
IS  - 4
N2  - The Ability of cocaine to block the dopamine transporter (DAT) in the nucleus accumbens, as well as its non-striatal and non-DAT actions, appears to be crucial for its reinforcing/rewardig effects. However, we have been unable to use PET and [11C]cocaine to map small regions with greater sensitivity due in part to the low specific to non-specific binding ration of [11C]cocaine. In order to increase the signal to noise ratio of the individual [11]cocaine images, we averaged the distribution volume (DV) PET images of 17 normal controls. In addition we also obtained averaged images for the dynamic set (14 time frames) and for the K1 values. The dynamic images were used to generate the average time activity curves from which we obtained the time required to half maximum clearance (T50). Twenty-nine ROIs were identified in the Talarach-Tournoux atlas and were then projected to the corregistered average PET image. The brain regions clustered in 3 groups according to their DV values. The highest activity (Group DV.1, 4.6-3.7) included putamen > accumbens > caudate. Intermediate DVs (Group DV.2, 3.2-2.8) included thalamus (mediodorsal and ventrolateral nucleus) > precuneus and posterior cingulate gyrus > amygdala, hippocampus, and temporal pole. Group DV.3 with low DVs (2.6-2.1) included the orbital cortex, precentral gyrus, and cerebellum. The brain regions clustered in 3 groups according to their T50 values. Regions with the faster clearance rates (15-20 minutes) included the orbital cortex, posterior cingulate, dorsomedial thalamus, precuneus, and cerebellum. Intermediate clearance rates (20-25 minutes) included caudate, putamen and accumbens regions with the slowest clearance rates (25-30 minuters) included caudate, putamen, and accumbens. In addition to the previously documented high binding of cocaine in striatum and moderate binding in thalamus in the living human brain this study also documents binding of cocaine in limbic and paralimbic brain regions. Further work is required to characterize the binding properties of cocaine in these brain areas and to elucidate their role in the reinforcing and addictive properties of cocaine
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. ftelang@bnl.gov PMID- 0010051110
ER  - 

TY  - JOUR
T1  - Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Gatley,S.J.
A1  - Dewey,S.L.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Franceschi,D.
A1  - Gifford,A.
A1  - Morgan,A.
A1  - Pappas,N.
A1  - King,P.
Y1  - 1999/01//
N1  - Eng
SP  - 59
EP  - 66
JF  - Synapse
VL  - 31
IS  - 1
N2  - Though the blockade of dopamine transporters (DAT) is associated with cocaine's and methylphenidate's reinforcing effects, it is the stimulation of dopamine (DA) receptors, achieved by increases in synaptic DA, that enables these effects to occur. Positron emission tomography (PET) and [11C]raclopride were used to assess the levels of occupancy of DA D2 receptors by dopamine achieved by doses of cocaine or methylphenidate previously documented to block over 70% of DAT. Studies were performed in five baboons using a paired scan protocol designed to measure DA D2 receptor availability (Bmax/Kd) at baseline conditions and after intravenous administration of either cocaine or methylphenidate. Cocaine (1-2 mg/kg) or methylphenidate (0.5 mg/kg) administered 5 min prior to [11C]raclopride decreased Bmax/Kd by 29+/- 3% and 32 + 4%, respectively. Smaller reductions in Bmax/Kd (13% for cocaine given 30 min before [11C]raclopride and 25+/-10% for methylphenidate given 40 min before [11C]raclopride) were seen with longer periods between drug and radioligand. These observations are consistent with the slower striatal clearance kinetics of [11C]methylphenidate than [1C]cocaine observed in previous PET experiments and with the approximately twofold higher potency of methylphenidate than cocaine in in vitro experiments. Though the elevation of synaptic DA induced by >70% occupancy of DAT by these drugs lead to a modest increase in occupancy of D2 receptors (25-30%), further studies are required to assess if this is an underestimation because of differences in D2 receptor binding kinetics between raclopride and DA
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov PMID- 0010025684
ER  - 

TY  - JOUR
T1  - Oxygen consumption of cerebral cortex fails to increase during continued vibrotactile stimulation
A1  - Fujita,H.
A1  - Kuwabara,H.
A1  - Reutens,D.C.
A1  - Gjedde,A.
Y1  - 1999/03//
N1  - Eng
SP  - 266
EP  - 271
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 3
N2  - The coupling of oxidative metabolism to the blood flow of the sensory motor hand area is uncertain. The authors tested the hypothesis that continued vibrotactile stimulation ultimately must lead to increased oxygen consumption consumption. Twenty-two healthy right-handed young volunteers underwent positron emission tomography (PET) with the [(15)O]water bolus injection method to measure water clearance (K1H2O an index of blood flow (CBF), and with the [(15)O]oxygen bolus inhalation method to measure CMR(O2). The CMR(O2) was measured 30 seconds and 20 minutes after onset of intermittent (1 second on, 1 second off) vibrotactile stimulation (110 Hz) and compared with baseline measurements without stimulation. The K1H2O and CMR(O2) changes (delta K1H2O and delta CMR(O2)) were determined using intersubject averaging, together with magnetic resonance imaging based stereotaxic registration technique. The K1H2O increase was 21 +/- 4% and 12 +/- 4% at 30 seconds and 20 minutes after onset of stimulation, respectively. No significant increase of CMR(O2) was found until 30 minutes after the onset of stimulation. The authors conclude that blood flow and oxidative metabolism undergo uncoupling during sustained phasic stimulation of the sensory hand area. Therefore, neuronal activity stimulated in this manner does not rely on significantly increased oxidative phosphorylation
AD  - McConnell Brain Imaging Center, Montreal Neurological Institute, Canada. PMID- 0010078878
ER  - 

TY  - JOUR
T1  - Limbic activation during cue-induced cocaine craving
A1  - Childress,A.R.
A1  - Mozley,P.D.
A1  - McElgin,W.
A1  - Fitzgerald,J.
A1  - Reivich,M.
A1  - O'Brien,C.P.
Y1  - 1999/01//
N1  - Eng
SP  - 11
EP  - 18
JA  - Am.J.Psychiatry
VL  - 156
IS  - 1
N2  - OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug- related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards
AD  - Addiction Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. childress@research.trc.upenn.edu PMID- 0009892292
ER  - 

TY  - JOUR
T1  - Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography
A1  - Duncan,G.H.
A1  - Kupers,R.C.
A1  - Marchand,S.
A1  - Villemure,J.G.
A1  - Gybels,J.M.
A1  - Bushnell,M.C.
Y1  - 1998/12//
N1  - Eng
SP  - 3326
EP  - 3330
JA  - J.Neurophysiol.
VL  - 80
IS  - 6
N2  - Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information
AD  - Departement de stomatologie, Faculte de medecine dentaire, Universite de Montreal, Quebec, Canada, H3C 3J7. PMID- 0009862926
ER  - 

TY  - JOUR
T1  - A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy
A1  - Petrovic,P.
A1  - Ingvar,M.
A1  - Stone-Elander,S.
A1  - Petersson,K.M.
A1  - Hansson,P.
Y1  - 1999/12/01/
N1  - ENG
SP  - 459
EP  - 470
JF  - Pain
VL  - 83
IS  - 3
N2  - The objective of this study was to investigate the central processing of dynamic mechanical allodynia in patients with mononeuropathy. Regional cerebral blood flow, as an indicator of neuronal activity, was measured with positron emission tomography. Paired comparisons were made between three different states; rest, allodynia during brushing the painful skin area, and brushing of the homologous contralateral area. Bilateral activations were observed in the primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2) during allodynia compared to rest. The S1 activation contralateral to the site of the stimulus was more expressed during allodynia than during innocuous touch. Significant activations of the contralateral posterior parietal cortex, the periaqueductal gray (PAG), the thalamus bilaterally and motor areas were also observed in the allodynic state compared to both non-allodynic states. In the anterior cingulate cortex (ACC) there was only a suggested activation when the allodynic state was compared with the non-allodynic states. In order to account for the individual variability in the intensity of allodynia and ongoing spontaneous pain, rCBF was regressed on the individually reported pain intensity, and significant covariations were observed in the ACC and the right anterior insula. Significantly decreased regional blood flow was observed bilaterally in the medial and lateral temporal lobe as well as in the occipital and posterior cingulate cortices when the allodynic state was compared to the non-painful conditions. This finding is consistent with previous studies suggesting attentional modulation and a central coping strategy for known and expected painful stimuli. Involvement of the medial pain system has previously been reported in patients with mononeuropathy during ongoing spontaneous pain. This study reveals a bilateral activation of the lateral pain system as well as involvement of the medial pain system during dynamic mechanical allodynia in patients with mononeuropathy
AD  - Clinical Neurophysiology, Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden PMID- 0010568854 PID - S0304395999001505
ER  - 

TY  - JOUR
T1  - Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient
A1  - Piccini,P.
A1  - Brooks,D.J.
A1  - Bjrklund,A.
A1  - Gunn,R.N.
A1  - Grasby,P.M.
A1  - Rimoldi,O.
A1  - Brundin,P.
A1  - Hagell,P.
A1  - Rehncrona,S.
A1  - Widner,H.
A1  - Lindvall,O.
Y1  - 1999/12//
N1  - ENG
SP  - 1137
EP  - 1140
JA  - Nat.Neurosci.
VL  - 2
IS  - 12
N2  - Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief
AD  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. PMID- 0010570493 4099- http://library.neurosci.nature.com/server- java/Propub/neuro/nn1299_1137.fulltext 4100- http://library.neurosci.nature.com/server- java/Propub/neuro/nn1299_1137.abstract
ER  - 

TY  - JOUR
T1  - The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins
A1  - Piccini,P.
A1  - Burn,D.J.
A1  - Ceravolo,R.
A1  - Maraganore,D.
A1  - Brooks,D.J.
Y1  - 1999/05//
N1  - Eng
SP  - 577
EP  - 582
JA  - Ann.Neurol.
VL  - 45
IS  - 5
N2  - Despite the major finding of a genetic defect being responsible for the Parkinson's disease (PD) phenotype in some kindreds with dominantly transmitted PD, the role of inheritance in the cause of the more widespread sporadic form of the disease is still unclear. Twin studies are a classic tool for assessing the influence of hereditary factors in diseases; however, the application of this approach to late-onset illnesses, like PD, poses some problems because of the identification of subclinical cases. In the present longitudinal study we have used [18F]dopa and positron emission tomography to study dopaminergic function in twin pairs at baseline clinically discordant for PD. At baseline, the concordance for subclinical striatal dopaminergic dysfunction was found to be significantly higher in 18 monozygotic than in 16 dizygotic twin pairs (55% vs 18%, respectively). The asymptomatic monozygotic cotwins all showed progressive loss of dopaminergic function over 7 years and 4 developed clinical PD. None of the dizygotic twin pairs became clinically concordant. At follow-up, the combined concordance levels for subclinical dopaminergic dysfunction and clinical PD were 75% in the 12 monozygotic and 22% in the 9 dizygotic twin pairs evaluated twice. Our findings suggest a substantial role for inheritance in sporadic PD
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK. PMID- 0010319879
ER  - 

TY  - JOUR
T1  - Phenotypic variation in hereditary frontotemporal dementia with tau mutations
A1  - van Swieten,J.C.
A1  - Stevens,M.
A1  - Rosso,S.M.
A1  - Rizzu,P.
A1  - Joosse,M.
A1  - de,Koning,I
A1  - Kamphorst,W.
A1  - Ravid,R.
A1  - Spillantini,M.G.
A1  - Niermeijer
A1  - Heutink,P.
Y1  - 1999/10//
N1  - Eng
SP  - 617
EP  - 626
JA  - Ann.Neurol.
VL  - 46
IS  - 4
N2  - Several mutations in the tau gene have been found in families with hereditary frontotemporal dementia and parkinsonism linked to chromosome 17q21-22 (FTDP-17). This study is the first attempt to correlate genotype and phenotype in six families with FTDP-17 with mutations in the tau gene (deltaK280, G272V, P301L, and R406W). We have investigated tau pathology in 1 P301L and 1 R406W patient. The R406W family showed a significantly higher age at onset (59.2 +/- 5.5 years) and longer duration of illness (12.7 +/- 1.5 years) than the families with the other mutations. The six families showed considerable variation in clinical presentation, but none of them had early parkinsonism. Mutism developed significantly later in the R406W family than in the other families. Frontotemporal atrophy on neuroimaging in the R406W family was less severe than in the P301L and deltaK280 families. The P301L brain contained many pretangles in the frontal and temporal cortex, and the dentate gyrus of hippocampus, showing three tau bands (64, 68, and 72 kd) of extracted tau from the frontal cortex. The presence of many neurofibrillary tangles, many diffuse and classic neuritic plaques in the temporal and parietal cortex, and the hippocampus of the same P301L brain correlated with the presence of four sarkosyl-insoluble (60, 64, 68, and 72 kd) tau bands. The coexistence of characteristic P301L and Alzheimer pathology in the same brain needs further explanation. The R406W brain showed abundant neurofibrillary tangles in several brain regions, and four tau bands (60, 64, 68, and 72 kd) of extracted tau from these regions. The slower progression of the disease in the R406W family might be explained by the microtubule-binding properties of the mutant protein
AD  - Department of Neurology, Erasmus University Rotterdam, The Netherlands
ER  - 

TY  - JOUR
T1  - Functional brain mapping using positron emission tomography scanning in preoperative neurosurgical planning for pediatric brain tumors
A1  - Kaplan,A.M.
A1  - Bandy,D.J.
A1  - Manwaring,K.H.
A1  - Chen,K.
A1  - Lawson,M.A.
A1  - Moss,S.D.
A1  - Duncan,J.D.
A1  - Wodrich,D.L.
A1  - Schnur,J.A.
A1  - Reiman,E.M.
Y1  - 1999/11//
N1  - Eng
SP  - 797
EP  - 803
JA  - J.Neurosurg.
VL  - 91
IS  - 5
N2  - OBJECT: The purpose of this report is to demonstrate the value of functional brain mapping using the positron emission tomography (PET) method for preoperative neurosurgical planning in children with brain tumors. Brain maps were used to characterize the relationship between potentially resectable tumors and functionally eloquent brain areas. METHODS: Five children, ranging in age from 3 to 13 years, with hemispheric brain tumors adjacent to eloquent cortex were studied. Magnetic resonance (MR) imaging was used to identify the brain tumors; PET imaging after injection of [18F] fluorodeoxyglucose (FDG), [11C]L- methionine (CMET), or a combination of the two was performed to grade the tumors; and a [15O] H2O uptake study was used to characterize the anatomical relationships of the tumors to functional cortex. The cortical activation maps were obtained during control periods and during behavioral tasks and were used to document motor, visual, and speech and language organizational areas. Wada tests were performed in two patients. Language and speech activation was concordant with the results of Wada testing. CONCLUSIONS: Functional brain mapping using PET scans and coregistered MR images provided the neurosurgeon with precise definitions of structural and functional cortical areas; this altered surgical management in some cases and/or was used to predict outcome. The combination of PET imaging with FDG and/or CMET and measurements of [15O] water uptake was useful in characterizing and grading tumors and instrumental in achieving effective neurosurgical planning. Postoperative results in the five cases suggest that preoperative functional brain mapping has the potential to improve outcome by defining a surgical plan to maximize resection and minimize the risk of neurological sequelae
AD  - Department of Child Neurology, Phoenix Children's Hospital/Good Samaritan Regional Medical Center, Arizona 85006, USA. PMID- 0010541237
ER  - 

TY  - JOUR
T1  - Norms for the Mini-Mental State Examination in a healthy population
A1  - Grigoletto,F.
A1  - Zappala,G.
A1  - Anderson,D.W.
A1  - Lebowitz,B.D.
Y1  - 1999/07/22/
N1  - Eng
SP  - 315
EP  - 320
JF  - Neurology
VL  - 53
IS  - 2
N2  - BACKGROUND: Although the Mini-Mental State Examination (MMSE) is widely used in clinical practice, few norms exist for healthy populations covering a broad range of ages. OBJECTIVE: To obtain MMSE norms specific for age, gender, and education in healthy adults. METHODS: From the population registers of seven communities across Italy, we selected a proportionate random sample of residents age 20 to 79 years to evaluate their health status with respect to conditions affecting cognitive performance. This sample yielded 908 persons who were deemed to be without cognitive impairment and who were then given the MMSE. We calculated fifth percentile norms and presented them as step functions. We then validated the norms as a screening tool for dementia in persons age 65 to 79 years. The validation was based on unpublished data from a separate study and involved estimates of sensitivity and specificity. RESULTS: The norms declined with advancing age, especially for less educated women. Given any age and sex, the norms were higher for individuals with higher educational levels. In screening for dementia, the norms had a sensitivity of 85% and a specificity of 89%. CONCLUSIONS: When using MMSE scores, it is important to account for age, gender, and education, especially in populations where the educational level is low. Expressing MMSE norms as step functions provides an easy-to-use tool for neurologists and other clinicians
AD  - Institute of Hygiene, University of Padua, Italy. PMID- 0010430420
ER  - 

TY  - JOUR
T1  - Dementia with leukoaraiosis: clinical differentiation by temporoparietal hypometabolism on (18)FDG-PET imaging
A1  - Mendez,M.F.
A1  - Ottowitz,W.
A1  - Brown,C.V.
A1  - Cummings,J.L.
A1  - Perryman,K.M.
A1  - Mandelkern,M.A.
Y1  - 1999/11//
N1  - Eng
SP  - 518
EP  - 525
JA  - Dement.Geriatr.Cogn Disord.
VL  - 10
IS  - 6
N2  - Patients with dementia and leukoaraiosis may have either Alzheimer's disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on (18)FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD. Copyrightz1999S.KargerAG,Basel
AV  - Ordner "Versch ZS"
AD  - Psychiatry, VA Greater Los Angeles Healthcare System, UCLA School of Medicine, Los Angeles, Calif., USA
ER  - 

TY  - JOUR
T1  - Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging
A1  - Rosier,A.
A1  - Dupont,P.
A1  - Peuskens,J.
A1  - Bormans,G.
A1  - Vandenberghe,R.
A1  - Maes,M.
A1  - de Groot,T.
A1  - Schiepers,C.
A1  - Verbruggen,A.
A1  - Mortelmans,L.
Y1  - 1996/11/25/
N1  - Eng
SP  - 11
EP  - 22
JA  - Psychiatry Res.
VL  - 68
IS  - 1
N2  - We used [18F]altanserin and positron emission tomography (PET) to image serotonin 5-HT2A receptors in humans. The highest [18F]altanserin uptake is found in the cerebral cortex, with specific-to-nonspecific binding ratios varying from 0.53 to 1.91 in humans between 24 and 48 years of age. In all neocortical regions studied, [18F]altanserin uptake correlates negatively with age. No correlations were found between age and uptake in the cerebellum, the regional cerebral blood flow, or the time course of metabolization of [18F]altanserin. The reduction in cerebral 5-HT2A receptor binding thus directly reflects the loss of specific 5-HT2A receptors with age
AD  - Laboratory for Neuro- and Psychophysiology, Medical School, K.U. Leuven, Belgium. PMID- 0009027929 4102- 1996/11/25 00:00 4103- 1996/11/25 00:00
ER  - 

TY  - JOUR
T1  - Regional brain activity during transient self-induced anxiety and anger in healthy adults
A1  - Kimbrell,T.A.
A1  - George,M.S.
A1  - Parekh,P.I.
A1  - Ketter,T.A.
A1  - Podell,D.M.
A1  - Danielson,A.L.
A1  - Repella,J.D.
A1  - Benson,B.E.
A1  - Willis,M.W.
A1  - Herscovitch,P.
A1  - Post,R.M.
Y1  - 1999/08/15/
N1  - Eng
SP  - 454
EP  - 465
JA  - Biol.Psychiatry
VL  - 46
IS  - 4
N2  - BACKGROUND: Several studies have demonstrated that transient self- induced sadness activates anterior paralimbic structures. To further examine the specificity of these findings and the neural substrates involved in anger and anxiety, we studied the neural correlates of the induction of anxiety and anger in healthy adults. METHODS: We used H2(15)O and positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in 16 healthy adults during the induction of transient anxiety, anger, and neutral emotions. Subjects achieved differential emotions by recalling prior life events while viewing affect-appropriate faces. RESULTS: Both the anxiety and anger conditions were associated with increased normalized rCBF in left inferior frontal and left temporal pole regions and decreased rCBF in right posterior temporal/parietal and right superior frontal cortex, compared to the neutral induction. Additionally, compared to neutral induction, anxiety was associated with increased rCBF in the left anterior cingulate and cuneus and decreased rCBF in right medial frontal cortex, while the anger induction was uniquely associated with increased rCBF in right temporal pole and thalamus. CONCLUSIONS: Self- generated transient states of anxiety and anger are associated with both overlapping and distinct regional brain activity patterns and provide a template for further dissection of specific components of normal and pathologic emotions
AD  - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1272, USA. PMID- 0010459394 EDAT- 1999/08/25 09:00 MHDA- 1999/08/25 09:00
ER  - 

TY  - JOUR
T1  - Incorporating prior knowledge into image registration
A1  - Ashburner,J.
A1  - Neelin,P.
A1  - Collins,D.L.
A1  - Evans,A.
A1  - Friston,K.
Y1  - 1997/11//
N1  - Eng
SP  - 344
EP  - 352
JF  - Neuroimage
VL  - 6
IS  - 4
N2  - The first step in the spatial normalization of brain images is usually to determine the affine transformation that best maps the image to a template image in a standard space. We have developed a rapid and automatic method for performing this registration, which uses a Bayesian scheme to incorporate prior knowledge of the variability in the shape and size of heads. We compared affine registrations with and without incorporating the prior knowledge. We found that the affine transformations derived using the Bayesian scheme are much more robust and that the rate of convergence is greater. Copyright 1997 Academic Press
AD  - Wellcome Department of Cognitive Neurology, Institute of Neurology, London, WC1N 3BG, United Kingdom. PMID- 0009417976 EDAT- 1998/02/07 08:35 MHDA- 1998/02/07 08:35
ER  - 

TY  - JOUR
T1  - A functional MRI study of subjects recovered from hemiparetic stroke
A1  - Cramer,S.C.
A1  - Nelles,G.
A1  - Benson,R.R.
A1  - Kaplan,J.D.
A1  - Parker,R.A.
A1  - Kwong,K.K.
A1  - Kennedy,D.N.
A1  - Finklestein,S.P.
A1  - Rosen,B.R.
Y1  - 1997/12//
N1  - Eng
SP  - 2518
EP  - 2527
JF  - Stroke
VL  - 28
IS  - 12
N2  - BACKGROUND AND PURPOSE: Stroke recovery mechanisms remain incompletely understood, particularly for subjects with cortical stroke, in whom limited data are available. We used functional magnetic resonance imaging to compare brain activations in normal controls and subjects who recovered from hemiparetic stroke. METHODS: Functional magnetic resonance imaging was performed in ten stroke subjects with good recovery, five with deep, and five with cortical infarcts. Brain activation was achieved by index finger-tapping. Statistical parametric activation maps were obtained using a t test and a threshold of P < .001. In five bilateral motor regions, the volume of activated brain for each stroke subject was compared with the distribution of activation volumes among nine controls. RESULTS: Control subjects activated several motor regions. During recovered hand finger-tapping, stroke subjects activated the same regions as controls, often in a larger brain volume. In the unaffected hemisphere, sensorimotor cortex activation was increased in six of nine stroke subjects compared with controls. Cerebellar hemisphere contralateral and premotor cortex ipsilateral to this region, as well as supplementary motor areas, also had increased activation. In the stroke hemisphere, activation exceeding controls was uncommon, except that three of five cortical strokes showed peri-infarct activation foci. During unaffected hand finger-tapping, increased activation by stroke subjects compared with controls was uncommon; however, decreased activation was seen in unaffected sensorimotor cortex, suggesting that this region's responsiveness increased to the ipsilateral hand and decreased to contralateral hand movements. Use of a different threshold for defining activation (P < .01) did not change the overall findings (kappa = .75). CONCLUSIONS: Recovered finger-tapping by stroke subjects activated the same motor regions as controls but to a larger extent, particularly in the unaffected hemisphere. Increased reliance on these motor areas may represent an important component of motor recovery. Functional magnetic resonance imaging studies of subjects who recovered from stroke provide evidence for several processes that may be related to restoration of neurologic function
AD  - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA. cramers@uwashington.edu PMID- 0009412643 EDAT- 1997/12/31 23:52 MHDA- 1997/12/31 23:52
ER  - 

TY  - JOUR
T1  - Huntington's disease progression: PET and clinical observations
A1  - Andrews,T.C.
A1  - Weeks,R.A.
A1  - Turjanski,N.
A1  - Gunn,R.N.
A1  - Watkins,L.H.
A1  - Sahakian,B.
A1  - Hodges,J.R.
A1  - Rosser,A.E.
A1  - Wood,N.W.
A1  - Brooks,D.J.
Y1  - 1999/12//
N1  - Eng
SP  - 2353
EP  - 2363
JF  - Brain
VL  - 122
IS  - Pt 12
N2  - Using serial [(11)C]SCH 23390- and [(11)C]raclopride-PET, we have measured the rate of loss of striatal dopamine D1 and D2 receptor binding over a mean of 40 months in nine asymptomatic adult Huntington's disease mutation carriers, four patients with symptomatic disease, seven mutation-negative controls and three subjects at risk for the disease. Eight of the nine asymptomatic Huntington's disease mutation carriers had serial [(11)C]raclopride-PET and showed a mean annual loss of striatal D2 binding of 4.0%. Only five of these eight, however, showed active progression, and they had a mean annual loss of D2 binding of 6.5%. All nine asymptomatic mutation carriers had serial [(11)C]SCH 23390-PET and showed a mean annual loss of striatal D1 binding of 2. 0%. Four of these subjects demonstrated active progression and they had a mean annual loss of 4.5%. Our four symptomatic Huntington's disease patients showed a mean annual loss of D2 binding of 3.0% and of D1 binding of 5.0%. Loss of striatal D1 and D2 binding was significantly greater in the known mutation carriers than in the combined at-risk and gene-negative groups (P < 0.05). At follow-up PET all subjects were clinically assessed using the Unified Huntington's Disease Rating Scale. Scores for motor function and total functional capacity correlated with PET measures of striatal dopamine receptor binding both in the asymptomatic mutation carriers (D1, P < 0.01) and across the combined asymptomatic and clinically affected Huntington's disease mutation carrier group (D1 and D2, P < 0.001). We conclude that PET measures of striatal D1 and D2 dopamine binding can be used to identify asymptomatic Huntington's disease mutation carriers who are actively progressing and who would thus be suitable for putative neuroprotective therapies. Measures of disease progression rates in Huntington's disease patients and asymptomatic mutation carriers will be of critical importance in future trials of experimental restorative treatments
AD  - MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, London and MRC Centre for Brain Repair, Addenbrooke's Hospital and MRC Cognition and Brain Sciences Unit, Cambridge UK
ER  - 

TY  - JOUR
T1  - [11C]flumazenil PET: activity images versus parametric images for the detection of neocortical epileptic foci
A1  - Niimura,K.
A1  - Muzik,O.
A1  - Chugani,D.C.
A1  - Shen,C.
A1  - Chugani,H.T.
Y1  - 1999/12//
N1  - Eng
SP  - 1985
EP  - 1991
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 12
N2  - [11C]flumazenil (FMZ) imaged with PET allows the computation of parametric images of both tracer influx (K1) and volume of distribution (VD). The VD images, which allow visualization of a quantitative measure of benzodiazepine receptor binding, are reported to have high sensitivity and specificity for the delineation of epileptic foci. However, the clinical feasibility of this method is compromised by the necessity of arterial blood sampling. We therefore compared the performance of parametric VD images against simple FMZ activity images for the detection of neocortical epileptic foci. METHODS: FMZ PET data from 7 children with extratemporal lobe epilepsy (mean age [+/- SD] 9.8+/-4.4 y) and 6 healthy adult volunteers (mean age [+/- SD] 40+/-8 y) were analyzed using a semiautomated analysis algorithm. FMZ activity images and parametric VD images were analyzed for asymmetry with cutoff thresholds of 8%, 10% and 12%. RESULTS: The time frame between 10 and 20 min after injection represented overall the best agreement between FMZ activity and VD images independent of the threshold. The normal asymmetry in VD images was determined as 6.4%+/-1.4% and was significantly higher in the FMZ activity images (7.6%+/-1.4%, P = 0.001). Increasing the cutoff threshold resulted in a significant decrease in the area defined as abnormal in both the VD and the FMZ activity images. Abnormalities defined in FMZ activity images identified additional brain regions as abnormal at the 8% threshold, but there was good agreement with VD images at the 10% asymmetry threshold. In those regions where abnormalities in VD and FMZ activity images were not matched, the asymmetry indices obtained from K1 images were significantly higher than those derived from the VD images (P = 0.01). CONCLUSION: Differences between VD and activity images above the 8% threshold are mainly due to K1. Abnormalities defined in FMZ activity images using a threshold of 10% agree well with those obtained from parametric VD images, indicating that activity images obtained from the time frame of 10-20 min are essentially equivalent to VD images with regard to detection of regions of abnormality for seizure focus localization
AD  - Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201, USA
ER  - 

TY  - JOUR
T1  - Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism
A1  - Chugani,D.C.
A1  - Muzik,O.
Y1  - 2000/01//
N1  - Eng
SP  - 2
EP  - 9
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
IS  - 1
N2  - Alpha[C-11]methyl-L-tryptophan (AMT) is an analog of tryptophan used with positron emission tomography for the measurement of serotonin synthesis in humans. Several attempts have been made to estimate the serotonin synthesis rate from plasma and brain kinetic data of AMT using the same model as that applied for the measurement of the glucose metabolic rate with 2-deoxyglucose. However, although AMT is similar to 2-deoxyglucose with regard to an irreversible pool of tracer uptake, there are important differences between the two tracers and how the model can be applied. These differences include transport at the blood- brain barrier and the presence of a large unmetabolized pool of AMT, precluding the method from providing the absolute serotonin synthesis rate. Despite this limitation, the unidirectional uptake rate constant (K-complex) values have been found to be stable within an individual, and the rank order of regional brain values for K-complex are consistent with the rank order for serotonin content in human brain. Furthermore, changes in K-complex with age, gender, and disease states are consistent with previously reported biochemical measurements of serotonin in brain tissue. The authors suggest, therefore, that the K- complex is an index of serotonin synthesis which they have termed the "serotonin synthesis capacity." The authors argue that AMT is a useful tracer for study of serotonergic mechanisms, and under certain pathologic states, of metabolism by means of the kynurenine pathway
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA
ER  - 

TY  - JOUR
T1  - Increased brain serotonin synthesis in migraine
A1  - Chugani,D.C.
A1  - Niimura,K.
A1  - Chaturvedi,S.
A1  - Muzik,O.
A1  - Fakhouri,M.
A1  - Lee,M.L.
A1  - Chugani,H.T.
Y1  - 1999/10/22/
N1  - Eng
SP  - 1473
EP  - 1479
JF  - Neurology
VL  - 53
IS  - 7
N2  - OBJECTIVE: To measure brain serotonin synthesis with PET using the tracer alpha-[11C]methyl-L-tryptophan in migraine patients. BACKGROUND: Although the cause of migraine remains poorly understood, there is considerable evidence to support a role of the neurotransmitter serotonin in the pathophysiology of migraine. METHODS: We studied 11 women (aged 33+/-7.7 years) with a diagnosis of migraine according to International Headache Society criteria and 8 healthy women (aged 29+/- 9.2 years). Five patients were studied before and after chronic treatment with propranolol or nadolol. RESULTS: Serotonin synthesis capacity (K-complex) values in migraine patients were higher than those measured in controls throughout the brain (p = 0.016); mean K-complex for whole brain was 0.0077 + 0.0020 mL/g/min in patients with migraine and 0.0054+/-0.0003 mL/g/min in controls. The regional pattern did not differ between the two groups. However, the K-complex for whole brain in the subgroup of migraine patients with aura (n = 3) did not differ from that of the control group (p = 0.32). In the five patients studied twice (before and after treatment), we found a trend of increased whole- brain K-complex after drug treatment (p = 0.06). CONCLUSIONS: Our findings indicating increased brain serotonin synthesis capacity in migraine patients are consistent with previous reports of systemic alteration of serotonin metabolism in patients without aura. Our results also suggest that the mechanism of action of beta-adrenergic antagonists for migraine prophylaxis may involve regulation of serotonin synthesis
AD  - Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine 48201, USA. PMID- 0010534254 EDAT- 1999/10/26 09:00 MHDA- 1999/10/26 09:00
ER  - 

TY  - JOUR
T1  - Basic mechanisms of childhood epilepsies: studies with positron emission tomography
A1  - Chugani,H.T.
A1  - Chugani,D.C.
Y1  - 1999///
N1  - Eng
SP  - 883
EP  - 891
JA  - Adv.Neurol.
VL  - 79
N2  - Although functional imaging with positron emission tomography (PET) and single-photon emission computed tomography are useful in the clinical evaluation of intractable epilepsy, these techniques have not been widely applied to understanding the basic mechanisms of the epilepsies. Among patients with infantile spasms, PET studies with 2-deoxy- 2[18F]fluoro-D-glucose (FDG) suggest that the spasms are the result of secondary generalization from cortical foci and that maturational factors result in the recruitment of basal ganglia and brainstem serotonin mechanisms that lead to secondary generalization and the unique semiology of the spasms. Attempts to develop an animal model of infantile spasms have not been successful. Glucose utilization studies in the Lennox-Gastaut syndrome also indicate cortical lesions and further suggest that the electroencephalographic pattern of 1 to 2.5 Hz spike-wave activity (slow spike-wave pattern) is an interictal phenomenon. There is a remarkable consistency between 14C-2- deoxyglucose autoradiographic findings and PET observations of glucose utilization performed for patients in the ictal, interictal, and postictal states. Although three patterns of ictal glucose hypermetabolism have been described, hypermetabolism also can be seen in the postictal and interictal clinical states and in various animal models. Preliminary studies of benzodiazepine receptor binding with PET have found that the cortical epileptic region of decreased binding is smaller than the region of hypometabolism on glucose utilization studies, but detailed electrophysiologic comparisons have not been made. Development of new PET methods for the study of presynaptic and postsynaptic neurotransmitter functions will offer unique opportunities in the study of epileptic mechanisms
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA
ER  - 

TY  - JOUR
T1  - Altered in vitro and in vivo flumazenil binding in human epileptogenic neocortex
A1  - Nagy,F.
A1  - Chugani,D.C.
A1  - Juhasz,C.
A1  - Da Silva,E.A.
A1  - Muzik,O.
A1  - Kupsky,W.
A1  - Canady,A.
A1  - Watson,C.
A1  - Shah,J.
A1  - Chugani,H.T.
Y1  - 1999/09//
N1  - Eng
SP  - 939
EP  - 947
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 9
N2  - In vitro and in vivo parameters of flumazenil (FMZ) binding were measured in spiking and nonspiking neocortex identified by intraoperative electrocorticography in epileptic patients who underwent cortical resection for seizure control. In vitro measures of receptor affinity (K(D)), number (Bmax) and laminar distribution for [3H]-FMZ binding in the epileptic focus (n = 38) were compared to nonspiking cortex from a subgroup of the patients (n = 12) and to tissue obtained from trauma patients (n = 5). The in vitro binding parameters were compared to in vivo [11C]-FMZ binding measured with positron emission tomography (PET) (n = 19). The Bmax was higher in the 38 spiking tissues as compared to the 12 nonspiking tissues (P = .012). Paired comparison of spiking versus nonspiking binding in the 12 patients from whom nonspiking tissue was available showed increases in both K(D) (P = .037) and Bmax (P = .0047) in spiking cortex. A positive correlation was found between K(D) and Bmax values for 38 patients (r = 0.55, P < .0001), the magnitude of the K(D) increase being twice that of the Bmax increase. In addition, there was a significant correlation between the asymmetry indices of the in vivo FMZ binding on PET and in vitro K(D) of spiking cortex (n = 19, r = 0.52, P = .02). The laminar distribution of [3H]-FMZ showed increased FMZ binding in cortical layers V-VI in spiking cortex compared to nonspiking and control cortex. The increased receptor number in spiking cortical layers V-VI may be a compensatory mechanism to decreased GABAergic input. The increased Bmax in spiking cortex was accompanied by a larger decrease in the affinity of FMZ for the receptor suggesting that decreased FMZ binding in the epileptic focus measured with PET is due to a decrease in the affinity of the tracer for the receptor
AD  - Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University, USA. PMID- 0010478645 EDAT- 1999/09/09 09:00 MHDA- 1999/09/09 09:00
ER  - 

TY  - JOUR
T1  - Improved resolution for PET volume imaging through three-dimensional iterative reconstruction
A1  - Liow,J.S.
A1  - Strother,S.C.
A1  - Rehm,K.
A1  - Rottenberg,D.A.
Y1  - 1997/10//
N1  - Eng
SP  - 1623
EP  - 1631
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 10
N2  - It has been demonstrated that in two-dimensional iterative reconstruction, a resolution model can improve image resolution while controlling noise. With the lower noise levels of three-dimensional PET volume imaging, these iterative reconstruction advantages may be extended to three dimensions to further improve the reconstructed image resolution. METHODS: We have implemented three-dimensional versions of iterative filtered backprojection (IFBP) and the maximum likelihood by expectation maximization (ML-EM) reconstruction algorithms and applied them to three-dimensional PET volume datasets. The results were compared to images obtained using the standard three-dimensional reprojection reconstruction (3DRP) algorithm. RESULTS: For IFBP with 15 iterations and no regularization compared to 3DRP, both using a ramp filter, the transaxial resolution improved 52%, and the axial resolution improved 39%. With a strong regularization, the transaxial and axial resolution improvements were reduced to 6% and 5%, respectively. If a Hanning roll-off is applied to the ramp filter in the transaxial direction, the transaxial resolution for IFBP without regularization improved 35% compared to 3DRP; with regularization the improvement dropped to 19%. The axial resolution for IFBP and 3DRP was unaffected by this transaxial smoothing in the reconstruction filter. With the same Hanning roll-off, the noise for IFBP without regularization increased by a factor of 6 compared to 3DRP; with regularization the noise was increased only by a factor of 3. Compared to IFBP, the three-dimensional ML-EM reconstruction produced similar resolution improvements with a much smaller increase in noise and slower convergence. Resolution improvements from both IFBP and ML-EM reconstructions are visually apparent in three-dimensional FDG brain images and result in increased activation signals in a three- dimensional [15O]water functional activation study. CONCLUSION: Our results demonstrate that resolution improvement is possible for IFBP and ML-EM compared to 3DRP with or without noise increase
AD  - Veterans Administration Medical Center, Minneapolis, Minnesota 55147, USA. PMID- 0009379203 EDAT- 1997/10/23 22:31 MHDA- 1997/10/23 22:31
ER  - 

TY  - JOUR
T1  - Predicting human functional maps with neural net modeling
A1  - Horwitz,B.
A1  - Tagamets,M.A.
Y1  - 1999///
N1  - Eng
SP  - 137
EP  - 142
JA  - Hum.Brain Mapp.
VL  - 8
IS  - 2-3
N2  - Formidable difficulties exist in interpreting positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) hemodynamic signals in terms of the underlying neural activity. These include issues of spatial and temporal resolution and problems relating neuronal activity (i.e., action potentials) measured in nonhuman studies by single unit electrodes to hemodynamic measurements reflecting synaptic activity. Also, regional hemodynamic measurements correspond to a mixture of local and afferent synaptic activity. To surmount these difficulties, we propose using large-scale neurobiologically realistic models in which data at various spatial and temporal levels can be simulated and cross-validated by multiple disciplines, including functional neuroimaging. A delayed match-to- sample visual task is used to illustrate this approach
AD  - Language Section, Voice, Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. horwitz@helix.nih.gov
ER  - 

TY  - JOUR
T1  - Revealing interactions among brain systems with nonlinear PCA
A1  - Friston,K.
A1  - Phillips,J.
A1  - Chawla,D.
A1  - Buchel,C.
Y1  - 1999///
N1  - Eng
SP  - 92
EP  - 97
JA  - Hum.Brain Mapp.
VL  - 8
IS  - 2-3
N2  - In this work, we present a nonlinear principal component analysis (PCA) that identifies underlying sources causing the expression of spatial modes or patterns of activity in neuroimaging time series where these sources can interact to produce second-order modes. This nonlinear PCA uses a neural network architecture that embodies a specific form for the mixing of sources that is based on a second-order approximation to any general nonlinear mixing. The modes obtained have a unique rotation and scaling that does not depend on the biologically implausible constraints adopted by conventional PCA. Interactions among sources render the expression of any mode or brain system sensitive to the expression of others. The example considers interactions among functionally specialized brain systems (using a fMRI study of colour and motion processing)
AD  - The Wellcome Department of Cognitive Neurology, Institute of Neurology, Queen Square, London, UK. k.friston@fil.ion.ucl.ac.uk
ER  - 

TY  - JOUR
T1  - Cortical dysfunction in non-demented Parkinson's disease patients: A combined (31)P-MRS and (18)FDG-PET study
A1  - Hu,M.T.
A1  - Taylor-Robinson,S.D.
A1  - Chaudhuri,K.R.
A1  - Bell,J.D.
A1  - Labbe,C.
A1  - Cunningham,V.J.
A1  - Koepp,M.J.
A1  - Hammers,A.
A1  - Morris,R.G.
A1  - Turjanski,N.
A1  - Brooks,D.J.
Y1  - 2000/02//
N1  - ENG
SP  - 340
EP  - 352
JF  - Brain
VL  - 123
IS  - Pt 2
N2  - Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P- MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale-Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia. (31)P MR spectra from right and left temporo- parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. (31)P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), alpha-ATP, gamma-ATP and phosphocreatine (PCr) relative to beta-ATP were measured. Relative percentage peak areas of PMEs, P(i), PDEs, PCr, and alpha-, beta- and gamma-ATP signals were also measured with respect to the total (31)P-MRS signal. Significant bilateral increases in the P(i)/beta-ATP ratio were found in temporoparietal cortex (P = 0.002 right and P = 0.014 left cortex) for the non-demented Parkinson's disease patients compared with controls. In the right temporoparietal cortex, there was also a significant increase in the mean relative percentage P(i) (P = 0.001). (18)FDG-PET revealed absolute bilateral reductions in glucose metabolism after partial volume effect correction in posterior parietal and temporal cortical grey matter (P < 0.01 and P < 0.05, respectively) for the Parkinson's disease group, using both volume of interest analysis and statistical parametric mapping. There were significant correlations between right temporoparietal P(i)/beta-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/beta-ATP ratios correlated with full scale IQ and verbal IQ (r = -0.82, P = 0.006, r = -0.86, P = 0.003, respectively). In summary, temporoparietal cortical hypometabolism was seen in non- demented Parkinson's disease patients with both (31)P-MRS and (18)FDG- PET, suggesting that both glycolytic and oxidative pathways are impaired. This dysfunction may reflect either the presence of primary cortical pathology or deafferentation of striato-cortical projections. (31)P-MRS and (18)FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia
AD  - Robert Steiner MR Unit, Medical Research Council Cyclotron Unit, Division of Medicine and Division of Neuroscience, Imperial College School of Medicine, Hammersmith Hospital, Department of Neurosciences, Guys, King's, St Thomas's Hospital Medical School and Institute of Psychiatry and Institute of Neurology,London, UK. PMID- 0010648441 URLF- http://brain.oupjournals.org/cgi/content/full/123/2/340 URLS- http://brain.oupjournals.org/cgi/content/abstract/123/2/340
ER  - 

TY  - JOUR
T1  - [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis
A1  - Banati,R.B.
A1  - Goerres,G.W.
A1  - Myers,R.
A1  - Gunn,R.N.
A1  - Turkheimer,F.E.
A1  - Kreutzberg,G.W.
A1  - Brooks,D.J.
A1  - Jones,T.
A1  - Duncan,J.S.
Y1  - 1999/12/10/
N1  - Eng
SP  - 2199
EP  - 2203
JF  - Neurology
VL  - 53
IS  - 9
N2  - This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)- PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment
AD  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK. PMID- 0010599809
ER  - 

TY  - JOUR
T1  - Fluorodopa uptake and glucose metabolism in early stages of corticobasal degeneration
A1  - Laureys,S.
A1  - Salmon,E.
A1  - Garraux,G.
A1  - Peigneux,P.
A1  - Lemaire,C.
A1  - Degueldre,C.
A1  - Franck,G.
Y1  - 1999/12//
N1  - Eng
SP  - 1151
EP  - 1158
JF  - Journal of Neurology
JA  - J.Neurol.
VL  - 246
IS  - 12
N2  - Fluorodopa (FDOPA) and fluorodeoxyglucose (FDG) PET was performed in six patients in early stages of corticobasal degeneration (CBD) and compared to Parkinson's disease (PD) patients with a similar degree of bradykinesia and rigidity and to healthy controls. Statistical parametric mapping analysis comparing CBD to controls showed metabolic decrease in premotor, primary motor, supplementary motor, primary sensory, prefrontal, and parietal associative cortices, and in caudate and thalamus contralateral to the side of clinical signs. Except for the prefrontal regions a similar metabolic pattern was observed when CBD was compared to PD. Putamen FDOPA uptake was decreased in both CBD and PD. Caudate FDOPA uptake in CBD patients was decreased contralateral to clinical signs when compared to controls, but was higher than in PD. In early stages of CBD, FDOPA and FDG PET patterns differed from those observed in PD. In CBD the asymmetry in FDOPA uptake was less pronounced than that of clinical signs or metabolic impairment
AD  - Cyclotron Research Center, and Department of Neurology, University of Liege, Belgium. laureys@pet.crc.ulg.ac.be
ER  - 

TY  - JOUR
T1  - Relation between neuropsychological and neuroimaging findings in patients with late whiplash syndrome
A1  - Radanov,B.P.
A1  - Bicik,I.
A1  - Dvorak,J.
A1  - Antinnes,J.
A1  - von Schulthess,G.K.
A1  - Buck,A.
Y1  - 1999/04//
N1  - Eng
SP  - 485
EP  - 489
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 66
IS  - 4
N2  - OBJECTIVES: The interpretation of long term cognitive impairment after whiplash injury is still a problem for many physicians. On the grounds of nuclear medicine findings previous research speculated that brain damage is responsible for cognitive problems of patients with whiplash. To test this hypothesis the relation between neuroimaging and neuropsychological findings was analysed. METHODS: Twenty one patients (11 women, 10 men, mean age 42.2 (SD 8.6) years) with the late whiplash syndrome (average interval of trauma 26.1 (SD 20.7) months) referred for diagnostic action to the Department of Neurology were investigated. Assessment included computer assisted assessment of working memory and divided attention, neuroimaging (by the means of [99mTc]-HMPAO-SPECT, [15O]-H2O-PET and [18F]-FDG-PET), testing of emotional functioning (depression and anxiety ratings), and pain intensity at the time of testing. RESULTS: On average, scoring on tests of cognitive functioning was very low. However, no significant correlations were found between regional perfusion or metabolism in any brain area and the scores of divided attention or working memory. By contrast, significant relations were found between indices of impaired emotional functioning (state anxiety) and divided attention. In addition, low scoring in divided attention was significantly correlated with pain intensity at the time of testing. CONCLUSIONS: The present data do not provide evidence of a significant relation between detectable morphological or functional brain damage and impaired cognitive performance in the late whiplash syndrome. Results indicate triggering of emotional and cognitive symptoms on the basis of initial injury of the cervical spine
AD  - Department of Psychiatry, University of Berne, Inselspital, Switzerland. radanov@pupk.unibe.ch PMID- 0010201421 EDAT- 1999/04/14 02:03 MHDA- 1999/04/14 02:03
ER  - 

TY  - JOUR
T1  - Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies
A1  - Videbaek,C.
A1  - Ott,P.
A1  - Paulson,O.B.
A1  - Knudsen,G.M.
Y1  - 1999/09//
N1  - Eng
SP  - 948
EP  - 955
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 9
N2  - The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique. Cerebral blood flow was measured by intracarotid Xe-injection. The apparent permeability-surface product (PSapp) was measured while CBF or bolus composition was changed. Comparison of PSapp obtained in the absence and presence of 5% albumin in the injectate yielded f(avail), whereas f(eq) was measured by equilibrium dialysis. Iomazenil and flumazenil f(avail) was 62% and 82%, respectively, whereas f(eq) was significantly lower, 42% and 61%. The PSapp for iomazenil and flumazenil increased significantly by 89% and 161% after relative CBF increases of 259% and 201%, respectively. The results demonstrate that application of f(eq) in neuroreceptor studies underestimates the plasma input function to the brain. Model simulations render possible that the differences between f(avail) and f(eq) as well as the effect of CBF on PSapp can be caused by capillary heterogeneity
AD  - Department of Neurology, University Hospital Rigshospitalet, Copenhagen, Denmark. PMID- 0010478646 EDAT- 1999/09/09 09:00 MHDA- 1999/09/09 09:00
ER  - 

TY  - JOUR
T1  - Comparative evaluation of MR-based partial-volume correction schemes for PET
A1  - Meltzer,C.C.
A1  - Kinahan,P.E.
A1  - Greer,P.J.
A1  - Nichols,T.E.
A1  - Comtat,C.
A1  - Cantwell,M.N.
A1  - Lin,M.P.
A1  - Price,J.C.
Y1  - 1999/12//
N1  - Eng
SP  - 2053
EP  - 2065
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 12
N2  - Because of limitations of spatial resolution, quantitative PET measurements of cerebral blood flow, glucose metabolism and neuroreceptor binding are influenced by partial-volume averaging among neighboring tissues with differing tracer concentrations. METHODS: Two MR-based approaches to partial-volume correction of PET images were compared using simulations and a multicompartment phantom. The two-compartment method corrects PET data for the diluting effects of cerebrospinal fluid (CSF) spaces. The more complex three-compartment method also accounts for the effect of partial-volume averaging between gray and white matter. The effects of the most significant sources of error on MR-based partial-volume correction, including misregistration, resolution mismatch, segmentation errors and white matter heterogeneity, were evaluated. We also examined the relative usefulness of both approaches in PET studies of aging and neurodegenerative disease. RESULTS: Although the three-compartment method was highly accurate (with 100% gray matter recovery achieved in simulations), it was also more sensitive to all errors tested, particularly image segmentation and PET-MR registration. CONCLUSION: Based on these data, we conclude that the two-compartment approach is better suited for comparative PET studies, whereas the three-compartment algorithm is capable of greater accuracy for absolute quantitative measures
AD  - Department of Radiology, University of Pittsburgh, Pennsylvania 15213-2582, USA. PMID- 0010616886
ER  - 

TY  - JOUR
T1  - PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders
A1  - Meltzer,C.C.
A1  - Price,J.C.
A1  - Mathis,C.A.
A1  - Greer,P.J.
A1  - Cantwell,M.N.
A1  - Houck,P.R.
A1  - Mulsant,B.H.
A1  - Ben Eliezer,D.
A1  - Lopresti,B.
A1  - Dekosky,S.T.
A1  - Reynolds,C.F.,III
Y1  - 1999/12//
N1  - Eng
SP  - 1871
EP  - 1878
JA  - Am.J.Psychiatry
VL  - 156
IS  - 12
N2  - OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life
AD  - Department of Radiology, University of Pittsburgh, PA, USA. meltzer@radserv.arad.upmc.edu PMID- 0010588399 EDAT- 1999/12/10 09:00
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression
A1  - Smith,G.S.
A1  - Reynolds,C.F.,III
A1  - Pollock,B.
A1  - Derbyshire,S.
A1  - Nofzinger,E.
A1  - Dew,M.A.
A1  - Houck,P.R.
A1  - Milko,D.
A1  - Meltzer,C.C.
A1  - Kupfer,D.J.
Y1  - 1999/05//
N1  - Eng
SP  - 683
EP  - 689
JA  - Am.J.Psychiatry
VL  - 156
IS  - 5
N2  - OBJECTIVE: The treatment of geriatric depression is complicated by a variable and delayed response to antidepressant treatment. The present study was undertaken to test the hypothesis that combined total sleep deprivation and paroxetine treatment would produce a persistent reduction in glucose metabolism in the anterior cingulate cortex similar to that reported after long-term antidepressant treatment. METHOD: Six elderly depressed patients who met the DSM-IV criteria for major depressive disorder and six age-matched comparison subjects underwent serial positron emission tomography (PET) studies at baseline, after total sleep deprivation, after recovery sleep (after the initial paroxetine dose), and after 2 weeks of paroxetine treatment (patients only). The PET data were analyzed by using statistical parametric mapping methods. RESULTS: The patients' scores on a 13-item version of the Hamilton Depression Rating Scale were decreased after total sleep deprivation, after recovery sleep, and after 2 weeks of treatment. The Hamilton depression scores of the comparison subjects were not significantly altered. In the patients, the greatest reductions in normalized, relative glucose metabolism after sleep deprivation were observed in the anterior cingulate cortex (Brodmann area 24), and they persisted after recovery sleep and antidepressant treatment. The comparison subjects demonstrated increased metabolism in these areas. CONCLUSIONS: Improvement in the patients' depressive symptoms was accompanied by reduced glucose metabolism in the right anterior cingulate cortex and right medial frontal cortex. These preliminary data indicate that in elderly depressed patients, total sleep deprivation may accelerate the clinical and glucose metabolic response to antidepressant treatment
AD  - Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213, USA. smithgs@radserv.arad.upmc.edu PMID- 0010327899 EDAT- 1999/05/18 05:24 MHDA- 1999/05/18 05:24
ER  - 

TY  - JOUR
T1  - Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain
A1  - Smith,G.S.
A1  - Price,J.C.
A1  - Lopresti,B.J.
A1  - Huang,Y.
A1  - Simpson,N.
A1  - Holt,D.
A1  - Mason,N.S.
A1  - Meltzer,C.C.
A1  - Sweet,R.A.
A1  - Nichols,T.
A1  - Sashin,D.
A1  - Mathis,C.A.
Y1  - 1998/12//
N1  - Eng
SP  - 380
EP  - 392
JF  - Synapse
VL  - 30
IS  - 4
N2  - The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors
AD  - Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. gsmith@rad.arad.upmc.edu PMID- 0009826230 EDAT- 1998/11/24 03:03 MHDA- 1998/11/24 03:03
ER  - 

TY  - JOUR
T1  - Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction
A1  - Meltzer,C.C.
A1  - Smith,G.
A1  - Price,J.C.
A1  - Reynolds,C.F.,III
A1  - Mathis,C.A.
A1  - Greer,P.
A1  - Lopresti,B.
A1  - Mintun,M.A.
A1  - Pollock,B.G.
A1  - Ben Eliezer,D.
A1  - Cantwell,M.N.
A1  - Kaye,W.
A1  - Dekosky,S.T.
Y1  - 1998/11/30/
N1  - Eng
SP  - 167
EP  - 171
JA  - Brain Res.
VL  - 813
IS  - 1
N2  - The serotonin (5-HT) neurotransmitter system, which has a widespread distribution in the central nervous system, has been implicated in regulating mood and many human behaviors. There is evidence from postmortem human studies and limited information from prior in vivo studies to support a decline in 5-HT2A receptor density with aging. We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site. The PET data were corrected for differences in brain tissue volume between the young and elderly subjects using a magnetic resonance (MR) imaging-based partial volume correction method. Highly significant and widespread cortical reductions in 5-HT2A specific binding were demonstrated in the elderly group relative to young controls. Regional losses averaged 61% before and 57% following correction for effects of cerebral atrophy. This finding, which is consistent with prior postmortem and in vivo studies, has both etiological and potential therapeutic implications for behavioral changes commonly observed in the elderly, including geriatric depression. Copyright 1998 Published by Elsevier Science B.V
AD  - Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. meltzer@radserv.arad.upmc.edu PMID- 0009824691 EDAT- 1998/11/24 03:01 MHDA- 1998/11/24 03:01 URL - http://www.elsevier.com:80/cgi-bin/cas/tree/store/bres/cas_sub/browse/brow se.cgi?year=1998&volume=813&issue=1&aid=27861
ER  - 

TY  - JOUR
T1  - Age-dependent decline of dopamine D1 receptors in human brain: a PET study
A1  - Wang,Y.
A1  - Chan,G.L.
A1  - Holden,J.E.
A1  - Dobko,T.
A1  - Mak,E.
A1  - Schulzer,M.
A1  - Huser,J.M.
A1  - Snow,B.J.
A1  - Ruth,T.J.
A1  - Calne,D.B.
A1  - Stoessl,A.J.
Y1  - 1998/09//
N1  - Eng
SP  - 56
EP  - 61
JF  - Synapse
VL  - 30
IS  - 1
N2  - Radioligand binding studies in animals have demonstrated age-related loss of dopamine receptors in the caudate and putamen. In humans, while age-related declines in dopamine D2 receptors have been consistently reported, the effects of ageing on D1 receptors have been controversial. We used positron emission tomography (PET) with [11C]SCH 23390 to investigate dopamine D1 receptor binding in 21 normal volunteers aged 22-74 years. We also assessed their motor function with a Modified Columbia Score (MCS) and the Purdue Pegboard Test (PPBT). D1 binding potentials were derived using a graphical analysis with a cerebellar tissue input function. Standard linear regression techniques were used to determine the age-related rate of decline of D1 binding. We found an age-dependent decrease of D1 receptor binding in the caudate (6.9% per decade) and putamen (7.4% per decade). There was also a significant inverse correlation between [11C]SCH 23390 binding in the occipital cortex and age (8.6% decline per decade). PPBT score also decreased with age (P = 0.007). There was a direct correlation between PPBT score and D1 binding potential. We conclude that dopamine D1 receptor density declines with age and that the effects of physiological ageing may play a role in the expression of extrapyramidal disorders in the elderly
AD  - Neurodegenerative Disorders Centre and UBC-TRIUMF PET Group, Vancouver Hospital, UBC site, British Columbia, Canada. PMID- 0009704881 EDAT- 1998/08/15 02:14 MHDA- 1998/08/15 02:14
ER  - 

TY  - JOUR
T1  - Imaging brain tumor proliferative activity with [124I]iododeoxyuridine
A1  - Blasberg,R.G.
A1  - Roelcke,U.
A1  - Weinreich,R.
A1  - Beattie,B.
A1  - von Ammon,K.
A1  - Yonekawa,Y.
A1  - Landolt,H.
A1  - Guenther,I.
A1  - Crompton,N.E.
A1  - Vontobel,P.
A1  - Missimer,J.
A1  - Maguire,R.P.
A1  - Koziorowski,J.
A1  - Knust,E.J.
A1  - Finn,R.D.
A1  - Leenders,K.L.
Y1  - 2000/02/01/
N1  - Eng
SP  - 624
EP  - 635
JA  - Cancer Res.
VL  - 60
IS  - 3
N2  - Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [124I]IUdR in 20 patients with brain tumors, including meningiomas and gliomas. The PET images were directly compared with gadolinium contrast-enhanced or T2-weighted magnetic resonance images. Estimates for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct the 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standard uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also calculated from the 24-h image data. The Ki, SUV, and Tm/Br values were related to tumor type and grade, tumor labeling index, and survival after the PET scan. The plasma half-life of [124I]IUdR was short (2-3 min), and the arterial plasma input function was similar between patients (48 +/- 12 SUV*min). Plasma clearance of the major radiolabeled metabolite ([124I]iodide) varied somewhat between patients and was markedly prolonged in one patient with renal insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [124I]iodide) remained in the tumors after the 24-h washout period, and this fraction varied between the different tumor groups. Because the SUV and Tm:Br ratio values reflect both IUdR-DNA incorporated and exchangeable nonincorporated radioactivity, any residual nonincorporated radioactivity will amplify their values and distort their significance and interpretation. This was particularly apparent in the meningioma and glioblastoma multiforme groups of tumors. Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2.3 microl/min/g (peak value for glioblastoma multiforme, GBM). Comparable SUV and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and from 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. Thus, the range of values was much greater for Ki (approximately 8-fold) compared with that for SUV (approximately 2.2-fold) and Tm:Br (approximately 3-fold). The expected relationships between Ki, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient survival) were observed. However, greater image specificity and significance of the SUV and Tm:Br values would be obtained by achieving greater washout and clearance of the exchangeable fraction of residual (background) radioactivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [124I]IUdR administration
AD  - Cotzias Neuro-Oncology Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
ER  - 

TY  - JOUR
T1  - Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment
A1  - Sargent,P.A.
A1  - Kjaer,K.H.
A1  - Bench,C.J.
A1  - Rabiner,E.A.
A1  - Messa,C.
A1  - Meyer,J.
A1  - Gunn,R.N.
A1  - Grasby,P.M.
A1  - Cowen,P.J.
Y1  - 2000/02//
N1  - Eng
SP  - 174
EP  - 180
JA  - Arch.Gen.Psychiatry
VL  - 57
IS  - 2
N2  - BACKGROUND: Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin1A (5-HT1A) receptors. The aim of the present study was to use positron emission tomography with the selective 5-HT1A receptor antagonist [11C]WAY-100635 to measure 5-HT1A receptor binding in depressed patients before and during treatment with selective serotonin reuptake inhibitors. METHODS: Positron emission tomographic scans with [11C]WAY-100635 were performed on 25 patients with major depressive disorder. These included 15 unmedicated depressed patients. Ten of these unmedicated patients were scanned again during selective serotonin reuptake inhibitor treatment. A further 10 patients with major depressive disorder were scanned on one occasion only while taking selective serotonin reuptake inhibitors. Comparisons were made with [11C]WAY-100635 positron emission tomographic scans in 18 healthy volunteer subjects. Region of interest analysis and statistical parametric mapping were performed on binding potential images generated using a reference tissue model. RESULTS: Binding potential values were reduced across many of the regions examined, including frontal, temporal, and limbic cortex in both unmedicated and medicated depressed patients compared with healthy volunteers. Binding potential values in medicated patients were similar to those in unmedicated patients. CONCLUSIONS: Major depressive disorder is associated with a widespread reduction in 5-HT1A receptor binding. This reduced 5-HT1A receptor binding was not changed by selective serotonin reuptake inhibitor treatment
AD  - Medical Research Council Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, England
ER  - 

TY  - JOUR
T1  - Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography
A1  - Andree,B.
A1  - Thorberg,S.O.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 1999/06//
N1  - Eng
SP  - 303
EP  - 305
JA  - Psychopharmacology (Berl)
VL  - 144
IS  - 3
N2  - The augmentation effect of (-)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-11C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a clinical dose level (10 mg s.o.d.) occupies 5-HT1A receptors in the human brain in vivo. Three healthy males were recruited and each subject was used as his own control. The 5-HT1A receptor occupancy was calculated for the frontal and temporal cortex and the raphe nuclei, using and a ratio analysis with the cerebellar cortex as the reference region. Maximal pindolol plasma concentration was reached within 3 h after drug administration. Two hours after pindolol administration, the regional 5-HT1A receptor occupancy was within the range 7-21% in the three subjects. The study confirms that the 5-HT1A-receptor may be a clinically significant target for pindolol
AD  - Karolinska Institutet, Department of clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. bengt.andree@neuro.ks.se PMID- 0010435400 EDAT- 1999/08/06 10:00 MHDA- 1999/08/06 10:00
ER  - 

TY  - JOUR
T1  - A review of functional neuroimaging in mood disorders: positron emission tomography and depression
A1  - Kennedy,S.H.
A1  - Javanmard,M.
A1  - Vaccarino,F.J.
Y1  - 1997/06//
N1  - Eng
SP  - 467
EP  - 475
JA  - Can.J.Psychiatry
VL  - 42
IS  - 5
N2  - OBJECTIVE: To examine the progress of positron emission tomography (PET) as a tool for understanding the psychobiology of mood disorders, particularly major depression and bipolar disorder. METHOD: Review of the literature on functional imaging of mood disorders. RESULTS: Functional imaging techniques have been used in psychiatric research as a noninvasive method to study the behaviour and function of the brain. Techniques used so far have involved the manipulation of emotion in healthy volunteers, the evaluation of depressed (unipolar and bipolar as well as secondary depression), manic, and normal subjects under resting and various activation conditions, such as cognitive activation, acute pharmacological challenge, and chronic thymoleptic treatments. As a result, functional imaging studies tend to support abnormalities in specific frontal and limbic regions. CONCLUSION: Different PET methods demonstrate consistent abnormalities in the prefrontal, cingulate, and amygdala regions. These findings are in agreement with past animal and clinical anatomical correlates of mood and emotions
AD  - Department of Psychiatry, University of Toronto, Ontario
ER  - 

TY  - JOUR
T1  - Identification by positron emission tomography of neuronal loss in acute vegetative state
A1  - Rudolf,J.
A1  - Sobesky,J.
A1  - Grond,M.
A1  - Heiss,W.D.
Y1  - 2000/01/08/
N1  - Eng
SP  - 115
EP  - 116
JF  - Lancet
VL  - 355
IS  - 9198
N2  - Positron emission tomography with the benzodiazepine receptor ligand carbon-11-labelled flumazenil Identified the extent of neuronal damage in acute vegetative state and predicted the possibility of recovery of consciousness and function
ER  - 

TY  - JOUR
T1  - Robust smoothness estimation in statistical parametric maps using standardized residuals from the general linear model
A1  - Kiebel,S.J.
A1  - Poline,J.B.
A1  - Friston,K.J.
A1  - Holmes,A.P.
A1  - Worsley,K.J.
Y1  - 1999/12//
N1  - Eng
SP  - 756
EP  - 766
JA  - Neuroimage.
VL  - 10
IS  - 6
N2  - The assessment of significant activations in functional imaging using voxel-based methods often relies on results derived from the theory of Gaussian random fields. These results solve the multiple comparison problem and assume that the spatial correlation or smoothness of the data is known or can be estimated. End results (i. e., P values associated with local maxima, clusters, or sets of clusters) critically depend on this assessment, which should be as exact and as reliable as possible. In some earlier implementations of statistical parametric mapping (SPM) (SPM94, SPM95) the smoothness was assessed on Gaussianized t-fields (Gt-f) that are not generally free of physiological signal. This technique has two limitations. First, the estimation is not stable (the variance of the estimator being far from negligible) and, second, physiological signal in the Gt-f will bias the estimation. In this paper, we describe an estimation method that overcomes these drawbacks. The new approach involves estimating the smoothness of standardized residual fields which approximates the smoothness of the component fields of the associated t-field. Knowing the smoothness of these component fields is important because it allows one to compute corrected P values for statistical fields other than the t-field or the Gt-f (e.g., the F-map) and eschews bias due to deviation from the null hypothesis. We validate the method on simulated data and demonstrate it using data from a functional MRI study. Copyright 1999 Academic Press
AD  - Department of Neurology, Friedrich-Schiller-University, Jena, Germany. PMID- 0010600421 PID - nimg.1999.0508 DOI - 10.1006/nimg.1999.0508
ER  - 

TY  - JOUR
T1  - The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism
A1  - Spanaki,M.V.
A1  - Siegel,H.
A1  - Kopylev,L.
A1  - Fazilat,S.
A1  - Dean,A.
A1  - Liow,K.
A1  - Ben Menachem,E.
A1  - Gaillard,W.D.
A1  - Theodore,W.H.
Y1  - 1999/10/22/
N1  - Eng
SP  - 1518
EP  - 1522
JF  - Neurology
VL  - 53
IS  - 7
N2  - OBJECTIVE: To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET. BACKGROUND: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. METHODS: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. RESULTS: No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p < 0.01). CONCLUSIONS: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism
AD  - Clinical Epilepsy Section, Epilepsy Research Branch, NIH/NINDS, Bethesda, MD 20892-1408, USA. PMID- 0010534261 EDAT- 1999/10/26 09:00 MHDA- 1999/10/26 09:00
ER  - 

TY  - JOUR
T1  - Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation
A1  - Kumar,R.
A1  - Dagher,A.
A1  - Hutchison,W.D.
A1  - Lang,A.E.
A1  - Lozano,A.M.
Y1  - 1999/09/11/
N1  - Eng
SP  - 871
EP  - 874
JF  - Neurology
VL  - 53
IS  - 4
N2  - Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in a patient with severe idiopathic generalized dystonia resulted in immediate improvement of all aspects of dystonia. During joystick movement, GPi DBS reduced PET activation bilaterally in the primary motor, lateral premotor, supplementary motor, anterior cingulate, and prefrontal areas and ipsilaterally in the lentiform nucleus. Altering basal ganglia function with GPi DBS reverses the overactivity of certain motor cortical areas present in dystonia
AD  - Division of Neurology, Faculty of Medicine, University of Toronto, Canada. PMID- 0010489059 EDAT- 1999/09/17 09:00 MHDA- 1999/09/17 09:00
ER  - 

TY  - JOUR
T1  - PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease
A1  - Ilgin,N.
A1  - Zubieta,J.
A1  - Reich,S.G.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Frost,J.J.
Y1  - 1999/04/12/
N1  - Eng
SP  - 1221
EP  - 1226
JF  - Neurology
VL  - 52
IS  - 6
N2  - OBJECTIVE: To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). METHODS: We used the radiotracer [11C]-WIN 35,428 and PET. Regional striatal dopamine transporter binding was measured in the caudate, anterior putamen, and posterior putamen of six patients with L-dopa-responsive stage 2 PD, six patients with PSP, and six age-comparable healthy controls. RESULTS: In patients with idiopathic PD, the most marked abnormality was observed in the posterior putamen (77% reduction), whereas transporter density in the anterior putamen (60% reduction) and the caudate (44% reduction) was less affected. Unlike the patients with PD, the PSP group showed a relatively uniform degree of involvement in the caudate (40% reduction), anterior putamen (47% reduction), and posterior putamen (51% reduction). When posterior putamen/caudate ratios were calculated, these values were significantly lower in patients with PD than they were in patients with PSP (p = 0.0008) and the control group (p < 0.0001). CONCLUSIONS: Patients with PD have a more pronounced loss of dopamine transporters in the posterior putamen due to a subdivisional involvement of nigrostriatal dopaminergic projections in idiopathic PD. This technique is useful in the determination of neurochemical changes underlying PD and PSP, thus differentiating between them
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. PMID- 0010214747 EDAT- 1999/04/24 02:13 MHDA- 1999/04/24 02:13
ER  - 

TY  - JOUR
T1  - Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies
A1  - Turjanski,N.
A1  - Lees,A.J.
A1  - Brooks,D.J.
Y1  - 1999/03/23/
N1  - Eng
SP  - 932
EP  - 937
JF  - Neurology
VL  - 52
IS  - 5
N2  - OBJECTIVE: To use PET to study striatal dopaminergic function in restless legs syndrome (RLS). BACKGROUND: RLS is a common disorder experienced by as much as 5% of the population. It has been suggested that this condition is associated with a disturbance of dopaminergic transmission. METHODS: The authors measured nigrostriatal terminal dopamine storage with 18F-dopa and striatal D2 receptor binding with 11C-raclopride PET in 13 RLS patients, five of whom were receiving treatment with L-dopa at the time of scanning. RLS results were compared with those of age-matched control subjects. RESULTS: Mean caudate and putamen 18F-dopa uptake were mildly reduced in the RLS patients compared with control subjects, and this reached significance (p = 0.04) in the putamen. Mean D2 binding was reduced in the caudate (p = 0.01) and the putamen (p = 0.008) in RLS patients compared with control subjects. Six of the 13 RLS patients had caudate and putamen D2 binding reduced below the control range. Three other RLS patients showed only reduced putamen D2 binding. There were no significant differences in striatal 18F-dopa uptake or D2 binding between L-dopa-naive and L-dopa-treated RLS patients. CONCLUSIONS: These PET findings support the hypothesis of central dopaminergic dysfunction in RLS
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK. PMID- 0010102408
ER  - 

TY  - JOUR
T1  - Muscarinic cholinergic receptors in human narcolepsy: a PET study
A1  - Sudo,Y.
A1  - Suhara,T.
A1  - Honda,Y.
A1  - Nakajima,T.
A1  - Okubo,Y.
A1  - Suzuki,K.
A1  - Nakashima,Y.
A1  - Yoshikawa,K.
A1  - Okauchi,T.
A1  - Sasaki,Y.
A1  - Matsushita,M.
Y1  - 1998/11//
N1  - Eng
SP  - 1297
EP  - 1302
JF  - Neurology
VL  - 51
IS  - 5
N2  - OBJECTIVES: To investigate the function of the muscarinic cholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchRs. BACKGROUND: Muscarinic neural transmission serves as the main executive system in REM sleep. Studies in canine narcolepsy reported an increase in mAchRs in the pons. METHODS: The mAchRs of 11 drug naive/free patients with narcolepsy and 21 normal controls were investigated using PET with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB). Measurements were done in the pons, thalamus, striatum, and cerebral cortex. Seven of the 11 patients also underwent additional PET scans after the alleviation of symptoms by pharmacotherapy. RESULTS: There were no differences in [11C]NMPB binding between the control and drug naive/free patients in all areas analyzed. At the time of on-medication PET scan, [11C]NMPB binding in the thalamus was decreased, but only to a small degree compared with that by anticholinergic drugs. CONCLUSION: The present results do not support the notion that the mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy
AD  - Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan. sudo_y@nirs.go.jp PMID- 0009818849 EDAT- 1998/11/18 03:03 MHDA- 1998/11/18 03:03
ER  - 

TY  - JOUR
T1  - The underlying pathophysiology of ictal dystonia in temporal lobe epilepsy: an FDG-PET study
A1  - Dupont,S.
A1  - Semah,F.
A1  - Baulac,M.
A1  - Samson,Y.
Y1  - 1998/11//
N1  - Eng
SP  - 1289
EP  - 1292
JF  - Neurology
VL  - 51
IS  - 5
N2  - BACKGROUND: Unilateral dystonic posturing of limbs occurs frequently in medial temporal lobe epilepsy (MTLE) but its underlying anatomic basis is still unknown. OBJECTIVE: To investigate the pathophysiology of dystonic posturing, we examined the relation between the occurrence of dystonia and interictal cerebral metabolic abnormalities using fluorodeoxyglucose (FDG)-PET in MTLE patients. METHODS: Video recordings of 30 patients with documented MTLE were reviewed to assess the presence of ictal dystonic posturing. Interictal FDG-PET was performed in all patients. RESULTS: Eighteen patients exhibited dystonic posturing--contralateral to the seizure focus in 16 cases, bilateral in one, and ipsilateral in one. Dystonia was statistically associated with more severe hypometabolism in the striatal and in the orbitofrontal regions ipsilateral to the seizure focus. CONCLUSION: Hypometabolism observed in the striatal region of patients with ictal dystonic posturing suggests that the basal ganglia are involved in the generation of ictal dystonic posturing in MTLE
AD  - Unite d'Epileptologie, Clinique Neurologique Paul Castaigne Hopital de la Pitie-Salpetriere, Paris, France. PMID- 0009818847 EDAT- 1998/11/18 03:03 MHDA- 1998/11/18 03:03
ER  - 

TY  - JOUR
T1  - The metabolic anatomy of tremor in Parkinson's disease
A1  - Antonini,A.
A1  - Moeller,J.R.
A1  - Nakamura,T.
A1  - Spetsieris,P.
A1  - Dhawan,V.
A1  - Eidelberg,D.
Y1  - 1998/09//
N1  - Eng
SP  - 803
EP  - 810
JF  - Neurology
VL  - 51
IS  - 3
N2  - OBJECTIVE: To identify regional metabolic brain networks related specifically to the presence of tremor in PD. BACKGROUND: The pathophysiology of parkinsonian tremor is unknown. Because tremor in PD occurs mainly in repose, we used resting state PET with 18F-fluorodeoxyglucose (FDG) to identify specific metabolic brain networks associated with this clinical manifestation. METHODS: We studied two discrete groups of eight PD patients with and without tremor using FDG/PET. Both patient groups were matched for gender, age, and Unified Parkinson Disease Rating Scale ratings for akinesia and rigidity. Ten normal volunteer subjects served as controls. RESULTS: Network analysis with the Scaled Subprofile Model was performed in two steps. 1) We computed the expression of the PD-related pattern (PDRP) identified by us previously in each of the PD patients and control subjects. Although PDRP subject scores were abnormally elevated in the combined PD cohort (p < 0.005), these values did not differ in the PD patient groups with and without tremor (p = 0.36). 2) We used SSM to analyze the data from the combined PD cohort comprising both patient groups. We found that PD patients with tremor were characterized by increased expression of a metabolic network comprising the thalamus, pons, and premotor cortical regions. Subject scores for this pattern were elevated in the tremor group compared with the atremulous patient group and the normal control group (p < 0.005). CONCLUSIONS: The findings suggest that PD patients with tremor are characterized by distinct increases in the functional activity of thalamo-motor cortical projections. Modulation of this functional anatomic pathway is likely to be the mechanism for successful interventions for the relief of parkinsonian tremor
AD  - Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA. PMID- 0009748030 EDAT- 1998/09/25 02:03 MHDA- 1998/09/25 02:03
ER  - 

TY  - JOUR
T1  - Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease
A1  - Ibanez,V.
A1  - Pietrini,P.
A1  - Alexander,G.E.
A1  - Furey,M.L.
A1  - Teichberg,D.
A1  - Rajapakse,J.C.
A1  - Rapoport,S.I.
A1  - Schapiro,M.B.
A1  - Horwitz,B.
Y1  - 1998/06//
N1  - Eng
SP  - 1585
EP  - 1593
JF  - Neurology
VL  - 50
IS  - 6
N2  - OBJECTIVE: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. RESULTS: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue
AD  - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. PMID- 0009633698 EDAT- 1998/06/20 02:17 MHDA- 1998/06/20 02:17
ER  - 

TY  - JOUR
T1  - Cerebral oxygen metabolism in patients with progressive supranuclear palsy: a positron emission tomography study
A1  - Santens,P.
A1  - De Reuck,J.
A1  - Crevits,L.
A1  - Decoo,D.
A1  - Lemahieu,I.
A1  - Strijckmans,K.
A1  - Goethals,P.
Y1  - 1997///
N1  - Eng
SP  - 18
EP  - 22
JA  - Eur.Neurol.
VL  - 37
IS  - 1
N2  - To investigate cerebral oxygen metabolism in progressive supranuclear palsy (PSP), 5 patients with a clinical diagnosis of PSP and a variable degree of cognitive deficit were selected for positron emission tomography (PET) of the brain. In 4 of them, a significant decrease in oxygen metabolism was found in all cortical regions, without frontal accentuation. In the group as a whole, this decrease was even slightly more marked in parietal and temporal regions. These findings are not consistent with earlier PET studies that demonstrated frontal targeting of hypometabolism in PSP patients. Part of this discrepancy can be explained by differences in methodology, although the use of different clinical criteria and overlap of PSP with other neurodegenerative diseases must be taken into account. It is concluded that the absence of frontal hypometabolism on PET examination does not exclude the diagnosis of PSP
AD  - UZ/RUG PET Center, Department of Neurology, University Hospital Ghent, Belgium. PMID- 0009018027 EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:00
ER  - 

TY  - JOUR
T1  - The role of diaschisis in stroke recovery
A1  - Seitz,R.J.
A1  - Azari,N.P.
A1  - Knorr,U.
A1  - Binkofski,F.
A1  - Herzog,H.
A1  - Freund,H.J.
Y1  - 1999/09//
N1  - Eng
SP  - 1844
EP  - 1850
JF  - Stroke
VL  - 30
IS  - 9
N2  - BACKGROUND AND PURPOSE: Recovery from hemiparesis after stroke has been shown to involve reorganization in motor and premotor cortical areas. However, whether poststroke recovery also depends on changes in remote brain structures, ie, diaschisis, is as yet unresolved. To address this question, we studied regional cerebral blood flow in 7 patients (mean+/-SD age, 54+/-8 years) after their first hemiparetic stroke. METHODS: We analyzed imaging data voxel by voxel using a principal component analysis by which coherent changes in functional networks could be disclosed. Performance was assessed by a motor score and by the finger movement rate during the regional cerebral blood flow measurements. RESULTS: The patients had recovered (P<0. 001) from severe hemiparesis after on average 6 months and were able to perform sequential finger movements with the recovered hand. Regional cerebral blood flow at rest differentiated patients and controls (P<0.05) by a network that was affected by the stroke lesion. During blindfolded performance of sequential finger movements, patients were differentiated from controls (P<0.05) by a recovery-related network and a movement-control network. These networks were spatially incongruent, involving motor, sensory, and visual cortex of both cerebral hemispheres, the basal ganglia, thalamus, and cerebellum. The lesion-affected and recovery-related networks overlapped in the contralesional thalamus and extrastriate occipital cortex. CONCLUSIONS: Motor recovery after hemiparetic brain infarction is subserved by brain structures in locations remote from the stroke lesion. The topographic overlap of the lesion-affected and recovery-related networks suggests that diaschisis may play a critical role in stroke recovery
AD  - Department of Neurology, Heinrich-Heine University Dusseldorf, Germany. seitz@neurologie.uni-duesseldorf.de PMID- 0010471434 URLF- http://www.strokeaha.org/cgi/content/full/30/9/1844 URLS- http://www.strokeaha.org/cgi/content/abstract/30/9/1844 EDAT- 1999/09/02 09:00 MHDA- 1999/09/02 09:00
ER  - 

TY  - JOUR
T1  - Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion
A1  - Smith,K.A.
A1  - Morris,J.S.
A1  - Friston,K.J.
A1  - Cowen,P.J.
A1  - Dolan,R.J.
Y1  - 1999/06//
N1  - Eng
SP  - 525
EP  - 529
JA  - Br.J.Psychiatry
VL  - 174
N2  - BACKGROUND: Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients. AIMS: To identify brain regions which change their activity as an acute depressive relapse evolves and to determine how pathological mood might modulate neural activity during a cognitive task. METHOD: We used H2(15)O positron-emission tomography (PET) to study eight recovered depressed men after tryptophan depletion and after a control procedure. During both PET scan sessions, subjects performed a paced verbal fluency task which alternated with a control verbal repetition task. RESULTS: Increasing levels of depression after tryptophan depletion were associated with diminished neural activity in the ventral anterior cingulate, orbitofrontal cortex and caudate nucleus regions. In addition, depressive relapse attenuated cognitive task-related activation in the anterior cingulate cortex. CONCLUSIONS: Our data indicate that changes in neural activity in distinct brain regions mediate the clinical phenomena of depression and depression-related cognitive impairment following acute tryptophan depletion. These changes could be associated with the widespread distribution of serotonin neurons in brain pathways associated with the expression of affect and cognitive performance
AD  - University Department of Psychiatry, Warneford Hospital, Oxford. PMID- 0010616631
ER  - 

TY  - JOUR
T1  - Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, 18F-fallypride in nonhuman primates using positron emission tomography
A1  - Mukherjee,J.
A1  - Yang,Z.Y.
A1  - Lew,R.
A1  - Brown,T.
A1  - Kronmal,S.
A1  - Cooper,M.D.
A1  - Seiden,L.S.
Y1  - 1997/09//
N1  - Eng
SP  - 1
EP  - 13
JF  - Synapse
VL  - 27
IS  - 1
N2  - We have investigated the ability of dopamine to compete with the binding of the high affinity dopamine D2 receptor positron emission tomography (PET) radioligand, 18F-fallypride. In vitro dissociation of 18F-fallypride with dopamine in rat striatal homogenates exhibited a dissociation rate, k(off), of 1.76 x 10(-2) min(-1) while the association rate constant, k(on), was found to be 5.30 x 10(8) M(-1) min(-1). This resulted in a dissociation constant, K(D) of 33 pM for 18F-fallypride. For in vivo studies, we investigated the effects of reserpine and d-amphetamine treatment on 18F-fallypride in an attempt to study competition of endogenous dopamine with the radioligand at the receptor sites in rats and monkeys. PET experiments with 18F-fallypride in two male rhesus monkeys were carried out in a PETT VI scanner. In control experiments, rapid specific uptake of 18F-fallypride in the striata was observed (0.05-0.06% injected dose (ID)/g) while nonspecifically bound tracer cleared from other parts of the brain. Striata/cerebellum ratios for 18F-fallypride were approximately 8 at 80 min postinjection, respectively. The monkeys received various doses (0.25 to 1.50 mg/kg) of d-amphetamine (AMPH) pre- and postinjection of the radioligand. There was a decrease of specifically bound 18F-fallypride as well as evidence of an enhanced clearance of specifically bound 18F-fallypride after administering AMPH in the two monkeys. The dissociation rates, k(off), of 18F-fallypride without AMPH was <10(-4) min(-1) but after 25 min preadministration of AMPH (1 mg/kg), it was 4.1 x 10(-3) min(-1) and after 17, 45 and 90 min postadministration of AMPH (1 mg/kg) it was 3.6 x 10(-3) to 4.0 x 10(-3) min(-1). Lower doses of AMPH (0.25 mg/kg) had a reduced effect on the binding of 18F-fallypride. No effect was seen until about 30 minutes after the injection of AMPH. Studies with various doses indicated that 18F-fallypride has a maximum response at doses of 0.75-1.50 mg/kg, with an approximately 16%/hour reduction in binding. These results indicate that AMPH stimulated release of endogenous dopamine reduces the specific binding of 18F-fallypride
AD  - Franklin McLean Institute, Department of Radiology, University of Chicago, Illinois 60637, USA. j-mukherjee@uchicago.edu PMID- 0009268060 EDAT- 1997/09/01 00:00 MHDA- 1997/09/01 00:00
ER  - 

TY  - JOUR
T1  - Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide as an improved dopamine D-2 receptor tracer
A1  - Mukherjee,J.
A1  - Yang,Z.Y.
A1  - Das,M.K.
A1  - Brown,T.
Y1  - 1995/04//
N1  - Eng
SP  - 283
EP  - 296
JA  - Nucl.Med.Biol.
VL  - 22
IS  - 3
N2  - We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso-butyl) of the dopamine D-2 receptor antagonist, FPMB which result from modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As expected, all new derivatives showed higher apparent lipophilicity (log kw), with iso-butyl being the most lipophilic (log kw = 2.52), followed by the allyl derivative (log kw = 2.43). The allyl group showed the largest increase in affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl substituent, almost 10-fold), followed by the n-propyl substituent which showed approximately five-fold better affinity than did the ethyl substituent. Radiosynthesis of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide ([18F]fallypride) was carried out by nucleophilic substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl) methyl]-5-(3-tosyloxypropyl)-2,3-dimethoxybenzamide with no carrier added 18F-. [18F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g) of [18F]fallypride in rats was observed with striatal/cerebellar ratios of 17, 42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET experiments with [18F]fallypride in a cebus monkey showed a brain uptake of 0.10% injected dose/cc. In rhesus monkeys [18F]fallypride showed rapid specific uptake in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically bound [18F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life of 18 min in the rhesus monkey
AD  - Franklin McLean Institute, Department of Radiology, University of Chicago, IL 60637, USA. PMID- 0007627142
ER  - 

TY  - JOUR
T1  - PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis
A1  - Vowinckel,E.
A1  - Reutens,D.
A1  - Becher,B.
A1  - Verge,G.
A1  - Evans,A.
A1  - Owens,T.
A1  - Antel,J.P.
Y1  - 1997/10/15/
N1  - Eng
SP  - 345
EP  - 353
JA  - J.Neurosci.Res.
VL  - 50
IS  - 2
N2  - Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission tomography (PET) imaging with [11C]-PK11195 showed ligand uptake only at sites of active MS lesions defined by magnetic resonance imaging criteria. Our results indicate the potential to develop markers suitable for both in vitro and in vivo use, which will serve to help correlate phenotypic and functional properties of cells which participate in disease or injury responses within the CNS
AD  - Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada. PMID- 0009373043
ER  - 

TY  - JOUR
T1  - Specific high-affinity binding of peripheral benzodiazepine receptor ligands to brain tumors in rat and man
A1  - Black,K.L.
A1  - Ikezaki,K.
A1  - Santori,E.
A1  - Becker,D.P.
A1  - Vinters,H.V.
Y1  - 1990/01/01/
N1  - Eng
SP  - 93
EP  - 97
JF  - Cancer
VL  - 65
IS  - 1
N2  - Two types of benzodiazepine receptors have been identified in mammalian tissues: a central type which is localized to neuronal elements in the brain, and a peripheral type which is present on glial cells and in tissues outside the central nervous system such as kidney. The authors report an increase in specific binding of peripheral benzodiazepine receptor ligands in certain human brain tumors using computer assisted quantitative image analysis of autoradiograms. Higher densities of binding sites to a 3H-labeled selective peripheral benzodiazepine ligand, PK11195 [1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] were observed in human gliomas as the malignancy of these tumors increased. Specific binding was also present in some non-glial tumors but little binding was demonstrated in necrotic tissue or normal brain. In in vitro binding studies in rats, there was a significant increase in Bmax (1089.3 +/- 232.2 fmol/mg tissue) in C6 glial tumors and LK Walker 256 metastatic tumors (924.2 +/- 183.7) compared with normal brain (62.1 +/- 12.8 fmol/mg tissue). Binding affinities were, however, similar (Kd = 2.09, 2.17, and 2.04 nmol/l, respectively). These findings suggest that the number of peripheral benzodiazepine receptors are increased in brain tumors. These receptors could be utilized in positron emission tomography to image brain tumors
AD  - Department of Neurology, University of California Los Angeles Medical Center 90024. PMID- 0002152852
ER  - 

TY  - JOUR
T1  - Synthesis of a fluorine-18 labeled derivative of epibatidine for in vivo nicotinic acetylcholine receptor PET imaging
A1  - Dolci,L.
A1  - Dolle,F.
A1  - Valette,H.
A1  - Vaufrey,F.
A1  - Fuseau,C.
A1  - Bottlaender,M.
A1  - Crouzel,C.
Y1  - 1999/03//
N1  - Eng
SP  - 467
EP  - 479
JA  - Bioorg.Med.Chem.
VL  - 7
IS  - 3
N2  - Epibatidine (exo-2-(2'-chloro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a natural compound isolated from the skin of the Ecuadorian poison frog Epipedobates tricolor, is the most potent nicotinic acetylcholine receptor (nAChR) agonist reported to date. In order to visualize and quantify in vivo these receptors in human brain using Positron Emission Tomography (PET), [18F]norchlorofluoroepibatidine (exo-2-(2'-[18F]fluoro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a fluorine-18 (t(1/2): 110 min) radiolabeled derivative of epibatidine has been designed. The corresponding 2'-bromo-, 2'-iodo- and 2'-nitro exo-2-(5'-pyridyl)-7-azabicyclo[2.2.1]heptane analogues as labeling precursors, as well as norchlorofluoroepibatidine as a reference compound have been synthesized by reductive, stereoselective, palladium-catalyzed Heck-type coupling between an N-Boc protected azanorbornene and the corresponding halopyridine. [18F]Norchlorofluoroepibatidine has been radiolabeled with fluorine-18 by nucleophilic aromatic substitution from the corresponding Boc-protected halo- and nitro precursors using [18F]FK-K222 complex in DMSO by conventional heating (at 150-180 degrees C for 10 min) or microwave activations (at 100 Watt, for 1 to 2.5 min), followed by TFA-removal of the protective group. Typically, using the microwave activation procedure, 60-80 mCi (2.22-2.96 GBq) of pure [18F]norchlorofluoroepibatidine could be obtained in less than 2 h (110-115 min) from the bromo labeling precursor, with specific radioactivities of 1.5-2.5 Ci/micromol (55.5-92.5 GBq/micromol) calculated for End of Bombardment. The preliminary PET experiments in baboon (Papio papio) with [18F]norchlorofluoroepibatidine show a high uptake and a rapid accumulation of the radiotracer into the brain within 30 min. In the thalamus, a nAChR rich area, uptake of radioactivity reached a maximum at 40 min (10% I.D./100 mL tissue). The ratio of radioactivity thalamus/cerebellum (the latter being a nAChR poor area) was 2 at 40 min and increased with time, up to 4.3 at 160 min. Its specific regiodistribution and its high ratio of specific-to-nonspecific binding confirm the ideal profile of [18F]norchlorofluoroepibatidine as a suitable radioligand for PET imaging of nAChRs in the brain
AD  - Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA, Orsay, France. PMID- 0010220033 EDAT- 1999/04/29 02:03 MHDA- 1999/04/29 02:03
ER  - 

TY  - JOUR
T1  - Synthesis and evaluation of N-[11C]methylated analogues of epibatidine as tracers for positron emission tomographic studies of nicotinic acetylcholine receptors
A1  - Horti,A.G.
A1  - Scheffel,U.
A1  - Kimes,A.S.
A1  - Musachio,J.L.
A1  - Ravert,H.T.
A1  - Mathews,W.B.
A1  - Zhan,Y.
A1  - Finley,P.A.
A1  - London,E.D.
A1  - Dannals,R.F.
Y1  - 1998/10/22/
N1  - Eng
SP  - 4199
EP  - 4206
JA  - J.Med.Chem.
VL  - 41
IS  - 22
N2  - Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They were (+/-)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7-azabicyclo[2. 2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl analogues 1, 2, 3, and 4 inhibited the in vitro binding of [3H]epibatidine to nAChRs to a similar degree, with affinities in the 27-50 pM range. The binding affinity of N-ethylepibatidine (2b), however, was substantially lower. The N-[11C]methyl derivatives of 1, 2, and 3 were synthesized from high-specific radioactivity [11C]methyl iodide using a high-temperature/high-pressure technique. The corresponding radiolabeled compounds [11C]1a, [11C]2a, and [11C]3a were administrated to mice intravenously. The pattern of regional distribution of the three tracers in the mouse brain following intravenous administration matched those of [3H]epibatidine, [3H]norchloroepibatidine, and (+/-)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), which are highly specific nAChR probes. The initial brain uptake of the 11C analogues and the acute toxicity of the corresponding authentic nonlabeled compounds appeared to be related to their lipophilicity
AD  - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.ahorti@intra.nida.nih.gov PMID- 0009784094 PID - jm980233p DOI - 10.1021/jm980233p EDAT- 1998/10/23 02:02 MHDA- 1998/10/23 02:02 URL - http://dx.doi.org/10.1021/jm980233p
ER  - 

TY  - JOUR
T1  - Imaging nicotinic acetylcholine receptors with fluorine-18-FPH, an epibatidine analog
A1  - Villemagne,V.L.
A1  - Horti,A.
A1  - Scheffel,U.
A1  - Ravert,H.T.
A1  - Finley,P.
A1  - Clough,D.J.
A1  - London,E.D.
A1  - Wagner,H.N.,Jr.
A1  - Dannals,R.F.
Y1  - 1997/11//
N1  - Eng
SP  - 1737
EP  - 1741
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 11
N2  - Nicotinic acetylcholine receptors (nAChRs) have been implicated in a variety of central processes, such as learning and memory and analgesia. These receptors also mediate the reinforcing properties of nicotine in tobacco products and are increased in postmortem samples of brains of smokers. On the other hand, brains of individuals who have died from dementia of the Alzheimer type show abnormally low densities of nAChRs. In this study, the distribution and kinetics of [(+/-)-exo-2-(2-[18F] fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane (18F-FPH), a high-affinity nAChR agonist, was evaluated in a baboon using PET. METHODS: After intravenous injection of 5 mCi [185 MBq] 18F-FPH into a 25-kg anesthetized baboon, sequential quantitative tomographic data were acquired over a period of 150 min. Regions of interest were placed and time-activity curves were generated. Brain kinetics of the radiotracer were calculated, and the in vivo regional binding in the baboon brain was compared with the known in vitro regional distribution of nAChRs in the rat and human brain. RESULTS: Brain activity reached a plateau within 60 min after injection of the tracer, and the binding was reversible. Elimination of 18F-FPH was relatively rapid from the cerebellum (clearance t[1/2] = 3 hr), intermediate from the hypothalamus/midbrain (t[1/2] = 7 hr) and slow from the thalamus (t[1/2] = 16 hr). Radioactivity due to 18F-FPH at 130 min postinjection was highest in the thalamus and hypothalamus/midbrain, intermediate in the neocortex and hippocampus and lowest in the cerebellum. Subcutaneous injection of 1 mg/kg cytisine 45 min after injection of the radiotracer reduced brain activity at 130 min by 67%, 64%, 56% and 52% of control values in the thalamus, hypothalamus/midbrain, hippocampus and cerebellum, respectively. The regional binding of 18F-FPH at 130 min was highly correlated with the known densities of nAChR measured in vitro in human (r = 0.81) and rat brain (r = 0.90). CONCLUSION: These results demonstrate the feasibility of imaging nAChRs in vivo. Fluorine-18-FPH appears to be a suitable tracer to study nAChRs in the human brain
AD  - Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179, USA. PMID- 0009374343 EDAT- 1997/11/28 02:45 MHDA- 1997/11/28 02:45
ER  - 

TY  - JOUR
T1  - In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in rhesus monkeys
A1  - Sihver,W.
A1  - Fasth,K.J.
A1  - Ogren,M.
A1  - Lundqvist,H.
A1  - Bergstrom,M.
A1  - Watanabe,Y.
A1  - Langstrom,B.
A1  - Nordberg,A.
Y1  - 1999/08//
N1  - Eng
SP  - 633
EP  - 640
JA  - Nucl.Med.Biol.
VL  - 26
IS  - 6
N2  - The novel 11C-labeled nicotinic agonist (R,S)-1-[11C]methyl-2(3-pyridyl)azetidine ([11C]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylcholine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[11C]methyl-2-pyrrolidinyl)isoxazol ([11C]ABT-418) and (S)(-)[11C]nicotine. The nicotinic receptor agonist [11C]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [11C]nicotine and [11C]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [11C]MPA was decreased by 25% in the thalamus, 19% in the temporal cortex, and 11% in the cerebellum, whereas an increase was found for the uptake of (S)(-)[11C]nicotine and [11C]ABT-418. This finding indicates specific binding of [11C]MPA to nicotinic receptors in the brain in a simple classical displacement study. [11C]MPA seems to be a more promising radiotracer than (S)(-)[11C]nicotine or [11C]ABT-418 for PET studies to characterize nicotinic receptors in the brain
AD  - Subfemtomole Biorecognition Project, Japan Science and Technology Corporation, Osaka. Wiebke.Sihver@pet.uu.se PMID- 0010587101 EDAT- 1999/12/10 09:00
ER  - 

TY  - JOUR
T1  - Synthesis and characterization of binding of 5-[76Br]bromo-3-[[2(S)-azetidinyl]methoxy]pyridine, a novel nicotinic acetylcholine receptor ligand, in rat brain
A1  - Sihver,W.
A1  - Fasth,K.J.
A1  - Horti,A.G.
A1  - Koren,A.O.
A1  - Bergstrom,M.
A1  - Lu,L.
A1  - Hagberg,G.
A1  - Lundqvist,H.
A1  - Dannals,R.F.
A1  - London,E.D.
A1  - Nordberg,A.
A1  - Langstrom,B.
Y1  - 1999/09//
N1  - Eng
SP  - 1264
EP  - 1272
JA  - J.Neurochem.
VL  - 73
IS  - 3
N2  - 5-[76Br]Bromo-3-[[2(S)-azetidinyl]methoxy]pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/micromol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half-life of [76Br]BAP was 51 +/- 6 min in cortical membranes and 56 +/- 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (K(D)) values of 36 +/- 9 and 30 +/- 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 +/- 17 and 207 +/- 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [76Br]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [76Br]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [76Br]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by approximately 60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [76Br]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo
AD  - PET Centre Uppsala University, Sweden. PMID- 0010461920 EDAT- 1999/08/26 09:00 MHDA- 1999/08/26 09:00
ER  - 

TY  - JOUR
T1  - Quantitative autoradiography with short-lived positron emission tomography tracers: a study on muscarinic acetylcholine receptors with N-[(11)C]methyl-4-piperidylbenzilate
A1  - Sihver,S.
A1  - Sihver,W.
A1  - Bergstrom,M.
A1  - Hoglund,A.U.
A1  - Sjoberg,P.
A1  - Langstrom,B.
A1  - Watanabe,Y.
Y1  - 1999/08//
N1  - Eng
SP  - 917
EP  - 922
JA  - J.Pharmacol.Exp.Ther.
VL  - 290
IS  - 2
N2  - The present work demonstrates quantitative autoradiography by using positron emission tomography tracers and storage phosphorimaging plates. The uptake and association of [(11)C]N-methyl-4-piperidylbenzilate was measured in rat brain tissue cryosections of various thicknesses. The signal increased with increasing section thickness, but only in 10-micrometer-thick sections did the binding reach the steady state during a 50-min observation time. This violation of the equilibrium condition, potentially combined with perfusion limitations, leads to erroneous increased binding-site density and decreased affinity in the 25- and 50-micrometer-thick sections. For better imaging of receptor distribution it is reasonable to use thicker sections. For quantitative analysis of receptor-binding parameters, the specific properties of ligands at different thicknesses of cryosections need to be considered. Evidence is provided that the nonselective muscarinic antagonist N-methyl-4-piperidylbenzilate binds preferentially to the M(4) subtype of muscarinic acetylcholine receptors
AD  - Department of Neuroscience, Unit of Pharmacology, Faculty of Medicine, Uppsala University, Uppsala, Sweden. PMID- 0010411609 URLF- http://www.jpet.org/cgi/content/full/290/2/917 URLS- http://www.jpet.org/cgi/content/abstract/290/2/917 EDAT- 1999/07/20 10:00 MHDA- 1999/07/20 10:00
ER  - 

TY  - JOUR
T1  - Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent
A1  - Tan,P.Z.
A1  - Baldwin,R.M.
A1  - van Dyck,C.H.
A1  - Al Tikriti,M.
A1  - Roth,B.
A1  - Khan,N.
A1  - Charney,D.S.
A1  - Innis,R.B.
Y1  - 1999/08//
N1  - Eng
SP  - 601
EP  - 608
JA  - Nucl.Med.Biol.
VL  - 26
IS  - 6
N2  - This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography. In analogy to its analog ketanserin, we postulated 4-(4-fluorobenzoyl)piperidine (FBP) and altanserinol for the previously observed two polar radiometabolites, corresponding to dealkylation at the piperidine nitrogen and reduction at the ketone, respectively. To test this hypothesis and characterize the in vivo and in vitro behavior of the radiometabolites, we synthesized nonradioactive authentic compounds altanserinol, 1-(4-fluorophenyl)-1-(piperidin-4-yl)methanol (FBPOH), and isolated nonradioactive FBP metabolite from monkey plasma. [18F]Altanserinol was obtained by NaBH4 reduction of [18F]altanserin, followed by acid hydrolysis. Identification of radiometabolites was carried out by high performance liquid chromatography and thin layer chromatography comparison of the radioactive plasma after injection of tracers with five authentic compounds. Human studies revealed that at least four radiometabolites, one identified as [18F]altanserinol, resulted from reduction of the ketone functionality. The N-dealkylation product [18F]FBP was not detectable; however, a radiometabolite of FBP was present in plasma after administration of [18F]altanserin. Monkey studies showed nonradioactive FBP was converted rapidly to a less polar metabolite. In rat, altanserin and altanserinol were converted to each other in vivo, and all the radiometabolites likely penetrated the blood-brain barrier and entered the brain. Displacement binding of altanserin to cloned serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors showed Ki values of 0.3, 6.0, 1,756, and 15 nM; the binding of FBP and altanserinol to these four 5-HT subtypes was negligible. We conclude from these studies that the radiometabolites of [18F]altanserin from N-dealkylation and ketone reduction should not interfere with specific receptor quantification in an equilibrium paradigm
AD  - Yale University School of Medicine, Yale-VA Pet Center, West Haven, Connecticut 06511, USA. Tan@orpheus.med.yale.edu PMID- 0010587097 EDAT- 1999/12/10 09:00
ER  - 

TY  - JOUR
T1  - PET imaging of serotonin 1A receptor binding in depression
A1  - Drevets,W.C.
A1  - Frank,E.
A1  - Price,J.C.
A1  - Kupfer,D.J.
A1  - Holt,D.
A1  - Greer,P.J.
A1  - Huang,Y.
A1  - Gautier,C.
A1  - Mathis,C.
Y1  - 1999/11/15/
N1  - Eng
SP  - 1375
EP  - 1387
JA  - Biol.Psychiatry
VL  - 46
IS  - 10
N2  - BACKGROUND: The serotonin-1A (5HT1A) receptor system has been implicated in the pathophysiology of major depression by postmortem studies of suicide victims and depressed subjects dying of natural causes. This literature is in disagreement, however, regarding the brain regions where 5HT1A receptor binding differs between depressives and controls and the direction of such differences relative to the normal baseline, possibly reflecting the diagnostic heterogeneity inherent within suicide samples. PET imaging using the 5HT1A receptor radioligand, [11C]WAY-100635, may clarify the clinical conditions under which 5HT1A receptor binding potential (BP) is abnormal in depression. METHODS: Regional 5HT1A receptor BP values were compared between 12 unmedicated depressives with primary, recurrent, familial mood disorders and 8 healthy controls using PET and [carbonyl-11C]WAY-100635. Regions-of-interest (ROI) assessed were the mesiotemporal cortex (hippocampus-amygdala) and midbrain raphe, where previous postmortem studies suggested 5HT1A receptor binding is abnormal in depression. RESULTS: The mean 5HT1A receptor BP was reduced 41.5% in the raphe (p < .02) and 26.8% in the mesiotemporal cortex (p < .025) in the depressives relative to the controls. Post hoc comparisons showed the abnormal reduction in 5HT1A receptor BP was not limited to these regions, but extended to control ROI in the occipital cortex and postcentral gyrus as well. The magnitude of these abnormalities was most prominent in bipolar depressives (n = 4) and unipolar depressives with bipolar relatives (n = 4). CONCLUSIONS: Serotonin-1A receptor BP is abnormally decreased in the depressed phase of familial mood disorders in multiple brain regions. Of the regions tested, the magnitude of this reduction was most prominent in the midbrain raphe. Converging evidence from postmortem studies of mood disorders suggests these reductions of 5HT1A receptor BP may be associated with histopathological changes involving the raphe
AD  - Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, USA. PMID- 0010578452 EDAT- 1999/12/01 09:00
ER  - 

TY  - JOUR
T1  - Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration--a positron emission tomography study
A1  - Kanerva,H.
A1  - Vilkman,H.
A1  - Nagren,K.
A1  - Kilkku,O.
A1  - Kuoppamaki,M.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 1999/07//
N1  - Eng
SP  - 76
EP  - 81
JA  - Psychopharmacology (Berl)
VL  - 145
IS  - 1
N2  - RATIONALE: Deramciclane fumarate is a new 5-HT2A and 5-HT2C receptor antagonist with putative anxiolytic effects. In the present study the binding of deramciclane to serotonin 5-HT2A receptors in frontal cortex of healthy male volunteers was studied using [11C]-N-methyl spiperone ([11C]-NMSP) and positron emission tomography. METHODS: The receptor occupancy percentage was assessed by the means of inhibition of [11C]-NMSP from the 5-HT2A receptors in the frontal cortex. Single oral doses of 20, 50 and 150 mg deramciclane were given to three subjects at each dose level (total n = 9). The receptor occupancy was measured before deramciclane and at 3 and 6 h post-dosing except at the 20 mg dose level where only the 3-h measurement was done. The occupancy percentage was calculated with the ratio method using cerebellum as a reference area. RESULTS: Deramciclane inhibited [11C]-NMSP binding dose and concentration dependently. However, deramasciclane inhibited maximally only 52% of the [11C]-NMSP binding in the frontal cortex, indicating a non-5-HT2A receptor binding component of this radioligand in frontal cortex. On average, specific [11C]-NMSP binding cerebellum ratios below 0.355 were not possible to achieve in this population. The 52% inhibition was regarded to represent near 100% 5-HT2A receptor occupancy. The 50 and 90% receptor occupancies were reached at deramciclane plasma concentrations of 21 ng/ml and 70 ng/ml, respectively. CONCLUSIONS: Deramciclane penetrates the blood-brain barrier in humans. Deramciclane binds to the 5-HT2A receptors in the frontal cortex in a saturable manner in vivo. Consequently, the increase in deramciclane concentration in plasma above 70 ng/ml will not result in major increase in the 5-HT2A receptor occupancy in the brain
AD  - Orion Corporation, Orion Pharma, Espoo, Finland. PMID- 0010445375 EDAT- 1999/08/13 10:00 MHDA- 1999/08/13 10:00
ER  - 

TY  - JOUR
T1  - The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET
A1  - Meyer,J.H.
A1  - Cho,R.
A1  - Kennedy,S.
A1  - Kapur,S.
Y1  - 1999/06//
N1  - Eng
SP  - 279
EP  - 281
JA  - Psychopharmacology (Berl)
VL  - 144
IS  - 3
N2  - RATIONALE: Alterations in 5-HT2A receptor binding are implicated in suicidality and depression. 5-HT2A receptors may also be involved in the therapeutic effects of antidepressants. OBJECTIVES: The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT2A receptors after a single dose. METHODS: Seven subjects received a single dose of nefazodone 200 mg and five subjects received a single dose of paroxetine 20 mg. Before and after the dose, 5-HT2A binding potentials (Bmax/Kd) were determined in each subject using [18F]-setoperone PET. RESULTS: Nefazodone induced a significant change in 5-HT2A binding potential (-39+/-17%,, P = 0.003) while paroxetine showed no significant alteration of 5-HT2A binding potential (+3+/-13%, P = 0.73). CONCLUSIONS: The change in 5-HT2A binding potential seen with nefazodone represents blockade of 5-HT2A receptors by the drug. We do not find evidence for acute downregulation of 5-HT2A receptors with paroxetine within 9 h
AD  - The Mood and Anxiety Division and PET Centre, The Clarke Division of the Centre for Addictions and Mental Health, Toronto, Ontario, Canada. PMID- 0010435395 EDAT- 1999/08/06 10:00 MHDA- 1999/08/06 10:00
ER  - 

TY  - JOUR
T1  - Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity in MPTP-treated squirrel monkeys: in vivo and in vitro investigations [In Process Citation]
A1  - Yee,R.E.
A1  - Huang,S.C.
A1  - Stout,D.B.
A1  - Irwin,I.
A1  - Shoghi-Jadid,K.
A1  - Togaski,D.M.
A1  - DeLanney,L.E.
A1  - Langston,J.W.
A1  - Satyamurthy,N.
A1  - Farahani,K.F.
A1  - Phelps,M.E.
A1  - Barrio,J.R.
Y1  - 2000/03//
N1  - Eng
SP  - 1147
EP  - 1157
JA  - J.Neurochem.
VL  - 74
IS  - 3
N2  - Aromatic L-amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6-[18F]fluoro-L-DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro biochemical determinations of AAAD activity in caudate, putamen, substantia nigra, and nucleus accumbens were performed in the same animals to establish a direct comparison of in vivo and in vitro measurements. In vivo and in vitro AAAD activities in caudate/ putamen were substantially reduced in animals treated with the highest dose of MPTP (2.0 mg/kg). The percent change in the striatal FDOPA uptake (K(i)) and decarboxylation rate constant (k3) values resulting from MPTP treatment showed highly significant correlations with in vitro-determined AAAD activities. However, decarboxylase rates within individual animals presented as approximately 10-fold difference between in vivo and in vitro values. Lower in vivo k3 measurements may be attributed to several possibilities, including transport restrictions limiting substrate availability to AAAD within the neuron. In addition, reductions in AAAD activity in the substantia nigra did not parallel reductions in AAAD activity within the striatum, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously thought
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-6948, USA
ER  - 

TY  - JOUR
T1  - Validity of clinical criteria for the diagnosis of dementia with Lewy bodies
A1  - Verghese,J.
A1  - Crystal,H.A.
A1  - Dickson,D.W.
A1  - Lipton,R.B.
Y1  - 1999/12/10/
N1  - Eng
SP  - 1974
EP  - 1982
JF  - Neurology
VL  - 53
IS  - 9
N2  - OBJECTIVE: To assess the clinical validity of clinical diagnostic criteria for dementia with Lewy bodies (DLB). METHODS: We assessed the sensitivity, specificity, and positive and negative predictive values of the clinical criteria of the Consortium on dementia with Lewy Bodies (CDLB) in 18 patients with autopsy-proven DLB and in 76 patients with dementia not associated with Lewy bodies, using postmortem diagnosis as a gold standard. RESULTS: CDLB criteria had either high sensitivity or high specificity, but no set of criteria simultaneously provided both high sensitivity and high specificity. Clinical criteria had higher predictive validity in patients with pure DLB than in patients with DLB and AD. Seventy-eight percent of patients with pure DLB had two or more major criteria, compared with 44% of patients with DLB and AD (p<0.02). If the nine patients with DLB and AD were excluded from the DLB group, the CDLB criteria for probable DLB had sensitivity of 78% and specificity of 85%. CDLB criteria for probable DLB (two or more major criteria) distinguished DLB from AD with a sensitivity of 78% and a specificity of 64%. CONCLUSIONS: The proposed CDLB criteria have high negative predictive value and thus do well at excluding patients with DLB. Positive predictive value of 75% can be achieved by a combination of any three major or minor criteria, providing the analysis is confined to patients with mild to moderate dementia. Criteria were most accurate if confined to patients with pure DLB who had mild to moderate dementia
AD  - Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. PMID- 0010599768 MHDA- 1999/12/22 09:00 EDAT- 1999/12/22 09:00
ER  - 

TY  - JOUR
T1  - Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals
A1  - MacLaren,D.C.
A1  - Gambhir,S.S.
A1  - Satyamurthy,N.
A1  - Barrio,J.R.
A1  - Sharfstein,S.
A1  - Toyokuni,T.
A1  - Wu,L.
A1  - Berk,A.J.
A1  - Cherry,S.R.
A1  - Phelps,M.E.
A1  - Herschman,H.R.
Y1  - 1999/05//
N1  - Eng
SP  - 785
EP  - 791
JA  - Gene Ther.
VL  - 6
IS  - 5
N2  - Reporter genes (e.g. beta-galactosidase, chloramphenicol-acetyltransferase, green fluorescent protein, luciferase) play critical roles in investigating mechanisms of gene expression in transgenic animals and in developing gene delivery systems for gene therapy. However, measuring expression of these reporter genes requires biopsy or death. We now report a procedure to image reporter gene expression repetitively and non-invasively in living animals with positron emission tomography (PET), using the dopamine type 2 receptor (D2R) as a reporter gene and 3-(2'-[18F]fluoroethyl)spiperone (FESP) as a reporter probe. We use a viral delivery system to demonstrate the ability of this PET reporter gene/PET reporter probe system to image reporter gene expression following somatic gene transfer. In mice injected intravenously with replication-deficient adenovirus carrying a D2R reporter gene, PET in vivo measures of hepatic [18F] retention are proportional to in vitro measures of hepatic FESP retention, D2R ligand binding and D2R mRNA. We use tumor-forming cells carrying a stably transfected D2R gene to demonstrate imaging of this PET reporter gene/PET reporter probe system in 'tissues'. Tumors expressing the transfected D2R reporter gene retain substantially more FESP than control tumors. The D2R/FESP reporter gene/reporter probe system should be a valuable technique to monitor, in vivo, expression from both gene therapy vectors and transgenes
AD  - Crump Institute for Biological Imaging, UCLA School of Medicine, USA. PMID- 0010505102 EDAT- 1999/10/03 09:00 MHDA- 1999/10/03 09:00
ER  - 

TY  - JOUR
T1  - Decision analysis in nuclear medicine
A1  - Gambhir,S.S.
Y1  - 1999/09//
N1  - Eng
SP  - 1570
EP  - 1581
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 40
IS  - 9
N2  - This review focuses primarily on the methodology involved in properly reviewing the literature for performing a meta-analysis and on methods for performing a formal decision analysis using decision trees. Issues related to performing a detailed metaanalysis with consideration of particular issues, including publication bias, verification bias and patient spectrum, are addressed. The importance of collecting conventional measures of test performance (e.g., sensitivity and specificity) and of changes in patient management to model the cost-effectiveness of a management algorithm is detailed. With greater utilization of the techniques discussed in this review, nuclear medicine researchers should be well prepared to compete for the limited resources available in the current health care environment. Furthermore, nuclear medicine physicians will be better prepared to best serve their patients by using only those studies with a proven role in improving patient management
AD  - The Crump Institute for Biological Imaging and Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1770, USA. PMID- 0010492381 EDAT- 1999/09/24 09:00 MHDA- 1999/09/24 09:00
ER  - 

TY  - JOUR
T1  - Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine
A1  - Brody,A.L.
A1  - Saxena,S.
A1  - Silverman,D.H.
A1  - Alborzian,S.
A1  - Fairbanks,L.A.
A1  - Phelps,M.E.
A1  - Huang,S.C.
A1  - Wu,H.M.
A1  - Maidment,K.
A1  - Baxter,L.R.,Jr.
Y1  - 1999/10/11/
N1  - Eng
SP  - 127
EP  - 139
JA  - Psychiatry Res.
VL  - 91
IS  - 3
N2  - Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD
AD  - UCLA Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute and Hospital, Los Angeles, CA 90024, USA. abrody@ucla.edu PMID- 0010641577 MHDA- 2000/02/26 09:00 EDAT- 2000/01/21 09:00
ER  - 

TY  - JOUR
T1  - Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET)
A1  - Vollenweider,F.X.
A1  - Maguire,R.P.
A1  - Leenders,K.L.
A1  - Mathys,K.
A1  - Angst,J.
Y1  - 1998/09/28/
N1  - Eng
SP  - 149
EP  - 162
JA  - Psychiatry Res.
VL  - 83
IS  - 3
N2  - The effects of high euphorigenic doses of D-amphetamine (0.9-1.0 mg/kg p.o.) on regional cerebral glucose metabolism (rCMRglu) and psychological measures were investigated in 10 healthy human volunteers using a within-subject design and [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) and a variety of psychological assessments. At the dose tested, D-amphetamine produced a mania-like syndrome concomitantly with a widespread increase in absolute cerebral metabolism, which was significant in the anterior cingulate cortex, caudate nucleus, putamen, and thalamus. An exploratory analysis revealed that: (1) certain aspects of this mania-like syndrome correlated positively with the metabolic changes seen in the frontal cortex, caudate nucleus and putamen; and (2) some of the amphetamine-induced changes in CMRglu correlated with D-amphetamine plasma levels. The present findings of cortical and subcortical increases in cerebral metabolism after D-amphetamine application in humans accord with previous studies in animals, demonstrating that relatively high doses of D-amphetamine (presumably at least 1 mg/kg) are needed to increase cerebral glucose metabolism
AD  - Research Department, Psychiatric University Hospital Zurich, Switzerland. vollen@bli.unizh.ch PMID- 0009849724 EDAT- 1998/12/16 16:57 MHDA- 1998/12/16 16:57
ER  - 

TY  - JOUR
T1  - Effect of sertraline on regional metabolic rate in patients with affective disorder
A1  - Buchsbaum,M.S.
A1  - Wu,J.
A1  - Siegel,B.V.
A1  - Hackett,E.
A1  - Trenary,M.
A1  - Abel,L.
A1  - Reynolds,C.
Y1  - 1997/01/01/
N1  - Eng
SP  - 15
EP  - 22
JA  - Biol.Psychiatry
VL  - 41
IS  - 1
N2  - Seventeen patients with major affective disorder completed a 10-week, placebo-controlled, randomized trial of the serotonin reuptake inhibitor sertraline. Patients underwent positron emission tomography with 18F-deoxyglucose and were assessed with the Hamilton Depression Rating Scale at baseline and 10 weeks after treatment with sertraline or placebo. The middle frontal gyrus, an area previously characterized by decreased metabolic activity in depressive patients, showed relatively increased activity on both sides after sertraline when contrasted with temporal and some occipital areas. Sertraline was associated with a significantly increased relative metabolic rate in right parietal lobe and in left occipital area 19, and a decreased metabolic rate in right occipital area 18. Other areas that differed between controls and a larger cohort of 39 depressive patients--including medial frontal lobe, cingulate gyrus, and thalamus--also showed a normalization of metabolic rate after sertraline
AD  - Department of Psychiatry, Mt. Sinai School of Medicine, New York, New York 10029-6574, USA. PMID- 0008988791
ER  - 

TY  - JOUR
T1  - Regional brain metabolic response to lorazepam in subjects at risk for alcoholism
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Begleiter,H.
A1  - Hitzemann,R.
A1  - Pappas,N.
A1  - Burr,G.
A1  - Pascani,K.
A1  - Wong,C.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
Y1  - 1995/04//
N1  - Eng
SP  - 510
EP  - 516
JA  - Alcohol Clin.Exp.Res.
VL  - 19
IS  - 2
N2  - The mechanisms underlying the blunted response to alcohol administration observed in subjects at risk for alcoholism are poorly understood and may involve GABA-benzodiazepine receptors. The purpose of this study was to investigate if subjects at risk for alcoholism had abnormalities in brain GABA-benzodiazepine receptor function. This study measured the effects of 30 micrograms/kg (i.v.) of lorazepam, on regional brain glucose metabolism using positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in subjects with a positive family history for alcoholism (FP) (n = 12) and compared their response with that of subjects with a negative family history for alcoholism (FN) (n = 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam decreased whole-brain glucose metabolism, and FP subjects showed a similar response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum. Lorazepam-induced changes in cerebellar metabolism correlated with its motor effects. The decreased cerebellar baseline metabolism in FP as well as the blunted cerebellar response to lorazepam challenge may reflect disrupted activity of benzodiazepine-GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepines in FP subjects
AD  - Brookhaven National Laboratory, Upton, NY 11973, USA. PMID- 0007625590
ER  - 

TY  - JOUR
T1  - Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study
A1  - Pietrini,P.
A1  - Furey,M.L.
A1  - Alexander,G.E.
A1  - Mentis,M.J.
A1  - Dani,A.
A1  - Guazzelli,M.
A1  - Rapoport,S.I.
A1  - Schapiro,M.B.
Y1  - 1999/03//
N1  - Eng
SP  - 470
EP  - 473
JA  - Am.J.Psychiatry
VL  - 156
IS  - 3
N2  - OBJECTIVE: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest
AD  - Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA. pietrini@codon.nih.gov PMID- 0010080567 EDAT- 1999/03/18 03:03 MHDA- 1999/03/18 03:03
ER  - 

TY  - JOUR
T1  - Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography: a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas
A1  - Brock,C.S.
A1  - Young,H.
A1  - O'Reilly,S.M.
A1  - Matthews,J.
A1  - Osman,S.
A1  - Evans,H.
A1  - Newlands,E.S.
A1  - Price,P.M.
Y1  - 2000/02//
N1  - Eng
SP  - 608
EP  - 615
JA  - Br.J.Cancer
VL  - 82
IS  - 3
N2  - Quantitation of metabolic changes in tumours may provide an objective measure of clinical and subclinical response to anticancer therapy. This pilot study assesses the value of quantitation of metabolic rate of glucose (MRGlu) measured in mmol min(-1) ml(-1) to assess early subclinical response to therapy in a relatively non-responsive tumour. Nine patients receiving the CRC Phase II study schedule of temozolomide were assessed with [18F]fluorodeoxyglucose ([18F]FDG) dynamic positron emission tomography (PET) scans prior to and 14 days after treatment with temozolomide given as 750-1000 mg m(-2) over 5 days every 28 days. Tumour MRGlu was calculated and compared with objective response at 8 weeks. Pretreatment MRGlu was higher in responders than non-responders. The responding patient group had a greater than 25% reduction in MRGlu in regions of high focal tumour uptake (HFU). Whole tumour changes in MRGlu did not correlate with response. Percentage change in HFU standardized uptake value (SUV) did discriminate the responding from the non-responding patients, but not as well as with MRGlu. Large differences also occurred in the normal brain SUV following treatment. Thus, MRGlu appeared to be a more sensitive discriminator of response than the simplified static SUV analysis. Changes in MRGlu may reflect the degree of cell kill following chemotherapy and so may provide an objective, quantitative subclinical measure of response to therapy
AD  - MRC Cyclotron Unit, Hammersmith Campus, Imperial College of Science and Medicine, London, UK. PMID- 0010682673 MHDA- 2000/03/04 09:00 EDAT- 2000/02/22 09:00
ER  - 

TY  - JOUR
T1  - In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism
A1  - Herholz,K.
A1  - Bauer,B.
A1  - Wienhard,K.
A1  - Kracht,L.
A1  - Mielke,R.
A1  - Lenz,O.
A1  - Strotmann,T.
A1  - Heiss,W.-D.
Y1  - 2000///
SP  - 1457
EP  - 1468
JA  - J.Neural Transm.
VL  - 12
ER  - 

TY  - JOUR
T1  - PET-Determination of robalzotan (NAD-299) induced 5-HT(1A) receptor occupancy in the monkey brain
A1  - Farde,L.
A1  - Andree,B.
A1  - Ginovart,N.
A1  - Halldin,C.
A1  - Thorberg,S.
Y1  - 2000/04//
N1  - Eng
SP  - 422
EP  - 429
JF  - Neuropsychopharmacology
VL  - 22
IS  - 4
N2  - The serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor subtype is of central interest in research, particularly in the area of pathophysiology and pharmacological treatment of psychiatric disorders. Robalzotan (generic name for NAD-299) is a new putative drug that binds with high selectivity and affinity to 5-HT(1A)-receptors in the rodent brain in vitro and in vivo. The aim of this positron emission tomography study was to determine 5-HT(1A) receptor occupancy in the cynomolgus monkey brain in vivo after IV injection of robalzotan. Two healthy monkeys were examined with Positron Emission Tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635, the first after IV administration of 2 &mgr;g/kg and 20 &mgr;g/kg, and the second after 10 &mgr;g/kg and 100 &mgr;g/kg IV. 5-HT(1A) receptor occupancy was calculated using an equilibrium-ratio analysis. Robalzotan occupied 5-HT(1A) receptors in a dose-dependent and saturable manner. The highest 5-HT(1A) receptor occupancy (70-80%) was attained after 100 &mgr;g/kg. The relationship between robalzotan drug concentration and 5-HT(1A) receptor occupancy could be described by a hyperbolic function, which can be used to guide the selection of appropriate doses for the initial studies in man. The study further corroborates that quantitative neuroimaging of receptor binding has potentials for the evaluation and dose finding of new CNS drugs
AD  - Karolinska Institutet, Stockholm, Sweden
ER  - 

TY  - JOUR
T1  - Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex
A1  - Volkow,N.D.
A1  - Fowler,J.S.
Y1  - 2000/03//
N1  - Eng
SP  - 318
EP  - 325
JA  - Cereb.Cortex
VL  - 10
IS  - 3
N2  - Understanding the changes in the brain which occur in the transition from normal to addictive behavior has major implications in public health. Here we postulate that while reward circuits (nucleus accumbens, amygdala), which have been central to theories of drug addiction, may be crucial to initiate drug self-administration, the addictive state also involves disruption of circuits involved with compulsive behaviors and with drive. We postulate that intermittent dopaminergic activation of reward circuits secondary to drug self-administration leads to dysfunction of the orbitofrontal cortex via the striato-thalamo-orbitofrontal circuit. This is supported by imaging studies showing that in drug abusers studied during protracted withdrawal, the orbitofrontal cortex is hypoactive in proportion to the levels of dopamine D2 receptors in the striatum. In contrast, when drug abusers are tested shortly after last cocaine use or during drug-induced craving, the orbitofrontal cortex is hypermetabolic in proportion to the intensity of the craving. Because the orbitofrontal cortex is involved with drive and with compulsive repetitive behaviors, its abnormal activation in the addicted subject could explain why compulsive drug self-administration occurs even with tolerance to the pleasurable drug effects and in the presence of adverse reactions. This model implies that pleasure per se is not enough to maintain compulsive drug administration in the drugaddicted subject and that drugs that could interfere with the activation of the striato-thalamo-orbitofrontal circuit could be beneficial in the treatment of drug addiction
AD  - Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY 11973 and Department of Psychiatry, SUNY-Stony Brook, Stony Brook, NY 11794, USA
ER  - 

TY  - JOUR
T1  - Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wang,G.J.
Y1  - 1999/12//
N1  - Eng
SP  - 337
EP  - 345
JA  - J.Psychopharmacol.
VL  - 13
IS  - 4
N2  - We summarize our studies with positron emission tomography investigating the role of dopamine (DA) in the reinforcing effects of cocaine and methylphenidate in humans and its involvement in cocaine addiction. These studies have shown that the rate at which cocaine and methylphenidate enter the brain and block the dopamine transporters (DAT) is the variable associated with the 'high', rather than the presence per se of the drug in the brain. Our studies also show that, while the level of DAT blockade is important in predicting the intensity of the 'high' induced by these drugs (DAT blockade > 50% is required for these drugs to induce a 'high'), the rate at which DAT are blocked determines whether the 'high' is perceived or not. Thus, oral methylphenidate, which leads to slow DAT blockade, does not induce a 'high', even at doses which block DAT more than 60%. In cocaine abusers, we have shown significant reductions in DA D2 receptors that are associated with decreased metabolism in cingulate gyrus and in orbitofrontal cortex. We suggest that this is one of the mechanisms by which DA disruption leads to compulsive drug administration in cocaine addiction. Cocaine abusers also show significant decreases in DA release, which coupled with the reduction in D2 receptors may result in decreased activation of reward circuits by physiological reinforcers and may perpetuate cocaine use as a means to compensate for this deficit. Thus, strategies to enhance DA brain function in ways that mimic physiological DA activity may be of help in overcoming cocaine addiction
AD  - Department of Medicine, Brookhaven National Laboratory, Upton, New York, NY 11973, USA. volkow@bnl.gov
ER  - 

TY  - JOUR
T1  - Occupancy of brain nicotinic acetylcholine receptors by nicotine doses equivalent to those obtained when smoking a cigarette [In Process Citation]
A1  - Ding,Y.S.
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - Garza,V.
A1  - Pappas,N.
A1  - King,P.
A1  - Fowler,J.S.
Y1  - 2000/03/01/
N1  - Eng
SP  - 234
EP  - 237
JF  - Synapse
VL  - 35
IS  - 3
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York
ER  - 

TY  - JOUR
T1  - Toxicodynamics and long-term toxicity of the recreational drug, 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy')
A1  - Ricaurte,G.A.
A1  - McCann,U.D.
A1  - Szabo,Z.
A1  - Scheffel,U.
Y1  - 2000/03/15/
N1  - ENG
SP  - 143
EP  - 146
JA  - Toxicol.Lett.
VL  - 112-113
IS  - 8
N2  - The recreational drug, (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), is a potent serotonin (5-HT) neurotoxin in animals. Whether humans who use MDMA incur 5-HT neural injury is unknown. The present studies utilized positron emission tomography (PET) in conjunction with the 5-HT transporter ligand, [11C]McN-5652 to assess the status of brain 5-HT neurons in human MDMA users. Like nonhuman primates treated with neurotoxic doses of MDMA, humans with a history of MDMA use showed lasting decrements in global brain [11C]McN-5652 binding, with decreases in [11C]McN-5652 binding positively correlated to the extent of previous MDMA use. These results suggest that human MDMA use results in brain 5-HT neurotoxicity
AD  - Department of Neurology, Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Baltimore, MD, USA PMID- 0010720723 PID - S0378427499002167 PST - ppublish
ER  - 

TY  - JOUR
T1  - Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand
A1  - Szabo,Z.
A1  - Scheffel,U.
A1  - Mathews,W.B.
A1  - Ravert,H.T.
A1  - Szabo,K.
A1  - Kraut,M.
A1  - Palmon,S.
A1  - Ricaurte,G.A.
A1  - Dannals,R.F.
Y1  - 1999/09//
N1  - Eng
SP  - 967
EP  - 981
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 9
N2  - The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](-)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (f(max)), its retention value at 75 minutes (fT), and its normalized retention (f(rel) = fT/f(max)) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DV(T)) and its specific binding component (DV(S)). Both the noncompartmental (fT,f(rel)) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](-)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter f(rel) demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, f(rel) demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform lnDV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental f(rel) with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters (k1, k2, and BV), and that both the noncompartmental parameter f(rel) and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted
AD  - Division of Nuclear Medicine, Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. PMID- 0010478648 EDAT- 1999/09/09 09:00 MHDA- 1999/09/09 09:00
ER  - 

TY  - JOUR
T1  - Dose-response and duration effects of acute administrations of cocaine and GBR12909 on dopamine synthesis and transporter in the conscious monkey brain: PET studies combined with microdialysis
A1  - Tsukada,H.
A1  - Harada,N.
A1  - Nishiyama,S.
A1  - Ohba,H.
A1  - Kakiuchi,T.
Y1  - 2000/03/31/
N1  - ENG
SP  - 141
EP  - 148
JA  - Brain Res.
VL  - 860
IS  - 1-2
N2  - The dose-response and duration effects of acute administration of the dopamine transporter (DAT) blocker cocaine and GBR12909 on dopamine synthesis and transporter availability were evaluated in the brains of conscious monkeys using high-resolution positron emission tomography (PET) in combination with microdialysis. Rate of dopamine synthesis and DAT availability were evaluated using L-[beta-11C]DOPA and [11C]beta-CFT (WIN35,428), respectively. Administration of cocaine (0.5, 2 and 5 mg/kg) resulted in dose-dependent elevation of dopamine level in the striatal extracellular fluid (ECF) at 0.5 h after injection, and returned to the baseline level within 1.5 h post-injection. At 0.5 post-injection, cocaine reduced dopamine synthesis rate and DAT availability in a dose-dependent manner. The reduction of DAT availability by cocaine (2 mg/kg) returned to baseline level at 3 h post-injection and thereafter. Interestingly, dopamine synthesis rate was significantly higher at 3 h than baseline level and returned to baseline level 5.5 h post-injection. When GBR12909 (0.5, 2 and 5 mg/kg) was administered 0.5 h before tracer injection, dopamine synthesis rate and DAT availability were significantly decreased in a dose-dependent manner. These reductions induced by GBR12909 (2 mg/kg) lasted at least until 5.5 h post-injection. GBR12909 induced dose-dependent elevation of dopamine level in ECF, and the elevation lasted up to 7 h. The present results indicated that cocaine and GBR12909 affect dopamine synthesis rate and DAT availability in the striatum with difference time courses as measured by PET in the conscious monkey brains
AD  - Central Research Laboratory, Hamamatsu Photonics, 5000 Hirakuchi, Hamakita, Japan PMID- 0010727633 PID - S0006899300020576 URLF- http://www.elsevier.com:80/cgi-bin/cas/tree/store/bres/cas_sub/browse/brow se.cgi?year=2000&volume=860&issue=1-2&aid=16377 PST - ppublish
ER  - 

TY  - JOUR
T1  - Functional changes in brain activity during priming in Alzheimer's disease
A1  - Backman,L.
A1  - Almkvist,O.
A1  - Nyberg,L.
A1  - Anderson,J.
Y1  - 2000/01//
N1  - Eng
SP  - 134
EP  - 141
JA  - J.Cogn Neurosci.
VL  - 12
IS  - 1
N2  - Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Using positron emission tomography (PET), we here provide direct support for this view. Compared with normal old adults, AD patients showed reduced priming on a word-stem completion task. The normal old showed decreased activity in right occipital cortex (area 19), whereas the AD patients showed increased activity in this region during priming. To the extent that decreased activity during priming reflects an experience-dependent reduction of the neuronal population involved, these results indicate that shaping of the relevant neurons is slower in AD, possibly as a result of inadequate initial stimulus-processing
AD  - Uppsala University, Stockholm Gerontology Research Center, and Karolinska Institute
ER  - 

TY  - JOUR
T1  - 6-[18F]Fluoro-A-85380: an in vivo tracer for the nicotinic acetylcholine receptor [In Process Citation]
A1  - Scheffel,U.
A1  - Horti,A.G.
A1  - Koren,A.O.
A1  - Ravert,H.T.
A1  - Banta,J.P.
A1  - Finley,P.A.
A1  - London,E.D.
A1  - Dannals,R.F.
Y1  - 2000/01//
N1  - Eng
SP  - 51
EP  - 56
JA  - Nucl.Med.Biol.
VL  - 27
IS  - 1
N2  - 6-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380 or 6-[18F]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [18F] fluorination of 6-iodo-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[18F]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect
AD  - Division of Nuclear Medicine and Radiation Health Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179, USA
ER  - 

TY  - JOUR
T1  - 11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI
A1  - Koepp,M.J.
A1  - Hammers,A.
A1  - Labbe,C.
A1  - Woermann,F.G.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 2000/01/25/
N1  - Eng
SP  - 332
EP  - 339
JF  - Neurology
VL  - 54
IS  - 2
N2  - BACKGROUND: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE). OBJECTIVE: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI. METHODS: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis. RESULTS: Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings. CONCLUSIONS: 11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK. PMID- 0010668692 MHDA- 2000/02/26 09:00 EDAT- 2000/02/11 09:00
ER  - 

TY  - JOUR
T1  - A common language network for comprehension and production: A contribution to the definition of language epicenters with PET [In Process Citation]
A1  - Papathanassiou,D.
A1  - Etard,O.
A1  - Mellet,E.
A1  - Zago,L.
A1  - Mazoyer,B.
A1  - Tzourio-Mazoyer,N.
Y1  - 2000/04//
N1  - Eng
SP  - 347
EP  - 357
JA  - Neuroimage.
VL  - 11
IS  - 4
N2  - In this paper, we report on a PET activation study designed to assess whether functional neuroimaging would help to uncover essential language areas in normal volunteers and to provide a more accurate definition of their localization. Regional cerebral blood flow was repeatedly monitored in eight right-handed male volunteers, while performing a language comprehension task (listening to factual stories) and a language production task (covert generation of verbs semantically related to heard nouns), using silent resting as a control condition. The conjunction analysis, conducted with SPM, was used to uncover the network of activations common to both task that included three left hemisphere areas, namely (1) the pars opercularis and triangularis of the inferior frontal gyrus, (2) the posterior part of the superior temporal cortex centered around the superior temporal sulcus, extending to the planum temporale posterior part but sparing the supramarginalis and angular gyri, and (3) the most anterior part of the left inferior temporal gyrus at the junction with the anterior fusiform gyrus. The inferior and lateral parts of the right cerebellar cortex were also included in the conjunction network. Each of the three cortical areas, when they are site of lesion or electrical stimulation, elicit impairment in both language comprehension and production and can thus be considered as essential to language. Accordingly, the present results provide conservative anatomofunctional definitions of the Broca, Wernicke, and basal language areas. Interestingly, contralateral homologues of Broca's and Wernicke's areas also lighted up in the conjunction analysis that could be related to the interindividual variability of hemispheric language dominance. Copyright 2000 Academic Press
AD  - Groupe d'Imagerie Neurofonctionnelle (GIN), UPRES EA 2127 Universite de Caen & CEA LRC 13V, GIP Cyceron, Bld Henri Becquerel, 14074 Caen Cedex, France
ER  - 

TY  - JOUR
T1  - Benign prognosis of never-symptomatic carotid occlusion
A1  - Powers,W.J.
A1  - Derdeyn,C.P.
A1  - Fritsch,S.M.
A1  - Carpenter,D.A.
A1  - Yundt,K.D.
A1  - Videen,T.O.
A1  - Grubb,R.L.,Jr.
Y1  - 2000/02/22/
N1  - Eng
SP  - 878
EP  - 882
JF  - Neurology
VL  - 54
IS  - 4
N2  - OBJECTIVE: To determine the prognosis of asymptomatic carotid artery occlusion. BACKGROUND: As opposed to symptomatic carotid occlusion, little information is available on the prognosis of asymptomatic carotid occlusion. METHOD: Thirty never-symptomatic and 81 symptomatic patients with carotid occlusion underwent baseline assessment of 15 risk factors together with PET measurements of oxygen extraction fraction (OEF). Every 6-month telephone contact recorded interval medical treatment and subsequent stroke occurrence during an average follow-up of 32 months. Patients, treating physicians, and an end point adjudicator were blinded to PET results. RESULTS: Ischemic stroke occurred in 1 of 30 of never-symptomatic patients (3.3%) and 15 of 81 of symptomatic patients (18.5%; p = 0.03). No strokes in the carotid territory distal to the occluded vessel occurred in the never-symptomatic patients. Multivariate analysis of baseline risk factors for all 111 patients revealed that age, plasma fibrinogen level, and PET findings of high OEF distal to the occluded carotid artery were the only independent predictors of subsequent stroke (p < 0.05). Previous ipsilateral hemispheric or retinal symptoms was not a significant predictive variable. The lower risk of stroke in never-symptomatic patients was associated with a lower incidence of high OEF (4 of 30) as opposed to symptomatic patients (39 of 81; p = 0.002), but there was no significant difference in age or fibrinogen level. CONCLUSIONS: Never-symptomatic carotid occlusion carries a very low risk of subsequent ischemic stroke. This benign prognosis is associated with a low incidence of cerebral hemodynamic compromise in these patients. These data support further the importance of hemodynamic factors in the pathogenesis of ischemic stroke in patients with carotid occlusion
AD  - Department of Neurology and Neurological Surgery, Edward Mallinckrodt Institute of Radiology, St. Louis, MO, USA. PMID- 0010690980 MHDA- 2000/04/01 09:00 EDAT- 2000/02/26 09:00
ER  - 

TY  - JOUR
T1  - High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635
A1  - Le Bars,D.
A1  - Lemaire,C.
A1  - Ginovart,N.
A1  - Plenevaux,A.
A1  - Aerts,J.
A1  - Brihaye,C.
A1  - Hassoun,W.
A1  - Leviel,V.
A1  - Mekhsian,P.
A1  - Weissmann,D.
A1  - Pujol,J.F.
A1  - Luxen,A.
A1  - Comar,D.
Y1  - 1998/05//
N1  - Eng
SP  - 343
EP  - 350
JA  - Nucl.Med.Biol.
VL  - 25
IS  - 4
N2  - No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis. Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand
AD  - CERMEP, Lyon, France. lebars@univ-lyon1.fr PMID- 0009639295 EDAT- 1998/06/25 02:04 MHDA- 1998/06/25 02:04
ER  - 

TY  - JOUR
T1  - Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures
A1  - Studholme,C.
A1  - Hill,D.L.
A1  - Hawkes,D.J.
Y1  - 1997/01//
N1  - Eng
SP  - 25
EP  - 35
JA  - Med.Phys.
VL  - 24
IS  - 1
N2  - Approaches using measures of voxel intensity similarity are showing promise in fully automating magnetic resonance (MR) and positron emission tomography (PET) image registration in the head, without requiring extraction and identification of corresponding structures. In this paper a method of multiresolution optimization of these measures is described and five alternative measures are compared: cross correlation, minimization of corresponding PET intensity variation, moments of the distribution of values in the intensity feature space, entropy of the intensity feature space and mutual information. Their ability to recover registration is examined for ten clinically acquired image pairs with respect to the size of initial misregistration, the precision of the final result, and the accuracy assessed by visual inspection. The mutual information measure proved the most robust to initial starting estimate, successfully registering 98.8% of 900 trial misregistrations. Success is defined as providing a visually acceptable solution to a trained observer. A high resolution search (1/16 mm step size) of 30 trial misregistrations showed that optimization using the mutual information measure provided solutions with 0.13 mm, 0.11 mm and 0.17 mm standard deviations in the three Cartesian axes of the translation vector and 0.2 degree, 0.3 degree and 0.2 degree standard deviations for rotations about the three axes. The algorithm takes between 4 and 8 minutes to run on a typical workstation, including visual inspection of the result
AD  - Division of Radiological Sciences, United Medical School of Guy's Hospital, London, United Kingdom. PMID- 0009029539 EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:00
ER  - 

TY  - JOUR
T1  - Language dominance in neurologically normal and epilepsy subjects: a functional MRI study [see comments]
A1  - Springer,J.A.
A1  - Binder,J.R.
A1  - Hammeke,T.A.
A1  - Swanson,S.J.
A1  - Frost,J.A.
A1  - Bellgowan,P.S.
A1  - Brewer,C.C.
A1  - Perry,H.M.
A1  - Morris,G.L.
A1  - Mueller,W.M.
Y1  - 1999/11//
N1  - Eng
SP  - 2033
EP  - 2046
JF  - Brain
VL  - 122
IS  - Pt 11
N2  - Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness
AD  - University of Iowa Hospital and Clinics, Iowa City, USA
ER  - 

TY  - JOUR
T1  - Functional MR of frontal lobe activation: comparison with Wada language results
A1  - Yetkin,F.Z.
A1  - Swanson,S.
A1  - Fischer,M.
A1  - Akansel,G.
A1  - Morris,G.
A1  - Mueller,W.
A1  - Haughton,V.
Y1  - 1998/06//
N1  - Eng
SP  - 1095
EP  - 1098
JA  - AJNR Am.J.Neuroradiol.
VL  - 19
IS  - 6
N2  - PURPOSE: Our purpose was to determine the utility of functional MR imaging in conjunction with a word-generation paradigm in the assessment of language lateralization. METHODS: Functional MR imaging and Wada testing for language lateralization was performed in patients with complex partial seizures during the performance of word-generation tasks. A language lateralization quotient was calculated from the number of activated pixels in the right and left hemispheres. A language laterality score was derived from the Wada results as the percentage of correct responses during right internal carotid artery injection minus the percentage of correct responses during left internal carotid injection. A correlation coefficient between the functional MR imaging results and the Wada language laterality scores was calculated. RESULTS: In 13 patients, hemispheric dominance based on Wada testing was confirmed by functional MR imaging during silent word generation. The Wada laterality scores varied from 100 to -100 and the functional MR imaging scores varied from 100 to -10. The language lateralization scores determined by functional MR imaging correlated significantly with the language lateralization scores derived from Wada testing. CONCLUSION: Functional MR imaging performed during word generation is an accurate method for lateralizing language function in patients with complex partial epilepsy
AD  - Department of Radiology, Medical College of Wisconsin, Milwaukee 53226, USA. PMID- 0009672017 EDAT- 1998/07/22 02:14 MHDA- 1998/07/22 02:14
ER  - 

TY  - JOUR
T1  - Neuronal nicotinic receptors in the human brain [In Process Citation]
A1  - Paterson,D.
A1  - Nordberg,A.
Y1  - 2000/05//
N1  - Eng
SP  - 75
EP  - 111
JA  - Prog.Neurobiol.
VL  - 61
IS  - 1
N2  - Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multiple subtypes of these receptors exist, each with individual pharmacological and functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural processes and are additionally implicated in a number of pathological conditions such as Alzheimer's disease, Parkinson's disease and schizophrenia. The nAChRs have a pentameric structure composed of five membrane spanning subunits, of which nine different types have thus far been identified and cloned. The multiple subunits identified provide the basis for the heterogeneity of structure and function observed in the nAChR subtypes and are responsible for the individual characteristics of each. A substantial amount of information on human nAChR structure and function has come from studies on neuroblastoma cell lines which naturally express nAChRs and from recombinant nAChRs expressed in Xenopus oocytes. In vitro brain nAChR distribution can be mapped with a number of appropriate agonist and antagonist radioligands and subunit distribution may be mapped by in situ hybridization using subunit specific mRNA probes. Receptor distribution in the living human brain can be studied with noninvasive imaging techniques such as PET and SPECT, with a significant reduction in nAChRs in the brains of Alzheimer's patients having been identified with [11C] nicotine in PET studies. Despite the significant body of knowledge now accumulated about nAChRs, much remains to be elucidated. This review will attempt to describe the current knowledge on the nAChR subtypes in the human brain, their functional roles and neuropathological involvement
AD  - Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Karolinska Institute, Huddinge Univerity Hospital, Sweden
ER  - 

TY  - JOUR
T1  - Movement-related cortical potentials and regional cerebral blood flow change in patients with stroke after motor recovery
A1  - Honda,M.
A1  - Nagamine,T.
A1  - Fukuyama,H.
A1  - Yonekura,Y.
A1  - Kimura,J.
A1  - Shibasaki,H.
Y1  - 1997/03/10/
N1  - Eng
SP  - 117
EP  - 126
JA  - J.Neurol.Sci.
VL  - 146
IS  - 2
N2  - We investigated brain activity during the self-initiated, simple, repetitive hand movement in two patients with hemiparesis due to stroke, who showed relatively good motor recovery, using movement-related cortical potential (MRCP) and regional cerebral blood flow (rCBF) measurements with positron emission tomography (PET). One patient had cortical lesions in the left premotor and left parietal cortices due to cerebral thrombosis, and the other had lesions in the right Rolandic area and several subcortical areas due to the occlusion of the right internal carotid artery. MRCPs in both patients showed lack of the contralateral predominance in amplitude of the late component of slow negative shift prior to the movement of the recovered hand. PET activation study showed increased rCBF in the ipsilateral hemisphere during the movement of the recovered hand. These findings suggest that the ipsilateral hemisphere to the recovered hand may play an important role in the process of motor recovery in patients with cortical infarction, especially within the time period of several hundred ms before the onset of each movement
AD  - Department of Brain Pathophysiology, Kyoto University School of Medicine, Sakyo-ku, Japan. honda@nih.gov PMID- 0009077507 EDAT- 1997/03/10 00:00 MHDA- 1997/03/10 00:00
ER  - 

TY  - JOUR
T1  - Role of the premotor cortex in recovery from middle cerebral artery infarction
A1  - Seitz,R.J.
A1  - Hoflich,P.
A1  - Binkofski,F.
A1  - Tellmann,L.
A1  - Herzog,H.
A1  - Freund,H.J.
Y1  - 1998/08//
N1  - Eng
SP  - 1081
EP  - 1088
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 55
IS  - 8
N2  - OBJECTIVE: To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. INTERVENTIONS: Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. RESULTS: The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. CONCLUSIONS: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated
AD  - Department of Neurology, Heinrich-Heine-University Dusseldorf, Germany. Seitz@neurologie.uni-duesseldorf.de PMID- 0009708958 EDAT- 1998/08/26 02:18 MHDA- 1998/08/26 02:18
ER  - 

TY  - JOUR
T1  - Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease
A1  - Small,G.W.
A1  - Ercoli,L.M.
A1  - Silverman,D.H.
A1  - Huang,S.C.
A1  - Komo,S.
A1  - Bookheimer,S.Y.
A1  - Lavretsky,H.
A1  - Miller,K.
A1  - Siddarth,P.
A1  - Rasgon,N.L.
A1  - Mazziotta,J.C.
A1  - Saxena,S.
A1  - Wu,H.M.
A1  - Mega,M.S.
A1  - Cummings,J.L.
A1  - Saunders,A.M.
A1  - Pericak-Vance,M.A.
A1  - Roses,A.D.
A1  - Barrio,J.R.
A1  - Phelps,M.E.
Y1  - 2000/05/23/
N1  - Eng
SP  - 6037
EP  - 6042
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 97
IS  - 11
N2  - The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments
AD  - Center on Aging and Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu PMID- 0010811879 PID - 090106797 DOI - 10.1073/pnas.090106797 PST - ppublish EDAT- 2000/05/17 09:00 MHDA- 2000/07/08 11:00
ER  - 

TY  - JOUR
T1  - Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability
A1  - Chui,H.C.
A1  - Mack,W.
A1  - Jackson,J.E.
A1  - Mungas,D.
A1  - Reed,B.R.
A1  - Tinklenberg,J.
A1  - Chang,F.L.
A1  - Skinner,K.
A1  - Tasaki,C.
A1  - Jagust,W.J.
Y1  - 2000/02//
N1  - Eng
SP  - 191
EP  - 196
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 57
IS  - 2
N2  - BACKGROUND: Several clinical criteria have been developed to standardize the diagnosis of vascular dementia (VaD). Significant differences in patient classification have been reported, depending on the criteria used. Few studies have examined interrater reliability. OBJECTIVE: To assess the concordance in classification and interrater reliability for the following 4 clinical definitions of VaD: the Hachinski Ischemic Score (HIS), the Alzheimer Disease Diagnostic and Treatment Centers (ADDTC), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). METHODS: Structured diagnostic checklists were developed for 4 criteria for VaD, 2 criteria for Alzheimer disease (AD), and 4 criteria for dementia. Twenty-five case vignettes, representing a spectrum of cognitive impairment and subtypes of dementia, were prepared in a standardized clinical format. Concordance in case classification using different criteria and interrater reliability among 7 ADDTCs given a specific set of criteria was assessed using the kappa statistic. RESULTS: The frequency of a diagnosis of VaD was highest using the modified HIS or DSM-IV criteria, intermediate using the original HIS and ADDTC criteria, and lowest using the NINDS-AIREN criteria. Scores for interrater reliability ranged from kappa = 0.30 (ADDTC) to kappa = 0.61 (original HIS). CONCLUSIONS: Clinical criteria for VaD are not interchangeable. Depending on the criteria selected, the reported prevalence of VaD will vary significantly. The traditional HIS has higher interrater reliability than the newer criteria for VaD. Prospective longitudinal studies with clinical-pathological correlation are needed to compare validity
AD  - Geriatric Neurobehavior and Alzheimer Center, Rancho Los Amigos National Rehabilitation Center, Downey, CA 90242, USA. chui@hsc.usc.edu
ER  - 

TY  - JOUR
T1  - Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: a positron emission tomography study
A1  - Shinotoh,H.
A1  - Namba,H.
A1  - Fukushi,K.
A1  - Nagatsuka,S.
A1  - Tanaka,N.
A1  - Aotsuka,A.
A1  - Ota,T.
A1  - Tanada,S.
A1  - Irie,T.
Y1  - 2000/08//
N1  - Eng
SP  - 194
EP  - 200
JA  - Ann.Neurol.
VL  - 48
IS  - 2
N2  - We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three- compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD
AD  - Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan
ER  - 

TY  - JOUR
T1  - Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain
A1  - Thompson,P.M.
A1  - Woods,R.P.
A1  - Mega,M.S.
A1  - Toga,A.W.
Y1  - 2000/02//
N1  - Eng
SP  - 81
EP  - 92
JA  - Hum.Brain Mapp.
VL  - 9
IS  - 2
N2  - Striking variations in brain structure, especially in the gyral patterns of the human cortex, present fundamental challenges in human brain mapping. Probabilistic brain atlases, which encode information on structural and functional variability in large human populations, are powerful research tools with broad applications. Knowledge-based imaging algorithms can also leverage atlased information on anatomic variation. Applications include automated image labeling, pathology detection in individuals or groups, and investigating how regional anatomy is altered in disease, and with age, gender, handedness and other clinical or genetic factors. In this report, we illustrate some of the mathematical challenges involved in constructing population-based brain atlases. A disease-specific atlas is constructed to represent the human brain in Alzheimer's disease (AD). Specialized strategies are developed for population-based averaging of anatomy. Sets of high-dimensional elastic mappings, based on the principles of continuum mechanics, reconfigure the anatomy of a large number of subjects in an anatomic image database. These mappings generate a local encoding of anatomic variability and are used to create a crisp anatomical image template with highly resolved structures in their mean spatial location. Specialized approaches are also developed to average cortical topography. Since cortical patterns are altered in a variety of diseases, gyral pattern matching is used to encode the magnitude and principal directions of local cortical variation. In the resulting cortical templates, subtle features emerge. Regional asymmetries appear that are not apparent in individual anatomies. Population-based maps of cortical variation reveal a mosaic of variability patterns that segregate sharply according to functional specialization and cytoarchitectonic boundaries
AD  - Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769, USA. thompson@loni.ucla.edu PMID- 0010680765 MHDA- 2000/03/04 09:00 EDAT- 2000/02/19 09:00 PID - 10.1002/(SICI)1097-0193(200002)9:2&#60;81::AID-HBM3&#62;3.0.CO;2-8
ER  - 

TY  - JOUR
T1  - Analyzing functional brain images in a probabilistic atlas: a validation of subvolume thresholding
A1  - Dinov,I.D.
A1  - Mega,M.S.
A1  - Thompson,P.M.
A1  - Lee,L.
A1  - Woods,R.P.
A1  - Holmes,C.J.
A1  - Sumners,D.W.
A1  - Toga,A.W.
Y1  - 2000/01//
N1  - Eng
SP  - 128
EP  - 138
JA  - J.Comput.Assist.Tomogr.
VL  - 24
IS  - 1
N2  - PURPOSE: The development of structural probabilistic brain atlases provides the framework for new analytic methods capable of combining anatomic information with the statistical mapping of functional brain data. Approaches for statistical mapping that utilize information about the anatomic variability and registration errors of a population within the Talairach atlas space will enhance our understanding of the interplay between human brain structure and function. METHOD: We present a subvolume thresholding (SVT) method for analyzing positron emission tomography (PET) and single photon emission CT data and determining separately the statistical significance of the effects of motor stimulation on brain perfusion. Incorporation of a priori anatomical information into the functional SVT model is achieved by selecting a proper anatomically partitioned probabilistic atlas for the data. We use a general Gaussian random field model to account for the intrinsic differences in intensity distribution across brain regions related to the physiology of brain activation, attenuation effects, dead time, and other corrections in PET imaging and data reconstruction. RESULTS: H2(15)O PET scans were acquired from six normal subjects under two different activation paradigms: left-hand and right-hand finger-tracking task with visual stimulus. Regional region-of-interest and local (voxel) group differences between the left and right motor tasks were obtained using nonparametric stochastic variance estimates. As expected from our simple finger movement paradigm, significant activation (z = 6.7) was identified in the left motor cortex for the right movement task and significant activation (z = 6.3) for the left movement task in the right motor cortex. CONCLUSION: We propose, test, and validate a probabilistic SVT method for mapping statistical variability between groups in subtraction paradigm studies of functional brain data. This method incorporates knowledge of, and controls for, anatomic variability contained in modern human brain probabilistic atlases in functional statistical mapping of the brain
AD  - Department of Neurology, University of California at Los Angeles, 90095-1769, USA. PMID- 0010667672 MHDA- 2000/02/19 09:00 EDAT- 2000/02/10 09:00
ER  - 

TY  - JOUR
T1  - Mapping biochemistry to metabolism: FDG-PET and amyloid burden in Alzheimer's disease
A1  - Mega,M.S.
A1  - Chu,T.
A1  - Mazziotta,J.C.
A1  - Trivedi,K.H.
A1  - Thompson,P.M.
A1  - Shah,A.
A1  - Cole,G.
A1  - Frautschy,S.A.
A1  - Toga,A.W.
Y1  - 1999/09/29/
N1  - Eng
SP  - 2911
EP  - 2917
JF  - Neuroreport
VL  - 10
IS  - 14
N2  - We evaluated the relationship between amyloid-beta protein (A beta) concentration and the metabolic abnormality in an Alzheimer's disease (AD) patient as measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Across most regions there were significant inverse correlations among FDG-PET intensity values and both insoluble. The temporal lobe samples showed no significant correlation between FDG-PET values and A beta deposition. Findings support A beta as contributing to the hypometabolism in regions of the AD brain that are still relatively viable metabolically; those regions with chronic pathologic damage, such as temporal cortex, may have other factors that contribute to metabolic deficits
AD  - Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA. PMID- 0010549796 EDAT- 1999/11/05 08:00 MHDA- 1999/11/05 08:00
ER  - 

TY  - JOUR
T1  - PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD
A1  - Kemppainen,N.
A1  - Ruottinen,H.
A1  - Nagren,K.
A1  - Rinne,J.O.
Y1  - 2000/07/25/
N1  - Eng
SP  - 205
EP  - 209
JF  - Neurology
VL  - 55
IS  - 2
N2  - OBJECTIVE: To study dopamine D1 and D2 receptors in the putamen and the caudate nucleus in patients with AD and age-matched healthy controls by means of PET. METHODS: A dopamine D1 receptor antagonist ([11C]NNC 756) and a D2 receptor antagonist ([11C]raclopride) were used as ligands. The uptake of these ligands was calculated as a distribution volume ratio of the putamen and the caudate nucleus to the cerebellum. RESULTS: The mean [11C]NNC 756 uptake in AD was reduced by 14% from the mean control value both in the putamen (p = 0.004) and the caudate nucleus (p = 0.009). There was no significant reduction in the mean [11C]raclopride uptake in either the putamen or the caudate nucleus in AD. There was no correlation between [11C]NNC 756 or [11C]raclopride uptake and Mini-Mental State Examination or motor Unified PD Rating Scale scores in patients with AD. CONCLUSIONS: There are changes in striatal D1 but not in D2 receptors in AD
AD  - Department of Neurology, University of Turku, Finland. PMID- 0010908891 PST - ppublish MHDA- 2000/08/19 11:00 EDAT- 2000/07/26 11:00
ER  - 

TY  - JOUR
T1  - The influence of age on stroke outcome. The Copenhagen Stroke Study
A1  - Nakayama,H.
A1  - Jorgensen,H.S.
A1  - Raaschou,H.O.
A1  - Olsen,T.S.
Y1  - 1994/04//
N1  - Eng
SP  - 808
EP  - 813
JF  - Stroke
VL  - 25
IS  - 4
N2  - BACKGROUND AND PURPOSE: This study was undertaken to elucidate whether and how age influences stroke outcome. METHODS: This prospective and community-based study comprised 515 consecutive acute stroke patients. Computed tomographic scan was performed in 79% of patients. Activities of daily living (ADL) and neurological status were assessed weekly during hospital stay using the Barthel Index (BI) and the Scandinavian Stroke Scale (SSS), respectively. Information regarding social condition and comorbidity before stroke was also registered. A multiple regression model was used to analyze the independent influence of age on stroke outcome. RESULTS: Age was not related to the type of stroke lesion or infarct size. However, age independently influenced initial BI (-4 points per 10 years, P < .01), initial SSS (-2 points per 10 years, P = .01), and discharge BI (-3 points per 10 years, P < .01). No independent influence of age was found regarding mortality within 3 months, discharge SSS, length of hospital stay, and discharge placement. ADL improvement was influenced independently by age (-3 points per 10 years, P < .01), whereas age had no influence on neurological improvement or on speed of recovery. CONCLUSIONS: Age independently influences stroke outcome selectively in ADL-related aspects (BI) but not in neurological aspects (SSS), suggesting a poorer compensatory ability in elderly stroke patients. Therefore, rehabilitation of elderly stroke patients should be focused more on ADL and compensation rather than on the recovery of neurological status, and age itself should not be a selection criterion for rehabilitation
AD  - Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. PMID- 0008160225 EDAT- 1994/04/01 00:00 MHDA- 1994/04/01 00:00
ER  - 

TY  - JOUR
T1  - Radiosynthesis of 3'-deoxy-3'-[(18)F]fluorothymidine: [(18)F]FLT for imaging of cellular proliferation in vivo
A1  - Grierson,J.R.
A1  - Shields,A.F.
Y1  - 2000/02//
N1  - Eng
SP  - 143
EP  - 156
JA  - Nucl.Med.Biol.
VL  - 27
IS  - 2
N2  - A reliable radiosynthesis of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) has been developed based on [(18)10 mCi (370 MBq) of radiochemically pure [(18)1 Ci/micromol (37 GBq/&mgr;mol) at EOS within 100 min and in 13% radiochemical yield (end of bombardment (EOB); 7% end of synthesis (EOS)). [(18)F]FLT has been designed as a new positron emission tomography imaging agent for visualizing cellular proliferation in vivo based on the metabolism of thymidine
AD  - Research Imaging Laboratory, University of Washington Medical Center, Seattle, Washington 98195, USA. grierson@u.washington.edu PMID- 0010773543 PID - S0969805199001043 PST - ppublish MHDA- 2000/08/01 11:00 EDAT- 2000/04/25 09:00
ER  - 

TY  - JOUR
T1  - O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study [In Process Citation]
A1  - Weber,W.A.
A1  - Wester,H.J.
A1  - Grosu,A.L.
A1  - Herz,M.
A1  - Dzewas,B.
A1  - Feldmann,H.J.
A1  - Molls,M.
A1  - Stocklin,G.
A1  - Schwaiger,M.
Y1  - 2000/05//
N1  - Eng
SP  - 542
EP  - 549
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 27
IS  - 5
N2  - O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of L-[methyl-11C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1+/-0.2, 0.8+/-0.2 and 2.7+/-0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4+/-0.2, 0.9+/-0.1 and 3.3+/-1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0+/-0.1 SUV) was significantly lower than in tumour tissue (P = 0.007). For all lesions there was a close correlation (r = 0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions
AD  - Department of Nuclear Medicine, Technische Universitat Munchen, Germany. W.Weber@lrz.tu-muenchen.de
ER  - 

TY  - JOUR
T1  - Pre-surgical evaluation for epilepsy surgery - European standards
A1  - European Federation of Neurological Societies Task Force
Y1  - 2000///
SP  - 119
EP  - 122
JF  - European Journal of Neurology
JA  - Eur J Neurol
VL  - 7
ER  - 

TY  - JOUR
T1  - Mild cognitive impairment or questionable dementia? [editorial; comment]
A1  - Petersen,R.C.
Y1  - 2000/05//
N1  - Eng
SP  - 643
EP  - 644
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 57
IS  - 5
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in humans: preliminary analyses
A1  - Martinez,D.
A1  - Mawlawi,O.
A1  - Hwang,D.
A1  - Kent,J.
A1  - Simpson,N.
A1  - Parsey,R.V.
A1  - Hashimoto,T.
A1  - Slifstein,M.
A1  - Huang,Y.
A1  - Van Heertum,R.
A1  - Abi-Dargham,A.
A1  - Caltabiano,S.
A1  - Malizia,A.
A1  - Cowley,H.
A1  - Mann,J.J.
A1  - Laruelle,M.
Y1  - 2000/07/01/
N1  - ENG
SP  - 523
EP  - 527
JA  - Nucl.Med.Biol.
VL  - 27
IS  - 5
N2  - Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT(1A) receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT(1A) antagonist [carbonyl-(11)C]WAY-100635 or [carbonyl-(11)C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexanecar boxamide abbreviated as [(11)C]WAY-100635. Pindolol dose-dependently decreased [(11)C]WAY-100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/- 8% at scan 3, and 44 +/- 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT(1A) receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT(1A) receptors was higher in the DRN compared to cortical regions, demonstrating a significant in vivo selectivity for DRN 5-HT(1A) autoreceptors relative to cortico-limbic postsynaptic receptors. This selectivity is necessary for the potentiation of 5-HT transmission, and this finding represents an important proof of concept in the development of 5-HT(1A) agents for this application. Early evaluation of new drugs with PET imaging will enable rapid screening of compounds based on DRN selectivity and more appropriate determination of doses for clinical trials
AD  - Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, New York, USA PMID- 0010962261 PID - S0969805100001220 PST - ppublish MHDA- 2000/08/30 11:00 EDAT- 2000/08/30 11:00
ER  - 

TY  - JOUR
T1  - Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tisssue input functions
A1  - Parsey,R.V.
A1  - Slifstein,M.
A1  - Hwang,D.R.
A1  - Abi-Dargham,A.
A1  - Simpson,N.
A1  - Mawlawi,O.
A1  - Guo,N.N.
A1  - Van Heertum,R.
A1  - Mann,J.J.
A1  - Laruelle,M.
Y1  - 2000/07//
N1  - Eng
SP  - 1111
EP  - 1133
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
IS  - 7
N2  - Serotonin 5-HT(1A) receptors are implicated in the pathophysiology of neuropsychiatric conditions. The goal of this study was to evaluate methods to derive 5-HT(1A) receptor parameters in the human brain with positron emission tomography (PET) and [carbonyl-(11)C]WAY 100635. Five healthy volunteer subjects were studied twice. Three methods of analysis were used to derive the binding potential (BP), and the specific to nonspecific equilibrium partition coefficient (k3/k4). Two methods, kinetic analysis based on a three compartment model and graphical analysis, used the arterial plasma time-activity curves as the input function to derive BP and k3/k4. A third method, the simplified reference tissue model (SRTM), derived the input function from uptake data of a region of reference, the cerebellum, and provided only k3/k4. All methods provided estimates of regional 5-HT(1A) receptor parameters that were highly correlated. Results were consistent with the known distribution of 5-HT(1A) receptors in the human brain. Compared with kinetic BP, graphical analysis slightly underestimated BP, and this phenomenon was mostly apparent in small size-high noise regions. Compared with kinetic k3/k4, the reference tissue method underestimated k3/k4 and the underestimation was apparent primarily in regions with high receptor density. Derivation of BP by both kinetic and graphical analysis was highly reliable, with an intraclass correlation coefficient (ICC) of 0.84 +/- 0.14 (mean +/- SD of 15 regions) and 0.84 +/- 0.19, respectively. In contrast, the reliability of k3/k4 was lower, with ICC of 0.53 +/- 0.28, 0.47 +/- 0.28, and 0.55 +/- 0.29 for kinetic, graphical, and reference tissue methods, respectively. In conclusion, derivation of BP by kinetic analysis using the arterial plasma input function appeared as the method of choice because of its higher test-retest reproducibility, lower vulnerability to experimental noise, and absence of bias
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA. PMID- 0010908045 MHDA- 2000/08/06 11:00 EDAT- 2000/07/25 11:00
ER  - 

TY  - JOUR
T1  - Increased baseline occupancy of D2 receptors by dopamine in schizophrenia [see comments]
A1  - Abi-Dargham,A.
A1  - Rodenhiser,J.
A1  - Printz,D.
A1  - Zea-Ponce,Y.
A1  - Gil,R.
A1  - Kegeles,L.S.
A1  - Weiss,R.
A1  - Cooper,T.B.
A1  - Mann,J.J.
A1  - Van Heertum,R.L.
A1  - Gorman,J.M.
A1  - Laruelle,M.
Y1  - 2000/07/05/
N1  - Comment in: Proc Natl Acad Sci U S A 2000 Jul 5;97(14):7673-5 PMID- 0010884434 PID - 97/14/8104 PST - ppublish MHDA- 2000/08/12 11:00 EDAT- 2000/07/08 11:00
SP  - 8104
EP  - 8109
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 97
IS  - 14
N2  - The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D(2) receptor. We measured in vivo occupancy of striatal D(2) receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D(2) receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (19% +/- 11%) compared with control subjects (9% +/- 7%, P = 0.003). The increased occupancy of D(2) receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D(2) receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons
AD  - Departments of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. aadar@neuron.cpmc.columbia.edu
ER  - 

TY  - JOUR
T1  - Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review
A1  - Laruelle,M.
Y1  - 2000/03//
N1  - Eng
SP  - 423
EP  - 451
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
IS  - 3
N2  - Several groups have provided evidence that positron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuroreceptor imaging techniques might be applied to measure acute fluctuations in dopamine (DA) synaptic concentration in the living human brain. Competition between DA and radioligands for binding to D2 receptor is the principle underlying this approach. This new application of neuroreceptor imaging provides a dynamic measurement of neurotransmission that is likely to be informative to our understanding of neuropsychiatric conditions. This article reviews and discusses the body of data supporting the feasibility and potential of this imaging paradigm. Endogenous competition studies performed in rodents, nonhuman primates, and humans are first summarized. After this overview, the validity of the model underlying the interpretation of these imaging data is critically assessed. The current reference model is defined as the occupancy model, since changes in radiotracer binding potential (BP) are assumed to be directly caused by changes in occupancy of D2 receptors by DA. Experimental data supporting this model are presented. The evidence that manipulation of DA synaptic levels induces change in the BP of several D2 radiotracers (catecholamines and benzamides) is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The relationship between the magnitude of BP changes measured with PET or SPECT and the magnitude of changes in DA concentration measured by microdialysis supports the use of these noninvasive techniques to measure changes in neurotransmission. On the other hand, several observations remain unexplained. First, the amphetamine-induced changes in the BP of D2 receptor antagonists [123I]IBZM and [11C]raclopride last longer than amphetamine-induced changes in DA extracellular concentration. Second, nonbenzamide D2 receptor antagonists, such as spiperone and pimozide, are not affected by changes in DA release, or are affected in a direction opposite to that predicted by the occupancy model. Similar observations are reported with D1 radiotracers. These results suggest that the changes in BP following changes in DA concentration might not be fully accounted by a simple occupancy model. Specifically, the data are reviewed supporting that agonist-mediated receptor internalization might play an important role in characterizing receptor-ligand interactions. Finally, it is proposed that a better understanding of the mechanism underlying the effects observed with benzamides is essential to develop this imaging technique to other receptor systems
AD  - Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York 10032, USA
ER  - 

TY  - JOUR
T1  - Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility
A1  - Abi-Dargham,A.
A1  - Martinez,D.
A1  - Mawlawi,O.
A1  - Simpson,N.
A1  - Hwang,D.R.
A1  - Slifstein,M.
A1  - Anjilvel,S.
A1  - Pidcock,J.
A1  - Guo,N.N.
A1  - Lombardo,I.
A1  - Mann,J.J.
A1  - Van Heertum,R.
A1  - Foged,C.
A1  - Halldin,C.
A1  - Laruelle,M.
Y1  - 2000/02//
N1  - Eng
SP  - 225
EP  - 243
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
IS  - 2
N2  - To evaluate the postulated role of extrastriatal D1 receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [11C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D1 receptor. The goal of this study was to develop and evaluate methods to derive D1 receptor parameters in striatal and extrastriatal regions of the human brain with [11C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient (k3/k4). Both kinetic and graphic analyses provided BP and k3/k4 values in good agreement with the known distribution of D1 receptors (striatum > limbic regions = neocortical regions > thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k3/k4 by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90+/-0.06 (mean +/- SD of 12 regions) and 0.84+/-0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72+/-0.17 and 0.58+/-0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [11C]NNC 112 uptake provides an appropriate method with which to derive D1 receptor parameters in regions with both high (striatal) and low (extrastriatal) D1 receptor density
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA. PMID- 0010698059 MHDA- 2000/03/11 09:00 EDAT- 2000/03/04 09:00
ER  - 

TY  - JOUR
T1  - Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex [In Process Citation]
A1  - Kuhl,D.E.
A1  - Minoshima,S.
A1  - Frey,K.A.
A1  - Foster,N.L.
A1  - Kilbourn,M.R.
A1  - Koeppe,R.A.
Y1  - 2000/09//
N1  - Eng
SP  - 391
EP  - 395
JA  - Ann.Neurol.
VL  - 48
IS  - 3
N2  - Based on surrogate assays of peripheral red blood cells, reports state that widely prescribed doses of donepezil hydrochloride provide nearly complete inhibition of cerebral cortical acetylcholinesterase activity in the treatment of Alzheimer's disease (AD). To test this, direct positron emission tomography measures of cerebral acetylcholinesterase activity were made in AD patients before and after treatment with donepezil (5 and 10 mg/day) for at least 5 weeks and compared with similar measures in normal controls who were untreated or after acute administration of another AChE inhibitor, physostigmine salicylate (1.5 mg/hr). After physostigmine, acetylcholinesterase inhibition averaged 52% in normal cerebral cortex. After donepezil, cerebral cortical inhibition in AD brain averaged only 27%. Clinical trials of this donepezil dose schedule are not testing the effect of nearly complete cerebral cortical inhibition
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, USA
ER  - 

TY  - JOUR
T1  - Neuroimaging in neurotoxicology [In Process Citation]
A1  - Frey,K.A.
Y1  - 2000/08//
N1  - Eng
SP  - 615
EP  - 630
JA  - Neurol.Clin.
VL  - 18
IS  - 3
N2  - The development of imaging technology over the past 25 years has had a profound impact on the clinical practices of a number of medical disciplines. In this article, the author reviews the various neuroimaging modalities and the neurologic processes that they can address
AD  - Professor, Department of Internal Medicine, Division of Nuclear Medicine, and the Department of Neurology, University of Michigan, Ann Arbor, Michigan
ER  - 

TY  - JOUR
T1  - Decreased striatal monoaminergic terminals in Huntington disease
A1  - Bohnen,N.I.
A1  - Koeppe,R.A.
A1  - Meyer,P.
A1  - Ficaro,E.
A1  - Wernette,K.
A1  - Kilbourn,M.R.
A1  - Kuhl,D.E.
A1  - Frey,K.A.
A1  - Albin,R.L.
Y1  - 2000/05/09/
N1  - Eng
SP  - 1753
EP  - 1759
JF  - Neurology
VL  - 54
IS  - 9
N2  - OBJECTIVE: To evaluate the integrity of the dorsal striatal dopaminergic innervation in rigid and choreic Huntington disease (HD). BACKGROUND: Some patients with HD have an akinetic-rigid phenotype. It has been suggested that nigrostriatal in addition to striatal pathology is present in this subgroup. The authors sought to determine whether in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding could distinguish patients with akinetic-rigid (HDr) from typical choreiform (HDc) HD. METHODS: Nineteen patients with HD (mean age 48 +/- 16 years) and 64 normal controls (mean age 50 +/- 14 years) underwent (+)-alpha-[11C]dihydrotetrabenazine (DTBZ) PET imaging. DTBZ blood to brain ligand transport (K1) and tissue to plasma distribution volume (DV) in the caudate nucleus, anterior putamen, and posterior putamen were normalized to the occipital cortex. RESULTS: The normalized striatal specific DV was reduced in HDr (n = 6) when compared with controls: caudate nucleus -33% (p < 0.001), anterior putamen -56% (p < 0.0001), and posterior putamen -75% (p < 0.0001). Patients with HDc (n = 13) also had reduced striatal DV: caudate nucleus -6% (NS), anterior putamen -19% (p < 0.01), and posterior putamen -35% (p < 0.0001). Patients with HDr had significantly lower striatal (+)-alpha-[11C]DTBZ binding than HDc patients. After correction for tissue atrophy effects, normalized DV differences were less significant, with values somewhat increased in the caudate, slightly reduced in the anterior putamen, and moderately decreased in the posterior putamen. There were no significant regional differences in K1 reductions among caudate, anterior, and posterior putamen in HD. CONCLUSIONS: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype. Striatal DV reductions were most prominent in the posterior putamen, similar to PD
AD  - Department of Internal Medicine, (Division of Nuclear Medicine), The University of Michigan Medical School, Ann Arbor, MI, USA. PMID- 0010802780 PST - ppublish MHDA- 2000/06/03 09:00 EDAT- 2000/05/10 09:00
ER  - 

TY  - JOUR
T1  - Frontal lobe tasks do not reflect frontal lobe function in patients with probable Alzheimer's disease
A1  - Kessler,J.
A1  - Mielke,R.
A1  - Grond,M.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 2000///
SP  - 1
EP  - 15
JF  - International Journal of Neuroscience
VL  - 104
ER  - 

TY  - JOUR
T1  - Economic evaluation studies in nuclear medicine: a methodological review of the literature [In Process Citation]
A1  - Gambhir,S.S.
A1  - Schwimmer,J.
Y1  - 2000/06//
N1  - Eng
SP  - 121
EP  - 137
JA  - Q.J.Nucl.Med.
VL  - 44
IS  - 2
N2  - BACKGROUND: The growing need for evaluation of the utility of new nuclear medicine technologies has spawned a few economic studies ranging from preliminary indications of cost savings to complete decision analysis models incorporating costs and quality of life. The objective of the current study was to evaluate the methodological quality of economic analyses of nuclear medicine procedures which targeted cost-effectiveness or cost-utility issues published in the medical literature during the years 1985-1999. METHODS: A computerized literature search was used to identify original investigations from the medical literature which included an economic analysis of a nuclear medicine procedure. Each economic analysis article was evaluated by two independent reviewers for adherence to ten accepted methodological criteria. RESULTS: Of the 29 articles meeting the search criteria, only six (21%) conformed to all ten methodological criteria. CONCLUSIONS: Published economic analyses of nuclear medicine procedures usually do not meet accepted methodological standards and could be significantly improved to achieve overall better quality relative to similar analyses in the literature from other medical fields. Continued improvement in the number and quality of economic studies is critically needed for the future competitiveness of nuclear medicine studies
AD  - Crump Institute for Biological Imaging, UCLA School of Medicine 90095-1770, USA. sgambhir@mednet.ucla.edu
ER  - 

TY  - JOUR
T1  - Preserved function in brain invaded by tumor
A1  - Ojemann,J.G.
A1  - Miller,J.W.
A1  - Silbergeld,D.L.
Y1  - 1996/08//
N1  - Eng
SP  - 253
EP  - 258
JF  - Neurosurgery
VL  - 39
IS  - 2
N2  - OBJECTIVE: Intrinsic brain tumors can arise within regions of the cortex that are essential to language, motor, and somatosensory functions. Although it is commonly thought that such tumors can be safely resected, as long as the resection is limited to grossly abnormal cortex, functional mapping of the cerebral cortex during tumor resection does not support this contention. METHODS: We report our experience with 14 patients (9 men, 5 women; median age, 43 yr) with intrinsic brain tumors of varying degrees of malignancy (four glioblastomas multiforme, four anaplastic astrocytomas, two anaplastic oligodendrogliomas, one anaplastic mixed glioma, three gangliogliomas). Cortical mapping was performed either intraoperatively (n = 11) or extraoperatively via intracranial electrodes (n = 3). RESULTS: Tumors were found to grossly invade functioning cortices (frontal lobe language cortex, four tumors; temporal lobe language cortex, five tumors; motor cortex, four tumors; somatosensory cortex, one tumor). The gross invasion of functional cortex by tumor limited safe resection in all patients. Three patients experienced transient postoperative deficits caused by the proximity of the resection to functional cortex. One patient suffered a delayed postoperative hemorrhage, with resultant persistent motor aphasia. CONCLUSION: Intrinsic brain tumors grow by infiltration of normal brain. Consequently, brain that appears to be abnormal may remain functional, thus precluding safe tumor resection
AD  - Department of Neurological Surgery, Washington University Epilepsy Program, Washington University School of Medicine, St. Louis, Missouri, USA. PMID- 0008832661 EDAT- 1996/08/01 00:00 MHDA- 1996/08/01 00:00
ER  - 

TY  - JOUR
T1  - Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming
A1  - Naumann,M.
A1  - Magyar-Lehmann,S.
A1  - Reiners,K.
A1  - Erbguth,F.
A1  - Leenders,K.L.
Y1  - 2000/03//
N1  - Eng
SP  - 322
EP  - 328
JA  - Ann.Neurol.
VL  - 47
IS  - 3
N2  - Cervical dystonia is a disabling basal ganglia disorder characterized by an involuntary head deviation to one side. A typical but also mysterious feature is the impressive improvement of muscle spasms and involuntary head posture by application of a sensory facial stimulus (sensory trick). Here, we report the effect of a sensory trick on cortical activation patterns in 7 patients with cervical dystonia by using H2(15)O positron emission tomography. The application of the sensory trick stimulus, resulting in a near-neutral head position, led to an increased activation mainly of the superior and inferior parietal lobule (ipsilateral to the original head turn) and bilateral occipital cortex and to a decreased activity of the supplementary motor area and the primary sensorimotor cortex (contralateral to the head turn). We propose that a perceptual dysbalance induced by a sensory trick maneuver leads to a relative displacement of the egocentric midvertical reference to the opposite side and a decrease in motor cortex activity. This modulation of motor programming gives novel insights into the mechanisms involved in sensorimotor integration in movement disorders
AD  - Department of Neurology, University of Wurzburg, Germany. PMID- 0010716251 MHDA- 2000/05/16 09:00 EDAT- 2000/03/15 09:00
ER  - 

TY  - JOUR
T1  - Dopaminergic dysfunction in midbrain dystonia: anatomoclinical study using 3-dimensional magnetic resonance imaging and fluorodopa F 18 positron emission tomography
A1  - Vidailhet,M.
A1  - Dupel,C.
A1  - Lehericy,S.
A1  - Remy,P.
A1  - Dormont,D.
A1  - Serdaru,M.
A1  - Jedynak,P.
A1  - Veber,H.
A1  - Samson,Y.
A1  - Marsault,C.
A1  - Agid,Y.
Y1  - 1999/08//
N1  - Eng
SP  - 982
EP  - 989
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 56
IS  - 8
N2  - OBJECTIVE: To determine the role of damage to neuronal systems, especially the dopaminergic system, in patients with symptomatic dystonia and mesencephalic lesions. DESIGN: Stereotaxic magnetic resonance imaging analysis and positron emission tomography after the administration of fluorodopa F 18. PATIENTS: Of a group of 48 patients with unilateral dystonia following a stroke, 7 patients with a well-defined midbrain lesion were selected. RESULTS: All patients had unilateral dystonic posture of an upper extremity and cerebellar dysmetria or hypotonia. Cerebellar tremor was present in 1 patient. Two patients had resting and postural tremor, which showed a marked improvement with treatment with levodopa. In patients with dystonia only, dopaminergic lesions were mostly confined to the ventromesial mesencephalon and red nucleus area, including the substantia nigra and nigrostriatal and cerebellothalamic fibers. Dystonia was severe and did not resolve with time in patients with lesions involving the nigrostriatal pathway, and the degree of dopaminergic denervation revealed by positron emission tomography was correlated with the severity of dystonia. In patients with resting and postural tremor, lesions of the dopaminergic structures were larger and located more laterally and dorsally in the pars compacta, the perirubral and retrorubral areas, and extending to the central tegmental tract. CONCLUSIONS: Dopaminergic dysfunction plays a role in the occurrence and severity of midbrain dystonia, and additional lesions to dopaminergic neurons in the perirubral and retrorubral areas result in tremor that responds to levodopa treatment
AD  - The French Institute of Health and Medical Research INSERM U289, Paris. marie.vidailhet@sat.ap-hop-paris.fr PMID- 0010448804 EDAT- 1999/08/17 10:00 MHDA- 1999/08/17 10:00
ER  - 

TY  - JOUR
T1  - 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in propionic acidemia: clinical and MRI correlations
A1  - Al Essa,M.
A1  - Bakheet,S.
A1  - Patay,Z.
A1  - Al Shamsan,L.
A1  - Al Sonbul,A.
A1  - Al Watban,J.
A1  - Powe,J.
A1  - Ozand,P.T.
Y1  - 1999/07//
N1  - Eng
SP  - 312
EP  - 317
JA  - Brain Dev.
VL  - 21
IS  - 5
N2  - The clinical data and the imaging findings of the positron emission tomography (PET) and the magnetic resonance imaging (MRI) studies in five patients, previously diagnosed to have propionic acidemia, were retrospectively reviewed. The patients were all normal at birth. The first clinical signs, typically hypotonia and failure to thrive, appeared during the first 2 years of life. With progression of the disease, the neurological findings consisted of variable degrees of dementia and extrapyramidal symptoms, notably dystonia, choreoathetosis and rigidity of variable degrees. Initial cerebral PET and MRI studies were normal. Follow-up MRI examinations showed progressive basal ganglia degeneration, with evidence of atrophy and signal abnormalities within the caudate nuclei and the putamina. The thalamic structures were normal. The PET studies demonstrated increased uptake in the basal ganglia and thalami, followed by decreased uptake in the basal ganglia at a later stage of the disease. The structural (MRI) and the functional (PET) studies of the brain were found to be complementary in the evaluation of propionic acidemia, and were in good correlation with the clinical findings
AD  - Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. PMID- 0010413018 EDAT- 1999/07/21 10:00 MHDA- 1999/07/21 10:00
ER  - 

TY  - JOUR
T1  - Manganese neurotoxicity: a review of clinical features, imaging and pathology
A1  - Pal,P.K.
A1  - Samii,A.
A1  - Calne,D.B.
Y1  - 1999/04//
N1  - Eng
SP  - 227
EP  - 238
JF  - Neurotoxicology
VL  - 20
IS  - 2-3
N2  - Manganese intoxication can result in a syndrome of parkinsonism and dystonia. If these extrapyramidal findings are present, they are likely to be irreversible and even progress after termination of the exposure to manganese. Clinical features are usually sufficient to distinguish these patients from those with Parkinson's disease. The neurological syndrome does not respond to levodopa. Imaging of the brain may reveal MRI signal changes in the globus pallidus, striatum, and midbrain. Positron emission tomography reveals normal presynaptic and postsynaptic nigrostriatal dopaminergic function. The primary site of neurological damage has been shown by pathological studies to be the globus pallidus. The mechanism of toxicity is not clear
AD  - Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada
ER  - 

TY  - JOUR
T1  - Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients
A1  - Kessler,J.
A1  - Thiel,A.
A1  - Karbe,H.
A1  - Heiss,W.D.
Y1  - 2000/09//
N1  - Eng
SP  - 2112
EP  - 2116
JF  - Stroke
VL  - 31
IS  - 9
N2  - Background and Purpose-In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow. METHODS:-Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H(2)(15)O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images. RESULTS:-Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P:<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests. CONCLUSIONS:-Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere
AD  - Max-Planck-Institute for Neurological Research (J.K., A.T., W.D.H.) and University Clinic of Neurology (H.K., W.D.H.), Cologne, Germany
ER  - 

TY  - JOUR
T1  - Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry
A1  - Szelies,B.
A1  - Weber-Luxenburger,G.
A1  - Mielke,R.
A1  - Pawlik,G.
A1  - Kessler,J.
A1  - Pietrzyk,U.
A1  - Bauer,B.
A1  - Heiss,W.D.
Y1  - 2000/07//
N1  - Eng
SP  - 393
EP  - 400
JA  - Eur.J.Neurol.
VL  - 7
IS  - 4
N2  - The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients
AD  - Neurologische Universitatsklinik and Max-Planck-Institut fur neurologische Forschung, Cologne, Germany. PMID- 0010971598 PID - ene077 PST - ppublish MHDA- 2000/09/30 11:01 EDAT- 2000/09/06 11:00
ER  - 

TY  - JOUR
T1  - Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping
A1  - Petit-Taboue,M.C.
A1  - Landeau,B.
A1  - Desson,J.F.
A1  - Desgranges,B.
A1  - Baron,J.C.
Y1  - 1998/04//
N1  - Eng
SP  - 176
EP  - 184
JF  - Neuroimage
VL  - 7
IS  - 3
N2  - The aging process is thought to result in changes in synaptic activity reflecting both functional and structural cell derangement. However, previous PET reports on age-related changes in resting brain glucose utilization (CMRglc) have been discrepant, presumably because of methodological as well as subject screening differences. In contrast to other studies, which used a region of interest approach, the objective of the present work was to determine, by means of the SPM software, the changes in regional CMRglc as a function of age in 24 optimally healthy, unmedicated volunteers of ages from 20 to 67 years. Global CMRglc showed a significant decline with age (approximately 6% per decade, P < 0.05), which concerned all the voxels studied save for most of the occipital cortex and part of the cerebellum. The most significant effects (P < 0.001) concerned the association neocortex in perisylvian temporoparietal and anterior temporal areas, the insula, the inferior and posterior-lateral frontal regions, the anterior cingulate cortex, the head of caudate nucleus, and the anterior thalamus, in a bilateral and essentially symmetrical fashion. The high posterior parietal cortex was not sampled in this study. This distribution of changes in CMRglc with age may differ from that seen in Alzheimer' disease, where the earliest metabolic reduction has been shown to affect the posterior cingulate cortex
AD  - INSERM U320, Cyceron, CEA DSV/DRM, Universite de Caen, France. PMID- 0009597659 EDAT- 1998/05/23 02:16 MHDA- 1998/05/23 02:16
ER  - 

TY  - JOUR
T1  - Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging
A1  - Marchal,G.
A1  - Rioux,P.
A1  - Petit-Taboue,M.C.
A1  - Sette,G.
A1  - Travere,J.M.
A1  - Le Poec,C.
A1  - Courtheoux,P.
A1  - Derlon,J.M.
A1  - Baron,J.C.
Y1  - 1992/10//
N1  - Eng
SP  - 1013
EP  - 1020
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 49
IS  - 10
N2  - Using high-resolution positron emission tomography and the oxygen 15 continuous inhalation method, we examined the changes in cerebral metabolic rate of oxygen, blood flow, blood volume, and oxygen extraction fraction as a function of age in 25 optimally healthy, unmedicated volunteers who ranged in age from 20 to 68 years. Subjects were strictly selected for absence of cerebrovascular risk factors, dementia, or mental disorders; they had neither biological nor clinical abnormalities, and no focal anomaly on computed tomographic scan. Regions of interest were determined according to the anatomical structures defined on corresponding computed tomographic scan cuts obtained using a stereotaxic head-positioning method. This same method was also used for positron emission tomographic imaging. There was no significant effect of aging on PaCO2 values, hematocrit, arterial blood pressure, cholesterol and triglyceride levels, and blood glucose levels. In most cerebral cortex gyri, the cerebral metabolic rate of oxygen significantly decreased with age according to a linear pattern, with the same magnitude (about -6% per decade) in all four lobes and on both sides. This effect of age on cortical cerebral metabolic rate of oxygen persisted when the possible influence of cortical atrophy, gender, and head size were partialled out. In contrast, the white matter, deep gray nuclei, thalamus, and cerebellum were not significantly affected. The cerebral blood volume declined with a similar pattern to cerebral metabolic rate of oxygen, while changes in cerebral blood flow were less significant, presumably because of larger variance of data across subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - National Institute of Health and Medical Research U.320, Caen, France. PMID- 0001417508 EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:00
ER  - 

TY  - JOUR
T1  - Functional imaging correlates of recovery after stroke in humans
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 2000///
SP  - 1619
EP  - 1631
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
ER  - 

TY  - JOUR
T1  - Intersubject variability in cortical activations during a complex language task
A1  - Xiong,J.
A1  - Rao,S.
A1  - Jerabek,P.
A1  - Zamarripa,F.
A1  - Woldorff,M.
A1  - Lancaster,J.
A1  - Fox,P.T.
Y1  - 2000/09//
N1  - Eng
SP  - 326
EP  - 339
JF  - Neuroimage
VL  - 12
IS  - 3
N2  - Intersubject variability in the functional organization of the human brain has theoretical and practical importance for basic and clinical neuroscience. In the present study, positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) were used to study the functional anatomy of language processes. Intersubject variability in task-induced activations in six brain regions was assessed in 20 normal subjects (10 men and 10 women) for frequency of occurrence, location, intensity, and extent. A complex, but well-studied task (overt verb generation) was compared to a simple baseline (visual fixation) to induce activations in brain areas serving perceptual, motoric, and cognitive functions. The frequency of occurrence was high for all selected brain areas (80-95%). The variability in response location in Talairach space, expressed as the standard deviation along each axis (x, y, z), ranged from 5.2 to 9.9 mm. This variability appears to be uniformly distributed across the brain, uninfluenced by regional differences in the complexity of gyral anatomy or mediated behavior. The variability in response location, expressed as the average Euclidean distances (averaged across subjects) about mean locations of activations, varied from 9.40 to 13.36 mm and had no significant differences by region (P>0.05, beta = 0.20). Intensity variability was also relatively small and homogenous across brain regions. In contrast, response extent was much more variable both across subjects and across brain regions (0.79 to 1.77, coefficient of variation). These findings are in good agreement with previous PET studies of intersubject variability and bode well for the possibility of using functional neuroimaging to study neural plasticity subsequent to congenital and acquired brain lesions. Copyright 2000 Academic Press
AD  - Research Imaging Center, The University of Texas Health Science Center, San Antonio, Texas, USA. PMID- 0010944415 PID - nimg.2000.0621 DOI - 10.1006/nimg.2000.0621 PST - ppublish MHDA- 2000/10/14 11:01 EDAT- 2000/08/17 11:00
ER  - 

TY  - JOUR
T1  - Image registration using a symmetric prior--in three dimensions
A1  - Ashburner,J.
A1  - Andersson,J.L.
A1  - Friston,K.J.
Y1  - 2000/04//
N1  - Eng
SP  - 212
EP  - 225
JA  - Hum.Brain Mapp.
VL  - 9
IS  - 4
N2  - This paper describes a Bayesian method for three-dimensional registration of brain images. A finite element approach is used to obtain a maximum a posteriori estimate of the deformation field at every voxel of a template volume. The priors used by the MAP estimate penalize unlikely deformations and enforce a continuous one-to-one mapping. The deformations are assumed to have some form of symmetry, in that priors describing the probability distribution of the deformations should be identical to those for the inverses (i.e., warping brain A to brain B should not be different probablistically from warping B to A). A gradient descent algorithm is presented for estimating the optimum deformations
AD  - The Wellcome Department of Cognitive Neurology, Institute of Neurology, London, United Kingdom. j.ashburner@fil.ion.ucl.ac.uk PMID- 0010770230 MHDA- 2000/06/10 09:00 EDAT- 2000/04/19 09:00 PID - 10.1002/(SICI)1097-0193(200004)9:4<212::AID-HBM3>3.0.CO;2-#
ER  - 

TY  - JOUR
T1  - Usefulness of a dopamine transporter PET ligand [(18)F]beta-CFT in assessing disability in Parkinson's disease
A1  - Rinne,J.O.
A1  - Ruottinen,H.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Sonninen,P.
A1  - Solin,O.
Y1  - 1999/12//
N1  - Eng
SP  - 737
EP  - 741
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 67
IS  - 6
N2  - OBJECTIVES: The usefulness of a novel dopamine transporter PET ligand, [(18)F]beta-CFT in assessing disability in Parkinson's disease was studied. METHODS: Twenty seven patients with Parkinson's disease in different disability stages (of which nine were patients with early disease) and nine healthy controls were studied. The regions of interest were drawn on a magnetic resonance image resliced according to the PET image. RESULTS: There was a significant reduction in [(18)F]beta-CFT uptake in the posterior putamen (to 18% of the control mean, p<0.00001), anterior putamen (28%, p<0.00001), and caudate nucleus (51%, p<0.00001) in the total population of patients with Parkinson's disease. The reduction in [(18)F]beta-CFT uptake was more pronounced with more severe disability of the patients, the correlations between the total motor score of the unified Parkinson's disease rating scale (UPDRS) and [(18)F]beta-CFT uptake being significant in the posterior putamen (r=-0.62 p=0.0005), anterior putamen (r=-0.64, p=0.0003), and the caudate nucleus (r=-0.62, p=0.0006). There was a significant negative correlation with putaminal [(18)F]beta-CFT uptake and the hypokinesia and rigidity scores, but not with the tremor score of the UPDRS motor part. In nine patients with early disease and without any antiparkinsonian medication the reduction in the [(18)F]beta-CFT uptake (average of ipsilateral and contralateral side) was reduced in the total putamen to 34% of the mean control value (p<0.00001). The corresponding figures in the other brain areas were: posterior putamen 21% (p<0.00001), anterior putamen 43% (p<0.00001), and caudate nucleus 76% (p<0.01). The reductions in [(18)F]beta-CFT uptake were more severe in the contralateral than in the ipsilateral side. Individually, [(18)F]beta-CFT uptake in the putamen in all patients was below 3 SD from the control mean. CONCLUSIONS: [(18)F]beta-CFT is a sensitive marker of nigrostriatal dopaminergic dysfunction in Parkinson's disease and can be used in the diagnosis, assessment of disease severity, and follow up of patients
AD  - Department of Neurology, University of Turku; Turku PET Centre, Turku, Finland. juha.rinne@pet.tyks.fi PMID- 0010567489 URLF- http://www.jnnp.com/cgi/content/full/67/6/737 URLS- http://www.jnnp.com/cgi/content/abstract/67/6/737 EDAT- 1999/11/24 09:00 MHDA- 1999/11/24 09:00
ER  - 

TY  - JOUR
T1  - Progression in Parkinson's disease: a positron emission tomography study with a dopamine transporter ligand [18F]CFT
A1  - Nurmi,E.
A1  - Ruottinen,H.M.
A1  - Kaasinen,V.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Rinne,J.O.
Y1  - 2000/06//
N1  - Eng
SP  - 804
EP  - 808
JA  - Ann.Neurol.
VL  - 47
IS  - 6
N2  - We studied the rate of progression of striatal dopamine transporter function in Parkinson's disease (PD). Eight patients with early PD without antiparkinsonian medication and 7 healthy volunteers were investigated with [18F]CFT positron emission tomography (PET). The PET scan was carried out twice at an approximate 2-year interval. The uptake of [18F]CFT was calculated as a region-cerebellum:cerebellum ratio at 180 to 210 minutes after injection. At the first PET scan, the [18F]CFT uptake in PD patients in the putamen was 1.45 +/- 0.45 (mean +/- SD) (42% of the control mean) and 2.43 +/- 0.59 in the caudate nucleus (76% of the control mean). The ratios declined by the time of the second PET scan, and the rate of annual decline of the baseline mean in PD patients was 13.1% in the putamen and 12.5% in the caudate nucleus. In controls, the corresponding figures were 2.1% for the putamen and 2.9% for the caudate nucleus. The decline in [18F]CFT uptake was significantly higher in PD patients than in controls. Thus, dopamine transporter ligands such as [18F]CFT seem to be sensitive markers for the rate of progression in PD
AD  - Department of Neurology, University of Turku, Finland. PMID- 0010852547 MHDA- 2000/07/06 11:00 EDAT- 2000/06/14 09:00
ER  - 

TY  - JOUR
T1  - Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: a comparative PET study with [11C] raclopride and [11C]N-methylspiperone
A1  - Kaasinen,V.
A1  - Ruottinen,H.M.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Oikonen,V.
A1  - Rinne,J.O.
Y1  - 2000/01//
N1  - Eng
SP  - 65
EP  - 70
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 41
IS  - 1
N2  - Dopamine D2 receptor function was assessed in a PET study with 2 dopamine D2 receptor PET ligands, [11C]raclopride (RAC) and [11C]N-methylspiperone (NMSP), in early Parkinson's disease. METHODS: Seven patients with early Parkinson's disease and 5 healthy volunteers were studied. Each underwent PET both with reversible [11C]RAC and with irreversible [11C]NMSP. RESULTS: Upregulation of dopamine D2 receptors in the putamen contralateral to the predominant symptoms of Parkinson's disease was confirmed using both [11C]RAC and [11C]NMSP. Uptake of [11C]RAC in the contralateral putamen was 105% of uptake in the opposite putamen (P = 0.020). For [11C]NMSP, uptake in the contralateral putamen was 105% of uptake in the ipsilateral putamen (P = 0.011). No significant differences between Parkinson's disease patients and healthy volunteers were detected in any of the studied brain regions using either [11C]RAC or [11C]NMSP. No significant differences between [11C]RAC and [11C]NMSP uptake were detected in the striatum, whereas in the extrastriatal regions, [11C]NMSP showed significantly higher uptake than [11C]RAC both in healthy volunteers and in Parkinson's disease patients. CONCLUSION: This study confirms an increase in dopamine D2 receptors in the putamen contralateral to the predominant symptoms, compared with the ipsilateral putamen, in early Parkinson's disease. This increase was seen both with reversible ligand [11C]RAC and with irreversible ligand [11C]NMSP and thus does not seem a consequence of depleted endogenous dopamine
AD  - Department of Neurology, University of Turku, Finland. PMID- 0010647606 MHDA- 2000/02/26 09:00 EDAT- 2000/01/27 09:00
ER  - 

TY  - JOUR
T1  - 6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors
A1  - Horti,A.G.
A1  - Chefer,S.I.
A1  - Mukhin,A.G.
A1  - Koren,A.O.
A1  - Gundisch,D.
A1  - Links,J.M.
A1  - Kurian,V.
A1  - Dannals,R.F.
A1  - London,E.D.
Y1  - 2000/06/16/
N1  - Eng
SP  - 463
EP  - 469
JA  - Life Sci.
VL  - 67
IS  - 4
N2  - A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380, 6-[18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[18F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (Kd 28 pM). In PET studies, 6-[18F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the alpha4beta2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [18F]FPH. In contrast to [18F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain
AD  - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. PMID- 0011003056 MHDA- 2000/10/07 11:01 EDAT- 2000/09/26 11:00
ER  - 

TY  - JOUR
T1  - Robustness of anatomically guided pixel-by-pixel algorithms for partial volume effect correction in positron emission tomography
A1  - Strul,D.
A1  - Bendriem,B.
Y1  - 1999/05//
N1  - Eng
SP  - 547
EP  - 559
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 19
IS  - 5
N2  - Several algorithms have been proposed to improve positron emission tomography quantification by combining anatomical and functional information in a pixel-by-pixel correction scheme. The precision of these methods when applied to real data depends on the precision of the manifold correction steps, such as full-width half-maximum modeling, magnetic resonance imaging-positron emission tomography registration, tissue segmentation, or background activity estimation. A good understanding of the influence of these parameters thus is critical to the effective use of the algorithms. In the current article, the authors present a monodimensional model that allows a simple theoretical and experimental evaluation of correction imprecision. The authors then assess correction robustness in three dimensions with computer simulations, and evaluate the validity of regional SD as a correction performance criterion
AD  - Service Hospitalier Frederic Joliot, CEA, Orsay, France. PMID- 0010326722 EDAT- 1999/05/18 05:23 MHDA- 1999/05/18 05:23
ER  - 

TY  - JOUR
T1  - PET measurement of cerebral acetylcholine esterase activity without blood sampling
A1  - Herholz,K.
A1  - Lercher,M.
A1  - Wienhard,K.
A1  - Bauer,B.
A1  - Lenz,O.
A1  - Heiss,W.-D.
Y1  - 2001///
SP  - 472
EP  - 477
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 28
ER  - 

TY  - JOUR
T1  - Delayed intrahemispheric remote hypometabolism. Correlations with early recovery after stroke
A1  - Iglesias,S.
A1  - Marchal,G.
A1  - Viader,F.
A1  - Baron,J.C.
Y1  - 2000/09//
N1  - Eng
SP  - 391
EP  - 402
JA  - Cerebrovasc.Dis.
VL  - 10
IS  - 5
N2  - Although 'intrahemispheric diaschisis' (i.e. a hypometabolism affecting the cerebral hemisphere ipsilateral to but remote from the infarct) may classically exacerbate acute-stage neurological deficit and influence early recovery, it has been studied only rarely. Out of a series of 30 patients with first-ever middle cerebral artery (MCA) territory stroke, we analyzed the data from 19 survivors investigated by (15)O positron emission tomography (PET) both in the acute (within 5-18 h of clinical onset) and subacute (approximately 3 weeks later) stage, and for whom chronic-stage CT coregistered with PET was available to assess infarct topography and size. Orgogozo's MCA scale was used to assess neurological deficits at the time of, and recovery between, the PET studies. Oxygen consumption was obtained for both PET sessions for the whole ipsilateral hemisphere (excluding ventricles and infarct), as well as for the thalamus and the occipital and mesial-prefrontal cortex (i.e. potentially deafferented tissue outside the MCA territory). In all regions except the occipital cortex, the oxygen consumption significantly decreased between the first and the second session, without significant correlation with the concomitant changes in MCA scores. However, acute-stage mesial-prefrontal metabolism was significantly correlated with neurological recovery. Also, both the hemisphere and the mesial-prefrontal metabolism at the second session were significantly correlated with both infarct size and concomitant MCA scores, but the latter relationship became insignificant when infarct size was taken into account. This study reveals no evidence of acute intrahemispheric diaschisis after MCA territory stroke in man. However, it documents for the first time a phenomenon of delayed intrahemispheric remote hypometabolism developing while the patients clinically recover. Because the degree of this secondary phenomenon is a function of infarct size, a mechanism of degeneration of the damaged neuron terminals is likely. Finally, contrary to other reports, neurological recovery was not a function of thalamic hypometabolism, but appeared to be influenced by acute-stage mesial-frontal metabolism, perhaps because this region is part of a network that has an important compensatory role in motor recovery. Copyright 2000 S. Karger AG, Basel
AD  - INSERM U 320, Cyceron, France. PMID- 0010971026 PID - ced10391 URLF- http://www.online.karger.com/library/karger/renderer/dataset.exe?jcode=CED &action=render&rendertype=fulltext&uid=CED.ced10391 PST - ppublish MHDA- 2000/10/14 11:01 EDAT- 2000/09/06 11:00
ER  - 

TY  - JOUR
T1  - Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease
A1  - Kordower,J.H.
A1  - Emborg,M.E.
A1  - Bloch,J.
A1  - Ma,S.Y.
A1  - Chu,Y.
A1  - Leventhal,L.
A1  - McBride,J.
A1  - Chen,E.Y.
A1  - Palfi,S.
A1  - Roitberg,B.Z.
A1  - Brown,W.D.
A1  - Holden,J.E.
A1  - Pyzalski,R.
A1  - Taylor,M.D.
A1  - Carvey,P.
A1  - Ling,Z.
A1  - Trono,D.
A1  - Hantraye,P.
A1  - Deglon,N.
A1  - Aebischer,P.
Y1  - 2000/10/27/
N1  - PET Figure: Powerpoint-File
SP  - 767
EP  - 773
JF  - Science
VL  - 290
IS  - 5492
N2  - Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients
AD  - Department of Neurological Sciences and Department of Pharmacology, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerla
ER  - 

TY  - JOUR
T1  - Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study [In Process Citation]
A1  - Thobois,S.
A1  - Dominey,P.F.
A1  - Decety,P.J.
A1  - Pollak,P.P.
A1  - Gregoire,M.C.
A1  - Le Bars,P.D.
A1  - Broussolle,E.
Y1  - 2000/10/10/
N1  - Eng
SP  - 996
EP  - 1002
JF  - Neurology
VL  - 55
IS  - 7
N2  - OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement
AD  - Department of Neurology and CERMEP, Neurological Hospital Pierre Wertheimer, Lyon, France
ER  - 

TY  - JOUR
T1  - Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study
A1  - Playford,E.D.
A1  - Jenkins,I.H.
A1  - Passingham,R.E.
A1  - Nutt,J.
A1  - Frackowiak,R.S.
A1  - Brooks,D.J.
Y1  - 1992/08//
N1  - Eng
SP  - 151
EP  - 161
JA  - Ann.Neurol.
VL  - 32
IS  - 2
N2  - Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom. PMID- 0001510355 EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:00
ER  - 

TY  - JOUR
T1  - 18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with lewy bodies
A1  - Hu,X.S.
A1  - Okamura,N.
A1  - Arai,H.
A1  - Higuchi,M.
A1  - Matsui,T.
A1  - Tashiro,M.
A1  - Shinkawa,M.
A1  - Itoh,M.
A1  - Ido,T.
A1  - Sasaki,H.
Y1  - 2000/11/28/
N1  - Eng
SP  - 1575
EP  - 1577
JF  - Neurology
VL  - 55
IS  - 10
N2  - Using (18)F-fluorodopa PET and a constant 0.0062 influx rate in the putamen, dementia with Lewy bodies (n = 7) was distinguished from AD (n = 10) with a sensitivity of 86% and a specificity of 100%. A constant 0.0071 influx rate in the caudate yielded a sensitivity of 71% and a specificity of 100% for distinction of the two disorders. Despite a limited sample size, these findings suggest that assessing nigrostriatal dopaminergic function with (18)F-fluorodopa PET may be a useful diagnostic aid in cases of dementia with Lewy bodies while patients are alive.
AD  - Department of Geriatric Medicine (Drs. Hu, Okamura, Arai, Higuchi, Matsui, Tashiro, Shinkawa, and Sasaki), Tohoku University School of Medicine, and the Cyclotron and Radioisotope Center (Drs. Itoh and Ido), Tohoku University, Sendai, Miyagi, Japan
ER  - 

TY  - JOUR
T1  - Reproducibility of PET brain mapping of cancer patients
A1  - Tashiro,M.
A1  - Juengling,F.D.
A1  - Reinhardt,M.J.
A1  - Brink,I.
A1  - Hoegerle,S.
A1  - Mix,M.
A1  - Kubota,K.
A1  - Yamaguchi,K.
A1  - Itoh,M.
A1  - Sasaki,H.
A1  - Moser,E.
A1  - Nitzsche,E.U.
Y1  - 2000/03//
N1  - Eng
SP  - 157
EP  - 163
JA  - Psychooncology.
VL  - 9
IS  - 2
N2  - Twenty German cancer patients (56.9+/-12.7 years old) without brain metastasis underwent neurological PET. The acquired brain data were compared to the data of ten age and sex-matched controls (53.6+/-15. 7). Scores of Zung's Self-rating Depression Scale (SDS) obtained from 15 out of the 20 patients suggested they might be mildly depressed. Scores of Taylor's Manifest Anxiety Scale (MAS), used for additional psychological evaluation, were close to normal distribution. Hypometabolic areas in the German cancer patients were compared with those demonstrated in our previous study in Japanese cancer patients. Common findings in both studies were observed in the limbic structures, such as the anterior and posterior cingulate gyri, the basolateral frontal cortices, as well as in the basal ganglia (especially the caudate nucleus) and frontal cortex. These results are in accordance with many previous PET studies on major depression. The results show that the positron emission tomography and (18)F-fluoro-deoxyglucose ((18)FDG-PET) brain mapping results could be partially reproduced, and suggest that PET brain mapping of cancer patients has a potential clinical application to the field of psycho-oncology and cancer patient care. Copyright 2000 John Wiley & Sons, Ltd
AD  - Division of Nuclear Medicine, Albert Ludwigs University Hospital, Freiburg im Breisgau, Germany. tashiro@cyric.tohoku.ac.jp PMID- 0010767753 PID - 10.1002/(SICI)1099-1611(200003/04)9:2<157::AID-PON452>3.0.CO;2-Y PST - ppublish MHDA- 2000/06/24 11:00 EDAT- 2000/04/18 09:00
ER  - 

TY  - JOUR
T1  - Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies
A1  - Higuchi,M.
A1  - Tashiro,M.
A1  - Arai,H.
A1  - Okamura,N.
A1  - Hara,S.
A1  - Higuchi,S.
A1  - Itoh,M.
A1  - Shin,R.W.
A1  - Trojanowski,J.Q.
A1  - Sasaki,H.
Y1  - 2000/04//
N1  - Eng
SP  - 247
EP  - 256
JA  - Exp.Neurol.
VL  - 162
IS  - 2
N2  - Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism in the DLB group, the metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB. Copyright 2000 Academic Press
AD  - Department of Geriatric Medicine, Tohoku University School of Medicine, Miyagi, Sendai, 980, Japan. PMID- 0010739631 PID - exnr.2000.7342 DOI - 10.1006/exnr.2000.7342 PST - ppublish MHDA- 2000/06/08 09:00 EDAT- 2000/03/31 09:00
ER  - 

TY  - JOUR
T1  - Effect of partial volume correction on estimates of the influx and cerebral metabolism of 6-[(18)F]fluoro-L-dopa studied with PET in normal control and Parkinson's disease subjects
A1  - Rousset,O.G.
A1  - Deep,P.
A1  - Kuwabara,H.
A1  - Evans,A.C.
A1  - Gjedde,A.H.
A1  - Cumming,P.
Y1  - 2000/08//
N1  - Eng
SP  - 81
EP  - 89
JF  - Synapse
VL  - 37
IS  - 2
N2  - The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The radioactivity concentration in a region-of-interest is consequently altered by loss of signal from that structure and contamination from adjacent brain regions, phenomena known as partial volume effects. We now apply an MRI-based algorithm to compensate for partial volume effects in the special case of compartmental modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous substrate of dopa decarboxylase. High-resolution MRI scans were obtained from normal volunteers (n = 4) and patients with Parkinson's disease (n = 4) in order to segment specific brain regions and calculate the partial volume correction factors. Dynamic 2D PET scans were acquired during 90 min following intravenous infusion of FDOPA. After partial volume correction, the apparent net blood-brain clearance of FDOPA (K(i)) was greatly increased in caudate and putamen of normal subjects and in caudate of Parkinson's disease patients. The equilibrium distribution volume of FDOPA (V(D)(e)) in cerebral cortex increased by 35% in all subjects. Using a two-compartment model, the relative activity of dopa decarboxylase with respect to FDOPA (k(D)(3)) in the basal ganglia was increased 2-3 times in normal subjects, to the range obtained previously in brain of living rat. The partial volume correction also increased the magnitude of k(D)(3) in caudate of Parkinson's disease patients, but did not alter k(D)(3) in putamen. A three-compartment model correcting for elimination of decarboxylated metabolites also yielded higher estimates of k(D)(3), but with a penalty in precision of the estimates. Together, these observations suggest that the limited spatial resolution of PET results in substantial underestimation of the true rate of FDOPA uptake and metabolism in vivo, and may also tend to obscure regional heterogeneity in the neurochemical pathology of Parkinson's disease. Copyright 2000 Wiley-Liss, Inc
AD  - McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada. PMID- 0010881028 PID - 10.1002/1098-2396(200008)37:2<81::AID-SYN1>3.0.CO;2-# PST - ppublish MHDA- 2000/08/29 11:01 EDAT- 2000/07/06 11:00
ER  - 

TY  - JOUR
T1  - Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene
A1  - Hilker,R.
A1  - Klein,C.
A1  - Ghaemi,M.
A1  - Kis,B.
A1  - Strotmann,T.
A1  - Ozelius,L.J.
A1  - Lenz,O.
A1  - Vieregge,P.
A1  - Herholz,K.
A1  - Heiss,W.-D.
A1  - Pramstaller,P.P.
Y1  - 2001///
SP  - 367
EP  - 376
JF  - Annals of Neurology
VL  - 49
N2  - A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects
ER  - 

TY  - JOUR
T1  - Correlation of intellectual impairment in Parkinson's disease with FDG PET scan [In Process Citation]
A1  - Wu,J.C.
A1  - Iacono,R.
A1  - Ayman,M.
A1  - Salmon,E.
A1  - Lin,S.D.
A1  - Carlson,J.
A1  - Keator,D.
A1  - Lee,A.
A1  - Najafi,A.
A1  - Fallon,J.
Y1  - 2000/07/14/
N1  - Eng
SP  - 2139
EP  - 2144
JF  - Neuroreport
VL  - 11
IS  - 10
N2  - This study investigated the relationship between regional glucose metabolism with intellectual impairment in patients with Parkinson's disease using statistical parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used the intellectual impairment score from the UPDRS. PET scans were analyzed with SPM96. Patients showed significant positive correlations with left limbic structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal gyrus. Patients showed significant negative correlations with associative neocortical posterior structures such as bilateral parietal and occipital gyrus. There were significant relationships between regional glucose metabolism and intellectual impairment
AD  - Brain Imaging Center, Department of Psychiatry and Human Behavior, Loma Linda University School of Medicine, Irvine, CA 92697, USA
ER  - 

TY  - JOUR
T1  - Voxel-based analysis of confounding effects of age and dementia severity on cerebral metabolism in Alzheimer's disease
A1  - Salmon,E.
A1  - Collette,F.
A1  - Degueldre,C.
A1  - Lemaire,C.
A1  - Franck,G.
Y1  - 2000/05//
N1  - Eng
SP  - 39
EP  - 48
JA  - Hum.Brain Mapp.
VL  - 10
IS  - 1
N2  - Alzheimer's disease is characterized by early hippocampal lesions, but neuropathological and functional imaging studies have also demonstrated involvement of associative cortices in patients suffering from this illness. New image-processing technologies have led to demonstration of predominant posteromedial cortical metabolic impairment in the disease. Confounding effects of both age and dementia severity on brain metabolism were assessed using categorical and correlational analyses performed with Statistical Parametric Mapping. Posterior cingulate and precuneus metabolism, assessed by positron emission tomography, was significantly correlated with age in a population of 46 patients with probable Alzheimer's disease. Metabolism in posterior cingulate and precuneus was higher in elderly than in younger patients with a diagnosis of Alzheimer's disease, even when dementia severity was taken as a confounding covariate. The data suggest that the sensitivity of positron emission tomography for the diagnosis of Alzheimer's disease is reduced in elderly cases, where less severe pathology is sufficient to induce clinical symptoms of dementia. Conversely, higher posteromedial metabolic impairment in early onset cases may reflect greater density of regional cerebral lesions or major decrease of functional afferences in a richly connected multimodal associative area. Posterior cingulate metabolism was also correlated to dementia severity, even when age was taken as a confounding covariate, whereas metabolism in the hippocampal formation was not shown to correlate with global cognitive deficit. Functional correlation was maintained between posterior cingulate and middle frontal cortex in demented patients as in elderly controls. The key role of posteromedial cortex in cognitive dysfunction assessed in Alzheimer's disease is probably related to its highly integrated position within attentional, visuospatial and memory neuronal networks
AD  - Department of Neurology, University of Liege, Belgium. salmon@pet.crc.ulg.ac.be PMID- 0010843517 MHDA- 2000/09/19 11:01 EDAT- 2000/06/08 09:00 PID - 10.1002/(SICI)1097-0193(200005)10:1<39::AID-HBM50>3.0.CO;2-B
ER  - 

TY  - JOUR
T1  - Commission on Diagnostic Strategies: recommendations for functional neuroimaging of persons with epilepsy [In Process Citation]
A1  - Neuroimaging Subcommission of the International League Against Epilepsy
Y1  - 2000/10//
N1  - Eng
SP  - 1350
EP  - 1356
JF  - Epilepsia
VL  - 41
IS  - 10
ER  - 

TY  - JOUR
T1  - FDG PET imaging in patients with pathologically verified dementia
A1  - Hoffman,J.M.
A1  - Welsh-Bohmer,K.A.
A1  - Hanson,M.
A1  - Crain,B.
A1  - Hulette,C.
A1  - Earl,N.
A1  - Coleman,R.E.
Y1  - 2000/11//
N1  - Eng
SP  - 1920
EP  - 1928
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 41
IS  - 11
N2  - The purpose of this study was to confirm with pathologic verification 2 beliefs related to Alzheimer's disease (AD): (a) the long-standing impression that bilateral temporo-parietal hypometabolism, as noted on FDG PET imaging, is the metabolic abnormality associated with Alzheimer's disease (AD) and (b) that the sensitivity, specificity, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism allows differentiation between other degenerative causes of dementia. METHODS: Twenty two individuals (8 women, 14 men) with difficult-to-characterize memory loss or dementia (using standard clinical criteria), and who eventually received pathologic confirmation of diagnosis, were evaluated. FDG PET brain scans were obtained and visually graded by an experienced nuclear medicine physician as to the presence of classic bilateral temporo-parietal hypometabolism as seen in Alzheimer's type dementia. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism were determined using pathologic diagnosis as the gold standard. RESULTS: The clinical diagnosis of possible or probable AD was determined as the primary cause of dementia in 12 patients. The sensitivity and specificity of the clinical diagnosis for probable AD were 63% and 100%, respectively. The sensitivity and specificity of the clinical diagnosis for possible and probable AD were 75% and 100%, respectively. The sensitivity, specificity, and diagnostic accuracy of bilateral temporo-parietal hypometabolism being associated with AD were 93%, 63%, and 82%, respectively. CONCLUSION: This study confirms that bilateral temporo-parietal hypometabolism is indeed the classic metabolic abnormality associated with AD. Furthermore, in individuals with dementia whose FDG PET scans indicated a metabolic pattern other than bilateral temporo-parietal hypometabolism, a cause of dementia other than AD should be suspected. These observations may be of clinical importance in differentiating dementia syndromes. The sensitivity, specificity, and diagnostic accuracy of FDG PET are acceptable as tests to be used in the evaluation of dementia and particularly to confirm the clinical suspicion of AD
AD  - National Cancer Institute, Diagnostic Imaging Program, Bethesda, Maryland 20892-7440, USA
ER  - 

TY  - JOUR
T1  - Morphological substrates of mental dysfunction in Lewy body disease: an update
A1  - Jellinger,K.A.
Y1  - 2000///
N1  - Eng
SP  - 185
EP  - 212
JA  - J.Neural Transm.Suppl
VL  - 59
IS  - 1-2
N2  - Mental dysfunction including cognitive, behavioural changes, mood disorders, and psychosis are increasingly recognized in patients with Parkinson's disease (PD) and related disorders. Their morphological correlates are complex due to multiple system degeneration. CNS changes contributing to cognitive changes in PD include 1. Dysfunction of subcorticocortical networks with neuron losses in a) the dopaminergic nigrostriatal loop, causing striato-(pre)frontal deafferentation and mesocortico-limbic system (medial substantia nigra, ventral tegmentum); b) noradrenergic (locus coeruleus), and serotonergic systems (dorsal raphe nuclei), c) cholinergic forebrain system (nucleus basalis of Meynert, etc), and d) specific nuclei of amygdala and limbic system (thalamic nuclei, hippocampus); 2. Limbic and/or cortical Lewy body and Alzheimer type pathologies with loss of neurons and synapses, 3. Combination of subcortical, cortical, and other pathologies. In general, degeneration of subcortical and striato-frontal networks causes cognitive, executive, behavioural, and mood disorders but less severe dementia than cortical changes which, when present in sufficient numbers, are important factors for overt dementia. In PD, cortical tau pathology with similar or differential patterns than in Alzheimer disease (AD) shows significant linear correlation with cognitive decline. In dementia with Lewy bodies (DLB), the second most frequent cause of dementia in the elderly, cortical Lewy bodies (LB) may or may not be associated with amyloid plaques and neuritic AD lesions. They predominantly affect the limbic system with less frequent isocortical Braak stages, whereas the cholinergic forebrain system is more severely affected than in AD. Both neuritic degeneration in limbic system in PD and DLB and the density of cortical synapse markers correlate with neuritic AD pathology and less with cortical LB counts. Apolipoprotein E epsilon4 allele frequency may represent a common genetic background for both AD and LB pathologies but there are different proportions of plaques between DLB (less Abeta1-40) and AD (more frequent Abeta1-40). Familial parkinsonism with dementia, linked to chromosome 17 (frontotemporal dementia with Parkinsonism (FTDP-17), and other tauopathies pathologically resembling PD plus AD, are often related to mutations of the tau gene, whereas familial PD with alpha-synuclein and Parkin mutations usually show no cognitive impairment. Mood disorders, in particular depression, and psychotic complications in both PD and DLB are related to complex involvement of noradrenergic and serotonergic systems, not confirmed in AD with depression, and both the prefrontal and limbic dopaminergic systems. The specific contributions of cortical and subcortical pathologies to mental dysfunction in PD and related disorders, their relationship to AD, and their genetic and aetiological backgrounds await further elucidation
AD  - Ludwig Boltzmann Institute of Clinical Neurobiology, Vienna, Austria. kurt.jellinger@univie.ac.at
ER  - 

TY  - JOUR
T1  - Quantitative Measurement of Cerebral Acetylcholinesterase Using [11C]physostigmine
A1  - Blomqvist,G.
A1  - Tavitian,B.
A1  - Pappata,S.
A1  - Crouzel,C.
A1  - Jobert,A.
A1  - Doignon,I.
A1  - Di Giamberardino,L.
Y1  - 2001///
N1  - ENG
SP  - 114
EP  - 131
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 21
N2  - SUMMARY: [11C]physostigmine, an acetylcholinesterase inhibitor, has been shown to be a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantitative and noninvasive method to measure the regional acetylcholinesterase concentration in the brain is presented. The method is based on the observation that the ratio between regions rich in acetylcholinesterase and white matter, a region almost entirely deprived of this enzyme, was found to become approximately constant after 20 to 30 minutes, suggesting that at late time points the uptake mainly contains information about the distribution volume. Taking the white matter as the reference region, a simplified reference tissue model, with effectively one reversible tissue compartment and three parameters, was found to give a good description of the data in baboons. One of these parameters, the ratio between the total distribution volumes in the target and reference regions, showed a satisfactory correlation with the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional enzyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of human brain
AD  - INSERM U334, Service Hospitalier Frederic Joliot, Orsay Cedex, France; and Uppsala University PET Center, Uppsala, Sweden
ER  - 

TY  - JOUR
T1  - PET evaluation of bilingual language compensation following early childhood brain damage
A1  - Tierney,M.C.
A1  - Varga,M.
A1  - Hosey,L.
A1  - Grafman,J.
A1  - Braun,A.
Y1  - 2001///
N1  - ENG
SP  - 114
EP  - 121
JF  - Neuropsychologia
VL  - 39
N2  - We report a positron emission tomography (PET) study in a 37-year-old, right handed, bilingual (English and American Sign Language) male with left frontal lobe damage, without evidence of language or general intellectual dysfunction. A brain MRI scan demonstrated an atrophic lesion of the left dorsolateral prefrontal, orbital, and opercular cortices extending from the frontal pole to precentral gyrus and including parts of anterior cingulate cortex, due to an probable infantile encephalitis. H(2) 15O PET scans found evidence of increased right hemisphere activity compared to normal controls during spontaneous generation of narrative in both English and ASL. Neuropsychological data were within normal limits with the exception of visuospatial function. The results suggest the possibility that plasticity, unmasking of neural pathways, and or other adaptations of language function in the right hemisphere may have occurred, and are discussed with regard to the crowding hypothesis
AD  - Cognitive Neuroscience Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5C 205, 20892, Bethesda, MD, USA
ER  - 

TY  - JOUR
T1  - Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET
A1  - Shinotoh,H.
A1  - Aotsuka,A.
A1  - Fukushi,K.
A1  - Nagatsuka,S.
A1  - Tanaka,N.
A1  - Ota,T.
A1  - Tanada,S.
A1  - Irie,T.
Y1  - 2001/01/13/
N1  - ENG
SP  - 408
EP  - 410
JF  - Neurology
VL  - 56
IS  - 3
N2  - Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[(11)C]methylpiperidin-4-yl acetate. Donepezil reduced k(3) values, an index of AChE activity, in the cerebral cortex by 39 +/- 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain
AD  - Division of Advanced Technology for Medical Imaging (Drs. Shinotoh, Fukushi, Nagatsuka, Aotsuka, Tanaka, Ota, Tanada, and Irie), National Institute of Radiological Sciences, Chiba
ER  - 

TY  - JOUR
T1  - Acetylcholinesterase inhibition increases in vivo N-(2-[18F]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors
A1  - Skaddan,M.B.
A1  - Kilbourn,M.R.
A1  - Snyder,S.E.
A1  - Sherman,P.S.
Y1  - 2001/02//
N1  - eng
SP  - 144
EP  - 148
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 21
IS  - 2
N2  - Although the inhibition of acetylcholinesterase remains the primary treatment of Alzheimer's disease, little is known of the results of increased acetylcholine levels on muscarinic receptor occupancy or function. Using N-(2-[18F]fluoroethyl)-4-piperidyl benzilate ([18F]FEPB), a moderate affinity (Ki = 1.7 nmol/L) nonsubtype-selective muscarinic receptor antagonist, the authors examined the sensitivity of equilibrium in vivo radioligand binding in rat brain with changes in endogenous acetylcholine levels produced by treatments with acetylcholinesterase inhibitors. Phenserine administration 30 minutes before resulted in a dose-dependent into muscarinic cholinergic receptors, reaching a maximum increase of 90% in the striatum at a dose of 5 mg/kg intraperitoneally. Constant infusion of physostigmine at a dosage of 250 microg/kg/min produced an identical increase in radioligand binding. This agonist-induced increase of in vivo mAChR radioligand binding offers a new method for monitoring of the efficacy of acetylcholinesterase inhibitors or other drugs to enhance acetylcholine actions at the muscarinic receptors
AD  - Department of Radiology, University of Michigan Medical School, Ann Arbor 48109-0552, USA
ER  - 

TY  - JOUR
T1  - Radiolabeled cholinesterase substrates: in vitro methods for determining structure-activity relationships and identification of a positron emission tomography radiopharmaceutical for in vivo measurement of butyrylcholinesterase activity
A1  - Snyder,S.E.
A1  - Gunupudi,N.
A1  - Sherman,P.S.
A1  - Butch,E.R.
A1  - Skaddan,M.B.
A1  - Kilbourn,M.R.
A1  - Koeppe,R.A.
A1  - Kuhl,D.E.
Y1  - 2001/02//
N1  - eng
SP  - 132
EP  - 143
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 21
IS  - 2
N2  - There is currently great interest in developing radiolabeled substrates for acetylcholinesterase and butyrylcholinesterase that would be useful in the in vivo imaging of patients with Alzheimer's disease. Using a simple in vitro spectrophotometric assay for determination of enzymatic cleavage rates, the structure-activity relationship for a short series of 1-methyl-4-piperidinyl esters was investigated. Relative enzymatic hydrolysis rates for the well-characterized 1-methyl-4-piperidinyl acetate, propionate, and i-butyrate esters were in agreement with literature values. The 4 and 5 carbon esters of 1-methyl-4-piperidinol were specific for butyrylcholinesterase and cleaved in the rank order n-valerate > n-butyrate >> 2-methylbutyrate, iso-valerate. These spectrophotometric results were also in agreement with in vitro hydrolysis rates in mouse blood and with in vivo regional retention of radioactivity in mouse brain of 11C-labeled analogs. Brain uptake and apparent enzymatic rate constants for 1-[11C]methyl-4-piperidinyl n-butyrate and n-valerate were calculated from in vivo measurements in M. nemistrina using positron emission tomography. Based on higher brain uptake of radioactivity and superior pharmacokinetics, 1-[11C]methyl-4-piperidinyl n-butyrate was identified as a new radiopharmaceutical for the in vivo measurement of butyrylcholinesterase activity
AD  - Department of Radiology, University of Michigan Medical Center, Ann Arbor 48109-0028, USA
ER  - 

TY  - JOUR
T1  - Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study
A1  - Fiset,P.
A1  - Paus,T.
A1  - Daloze,T.
A1  - Plourde,G.
A1  - Meuret,P.
A1  - Bonhomme,V.
A1  - Hajj-Ali,N.
A1  - Backman,S.B.
A1  - Evans,A.C.
Y1  - 1999/07/01/
N1  - eng
SP  - 5506
EP  - 5513
JA  - J.Neurosci.
VL  - 19
IS  - 13
N2  - In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain
AD  - Department of Anesthesiology, McGill University, Montreal, Quebec, Canada, H3A 1A1
ER  - 

TY  - JOUR
T1  - Transplantation of embryonic dopamine neurons for severe Parkinson's disease
A1  - Freed,C.R.
A1  - Greene,P.E.
A1  - Breeze,R.E.
A1  - Tsai,W.Y.
A1  - DuMouchel,W.
A1  - Kao,R.
A1  - Dillon,S.
A1  - Winfield,H.
A1  - Culver,S.
A1  - Trojanowski,J.Q.
A1  - Eidelberg,D.
A1  - Fahn,S.
Y1  - 2001/03/08/
N1  - eng
SP  - 710
EP  - 719
JA  - N.Engl.J.Med.
VL  - 344
IS  - 10
N2  - BACKGROUND: Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. METHODS: We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. RESULTS: The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. CONCLUSIONS: Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients
AD  - Division of Clinical Pharmacology, University of Colorado School of Medicine, Denver 80262, USA
ER  - 

TY  - JOUR
T1  - Parkinsonism induced by solvent abuse
A1  - Uitti,R.J.
A1  - Snow,B.J.
A1  - Shinotoh,H.
A1  - Vingerhoets,F.J.
A1  - Hayward,M.
A1  - Hashimoto,S.
A1  - Richmond,J.
A1  - Markey,S.P.
A1  - Markey,C.J.
A1  - Calne,D.B.
Y1  - 1994/05//
N1  - eng
SP  - 616
EP  - 619
JA  - Ann.Neurol.
VL  - 35
IS  - 5
N2  - We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits were indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals
AD  - Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada
ER  - 

TY  - JOUR
T1  - Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method
A1  - Wakita,K.
A1  - Imahori,Y.
A1  - Ido,T.
A1  - Fujii,R.
A1  - Horii,H.
A1  - Shimizu,M.
A1  - Nakajima,S.
A1  - Mineura,K.
A1  - Nakamura,T.
A1  - Kanatsuna,T.
Y1  - 2000/09//
N1  - eng
SP  - 1484
EP  - 1490
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 41
IS  - 9
N2  - The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET
AD  - Clinical PET Center, Nishijin Hospital, Kyoto, Japan. PMID- 10994726 DCOM- 20001005
ER  - 

TY  - JOUR
T1  - Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts
A1  - Kling,M.A.
A1  - Carson,R.E.
A1  - Borg,L.
A1  - Zametkin,A.
A1  - Matochik,J.A.
A1  - Schluger,J.
A1  - Herscovitch,P.
A1  - Rice,K.C.
A1  - Ho,A.
A1  - Eckelman,W.C.
A1  - Kreek,M.J.
Y1  - 2000/12//
N1  - eng
SP  - 1070
EP  - 1076
JA  - J.Pharmacol.Exp.Ther.
VL  - 295
IS  - 3
N2  - Stabilized methadone-maintained former heroin addicts (MTPs) treated with effective doses of methadone have markedly reduced drug craving; reduction or elimination of heroin use; normalized stress-responsive hypothalamic-pituitary-adrenal, reproductive, and gastrointestinal function; and marked improvement in immune function and normal responses to pain, all of which are physiological indices modulated in part by endogenous and exogenous opioids directed at the mu and, in some cases, the kappa-opioid systems. This study was performed to explore opioid receptor binding in MTPs. Fourteen normal, healthy volunteers and 14 long-term MTPs in treatment for 2 to 27 years and receiving 30 to 90 mg/day of methadone were studied with positron emission tomography using tracer amounts of [(18)F]cyclofoxy, an opioid antagonist that labels mu and kappa opioid receptors. Imaging was performed in the morning, 22 h after the last dose of methadone in patients, and concurrent plasma levels of methadone were determined. Five brain regions of specific interest for addiction and pain research (thalamus, amygdala, caudate, anterior cingulate cortex, and putamen) were among the six regions of highest [(18)F]cyclofoxy binding. Specific binding of [(18)F]cyclofoxy was lower by 19 to 32% in these regions in MTPs compared with those in normal volunteers. The degree to which specific binding was lower in caudate and putamen correlated with methadone plasma levels (P <.01 and P <.05, respectively), suggesting that these lower levels of binding may be related to receptor occupancy with methadone and that significant numbers of opioid receptors may be available to function in their normal physiological roles
AD  - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
ER  - 

TY  - JOUR
T1  - Effects of nicotine on regional cerebral glucose metabolism in awake resting tobacco smokers
A1  - Domino,E.F.
A1  - Minoshima,S.
A1  - Guthrie,S.K.
A1  - Ohl,L.
A1  - Ni,L.
A1  - Koeppe,R.A.
A1  - Cross,D.J.
A1  - Zubieta,J.
Y1  - 2000///
N1  - eng
SP  - 277
EP  - 282
JF  - Neuroscience
VL  - 101
IS  - 2
N2  - Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study. In each subject, positron emission tomographic images of regional cerebral metabolism of glucose with [18F]fluorodeoxyglucose were obtained in two conditions in the morning on different days: about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design. A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used. The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained. Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model. Peak plasma nicotine levels varied three-fold and the areas under the curve(0-30min) varied seven-fold among the individual subjects. Nicotine caused a small overall reduction in global cerebral metabolism of glucose but, when the data were normalized, several brain regions showed relative increases in activity. Cerebral structures specifically activated by nicotine (nicotine minus pepper, Z score >4.0) included: left inferior frontal gyrus, left posterior cingulate gyrus and right thalamus. The visual cortex, including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis, also showed an increase in regional cerebral metabolism of glucose with Z scores >3. 6. Structures with a decrease in regional cerebral metabolism of glucose (pepper minus nicotine) were the left insula and right inferior occipital gyrus, with Z scores >3.5.Especially important is the fact that the thalamus is activated by nicotine. This is consistent with the high density of nicotinic cholinoceptors in that brain region. However, not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors. The results are discussed in relation to the cognitive effects of nicotine
AD  - Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-0632, USA. efdabcde@umich.edu
ER  - 

TY  - JOUR
T1  - Regional brain metabolism during alcohol intoxication
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Franceschi,D.
A1  - Fowler,J.S.
A1  - Thanos,P.K.
A1  - Scherbaum,N.
A1  - Pappas,N.
A1  - Wong,C.T.
A1  - Hitzemann,R.J.
A1  - Felder,C.A.
Y1  - 2000/06//
N1  - eng
SP  - 822
EP  - 829
JA  - Alcohol Clin.Exp.Res.
VL  - 24
IS  - 6
N2  - BACKGROUND: Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of gamma-aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right-handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neurotransmission. METHODS: The subjects were scanned with positron emission tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 microg/kg). RESULTS: Ethanol significantly increased self-reports of "high" (p < or = 0.0001), dizziness (p < or = 0.004), and intoxication (p < or = 0.0001). Ethanol significantly decreased whole brain (-25 +/- 6%, p < or = 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (-4.9 +/- 4.1%, p < or = 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 +/- 2.9%, p < or = 0.006) and left basal ganglia (+9 +/- 6.3%, p < or = 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (-7.8 +/- 4.8%) and relative increases in left temporal cortex (+3.8 +/- 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 +/- 7.2%). CONCLUSIONS: These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. gjwang@bnl.gov
ER  - 

TY  - JOUR
T1  - Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury
A1  - Bergsneider,M.
A1  - Hovda,D.A.
A1  - Lee,S.M.
A1  - Kelly,D.F.
A1  - McArthur,D.L.
A1  - Vespa,P.M.
A1  - Lee,J.H.
A1  - Huang,S.C.
A1  - Martin,N.A.
A1  - Phelps,M.E.
A1  - Becker,D.P.
Y1  - 2000/05//
N1  - eng
SP  - 389
EP  - 401
JA  - J.Neurotrauma
VL  - 17
IS  - 5
N2  - Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness
AD  - UCLA Division of Neurosurgery, Harbor-UCLA Medical Center, UCLA Brain Research Institute, Los Angeles, California 90095-7039, USA. mbergsneider@mednet.ucla.edu
ER  - 

TY  - JOUR
T1  - Functional neuroimaging and quantitative electroencephalography in adult traumatic head injury: clinical applications and interpretive cautions
A1  - Ricker,J.H.
A1  - Zafonte,R.D.
Y1  - 2000/04//
N1  - eng
SP  - 859
EP  - 868
JA  - J.Head Trauma Rehabil.
VL  - 15
IS  - 2
N2  - Functional neuroimaging and quantitative electroencephalographic procedures are being used increasingly in brain injury research and clinical care. These procedures are also seeing increased use in the context of forensic evaluations, particularly in cases of mild head trauma. This article provides an overview of the use of procedures such as positron emission tomography, single photon emission computed tomography, and quantitative electroencephalogram in adults. Also discussed are the clinical limitations of each procedure within the context of myriad interpretive confounds that can interfere with accurate differential diagnosis of mild head trauma
AD  - Neuropsychology and Neuroscience Laboratory, Kessler Medical Rehabilitation Research and Education Corporation, West Orange, NJ 07052, USA
ER  - 

TY  - JOUR
T1  - Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Franceschi,D.
A1  - Thanos,P.K.
A1  - Wong,C.
A1  - Gatley,S.J.
A1  - Ding,Y.S.
A1  - Molina,P.
A1  - Schlyer,D.
A1  - Alexoff,D.
A1  - Hitzemann,R.
A1  - Pappas,N.
Y1  - 2000/02/11/
N1  - eng
SP  - L161
EP  - L167
JA  - Life Sci.
VL  - 66
IS  - 12
N2  - Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices. CONCLUSIONS: The blunted response to alcohol in cocaine abusers contrasts with their enhanced sensitivity to benzodiazepines suggesting that targets other than GABA-benzodiazepine receptors are involved in the blunted sensitivity to alcohol and that the toxicity from combined cocaine-alcohol use is not due to an enhanced sensitivity to alcohol in cocaine abusers. The blunted response to alcohol in limbic regions and in cortical regions connected to limbic areas could result from a decreased sensitivity of reward circuits in cocaine abusers
AD  - Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov
ER  - 

TY  - JOUR
T1  - Effect of nicotine on brain activation during performance of a working memory task
A1  - Ernst,M.
A1  - Matochik,J.A.
A1  - Heishman,S.J.
A1  - Van Horn,J.D.
A1  - Jons,P.H.
A1  - Henningfield,J.E.
A1  - London,E.D.
Y1  - 2001/04/10/
N1  - ENG
SP  - 4728
EP  - 4733
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 8
N2  - Nicotine influences cognition and behavior, but the mechanisms by which these effects occur are unclear. By using positron emission tomography, we measured cognitive activation (increases in relative regional cerebral blood flow) during a working memory task [2-back task (2BT)] in 11 abstinent smokers and 11 ex-smokers. Assays were performed both after administration of placebo gum and 4-mg nicotine gum. Performance on the 2BT did not differ between groups in either condition, and the pattern of brain activation by the 2BT was consistent with reports in the literature. However, in the placebo condition, activation in ex-smokers predominated in the left hemisphere, whereas in smokers, it occurred in the right hemisphere. When nicotine was administered, activation was reduced in smokers but enhanced in ex-smokers. The lateralization of activation as a function of nicotine dependence suggests that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategies used to perform the memory task. Furthermore, the lack of enhancement of activation after nicotine administration in smokers likely reflects tolerance
AD  - Brain Imaging Center and Clinical Pharmacology and Therapeutics Branch, National Institute on Drug Abuse, Baltimore, MD 21224; Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21205; and Pinney Associates, Bethesda, MD 20814
ER  - 

TY  - JOUR
T1  - Imaging cerebral vasculitis in refractory epilepsy using [(11)C](R)-PK11195 positron emission tomography
A1  - Goerres,G.W.
A1  - Revesz,T.
A1  - Duncan,J.
A1  - Banati,R.B.
Y1  - 2001/04//
N1  - eng
SP  - 1016
EP  - 1018
JA  - AJR Am.J.Roentgenol.
VL  - 176
IS  - 4
AD  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, DuCane Rd., London W12 ONN, United Kingdom
ER  - 

TY  - JOUR
T1  - Positron emission tomography in neocortical epilepsies
A1  - Theodore,W.H.
A1  - Gaillard,W.D.
Y1  - 2000///
N1  - eng
SP  - 435
EP  - 446
JA  - Adv.Neurol.
VL  - 84
AD  - National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, Maryland 20892-1428, USA
ER  - 

TY  - JOUR
T1  - Postoperative changes in cerebral metabolism in temporal lobe epilepsy
A1  - Spanaki,M.V.
A1  - Kopylev,L.
A1  - DeCarli,C.
A1  - Gaillard,W.D.
A1  - Liow,K.
A1  - Fazilat,S.
A1  - Fazilat,S.
A1  - Reeves,P.
A1  - Sato,S.
A1  - Kufta,C.
A1  - Theodore,W.H.
Y1  - 2000/10//
N1  - eng
SP  - 1447
EP  - 1452
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 57
IS  - 10
N2  - BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452
AD  - Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Spanaki-Postoperative.pdf
ER  - 

TY  - JOUR
T1  - Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans
A1  - Hasselbalch,S.G.
A1  - Knudsen,G.M.
A1  - Capaldo,B.
A1  - Postiglione,A.
A1  - Paulson,O.B.
Y1  - 2001/05//
N1  - eng
SP  - 1986
EP  - 1990
JA  - J.Clin.Endocrinol.Metab
VL  - 86
IS  - 5
N2  - It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 &mgr;mol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc)
AD  - Neurobiology Research Unit, Department of Neurology, and the PET and Cyclotron Unit, University Hospital, Rigshospitalet (S.G.H., G.M.K., O.B.P.), DK-2100 Copenhagen, Denmark
ER  - 

TY  - JOUR
T1  - Comparative analysis of mr imaging, positron emission tomography, and ictal single-photon emission ct in patients with neocortical epilepsy
A1  - Hwang,S.I.
A1  - Kim,J.H.
A1  - Park,S.W.
A1  - Han,M.H.
A1  - Yu,I.K.
A1  - Lee,S.H.
A1  - Lee,D.S.
A1  - Lee,S.K.
A1  - Chung,C.K.
A1  - Chang,K.H.
Y1  - 2001/05//
N1  - eng
SP  - 937
EP  - 946
JA  - AJNR Am.J.Neuroradiol.
VL  - 22
IS  - 5
N2  - BACKGROUND AND PURPOSE: MR imaging, positron emission tomography (PET), and single-photon emission CT (SPECT) play important roles in presurgical localization of epileptic foci. However, comparative study of these imaging methods for cases of neocortical epilepsy has been limited. The purpose of this study was to compare the sensitivities of these three imaging methods for presurgical localization of neocortical epileptogenic foci. METHODS: We studied 117 consecutive patients who underwent surgery for intractable neocortical epilepsy. The pathologic substrates were neuronal migration disorder (n = 77), tumor (n = 15), and others (n = 25). MR imaging was compared retrospectively with (18)F-fluorodeoxyglucose PET and ictal technetium-99m hexamethylpropyleneamine oxime SPECT regarding their capability to correctly localize the epileptogenic foci. The pathologic findings were used as the standard of reference. RESULTS: Overall, MR imaging, PET, and ictal SPECT correctly localized the lesions for 59.8%, 77.7%, and 70.3% of the patients, respectively, with a 38% concordance rate among the three methods. PET was most sensitive (71-100%) in detecting all substrates. MR imaging was as sensitive (100%) as PET in detecting tumor but was least sensitive (48.1%) in detecting neuronal migration disorder. Ictal SPECT was more sensitive (75.8%) than MR imaging in detecting neuronal migration disorder. Patients with imaging abnormalities achieved good outcomes in 81.4% of the cases, in contrast to 59.5% for those without imaging abnormalities (P <.05). CONCLUSION: PET and ictal SPECT were overall more sensitive than was MR imaging, despite the low concordance rate and variable sensitivity depending on substrates. The detection of abnormalities by MR imaging was associated with good outcome. PET or ictal SPECT can be well used as complementary tools, particularly in cases of negative MR imaging findings
AD  - Departments of Radiology (S.-I.H., S.W. P., M.H.H., I.K.Y., S.H.L., K.-H.C.), Nuclear Medicine (D.S.L.), Neurology (S.K.L.), and Neurosurgery (C-K.C.), Seoul National University College of Medicine, Seoul
ER  - 

TY  - JOUR
T1  - Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note
A1  - Braun,V.
A1  - Dempf,S.
A1  - Tomczak,R.
A1  - Wunderlich,A.
A1  - Weller,R.
A1  - Richter,H.P.
Y1  - 2001/05//
N1  - eng
SP  - 1178
EP  - 1181
JF  - Neurosurgery
VL  - 48
IS  - 5
N2  - OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip)
AD  - Department of Neurosurgery, University of Ulm, Gunzburg, Germany. veit.braun@medizin.uni-ulm.de
ER  - 

TY  - JOUR
T1  - Parieto-occipital glucose hypometabolism in Parkinson's disease with autonomic failure
A1  - Arahata,Y.
A1  - Hirayama,M.
A1  - Ieda,T.
A1  - Koike,Y.
A1  - Kato,T.
A1  - Tadokoro,M.
A1  - Ikeda,M.
A1  - Ito,K.
A1  - Sobue,G.
Y1  - 1999/03/01/
N1  - eng
SP  - 119
EP  - 126
JA  - J.Neurol.Sci.
VL  - 163
IS  - 2
N2  - To investigate the characteristics of regional cerebral metabolism in a subgroup of patients with Parkinson's disease and autonomic failure, we studied seven patients with Parkinson's disease with autonomic failure (PA group), 11 patients with Parkinson's disease without apparent autonomic failure (PD group), and nine normal controls using fluoro-deoxyglucose positron emission tomography (FDG-PET). To determine differences in metabolic distribution among these groups, regional relative glucose metabolic rates (RGMR), which were normalized with cerebellar values, were calculated and age-adjusted covariance analyses were done. When compared with that of controls. RGMR in the cerebral cortex of the PA group was markedly reduced in the occipital cortex (P<0.001), inferior parietal cortex (P<0.005) and superior parietal cortex (P<0.005), but without a decrease in the sensory motor and medial temporal cortices, putamen and thalamus. In contrast, the PD group did not show significant focal hypometabolic distribution. Our findings raise the possibility that Parkinson's disease with autonomic failure may overlap with the features of dementia with Lewy bodies
AD  - Department of Neurology, Nagoya University School of Medicine, Japan
ER  - 

TY  - JOUR
T1  - Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia
A1  - Heiss,W.D.
A1  - Kracht,L.W.
A1  - Thiel,A.
A1  - Grond,M.
A1  - Pawlik,G.
Y1  - 2001/01//
N1  - eng
SP  - 20
EP  - 29
JF  - Brain
VL  - 124
IS  - Pt 1
N2  - Active treatment of acute ischaemic stroke can only be successful as long as tissue in the area of ischaemic compromise is still viable. Therefore, the identification of the area of irreversible damage, and its distinction from the penumbral zone, may improve the estimation of the potential efficacy of various therapeutic strategies. Ten patients (seven male, three female, aged 52-75 years) with acute ischaemic stroke, in whom MRI delineated an infarct involving the cortex 3 weeks after the attack, were studied by [(11)C]flumazenil (FMZ) PET to assess their neuronal integrity, and regional cerebral blood flow (CBF) was measured by H(2)(15)O PET 2-12 h (median interval 6 h) after onset of symptoms. Cortical volumes of interest (3 mm radius) were placed on co-registered CBF, FMZ and on late MRI scans. Using initial CBF and FMZ binding data from volumes of interest finally located within or outside the cortical infarct, cumulative probability curves were computed to predict eventual infarction or non-infarction. Positive (at least 95% chance of infarct) and negative (at least 95% chance of non-infarct) prediction limits for CBF (4.8 and 14.1 ml/100 g/min, respectively) and for FMZ binding (3.4 and 5.5 times the mean of normal white matter, respectively) were determined to define the penumbral range. Using the lower FMZ binding threshold of 3.4 for irreversible tissue damage and the upper CBF value of 14.1 ml/ 100 g/min for the threshold of critical perfusion at or above which tissue will likely be preserved, various cortical subcompartments were identified: of the final cortical infarct (median size 25.7 cm(3)) a major portion comprising, on average, 55.1% showed FMZ binding critically decreased, thus predicting necrosis. In 20.5% of the final infarct, on average, CBF was in the penumbral range (<14.1 ml/100 g/min) and FMZ binding was above the critical threshold of irreversible damage. Only 12.9% of the final infarct exhibited neuronal integrity and CBF values above the penumbral range. Therefore, most of the final infarct is irreversibly damaged already at the time of the initial evaluation, when studied several hours after stroke onset. A much smaller portion is still viable but suffers from insufficient blood supply: this tissue may be salvaged by effective reperfusion. Only an even smaller compartment is viable and sufficiently perfused, but eventually becomes necrotic, mainly owing to delayed mechanisms, and may benefit from neuroprotective or other measures targeted at secondary damage. Therefore, early reperfusion is crucial in acute ischaemic stroke
AD  - Max-Planck-Institut fur neurologische Forschung and Neurologische Universitatsklinik Koln, Koln, Germany. wdh@pet.mpin-koeln.mpg.de
ER  - 

TY  - JOUR
T1  - Statistical modeling of positron emission tomography images in wavelet space
A1  - Turkheimer,F.E.
A1  - Brett,M.
A1  - Aston,J.A.
A1  - Leff,A.P.
A1  - Sargent,P.A.
A1  - Wise,R.J.
A1  - Grasby,P.M.
A1  - Cunningham,V.J.
Y1  - 2000/11//
N1  - UI - 20534207
SP  - 1610
EP  - 1618
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 20
IS  - 11
N2  - A new method is introduced for the analysis of multiple studies measured with emission tomography. Traditional models of statistical analysis (ANOVA, ANCOVA and other linear models) are applied not directly on images but on their correspondent wavelet transforms. Maps of model effects estimated from these models are filtered using a thresholding procedure based on a simple Bonferroni correction and then reconstructed. This procedure inherently represents a complete modeling approach and therefore obtains estimates of the effects of interest (condition effect, difference between conditions, covariate of interest, and so on) under the specified statistical risk. By performing the statistical modeling step in wavelet space. the procedure allows the direct estimation of the error for each wavelet coefficient; hence, the local noise characteristics are accounted for in the subsequent filtering. The method was validated by use of a null dataset and then applied to typical examples of neuroimaging studies to highlight conceptual and practical differences from existing statistical parametric mapping approaches
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:11083236
ER  - 

TY  - JOUR
T1  - The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity
A1  - Banati,R.B.
A1  - Newcombe,J.
A1  - Gunn,R.N.
A1  - Cagnin,A.
A1  - Turkheimer,F.
A1  - Heppner,F.
A1  - Price,G.
A1  - Wegner,F.
A1  - Giovannoni,G.
A1  - Miller,D.H.
A1  - Perkin,G.D.
A1  - Smith,T.
A1  - Hewson,A.K.
A1  - Bydder,G.
A1  - Kreutzberg,G.W.
A1  - Jones,T.
A1  - Cuzner,M.L.
A1  - Myers,R.
Y1  - 2000/11//
SP  - 2321
EP  - 2337
JF  - Brain
VL  - 123 ( Pt 11)
N2  - This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain
AD  - MRC Cyclotron Unit and Robert Steiner Magnetic Resonance Imaging Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
UR  - PM:11050032
ER  - 

TY  - JOUR
T1  - Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease
A1  - Grady,C.L.
A1  - Furey,M.L.
A1  - Pietrini,P.
A1  - Horwitz,B.
A1  - Rapoport,S.I.
Y1  - 2001/04//
SP  - 739
EP  - 756
JF  - Brain
VL  - 124
IS  - Pt 4
N2  - To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion- related network of regions
AD  - Rotman Research Institute, Baycrest Centre for Geriatric Care, University of Toronto, Toronto, Ontario, Canada cgrady@rotman- baycrestonca
UR  - PM:11287374
ER  - 

TY  - JOUR
T1  - Cerebral energetics and the glycogen shunt: Neurochemical basis of functional imaging
A1  - Shulman,R.G.
A1  - Hyder,F.
A1  - Rothman,D.L.
Y1  - 2001/05/22/
N1  - eng
SP  - 6417
EP  - 6422
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 11
N2  - Positron-emission tomography and functional MRS imaging signals can be analyzed to derive neurophysiological values of cerebral blood flow or volume and cerebral metabolic consumption rates of glucose (CMR(Glc)) or oxygen (CMR(O(2))). Under basal physiological conditions in the adult mammalian brain, glucose oxidation is nearly complete so that the oxygen-to-glucose index (OGI), given by the ratio of CMR(O(2))/CMR(Glc), is close to the stoichiometric value of 6. However, a survey of functional imaging data suggests that the OGI is activity dependent, moving further below the oxidative value of 6 as activity is increased. Brain lactate concentrations also increase with stimulation. These results had led to the concept that brain activation is supported by anaerobic glucose metabolism, which was inconsistent with basal glucose oxidation. These differences are resolved here by a proposed model of glucose energetics, in which a fraction of glucose is cycled through the cerebral glycogen pool, a fraction that increases with degree of brain activation. The "glycogen shunt," although energetically less efficient than glycolysis, is followed because of its ability to supply glial energy in milliseconds for rapid neurotransmitter clearance, as a consequence of which OGI is lowered and lactate is increased. The value of OGI observed is consistent with passive lactate efflux, driven by the observed lactate concentration, for the few experiments with complete data. Although the OGI changes during activation, the energies required per neurotransmitter release (neuronal) and clearance (glial) are constant over a wide range of brain activity
AD  - Departments of Diagnostic Radiology and Molecular Biophysics and Biochemistry, and Section of Bioimaging Sciences, Yale University, New Haven, CT 06510
ER  - 

TY  - JOUR
T1  - Neuroanatomic correlates for deficits in decision making in Parkinson's disease: a PET study
A1  - Thiel,A.
A1  - Hilker,R.
A1  - Kessler,J.
A1  - Habedank,B.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 2001///
SP  - S301
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 21 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - PET functional parametric images of acetylcholine esterase activity without blood sampling
A1  - Herholz,K.
A1  - Zndorf,G.
A1  - Lercher,M.
A1  - Wienhard,K.
A1  - Bauer,B.
A1  - Weisenbach,S.
A1  - Heiss,W.-D.
Y1  - 2001///
SP  - S528
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 21 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Registration, segmentation, and visualization of multimodal brain images
A1  - Viergever,M.A.
A1  - Maintz,J.B.
A1  - Niessen,W.J.
A1  - Noordmans,H.J.
A1  - Pluim,J.P.
A1  - Stokking,R.
A1  - Vincken,K.L.
Y1  - 2001/03//
N1  - eng
SP  - 147
EP  - 151
JA  - Comput.Med.Imaging Graph.
VL  - 25
IS  - 2
N2  - This paper gives an overview of the studies performed at our institute over the last decade on the processing and visualization of brain images, in the context of international developments in the field. The focus is on multimodal image registration and multimodal visualization, while segmentation is touched upon as a preprocessing step for visualization. The state-of-the-art in these areas is discussed and suggestions for future research are given
AD  - Image Sciences Institute, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. max@isi.uu.nl
ER  - 

TY  - JOUR
T1  - The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery
A1  - Chao,S.T.
A1  - Suh,J.H.
A1  - Raja,S.
A1  - Lee,S.Y.
A1  - Barnett,G.
Y1  - 2001/06/20/
N1  - eng
SP  - 191
EP  - 197
JA  - Int.J.Cancer
VL  - 96
IS  - 3
N2  - Radiation necrosis and recurrent brain tumor have similar symptoms and are indistinguishable on both magnetic resonance imaging (MRI) and computed tomograph scans. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been proposed as a diagnostic alternative, particularly when co-registered with MRI. We studied 47 patients with brain tumors treated with stereotactic radiosurgery and followed with FDG PET. For all tumor types, the sensitivity of FDG PET for diagnosing tumor was 75% and the specificity was 81%. For brain metastasis without MRI co-registration, FDG PET had a sensitivity of 65% and a specificity of 80%. For brain metastasis with MRI co-registration, FDG PET had a sensitivity of 86% and specificity of 80%. MRI co-registration appears to improve the sensitivity of FDG PET, making it a useful modality to distinguish between radiation necrosis and recurrent brain metastasis. Copyright 2001 Wiley-Liss, Inc
AD  - Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio
ER  - 

TY  - JOUR
T1  - [18F]FDG-PET Reveals Temporal Hypometabolism in Patients With Temporal Lobe Epilepsy Even When Quantitative MRI and Histopathological Analysis Show Only Mild Hippocampal Damage
A1  - Lamusuo,S.
A1  - Jutila,L.
A1  - Ylinen,A.
A1  - Kalviainen,R.
A1  - Mervaala,E.
A1  - Haaparanta,M.
A1  - Jaaskelainen,S.
A1  - Partanen,K.
A1  - Vapalahti,M.
A1  - Rinne,J.
Y1  - 2001/06//
N1  - ENG
SP  - 933
EP  - 939
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 58
IS  - 6
N2  - BACKGROUND: The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([(18)F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. OBJECTIVE: To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. PATIENTS AND METHODS: Sixteen patients with drug-resistant temporal lobe epilepsy underwent [(18)F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. RESULTS: Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [(18)F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. CONCLUSIONS: [(18)F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD
AD  - Department of Neurology, University of Turku, PO Box 52, FIN-20521 Turku, Finland. juha.rinne@pet.tyks.fi
ER  - 

TY  - JOUR
T1  - [11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology
A1  - Lamusuo,S.
A1  - Pitkanen,A.
A1  - Jutila,L.
A1  - Ylinen,A.
A1  - Partanen,K.
A1  - Kalviainen,R.
A1  - Ruottinen,H.M.
A1  - Oikonen,V.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Vapalahti,M.
A1  - Vainio,P.
A1  - Rinne,J.O.
Y1  - 2000/06/27/
N1  - eng
SP  - 2252
EP  - 2260
JF  - Neurology
VL  - 54
IS  - 12
N2  - OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI
AD  - Department of Neurology, University of Turku, Finland
ER  - 

TY  - JOUR
T1  - Comparison of [18F]FDG-PET, [99mTc]-HMPAO-SPECT, and [123I]-iomazenil-SPECT in localising the epileptogenic cortex
A1  - Lamusuo,S.
A1  - Ruottinen,H.M.
A1  - Knuuti,J.
A1  - Harkonen,R.
A1  - Ruotsalainen,U.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Mervaala,E.
A1  - Nousiainen,U.
A1  - Jaaskelainen,S.
A1  - Ylinen,A.
A1  - Kalviainen,R.
A1  - Rinne,J.K.
A1  - Vapalahti,M.
A1  - Rinne,J.O.
Y1  - 1997/12//
N1  - eng
SP  - 743
EP  - 748
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 63
IS  - 6
N2  - OBJECTIVES: Firstly, to compare the findings of interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and of single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene-amine-oxime (HMPAO) and 123I-iomazenil in localising the epileptogenic cortex in patients who were candidates for epilepsy surgery, but in whom clinical findings, video EEG monitoring (V-EEG), MRI, and neuropsychological evaluations did not give any definite localisation of the seizure onset. Secondly, to assess the ability of these functional methods to help in the decision about the epilepsy surgery. METHODS: Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT. HMPAO-SPECT was performed in 11 of these 18 patients. Two references for localisation was used--ictal subdural EEG recordings (S-EEG) and the operated region. RESULTS: Fifteen of 18 patients had localising findings in S-EEG. FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients. HMPAO-SPECT visualised the focus less accurately than the two other methods. In three patients S-EEG showed independent bitemporal seizure onset. In these patients FDG-PET showed no lateralisation. However, iomazenil-SPECT showed temporal lobe lateralisation in two of them. CONCLUSION: FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy
AD  - Department of Neurology, University of Turku, Finland
ER  - 

TY  - JOUR
T1  - Selective pharmacological activation of limbic structures in human volunteers: a positron emission tomography study
A1  - Servan-Schreiber,D.
A1  - Perlstein,W.M.
A1  - Cohen,J.D.
A1  - Mintun,M.
Y1  - 1998///
N1  - eng
SP  - 148
EP  - 159
JA  - J.Neuropsychiatry Clin.Neurosci.
VL  - 10
IS  - 2
N2  - Using a pharmacological probe, procaine hydrochloride, the authors elicited consistent and selective activation of anterior limbic and paralimbic structures in normal human volunteers as documented by H215O positron emission tomography. This activation was associated with a range of emotional, somatic, and visceral experiences, often similar to those experienced during the aura of temporal lobe epilepsy. Several subjects also experienced panic attacks. This study confirms that selective anterior limbic/paralimbic activity in normal human volunteers evokes many emotional phenomena as well as common "ill-defined" symptoms observed in clinical conditions. The present combination of procaine challenge and neuroimaging provides a noninvasive procedure to probe the contribution of different anterior limbic and paralimbic structures to normal human emotions and to neuropsychiatric disorders
AD  - Department of Psychiatry, School of Medicine, University of Pittsburgh, Pennsylvania, USA
ER  - 

TY  - JOUR
T1  - Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography
A1  - Adler,L.J.
A1  - Gyulai,F.E.
A1  - Diehl,D.J.
A1  - Mintun,M.A.
A1  - Winter,P.M.
A1  - Firestone,L.L.
Y1  - 1997/01//
N1  - eng
SP  - 120
EP  - 126
JA  - Anesth.Analg.
VL  - 84
IS  - 1
N2  - Recent positron emission tomography (PET) studies have demonstrated areas of pain processing in the human brain. Given the inhibitory effects of opioids on neuronal activity, we predicted that fentanyl's analgesic effects would be associated with suppression of pain-evoked responses in these distinct brain areas. To test this, PET was used to measure cerebral blood flow responses, as reflections of regional neuronal activity, to painful and nonpainful thermal stimuli both in the absence and presence of fentanyl in humans. During each PET scan in nine healthy volunteers a tonic heat source was placed against the subject's left forearm, delivering a preset temperature of either 40 degrees C (nonpainful) or 47-48 degrees C (painful). Subjects underwent eight blood flow studies, each consisting of 50 mCi [15O]water injection and a PET scan. The first four studies were performed during placebo administration in the stimulus sequence: nonpainful, painful, painful, nonpainful. This sequence was then repeated during intravenous (i.v.) administration of fentanyl 1.5 micrograms/kg [corrected]. Significant differences in regional cerebral blood flow (rCBF) between the placebo and the fentanyl conditions during nonpainful and painful stimuli were identified using statistical parametric mapping. It was found that pain increased rCBF in the anterior cingulate, ipsilateral thalamus, prefrontal cortex, and contralateral supplementary motor area. Fentanyl increased rCBF in the anterior cingulate and contralateral motor cortices, and decreased rCBF in the thalamus (bilaterally) and posterior cingulate during both stimuli. During combined pain stimulation and fentanyl administration, fentanyl significantly augmented pain-related rCBF increases in the supplementary motor area and prefrontal cortex. This activation pattern was associated with decreased pain perception, as measured on a visual analog scale. In contrast to our hypothesis, these data indicate that fentanyl analgesia involves augmentation of pain-evoked cerebral responses in certain areas, as well as both activation and inhibition in other brain regions unresponsive to pain stimulation alone
AD  - Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, USA
ER  - 

TY  - JOUR
T1  - Increased pineal Fdopa uptake is related to severity of Parkinson's disease--a PET study
A1  - Ghaemi,M.
A1  - Rudolf,J.
A1  - Hilker,R.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 2001/05//
N1  - eng
SP  - 213
EP  - 219
JA  - J.Pineal Res.
VL  - 30
IS  - 4
N2  - We investigated regional L-3,4-dihydroxy-6-[18F]fluoro-phenyl-alanine (Fdopa) uptake within the pineal gland using co-registration of Fdopa PET and MRI images. Data from 12 early Parkinson's disease (PD) and 9 advanced PD patients were compared with those from 13 age-matched healthy controls. We found a significant increase of Fdopa influx constants (Ki) and relative Fdopa tracer activity in the pineal gland of PD patients. Additionally, significant correlations were found between Ki and the Hoehn and Yahr (H&Y) scores, and between the relative Fdopa activity and the parameters disease duration, H&Y disease score and Unified Parkinson's Disease Rating Scale (UPDRS). Our studies in patients with PD indicate a participation of extrastriatal dopaminergic structures within the scope of pathophysiological processes in PD. The result may be explained as a compensatory upregulation of monoaminergic transmitter systems outside the basal ganglia. Increased Fdopa uptake in the pineal gland may reflect pineal dysfunction in PD patients
AD  - Klinik fur Neurologie der Universitat zu Koln, Germany
ER  - 

TY  - JOUR
T1  - A global estimator unbiased by local changes
A1  - Andersson,J.L.
A1  - Ashburner,J.
A1  - Friston,K.
Y1  - 2001/06//
N1  - eng
SP  - 1193
EP  - 1206
JF  - Neuroimage
VL  - 13
IS  - 6
N2  - The global activity is an important confound when analyzing PET data in that its inclusion in the statistical model can substantially reduce error variance and increase sensitivity. However, by defining global activity as the average over all voxels one introduces a bias that is collinear with experimental factors. This leads to an underestimation of true activations and the introduction of artefactual deactivations. We propose a novel estimator for the global activity based on the notion of finding a maximally nonlocal mode in a multivariate characterization of the data, while maximizing the locality of the remaining modes. The approach uses singular value decomposition (SVD) to find a provisional set of modes, which are subsequently rotated such that a metric based on the above heuristic is maximized. This metric is a version of the stochastic sign change (SSC) criterion that has been used previously for normalizing medical images with focal defects. The estimator was evaluated on simulated and real functional imaging (PET) data. The simulations show that the bias of the global mean, introduced by focal activations, is reduced by 80-90% with the new estimator. Comparison with a previous unbiased estimator, using the empirical data, yielded similar results. The advantage of the new estimator is that it is not informed of experimental design and relies only on general assumptions regarding the nature of the signal. Copyright 2001 Academic Press
AD  - The Wellcome Department of Cognitive Neurology, London, United Kingdom
ER  - 

TY  - JOUR
T1  - FDG-PET analysis and findings in amnesia resulting from hypoxia
A1  - Reed,L.J.
A1  - Marsden,P.
A1  - Lasserson,D.
A1  - Sheldon,N.
A1  - Lewis,P.
A1  - Stanhope,N.
A1  - Guinan,E.
A1  - Kopelman,M.D.
Y1  - 1999/09//
N1  - eng
SP  - 599
EP  - 612
JF  - Memory
VL  - 7
IS  - 5-6
N2  - The assumptions underlying neuroimaging, and problems in its analysis and interpretation, are commonly underestimated in neuropsychology. The ways in which fluoro-deoxy-glucose (FDG) positron emission tomography (PET) data can be analysed are discussed. PET findings from four patients who had suffered severe amnesia, following episodes of acute hypoxia, are presented. These patients had shown evidence of medial temporal (hippocampal and parahippocampal) atrophy on MRI brain scans. The PET data were analysed in several different ways. The converging findings were that the patients showed bilateral thalamic hypometabolism, and there was also evidence of retrosplenial hypometabolism bilaterally. Cognitively, these patients performed most like other patients with medial temporal lesions, but the results indicate that structural lesions can have distal metabolic effects on structures elsewhere. These findings are interpreted in the light of neuroanatomical observations concerning parallel projections between medial temporal lobe structures and the thalamus, some of which pass via the retrosplenium
AD  - St Thomas's Hospital, London, UK
ER  - 

TY  - JOUR
T1  - Plasticity of language networks in patients with brain tumors. A positron emission tomography activation study
A1  - Thiel,A.
A1  - Herholz,K.
A1  - Koyuncu,A.
A1  - Ghaemi,M.
A1  - Kracht,L.-W.
A1  - Habedank,B.
A1  - Heiss,W.-D.
Y1  - 2001///
SP  - 620
EP  - 629
JF  - Annals of Neurology
VL  - 50
ER  - 

TY  - CHAP
T1  - PET functional parametric images of acetylcholine esterase activity without blood sampling
A1  - Zndorf,G.
A1  - Herholz,K.
A1  - Lercher,M.
A1  - Wienhard,K.
A1  - Bauer,B.
A1  - Weisenbach,S.
A1  - Heiss,W.-D.
Y1  - 2002///
SP  - 41
EP  - 46
T2  - Brain imaging using PET
A2  - Senda,M.
A2  - Kimura,Y.
A2  - Herscovitch,P.
IS  - 7
CY  - San Diego, Ca.
PB  - Academic Press
ER  - 

TY  - JOUR
T1  - Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo
A1  - Doubrovin,M.
A1  - Ponomarev,V.
A1  - Beresten,T.
A1  - Balatoni,J.
A1  - Bornmann,W.
A1  - Finn,R.
A1  - Humm,J.
A1  - Larson,S.
A1  - Sadelain,M.
A1  - Blasberg,R.
A1  - Gelovani,Tjuvajev J.
Y1  - 2001/07/31/
N1  - eng
SP  - 9300
EP  - 9305
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 16
N2  - A noninvasive method for molecular imaging of the activity of different signal transduction pathways and the expression of different genes in vivo would be of considerable value. It would aid in understanding the role specific genes and signal transduction pathways have in various diseases, and could elucidate temporal dynamics and regulation at different stages of disease and during various therapeutic interventions. We developed and assessed a method for monitoring the transcriptional activation of endogenous genes by positron-emission tomography (PET) imaging. The HSV1-tk/GFP (TKGFP) dual reporter gene was used to monitor transcriptional activation of p53-dependent genes. A retrovirus bearing the Cis-p53/TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting p53-specific enhancer. U87 glioma and SaOS-2 osteosarcoma cells were transduced with this retrovirus and used to establish xenografts in rats. We demonstrated that DNA damage-induced up-regulation of p53 transcriptional activity correlated with the expression of p53-dependent downstream genes, such as p21, in U87 (wild-type p53), but not in SaOS-2 osteosarcoma (p53 -/-) cells. We showed that PET, with [(124)I]FIAU (2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-[(124)I]iodouracil) and the Cis-p53TKGFP reporter system, is sufficiently sensitive to image the transcriptional regulation of genes in the p53 signal transduction pathway. These imaging results were confirmed by independent measurements of p53 activity and the expression levels of downstream genes (e.g., p21) by using conventional molecular-biological assays. PET imaging of p53 transcriptional activity in tumor xenografts by using the Cis-p53TKGFP reporter system may be useful in assessing novel therapeutic approaches
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
ER  - 

TY  - JOUR
T1  - Regional mu opioid receptor regulation of sensory and affective dimensions of pain
A1  - Zubieta,J.K.
A1  - Smith,Y.R.
A1  - Bueller,J.A.
A1  - Xu,Y.
A1  - Kilbourn,M.R.
A1  - Jewett,D.M.
A1  - Meyer,C.R.
A1  - Koeppe,R.A.
A1  - Stohler,C.S.
Y1  - 2001/07/13/
N1  - eng
SP  - 311
EP  - 315
JF  - Science
VL  - 293
IS  - 5528
N2  - The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and mu-opioid receptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the regional release of endogenous opioids interacting with mu-opioid receptors in a number of cortical and subcortical brain regions. The activation of the mu-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience, with distinct neuroanatomical involvements. These data demonstrate the central role of the mu-opioid receptors and their endogenous ligands in the regulation of sensory and affective components of the pain experience
AD  - Department of Psychiatry and Mental Health Research Institute, Medical School, The University of Michigan, Ann Arbor, MI 48104-1687, USA. zubieta@umich.edu
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow effects of nicotine in overnight abstinent smokers
A1  - Zubieta,J.
A1  - Lombardi,U.
A1  - Minoshima,S.
A1  - Guthrie,S.
A1  - Ni,L.
A1  - Ohl,L.E.
A1  - Koeppe,R.A.
A1  - Domino,E.F.
Y1  - 2001/06/01/
N1  - eng
SP  - 906
EP  - 913
JA  - Biol.Psychiatry
VL  - 49
IS  - 11
N2  - Background: Most people agree that dependence to tobacco is mediated by the effects of nicotine on the central nervous system, albeit the neural pathways involved are not clearly delineated. We investigated the effect of nasal nicotine spray on regional cerebral blood flow (rCBF) in a sample of habitual smokers, with H(2)(15)O and positron emission tomography (PET).Methods: Eighteen volunteer smokers were studied after 12 hours of smoking deprivation. Regional cerebral blood flow measures were obtained with PET and 50 mCi H(2)(15)O in six consecutive scans. Nicotine spray and a placebo spray were administered in a single-blind design, preceded and followed by baseline studies. Images were coregistered and anatomically standardized. Square (9-mm side) regions of interest were placed in 10 preselected brain regions, bilaterally. The effects of the experimental condition and gender were tested with two-way repeated-measures analysis of variance in each of the regions studied.Results: Nicotine reduced rCBF in the left anterior temporal cortex and in the right amygdala. Increases were noted in the right anterior thalamus.Conclusions: In habitual smokers after overnight abstinence, nicotine induced differing effects on regional blood flow relative to whole brain blood flow. Increases were observed in the thalamus, a region rich in nicotinic receptors, and reductions in limbic and paralimbic (amygdala, anterior temporal cortex) regions
AD  - Department of Psychiatry, The University of Michigan, (J-KZ, SG), Ann Arbor, Michigan, USA
ER  - 

TY  - JOUR
T1  - Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET
A1  - Zubieta,J.K.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Kilbourn,M.R.
A1  - Mangner,T.J.
A1  - Foster,N.L.
A1  - Kuhl,D.E.
Y1  - 2001/03/15/
N1  - eng
SP  - 275
EP  - 287
JF  - Synapse
VL  - 39
IS  - 4
N2  - Cerebral cholinergic deficits have been described in Alzheimer disease (AD) and as a result of normal aging. At the present time, there are very limited options for the quantification of cholinergic receptors with in vivo imaging techniques such as PET. In the present study, we examined the feasibility of utilizing [11C]N-methyl-4-piperidyl benzilate (NMPB), a nonselective muscarinic receptor ligand, in the study of aging and neurodegenerative processes associated with cholinergic dysfunction. Based on prior data describing the accuracy of various kinetic methods, we examined the concentration of muscarinic receptors with [11C]NMPB and PET using two- and three-compartment kinetic models. Eighteen healthy subjects and six patients diagnosed with probable AD were studied. Pixel-by-pixel two-compartment model fits showed acceptable precision in the study of normal aging, with comparable results to those obtained with a more complex and less precise three-compartment model. Normal aging was associated with a reduction in muscarinic receptor binding in neocortical regions and thalamus. In AD patients, the three-compartment model appeared capable of dissociating changes in tracer transport from changes in receptor binding, but suffered from statistical uncertainty, requiring normalization to a reference region, and therefore limiting its potential use in the study of neurodegenerative processes. After normalization, no regional changes in muscarinic receptor concentrations were observed in AD. Copyright 2001 Wiley-Liss, Inc
AD  - Department of Psychiatry, The University of Michigan, Neuroscience Building, 1103 East Huron Street, Ann Arbor, MI 48104-1687, USA. zubieta@umich.edu
ER  - 

TY  - JOUR
T1  - Persistent postictal hyperperfusion demonstrated with PET
A1  - Tatlidil,R.
Y1  - 2000/12//
N1  - eng
SP  - 83
EP  - 88
JA  - Epilepsy Res.
VL  - 42
IS  - 2-3
N2  - Four patients with complex partial seizure disorder whose positron emission tomography (PET) scans show sustained hyperperfusion of the epileptiform focus 12-24 h after a seizure episode are presented. Three of these patients underwent same day Fluorine-18 (18F) deoxyglucose (FDG) PET scans, which showed hypometabolism of the epileptic temporal lobe. In one patient who underwent repeated blood flow and concurrent glucose metabolism scans 4 days after a seizure, hyperperfusion was not present and the FDG-PET demonstrated hypometabolism. Persistent hyperperfusion was noted in six out of 65 cases studied. Four out of six patients who were followed clinically were presented in this report. The cause of the rare occurrence of persistent postictal or interictal hyperperfusion and the differences of postictal blood flow dynamics and glucose metabolism need to be clarified further with future studies
AD  - Research Imaging Center, University of Texas Health Sciences Center, San Antonio, TX, USA
ER  - 

TY  - JOUR
T1  - Presurgical lateralization of seizure focus and language dominant hemisphere with O-15 water PET imaging
A1  - Tatlidil,R.
A1  - Xiong,J.
A1  - Luther,S.
Y1  - 2000/08//
N1  - eng
SP  - 73
EP  - 80
JA  - Acta Neurol.Scand.
VL  - 102
IS  - 2
N2  - OBJECTIVES: The purpose of this study was to assess the value of same day blood flow PET in both the identification of the language dominant hemisphere and in the lateralization of the epileptic focus in patients who were preoperatively evaluated for complex partial seizures. METHODS: The charts of 24 patients who had temporal lobectomies for seizures were retrospectively reviewed. All PET scans were acquired by using O-15 water tracer (H2(15)O) in both resting and language activation conditions. PET language laterality results were compared to Intracarotid amytal procedure (IAP) results. For epileptic focus lateralizations, regions of interest (ROI) analysis of temporal lobes was performed on resting scans. RESULTS: IAP testing was discordant with PET language mapping in 1 out of 24 cases. This patient had a decline in cognitive abilities as measured by postoperative neuropsychologic testing. For epileptic focus lateralization, the PET was highly sensitive (87%) and specific (100%). Lateralizations with the PET were in agreement with surgical sites in all cases. Eighteen patients (75%) were seizure free and 4 patients (17%) were significantly improved after surgery. CONCLUSION: The results suggest that O-15 water PET is sensitive and specific in both the lateralization of epileptic focus and the language dominant hemisphere and can be a cost-effective and noninvasive method in presurgical evaluation of patients with complex partial seizures
AD  - Research Imaging Center, University of Texas Health Science Center in San Antonio, USA
ER  - 

TY  - JOUR
T1  - Prediction of cognitive decline in normal elderly subjects with 2-F-18-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG PET)
A1  - de Leon,M.J.
A1  - Convit,A.
A1  - Wolf,O.T.
A1  - Tarshish,C.Y.
A1  - DeSanti,S.
A1  - Rusinek,H.
A1  - Tsui,W.
A1  - Kandil,E.
A1  - Scherer,A.J.
A1  - Roche,A.
A1  - Imossi,A.
A1  - Thorn,E.
A1  - Bobinski,M.
A1  - Caraos,C.
A1  - Lesbre,P.
A1  - Schlyer,D.
A1  - Poirier,J.
A1  - Reisberg,B.
A1  - Fowler,J.
Y1  - 2001/08/28/
N1  - ENG
SP  - 10966
EP  - 10971
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 19
N2  - Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal
AD  - New York University School of Medicine, New York, NY 10016; Nathan Kline Institute, Orangeburg, NY 10962; University of Duesseldorf, Duesseldorf D-40225, Germany; Brookhaven National Laboratory, Upton, NY 11973; and McGill University, Montreal, QC, Canada H4H IR3
ER  - 

TY  - JOUR
T1  - In-vivo measurement of activated microglia in dementia
A1  - Cagnin,A.
A1  - Brooks,D.J.
A1  - Kennedy,A.M.
A1  - Gunn,R.N.
A1  - Myers,R.
A1  - Turkheimer,F.E.
A1  - Jones,T.
A1  - Banati,R.B.
Y1  - 2001/08/11/
N1  - eng
SP  - 461
EP  - 467
JF  - Lancet
VL  - 358
IS  - 9280
N2  - BACKGROUND: Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. METHODS: We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site. FINDINGS: In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. INTERPRETATION: In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease
AD  - MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK
ER  - 

TY  - JOUR
T1  - Memory failure has different mechanisms in subcortical stroke and Alzheimer's disease
A1  - Reed,B.R.
A1  - Eberling,J.L.
A1  - Mungas,D.
A1  - Weiner,M.W.
A1  - Jagust,W.J.
Y1  - 2000/09//
N1  - eng
SP  - 275
EP  - 284
JA  - Ann.Neurol.
VL  - 48
IS  - 3
N2  - Patients with extensive subcortical cerebrovascular disease may have impaired memory, often despite the absence of medial temporal or diencephalic strokes. In this group, episodic memory failure may arise from frontal lobe dysfunction based on disruption of frontosubcortical loops caused by lacunae. We tested this idea by studying cognitively impaired subcortical stroke (CIS) patients and Alzheimer's disease (AD) patients with [18F]-fluorodeoxyglucose positron emission tomography using a continuous verbal memory task during the period of tracer uptake. Patients were matched on severity of cognitive impairment and overall memory task performance. As hypothesized, we found a double dissociation in the relations between metabolism and memory in these groups, such that memory in CIS (but not in AD) correlates with prefrontal lobe metabolism, whereas in AD (but not in CIS), memory correlates with left hippocampal and temporal lobe metabolism. Analysis of memory subscores showed that CIS patients made more errors on short-delay trials, which is consistent with working memory failure. It seems that different pathogenic mechanisms underlie episodic memory failure in subcortical cerebrovascular disease and AD
AD  - Department of Neurology, University of California at Davis, 94553, USA
ER  - 

TY  - JOUR
T1  - Spatial registration and normalisation of images
A1  - Friston,K.J.
A1  - Ashburner,J.
A1  - Poline,J.B.
A1  - Frith,C.D.
A1  - Heather,J.D.
A1  - Frackowiak,R.S.J.
Y1  - 1995///
SP  - 165
EP  - 189
JA  - Hum.Brain Mapp.
VL  - 2
N2  - This paper concerns the spatial and intensity transformations that may one image onto another. We present a general technique that facilitates nonlinear spatial (stereotactic) normalization and image realignment. This technique minimizes the sum of squares between two images following nonlinear spatial deformations and transformations of the voxel (intensity) values. The spatial and intensity transformations are obtained simultaneously, and explicitly, using a least squares solution and a series of linearising devices. The approach is completely noninteractive (automatic), nonlinear, and noniterative. It can be applied in any number of dimensions. Various applications are considered, including the realignment of functional magnetic resonance imaging (MRI) time-series, the linear (affine) and nonlinear spatial normalization of positron emission tomography (PET) and structural MRI images, the coregistration of PET to structural MRI, and, implicitly, the conjoining of PET and MRI to obtain high resolution functional images.
ER  - 

TY  - JOUR
T1  - Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction
A1  - Meltzer,C.C.
A1  - Cantwell,M.N.
A1  - Greer,P.J.
A1  - Ben Eliezer,D.
A1  - Smith,G.
A1  - Frank,G.
A1  - Kaye,W.H.
A1  - Houck,P.R.
A1  - Price,J.C.
Y1  - 2000/11//
N1  - eng
SP  - 1842
EP  - 1848
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 41
IS  - 11
N2  - It remains a matter of controversy as to whether cerebral perfusion declines with healthy aging. In vivo imaging with PET permits quantitative evaluation of brain physiology; however, previous PET studies have inconsistently reported aging reductions in cerebral blood flow (CBF), oxygen metabolism, and glucose metabolism. In part, this may be because of a lack of correction for the dilution effect of age-related cerebral volume loss on PET measurements. METHODS: CBF PET scans were obtained using [15O]H2O in 27 healthy individuals (age range, 19-76 y) and corrected for partial-volume effects from cerebral atrophy using an MR-based algorithm. RESULTS: There was a significant difference (P = 0.01) in mean cortical CBF between young/midlife (age range, 19-46 y; mean +/- SD, 56+/-10 mL/100 mL/min) and elderly (age range, 60-76 y; mean +/- SD, 49+/-2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects. However, this group difference resolved after partial-volume correction (young/midlife: mean +/- SD, 62+/-10 mL/100 mL/min; elderly: mean +/- SD, 61+/-4.8 mL/100 mL/min; P = 0.66). When all subjects were considered, a mild but significant inverse correlation between age and cortical CBF measurements was present in the uncorrected but not the corrected data. CONCLUSION: This study suggests that CBF may not decline with age in healthy individuals and that failure to correct for the dilution effect of age-related cerebral atrophy may confound interpretation of previous PET studies that have shown aging reductions in physiologic measurements
AD  - Department of Radiology, University of Pittsburgh, Pennsylvania, USA
ER  - 

TY  - JOUR
T1  - Die Wertigkeit funktionell bildgebender Verfahren (PET und SPECT) in der Begutachtung neurotoxischer zerebraler Schdigungen
A1  - Herholz,K.
Y1  - 2001///
SP  - 181
EP  - 184
JF  - Der medizinische Sachverstndige
VL  - 97
IS  - 5
ER  - 

TY  - JOUR
T1  - A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM)
A1  - Mazziotta,J.
A1  - Toga,A.
A1  - Evans,A.
A1  - Fox,P.
A1  - Lancaster,J.
A1  - Zilles,K.
A1  - Woods,R.
A1  - Paus,T.
A1  - Simpson,G.
A1  - Pike,B.
A1  - Holmes,C.
A1  - Collins,L.
A1  - Thompson,P.
A1  - Macdonald,D.
A1  - Iacoboni,M.
A1  - Schormann,T.
A1  - Amunts,K.
A1  - Palomero-Gallagher,N.
A1  - Geyer,S.
A1  - Parsons,L.
A1  - Narr,K.
A1  - Kabani,N.
A1  - Le Goualher,G.
A1  - Boomsma,D.
A1  - Cannon,T.
A1  - Kawashima,R.
A1  - Mazoyer,B.
Y1  - 2001/08/29/
N1  - eng
SP  - 1293
EP  - 1322
JA  - Philos.Trans.R.Soc.Lond B Biol.Sci.
VL  - 356
IS  - 1412
N2  - Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients
AD  - Ahmanson-Lovelace Brain Mapping Center, UCLA School of Medicine, 660 Charles E. Young Drive, South Los Angeles, CA
ER  - 

TY  - JOUR
T1  - Functional MR evaluation of temporal and frontal language dominance compared with the Wada test
A1  - Lehericy,S.
A1  - Cohen,L.
A1  - Bazin,B.
A1  - Samson,S.
A1  - Giacomini,E.
A1  - Rougetet,R.
A1  - Hertz-Pannier,L.
A1  - Le Bihan,D.
A1  - Marsault,C.
A1  - Baulac,M.
Y1  - 2000/04/25/
N1  - eng
SP  - 1625
EP  - 1633
JF  - Neurology
VL  - 54
IS  - 8
N2  - OBJECTIVE: To evaluate the reliability of temporal and frontal functional MRI (fMRI) activation for the assessment of language dominance, as compared with the Wada test. PATIENTS AND METHODS: Ten patients with temporal lobe epilepsy were studied using blood oxygen level dependent fMRI and echoplanar imaging (1.5-T). Three tasks were used: semantic verbal fluency, covert sentence repetition, and story listening. Data were analyzed using pixel by pixel autocorrelation and cross-correlation. fMRI laterality indices were defined for several regions of interest as the ratio (L - R)/(L + R), L being the number of activated voxels in the left hemisphere and R in the right hemisphere. Wada laterality indices were defined as the difference in the percentages of errors in language tests between left and right carotid injections. RESULTS: Semantic verbal fluency: The asymmetry of frontal activation was correlated with Wada laterality indices. The strongest correlation was observed in the precentral/middle frontal gyrus/inferior frontal sulcus area. Story listening: The asymmetry of frontal, but not temporal, activation was correlated with Wada laterality indices. Covert sentence repetition: No correlation was observed. CONCLUSIONS: There was a good congruence between hemispheric dominance for language as assessed with the Wada test and fMRI laterality indices in the frontal but not in the temporal lobes. The story listening and the covert sentence repetition tasks increased the sensitivity of detection of posterior language sites that may be useful for brain lesion surgery
AD  - Departments of Neurology, Hopital de la Salpetriere, Paris, France. stephane.lehericy@psl.ap-hop-paris.fr
ER  - 

TY  - JOUR
T1  - Localization of language cortices by functional MR imaging compared with intracarotid amobarbital hemispheric sedation
A1  - Bahn,M.M.
A1  - Lin,W.
A1  - Silbergeld,D.L.
A1  - Miller,J.W.
A1  - Kuppusamy,K.
A1  - Cook,R.J.
A1  - Hammer,G.
A1  - Wetzel,R.
A1  - Cross,D.,III
Y1  - 1997/08//
N1  - eng
SP  - 575
EP  - 579
JA  - AJR Am.J.Roentgenol.
VL  - 169
IS  - 2
N2  - OBJECTIVE: We undertook this study to investigate functional MR imaging as a new clinical method for determining hemispheric language dominance. Seven patients undergoing surgical evaluation for chronic intractable epilepsy were studied. Intracarotid amobarbital injection was also performed and the findings compared with the functional MR imaging results. CONCLUSION: Functional MR imaging studies enabled localization of the frontal and temporal lobe language cortices. The results of functional MR imaging and intracarotid amobarbital testing of hemispheric language dominance agreed in all seven patients, including two right-handed patients with right-hemisphere language dominance. These preliminary results show that functional MR imaging is an accurate noninvasive method of determining language dominance that may replace the amobarbital test for some purposes if confirmed by additional research
AD  - Department of Radiology, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA
ER  - 

TY  - JOUR
T1  - Voxel-based mapping of brain hypometabolism in permanent amnesia with PET
A1  - Aupee,A.M.
A1  - Desgranges,B.
A1  - Eustache,F.
A1  - Lalevee,C.
A1  - de,la Sayette,V
A1  - Viader,F.
A1  - Baron,J.C.
Y1  - 2001/06//
N1  - eng
SP  - 1164
EP  - 1173
JF  - Neuroimage
VL  - 13
IS  - 6 Pt 1
N2  - In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology. Copyright 2001 Academic Press
AD  - INSERM U320, Cyceron and Department of Neurology, University of Caen, France
ER  - 

TY  - JOUR
T1  - An efficient algorithm for topologically correct segmentation of the cortical sheet in anatomical mr volumes
A1  - Kriegeskorte,N.
A1  - Goebel,R.
Y1  - 2001/08//
N1  - eng
SP  - 329
EP  - 346
JF  - Neuroimage
VL  - 14
IS  - 2
N2  - Polygon-mesh representations of the cortices of individual subjects are of anatomical interest, aid visualization of functional imaging data and provide important constraints for their statistical analysis. Due to noise and partial volume sampling, however, conventional segmentation methods rarely yield a voxel object whose outer boundary represents the folded cortical sheet without topological errors. These errors, called handles, have particularly deleterious effects when the polygon mesh constructed from the segmented voxel representation is inflated or flattened. So far handles had to be removed by cumbersome manual editing, or the computationally more expensive method of reconstruction by morphing had to be used, incorporating the a priori constraint of simple topology into the polygon-mesh model. Here we describe a linear time complexity algorithm that automatically detects and removes handles in presegmentations of the cortex obtained by conventional methods. The algorithm's modifications reflect the true structure of the cortical sheet. The core component of our method is a region growing process that starts deep inside the object, is prioritized by the distance-to-surface of the voxels considered for inclusion and is selftouching-sensitive, i.e., voxels whose inclusion would add a handle are never included. The result is a binary voxel object identical to the initial object except for "cuts" located in the thinnest part of each handle. By applying the same method to the inverse object, an alternative set of solutions is determined, correcting the errors by addition instead of deletion of voxels. For each handle separately, the solution more consistent with the intensities of the original anatomical MR scan is chosen. The accuracy of the resulting polygon-mesh reconstructions has been validated by visual inspection, by quantitative comparison to an expert's manual corrections, and by crossvalidation between reconstructions from different scans of the same subject's cortex. Copyright 2001 Academic Press
AD  - Faculty of Psychology, Department of Cognitive Neuroscience, Universiteit Maastricht, Universiteitssingel 40, Maastricht, 6229 ET, The Netherlands
ER  - 

TY  - JOUR
T1  - Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex
A1  - Ceballos-Baumann,A.O.
A1  - Boecker,H.
A1  - Fogel,W.
A1  - Alesch,F.
A1  - Bartenstein,P.
A1  - Conrad,B.
A1  - Diederich,N.
A1  - von,Falkenhayn,I
A1  - Moringlane,J.R.
A1  - Schwaiger,M.
A1  - Tronnier,V.M.
Y1  - 2001/05/22/
N1  - eng
SP  - 1347
EP  - 1354
JF  - Neurology
VL  - 56
IS  - 10
N2  - BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany. a.ceballos@lrz.tum.de
ER  - 

TY  - JOUR
T1  - Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas
A1  - Jacobs,A.
A1  - Voges,J.
A1  - Reszka,R.
A1  - Lercher,M.
A1  - Gossmann,A.
A1  - Kracht,L.
A1  - Kaestle,C.
A1  - Wagner,R.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 2001/09/01/
N1  - eng
SP  - 727
EP  - 729
JF  - Lancet
VL  - 358
IS  - 9283
N2  - In clinical gene-therapy trials for recurrent glioblastomas, transduction of the herpes simplex virus type-1 thymidine kinase (HSV-1-tk) gene with subsequent prodrug activation by ganciclovir was found to be safe, but clinical response was poor. We used positron-emission tomography (PET) with I-124-labelled 2'-fluoro-2'-deoxy-1b-D-arabino-furanosyl-5-iodo-uracil ([124I]-FIAU)-a specific marker substrate for gene expression of HSV-1-tk-to identify the location, magnitude, and extent of vector-mediated HSV-1-tk gene expression in a phase I/II clinical trial of gene therapy for recurrent glioblastoma in five patients. The extent of HSV-1-tk gene expression seemed to predict the therapeutic response. The expression of an exogenous gene introduced by gene therapy into patients with gliomas can be monitored non-invasively by PET
AD  - Max-Planck-Institute for Neurological Research, 50931, Cologne, Germany
ER  - 

TY  - JOUR
T1  - Altered serotonin 2A receptor activity in women who have recovered from bulimia nervosa
A1  - Kaye,W.H.
A1  - Frank,G.K.
A1  - Meltzer,C.C.
A1  - Price,J.C.
A1  - McConaha,C.W.
A1  - Crossan,P.J.
A1  - Klump,K.L.
A1  - Rhodes,L.
Y1  - 2001/07//
N1  - eng
SP  - 1152
EP  - 1155
JA  - Am.J.Psychiatry
VL  - 158
IS  - 7
N2  - OBJECTIVE: The authors' goal was to confirm that brain serotonin (5-HT) alterations are present in patients who have recovered from bulimia nervosa. Positron emission tomography imaging with [(18)F]altanserin was used to characterize binding of the 5-HT(2A) receptor, which might contribute to altered feeding, mood, or impulse control. METHOD: Nine women who had recovered from bulimia nervosa (they had no episodes of binge eating or purging, were at normal weight, and had regular menstrual cycles for more than 1 year) were compared with 12 female volunteers who had never had bulimia. RESULTS: The healthy volunteers, but not the women who had recovered from bulimia nervosa, had an age-related decline in 5-HT(2A) binding. Women who had recovered from bulimia nervosa had a reduction of medial orbital frontal cortex 5-HT(2A) binding. CONCLUSIONS: The lack of age-related changes in 5-HT activity is further evidence of 5-HT alterations in subjects who have recovered from bulimia nervosa. In addition, vulnerabilities for eating disorders, impulse dyscontrol, and mood disturbances may involve 5-HT and frontal lobe activity
AD  - Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. kayewh@msx.upmc.edu
ER  - 

TY  - JOUR
T1  - Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98)
A1  - Kanai,Y.
A1  - Segawa,H.
A1  - Miyamoto,Ki
A1  - Uchino,H.
A1  - Takeda,E.
A1  - Endou,H.
Y1  - 1998/09/11/
N1  - eng
SP  - 23629
EP  - 23632
JA  - J.Biol.Chem.
VL  - 273
IS  - 37
N2  - A cDNA was isolated from rat C6 glioma cells by expression cloning which encodes a novel Na+-independent neutral amino acid transporter designated LAT1. For functional expression in Xenopus oocytes, LAT1 required the heavy chain of 4F2 cell surface antigen (CD98), a type II membrane glycoprotein. When co-expressed with 4F2 heavy chain, LAT1 transported neutral amino acids with branched or aromatic side chains and did not accept basic amino acids or acidic amino acids. The transport via LAT1 was Na+-independent and sensitive to a system L-specific inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. These functional properties correspond to those of the classically characterized amino acid transport system L, a major nutrient transporter. In in vitro translation, LAT1 was shown to be a nonglycosylated membrane protein consistent with the property of 4F2 light chain, suggesting LAT1 is at least one of the proteins formerly referred to as 4F2 light chain. LAT1 exhibits relatively low but significant amino acid sequence similarity to mammalian cationic amino acid transporters and amino acid permeases of bacteria and yeasts, indicating LAT1 is a new member of the APC superfamily. Because of highly regulated nature and high level of expression in tumor cell lines, LAT1 is thought to be up-regulated to support the high protein synthesis for cell growth and cell activation. The cloning of LAT1 is expected to facilitate the research on the protein-protein interaction in the transporter field and to provide a clue to the search for still unidentified transporters
AD  - Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181, Japan
ER  - 

TY  - JOUR
T1  - Predominant functional activity of the large, neutral amino acid transporter (LAT1) isoform at the cerebrovasculature
A1  - Killian,D.M.
A1  - Chikhale,P.J.
Y1  - 2001/06/22/
N1  - eng
SP  - 1
EP  - 4
JA  - Neurosci.Lett.
VL  - 306
IS  - 1-2
N2  - In this study, we identify the predominant functional expression of the large, neutral amino acid transporter (LAT1) isoform at the blood-brain barrier (BBB). An in situ rat brain perfusion technique allowed perfusion of the radiotracer [(14)C]-L-Leu (a ligand for both LAT1 and LAT2) alone or competed with excess concentration of either LAT1 or LAT2 specific amino acids. The LAT2 specific amino acid, [(14)C]-L-Asn, was perfused alone or with excess concentration of various amino acids. The brain uptake of [(14)C]-L-Leu was not significantly inhibited by LAT2 specific amino acids, but was inhibited significantly (up to 90%) by the LAT1 specific amino acid, D-Met. L-Asn did not demonstrate saturable brain uptake. These data clearly demonstrate that LAT1 is the functionally predominant isoform expressed at the BBB which is responsible for brain uptake of large, neutral amino acids. In addition, the functional activity of cerebrovascular LAT2 is insignificant, or absent
AD  - Department of Pharmaceutical Sciences, 20 North Pine Street, University of Maryland, Baltimore, MD 21201, USA
ER  - 

TY  - JOUR
T1  - Expression of a system L neutral amino acid transporter at the blood-brain barrier
A1  - Matsuo,H.
A1  - Tsukada,S.
A1  - Nakata,T.
A1  - Chairoungdua,A.
A1  - Kim,D.K.
A1  - Cha,S.H.
A1  - Inatomi,J.
A1  - Yorifuji,H.
A1  - Fukuda,J.
A1  - Endou,H.
A1  - Kanai,Y.
Y1  - 2000/11/09/
N1  - eng
SP  - 3507
EP  - 3511
JF  - Neuroreport
VL  - 11
IS  - 16
N2  - Amino acid transport system L has been proposed to be one of the major nutrient transport systems at the blood-brain barrier. Using immunohistochemical analyses, a system L transporter LAT1 was shown to be expressed in the brain capillary endothelial cells in rats. Because LAT1 was coexpressed with 4F2 heavy chain which brings LAT1 to the plasma membrane, LAT1 is proposed to be functional in the plasma membrane of brain capillary endothelial cells. Both LAT1 and 4F2hc immunoreactivities were detected in a double line appearance surrounding endothelial cell nuclei, suggesting both proteins are present in the luminal and abluminal membranes. LAT1 is, thus, a blood-brain barrier system L transporter responsible for the permeation of aromatic or branched-chain amino acids and amino acid-related drugs such as L-DOPA
AD  - Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo Japan
ER  - 

TY  - JOUR
T1  - Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation
A1  - Minoshima,S.
A1  - Foster,N.L.
A1  - Sima,A.A.
A1  - Frey,K.A.
A1  - Albin,R.L.
A1  - Kuhl,D.E.
Y1  - 2001/09//
N1  - eng
SP  - 358
EP  - 365
JA  - Ann.Neurol.
VL  - 50
IS  - 3
N2  - Seeking antemortem markers to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Eleven DLB patients (7 Lewy body variant of AD [LBVAD] and 4 pure diffuse Lewy body disease [DLBD]) who had antemortem position emission tomography imaging and autopsy confirmation were compared to 10 autopsy-confirmed pure AD patients. In addition, 53 patients with clinically-diagnosed probable AD, 13 of whom later fulfilled clinical diagnoses of DLB, were examined. Autopsy-confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortices. Only DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex (LBVAD -23% and DLBD -29% vs AD -8%), which distinguished DLB versus AD with 90% sensitivity and 80% specificity. Multivariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. Analysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled later dinical criteria for DLB. In these patients, occipital hypometabolism preceded some clinical features of DLB. Occipital hypometabolism is a potential antemortem marker to distinguish DLB versus AD
AD  - Department of Internal Medicine, University of Michigan Medical School, Geriatrics Research, Education, and Clinical Center, Ann Arbor, USA. minoshim@u.washington.edu
ER  - 

TY  - JOUR
T1  - Direct comparison of spatially normalized PET and SPECT scans in Alzheimer disease
A1  - Herholz,K.
A1  - Schopphoff,H.
A1  - Schmidt,M.
A1  - Mielke,R.
A1  - Eschner,W.
A1  - Scheidhauer,K.
A1  - Schicha,H.
A1  - Heiss,W.-D.
A1  - Ebmeier,K.P.
Y1  - 2002///
SP  - 21
EP  - 26
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 43
IS  - 1
ER  - 

TY  - JOUR
T1  - Association between 5-HT(2A) receptor polymorphism and psychotic symptoms in Alzheimer's disease
A1  - Nacmias,B.
A1  - Tedde,A.
A1  - Forleo,P.
A1  - Piacentin,S.
A1  - Guarnieri,B.M.
A1  - Bartoli,A.
A1  - Ortenzi,L.
A1  - Petruzzi,C.
A1  - Serio,A.
A1  - Marcon,G.
A1  - Sorbi,S.
Y1  - 2001/09/15/
N1  - eng
SP  - 472
EP  - 475
JA  - Biol.Psychiatry
VL  - 50
IS  - 6
N2  - Background: The aim of this study is to analyze the segregation of the 102T/C polymorphism in the serotonin 2A receptor gene in patients affected by sporadic and familial Alzheimer's disease (FAD) with and without psychotic symptoms.Methods: The polymorphism was analyzed in 275 subjects. A semistructured interview was used to obtain information about delusions, hallucinations, and other specific behavioral signs occurring during the disease.Results: Fifty-two percent of AD patients with psychotic symptoms were homozygous for the C102 allele, as compared with 6.9% of AD patients without psychosis. Similarly, the C102/C102 genotype was significantly more frequent in FAD patients with psychosis than in FAD patients without (46.5% vs. 7.8%).Conclusions: Our data strongly confirm and extend to FAD previous studies suggesting that the genetic variation at this locus is associated with prominent psychotic features in AD and that the 102C allele could play an important role in late-onset AD
AD  - Department of Neurological and Psychiatric Sciences, University of Florence, (BN, AT, PF, SP, SS), Florence, Italy
ER  - 

TY  - JOUR
T1  - The role of [(18)F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders
A1  - Rees,J.H.
A1  - Hain,S.F.
A1  - Johnson,M.R.
A1  - Hughes,R.A.
A1  - Costa,D.C.
A1  - Ell,P.J.
A1  - Keir,G.
A1  - Rudge,P.
Y1  - 2001/11//
N1  - National Hospital for Neurology and Neurosurgery, Clinical PET Centre, St Thomas' Hospital, Department of Neurology, Guy's Hospital, Institute of Nuclear Medicine, UCL Medical School and Department of Neuroimmunology, Institute of Neurology, London, UK
SP  - 2223
EP  - 2231
JF  - Brain
VL  - 124
IS  - Pt 11
N2  - The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [18F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique
ER  - 

TY  - JOUR
T1  - Statistical brain mapping of 18F-FDG PET in Alzheimer's disease: validation of anatomic standardization for atrophied brains
A1  - Ishii,K.
A1  - Willoch,F.
A1  - Minoshima,S.
A1  - Drzezga,A.
A1  - Ficaro,E.P.
A1  - Cross,D.J.
A1  - Kuhl,D.E.
A1  - Schwaiger,M.
Y1  - 2001/04//
N1  - Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany
SP  - 548
EP  - 557
JA  - J Nucl.Med
VL  - 42
IS  - 4
N2  - Despite the increased use of statistical mapping to detect brain functional changes in Alzheimer's disease (AD), potential artifacts introduced by stereotactic anatomic standardization of atrophied brains have not been examined carefully. We investigated the effects of anatomic standardization by Statistical Parametric Mapping (SPM) and NEUROSTAT. METHODS: First, 10 AD patients and 10 age-matched healthy volunteers underwent 18F-FDG brain PET imaging. Each image set was standardized to a stereotactic brain template using SPM or NEUROSTAT, followed by pixel normalization to the global or cerebellar activity. Within-group comparisons of standardized image sets by each method and a between-group comparison of healthy volunteers and AD patients were performed using the statistical analysis routines of SPM. Second, simulated PET image sets were generated from segmented MR image sets of 5 healthy volunteers and 5 AD patients. Using the anatomic standardization parameters estimated on the simulated image sets, original gray matter MR image sets were transformed to the stereotactic coordinate system. Between-group subtraction analyses of the transformed gray matter image sets between healthy volunteers and AD groups were performed to examine the accuracy of cortical gray matter matching. RESULTS: Between-group comparison by SPM or NEUROSTAT showed generally similar areas of hypometabolism in bilateral temporoparietal, posterior cingulate, and left frontal cortices. Both methods showed possible deformation artifacts in the anterior part of the corpus callosum. The localization of the peak hypometabolism varied considerably between the two methods when global normalization was applied. The use of a common brain template for standardization resulted in asymmetric differences in cortical margins, indicating systematic differences in the deformation algorithms. The realistic simulation study revealed gray matter mismatches to be 20% greater with SPM than with NEUROSTAT. CONCLUSION: Although different statistical mapping methods may yield grossly similar patterns of hypometabolism in AD, the extent, severity, and peak location of metabolic changes can be inconsistent. Deformation accuracy appears to be more prone to atrophy. These limitations need to be considered carefully in the application and interpretation of brain mapping analysis in atrophied brains
ER  - 

TY  - JOUR
T1  - Phantom limb pain in the human brain: unraveling neural circuitries of phantom limb sensations using positron emission tomography
A1  - Willoch,F.
A1  - Rosen,G.
A1  - Tolle,T.R.
A1  - Oye,I.
A1  - Wester,H.J.
A1  - Berner,N.
A1  - Schwaiger,M.
A1  - Bartenstein,P.
Y1  - 2000/12//
N1  - Department of Nuclear Medicine, Technische Universitat Munchen, Munich, Germany
SP  - 842
EP  - 849
JA  - Ann.Neurol.
VL  - 48
IS  - 6
N2  - Pain and other phantom limb (PL) sensations have been proposed to be generated in the brain and to be reflected in activation of specific neural circuits. To test this hypothesis, hypnosis was used as a cognitive tool to alternate between the sensation of PL movement and pain in 8 amputees. Brain activity was measured using positron emission tomography. PL movement and pain were represented by a propagation of neuronal activity within the corresponding sensorimotor and pain-processing networks. The sensation of movement was significantly (corrected for multiple comparisons) related to activity in the supplementary motor area and the primary sensorimotor cortex. The sensation of a painful PL posture activated the same brain areas but was weaker and less extended in the supplementary motor area. In contrast to the sensation of movement, pain was significantly related to activity in the thalamus, anterior cingulate, and lateral prefrontal cortex. Subjectively rated PL pain sensation correlated positively to activations in the anterior and posterior cingulate. These findings provide evidence that PL sensations are produced by the same central nervous processes that underlie the experience of the body when it is intact and that the corporeal awareness of PL pain is encoded in a thalamocortical network
ER  - 

TY  - JOUR
T1  - Discrimination between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET
A1  - Herholz,K.
A1  - Salmon,E.
A1  - Perani,D.
A1  - Baron,J.C.
A1  - Holthoff,V.
A1  - Frlich,L.
A1  - Ito,K.
A1  - Mielke,R.
A1  - Kalbe,E.
A1  - Zndorf,G.
A1  - Delbeuck,X.
A1  - Pelati,O.
A1  - Anchisi,D.
A1  - Fazio,F.
A1  - Kerrouche,N.
A1  - Calautti,C.
A1  - Beuthien-Baumann,B.
A1  - Menzel,C.
A1  - Schrder,J.
A1  - Kato,T.
A1  - Arahata,Y.
A1  - Henze,M.
A1  - Heiss,W.-D.
Y1  - 2002///
SP  - 302
EP  - 316
JF  - Neuroimage
VL  - 17
ER  - 

TY  - JOUR
T1  - Fluoro-DOPA and FDG positron emission tomography in a case of pathologically verified pure diffuse Lewy body disease
A1  - Hisanaga,K.
A1  - Suzuki,H.
A1  - Tanji,H.
A1  - Mochizuki,H.
A1  - Iwasaki,Y.
A1  - Sato,N.
A1  - Jin,K.
Y1  - 2001/10//
N1  - Severe reduction of FDG uptake in frontal, temporal and occipital cortex
SP  - 905
EP  - 906
JA  - J Neurol.
VL  - 248
IS  - 10
ER  - 

TY  - JOUR
T1  - Brain metabolic changes associated with symptom factor improvement in major depressive disorder
A1  - Brody,A.L.
A1  - Saxena,S.
A1  - Mandelkern,M.A.
A1  - Fairbanks,L.A.
A1  - Ho,M.L.
A1  - Baxter,L.R.
Y1  - 2001/08/01/
N1  - Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, California 90095, USA
SP  - 171
EP  - 178
JA  - Biol.Psychiatry
VL  - 50
IS  - 3
N2  - BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment
ER  - 

TY  - JOUR
T1  - Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently
A1  - Saxena,S.
A1  - Brody,A.L.
A1  - Ho,M.L.
A1  - Alborzian,S.
A1  - Ho,M.K.
A1  - Maidment,K.M.
A1  - Huang,S.C.
A1  - Wu,H.M.
A1  - Au,S.C.
A1  - Baxter,L.R.,Jr.
Y1  - 2001/08/01/
N1  - Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, California 90095, USA
SP  - 159
EP  - 170
JA  - Biol.Psychiatry
VL  - 50
IS  - 3
N2  - BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients
ER  - 

TY  - JOUR
T1  - Metabolic changes following subthalamotomy for advanced Parkinson's disease
A1  - Su,P.C.
A1  - Ma,Y.
A1  - Fukuda,M.
A1  - Mentis,M.J.
A1  - Tseng,H.M.
A1  - Yen,R.F.
A1  - Liu,H.M.
A1  - Moeller,J.R.
A1  - Eidelberg,D.
Y1  - 2001/10//
N1  - Department of Neurology, National Taiwan University Hospital, Taipei
SP  - 514
EP  - 520
JA  - Ann.Neurol.
VL  - 50
IS  - 4
N2  - We studied 6 advanced-stage Parkinson's disease patients with [18F] fluorodeoxyglucose/positron emission tomography before and 3 months after unilateral ablation of the subthalamic nucleus performed with microelectrode mapping. Operative changes in glucose metabolism were assessed by comparing baseline and postoperative scans. We also quantified operative changes in the activity of an abnormal Parkinson's disease-related metabolic network that we had identified in previous [18F] fluorodeoxyglucose/positron emission tomography studies. Following unilateral subthalamic nucleus ablation, a highly significant reduction in glucose utilization was present in the midbrain ipsilateral to the lesion site, most pronounced in the vicinity of the substantia nigra pars reticularis. Significant metabolic reductions were also present in the ipsilateral internal globus pallidus, ventral thalamus, and pons. Operative changes in Parkinson's disease network activity differed significantly for the lesioned and unlesioned hemispheres. In the lesioned hemisphere, network activity declined significantly following surgery, but was unaltered in the contralateral, unlesioned hemisphere. These results suggest that subthalamotomy reduces basal ganglia output through internal globus pallidus/substantia nigra pars reticularis and also influences downstream neural activity in the pons and ventral thalamus. This procedure also reduces the activity of abnormal Parkinson's disease-related metabolic brain networks, suggesting a widespread modulation of motor circuitry
ER  - 

TY  - JOUR
T1  - Networks mediating the clinical effects of pallidal brain stimulation for Parkinson's disease: a PET study of resting-state glucose metabolism
A1  - Fukuda,M.
A1  - Mentis,M.J.
A1  - Ma,Y.
A1  - Dhawan,V.
A1  - Antonini,A.
A1  - Lang,A.E.
A1  - Lozano,A.M.
A1  - Hammerstad,J.
A1  - Lyons,K.
A1  - Koller,W.C.
A1  - Moeller,J.R.
A1  - Eidelberg,D.
Y1  - 2001/08//
N1  - Center for Neurosciences, North Shore-Long Island Jewish Research Institute, Manhasset, New York 11030, USA
SP  - 1601
EP  - 1609
JF  - Brain
VL  - 124
IS  - Pt 8
N2  - Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic changes occur in Parkinson's disease patients treated with deep brain stimulation (DBS) of the GPi. We studied seven Parkinson's disease patients with FDG-PET to measure resting regional cerebral glucose utilization on and off GPi stimulation. We used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. We also quantified stimulation-related changes in the expression of a specific abnormal Parkinson's disease-related pattern of metabolic covariation (PDRP) that had been identified in earlier FDG-PET studies. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings (36%, P < 0.001) and significantly increased regional glucose metabolism in the premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi DBS also resulted in a significant (P < 0.01) decline in PDRP activity ipsilateral to stimulation, which correlated significantly with clinical improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS is associated with reduced expression of an abnormal Parkinson's disease-related metabolic network involving elements of the cortico-striato-pallido-thalamocortical and the cerebello-cortical motor loops
ER  - 

TY  - JOUR
T1  - Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome
A1  - Silverman,D.H.
A1  - Small,G.W.
A1  - Chang,C.Y.
A1  - Lu,C.S.
A1  - Kung de Aburto,M.A.
A1  - Chen,W.
A1  - Czernin,J.
A1  - Rapoport,S.I.
A1  - Pietrini,P.
A1  - Alexander,G.E.
A1  - Schapiro,M.B.
A1  - Jagust,W.J.
A1  - Hoffman,J.M.
A1  - Welsh-Bohmer,K.A.
A1  - Alavi,A.
A1  - Clark,C.M.
A1  - Salmon,E.
A1  - de Leon,M.J.
A1  - Mielke,R.
A1  - Cummings,J.L.
A1  - Kowell,A.P.
A1  - Gambhir,S.S.
A1  - Hoh,C.K.
A1  - Phelps,M.E.
Y1  - 2001/11/07/
N1  - Ahmanson Biological Imaging Center, CHS AR-144, Department of Molecular and Medical Pharmacology, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095-6942, USA dsilver@uclaedu
SP  - 2120
EP  - 2127
JF  - JAMA
VL  - 286
IS  - 17
N2  - CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur
ER  - 

TY  - JOUR
T1  - Metabolic and electrophysiological validation of functional MRI
A1  - Krings,T.
A1  - Schreckenberger,M.
A1  - Rohde,V.
A1  - Foltys,H.
A1  - Spetzger,U.
A1  - Sabri,O.
A1  - Reinges,M.H.
A1  - Kemeny,S.
A1  - Meyer,P.T.
A1  - Moller-Hartmann,W.
A1  - Korinth,M.
A1  - Gilsbach,J.M.
A1  - Buell,U.
A1  - Thron,A.
Y1  - 2001/12//
N1  - Department of Neuroradiology, University Hospital of the Technical University, Pauwelsstrasse 30, 52057 Aachen, Germany
SP  - 762
EP  - 771
JA  - J Neurol.Neurosurg.Psychiatry
VL  - 71
IS  - 6
N2  - OBJECTIVES: Although functional MRI is widely used for preoperative planning and intraoperative neuronavigation, its accuracy to depict the site of neuronal activity is not exactly known. Experience with methods that may validate fMRI data and the results obtained when coregistering fMRI with different preoperative and intraoperative mapping modalities including metabolically based (18)F-fluorodeoxyglucose PET, electrophysiologcally based transcranial magnetic stimulation (TMS), and direct electrical cortical stimulation (DECS) are described. METHODS: Fifty patients were included. PET was performed in 30, TMS in 10, and DECS in 41 patients. After coregistration using a frameless stereotactic system, results were grouped into overlapping (<1 cm distance), neighbouring (<2 cm), or contradictory (>2 cm). RESULTS: Comparing fMRI with PET, 18 overlapping, seven neighbouring, and one contradictory result were obtained. In four patients no comparison was possible (because of motion artefacts, low signal to noise ratio, and unusual high tumour metabolism in PET). The comparison of TMS and fMRI showed seven overlapping and three neighbouring results. In three patients no DECS results could be obtained. Of the remaining 38 patients, fMRI hand motor tasks were compared with DECS results of the upper limb muscles in 36 patients, and fMRI foot motor tasks were compared with DECS results of the lower limb on 13 occasions. Of those 49 studies, overlapping results were obtained in 31 patients, and neighbouring in 14. On four occasions fMRI did not show functional information (because of motion artefacts and low signal to noise). CONCLUSIONS: All validation techniques have intrinsic limitations that restrict their spatial resolution. However, of 50 investigated patients, there was only one in whom results contradictory to fMRI were obtained. Although it is not thought that fMRI can replace the intraoperatively updated functional information (DECS), it is concluded that fMRI is an important adjunct in the preoperative assessment of patients with tumours in the vicinity of the central region
ER  - 

TY  - JOUR
T1  - Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2
A1  - Li,J.Y.
A1  - Boado,R.J.
A1  - Pardridge,W.M.
Y1  - 2001/08//
N1  - Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
SP  - 929
EP  - 936
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 8
N2  - Adenosine transport into brain is regulated by the activity of the adenosine transporter located at the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo. To facilitate cloning of BBB adenosine transporters, poly A+ RNA was purified from isolated rat brain capillaries for production of a rat BBB cDNA library in the pSPORT vector. The cloned RNA (cRNA) generated from in vitro transcription of this library was injected into frog oocytes followed by measurement of [3H]-adenosine uptake. After dilutional cloning, a full-length, 2905-nucleotide adenosine transporter cDNA, designated clone A-11, was isolated. The A-11 clone yielded [3H]-adenosine flux ratios of 400 to 500 after injection of cRNA in oocytes. The adenosine uptake was sodium-dependent and insensitive to inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBTI). The Km and Vmax of adenosine transport in the cRNA-injected oocytes were 23.1 +/- 3.7 &mgr;mol/L and 10.8 +/- 0.9 pmol/oocyte. min. The K0.5 for sodium was 2.4 +/- 0.1 mmol/L, with a Hill coefficient (n) of 1.06 +/- 0.07. DNA sequence analysis indicated the rat BBB A-11 adenosine cDNA was identical to rat concentrative nucleoside transporter type 2 (CNT2). The adenosine transporter activity of the rat BBB A-11 CNT2 clone is 50-fold more active than previously reported rat CNT2 clones. In summary, these studies describe the expression cloning of CNT2 from a rat BBB library and show that the pattern of sodium dependency and NBTI insensitivity of the cloned CNT2 are identical to patterns of adenosine transport across the BBB in vivo. These results suggest that BBB adenosine transport in vivo is mediated by CNT2, which would make CNT2 one of the few known sodium-dependent cotransporters that mediate substrate transport across the BBB in the blood to brain direction
ER  - 

TY  - JOUR
T1  - Blood-brain barrier genomics
A1  - Li,J.Y.
A1  - Boado,R.J.
A1  - Pardridge,W.M.
Y1  - 2001/01//
N1  - Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1682, USA
SP  - 61
EP  - 68
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 1
N2  - The blood-brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction-based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IkappaB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level
ER  - 

TY  - JOUR
T1  - Antisense imaging of gene expression in the brain in vivo
A1  - Shi,N.
A1  - Boado,R.J.
A1  - Pardridge,W.M.
Y1  - 2000/12//
N1  - Department of Medicine, University of California School of Medicine, Los Angeles, CA 90095-1682, USA
SP  - 14709
EP  - 14714
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 97
IS  - 26
N2  - Antisense radiopharmaceuticals could be used to image gene expression in the brain in vivo, should these polar molecules be made transportable through the blood-brain barrier. The present studies describe an antisense imaging agent comprised of an iodinated peptide nucleic acid (PNA) conjugated to a monoclonal antibody to the rat transferrin receptor by using avidin-biotin technology. The PNA was a 16-mer antisense to the sequence around the methionine initiation codon of the luciferase mRNA. C6 rat glioma cells were permanently transfected with a luciferase expression plasmid, and C6 experimental brain tumors were developed in adult rats. The expression of the luciferase transgene in the tumors in vivo was confirmed by measurement of luciferase enzyme activity in the tumor extract. The [(125)I]PNA conjugate was injected intravenously in anesthetized animals with brain tumors and killed 2 h later for frozen sectioning of brain and film autoradiography. No image of the luciferase gene expression was obtained after the administration of either the unconjugated antiluciferase PNA or a PNA conjugate that was antisense to the mRNA of a viral transcript. In contrast, tumors were imaged in all rats administered the [(125)I]PNA that was antisense to the luciferase sequence and was conjugated to the targeting antibody. In conclusion, these studies demonstrate gene expression in the brain in vivo can be imaged with antisense radiopharmaceuticals that are conjugated to a brain drug-targeting system
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Shi-antisense-imaging.pdf
ER  - 

TY  - JOUR
T1  - Selective expression of the large neutral amino acid transporter at the blood-brain barrier
A1  - Boado,R.J.
A1  - Li,J.Y.
A1  - Nagaya,M.
A1  - Zhang,C.
A1  - Pardridge,W.M.
Y1  - 1999/10/12/
N1  - Department of Medicine, University of California School of Medicine, Los Angeles, CA 90095, USA rboado@mednetuclaedu
SP  - 12079
EP  - 12084
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 96
IS  - 21
N2  - Amino acid supply in brain is regulated by the activity of the large neutral amino acid transporter (LAT) at the brain capillary endothelial cell, which forms the blood-brain barrier (BBB) in vivo. Bovine BBB poly(A)(+) RNA was isolated from 2.0 kg of fresh bovine brain and size fractionated on a sucrose density gradient, and a size-fractionated bovine BBB cDNA library in the pSPORT vector was prepared. The full-length cDNA encoding the bovine BBB LAT was isolated from this library, and the predicted amino acid sequence was 89-92% identical to the LAT1 isoform. The bovine BBB LAT1 mRNA produced a 10-fold enhancement in tryptophan transport into frog oocytes coinjected with bovine BBB LAT1 mRNA and the mRNA for 4F2hc, which encodes the heavy chain of the heterodimer. Tryptophan transport into the mRNA-injected oocytes was sodium independent and was specifically inhibited by other large neutral amino acids, and the K(m) of tryptophan transport was 31.5 +/- 5.5 &mgr;M. Northern blotting with the bovine BBB LAT1 cDNA showed that the LAT1 mRNA is 100-fold higher in isolated bovine brain capillaries compared with C6 rat glioma cells or rat brain, and the LAT1 mRNA was not detected in rat liver, heart, lung, or kidney. These studies show that the LAT1 transcript is selectively expressed at the BBB compared with other tissues, and the abundance of the LAT1 mRNA at the BBB is manyfold higher than that of transcripts such as the 4F2hc antigen, actin, or the Glut1 glucose transporter
ER  - 

TY  - JOUR
T1  - An efficient principal component analysis for multivariate 3D voxel-based mapping of brain functional imaging data sets as applied to FDG-PET and normal aging
A1  - Zndorf,G.
A1  - Kerrouche,N.
A1  - Herholz,K.
A1  - Baron,J.C.
Y1  - 2003///
SP  - 13
EP  - 21
JA  - Hum.Brain Mapp.
VL  - 18
IS  - 1
N2  - Principal component analysis (PCA) is a well-known technique for reduction of dimensionality of functional imaging data. PCA can be looked at as the projection of the original images onto a new orthogonal coordinate system with lower dimensions. The new axes explain the variance in the images in decreasing order of importance, showing correlations between brain regions. We used an efficient, stable and analytical method to work out the PCA of Positron Emission Tomography (PET) images of 74 normal subjects using [(18)F]fluoro-2-deoxy-D-glucose (FDG) as a tracer. Principal components (PCs) and their relation to age effects were investigated. Correlations between the projections of the images on the new axes and the age of the subjects were carried out. The first two PCs could be identified as being the only PCs significantly correlated to age. The first principal component, which explained 10% of the data set variance, was reduced only in subjects of age 55 or older and was related to loss of signal in and adjacent to ventricles and basal cisterns, reflecting expected age-related brain atrophy with enlarging CSF spaces. The second principal component, which accounted for 8% of the total variance, had high loadings from prefrontal, posterior parietal and posterior cingulate cortices and showed the strongest correlation with age (r = -0.56), entirely consistent with previously documented age-related declines in brain glucose utilization. Thus, our method showed that the effect of aging on brain metabolism has at least two independent dimensions. This method should have widespread applications in multivariate analysis of brain functional images. Copyright 2002 Wiley-Liss, Inc.
ER  - 

TY  - JOUR
T1  - Familial progressive supranuclear palsy: detection of subclinical cases using 18F-dopa and 18fluorodeoxyglucose positron emission tomography
A1  - Piccini,P.
A1  - de Yebenez,J.
A1  - Lees,A.J.
A1  - Ceravolo,R.
A1  - Turjanski,N.
A1  - Pramstaller,P.
A1  - Brooks,D.J.
Y1  - 2001/11//
N1  - MRC Clinical Science Center, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, W12 ONN London, England paolapiccini@cscmrcacuk
SP  - 1846
EP  - 1851
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 58
IS  - 11
N2  - BACKGROUND: Progressive supranuclear palsy (PSP) is generally considered to be a sporadic disease; however, occasional cases of familial PSP have been described. The rarity of reports of familial PSP may be attributed in part to an inability to detect subclinical disease in affected relatives who subsequently die before symptoms clinically develop. OBJECTIVE: To study regional cerebral dopaminergic function and glucose metabolism in members of 2 large kindreds with familial PSP to identify subclinical cases. METHODS: Three clinically affected members from the 2 PSP kindreds were scanned with both (18)F-dopa and (18)fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). Fifteen asymptomatic first-degree relatives were scanned with (18)F-dopa PET; 10 of them also underwent a second PET study with (18)FDG. RESULTS: All 3 clinically affected PSP patients showed a significant reduction in caudate and putamen (18)F-dopa uptake along with a significant reduction in striatal, lateral, and medial premotor area and dorsal prefrontal cortex glucose metabolism. In 4 of the 15 asymptomatic relatives, caudate and putamen (18)F-dopa uptake was 2.5 SDs lower than the normal mean. These 4 subjects and a fifth asymptomatic relative with normal (18)F-dopa uptake showed a significant reduction of cortical and striatal glucose metabolism in a pattern similar to that of their affected relatives. CONCLUSION: (18)F-dopa and (18)FDG PET allowed us to identify 5 cases with subclinical metabolic dysfunction among 15 subjects (33%) at risk for PSP, suggesting that this approach is useful for characterizing the pattern of aggregation in PSP kindreds
ER  - 

TY  - JOUR
T1  - Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts
A1  - Piccini,P.
A1  - Lindvall,O.
A1  - Bjorklund,A.
A1  - Brundin,P.
A1  - Hagell,P.
A1  - Ceravolo,R.
A1  - Oertel,W.
A1  - Quinn,N.
A1  - Samuel,M.
A1  - Rehncrona,S.
A1  - Widner,H.
A1  - Brooks,D.J.
Y1  - 2000/11//
N1  - Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK
SP  - 689
EP  - 695
JA  - Ann.Neurol.
VL  - 48
IS  - 5
N2  - Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD
ER  - 

TY  - JOUR
T1  - Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
A1  - Brundin,P.
A1  - Pogarell,O.
A1  - Hagell,P.
A1  - Piccini,P.
A1  - Widner,H.
A1  - Schrag,A.
A1  - Kupsch,A.
A1  - Crabb,L.
A1  - Odin,P.
A1  - Gustavii,B.
A1  - Bjorklund,A.
A1  - Brooks,D.J.
A1  - Marsden,C.D.
A1  - Oertel,W.H.
A1  - Quinn,N.P.
A1  - Rehncrona,S.
A1  - Lindvall,O.
Y1  - 2000/07//
N1  - Section for Neuronal Survival, Division of Neurobiology, Department of Physiological Sciences, Lund University, Sweden
SP  - 1380
EP  - 1390
JF  - Brain
VL  - 123
IS  - Pt 7
N2  - Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals
ER  - 

TY  - JOUR
T1  - Positron emission tomography with injection of methionine as a prognostic factor in glioma
A1  - De Witte,O.
A1  - Goldberg,I.
A1  - Wikler,D.
A1  - Rorive,S.
A1  - Damhaut,P.
A1  - Monclus,M.
A1  - Salmon,I.
A1  - Brotchi,J.
A1  - Goldman,S.
Y1  - 2001/11//
N1  - Department of Neurosurgery, Hjpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium odewitte@ulbacbe
SP  - 746
EP  - 750
JA  - J Neurosurg.
VL  - 95
IS  - 5
N2  - OBJECT: Positron emission tomography with L-[methyl-11C]methionine (MET-PET) provides information on the metabolism of gliomas. The aim of this study was to determine the predictive value of MET-PET in the treatment of patients with gliomas. METHODS: Since 1992, 85 patients with a World Health Organization (WHO) classification-verified glioma underwent PET studies in which MET was injected before (74 cases) or after treatment (11 cases). Analysis of PET data was conducted by the same investigator using two scales: a qualitative visual grading scale and a quantitative scale (ratio between tumor uptake and normal brain uptake, classified on a seven-level scale). Uptake of MET was present in 98% of gliomas. The investigator judged this uptake to be moderate to very high based on visual inspection (qualitative scale). For all grades of gliomas, a visual grade of 3 was statistically associated with a shorter patient survival period (p < 0.005). The tumor/normal brain uptake ratio was significantly influenced by the histological grade of the tumor. A statistically poor outcome was demonstrated when this ratio was higher than a threshold of 2.2 for a WHO Grade II tumor and 2.8 for WHO Grade III tumor. For Grade II and III tumors, oligodendrogliomas had a higher uptake of MET than astrocytomas. CONCLUSIONS: Uptake of MET was present in 98% of the gliomas studied. A high uptake is statistically associated with a poor survival time. The intensity of MET uptake represents a prognostic factor for WHO Grade II and III tumors considered separately
ER  - 

TY  - JOUR
T1  - Quantitative kinetics of [124I]FIAU in cat and man
A1  - Jacobs,A.
A1  - Braunlich,I.
A1  - Graf,R.
A1  - Lercher,M.
A1  - Sakaki,T.
A1  - Voges,J.
A1  - Hesselmann,V.
A1  - Brandau,W.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 2001/03//
N1  - UI - 21235388
SP  - 467
EP  - 475
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 42
IS  - 3
N2  - For the assessment of the efficacy of clinical gene therapy trials, different imaging modalities have been developed that enable a noninvasive assessment of location, magnitude, and duration of transduced gene expression in vivo. These imaging methods rely on a combination of an appropriate marker gene and a radiolabeled or paramagnetic marker substrate that can be detected by PET or MRI. Here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (FIAU), a specific marker substrate for herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression, penetrates the blood-brain barrier (BBB) as an essential prerequisite for a noninvasive assessment of HSV-1-tk gene expression in gliomas. METHODS: No-carrier-added [(124)I]FIAU was synthesized by reacting the precursor 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyluracil (FAU) with carrier-free [(124)I]NaI. The course of biodistribution of [(124)I]FIAU was investigated in anesthetized cats (n = 3; organs) and in one patient with a recurrent glioblastoma (plasma and brain) by PET imaging over several hours (cats, 1-22 h) to several days (patient, 1-68 h). FIAU PET was performed in conjunction with multitracer PET imaging (cerebral blood flow and cerebral metabolic rate of O(2) in cats only; cerebral metabolic rate of glucose and [(11)C]methionine in all subjects). A region-of-interest analysis was performed on the basis of coregistered high-resolution MR images. The average radioactivity concentration was determined, decay corrected, and recalculated as percentage injected dose per gram of tissue (%ID/g) or as standardized uptake values (SUVs). RESULTS: The average chemical yield of [(124)I]FIAU synthesis was 54.6% +/- 6.8%. The chemical and radiochemical purities of [(124)I]FIAU were found to be >98% and >95%, respectively. In cats, the kinetic analysis of [(124)I]FIAU-derived radioactivity showed an early peak (1-2 min after injection) in heart and kidneys (0.20 %ID/g; SUV, 4.0) followed by a second peak (10-20 min after injection) in liver and spleen (0.16 %ID/g; SUV, 3.2) with subsequent clearance from tissues and a late peak in the bladder (10-15 h after injection). In the unlesioned cat brain, no substantial [(124)I]FIAU uptake occurred throughout the measurement (<0.02 %ID/g; SUV, <0.4). In the patient, [(124)I]FIAU uptake in normal brain was also very low (<0.0002 %ID/g; SUV, <0.16). In contrast, the recurrent glioblastoma revealed relatively high levels of [(124)I]FIAU-derived radioactivity (5-10 min after injection; 0.001 %ID/g; SUV, 0.8), which cleared slowly over the 68-h imaging period. CONCLUSION: The PET marker substrate FIAU does not penetrate the intact BBB significantly and, hence, is not the marker substrate of choice for the noninvasive localization of HSV-1-tk gene expression in the central nervous system under conditions in which the BBB is likely to be intact. However, substantial levels of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption (e.g., glioblastoma), which is an essential prerequisite for imaging clinically relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by FIAU PET. For this purpose, washout of nonspecific radioactivity should be allowed for several days
AD  - Max-Planck-Institute for Neurological Research, Center for Molecular Medicine, and Department of Neurology, University of Cologne, Cologne, Germany
UR  - PM:11337525
ER  - 

TY  - JOUR
T1  - Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology
A1  - Petersen,R.C.
A1  - Stevens,J.C.
A1  - Ganguli,M.
A1  - Tangalos,E.G.
A1  - Cummings,J.L.
A1  - Dekosky,S.T.
Y1  - 2001/05/08/
N1  - UI - 21241016
SP  - 1133
EP  - 1142
JF  - Neurology
VL  - 56
IS  - 9
N2  - OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia
AD  - Department of Neurology, Mayo Clinic, Rochester, MN, USA
UR  - PM:11342677
ER  - 

TY  - JOUR
T1  - Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology
A1  - Knopman,D.S.
A1  - Dekosky,S.T.
A1  - Cummings,J.L.
A1  - Chui,H.
A1  - Corey-Bloom,J.
A1  - Relkin,N.
A1  - Small,G.W.
A1  - Miller,B.
A1  - Stevens,J.C.
Y1  - 2001/05/08/
N1  - UI - 21241017
SP  - 1143
EP  - 1153
JF  - Neurology
VL  - 56
IS  - 9
N2  - OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy
AD  - Department of Neurology, Mayo Clinic, Rochester, MN, USA
UR  - PM:11342678
ER  - 

TY  - JOUR
T1  - Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride
A1  - Mukherjee,J.
A1  - Christian,B.T.
A1  - Narayanan,T.K.
A1  - Shi,B.
A1  - Mantil,J.
Y1  - 2001/10//
SP  - 476
EP  - 488
JF  - Neuropsychopharmacology
VL  - 25
IS  - 4
N2  - We have used the high-affinity dopamine D-2 receptor radioligand, 18F-fallypride for evaluating receptor occupancy by the antipsychotic drugs, clozapine, risperidone, and haloperidol in rodents and nonhuman primates. In rodents, clozapine (0.1 mg/kg to 100 mg/kg) competed with 18F-fallypride at all the doses administered. At doses over 40 mg/kg, clozapine was able to displace all the administered 18F-fallypride. A pseudobiphasic profile of receptor occupancy by clozapine was observed. This behavior was compared with such other neuroleptics as risperidone and haloperidol that exhibited over 90% receptor occupancy at doses over 0.1 mg/kg and did not exhibit a biphasic nature. Dopamine D-2 receptor occupancy in the monkeys was studied using positron emission tomography (PET) after acute subcutaneous doses of the various drugs. At therapeutically relevant doses, clozapine, risperidone, and haloperidol were able to compete significantly with the binding of 18F-fallypride in all brain regions in rhesus monkeys, and our analyses indicate that these drugs (clozapine, risperidone, and haloperidol) do not discriminate between the striatal (caudate and putamen) and the extrastriatal (thalamus and cortical regions) dopamine receptors. The following extent of D-2 receptor occupancies were measured in the monkey brain using PET: clozapine approximately 70% (dose of 9.7 mg/kg), risperidone approximately 75% (0.05 mg/kg), and haloperidol approximately 90% (0.05 mg/kg)
AD  - Department of Internal Medicine/Nuclear Medicine, Kettering Medical Center, Wright State University, Dayton, OH, USA. mukherjj@uci.edu
UR  - PM:11557161
ER  - 

TY  - JOUR
T1  - 18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease
A1  - Ceravolo,R.
A1  - Piccini,P.
A1  - Bailey,D.L.
A1  - Jorga,K.M.
A1  - Bryson,H.
A1  - Brooks,D.J.
Y1  - 2002/03//
N1  - UI - 21653461
SP  - 201
EP  - 207
JF  - Synapse
VL  - 43
IS  - 3
N2  - Tolcapone is a potent, selective, and reversible inhibitor of cathecol-O-methyl-transferase (COMT). This enzyme plays a crucial role in the extraneural inactivation of catecholamine neurotransmitters. Tolcapone's ability to inhibit central COMT in humans at therapeutic concentrations is not yet clear. The aim was to determine the effect of tolcapone on central COMT activity in Parkinson's disease (PD) using (18)F-dopa positron emission tomography (PET). The study was a randomized two-way crossover study. Twelve PD patients were recruited. On the treatment days patients were given either tolcapone (200 mg) or placebo together with levodopa/carbidopa (100/125 mg) 1 h before the injection of (18)F-dopa. Data were acquired in 25 frames over 94 min for the first PET scan period. At the end of this period the patients were removed from the scanner for 90 min and subsequently repositioned and data acquired in six 10-min time frames over 60 min. Influx constants (Ki) were computed using a graphical approach with a plasma input function. Mean (18)F-dopa putamen Ki's for the first 30-90 min, primarily reflecting central dopa decarboxylase (DDC) activity, were similar in PD patients whether tolcapone was present (0.0078 +/- 0.0031 min(-1)) or absent (0.0078 +/- 0.0030 min(-1)). Mean putamen Ki values calculated 180-240 min after injection of (18)F-dopa, reflecting both central DDC and COMT activity, were unchanged from 30-90' values in the presence of tolcapone (0.0079 +/- 0.0030), implying blockade of central COMT, but were significantly reduced (0.0059 +/- 0.0028) in the absence of this drug. These findings are compatible with clinical doses of tolcapone having a significant blocking effect on peripheral and central COMT but not DDC activity in PD
AD  - MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, London, UK
UR  - PM:11793426
ER  - 

TY  - JOUR
T1  - Functional imaging studies on dopamine and motor control
A1  - Brooks,D.J.
Y1  - 2001///
N1  - UI - 21619141
SP  - 1283
EP  - 1298
JA  - J.Neural Transm.
VL  - 108
IS  - 11
N2  - In this review, the insights that PET and MR activation studies have given us concerning the role of dopamine in motor control are reviewed. Regional cerebral blood flow (rCBF) changes when normal subjects and Parkinson's disease patients perform simple finger movements, motor sequence learning, problem solving, and tasks financially rewarded according to success are compared. Additionally, dopamine release during rewarded and unrewarded actions, as reflected by relative levels of striatal binding of the reversible dopamine antagonist 11C-raclopride, are contrasted. It is argued that during unrewarded familiar actions tonic dopamine release in the basal ganglia acts to focus and filter cortical output so optimising the running of motor programmes. During motor learning, novel, and financially rewarded tasks additional dopamine is phasically released, acting to both alert the subject and to reinforce motor learning
AD  - MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Brooks-dopamine-motor.pdf
ER  - 

TY  - JOUR
T1  - Benzodiazepine-GABA(A) receptor binding is very low in dysembryoplastic neuroepithelial tumor: a PET study
A1  - Richardson,M.P.
A1  - Hammers,A.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 2001/10//
N1  - UI - 21600872
SP  - 1327
EP  - 1334
JF  - Epilepsia
VL  - 42
IS  - 10
N2  - PURPOSE: To determine the nature of abnormalities of gamma-aminobutyric acid (GABA)A-central benzodiazepine (BZD) receptor binding in patients with dysembryoplastic neuroepithelial tumor (DNET) in comparison with normal controls. METHODS: Five patients with DNET and 24 normal controls underwent (11C)flumazenil positron emission tomography (PET) to measure (11C)flumazenil volume of distribution (FMZVD) at the voxel level. Patients were compared with normal controls by using statistical parametric mapping (SPM) and also a partial-volume effect (PVE) corrected volume-of-interest (VOI) analysis covering the entire brain. First, using SPM, the highest Z-score for the entire image representing FMZVD decreases in comparison with the normals was found. Second, regions of abnormal FMZVD were located using SPM, p < 0.001 uncorrected, corrected p < 0.05. Finally, PVE-corrected measures of FMZVD were calculated for each patient VOI and compared wih those of normals, using significance levels of >2.5 standard deviations (SD) for the DNET and >3 SD for all other regions. RESULTS: In all cases, the highest Z-score across the whole image representing decreased FMZVD was within the DNET. In three cases SPM revealed a single region of significantly reduced FMZVD, within the DNET in all three. VOI analysis showed PVE-corrected FMZVD was significantly low in the DNET in four cases. VOI analysis also showed seven other regions of abnormal FMZVD; three were adjacent to a DNET, and two were in mesial temporal areas not affected by DNET. CONCLUSIONS: FMZVD is low in DNET, probably contributing to epileptogenicity
AD  - Epilepsy Research Group, London, England. m.richardson@ion.ucl.ac.uk
UR  - PM:11737168
ER  - 

TY  - JOUR
T1  - Central benzodiazepine receptors in malformations of cortical development: A quantitative study
A1  - Hammers,A.
A1  - Koepp,M.J.
A1  - Richardson,M.P.
A1  - Labbe,C.
A1  - Brooks,D.J.
A1  - Cunningham,V.J.
A1  - Duncan,J.S.
Y1  - 2001/08//
N1  - UI - 21352634
SP  - 1555
EP  - 1565
JF  - Brain
VL  - 124
IS  - Pt 8
N2  - We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomical template for correction for partial volume effect. Nine of 10 patients showed single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Flumazenil binding was decreased in some MCDs with increased grey matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond MRI- detectable structural changes
AD  - MRC Cyclotron Unit, Clinical Sciences Centre, Hammersmith Hospital and National Society for Epilepsy, Institute of Neurology, London, UK
UR  - PM:11459747
ER  - 

TY  - JOUR
T1  - Neocortical abnormalities of [11C]-flumazenil PET in mesial temporal lobe epilepsy
A1  - Hammers,A.
A1  - Koepp,M.J.
A1  - Labbe,C.
A1  - Brooks,D.J.
A1  - Thom,M.
A1  - Cunningham,V.J.
A1  - Duncan,J.S.
Y1  - 2001/04/10/
N1  - UI - 21192588
SP  - 897
EP  - 906
JF  - Neurology
VL  - 56
IS  - 7
N2  - OBJECTIVE: To characterize abnormalities in neocortical central benzodiazepine receptor (cBZR) binding in patients with mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis (HS) using [(11)C]-flumazenil-(FMZ) PET and complementary voxel-based and quantitative volume-of-interest (VOI) methods. METHODS: The authors studied 13 control subjects and 15 patients with refractory mTLE and unilateral HS with [(11)C]-FMZ PET. Data were corrected for partial volume effect in the interactively outlined hippocampus and in 28 cortical VOI using an individualized template. A voxel-based analysis was also performed using statistical parametric mapping (SPM). RESULTS: Fourteen patients with mTLE had reduced [(11)C]-FMZ volume distribution (V(d)) in the hippocampus ipsilateral to the EEG focus, extending into the amygdala in four. Five patients showed additional significant neocortical abnormalities of [(11)C]-FMZ binding: temporal neocortical increases (1), extratemporal decreases (2), extratemporal increases only (1), and temporal and extratemporal neocortical increases (1). Group VOI analysis revealed significant reductions only in the ipsilateral hippocampus. SPM showed decreased [(11)C]-FMZ-V(d) in the ipsilateral hippocampus in 13 of 15 patients, extending into the amygdala in eight. Five patients showed additional neocortical abnormalities: temporal neocortical increases only (3), extratemporal decreases (1), or both temporal neocortical and extratemporal decreases (1). Group analysis showed significant reductions in the ipsilateral hippocampus only. CONCLUSIONS: A combination of VOI- and voxel-based analysis of [(11)C]-FMZ PET detected extrahippocampal changes of cBZR binding in eight of 15 patients with mTLE due to HS. The finding of abnormalities in patients who were thought to have unilateral HS only based on MRI suggests that more widespread abnormalities are present in HS
AD  - National Society for Epilepsy and Institute of Neurology, Queen Square, London
UR  - PM:11294927
ER  - 

TY  - JOUR
T1  - Cobalt-55 positron emission tomography in vascular dementia: significance of white matter changes
A1  - De Reuck,J.
A1  - Santens,P.
A1  - Strijckmans,K.
A1  - Lemahieu,I.
Y1  - 2001/12/15/
N1  - UI - 21576353
SP  - 1
EP  - 6
JA  - J.Neurol.Sci.
VL  - 193
IS  - 1
N2  - BACKGROUND: Vascular dementia (VaD) is still used as a covering term to indicate the relationship between cerebrovascular disease and the progressive cognitive disorder. The contribution of white matter changes (WMCs), seen with computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, to dementia had not been fully elucidated. Cobalt-55 (55Co) positron emission tomography (PET) allows us to distinguish between recent and old infarcts. Purpose: The present study investigates whether 55Co PET can detect the lesions responsible for the progression of the cognitive disorder in VaD patients. PATIENTS AND METHODS: 20 consecutive patients with a previous history of repeated strokes occurring more than 6 months before and with multiple cortical infarcts, lacunes and WMCs on CT and 5 age-matched controls were investigated with 55Co PET. The stroke patients were divided in two groups: 8 with and 12 without VaD. Average 55Co counts in cerebral cortex, deep gray nuclei and white matter were compared to the value in the cerebellum used as reference. RESULTS: In the control group, the 55Co uptake was identical in the cerebral cortex and in the cerebellum, but lower in the deep gray nuclei and the cerebral white matter. When comparing the stroke groups with the control, the 55Co uptake was similar for the cerebral cortex and deep gray nuclei, but significantly increased in the cerebral white matter. The 55Co uptake was also more increased in the stroke group with VaD compared to the non-demented group. CONCLUSION: 55Co PET shows that the WMCs are due to the ongoing damage of probably ischaemic origin which is more prominent in stroke patients with progressive cognitive decline
AD  - Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium. jacques.dereuck@yucom.be
UR  - PM:11718742
ER  - 

TY  - JOUR
T1  - Cobalt-55 positron emission tomography in late-onset epileptic seizures after thrombo-embolic middle cerebral artery infarction
A1  - De Reuck,J.
A1  - Vonck,K.
A1  - Santens,P.
A1  - Boon,P.
A1  - De Bleecker,J.
A1  - Strijckmans,K.
A1  - Lemahieu,I.
Y1  - 2000/12/01/
N1  - UI - 20553469
SP  - 13
EP  - 18
JA  - J.Neurol.Sci.
VL  - 181
IS  - 1-2
N2  - The pathogenesis of late-onset epileptic seizures after thrombo-embolic cerebral infarction is poorly understood. Our previous positron emission tomographic (PET) studies with 15O have demonstrated that post-apoplectic epilepsy is associated with more severe brain ischemia, but we were unable to determine if this was the cause or the consequence of the seizures. Using cobalt-55 (55Co) as PET tracer we can now distinguish recurrent, recent infarction in patients with a previous old infarct in the same vascular territory. In seven out of twelve patients with post-apoplectic seizures an increased uptake of 55Co was observed in the border area and in two of them also within the old infarct core. In the control group, composed of eight seizure-free patients with also an old infarct involving the cortical territory of the middle cerebral artery, no increase in 55Co uptake was observed on PET examination. The present study indicates that in a significant number of patients late-onset epilepsy is the clinical expression of recurrent strokes, occurring in the same vascular territory
AD  - Department of Neurology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. jacques.dereuck@yucom.be
UR  - PM:11099706
ER  - 

TY  - JOUR
T1  - 55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI
A1  - Stevens,H.
A1  - Jansen,H.M.
A1  - De Reuck,J.
A1  - Lemmerling,M.
A1  - Strijckmans,K.
A1  - Goethals,P.
A1  - Lemahieu,I.
A1  - de Jong,B.M.
A1  - Willemsen,A.T.
A1  - Korf,J.
Y1  - 1999/12/01/
N1  - UI - 20035325
SP  - 11
EP  - 18
JA  - J.Neurol.Sci.
VL  - 171
IS  - 1
N2  - Several studies have shown the feasibility of divalent cobalt (Co)-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and traumatic brain injury. Little is known how regional Co uptake relates to other pathophysiological changes after stroke. Therefore, we compared 55Co-PET with functional parameters such as regional cerebral blood flow (rCBF) using C(15)O(2), regional oxygen metabolism (rCMRO(2)) using 15O(2), regional cerebral blood volume (rCBV) and post-gadolinium (Gd) T(1)w-MRI to assess the permeability of the blood-brain-barrier (BBB). Sixteen patients (10 female; six male) aged 43 to 84 (mean 69) years with first ever stroke, as shown by CT or MRI, were examined with 55Co-PET and C(15)O(2)-, 15O(2)- and C(15)O-PET in one single session, in a period varying from 0 to 30 days after stroke-onset. Regions of infarction on C(15)O(2)- and 15O(2)-PET (defined by rCMRO(2)<65% or rCBF<45% of the contralateral value) were subsequently superimposed on the 55Co-PET scan. Clinical status was established using the Orgogozo stroke scale, which was assessed both at day 1 and at discharge (at least 6 weeks after day 1). Accumulation of 55Co was seen in eight out of 16 patients, occurring in areas showing a diminished oxygen metabolism, was only partially related to blood flow, and was located mainly outside the extent of the infarction or luxury perfusion as seen on post-Gd T(1)w-MRI. Statistical analysis showed a negative correlation between the Orgogozo score at discharge and the uptake of radioactive cobalt
AD  - PET-Center University Hospital Gent/University of Gent, Gent, Belgium
UR  - PM:10567044
ER  - 

TY  - JOUR
T1  - Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks
A1  - Moresco,R.M.
A1  - Tettamanti,M.
A1  - Gobbo,C.
A1  - Del Sole,A.
A1  - Ravasi,L.
A1  - Messa,C.
A1  - Paulesu,E.
A1  - Lucignani,G.
A1  - Perani,D.
A1  - Fazio,F.
Y1  - 2001/04//
SP  - 399
EP  - 404
JA  - Nucl.Med.Commun.
VL  - 22
IS  - 4
N2  - The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies
AD  - INB-CNR, University of Milan-Statale, University of Milan-Bicocca, H. S. Raffaele, Milano, Italy
UR  - PM:11338050
ER  - 

TY  - JOUR
T1  - Functional MRI of language processing: dependence on input modality and temporal lobe epilepsy
A1  - Carpentier,A.
A1  - Pugh,K.R.
A1  - Westerveld,M.
A1  - Studholme,C.
A1  - Skrinjar,O.
A1  - Thompson,J.L.
A1  - Spencer,D.D.
A1  - Constable,R.T.
Y1  - 2001/10//
N1  - UI - 21600862
SP  - 1241
EP  - 1254
JF  - Epilepsia
VL  - 42
IS  - 10
N2  - PURPOSE: Functional magnetic resonance imaging (MRI) using two language-comprehension tasks was evaluated to determine its ability to lateralize language processing and identify regions that must be spared in surgery. METHODS: Two parallel cognitive language tasks, one using auditory input and the other visual input, were tested in a group of control subjects and in temporal lobe epilepsy patients who were candidates for surgical intervention. The patient studies provide an opportunity to compare functional MRI language localization with that obtained using Wada testing and electrocorticography. All of the patients in this study underwent all three procedures and a battery of neuropsychological testing. Such studies provide an opportunity not only to validate the fMRI findings but also, by comparing the patient results with those obtained in control subjects, to provide insight into the impact of a pathology such as epilepsy on cortical organization or functional patterns of activation. RESULTS: The results reveal both modality-dependent and modality-independent language-processing patterns for visual versus auditory task presentation. The visual language task activated distinct sites in Broca's area, BA (Brodmann area) 44 that were not activated in the auditory language task. The auditory language task strongly activated contralateral right BA22-21 area (homologous to Wernicke's area on the left). Language lateralization scores were significantly stronger for visual than for auditory task presentation. The conjunction of activation from the two different input modalities (modality-independent areas) likely highlights regions that perform more abstract computations (e.g., syntactic or pragmatic processing) in language processing. Modality-specific areas (e.g., right Wernicke, left fusiform gyrus, Broca BA44, supramarginal gyrus), appear to cope with the computations relevant to making contact with these more abstract dimensions. Patients showed recruitment of contralateral homologous language areas (p < 0.005) that was significantly above that found in a normal control group. Extra- and intraoperative cortical stimulations were concordant with the fMRI data in eight of 10 cases. The fMRI lateralization scores were also consistent with the Wada testing in 8/10 patients. CONCLUSIONS: The fMRI results demonstrate that the epileptic brain may be a progressive model for cortical plasticity
AD  - Department of Diagnostic Radiology, Yale University School of Medicine, and Haskins Laboratories, New Haven, Connecticut 06520-8082, USA
UR  - PM:11737158
ER  - 

TY  - JOUR
T1  - Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment
A1  - Terry,R.D.
A1  - Masliah,E.
A1  - Salmon,D.P.
A1  - Butters,N.
A1  - DeTeresa,R.
A1  - Hill,R.
A1  - Hansen,L.A.
A1  - Katzman,R.
Y1  - 1991/10//
N1  - UI - 92161745
SP  - 572
EP  - 580
JA  - Ann.Neurol.
VL  - 30
IS  - 4
N2  - We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength
AD  - Department of Neurosciences, University of California-San Diego, La Jolla 92093-0624
UR  - PM:1789684
ER  - 

TY  - JOUR
T1  - Kinetic analysis of [(11)C]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling
A1  - Nagatsuka,S.
A1  - Fukushi,K.
A1  - Shinotoh,H.
A1  - Namba,H.
A1  - Iyo,M.
A1  - Tanaka,N.
A1  - Aotsuka,A.
A1  - Ota,T.
A1  - Tanada,S.
A1  - Irie,T.
Y1  - 2001/11//
N1  - UI - 21558510
SP  - 1354
EP  - 1366
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 11
N2  - N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies
AD  - Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan
UR  - PM:11702050
ER  - 

TY  - JOUR
T1  - Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo
A1  - Jacobs,A.
A1  - Tjuvajev,J.G.
A1  - Dubrovin,M.
A1  - Akhurst,T.
A1  - Balatoni,J.
A1  - Beattie,B.
A1  - Joshi,R.
A1  - Finn,R.
A1  - Larson,S.M.
A1  - Herrlinger,U.
A1  - Pechan,P.A.
A1  - Chiocca,E.A.
A1  - Breakefield,X.O.
A1  - Blasberg,R.G.
Y1  - 2001/04/01/
SP  - 2983
EP  - 2995
JA  - Cancer Res.
VL  - 61
IS  - 7
N2  - To evaluate the efficiency of gene delivery in gene therapy strategies for malignant brain tumors, it is important to determine the distribution and magnitude of transgene expression in target tumor cells over time. Here, we assess the time- and vector dose-dependent kinetics of recombinant herpes simplex virus (HSV)-1 vector-mediated gene expression and vector replication in culture and in vivo by a recently developed radiotracer method for noninvasive imaging of gene expression (J. G. Tjuvajev et al., Cancer Res., 55: 6126-6132, 1995). The kinetics of viral infection of rat 9L gliosarcoma cells by the replication-conditional HSV-1 vector, hrR3, was studied by measuring the accumulation rate of 2-[14C]-fluoro-5-iodo-1-beta-D-arabinofuranosyl-uracil (FIAU), a selective substrate for viral thymidine kinase (TK). The level of viral TK activity in 9L cells was monitored by the radiotracer assay to assess various vector doses and infection times, allowing vector replication and spread. In parallel, viral yields and levels of Escherichia coli beta-galactosidase activity were assessed quantitatively. To study vector replication, spread and HSV-1-tk and lacZ gene coexpression in vivo, first- or second-generation recombinant HSV-1 vectors (hrR3 or MGH-1) were injected into s.c. growing rat 9L or human U87 deltaEGFR gliomas in nude rats at various times (8 h to 8 days) and at various vector doses [1 x 10(6) to 2 x 10(9) plaque-forming units (PFUs)] prior to imaging. For noninvasive assessment of HSV-1-tk gene expression (124I-labeled FIAU % dose/g), 0.15 mCi of 124I-labeled FIAU was injected i.v. 8 h after the last vector administration, and FIAU positron emission tomography (PET) was performed 48 h later. For the assessment of HSV-1-tk and lacZ gene coexpression, 0.2 mCi of 131I-labeled FIAU was injected i.v. 24 h after the last vector administration. Forty-eight h later, animals were killed, and tumors were dissected for quantitative autoradiographical and histochemical assessment of regional distribution of radioactivity (TK expression measured as 131I-labeled FIAU % dose/g) and coexpressed lacZ gene activity. The rates of FIAU accumulation (Ki) in hrR3-infected 9L cells in culture, which reflect the levels of HSV-1-tk gene expression, ranged between 0.12 and 3.4 ml/g/min. They increased in a vector dose- and infection time-dependent manner and correlated with the virus yield (PFUs/ml), where the PFUs:Ki ratios remained relatively constant over time. Moreover, a linear relationship was observed between lacZ gene expression and FIAU accumulation 5-40 h after infection of 9L cells with a multiplicity of infection of 1.5. At later times (> 52 h postinjection), high vector doses (multiplicity of infection, 1.5) led to a decrease of FIAU accumulation rates, viral yield, and cell pellet weights, indicating vector-mediated cell toxicity. Various levels of HSV-1-tk gene expression could be assessed by FIAU-PET after in vivo infection of s.c. tumors. The levels of FIAU accumulation were comparatively low (approximately ranging from 0.00013 to 0.003% injected dose/g) and were spatially localized; this may reflect viral-induced cytolysis of infected tumor cells and limited lateral spread of the virus. Image coregistration of tumor histology, HSV-1-tk related radioactivity (assessed by autoradiography), and lacZ gene expression (assessed by beta-galactosidase staining) demonstrated a characteristic pattern of gene expression around the injection sites. A rim of lacZ gene expression immediately adjacent to necrotic tumor areas was observed, and this zone was surrounded by a narrow band of HSV-1-tk-related radioactivity, primarily in viable-appearing tumor tissue. These results demonstrate that recombinant HSV-1 vector-mediated HSV-1-tk gene expression can be monitored noninvasively by PET, where the areas of FIAU-derived radioactivity identify the viable portion of infected tumor tissue that retains FIAU accumulation ability, and that the accumulation rate of FIAU in culture, Ki, reflects the number of HSV-1 viral particles in the infected tumor cell population [4.1 +/- 0.6 x 10(6) PFUs/Ki unit (PFUs divided by ml/min/g)]. Moreover, time-dependent and spatial relationships of HSV-1-tk and lacZ gene coexpression in culture and in vivo indicate the potential for indirect in vivo imaging of therapeutic gene expression in tumor tissue infected with any recombinant HSV-1 vector where a therapeutic gene is substituted for the lacZ gene
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
UR  - PM:11306477
ER  - 

TY  - JOUR
T1  - A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase
A1  - Tjuvajev,J.G.
A1  - Joshi,A.
A1  - Callegari,J.
A1  - Lindsley,L.
A1  - Joshi,R.
A1  - Balatoni,J.
A1  - Finn,R.
A1  - Larson,S.M.
A1  - Sadelain,M.
A1  - Blasberg,R.G.
Y1  - 1999/10//
N1  - UI - 20388529
SP  - 315
EP  - 320
JA  - Neoplasia.
VL  - 1
IS  - 4
N2  - Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
UR  - PM:10935486
ER  - 

TY  - JOUR
T1  - Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly
A1  - Perry,R.H.
A1  - Irving,D.
A1  - Blessed,G.
A1  - Fairbairn,A.
A1  - Perry,E.K.
Y1  - 1990/02//
N1  - UI - 90218162
SP  - 119
EP  - 139
JA  - J Neurol.Sci.
VL  - 95
IS  - 2
N2  - A dementing syndrome has been identified in a group of psychiatric cases aged 71-90 years, presenting initially with a subacute/acute confusional state, often fluctuating and associated with visual hallucinations and behavioural disturbances. Clinically, these cases did not meet criteria for a diagnosis of Alzheimer's disease, and many were assigned to the multiinfarct dementia group, although no significant ischaemic lesions were evident at autopsy. Mild extrapyramidal features were apparent in a number of cases but the characteristic clinical triad of Parkinson's disease, i.e., tremor, rigidity, and akinesia, was absent. Detailed neuropathological examination revealed Lewy body formation and selective neuronal loss in brain stem and other subcortical nuclei, accompanied by Lewy body formation in neo- and limbic cortex, at densities well below those previously reported in diffuse Lewy body disease. A variable degree of senile degenerative change was present; numerous senile plaques and minimal neurofibrillary tangles in most cases. Neither the clinical nor the neuropathological features of this group are typical of Parkinson's or Alzheimer's disease, but suggest a distinct neurodegenerative disorder, part of the Lewy body disease spectrum, in which mental symptoms predominate over motor disabilities and lead to eventual psychogeriatric hospital admission. In a sequential series of autopsies conducted on clinically assessed demented patients, neuropathological analysis has indicated that such cases may comprise up to 20% of a hospitalized population of demented old people over the age of 70 years, an observation clearly relevant to the diagnosis and management of dementia in the elderly
AD  - Department of Neuropathology, Newcastle General Hospital, U.K
UR  - PM:2157823
ER  - 

TY  - JOUR
T1  - Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study
A1  - Bouilleret,V.
A1  - Dupont,S.
A1  - Spelle,L.
A1  - Baulac,M.
A1  - Samson,Y.
A1  - Semah,F.
Y1  - 2002/02//
N1  - UI - 21823271
SP  - 202
EP  - 208
JA  - Ann.Neurol.
VL  - 51
IS  - 2
N2  - Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo-amygdalar complex involvement. Recent stereo-electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose ((18)F-FDG) and flumazenil ((11)C-FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil-positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy
AD  - Service Hospitalier Frederic Joliot, CEA, Orsay, France
UR  - PM:11835376
ER  - 

TY  - JOUR
T1  - Increase in Dopamine Turnover Occurs Early in Parkinson's Disease: Evidence From a New Modeling Approach to PET 18 F-Fluorodopa Data
A1  - Sossi,V.
A1  - Fuente-Fernandez,R.
A1  - Holden,J.E.
A1  - Doudet,D.J.
A1  - McKenzie,J.
A1  - Stoessl,A.J.
A1  - Ruth,T.J.
Y1  - 2002/02//
N1  - UI - 21681650
SP  - 232
EP  - 239
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 2
N2  - SUMMARY: An increase in dopamine turnover has been hypothesized to occur early in Parkinson's disease (PD) as a compensatory mechanism for dopaminergic neuronal loss. A new approach to the determination of dopamine turnover was developed using 4-hour-long 18 F-fluorodopa (FD) positron emission tomography (PET) data. An effective dopamine turnover, an estimate of dopamine turnover, has been measured using its inverse, the effective dopamine distribution volume (EDV). This new method is based on a reversible tracer approach and determines the EDV using a graphical method. Six healthy subjects and 10 subjects with very early PD underwent a 4-hour-long FD scan. The EDV and the plasma uptake rate constant K i, a marker of dopamine synthesis and storage, were compared according to their ability to separate the PD group from the healthy group. The EDV was the better discriminator (93.8% correct classification versus 81.3% for K i ). Effective dopamine distribution volume decreased by 65% in the PD group relative to the healthy group, whereas the decrease in K i was 39%. These results show that changes in EDV are measurable with PET earlier than changes in the dopamine synthesis and storage rate, indicating that EDV is a sensitive marker for early PD and that a dopamine turnover increase likely serves as an early compensatory mechanism
AD  - University of British Columbia/TRIUMF, University of British Columbia, Vancouver, Canada; and University of Wisconsin, Madison, Wisconsin, U.S.A
UR  - PM:11823721
ER  - 

TY  - CHAP
T1  - Registration of MRI and PET images for clinical applications
A1  - Pietrzyk,U.
Y1  - 2001///
SP  - 199
EP  - 216
T2  - Medical image registration
A2  - Hajnal,J.V.
A2  - Hill,D.L.G.
A2  - Hawkes,D.J.
IS  - 9
CY  - Boca Raton
PB  - CRC Press
ER  - 

TY  - JOUR
T1  - Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels
A1  - Drevets,W.C.
A1  - Price,J.L.
A1  - Bardgett,M.E.
A1  - Reich,T.
A1  - Todd,R.D.
A1  - Raichle,M.E.
Y1  - 2002/03//
N1  - UI - 21819307
SP  - 431
EP  - 447
JA  - Pharmacol.Biochem.Behav.
VL  - 71
IS  - 3
N2  - In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1<P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function
AD  - Section on Neuroimaging of Mood and Anxiety Disorders, Molecular Imaging Branch, Mood and Anxiety Disorders Program, NIH/National Institute of Mental Health, Building 1, Room B3-10, 1 Center Drive, MSC-0135, 20892-0135, Bethesda, MD, USA
UR  - PM:11830178
ER  - 

TY  - JOUR
T1  - Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease
A1  - Mega,M.S.
A1  - Cummings,J.L.
A1  - O'Connor,S.M.
A1  - Dinov,I.D.
A1  - Reback,E.
A1  - Felix,J.
A1  - Masterman,D.L.
A1  - Phelps,M.E.
A1  - Small,G.W.
A1  - Toga,A.W.
Y1  - 2001/01//
SP  - 63
EP  - 68
JA  - Neuropsychiatry Neuropsychol.Behav.Neurol.
VL  - 14
IS  - 1
N2  - OBJECTIVE: The objective of this study was to identify the relation between the cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six patients with mild to moderate Alzheimer disease (AD) were evaluated before and after treatment with the long-lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group's mean intensity levels and subjected to voxel-by-voxel subtraction of the posttreatment minus pretreatment studies. Subvolume thresholding corrected random lobar noise to produce a three-dimensional functional significance map. RESULTS: The criteria for cognitive improvement with treatment were met for the MMSE (>2 points improvement from baseline), and the drawing subscale of the ADAS-cog was significantly improved with treatment. The three-dimensional significance map revealed a significant metabolic increase of the dorsolateral frontoparietal network on the left and bilateral temporal cortex with metrifonate treatment. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks
AD  - Department of Neurology, University of California at Los Angeles School of Medicine, 90095-1769, USA
UR  - PM:11234910
ER  - 

TY  - JOUR
T1  - Pharmacological evaluation of [11C]donepezil as a tracer for visualization of acetylcholinesterase by PET
A1  - De Vos,F.
A1  - Santens,P.
A1  - Vermeirsch,H.
A1  - Dewolf,I.
A1  - Dumont,F.
A1  - Slegers,G.
A1  - Dierckx,R.A.
A1  - De Reuck,J.
Y1  - 2000/11//
N1  - UI - 21067391
SP  - 745
EP  - 747
JA  - Nucl Med Biol.
VL  - 27
IS  - 8
N2  - Donepezil is a highly potent and selective reversible achetylcholinesterase inhibitor. [(11)C]Donepezil is prepared by methylation with [(11)C]CH(3)I of the corresponding 6'-O-desmethylprecursor. Tissue distribution in mice revealed a high uptake in brain and rapid clearance from the blood. Metabolization studies in mice indicated the formation of one (11)C-labeled polar metabolite that didn't penetrate the blood-brain barrier. Regional brain distribution in rabbits didn't reflect the measured achetylcholinesterase distribution in rabbit brain
AD  - Department of Radiopharmacy, University Hospital of Gent, Gent, Belgium. filipx.devos@rug.ac.be
UR  - PM:11150706
ER  - 

TY  - JOUR
T1  - In vivo PET study of cerebral [11C] methyl- tetrahydroaminoacridine distribution and kinetics in healthy human subjects
A1  - Traykov,L.
A1  - Tavitian,B.
A1  - Jobert,A.
A1  - Boller,F.
A1  - Forette,F.
A1  - Crouzel,C.
A1  - Di Giamberardino,L.
A1  - Pappata,S.
Y1  - 1999/05//
N1  - UI - 99228794
SP  - 273
EP  - 278
JA  - Eur.J Neurol.
VL  - 6
IS  - 3
N2  - It is unclear whether the palliative effects of tetrahydroaminoacridine (THA) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzheimer's disease (AD) are the result of its inhibitory activity on acetylcholinesterase or on other complex sites of action. In order to investigate the cerebral distribution and kinetics of THA in the human brain in vivo, we performed positron emission tomography (PET) imaging with [11C]N-methyl-tetrahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [11C]MTHA crossed the blood-brain barrier and reached its maximum uptake between 10 and 40 minutes, depending on the brain regions. Uptake was higher in the grey matter structures, and lower in the white matter. After this peak, the radioactivity remained quasi- constant until 60 minutes in all regions with a half-life varying from 2.44 hours in the thalamus to 3.42 hours in the cerebral cortex. The ratios of regional to whole cerebral cortex brain radioactivity calculated between 50 and 70 minutes after the tracer injection were 1.14 +/- 0.04, 1.07 +/- 0. 03 and 1.06 +/- 0.04 in the putamen, cerebellum and thalamus, respectively. Overall, these results show that: (1) [11C]MTHA crosses the blood-brain barrier easily and is highly concentrated in the brain; (2) the regional brain distribution of [11C]MTHA does not parallel that of in vivo acetylcholinesterase (AChE) concentrations; and (3) the cerebral kinetics of [11C]MTHA are consistent with known plasmatic pharmacokinetics of THA in AD patients. We conclude that PET imaging with [11C]MTHA is a useful method for assessing the cerebral distribution and kinetics of THA in vivo
AD  - 1 INSERM Unit 334, Service Hospitalier Frederic Joliot, CEA/DSV/DRM, Orsay, France and INSERM Unit 324, Paris, France
UR  - PM:10210906
ER  - 

TY  - JOUR
T1  - Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [11C]-flumazenil PET
A1  - Szelies,B.
A1  - Sobesky,J.
A1  - Pawlik,G.
A1  - Mielke,R.
A1  - Bauer,B.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 2002/03//
N1  - UI - 21876970
SP  - 137
EP  - 142
JA  - Eur.J Neurol.
VL  - 9
IS  - 2
N2  - Individual benzodiazepine receptor (BZR) binding of peri-lesional cortex was investigated in symptomatic epilepsies. Eleven patients aged 19--44 years were studied whose diagnosis was established by medical history, clinical, electroencephalographic, and magnetic resonance imaging (MRI) findings. Three-dimensional [11C]-flumazenil (FMZ) positron emission tomography and MRI scans were obtained and coregistered. Lesions (five low-grade brain tumours, one AV malformation, one cavernoma, one cystic lesion of unknown aetiology, one traumatic brain injury, one post-operative and one post-haemorrhagic defect) were outlined on individual MRI scans. Adjacent to those lesions, and in homologous contralateral structures, FMZ binding was analysed in four pairs of cortical 9 x 9-mm regions of interest (ROIs) placed on transaxial and coronal slices, respectively, as well as in the lesion volume and its mirror region. Percentage asymmetry ratios were calculated and those at or outside the 90--110% range were operationally defined significant. Peri-lesional FMZ binding asymmetries ranged from 70 to 125%, lesional asymmetries from 38 to 82%. Only one patient showed no significant change, whilst nine exhibited significant reductions of FMZ binding in at least one ROI (3 x 1, 4 x 2, 1 x 3, 1 x 4), and significant increases were observed in two ROIs of another patient. Therefore, peri-lesional disturbances of BZR binding are common but variable in location. Because a close correlation between regional decreases in FMZ binding and spiking activity was recently demonstrated in neocortical epilepsies, abnormal peri-lesional FMZ binding may bear some relation to the mechanisms of epileptogenesis in symptomatic epilepsies
AD  - Neurologische Universitatsklinik and Max-Planck-Institut fur neurologische Forschung, Cologne, Germany
UR  - PM:11882054
ER  - 

TY  - JOUR
T1  - Positron emission tomography shows that impaired frontal lobe functioning in Parkinson's disease is related to dopaminergic hypofunction in the caudate nucleus
A1  - Bruck,A.
A1  - Portin,R.
A1  - Lindell,A.
A1  - Laihinen,A.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Rinne,J.O.
Y1  - 2001/09/28/
N1  - UI - 21453802
SP  - 81
EP  - 84
JA  - Neurosci.Lett.
VL  - 311
IS  - 2
N2  - We examined the relation between the dopaminergic function and the cognitive performance of patients with Parkinson's disease (PD). The subject sample consisted of ten patients in the early course of PD and with no previous antiparkinsonian medication. The dopaminergic function of the caudate nucleus and the putamen was studied with [(18)F]fluorodopa positron emission tomography, and the cognitive performance with a comprehensive battery of neuropsychological tests including tests sensitive to frontal lobe function. The decreased [(18)F]fluorodopa uptake in the right caudate nucleus was found to be related to slow processing time, measured as the difference between the incongruent and the congruent subtests of the Stroop Test (r=-0.85, P=0.002), a similar trend was seen in the left caudate (r=-0.60, P=0.07). Similar correlation was not detected in the putamen. The present findings provide evidence that the decreased dopaminergic function in the right caudate nucleus is related to the impaired performance in tests sensitive to frontal lobe function in patients at an early stage of PD and with no antiparkinsonian medication
AD  - Turku PET Centre, University of Turku, FIN-20520, Turku, Finland
UR  - PM:11567783
ER  - 

TY  - JOUR
T1  - Rate of progression in Parkinson's disease: a 6-[18F]fluoro-L-dopa PET study
A1  - Nurmi,E.
A1  - Ruottinen,H.M.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Sonninen,P.
A1  - Rinne,J.O.
Y1  - 2001/07//
N1  - UI - 21374311
SP  - 608
EP  - 615
JA  - Mov Disord.
VL  - 16
IS  - 4
N2  - The aim of this study was to investigate the rate of progression in Parkinson's disease (PD) with 6-[(18)F]fluoro-L-dopa (FDOPA) positron emission tomography (PET). We investigated 21 patients with PD and eight healthy controls. Ten of the patients were de novo at the time of the first PET scan and antiparkinsonian medication was started thereafter, with a favourable response. A FDOPA PET scan was carried out twice at an approximately 5-year interval. The regions of interest were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images. At the first PET scan, in PD patients the mean k(i)(occ) (x 10(-3) min(-1)) in the anterior putamen was 5.6 +/- 2.7 (mean +/- S.D.; 55% of the control mean) and in the posterior putamen 4.5 +/- 2.4 (45% of the control mean). The k(i)(occ) value for the caudate nucleus was 7.5 +/- 2.1 (x 10(-3) min(-1); 76% of the control mean). The FDOPA uptake declined by the time of the second PET scan and the annual rate of decline was 8.3 +/- 6.3% (P < 0.001) of the baseline mean in the anterior putamen and 10.3 +/- 4.8% (P < 0.001) in the posterior putamen. In the caudate nucleus, FDOPA uptake decreased by 5.9 +/- 5.1% (P < 0.001) of the baseline mean per year. The estimated preclinical period was longest for the posterior putamen being 6.5 years. For the anterior putamen the preclinical period was 4.6 years. In the caudate nucleus, the estimated FDOPA uptake was at normal level at disease onset. In healthy controls, there was no significant decline in FDOPA uptake in any striatal subregion. Our results suggest that the disease process in PD first affects posterior putamen, followed by the anterior putamen and the caudate nucleus, but once started, the absolute rate of decline is the same. In healthy controls, no significant decline in FDOPA was detected
AD  - Department of Neurology, and Turku PET Centre, University of Turku, Turku, Finland
UR  - PM:11481683
ER  - 

TY  - JOUR
T1  - Increased frontal [(18)F]fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex
A1  - Kaasinen,V.
A1  - Nurmi,E.
A1  - Bruck,A.
A1  - Eskola,O.
A1  - Bergman,J.
A1  - Solin,O.
A1  - Rinne,J.O.
Y1  - 2001/06//
N1  - UI - 21252969
SP  - 1125
EP  - 1130
JF  - Brain
VL  - 124
IS  - Pt 6
N2  - Previous imaging studies in Parkinson's disease have focused mainly on the striatum, a region with very high dopaminergic activity. Using modern high-sensitivity 3D [(18)F]fluorodopa (Fdopa)-PET, mesocortical monoamine projections can be studied. To study the frontal monoaminergic system in unmedicated early Parkinson's disease in vivo, we examined 20 early Parkinson's disease patients (10 women, 10 men) and 16 healthy subjects (nine women, seven men) with 3D Fdopa-PET, using standard region-of-interest-based analysis with MRI co-registration. Women with Parkinson's disease had 87% higher Fdopa uptake in the right dorsolateral prefrontal cortex (area 46) compared with men with Parkinson's disease, whereas there was no sex difference in the control group (sex x disease interaction, P = 0.03). The uptake in the right dorsolateral prefrontal cortex was 82% higher in men with Parkinson's disease and 219% higher in women with Parkinson's disease compared with control groups (effect of disease, P < 0.0001). Also in the left dorsolateral prefrontal cortex and in the medial frontal cortex, early Parkinson's disease patients had significantly (18-94%) higher Fdopa uptake compared with healthy controls. In the putamen, both men and women with Parkinson's disease had a significantly lower (27-46%) uptake compared with healthy controls. These results indicate that frontal monoaminergic activity is increased and that there is a sex difference in the prefrontal monoaminergic system in early Parkinson's disease. The reported sex difference may be linked to clinical sex differences in the symptoms and treatment response in Parkinson's disease
AD  - Department of Neurology, University of Turku, PO Box 52, FIN-20521 Turku, Finland. valtteri.kaasinen@pet.tyks.fi
UR  - PM:11353728
ER  - 

TY  - JOUR
T1  - Molecular imaging of small animals with dedicated PET tomographs
A1  - Chatziioannou,A.F.
Y1  - 2002/01//
N1  - UI - 21665946
SP  - 98
EP  - 114
JA  - Eur.J Nucl Med
VL  - 29
IS  - 1
N2  - Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology
AD  - Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Box 951770 UCLA, Los Angeles, CA 90095-1770, USA. archatziioann@mednet.ucla.edu
UR  - PM:11807613
ER  - 

TY  - JOUR
T1  - Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Abeta peptide radiopharmaceutical
A1  - Lee,H.J.
A1  - Zhang,Y.
A1  - Zhu,C.
A1  - Duff,K.
A1  - Pardridge,W.M.
Y1  - 2002/02//
N1  - UI - 21681649
SP  - 223
EP  - 231
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 2
N2  - Abeta 1-40 is a potential peptide radiopharmaceutical that could be used to image the brain Abeta amyloid of Alzheimer disease in vivo, should this peptide be made transportable through the blood-brain barrier in vivo. The blood-brain barrier transport of [ 125 I]-Abeta 1-40 in a transgenic mouse model was enabled by conjugation to the rat 8D3 monoclonal antibody to the mouse transferrin receptor. The Abeta 1-40 -8D3 conjugate is a bifunctional molecule that binds the blood-brain barrier TfR and undergoes transport into brain and binds the Abeta amyloid plaques of Alzheimer disease. App SW /Psen1 double-transgenic and littermate control mice were administered either unconjugated Abeta 1-40 or the Abeta 1-40 -8D3 conjugate intravenously, and brain scans were obtained 6 hours later. Immunocytochemical analysis showed abundant Abeta immunoreactive plaques in the brains of the App SW /Psen1 transgenic mice and there was a selective retention of radioactivity in the brains of these mice at 6 hours after intravenous administration of the conjugate. In contrast, there was no selective sequestration either of the conjugate in control littermate mouse brain or of unconjugated Abeta 1-40 in transgenic mouse brain. In conclusion, the results show that it is possible to image the Abeta amyloid burden in the brain in vivo with an amyloid imaging agent, provided the molecule is conjugated to a blood-brain barrier drug-targeting system
AD  - Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
UR  - PM:11823720
ER  - 

TY  - JOUR
T1  - Development of a functional magnetic resonance imaging protocol for intraoperative localization of critical temporoparietal language areas
A1  - Rutten,G.J.
A1  - Ramsey,N.F.
A1  - van Rijen,P.C.
A1  - Noordmans,H.J.
A1  - van Veelen,C.W.
Y1  - 2002/03//
N1  - UI - 21888198
SP  - 350
EP  - 360
JA  - Ann.Neurol.
VL  - 51
IS  - 3
N2  - The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging must fulfill for clinical implementation: high predictive power for the presence as well as the absence of critical language function in regions of the brain, user-independent statistical methodology, and high spatial accuracy. Thirteen patients with temporal lobe epilepsy performed four different functional magnetic resonance imaging language tasks (ie, verb generation, picture naming, verbal fluency, and sentence comprehension) before epilepsy surgery that included intraoperative electrocortical stimulation mapping. To assess the optimal statistical threshold for functional magnetic resonance imaging, images were analyzed with three different statistical thresholds. Functional magnetic resonance imaging information was read into a surgical guidance system for identification of cortical areas of interest. Intraoperative electrocortical stimulation mapping was recorded by video camera, and stimulation sites were digitized. Next, a computer algorithm indicated whether significant functional magnetic resonance imaging activation was present or absent within the immediate vicinity (<6.4mm) of intraoperative electrocortical stimulation mapping sites. In 2 patients, intraoperative electrocortical stimulation mapping failed during surgery. Intraoperative electrocortical stimulation mapping detected critical language areas in 8 of the remaining 11 patients. Correspondence between functional magnetic resonance imaging and intraoperative electrocortical stimulation mapping depended heavily on statistical threshold and varied between patients and tasks. In 7 of 8 patients, sensitivity of functional magnetic resonance imaging was 100% with a combination of 3 functional magnetic resonance imaging tasks (ie, functional magnetic resonance imaging correctly detected all critical language areas with high spatial accuracy). In 1 patient, sensitivity was 38%; in this patient, functional magnetic resonance imaging was included in a larger area found with intraoperative electrocortical stimulation mapping. Overall, specificity was 61%. Functional magnetic resonance imaging reliably predicted the absence of critical language areas within the region exposed during surgery, indicating that such areas can be safely resected without the need for intraoperative electrocortical stimulation mapping. The presence of functional magnetic resonance imaging activity at noncritical language sites limited the predictive value of functional magnetic resonance imaging for the presence of critical language areas to 51%. Although this precludes current replacement of intraoperative electrocortical stimulation mapping, functional magnetic resonance imaging can at present be used to speed up intraoperative electrocortical stimulation mapping procedures and to guide the extent of the craniotomy
AD  - Departments of Neurosurgery and
UR  - PM:11891830
ER  - 

TY  - JOUR
T1  - The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service
A1  - Hughes,A.J.
A1  - Daniel,S.E.
A1  - Ben Shlomo,Y.
A1  - Lees,A.J.
Y1  - 2002/04//
N1  - UI - 21909247
SP  - 861
EP  - 870
JF  - Brain
VL  - 125
IS  - Pt 4
N2  - We have reviewed the clinical and pathological diagnoses of 143 cases of parkinsonism seen by neurologists associated with the movement disorders service at The National Hospital for Neurology and Neurosurgery in London who came to neuropathological examination at the United Kingdom Parkinson's Disease Society Brain Research Centre, over a 10-year period between 1990 and the end of 1999. Seventy-three (47 male, 26 female) cases were diagnosed as having idiopathic Parkinson's disease (IPD) and 70 (42 male, 28 female) as having another parkinsonian syndrome. The positive predictive value of the clinical diagnosis for the whole group was 85.3%, with 122 cases correctly clinically diagnosed. The positive predictive value of the clinical diagnosis of IPD was extremely high, at 98.6% (72 out of 73), while for the other parkinsonian syndromes it was 71.4% (50 out of 70). The positive predictive values of a clinical diagnosis of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) were 85.7 (30 out of 35) and 80% (16 out of 20), respectively. The sensitivity for IPD was 91.1%, due to seven false-negative cases, with 72 of the 79 pathologically established cases being diagnosed in life. For MSA, the sensitivity was 88.2% (30 out of 34), and for PSP it was 84.2% (16 out of 19). The diagnostic accuracy for IPD, MSA and PSP was higher than most previous prospective clinicopathological series and studies using the retrospective application of clinical diagnostic criteria. The seven false-negative cases of IPD suggest a broader clinical picture of disease than previously thought acceptable. This study implies that neurologists with particular expertise in the field of movement disorders may be using a method of pattern recognition for diagnosis which goes beyond that inherent in any formal set of diagnostic criteria
AD  - The United Kingdom Parkinson's Disease Society Brain Research Centre, Institute of Neurology, London, Department of Social Medicine, University of Bristol, Bristol, UK and Neurology Department, Austin and Repatriation Medical Centre, Melbourne, Australia
UR  - PM:11912118
ER  - 

TY  - JOUR
T1  - Activation of Thalamo - Cortical Systems in Post-Traumatic Flashbacks: A Positron Emission Tomography Study
A1  - Huber,M.
A1  - Siol,T.
A1  - Herholz,K.
A1  - Lenz,O.
A1  - Khle,K.
A1  - Heiss,W.-D.
Y1  - 2001///
SP  - 131
EP  - 141
JF  - Traumatology
VL  - 7
IS  - 4
N2  - Trauma victims with post-traumatic stress disorder (PTSD) often experience 'flashbacks' that are described as being different from memories of other fearful biographic situations. We used Positron Emission Tomography and Statistical Parametric Mapping to compare in the same subject brain activation patterns during induced flashbacks with recall of fearful non-traumatic situations. During fearful recall there were significant activations of right precuneus. When traumatic memories were compared to neutral, right lingual gyrus, right thalamus / mamillary bodies, and right cerebellum were significantly activated. When brain activation during flashbacks was compared to simple fear, right mediodorsal thalamus (MD), right precuneus, and right cerebellum were significantly more active. With respect to recent experimental evidence concerning the function of thalamo-cortical systems, we hypothesize that post-traumatic flashback experiences are based on hyperactive thalamo-cortical 'closed loop' networks. 
UR  - http://www.fsu.edu/~trauma/v7/Activation.pdf
ER  - 

TY  - JOUR
T1  - Dopaminergic function and dopamine transporter binding assessed with positron emission tomography in Parkinson disease
A1  - Ribeiro,M.J.
A1  - Vidailhet,M.
A1  - Loc'h,C.
A1  - Dupel,C.
A1  - Nguyen,J.P.
A1  - Ponchant,M.
A1  - Dolle,F.
A1  - Peschanski,M.
A1  - Hantraye,P.
A1  - Cesaro,P.
A1  - Samson,Y.
A1  - Remy,P.
Y1  - 2002/04//
N1  - UI - 21937706
SP  - 580
EP  - 586
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 59
IS  - 4
N2  - BACKGROUND: Measuring progression of Parkinson disease (PD) using positron emission tomography may help demonstrate the efficacy of neuroprotective treatments. To date, (18)F-dopa has been the gold standard to measure presynaptic dopaminergic function in PD, but this tracer might overestimate the rate of neuronal death in PD because its uptake also depends on dopamine turnover rather than exclusively on the density of dopaminergic terminals in the striatum. The latter might be assessed using newly developed ligands of the membrane dopamine transporter. OBJECTIVE: To compare the striatal uptakes of (18)F-dopa and (76)Br-FE-CBT, a dopamine transporter ligand, in patients with PD. PATIENTS AND METHODS: The striatal uptakes of (76)Br-FE-CBT and (18)F-dopa were compared using positron emission tomography in 10 patients with early PD and 8 with advanced PD. Correlation of uptakes with motor performance was investigated. RESULTS: The reduction in (76)Br-FE-CBT binding to 43% of control values was more severe than the reduction in (18)F-dopa uptake (63% of control values) in the putamen of patients with early PD. No significant difference was found between either tracer's uptake in the putamen of patients with advanced PD. Motor performance was highly correlated to (18)F-dopa uptake, whereas correlation to (76)Br-FE-CBT binding was weak. CONCLUSIONS: Uptake of (18)F-dopa may be up-regulated in early PD, suggesting a compensatory increase of dopamine synthesis in surviving dopaminergic terminals. Positron emission tomography dopamine transporter ligands and (18)F-dopa give complementary information on the presynaptic status of the nigrostriatal dopaminergic system and might be associated to investigate the efficacy of neuroprotective treatments in PD
AD  - URA CEA-CNRS 2210, Service Hospitalier Frederic Joliot, 4, place du General Leclerc, 91401 Orsay, CEDEX, France. remy@shfj.cea.fr
UR  - PM:11939892
ER  - 

TY  - JOUR
T1  - When is positron emission tomography really necessary in epilepsy diagnosis?
A1  - Theodore,W.H.
Y1  - 2002/04//
N1  - UI - 21920594
SP  - 191
EP  - 195
JA  - Curr.Opin.Neurol.
VL  - 15
IS  - 2
N2  - Positron emission tomography can be used for localization of epileptic foci, and preoperative functional mapping. Rapid improvements in magnetic resonance imaging, however, have restricted the need for positron emission tomography to a minority of patients who have unrevealing magnetic resonance imaging scans. Positron emission tomography will continue to be of value in investigations of the pathophysiology of seizure disorders
AD  - Clinical Epilepsy Section, National Institutes of Health, Bethesda, Maryland, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Theodore-PET-Epilepsy.pdf
ER  - 

TY  - JOUR
T1  - Different pattern of decreased cortical acetylcholine esterase in Alzheimer's and Parkinson's disease: A PET study
A1  - Weisenbach,S.
A1  - Hilker,R.
A1  - Herholz,K.
A1  - Kalbe,E.
A1  - Zndorf,G.
A1  - Bauer,B.
A1  - Heiss,W.D.
Y1  - 2002///
SP  - A144
JF  - Neurology
VL  - 58 (Suppl. 3)
ER  - 

TY  - JOUR
T1  - Limitations of stereotactic biopsy in the initial management of gliomas
A1  - Jackson,R.J.
A1  - Fuller,G.N.
A1  - Abi-Said,D.
A1  - Lang,F.F.
A1  - Gokaslan,Z.L.
A1  - Shi,W.M.
A1  - Wildrick,D.M.
A1  - Sawaya,R.
Y1  - 2001/07//
N1  - UI - 21357927
SP  - 193
EP  - 200
JA  - Neuro.-oncol.
VL  - 3
IS  - 3
N2  - Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. At The University of Texas M. D. Anderson Cancer Center, we retrospectively reviewed a consecutive series of 81 patients whose imaging studies suggested glioma and who underwent stereotactic biopsy followed by craniotomy/resection (within 60 days) between 1993 and 1998. All relevant clinical and imaging information was reviewed, including computerized volumetric analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy was performed at institutions other than M. D. Anderson in 78 (96%) of 81 patients. The majority of tumors were located either in eloquent brain (36 of 81 = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the rationale cited for performing stereotactic biopsy. Gross total resection (>95%) was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96% for this series. Diagnoses based on biopsy or resection in the same patient differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80 cases when the biopsy slides were reviewed preoperatively by each of three neuropathologists at M. D. Anderson. Major neurologic complications occurred in 10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy. Surgical morbidity was probably higher in our series than it would be for glioma patients in general because our patients represent a highly selected subset of glioma patients whose tumors present a technical challenge to remove. Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and is associated with additional risk and cost. If stereotactic biopsy is performed, expert neuropathology consultation should be sought
AD  - Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA
UR  - PM:11465400
ER  - 

TY  - JOUR
T1  - The value of F-18-fluorodeoxyglucose PET for the 3-D radiation treatment planning of malignant gliomas
A1  - Gross,M.W.
A1  - Weber,W.A.
A1  - Feldmann,H.J.
A1  - Bartenstein,P.
A1  - Schwaiger,M.
A1  - Molls,M.
Y1  - 1998/07/15/
N1  - UI - 98383589
SP  - 989
EP  - 995
JA  - Int.J Radiat.Oncol.Biol.Phys.
VL  - 41
IS  - 5
N2  - PURPOSE: The aim of the study was to determine the impact of positron emission tomography using the glucose analogue fluorine-18-fluorodeoxyglucose (FDG-PET) on the delineation of the target volume in three-dimensional radiation treatment planning of primary brain tumors. METHODS AND MATERIALS: In 18 patients with histologically proven (8x biopsy, 10x subtotal resection) primary brain tumors (8 astrocytomas grade III, one mixed glioma grade III, and 9 glioblastomas), magnetic resonance imaging (MRI) with gadolinium-DTPA and FDG-PET were performed in radiation treatment position within the same week. A computer program was developed for fusion of the PET and MR images. On corresponding axial slices, FDG uptake was compared to contrast enhancement in T1-weighted and to signal hyperintensity in T2-weighted MR images. Based on PET and MRI data, three-dimensional treatment planning was performed. All patients underwent linear accelerator (LINAC) radiotherapy. RESULTS: In MRI, all tumors and the surrounding edema were visible as hyperintense lesions in the T2-weighted images. 17/18 tumors showed contrast enhancement. In FDG-PET, 16 tumors showed hypermetabolism compared to normal white matter, whereas only 8/18 tumors showed hypermetabolism compared to normal gray matter. White matter edema was associated with decreased FDG uptake in all patients. The area of increased FDG uptake correlated closely with contrast enhancement, only in one case the volume of increased FDG uptake was larger than the area of contrast enhancement. Mean tumor volumes obtained by MRI T1 + Gd, T2, and PET were 30, 106, and 10 ml, respectively. Survival was comparable to data in the literature with a 1-year survival of 39% and a median survival of 310 days. CONCLUSION: Only in a minority of patients did FDG-PET provide additional information for radiation treatment planning. This is mainly caused by the high intensity of FDG uptake in normal brain tissue. PET may be of greater value in the definition of regions that should obtain a radiation dose boost
AD  - Klinik und Poliklinik fur Strahlentherapie und Radiologische Onkologie, Technische Universitat Munchen, Germany
UR  - PM:9719107
ER  - 

TY  - JOUR
T1  - Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET
A1  - Chung,J.K.
A1  - Kim,Y.K.
A1  - Kim,S.K.
A1  - Lee,Y.J.
A1  - Paek,S.
A1  - Yeo,J.S.
A1  - Jeong,J.M.
A1  - Lee,D.S.
A1  - Jung,H.W.
A1  - Lee,M.C.
Y1  - 2002/02//
N1  - UI - 21923324
SP  - 176
EP  - 182
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 29
IS  - 2
N2  - The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients
AD  - Department of Nuclear Medicine, Seoul National University Hospital, Korea. jkchung@plaza.snu.ac.kr
UR  - PM:11926379
ER  - 

TY  - JOUR
T1  - Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach
A1  - Bankiewicz,K.S.
A1  - Eberling,J.L.
A1  - Kohutnicka,M.
A1  - Jagust,W.
A1  - Pivirotto,P.
A1  - Bringas,J.
A1  - Cunningham,J.
A1  - Budinger,T.F.
A1  - Harvey-White,J.
Y1  - 2000/07//
SP  - 2
EP  - 14
JA  - Exp.Neurol.
VL  - 164
IS  - 1
N2  - Using an approach that combines gene therapy with aromatic l-amino acid decarboxylase (AADC) gene and a pro-drug (l-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral l-dopa to dopamine and may therefore provide a buffer for unmetabolized l-dopa. This approach to treating Parkinson's disease may reduce the need for l-dopa/carbidopa, thus providing a better clinical response with fewer side effects. In addition, the imbalance in dopamine production between the nigrostriatal and mesolimbic dopaminergic systems can be corrected by using AADC gene delivery to the striatum. We have also demonstrated that a fundamental obstacle in the gene therapy approach to the central nervous system, i.e., the ability to deliver viral vectors in sufficient quantities to the whole brain, can be overcome by using convection-enhanced delivery. Finally, this study demonstrates that positron emission tomography and the AADC tracer, 6-[(18)F]fluoro-l-m-tyrosine, can be used to monitor gene therapy in vivo. Our therapeutic approach has the potential to restore dopamine production, even late in the disease process, at levels that can be maintained during continued nigrostriatal degeneration
AD  - Molecular Therapeutics Section, LMMN, NINDS, Bethesda, Maryland 20892, USA
UR  - PM:10877910
ER  - 

TY  - JOUR
T1  - Decreased presynaptic dopamine function in the left caudate of depressed patients with affective flattening and psychomotor retardation
A1  - Martinot,M.
A1  - Bragulat,V.
A1  - Artiges,E.
A1  - Dolle,F.
A1  - Hinnen,F.
A1  - Jouvent,R.
A1  - Martinot,J.
Y1  - 2001/02//
N1  - UI - 21090874
SP  - 314
EP  - 316
JA  - Am.J Psychiatry
VL  - 158
IS  - 2
N2  - OBJECTIVE: The study assessed striatal presynaptic dopamine function in patients with different subtypes of depression. METHOD: Magnetic resonance imaging and positron emission tomography with [(18)F]fluorodopa ([(18)F]DOPA) were used to compare six depressed patients with marked affective flattening and psychomotor retardation, six depressed patients with marked impulsivity and anxiety, and 10 healthy comparison subjects. Depressed patient groups were matched for severity of depression. RESULTS: [(18)F]DOPA uptake K(i) values in the left caudate were significantly lower in patients with psychomotor retardation than in patients with high impulsivity and in comparison subjects. CONCLUSIONS: These results suggest that left caudate dopamine function differs between depressed patients with psychomotor retardation and those with impulsivity and provide direct evidence of a link between dopamine hypofunction and psychomotor retardation in depression
AD  - Service de Psychiatrie Hopital de la Salpetriere, Paris, France. ml.paillere@psl.ap-hop-paris.fr
UR  - PM:11156819
ER  - 

TY  - JOUR
T1  - Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies
A1  - Alexander,G.E.
A1  - Chen,K.
A1  - Pietrini,P.
A1  - Rapoport,S.I.
A1  - Reiman,E.M.
Y1  - 2002/05//
N1  - UI - 21981597
SP  - 738
EP  - 745
JA  - Am.J Psychiatry
VL  - 159
IS  - 5
N2  - OBJECTIVE: It is well established that regional cerebral metabolic rates for glucose assessed by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with Alzheimer's disease in the mental resting state (eyes and ears covered) provide a sensitive, in vivo metabolic index of Alzheimer's disease dementia. Few studies, however, have evaluated longitudinal declines in regional cerebral glucose metabolism in patients with dementia caused by Alzheimer's disease. In addition, the available studies have not used recently developed brain mapping algorithms to characterize the progression of Alzheimer's disease throughout the brain, and none considered the statistical power of regional cerebral glucose metabolism in testing the ability of treatments to attenuate the progression of dementia. METHOD: The authors used FDG PET and a brain mapping algorithm to investigate cross-sectional reductions in regional cerebral glucose metabolism, longitudinal decline in regional cerebral glucose metabolism after a 1-year follow-up, and the power of this method to evaluate treatments for Alzheimer's disease in patients with mild to moderate dementia. PET scans were initially acquired in 14 patients with Alzheimer's disease and 34 healthy comparison subjects of similar age and sex. Repeat scans were obtained in the patients 1 year later. Power analyses for voxels showing maximal decline over the 1-year period in regional cerebral glucose metabolism (mg/100 g per minute) were computed to estimate the sample sizes needed to detect a significant treatment response in a 1-year, double-blind, placebo-controlled treatment study. RESULTS: The patients with Alzheimer's disease had significantly lower glucose metabolism than healthy comparison subjects in parietal, temporal, occipital, frontal, and posterior cingulate cortices. One year later, the patients with Alzheimer's disease had significant declines in glucose metabolism in parietal, temporal, frontal, and posterior cingulate cortices. Using maximal glucose metabolism reductions in the left frontal cortex, we estimated that as few as 36 patients per group would be needed to detect a 33% treatment response with one-tailed significance of p</=0.005 and 80% power in a 1-year, double-blind, placebo-controlled treatment study. CONCLUSIONS: These findings indicate that brain metabolism as assessed by FDG PET during mental rest is a sensitive marker of disease progression in Alzheimer's disease over a 1-year period. These findings also support the feasibility of using FDG PET as an outcome measure to test the ability of treatments to attenuate the progression of Alzheimer's disease
UR  - PM:11986126
ER  - 

TY  - JOUR
T1  - Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus
A1  - Strafella,A.P.
A1  - Paus,T.
A1  - Barrett,J.
A1  - Dagher,A.
Y1  - 2001/08/01/
N1  - UI - 21359653
SP  - 1
EP  - 4
JA  - J Neurosci.
VL  - 21: RC157
IS  - 15
N2  - Dopamine is implicated in movement, learning, and motivation, and in illnesses such as Parkinson's disease, schizophrenia, and drug addiction. Little is known about the control of dopamine release in humans, but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures. Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in healthy human subjects. Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal caudate nucleus compared with rTMS of the left occipital cortex. There were no changes in binding in the putamen, nucleus accumbens, or right caudate. This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral caudate nucleus. This finding has implications for the therapeutic and research use of rTMS in neurological and psychiatric disorders
AD  - Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4. antonio@bic.mni.mcgill.ca
UR  - PM:11459878
ER  - 

TY  - JOUR
T1  - Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain
A1  - Schiff,N.D.
A1  - Ribary,U.
A1  - Moreno,D.R.
A1  - Beattie,B.
A1  - Kronberg,E.
A1  - Blasberg,R.
A1  - Giacino,J.
A1  - McCagg,C.
A1  - Fins,J.J.
A1  - Llinas,R.
A1  - Plum,F.
Y1  - 2002/06//
N1  - UI - 0
SP  - 1210
EP  - 1234
JF  - Brain
VL  - 125
IS  - Pt 6
N2  - This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains
AD  - Departments of Neurology and Neuroscience, Medicine and Psychiatry, Weill Medical College of Cornell University, Center for Neuromagnetism, Department of Physiology and Neuroscience, New York University School of Medicine, Memorial Sloan Kettering Cancer Center, Department of Neurology, New York, JFK Medical Center, JFK Johnson Rehabilitation Institute, Center for Head Injuries, Edison, New Jersey, USA
UR  - PM:12023311
ER  - 

TY  - JOUR
T1  - Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[(18)F]fluoro-L-dopa PET study
A1  - Ito,K.
A1  - Nagano-Saito,A.
A1  - Kato,T.
A1  - Arahata,Y.
A1  - Nakamura,A.
A1  - Kawasumi,Y.
A1  - Hatano,K.
A1  - Abe,Y.
A1  - Yamada,T.
A1  - Kachi,T.
A1  - Brooks,D.J.
Y1  - 2002/06//
N1  - UI - 0
SP  - 1358
EP  - 1365
JF  - Brain
VL  - 125
IS  - Pt 6
N2  - We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[(18)F]fluoro-L-dopa ((18)F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. (18)F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the (18)F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Com pared with the normal group, the PDD group showed reduced (18)F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in (18)F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function
AD  - Department of Biofunctional Research, National Institute for Longevity Sciences and Department of Neurology, Chubu National Hospital, Obu, Japan, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London and Institute of Neurology, Queen Square, London, UK
UR  - PM:12023324
ER  - 

TY  - JOUR
T1  - The neuronal channelopathies
A1  - Kullmann,D.M.
Y1  - 2002/06//
N1  - UI - 22017786
SP  - 1177
EP  - 1195
JF  - Brain
VL  - 125
IS  - Pt 6
N2  - This review addresses the molecular and cellular mechanisms of diseases caused by inherited mutations of ion channels in neurones. Among important recent advances is the elucidation of several dominantly inherited epilepsies caused by mutations of both voltage-gated and ligand-gated ion channels. The neuronal channelopathies show evidence of phenotypic convergence; notably, episodic ataxia can be caused by mutations of either calcium or potassium channels. The channelopathies also show evidence of phenotypic divergence; for instance, different mutations of the same calcium channel gene are associated with familial hemiplegic migraine, episodic or progressive ataxia, coma and epilepsy. Future developments are likely to include the discovery of other ion channel genes associated with inherited and sporadic CNS disorders. The full range of manifestations of inherited ion channel mutations remains to be established
AD  - Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
UR  - PM:12023309
ER  - 

TY  - JOUR
T1  - Pathological changes in the nucleus basalis of Meynert in Alzheimer's and Parkinson's disease
A1  - Candy,J.M.
A1  - Perry,R.H.
A1  - Perry,E.K.
A1  - Irving,D.
A1  - Blessed,G.
A1  - Fairbairn,A.F.
A1  - Tomlinson,B.E.
Y1  - 1983///
SP  - 277
EP  - 289
JA  - J Neurol.Sci.
VL  - 59
ER  - 

TY  - JOUR
T1  - Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study
A1  - Ouchi,Y.
A1  - Yoshikawa,E.
A1  - Futatsubashi,M.
A1  - Okada,H.
A1  - Torizuka,T.
A1  - Sakamoto,M.
Y1  - 2002/06//
N1  - UI - 22040517
SP  - 746
EP  - 752
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 6
N2  - SUMMARY: To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD
AD  - Positron Medical Center, Department of Neurology, Hamamatsu Medical Center, Hamamatsu, and Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan
UR  - PM:12045673
ER  - 

TY  - ABST
T1  - Individual classification of Alzheimer's disease and depression by linear subspace analysis of FDG PET
A1  - Zndorf,G.
A1  - Holthoff,V.
A1  - Kerrouche,N.
A1  - Beuthien-Baumann,B.
A1  - Herholz,K.
Y1  - 2002///
SP  - 741
JF  - Human Brain Mapping 2002 Meeting
ER  - 

TY  - JOUR
T1  - The problem of functional localization in the human brain
A1  - Brett,M.
A1  - Johnsrude,I.S.
A1  - Owen,A.M.
Y1  - 2002/03//
N1  - UI - 21990458
SP  - 243
EP  - 249
JA  - Nat.Rev.Neurosci.
VL  - 3
IS  - 3
N2  - Functional imaging gives us increasingly detailed information about the location of brain activity. To use this information, we need a clear conception of the meaning of location data. Here, we review methods for reporting location in functional imaging and discuss the problems that arise from the great variability in brain anatomy between individuals. These problems cause uncertainty in localization, which limits the effective resolution of functional imaging, especially for brain areas involved in higher cognitive function
AD  - MRC Cognition and Brain Sciences Unit, Cambridge, UK. matthew.brett@mrc- cbu.cam.ac.uk
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Brett-Localization-Review.pdf
ER  - 

TY  - JOUR
T1  - Implementation and application of a brain template for multiple volumes of interest
A1  - Hammers,A.
A1  - Koepp,M.J.
A1  - Free,S.L.
A1  - Brett,M.
A1  - Richardson,M.P.
A1  - Labbe,C.
A1  - Cunningham,V.J.
A1  - Brooks,D.J.
A1  - Duncan,J.
Y1  - 2002/03//
N1  - UI - 21823852
SP  - 165
EP  - 174
JA  - Hum.Brain Mapp.
VL  - 15
IS  - 3
N2  - We present a region template and a protocol for transforming that template to define anatomical volumes of interest (VOIs) in the human brain without operator intervention, based on software contained in the SPM99 package (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK). We used an MRI of a reference brain to create an anatomical template of 41 VOIs, covering the entire brain, that can be spatially transformed to fit individual brain scans. Modified software allows for the reslicing and adaptation of the transformed template to any type of coregistered functional data. Individually defined VOIs can be added. We present an assessment of the necessary spatial transformations and compare results obtained for scans acquired in two different orientations. To evaluate the spatial transformations, 11 landmarks distributed throughout the brain were chosen. Euclidean distances between repeat samples at each landmark were averaged across all landmarks to give a mean difference of 1.3 plus minus 1.0 mm. Average Euclidean distances between landmarks (MRI:transformed template) were 8.1 plus minus 3.7 mm in anterior- posterior commissure (ACPC) and 7.6 plus minus 3.7 mm in temporal lobe (TL) orientation. In this study, we use [(11)C]-flumazenil-(FMZ-)PET as an example for the application of the region template. Thirty-four healthy volunteers were scanned, 21 in standard ACPC orientation, 13 in TL orientation. All had high resolution MRI and FMZ-PET. The average coefficient of variation (CV) of FMZ binding for cortical regions was 0.15, comparable with CVs from manually defined VOIs. FMZ binding was significantly different in 6/19 anatomical areas in the control groups obtained in the different orientations, probably due to anisotropic voxel dimensions. This new template allows for the reliable and fast definition of multiple VOIs. It can be used for different imaging modalities and in different orientations. It is necessary that imaging data for groups compared are acquired in the same orientation
AD  - Neuroscience Group of the Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, United Kingdom
UR  - PM:11835607
ER  - 

TY  - JOUR
T1  - Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography
A1  - Hartvig,P.
A1  - Nordberg,A.
A1  - Torstenson,R.
A1  - Sjoberg,P.
A1  - Fasth,K.J.
A1  - Langstrom,B.
Y1  - 2002///
N1  - UI - 22001107
SP  - 199
EP  - 204
JA  - Dement.Geriatr.Cogn Disord.
VL  - 13
IS  - 4
N2  - The effects on the binding to cholinergic and dopaminergic receptors in the brain during continuous intravenous infusion of the muscarinic cholinergic receptor agonist milameline (CI-979) were studied in the rhesus monkey by means of positron emission tomography. Binding to milameline cholinergic receptors was quantified using the muscarinic receptor antagonist [(11)C]-N-methyl-4-piperidinylbenzilate ([(11)C]NMP), and the effects on nicotine receptor binding were measured with (S)-[(11)C-methyl]nicotine. Changes in the binding of the D(2) dopamine receptor antagonist [(11)C]raclopride were measured as well. The binding of [(11)C]NMP increased in most brain regions with the infusion of increasing doses of milameline from 0.5 to 10 microg/kg/h. (S)-[(11)C-methyl]nicotine binding was unchanged or increased somewhat. Binding of [(11)C]raclopride to the D(2) dopaminergic receptors in the striatum of the brain increased by 10 +/- 4% following 2 microg/kg/h of milameline. The results suggest a possible action of milameline both on presynaptic muscarinic receptor subtypes as well as dopamine levels dependent on the receptor reserve of the muscarinic receptor subtypes
AD  - Uppsala University PET Centre and Hospital Pharmacy, University Hospital, University of Uppsala, Huddinge, Sweden. per.hartvig@pet.uu.se
UR  - PM:12006729
ER  - 

TY  - JOUR
T1  - Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment
A1  - Arnaiz,E.
A1  - Jelic,V.
A1  - Almkvist,O.
A1  - Wahlund,L.O.
A1  - Winblad,B.
A1  - Valind,S.
A1  - Nordberg,A.
Y1  - 2001/03/26/
N1  - UI - 21171194
SP  - 851
EP  - 855
JF  - Neuroreport
VL  - 12
IS  - 4
N2  - The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy, and Elderly Care Research (NEUROTEC), Huddinge University Hospital, Sweden
UR  - PM:11277595
ER  - 

TY  - JOUR
T1  - Ligands for in vivo imaging of nicotinic receptor subtypes in Alzheimer brain
A1  - Sihver,W.
A1  - Langstrom,B.
A1  - Nordberg,A.
Y1  - 2000///
SP  - 27
EP  - 33
JA  - Acta Neurol.Scand.Suppl
VL  - 176
N2  - The neuronal nicotinic acetylcholine receptors (nAChR) are involved in functional processes in brain including cognitive function and memory. A severe loss of the nAChRs has been detected in brain of patients with Alzheimer's disease (AD). There is a great interest to image nAChRs noninvasive for detection of receptor impairments even at a presymptomatic stage of AD as well for monitoring outcome of drug treatment. (S) [11C]Nicotine, has so far been the only nAChR ligand used in positron emission tomography (PET) studies for visualizing nAChRs in human brain. In order to develop PET/SPECT nAChRs ligands for detection of subtypes of nAChRs nicotine analogues, epibatidine and A-85380 compounds have been characterized in vitro and investigated in vivo. Epibatidine and A-85380 have been found to have higher specific signals and more favorable kinetic parameters than nicotine and its analogues. The epibatidine and A-85380 compounds can also be radiolabeled with high specific radioactivity, show affinities for the nAChRs in the pM range and readily cross the blood-brain barrier. In addition they reversibly bind to the nAChRs and show low non-specific binding and moderately fast metabolism. Due to a probably high alpha4beta2 nAChR selectivity combined with low toxicity, the A-85380 analogs presently seem to be the most promising nAChR ligand imaging of subtypes of nAChRs in human brain
AD  - PET-Center/Institute of Chemistry, Uppsala University, Sweden
UR  - PM:11261802
ER  - 

TY  - JOUR
T1  - Noninvasive, repetitive, quantitative measurement of gene expression from a bicistronic message by positron emission tomography, following gene transfer with adenovirus
A1  - Liang,Q.
A1  - Gotts,J.
A1  - Satyamurthy,N.
A1  - Barrio,J.
A1  - Phelps,M.E.
A1  - Gambhir,S.S.
A1  - Herschman,H.R.
Y1  - 2002/07//
N1  - UI - 22091001
SP  - 73
EP  - 82
JA  - Mol.Ther.
VL  - 6
IS  - 1
N2  - Gene therapy protocols are hampered by the inability to monitor the location, magnitude, and duration of ectopic gene expression following DNA delivery. Consequently, it is difficult to establish quantitative correlations and/or causal relationships between therapeutic gene expression and phenotypic responses in treated individuals. One approach to monitor "therapeutic gene" expression indirectly is to incorporate reporter genes that can be imaged in vivo into bicistronic transcription units, along with the therapeutic genes. Expression of the dopamine D2 receptor (D2R) and herpes simplex virus thymidine kinase (HSV1-TK) can both be monitored, in vivo, by positron-emission tomography (PET). We created ad.DTm, an adenovirus containing a cytomegalovirus (CMV) early promoter-driven transcription unit, in which the D2R gene is placed proximal to an encephalomyocarditis virus internal ribosomal entry site (IRES) and a modified HSV1-tk gene is placed distal to the IRES. Following intravenous ad.DTm injection into mice, correlated hepatic D2R and HSV1-sr39tk PET reporter gene expression was demonstrated. Repeated microPET scanning quantitated both D2R-dependent sequestration of a positron-emitting ligand and HSV1- TK-dependent sequestration of a positron-emitting product. It is possible, in living mice, to investigate noninvasively and to measure quantitatively and repeatedly correlated expression of two coding regions from a bicistronic transcription unit over a 3-month period following adenovirus delivery. (c)2002 Elsevier Science (USA)
AD  - The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, California, 90095, USA
UR  - PM:12095306
ER  - 

TY  - JOUR
T1  - Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma
A1  - Basso,U.
A1  - Brandes,A.A.
Y1  - 2002/07//
N1  - UI - 22085968
SP  - 1298
EP  - 1312
JA  - Eur.J Cancer
VL  - 38
IS  - 10
N2  - Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma arising in the brain. Recent increase in its incidence has been noted both in immunocompetent individuals and patients with immunodeficiency. This review will focus on the epidemiology, pathogenesis, diagnosis and treatment of this aggressive extranodal lymphoma in immunocompetent patients. Stereotactic biopsy is usually required for diagnosis, while molecular biology and/or cytofluorimetric analysis may confirm the presence of clonal proliferation in the cerebrospinal fluid (CSF). Methotrexate-based chemotherapy plus whole- brain radiotherapy are the standard treatment for PCNSL and achieve a high rate of complete remissions (CR), but long-term neurotoxicity may heavily compromise the patient's quality of life. The metabolic rate of controversial gadolinium-enhancing lesions on magnetic resonance (MR) scans may be assessed with positron emission tomography (PET), which discriminates radiation necrosis from true recurrence. Withholding radiotherapy in patients achieving CR after first-line chemotherapy is a new and interesting treatment option, while the role of high-dose chemotherapy with stem cell rescue is still uncertain
AD  - Department of Medical Oncology, Azienda Ospedale-Universita, Via Giustiniani 2, 35100, Padova, Italy
UR  - PM:12091059
ER  - 

TY  - JOUR
T1  - In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography
A1  - Wilson,A.A.
A1  - Ginovart,N.
A1  - Hussey,D.
A1  - Meyer,J.
A1  - Houle,S.
Y1  - 2002/07//
N1  - UI - 22084412
SP  - 509
EP  - 515
JA  - Nucl Med Biol.
VL  - 29
IS  - 5
N2  - 3-Amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, labeled with carbon-11 ([11C]-DASB), is a recently introduced radiotracer for imaging the serotonin transporter (SERT) by positron emission tomography (PET). A series of in vitro and in vivo experiments were performed to further characterise the properties of [11C]-DASB as an in vivo imaging agent for SERT. In vitro binding assays confirmed that DASB binds specifically to SERT with nanomolar affinity and high selectivity over a large number of other receptors, ion-channels and enzymes in the central nervous system. Ex vivo, [11C]-DASB binding in rat brain was shown to be saturable (ED(50) of 56 nmoles/kg), and sensitive to both the number of available SERT binding sites and the number of viable serotonin neurons. Estimates of the radiation dose in man were extrapolated from rat biodistribution data (effective dose 5.5 E-03 mSv/MBq; critical organ -urinary bladder wall). Together with previous studies, the present findings indicate that [11C]-DASB is a very useful radiopharmaceutical for probing changes in SERT densities using PET imaging in the living human brain
AD  - PET Centre, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, M5T 1R8, Toronto, Ontario, Canada
UR  - PM:12088720
ER  - 

TY  - JOUR
T1  - Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652
A1  - Ichimiya,T.
A1  - Suhara,T.
A1  - Sudo,Y.
A1  - Okubo,Y.
A1  - Nakayama,K.
A1  - Nankai,M.
A1  - Inoue,M.
A1  - Yasuno,F.
A1  - Takano,A.
A1  - Maeda,J.
A1  - Shibuya,H.
Y1  - 2002/05/01/
N1  - UI - 21978836
SP  - 715
EP  - 722
JA  - Biol.Psychiatry
VL  - 51
IS  - 9
N2  - Background: Several lines of studies have suggested the involvement of serotonin transporter (5-HTT) in the pathophysiology of mood disorders. The aim of this study was to examine whether 5-HTT binding was altered in patients with mood disorders using positron emission tomography (PET).Methods: Thirteen antidepressant-naive or -free patients with mood disorders and 21 age-matched healthy control subjects participated in this study. The patients consisted of 7 with major depressive disorder (MDD) and 6 with bipolar disorder (BD). Positron emission tomography scans were performed using a selective ligand for 5-HTT, [11C](+)McN5652. The uptake was quantified in the thalamus and midbrain by graphical method with reference tissue, and binding potential (BP) was used for the index of 5-HTT binding.Results: Binding potential in the thalamus was significantly increased in patients with mood disorders as compared to control subjects, whereas BP in the midbrain did not differ between the groups. Subgroup comparison showed that MDD patients had significantly higher BP in the thalamus compared to control subjects. Binding potential of the thalamus was higher by approximately 22% in the combined patients and 23% in MDD patients relative to control subjects.Conclusions: These findings may suggest the possibility of altered 5-HTT in patients with mood disorders. Functional abnormality in the thalamus may be involved in the pathophysiology of mood disorders
AD  - Brain Imaging Project, National Institute of Radiological Sciences, (TI, TS, YS, YO, MI, FY, AT, JM), Chiba, Japan
UR  - PM:11983185
ER  - 

TY  - JOUR
T1  - Potential significance of (11)C-methionine PET as a marker for the radiosensitivity of low-grade gliomas
A1  - Ribom,D.
A1  - Engler,H.
A1  - Blomquist,E.
A1  - Smits,A.
Y1  - 2002/05//
N1  - UI - 21972480
SP  - 632
EP  - 640
JA  - Eur.J Nucl Med
VL  - 29
IS  - 5
N2  - The role for radiotherapy in patients with low-grade gliomas remains controversial. Two large prospective studies have failed to demonstrate a radiotherapeutic dose-response effect, and EORTC trial 22845 found no difference in survival between patients receiving adjuvant radiotherapy and those who received radiotherapy at tumour progression. The aim of this retrospective study was to analyse the patterns of carbon-11 methionine (MET) uptake on positron emission tomography (PET) in tumours treated with immediate radiotherapy and in those treated with delayed radiotherapy at the time of tumour progression. The 21 adult patients studied had histologically confirmed low-grade gliomas and had undergone a pre-treatment PET scan and a follow-up PET scan at the time of progression. Eleven of the patients had undergone initial radiotherapy a median of 5 weeks after the surgical procedure. The median time to progression was 3.5 years for this group, compared with 1.6 years for the group with delayed radiotherapy ( P=0.06). At the time of progression, non-irradiated tumours had a significantly higher MET uptake ( P=0.02) and a larger uptake volume ( P=0.008) compared with baseline, whereas irradiated tumours showed no statistically significant change. We observed a correlation between high pre- treatment uptake of MET and reduction in MET uptake in response to radiotherapy ( P=0.008). All irradiated tumours recurred within the radiation field. In conclusion, our results demonstrate signs of a residual radiation effect at the time of tumour progression in low- grade gliomas with high pre-treatment uptake of MET. Pre-treatment methionine uptake may be a marker for the radiosensitivity of low-grade gliomas
AD  - Department of Neuroscience, Neurology, University Hospital, SE-751 85 Uppsala, Sweden, dan.ribom@neurologi.uu.se
UR  - PM:11976801
ER  - 

TY  - JOUR
T1  - Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC analyses
A1  - Meyer,P.T.
A1  - Schreckenberger,M.
A1  - Spetzger,U.
A1  - Meyer,G.F.
A1  - Sabri,O.
A1  - Setani,K.S.
A1  - Zeggel,T.
A1  - Buell,U.
Y1  - 2001/02//
N1  - UI - 21198867
SP  - 165
EP  - 174
JA  - Eur.J Nucl Med
VL  - 28
IS  - 2
N2  - Several studies have suggested that the use of simple visual interpretation criteria for the investigation of brain tumours by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG- PET) might be similarly or even more accurate than quantitative or semi- quantitative approaches. We investigated this hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a proposed six-step visual grading scale (VGS; applied by three independent observers unaware of the clinical history and the results of histopathology) and three different region of interest (ROI) ratios (maximal tumour uptake compared with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas of grade III-IV, 7 non-gliomatous tumours) tumours. The VGS results were highly correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (kappa=0.63, 0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of gliomatous and non-gliomatous lesions were not significantly different. For all measures, high-grade lesions showed significantly higher FDG uptake than low-grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal logistic regressions and receiver operating characteristic (ROC) analyses were used to calculate cut-off values to differentiate low- from high-grade lesions. The predicted (by ROC) diagnostic sensitivity/specificity of the different tests (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM: 0.93/0.80 (1.3). Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but >> WM). The VGS yielded the highest Az (+/-SE) value (i.e. area under the ROC curve as a measure of predicted accuracy), 0.97+/-0.03, which showed a strong tendency towards being significantly greater than the Az of Tu/Tis (0.88+/-0.06; P=0.06). Tu/GM (0.92+/-0.04) and Tu/WM (0.91+/-0.05) reached intermediate Az values (not significantly different from any other value). We conclude that the VGS represents a measure at least as accurate as the Tu/GM and Tu/WM ratios. The Tu/Tis ratio is less valid owing to the high dependence on the location of the lesion. Depending on the investigator's experience and the structure of the lesions, the easily used VGS might be the most favourable grading criterion
AD  - Department of Nuclear Medicine, Aachen University of Technology, Germany. philipptobias.meyer@post.rwth-aachen.de phillipptobias.meyer@post.rwth-aachen.de
UR  - PM:11303886
ER  - 

TY  - JOUR
T1  - The ECAT HRRT: performance and first clinical application of the new high resolution research tomograph
A1  - Wienhard,K.
A1  - Schmand,M.
A1  - Casey,M.E.
A1  - Baker,K.
A1  - Bao,J.
A1  - Eriksson,L.
A1  - Jones,W.F.
A1  - Knoess,C.
A1  - Lenox,M.
A1  - Lercher,M.
A1  - Luk,P.
A1  - Michel,C.
A1  - Reed,J.H.
A1  - Richerzhagen,N.
A1  - Treffert,J.
A1  - Vollmar,S.
A1  - Young,J.W.
A1  - Heiss,W.D.
A1  - Nutt,R.
Y1  - 2002///
SP  - 104
EP  - 110
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 1
ER  - 

TY  - JOUR
T1  - Functional reorganisation of memory after traumatic brain injury: a study with H2150 positron emission tomography
A1  - Levine,B.
A1  - Cabeza,R.
A1  - McIntosh,A.R.
A1  - Black,S.E.
A1  - Grady,C.L.
A1  - Stuss,D.T.
Y1  - 2002/08/01/
SP  - 173
EP  - 181
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 73
IS  - 2
N2  - Objective: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval. Methods: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H2150 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed. Results: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI. Conclusions: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes
UR  - http://jnnp.bmjjournals.com/cgi/content/abstract/73/2/173
ER  - 

TY  - JOUR
T1  - Reorganization of motor representation in a patient with epilepsia partialis continua as shown by [O15]-labeled butanol positron emission tomography and functional magnetic resonance imaging
A1  - Stoeckel,M.C.
A1  - Kleinschmidt,A.
A1  - Ebner,A.
A1  - Witte,O.W.
A1  - Seitz,R.J.
Y1  - 2002/07//
N1  - UI - 22112119
SP  - 276
EP  - 281
JA  - J Neuroimaging
VL  - 12
IS  - 3
N2  - The authors investigated a 38-year-old patient with focal cortical dysplasia in the right precentral cortex using positron emission tomography and functional magnetic resonance imaging to localize the hand and finger motor representations. The patient presented clinically with epilepsia partialis continua, supposed to originate from the perirolandic area harboring the cortical malformation. Both methods revealed an abnormal bilateral activation of motor cortex during left- hand finger movements. The results suggest that the so-called eloquent but nevertheless pathological dysplastic cortex accommodates motor representations
AD  - Department of Neurology, University Hospital Dusseldorf, Moorenstr. 5, 40225 Dusseldorf, Germany. stoeckco@uni-duesseldorf.de
UR  - PM:12116749
ER  - 

TY  - JOUR
T1  - Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4- methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography
A1  - Adonai,N.
A1  - Nguyen,K.N.
A1  - Walsh,J.
A1  - Iyer,M.
A1  - Toyokuni,T.
A1  - Phelps,M.E.
A1  - McCarthy,T.
A1  - McCarthy,D.W.
A1  - Gambhir,S.S.
Y1  - 2002/03/05/
N1  - UI - 21874130
SP  - 3030
EP  - 3035
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 99
IS  - 5
N2  - We have used copper-64-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-PTSM) to radiolabel cells ex vivo for in vivo positron-emission tomography (PET) imaging studies of cell trafficking in mice and for eventual application in patients. 2-[18F]-Fluoro-2-deoxy-D-glucose (FDG) cell labeling also was evaluated for comparison. 64Cu-PTSM uptake by C6 rat glioma (C6) cells increased for 180 min and then stabilized. The labeling efficiency was directly proportional to 64Cu-PTSM concentration and influenced negatively by serum. Label uptake per cell was greater with 64Cu-PTSM than with FDG. However, both 64Cu-PTSM- and FDG-labeled cells showed efflux of cell activity into supernatant. The 64Cu-PTSM labeling procedure did not interfere significantly with C6 cell viability and proliferation rate. MicroPET images of living mice indicate that tail-vein-injected labeled C6 cells traffic to the lungs and liver. In addition, transient splenic accumulation of radioactivity was clearly detectable in a mouse scanned at 3.33 h postinfusion of 64Cu-PTSM-labeled lymphocytes. In contrast, the liver was the principal organ of tracer localization after tail-vein administration of 64Cu-PTSM alone. These results indicate that in vivo imaging of cell trafficking is possible with 64Cu-PTSM-labeled cells. Given the longer t1/2 of 64Cu (12.7 h) relative to 18F (110 min), longer cell-tracking periods (up to 24-36 h) should be possible now with PET. 
AD  - The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA
UR  - PM:11867752
ER  - 

TY  - JOUR
T1  - Gender differences in cerebral glucose metabolism: a PET study
A1  - Kawachi,T.
A1  - Ishii,K.
A1  - Sakamoto,S.
A1  - Matsui,M.
A1  - Mori,T.
A1  - Sasaki,M.
Y1  - 2002/07/15/
N1  - UI - 22079907
SP  - 79
EP  - 83
JA  - J Neurol Sci.
VL  - 199
IS  - 1-2
N2  - OBJECTIVE: Some studies have examined gender differences in brain function based on cerebral blood flow and cerebral metabolism by using positron emission tomography (PET). However, the findings of these studies are controversial and most of them were analyzed by the regions of interest (ROIs) method. Here, we evaluated gender differences of cerebral glucose metabolism under the resting state in a voxel-based analysis. METHODS: We studied 44 healthy volunteers (22 females, 63.0+/- 6.3 years, and 22 males, 63.1+/-8.4 years). Cerebral glucose metabolic images were obtained with 18F-fluorodeoxyglucose (FDG) and PET. All individual data were transformed to standard brain space and the male and female groups were compared using statistical parametric mapping (SPM). RESULTS: The males had significantly higher glucose metabolism in the right insula, middle temporal gyrus, and medial frontal lobe than the females. Glucose metabolism in the hypothalamus was significantly higher in females than in males. There was a significant correlation between aging and glucose metabolism in the left thalamus in males and in the left caudate nucleus and hypothalamus in females. In males, but not females, there was a significant asymmetry between the bilateral hemispheres. CONCLUSION: We found that there were obvious gender differences in regional cerebral glucose metabolism and this is the first report of higher glucose metabolism in the hypothalamus in females than in males
AD  - Division of Imaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-Ko, Hyogo 670-0981, Himeji, Japan
UR  - PM:12084447
ER  - 

TY  - JOUR
T1  - Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration
A1  - Hosaka,K.
A1  - Ishii,K.
A1  - Sakamoto,S.
A1  - Mori,T.
A1  - Sasaki,M.
A1  - Hirono,N.
A1  - Mori,E.
Y1  - 2002/07/15/
N1  - UI - 22079905
SP  - 67
EP  - 71
JA  - J Neurol Sci.
VL  - 199
IS  - 1-2
N2  - OBJECTIVES: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. RESULTS: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). CONCLUSIONS: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments
AD  - Division of Imaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-Ko, Hyogo 670-0981, Himeji, Japan
UR  - PM:12084445
ER  - 

TY  - JOUR
T1  - Assessment and cost comparison of sleep-deprived EEG, MRI and PET in the prediction of surgical treatment for epilepsy
A1  - DellaBadia,J.,Jr.
A1  - Bell,W.L.
A1  - Keyes,J.W.,Jr.
A1  - Mathews,V.P.
A1  - Glazier,S.S.
Y1  - 2002/07//
N1  - UI - 22072754
SP  - 303
EP  - 309
JA  - Seizure.
VL  - 11
IS  - 5
N2  - Our aim was to determine if less expensive interictal indices can predict which epilepsy patients may benefit from the more expensive comprehensive pre-surgical evaluation. Surgical treatment was determined based on the results of a comprehensive inpatient continuous video-EEG monitoring. This evaluation included three interictal tests, which were reviewed retrospectively-2 hour-sleep-deprived electroencephalogram (SDEEG), magnetic resonance imaging (MRI), and positron emission tomography (PET). Sixty-nine patients were evaluated with 35 patients having focal resection (33 temporal, two frontal). When two or more interictal tests were positive, 77% (27 /35) went to surgery, but when one test was positive 23% (8 /34) had surgery. When all tests were negative, only a single patient (1 /13 or 7.7%) had surgery, a frontal resection. The positive predictive value for any single interictal test was 68%, while it was higher for any combination of two positive tests (77-83%). PET was the most sensitive (0.86) single interictal test, compared to SDEEG (0.66) and MRI (0.66). The odds ratio for predicting surgical treatment for a positive PET, SDEEG, or MRI was 8.57, 4.01, and 4.01, respectively. MRI was three and PET was six times the cost of a SDEEG. The combination of SDEEG and MRI had the best cost/PPV ratio. Seventy-nine percent (11 /14) of the patients with three positive tests were seizure free following focal resection compared to 43% (9 /21) when less than three tests were positive ( P</= 0.05). Interictal tests may predict which patients are most likely to benefit from comprehensive pre-surgical evaluation. Two or more positive tests are the most predictive. If all tests are negative, it is unlikely that the patient would qualify for surgical treatment. The combination of SDEEG and MRI may be more cost-effective as outpatient screening tools
AD  - Department of Neurology, Louisiana State University Health Science Center, School of Medicine in Shreveport, Shreveport, Louisiana, USA
UR  - PM:12076102
ER  - 

TY  - JOUR
T1  - Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats
A1  - Meissner,Wassilios
A1  - Harnack,Daniel
A1  - Paul,Gesine
A1  - Reum,Torsten
A1  - Sohr,Reinhard
A1  - Morgenstern,Rudolf
A1  - Kupsch,Andreas
Y1  - 2002/08/09/
SP  - 105
EP  - 108
JF  - Neuroscience Letters
VL  - 328
IS  - 2
N2  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates Parkinson's disease (PD) symptoms. Although widely used, the mechanisms of action are still unknown. In an attempt to elucidate those mechanisms, we have previously demonstrated that STN-DBS increases striatal extracellular dopamine (DA) metabolites in anaesthetized rats. PD being a movement disorder, it remains to be determined whether these findings are related to any relevant motor or behavioural changes. Thus, this study investigates concomitant behavioural changes during STN-DBS and extracellular striatal DA metabolites measured using microdialysis in freely moving 6-hydroxydopamine-lesioned rats. STN-DBS induced an increase of striatal DA metabolites in awake, freely moving animals. Furthermore, we observed concomitant contralateral circling behaviour. Taken together, these results suggest that STN-DBS could disinhibit (consequently activate) substantia nigra compacta neurons via inhibition of gamma-aminobutyric acid-ergic substantia nigra reticulata neurons
UR  - http://www.sciencedirect.com/science/article/B6T0G-45TTWCG-5/1/93880367497e8c63864f1b0aad1b4297
ER  - 

TY  - JOUR
T1  - Cerebral acetylcholinesterase activity in patients with Parkinson's disease with and without dementia and Alzheimer's disease
A1  - Bohnen,N.I.
A1  - Kaufer,D.I.
A1  - Lopresti,B.
A1  - Koeppe,R.A.
A1  - Mathis,C.A.
A1  - Dekosky,S.T.
A1  - Moore,R.Y.
Y1  - 2002///
SP  - 63P
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 43 (Suppl.)
IS  - 5
ER  - 

TY  - JOUR
T1  - Phases of A beta-deposition in the human brain and its relevance for the development of AD
A1  - Thal,D.R.
A1  - Rub,U.
A1  - Orantes,M.
A1  - Braak,H.
Y1  - 2002/06/25/
N1  - UI - 22080024
SP  - 1791
EP  - 1800
JF  - Neurology
VL  - 58
IS  - 12
N2  - BACKGROUND: The deposition of the amyloid beta protein (Abeta) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Abeta-deposition. OBJECTIVE: To clarify whether there is a hierarchical involvement of the regions of the entire brain as well and whether there are differences in the expansion of Abeta-pathology between clinically proven AD cases and nondemented cases with AD-related pathology, the authors investigated 47 brains from demented and nondemented patients with AD-related pathology covering all phases of beta-amyloidosis in the MTL (AbetaMTL phases) and four control brains without any AD-related pathology. METHODS: Abeta deposits were detected by the use of the Campbell- Switzer silver technique and by immunohistochemistry in sections covering all brain regions and brainstem nuclei. It was analyzed how often distinct regions exhibited Abeta deposits. RESULTS: In the first of five phases in the evolution of beta-amyloidosis Abeta deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Abeta deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Abeta-deposition. The 17 clinically proven AD cases exhibit Abeta-phases 3, 4, or 5. The nine nondemented cases with AD-related Abeta pathology show Abeta-phases 1, 2, or 3. CONCLUSIONS: Abeta-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Abeta- deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Abeta. There are also indications that clinically proven AD cases with full-blown beta- amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Abeta pathology
AD  - Department of Anatomy, J. W. Goethe University, Frankfurt am Main, Germany. Dietmar.Thal@uni-bonn.de
UR  - PM:12084879
ER  - 

TY  - JOUR
T1  - Cerebral metabolic changes associated with Lyme disease
A1  - Newberg,A.
A1  - Hassan,A.
A1  - Alavi,A.
Y1  - 2002/08//
N1  - UI - 22120446
SP  - 773
EP  - 777
JA  - Nucl Med Commun.
VL  - 23
IS  - 8
N2  - SUMMARY: There are no positron emission tomography (PET) studies reported in the literature with regards to brain metabolism and function in patients with Lyme disease. These patients frequently present with various neurological symptoms, including memory problems. We used [18F]fluorodeoxyglucose (FDG) PET to determine the metabolic landscape in 23 patients with Lyme disease. Images were evaluated for cortical and subcortical abnormalities by two experienced reviewers blinded to the clinical information. The most striking finding was hypometabolism in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism. The involvement of the temporal lobes in both patterns is likely associated with the memory disturbances described in many of these patients. Although there was no clear diagnostic pattern, and many of the defects were mild, FDG PET imaging may provide important information regarding the areas of the brain affected in patients with neurological symptoms associated with Lyme disease
AD  - Division of Nuclear Medicine, Hospital of the University of Pennsylvania, USA
UR  - PM:12124483
ER  - 

TY  - JOUR
T1  - A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain
A1  - Mathis,C.A.
A1  - Bacskai,B.J.
A1  - Kajdasz,S.T.
A1  - McLellan,M.E.
A1  - Frosch,M.P.
A1  - Hyman,B.T.
A1  - Holt,D.P.
A1  - Wang,Y.
A1  - Huang,G.F.
A1  - Debnath,M.L.
A1  - Klunk,W.E.
Y1  - 2002/02/11/
N1  - studied in APP x PS1 transgenic mice
SP  - 295
EP  - 298
JA  - Bioorg.Med Chem.Lett.
VL  - 12
IS  - 3
N2  - The synthesis of a new lipophilic thioflavin-T analogue (2-[4' -(methylamino)phenyl]benzothiazole, 6) with high affinity for amyloid is reported. Intravenous injection of [(11)C]-labeled 6 in control mice resulted in high brain uptake. Amyloid deposits were imaged with multiphoton microscopy in the brains of living transgenic mice following the systemic injection of unlabeled 6. [(11)C]6 is a promising amyloid imaging agent for Alzheimer's disease
AD  - PET Facility, Department of Radiology, University of Pittsburgh, PA 15213, USA. mathisca@msx.upmc.edu
UR  - PM:11814781
ER  - 

TY  - JOUR
T1  - Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease
A1  - Reiman,E.M.
A1  - Caselli,R.J.
A1  - Chen,K.
A1  - Alexander,G.E.
A1  - Bandy,D.
A1  - Frost,J.
Y1  - 2001/03/13/
SP  - 3334
EP  - 3339
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 6
N2  - Cross-sectional positron emission tomography (PET) studies find that cognitively normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral metabolic rate for glucose (CMRgl) in the same regions as patients with Alzheimer's dementia. In this article, we characterize longitudinal CMRgl declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET to test the efficacy of treatments to attenuate these declines in 2 years, and consider how this paradigm could be used to efficiently test the potential of candidate therapies for the prevention of Alzheimer's disease. We studied 10 cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years of age with a reported family history of Alzheimer's dementia before and after an interval of approximately 2 years. The epsilon4 heterozygotes had significant CMRgl declines in the vicinity of temporal, posterior cingulate, and prefrontal cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines were significantly greater than those in the epsilon4 noncarriers. In testing candidate primary prevention therapies, we estimate that between 50 and 115 cognitively normal epsilon4 heterozygotes are needed per active and placebo treatment group to detect a 25% attenuation in these CMRgl declines with 80% power and P = 0.005 in 2 years. Assuming these CMRgl declines are related to the predisposition to Alzheimer's dementia, this study provides a paradigm for testing the potential of treatments to prevent the disorder without having to study thousands of research subjects or wait many years to determine whether or when treated individuals develop symptoms
AD  - Department of Psychiatry, University of Arizona, Tucson, AZ 85724, USA. reiman@samaritan.edu
UR  - PM:11248079
ER  - 

TY  - JOUR
T1  - MR atlas of the baboon brain for functional neuroimaging
A1  - Greer,P.
A1  - Villemagne,V.
A1  - Ruszkiewicz,J.
A1  - Graves,A.
A1  - Meltzer,C.
A1  - Mathis,C.
A1  - Price,J.
Y1  - 2002/08//
N1  - UI - 22170522
SP  - 429
JA  - Brain Res.Bull.
VL  - 58
IS  - 4
N2  - Mathematical co-registration of functional image data (e.g., positron emission tomography, PET) to anatomical magnetic resonance (MR) imaging data allows for objective associations between function and anatomy. Baboons are often used as non-human primate models for functional neuroimaging studies. In this work, a digital MR-based high-resolution atlas of the baboon brain was generated and evaluated for PET. The atlas was generated from six SPGR-MR datasets (centered at mid-sagittal line, AC-PC orientation) that were transformed into the space of one representative MR, averaged and resampled into PET space. The atlas was evaluated by comparing blood flow and dopamine receptor and serotonin transporter binding measures determined using regions-of-interest (ROIs) generated on each individual co-registered MR (ROI(i)) and the atlas-defined ROI template (ROI(ATLAS)). Common ROIs applied to all data included frontal cortex, temporal cortex, thalamus, caudate, putamen and cerebellum. High correlations (r(2)>0.87) were found between the ROI(i) and ROI(ATLAS) data for all radiotracers (linear regression across ROIs for each baboon). The average regression slope values ranged from 0.95 to 1.02 across radiotracers. Lastly, use of the atlas for statistical parametric mapping (SPM) of [15O]water data yielded good agreement with previous ROI(i) results. Overall, the digital MR-based atlas allowed for automatic co-registration, proved useful across a range of PET Studies, and is accessible electronically via the Internet
AD  - University of Pittsburgh PET Facility, Pittsburgh, PA, USA
UR  - PM:12183022
ER  - 

TY  - JOUR
T1  - Sequential H(2)(15)O PET studies in baboons: before and after amphetamine
A1  - Price,J.C.
A1  - Drevets,W.C.
A1  - Ruszkiewicz,J.
A1  - Greer,P.J.
A1  - Villemagne,V.L.
A1  - Xu,L.
A1  - Mazumdar,S.
A1  - Cantwell,M.N.
A1  - Mathis,C.A.
Y1  - 2002/08//
SP  - 1090
EP  - 1100
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 43
IS  - 8
N2  - PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS: Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION: These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters
AD  - Department of Radiology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. price@pet.upmc.edu
UR  - PM:12163636
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow during light sleep - a H215O-PET study
A1  - Kjaer,T.W.
A1  - Law,I.
A1  - Wiltschiotz,G.
A1  - Paulson,O.B.
A1  - Madsen,P.L.
Y1  - 2002/09//
N1  - UI - 0
SP  - 201
EP  - 207
JA  - J Sleep Res.
VL  - 11
IS  - 3
N2  - This is the first report on the distribution of regional cerebral blood flow (rCBF) changes during stage-1 sleep or somnolence. Two hypotheses were tested: (A) that rCBF differed between the awake relaxed state and stage-1 sleep, (B) that hypnagogic hallucinations frequently experienced at sleep onset would be accompanied by measurable changes in rCBF using positron emission tomography (PET). Eight subjects were PET-scanned with 15O-labeled water injection in three conditions: awake, stage-1 sleep with reportable experiences and stage-1 sleep without reportable experiences. Electroencephalography (EEG) was performed continuously during the experiment. Sleep interviews were performed after each scan. The EEG was scored blindly to determine sleep stage. The sleep interviews revealed a substantial increase in how unrealistic and how leaping the thoughts were during stage-1 sleep. During sleep there was a relative flow increase in the occipital lobes and a relative flow decrease in the bilateral cerebellum, the bilateral posterior parietal cortex, the right premotor cortex and the left thalamus. Hypnagogic experiences seemed not to be associated with any relative flow changes. The topography of the occipital activation during stage-1 sleep supports a hypothesis of this state being a state of imagery. The rCBF decreases in premotor cortex, thalamus and cerebellum could be indicative of a general decline in preparedness for goal directed action during stage-1 sleep. Stage-1 sleep seems more similar to other forms of altered awareness, for example, relaxation meditation than to deeper sleep stages. We are of the opinion that stage-1 sleep represents the dreaming state of wakefulness, while rapid eye movement (REM) sleep reflects the dreaming state of the unaware, sleeping brain
AD  - Department of Neuropaediatrics, The John F. Kennedy Institute, Glostrup, Denmark, The PET & Cyclotron Unit, The Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, The Neurobiology Research Unit, The Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark and Department of Psychiatry, The Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
UR  - PM:12220315
ER  - 

TY  - JOUR
T1  - Activation-induced resetting of cerebral metabolism and flow is abolished by beta-adrenergic blockade with propranolol
A1  - Schmalbruch,I.K.
A1  - Linde,R.
A1  - Paulson,O.B.
A1  - Madsen,P.L.
Y1  - 2002/01//
N1  - UI - 21638927
SP  - 251
EP  - 255
JF  - Stroke
VL  - 33
IS  - 1
N2  - BACKGROUND AND PURPOSE: It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR(glc)) in excess of cerebral oxygen uptake (CMRO(2)). Our purpose was to investigate the influence of beta-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism. METHODS: Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(a-v)(O2)], glucose [(a- v)(glc)], and lactate [(a-v)(lac)] both under baseline conditions and during activation. The molar ratio between CMRO(2) and CMR(glc), the oxygen-glucose index (OGI), was calculated. RESULTS: Without beta- adrenergic blockade, activation decreased the (a-v)(O2) but not the (a- v)(glc), reducing the OGI from 6.1 during baseline conditions to 4.0 under activation (P<0.01). The (a-v)(O2) decreased, indicating that the ratio CBF/CMRO(2) had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but beta-adrenergic blockade totally abolished the activation-induced uncoupling of (a-v)(O2) from (a-v)(glc), because both remained constant with an unchanged OGI. The unchanged (a-v)(O2) indicates that CBF remained unchanged compared with CMRO(2). CONCLUSIONS: beta-Adrenergic blockade by propranolol abolishes the activation-induced uncoupling of cerebral oxygen to glucose metabolism and the changes in (a-v)(O2). This may be of most significance to studies of cerebral activation by the blood oxygen level-dependent fMRI method
AD  - Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
UR  - PM:11779918
ER  - 

TY  - JOUR
T1  - Imaging Amyloid-beta Deposits In Vivo
A1  - Bacskai,B.J.
A1  - Klunk,W.E.
A1  - Mathis,C.A.
A1  - Hyman,B.T.
Y1  - 2002/09//
N1  - UI - 22206653
SP  - 1035
EP  - 1041
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 9
N2  - Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-beta plaques. An imaging technique that permitted detection of NFTs or amyloid-beta plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-beta deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-beta deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-beta with high sensitivity and specificity. This review describes the progress in developing reagents suitable for imaging of senile plaques
UR  - PM:12218409
ER  - 

TY  - JOUR
T1  - Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression
A1  - Smith,G.S.
A1  - Reynolds III,C.F.
A1  - Houck,P.R.
A1  - Dew,M.A.
A1  - Ma,Y.
A1  - Mulsant,B.H.
A1  - Pollock,B.G.
Y1  - 2002/09//
N1  - UI - 22201656
SP  - 561
EP  - 567
JA  - Am.J Geriatr.Psychiatry
VL  - 10
IS  - 5
N2  - OBJECTIVE: The variable speed and durability of response to antidepressant medications in geriatric depression is a significant clinical problem. The authors evaluated changes in cerebral glucose metabolism measured with positron emission tomography (PET) during a clinical trial designed to accelerate medication response by the use of one night of total sleep deprivation (TSD), and they asked whether changes would correlate with treatment outcome after 12 weeks of antidepressant treatment. METHODS: Twelve elderly, unipolar depressed patients underwent serial PET studies at baseline, post-TSD, post- recovery sleep (after an initial paroxetine dose), and after 2 weeks of paroxetine treatment. RESULTS: Decreased regional glucose metabolism after TSD, recovery sleep, and 2 weeks of treatment was associated with clinical improvement at 12 weeks. The right cingulate gyrus area was consistently correlated with clinical improvement across treatment conditions. CONCLUSION: These data indicate that the early metabolic alterations in the right cingulate gyrus and the persistence of these adaptive changes are associated with improvement in depressive symptoms
AD  - Received June 4, 2001
UR  - PM:12213690
ER  - 

TY  - JOUR
T1  - Abnormalities of grey and white matter [11C]flumazenil binding in temporal lobe epilepsy with normal MRI
A1  - Hammers,A.
A1  - Koepp,M.J.
A1  - Hurlemann,R.
A1  - Thom,M.
A1  - Richardson,M.P.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 2002/10/01/
SP  - 2257
EP  - 2271
JF  - Brain
VL  - 125
IS  - 10
N2  - In 20% of potential surgical candidates with refractory epilepsy, current optimal MRI does not identify the cause. GABA is the principal inhibitory neurotransmitter in the brain, and GABAA receptors are expressed by most neurones. [11C]Flumazenil (FMZ) PET images the majority of GABAA receptor subtypes. We investigated abnormalities of FMZ binding in grey and white matter in 18 patients with refractory temporal lobe epilepsy (TLE) and normal quantitative MRI. Parametric images of FMZ volume of distribution (FMZ-Vd) were calculated. Twenty-one healthy controls were scanned for comparison. Statistical parametric mapping (SPM99) was used to localize significant changes in FMZ-Vd in individual patients and between groups, specifically including the entire white matter in all subjects through explicit masking. Sixteen of 18 patients showed single or multiple abnormalities of FMZ-Vd. Six had hippocampal decreases of FMZ-Vd. Eleven patients showed increased FMZ-Vd in the temporal lobe white matter (TLWM). Outside the mesial temporal structures, seven showed multiple areas of increase or decrease and only one a single area of decrease. In seven of the 16 patients with abnormalities, findings were concordant with EEG and clinical data, enabling further presurgical evaluation. Group findings were: (i) decreased FMZ-Vd in the ipsilateral (Z = 3.01) and contralateral (Z = 2.56) hippocampus; (ii) increased FMZ-Vd in the ipsilateral (Z = 3.71) and contralateral TLWM (two clusters, Z = 3.11 and 2.79); and (iii) increased FMZ-Vd in the ipsilateral frontal lobe white matter between the superior and medial frontal gyrus (Z = 3.80) with similar changes contralaterally (Z = 4.87). No changes were found in the thalamus and basal ganglia. Region-of-interest analyses indicated an average increase in FMZ binding of 16% in the TLWM ipsilateral to the epileptic focus. PET findings were corroborated by invasive EEG or pathol ogy in five cases. FMZ-PET, analysed by SPM with explicit masking, was sensitive in patients with normal MRI, and hippocampal abnormalities were detected in a third of these patients. Furthermore, increases in FMZ binding in TLWM, indicating microdysgenesis, were detected in the majority of these patients and may represent the structural basis of their epilepsy
UR  - http://brain.oupjournals.org/cgi/content/abstract/125/10/2257
ER  - 

TY  - JOUR
T1  - Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin
A1  - Herbst,R.S.
A1  - Mullani,N.A.
A1  - Davis,D.W.
A1  - Hess,K.R.
A1  - McConkey,D.J.
A1  - Charnsangavej,C.
A1  - O'Reilly,M.S.
A1  - Kim,H.W.
A1  - Baker,C.
A1  - Roach,J.
A1  - Ellis,L.M.
A1  - Rashid,A.
A1  - Pluda,J.
A1  - Bucana,C.
A1  - Madden,T.L.
A1  - Tran,H.T.
A1  - Abbruzzese,J.L.
Y1  - 2002/09/15/
N1  - UI - 22215752
SP  - 3804
EP  - 3814
JA  - J Clin.Oncol.
VL  - 20
IS  - 18
N2  - PURPOSE: Angiogenesis is a target for the treatment of cancer and other diseases, and its complex biology suggests that establishing the appropriate dose and schedule for antiangiogenic treatment will require extensive study. We present the initial results of a dose-finding clinical trial of recombinant human endostatin (rh-Endo) that examined potential surrogates for response to antiangiogenic therapy. PATIENTS AND METHODS: Twenty-five patients were treated with escalating doses of rh-Endo. Positron emission tomography (PET) was used to assess tumor blood flow (with [15O]H2O) and metabolism (with [18F]fluorodeoxyglucose) before the start of therapy and then every 4 weeks. To directly assess the effects of rh-Endo on endothelial cells within the tumors, biopsy specimens of tumor tissue were obtained before therapy and again at 8 weeks and evaluated for endothelial cell and tumor cell apoptosis. RESULTS: Tumor blood flow and metabolism as measured by PET scans generally decreased with increasing doses of rh-Endo; however, the effects were complex and in some analyses nonlinear. Tumor biopsy analysis revealed a significant increase in tumor cell apoptosis (P =.027) and endothelial cell apoptosis (P =.027) after 8 weeks of therapy. However, there was no statistically significant relationship between rh-Endo dose and induction of tumor cell or endothelial cell apoptosis. CONCLUSION: These initial data suggest that rh-Endo has measurable effects on tumor blood flow and metabolism and induces endothelial and tumor cell apoptosis even in the absence of demonstrable anticancer effects. Further study and validation of these biomarkers in the context of antiangiogenic therapy will be required
AD  - Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. rherbst@mdanderson.org
UR  - PM:12228200
ER  - 

TY  - JOUR
T1  - Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment
A1  - Huang,C.
A1  - Wahlund,L.O.
A1  - Svensson,L.
A1  - Winblad,B.
A1  - Julin,P.
Y1  - 2002/09/12/
N1  - UI - 0
SP  - 9
JA  - BMC.Neurol
VL  - 2
IS  - 1
N2  - BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%-76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Divison of Geriatric Medicine, Huddinge University Hospital, Sweden. chaorui.huang@neurotec.ki.se
UR  - PM:12227833
ER  - 

TY  - JOUR
T1  - Metabolic characterization of childhood brain tumors: comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography
A1  - Utriainen,M.
A1  - Metsahonkala,L.
A1  - Salmi,T.T.
A1  - Utriainen,T.
A1  - Kalimo,H.
A1  - Pihko,H.
A1  - Makipernaa,A.
A1  - Harila-Saari,A.
A1  - Jyrkkio,S.
A1  - Laine,J.
A1  - Nagren,K.
A1  - Minn,H.
Y1  - 2002/09/15/
N1  - UI - 22203813
SP  - 1376
EP  - 1386
JF  - Cancer
VL  - 95
IS  - 6
N2  - BACKGROUND: Positron emission tomography (PET) scans of primary brain tumors were performed in pediatric patients to examine whether metabolic characteristics could be used as an index of clinical aggressiveness. METHODS: Twenty-seven pediatric patients with untreated primary central nervous system neoplasms were studied with PET scans using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) and/or L-[methyl-(11)C] methionine (MET). Metabolic characteristics as assessed with FDG and MET standardized uptake values (SUV) and SUV-to-normal brain ratios were compared with histopathology and selected histochemical features such as proliferation activity (Ki-67(MIB-1)) and apoptotic, vascular, and cell density indices. The median followup time was 43 months. RESULTS: The accumulation of both FDG and MET was significantly higher in high-grade than in low-grade tumors, but a considerable overlap was found. The accumulation of both tracers was associated positively with age. High-grade tumors showed higher proliferative activity and vascularity than the low-grade tumors. In univariate analysis, FDG-PET, MET-PET, and apoptotic index were independent predictors of event-free survival. CONCLUSION: We found that both FDG and MET uptake in pediatric brain tumors are associated with malignancy grade. However, no clear limits of SUVs and SUV-to-normal brain ratios can be set between low-grade and high-grade tumors, which makes the assessment of malignancy grade using metabolic imaging with PET scan difficult in individual cases. Although FDG-PET and MET-PET do not compensate for histopathologic evaluation, they may give valuable additional information especially if invasive procedures to obtain histopathologic samples are not feasible
AD  - Turku PET Centre, University of Turku, Finland. meri.utriainen@hus.fi
UR  - PM:12216107
ER  - 

TY  - JOUR
T1  - Comparative effects of methamphetamine and nicotine on the striatal [(11)C]raclopride binding in unanesthetized monkeys
A1  - Tsukada,H.
A1  - Miyasato,K.
A1  - Kakiuchi,T.
A1  - Nishiyama,S.
A1  - Harada,N.
A1  - Domino,E.F.
Y1  - 2002/09/15/
SP  - 207
EP  - 212
JF  - Synapse
VL  - 45
IS  - 4
N2  - Although a very large literature exists on the in vitro, ex vivo, and in vivo effects of nicotine on dopamine release in rodents, similar data in primates are scant. This study was initiated to compare methamphetamine to nicotine given i.v. to normal unanesthetized monkeys using positron emission tomography (PET) techniques. Release of dopamine in the striatum using [(11)C]raclopride was determined indirectly in four nicotine-naive adult Macaca mulatta monkeys under conscious and isoflurane-anesthetized conditions using high-resolution PET. [(11)C]Raclopride was given i.v. as a bolus injection followed by continuous infusion with steady state over 30-45 min. Nicotine bitartrate was then given as a bolus plus infusion for 30 min in doses of 32 microg/kg + 0.8 microg/kg/min or 100 microg/kg + 2.53 microg/kg/min as base. The larger doses of nicotine caused significant cardiovascular effects; these doses did not displace [(11)C]raclopride binding in either dorsal or ventral striatum under the anesthetized conscious condition. In contrast, isoflurane-anesthesia induced a slight but significant dose-dependent reduction of [(11)C]raclopride binding by nicotine even at the same doses used in the anesthetized condition. Methamphetamine in bolus doses of 0.1, 0.3, and 1.0 mg/kg i.v. under conscious condition caused a significant displacement of [(11)C]raclopride and isoflurane-anesthesia facilitated the displacement induced by nicotine. These results indicate that nicotine, in high tobacco-smoking-related doses, does not release sufficient brain dopamine to displace [(11)C]raclopride in the striatum in the awake and fully conscious state, in contrast to small doses of methamphetamine
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
UR  - PM:12125041
ER  - 

TY  - JOUR
T1  - The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update
A1  - Hoyer,S.
Y1  - 2002/03//
N1  - Fig. 4: Overview, scanned
SP  - 341
EP  - 360
JA  - J Neural Transm.
VL  - 109
IS  - 3
N2  - Nosologically, Alzheimer disease may not be considered to be a single disorder in spite of a common clinical phenotype. Only a small proportion of about 5% to 10% of all Alzheimer cases is due to genetic mutations (type I) whereas the great majority of patients was found to be sporadic in origin. It may be assumed that susceptibility genes along with lifestyle risk factors contribute to the causation of the age-related sporadic Alzheimer disease (type II). In this context, the desensitization of the neuronal insulin receptor similar to not-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in brain insulin concentration is assumed to induce a cascade-like process of disturbances including cellular glucose, acetylcholine, cholesterol, and ATP associated with abnormalities in membrane pathology and the formation of both amyloidogenic derivatives and hyperphosphorylated tau protein. Sporadic Alzheimer disease may, thus, be considered to be the brain type of diabetes mellitus II. Experimental evidence is provided and discussed
AD  - Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Federal Republic of Germany. siegfried_hoyer@ukl.uni- heidelberg.de
UR  - PM:11956956
ER  - 

TY  - JOUR
T1  - Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson's disease: measuring the on- and off-conditions with FDG-PET
A1  - Hilker,R.
A1  - Voges,J.
A1  - Thiel,A.
A1  - Ghaemi,M.
A1  - Herholz,K.
A1  - Sturm,V.
A1  - Heiss,W.-D.
Y1  - 2002///
SP  - 1257
EP  - 1264
JF  - Journal of Neural Transmission
VL  - 10
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Hilker-JNT-12589.pdf
ER  - 

TY  - JOUR
T1  - Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria
A1  - Halliday,G.
A1  - Ng,T.
A1  - Rodriguez,M.
A1  - Harding,A.
A1  - Blumbergs,P.
A1  - Evans,W.
A1  - Fabian,V.
A1  - Fryer,J.
A1  - Gonzales,M.
A1  - Harper,C.
A1  - Kalnins,R.
A1  - Masters,C.L.
A1  - McLean,C.
A1  - Milder,D.G.
A1  - Pamphlett,R.
A1  - Scott,G.
A1  - Tannenberg,A.
A1  - Kril,J.
Y1  - 2002/07//
N1  - UI - 22064753
SP  - 72
EP  - 78
JA  - Acta Neuropathol.(Berl)
VL  - 104
IS  - 1
N2  - The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted
AD  - Prince of Wales Medical Research Institute, High Street, Randwick, 2031 New South Wales, Australia. G.Halliday@unsw.edu.au
UR  - PM:12070667
ER  - 

TY  - JOUR
T1  - Results on coregistration of mediotemporal 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) hyperactivity and 3D magnetic resonance imaging hyperintense lesions in limbic encephalitis
A1  - Salmon,E.
A1  - Sadzot,B.
A1  - Maquet,P.
A1  - Franck,G.
Y1  - 2002/07//
N1  - UI - 22112120
SP  - 282
EP  - 283
JA  - J Neuroimaging
VL  - 12
IS  - 3
UR  - PM:12116750
ER  - 

TY  - JOUR
T1  - Integration of the metabolic data of positron emission tomography in the dosimetry planning of radiosurgery with the gamma knife: early experience with brain tumors. Technical note
A1  - Levivier,M.
A1  - Wikier,D.
A1  - Goldman,S.
A1  - David,P.
A1  - Metens,T.
A1  - Massager,N.
A1  - Gerosa,M.
A1  - Devriendt,D.
A1  - Desmedt,F.
A1  - Simon,S.
A1  - Van Houtte,P.
A1  - Brotchi,J.
Y1  - 2000/12//
N1  - UI - 21004912
SP  - 233
EP  - 238
JA  - J Neurosurg
VL  - 93 Suppl 3
N2  - The purpose of this study was to assess the use of positron emission tomography (PET) as a stereotactic planning modality for gamma knife radiosurgery (GKS). The authors developed and validated a technique for fiducial marker imaging, importation, and handling of PET data for integration into GammaPlan planning software. The clinical feasibility in applying this approach to a selected group of patients presenting with recurrent glial tumors or metastases was evaluated. Positron emission tomography data can be integrated into GammaPlan, allowing a high spatial accuracy, as validated using a phantom. Positron emission tomography data were successfully combined with magnetic resonance (MR) images to define the target volume for the radiosurgical treatment of patients with recurrent glioma or metastasis. This approach may contribute to optimizing target selection for infiltrating or ill-defined brain lesions. Because PET is also useful for the pretreatment and follow-up evaluation, the use of stereotactic PET in these patients can enable an accurate comparison of PET-based metabolic data with MR-based anatomical data. This could give a better understanding of the metabolic changes following radiosurgery. The ability to use PET data in GKS represents a crucial step toward further developments in radiosurgery, as this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors
AD  - Gamma Knife Center of the Universite Libre de Bruxelles, Brussels, Belgium. Marc.Levivier@ulb.ac.be
UR  - PM:11143256
ER  - 

TY  - JOUR
T1  - Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma
A1  - Nuutinen,J.
A1  - Sonninen,P.
A1  - Lehikoinen,P.
A1  - Sutinen,E.
A1  - Valavaara,R.
A1  - Eronen,E.
A1  - Norrgard,S.
A1  - Kulmala,J.
A1  - Teras,M.
A1  - Minn,H.
Y1  - 2000/08/01/
N1  - UI - 20384639
SP  - 43
EP  - 52
JA  - Int.J Radiat.Oncol.Biol.Phys.
VL  - 48
IS  - 1
N2  - PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign
AD  - Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
UR  - PM:10924970
ER  - 

TY  - JOUR
T1  - Distinguishing recurrent tumor and radiation necrosis with positron emission tomography versus stereotactic biopsy
A1  - Thompson,T.P.
A1  - Lunsford,L.D.
A1  - Kondziolka,D.
Y1  - 1999///
N1  - UI - 20312951
SP  - 9
EP  - 14
JA  - Stereotact.Funct.Neurosurg
VL  - 73
IS  - 1-4
N2  - With the recent approval of reimbursement for positron emission tomography (PET), it has become important to clarify the utility of this diagnostic study. We evaluated the utility of PET to distinguish radiation necrosis from recurrent tumor in a retrospective review of patients with primary glial neoplasms. Fifteen patients had preoperative contrast-enhanced MRI and PET images followed by stereotactic biopsy or craniotomy and histological confirmation. The sensitivity of PET was 43% (6/14) and the specificity was 100% (1/1). We examined the sensitivity of PET as a function of volumetric contrast enhancement on MRI. Eighty percent of true-positive PET studies occurred with volume enhancement greater than 10 cm(3). Seventy-five percent of false negatives occurred with volume enhancement less than 6 cm(3). Given the clinical significance of distinguishing tumor progression from radiation necrosis, we believe that PET is insufficient to resolve radiation necrosis versus tumor progression
AD  - University of Pittsburgh School of Medicine and The Center for Image Guided Neurosurgery, PA 15213, USA. thompo@neuronet.pitt.edu
UR  - PM:10853090
ER  - 

TY  - JOUR
T1  - Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II
A1  - Imahori,Y.
A1  - Ueda,S.
A1  - Ohmori,Y.
A1  - Sakae,K.
A1  - Kusuki,T.
A1  - Kobayashi,T.
A1  - Takagaki,M.
A1  - Ono,K.
A1  - Ido,T.
A1  - Fujii,R.
Y1  - 1998/08//
N1  - UI - 98381909
SP  - 1833
EP  - 1841
JA  - Clin.Cancer Res.
VL  - 4
IS  - 8
N2  - Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study
AD  - Department of Neurosurgey, Kyoto Prefectural University of Medicine, Japan. imahori@koto.kpu-m.ac.jp
UR  - PM:9717809
ER  - 

TY  - JOUR
T1  - Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part I
A1  - Imahori,Y.
A1  - Ueda,S.
A1  - Ohmori,Y.
A1  - Sakae,K.
A1  - Kusuki,T.
A1  - Kobayashi,T.
A1  - Takagaki,M.
A1  - Ono,K.
A1  - Ido,T.
A1  - Fujii,R.
Y1  - 1998/08//
N1  - UI - 98381908
SP  - 1825
EP  - 1832
JA  - Clin.Cancer Res.
VL  - 4
IS  - 8
N2  - Determination of tumor boron-10 (10B) levels is required for accurate neutron dosimetry during boron neutron capture therapy. We assessed a new method for quantitative measurement of boronated drug uptake in high-grade gliomas. This method uses positron emission tomography (PET) with fluorine-18-labeled L-fluoroborono-phenylalanine (L-18F-10B-FBPA), which was synthesized as an analogue of L-boronophenylalanine. We studied the accumulation of L-18F-10B-FBPA by PET in patients with high-grade gliomas. Dynamic PET studies of brain tumors revealed that L-18F-10B-FBPA accumulated gradually after bolus injection, and the value of PET activity divided by the integrated plasma activity reached a constant level 42 min after injection, which was defined as the incorporation constant (Ic*). This constant reflected the appropriate L-18F-10B-FBPA accumulation in tumor tissue. Based on the Ic* constant, the methods for estimating tumor 10B concentration were devised. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This method was based solely on PET and can potentially provide data that would assist in the selection of patients for future treatment with boron neutron capture therapy after surgical resection of their brain tumors
AD  - Department of Neurosurgery, Kyoto Prefectural University of Medicine, Japan. imahori@koto.kpu-m.ac.jp
UR  - PM:9717808
ER  - 

TY  - JOUR
T1  - PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome
A1  - Valk,P.E.
A1  - Budinger,T.F.
A1  - Levin,V.A.
A1  - Silver,P.
A1  - Gutin,P.H.
A1  - Doyle,W.K.
Y1  - 1988/12//
SP  - 830
EP  - 838
JA  - J Neurosurg
VL  - 69
IS  - 6
N2  - Positron emission tomography (PET) with rubidium-82 (82Rb) and fluorine-18-fluorodeoxyglucose (18F-FDG) was used to diagnose active tumor recurrence and to differentiate this from radiation injury after interstitial irradiation of malignant gliomas. Patients were studied when they presented with radiological or clinical deterioration after an initial period of posttreatment stabilization. Forty studies were performed in 34 patients. The 82Rb was used as a blood-brain barrier tracer to localize the lesion. Uptake of 18F-FDG by the lesion was then compared to uptake by adjacent brain in order to make a diagnosis of active tumor recurrence (higher or equal lesion uptake) or no active tumor (lower uptake). Radiation injury was diagnosed by the exclusion of active tumor. A retrospective clinical diagnosis was established in 38 cases by following the patients' progress for 8 to 142 weeks after the PET study. In two cases, no follow-up diagnosis could be determined. The PET results agreed with the follow-up diagnosis in 15 of 17 cases of active tumor and 17 of 21 cases of radiation injury. Histological examination of surgically resected tissue obtained after the PET study was performed in 18 patients (nine with tumor regrowth and nine with radiation injury). This showed apparently viable tumor as well as necrosis in all cases, regardless of eventual clinical outcome. Some cells from the irradiated volume may appear morphologically intact, but have little or no metabolic or clinical activity. The functional nature of the PET-FDG technique allows diagnosis of tumor activity, which cannot be demonstrated by anatomic imaging studies or by histological examination. The addition of a blood-brain barrier tracer to the 18F-FDG study aids in differentiating normal brain uptake from tumor activity and improves the accuracy of the technique
AD  - Donner Laboratory, University of California, Berkeley
UR  - PM:2848111
ER  - 

TY  - JOUR
T1  - 18-Fluorodeoxyglucose uptake and survival of patients with suspected recurrent malignant glioma
A1  - Barker,F.G.
A1  - Chang,S.M.
A1  - Valk,P.E.
A1  - Pounds,T.R.
A1  - Prados,M.D.
Y1  - 1997/01/01/
N1  - UI - 97142713
SP  - 115
EP  - 126
JF  - Cancer
VL  - 79
IS  - 1
N2  - BACKGROUND: After intensive initial radiation therapy for malignant glioma, magnetic resonance imaging (MRI) and computerized tomography (CT) cannot distinguish tumor progression from radiation injury. METHODS: The authors studied the prognostic value of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in 55 patients with malignant glioma for whom MRI obtained after initial surgery and radiation therapy demonstrated enlarging, enhancing lesions consistent with either tumor progression or radiation necrosis. Forty patients (73%) had an initial diagnosis of Grade 4 malignant glioma and 15 (27%) had Grade 3 malignant glioma. The FDG-PET scans were graded visually on a four-level scale at the time of acquisition. RESULTS: In univariate analysis, the FDG-PET score was a significant predictor of survival time after FDG-PET scanning (P = 0.005). Median survival was 10 months for patients with FDG-PET scores of 2 or 3 (glucose uptake > or = adjacent cortex) and 20 months for those with scores of 0 or 1 (glucose uptake < adjacent cortex). In multivariate proportional hazards analysis, the FDG-PET score was a significant predictor of survival (P = 0.019) in a model that included patient age, recurrence number, and FDG-PET score. There was no significant difference in the FDG-PET score hazard ratio for patients with Grade 3 or 4 tumors at initial diagnosis, first or later suspected recurrence, initial photon irradiation given with standard fractions or hyperfractionation, or stereotactic irradiation prior to FDG-PET scanning. CONCLUSIONS: This analysis demonstrates that FDG-PET scanning has prognostic value in a cohort limited to patients with suspected recurrent high grade glioma
AD  - Department of Neurological Surgery, School of Medicine, University of California, San Francisco, USA
UR  - PM:8988735
ER  - 

TY  - JOUR
T1  - Altered regional brain glucose metabolism in Duchenne muscular dystrophy: A pet study
A1  - Lee,J.S.
A1  - Pfund,Z.
A1  - Juhasz,C.
A1  - Behen,M.E.
A1  - Muzik,O.
A1  - Chugani,D.C.
A1  - Nigro,M.A.
A1  - Chugani,H.T.
Y1  - 2002/10//
N1  - UI - 22249295
SP  - 506
EP  - 512
JA  - Muscle Nerve
VL  - 26
IS  - 4
N2  - The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region- specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, 3901 Beaubien Blvd., Detroit, Michigan 48201, USA
UR  - PM:12362416
ER  - 

TY  - JOUR
T1  - Imaging the metabolic footprint of Glut1 deficiency on the brain
A1  - Pascual,J.M.
A1  - Van Heertum,R.L.
A1  - Wang,D.
A1  - Engelstad,K.
A1  - De Vivo,D.C.
Y1  - 2002/10//
N1  - UI - 22235340
SP  - 458
EP  - 464
JA  - Ann.Neurol
VL  - 52
IS  - 4
N2  - Cerebral (18)F-fluorodeoxyglucose positron emission tomography in 14 patients with microcephaly, developmental delay, seizures, and mutations of the glucose transporter Glut1 (Glut1 deficiency syndrome) showed distinct abnormalities. Within a global context of diminished cortical uptake, more severe hypometabolism was found in the mesial temporal regions and thalami, accentuating a relative signal increase in the basal ganglia. In contrast, the structure of the brain appeared preserved in patients additionally investigated by magnetic resonance imaging. This metabolic footprint was relatively constant in all patients regardless of age, seizure history, or therapies and therefore constitutes a radiological signature of the disease. The full expression of the signature in the youngest patient (aged 19 months) indicates that the state of haploinsufficiency caused by Glut1 mutation leaves a permanent footprint on the nervous system from its earlier postnatal stages of development. The potential benefit of prompt diagnosis, aided by (18)F-fluorodeoxyglucose positron emission tomography, and early initiation of available therapies is underscored by our results
AD  - Colleen Giblin Laboratories, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY
UR  - PM:12325075
ER  - 

TY  - JOUR
T1  - Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging
A1  - Ghaemi,M.
A1  - Hilker,R.
A1  - Rudolf,J.
A1  - Sobesky,J.
A1  - Heiss,W.D.
Y1  - 2002/11/01/
SP  - 517
EP  - 523
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 73
IS  - 5
N2  - Objectives: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities. Methods: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[18F]-fluoro-L-dopa (FDOPA), [18F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed. Results: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P. Conclusions: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy
UR  - http://jnnp.bmjjournals.com/cgi/content/abstract/73/5/517
ER  - 

TY  - JOUR
T1  - Alzheimer's Disease Is a Synaptic Failure
A1  - Selkoe,Dennis J.
Y1  - 2002/10/25/
SP  - 789
EP  - 791
JF  - Science
VL  - 298
IS  - 5594
UR  - http://www.sciencemag.org/cgi/content/abstract/298/5594/789
ER  - 

TY  - JOUR
T1  - In-vivo Study of Acetylcholine Esterase in Basal Forebrain, Amygdala, and Cortex in Mild to Moderate Alzheimer disease
A1  - Herholz,K.
A1  - Weisenbach,S.
A1  - Zndorf,G.
A1  - Lenz,O.
A1  - Schrder,H.
A1  - Bauer,B.
A1  - Kalbe,E.
A1  - Heiss,W.-D.
Y1  - 2004///
SP  - 136
EP  - 143
JF  - Neuroimage
VL  - 21
IS  - 1
ER  - 

TY  - JOUR
T1  - Cortical deactivation induced by visual stimulation in human slow-wave sleep
A1  - Born,A.P.
A1  - Law,I.
A1  - Lund,T.E.
A1  - Rostrup,E.
A1  - Hanson,L.G.
A1  - Wildschiodtz,G.
A1  - Lou,H.C.
A1  - Paulson,O.B.
Y1  - 2002/11//
N1  - UI - 22302627
SP  - 1325
EP  - 1335
JF  - Neuroimage
VL  - 17
IS  - 3
N2  - It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation. It is unresolved whether this negative BOLD response pattern is of developmental neurobiological origin particular to a given age or to a general effect of sleep or sedative drugs. To further elucidate this issue, we used fMRI and positron emission tomography (PET) to study the brain activation pattern during visual stimulation in spontaneously sleeping adult volunteers. In five sleeping volunteers fMRI studies confirmed a robust signal decrease during stimulation in the rostro-medial occipital cortex. A similar relative decrease at the same location was found during visual stimulation and polysomnographically verified slow-wave sleep in a separate group of six subjects using H(2)(15)O PET measures of the regional cerebral blood flow (rCBF). This decrease was more rostro-dorsal compared to the relative rCBF increase along the calcarine sulcus found during visual stimulation in the awake state. This study reconfirms the previously described paradoxical stimulation-correlated negative BOLD signal change in the rostro-medial occipital cortex, expanding this response mode to an age spectrum ranging from the newborn to the adult. Further, the use of complementary brain mapping techniques suggests that this decrease was secondary to a relative rCBF decrease. Possible mechanisms for the paradoxical response pattern during sleep include an active inhibition of the visual cortex or a disruption of an energy-consuming process
AD  - Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Glostrup, Rigshospitalet, Rigshospitalet, Copenhagen, Denmark
UR  - PM:12414272
ER  - 

TY  - JOUR
T1  - Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease
A1  - Okamura,N.
A1  - Arai,H.
A1  - Maruyama,M.
A1  - Higuchi,M.
A1  - Matsui,T.
A1  - Tanji,H.
A1  - Seki,T.
A1  - Hirai,H.
A1  - Chiba,H.
A1  - Itoh,M.
A1  - Sasaki,H.
Y1  - 2002/03//
N1  - UI - 21858210
SP  - 474
EP  - 476
JA  - Am.J Psychiatry
VL  - 159
IS  - 3
N2  - OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment
AD  - Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
UR  - PM:11870015
ER  - 

TY  - JOUR
T1  - Reduced 5-HT2A receptor binding after recovery from anorexia nervosa
A1  - Frank,G.K.
A1  - Kaye,W.H.
A1  - Meltzer,C.C.
A1  - Price,J.C.
A1  - Greer,P.
A1  - McConaha,C.
A1  - Skovira,K.
Y1  - 2002/11/01/
N1  - UI - 22286031
SP  - 896
EP  - 906
JA  - Biol.Psychiatry
VL  - 52
IS  - 9
N2  - Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN.To avoid the confounding effects of malnutrition, we studied 16 women recovered from AN (REC AN, >1 year normal weight, regular menstrual cycles, no bingeing or purging) compared with 23 healthy control women (CW) using [18F]altanserin, a specific 5-HT2A receptor antagonist on PET imaging.REC AN women had significantly reduced [18F]altanserin binding relative to CW in mesial temporal (amygdala and hippocampus), as well as cingulate cortical regions. In a subset of subjects (11 CW and 16 REC AN), statistical parametric mapping (SPM) confirmed reduced mesial temporal cortex 5HT2A receptor binding and, in addition, showed reduced occipital and parietal cortex binding.This study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from AN and may be related to disturbances of mesial temporal lobe function. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of AN
AD  - Department of Psychiatry, Western Psychiatric Institute and Clinic (GKF, WHK, CM, KS), Pittsburgh, Pennsylvania, USA
UR  - PM:12399143
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow after recovery from bulimia nervosa
A1  - Frank,G.K.
A1  - Kaye,W.H.
A1  - Greer,P.
A1  - Meltzer,C.C.
A1  - Price,J.C.
Y1  - 2000/11/20/
N1  - UI - 20545810
SP  - 31
EP  - 39
JA  - Psychiatry Res.
VL  - 100
IS  - 1
N2  - When ill, women with bulimia nervosa (BN) show alterations of regional cerebral blood flow (rCBF). In this study we investigated rCBF in nine women in long-term recovery from BN (RBN, n=9), i.e. more than 1 year without bingeing/purging behavior, normal weight, stable food intake, and regular menses, and compared them with age-matched healthy control women (CW, n=13). Positron emission tomography (PET) was used for the assessment of rCBF. There were no significant differences in rCBF between groups. However, rCBF was significantly inversely related to length of recovery in RBN for the left and right prefrontal cortex (BA 10), right medial orbital frontal cortex (BA 11), left subgenual cingulate (BA 25), right anterior cingulate (BA 32), left sensory motor cortex (BA 1,2,3,4), left and right lateral temporal (BA 21), and left occipital cortex (BA 17), as well as left thalamus. This finding suggests that previously reported alterations in rCBF during the ill state of BN may be a state-related phenomenon that remits with recovery. It is also possible that reductions in rCBF occur in a later stage of recovery from BN
AD  - Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O'Hara Street, E-724, Pittsburgh, PA 15213, USA
UR  - PM:11090723
ER  - 

TY  - JOUR
T1  - Multimodal functional imaging of prolonged neurological deficits in a patient suffering from familial hemiplegic migraine
A1  - Gutschalk,A.
A1  - Kollmar,R.
A1  - Mohr,A.
A1  - Henze,M.
A1  - Ille,N.
A1  - Schwaninger,M.
A1  - Hartmann,M.
A1  - Hahnel,S.
A1  - Haberkorn,U.
A1  - Rupp,A.
A1  - Meyding-Lamade,U.
Y1  - 2002/10/31/
N1  - UI - 22272337
SP  - 115
JA  - Neurosci.Lett.
VL  - 332
IS  - 2
N2  - The case of a patient with familial hemiplegic migraine (FHM) suffering from prolonged right sided hemiparesis and aphasia that persisted for more than 10 days is reported. The symptoms were accompanied by slowing of the magnetoencephalogram over the left hemisphere, which normalized parallel to the clinical improvement. Positron emission tomography obtained on the 6th day revealed glucose-hypometabolism (hemispheric difference >/=10%) in left hemisphere's fronto-basal cortex, caudate nucleus, and thalamus. In contrast, magnetic resonance imaging including perfusion and diffusion weighted imaging was normal and did not show significant alterations of cortical perfusion or water mobility during the episode. We hypothesize that this finding provides evidence for a primary neuronal dysfunction causing the prolonged neurological deficits in FHM
AD  - Department of Neurology, University of Heidelberg, 69120, Heidelberg, Germany
UR  - PM:12384224
ER  - 

TY  - JOUR
T1  - Visualising microglial activation in vivo
A1  - Banati,R.B.
Y1  - 2002/11//
N1  - UI - 22267066
SP  - 206
EP  - 217
JF  - GLIA
VL  - 40
IS  - 2
N2  - In health, microglia reside as quiescent guardian cells ubiquitously, but isolated without any cell-cell contacts amongst themselves, throughout the normal CNS. In disease, however, they act as swift "sensors" for pathological events, including subtle ones without any obvious structural damage. Once activated, microglia show a territorially highly restricted involvement in the disease process. This property, peculiar to microglia, confers to them diagnostic value for the accurate spatial localisation of any active disease process, acute or chronic. In the brain, the isoquinoline PK11195, a ligand for the peripheral benzodiazepine binding site (PBBS), binds with relative cellular selectivity to activated, but not resting, microglia. Labelled with carbon-11, (R)-PK11195 and positron emission tomography (PET) have been used for the study of inflammatory and neurodegenerative brain disease in vivo. These studies demonstrate meaningfully distributed patterns of regional [(11)C](R)-PK11195 signal increases that correlate with clinically observed loss of function. Increased [(11)C](R)-PK11195 binding closely mirrors the histologically well-described activation of microglia in the penumbra of focal lesions, as well as in the distant, anterograde, and retrograde projection areas of the lesioned neural pathway. There is also some indication that in long-standing alterations of a neural network with persistent abnormal input, additional signals of glial activation may also emerge in transsynaptic areas. These data suggest that the injured brain is less static than commonly thought and shows subtle glial responses even in macroanatomically stable appearing regions. This implies that glial activation is not solely a sign of tissue destruction, but possibly of disease-induced adaptation or plasticity as well. Whilst further technological and methodological advances are necessary to achieve routine clinical value and feasibility, a systematic attempt to image glial cells in vivo is likely to furnish valuable information on the cellular pathology of CNS diseases and their progression within the distributed neural architecture of the brain. GLIA 40:206-217, 2002. Copyright 2002 Wiley-Liss, Inc
AD  - Department of Neuropathology, Departments of Psychiatry, Molecular Neuropsychiatry, Charing Cross Hospital, Imperial College School of Medicine, and MRC Clinical Sciences Centre (PET Neurology), Hammersmith Hospital, London, United Kingdom
UR  - PM:12379908
ER  - 

TY  - JOUR
T1  - In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion
A1  - Cagnin,A.
A1  - Myers,R.
A1  - Gunn,R.N.
A1  - Lawrence,A.D.
A1  - Stevens,T.
A1  - Kreutzberg,G.W.
A1  - Jones,T.
A1  - Banati,R.B.
Y1  - 2001/10//
N1  - UI - 21455221
SP  - 2014
EP  - 2027
JF  - Brain
VL  - 124
IS  - Pt 10
N2  - A major challenge in the assessment of brain injury and its relationship to the ensuing functional deficits is the accurate delineation of the areas of damage. Here, we test the hypothesis that the anatomical distribution pattern of activated microglia, a normally dormant population of resident brain macrophages, can be used as a surrogate marker of neuronal injury not only at the primary lesion site but also in the antero- and retrograde projection areas of the lesioned neurones. Two patients with asymmetrical herpes simplex encephalitis were serially scanned 6 and 12 months after the acute illness using PET with [11C] (R)-PK11195, a marker of activated microglia/brain macrophages. The evolving structural changes in the brain were measured by volumetric MRI and compared with the pattern of [11C](R)-PK11195 binding. Corresponding to the clinically observed cognitive deficits, quantitative [11C](R)-PK11195-PET revealed highly significant signal increases within the affected limbic system and additionally in areas connected to the limbic system by neural pathways, including the lingual gyrus in the occipital lobe and the inferior parietal lobe, which had normal morphology on structural MRI. The increased [11C](R)-PK11195 binding, signifying the presence of activated microglia, persisted many months (>12) after antiviral treatment. Cortical areas that showed early high [11C](R)-PK11195 binding subsequently underwent atrophy. These observations demonstrate that in vivo imaging of activated microglia/brain macrophages provides a dynamic measure of active tissue changes following an acute focal lesion. Importantly, the glial tissue response in the wake of neuronal damage is protracted and widespread within the confines of the affected distributed neural system and can be related to the long-term functional deficits
AD  - MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Hammersmith Hospital, UK
UR  - PM:11571219
ER  - 

TY  - JOUR
T1  - Comparative Evaluation in Nonhuman Primates of Five PET Radiotracers for Imaging the Serotonin Transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM
A1  - Huang,Y.
A1  - Hwang,D.R.
A1  - Narendran,R.
A1  - Sudo,Y.
A1  - Chatterjee,R.
A1  - Bae,S.A.
A1  - Mawlawi,O.
A1  - Kegeles,L.S.
A1  - Wilson,A.A.
A1  - Kung,H.F.
A1  - Laruelle,M.
Y1  - 2002/11//
N1  - UI - 22326495
SP  - 1377
EP  - 1398
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 11
N2  - The recent introduction of a number of new radiotracers suitable for imaging the serotonin transporters (SERT) has radically changed the field of SERT imaging. Whereas, until recently, only one selective SERT radiotracer was available ([ C]McN 5652) for SERT imaging with positron emission tomography (PET), several new C-11-labeled radiotracers of the -dimethyl-2-(arylthio)benzylamine class have been described as appropriate imaging agents for the SERT. The aim of this study was to conduct a comparative evaluation of four of the most promising agents in this class ([ C]ADAM, [ C]DASB, [ C]DAPA, and [ C]AFM) with the reference tracer [ C]McN 5652 under standardized experimental conditions. This evaluation included measurements of affinity and lipophilicity, and PET imaging experiments in baboons. DASB displayed significantly lower affinity for SERT than the other four tracers. In the blood, [ C]DASB and [ C]AFM display faster clearance and higher free fractions. Brain uptake was analyzed with kinetic modeling using a one-tissue compartment model and the metabolite-corrected arterial input function. The kinetic uptake of [ C]DASB was significantly faster compared with the other compounds, and the scan duration required to derive time-independent estimates of regional distribution volumes was shorter. [ C]DAPA exhibited the slowest brain kinetic. Regional- specific-to-nonspecific equilibrium partition coefficient (V ") was the highest for [ C]AFM, followed by [ C]DASB and [ C]DAPA, which in turn provided higher V " values than [ C]ADAM and [ C]McN 5652. From these experiments, two ligands emerged as superior radiotracers that provide a significant improvement over [ C]McN 5652 for PET imaging of SERT: [ C]DASB, because it enables the measurement of SERT availability in a shorter scanning time, and [ C]AFM, because its higher signal-to-noise ratios provide a more reliable measurement of SERT availability in brain regions with relatively low density of SERT, such as in the limbic system.(3) (3)
UR  - PM:12439295
ER  - 

TY  - JOUR
T1  - Kinetic compartment modeling of [11C]-5-hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain
A1  - Hagberg,G.E.
A1  - Torstenson,R.
A1  - Marteinsdottir,I.
A1  - Fredrikson,M.
A1  - Langstrom,B.
A1  - Blomqvist,G.
Y1  - 2002/11//
N1  - UI - 22326493
SP  - 1352
EP  - 1366
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 11
N2  - The substrate for the second enzymatic step in serotonin synthesis, 5- hydroxy-L-tryptophan, labeled in the beta-position ([11C]-HTP), was used for positron emission tomography (PET) measurements in six healthy human participants, examined on two occasions. One- and two-tissue kinetic compartment modeling of time-radioactivity curves was performed, using arterial, metabolite-corrected [11C]-HTP values as input function. The availability of unchanged tracer in arterial blood plasma was > or = 80% up to 60 minutes after injection, while [11C]- hydroxyindole acetic acid and [11C]-serotonin accounted for the remaining radioactivity, amounting to < or = 16% and < or = 4%, respectively. Compartment modeling was performed for brain stem, putamen, caudate nucleus, anterior cingulate, white matter, and superior occipital, occipitotemporal, and temporal cortices. The average biologic half-life for plasma-to-tissue equilibrium was 7 to 12 minutes, and the volume of distribution was 0.2 to 0.5 microL.mL(-1). In all regions except white matter, the kinetic compartment model that included irreversible [11C]-HTP trapping showed significantly improved model fits with respect to a one-tissue compartment model. The [11C]- HTP trapping rate constant depended on the estimated tissue availability of the serotonin precursor tryptophan, known to reflect serotonin synthesis in healthy individuals, and correlated with serotonin tissue concentration and synthesis rates reported previously in literature. These findings suggest the use of [11C]-HTP PET measurements to investigate serotonin synthesis
AD  - Uppsala University PET center, Institute of Psychiatry, Sweden. g.hagberg@hsantalucia.it
UR  - PM:12439293
ER  - 

TY  - JOUR
T1  - In Vivo Validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a Proliferation Imaging Tracer in Humans: Correlation of [(18)F]FLT Uptake by Positron Emission Tomography with Ki-67 Immunohistochemistry and Flow Cytometry in Human Lung Tumors
A1  - Vesselle,H.
A1  - Grierson,J.
A1  - Muzi,M.
A1  - Pugsley,J.M.
A1  - Schmidt,R.A.
A1  - Rabinowitz,P.
A1  - Peterson,L.M.
A1  - Vallieres,E.
A1  - Wood,D.E.
Y1  - 2002/11//
N1  - UI - 22316652
SP  - 3315
EP  - 3323
JA  - Clin.Cancer Res.
VL  - 8
IS  - 11
N2  - PURPOSE: Tumor proliferation has prognostic value in resected early stage non-small cell lung cancer (NSCLC) and can, therefore, predict which NSCLCs are at high risk for recurrence after resection and would benefit from additional therapy. It may also predict which tumor will respond to cell cycle-targeted chemotherapy and help assess the tumor response, besides helping to differentiate benign from malignant lung lesions. We evaluated whether the uptake of the new positron emission tomography (PET) tracer 3'deoxy-3'-[(18)F]fluorothymidine (FLT) in a series of suspected NSCLCs correlated with tumor proliferation assessed by Ki-67 immunohistochemistry and flow cytometry. Experimental Design: Ten patients with 11 biopsy-proven or clinically suspected NSCLC underwent 2-h dynamic PET imaging after i.v. injection of 0.07 mCi/kg FLT. Tumor FLT uptake was quantitated with the maximum pixel standardized uptake value (maxSUV), the partial volume corrected maxSUV (PV-corr-maxSUV), the average SUV over a small region-of-interest (aveSUV) and with Patlak analysis of FLT flux (aveFLTflux). The lesion diameter from computed tomography was used to correct the maxSUV for PV effects using recovery coefficients determined for the General Electric Advance PET scanner. Two of the 11 lesions were benign inflammatory lesions and 9 were NSCLCs. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all 11 tissue specimens (10 resections, 1 NSCLC percutaneous biopsy), and the S-phase fraction (SPF) from flow cytometry could be determined for 10. The specimens were reviewed for histology and cellular differentiation (poor, moderate, well). Lesions ranged from 1.6 to 7.7 cm. RESULTS: Excellent correlations were found between SUV measures of FLT uptake and Ki-67 scores [percentage of positive cells; maxSUV versus Ki-67: Rho = 0.78, P = 0.0043 (n = 11); PV-corr-maxSUV versus Ki-67: Rho = 0.83, P =
ER  - 

TY  - JOUR
T1  - Cerebral regional hypometabolism caused by propofol-induced sedation in children with severe myoclonic epilepsy: a study using fluorodeoxyglucose positron emission tomography and statistical parametric mapping
A1  - Juengling,Freimut D.
A1  - Kassubek,Jan
A1  - Martens-Le Bouar,Heike
A1  - Reinhardt,Michael J.
A1  - Krause,Thomas
A1  - Nitzsche,Egbert U.
A1  - Moser,Ernst
A1  - Korinthenberg,Rudolf
Y1  - 2002/12/25/
SP  - 79
EP  - 82
JF  - Neuroscience Letters
VL  - 335
IS  - 2
N2  - Cerebral positron emission tomography (PET) in children often requires sedation. This study evaluated sedation-associated effects on cerebral glucose metabolism in 30 children with severe myoclonic epilepsy as investigated by cerebral 18F-fluorodeoxyglucose (FDG)-PET. Prior to the PET acquisition, 24 children underwent propofol sedation. Pixel-based t-statistics were calculated using statistical parametric mapping (SPM99) for comparisons of the patients' PET scans with both a healthy adult control group and an age-matched child intra-group control. In both analyses, statistically significant hypometabolic areas were found in the medial parieto-occipital cortex bilaterally, including the lingual gyrus, cuneus, posterior cingulate and middle occipital gyrus in all sedated children. All these localizations correlated in a covariate analysis with the injected dose of propofol (P<0.01, corrected). The bilateral parieto-occipital hypometabolism is likely to be a sedation-specific effect and should be taken into account when evaluating cerebral FDG-PET scans in sedated children
UR  - http://www.sciencedirect.com/science/article/B6T0G-478B898-K/1/5e462baa14da63c9ff6a3523b1369dfe
ER  - 

TY  - JOUR
T1  - The pathology of ischemic-vascular dementia: An update
A1  - Jellinger,Kurt A.
Y1  - 2002/11/15/
SP  - 153
EP  - 157
JF  - Journal of the Neurological Sciences
VL  - 203-204
N2  - In Western memory clinic-based series, ischemic-vascular dementia (IVD) is seen in 8-10% of cognitively impaired elderly subjects. Its prevalence in autopsy series ranges from 0.03% to 58% with reasonable values of 4-10%, while in Japan, IVD is seen in 22-35% and mixed-type dementia (MTD) (Alzheimer disease/AD+IVD) in 6-11%. In a large Viennese autopsy series, "pure" IVD was observed in 9.4% of demented elderly and in 2.9% of those clinically diagnosed as possible/probable AD MTD was observed in 3.1% and 1.3% respectively. The major morphological types of IVD are multi-infarct encephalopathy (MIE), small vessel infarct type-strategic infarct dementia (SID), subcortical arteriosclerotic leukoencephalopathy (Binswanger), multilacunar state, mixed cortico-subcortical type, granular cortical atrophy, and post-ischemic encephalopathy. In contrast to previous suggestions that IVD is mainly the result of large hemispheral infarcts or losses of over 100 ml of brain tissue, recent data indicate that cognitive decline is commonly associated with widespread small ischemic or vascular lesions (microinfarcts, lacunes) throughout the brain with predominant involvement of the basal ganglia, white matter, and hippocampus. The lesion pattern of "pure" IVD, which is related to arteriolosclerosis and hypertensive microangiopathy, differs from that in mixed-type dementia, more often showing large infarcts. Although recent studies suggest that concomitant small cerebral infarcts do not significantly influence the overall rate of cognitive decline in AD patients or may be important for mental decline in early AD, both mild AD pathology and microvascular cerebral lesions appear to be common and may interact in "unmasking" or promoting dementia
UR  - http://www.sciencedirect.com/science/article/B6T06-46T49CB-3/1/9d1436b911b5bac1cd42286e62bbd490
ER  - 

TY  - JOUR
T1  - Positron emission tomography in cochlear implant and auditory brainstem implant recipients
A1  - Miyamoto,R.T.
A1  - Wong,D.
Y1  - 2001/11//
N1  - UI - 21582294
SP  - 473
EP  - 478
JA  - J Commun.Disord.
VL  - 34
IS  - 6
N2  - Positron emission tomography (PET) imaging was used to evaluate the brain's response to auditory stimulation, including speech. Five cases of adults illustrate the utility of PET to illuminate auditory processing with cochlear or brainstem implants. Subjects showed varying degrees of success in processing speech, which was reflected in the resulting PET images. Functional speech processing was associated with activation in areas classically associated with speech processing. In one patient who did not achieve functional speech processing, activation in frontal regions suggests that the subject used other cognitive strategies to assist auditory processing. Learning outcomes: As a result of this activity, the participant will be introduced to the principles of PET and the application of this technology to deaf patients who have received an implanted auditory prosthesis
AD  - Department of Otolaryngology, School of Medicine, Indiana University, Indianapolis 46202-5230, USA. rmiyamot@iupui.edu
UR  - PM:11725859
ER  - 

TY  - JOUR
T1  - Functional plasticity of language-related brain areas after cochlear implantation
A1  - Giraud,A.L.
A1  - Price,C.J.
A1  - Graham,J.M.
A1  - Frackowiak,R.S.
Y1  - 2001/07//
N1  - UI - 21301266
SP  - 1307
EP  - 1316
JF  - Brain
VL  - 124
IS  - Pt 7
N2  - Using PET, the cerebral network engaged by heard language processing in normal hearing subjects was compared with that in patients who received a cochlear implant after a period of profound deafness. The experimental conditions were words, syllables and environmental sounds, each controlled by a noise baseline. Four categories of effect were observed: (i) regions that were recruited by patients and controls under identical task conditions: the left and right superior temporal cortices and the left insula were activated in both groups in all conditions; (ii) new regions, which were recruited by patients only: the left dorsal occipital cortex showed systematic activation in all conditions versus noise baselines; (iii) regions that were recruited by both groups with a different functional specificity; e.g. Wernicke's area responded specifically to speech sounds in controls but was not specialized in patients; and (iv) regions that were activated in one group more than the other: the precuneus and parahippocampal gyrus (patients more than controls) and the left inferior frontal, left posterior inferior temporal and left and right temporoparietal junction regions (controls more than patients). These data provide evidence for altered functional specificity of the superior temporal cortex, flexible recruitment of brain regions located within and outside the classical language areas and automatic contribution of visual regions to sound recognition in implant patients
AD  - Wellcome Department of Cognitive Neurology, The Functional Imaging Laboratory, Institute of Neurology, The Royal National ENT Hospital, London, UK. Giraud@em.uni-frankfurt.de
UR  - PM:11408326
ER  - 

TY  - JOUR
T1  - Added Clinical Benefit of Incorporating 2-Deoxy-2-[18F]Fluoro-D-Glucose with Positron Emission Tomography into the Clinical Evaluation of Patients with Cognitive Impairment
A1  - Silverman,Daniel H.S.
A1  - Cummings,Jeffrey L.
A1  - Small,Gary W.
A1  - Gambhir,Sanjiv S.
A1  - Chen,Wei
A1  - Czernin,Johannes
A1  - Phelps,Michael E.
Y1  - 2002///
SP  - 283
EP  - 293
JA  - Molecular Imaging & Biology
VL  - 4
IS  - 4
N2  - Purpose: Growing evidence indicates that appropriate incorporation of positron emission tomography (PET) into the evaluation of patients with early symptoms of cognitive decline can improve diagnostic and prognostic accuracy. In the present work, an explicitly defined role for PET and its associated impact on expected clinical outcomes were systematically examined.Procedures: We compared the relative value of two strategies for assessing whether Alzheimer's disease (AD) was responsible for cognitive decline in geriatric patients, and in subsequently managing those patients according to the recommended standards of the American Academy of Neurology (AAN). The first strategy was based on an approach already endorsed by the AAN, following evidence-based reviews carried out by its quality standards subcommittee. The second approach was based on many of the same AAN recommendations--with respect to initial general medical and neurologic examination, structural imaging and laboratory tests, as well as ultimate management--but additionally incorporated PET in appropriate cases, to determine the presence or absence of a pattern of regional cerebral metabolism characteristic of AD. Clinical outcomes accruing to each strategy were calculated using formalized tools of decision analysis.Results: The strategy making use of PET increased diagnostic accuracy, yielding decreased rates of both false negative (from 8.3 to 3.1%) and false positive (from 23.0 to 11.9%) diagnoses for AD, compared with the conventional strategy. When coupled with AAN treatment recommendations for patients having (or not having) non-severe AD, these differences in diagnostic accuracy corresponded to approximately a 62% decrease in avoidable months of nursing home care, and a 48% decrease in months of unnecessary drug therapy resulting from inaccurate diagnoses. The benefit in clinical outcome of the proposed strategy was maintained over a wide range of values for sensitivity, specificity, and projected impact on need for nursing home care.Conclusion: Use of PET for evaluating early cognitive decline in geriatric patients can add valuable information to the clinical assessment, resulting in a greater number of patients being accurately diagnosed and properly treated. PET can be used to diminish disease-related and treatment-related morbidity of dementia, through earlier institution of appropriate management
UR  - http://www.sciencedirect.com/science/article/B6X15-47241KX-5/1/82e63a8af3b6ee56ff097fe845eb6ce9
ER  - 

TY  - JOUR
T1  - Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: An 18F-dopa PET study
A1  - Khan,N.L.
A1  - Valente,E.M.
A1  - Bentivoglio,A.R.
A1  - Wood,N.W.
A1  - Albanese,A.
A1  - Brooks,D.J.
A1  - Piccini,P.
Y1  - 2002/12//
N1  - UI - 22334762
SP  - 849
EP  - 853
JA  - Ann.Neurol
VL  - 52
IS  - 6
N2  - PARK6, a locus for early-onset recessive parkinsonism, has been causally implicated in nine unrelated families from four different countries. The gene is still unidentified and hence the importance of PARK6 as a cause of Parkinson's disease is unknown. To date, no pathology or functional imaging studies are available on PARK6-linked parkinsonism. We have used (18)F-dopa positron emission tomography to study four patients who are homozygous and three asymptomatic relatives who are heterozygous for PARK6. The clinically affected PARK6 subjects had a similar 85% reduction in posterior dorsal putamen (18)F-dopa uptake to a group of idiopathic Parkinson's disease patients matched for clinical disease severity and duration but showed significantly greater involvement of head of caudate and anterior putamen. The group of asymptomatic PARK6 carriers showed a significant mean 20 to 30% reduction in caudate and putamen (18)F-dopa uptake in comparison with controls, individual values falling toward the bottom of the normal range. Our results indicate that PARK6 pathology results in a more uniform loss of striatal dopamine terminal function than Parkinson's disease. The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect
AD  - Department of Molecular Pathogenesis, Institute of Neurology, London, United Kingdom
UR  - PM:12447943
ER  - 

TY  - JOUR
T1  - Schwannoma of the extremities: the role of PET in preoperative planning
A1  - Ahmed,A.R.
A1  - Watanabe,H.
A1  - Aoki,J.
A1  - Shinozaki,T.
A1  - Takagishi,K.
Y1  - 2001/10//
N1  - UI - 21543636
SP  - 1541
EP  - 1551
JA  - Eur.J Nucl Med
VL  - 28
IS  - 10
N2  - The aim of this study was to determine the relative utility of various preoperative diagnostic imaging modalities for the evaluation of benign schwannoma, including positron emission tomography (PET) utilising fluorine-18 fluoro-2-deoxy-D-glucose (FDG) and fluorine- 18 alpha-methyl tyrosine (FMT). computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). We retrospectively reviewed imaging findings in 22 patients with 25 histopathologically documented benign schwannomas of the extremities. Pre-operative imaging included: FDG-PET (n=22), FMT-PET (n=17), MRI (n=25), CT (n=16) and DSA (n=17). All 22 lesions examined by PET with FDG and/or FMT showed accumulation. The standardised uptake values (SUVs) for FDG-PET for the 22 examined tumours ranged from 0.33 to 3.7, and eight of them (36.4%) were assessed as malignant on the basis of their uptake. The SUVs for FMT ranged from 0.44 to 1.47, and 15 out of the 17 evaluated (88.2%) showed values indicating the tumour to be benign. CT demonstrated variable attenuation and contrast enhancement. MRI signal characteristics were relatively consistent: iso-signal or darker than skeletal muscle on T1-weighted and isosignal or brighter than subcutaneous fat on T2-weighted images. The venous tumour staining depicted on DSA was found to be significantly correlated with FDG accumulation. All tumours but one were treated by surgical enucleation. One tumour suspected to be malignant on the basis of imaging findings was treated with primary wide resection. Although CT, MRI and PET studies are all useful for the detection and localisation of schwannoma, our findings suggest that, among the imaging modalities studied, FMT-PET may be the most reliable technique for the differentiation of benign schwannoma from malignancy
AD  - Department of Orthopedic Surgery, Gunma University Faculty of Medicine, Showa, Maebashi, Gunma, Japan
UR  - PM:11685498
ER  - 

TY  - JOUR
T1  - Combined diagnostic imaging for retroperitoneal schwannoma
A1  - Hirai,K.
A1  - Umesaki,N.
A1  - Sumi,T.
A1  - Ishiko,O.
A1  - Kanaoka,Y.
A1  - Ogita,S.
A1  - Koyama,K.
A1  - Kawabe,J.
A1  - Okamura,T.
A1  - Ochi,H.
Y1  - 2001/07//
N1  - UI - 21304089
SP  - 773
EP  - 775
JA  - Oncol.Rep.
VL  - 8
IS  - 4
N2  - Retroperitoneal tumors are occasionally encountered by gynecologists, and differential diagnosis from adnexal tumors is important, however, it is difficult in many cases. We report a case in which we preoperatively diagnosed a benign solid tumor in the retroperitoneum of the pelvic cavity on the basis of a variety of diagnostic images, including FDG-PET. Postoperative histological examination showed a benign schwannoma in the pelvis. We discuss the usefulness of FDG-PET combined with MRI and other diagnostic images as a means of differentiating between the characteristics of retroperitoneal tumors
AD  - Department of Obstetrics and Gynecology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. hiraik@med.osaka-cu.ac.jp
UR  - PM:11410781
ER  - 

TY  - JOUR
T1  - High FDG uptake in a schwannoma: a PET study
A1  - Shah,N.
A1  - Sibtain,A.
A1  - Saunders,M.I.
A1  - Townsend,E.
A1  - Wong,W.L.
Y1  - 2000/01//
N1  - UI - 20129121
SP  - 55
EP  - 56
JA  - J Comput.Assist.Tomogr.
VL  - 24
IS  - 1
AD  - Marie Curie Research Wing, Mount Vernon Hospital, Northwood, UK
UR  - PM:10667659
ER  - 

TY  - JOUR
T1  - Inter-modality comparisons of seizure focus lateralization in complex partial seizures
A1  - Meyer,P.T.
A1  - Cortes-Blanco,A.
A1  - Pourdehnad,M.
A1  - Levy-Reis,I.
A1  - Desiderio,L.
A1  - Jang,S.
A1  - Alavi,A.
Y1  - 2001/10//
SP  - 1529
EP  - 1540
JA  - Eur.J Nucl Med
VL  - 28
IS  - 10
N2  - Anterior temporal lobectomy offers a high chance of seizure-free outcome in patients suffering from drug-refractory complex partial seizure (CPS) originating from the temporal lobe. Other than EEG, several functional and morphologic imaging methods are used to define the spatial seizure origin. The present study was undertaken to compare the merits of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) and single-voxel proton MR spectroscopy (MRS) for the lateralization of temporal lobe seizure foci. The clinical charts and imaging data of 43 consecutive CPS patients were reviewed. Based on surface EEG, 31 patients were classified with temporal lobe epilepsy (TLE; 25 lateralized, 6 not lateralized) and 12 with non-temporal lobe epilepsy. All were examined by FDG-PET, MRS and MRI within 6 weeks. FDG-PET and MRI were interpreted visually, while the N-acetyl-aspartate to creatine ratio was used for MRS interpretation. One FDG-PET scan was invalid due to seizure activity post injection. The MR spectra could not be evaluated in five cases bilaterally and three cases unilaterally for technical reasons. A total of 15 patients underwent anterior temporal lobectomy. All showed a beneficial postoperative outcome. When the proportions of agreement between FDG-PET (0.77), MRI (0.58) and MRS (0.56) and surface EEG in TLE cases were compared, there were no significant differences (P>0.10). However, FDG-PET showed a significantly higher agreement (0.93) than MRI (0.60; P=0.03) with the side of successful temporal lobectomy. The concordance of MRS with the side of successful temporal lobectomy was intermediate (0.75). When the results of functional and morphologic imaging were combined, no significant differences were found between the rates of agreement of FDG-PET/MRI and MRS/MRI with EEG (0.80 vs 0.68; P=0.50) and with the side of successful temporal lobectomy (0.87 vs 0.92; P=0.50) in TLE cases. However, MRS/MRI showed significantly more lateralized temporal lobe abnormalities in non-temporal lobe epilepsy cases than FDG-PET/MRI (0.90 vs. 0.17; P<0.01). Although FDG-PET seems to be the most reliable and stable method for this purpose, we conclude that in TLE cases it may be justified to perform MRS, which is less expensive, faster and has no radiation exposure, in combination with MRI before FDG-PET, since FDG-PET offers little additional diagnostic information if MRS and MRI indicate the same seizure focus lateralization
AD  - Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA
UR  - PM:11685497
ER  - 

TY  - JOUR
T1  - First symptoms--frontotemporal dementia versus Alzheimer's disease
A1  - Lindau,M.
A1  - Almkvist,O.
A1  - Kushi,J.
A1  - Boone,K.
A1  - Johansson,S.E.
A1  - Wahlund,L.O.
A1  - Cummings,J.L.
A1  - Miller,B.L.
Y1  - 2000/09//
N1  - UI - 20400799
SP  - 286
EP  - 293
JA  - Dement.Geriatr.Cogn Disord.
VL  - 11
IS  - 5
N2  - Frontotemporal dementia (FTD) is often misdiagnosed as Alzheimer's disease (AD). We hypothesized that the first symptoms associated with FTD would be different from those seen in AD and that the first symptoms in FTD would reflect loss of function in the frontal region with the greatest degree of degeneration. The objective of the study was to compare the earliest symptoms in patients with FTD and AD, and to delineate the symptoms that were associated with right, left or bilateral frontotemporal degeneration in FTD. The first symptoms in 52 FTD and 101 AD patients were determined in retrospect. Based on functional imaging studies, the FTD patients were divided into those with predominantly bilateral (n = 15), left-sided (n = 19) and right-sided (n = 18) patterns of atrophy. The results showed that disinhibition, social awkwardness, passivity and loss of executive function were more common in FTD, while memory loss was more common in AD. Disinhibition was greatest in the asymmetric right-sided group, language dysfunction was commonest in the asymmetric left-sided group and loss of executive function was most frequent in the bilateral group. In summary, different first symptoms appeared in FTD and AD, which may help distinguish between the diseases. The anatomic site for FTD largely determined the kind of first symptoms
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden
UR  - PM:10940680
ER  - 

TY  - JOUR
T1  - Long-term frontal brain metabolic changes in cocaine abusers
A1  - Volkow,N.D.
A1  - Hitzemann,R.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Dewey,S.L.
A1  - Handlesman,L.
Y1  - 1992/07//
N1  - [erratum appears in Synapse 1992 Sep;12(1):86]
SP  - 184
EP  - 190
JF  - Synapse
VL  - 11
IS  - 3
N2  - Neurological complications from cocaine use are well recognized. We propose that chronic cocaine use can also cause clinically silent brain dysfunction. We investigated brain glucose metabolism with positron emission tomography (PET) and 2-deoxy-2[18F] fluoro-D-glucose (FDG) in 21 neurologically intact chronic cocaine abusers (C) and 18 normal controls (N). The cocaine abusers were tested 1-6 weeks after the last use of cocaine and seven were retested after a 3 month drug-free period. Global cerebral glucose metabolism was not significantly different between controls and cocaine abusers (N = 38.4 +/- 3, C = 36.5 +/- 5 mumol/100 g of tissue, min). However, cocaine abusers had significantly (P less than 0.05) lower metabolic activity in 16 of the 21 left frontal regions and 8 of the 21 right frontal regions. These decreases persisted after 3-4 months of detoxification and were correlated with the dose (P less than or equal to 0.01) and the years of cocaine use (P less than or equal to 0.05). This study shows reduced rates of frontal metabolism in neurologically intact cocaine abusers that persist even after 3-4 months of detoxification
AD  - Brookhaven National Laboratory, Upton, New York 11973
UR  - PM:1636149
ER  - 

TY  - JOUR
T1  - Transient global amnesia: concomitant episodic memory and positron emission tomography assessment in two additional patients
A1  - Guillery,B.
A1  - Desgranges,B.
A1  - de,la Sayette,V
A1  - Landeau,B.
A1  - Eustache,F.
A1  - Baron,J.C.
Y1  - 2002/05/31/
N1  - UI - 22018353
SP  - 62
EP  - 66
JA  - Neurosci.Lett.
VL  - 325
IS  - 1
N2  - Transient global amnesia (TGA) is characterized by a profound but transient deficit of episodic memory. The study of cerebral blood flow and oxygen metabolism with positron emission tomography (PET) provides relevant pathophysiologic data, but only three patients have been reported so far and in only one was concomitant neuropsychological testing performed. We report here the concomitant neuropsychological and PET assessment of two additional patients. Episodic disturbance was characterized by a storage disturbance for one case and an incapacity to learn episodic associations in the other, illustrating cognitive heterogeneity despite similar neurological presentation. PET findings disclosed mild but significant changes in the amygdala (right or left) and left posterior hippocampus, which could account for both the storage disturbance and the inability to associate episodic components. The PET findings also argued in favor of a vascular disturbance accompanying TGA
UR  - PM:12023067
ER  - 

TY  - JOUR
T1  - The neural substrates of episodic memory impairment in Alzheimer's disease as revealed by FDG-PET: relationship to degree of deterioration
A1  - Desgranges,B.
A1  - Baron,J.C.
A1  - Lalevee,C.
A1  - Giffard,B.
A1  - Viader,F.
A1  - de,la Sayette,V
A1  - Eustache,F.
Y1  - 2002/05//
SP  - 1116
EP  - 1124
JF  - Brain
VL  - 125
IS  - Pt 5
N2  - In a previous investigation, we raised the hypothesis that in Alzheimer's disease the cerebral structures implicated in episodic memory deficits may differ according to the severity of cognitive impairment. To test this hypothesis, Story Recall test scores and PET measurements of resting cerebral glucose utilization, a measure of synaptic integrity, were obtained in 40 patients. Using SPM96 (statistical parametric mapping 1996), positive correlations between the two sets of data were calculated on a voxel basis, first in the whole patient sample and then separately in the two subgroups of 20 patients differing in Mini-Mental State Examination score, i.e. those with least impaired and those with most impaired performance ('less severe' and 'more severe' subgroups, respectively). In the whole sample, significant correlations (P < 0.05, corrected for multiple tests) involved bilaterally not only several limbic structures (the hippocampal/rhinal cortex regions, posterior cingulate gyrus and retrosplenial cortex) but also, and less expectedly, some temporo-occipital association areas. However, the subgroup analysis disclosed that, in the less severe subgroup, all significant correlations (P < 0.005, uncorrected) were restricted to the parahippocampal gyrus and retrosplenial cortex, in accordance with both the distribution of changes in tau in early Alzheimer's disease and the known involvement of this network in normal and impaired memory function, while in the more severe subgroup they mainly involved the left temporal neocortex, which is known to be implicated in semantic memory. These findings suggest that, when episodic memory is mildly impaired, limbic functions are still sufficient to subserve the remaining performance, whereas with more severe memory deficit resulting from accumulated pathology the neocortical areas that are normally involved in semantic memory are recruited, perhaps as a form of (inadequate) compensatory mechanism
AD  - EMI INSERM-Unive Laboratoire de Neuropsychologie, CHU Cote de Nacre, Centre CYCERON, France. desgranges-b@chu-caen.fr
UR  - PM:11960900
ER  - 

TY  - JOUR
T1  - Cerebral perfusion in chronic fatigue syndrome and depression
A1  - MacHale,S.M.
A1  - Lawrie,S.M.
A1  - Cavanagh,J.T.
A1  - Glabus,M.F.
A1  - Murray,C.L.
A1  - Goodwin,G.M.
A1  - Ebmeier,K.P.
Y1  - 2000/06//
N1  - UI - 20430660
SP  - 550
EP  - 556
JA  - Br.J Psychiatry
VL  - 176
N2  - BACKGROUND: Patients with chronic fatigue syndrome (CFS) and depressive illness share many, but not all, features. AIMS: To test the hypothesis that patients with CFS have abnormal cerebral perfusion, that differs from that in patients with depressive illness. METHOD: We recruited 30 patients with CFS who were not depressed, 12 depressed patients and 15 healthy volunteers. Regional cerebral perfusion at rest was assessed using region of interest (ROI) and voxel-based statistical parametric mapping (SPM) techniques. RESULTS: On SPM analysis there was increased perfusion in the right thalamus, pallidum and putamen in patients with CFS and in those with depressive illness. CFS patients also had increased perfusion in the left thalamus. Depressed patients differed from those with CFS in having relatively less perfusion of the left prefrontal cortex. The results were similar on ROI analysis. CONCLUSIONS: Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients with depressive illness. Thalamic overactivity may be a correlate of increased attention to activity in CFS and depression; reduced prefrontal perfusion in depression may be associated with the greater neuropsychological deficits in that disorder
AD  - University Department of Psychiatry, Royal Edinburgh Hospital
UR  - PM:10974961
ER  - 

TY  - JOUR
T1  - Searching for a baseline: functional imaging and the resting human brain
A1  - Gusnard,D.A.
A1  - Raichle,M.E.
A1  - Raichle,M.E.
Y1  - 2001/10//
N1  - UI - 21468446
SP  - 685
EP  - 694
JA  - Nat.Rev.Neurosci.
VL  - 2
IS  - 10
N2  - Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function
AD  - The Mallinckrodt Institute of Radiology, Washington University, St Louis, Missouri 63110, USA
UR  - PM:11584306
ER  - 

TY  - JOUR
T1  - Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety
A1  - Simpson,J.R.,Jr.
A1  - Drevets,W.C.
A1  - Snyder,A.Z.
A1  - Gusnard,D.A.
A1  - Raichle,M.E.
Y1  - 2001/01/16/
N1  - UI - 21143370
SP  - 688
EP  - 693
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 98
IS  - 2
N2  - Regional cerebral blood flow (BF) was examined in the human medial prefrontal cortex (MPFC) with positron emission tomography during anticipatory anxiety. Transient anxiety was induced in normal subjects by having them anticipate a painful shock to the fingers of one hand. BF was decreased during anticipatory anxiety, relative to an eyes-closed resting condition, in two regions of the MPFC (Brodmann Areas 10/32 and 24/25). BF decreases in these areas were inversely correlated with anxiety self rating, such that the least anxious subjects exhibited the largest BF reductions, whereas the most anxious subjects showed no significant BF reduction or a slight increase. BF changes in MPFC and in the midbrain were correlated with each other and with anxiety self rating. These results are consistent with the hypothesis that BF reductions in MPFC, previously observed in cognitive tasks, reflect a dynamic balance between focused attention and subject anxiety and may occur from a functionally active baseline or default state. The characterization of such relationships within the human brain enables new insights into the integration of cognition and emotion
AD  - Mallinckrodt Institute of Radiology, and Departments of Anatomy and Neurobiology, Psychiatry and Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
UR  - PM:11209066
ER  - 

TY  - JOUR
T1  - Increased prevalence of vascular dementia in Japan: a community-based epidemiological study
A1  - Ikeda,M.
A1  - Hokoishi,K.
A1  - Maki,N.
A1  - Nebu,A.
A1  - Tachibana,N.
A1  - Komori,K.
A1  - Shigenobu,K.
A1  - Fukuhara,R.
A1  - Tanabe,H.
Y1  - 2001/09/11/
N1  - UI - 21436224
SP  - 839
EP  - 844
JF  - Neurology
VL  - 57
IS  - 5
N2  - BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation
AD  - Department of Neuropsychiatry, Ehime University School of Medicine, Japan. mikeda@m.ehime-u.ac.jp
UR  - PM:11552014
ER  - 

TY  - JOUR
T1  - Effect of tetrabenazine on the striatal uptake of exogenous L-DOPA in vivo: a PET study in young and aged rhesus monkeys
A1  - DeJesus,O.T.
A1  - Shelton,S.E.
A1  - Roberts,A.D.
A1  - Nickles,R.J.
A1  - Holden,J.E.
Y1  - 2002/06/15/
SP  - 246
EP  - 251
JF  - Synapse
VL  - 44
IS  - 4
N2  - The effect of tetrabenazine (TBZ) pretreatment on the striatal uptake of exogenous L-DOPA in vivo was assessed noninvasively in rhesus monkeys by positron emission tomography (PET) using the tracer [(18)F]-FluoroDOPA (FDOPA). Paired studies were done comparing baseline vs. TBZ treatment on the uptake of FDOPA, a measure of aromatic L-amino acid decarboxylase (AAAD) activity. Results show increased AAAD activity with TBZ treatment. These results suggest that the action of TBZ as a dopamine antagonist dominates more than its expected action as a potent vesicular monoamine transporter (VMAT2) inhibitor. Results also showed diminished responsivity of AAAD to TBZ challenge in aged monkey brain
AD  - Medical Physics Department, University of Wisconsin Medical School, 1530 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA. odejesus@facstaff.wisc.edu
UR  - PM:11984859
ER  - 

TY  - JOUR
T1  - PET imaging of dopamine transporters in the human brain using [(11)C]-beta-CPPIT, a cocaine derivative lacking the 2 beta-ester function
A1  - Schonbachler,R.D.
A1  - Gucker,P.M.
A1  - Arigoni,M.
A1  - Kneifel,S.
A1  - Vollenweider,F.X.
A1  - Buck,A.
A1  - Burger,C.
A1  - Berthold,T.
A1  - Bruhlmeier,M.
A1  - Schubiger,P.A.
A1  - Ametamey,S.M.
Y1  - 2002/01//
SP  - 19
EP  - 27
JA  - Nucl Med Biol.
VL  - 29
IS  - 1
N2  - The compound 3 beta-(4'-chlorophenyl)-2 beta-(3'-phenylisoxazol-5'-yl)tropane (CPPIT or RTI 177) is a 2beta-heterocyclic substituted cocaine congener with high in vitro selectivity and affinity for the dopamine transporter relative to serotonin and norepinephrine transporters. The aim of the present study was to evaluate the in vivo selectivity of [(11)C]-beta-CPPIT and to determine whether [(11)C]-beta-CPPIT may be a suitable alternative to existing DAT PET radioligands. [(11)C]-beta-CPPIT was prepared by N-alkylation of the free amine with [(11)C]methyl iodide. In mouse brain, the striatal binding of [(11)C]-beta-CPPIT was reduced significantly by preinjecting the dopamine reuptake antagonist GBR 12909 (5 mg/kg). By contrast, radioactivity uptake in the brain was not affected significantly by the preinjection of citalopram (5 mg/kg) and desipramine (5 mg/kg), inhibitors for the serotonin and norepinephrine transporters, respectively. No effect was also observed by pretreatment with ketanserin (2.5 mg/kg) a compound with high affinity for the 5-HT(2A)-receptor and the vesicular monoamine transporter. In a PET study with six healthy volunteers high striatal uptake was observed. The distribution pattern of [(11)C]-beta-CPPIT was similar to the known distribution of the dopamine transporter in the human brain. Compared to (123)I labeled beta-CIT, the rate of metabolic degradation of [(11)C]-beta-CPPIT was almost twofold slower suggesting that bioisosteric heterocyclic substitution of the ester group at the 2 beta-position of the tropane ring does have an influence on the rate of metabolism of [(11)C]-beta-CPPIT. The rank order of the distribution volumes obtained via the one-tissue compartment model is also similar to the reported distribution of DAT. These preliminary results suggest that [(11)C]-beta-CPPIT may be a useful PET radioligand for the visualization and quantification of dopamine transporters in man
AD  - Center for Radiopharmaceutical Science, 5232 Villigen PSI, Switzerland
UR  - PM:11786272
ER  - 

TY  - JOUR
T1  - Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+)[11C]dihydrotetrabenazine and positron emission tomography
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Adams,K.M.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Johnson-Greene,D.
A1  - Martorello,S.
A1  - Heumann,M.
A1  - Bandekar,R.
Y1  - 1998/09//
SP  - 326
EP  - 333
JA  - Ann.Neurol
VL  - 44
IS  - 3
N2  - We used (+)[11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter, with positron emission tomography to study striatal monoaminergic presynaptic terminals in 7 male severe chronic alcoholic subjects without Wernicke-Korsakoff disease compared with 7 male normal controls of similar ages. We found reduced specific binding in the caudate nucleus and putamen in the alcoholic group, and the difference reached significance in the putamen. Specific binding was not decreased in the thalamus, which was examined as a reference structure. We also detected deficits in blood-to-brain transfer rate, K1, in the same regions of the alcoholic group, with a significant difference in the putamen. K1 was unchanged in the thalamus. The finding of reduced striatal VMAT2 in severe chronic alcoholic patients suggests that nigrostriatal monoaminergic terminals are reduced, with or without loss of neurons from the substantia nigra. The findings suggest that the damaging effects of severe chronic alcoholism on the central nervous system are more extensive than previously considered
AD  - Department of Neurology, University of Michigan, and University of Michigan Alcohol Research Center, Ann Arbor, USA
UR  - PM:9749598
ER  - 

TY  - JOUR
T1  - The nucleus basalis of Meynert in multi-infarct (vascular) dementia
A1  - Mann,D.M.
A1  - Yates,P.O.
A1  - Marcyniuk,B.
Y1  - 1986///
N1  - UI - 87096415
SP  - 332
EP  - 337
JA  - Acta Neuropathol.(Berl)
VL  - 71
IS  - 3-4
N2  - The number and nucleolar volume of nerve cells within the nucleus basalis of Meynert were estimated in 10 patients with Alzheimer's disease, 12 with multi-infarct dementia, 9 with a mixed Alzheimer/multi-infarct dementia and in 10 age-matched controls. As reported previously in Alzheimer's disease, both the number and nucleolar volume of surviving cells was reduced, whereas in multi-infarct dementia no significant change in either measure was noted. In patients with Alzheimer's disease/multi-infarct dementia the loss of nerve cells and reduction in nucleolar volume varied greatly in severity from patient to patient according to the relative balance of Alzheimer and vascular type pathological changes present within each patient
UR  - PM:3799146
ER  - 

TY  - JOUR
T1  - Pick's disease, frontotemporal dementia, and Pick complex: emerging concepts
A1  - Kertesz,A.
A1  - Munoz,D.
Y1  - 1998/03//
N1  - Tab1: C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LECTURE\Kertesz-Pick-complex.doc
SP  - 302
EP  - 304
JA  - Arch.Neurol
VL  - 55
IS  - 3
AD  - Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada
UR  - PM:9520003
ER  - 

TY  - JOUR
T1  - Ictal SPECT in children with epilepsy: comparison with intracranial EEG and relation to postsurgical outcome
A1  - Kaminska,A.
A1  - Chiron,C.
A1  - Ville,D.
A1  - Dellatolas,G.
A1  - Hollo,A.
A1  - Cieuta,C.
A1  - Jalin,C.
A1  - Delalande,O.
A1  - Fohlen,M.
A1  - Vera,P.
A1  - Soufflet,C.
A1  - Dulac,O.
Y1  - 2003/01/01/
SP  - 248
EP  - 260
JF  - Brain
VL  - 126
IS  - 1
N2  - In order to validate the ability of ictal single photon emission computed tomography (SPECT) to localize the epileptogenic zone (EZ) in children, we compared in 20 patients aged from 10 months to 17 years (mean 6.5 years) the topography of the area of increased ictal perfusion (IPA), determined on the basis of ictal minus interictal scan values, with that of the EZ determined by intracranial EEG recordings and assessed its relationship with the postsurgical outcome. Eighteen patients had symptomatic epilepsy and 10 had extratemporal epilepsy. All patients except one had an ictal injection (mean time lag from clinical seizure onset was 18 s). Ictal and interictal SPECT images were successively co-registered, normalized, subtracted, smoothed and superimposed on MRI. All patients with ictal injection exhibited one or several IPAs. The topography of the highest' IPA, i.e. the maximal cerebral blood flow (CBF) change between ictal and interictal SPECT, significantly colocalized with the site of onset of the discharge, and that of the lower IPAs with that of the area of propagation (P < 0.0001). At a threshold of 30% of the maximal CBF change, the IPAs detected the onset of the discharge with a sensitivity of 0.80 and a specificity of 0.70. The highest IPA localized the EZ in 12 out of 15 patients. In the three others it missed the EZ and showed the area of propagation because of rapid seizure propagation or of infraclinical seizure onset. Among the patients with favourable surgery outcome, the highest IPA colocalized with the resected area in 70% of cases. Ictal SPECT could therefore plays an important role as a non-invasive presurgical method of investigation by optimizing the placement of intracranial electrodes, thus improving the postsurgery outcome of paediatric partial epilepsy
UR  - http://brain.oupjournals.org/cgi/content/abstract/126/1/248
ER  - 

TY  - JOUR
T1  - Neural systems and cue-induced cocaine craving
A1  - Bonson,K.R.
A1  - Grant,S.J.
A1  - Contoreggi,C.S.
A1  - Links,J.M.
A1  - Metcalfe,J.
A1  - Weyl,H.L.
A1  - Kurian,V.
A1  - Ernst,M.
A1  - London,E.D.
Y1  - 2002/03//
N1  - UI - 21839738
SP  - 376
EP  - 386
JF  - Neuropsychopharmacology
VL  - 26
IS  - 3
N2  - We have extended our previous work investigating the neural correlates of cue-induced cocaine craving through the use of positron emission tomography with greater spatial resolution (<4.6 mm), an evocative script, and a pixel-by-pixel analysis. Craving and cerebral glucose metabolism were measured after presentation of cocaine-related or neutral cues to 11 cocaine abusers. Cocaine cues elicited a higher degree of craving than has been previously reported and resulted in left hemispheric activation of lateral amygdala, lateral orbitofrontal cortex, and rhinal cortex and right hemispheric activation of dorsolateral prefrontal cortex and cerebellum. The intensity of activation in these areas (except cerebellum), as well as left insula, was also correlated with craving. Deactivation occurred in left ventral pole and left medial prefrontal cortex. The results suggest that induction of drug craving involves a neural network that assigns incentive motivational value to environmental stimuli through the coactivation of brain regions that process information about memories and emotions
AD  - Brain Imaging Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. bonsonk@cder.fda.gov
UR  - PM:11850152
ER  - 

TY  - JOUR
T1  - Evaluation of 11C-colchicine for PET imaging of multiple drug resistance
A1  - Levchenko,A.
A1  - Mehta,B.M.
A1  - Lee,J.B.
A1  - Humm,J.L.
A1  - Augensen,F.
A1  - Squire,O.
A1  - Kothari,P.J.
A1  - Finn,R.D.
A1  - Leonard,E.F.
A1  - Larson,S.M.
Y1  - 2000/03//
N1  - UI - 20179069
SP  - 493
EP  - 501
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 41
IS  - 3
N2  - Overexpression of P-glycoprotein (P-gp) can confer multiple drug resistance (MDR) phenotype on cancer cells and tumors by reducing intracellular accumulation of various cytotoxic agents. Early diagnosis of MDR in the clinic will serve to improve the efficacy of chemotherapeutic intervention and the quality of life of patients. In this article we describe use of a positron-emitting MDR tracer, 11C-colchicine (CHC), to evaluate MDR by PET imaging. Unlike existing MDR tracers such as 99mTc-sestamibi, this compound is electroneutral, with biodistribution not affected by perturbations of membrane potential. METHODS: In vitro studies showed that resistance to CHC is correlated to resistance to Taxol (paclitaxel). The results of biodistribution experiments were found to be consistent with previously reported experiments with CHC labeled with other isotopes. On the basis of in vitro experiments with a series of drug-resistant variants of the human neuroblastoma BE (2)-C cell line, a mathematic model of 11C-CHC distribution in tumors was formulated. Dynamic PET 11C-CHC imaging experiments were performed with nude rats xenografted with the BE (2)-C-sensitive and -resistant strains. Each scan was accompanied by a transmissions scan and a static FDG scan. These scans allowed improved image localization. RESULTS: We observed an approximately 2-fold difference between 11C-CHC accumulation in sensitive and resistant tumors. Imaging data were analyzed using the mathematic model, and various parameters characterizing resistance could be identified and estimated. In particular, the parameter r, proportional to the level of resistance of the tumors, was obtained. We showed that the ratio of these r parameters determined from the sensitive and resistant tumors was identical to the ratio of CHC accumulation in the corresponding sensitive and resistant cell lines used for xenografting. CONCLUSION: These in vivo experiments provided additional evidence for the indirect effect of P-gp action on CHC-to-tubulin binding, which in turn determines CHC uptake in tumors. The significance of these findings and future plans is discussed
AD  - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
UR  - PM:10716325
ER  - 

TY  - JOUR
T1  - Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain
A1  - Fischl,B.
A1  - Salat,D.H.
A1  - Busa,E.
A1  - Albert,M.
A1  - Dieterich,M.
A1  - Haselgrove,C.
A1  - Van der Kouwe,A.
A1  - Killiany,R.
A1  - Kennedy,D.
A1  - Klaveness,S.
A1  - Montillo,A.
A1  - Makris,N.
A1  - Rosen,B.
A1  - Dale,A.M.
Y1  - 2002/01/31/
N1  - UI - 21822657
SP  - 341
EP  - 355
JF  - Neuron
VL  - 33
IS  - 3
N2  - We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease
AD  - Massachusetts General Hospital, Nuclear Magnetic Resonance Center, Rm. 2328, Building 149, 13th Street, Charlestown, MA 02129, USA
UR  - PM:11832223
ER  - 

TY  - JOUR
T1  - Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease
A1  - Shoghi-Jadid,K.
A1  - Small,G.W.
A1  - Agdeppa,E.D.
A1  - Kepe,V.
A1  - Ercoli,L.M.
A1  - Siddarth,P.
A1  - Read,S.
A1  - Satyamurthy,N.
A1  - Petric,A.
A1  - Huang,S.C.
A1  - Barrio,J.R.
Y1  - 2002/01//
SP  - 24
EP  - 35
JA  - Am.J Geriatr.Psychiatry
VL  - 10
IS  - 1
N2  - The authors used 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononi trile ([18F]FDDNP), a hydrophobic radiofluorinated derivative of 2-(1-[6-(dimethylamino)-2-naphthyl]ethylidene)malononitrile (DDNP), in conjunction with positron emission tomography to determine the localization and load of neurofibrillary tangles (NFTs) and beta-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. Previous work illustrated the in vitro binding characteristics of [18F]FDDNP to synthetic beta-amyloid(1-40) fibrils and to NFTs and APs in human AD brain specimens. In the present study, greater accumulation and slower clearance was observed in AP- and NFT-dense brain areas and correlated with lower memory performance scores. The relative residence time of the probe in brain regions affected by AD was significantly greater in patients with AD (n=9) than in control subjects (n=7; p=0.0007). This noninvasive technique for monitoring AP and NFT development is expected to facilitate diagnostic assessment of patients with AD and assist in response-monitoring during experimental treatments
AD  - Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA, USA
UR  - PM:11790632
ER  - 

TY  - JOUR
T1  - Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease
A1  - Agdeppa,E.D.
A1  - Kepe,V.
A1  - Liu,J.
A1  - Flores-Torres,S.
A1  - Satyamurthy,N.
A1  - Petric,A.
A1  - Cole,G.M.
A1  - Small,G.W.
A1  - Huang,S.C.
A1  - Barrio,J.R.
Y1  - 2001/12/15/
SP  - RC189
JA  - J Neurosci.
VL  - 21
IS  - 24
N2  - Senile plaques (SPs) and neurofibrillary tangles (NFTs) are hallmark pathologies accompanying the neurodegeneration involved in Alzheimer's disease (AD), for which beta-amyloid (Abeta) peptide is a major constituent of SPs. Our laboratories previously developed the hydrophobic, fluorescent molecular-imaging probe 2-(1-(6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malono nitrile ([(18)F]FDDNP), which crosses the blood-brain barrier and determines the localization and load of SPs and NFTs in vivo in AD patients. In this report, we used fluorimetric and radioactive binding assays to determine the binding affinities of FDDNP and its analog, 1-(6-[(2-[(18)F]fluoroethyl)(methyl)amino]naphthalen-2-yl)ethanone ([(18)F]FENE), to synthetic fibrils of Abeta(1-40). FDDNP and FENE both appeared to bind to two kinetically distinguishable binding sites on Abeta(1-40) fibrils. Fluorescence titrations yielded apparent K(d) values of 0.12 and 0.16 nm for high-affinity binding sites for FDDNP and FENE, respectively, and apparent K(d) values of 1.86 and 71.2 nm for the low-affinity binding sites. The traditional radioactive binding assays also produced apparent K(d) values in the low nanomolar range. The presence of two kinetically distinguishable binding sites for FDDNP and FENE suggests multiple binding sites for SPs and identifies the parameters that allow for the structural optimization of this family of probes for in vivo use. The high-affinity binding of the probes to multiple binding sites on fibrils are consistent with results obtained with digital autoradiography, immunohistochemistry, and confocal fluorescence microscopy using human brain specimens of AD patients
AD  - Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Agdeppa-FDDNP-Binding.pdf
ER  - 

TY  - JOUR
T1  - Imaging brain cholinergic activity with positron emission tomography: its role in the evaluation of cholinergic treatments in Alzheimer's dementia
A1  - Volkow,N.D.
A1  - Ding,Y.S.
A1  - Fowler,J.S.
A1  - Gatley,S.J.
Y1  - 2001/02/01/
N1  - UI - 21141932
SP  - 211
EP  - 220
JA  - Biol.Psychiatry
VL  - 49
IS  - 3
N2  - One of the strategies in the treatment of Alzheimer's disease is the use of drugs that enhance cholinergic brain function, since it is believed that cholinergic dysfunction is one of the factors that contributes to cognitive deterioration. Positron emission tomography is a medical imaging method that can be used to measure the concentration, kinetics, and distribution of cholinergic-enhancing drugs directly in the human brain and assess the effects of the drugs at markers of cholinergic cell viability (vesicular transporters, acetylcholinesterase), at muscarininc and nicotinic receptors, at extracellular acetylcholine, at markers of brain function (glucose metabolism and blood flow), and on amyloid plaque burden in vivo in the brains of patients with Alzheimer's disease. In addition, these measures can be applied to assess the drugs' pharmacokinetic and pharmacodynamic properties in the human brain. Since the studies are done in living human subjects, positron emission tomography can evaluate the relationship between the drugs' biological, behavioral, and cognitive effects; monitor changes in brain function in response to chronic treatment; and determine if pharmacologic interventions are neuroprotective. Moreover, because positron emission tomography has the potential to identify Alzheimer's disease during early disease, it can be used to establish whether early interventions can prevent or delay further development
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:11230872
ER  - 

TY  - JOUR
T1  - In vivo serotonin 5HT(2A) receptor binding and personality traits in healthy subjects: a positron emission tomography study
A1  - Moresco,F.M.
A1  - Dieci,M.
A1  - Vita,A.
A1  - Messa,C.
A1  - Gobbo,C.
A1  - Galli,L.
A1  - Rizzo,G.
A1  - Panzacchi,A.
A1  - De Peri,L.
A1  - Invernizzi,G.
A1  - Fazio,F.
Y1  - 2002/11//
N1  - UI - 22302641
SP  - 1470
EP  - 1478
JF  - Neuroimage
VL  - 17
IS  - 3
N2  - Using positron emission tomography (PET) and [(11)C]raclopride, an association between striatal D(2) dopamine receptors and emotional detachment has been recently reported. Several laboratory findings indicate a link between the serotoninergic system and harm avoidance. In this study we investigated, in a group of healthy volunteers, the relationship between the in vivo binding of 3-(2'-[(18)F]fluoroethyl)spiperone ([(18)F]FESP) to cortical 5HT(2) and striatal D(2) receptors and three personality dimensions, i.e., "novelty seeking," "reward dependence," and "harm avoidance." Eleven healthy volunteers were evaluated by means of the Tridimensional personality Questionnaire (C. R., Arch. Gen. Psychiatry 44: 573-588.) and underwent a PET scan with [(18)F]FESP. Harm avoidance showed a significant inverse correlation with [(18)F]FESP binding in the cerebral cortex, particularly in the frontal cortex (R(2) = -0.709, P = 0.0145) and left parietal cortex (R = -0.629, P = 0.038) but not in the basal ganglia (r = -0.176, P = 0.651). Similar results were obtained using SPM at a P threshold of 0.05. No significant correlation was observed with novelty seeking or reward dependence. In the cerebral cortex, high values of [(18)F]FESP binding values are associated with a high tendency to avoid danger, indicating involvement of the serotoninergic system and, in particular, 5HT(2A) receptors, in this trait of personality. The results of this as well as of previous studies on personality dimensions indicate the existence of a relationship between behavioral and neurobiological factors. In addition these results support the concept that the variability of PET data may be explained by neurochemical differences related to the prevalence of specific personality traits
AD  - INB-CNR, University of Milan--Bicocca, Scientific Institute H San Raffaele, Department of Mental Health, Milan, Italy
UR  - PM:12414286
ER  - 

TY  - JOUR
T1  - Metabolic characterization of spinocerebellar ataxia type 6
A1  - Soong,B.
A1  - Liu,R.
A1  - Wu,L.
A1  - Lu,Y.
A1  - Lee,H.
Y1  - 2001/02//
N1  - UI - 21092263
SP  - 300
EP  - 304
JA  - Arch.Neurol
VL  - 58
IS  - 2
N2  - BACKGROUND: Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder characterized by slowly progressive ataxia and dysarthria. The mutational basis is an expanded CAG repeat sequence within the coding regions of the CACNL1A4 gene. Basic clinical, neuroimaging, and pathological, and epidemiological features have been described in the literature. However, the metabolic features of SCA6 have not been elucidated. OBJECTIVE: To investigate the metabolic features of SCA6. PATIENTS AND METHODS: Seven patients with SCA6 and 7 healthy individuals underwent positron emission tomography using fluorodeoxyglucose F 18. RESULTS: Cerebral glucose utilization in the 7 patients with SCA6 was characterized by significant hypometabolism in widespread structures, including cortical regions and basal ganglia, as well as the cerebellar hemispheres and brainstem. CONCLUSIONS: The results of the multiple-regional brain hypometabolism suggest that brain dysfunction associated with SCA6 may not be limited to the cerebellum and inferior olive, as previously suggested by the results of other pathologic studies
AD  - Neurological Institute, Veterans General Hospital-Taipei, Taipei, Taiwan 112, Republic of China. bwsoong@vghtpe.gov.tw
UR  - PM:11176970
ER  - 

TY  - JOUR
T1  - PET scans and technology assessment
A1  - Chalmers,T.C.
Y1  - 1988/11/11/
N1  - UI - 89037486
SP  - 2713
EP  - 2715
JF  - JAMA
VL  - 260
IS  - 18
UR  - PM:3263513
ER  - 

TY  - JOUR
T1  - Use of methodological standards in diagnostic test research. Getting better but still not good
A1  - Reid,M.C.
A1  - Lachs,M.S.
A1  - Feinstein,A.R.
Y1  - 1995/08/23/
N1  - UI - 95364150
SP  - 645
EP  - 651
JF  - JAMA
VL  - 274
IS  - 8
N2  - OBJECTIVE--To determine the frequency and temporal changes in application of seven accepted methodological standards for the evaluation of diagnostic tests. DATA SOURCES--A search of the MEDLINE database yielded 1302 articles about diagnostic test studies, during a 16-year secular interval, 1978 through 1993, in four prominent general medical journals. STUDY SELECTION--In the 112 eligible studies, the test was intended for clinical use, indexes of accuracy (sensitivity and specificity or likelihood ratios) were provided, and more than 10 patients were enrolled. DATA EXTRACTION--Although each study was critically reviewed by one primary observer, a subset was independently evaluated for interrater consistency. DATA SYNTHESIS--The percentage of studies that fulfilled criteria for each of the seven methodological standards are as follows: (1) specify spectrum of evaluated patients, 27%; (2) report test indexes for clinical subgroups, 8%; (3) avoid workup bias, 46%; (4) avoid review bias, 38%; (5) provide numerical precision for test indexes, 11%; (6) report frequency and management of indeterminate results when calculating test indexes, 22%; and (7) specify test reproducibility, 23%. Secular increases were found for six of the seven standards in ranges of use from 14% to 31% during 1978-1981 to 1990-1993. Nevertheless, only one standard, avoidance of workup bias, was fulfilled by more than 50% of studies in the most recent secular interval. CONCLUSIONS--These results indicate that most diagnostic tests are still inadequately appraised. The routine demand for methodological standards could raise the quality of diagnostic test information, and the careful predissemination evaluation of diagnostic tests could eliminate useless tests before they receive widespread application
AD  - Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06520-8025, USA
UR  - PM:7637146
ER  - 

TY  - JOUR
T1  - Positron Emission Tomography Drug Products; Safety and Effectiveness of Certain PET Drugs for Specific Indications
A1  - FDA
Y1  - 2000///
SP  - 12999
EP  - 13010
JF  - Federal Register
VL  - 65
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\FDA-PET-031000a.pdf
ER  - 

TY  - JOUR
T1  - Delineation and quantitation of brain lesions by fuzzy clustering in positron emission tomography
A1  - Boudraa,A.E.
A1  - Champier,J.
A1  - Cinotti,L.
A1  - Bordet,J.C.
A1  - Lavenne,F.
A1  - Mallet,J.J.
Y1  - 1996/01//
N1  - UI - 97046499
SP  - 31
EP  - 41
JA  - Comput.Med Imaging Graph.
VL  - 20
IS  - 1
N2  - In this study, we investigate the application of the fuzzy clustering to the anatomical localization and quantitation of brain lesions in Positron Emission Tomography (PET) images. The method is based on the Fuzzy C-Means (FCM) algorithm. The algorithm segments the PET image data points into a given number of clusters. Each cluster is an homogeneous region of the brain (e.g. tumor). A feature vector is assigned to a cluster which has the highest membership degree. Having the label affected by the FCM algorithm to a cluster, one may easily compute the corresponding spatial localization, area and perimeter. Studies concerning the evolution of a tumor after different treatments in two patients are presented
AD  - Laboratoire de Biophysique, Faculte de Medecine Alexis Carrel, Lyon, France. boudra@cimac-res.univ-lyonl.fr
UR  - PM:8891420
ER  - 

TY  - BOOK
T1  - Behandlungsleitlinie Demenz
A1  - Deutsche Gesellschaft fr Psychiatrie,Psychotherapie und Nervenheilkunde (DGPPN)
Y1  - 2000///
IS  - 3
CY  - Darmstadt
PB  - Steinkopff
T3  - Praxisleitlinien in Psychiatrie und Psychotherapie
UR  - http://www.uni-duesseldorf.de/WWW/AWMF/ll/psypn06.htm
ER  - 

TY  - RPRT
T1  - Diagnose und Therapie der Alzheimer-Demenz (AD) und der Demenz mit Lewy-Krperchen (DLB)
A1  - Deutsche Gesellschaft fr Neurologie
Y1  - 2002///
UR  - http://www.uni-duesseldorf.de/WWW/AWMF/ll/neur-029.htm
ER  - 

TY  - JOUR
T1  - Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose
A1  - Friedland,R.P.
A1  - Budinger,T.F.
A1  - Ganz,E.
A1  - Yano,Y.
A1  - Mathis,C.A.
A1  - Koss,B.
A1  - Ober,B.A.
A1  - Huesman,R.H.
A1  - Derenzo,S.E.
Y1  - 1983/08//
N1  - UI - 83239217
SP  - 590
EP  - 598
JA  - J Comput.Assist.Tomogr.
VL  - 7
IS  - 4
N2  - Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using [18F]fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in all the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia
UR  - PM:6602819
ER  - 

TY  - JOUR
T1  - Genetic, Clinical, and Radiographic Delineation of Hallervorden-Spatz Syndrome
A1  - Hayflick,Susan J.
A1  - Westaway,Shawn K.
A1  - Levinson,Barbara
A1  - Zhou,Bing
A1  - Johnson,Monique A.
A1  - Ching,Katherine H.L.
A1  - Gitschier,Jane
Y1  - 2003/01/02/
SP  - 33
EP  - 40
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 348
IS  - 1
N2  - Background Hallervorden-Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients with this disease have mutations in the gene encoding pantothenate kinase 2 (PANK2); these patients are said to have pantothenate kinase-associated neurodegeneration. In this study, we compared the clinical and radiographic features of patients with Hallervorden-Spatz syndrome with and without mutations in PANK2. Methods One hundred twenty-three patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome were classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). Their genomic DNA was sequenced for PANK2 mutations. Results All patients with classic Hallervorden-Spatz syndrome and one third of those with atypical disease had PANK2 mutations. Whereas almost all mutations in patients with atypical disease led to amino acid changes, those in patients with classic disease more often resulted in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance imaging (MRI) of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations. Conclusions PANK2 mutations are associated with all cases of classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. Predicted levels of pantothenate kinase 2 protein correlate with the severity of disease
UR  - http://content.nejm.org/cgi/content/abstract/348/1/33
ER  - 

TY  - JOUR
T1  - Iodine-124 labelled Annexin-V as a potential radiotracer to study apoptosis using positron emission tomography
A1  - Glaser,M.
A1  - Collingridge,D.R.
A1  - Aboagye,E.O.
A1  - Bouchier-Hayes,L.
A1  - Hutchinson,O.C.
A1  - Martin,S.J.
A1  - Price,P.
A1  - Brady,F.
A1  - Luthra,S.K.
Y1  - 2003/01//
N1  - UI - 22373044
SP  - 55
EP  - 62
JA  - Appl.Radiat.Isot.
VL  - 58
IS  - 1
N2  - Annexin-V is a calcium-dependent protein that binds with high affinity to phosphaditylserine exposed during apoptosis. The aim of this study was to radiolabel annexin-V with iodine-124 for use as a potential probe of apoptosis by positron emission tomography. Annexin-V was radioiodinated directly using the cyclotron-produced positron emitter iodine-124 by the chloramine-T (CAT) method and indirectly by the pre-labelled reagent N-succinimidyl 3-[124I]iodobenzoate ([124I]m-SIB). Some reaction parameters of the CAT method such as reaction time and pH were optimised to give radiochemical yields of 22.3+/-2.6%(n=3, gel-filtration). After incubation with [124I]m-SIB, radiolabelled annexin-V was obtained in 14% and 25% yield by FPLC and gel-filtration, respectively. The radiochemical purities from direct and indirect labelling were 97.7+/-1.0%(n=3) and 96.7+/-2.1%(n=3), respectively. The new radiotracers could be stored for up to four days without significant de-iodination. The biological activity of radiolabelled annexin-V was tested in control and camptothecin-treated (i.e. apoptotic) human leukaemic HL60 cells. A significantly higher (21%) binding in treated cells was observed with [125I]m-SIB-annexin-V. The binding of [125I]m-SIB labelled annexin-V to camptothecin treated cells was blocked (68%) by a 100-fold excess of unlabelled annexin-V.ABBREVIATIONS: Fast protein liquid chromatography (FPLC), Instant thin layer chromatography (ITLC), Sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), 3-iodobenzoate (m-IBA), N-succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE)
AD  - Imaging Research Solutions Ltd., Hammersmith Hospital, Du Cane Road, W12 0NN, London, UK
UR  - PM:12485664
ER  - 

TY  - JOUR
T1  - Long-lasting occupancy of central nicotinic acetylcholine receptors after smoking: a PET study in monkeys
A1  - Valette,H.
A1  - Bottlaender,M.
A1  - Dolle,F.
A1  - Coulon,C.
A1  - Ottaviani,M.
A1  - Syrota,A.
Y1  - 2003/01//
N1  - UI - 22373920
SP  - 105
EP  - 111
JA  - J Neurochem.
VL  - 84
IS  - 1
N2  - The aim of this study was to compare the degree of occupancy of central nicotinic acetylcholine receptors (nAChR) in isoflurane anaesthetized baboon brain following inhalation of tobacco smoke (one cigarette containing 0.9 mg nicotine) or i.v. nicotine (0.6 mg i.v.). [18F]Fluoro-A-85380 and positron emission tomography (PET) were used to assess the distribution volumes (DV) of the radiotracer in selected brain areas using a one-compartment model. Eighty minutes after nicotine i.v., DV was reduced by 50 and 66% in the thalamus and putamen, respectively. Six hours after nicotine, a reduction in DV (27% in the thalamus) was still observed. Eighty minutes after inhalation of tobacco smoke, DV was decreased by 52 and 65% in the thalamus and putamen, respectively. Previous PET experiments have demonstrated a short-lasting interaction of [11C]nicotine with nAChRs. Thus, we hypothesized that a metabolite of nicotine with high affinity and long half-live (several hours) could bind at nAChRs. Eighty minutes after a high dose of nornicotine (0.5 mg i.v.), DV was reduced by 53 and 31% in thalamus and putamen, respectively. No significant effect was observed following 0.15 mg nornicotine. Therefore, nornicotine could contribute to the long-lasting occupancy of central nAChRs after smoking
AD  - Service Hospitalier Frederic Joliot, DRM-DSV-CEA, Orsay, France
UR  - PM:12485406
ER  - 

TY  - JOUR
T1  - Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [(18)F]FDG-PET
A1  - Berding,G.
A1  - Odin,P.
A1  - Brooks,D.J.
A1  - Nikkhah,G.
A1  - Matthies,C.
A1  - Peschel,T.
A1  - Shing,M.
A1  - Kolbe,H.
A1  - Van Den Hoff,J.
A1  - Fricke,H.
A1  - Dengler,R.
A1  - Samii,M.
A1  - Knapp,W.H.
Y1  - 2001/11//
SP  - 1014
EP  - 1022
JA  - Mov Disord.
VL  - 16
IS  - 6
N2  - Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment
AD  - Department of Nuclear Medicine, University Medical School, Hannover, Germany. berding.georg@mh-hannover.de
UR  - PM:11748732
ER  - 

TY  - JOUR
T1  - Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumour progression?
A1  - Belohlavek,O.
A1  - Simonova,G.
A1  - Kantorova,I.,I
A1  - Novotny,Jr J.
A1  - Liscak,R.
Y1  - 2003/01//
N1  - UI - 0
SP  - 96
EP  - 100
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 1
N2  - Stereotactic radiosurgery (SRS) using the Leksell gamma knife promotes acute and chronic local changes in glucose metabolism. We have been able to find very few papers on Medline on the subject of assessment of metastases by 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) after SRS. The aim of this work was to specify the additional value of FDG PET, in comparison with magnetic resonance imaging (MRI), in differentiating SRS-induced radionecrosis from viable brain metastasis in a clinical setting. Fifty-seven metastases in 25 patients were treated by SRS. An average of 33 weeks later, all the patients underwent FDG PET. At the same time (SD=2 weeks) all the patients underwent MRI. The sensitivity, specificity and accuracy of both FDG PET and MRI examinations were calculated with reference to clinical and radiological follow-up or biopsies. The additional value derived from use of FDG PET after MRI was assessed and progression-free survival rates were compared. The difference in progression-free survival rates between the negative and positive subgroups was significant ( P=0.0005) for MRI and even more so ( P<0.00001) for FDG PET. Sensitivity, specificity and accuracy were 75% (6/8), 93.9% (46/49) and 91.2% (52/57) for FDG PET, and 100% (8/8), 65.3% (32/49) and 70.2% (40/57) for MRI. In the subgroup of patients with positive or non-diagnostic MRI, the probability of presence of a viable tumour was only 32% (8/25). This probability increased to 100% (5/5) when subsequent FDG PET was positive and decreased to 11.1% (2/18) when FDG PET was negative. The frequency of a viable neoplasm was significantly different ( P=0.001) in the FDG PET negative and positive subgroups. MRI and FDG PET both have an important predictive value for persistent viable metastases after treatment by SRS. Neither sensitive but non-specific MRI nor specific but insensitive FDG PET is reliable on its own. While FDG PET significantly improved the diagnostic accuracy in the subgroup of patients with positive and non-diagnostic MRI, it provided no additional value in the MRI-negative subgroup
AD  - Department of Nuclear Medicine - PET Centre, Na Homolce Hospital, Roentgenova 2, 150 30 Prague 5, Czech Republic, otakar.belohlavek@homolka.cz
UR  - PM:12483415
ER  - 

TY  - JOUR
T1  - Multitracer study with positron emission tomography in Creutzfeldt-Jakob disease
A1  - Engler,H.
A1  - Lundberg,P.O.
A1  - Ekbom,K.
A1  - Nennesmo,I.
A1  - Nilsson,A.
A1  - Bergstrom,M.
A1  - Tsukada,H.
A1  - Hartvig,P.
A1  - Langstrom,B.
Y1  - 2003/01//
N1  - UI - 22370732
SP  - 85
EP  - 95
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 1
N2  - During the period February 1997 to April 2000, 15 patients with clinical symptoms of Creutzfeldt-Jakob disease (CJD) were referred to Uppsala University PET Centre. Positron emission tomography (PET) was performed to detect characteristic signs of the disease, e.g. neuronal death and/or astrocytosis in the brain. The examinations were performed in one session starting with oxygen-15 labelled water scan to measure regional cerebral blood flow, followed by imaging with the monoamine oxidase B inhibitor N-[(11)C-methyl]- L-deuterodeprenyl (DED) to assess astrocytosis in the brain and finally imaging with fluorine-18 2-fluorodeoxyglucose (FDG) to assess regional cerebral glucose metabolism (rCMR(glu)). Nine of the patients fulfilled the clinical criteria of probable CJD. In eight of them, FDG and DED imaging revealed, in comparison with normal controls, a typical pattern characterized by a pronounced regional decrease (<2SD) in glucose brain metabolism, indicative of neuronal dysfunction; this was accompanied by a similar increase (>2SD) in DED binding, indicating astrocytosis. These changes were most pronounced in the cerebellum and the frontal, occipital and parietal cortices, whereas the pons, the thalamus and the putamen were less affected and the temporal cortex appeared unaffected. The cerebral blood flow showed a pattern similar to that observed with FDG. In the ninth patient, analysis with DED was not possible. The diagnosis of definite CJD according to international consensus criteria was confirmed in six of these patients. In one patient with probable CJD, protease-resistant prion protein (PrPres) could not be demonstrated. In two patients with probable CJD, autopsy was not allowed. Computed tomography and magnetic resonance imaging, performed in four and seven of these nine patients respectively, showed unspecific, mainly atrophic changes. In six other patients, the PET examinations gave a different pattern. In three of them, high rCMR(glu) was noticed in parts of the brain, particularly in the temporal lobes and basal ganglia, which could suggest encephalitis. One of the patients had Sjogren's syndrome, one had paraneoplastic limbic encephalitis and the third recovered spontaneously. In the other three patients, the DED binding was normal despite a hypometabolic glucose pattern. In conclusion, the PET findings obtained using DED and FDG paralleled neuropathological findings indicating neuronal dysfunction and astrocytosis, changes that are found in CJD
AD  - Department of Neurology, Uppsala University Hospital, Uppsala, Sweden, henry.engler@pet.uu.se
UR  - PM:12483414
ER  - 

TY  - JOUR
T1  - S-[18F]fluoromethyl-(+)-McN5652, a PET tracer for the serotonin transporter: Evaluation in rats
A1  - Marjamaki,P.
A1  - Zessin,J.
A1  - Eskola,O.
A1  - Gronroos,T.
A1  - Haaparanta,M.
A1  - Bergman,J.
A1  - Lehikoinen,P.
A1  - Forsback,S.
A1  - Brust,P.
A1  - Steinbach,J.
A1  - Solin,O.
Y1  - 2003/01//
N1  - UI - 22309725
SP  - 45
EP  - 53
JF  - Synapse
VL  - 47
IS  - 1
N2  - The [(18)F]fluoromethyl analog of (+)-McN5652 ([(18)F]FMe-McN) for imaging serotonin transporter (SERT) with positron emission tomography (PET) has recently been synthesized. We describe here the biological evaluation of [(18)F]FMe-McN in rats. Biodistribution studies of [(18)F]FMe-McN in rat brain ex vivo after an intravenous injection showed a high accumulation of radioactivity in the regions rich in SERT, such as raphe nuclei, hypothalamus, thalamus, substantia nigra, locus coeruleus, and amygdala. Region-to-cerebellum ratios reached a maximum value of 9 in raphe nuclei within 3.5 h after administration. The specificity and selectivity of [(18)F]FMe-McN binding to SERT was studied by preinjecting blocking doses of serotonin, norepinephrine, and dopamine transporter inhibitors. Fluoxetine, a specific inhibitor for SERT, decreased the specific binding of [(18)F]FMe-McN in raphe nuclei by 91 +/- 4%; in other regions rich in SERT, similar results were obtained. GBR12909 and nisoxetine, selective inhibitors for dopamine transporter (DAT) and norepinephrine transporter (NET), respectively, showed no significant effects on the uptake of [(18)F]FMe-McN. Our studies show that [(18)F]FMe-McN has a clear potential as a tracer for studies with PET of SERT function in humans. Synapse 47:45-53, 2003
AD  - MediCity PET Laboratory, Turku PET Centre, Turku, Finland
UR  - PM:12422372
ER  - 

TY  - JOUR
T1  - Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid
A1  - McConathy,J.
A1  - Martarello,L.
A1  - Malveaux,E.J.
A1  - Camp,V.M.
A1  - Simpson,N.E.
A1  - Simpson,C.P.
A1  - Bowers,G.D.
A1  - Olson,J.J.
A1  - Goodman,M.M.
Y1  - 2002/05/23/
N1  - UI - 22010289
SP  - 2240
EP  - 2249
JA  - J Med Chem.
VL  - 45
IS  - 11
N2  - Novel radiopharmaceuticals, including amino acids, that target neoplasms through their altered metabolic states have shown promising results in preclinical and clinical studies. Two fluorinated analogues of alpha-aminoisobutyric acid, 2-amino-3-fluoro-2-methylpropanoic acid (FAMP) and 3-fluoro-2-methyl-2-(methylamino)propanoic acid (N-MeFAMP), have been radiolabeled with fluorine-18, characterized in amino acid uptake assays, and evaluated in vivo in normal rats and a rodent tumor model. The key steps in the syntheses of both radiotracers involved the preparation of cyclic sulfamidate precursors. Radiosyntheses of both [18F]FAMP and [18F]N-MeFAMP via no-carrier-added nucleophilic substitution provided high yields (>78% decay-corrected) in high radiochemical purity (>99%). Amino acid transport assays using 9L gliosarcoma cells demonstrated that both compounds are substrates for the A type amino acid transport system, with [18F]N-MeFAMP showing higher specificity than [18F]FAMP for A type transport. Tissue distribution studies in normal Fischer rats and Fischer rats implanted intracranially with 9L gliosarcoma tumor cells were also performed. At 60 min postinjection, the tumor vs normal brain ratio of radioactivity was 36:1 in animals receiving [18F]FAMP and 104:1 in animals receiving [18F]N-MeFAMP. On the basis of these studies, both [18F]FAMP and [18F]N-MeFAMP are promising imaging agents for the detection of intracranial neoplasms via positron emission tomography
AD  - Department of Radiology at Emory University Hospital, School of Medicine, 1364 Clifton Road Northeast, Atlanta, Georgia 30322, USA
UR  - PM:12014962
ER  - 

TY  - JOUR
T1  - Biodistribution of [11C] methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo
A1  - Sutinen,E.
A1  - Jyrkkio,S.
A1  - Gronroos,T.
A1  - Haaparanta,M.
A1  - Lehikoinen,P.
A1  - Nagren,K.
Y1  - 2001/07//
N1  - UI - 21394830
SP  - 847
EP  - 854
JA  - Eur.J Nucl Med
VL  - 28
IS  - 7
N2  - [N-methyl-11C]alpha-Methylaminoisobutyric acid (11C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. 11C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of 11C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of 11C-MeAIB, and the tissue samples were weighed and counted for 11C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with 11C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (Ki values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (Ki) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039+/-0.008 min(-1) and 0.013+/-0.006 min(-1), respectively. The Ki value of the tumour (n=1) was 0.064 min(-1). Higher uptake of 11C-MeAIB into the tumour tissue was encountered. These results encourage further 11C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection
AD  - Department of Oncology and Radiotherapy, Turku University Central Hospital, Finland. eija.sutinen@pet.tyks.fi
UR  - PM:11504081
ER  - 

TY  - JOUR
T1  - Loss of metabolites from monkey striatum during PET with FDOPA
A1  - Cumming,P.
A1  - Munk,O.L.
A1  - Doudet,D.
Y1  - 2001/09/01/
N1  - UI - 21287465
SP  - 212
EP  - 218
JF  - Synapse
VL  - 41
IS  - 3
N2  - The decarboxylation of 6-[(18)F]fluorodopa (FDOPA) and retention of the product [(18)F]fluorodopamine within vesicles of catecholamine fibers results in the labeling of dopamine-rich brain regions during FDOPA/PET studies. However, this metabolic trapping is not irreversible due to the eventual diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss of decarboxylated metabolites from brain
AD  - PET Center, Arhus Kommunehospital, Arhus, Denmark. paul@pet.auh.dk
UR  - PM:11391782
ER  - 

TY  - JOUR
T1  - A probe for intracerebral aromatic amino-acid decarboxylase activity: distribution and kinetics of [18F]6-fluoro-L-m-tyrosine in the human brain
A1  - Nahmias,C.
A1  - Wahl,L.
A1  - Chirakal,R.
A1  - Firnau,G.
A1  - Garnett,E.S.
Y1  - 1995/05//
N1  - UI - 95379877
SP  - 298
EP  - 304
JA  - Mov Disord.
VL  - 10
IS  - 3
N2  - Positron tomography, using [18F]6-fluoro-L-dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6-fluoro-L-m-tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine-rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a two-compartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. The FmT decarboxylation rate constant (k21) was found to be 0.0108 min-1. Because the peripheral metabolism of FmT is simpler than that of [18F]6-fluoro-L-dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans
AD  - Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada
UR  - PM:7651447
ER  - 

TY  - JOUR
T1  - The distribution and kinetics of [18F]6-fluoro-3-O-methyl-L-dopa in the human brain
A1  - Wahl,L.
A1  - Chirakal,R.
A1  - Firnau,G.
A1  - Garnett,E.S.
A1  - Nahmias,C.
Y1  - 1994/07//
N1  - UI - 94284306
SP  - 664
EP  - 670
JA  - J Cereb.Blood Flow Metab
VL  - 14
IS  - 4
N2  - The analysis of positron tomographic studies of 3,4-dihydroxyphenylethylamine (dopamine) metabolism in which [18F]6-fluoro-L-3,4-dihydroxyphenylalanine (F-dopa) is used as a tracer is confounded by the presence of [18F]6-fluoro-3-O-methyl-L-3,4-dihydroxyphenylalanine (OMFD). This labeled molecule, formed by the action of peripheral catechol-O-methyltransferase on F-dopa, crosses the blood-brain barrier and contributes to the radioactivity measured by the tomograph. Corrections for this radioactivity in the brain have been proposed. They rely upon the assumption that regional variations in the handling of this molecule by the brain are negligible. Although this assumption is pivotal for the proper quantification of dopamine metabolism using F-dopa, the distribution and kinetics of OMFD have never been studied in humans. We present results in humans that show that there is little selective regional 18F accumulation in the brain, that the distribution volume of OMFD is close to unity, and that a single, reversible compartment is adequate to model the measured time course of radioactivity after an OMFD injection. Analysis of plasma samples for labeled metabolites showed that more than 95% of the radioactivity was associated with OMFD at all times. Our results for OMFD kinetics are in accord with published results obtained in nonhuman primates and for the bidirectional transport of large neutral amino acids across the blood-brain barrier measured using a synthetic amino acid.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada
UR  - PM:8014214
ER  - 

TY  - JOUR
T1  - Metabolites of 6-[18F]fluoro-L-dopa in human blood
A1  - Firnau,G.
A1  - Sood,S.
A1  - Chirakal,R.
A1  - Nahmias,C.
A1  - Garnett,E.S.
Y1  - 1988/03//
N1  - UI - 88155056
SP  - 363
EP  - 369
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 29
IS  - 3
N2  - The metabolites of 6-[18F]fluoro-L-dopa in the blood plasma of healthy humans have been identified as 3-O-sulfato-6[18F]fluoro-L-dopa, 3-O-methyl-6-[18F]fluoro-L-dopa, 6-[18F] fluorodopamine, and 6-[18F]fluorohomovanillic acid. The time course of these metabolites was followed up to 2 hr. The findings have implications for the use of 6-[18F]fluoro-L-dopa as tracer for cerebral dopamine metabolism. Despite the variety of metabolites in the peripheral blood there are only two 18F-carrying compounds, 6-[18F]fluoro-L-dopa and 3-O-methyl-6-[18F]fluoro-L-dopa, that can cross the blood-brain barrier. After 1 hr, the plasma concentration of 3-O-methyl-6-[18F]fluoro-L-dopa reaches approximately 20% that of 6-[18F]fluoro-L-dopa but the mean concentration of the O-methylated metabolite over the same interval is less than 5% that of 6-[18F]-fluoro-L-dopa
AD  - McMaster University Medical Centre, Chedoke-McMaster Hospitals, Section of Radiology, Hamilton, Ontario, Canada
UR  - PM:3126278
ER  - 

TY  - JOUR
T1  - A rostrocaudal gradient for aromatic acid decarboxylase in the human striatum
A1  - Garnett,E.S.
A1  - Lang,A.E.
A1  - Chirakal,R.
A1  - Firnau,G.
A1  - Nahmias,C.
Y1  - 1987/08//
N1  - UI - 88052285
SP  - 444
EP  - 447
JA  - Can.J Neurol Sci.
VL  - 14
IS  - 3 Suppl
N2  - The local concentration of 6-[18F]fluoro-L-dopa(18F) reflects the activity of aromatic acid decarboxylase (AADC), the enzyme that generates dopamine from its precursor amino acid, L-dopa. In young healthy adults, the local concentration of 18F, and hence AADC activity, is constant in coronal slices taken in a rostrocaudal direction. With increasing age a gradient representing decreasing activity in the putamen develops. This decrease is less marked than was expected from the literature. In five children with primary dystonia, the striatal distribution of 18F resembled that seen in the normal older adults. In established clinical Parkinson's disease the rostrocaudal gradient becomes steep; the putamen is more damaged
AD  - Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada
UR  - PM:3119181
ER  - 

TY  - JOUR
T1  - Cerebral metabolism of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine in the primate
A1  - Firnau,G.
A1  - Sood,S.
A1  - Chirakal,R.
A1  - Nahmias,C.
A1  - Garnett,E.S.
Y1  - 1987/04//
N1  - UI - 87140045
SP  - 1077
EP  - 1082
JA  - J Neurochem.
VL  - 48
IS  - 4
N2  - The tracers 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (6-[18F]fluoro-L-DOPA) and L-[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6-[18F]fluoro-L-DOPA was metabolized to 6-[18F]fluorodopamine, 3,4-dihydroxy-6-[18F]fluorophenylacetic acid, and 6-[18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of L-[14C]DOPA. 6-[18F]Fluorodopamine was synthesized faster than [14C]dopamine. In the frontal cortex, the major metabolite was also 6-[18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3-O-methyl-6-[18F]fluoro-L-DOPA. On the basis of these data, the images obtained with 6-[18F]fluoro-L-DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms
UR  - PM:3102690
ER  - 

TY  - JOUR
T1  - Noninvasive assessment of aromatic L-amino acid decarboxylase activity in aging rhesus monkey brain in vivo
A1  - DeJesus,O.T.
A1  - Endres,C.J.
A1  - Shelton,S.E.
A1  - Nickles,R.J.
A1  - Holden,J.E.
Y1  - 2001/01//
N1  - UI - 20524155
SP  - 58
EP  - 63
JF  - Synapse
VL  - 39
IS  - 1
N2  - The effect of aging on aromatic L-amino acid decarboxylase (AAAD) activity in rhesus monkey striatum was assessed in vivo using PET imaging. Two analogs of L-DOPA, 6-fluoro-m-tyrosine (FMT) and 6-fluoro-L-DOPA (FDOPA), were used to image rhesus monkeys of various ages. Results show that when the animals were grouped between young (3-11 years) and aged (25-37 years), FDOPA uptake in the older animals showed a 21% decline (P < 0.0005), while FMT uptake in young and older animals were not different. On the other hand, when individual uptake values were plotted vs. age, linear regression analysis showed FDOPA uptake similarly declined with age (r = -0.84, P < 0.001) while FMT uptake increased with age (r = 0.66, P < 0.05). Since FMT pharmacokinetics has been shown to be unaffected by metabolic steps occurring after the AAAD step, while FDOPA traces all the steps involved in L-DOPA metabolism, FMT is a suitable tracer to assess AAAD activity while FDOPA traces dopamine turnover. Based on these tracer characteristics, this study found that AAAD activity is maintained or increased in the aging rhesus monkey striatum while the FDOPA uptake decreases with age consistent with age-related declines in neuronal mechanisms whose overall effect is increased striatal dopamine turnover and clearance. Furthermore, comparison of results of this study with previous studies support the notion that the effect of aging in the dopamine system is different from that of MPTP-induced parkinsonism
AD  - Department of Medical Physics, University of Wisconsin Medical School Madison, Wisconsin 53706, USA. odejesus@facstaff.wisc.edu
UR  - PM:11071710
ER  - 

TY  - JOUR
T1  - FluoroDOPA PET shows the nondopaminergic as well as dopaminergic destinations of levodopa
A1  - Brown,W.D.
A1  - Taylor,M.D.
A1  - Roberts,A.D.
A1  - Oakes,T.R.
A1  - Schueller,M.J.
A1  - Holden,J.E.
A1  - Malischke,L.M.
A1  - DeJesus,O.T.
A1  - Nickles,R.J.
Y1  - 1999/10/12/
N1  - UI - 99450710
SP  - 1212
EP  - 1218
JF  - Neurology
VL  - 53
IS  - 6
N2  - OBJECTIVE: To evaluate the visible and quantitative anatomic distribution of fluorine-18-labeled L-DOPA in the healthy human brain, to thereby expand the understanding of extrastriatal sites of levodopa function, and to provide a broader foundation for clinical and research studies of fluoroDOPA accumulation in patients. METHODS: The authors performed dynamic three-dimensional fluoroDOPA PET imaging in 10 healthy volunteers and analyzed the images visually and quantitatively. Twenty-eight regions of interest were applied to parametric images of the uptake rate constant (using the multiple-time graphic plot method with cortical input function) and also were used to quantitate regional radioactivity at 80 to 90 minutes. The authors correlated the uptake constants with published human regional neurotransmitter and decarboxylation data. RESULTS: PET imaging with fluoroDOPA demonstrates trapping of labeled dopamine or its metabolites in substantial quantities in many areas of the brain other than the mesostriatal pathways, including considerable uptake in the serotonergic and noradrenergic areas of the hypothalamus and brainstem as well as in extrastriatal cerebral sites. Total fluoroDOPA uptake correlates best with the sum of catecholamine and indolamine concentrations in the brain and moderately well with regional activity of aromatic L-amino acid decarboxylase, but correlates poorly with extrastriatal dopamine concentration. CONCLUSION: Neither L-DOPA nor its radiolabeled analog fluoroDOPA is metabolized or accumulates specifically in dopaminergic or even catecholaminergic neurons. Substantial dopamine production within serotonin and norepinephrine neurons may play a role in either therapeutic effects or adverse effects of therapy with L-DOPA
AD  - Department of Radiology, University of Wisconsin-Madison, USA
UR  - PM:10522875
ER  - 

TY  - JOUR
T1  - Localization of trapping of 6-[(18)F]fluoro-L-m-tyrosine, an aromatic L-amino acid decarboxylase tracer for PET
A1  - Brown,W.D.
A1  - DeJesus,O.T.
A1  - Pyzalski,R.W.
A1  - Malischke,L.
A1  - Roberts,A.D.
A1  - Shelton,S.E.
A1  - Uno,H.
A1  - Houser,W.D.
A1  - Nickles,R.J.
A1  - Holden,J.E.
Y1  - 1999/11//
N1  - UI - 99432304
SP  - 111
EP  - 123
JF  - Synapse
VL  - 34
IS  - 2
N2  - The purpose of this study was to address four major questions regarding 6-FMT, a noncatecholic PET tracer for AAAD: 1) Where is the specific uptake of 6-FMT? 2) Why does it accumulate where and to the degree that it does? 3) How does its uptake differ from that of fluoroDOPA globally? and 4) Does its regional uptake differ significantly from that of fluoroDOPA? High-resolution PET scans were obtained in three rhesus monkeys using 6-FMT and in two of them using fluoroDOPA. Anatomic distribution was analyzed visually and quantitative uptake of 6-FMT was compared with published regional decarboxylase activity and monoamine neurotransmitter concentrations. In addition to high uptake in the dopamine-rich striatal nuclei, there was specific uptake of 6-FMT in brain regions which have little dopaminergic innervation but which have other amines in significant concentration. 6-FMT uptake correlated best with regional AAAD activity (r = 0.97). It correlated slightly less well with the sum of catecholamine and indolamine neurotransmitter concentrations, but does not correlate with dopamine concentration. The uptake of 6-FMT is greater than that of fluoroDOPA, with only slight differences in their regional distributions. Radiolabeled analogs of DOPA are often implicitly or explicitly regarded as tracers for presynaptic dopaminergic function. However, localization of these tracers more broadly includes many regions with relatively high concentrations of norepinephrine and serotonin. This may be especially important in diseases or experimental states in which dopaminergic neurons are selectively reduced, and may allow for the study of nondopaminergic neuronal systems in vivo with this tracer
AD  - Department of Radiology, University of Wisconsin-Madison, USA. wbrown@facstaff.wisc.edu
UR  - PM:10502310
ER  - 

TY  - JOUR
T1  - Evaluation of dopaminergic presynaptic integrity: 6-[18F]fluoro-L-dopa versus 6-[18F]fluoro-L-m-tyrosine
A1  - Doudet,D.J.
A1  - Chan,G.L.
A1  - Jivan,S.
A1  - DeJesus,O.T.
A1  - McGeer,E.G.
A1  - English,C.
A1  - Ruth,T.J.
A1  - Holden,J.E.
Y1  - 1999/03//
SP  - 278
EP  - 287
JA  - J Cereb.Blood Flow Metab
VL  - 19
IS  - 3
N2  - The effectiveness of 6-[18F]fluoro-L-m-tyrosine (6FMT) to evaluate dopamine presynaptic integrity was compared to that of 6-[18F]fluoro-L-dopa (6FDOPA) in vivo by positron emission tomography (PET). Six normal and six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys received 6FDOPA and 6FMT PET scans on separate occasions with identical scanning protocols. Four measures, the rate of uptake of tracer into striatum using either the arterial input function (Ki) or the activity in the occipital cortex as the input function (Kc), the rate of loss of striatal radioactivity (k(loss)), and an index of "effective turnover" of dopamine (k(loss)/Ki), were obtained for both tracers during extended PET studies. 6-[18F]Fluoro-L-m-tyrosine was as effective as 6FDOPA in separating normals from MPTP-lesioned subjects on the basis of the uptake rate constants Ki and Kc. However, in contrast to 6FDOPA, it was not possible to differentiate the normal from the lesioned animal using k(loss) or k(loss)/Ki for 6FMT. Thus, FMT appears to be a reasonable, highly specific tracer for studying the activity of aromatic dopa decarboxylase enzyme as an index of presynaptic integrity. However, if one is interested in investigating further the metabolic pathway and obtaining an in vivo estimate of the effective turnover of dopamine (after pharmacologic manipulation, for example), 6FDOPA remains the tracer of choice
AD  - Department of Medicine, University of British Columbia, Vancouver, Canada
UR  - PM:10078880
ER  - 

TY  - JOUR
T1  - Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment
A1  - Brown,W.D.
A1  - Oakes,T.R.
A1  - DeJesus,O.T.
A1  - Taylor,M.D.
A1  - Roberts,A.D.
A1  - Nickles,R.J.
A1  - Holden,J.E.
Y1  - 1998/11//
N1  - UI - 99045041
SP  - 1884
EP  - 1891
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 39
IS  - 11
N2  - This article presents dosimetry based on the measurement of fluoro-DOPA activity in major tissues and in the bladder contents in humans after oral pretreatment with 100 mg carbidopa. METHODS: Bladder activity was measured continuously by external probe and calibrated using complete urine collections. Quantitative dynamic PET scans provided time-activity curves for the major organs. Bladder wall dosimetry was calculated using the methods of MIRD Pamphlet No. 14. Effective dose was calculated as described in ICRP Publication 60. RESULTS: Mean absorbed dose to the bladder wall surface per unit administered activity was 0.150 mGy/MBq (0.556 rad/mCi) with the realistic void schedule used in our studies. The dose was 0.027 mGy/MBq (0.101 rad/mCi) to the kidneys, 0.0197 mGy/MBq (0.0728 rad/mCi) to the pancreas, and 0.0186 mGy/MBq (0.0688 rad/mCi) to the uterus. Absorbed doses to other organs were an order of magnitude or more lower than the bladder, 0.009-0.015 mGy/MBq. The effective dose per unit administered activity was 0.0199 mSv/MBq (0.0735 rem/mCi.) CONCLUSION: Urinary excretion of fluoro-DOPA was altered significantly by pretreatment with carbidopa. In general, any manipulation of tracer metabolism in the body should be expected to produce changes in biodistribution and dosimetry. The largest radiation dose was to the bladder wall, for which our estimate was one-fifth of that from the original report. The methods used reflect realistic urinary physiology and typical use of this tracer. The principles of MIRD Pamphlet No. 14 should be used in planning studies using tracers excreted in the urine to minimize the absorbed dose
AD  - Department of Radiology, University of Wisconsin-Madison Medical School, USA
UR  - PM:9829576
ER  - 

TY  - CHAP
T1  - Biochemistry and evaluation of fluoroamino acids
A1  - Coenen,H.H.
Y1  - 1993///
SP  - 109
EP  - 129
T2  - PET studies on amino acid metabolism and protein synthesis
A2  - Mazoyer,B.M.
A2  - Heiss,W.D.
A2  - Comar,D.
CY  - Dordrecht
PB  - Kluwer Academic Publishers
T3  - Developments in nuclear medicine
A3  - Cox,P.H.
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Alternating two finger tapping with contralateral activation is an objective measure of clinical severity in Parkinson's disease and correlates with PET
A1  - Pal,P.K.
A1  - Lee,C.S.
A1  - Samii,A.
A1  - Schulzer,M.
A1  - Stoessl,A.J.
A1  - Mak,E.K.
A1  - Wudel,J.
A1  - Dobko,T.
A1  - Tsui,J.K.
Y1  - 2001/10//
N1  - UI - 0
SP  - 305
EP  - 309
JA  - Parkinsonism Relat Disord.
VL  - 7
IS  - 4
N2  - We explored an objective method of measuring clinical severity of Parkinson's disease. Eighty-six patients with PD and 136 healthy subjects were studied. We serially carried out four types of finger tapping (FT) using a computerized drum machine: (i) repetitive one-finger tapping with an index-finger (F1K1); (ii) one-finger tapping on two keys separated by 20cm (F1K2); (iii) alternate tapping with index and middle fingers on two adjacent keys (F2K2); and (iv) F2K2 with contralateral activation (aF2K2). Analyses on FT included: (i) age and gender effects in healthy volunteers and Parkinson's disease; (ii) comparison between Parkinson patients and controls of similar age distribution; (iii) correlation with the Purdue Pegboard and Modified Columbia Scale in Disease; and (iv) in a subset of patients in whom PET scans were performed (n=30), correlation with 18F-DOPA uptake constant (Ki). In healthy subjects, there was a negative age effect on FT scores and a gender effect, with males scoring higher than females. All FT scores were significantly lower in the Parkinson patients, correlated with Purdue Peg Board, and inversely with the duration of illness, and with the Modified Columbia Scale. The 18F-DOPA Ki correlated significantly with aF2K2 (p=0.024), less so with PPB (p=0.038), but not with the Modified Columbia Scale. We conclude that alternating two-finger tapping with contralateral hand activation is a simple, objective test for measuring the severity of Parkinson's disease
AD  - Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Purdy Pavilion, 2221 Westbrook Mall, British Columbia, V6T 2B5, Vancouver, Canada
UR  - PM:11344014
ER  - 

TY  - JOUR
T1  - In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease
A1  - Lee,C.S.
A1  - Samii,A.
A1  - Sossi,V.
A1  - Ruth,T.J.
A1  - Schulzer,M.
A1  - Holden,J.E.
A1  - Wudel,J.
A1  - Pal,P.K.
A1  - Fuente-Fernandez,R.
A1  - Calne,D.B.
A1  - Stoessl,A.J.
Y1  - 2000/04//
SP  - 493
EP  - 503
JA  - Ann.Neurol
VL  - 47
IS  - 4
N2  - Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD
AD  - Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada
UR  - PM:10762161
ER  - 

TY  - JOUR
T1  - Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease
A1  - Frost,J.J.
A1  - Rosier,A.J.
A1  - Reich,S.G.
A1  - Smith,J.S.
A1  - Ehlers,M.D.
A1  - Snyder,S.H.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
Y1  - 1993/09//
SP  - 423
EP  - 431
JA  - Ann.Neurol
VL  - 34
IS  - 3
N2  - Parkinson's Disease (PD) is characterized by a selective loss of nigrostriatal dopaminergic neurons that results in a marked reduction of dopaminergic nerve terminals in the striatum. Recently, 11C-WIN 35,428, a cocaine analogue that specifically labels the dopamine transporter, was developed and can be used to label dopaminergic nerve terminals in vivo by positron emission tomography. In healthy control subjects, binding of 11C-WIN 35,428 is highest in the striatum. In addition, 2 symmetrical focal areas of low binding were observed in the midbrain. The cerebellum functioned as an appropriate region for nonspecific binding. The binding of 11C-WIN 35,428 in patients with PD (Hoehn-Yahr II) was compared with that in healthy control subjects by using the (region-cerebellum)/cerebellum ratio for data acquired 34 to 82 minutes after injection. In control subjects, this ratio varied, at approximately 2, in the striatum. In patients with PD, binding in the posterior putamen was reduced by 78%, whereas the anterior putamen and the caudate nucleus showed a reduction of 59 and 39%, respectively. The reduction in 11C-WIN 35,428 binding was highest in the midbrain (84%). The high specific/nonspecific binding ratio and the pronounced reduction in binding in mild PD may permit detection of even earlier stages of PD or presymptomatic individuals with dopaminergic cell loss
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD
UR  - PM:8363363
ER  - 

TY  - JOUR
T1  - The status of dopamine nerve terminals in Parkinson's disease and essential tremor: a PET study with the tracer [11-C]FE-CIT
A1  - Antonini,A.
A1  - Moresco,R.M.
A1  - Gobbo,C.
A1  - De Notaris,R.
A1  - Panzacchi,A.
A1  - Barone,P.
A1  - Calzetti,S.
A1  - Negrotti,A.
A1  - Pezzoli,G.
A1  - Fazio,F.
Y1  - 2001/02//
N1  - UI - 21379309
SP  - 47
EP  - 48
JA  - Neurol Sci.
VL  - 22
IS  - 1
N2  - Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD
AD  - Department of Neurosciences, Istituti Clinici di Perfezionamento, Milan, Italy
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Antonini-essential-tremor.pdf
ER  - 

TY  - JOUR
T1  - Complementary positron emission tomographic studies of the striatal dopaminergic system in Parkinson's disease
A1  - Antonini,A.
A1  - Vontobel,P.
A1  - Psylla,M.
A1  - Gunther,I.
A1  - Maguire,P.R.
A1  - Missimer,J.
A1  - Leenders,K.L.
Y1  - 1995/12//
SP  - 1183
EP  - 1190
JA  - Arch.Neurol
VL  - 52
IS  - 12
N2  - OBJECTIVE: To assess the relationship between striatal dopa decarboxylase capacity, D2 dopamine receptor binding, and energy metabolism in Parkinson's disease (PD). DESIGN: Positron emission tomographic (PET) studies of glucose and dopa metabolism and D2 dopamine receptor binding in the caudate nucleus and putamen of patients with PD at different Hoehn and Yahr (HY) stages using PET and the tracers 18F-fluorodeoxyglucose (FDG), 6-18F-fluoro-L-dopa (FDOPA), and 11C-raclopride (RACLO). SETTING: Positron emission tomography research program at the Paul Scherrer Institute. SUBJECTS: Twenty patients with PD at different stages of the disease (HY stages I through IV; five patients for each stage) compared with separate groups of age-matched healthy subjects. MAIN OUTCOME MEASURES: Influx constant (Ki) for specific FDOPA uptake; uptake index ratio for RACLO binding to D2 dopamine receptors; normalized to global FDG metabolic rate for glucose consumption; and semiquantitative score for assessment of tremor, rigidity, and bradykinesia in PD. RESULTS: Patients with PD at HY stages I to II (hereafter HY-I-II PD) revealed reduced FDOPA metabolism, particularly in the putamen. The FDOPA uptake in the putamen and caudate nucleus declined with increasing HY staging and scoring for bradykinesia and rigidity. Putamen RACLO binding to D2 dopamine receptors was up-regulated in patients with HY-I-II PD but declined toward control values, with increasing disease severity. Putamen side-to-side asymmetries of FDOPA metabolism and RACLO binding revealed a significant correlation. Putamen FDG metabolism showed a relative increase in all patients with PD. CONCLUSIONS: Our results show that FDOPA, RACLO, and FDG PET measurements provide complementary information to characterize metabolic and receptor changes in the striatum of PD with different degrees of motor disability. The FDOPA uptake reflects the best motor-related pathologic features, as indicated by the significant correlation between Ki values and clinical scores. The significant association between RACLO and FDOPA in the putamen suggests that D2 dopamine receptor changes are related to the reduction of presynaptic dopaminergic nerve terminals. Putamen FDG increase is probably the result of more complex feedback mechanisms that are primarily induced by striatal dopamine deficiency
AD  - PET Department, Paul Scherrer Institute, Villigen, Switzerland
UR  - PM:7492293
ER  - 

TY  - JOUR
T1  - Dynamics of multidrug resistance: P-glycoprotein analyses with positron emission tomography
A1  - Hendrikse,N.H.
A1  - Vaalburg,W.
Y1  - 2002/07//
N1  - UI - 22171113
SP  - 228
EP  - 233
JA  - Methods
VL  - 27
IS  - 3
N2  - Multidrug resistance (MDR) is characterized by the occurrence of cross-resistance to a broad range of structurally and functionally unrelated drugs. Several mechanisms are involved in MDR. One of the most well-known mechanisms is the overexpression of P-glycoprotein (P-gp), encoded by the MDR1 gene in humans and by the mdr1a and mdr1b genes in rodents. P-gp is extensively expressed in the human body, e.g., in the blood-brain barrier and also in solid tumor tissue. Overexpression of P-gp on tumor membranes might result in MDR of human tumors. To circumvent this resistant phenotype, several P-gp modulators such as cyclosporin A (CsA) are available. Competition between P-gp drugs and modulators results in decreased transport of the drug out of tumor tissue and an increased cellular level of these drugs. For effective clinical treatment it is important to have knowledge about P-gp functionality in tumors. Therefore, we have developed a method to measure the P-gp functionality in vivo with PET and [(11)C]verapamil as a positron-emitting P-gp substrate. The results obtained in rodents and in cancer patients are described in this article
AD  - PET Center, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. n.h.hendrikse@pet.azg.nl
UR  - PM:12183111
ER  - 

TY  - JOUR
T1  - Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection
A1  - Costes,N.
A1  - Merlet,I.
A1  - Zimmer,L.
A1  - Lavenne,F.
A1  - Cinotti,L.
A1  - Delforge,J.
A1  - Luxen,A.
A1  - Pujol,J.F.
A1  - Le Bars,D.
Y1  - 2002/06//
SP  - 753
EP  - 765
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 6
N2  - The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2;-methoxyphenyl)-1-[2;-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperaz ine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9 pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to Bmax. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols
AD  - Centre d'Exploration et de Recherche Medicales par Emission de Positons, Lyon, France. costes@cermep.fr
UR  - PM:12045674
ER  - 

TY  - JOUR
T1  - Analyses of [(18)F]altanserin bolus injection PET data. II: consideration of radiolabeled metabolites in humans
A1  - Price,J.C.
A1  - Lopresti,B.J.
A1  - Meltzer,C.C.
A1  - Smith,G.S.
A1  - Mason,N.S.
A1  - Huang,Y.
A1  - Holt,D.P.
A1  - Gunn,R.N.
A1  - Mathis,C.A.
Y1  - 2001/07//
SP  - 11
EP  - 21
JF  - Synapse
VL  - 41
IS  - 1
N2  - Imaging serotonin-2A (5-HT(2A)) neuroreceptors with positron emission tomography (PET) and [(18)F]altanserin has been the focus of a series of PET studies, as [(18)F]altanserin is one of the most selective 5-HT(2A) antagonist radiotracers. Previous animal studies showed that radiolabeled metabolites (radiometabolites) of [(18)F]altanserin crossed the blood-brain barrier (BBB) to localize nonspecifically in brain, consistent with a constant radioactivity "background." In this work, we evaluated human bolus injection [(18)F]altanserin PET data with detailed consideration of the impact of BBB-permeable metabolites on the specific binding parameters. Data were quantified using either single (parent radiotracer), dual (parent radiotracer and radiometabolites), or no arterial input function(s) (cerebellum as reference tissue input function). A step-gradient high-performance liquid chromatography (HPLC) analysis provided distinct separation of [(18)F]altanserin and four radiolabeled components in plasma. After [(18)F]altanserin injection, the step-gradient data showed that the major BBB-permeable radiometabolites approached constant levels in plasma (>50 min), consistent with a constant metabolite "background." The single-input Logan graphical results were highly correlated with the dual-input results and its bias was fairly constant across regions and subjects, as similarly observed for a nongraphical reference tissue method. The most comprehensive and quantitatively valid analysis for bolus [(18)F]altanserin PET data was the dual-input method that specifically accounted for BBB-permeable metabolites, although the Logan analysis was preferred because it provided a good compromise between validity, sensitivity, and reliability of implementation. Further study is needed to better understand how the cerebellar kinetics of [(18)F]altanserin and its radiometabolites impact the reference tissue measures
AD  - Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. price@pet.upmc.edu
UR  - PM:11354009
ER  - 

TY  - JOUR
T1  - Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression
A1  - Oquendo,M.A.
A1  - Placidi,G.P.
A1  - Malone,K.M.
A1  - Campbell,C.
A1  - Keilp,J.
A1  - Brodsky,B.
A1  - Kegeles,L.S.
A1  - Cooper,T.B.
A1  - Parsey,R.V.
A1  - Van Heertum,R.L.
A1  - Mann,J.J.
Y1  - 2003/01//
N1  - UI - 22399424
SP  - 14
EP  - 22
JA  - Arch.Gen.Psychiatry
VL  - 60
IS  - 1
N2  - BACKGROUND: Lower serotonergic activity correlates with high-lethality suicide attempts in major depression. Postmortem studies of serotonin receptors in suicides localize changes to the ventral prefrontal cortex (PFC). We studied serotonergic response in ventral PFC in depressed patients surviving a high-lethality suicide attempt. METHODS: Depressed patients with a history of a high-lethality suicide attempt (n = 16) were compared with those with low-lethality attempts (n = 9) for level of depression, suicidal intent and ideation, impulsivity, aggression, and neuropsychological test performance. Subjects were scanned while medication free after a single-blind placebo and after fenfluramine hydrochloride administration on a second day. Brain responses were measured by positron emission tomography imaging of fludeoxyglucose F 18 and serial prolactin levels. Scans were compared by means of statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical and neuropsychological measures were assessed. RESULTS: Depressed high-lethality suicide attempters had lower rCMRglu in ventral, medial, and lateral PFC compared with low-lethality attempters. This difference was more pronounced after fenfluramine administration. Lower ventromedial PFC activity was associated with lower lifetime impulsivity, higher suicidal intent (planning), and higher-lethality suicide attempts. Higher verbal fluency was positively correlated with rCMRglu in the same regions. CONCLUSIONS: Prefrontal localized hypofunction and impaired serotonergic responsivity are proportional to the lethality of the suicide attempt and may mediate the effects of suicide intent and impulsivity on lethality. Positron emission tomographic neuroreceptor studies are needed to determine whether postmortem serotonin receptor findings are also present in vivo and contribute to the abnormal rCMRglu responses
AD  - Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Dr, New York, NY 10032. mao4@columbia.edu
UR  - PM:12511168
ER  - 

TY  - JOUR
T1  - Screening for Cerebral Metastases with FDG PET in Patients Undergoing Whole-Body Staging of Non-Central Nervous System Malignancy
A1  - Rohren,E.M.
A1  - Provenzale,J.M.
A1  - Barboriak,D.P.
A1  - Coleman,R.E.
Y1  - 2003/01//
N1  - UI - 22400034
SP  - 181
EP  - 187
JF  - Radiology
VL  - 226
IS  - 1
N2  - PURPOSE: To compare fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) with the current standard, magnetic resonance (MR) imaging, to determine the sensitivity and specificity of FDG PET for detection of cerebral metastases and to determine the factors that may affect lesion conspicuity. MATERIALS AND METHODS: Forty patients underwent brain PET and contrast material-enhanced brain MR imaging, with a maximum of 30 days between examinations. PET and MR images were each retrospectively reviewed by two independent readers who were blinded to the clinical history and results of the other technique. Presence of metastatic disease was recorded for each modality. Sensitivity and specificity of FDG PET were determined with MR imaging as the standard. Statistical analysis was performed with the Fisher exact test and the logistic regression model. RESULTS: Sixteen patients had cerebral metastases at MR imaging, and in 12 of these, PET scans were interpreted as showing metastatic disease (in four, scans were false-negative). Twenty-four patients had no cerebral metastases at MR imaging, and 20 of these had PET scans interpreted as normal (in four, scans were false-positive). For identification of patients with cerebral metastases, FDG PET had a sensitivity of 75% (12 of 16) and a specificity of 83% (20 of 24). Thirty-eight metastatic lesions were seen at MR imaging; 23 (61%) of these were identified at PET. Size was a statistically significant factor that influenced lesion detection at PET (P <.001). CONCLUSION: Only 61% of metastatic lesions in the brain were identified at PET. In particular, detection of small lesions was difficult. Copyright RSNA, 2002
AD  - Department of Radiology, Duke University Medical Center, Durham, NC. From the 2000 RSNA scientific assembly. Received May 14, 2001
UR  - PM:12511688
ER  - 

TY  - JOUR
T1  - Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression
A1  - Tjuvajev,J.G.
A1  - Doubrovin,M.
A1  - Akhurst,T.
A1  - Cai,S.
A1  - Balatoni,J.
A1  - Alauddin,M.M.
A1  - Finn,R.
A1  - Bornmann,W.
A1  - Thaler,H.
A1  - Conti,P.S.
A1  - Blasberg,R.G.
Y1  - 2002/08//
SP  - 1072
EP  - 1083
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 43
IS  - 8
N2  - The efficacy of 3 radiolabeled probes of current interest for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) expression in vivo with PET, including (124)I- or (131)I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU), (18)F-labeled 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine (FHBG), and (18)F-labeled 9-[3-fluoro-1-hydroxy-2-propoxymethyl]guanine (FHPG), was compared. METHODS: Two established rat glioma cell lines, stably transduced RG2TK+ and wild-type RG2, were used for paired comparisons of probe accumulation in vitro and for paired comparisons of subcutaneous xenografts produced from these cell lines in athymic rnu/rnu rats. RESULTS: The in vitro paired probe uptake (0-3 h) comparisons in RG2TK+ cells showed that FIAU accumulation was 15-fold greater than that of FHBG and 41-fold greater than that of FHPG. The net accumulation rate values (+/-SD) calculated for RG2TK+ cells were 0.317 +/- 0.066, 0.022 +/- 0.001, and 0.0077 +/- 0.0003 mL/min/g cells for FIAU, FHBG, and FHPG, respectively. These results and similar uptake studies in RG2 wild-type cells suggest a possible cell membrane transport limitation for FHBG and FHPG. The paired 2-h in vivo uptake studies produced similar differences in RG2TK+ xenografts for FIAU and FHBG (1.22 +/- 0.21 vs. 0.074 +/- 0.49 %dose/g) and for FIAU and FHPG (1.27 +/- 0.14 vs. 0.023 +/- 0.008 %dose/g). These differences were clearly visible on the images. FIAU accumulation at 24 h was 1.53 +/- 0.40 %dose/g. Plasma clearance was FHBG > FHPG >> FIAU. The FIAU images showed significant stomach and some intestinal background radioactivities, whereas hepatobiliary and intestinal background activities were very high for the guanosine analogs (FHBG > FHPG). Dynamic imaging showed early ( approximately 10 min) selective localization of FIAU in RG2TK+ xenografts, whereas FHBG and FHPG are being cleared from the HSV1-tk transduced and wild-type xenografts over the initial 2-h imaging period. CONCLUSION: The in vitro and in vivo results (including the PET images) show that FIAU is a substantially more efficient probe than FHBG or FHPG for imaging HSV1-tk expression, with greater sensitivity and contrast as well as lower levels of abdominal background radioactivity at 2 and 24 h
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
UR  - PM:12163634
ER  - 

TY  - JOUR
T1  - Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo
A1  - Ponomarev,V.
A1  - Doubrovin,M.
A1  - Lyddane,C.
A1  - Beresten,T.
A1  - Balatoni,J.
A1  - Bornman,W.
A1  - Finn,R.
A1  - Akhurst,T.
A1  - Larson,S.
A1  - Blasberg,R.
A1  - Sadelain,M.
A1  - Tjuvajev,J.G.
Y1  - 2001/11//
SP  - 480
EP  - 488
JA  - Neoplasia.
VL  - 3
IS  - 6
N2  - A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR)-dependent nuclear factor of activated T cells (NFAT)-mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP)] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OFI and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [(124)I]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs
AD  - Departments of Neurology and Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
UR  - PM:11774030
ER  - 

TY  - JOUR
T1  - Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy
A1  - Tjuvajev,J.G.
A1  - Finn,R.
A1  - Watanabe,K.
A1  - Joshi,R.
A1  - Oku,T.
A1  - Kennedy,J.
A1  - Beattie,B.
A1  - Koutcher,J.
A1  - Larson,S.
A1  - Blasberg,R.G.
Y1  - 1996/09/15/
N1  - UI - 96390585
SP  - 4087
EP  - 4095
JA  - Cancer Res.
VL  - 56
IS  - 18
N2  - Noninvasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is possible with a clinical gamma camera and by single-photon emission tomography (SPECT) using 131I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil (FIAU). Studies were performed in rats bearing s.c. tumors. Tumors were produced by injection of wild-type RG2 glioma or W256 mammary carcinoma cells into one flank and RG2TK+ glioma or W256TK+ mammary carcinoma cells (that had been transduced in vitro with the HSV1-tk gene) into the opposite flank. In some animals, HSV1-tk gene transduction of the pre-established wild-type tumors was accomplished in vivo by direct intratumoral injection of retroviral vector-producer cells. Imaging studies were performed 2 weeks after tumor transduction to allow time for production and spread of the retroviruses through the tumor and for sufficient growth and increase in size of the tumors to facilitate imaging. The gamma camera and SPECT images revealed highly specific localization of [131I]FIAU-derived radioactivity to areas of HSV1-tk gene expression at 24, 36, and 48 h after i.v. administration of 1.6-2.8 mCi of [131I]FIAU. Comparative analysis of quantitative autoradiographic images obtained from the same tumors confirmed that the high levels of [131I]FIAU-derived radioactivity (> 1% dose) were localized to areas of HSV1-tk gene expression demonstrated by immunohistochemical staining for HSV1-tk protein. In contrast, significantly lower levels of [131I]FIAU-derived radioactivity (< 0.01%) were observed in the surrounding nontransduced tumor tissue, contralateral wild-type tumors, and other tissues that showed no immunohistochemical staining for the HSV1-tk protein. The magnitude of FIAU accumulation in RG2TK+, W256TK+, and wild-type tumors corresponded to the in vitro ganciclovir sensitivity of the cell lines used to produce these tumors, which indicates that the magnitude of FIAU accumulation reflects the level of HSV1-tk gene expression. We suggest that "clinically relevant" levels of HSV1-tk gene expression in transfected tissue can be imaged with [131I]FIAU and a gamma camera or SPECT, and that a significant improvement in imaging sensitivity and resolution is expected with [124I]FIAU and PET
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York New York 10021, USA
UR  - PM:8797571
ER  - 

TY  - JOUR
T1  - Imaging the expression of transfected genes in vivo
A1  - Tjuvajev,J.G.
A1  - Stockhammer,G.
A1  - Desai,R.
A1  - Uehara,H.
A1  - Watanabe,K.
A1  - Gansbacher,B.
A1  - Blasberg,R.G.
Y1  - 1995/12/15/
N1  - UI - 96105031
SP  - 6126
EP  - 6132
JA  - Cancer Res.
VL  - 55
IS  - 24
N2  - Imaging the expression of successful gene transduction has been demonstrated in vivo for the first time by using an appropriate combination of "marker gene" and "marker substrate" in an experimental animal model. The herpes simplex virus 1 thymidine kinase (HSV1-tk) gene was selected as an example of a marker gene, and the recombinant STK retrovirus containing HSV1-tk was used to transduce RG2 glioma cells in vitro and in vivo. RG2TK+ cell lines expressing the HSV1-tk gene and three potential marker substrates for the HSV1-TK enzyme were evaluated. Radiolabeled 5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) was shown to be a substantially better marker substrate for the HSV1-TK enzyme than 5-iodo-2'-deoxyuridine or ganciclovir. The magnitude of FIAU accumulation in different RG2TK+ clones corresponded to their sensitivity to ganciclovir and to the level of HSV1-tk mRNA expression. Imaging the expression of HSV1-tk in transduced RG2 tumor cells was demonstrated in animals using quantitative autoradiography; 2-[14C]FIAU accumulation was shown to be high in RG2TK+ brain tumors growing in one hemisphere and very low in nontransduced RG2 tumors in the contralateral hemisphere. Transduction of RG2 tumor cells with the HSV-tk gene in vivo resulted in tumors which accumulated FIAU to high levels and produced clearly defined images. Given the level of FIAU accumulation in the transduced tumors, it is likely that a clinically applicable method for imaging HSV1-tk gene expression can be implemented using existing clinical imaging techniques
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
UR  - PM:8521403
ER  - 

TY  - JOUR
T1  - Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B
A1  - McKenzie,R.
A1  - Fried,M.W.
A1  - Sallie,R.
A1  - Conjeevaram,H.
A1  - Di Bisceglie,A.M.
A1  - Park,Y.
A1  - Savarese,B.
A1  - Kleiner,D.
A1  - Tsokos,M.
A1  - Luciano,C.
Y1  - 1995/10/26/
N1  - UI - 96013503
SP  - 1099
EP  - 1105
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 333
IS  - 17
N2  - BACKGROUND. We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. METHODS. Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. RESULTS. During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. CONCLUSIONS. In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues
AD  - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
UR  - PM:7565947
ER  - 

TY  - JOUR
T1  - PET imaging of gene expression
A1  - Blasberg,R.
Y1  - 2002/11//
N1  - UI - 22275740
SP  - 2137
EP  - 2146
JA  - Eur.J Cancer
VL  - 38
IS  - 16
N2  - Noninvasive in vivo molecular imaging has developed over the past decade and involves nuclear (Positron emission tomography (PET), gamma camera), magnetic resonance, and in vivo optical imaging systems. Most current in vivo molecular imaging strategies are "indirect" and involve the coupling of a "reporter gene" with a complimentary "reporter probe". Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. Reporter gene constructs are driven by upstream promoter/enhancer elements; they can be constitutive leading to continuous transcription and used to identify the site of transduction and to monitor the level and duration of gene (vector) activity. Alternatively, they can be inducible leading to controlled gene expression, or they can function as a sensor element to monitor the level of endogenous promoters and transcription factors. Several examples of imaging endogenous biological processes in animals using reporter constructs, radiolabelled probes and PET imaging are reviewed (p53-dependent gene expression and T-cell receptor-dependent activation of T-lymphocytes). Issues related to the translation of non-invasive molecular imaging technology into the clinic are discussed
AD  - Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. blasberg@neuro1.mskcc.org
UR  - PM:12387839
ER  - 

TY  - JOUR
T1  - The development of [(124)I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography
A1  - Collingridge,D.R.
A1  - Carroll,V.A.
A1  - Glaser,M.
A1  - Aboagye,E.O.
A1  - Osman,S.
A1  - Hutchinson,O.C.
A1  - Barthel,H.
A1  - Luthra,S.K.
A1  - Brady,F.
A1  - Bicknell,R.
A1  - Price,P.
A1  - Harris,A.L.
Y1  - 2002/10/15/
SP  - 5912
EP  - 5919
JA  - Cancer Res.
VL  - 62
IS  - 20
N2  - The development of anticancer therapies that target the angiogenic process is an area of major growth in oncology. A method of noninvasively measuring tumor vascular endothelial growth factor (VEGF) in vivo could provide important efficacy information for VEGF-dependent antiangiogenic agents and the role of VEGF in cancer biology. We have developed a novel radiotracer for use with positron emission tomography (PET) that enables noninvasive imaging of VEGF. This radiotracer comprises an IgG1 monoclonal antibody, known as VG76e, that binds to human VEGF, labeled with a positron-emitting radionuclide, iodine-124 ([(124)I]-SHPP-VG76e). Three radiolabeling strategies were evaluated to synthesize the radiotracer with optimal radiochemical yield, purity, and immunoreactivity. To evaluate the pharmacokinetics and VEGF-specific localization of [(124)I]-SHPP-VG76e, two subclones of the HT1080 human fibrosarcoma selected on the basis of differing VEGF production (26.6 and 1/3C, the former producing 2-4-fold more in vitro) were established in culture and grown as solid tumor xenografts in immune-deficient mice. A single i.v. injection of the radiotracer into tumor-bearing mice revealed a time dependent and specific localization of [(125)I]-SHPP-VG76e to the tumor tissue. Three validation studies established the VEGF specificity and potential for use of [(124)I]-SHPP-VG76e in vivo: (a) uptake of [(125)I]-SHPP-VG76e was 1.8-fold higher in HT1080-26.6 compared with HT1080-1/3C tumors (P < 0.05); (b) uptake of [(125)I]-SHPP-VG76e in HT1080-26.6 tumors was specifically blocked by prior administration of excess unlabeled VG76e (P < 0.05); and (c) tumor uptake of the IgG1, [(125)I]-SHPP-CIP5, which has a similar molecular weight as [(125)I]-SHPP-VG76e but does not recognize VEGF, was the same for both HT1080-26.6 and HT1080-1/3C (P > 0.05). Other than tumor localization, [(125)I]-SHPP-VG76e was present in urine and blood and to a lesser extent in heart, lungs, liver, kidney, and spleen. Whole-animal PET imaging studies revealed a high tumor-to-background contrast and also revealed [(124)I]-SHPP-VG76e distributions in the major organs. These studies support further development of [(124)I]-SHPP-VG76e as a radiotracer for measuring tumor levels of VEGF in humans
AD  - Cancer Research UK Positron Emission Tomography Oncology Group, Department of Cancer Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0NN
UR  - PM:12384557
ER  - 

TY  - JOUR
T1  - Applications of adenosine receptor ligands in medical imaging by positron emission tomography
A1  - Holschbach,M.H.
A1  - Olsson,R.A.
Y1  - 2002///
N1  - UI - 22257398
SP  - 2345
EP  - 2352
JA  - Curr.Pharm.Des
VL  - 8
IS  - 26
N2  - In the last decade the field of purinergic pharmacology has continued to grow as the complexity of the receptor families and the various enzymes involved in purine metabolism have been defined in molecular terms. Adenosine receptors (ARs) are currently divided into the four subclasses A(1)-, A(2A)-, A(2B)- and A(3)AR. The most intensively studied subtypes are the high-affinity A(1) and A(2A) receptors, which are activated by adenosine in nano- to submicromolar concentrations. The clinical importance of the A(1) adenosine receptor (A(1)AR) and the A(2A)adenosine receptor (A(2A)AR) makes them attractive targets for radionuclide in vivo imaging. Positron Emission Tomography (PET) is an imaging modality which can determine biochemical and physiological processes in vivo in a quantitative way by using radiopharmaceuticals labeled with positron emitting radionuclides as (11)C, (13)N, (15)O and (18)F and by measuring the annihilation radiation using a coincidence technique. This includes also measurement of the pharmacokinetics of labeled drugs and the assessment of the effects of drugs on metabolism. In the present article we review the radioligands which are currently available for visualisation and quantification of ARs using PET with a special focus on the A(1)AR and A(2A)AR
AD  - Institut fur Nuklearchemie, Forschungszentrum Julich GmbH, Germany. m.holschbach@fz-juelich.de
UR  - PM:12369949
ER  - 

TY  - JOUR
T1  - Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies
A1  - Jayson,G.C.
A1  - Zweit,J.
A1  - Jackson,A.
A1  - Mulatero,C.
A1  - Julyan,P.
A1  - Ranson,M.
A1  - Broughton,L.
A1  - Wagstaff,J.
A1  - Hakannson,L.
A1  - Groenewegen,G.
A1  - Bailey,J.
A1  - Smith,N.
A1  - Hastings,D.
A1  - Lawrance,J.
A1  - Haroon,H.
A1  - Ward,T.
A1  - McGown,A.T.
A1  - Tang,M.
A1  - Levitt,D.
A1  - Marreaud,S.
A1  - Lehmann,F.F.
A1  - Herold,M.
A1  - Zwierzina,H.
Y1  - 2002/10/02/
SP  - 1484
EP  - 1493
JA  - J Natl.Cancer Inst.
VL  - 94
IS  - 19
N2  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. METHODS: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 (0.3, 1, 3, or 10 mg/kg). Positron emission tomography with (124)I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (k(fp)) to determine tumor vascular permeability. RESULTS: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic endpoints could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumors. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in k(fp) 48 hours after the first treatment (median = 44%; range = 4%-91%). CONCLUSIONS: Because of the heterogeneity in tumor biology with respect to antibody uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with antiangiogenic compounds like HuMV833
AD  - Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK. Gordon.Jayson@christie-tr.nwest.nhs.uk
UR  - PM:12359857
ER  - 

TY  - JOUR
T1  - Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations
A1  - Wu,R.M.
A1  - Shan,D.E.
A1  - Sun,C.M.
A1  - Liu,R.S.
A1  - Hwu,W.L.
A1  - Tai,C.H.
A1  - Hussey,J.
A1  - West,A.
A1  - Gwinn-Hardy,K.
A1  - Hardy,J.
A1  - Chen,J.
A1  - Farrer,M.
A1  - Lincoln,S.
Y1  - 2002/07//
SP  - 670
EP  - 675
JA  - Mov Disord.
VL  - 17
IS  - 4
N2  - We report on clinical (18)F-labeled 6-fluorodopa ((18)F-dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early-onset Parkinson's disease. As described in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive-compulsive disorders were manifest. The (18)F-dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function
AD  - Department of Neurology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, Republic of China
UR  - PM:12210855
ER  - 

TY  - JOUR
T1  - Synthesis and evaluation of 4-bromo-1-(3-[18F]fluoropropyl)-2-nitroimidazole with a low energy LUMO orbital designed as brain hypoxia-targeting imaging agent
A1  - Yamamoto,F.
A1  - Aoki,M.
A1  - Furusawa,Y.
A1  - Ando,K.
A1  - Kuwabara,Y.
A1  - Masuda,K.
A1  - Sasaki,S.
A1  - Maeda,M.
Y1  - 2002/05//
SP  - 616
EP  - 621
JA  - Biol.Pharm.Bull.
VL  - 25
IS  - 5
N2  - In order to develop new imaging markers for brain hypoxia, 4-bromo-1-(3-fluoropropyl)-2-nitroimidazole (4-BrFPN) was designed based on molecular orbital calculations, synthesized and labeled with fluorine-18 as a lipophilic nitroimidazole analog with a lower energy LUMO orbital than those for fluoromisonidazole (FMISO) and 1-(3-fluoropropyl)-2-nitroimidazole (FPN). In an in vitro radiosensitization study, the sensitizer enhancement ratio for 4-BrFPN was found to be 1.65 at a I mM concentration, in comparison to 1.81 for FMISO. The preparation of 18F-labeled 4-BrFPN (4-Br18FPN) was achieved by [18F]fluoride ion displacement reaction of the tosylate precursor, in a reasonable radiochemical yield (33%, not corrected for decay). Metabolites in tumor and muscle extracts from methylcholanthrene-induced fibrosarcoma mice, as well as the tissue distribution of 4-Br18FPN in normal rats, were studied. The initial uptake into rat brain of 4-Br18FPN was significantly higher relative to 18F-labeled FMISO (18FMISO), followed by a rapid washout from the brain. The tumor uptake of 4-Br18FPN was somewhat enhanced compared to those obtained with 18FMISO and 18F-labeled FPN (18FPN), but with lower tumor localization than 18FMISO. Analyses of tumor and muscle extracts showed metabolites remaining base line on the radio-TLC plates, and they were produced to a greater extent in tumor than muscle. The use of two drugs which increase hypoxic cell fraction in tumor, hydralazine or nitro-L-arginine, produced a significant increase in tumor levels of 4-Br18FPN, suggestive of a hypoxic mechanism of accumulation. The results imply that lowering of the LUMO energy of a molecule alone is not sufficient to improve its biodistribution properties for better imaging of regions of hypoxia
AD  - Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
UR  - PM:12033502
ER  - 

TY  - JOUR
T1  - Noninvasive imaging of protein-protein interactions in living animals
A1  - Luker,G.D.
A1  - Sharma,V.
A1  - Pica,C.M.
A1  - Dahlheimer,J.L.
A1  - Li,W.
A1  - Ochesky,J.
A1  - Ryan,C.E.
A1  - Piwnica-Worms,H.
A1  - Piwnica-Worms,D.
Y1  - 2002/05/14/
SP  - 6961
EP  - 6966
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 99
IS  - 10
N2  - Protein-protein interactions control transcription, cell division, and cell proliferation as well as mediate signal transduction, oncogenic transformation, and regulation of cell death. Although a variety of methods have been used to investigate protein interactions in vitro and in cultured cells, none can analyze these interactions in intact, living animals. To enable noninvasive molecular imaging of protein-protein interactions in vivo by positron-emission tomography and fluorescence imaging, we engineered a fusion reporter gene comprising a mutant herpes simplex virus 1 thymidine kinase and green fluorescent protein for readout of a tetracycline-inducible, two-hybrid system in vivo. By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs. Imaging protein-binding partners in vivo will enable functional proteomics in whole animals and provide a tool for screening compounds targeted to specific protein-protein interactions in living animals
AD  - Molecular Imaging Center, Mallinckrodt Institute of Radiology and Department of Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Luker-protein-interactions.pdf
ER  - 

TY  - JOUR
T1  - Cells exposed to antifolates show increased cellular levels of proteins fused to dihydrofolate reductase: a method to modulate gene expression
A1  - Mayer-Kuckuk,P.
A1  - Banerjee,D.
A1  - Malhotra,S.
A1  - Doubrovin,M.
A1  - Iwamoto,M.
A1  - Akhurst,T.
A1  - Balatoni,J.
A1  - Bornmann,W.
A1  - Finn,R.
A1  - Larson,S.
A1  - Fong,Y.
A1  - Gelovani,Tjuvajev J.
A1  - Blasberg,R.
A1  - Bertino,J.R.
Y1  - 2002/03/19/
SP  - 3400
EP  - 3405
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 99
IS  - 6
N2  - Human cells exposed to antifolates show a rapid increase in the levels of the enzyme dihydrofolate reductase (DHFR). We hypothesized that this adaptive response mechanism can be used to elevate cellular levels of proteins fused to DHFR. In this study, mouse cells transfected to express a green fluorescent protein-DHFR fusion protein and subsequently exposed to the antifolate trimetrexate (TMTX) showed a specific and time-dependent increase in cellular levels of the fusion protein. Next, human HCT-8 and HCT-116 colon cancer cells retrovirally transduced to express a DHFR-herpes simplex virus 1 thymidine kinase (HSV1 TK) fusion protein and treated with the DHFR inhibitor TMTX exhibited increased levels of the DHFR-HSV1 TK fusion protein and an increase in ganciclovir sensitivity by 250-fold. The level of fusion protein in antifolate-treated human tumor cells was increased in response to a 24-h exposure of methotrexate, trimetrexate, as well as dihydrofolate. This effect depended on the antifolate concentration and was independent of the fusion-protein mRNA levels, consistent with this increase occurring at a translational level. In a xenograft model, nude rats bearing DHFR-HSV1 TK-transduced HCT-8 tumors and treated with TMTX showed, after 24 h, a 2- to 4-fold increase of fusion-protein levels in tumor tissue from treated animals compared with controls, as determined by Western blotting. The fusion-protein increase was imaged with positron-emission tomography, where a substantially enhanced signal of the transduced tumor was detected in animals after antifolate administration. Drug-mediated elevation of cellular DHFR-fused proteins is a very useful method to modulate gene expression in vivo for imaging as well as therapeutic purposes
AD  - Molecular Pharmacology and Therapeutics Program, Department of Surgery, Nuclear Medicine Service, Radiochemistry/ Cyclotron, and Preparative Synthesis Chemistry Core Facilities, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Meyer-Kuckuk-gene-expression.pdf
ER  - 

TY  - JOUR
T1  - Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET)
A1  - Bencherif,B.
A1  - Fuchs,P.N.
A1  - Sheth,R.
A1  - Dannals,R.F.
A1  - Campbell,J.N.
A1  - Frost,J.J.
Y1  - 2002/10//
N1  - UI - 22294890
SP  - 589
EP  - 598
JF  - Pain
VL  - 99
IS  - 3
N2  - The role of the supraspinal endogenous opioid system in pain processing has been investigated in this study using positron emission tomography imaging of [11C]-carfentanil, a synthetic, highly specific mu opioid receptor (mu-OR) agonist. Eight healthy volunteers were studied during a baseline imaging session and during a session in which subjects experienced pain induced by applying capsaicin topically to the dorsal aspect of the left hand. A pain-related decrease in brain mu-OR binding was observed in the contralateral thalamus consistent with competitive binding between [11C]-carfentanil and acutely released endogenous opioid peptides. This decrease varied directly with ratings of pain intensity. These results suggest that the supraspinal mu-opioid system is activated by acute pain and thus may play a substantial role in pain processing and modulation in pain syndromes
AD  - Department of Radiology, The Johns Hopkins University School of Medicine, JHOC 3225, 601 N Caroline Street, Baltimore, MD 21287, USA
UR  - PM:12406535
ER  - 

TY  - JOUR
T1  - PET imaging of brain acetylcholinesterase using [11C]CP-126,998, a brain selective enzyme inhibitor
A1  - Bencherif,B.
A1  - Endres,C.J.
A1  - Musachio,J.L.
A1  - Villalobos,A.
A1  - Hilton,J.
A1  - Scheffel,U.
A1  - Dannals,R.F.
A1  - Williams,S.
A1  - Frost,J.J.
Y1  - 2002/07//
N1  - UI - 22107790
SP  - 1
EP  - 9
JF  - Synapse
VL  - 45
IS  - 1
N2  - PET and [(11)C]CP-126,998, an N-benzylpiperidinebenzisoxazole, were used to image brain acetylcholinesterase (AChE) distribution in healthy controls before and after administration of 5 mg donepezil p.o., a reversible AChE inhibitor. Logan plots were used to compute distribution volumes (V(T)). The V(T) of [(11)C]CP-126,998 was highest in the basal ganglia and cerebellum and lowest in the cerebral cortex, thalamus, amygdala, and hippocampus. The regional V(T) values correlated well with AChE concentration measured in vitro. Donepezil, given 4 h before PET scanning, induced a substantial inhibition of [(11)C]CP-126,998 binding (43-62%) in all brain regions when compared to the baseline PET study. The results of this study indicate that PET imaging of [(11)C]CP-126,998 may be useful in quantifying the distribution of regional brain AChE. This new PET radiotracer may potentially be employed in the diagnosis and treatment of patients with disorders of cholinergic neurotransmission, such as Alzheimer's disease
AD  - Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
UR  - PM:12112408
ER  - 

TY  - JOUR
T1  - Radiosynthesis and mouse brain distribution studies of [11C] CP-126,998: a PET ligand for in vivo study of acetylcholinesterase
A1  - Musachio,J.L.
A1  - Flesher,J.E.
A1  - Scheffel,U.A.
A1  - Rauseo,P.
A1  - Hilton,J.
A1  - Mathews,W.B.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 2002/07//
N1  - UI - 22084416
SP  - 547
EP  - 552
JA  - Nucl Med Biol.
VL  - 29
IS  - 5
N2  - The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxaz ol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/micromol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase
AD  - Johns Hopkins University School of Medicine, Department of Radiology, Division of Nuclear Medicine, Baltimore, MD 21287, USA. jlmusachio@petscan.nm.jhu.edu
UR  - PM:12088724
ER  - 

TY  - JOUR
T1  - Strategies to improve neuroreceptor parameter estimation by linear regression analysis
A1  - Ichise,M.
A1  - Toyama,H.
A1  - Innis,R.B.
A1  - Carson,R.E.
Y1  - 2002/10//
N1  - UI - 22254937
SP  - 1271
EP  - 1281
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 10
N2  - In an attempt to improve neuroreceptor distribution volume (V) estimates, the authors evaluated three alternative linear methods to Logan graphical analysis (GA): GA using total least squares (TLS), and two multilinear analyses, MA1 and MA2, based on mathematical rearrangement of GA equation and two-tissue compartments, respectively, using simulated and actual PET data of two receptor tracers, [(18)F]FCWAY and [(11)C]MDL 100,907. For simulations, all three methods decreased the noise-induced GA bias (up to 30%) at the expense of increased variability. The bias reduction was most pronounced for MA1, moderate to large for MA2, and modest to moderate for TLS. In addition, GA, TLS, and MA1, methods that used only a portion of the data (T > t*, chosen by an automatic process), showed a small underestimation for [(11)C]MDL 100,907 with its slow kinetics, due to selection of t* before the true point of linearity. These noniterative methods are computationally simple, allowing efficient pixelwise parameter estimation. For tracers with kinetics that permit t* to be accurately identified within the study duration, MA1 appears to be the best. For tracers with slow kinetics and low to moderate noise, however, MA2 may provide the lowest bias while maintaining computational ease for pixelwise parameter estimation
AD  - Molecular Imaging Branch, National Institutes of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. masanori.ichise@nih.gov
UR  - PM:12368666
ER  - 

TY  - JOUR
T1  - Brain metabolic changes during cigarette craving
A1  - Brody,A.L.
A1  - Mandelkern,M.A.
A1  - London,E.D.
A1  - Childress,A.R.
A1  - Lee,G.S.
A1  - Bota,R.G.
A1  - Ho,M.L.
A1  - Saxena,S.
A1  - Baxter,L.R.,Jr.
A1  - Madsen,D.
A1  - Jarvik,M.E.
Y1  - 2002/12//
N1  - UI - 22358254
SP  - 1162
EP  - 1172
JA  - Arch.Gen.Psychiatry
VL  - 59
IS  - 12
N2  - BACKGROUND: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. METHODS: Twenty heavy smokers (who smoked >/=20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). RESULTS: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. CONCLUSIONS: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances
AD  - Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA 90095. abrody@ucla.edu
UR  - PM:12470133
ER  - 

TY  - JOUR
T1  - The type 2 human somatostatin receptor as a platform for reporter gene imaging
A1  - Zinn,K.R.
A1  - Chaudhuri,T.R.
Y1  - 2002/03//
N1  - UI - 21997392
SP  - 388
EP  - 399
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 29
IS  - 3
N2  - The human somatostatin receptor subtype 2A (hSSTr2) is under evaluation as a reporter gene for molecular imaging applications. Two approved somatostatin analogues are already available for imaging expression of the reporter gene following delivery with adenoviral (Ad) vectors or other genetic targeting strategies. In animal models, Ad-mediated expression of hSSTr2 in subcutaneous and intraperitoneal tumors was detected by non-invasive gamma camera imaging. This review discusses the rationale and strategy for using the hSSTr2 reporter gene as a platform for imaging applications
AD  - Department of Radiology, University of Alabama at Birmingham, 35294, USA. kurtzinn@uab.edu
UR  - PM:12002716
ER  - 

TY  - JOUR
T1  - In vivo localization of [(111)In]-DTPA-D-Phe1-octreotide to human ovarian tumor xenografts induced to express the somatostatin receptor subtype 2 using an adenoviral vector
A1  - Rogers,B.E.
A1  - McLean,S.F.
A1  - Kirkman,R.L.
A1  - Della,Manna D.
A1  - Bright,S.J.
A1  - Olsen,C.C.
A1  - Myracle,A.D.
A1  - Mayo,M.S.
A1  - Curiel,D.T.
A1  - Buchsbaum,D.J.
Y1  - 1999/02//
N1  - UI - 99154792
SP  - 383
EP  - 393
JA  - Clin.Cancer Res.
VL  - 5
IS  - 2
N2  - Adenoviral vectors, encoding genes for cell surface antigens or receptors, have been used to induce their high level expression on tumor cells in vitro and in vivo. These induced antigens and receptors can then be targeted with radiolabeled antibodies or peptides for potential radiotherapeutic applications. The purpose of this study was to determine a dosing schema of an adenoviral vector encoding the human somatostatin receptor subtype 2 (AdCMVhSSTr2) for achieving the highest tumor localization of [(111)In]-DTPA-D-Phe1-octreotide, which binds to this receptor, in a human ovarian cancer model as a prelude to future therapy studies. AdCMVhSSTr2 was produced and used to induce hSSTr2 on A427 human nonsmall cell lung cancer cells and on SKOV3.ipl human ovarian cancer cells in vitro, as demonstrated by competitive binding assays using [125I]-Tyr1-somatostatin and [(111)In]-DTPA-D-Phe1-octreotide. Mice bearing i.p. SKOV3.ip1 tumors administered 1 x 10(9) plaque-forming units of AdCMVhSSTr2 i.p. 5 days after tumor cell inoculation, followed by an i.p. injection of [(111)In]-DTPA-D-Phe1-octreotide 2 days later, showed a range of 15.3-60.4% median injected dose/gram (ID/g) in tumor at 4 h after injection compared with 3.5% ID/g when [125I]-Tyr1-somatostatin was administered and 0.3% ID/g when the negative control peptide [125I]-mIP-bombesin was administered. Mice administered a control adenoviral vector encoding the gastrin-releasing peptide receptor did not have tumor localization of [(111)In]-DTPA-D-Phe1-octreotide (<1.6% ID/g), demonstrating specificity of [(111)In]-DTPA-D-Phe1-octreotide for the AdCMVhSSTr2 induced tumor cells. In another set of experiments, the tumor localization of [(111)In]-DTPA-D-Phe1-octreotide was not different 1, 2, or 4 days after AdCMVhSSTr2 injection (31.8, 37.7, and 40.7% ID/g, respectively; P = 0.88), indicating that multiple injections of radiolabeled peptide can be administered with equivalent uptake over a 4-day period. [(111)In]-DTPA-D-Phe1-octreotide tumor localization in animals administered AdCMVhSSTr2 on consecutive days or 2 days apart was 22.4% ID/g and 53.2% ID/g, respectively (P = 0.009) when [(111)In]-DTPA-D-Phe1-octreotide was given 1 day after the second AdCMVhSSTr2 injection. There was no difference in [(111)In]-DTPA-D-Phe1-octreotide localization after a single AdCMVhSSTr2 injection (40.7% ID/g) or two injections of AdCMVhSSTr2 given 1 (45.9% ID/g) or 2 (53.2% ID/g) days apart, where [(111)In]-DTPA-D-Phe1-octreotide was given in each case 4 days after the first AdCMVhSSTr2 injection (P = 0.65). Therefore, two AdCMVhSSTr2 injections did not increase [(111)In]-DTPA-D-Phe1-octreotide tumor localization compared with one injection, which eliminates concerns about an immune response to a second dose of AdCMVhSSTr2. This will be the basis for a therapeutic protocol with multiple administrations of an octreotide analogue labeled with a therapeutic radioisotope
AD  - Department of Radiation Oncology, University of Alabama at Birmingham, 35294, USA
UR  - PM:10037188
ER  - 

TY  - JOUR
T1  - Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers
A1  - DeGrado,T.R.
A1  - Baldwin,S.W.
A1  - Wang,S.
A1  - Orr,M.D.
A1  - Liao,R.P.
A1  - Friedman,H.S.
A1  - Reiman,R.
A1  - Price,D.T.
A1  - Coleman,R.E.
Y1  - 2001/12//
N1  - UI - 21624034
SP  - 1805
EP  - 1814
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 42
IS  - 12
N2  - Elevated levels of choline (trimethyl-2-hydroxyethylammonium) and choline kinase (CK) activity in neoplasms have motivated the development of positron-labeled choline analogs for noninvasive detection of cancer using PET. The aim of this study was to further evaluate [(18)F]fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) as an oncologic probe in comparison with several other closely related molecules. METHODS: FCH, [(18)F]fluoromethyl-methylethyl-2-hydroxyethylammonium (FMEC), [(18)F]fluoroethyl-dimethyl-2-hydroxyethylammonium (FEC), and [(18)F]fluoropropyl-dimethyl-2-hydroxyethylammonium (FPC) were synthesized through [(18)F]fluoroalkylation reactions. In vitro phosphorylation rates of the (18)F-labeled choline analogs and [methyl-(14)C]choline (CH) were studied using yeast CK. Several choline radiotracers were also evaluated in cultured PC-3 human prostate cancer cells. Data on chemical stability, radiation dosimetry, and toxicity of FCH were obtained. PET studies with FCH were performed on a patient with prostate cancer and a patient with a brain tumor. RESULTS: FCH and FMEC revealed in vitro phosphorylation by CK that was similar to that of choline, whereas rates of phosphorylation of FEC and FPC were 30% (P < 0.01) and 60% (P < 0.01) lower, respectively. Accumulations of FCH, CH, and FPC in cultured PC-3 cancer cells were comparable, whereas uptake of FEC was approximately one fifth that of FCH. Dosimetry estimates using FCH biodistribution data in mice indicated that the kidneys are radiation-dose-critical organs for FCH. PET images of a patient with recurrent prostate cancer showed uptake of FCH in the prostatic bed and in metastases to lymph nodes. FCH PET showed uptake in malignancies in a patient with metastatic breast cancer. PET revealed FCH uptake in biopsy-proven recurrent brain tumor with little confounding uptake by normal brain tissues. CONCLUSION: The fluoromethyl choline analog FCH may serve as a probe of choline uptake and phosphorylation in cancer cells, whereas fluoroethyl (FEC) and fluoropropyl (FPC) analogs appear to have relatively poorer biologic compatibility. Preliminary PET studies on patients with prostate cancer and with breast cancer and brain tumor support further studies to evaluate the usefulness of FCH as an oncologic probe
AD  - Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA
UR  - PM:11752077
ER  - 

TY  - JOUR
T1  - Brain tumors: detection with C-11 choline PET
A1  - Shinoura,N.
A1  - Nishijima,M.
A1  - Hara,T.
A1  - Haisa,T.
A1  - Yamamoto,H.
A1  - Fujii,K.
A1  - Mitsui,I.
A1  - Kosaka,N.
A1  - Kondo,T.
A1  - Hara,T.
Y1  - 1997/02//
N1  - UI - 97167391
SP  - 497
EP  - 503
JF  - Radiology
VL  - 202
IS  - 2
N2  - PURPOSE: To evaluate the effectiveness of positron emission tomography (PET) with carbon-11 choline in brain tumor imaging. MATERIALS AND METHODS: A rat glioma cell line (C6) was incubated with C-14 choline; the time course of uptake and metabolism was determined in vitro. C-11 choline was injected intravenously in tumor-bearing rats; the time course of distribution in organs was determined. C-11 choline also was injected intravenously in 20 patients (aged 6-86 years) with brain tumors and two volunteers (aged 38 and 58 years); distribution of the tracer in the brain was determined. Regional cerebral blood flow was measured by using oxygen-15 water on the same day. RESULTS: C-14 choline was metabolized to phosphoryl choline in glioma cells. The uptake of C-11 choline by glioblastoma cells was three to four times higher than that in the rat brain. All brain tumors took up more C-11 choline than did normal brain; thus, brain tumors that were not treated, as well as those that were treated with surgery or radiation therapy, were depicted. The tumor-normal brain uptake ratio of C-11 choline in brain tumor did not correlate with the O-15 water regional blood flow in the corresponding area. CONCLUSION: C-11 choline PET can depict brain tumors effectively. This method was clinically useful in patients who had undergone surgery
AD  - Department of Neurosurgery, International Medical Center, Tokyo, Japan
UR  - PM:9015080
ER  - 

TY  - JOUR
T1  - PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas
A1  - Henze,M.
A1  - Schuhmacher,J.
A1  - Hipp,P.
A1  - Kowalski,J.
A1  - Becker,D.W.
A1  - Doll,J.
A1  - Macke,H.R.
A1  - Hofmann,M.
A1  - Debus,J.
A1  - Haberkorn,U.
Y1  - 2001/07//
N1  - UI - 21331980
SP  - 1053
EP  - 1056
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 42
IS  - 7
N2  - Imaging of somatostatin receptors (SSTRs) using [(111)In]diethylenetriaminepentaacetic-acid-octreotide (DTPAOC) has proven to be helpful in the differentiation of meningiomas, neurinomas or neurofibromas, and metastases as well as in the follow-up of meningiomas. A drawback of the SPECT method is its limited sensitivity in detecting small meningiomas. Because of PET's increased spatial resolution and its ability to absolutely quantify biodistribution, a PET tracer for SSTR imaging would be desirable. METHODS: 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic-acid-D-Phe(1)-Tyr(3 )-octreotide (DOTATOC) was labeled using the positron-emitting generator nuclide (68)Ga. We acquired dynamic PET images over 120 min after intravenous injection of 175 MBq [(68)Ga]DOTATOC in 3 patients suffering from 8 meningiomas (WHO I degrees; 7- to 25-mm diameter). Patients' heads had been fixed using individually shaped fiber masks equipped with an external stereotactic localizer system to match PET, CT, and MRI datasets. RESULTS: [(68)Ga]DOTATOC was rapidly cleared from the blood (half-life alpha, 3.5 min; half-life beta, 63 min). Standardized uptake values (SUVs) of meningiomas increased immediately after injection and reached a plateau 60-120 min after injection (mean SUV, 10.6). No tracer could be found in the surrounding healthy brain tissue. All meningiomas (even the 3 smallest [7- to 8-mm diameter]) showed high tracer uptake and could be visualized clearly. Tracer boundaries showed a good correspondence with the matched CT and MRI images. PET provided valuable additional information regarding the extent of meningiomas located beneath osseous structures, especially at the base of the skull. CONCLUSION: According to our initial experiences, [(68)Ga]DOTATOC seems to be a very promising new PET tracer for imaging SSTRs even in small meningiomas, offering excellent imaging properties and a very high tumor-to-background ratio
AD  - Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany
UR  - PM:11438627
ER  - 

TY  - JOUR
T1  - Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders
A1  - Kegeles,L.S.
A1  - Malone,K.M.
A1  - Slifstein,M.
A1  - Ellis,S.P.
A1  - Xanthopoulos,E.
A1  - Keilp,J.G.
A1  - Campbell,C.
A1  - Oquendo,M.
A1  - Van Heertum,R.L.
A1  - Mann,J.J.
Y1  - 2003/01//
N1  - UI - 22392332
SP  - 76
EP  - 82
JA  - Am.J Psychiatry
VL  - 160
IS  - 1
N2  - OBJECTIVE: In subjects with mood disorders, positron emission tomography (PET) with [(18)F]fluorodeoxyglucose has shown prefrontal cortical metabolism deficits, including in a subgenual region in subjects with familial illness. The authors applied a dl-fenfluramine challenge method to study metabolic response in this region to serotonergic challenge in familial major depression. METHOD: The study group consisted of 19 depressed subjects with major depressive disorder or bipolar disorder, all of whom had at least one first-degree relative with history of major depression, and 10 healthy volunteers with similar age and gender distributions. PET images were acquired under placebo and challenge conditions, and volumetric MRI scans were also obtained. Group comparisons of metabolic and volumetric data were performed. Ratings of acute mood change during serotonergic challenge were compared with the imaging data. RESULTS: Within Brodmann's area 32, a glucose metabolism deficit in the depressed subjects on placebo day was observed by voxel-level analysis, but no volumetric deficit was found in the subgenual regions examined. Under challenge, both groups suppressed metabolism similarly. Within the patient group, the correlation between acute mood improvement during challenge and greater metabolic suppression approached significance. CONCLUSIONS: In familial mood disorders, a ventromedial prefrontal cortical deficit in baseline metabolism is not due to altered structural volume, and the response to serotonergic challenge appears predictive of acute mood response. The potential to predict treatment response can be tested by a combined challenge and treatment study
UR  - PM:12505804
ER  - 

TY  - JOUR
T1  - Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT(1A) receptor binding potential measured by PET using [C-11]WAY-100635
A1  - Parsey,R.V.
A1  - Oquendo,M.A.
A1  - Simpson,N.R.
A1  - Ogden,R.T.
A1  - Van Heertum,R.
A1  - Arango,V.
A1  - Mann,J.J.
Y1  - 2002/11/08/
N1  - UI - 22301317
SP  - 173
EP  - 182
JA  - Brain Res.
VL  - 954
IS  - 2
N2  - Serotonin (5-HT) 1A receptors have been implicated in a variety of conditions including, depression, suicidal behavior, and aggression. Post-mortem brain studies and in vivo imaging studies report a variety of age and sex effects on brain 5-HT(1A) binding. Behavioral data from 5-HT(1A) specific pharmacological challenges suggest a role for 5-HT(1A) receptors in aggression. The goal of the present study was to determine age, sex, and severity of life-time aggression effects on 5-HT(1A) binding potential (BP) in vivo using positron emission tomography (PET) and the high affinity 5-HT(1A) antagonist, [carbonyl-C-11]WAY-100635 in 12 healthy females (ages 41.0+/-15.7 years) and 13 healthy males (ages 39.6+/-15.5 years). Regions of interest included the dorsal raphe, anterior cingulate cortex, cingulate body, hippocampus, amygdala, medial prefrontal cortex (PFC), and orbital PFC. No significant correlation between age and BP was detected in any brain region. MANOVA of the first three principle components demonstrated a significantly higher BP in females compared with males (P=0.0127). Post-hoc tests confirmed sex differences (P<0.05) in the following regions: dorsal raphe, amygdala, anterior cingulate, cingulate body, medial PFC, and orbital PFC. The cerebellar volume of distribution was also significantly higher in females. There is a significant negative correlation between binding in several regions and lifetime aggression. We have replicated our post-mortem finding of higher 5-HT(1A) binding in females compared to males. We did not detect an age dependent decrease in binding in males or females. Lower 5-HT(1A) binding in more aggressive individuals is consistent with pharmacological challenge studies. Future studies should determine whether the binding is a state or trait effect
AD  - Division of Neuroscience, Departments of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 10032, New York, NY, USA
UR  - PM:12414100
ER  - 

TY  - JOUR
T1  - Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET
A1  - Alauddin,M.M.
A1  - Shahinian,A.
A1  - Gordon,E.M.
A1  - Bading,J.R.
A1  - Conti,P.S.
Y1  - 2001/11//
SP  - 1682
EP  - 1690
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 42
IS  - 11
N2  - The gene for herpes simplex virus thymidine kinase (HSV-tk) is widely used as a suicide gene in experimental gene therapy of cancer. 9-(4-Fluoro-3-hydroxymethylbutyl)guanine (FHBG) is an antiviral nucleoside analog that is rapidly phosphorylated by viral thymidine kinase but is a poor substrate for mammalian thymidine kinase. Recently, FHBG labeled in the 4-fluoro position with (18)F has shown promise relative to other similar compounds for imaging in vivo expression of HSV-tk using PET. In this study, we evaluated the uptake of [(18)F]FHBG in vitro and in vivo using transduced and wild-type human colon cancer cells (HT-29). We also imaged [(18)F]FHBG and measured the radioactivity concentrations of circulating [(18)F]FHBG and its metabolites in monkeys. METHODS: Sterile, pyrogen-free [(18)F]FHBG was produced routinely in good yields. Cells were transduced with the retroviral vector G1Tk1SvNa containing HSV-tk gene. In vitro uptake studies were performed by incubating cells with [(18)F]FHBG at 37 degrees C for 1 and 5 h. Biodistribution studies were performed at 2 and 5 h after injection in nude mice bearing tumors grown from wild-type or transduced cells. Sequential, whole-body PET scans of cynomolgus monkeys were obtained over a period of >2 h after intravenous injection of [(18)F]FHBG. Arterial plasma samples obtained from monkeys 15-120 min after intravenous injection were subjected to acid extraction, and the acid-soluble fractions were analyzed by high-performance liquid chromatography. RESULTS: In vitro studies showed 31 and 71 (P < 0.001) times higher uptake of the probe at 1 and 5 h, respectively, in transduced cells compared with nontransduced cells. In vivo studies in mice showed that tumor uptake of the radiotracer was 4-fold (P < 0.05) and 13-fold (P < 0.001) higher at 2 and 5 h, respectively, in tumors grown from transduced cells compared with control cells. Transduced tumor-to-normal tissue ratios ranged from 2 to 25 at 2 h and from 2 to 22 at 5 h. Recirculating labeled metabolites had only a minor effect on the biodistribution of radiolabel from [(18)F]FHBG in monkeys. CONCLUSION: These results indicate that [(18)F]FHBG may yield high-contrast PET images of HSV-tk expression in tumors and, therefore, it is a very promising radiotracer for monitoring of gene therapy of cancer with PET
AD  - Department of Radiology, PET Imaging Science Center, University of Southern California, Los Angeles 90033-4609, USA
UR  - PM:11696640
ER  - 

TY  - JOUR
T1  - Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET
A1  - Alauddin,M.M.
A1  - Conti,P.S.
Y1  - 1998/04//
N1  - UI - 98281942
SP  - 175
EP  - 180
JA  - Nucl Med Biol.
VL  - 25
IS  - 3
N2  - Synthesis and preliminary biological evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)-guanine ([18F]FHBG) is reported. 9-(4-Hydroxy-3-hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N2, O-bis-(methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl chloride followed by tosylation. The tosylate 7 was reacted with either tetrabutylammonium fluoride or KF in the presence of kryptofix 2.2.2. to produce the 4-fluoro-N2-O-bis-(methoxytrityl) derivative 8. Removal of the methoxytrityl groups by acidic hydrolysis produced FHBG 5. Radiolabeled product [18F]FHBG was prepared by fluorination of the tosylate 7 with [18F]KF and kryptofix 2.2.2. The labeled product was isolated by HPLC purification on a reverse-phase C18 column, and eluted at 12 min with 15% acetonitrile in water at a flow rate of 2.25 mL/min. Radiochemical yield was 8.0-22.3% with an average of 12% in 7 runs (corrected for decay). Synthesis time was 90 to 100 min including HPLC purification with radiochemical purity >99%, and average specific activity of 320 mCi/micromol. In vitro studies of the compound in HT-29 colon cancer cells revealed 18.2-fold higher uptake into transduced cells compared to control in 3 h. The agent may be useful for imaging viral infection or transfected cells in gene therapy
AD  - PET Imaging Science Center, University of Southern California, School of Medicine, Los Angeles 90033, USA
UR  - PM:9620620
ER  - 

TY  - JOUR
T1  - Synthesis of 2'-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET
A1  - Conti,P.S.
A1  - Alauddin,M.M.
A1  - Fissekis,J.R.
A1  - Schmall,B.
A1  - Watanabe,K.A.
Y1  - 1995/08//
N1  - UI - 96079333
SP  - 783
EP  - 789
JA  - Nucl Med Biol.
VL  - 22
IS  - 6
N2  - Rapid in vivo catabolism limits the use of currently available radiotracers used in tumor proliferation studies with PET. This is manifested by the need to develop complex mathematical models to interpret kinetic and metabolite data obtained from imaging studies with agents such as carbon-11 labeled thymidine. A potential carbon-11 labeled radiotracer for cellular proliferation, 2'-fluoro-5-([11C]-methyl)-1-beta-D-arabinofuranosyluracil (FMAU), has been prepared using a previously described method for preparation of [11C]methyl-thymidine where selective alkylation of a pyrimidyl dianion is accomplished with [11C]methyl iodide at the 5-position of the pyrimidine ring. FMAU shares many in vivo characteristics of thymidine, including cellular transport, phosphorylation by mammalian kinase, and incorporation into DNA. Most importantly, in vivo catabolism of FMAU is limited, potentially yielding simplified kinetic models for determination of cellular proliferation with positron emission tomography
AD  - PET Imaging Science Center, University of Southern California, School of Medicine, Los Angeles, CA 90033, USA
UR  - PM:8535339
ER  - 

TY  - JOUR
T1  - Regulation of human thymidine kinase during the cell cycle
A1  - Sherley,J.L.
A1  - Kelly,T.J.
Y1  - 1988/06/15/
N1  - UI - 88228066
SP  - 8350
EP  - 8358
JA  - J Biol.Chem.
VL  - 263
IS  - 17
N2  - As an approach to defining the molecular basis for the periodic expression of thymidine kinase activity during the cell cycle, we have examined properties of the cytosolic enzyme in cycling HeLa cells synchronized by centrifugal elutriation and mitotic selection. By immunoblot analyses with a specific antiserum raised against the purified HeLa enzyme, we have demonstrated that changes in the levels of thymidine kinase activity reflect similar changes in the levels of thymidine kinase polypeptide. In contrast, the steady state levels of thymidine kinase mRNA show relatively small changes during the cell cycle. Using pulse labeling methods, we have shown that the synthetic rate of thymidine kinase protein is about 10-fold greater in S phase than in G1 phase, indicating that the efficiency of translation of thymidine kinase mRNA increases as cells begin DNA replication. In addition, the stability of thymidine kinase protein dramatically decreases upon cell division, resulting in the rapid clearance of the enzyme from newly divided G1 cells. Thus, two different post-transcriptional mechanisms largely account for the periodic behavior of the enzyme activity during the cell cycle
AD  - Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
UR  - PM:3372530
ER  - 

TY  - JOUR
T1  - Properties and levels of deoxynucleoside kinases in normal and tumor cells; implications for chemotherapy
A1  - Eriksson,S.
A1  - Arner,E.
A1  - Spasokoukotskaja,T.
A1  - Wang,L.
A1  - Karlsson,A.
A1  - Brosjo,O.
A1  - Gunven,P.
A1  - Julusson,G.
A1  - Liliemark,J.
Y1  - 1994///
SP  - 13
EP  - 25
JA  - Adv.Enzyme Regul.
VL  - 34
N2  - Deoxynucleoside kinases are key enzymes in deoxyribonucleoside salvage, activating several clinically important chemotherapeutic drugs. The four known kinases, cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK) and the mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK), have been purified and characterized as to the subunit structure as well as specificity with a large number of analogs. These results are summarized and used to establish selective assays for the four enzymes in crude extracts of normal and malignant human peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas. TK2 and dGK activities were found at low levels in all tissues, possibly correlated to the content of mitochondria. TK1 activity was detected only in samples containing a significant number of S phase cells. We have measured dCK activity as well as dCK polypeptide level by immuno blotting in these extracts. High levels of dCK were found in normal mononuclear leukocytes (91-145 ng dCK/mg protein) and in B-cell chronic lymphocytic leukemia (80 +/- 30 ng/mg, n = 23). Hairy cell leukemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did unexpectedly three samples of T-cell chronic lymphocytic leukemia (18 +/- 14 ng/mg). Phytohemaglutinine stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or expression (less than 2.5-fold). In colon adenocarcinomas, the dCK content was significantly higher (21 +/- 9.3 ng/mg, n = 20) than in normal colon mucosa (8.2 +/- 3.7 ng/mg, n = 19, p < 0.05). A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal ventricular mucosa (6.2 +/- 5.4 ng/mg, n = 5, p < 0.15). One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. 2-Chlorodeoxyadenosine (CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme. A study was performed to investigate if there was a correlation between the dCK levels and the response to CdA treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
AD  - Department of Biochemistry, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden
UR  - PM:7942271
ER  - 

TY  - JOUR
T1  - Occurrence, regulation, and significance of progesterone receptors in human meningioma
A1  - Blankenstein,M.A.
A1  - Verheijen,F.M.
A1  - Jacobs,J.M.
A1  - Donker,T.H.
A1  - van Duijnhoven,M.W.
A1  - Thijssen,J.H.
Y1  - 2000/10//
N1  - UI - 20562922
SP  - 795
EP  - 800
JA  - Steroids
VL  - 65
IS  - 10-11
N2  - The abundant expression of progesterone receptors (PR) in human meningiomas is well established. It is unknown, however, how PR expression is regulated, especially since estrogen receptors (ER) are virtually absent in these tumors. At the mRNA level, ER splice variants occur in meningioma but these appear not to be involved in the apparently autonomous PR expression. In an earlier study, because other ER-inducible proteins were either not expressed at all (pS2) or were expressed at a very low level compared to their expression in breast cancer (Cathepsin-D), the authors have postulated that the autonomous PR expression in meningioma is PR promoter-related rather than ER-related and have studied PR expression in cultured meningioma cells. PR levels appeared to decrease rapidly in vitro in monolayer as well as in three dimensional spheroid cultures. Culture conditions thus are not yet sufficient for the quantitative evaluation of PR expression. To evaluate whether PR deterioration is associated with cell turnover (meningiomas grow much faster in vitro than in vivo), the relationship between expression of the apoptotic proteins Bcl-2 and Bax and PR expression was investigated. Bcl-2 expression was found to be highest in meningioma with low PR levels, and in breast cancer tissue with high PR levels. Bax expression was not related to PR expression in any of the two tissues. Given the potential benefit of antiprogestin treatment and the occurrence in meningiomas of a protein capable of binding to the estrogen-responsive element, the expression of PR in meningioma remains a fascinating phenomenon which requires further investigation
AD  - Department of Endocrinology, KE 03_139.2, University Medical Center Utrecht, P.O. Box 85090, NL 3508 AB, Utrecht, The Netherlands. m.a.blankenstein@lab.azu.nl
UR  - PM:11108890
ER  - 

TY  - JOUR
T1  - The development of estrogen and progestin radiopharmaceuticals for imaging breast cancer
A1  - Katzenellenbogen,J.A.
A1  - Welch,M.J.
A1  - Dehdashti,F.
Y1  - 1997/05//
SP  - 1573
EP  - 1576
JA  - Anticancer Res.
VL  - 17
IS  - 3B
N2  - BACKGROUND: The presence of receptors for estrogens and progestins in many breast tumors provides a means for imaging these tumors using positron emission tomography (PET) with appropriate fluorine-18 labeled estrogen and progestin radiopharmaceuticals. In this context, the estrogen analog 16 alpha-[18F]fluoroestradiol (FES) has already proven to be an effective imaging agent for estrogen receptor-positive tumors. METHODS: Clinical studies comparing FES images with those based on the metabolic probe 2-[18F]fluoro-2-deoxyglucose (FDG) in patients before and after tamoxifen hormone therapy are underway. Several fluorine-18 labeled progestins have been prepared, and efforts are underway to develop methods for labeling steroid receptor imaging agents with the widely available radionuclide technetium-99m, using both pendant and integrated approaches. RESULTS AND CONCLUSION: Breast tumor imaging with FES and FDG shows an interesting relationship between tumor metabolic response (assessed with FDG) and tumor estrogen receptor levels (assessed with FES). The fluorine-18 labeled progestins show excellent target tissue selective distribution in experimental animals and are ready for imaging studies in humans. The development of steroids labeled with technetium-99m poses special challenges because of the metallic nature of this radioisotope
AD  - Department of Chemistry, University of Illinois, Urbana 61801, USA
UR  - PM:9179196
ER  - 

TY  - JOUR
T1  - Receptor-mediated delivery of an antisense gene to human brain cancer cells
A1  - Zhang,Y.
A1  - Jeong,Lee H.
A1  - Boado,R.J.
A1  - Pardridge,W.M.
Y1  - 2002/03//
SP  - 183
EP  - 194
JA  - J Gene Med
VL  - 4
IS  - 2
N2  - BACKGROUND: The goal of this work was the development of a gene targeting technology that will enable the delivery of therapeutic genes to brain cancer cells in vivo following intravenous administration. High-grade brain gliomas overexpress the epidermal growth factor receptor (EGFR) and EGFR antisense gene therapy could reduce the growth of EGFR-dependent gliomas. METHODS: A human EGFR antisense gene driven by the SV40 promoter in a non-viral plasmid carrying elements that facilitate extra-chromosomal replication was packaged in the interior of 85 nm pegylated immunoliposomes (PILs). The PILs were targeted to U87 human glioma cells with the 83-14 murine monoclonal antibody (MAb) to the human insulin receptor (HIR). RESULTS: Confocal fluorescent microscopy demonstrated that the unconjugated HIR MAb is rapidly internalized by the glioma cells. Endocytosis followed by entry into the nucleus was also demonstrated for the HIR MAb conjugated PILs carrying fluorescein-labeled plasmid DNA. The PILs delivered exogenous genes to virtually all cells in culture, based on beta-galactosidase histochemistry. The targeting of a luciferase gene to the U87 cells with the PILs resulted in luciferase levels in excess of 150 pg/mg protein after 72 h of incubation. The level of luciferase gene expression in the U87 cells achieved with the PIL gene targeting system was comparable to that with lipofectamine. Targeting the EGFR antisense gene to U87 glioma cells with the PILs resulted in more than 70% reduction in [(3)H]thymidine incorporation into the cells; this was paralleled by a 79% reduction in the level of immunoreactive EGFR. CONCLUSION: The present work describes the targeting of an EGFR antisense gene to human brain cancer cells, which results in a 70-80% inhibition in cancer cell growth. PILs provide a new approach to gene targeting that is effective in vivo following intravenous administration without viral vectors
AD  - Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA
UR  - PM:11933219
ER  - 

TY  - JOUR
T1  - Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor
A1  - Coloma,M.J.
A1  - Lee,H.J.
A1  - Kurihara,A.
A1  - Landaw,E.M.
A1  - Boado,R.J.
A1  - Morrison,S.L.
A1  - Pardridge,W.M.
Y1  - 2000/03//
N1  - UI - 20259152
SP  - 266
EP  - 274
JA  - Pharm.Res.
VL  - 17
IS  - 3
N2  - PURPOSE: Brain drug targeting may be achieved by conjugating drugs, that normally do not cross the blood-brain barrier (BBB), to brain drug delivery vectors. The murine 83-14 MAb to the human insulin receptor (HIR) is a potential brain drug targeting vector that could be used in humans, if this MAb was genetically engineered to form a chimeric antibody. where most of the immunogenic murine sequences are replaced by human antibody sequence. METHODS: The present studies describe the production of the gene for the chimeric HIRMAb, expression and characterization of the protein, radiolabeling of the chimeric HIRMAb with 111-indium and 125-iodine, and quantitative autoradiography of living primate brain taken 2 hours after intravenous administration of the [111In]chimeric HIRMAb. RESULTS: The chimeric HIRMAb had identical affinity to the target antigen as the murine HIRMAb based on Western blotting and immunoradiometric assay using partially purified HIR affinity purified from serum free conditioned media produced by a CHO cell line secreting soluble HIR. The [125I]chimeric HIRMAb was avidly bound to isolated human brain capillaries, and this binding was blocked by the murine HIRMAb. The [111In]chimeric HIRMAb was administered intravenously to an anesthetized Rhesus monkey, and the 2 hour brain scan showed robust uptake of the chimeric antibody by the living primate brain. CONCLUSIONS: A genetically engineered chimeric HIRMAb has been produced, and the chimeric antibody has identical reactivity to the human and primate BBB HIR as the original murine antibody. This chimeric HIRMAb may be used in humans for drug targeting through the BBB of neurodiagnostic or neurotherapeutic drugs that normally do not cross the BBB
AD  - Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095, USA
UR  - PM:10801214
ER  - 

TY  - JOUR
T1  - Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor
A1  - Wu,D.
A1  - Yang,J.
A1  - Pardridge,W.M.
Y1  - 1997/10/01/
N1  - UI - 97460007
SP  - 1804
EP  - 1812
JA  - J Clin.Invest
VL  - 100
IS  - 7
N2  - Peptide radiopharmaceuticals are potential imaging agents for brain disorders, should these agents be enabled to undergo transport through the blood-brain barrier (BBB) in vivo. Radiolabeled Abeta1-40 images brain amyloid in tissue sections of Alzheimer's disease autopsy brain, but this peptide radiopharmaceutical cannot be used to image brain amyloid in vivo owing to negligible transport through the BBB. In these studies, 125I-Abeta1-40 was monobiotinylated (bio) and conjugated to a BBB drug delivery and brain targeting system comprised of a complex of the 83-14 monoclonal antibody (mAb) to the human insulin receptor, which is tagged with streptavidin (SA). A marked increase in rhesus monkey brain uptake of the 125I-bio-Abeta1-40 was observed after conjugation to the 8314-SA delivery system at 3 h after intravenous injection. In contrast, no measurable brain uptake of 125I-bio-Abeta1-40 was observed in the absence of a BBB drug delivery system. The peptide radiopharmaceutical was degraded in brain with export of the iodide radioactivity, and by 48 h after intravenous injection, 90% of the radioactivity was cleared from the brain. In conclusion, these studies describe a methodology for BBB drug delivery and brain targeting of peptide radiopharmaceuticals that could be used for imaging amyloid or other brain disorders
AD  - Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1682, USA
UR  - PM:9312181
ER  - 

TY  - JOUR
T1  - Visualization of multidrug resistance in vivo
A1  - Hendrikse,N.H.
A1  - Franssen,E.J.
A1  - van der Graaf,W.T.
A1  - Vaalburg,W.
A1  - de Vries,E.G.
Y1  - 1999/03//
SP  - 283
EP  - 293
JA  - Eur.J Nucl Med
VL  - 26
IS  - 3
N2  - Various mechanisms are involved in multidrug resistance (MDR) for chemotherapeutic drugs, such as the drug efflux pumps, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP). In this review the mechanisms involved in MDR are described and results are reviewed with particular attention to the in vivo imaging of Pgp and MRP. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However, these methods do not yield information about the dynamic function of Pgp and MRP in vivo. For the study of Pgp- and MRP-mediated transport, single-photon emission tomography (SPET) and positron emission tomography (PET) are available. Technetium-99m sestamibi is a substrate for Pgp and MRP, and has been used in clinical studies for tumour imaging, and to visualize blockade of Pgp-mediated transport after modulation of the Pgp pump. Other 99mTc radiopharmaceuticals, such as 99mTc-tetrofosmin and several 99Tc-Q complexes, are also substrates for Pgp, but to date only results from in vitro and animal studies are available for these compounds. Several agents, including [11C]colchicine, [11C]verapamil and [11C]daunorubicin, have been evaluated for the quantification of Pgp-mediated transport with PET in vivo. The results suggest that radiolabelled colchicine, verapamil and daunorubicin are feasible substrates with which to image Pgp function in tumours. Uptake of [11C]colchicine and [11C]verapamil is relatively high in the chest area, reducing the value of both tracers for monitoring Pgp-mediated drug transport in tumours located in this region. In addition, it has to be borne in mind that only comparison of Pgp-mediated transport of radioalabelled substrates in the absence and in the presence of Pgp blockade gives quantitative information on Pgp-mediated pharmacokinetics. Leukotrienes are specific substrates for MRP. Therefore, N-[11C]acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively. Results obtained in MRP2 mutated GY/TR rats have demonstrated visualization of MRP-mediated transport. This tracer permits the study of MRP transport function abnormalities in vivo, e.g. in Dubin-Johnson patients, who are MRP2 gene deficient. Results obtained show the feasibility of using SPET and PET to study the functionality of MDR transporters in vivo
AD  - PET Center, University Hospital, Groningen, The Netherlands
UR  - PM:10079321
ER  - 

TY  - JOUR
T1  - New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET [11C]raclopride study
A1  - Moresco,R.M.
A1  - Volonte,M.A.
A1  - Messa,C.
A1  - Gobbo,C.
A1  - Galli,L.
A1  - Carpinelli,A.
A1  - Rizzo,G.
A1  - Panzacchi,A.
A1  - Franceschi,M.
A1  - Fazio,F.
Y1  - 2002/10//
SP  - 1265
EP  - 1274
JA  - J Neural Transm.
VL  - 109
IS  - 10
N2  - Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [(11)C]raclopride binding to striatal D(2) dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10-14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [(11)C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (-7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D(2) receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D(2) receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D(2) receptors may represent a reinforcing mechanism of drug efficacy
AD  - INB-CNR, University of Milan-Bicocca, Italy
UR  - PM:12373560
ER  - 

TY  - JOUR
T1  - Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia
A1  - Arnold,S.
A1  - Berthele,A.
A1  - Drzezga,A.
A1  - Tolle,T.R.
A1  - Weis,S.
A1  - Werhahn,K.J.
A1  - Henkel,A.
A1  - Yousry,T.A.
A1  - Winkler,P.A.
A1  - Bartenstein,P.
A1  - Noachtar,S.
Y1  - 2000/07//
N1  - UI - 20357673
SP  - 818
EP  - 824
JF  - Epilepsia
VL  - 41
IS  - 7
N2  - PURPOSE: Comparison of regional reduction of GABA receptor binding and seizure onset zone in patients with extratemporal epilepsy due to focal cortical dysplasia. METHODS: Two patients with frontal lobe epilepsy who remained seizure free after partial frontal lobe resection were investigated with magnetic resonance imaging, positron emission tomography (PET) with 18F-fluoro-deoxy-glucose (FDG) and 11C-flumazenil, subdural EEG-video recordings, and postoperative benzodiazepine (BDZ)-receptor autoradiography. RESULTS: The area of reduced BDZ-receptor binding as documented by preoperative flumazenil-PET and postoperative BDZ-receptor autoradiography corresponded to the seizure onset zone and was smaller than the interictal hypometabolism documented by FDG-PET. CONCLUSION: Flumazenil-PET is a useful tool for localization of the epileptogenic zone in patients with extratemporal epilepsy caused by focal cortical dysplasia. Neuronal distribution of BDZ-receptor density confirms in vivo flumazenil-PET findings. The regional reduction of BDZ-receptor binding in focal cortical dysplasia seems to be confined to the seizure onset zone and not to the extent of dysplastic cortex
AD  - Department of Neurology, University of Munich, Germany
UR  - PM:10897152
ER  - 

TY  - JOUR
T1  - Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride
A1  - Grunder,G.
A1  - Siessmeier,T.
A1  - Piel,M.
A1  - Vernaleken,I.
A1  - Buchholz,H.G.
A1  - Zhou,Y.
A1  - Hiemke,C.
A1  - Wong,D.F.
A1  - Rosch,F.
A1  - Bartenstein,P.
Y1  - 2003/01//
N1  - UI - 22404021
SP  - 109
EP  - 116
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 1
N2  - Substituted benzamides such as (11)C-raclopride or (123)I-iodobenzamide are selective radiotracers for PET and SPECT imaging of D(2)-like dopamine (DA) receptors. (18)F-Desmethoxyfallypride ((18)F-DMFP) is a benzamide tracer with the advantage of an (18)F label. We optimized the synthesis and evaluated (18)F-DMFP in PET studies on healthy human volunteers. METHODS: The affinity of DMFP for D(2)-like DA receptors was characterized in vitro using membrane preparations from rat striatum and the DA receptor ligand (3)H-spiperone. PET studies on 10 healthy human volunteers were performed using a whole-body PET scanner after injection of 214 +/- 54 MBq (mean +/- SD) (18)F-DMFP. Brain images were acquired dynamically over 124 min, and metabolite-corrected plasma activity was used as the input function. Data analysis was performed using several different approaches (compartmental, graphical, equilibrium methods). RESULTS: The mean inhibition constant (K(i)) of DMFP was 15 +/- 9 nmol/L. In human brain, the striatum-to-cerebellum ratio reached a maximum of about 4 between 60 and 120 min. When specific binding in the striatum was expressed as the difference between binding in the striatum and the cerebellum, it reached a maximum at approximately 60 min after injection and remained almost constant until the end of data acquisition. The ratio of specific striatal to nonspecific cerebellar binding was about 3:1 at 120 min after injection. A small, but significant specific tracer binding could also be detected in the thalamus. Treatment of a schizophrenic patient with a high dose (1,000 mg/d) of another substituted benzamide, amisulpride, resulted in a reduction of specific tracer uptake of about 90% in striatal regions. With regard to measured distribution volumes and binding potentials, there was an excellent agreement between all applied analytic methods. CONCLUSION: Our study demonstrates that (18)F-DMFP is a highly reliable tracer for PET imaging of D(2)-like DA receptors. It offers the major advantage that it can be used independently of an on-site cyclotron within a PET satellite network. Noninvasive analytic methods without blood sampling provide valid measurements of receptor quantities in human striatum. Because of the (18)F label and the favorable imaging properties, (18)F-DMFP could become an efficient substitute for (11)C-raclopride in a clinical context
AD  - Department of Psychiatry, University of Mainz, Mainz, Germany. gruender@mail.uni-mainz.de
UR  - PM:12515884
ER  - 

TY  - JOUR
T1  - [18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors
A1  - Grunder,G.
A1  - Siessmeier,T.
A1  - Lange-Asschenfeldt,C.
A1  - Vernaleken,I.
A1  - Buchholz,H.G.
A1  - Stoeter,P.
A1  - Drzezga,A.
A1  - Luddens,H.
A1  - Rosch,F.
A1  - Bartenstein,P.
Y1  - 2001/10//
N1  - UI - 21543626
SP  - 1463
EP  - 1470
JA  - Eur.J Nucl Med
VL  - 28
IS  - 10
N2  - 5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [18F]FEF and with [11C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4 +/- 2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [18F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [18F]FEF compared with [11C]flumazenil, while relative uptake of [18F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the alpha6 subunit. Metabolism of [18F]FEF was very rapid. Polar metabolites represented about 50%-60% of total plasma radioactivity at 5 min and 80%-90% at 20 min p.i. Although [11C]flumazenil has some advantages over [18F]FEF (higher affinity, slower metabolism, slower kinetics), our results indicate that [18F]FEF is a suitable PET ligand for quantitative assessment of central benzodiazepine receptors, which can be used independently of an on-site cyclotron
AD  - Department of Psychiatry, University of Mainz, Germany. gruender@mail.uni-mainz.de
UR  - PM:11685488
ER  - 

TY  - JOUR
T1  - Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier
A1  - Kreuter,J.
A1  - Shamenkov,D.
A1  - Petrov,V.
A1  - Ramge,P.
A1  - Cychutek,K.
A1  - Koch-Brandt,C.
A1  - Alyautdin,R.
Y1  - 2002/06//
SP  - 317
EP  - 325
JA  - J Drug Target
VL  - 10
IS  - 4
N2  - Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80. However, the mechanism of this transport so far was not known. In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated. Poly(butyl cyanoacrylate) nanoparticles loaded with the hexapeptide dalargin were coated with the apolipoproteins AII, B, CII, E, or J without or after precoating with polysorbate 80. In addition, loperamide-loaded nanoparticles were coated with apolipoprotein E alone or again after precoating with polysorbate 80. After intravenous injection to ICR mice the antinociceptive threshold was measured by the tail flick test. Furthermore, the antinociceptive threshold of polysorbate 80-coated dalargin-loaded nanoparticles was determined in ApoEtm1Unc and C57BL/6J mice. The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect. This effect was significantly higher after polysorbate-precoating and apolipoprotein B or E-overcoating. With the apolipoprotein E-deficient ApoEtm1Unc mice the antinociceptive effect was considerably reduced in comparison to the C57BL/6J mice. These results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB. Polysorbate 80-coated nanoparticles adsorb these apolipoproteins from the blood after injection and thus seem to mimic lipoprotein particles that could be taken up by the brain capillary endothelial cells via receptor-mediated endocytosis. Bound drugs then may be further transported into the brain by diffusion following release within the endothelial cells or, alternatively, by transcytosis
AD  - Institut fur Pharmazeutische Technologie, Biozentrum, J.W. Goethe-Universitat, Frankfurt, Germany. kreuter@em.uni-frankfurt.de
UR  - PM:12164380
ER  - 

TY  - JOUR
T1  - alpha-[11C]-Methyl-tryptophan PET identifies the epileptogenic tuber and correlates with interictal spike frequency
A1  - Fedi,Marco
A1  - Reutens,David C.
A1  - Andermann,Frederick
A1  - Okazawa,Hidehiko
A1  - Boling,Warren
A1  - White,Carole
A1  - Dubeau,Francois
A1  - Nakai,Akio
A1  - Gross,Donald W.
A1  - Andermann,Eva
A1  - Diksic,Mirko
Y1  - 2003/01//
SP  - 203
EP  - 213
JF  - Epilepsy Research
VL  - 52
IS  - 3
N2  - Epilepsy surgery has been successfully performed in patients with tuberous sclerosis complex (TSC) and seizures arising from a restricted epileptogenic area. The outcome of cortical excision depends on accurate pre-surgical identification of the epileptogenic tuber. [11C] [alpha]-methyl--tryptophan ([alpha]-MTrp) was originally developed to measure serotonin synthesis in vivo with positron emission tomography (PET). However in pathologic conditions its uptake may also depend on the synthesis of quinolinic or kynurenic acid via the kynurenine pathway. Increased levels of serotonin and quinolinic acid have been observed in epileptogenic lesions, raising the possibility that [alpha]-MTrp PET may localize the epileptogenic area. The aim of this study was to correlate [alpha]-MTrp PET uptake with the localization of the epileptogenic area and with interictal spike frequency in patients with TSC. [alpha]-MTrp uptake was measured in 8 patients (2 males, mean age 29.6+/-14.9 years, range 3-50 years) with intractable partial epilepsy due to TSC. All patients underwent scalp EEG monitoring during the PET scan. In four (50%), increased uptake of [alpha]-MTrp occurred in the epileptogenic area alone. Two (25%) patients showed multifocal abnormalities and the remaining two (25%) did not show focal changes. PET localization was mostly seen in patients with frequent interictal abnormalities on the EEG. Furthermore, there was a significant correlation between [alpha]-MTrp uptake and the frequency of interictal spikes (r=0.6; P<0.05). [alpha]-MTrp PET is a promising diagnostic tool in the localization of the epileptogenic area in patients with TSC
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Fedi-AMTpet_TSC.pdf
ER  - 

TY  - JOUR
T1  - In Vivo NMR Studies of the Glutamate Neurotransmitter Flux and Neuroenergetics: Implications for Brain Function
A1  - Rothman,D.L.
A1  - Behar,K.L.
A1  - Hyder,F.
A1  - Shulman,R.G.
Y1  - 2003/01/09/
N1  - UI - 0
JA  - Annu.Rev.Physiol
VL  - eprint
N2  - Until very recently, non-invasive measurement of the glutamate-glutamine cycle in the intact mammalian brain had not been possible. In this review, we describe some studies that have led to quantitative assessment of the glutamate-glutamine cycle (Vcyc), as well as other important metabolic fluxes (e.g., glucose oxidation, CMRglc(ox)), with (13)C magnetic resonance spectroscopy (MRS) in vivo. These (13)C MRS studies clearly demonstrate that glutamate released from presynaptic neurons is taken up by the astrocyte for subsequent glutamine synthesis. Contrary to the earlier concept of a small, metabolically inactive neurotransmitter pool, in vivo (13)C MRS studies demonstrate that glutamate release and recycling is a major metabolic pathway that cannot be distinguished from its actions of neurotransmission. Furthermore, the in vivo (13)C MRS studies demonstrate in the rat cerebral cortex that increases in Vcyc and neuronal CMRglc(ox) are linearly related with a close to 1:1 slope. Measurements in human cerebral cortex are in agreement with this result. This relationship is consistent with more than two thirds of the energy yielded by glucose oxidation being used to support events associated with glutamate neurotransmission, and it supports a molecular model of a stoichiometric coupling between glutamate neurotransmission and functional glucose oxidation. (13)C MRS measurements of resting human cerebral cortex have found a high level of glutamate-glutamine cycling. This high resting neuronal activity, which is subtracted away in brain mapping studies by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), has significant implications for the interpretations of functional imaging data. Here we review and discuss the importance of neurotransmission and neuroenergetics as measured by (13)C MRS for understanding brain function and interpreting fMRI
AD  - Magnetic Resonance Center, Yale University School of Medicine, New Haven, CT 06510
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Rothman-NMR-Glutamate.pdf
ER  - 

TY  - JOUR
T1  - Vascular reserve in chronic cerebral ischemia measured by the acetazolamide challenge test: comparison with positron emission tomography
A1  - Nariai,T.
A1  - Suzuki,R.
A1  - Hirakawa,K.
A1  - Maehara,T.
A1  - Ishii,K.
A1  - Senda,M.
Y1  - 1995/03//
N1  - UI - 95313681
SP  - 563
EP  - 570
JA  - AJNR Am.J Neuroradiol.
VL  - 16
IS  - 3
N2  - PURPOSE: To determine the value of the acetazolamide challenge test with stable xenon-enhanced CT (Xe CT) for making therapeutic decisions in patients with chronic cerebrovascular disease. METHODS: We compared the Xe CT-measured acetazolamide response with various measures obtained by positron emission tomography. We performed both a positron emission tomographic scan and a Xe CT study in 11 patients with chronic cerebral ischemic diseases within a 1-week interval. An increase of cerebral blood flow after injection of acetazolamide was expressed as delta AT. Regional cerebral blood flow, cerebral oxygen metabolism, oxygen extraction fraction, and cerebral blood volume were measured with oxygen-15-labeled gases by positron emission tomography. RESULTS: In low-cerebral blood flow regions, decreased delta AT was accompanied by a significant elevation of oxygen extraction fraction and cerebral blood volume, compared with oxygen extraction fraction and cerebral blood volume in regions of normal delta AT. Plotting of regional data indicated that delta was significantly dependent on oxygen extraction fraction and cerebral blood volume. The area of decreased vascular reserve determined by the Xe CT image corresponded to the area of "misery perfusion" determined by positron emission tomography. CONCLUSION: The acetazolamide challenge test with Xe CT may offer an alternative to positron-emission tomography in detecting lesions with elevated oxygen extraction fraction and cerebral blood volume (misery perfusion) that result from chronic hemodynamic stress
AD  - Department of Neurosurgery, Tokyo Medical and Dental University, Japan
UR  - PM:7793382
ER  - 

TY  - JOUR
T1  - Relationship between residual cerebral blood flow and oxygen metabolism as predictive of ischemic tissue viability: sequential multitracer positron emission tomography scanning of middle cerebral artery occlusion during the critical first 6 hours after stroke in pigs
A1  - Sakoh,M.
A1  - Ostergaard,L.
A1  - Rohl,L.
A1  - Smith,D.F.
A1  - Simonsen,C.Z.
A1  - Sorensen,J.C.
A1  - Poulsen,P.V.
A1  - Gyldensted,C.
A1  - Sakaki,S.
A1  - Gjedde,A.
Y1  - 2000/10//
N1  - UI - 20466472
SP  - 647
EP  - 657
JA  - J Neurosurg
VL  - 93
IS  - 4
N2  - OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke
AD  - Positron Emission Tomography Center, Department of Neuroradiology, Aarhus University Hospital, Denmark. sakoh@m.ehime-u.ac.jp
UR  - PM:11014544
ER  - 

TY  - JOUR
T1  - Computer-assisted imaging to assess brain structure in healthy and diseased brains
A1  - Ashburner,John
A1  - Csernansky,John G.
A1  - Davatzikos,Christos
A1  - Fox,Nick C.
A1  - Frisoni,Giovanni B.
A1  - Thompson,Paul M.
Y1  - 2003/02/01/
SP  - 79
EP  - 88
JA  - The Lancet Neurology
VL  - 2
IS  - 2
N2  - Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment. However, early in the progression of such diseases, neuroanatomical changes may be too mild, diffuse, or topologically complex to be detected by simple visual inspection or manually traced measurements of regions of interest. Computerised methods are being developed that can capture the extraordinary morphological variability of the human brain. These methods use mathematical models sensitive to subtle changes in the size, position, shape, and tissue characteristics of brain structures affected by neurodegenerative diseases. Neuroanatomical features can be compared within and between groups of individuals, taking into account age, sex, genetic background, and disease state, to assess the structural basis of normality and disease. In this review, we describe the strengths and limitations of algorithms of existing computer-assisted tools at the most advanced stage of development, together with available and foreseeable evidence of their usefulness at the clinical and research level
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Ashburner-Frisoni-Lancet.pdf
ER  - 

TY  - JOUR
T1  - Mild Cognitive Impairment: a Clinically Useful but Currently Ill-defined Concept?
A1  - Thompson,Sian A.
A1  - Hodges,John R.
Y1  - 2002/12/02/
SP  - 405
EP  - 410
JF  - Neurocase
VL  - 8
IS  - 6
N2  - The term mild cognitive impairment (MCI) has gained wide currency among clinicians, and particularly dementia researchers, to denote patients with memory deficits who do not yet fulfil the criteria for dementia, but are at high risk of conversion. MCI is therefore regarded as the prodromic or pre-dementia stage of Alzheimer's disease. The accurate categorization of these subjects has far-reaching implications, both for research in this field and for those individuals who fall within this diagnostic group. Despite a wealth of studies examining the neuropsychological, neuroimaging and biological profiles of this population, the characterization of MCI remains controversial. This brief overview discusses a number of the issues related to this topic and questions the currently accepted criteria
UR  - http://neucas.oupjournals.org/cgi/content/abstract/8/6/405
ER  - 

TY  - JOUR
T1  - Rat studies comparing 11C-FMAU, 18F-FLT, and 76Br-BFU as proliferation markers
A1  - Lu,L.
A1  - Samuelsson,L.
A1  - Bergstrom,M.
A1  - Sato,K.
A1  - Fasth,K.J.
A1  - Langstrom,B.
Y1  - 2002/12//
N1  - UI - 22356226
SP  - 1688
EP  - 1698
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 43
IS  - 12
N2  - We analyzed and compared 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-[methyl-(11)C]thymine ((11)C-FMAU), 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-[(76)Br]bromouracil ((76)Br-BFU) with respect to tissue uptake, DNA incorporation, and excretion modulation in rats. The goal of the investigation was to evaluate the efficiency of the 3 nucleoside tracers as potential tracers for measuring proliferation. METHODS: Sprague-Dawley rats were divided into 3 groups and administered 5 MBq (11)C-FMAU, 1 MBq (18)F-FLT, or 2 MBq (76)Br-BFU. For each tracer, a subgroup was also administered 6 mg/kg cimetidine. The rats in the (11)C-FMAU group were killed at 5, 20, 40, 60, and 80 min after injection; the rats in the (18)F-FLT group were killed at 80 min and 2 and 4 h; and the rats in the (76)Br-BFU group were killed at 5, 20, 40, and 80 min and 2, 4, 6, and 24 h. Samples of blood, liver, kidney, spleen, and intestine were taken, and the radioactivity was measured. DNA separation was made in the samples of spleen, and the radioactivity in the DNA fraction was measured. RESULTS: Maximal uptake of radioactivity was seen in the spleen and intestine, organs with active DNA synthesis. The highest relative radioactivity uptake was at 60 min in the (11)C-FMAU groups and at 4 h in the (18)F-FLT group. In the (76)Br-BFU group, the uptake increased gradually during the observation period, and uptake of radioactivity increased markedly in rats receiving cimetidine. Cimetidine did not affect radioactivity uptake in the (11)C-FMAU or (18)F-FLT groups. The fraction of radioactivity in DNA was 78% in spleen at 60 min in the (11)C-FMAU group, 80% at 60 min and 97% at 4 h in the (76)Br-BFU group. The DNA-incorporation was only 2% in the (18)F-FLT group. CONCLUSION: (76)Br-BFU predominantly incorporates into DNA and has great potential as a PET tracer for the assessment of proliferation in vivo. (11)C-FMAU also may have potential as a proliferation marker, but the observation time is limited. (18)F-FLT does not incorporate into DNA and is therefore not a direct marker of proliferation
AD  - PET Center, Uppsala University Hospital, Uppsala, Sweden
UR  - PM:12468521
ER  - 

TY  - JOUR
T1  - Volumetric analysis of 18F-FDG PET in glioblastoma multiforme: prognostic information and possible role in definition of target volumes in radiation dose escalation
A1  - Tralins,K.S.
A1  - Douglas,J.G.
A1  - Stelzer,K.J.
A1  - Mankoff,D.A.
A1  - Silbergeld,D.L.
A1  - Rostomilly,R.
A1  - Hummel,S.
A1  - Scharnhorst,J.
A1  - Krohn,K.A.
A1  - Spence,A.M.
Y1  - 2002/12//
N1  - UI - 22356223
SP  - 1667
EP  - 1673
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 43
IS  - 12
N2  - The use of (18)F-FDG PET for brain tumors has been shown to be accurate in identifying areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme (GBM) may lead to improved disease control. On the basis of these premises, we initiated a pilot study to investigate the use of (18)F-FDG PET for the guidance of radiation dose escalation in the treatment of GBM. METHODS: Patients were considered eligible to participate in the study if they had a diagnosis of GBM, were at least 18 y old, and had a score of at least 60 on the Karnofsky Scale. Patients were treated with standard conformal fractionated radiotherapy (1.8 Gy per fraction, to 59.4 Gy), with volumes defined by MRI. At a dose of 45-50.4 Gy, patients underwent (18)F-FDG PET for boost target delineation. Final noncoplanar fields (3-4) were designed to treat the volume of abnormal (18)F-FDG uptake plus a 0.5-cm margin for an additional 20 Gy (2 Gy per fraction), to a total dose of 79.4 Gy. If no abnormal (18)F-FDG uptake was observed, treatment was stopped after the conventional course of 59.4 Gy. Age, Karnofsky score, MRI-based volumes, and (18)F-FDG PET volume were analyzed as prognostic variables for time to tumor progression (TTP) and overall survival. (18)F-FDG PET volumes and MRI-based volumes were compared to assess concordance. RESULTS: For the 27 patients who could be evaluated, median actuarial TTP was 43 wk, and median actuarial survival was 70 wk. On univariate analysis, (18)F-FDG PET, T1-weighted MRI gadolinium enhancement (excluding nonenhancing resection cavity), and T2-weighted MRI volumes were significantly predictive of TTP. On multivariate analysis, only (18)F-FDG PET volume retained significance for predicting TTP. Similar results were obtained on analysis of these variables as prognostic factors for survival. When (18)F-FDG PET-based volumes were compared with MRI-based volumes, a difference of at least 25% was detected in all patients, with all but 2 having smaller (18)F-FDG PET volumes. Of patients in whom (18)F-FDG uptake was initially present but treatment subsequently failed, 83% demonstrated the first tumor progression within the region of abnormal (18)F-FDG uptake. CONCLUSION: In comparison with MRI, (18)F-FDG PET defined unique volumes for radiation dose escalation in the treatment of GBM. (18)F-FDG PET volumes were predictive of survival and time to tumor progression in the treatment of patients with GBM
AD  - Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington, USA
UR  - PM:12468518
ER  - 

TY  - JOUR
T1  - Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease
A1  - Soong,B.W.
A1  - Liu,R.S.
Y1  - 1998/04//
N1  - UI - 98236079
SP  - 499
EP  - 504
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 64
IS  - 4
N2  - OBJECTIVES: The metabolic changes in the brain of symptomatic subjects affected with Machado-Joseph disease have been previously documented using PET with fluorine-18-fluorodeoxyglucose (FDG). The aim of this study was to evaluate these changes in asymptomatic Machado-Joseph disease gene carriers. METHODS: Seven asymptomatic Machado-Joseph disease gene carriers, identified using a molecular test, and 10 normal control subjects were recruited for PET studies using FDG. Regional uptake ratios of FDG were calculated from the radioactivity of the cerebellar hemispheres, brainstem, and the temporal, parietal and occipital cortices, divided by the activity in the thalamus. RESULTS: In comparison with data obtained from normal control subjects, there was significantly decreased FDG utilisation in the cerebellar hemispheres, brainstem, and occipital cortex, and increased FDG metabolism in the parietal and temporal cortices of asymptomatic Machado-Joseph disease gene carriers, suggesting preclinical disease activity. Discriminant analysis of regional FDG uptake correctly classified genetic status (Machado-Joseph disease mutation carriers v mutation negative subjects) in 25 of 25 subjects (100% sensitivity and 100% specificity), and clinical status (asymptomatic mutation carriers v symptomatic patients) in 14 of 15 subjects (100% sensitivity and 85.7% specificity). CONCLUSION: Subclinical changes of FDG consumption, as measured by noninvasive PET, can act as an objective marker of preclinical disease activity in Machado-Joseph disease
AD  - Department of Neurology, National Yang-Ming University School of Medicine and National Defense Medical Center, Taipei, Taiwan, Republic of China. bwsoong@vghtpe.gov.tw
UR  - PM:9576542
ER  - 

TY  - JOUR
T1  - Positron emission tomography (PET) in Machado-Joseph disease
A1  - Taniwaki,T.
A1  - Sakai,T.
A1  - Kobayashi,T.
A1  - Kuwabara,Y.
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Masuda,K.
A1  - Goto,I.
Y1  - 1997/01//
N1  - UI - 97225760
SP  - 63
EP  - 67
JA  - J Neurol Sci.
VL  - 145
IS  - 1
N2  - Positron emission tomography studies on the regional cerebral glucose metabolism (rCMRglc) and 18F-fluorodopa (18F-Dopa) uptake were performed in 3 patients with Machado-Joseph disease (MJD), a dominantly inherited degenerative disease in the cerebellum, brainstem and basal ganglia. The rCMRglc in MJD was found to be significantly decreased in the cerebellum, brainstem, striatum and whole cerebral cortex in comparison to that in normal subjects. These results of rCMRglc were different from those for dominantly inherited olivopontocerebellar atrophy (dOPCA) or cerebellar cortical degeneration (CCD), however they were similar to those for sporadic olivopontocerebellar atrophy (sOPCA) and multiple system atrophy (MSA). The 18F-Dopa uptake in MJD was found to be significantly decreased in the putamen and relatively spared in the caudate, which was different from that of MSA. In addition, these results indicate that MJD showed a dysfunction, not only in the regions with apparent pathological involvement such as cerebellum, brainstem and nigro-striatal dopaminergic system, but also in the cerebral cortex and the striatum where no pathology could be observed using conventional morphological techniques
AD  - Department of Neurology, Faculty of Medicine, Kyushu University, Higashi-Ku, Fukuoka-City, Japan
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Taniwaki-Machado-Joseph.pdf
ER  - 

TY  - JOUR
T1  - Limbic encephalitis investigated by 18FDG-PET and 3D MRI
A1  - Kassubek,J.
A1  - Juengling,F.D.
A1  - Nitzsche,E.U.
A1  - Lucking,C.H.
Y1  - 2001/01//
N1  - UI - 21041087
SP  - 55
EP  - 59
JA  - J Neuroimaging
VL  - 11
IS  - 1
N2  - Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and 3-dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG-PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease
AD  - Department of Neurology, University of Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany. kassubek@nz.ukl.uni-freiburg.de
UR  - PM:11198529
ER  - 

TY  - JOUR
T1  - [18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies
A1  - Antoine,J.C.
A1  - Cinotti,L.
A1  - Tilikete,C.
A1  - Bouhour,F.
A1  - Camdessanche,J.P.
A1  - Confavreux,C.
A1  - Vighetto,A.
A1  - Renault-Mannel,V.
A1  - Michel,D.
A1  - Honnorat,J.
Y1  - 2000/07//
N1  - UI - 20350721
SP  - 105
EP  - 108
JA  - Ann.Neurol
VL  - 48
IS  - 1
N2  - The diagnosis of cancer is often difficult in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron emission tomography scanning is a highly sensitive and specific method to detect lung tumors. We investigated 15 patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of cancer in 12 patients, and test results were negative in 3. Whole-body [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in the mediastinum in these 3 patients in accordance with the expected location of the malignancy
AD  - Service de Neurologie, Hopital de Bellevue, Faculte de Medecine Jacques Lisfranc, Saint-Etienne, France
UR  - PM:10894223
ER  - 

TY  - JOUR
T1  - Limbic encephalitis and hyperactive foci on PET scan
A1  - Fakhoury,T.
A1  - Abou-Khalil,B.
A1  - Kessler,R.M.
Y1  - 1999/10//
N1  - UI - 20071183
SP  - 427
EP  - 431
JA  - Seizure.
VL  - 8
IS  - 7
N2  - Two cases of patients with paraneoplastic limbic encephalitis, difficult to control seizures, and unilateral hippocampal hypermetabolism on positron emission tomography (PET) are described. Two women aged 33 and 61 presented with uncontrolled complex partial seizures, profound memory loss and cognitive decline. One was later diagnosed with breast cancer and the other with lung cancer. Video-EEG on the first patient recorded multifocal sharp waves and bilateral independent seizure onsets. The second patient had no epileptiform discharges and bitemporal ictal onset, even though the clinical seizures suggested a right temporal onset. Magnetic resonance imaging (MRI) was normal in both patients. PET scans obtained in the interictal state showed right hippocampal hypermetabolism in both patients. In the second patient, the lung cancer was irradiated with resolution of seizures and improvement of memory function. A PET scan six months later was normal. Subsequent seizure recurrence and worsening of memory led to the discovery of widespread metastases. Limbic encephalitis should be considered in the differential diagnosis of intractable partial epilepsy, particularly if accompanied by severe memory loss and cognitive decline. Treatment of the underlying cancer may be lead to improved seizure control. Hippocampal hypermetabolism may be a common feature on PET, and may indicate subclinical seizure activity
AD  - Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA. Toufic.Fakhoury@mcmail.vanderbilt.edu
UR  - PM:10600585
ER  - 

TY  - JOUR
T1  - The metabolic anatomy of paraneoplastic cerebellar degeneration
A1  - Anderson,N.E.
A1  - Posner,J.B.
A1  - Sidtis,J.J.
A1  - Moeller,J.R.
A1  - Strother,S.C.
A1  - Dhawan,V.
A1  - Rottenberg,D.A.
Y1  - 1988/06//
N1  - UI - 88308452
SP  - 533
EP  - 540
JA  - Ann.Neurol
VL  - 23
IS  - 6
N2  - Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a "reverse cerebellar diaschisis."
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York 10021
UR  - PM:3261571
ER  - 

TY  - JOUR
T1  - Neuroimaging of epilepsy
A1  - Kuzniecky,R.I.
A1  - Knowlton,R.C.
Y1  - 2002/09//
N1  - UI - 22415894
SP  - 279
EP  - 288
JA  - Semin.Neurol
VL  - 22
IS  - 3
N2  - Neuroimaging has an important role in the investigation and treatment of patients with epilepsy. Diagnosis of the underlying substrate in a given patient with epilepsy determines prognosis with higher accuracy than electroencephalography. Neuroimaging techniques include computed tomography (CT) and magnetic resonance imaging (MRI), although CT has a diminished role for diagnosis. MRI is the most appropriate imaging technique in the initial investigation of patients with epilepsy. MRI is the most sensitive technique for the diagnosis of hippocampal sclerosis, tumors, and malformations of cortical development. MRI is also critical for neurosurgical planning. Other imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography are reserved for patients with intractable epilepsy when surgery is contemplated. New developments such as MR spectroscopy, receptor PET, and magnetic source imaging are becoming clinical tools and have the promise of improving diagnosis
AD  - UAB Epilepsy Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama
UR  - PM:12528053
ER  - 

TY  - JOUR
T1  - In vivo hippocampal metabolic dysfunction in human temporal lobe epilepsy
A1  - Knowlton,R.C.
A1  - Abou-Khalil,B.
A1  - Sawrie,S.M.
A1  - Martin,R.C.
A1  - Faught,R.E.
A1  - Kuzniecky,R.I.
Y1  - 2002/12//
N1  - UI - 22358269
SP  - 1882
EP  - 1886
JA  - Arch.Neurol
VL  - 59
IS  - 12
N2  - BACKGROUND: The nature of functional metabolic disturbances in mesial temporal lobe epilepsy remains unclear. OBJECTIVES: To compare in vivo measures of hippocampal metabolic abnormalities in mesial temporal lobe epilepsy, as acquired with fludeoxyglucose F 18 positron emission tomography and proton magnetic resonance spectroscopic imaging, and to determine the relationship between N-acetylaspartate (NAA) disturbances and well-established derangements of glucose metabolism. DESIGN: Measures of hippocampal glucose metabolism from fludeoxyglucose F 18 positron emission tomography were normalized to whole brain counts to provide a glucose uptake metabolic index. Proton magnetic resonance spectroscopic imaging was performed at 4.1 T, and measures of creatinine/NAA ratio were made from mostly hippocampal-only voxels. Direct comparisons and correlation analysis of measures were performed. SETTING: Presurgical evaluations for treatment of intractable epilepsy. PATIENTS: Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine were studied. RESULTS: The mean ipsilateral hippocampal glucose metabolic index (0.85) was normal, while the contralateral metabolic index (0.95) was nearly significant for an abnormally elevated measure. The mean ipsilateral hippocampal creatinine/NAA (1.26) was abnormally elevated; the mean contralateral creatinine/NAA (0.88) was normal. Hippocampal glucose and creatinine/NAA measures did not correlate; asymmetry measures also did not correlate. CONCLUSIONS: Hippocampal metabolic disturbances in mesial temporal lobe epilepsy as measured by fludeoxyglucose F 18 positron emission tomography vs proton magnetic resonance spectroscopic imaging reflect different mechanisms of biochemical dysfunction. This lack of correlation is hypothesized to reflect a differential effect of varying degrees of disturbed cellular energy metabolism on mechanisms of glucose use and biosynthesis of NAA
AD  - UAB Epilepsy Center, Department of Neurology, University of Alabama at Birmingham School of Medicine, 35294-0021, USA. knowlton@uab.edu
UR  - PM:12470175
ER  - 

TY  - JOUR
T1  - Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography
A1  - Giovacchini,G.
A1  - Chang,M.C.
A1  - Channing,M.A.
A1  - Toczek,M.
A1  - Mason,A.
A1  - Bokde,A.L.
A1  - Connolly,C.
A1  - Vuong,B.K.
A1  - Ma,Y.
A1  - Der,M.G.
A1  - Doudet,D.J.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
A1  - Rapoport,S.I.
A1  - Carson,R.E.
Y1  - 2002/12//
N1  - UI - 22356097
SP  - 1453
EP  - 1462
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 12
N2  - Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A2. The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K* of [11C]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [11C]CO2. K* and cerebral blood volume (Vb) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6+/-1.2 and 2.6+/-0.5 microL x min(-1) x mL(-1) in gray and white matter, respectively. K* and Vb values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [11C]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A2-signaling, PET and [11C]AA may be useful to measure signal transduction in the human brain
AD  - Brain Physiology and Metabolism Section, National Institute on Aging, Bethesda, Maryland, U.S.A
UR  - PM:12468890
ER  - 

TY  - JOUR
T1  - Brain incorporation of [1-11C]arachidonate in normocapnic and hypercapnic monkeys, measured with positron emission tomography
A1  - Chang,M.C.
A1  - Arai,T.
A1  - Freed,L.M.
A1  - Wakabayashi,S.
A1  - Channing,M.A.
A1  - Dunn,B.B.
A1  - Der,M.G.
A1  - Bell,J.M.
A1  - Sasaki,T.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
A1  - Rapoport,S.I.
Y1  - 1997/04/25/
N1  - UI - 97306074
SP  - 74
EP  - 83
JA  - Brain Res.
VL  - 755
IS  - 1
N2  - Positron emission tomography (PET) was used to determine brain incorporation coefficients k* of [1-11C]arachidonate in isoflurane-anesthetized rhesus monkeys, as well as cerebral blood flow (CBF) using [15O]water. Intravenously injected [1-11C]arachidonate disappeared from plasma with a half-life of 1.1 min, whereas brain radioactivity reached a steady-state by 10 min. Mean values of k* were the same whether calculated by a single-time point method at 20 min after injection began, or by least-squares fitting of an equation for total brain radioactivity to data at all time points. k* equalled 1.1-1.2 x 10(-4) ml x s(-1) x g(-1) in gray matter and was unaffected by a 2.6-fold increase in CBF caused by hypercapnia. These results indicate that brain incorporation of [1-11C]arachidonate can be quantified in the primate using PET, and that incorporation is flow-independent
AD  - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
UR  - PM:9163542
ER  - 

TY  - JOUR
T1  - Use of [11C]aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain
A1  - Koeppe,R.A.
A1  - Mangner,T.
A1  - Betz,A.L.
A1  - Shulkin,B.L.
A1  - Allen,R.
A1  - Kollros,P.
A1  - Kuhl,D.E.
A1  - Agranoff,B.W.
Y1  - 1990/09//
N1  - UI - 90346953
SP  - 727
EP  - 739
JA  - J Cereb.Blood Flow Metab
VL  - 10
IS  - 5
N2  - A quantitative positron emission tomographic (PET) method to measure amino acid blood-brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using 11C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show [11C]ACHC to have an influx rate constant in gray matter of approximately 0.03-0.04 ml g-1 min-1, indicating a single-pass extraction fraction of approximately 5-7%. The intersubject coefficient of variation was approximately 15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that [11C]-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain
AD  - Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0552
UR  - PM:2384544
ER  - 

TY  - JOUR
T1  - Positron emission tomography partial volume correction: estimation and algorithms
A1  - Aston,J.A.
A1  - Cunningham,V.J.
A1  - Asselin,M.C.
A1  - Hammers,A.
A1  - Evans,A.C.
A1  - Gunn,R.N.
Y1  - 2002/08//
SP  - 1019
EP  - 1034
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 8
N2  - Partial volume effects in positron emission tomography (PET) lead to quantitative under- and over-estimations of the regional concentrations of radioactivity in reconstructed images and corresponding errors in derived functional or parametric images. The limited resolution of PET leads to "tissue-fraction" effects, reflecting underlying tissue heterogeneity, and "spillover" effects between regions. Addressing the former problem in general requires supplementary data, for example, coregistered high-resolution magnetic resonance images, whereas the latter effect can be corrected for with PET data alone if the point-spread function of the tomograph has been characterized. Analysis of otherwise homogeneous region-of-interest data ideally requires a combination of tissue classification and correction for the point-spread function. The formulation of appropriate algorithms for partial volume correction (PVC) is dependent on both the distribution of the signal and the distribution of the underlying noise. A mathematical framework has therefore been developed to accommodate both of these factors and to facilitate the development of new PVC algorithms based on the description of the problem. Several methodologies and algorithms have been proposed and implemented in the literature in order to address these problems. These methods do not, however, explicitly consider the noise model while differing in their underlying assumptions. The general theory for estimation of regional concentrations, associated error estimation, and inhomogeneity tests are presented in a weighted least squares framework. The analysis has been validated using both simulated and real PET data sets. The relations between the current algorithms and those published previously are formulated and compared. The incorporation of tensors into the formulation of the problem has led to the construction of computationally rapid algorithms taking into account both tissue-fraction and spillover effects. The suitability of their application to dynamic and static images is discussed
AD  - McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Quebec, Canada
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Aston-petpartialjcbfm.pdf
ER  - 

TY  - JOUR
T1  - Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography
A1  - Lingford-Hughes,A.
A1  - Hume,S.P.
A1  - Feeney,A.
A1  - Hirani,E.
A1  - Osman,S.
A1  - Cunningham,V.J.
A1  - Pike,V.W.
A1  - Brooks,D.J.
A1  - Nutt,D.J.
Y1  - 2002/07//
N1  - UI - 22137918
SP  - 878
EP  - 889
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 7
N2  - There is evidence of marked variation in the brain distribution of specific subtypes of the GABA-benzodiazepine receptor and that particular subtypes mediate different functions. The alpha5-containing subtype is highly expressed in the hippocampus, and selective alpha5 inverse agonists (which decrease tonic GABA inhibition) are being developed as potential memory-enhancing agents. Evidence for such receptor localization and specialization in humans in vivo is lacking because the widely used probes for imaging the GABA-benzodiazepine receptors, [11C]flumazenil and [123I]iomazenil, appear to reflect binding to the alpha1 subtype, based on its distribution and affinity of flumazenil for this subtype. The authors characterized for positron emission tomography (PET) a radioligand from Ro15 4513, the binding of which has a marked limbic distribution in the rat and human brain in vivo. Competition studies in vivo in the rat revealed that radiolabeled Ro15 4513 uptake was reduced to nonspecific levels only by drugs that have affinity for the alpha5 subtype (flunitrazepam, RY80, Ro15 4513, L655,708), but not by the alpha1 selective agonist, zolpidem. Quantification of [11C]Ro15 4513 PET was performed in humans using a metabolite-corrected plasma input function. [11C]Ro15 4513 uptake was relatively greater in limbic areas compared with [11C]flumazenil, but lower in the occipital cortex and cerebellum. The authors conclude that [11C]Ro15 4513 PET labels in vivo the GABA-benzodiazepine receptor containing the alpha5 subtype in limbic structures and can be used to further explore the functional role of this subtype in humans
AD  - Psychopharmacology Unit, School of Medical Science, University of Bristol, UK. anne.lingfordhughes@bristol.ac.uk
UR  - PM:12142573
ER  - 

TY  - JOUR
T1  - Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C] diprenorphine and positron emission tomography
A1  - Jones,A.K.
A1  - Kitchen,N.D.
A1  - Watabe,H.
A1  - Cunningham,V.J.
A1  - Jones,T.
A1  - Luthra,S.K.
A1  - Thomas,D.G.
Y1  - 1999/07//
N1  - UI - 99339381
SP  - 803
EP  - 808
JA  - J Cereb.Blood Flow Metab
VL  - 19
IS  - 7
N2  - The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites
AD  - Human Physiology and Pain Research Laboratory, University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, United Kingdom
UR  - PM:10413036
ER  - 

TY  - JOUR
T1  - Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study
A1  - Malizia,A.L.
A1  - Cunningham,V.J.
A1  - Bell,C.J.
A1  - Liddle,P.F.
A1  - Jones,T.
A1  - Nutt,D.J.
Y1  - 1998/08//
N1  - UI - 98370879
SP  - 715
EP  - 720
JA  - Arch.Gen.Psychiatry
VL  - 55
IS  - 8
N2  - BACKGROUND: Positron emission tomography (PET) allows the measurement of benzodiazepine-gamma-aminobutyric acidA (GABA(A)) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand that labels the benzodiazepine site on the GABA(A) receptor, and fully quantitative, high-sensitivity PET to test the hypothesis that central benzodiazepine site binding is decreased in medication-free patients with panic disorder. METHODS: We compared 7 patients with panic disorder who had been off medication for at least 6 months and who had never abused alcohol with 8 healthy controls. The resulting parametric voxel-by-voxel maps were analyzed by voxel-based and region of interest-based methods using both parametric and nonparametric statistics. RESULTS: The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In addition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought to be essential in the central mediation of anxiety. CONCLUSION: These results must be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GABA(A) receptor and demonstrate that decreased flumazenil binding at this site may underlie panic disorder
AD  - Cyclotron Unit, Medical Research Council, Clinical Research Centre, Hammersmith Hospital, London, England
UR  - PM:9707382
ER  - 

TY  - JOUR
T1  - Ketamine does not decrease striatal dopamine D(2) receptor binding in man
A1  - Aalto,S.
A1  - Hirvonen,J.
A1  - Kajander,J.
A1  - Scheinin,H.
A1  - Nagren,K.
A1  - Vilkman,H.
A1  - Gustafsson,L.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 2002/12//
N1  - UI - 22345191
SP  - 401
EP  - 406
JA  - Psychopharmacology (Berl)
VL  - 164
IS  - 4
N2  - RATIONALE. A glutamate-dopamine interaction has been implicated in the psychosis-like effects of glutamate N-methyl- D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine. However, recent imaging studies addressing striatal glutamate-dopamine interaction directly in vivo in man have been controversial. OBJECTIVES. To examine whether the NMDA receptor antagonist ketamine in high subanesthetic concentrations decreases striatal [(11)C]raclopride binding potential in man. To further evaluate whether changes in striatal [(11)C]raclopride binding are associated with ketamine-induced behavioral effects. METHODS. The effect of computer-driven subanesthetic ketamine infusion on striatal dopamine release was studied in healthy male subjects using a controlled study design. Dopamine release was studied using positron emission tomography and the [(11)C]raclopride displacement paradigm. A conventional region of interest-based analysis and voxel-based analysis were applied to the positron emission tomography data. RESULTS. The average plasma ketamine concentration was 293+/-29 ng/ml. Ketamine did not alter striatal [(11)C]raclopride binding. Ketamine induced typical behavioral effects, such as hallucinations but there was no correlation between these effects and displacement of [(11)C]raclopride binding. CONCLUSIONS. This controlled study indicates that ketamine does not decrease striatal [(11)C]raclopride binding. Striatal dopamine release is of minor importance in the psychosis-like effects of ketamine
AD  - Neuropsychiatric Imaging, Turku PET Centre, Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Aalto-ketamine-raclopride.pdf
ER  - 

TY  - JOUR
T1  - Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach
A1  - Breier,A.
A1  - Adler,C.M.
A1  - Weisenfeld,N.
A1  - Su,T.P.
A1  - Elman,I.
A1  - Picken,L.
A1  - Malhotra,A.K.
A1  - Pickar,D.
Y1  - 1998/06//
SP  - 142
EP  - 147
JF  - Synapse
VL  - 29
IS  - 2
N2  - Agents that antagonize the glutamatergic N-methyl-d-aspartate (NMDA) receptor, such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA-dopaminergic interactions has been proposed as a mechanism for these behavioral effects. In this study, we examined the effects of ketamine on striatal dopamine release in healthy human subjects with a novel 11C-raclopride/PET displacement paradigm and compared these effects to administration of saline and the direct-acting dopamine agonist amphetamine. We found that the percent decreases (mean +/- SD) in specific 11C-raclopride binding from baseline for ketamine (11.2 +/- 8.9) was greater than for saline (1.9 +/- 3.7) (t = 2.4, df = 13, P = 0.003) indicating that ketamine caused increases in striatal synaptic dopamine concentrations. Ketamine-related binding changes were not significantly different than the decreases in percent change (mean +/- SD) in specific 11C-raclopride binding caused by amphetamine (15.5 +/- 6.2) (t = 1.3, df = 19, P = 0.21). Ketamine-induced changes in 11C-raclopride-specific binding were significantly correlated with induction of schizophrenia-like symptoms. The implications of this brain imaging method for studies of schizophrenia and the mechanism of action of antipsychotic drugs are discussed
AD  - Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Breier_Alan@Lilly.com
UR  - PM:9593104
ER  - 

TY  - JOUR
T1  - Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis
A1  - Tsukada,H.
A1  - Harada,N.
A1  - Nishiyama,S.
A1  - Ohba,H.
A1  - Sato,K.
A1  - Fukumoto,D.
A1  - Kakiuchi,T.
Y1  - 2000/08//
N1  - UI - 20342442
SP  - 95
EP  - 103
JF  - Synapse
VL  - 37
IS  - 2
N2  - The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the striatal dopaminergic system were evaluated multiparametrically in the monkey brain using high-resolution positron emission tomography (PET) in combination with microdialysis. L-[beta-(11)C]DOPA, [(11)C]raclopride, and [(11)C]beta-CFT were used to evaluate dopamine synthesis rate, D(2) receptor binding, and transporter availability, respectively, in conscious and ketamine-anesthetized animals. Dopamine concentrations in the striatal extracellular fluid (ECF) were simultaneously measured by PET. Thirty minutes prior to PET scan, intravenous administration of ketamine was started by continuous infusion at a rate of 3 or 10 mg/kg/h. Ketamine infusion dose-dependently decreased [(11)C]raclopride binding, but induced no significant changes in dopamine concentration in the striatal ECF as measured by microdialysis at any dose used. In contrast, ketamine increased both dopamine synthesis and DAT availability as measured by L-[beta-(11)C]DOPA and [(11)C]beta-CFT, respectively, in a dose-dependent manner. These results suggest that the inhibition of glutamatergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability to the same extent, resulting in no apparent changes in ECF dopamine concentration as measured by microdialysis. It also suggests that the alteration of [(11)C]raclopride binding in vivo as measured by PET might not simply be modulated by the static synaptic concentration of dopamine
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan. tsukada@crl.hpk.co.jp
UR  - PM:10881030
ER  - 

TY  - JOUR
T1  - 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man--a PET study with [11C]raclopride
A1  - Vollenweider,F.X.
A1  - Vontobel,P.
A1  - Hell,D.
A1  - Leenders,K.L.
Y1  - 1999/05//
SP  - 424
EP  - 433
JF  - Neuropsychopharmacology
VL  - 20
IS  - 5
N2  - The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states
AD  - Research Department, Psychiatric University Hospital Zurich, Switzerland
UR  - PM:10192823
ER  - 

TY  - JOUR
T1  - Dopamine release during sequential finger movements in health and Parkinson's disease: a PET study
A1  - Goerendt,Ines K.
A1  - Messa,Cristina
A1  - Lawrence,Andrew D.
A1  - Grasby,Paul M.
A1  - Piccini,Paola
A1  - Brooks,David J.
Y1  - 2003/02/01/
SP  - 312
EP  - 325
JF  - Brain
VL  - 126
IS  - 2
N2  - Parkinson's disease is associated with slowness, especially of sequential movements, and is characterized pathologically by degeneration of dopaminergic neurons, particularly targeting nigrostriatal projections. In turn, nigrostriatal dopamine has been suggested to be critical for the execution of sequential movements. The objective of this study was to investigate in vivo, with [11C]raclopride, PET changes in regional brain levels of dopamine in healthy volunteers and Parkinson's disease patients during the execution of paced, stereotyped sequential finger movements. Striatal [11C]raclopride binding reflects dopamine D2 receptor availability and is influenced by synaptic levels of endogenous dopamine. During execution of a pre-learned sequence of finger movements, a significant reduction in binding potential (BP) of [11C]raclopride was seen in both caudate and putamen in healthy volunteers compared with a resting baseline, consistent with release of endogenous dopamine. Parkinson's disease patients also showed attenuated [11C]raclopride BP reductions during the same motor paradigm in striatal areas less affected by the disease process. These findings confirm that striatal dopamine release is a component of movement sequencing and show that dopamine release can be detected in early Parkinson's disease during a behavioural manipulation
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Goerendt-dopamine-release-PD.pdf
ER  - 

TY  - JOUR
T1  - Imaging the glutamatergic system in vivo--relevance to schizophrenia
A1  - Bressan,R.A.
A1  - Pilowsky,L.S.
Y1  - 2000/11//
SP  - 1723
EP  - 1731
JA  - Eur.J Nucl Med
VL  - 27
IS  - 11
N2  - Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system
AD  - Institute of Psychiatry, Denmark Hill, London, UK
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Bressan-Glutamate-Imaging.pdf
ER  - 

TY  - JOUR
T1  - PET studies of 18F-memantine in healthy volunteers
A1  - Ametamey,S.M.
A1  - Bruehlmeier,M.
A1  - Kneifel,S.
A1  - Kokic,M.
A1  - Honer,M.
A1  - Arigoni,M.
A1  - Buck,A.
A1  - Burger,C.
A1  - Samnick,S.
A1  - Quack,G.
A1  - Schubiger,P.A.
Y1  - 2002/02//
N1  - UI - 21681924
SP  - 227
EP  - 231
JA  - Nucl Med Biol.
VL  - 29
IS  - 2
N2  - Previous studies in mice and PET investigations in a Rhesus monkey showed that the regional uptake of 18F-memantine could be blocked by pharmacological doses of memantine and (+)-MK-801. In the present study, the binding characteristics of 18F-memantine was examined in five healthy volunteers.In humans, 18F-memantine was homogeneously distributed in gray matter i.e. cortex and basal ganglia regions, as well as the cerebellum. No radioactive metabolites were detected in plasma during the time-frame of the PET studies. The uptake of 18F-memantine in receptor-rich regions such as striatum and frontal cortex could be well described by a 1-tissue compartment model. The DV" values of all gray matter regions were similar and ranged from 15 to 20 ml/ml. The white matter showed lower DV" values of 15 +/- 1.4 ml/ml. These results suggest that 18F-memantine distribution in human brain does not reflect the regional NMDA receptor concentration, and therefore, this radioligand is not suitable for the PET imaging of the NMDA receptors
AD  - Center for Radiopharmaceutical Science of ETH, PSI and USZ, CH-5232 -PSI, Villigen, Switzerland. simon-mensah.ametamey@psi.ch
UR  - PM:11823128
ER  - 

TY  - JOUR
T1  - PET studies of [18F]methyl-MK-801, a potential NMDA receptor complex radioligand
A1  - Blin,J.
A1  - Denis,A.
A1  - Yamaguchi,T.
A1  - Crouzel,C.
A1  - MacKenzie,E.T.
A1  - Baron,J.C.
Y1  - 1991/01/02/
N1  - UI - 91211884
SP  - 183
EP  - 186
JA  - Neurosci.Lett.
VL  - 121
IS  - 1-2
N2  - Using positron emission tomography (PET), the potential of 18F-labelled fluoro-methyl-MK-801([18F]FMM) as a radioligand for in vivo studies of the NMDA receptor complex was investigated in baboons. In baseline conditions, there was a slight differential retention of [18F]FMM in cerebral cortex and striatum relative to cerebellum, compatible with specific binding. However, neither pretreatment with pharmacological doses of MK-801 or phencyclidine, nor severe, transient brain hypoxia, were able to clearly alter [18]FMM brain regional kinetics, indicating limited usefulness of this radioligand for in vivo PET investigations of the NMDA receptor
AD  - Service Hospitalier Frederic Joliot, CEA, Departement de biologie, Orsay, France
UR  - PM:1826943
ER  - 

TY  - JOUR
T1  - Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine
A1  - Tagawa,M.
A1  - Kano,M.
A1  - Okamura,N.
A1  - Higuchi,M.
A1  - Matsuda,M.
A1  - Mizuki,Y.
A1  - Arai,H.
A1  - Iwata,R.
A1  - Fujii,T.
A1  - Komemushi,S.
A1  - Ido,T.
A1  - Itoh,M.
A1  - Sasaki,H.
A1  - Watanabe,T.
A1  - Yanai,K.
Y1  - 2001/11//
SP  - 501
EP  - 509
JA  - Br.J Clin.Pharmacol.
VL  - 52
IS  - 5
N2  - AIMS: Sedation induced by antihistamines is widely recognized to be caused by their penetration through the blood-brain-barrier and the consequent occupation of brain histamine H1-receptors. We previously studied the mechanism of sedation caused by antihistamines using positron emission tomography (PET). Recently, we revealed the nonsedative characteristic of ebastine, a second-generation antihistamine, with cognitive performance tests. In the present study, H1-receptor occupation by ebastine was examined in the human brain using PET. METHODS: Ebastine 10 mg and (+)-chlorpheniramine 2 or 6 mg were orally given to healthy male volunteers. PET scans with [11C]-doxepin, a potent H1-receptor antagonist, were conducted near tmax of respective drugs. Other volunteers in the control group also received PET scans. The binding potential of doxepin (BP = Bmax/Kd) for available brain H1-receptors was imaged on a voxel-by-voxel basis through graphical analysis. By setting regions of interest, the H1-receptor occupancy of drugs was calculated in several H1-receptor rich regions. RESULTS: Brain distribution of radioactivity after ebastine treatment was similar to that without any drugs. However, after the oral administration of 2 mg (+)-chlorpheniramine, the level was lower than after ebastine and nondrug treatments. Graphical analysis followed by statistical parametric mapping (SPM96) revealed that H1-receptor rich regions such as cortices, cingulate gyrus and thalamus were regions where the BPs after ebastine were significantly higher than after (+)-chlorpheniramine (2 mg). H1-receptor occupancies in cortex were approximately 10% by ebastine and > or = 50% by either dose of (+)-chlorpheniramine (95% confidence interval for difference in the mean receptor occupancies: 27%, 54% for 2 mg and 35%, 62% for 6 mg vs ebastine, respectively). Receptor occupancies increased with increasing plasma concentration of (+)-chlorpheniramine, but not with concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine (10 mg orally) causes brain histamine H1-receptor occupation of approximately 10%, consistent with its lower incidence of sedative effect, whereas (+)-chlorpheniramine occupied about 50% of brain H1-receptors even at a low but sedative dose of 2 mg; occupancy of (+)-chlorpheniramine was correlated with plasma (+)-chlorpheniramine concentration
AD  - Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan
UR  - PM:11736858
ER  - 

TY  - JOUR
T1  - Histamine H(1) receptors in patients with Alzheimer's disease assessed by positron emission tomography
A1  - Higuchi,M.
A1  - Yanai,K.
A1  - Okamura,N.
A1  - Meguro,K.
A1  - Arai,H.
A1  - Itoh,M.
A1  - Iwata,R.
A1  - Ido,T.
A1  - Watanabe,T.
A1  - Sasaki,H.
Y1  - 2000///
N1  - UI - 20432513
SP  - 721
EP  - 729
JF  - Neuroscience
VL  - 99
IS  - 4
N2  - Cerebral histamine H(1) receptor binding was measured in vivo in 11 normal subjects (six young and five old) and 10 patients with Alzheimer's disease by positron emission tomography and [11C]doxepin, a radioligand for H(1) receptors. The parametric images describing the tracer kinetics were generated by either compartmental or graphical analysis, and were examined statistically on region-of-interest and voxel-by-voxel bases. The binding potential of H(1) receptors showed a significant decrease particularly in the frontal and temporal areas of the Alzheimer's disease brain compared to the old, normal subjects. In addition, the receptor binding correlated closely to the severity of Alzheimer's disease assessed by the Mini-Mental State Examination score within several brain areas. The ratio of K1 values between the brain areas and the cerebellum was used as a relative measure of regional cerebral blood flow which decreased in the frontal and temporal areas of the Alzheimer's disease brain. However, the difference in the binding potential (total concentration of receptor/equilibrium dissociation constant) between the Alzheimer's disease patients and the old, normal subjects was greater than that in the cerebral blood flow, and the rate of decrease in the binding potential with the progression of Alzheimer's disease was greater than the rate of decrease in the cerebral blood flow.This study reveals the predominant disruption of the histaminergic neurotransmission in the neurodegenerative processes of Alzheimer's disease. This study suggests that the decline of the histamine receptor binding might play a substantial role in the cognitive deficits of Alzheimer's disease patients
AD  - Department of Geriatric Medicine, Tohoku University School of Medicine, 980-8574, Sendai, Japan
UR  - PM:10974435
ER  - 

TY  - JOUR
T1  - A consideration of the dopamine D2 receptor monomer-dimer equilibrium and the anomalous binding properties of the dopamine D2 receptor ligand, N-methyl spiperone
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Dewey,S.L.
A1  - Volkow,N.D.
A1  - Gatley,S.J.
Y1  - 2001///
N1  - UI - 21239093
SP  - 279
EP  - 286
JA  - J Neural Transm.
VL  - 108
IS  - 3
N2  - Some discrepancies between experimental results with the two D2 antagonists N-methyl spiperone (NMSP) and raclopride (RAC) have been observed. Among these are the observation that MK-801 increases NMSP binding but not RAC binding: pretreatment with reserpine increases RAC binding but decreases NMSP binding; and that the two ligands yield different values for Bmax. It has been observed that the D2 receptor can exist in both a monomer and dimer form and that a NMSP photolabel ligand binds primarily to the monomer form while a RAC-like photolabel ligand binds both. Using a model of the dimerization in which the equilibrium dissociation constant increases with increasing dopamine (DA) concentration, the free monomer concentration can be shown to go through a maximum value with increasing DA. Using this model with data from a baboon PET study, it can be shown that under certain conditions an increase in binding could be observed. Further research may show that there are clusters of D2 receptors forming oligomers with more than two receptors in which NMSP binds to more sites on clusters with fewer receptors. If increasing DA favors cluster with fewer receptors, an increase in NMSP binding sites may also occur under some circumstances with an increase in DA
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA. jlogan@bnl.gov
UR  - PM:11341479
ER  - 

TY  - JOUR
T1  - Long-term stability of neurotransmitter activity investigated with 11C-raclopride PET
A1  - Schlosser,R.
A1  - Brodie,J.D.
A1  - Dewey,S.L.
A1  - Alexoff,D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Volkow,N.
A1  - Logan,J.
A1  - Wolf,A.P.
Y1  - 1998/01//
SP  - 66
EP  - 70
JF  - Synapse
VL  - 28
IS  - 1
N2  - There is evidence for the shift of regulatory setpoints of functionally linked neurotransmitter systems as a basis of psychiatric disorders. 11C-raclopride PET, which has been shown to be sensitive to changes in endogenous dopamine and has a high short-term test-retest reliability, can be used to investigate different regulatory states of the dopaminergic system with respect to psychiatric diseases and pharmacological influences. Prior to these studies, the reliability of the method over time has to be established. The current study was performed in order to evaluate the long-term stability of the striatal dopaminergic system. Eight normal healthy subjects (mean age: 48.1 years; range: 24-75) were studied twice with 11C-raclopride PET two times under resting conditions with a mean time interval between the scans of 11.3 months (range: 1-19). The ratio of basal ganglia (BG) to cerebellar (CB) distribution volumes (DVs) revealed a mean absolute change of 6.94 (range: 0.0-12.87%) between study A and B. BG DVs mean absolute change was 6.30% (range: 0.55-30.46%), CB DVs mean absolute change was 8.65% (range: 3.51-16.33%). The mean change of the BG/CB ratio was -0.33% (range: 12.87-12.34%). BG DVs mean change was 4.55% (range: 4.2-30.46%), CB DVs mean change was 5.10% (range: -10.71-16.33%). The intraindividual differences between the two scans in our study were not significantly different as compared to the 24 hour interval test-retest data, which have been published earlier (repeated measures ANOVA with df = 11; F = 0.49; P = 0.50) [Volkow et al. (1993) J. Nucl. Med., 34:609-613]. The intraclass correlation of the DV ratio index was r = 0.81. The binding potential in the baseline scans and repeated scans showed a non-significant correlation with age (r = -0.58, P = 0.13). Interindividually, the DV ratio index revealed a mean of 3.18 (range = 2.55-3.68, SD = 0.42 in study A and of 3.16 (range 2.37-3.57, SD = 0.41) in study B. The intrasubject stability of the 11C-raclopride binding over a long-term period in normal human subjects suggests the feasibility of study designs investigating the long-term changes of the dopaminergic responsivity after pharmacological challenges. The baseline stability will also serve as a necessary reference for further dose-response studies and investigations of subchronical pharmacological interventions
AD  - Department of Psychiatry NYU Medical Center, New York, New York 10016, USA
UR  - PM:9414019
ER  - 

TY  - JOUR
T1  - Simultaneous molecular and anatomical imaging of the mouse in vivo
A1  - Goertzen,A.L.
A1  - Meadors,A.K.
A1  - Silverman,R.W.
A1  - Cherry,S.R.
Y1  - 2002/12/21/
N1  - UI - 22427413
SP  - 4315
EP  - 4328
JA  - Phys.Med Biol.
VL  - 47
IS  - 24
N2  - Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice
AD  - Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. agoertzen@mednet.ucla.edu
UR  - PM:12539974
ER  - 

TY  - JOUR
T1  - Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging
A1  - Chatziioannou,A.
A1  - Tai,Y.C.
A1  - Doshi,N.
A1  - Cherry,S.R.
Y1  - 2001/11//
N1  - UI - 21577377
SP  - 2899
EP  - 2910
JA  - Phys.Med Biol.
VL  - 46
IS  - 11
N2  - We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph
AD  - Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA. archatziioann@mednet.ucla.edu
UR  - PM:11720354
ER  - 

TY  - JOUR
T1  - Combining anatomy and function: the path to true image fusion
A1  - Townsend,D.W.
A1  - Cherry,S.R.
Y1  - 2001///
N1  - UI - 21558305
SP  - 1968
EP  - 1974
JA  - Eur.Radiol.
VL  - 11
IS  - 10
N2  - Modern imaging technologies visualize different aspects of disease in a non-invasive way. Considerable progress has been made in the fusion of images from different imaging modalities using software approaches. One goal of fusion software is to align anatomical and functional images and allow improved spatial localization of abnormalities. The resulting correlation of the anatomical and functional images may clarify the nature of the abnormality and help diagnose or stage the underlying disease. Whereas successful image fusion software has been developed for the brain, only limited success has been achieved for image alignment in other parts of the body. The development and current status of alternative approaches are presented. Dual-modality imaging is described with devices where two modalities are combined and mounted in a single gantry. The use of existing scanner technology ensures that no compromises are made in the clinical efficacy of either the anatomical or functional imaging modality. A combined positron emission tomography (PET) and computed tomography (CT) scanner has been developed and is undergoing clinical evaluation. Combining PET with MR is technologically more challenging because of the strong magnetic fields restricting the use of certain electronic components. An overview of the current status and future prospects of dual-modality imaging devices is presented
AD  - Department of Radiology, PET Facility, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. dave@pet.upmc.edu
UR  - PM:11702130
ER  - 

TY  - JOUR
T1  - Complementary emerging techniques: high-resolution PET and MRI
A1  - Jacobs,R.E.
A1  - Cherry,S.R.
Y1  - 2001/10//
N1  - UI - 21479323
SP  - 621
EP  - 629
JA  - Curr.Opin.Neurobiol.
VL  - 11
IS  - 5
N2  - Noninvasive imaging technologies provide a unique window on the anatomy, physiology and function of living organisms. Imaging systems and methods have been developed for the study of small animal model systems that offer exciting new possibilities in neuroscience. Advances in magnetic resonance microscopy and positron emission tomography, and their applications in brain imaging, have provided many benefits to neurobiology, ranging from detailed in vivo neuroanatomy to the measurement of specific molecular targets
AD  - Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA. rjacobs@caltech.edu
UR  - PM:11595498
ER  - 

TY  - JOUR
T1  - Performance evaluation of the microPET P4: a PET system dedicated to animal imaging
A1  - Tai,C.
A1  - Chatziioannou,A.
A1  - Siegel,S.
A1  - Young,J.
A1  - Newport,D.
A1  - Goble,R.N.
A1  - Nutt,R.E.
A1  - Cherry,S.R.
Y1  - 2001/07//
N1  - UI - 21366484
SP  - 1845
EP  - 1862
JA  - Phys.Med Biol.
VL  - 46
IS  - 7
N2  - The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8 x 8 array of 2.2 x 2.2 x 10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET. including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position
AD  - Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA
UR  - PM:11474929
ER  - 

TY  - JOUR
T1  - Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET
A1  - Chatziioannou,A.
A1  - Qi,J.
A1  - Moore,A.
A1  - Annala,A.
A1  - Nguyen,K.
A1  - Leahy,R.
A1  - Cherry,S.R.
Y1  - 2000/05//
N1  - UI - 20471714
SP  - 507
EP  - 512
JA  - IEEE Trans.Med Imaging
VL  - 19
IS  - 5
N2  - We have evaluated the performance of two three-dimensional (3-D) reconstruction algorithms with data acquired from microPET, a high resolution tomograph dedicated to small animal imaging. The first was a linear filtered-backprojection algorithm (FBP) with reprojection of the missing data, and the second was a statistical maximum a posteriori probability algorithm (MAP). The two algorithms were evaluated in terms of their resolution performance, both in phantoms and in vivo. Sixty independent realizations of a phantom simulating the brain of a baby monkey were acquired, each containing three million counts. Each of these realizations was reconstructed independently with both algorithms. The ensemble of the 60 reconstructed realizations was used to estimate the standard deviation as a measure of the noise for each reconstruction algorithm. More detail was recovered in the MAP reconstruction without an increase in noise relative to FBP. Studies in a simple cylindrical compartment phantom demonstrated improved recovery of known activity ratios with MAP. Finally, in vivo studies also demonstrated a clear improvement in spatial resolution using the MAP algorithm. The quantitative accuracy of the MAP reconstruction was also evaluated by comparison with autoradiography and direct well counting of tissue samples and was shown to be superior
AD  - Crump Institute for Biological Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA. archatziioann@mednet.ucla.edu
UR  - PM:11021693
ER  - 

TY  - JOUR
T1  - Dynamic changes in cerebral glucose metabolism in conscious infant monkeys during the first year of life as measured by positron emission tomography
A1  - Moore,A.H.
A1  - Hovda,D.A.
A1  - Cherry,S.R.
A1  - Villablanca,J.P.
A1  - Pollack,D.B.
A1  - Phelps,M.E.
Y1  - 2000/04/14/
N1  - UI - 21060513
SP  - 141
EP  - 150
JA  - Brain Res.Dev.Brain Res.
VL  - 120
IS  - 2
N2  - Recently, advances in spatial resolution have provided the opportunity to utilize positron emission tomography (PET) to examine local cerebral metabolic rates for glucose (lCMR(glc)) in large animals noninvasively, thereby allowing repeated lCMR(glc) measurements in the same animal. Previous studies have attempted to describe the ontogeny of cerebral glucose metabolism in anesthetized nonhuman primates using [18F]fluorodeoxyglucose (FDG) and PET. However, the use of sedation during the tracer uptake period may influence lCMR(glc). This study was conducted to describe lCMR(glc) in conscious infant vervet monkeys (Cercopithecus aethiops sabaeus) during the first year of life utilizing FDG-PET. Cross-sectional studies (n=23) displayed lowest and highest lCMR(glc) in all structures at the 2-3 and 8-9 month age groups, respectively. The metabolic pattern suggested an increase in lCMR(glc) values between 2 and 8 months of age with decreased metabolism observed at 10-12 months of age in all regions. Peak lCMR(glc) values at 8 months were an average of 84+/-24% higher than values seen at the youngest age examined quantitatively (2-3 months). The regions of greatest and smallest increases in lCMR(glc) at 8 months were the cerebellar hemispheres (90%) and the thalamus (39%), respectively. Longitudinal analysis in 4 animals supported this developmental pattern, demonstrating the ability to detect changes in cerebral glucose metabolism within animals and the potential for FDG-PET in nonhuman primate models of brain maturation. By determining the normative profile of lCMR(glc) during development in monkeys, future application of FDG-PET will provide the opportunity to longitudinally assess the effects of environmental or pharmacological intervention on the immature brain
AD  - Department of Medical and Molecular Pharmacology, UCLA, Los Angeles, CA 90095, USA
UR  - PM:10775767
ER  - 

TY  - JOUR
T1  - Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability
A1  - Umile,E.M.
A1  - Sandel,M.E.
A1  - Alavi,A.
A1  - Terry,C.M.
A1  - Plotkin,R.C.
Y1  - 2002/11//
N1  - UI - 22308722
SP  - 1506
EP  - 1513
JA  - Arch.Phys.Med Rehabil.
VL  - 83
IS  - 11
N2  - OBJECTIVE: To determine whether patients with mild traumatic brain injury (TBI) and persistent postconcussive symptoms have evidence of temporal lobe injury on dynamic imaging. DESIGN: Case series. SETTING: An academic medical center. PARTICIPANTS: Twenty patients with a clinical diagnosis of mild TBI and persistent postconcussive symptoms were referred for neuropsychologic evaluation and dynamic imaging. Fifteen (75%) had normal magnetic resonance imaging (MRI) and/or computed tomography (CT) scans at the time of injury. INTERVENTIONS: Neuropsychologic testing, positron-emission tomography (PET), and single-photon emission-computed tomography (SPECT). MAIN OUTCOME MEASURES: Temporal lobe findings on static imaging (MRI, CT) and dynamic imaging (PET, SPECT); neuropsychologic test findings on measures of verbal and visual memory. RESULTS: Testing documented neurobehavioral deficits in 19 patients (95%). Dynamic imaging documented abnormal findings in 18 patients (90%). Fifteen patients (75%) had temporal lobe abnormalities on PET and SPECT (primarily in medial temporal regions); abnormal findings were bilateral in 10 patients (50%) and unilateral in 5 (25%). Six patients (30%) had frontal abnormalities, and 8 (40%) had nonfrontotemporal abnormalities. Correlations between neuropsychologic testing and dynamic imaging could be established but not consistently across the whole group. CONCLUSIONS: Patients with mild TBI and persistent postconcussive symptoms have a high incidence of temporal lobe injury (presumably involving the hippocampus and related structures), which may explain the frequent finding of memory disorders in this population. The abnormal temporal lobe findings on PET and SPECT in humans may be analogous to the neuropathologic evidence of medial temporal injury provided by animal studies after mild TBI
AD  - Department of Rehabilitation Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA
UR  - PM:12422317
ER  - 

TY  - JOUR
T1  - Neurobehavioural dysfunction following mild traumatic brain injury in childhood: a case report with positive findings on positron emission tomography (PET)
A1  - Roberts,M.A.
A1  - Manshadi,F.F.
A1  - Bushnell,D.L.
A1  - Hines,M.E.
Y1  - 1995/07//
N1  - UI - 96053754
SP  - 427
EP  - 436
JA  - Brain Inj.
VL  - 9
IS  - 5
N2  - The present case study describes the neurobehavioural, neurodiagnostic, and positron emission tomography (PET) scan findings in a child who sustained a whiplash-type injury in a motor vehicle accident. Although neck and back pain were reported immediately, neurobehavioural symptoms, such as staring spells, gradually increased in frequency over a 2-year period following the accident. At 4 years after the accident the patient's symptoms persisted, as reported by teachers and parents, and more extensive diagnostic work-up was initiated. Standard EEG was normal while two ambulatory EEGs were abnormal and interpreted as epileptiform. A PET scan showed evidence of marked hypometabolism in both temporal lobes. Neuropsychological findings were consistent with PET findings and reflected verbal and visual memory deficits in the context of high average intelligence. Treatment with carbamazepine, verapamil, and fluoxetine greatly improved the patient's symptoms. The present case illustrates an example of a poor outcome in a paediatric case of mild traumatic brain injury, the importance of PET in demonstrating definitive evidence of brain dysfunction, and the child's positive response to anticonvulsant medication
AD  - Department of Pediatrics, University of Iowa College of Medicine, USA
UR  - PM:7550214
ER  - 

TY  - JOUR
T1  - Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography
A1  - Chugani,D.C.
A1  - Chugani,H.T.
A1  - Muzik,O.
A1  - Shah,J.R.
A1  - Shah,A.K.
A1  - Canady,A.
A1  - Mangner,T.J.
A1  - Chakraborty,P.K.
Y1  - 1998/12//
SP  - 858
EP  - 866
JF  - Annals of Neurology
VL  - 44
IS  - 6
N2  - Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC. [Journal Article; In English; United States]
UR  - http://www.sciencedirect.com/science/article/B6WVB-45D8793-2GY/1/2cf76c7c0bbd4457127cd3c529c7142a
ER  - 

TY  - JOUR
T1  - Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy
A1  - Choi,J.Y.
A1  - Kim,S.J.
A1  - Hong,S.B.
A1  - Seo,D.W.
A1  - Hong,S.C.
A1  - Kim,B.T.
A1  - Kim,S.E.
Y1  - 2003/01/30/
N1  - UI - 0
SP  - 581
EP  - 587
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - We investigated the relationship between the presence of extratemporal hypometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and seizure outcome after temporal lobectomy in patients with medically intractable temporal lobe epilepsy (TLE). In 47 patients with intractable unilateral mesial TLE, regional metabolic changes on FDG PET images obtained during the 2 months preceding anterior temporal lobectomy were compared with postoperative seizure outcome. Postoperative seizure outcome was evaluated with a mean follow-up period of 6.1+/-0.6 years (range 5.2-7.2 years). Forty-two (89%) of the 47 patients achieved a good postoperative seizure outcome (Engel class I or II). All patients had hypometabolism in the temporal cortex ipsilateral to the epileptogenic region on FDG PET scans. Fourteen (78%) of the 18 patients with hypometabolism only in the ipsilateral temporal cortex were completely seizure free (Engel class Ia) after surgery. In contrast, five (45%) of the 11 patients with extratemporal cortical hypometabolism confined to the ipsilateral cerebral hemisphere and only four (22%) of the 18 patients with hypometabolism in the contralateral cerebral cortex were completely seizure free after surgery. The postoperative seizure-free rates were significantly different across the three groups of patients with different cortical metabolic patterns ( P<0.005). Furthermore, all of the nine patients with a non-class I outcome (Engel class II-IV) had extratemporal (including contralateral temporal) cortical hypometabolism. Thalamic hypometabolism was noted in 20 (43%) of the 47 patients (ipsilateral in 12, bilateral in 8). Sixteen (59%) of the 27 patients with normal thalamic metabolism were completely seizure free after surgery, while only seven (35%) of the 20 patients with thalamic hypometabolism became completely seizure free ( P<0.05). Multivariate analysis revealed that among variables including clinical, EEG, magnetic resonance imaging, pathological and FDG PET metabolic findings, only cortical metabolic pattern was an independent factor for the prediction of postoperative seizure outcome ( P<0.005). It is concluded that extratemporal cortical hypometabolism outside the seizure focus, in particular hypometabolism in the contralateral cerebral cortex, may be associated with a poorer postoperative seizure outcome in TLE and may represent underlying pathology that is potentially epileptogenic. Thalamic hypometabolism, which was associated, but not independently, with a higher likelihood of postoperative seizures, may be secondary to extratemporal or temporal pathology
AD  - Department of Nuclear Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine, 50 Ilwon-dong, 135-710, Kangnam-ku, Seoul, Korea
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Choi-TLE.pdf
ER  - 

TY  - JOUR
T1  - Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole (18)F-EF5
A1  - Ziemer,S.
A1  - Evans,M.
A1  - Kachur,V.
A1  - Shuman,L.
A1  - Cardi,A.
A1  - Jenkins,T.
A1  - Karp,S.
A1  - Alavi,A.
A1  - Dolbier,R.,Jr.
A1  - Koch,J.
Y1  - 2003/02//
N1  - UI - 0
SP  - 259
EP  - 266
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 2
N2  - Tumor hypoxia is an important prognostic indicator for cancer therapy outcome. EF5 {2-(2-nitro-1[ H]-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)-acetamide} has been employed to measure tumor hypoxia in animals and humans using immunohistochemical methods. EF5 is a lipophilic molecule designed to have a very uniform biodistribution, a feature of obvious benefit for use in PET imaging. The present study represents the first demonstration of noninvasive PET imaging of rat tumors using fluorine-18 labeled EF5. Because of the small tumor size, partial volume effects may result in underestimation of concentration of the compound. Therefore, validation of the PET data was performed by gamma counting of the imaged tissue. The tumor models studied were the Morris 7777 (Q7) hepatoma ( n=5) and the 9L glioma ( n=2) grown subcutaneously in rats. Our previous studies have demonstrated that early passage 9L tumors are not severely hypoxic and that Q7 tumors are characterized by heterogeneous regions of tumor hypoxia (i.e., Q7 tumors are usually more hypoxic than early passage 9L tumors). The seven rats were imaged in the HEAD Penn-PET scanner at various time points after administration of 50-100 micro Ci (18)F-EF5 in 30 mg/kg carrier nonradioactive EF5. The carrier was used to ensure drug biodistribution comparable to prior studies using immunohistochemical methods. (18)F-EF5 was excreted primarily via the urinary system. Images obtained 10 min following drug administration demonstrated that the EF5 distributed evenly to all organ systems, including brain. Later images showed increased uptake in most Q7 tumors compared with muscle. Liver uptake remained relatively constant over the same time periods. Tumor to muscle ratios ranged from 0.82 to 1.73 (based on PET images at 120 min post injection) and 1.47 to 2.95 (based on gamma counts at ~180 min post injection). Tumors were easily visible by 60 min post injection when the final tumor to muscle ratios (based on gamma counts) were greater than 2. Neither of the 9L tumors nor the smallest Q7 tumor met this criterion, and these tumors were not seen on the PET images. These preliminary results suggest that (18)F-EF5 is a promising agent for noninvasive assessment of tumor hypoxia. Plans are underway to initiate a research project to determine the safety and preliminary evidence for the efficacy of this preparation in patients with brain tumors
AD  - University of Pennsylvania School of Veterinary Medicine, Section of Radiology, 3850 Spruce Street, Philadelphia, PA 19104, USA, lziemer@vet.upenn.edu
UR  - PM:12552344
ER  - 

TY  - JOUR
T1  - Quantitative cerebral H(2)(15)O perfusion PET without arterial blood sampling, a method based on washout rate
A1  - Treyer,V.
A1  - Jobin,M.
A1  - Burger,C.
A1  - Teneggi,V.
A1  - Buck,A.
Y1  - 2003/01/28/
N1  - UI - 0
SP  - 572
EP  - 580
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - The quantitative determination of regional cerebral blood flow (rCBF) is important in certain clinical and research applications. The disadvantage of most quantitative methods using H(2)(15)O positron emission tomography (PET) is the need for arterial blood sampling. In this study a new non-invasive method for rCBF quantification was evaluated. The method is based on the washout rate of H(2)(15)O following intravenous injection. All results were obtained with Alpert's method, which yields maps of the washin parameter K(1) (rCBF(K1)) and the washout parameter k(2) (rCBF(k2)). Maps of rCBF(K1) were computed with measured arterial input curves. Maps of rCBF(k2*) were calculated with a standard input curve which was the mean of eight individual input curves. The mean of grey matter rCBF(k2*) (CBF(k2*)) was then compared with the mean of rCBF(K1) (CBF(K1)) in ten healthy volunteer smokers who underwent two PET sessions on day 1 and day 3. Each session consisted of three serial H(2)(15)O scans. Reproducibility was analysed using the rCBF difference scan 3-scan 2 in each session. The perfusion reserve (PR = rCBF(acetazolamide)-rCBF(baseline)) following acetazolamide challenge was calculated with rCBF(k2*) (PR(k2*)) and rCBF(K1) (PR(K1)) in ten patients with cerebrovascular disease. The difference CBF(k2*)-CBF(K1) was 5.90+/-8.12 ml/min/100 ml (mean+/-SD, n=55). The SD of the scan 3-scan 1 difference was 6.1% for rCBF(k2*) and rCBF(K1), demonstrating a high reproducibility. Perfusion reserve values determined with rCBF(K1) and rCBF(k2*) were in high agreement (difference PR(k2*)-PR(K1)=-6.5+/-10.4%, PR expressed in percentage increase from baseline). In conclusion, a new non-invasive method for the quantitative determination of rCBF is presented. The method is in good agreement with Alpert's original method and the reproducibility is high. It does not require arterial blood sampling, yields quantitative voxel-by-voxel maps of rCBF, and is computationally efficient and easy to implement
AD  - PET Center, Division of Nuclear MedicineUniversity Hospital Zurich, Ramistrasse 100, 8091, Zurich, Switzerland
UR  - PM:12552334
ER  - 

TY  - JOUR
T1  - For: Is LSO the future of PET?
A1  - Nutt,R.
Y1  - 2002/11//
N1  - UI - 22424296
SP  - 1523
EP  - 1525
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 29
IS  - 11
UR  - PM:12537009
ER  - 

TY  - JOUR
T1  - Age-related reduction of [11C]MDL100,907 binding to central 5-HT(2A) receptors: PET study in the conscious monkey brain
A1  - Kakiuchi,T.
A1  - Nishiyama,S.
A1  - Sato,K.
A1  - Ohba,H.
A1  - Nakanishi,S.
A1  - Tsukada,H.
Y1  - 2000/11/10/
N1  - UI - 20519192
SP  - 135
EP  - 142
JA  - Brain Res.
VL  - 883
IS  - 1
N2  - Age-related alterations of serotonin (5-hydroxytryptamine; 5-HT) type 2A receptors (5-HT(2A)) in the living brains of young (6.0+/-1. 3 years old) and aged (19.2+/-3.0 years old) monkeys (Macaca mulatta) were evaluated with [11C]MDL100,907 in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of 5-HT(2A) binding in vivo, PET scan of [11C]MDL100,907 was performed with arterial blood sampling in each animal, and the metabolic-corrected arterial input function was used for Logan graphical analysis. Higher cerebral binding of [11C]MDL100, 907 was observed in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, regions known to contain high densities of 5-HT(2A), by in vitro assay. Binding was intermediate in the striatum and thalamus, and lower in the pons and cerebellum in both young and aged monkeys. The age-related decrease in [11C]MDL100,907 binding to 5-HT(2A) receptors was prominent in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, but not in the striatum, thalamus and pons. These observation demonstrated the usefulness of [11C]MDL100,907 as an labeled compound for assessment of the aging process of the cortical 5-HT(2A) measured by PET
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, 434-8601, Shizuoka, Japan
UR  - PM:11063997
ER  - 

TY  - JOUR
T1  - Autoradiographic localization of 5-HT(2A) receptors in the human brain using [(3)H]M100907 and [(11)C]M100907
A1  - Hall,H.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Lundkvist,C.
A1  - Sedvall,G.
Y1  - 2000/12/15/
SP  - 421
EP  - 431
JF  - Synapse
VL  - 38
IS  - 4
N2  - M100907 (MDL 100907, R-(+)-alpha-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol++ +) is a new selective antagonist of 5-HT(2A) receptors. The compound has been labeled with (11)C and proved useful for in vivo studies of 5-HT(2A) receptors using positron emission tomography (PET). In the present study the distribution of 5-HT(2A) receptors was examined in the postmortem human brain using whole hemisphere autoradiography and [(3)H]M100907 and [(11)C]M100907. The autoradiograms showed very dense binding to all neocortical regions, whereas the hippocampus was only weakly labeled with [(3)H]M100907. Other central brain regions, such as the basal ganglia and thalamus, showed low [(3)H]M100907 binding, reflecting low densities of 5-HT(2A) receptors. The cerebellum or structures of the brain stem were virtually devoid of 5-HT(2A) receptors. [(11)C]M100907 gave images qualitatively similar to those of [(3)H]M100907, although with lower spatial resolution. The labeling of human 5-HT(2A) receptors with [(3)H]M100907 was inhibited by the addition of the 5-HT(2A) receptor blockers ketanserin or SCH 23390 (10 microM), leaving a very low background of nonspecific binding. The 5-HT(1A) receptor antagonist WAY-100635 and the D(2)-dopamine receptor antagonist raclopride had no effect on the binding of [(3)H]M100907. The selective labeling of 5-HT(2A) receptors with [(3)H]M100907 clearly shows that this compound is suitable for further studies of the human 5-HT(2A) receptor subtype in vitro. The in vitro autoradiography of the distribution of 5-HT(2A) receptors obtained with radiolabeled M100907 provides detailed qualitative and quantitative information on the distribution of 5-HT(2A)-receptors in the human brain as well as reference information for the interpretation of previous initial results at much lower resolution in humans in vivo with PET and [(11)C]M100907
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm, Sweden. hakan.hall@psyk.ks.se
UR  - PM:11044889
ER  - 

TY  - JOUR
T1  - High 5HT2A receptor occupancy in M100907-treated schizophrenic patients
A1  - Talvik-Lotfi,M.
A1  - Nyberg,S.
A1  - Nordstrom,A.L.
A1  - Ito,H.
A1  - Halldin,C.
A1  - Brunner,F.
A1  - Farde,L.
Y1  - 2000/03//
SP  - 400
EP  - 403
JA  - Psychopharmacology (Berl)
VL  - 148
IS  - 4
N2  - RATIONALE: Selective drugs are required to test the hypothesis whether antipsychotic effects may be induced or modulated by 5HT(2A) receptor antagonism. M100907 (previously known as MDL 100,907) is a highly selective 5HT(2A) antagonist in clinical development. OBJECTIVE: To test if the suggested clinical dose of 20 mg M100907 daily induces high 5HT(2A) receptor occupancy in patients with schizophrenia. METHODS: The 5HT(2A) receptor occupancy was determined in two patients with schizophrenia treated with M100907, 20 mg once a day. Positron emission tomography (PET) with (11)C-labeled M100907, was performed prestudy and under steady state conditions. Clinical ratings were performed weekly. RESULTS: Clinical treatment with M100907, 20 mg daily induced a very high 5HT(2A) receptor occupancy in the frontal cortex of both patients (>90%). M100907 was well tolerated. One patient improved minimally and one patient became minimally worse during treatment. CONCLUSIONS: The results confirm that an oral dose of 20 mg per day ensures adequate 5HT(2A) receptor occupancy for clinical proof of concept. The sample is too small to allow conclusions about the clinical effect
AD  - Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. mirjaml@psyk.ks.se
UR  - PM:10928313
ER  - 

TY  - JOUR
T1  - Positron emission tomographic analysis of dose-dependent MDL 100,907 binding to 5-hydroxytryptamine-2A receptors in the human brain
A1  - Andree,B.
A1  - Nyberg,S.
A1  - Ito,H.
A1  - Ginovart,N.
A1  - Brunner,F.
A1  - Jaquet,F.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 1998/08//
SP  - 317
EP  - 323
JA  - J Clin.Psychopharmacol.
VL  - 18
IS  - 4
N2  - Selective 5-hydroxytryptamine-2A (5-HT2A) antagonism has been proposed as a mechanism of atypical antipsychotic drug action. MDL 100,907, a new selective 5-HT2A receptor antagonist, has high affinity in vitro for 5-HT2A receptors and is being developed as a potential antipsychotic drug. In this study, neocortical 5-HT2A receptor occupancy was measured in six healthy male volunteers after placebo and escalating single doses (1-72 mg) of MDL 100,907 using positron emission tomography and the nonspecific radioligand [11C]N-methylspiperone ([11C]NMSP). Receptor occupancy was calculated using a ratio-equilibrium analysis, assuming that maximal radioligand binding inhibition represents 100% 5-HT2A receptor occupancy. Plasma concentrations of MDL 100,907 were measured with high-pressure liquid chromatography. The pharmacokinetic parameters area under the curve and peak plasma concentration increased linearly with dose, with rapid absorption and a 6- to 9-hour elimination half-life. The neocortical binding of [11C]NMSP was inhibited dose-dependently. After administration of 6 mg of MDL 100,907 the inhibition was 70%, corresponding to a 5-HT2A receptor occupancy of 90%. The calculated maximal inhibition was 77%. These observations indicate that MDL 100,907 passes the blood-brain barrier and binds to 5-HT2A receptors in a saturable manner in the living human brain. Repeated doses of MDL 100,907, 10 mg/day or more, should induce a sustained 5-HT2A receptor occupancy in most patients. Thus, MDL 100,907 provides a suitable tool to evaluate the potential of selective 5-HT2A receptor antagonism in the treatment of schizophrenia
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. bengt.andree@neuro.ks.se
UR  - PM:9690698
ER  - 

TY  - JOUR
T1  - 5-Hydroxytryptamine1A receptor occupancy by novel full antagonist 2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzdioxyn-5-yl)-1-piperazinyl]butyl]-1, 2-benzisothiazol-3-(2H)-one-1,1-dioxide: a[11C][O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-py ridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) positron emission tomography study in humans
A1  - Rabiner,E.A.
A1  - Wilkins,M.R.
A1  - Turkheimer,F.
A1  - Gunn,R.N.
A1  - de Haes,J.U.
A1  - de Vries,M.
A1  - Grasby,P.M.
Y1  - 2002/06//
SP  - 1144
EP  - 1150
JA  - J Pharmacol.Exp.Ther.
VL  - 301
IS  - 3
N2  - 5-Hydroxytryptamine(1A) (5-HT(1A)) receptors have been implicated in the pathophysiology and treatment of anxiety and depression, and are a target for novel drug development. This is the first study examining the human brain in vivo occupancy by a novel, selective, silent 5-HT(1A) antagonist. 2-[4-[4-(7-Chloro-2,3-dihydro-1,4-benzdioxyn-5-yl)-1-piperazinyl]butyl]-1, 2-benzisothiazol-3-(2H)-one-1,1-dioxide (DU 125530), a compound in clinical development, has potential applications in the treatment of anxiety and mood disorders. Positron emission tomography (PET) and [(11)C][O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-p yridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635), were used to assess 5-HT(1A) autoreceptor and postsynaptic receptor occupancy in 12 healthy male volunteers. Over a 10- to 40-mg daily dose range, DU 125530 was well tolerated, and exhibited a dose-dependent occupancy from 0 to 72% at 2 h post the last dose. Occupancy correlated significantly with plasma levels of DU 125530, and a fitting of the data to a standard single-site binding model gave a maximum occupancy of approximately 80%, and a half-saturation concentration (ED(50)) of approximately 7 ng/ml. At 24 h after the last dose 5-HT(1A) occupancy was approximately 50% of that achieved at 2 h. This study demonstrates that high occupancy of the human brain 5-HT(1A) receptor can be achieved at doses producing minimal acute side effects
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, Imperial College School of Medicine, London, UK. Eugenii_A_Rabiner@gsk.com
UR  - PM:12023549
ER  - 

TY  - JOUR
T1  - Effect of endogenous serotonin on the binding of the 5-hT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic beta measurements combined with microdialysis
A1  - Zimmer,L.
A1  - Mauger,G.
A1  - Le Bars,D.
A1  - Bonmarchand,G.
A1  - Luxen,A.
A1  - Pujol,J.F.
Y1  - 2002/01//
SP  - 278
EP  - 286
JA  - J Neurochem.
VL  - 80
IS  - 2
N2  - By using a combination of an original beta+-sensitive intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of 18F-MPPF [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido]ethyl]pipe razine] to the serotonin-1A (5-HT1A) receptors was investigated in the hippocampus of the anaesthetized rat. Our beta-sensitive probe prototype was sensitive enough to obtain specific 18F-MPPF time-activity curves in the rodent (hippocampus/cerebellum ratio approximately 2). The serotonin neuronal release was pharmacologically enhanced using fenfluramine at three different doses (1, 2 and 10 mg/kg intravenous) multiplying by 2-15 the extracellular serotonin in the hippocampus. These extracellular variations of extracellular serotonin resulted in dose-ranging decreases in 18F-MPPF-specific binding in the same rat. Our results showed for the first time that 18F-MPPF binding could be modulated by modifications of extracellular serotonin in the rat hippocampus. These results were confirmed by the enhancement of extracellular radioactivity collected in dialysates after the displacement of 18F-MPPF by fenfluramine. After modelization, 18F-MPPF binding could constitute an interesting radiotracer for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain
AD  - CERMEP Biomedical Cyclotron, Lyon, France. zimmer@cermep.fr
UR  - PM:11902118
ER  - 

TY  - JOUR
T1  - PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor
A1  - Sandell,J.
A1  - Halldin,C.
A1  - Chou,Y.H.
A1  - Swahn,C.G.
A1  - Thorberg,S.O.
A1  - Farde,L.
Y1  - 2002/01//
N1  - UI - 21646669
SP  - 39
EP  - 45
JA  - Nucl Med Biol.
VL  - 29
IS  - 1
N2  - NAD-299 is a selective 5-HT(1A) receptor antagonist that is currently developed as a putative antidepressant drug. [(11)C]NAD-299 was examined in the cynomolgus monkey brain with positron emission tomography (PET). After radioligand injection high accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, regions known to contain a high density of 5-HT(1A) receptors. Peak equilibrium appeared already at about 10 min after i.v. injection. Pre-treatment with a high dose of the antagonist WAY-100635 reduced the amount of radioactivity in the cortex and the raphe to the level of the cerebellum. A strong pre-treatment effect could also be achieved using pindolol, a partial agonist at the 5-HT(1A)-receptors. The appearance of labeled metabolites in monkey plasma was measured with HPLC. At 45 minutes after injection 49% (range 27-55%, n = 5) of radioactivity in monkey plasma represented unchanged radioligand. [(11)C]NAD-299 was metabolized to more polar labeled metabolites of which one has the same chromatographic mobility as the descyclobutyl analogue of NAD-299 (NAD-272). The results indicate that [(11)C]NAD-299 has potential as a PET radioligand for studies of 5-HT(1A) receptors in the primate brain
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. Johan.E.Sandell@ks.se
UR  - PM:11786274
ER  - 

TY  - JOUR
T1  - Effects of aging on 5-HT(1A) receptors and their functional response to 5-HT(1a) agonist in the living brain: PET study with [carbonyl-(11)C]WAY-100635 in conscious monkeys
A1  - Tsukada,H.
A1  - Kakiuchi,T.
A1  - Nishiyama,S.
A1  - Ohba,H.
A1  - Harada,N.
Y1  - 2001/12/15/
SP  - 242
EP  - 251
JF  - Synapse
VL  - 42
IS  - 4
N2  - Age-related changes in the serotonin 5-HT(1A) receptors in the living brains of conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) were evaluated by [carbonyl-(11)C]WAY-100635 and high-resolution positron emission tomography (PET). The regional distribution pattern of [carbonyl-(11)C]WAY-100635 at 60-91 min postinjection was the highest in the cingulate gyrus and hippocampus, high in the frontal and temporal cortices, lower in the occipital cortex, striatum, thalamus, and raphe nuclei, and lowest in the cerebellum in both young and aged monkeys. Graphical Logan plot analysis with metabolite-corrected plasma radioactivity as an input function into the brain was applied to evaluate 5-HT(1A) receptor binding in vivo. Significant age-related decreases in 5-HT(1A) receptor binding were observed only in the frontal and temporal cortices. In the hippocampus, although 5-HT(1A) receptor binding indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the 5-HT(1A) receptor agonist 8-OH-DPAT was administered intravenously at a dose of 0.1, 0.3, or 1 mg/kg 30 min after tracer injection, binding of [carbonyl-(11)C]WAY-100635 was displaced in both age groups in a dose-dependent manner. However, the degree of displacement was more marked in young than in aged monkeys. These observations demonstrated the usefulness of [carbonyl-(11)C]WAY-100635 as an indicator of the age-related changes in cortical 5-HT(1A) receptors measured noninvasively by PET. In addition, these observations suggested that the age-related impairment of 5-HT(1A) receptor responses to 8-OH-DPAT might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
UR  - PM:11746722
ER  - 

TY  - JOUR
T1  - Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers
A1  - Tauscher,J.
A1  - Bagby,R.M.
A1  - Javanmard,M.
A1  - Christensen,B.K.
A1  - Kasper,S.
A1  - Kapur,S.
Y1  - 2001/08//
SP  - 1326
EP  - 1328
JA  - Am.J Psychiatry
VL  - 158
IS  - 8
N2  - OBJECTIVE: The authors investigated the relationship between anxiety--a facet of the Revised NEO Personality Inventory dimension of neuroticism--and serotonin 5-HT(1A) receptor binding potential. METHOD: Positron emission tomography with [(11)C]WAY-100635 was used to estimate regional 5-HT(1A) binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT(1A) binding potential and personality inventory measures. RESULTS: There was a significant negative correlation between 5-HT(1A) binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex. CONCLUSIONS: The inverse relationship between 5-HT(1A) receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT(1A) receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT(1A) agonists
AD  - Department of General Psychiatry, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. johannes.tauscher@akh-wien.ac.at
UR  - PM:11481173
ER  - 

TY  - JOUR
T1  - Effect of 5-HT on binding of [(11)C] WAY 100635 to 5-HT(IA) receptors in rat brain, assessed using in vivo microdialysis nd PET after fenfluramine
A1  - Hume,S.
A1  - Hirani,E.
A1  - Opacka-Juffry,J.
A1  - Myers,R.
A1  - Townsend,C.
A1  - Pike,V.
A1  - Grasby,P.
Y1  - 2001/08//
SP  - 150
EP  - 159
JF  - Synapse
VL  - 41
IS  - 2
N2  - By using a combination of positron emission tomography (PET) and postmortem tissue dissection, the effect of increased endogenous serotonin on specific binding of [(11)C]WAY 100635 to the 5-HT(1A) receptor was investigated in rat brain in vivo. The binding studies were complemented by in vivo microdialysis to monitor 5-HT levels in similarly treated isoflurane-anaesthetised rats, with the dialysis probe locations corresponding to two of the tissues sampled for specific binding of the radioligand. Fenfluramine treatment (10 mg/kg i.p.) resulted in a approximately 5-fold increase in extracellular 5-HT in medial prefrontal cortex and a approximately 15-fold increase in lateral hippocampus, maximal at approximately 40 min after injection. PET scan duration was either 60 or 90 min, beginning 30 min after fenfluramine injection. The specific binding of [(11)C]WAY 100635 was reduced by 10-20% in hippocampus, which showed highest binding in control animals. Specific binding, however, was unaffected in both prefrontal cortex and midbrain raphe, each additional high binding regions. The minimal effects are consistent with a low baseline occupancy of the 5-HT(1A) receptor by 5-HT in vivo, so that only a large change in endogenous agonist concentration will affect radioligand binding. This implies that utilisation of [(11)C]WAY 100635 in human PET to quantify 5-HT(1A) receptor expression can be extended to pathology where synaptic 5-HT levels are altered as a consequence of the disease state
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK. susan.hume@ic.ac.uk
UR  - PM:11400181
ER  - 

TY  - JOUR
T1  - New halogenated [11C]WAY analogues, [11C]6FPWAY and [11C]6BPWAY--radiosynthesis and assessment as radioligands for the study of brain 5-HT1A receptors in living monkey
A1  - Sandell,J.
A1  - Halldin,C.
A1  - Pike,V.W.
A1  - Chou,Y.H.
A1  - Varnas,K.
A1  - Hall,H.
A1  - Marchais,S.
A1  - Nowicki,B.
A1  - Wikstrom,H.V.
A1  - Swahn,C.G.
A1  - Farde,L.
Y1  - 2001/02//
SP  - 177
EP  - 185
JA  - Nucl Med Biol.
VL  - 28
IS  - 2
N2  - [Carbonyl-(11)C]WAY-100635 ([(11)C]WAY) is an established radioligand for the study of brain serotonin(1A) (5-HT(1A)) receptors in living animals and humans with positron emission tomography (PET). There is a recognised need to develop halogenated ligands for 5-HT(1A) receptors, either for labelling with longer-lived fluorine-18 for more widespread application with PET or with iodine-123 for application with single photon emission tomography (SPET). Here we used autoradiography and PET to assess two new halogenated analogues of WAY, namely 6BPWAY and 6FPWAY [N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(6-bromo-/fluoro-py ridinyl))cyclohexanecarboxamide] as prospective radioligands, initially using carbon-11 as the radiolabel. Labelling of 6BPWAY and 6FPWAY with carbon-11 was accomplished by acylation of the corresponding secondary amine precursors with [carbonyl-(11)C]cyclohexanecarbonyl chloride. After incubation of human brain crysections with [(11)C]6BPWAY or [(11)C]6FPWAY, the highest accumulation of radioactivity was observed in cortical areas and the hippocampal formation. Both radioligands had high nonspecific binding. There was a rapid accumulation of radioactivity in the monkey brain after intravenous injection of [(11)C]6BPWAY and [(11)C]6FPWAY. High accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, areas known to contain a high density of 5-HT(1A) receptors. The ratios of radioactivity in receptor-rich temporal cortex to that in receptor-poor cerebellum at peak equilibrium were 1.9 (at 10 min) and 3.0 at (at 20 min) for [(11)C]6BPWAY and [(11)C]6FPWAY, respectively. In pretreatment experiments with high doses of unlabelled WAY, the level of radioactivity in the frontal and temporal cortex and the raphe nuclei was reduced to the same level as in the cerebellum. Radioactive metabolites of [(11)C]6FPWAY appeared at a rate similar to those for [(11)C]WAY, with 17% of the radioactivity in plasma represented by unchanged radioligand after 40 min. Radioactive metabolites of [(11)C]6BPWAY appeared much more slowly. At 40 min after injection 45% of the radioactivity in plasma still represented unchanged radioligand. The results indicate that 6-pyridinyl radiohalogented analogues of WAY are new leads to radioligands for PET or SPET
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76, Stockholm, Sweden. Johan.Sandell@psyk.ks.se
UR  - PM:11295428
ER  - 

TY  - JOUR
T1  - Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C]WAY-100635 and PET
A1  - Tauscher,J.
A1  - Verhoeff,N.P.
A1  - Christensen,B.K.
A1  - Hussey,D.
A1  - Meyer,J.H.
A1  - Kecojevic,A.
A1  - Javanmard,M.
A1  - Kasper,S.
A1  - Kapur,S.
Y1  - 2001/05//
N1  - UI - 21178621
SP  - 522
EP  - 530
JF  - Neuropsychopharmacology
VL  - 24
IS  - 5
N2  - Positron emission tomography (PET) and [11C]WAY-100635 were used to examine the effect of age on serotonin-1A (5-HT1A) receptor binding potential (BP) in 19 healthy subjects. Regions of interest (ROI) were drawn on the co-registered magnetic resonance imaging (MRI) in orbitofrontal (OFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), lateral (LTC), and mediotemporal (MTC), parietal, occipital and cerebellar cortex, and the raphe nuclei. BP values were calculated using a simplified reference tissue method. In addition, a voxelwise analysis was performed using SPM99. Voxelwise analysis revealed a significant global decrease of 5-HT(1A) BP with age (set level <.001). ROI analysis revealed significant age-related 5-HT(1A) BP decreases in DLPFC (r = -0.56), ACC (r = -0.44), OFC (r = -0.42), LTC (r = -0.40), parietal (r = -0.65), and occipital cortex (r = -0.43), but not in MTC or raphe nuclei. Overall, cortical 5-HT(1A) BP declined by approximately 10% per decade, except for the MTC, where we did not find a significant age effect. Hence, careful age matching may be recommended for future studies using PET and [11C]WAY-100635 to examine 5-HT1A receptors
AD  - PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. jtauscher@camhpet.on.ca
UR  - PM:11282252
ER  - 

TY  - JOUR
T1  - Gender-specific aging effects on the serotonin 1A receptor
A1  - Meltzer,C.C.
A1  - Drevets,W.C.
A1  - Price,J.C.
A1  - Mathis,C.A.
A1  - Lopresti,B.
A1  - Greer,P.J.
A1  - Villemagne,V.L.
A1  - Holt,D.
A1  - Mason,N.S.
A1  - Houck,P.R.
A1  - Reynolds,C.F.,III
A1  - Dekosky,S.T.
Y1  - 2001/03/23/
SP  - 9
EP  - 17
JA  - Brain Res.
VL  - 895
IS  - 1-2
N2  - The effects of age on serotonergic function have been hypothesized to underlie age-related changes in mood and behaviors such as sleep and eating. Of particular interest is the serotonin type-1A (5-HT1A) receptor, due to its putative role in mediating the therapeutic efficacy of antidepressant treatment. Using positron emission tomography (PET) and [11C--carbonyl] WAY100635, we assessed 5-HT1A receptor binding in 21 healthy subjects (10 men, 11 women) ranging in age from 21 to 80 years. Regional binding potential values were generated using a reference tissue model and corrected for partial volume effects. We observed an inverse relationship between age and binding of [11C--carbonyl] WAY100635 to the 5-HT1A receptor in men, but not women. This finding is in accord with observations reported in the postmortem literature. Gender-specific effects of age on central serotonergic function may relate to differences between men and women in behavior, mood, and susceptibility to neuropsychiatric disease across the adult lifespan
AD  - Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15231, USA. meltzer@radserv.arad.upmc.edu
UR  - PM:11259754
ER  - 

TY  - JOUR
T1  - Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system
A1  - Passchier,J.
A1  - van Waarde,A.
Y1  - 2001/01//
SP  - 113
EP  - 129
JA  - Eur.J Nucl Med
VL  - 28
IS  - 1
N2  - The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-11C] WAY-100635 (WAY), [carbonyl-11C]desmethyl-WAY-100635 (DWAY), p-[18F]MPPF and [11C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET
AD  - PET Center, University Hospital Groningen, The Netherlands
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Passchier-5HT1A.pdf
ER  - 

TY  - JOUR
T1  - Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans
A1  - Martinez,D.
A1  - Hwang,D.
A1  - Mawlawi,O.
A1  - Slifstein,M.
A1  - Kent,J.
A1  - Simpson,N.
A1  - Parsey,R.V.
A1  - Hashimoto,T.
A1  - Huang,Y.
A1  - Shinn,A.
A1  - Van Heertum,R.
A1  - Abi-Dargham,A.
A1  - Caltabiano,S.
A1  - Malizia,A.
A1  - Cowley,H.
A1  - Mann,J.J.
A1  - Laruelle,M.
Y1  - 2001/03//
SP  - 209
EP  - 229
JF  - Neuropsychopharmacology
VL  - 24
IS  - 3
N2  - Augmentation of selective serotonin reuptake inhibitors (SSRIs) therapy by the 5-HT(1A) receptor agent pindolol may reduce the delay between initiation of antidepressant treatment and clinical response. This hypothesis is based on the ability of pindolol to block 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN) and to potentiate the increase in 5-HT transmission induced by SSRIs. However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors during treatment with pindolol controlled release (CR) in nine healthy volunteers with Positron Emission Tomography and [11C]WAY 100635. Subjects were studied four times: at baseline, following one week of pindolol CR 7.5 mg/day (4 and 10 hrs post dose), and following one dose of pindolol CR 30 mg(4 hrs post dose). Occupancy of the DRN was 40 +/- 29% on scan 2, 38 +/- 26% on scan 3, and 64 +/- 15% on scan 4. The average occupancy in all other regions was significantly lower at each doses (18 +/- 5% on scan 2, 12 +/- 3% on scan 3, and 42 +/- 4% on scan 4). These results suggest that the blockade in the DRN reached in clinical studies (7.5 mg/day) might be too low and variable to consistently augment the therapeutic effect of SSRIs. However, these data indicate that pindolol exhibits in vivo selectivity for the DRN 5-HT(1A) autoreceptors. As DRN selectivity is desirable for potentiation of 5-HT function, this observation represents an important proof of concept for the development of 5-HT(1A) agents in this application
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA
UR  - PM:11166513
ER  - 

TY  - JOUR
T1  - Serotonin type-1A receptor imaging in depression
A1  - Drevets,W.C.
A1  - Frank,E.
A1  - Price,J.C.
A1  - Kupfer,D.J.
A1  - Greer,P.J.
A1  - Mathis,C.
Y1  - 2000/07//
SP  - 499
EP  - 507
JA  - Nucl Med Biol.
VL  - 27
IS  - 5
N2  - Regional 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-(11)C]WAY-100635 inverted question mark[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2- pyridy l)cyclohexanecarboxamide inverted question mark. The mean 5-HT(1A) receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT(1A) receptor BP are consistent with in vivo evidence that 5-HT(1A) receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT(1A) receptor expression in primary mood disorders
AD  - Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. drevets@pet.upmc.edu
UR  - PM:10962258
ER  - 

TY  - JOUR
T1  - PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635
A1  - Carson,R.E.
A1  - Lang,L.
A1  - Watabe,H.
A1  - Der,M.G.
A1  - Adams,H.R.
A1  - Jagoda,E.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
Y1  - 2000/07//
N1  - UI - 20419728
SP  - 493
EP  - 497
JA  - Nucl Med Biol.
VL  - 27
IS  - 5
N2  - We synthesized [(18)F]FCWAY, an analog of [carbonyl-(11)C]WAY-100635, [(11)C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(pyridi nyl))cyclohexanecarboxamide, by replacing the cyclohexanecarbonyl group acid with a trans-4-fluorocyclohexanecarbonyl group (FC). Control and preblocking studies were performed in anesthetized monkeys. Plasma radioactive metabolite analysis showed the presence of [(18)F]FC and [(18)F]fluoride. Tissue time-radioactivity curves were corrected for metabolite contamination based on separate positron-emission tomography studies of these two labeled metabolites. Analysis using a two-tissue compartment model gave distribution volume (V) estimates (mL/mL) ranging from 33 in frontal cortex to 4 in cerebellum. Preblocking data showed uniform V of 2-3 mL/mL. These studies demonstrate that [(18)F]FCWAY has very similar kinetic characteristics to [(11)C]WAY-100635
AD  - Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C-401, 10 Center Dr., MSC 1180, Bethesda, Maryland 20892-1180, USA. richard-e-carson@nih.gov
UR  - PM:10962257
ER  - 

TY  - JOUR
T1  - Radioligands for the study of brain 5-HT(1A) receptors in vivo--development of some new analogues of way
A1  - Pike,V.W.
A1  - Halldin,C.
A1  - Wikstrom,H.
A1  - Marchais,S.
A1  - McCarron,J.A.
A1  - Sandell,J.
A1  - Nowicki,B.
A1  - Swahn,C.G.
A1  - Osman,S.
A1  - Hume,S.P.
A1  - Constantinou,M.
A1  - Andree,B.
A1  - Farde,L.
Y1  - 2000/07//
SP  - 449
EP  - 455
JA  - Nucl Med Biol.
VL  - 27
IS  - 5
N2  - [Carbonyl-(11)C]WAY-100635 (WAY) has proved to be a very useful radioligand for the imaging of brain 5-HT(1A) receptors in human brain in vivo with positron emission tomography (PET). WAY is now being applied widely for clinical research and drug development. However, WAY is rapidly cleared from plasma and is also rapidly metabolised. A comparable radioligand, with a higher and more sustained delivery to brain, is desirable since these properties might lead to better biomathematical modelling of acquired PET data. There are also needs for other types of 5-HT(1A) receptor radioligands, for example, ligands sensitive to elevated serotonin levels, ligands labelled with longer-lived fluorine-18 for distribution to "satellite" PET centres, and ligands labelled with iodine-123 for single photon emission computerised tomography (SPECT) imaging. Here we describe our progress toward these aims through the exploration of WAY analogues, including the development of [carbonyl-(11)C]desmethyl-WAY (DWAY) as a promising, more brain-penetrant radioligand for PET imaging of human 5-HT(1A) receptors, and (pyridinyl-6-halo)-analogues as promising leads for the development of radiohalogenated ligands
AD  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, London W12 ONN, United Kingdom
UR  - PM:10962249
ER  - 

TY  - JOUR
T1  - Beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy
A1  - Rabiner,E.A.
A1  - Gunn,R.N.
A1  - Castro,M.E.
A1  - Sargent,P.A.
A1  - Cowen,P.J.
A1  - Koepp,M.J.
A1  - Meyer,J.H.
A1  - Bench,C.J.
A1  - Harrison,P.J.
A1  - Pazos,A.
A1  - Sharp,T.
A1  - Grasby,P.M.
Y1  - 2000/09//
SP  - 285
EP  - 293
JF  - Neuropsychopharmacology
VL  - 23
IS  - 3
N2  - A novel strategy for improving the treatment of depressive illness is augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist. However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving inconsistent. We report how positron emission tomography (PET) and in vitro autoradiography can inform trials of antidepressant augmentation. We show that in healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not tertatolol (n = 4) occupy the human 5-HT(1A) receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT(1A) receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT(1A) autoreceptors versus the post-synaptic receptors both in vitro and in vivo. Our data reveal that pindolol doses used in antidepressant trials so far are suboptimal for significant occupancy at the 5-HT(1A) autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials
AD  - MRC Cyclotron Unit, Hammersmith Hospital, Imperial College School of Medicine, London, United Kingdom. ilan@cu.rpms.ac.uk
UR  - PM:10942852
ER  - 

TY  - JOUR
T1  - Pindolol occupancy of 5-HT(1A) receptors measured in vivo using small animal positron emission tomography with carbon-11 labeled WAY 100635
A1  - Hirani,E.
A1  - Opacka-Juffry,J.
A1  - Gunn,R.
A1  - Khan,I.
A1  - Sharp,T.
A1  - Hume,S.
Y1  - 2000/06/15/
SP  - 330
EP  - 341
JF  - Synapse
VL  - 36
IS  - 4
N2  - Positron emission tomography (PET), following an intravenous injection of [carbonyl-(11)C]WAY 100635, was used to image central 5-HT(1A) receptors in rat following pretreatment with graded doses of (-)-pindolol (0.001-3 mg/kg, i.v.). The use of PET had advantages over ex vivo radioligand binding methods in that it produced parametric image volumes and reduced errors due to inter-rat variability. Time-radioactivity curves from regions of interest (ROI) acquired from individual rats enabled the estimation of specific binding of the radioligand using a compartmental model with reference tissue input. Binding potential (BP) of [(11)C]WAY 100635 was estimated for frontal cortex and hippocampus (postsynaptic), and midbrain raphe nuclei (presynaptic). In the latter ROI, pindolol dose-dependently decreased BP. The saturation curve could be fitted to a single-site model up to the lowest dose of pindolol used, giving an ED(50) (dose to cause 50% occupancy) value of 0.26 +/- 0. 05 mg/kg, and inclusion of control (nonpindolol-treated) rats did not affect the fit. In contrast, in cortex and hippocampus ROI, low doses of pindolol caused an increase in BP compared with controls. Pindolol doses greater than approximately 0.1 mg/kg, resulted in a dose-dependent decrease in BP, and ED(50) values in cortex and hippocampus were estimated as 0.44 +/- 0.13 and 0.48 +/- 0.12 mg/kg, respectively. The increase in [(11)C]WAY 100635 binding at low pindolol doses is feasibly related to a decrease in basal receptor occupancy following reduced release of endogenous 5-HT. Considering the apparently greater potency of pindolol at the midbrain raphe ROI, this effect could be mediated via agonist activity at the autoreceptor
AD  - PET Methodology Group, MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:10819911
ER  - 

TY  - JOUR
T1  - P-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans
A1  - Shiue,C.Y.
A1  - Shiue,G.G.
A1  - Mozley,P.D.
A1  - Kung,M.P.
A1  - Zhuang,Z.P.
A1  - Kim,H.J.
A1  - Kung,H.F.
Y1  - 1997/02//
N1  - UI - 97174035
SP  - 147
EP  - 154
JF  - Synapse
VL  - 25
IS  - 2
N2  - The purpose of this study was to develop a radiopharmaceutical that could be used to selectively image 5-HT1A receptors with positron emission tomography (PET). No-carrier-added 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F] fluorobenzamido]ethylpiperazine (p-[18F]-MPPF, 2) was synthesized by the nucleophilic substitution of the corresponding nitro precursor 1 with K[18F]/Kryptofix 2.2.2. in dimethyl sulfoxide (DMSO) at 140 degrees C for 20 min followed by purification with high-performance liquid chromatography (HPLC) in 10% yield in a synthesis time of 90 min from end of bombardment (EOB). Specific activity was 1-4 Ci/microM. Biodistribution studies in rats showed that the initial uptake of 2 in the brain was high (0.7% dose/g tissue at 2 min). It was then rapidly eliminated. Rates of elimination were significantly slower in brain regions with high concentrations of 5-HT1A receptors (hippocampus, cortex, and hypothalamus) than in control regions. The maximum hippocampal/cerebellar ratio was 5.6:1 at 30 min postinjection. Uptake values in serotonergic, but not in control, regions were significantly reduced by prior treatment with either (+/-)-8-OH-DPAT (2 mg/kg, i.v., 5 min prior) or WAY 100635 (1 mg/kg, i.v., 5 min prior). Radioactivity in the femur did not increase with time, suggesting that in vivo defluorination may not be the major route of metabol sm. PET studies of 2 in a monkey demonstrated selective uptake and retention of 2 in the hippocampus. The hippocampal/cerebellar ratio was 3:1 at 30 min postinjection. The ratio was reduced to 1:1 by administering (+/-)-8-OH-DPAT (2 mg/kg, i.v.) 23 min postinjection of 2. Analyses of arterial plasma by HPLC revealed that 20% of radioactivity in the plasma remained as the parent compound 2 at 30 min postinjection. The results suggest that p-[18F]-MPPF may be a useful radioligand for studying cerebral 5-HT1A receptors in humans with PET techniques
AD  - Department of Radiology, University of Pennsylvania Medical Center, Philadelphia 19104, USA
UR  - PM:9021895
ER  - 

TY  - JOUR
T1  - Positron emission tomography: establishing priorities for health technology assessment
A1  - Robert,G.
A1  - Milne,R.
Y1  - 1999///
SP  - 1
EP  - 54
JA  - Health Technol.Assess.
VL  - 3
IS  - 16
N2  - BACKGROUND: Positron emission tomography (PET) is an expensive diagnostic imaging technology. Despite the long history of PET development, the costs and effectiveness of its use in routine clinical practice remain unknown. Against this background of uncertainty regarding the clinical role of PET, the UK Standing Group on Health Technology requested a review of its current and potential role which would enable research priorities in this area to be established. OBJECTIVES: This 3-month project had two explicit objectives: (1) to review the state of knowledge regarding the clinical applications of PET; (2) to determine the key health technology assessment (HTA) research questions relating to the use of PET in the UK. METHODS: A literature review to ascertain the state of knowledge regarding the clinical applications of PET and a three-round Delphi study to inform the key HTA research questions relating to the use of PET in the UK were undertaken. The results of an earlier systematic review, published by the Veteran's Health Administration (VHA) in the USA in 1996, were used as the starting point for the literature review. The VHA review was updated and extended by means of MEDLINE and Cochrane Library database searches. Participants in the Delphi study were selected by discussion with five individuals in the UK with an interest in, and awareness of, developments in PET. As a result of their suggestions, 43 individuals were initially invited to participate, of whom two did not feel appropriately qualified. Questionnaires were sent by facsimile to all invited participants, who were asked to return the completed forms by facsimile within a week. The content and structure of the Delphi study was informed by the results of the literature review. The responses and comments of the participants were a major source of information for this report. RESULTS: Clinical applications for PET have been advocated in three broad disease groups: oncology, cardiology and neuropsychiatric disorders. There are currently four PET modalities that need to be considered when assessing its potential clinical role in the UK: full ring PET scanners operating in two or three dimensions (available at five sites); partial ring rotating PET scanners (one currently operating in the UK); coincidence imaging with modified gamma camera technology; and high-energy collimator imaging of 511 keV photons with modified gamma camera technology. There is a paucity of available evidence relating to the cost-effectiveness of the various PET modalities in all of the clinical indications for which the technology is currently being advocated. In addition, many existing reports on the diagnostic accuracy of PET are limited because they are liable to bias and often relate only to very small patient numbers. The results of the Delphi study indicated that the four most important research priorities for the NHS, in descending order of their importance, are: (1) the relative cost-effectiveness of (a) full ring PET, (b) gamma camera PET using coincidence imaging and (c) existing diagnostic strategies to determine staging prior to operative intervention for lung cancer; (2) partial ring PET compared with full ring PET in oncology (3) the relative cost-effectiveness of (a) full ring PET, (b) gamma camera PET using coincidence imaging and (c) existing diagnostic strategies to stage and monitor treatment response in breast cancer; (4) the relative cost-effectiveness of (a) gamma camera PET using coincidence imaging and (b) 511 keV collimated positron imaging for assessing myocardial viability when selecting patients for revascularisation surgery. Vignettes describing each of the research priorities are provided in the main report. CONCLUSIONS: The findings of this project, which was undertaken rapidly in order to inform HTA research prioritization in the UK, provide a contemporary overview of the potential clinical role for PET in the NHS. Evidence is needed that using PET as a diagnostic
AD  - Health Economics Research Group, Brunel University, UK
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Robert-Milne-PET-Assessment.pdf
ER  - 

TY  - JOUR
T1  - Plasma membrane monoamine transporters: structure, regulation and function
A1  - Torres,G.E.
A1  - Gainetdinov,R.R.
A1  - Caron,M.G.
Y1  - 2003/01//
N1  - UI - 22399886
SP  - 13
EP  - 25
JA  - Nat.Rev.Neurosci.
VL  - 4
IS  - 1
N2  - The classical biogenic amine neurotransmitters - dopamine, noradrenaline, and 5-hydroxytryptamine - control a variety of functions including locomotion, autonomic function, hormone secretion, and the complex behaviours that are associated with affect, emotion and reward. A key step that determines the intensity and duration of monoamine signalling at synapses is the reuptake of the released transmitter into nerve terminals through high-affinity plasma membrane transporters. In recent years, molecular, pharmacological and genetic approaches have established the importance of monoamine transporters in the control of monoamine homeostasis and have provided insights into their regulation
AD  - Howard Hughes Medical Institute, Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Torres-Monoamine-Transporters.pdf
ER  - 

TY  - JOUR
T1  - PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy
A1  - Kumlien,E.
A1  - Nilsson,A.
A1  - Hagberg,G.
A1  - Langstrom,B.
A1  - Bergstrom,M.
Y1  - 2001/06//
N1  - UI - 21314827
SP  - 360
EP  - 366
JA  - Acta Neurol Scand.
VL  - 103
IS  - 6
N2  - OBJECTIVES: This study compares positron emission tomography (PET) using 11C-deuterium-deprenyl (DED) with PET using 18F-fluorodeoxyglucose(18F-FDG) for examining epileptogenic regions in patients with focal epilepsy. MATERIAL AND METHODS: Twenty-three patients undergoing evaluation for epilepsy surgery were subjected to PET with DED. Fourteen patients had mesial temporal lobe epilepsy (TLE) and 9 patients had seizures of neocortical origin. In addition, 6 healthy control subjects were examined. Pixel-by-pixel analysis was used to generate graphical images of tracer distribution volume (intercept) and the accumulation rate (slope). Asymmetries with respect to relative intercept and slope were compared in patients with temporal lobe epilepsy (TLE), in patients with extra-temporal lobe epilepsy (exTLE), and in the control subjects. The results were compared with 18F-FDG-PET. RESULTS: Among the patients with TLE, significant differences between the epileptogenic and the contralateral lobe were found with DED intercept and FDG-uptake. No significant differences were found with DED slope. The exTLE and the control groups showed no significant differences between sides or lobes. CONCLUSIONS: This study indicates that PET with 11C-deuterium-deprenyl is a useful method for identifying TLE and is equivalent to PET with 18F-FDG in this sense. The method has little localizing value in seizures originating from neocortical structures
AD  - Department of Neuroscience, Neurology and Uppsala University PET Centre, University Hospital, S-751 85 Uppsala, Sweden. Eva.Kumlien@neurologi.uu.se
UR  - PM:11421848
ER  - 

TY  - JOUR
T1  - Temporal lobe epilepsy visualized with PET with 11C-L-deuterium-deprenyl--analysis of kinetic data
A1  - Bergstrom,M.
A1  - Kumlien,E.
A1  - Lilja,A.
A1  - Tyrefors,N.
A1  - Westerberg,G.
A1  - Langstrom,B.
Y1  - 1998/10//
N1  - UI - 99023456
SP  - 224
EP  - 231
JA  - Acta Neurol Scand.
VL  - 98
IS  - 4
N2  - OBJECTIVES: The purpose of the study was to develop a simplified method for the acquisition and analysis of data from positron emission tomography (PET) using the ligand 11C-L-deuterium-deprenyl. This is motivated by an increased interest in methods to characterize gliosis in neurodegenerative diseases and epilepsy, which can be defined due to an increased expression of the enzyme MAO-B. METHODS: Seven patients with temporal lobe epilepsy were investigated with PET. The tracer kinetics in different brain structures was recorded and analyzed using different models with and without a plasma input function. The derived values were correlated to literature values of 3H-deprenyl binding in frozen sections from normal human brains. RESULTS: A good correlation was seen between in vivo binding and in vitro data, with the correlation being equally good irrespective of whether metabolite corrected plasma or modified cerebellar uptake values were used as input function. The epileptic lobe was, compared to non-epileptic, characterized by a lower initial distribution and an enhanced late accumulation of the tracer. With the applied method, it was possible to correctly identify the epileptic side in all 6 unilateral patients and I probable bilateral case. CONCLUSIONS: PET with 11C-L-deuterium-deprenyl gives a good correlation between calculated in vivo binding and MAO-B activity. The analysis can be simplified and blood sampling avoided if modified cerebellar time-activity data is used as a reference. Separate images of distribution volume and MAO-B binding can be generated
AD  - Uppsala University PET Centre, Uppsala University, Sweden
UR  - PM:9808270
ER  - 

TY  - JOUR
T1  - Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - MacGregor,R.R.
A1  - Shea,C.
Y1  - 2000/01//
SP  - 43
EP  - 49
JA  - Nucl Med Biol.
VL  - 27
IS  - 1
N2  - The purpose of this study was to assess the reproducibility of repeated positron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) in normal subjects and to validate the method used for estimating the kinetic constants from the irreversible 3-compartment model applied to the tracer binding. Five normal healthy subjects (age range 23-73 years) each received two PET scans with [11C]L-deprenyl-D2. The time interval between scans was 7-27 days. Time-activity data from eight regions of interest and an arterial plasma input function was used to calculate lambda k3, a model term proportional to MAO B, and K1, the plasma to brain transfer constant that is related to blood flow. Linear (LIN) and nonlinear least-squares (NLLSQ) estimation methods were used to calculate the optimum model constants. A comparison of time-activity curves for scan 1 and scan 2 showed that the percent of change for peak uptake varied from -18.5 to 15.0% and that increases and decreases in uptake on scan 2 were associated with increases and decreases in the value of the arterial input of the tracer. Calculation of lambda k3 showed a difference between scan 1 and scan 2 in the global value ranging between -6.97 and 4.5% (average -2.1 +/- 4.7%). The average percent change for eight brain regions for the five subjects was -2.84 +/- 7.07%. Values of lambda k3 for scan 1 and scan 2 were highly correlated (r2 = 0.98; p < 0.0001; slope 0.955). Similarly, values of K1 showed a significant correlation between scan 1 and scan 2 (r2 = 0.61; p < 0.0001; slope 0.638) though the values for scan 2 were generally lower than those of scan 1. There was essentially no difference between the values of model constants calculated using the NLLSQ or LIN methods. Regional brain uptake of [11C]L-deprenyl-D2 varied between scan 1 and scan 2, driven by the differences in arterial tracer input. Application of a 3-compartment model to regional time-activity data and arterial input function yielded lambda k3 values for scan 1 and scan 2 with an average difference of -2.84 +/- 7.07%. Linear regression applied to values of lambda k3 from the LIN and NLLSQ methods validated the use of the linear method for calculating lambda k3
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. jlogan@bnl.gov
UR  - PM:10755644
ER  - 

TY  - JOUR
T1  - Positron emission tomography studies of dopamine-enhancing drugs
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Ding,Y.S.
A1  - Wang,G.J.
A1  - Dewey,S.
A1  - Fischman,M.W.
A1  - Foltin,R.
A1  - Hitzemann,R.
Y1  - 1999/08//
SP  - 13S
EP  - 16S
JA  - J Clin.Pharmacol.
VL  - Suppl
N2  - Although PET is technologically complex because the restricted time scale requires that radioisotope production, radiotracer synthesis, and PET imaging be carried out in the same place, the payoff is that compounds labeled with these isotopes can be used to track the distribution and movement of drugs in the brain and also measure drug effects on specific molecular targets in the human brain. Provided that appropriate radiotracers are available, one can determine the amount of a drug that gets into the brain, the minimum effective dose, the duration of action, or the binding site occupancy required to elicit a particular therapeutic or behavioral effect with a relatively small number of PET studies. Because studies are carried out directly in humans, the relationship of these parameters to behavior and to therapeutic efficacy can be evaluated. The possibilities are enormous and are largely driven by advances in PET technology (including radiotracer chemistry and instrumentation) that synergize with advances in neuropharmacology
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:10434242
ER  - 

TY  - JOUR
T1  - Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Pappas,N.
A1  - Logan,J.
A1  - MacGregor,R.
A1  - Alexoff,D.
A1  - Wolf,A.P.
A1  - Warner,D.
A1  - Cilento,R.
A1  - Zezulkova,I.
Y1  - 1998///
SP  - 23
EP  - 34
JA  - J Addict.Dis.
VL  - 17
IS  - 1
N2  - We measured the concentration of brain monoamine oxidase B (MAO B; EC 1.4.3.4) in 8 smokers and compared it with that in 8 non-smokers and in 4 former smokers using positron emission tomography (PET) and deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) as a radiotracer for MAO B. Smokers had significantly lower brain MAO B than non-smokers as measured by the model term lambda k3 which is a function of MAO B activity. Reductions were observed in all brain regions. Low brain MAO B in the cigarette smoker appears to be a pharmacological rather than a genetic effect since former smokers did not differ from non-smokers. Brain MAO B inhibition by cigarette smoke is of relevance in light of the inverse association between smoking and Parkinson's disease and a high prevalence of smoking in psychiatric disorders and in substance abuse. Though nicotine is at the core of the neuropharmacological actions of tobacco smoke, MAO B inhibition may also be an important variable in understanding and treating tobacco smoke addiction
AD  - Department of Chemistry and Medicine, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:9549600
ER  - 

TY  - JOUR
T1  - Age-related increases in brain monoamine oxidase B in living healthy human subjects
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Pappas,N.
A1  - Shea,C.
A1  - MacGregor,R.
Y1  - 1997/07//
N1  - UI - 97472052
SP  - 431
EP  - 435
JA  - Neurobiol.Aging
VL  - 18
IS  - 4
N2  - Several studies of human brain postmortem report that monoamine oxidase B (MAO B) increases with age and it has been proposed that this increase reflects age-associated increases in glial cells. We measured brain MAO B in a group of normal healthy human subjects (n = 21; age range 23-86; 9 females and 12 males; nonsmokers) using [11C]L-deprenyl-D2 and positron emission tomography. Brain glucose metabolism was also measured with 18FDG in 15 of the subjects. MAO B increased (p < 0.004) in all brain regions examined except the cingulate gyrus. In contrast, subjects showed the expected regional age-related decreases in blood flow and metabolism. In the 15 subjects in whom both MAO B and LCMRglu was measured, there was a trend (p < 0.03) toward an inverse association between brain glucose metabolism and MAO B activity in the frontal and parietal cortices. Although the age-related increase in brain MAO B in living subjects is consistent with postmortem reports, the degree of increase is generally lower
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:9330975
ER  - 

TY  - JOUR
T1  - PET-methionine of skull base neuromas and meningiomas
A1  - Nyberg,G.
A1  - Bergstrom,M.
A1  - Enblad,P.
A1  - Lilja,A.
A1  - Muhr,C.
A1  - Langstrom,B.
Y1  - 1997/07//
N1  - UI - 97434314
SP  - 482
EP  - 489
JA  - Acta Otolaryngol.
VL  - 117
IS  - 4
N2  - Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as neuromas or meningiomas were studied with positron emission tomography (PET) using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the uptake of methionine in the tumours increased more rapidly and reached a higher level, and showed a slow decline after a peak occurring about 5 min after the injection. All the meningiomas exhibited considerably higher accumulation of the tracer compared with the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding structures (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in all meningiomas, which were all of the syncytial type. The neuromas showed lower contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean 1.48). Some neuromas displayed an irregular pattern with regions of decreased tracer uptake corresponding to small cystic areas within the neuroma. There was no overlap in methionine uptake between the two tumour groups. The results indicate that PET-methionine may contribute to the evaluation, treatment planning and follow-up of patients with skull base meningiomas and neuromas
AD  - Department of Neurosurgery, Uppsala University Hospital, Sweden
UR  - PM:9288200
ER  - 

TY  - JOUR
T1  - 11C-methionine PET imaging of leptomeningeal metastases from primary breast cancer--a case report
A1  - Padma,M.V.
A1  - Jacobs,M.
A1  - Kraus,G.
A1  - Collins,M.
A1  - Dunigan,K.
A1  - Mantil,J.
Y1  - 2001/10//
N1  - UI - 21662626
SP  - 39
EP  - 44
JA  - J Neurooncol.
VL  - 55
IS  - 1
N2  - Leptomeningeal metastases (LM) is often an elusive disease frequently diagnosed at an advanced clinical stage. Early diagnosis may allow for prompt initiation of treatment with minimal tumor burden and maximal chance of survival, especially in solid tumors such as breast cancer. Although the method of choice for imaging LM currently is by gadolinium enhanced magnetic resonance imaging (MRI), the technique has a high sensitivity but low specificity. We report the first case of Carbon 11-labelled methionine (Cmet) positron emission tomography (PET) imaging of leptomeningeal metastases in a patient with primary breast cancer. This patient presented with clinical features suggestive of LM, but had inconclusive cerebrospinal fluid (CSF) findings. Although, the contrast enhanced MRI revealed calvarial and meningeal lesions, it is known that meningeal enhancement on MRI does not always indicate metastases. In this clinical dilemma the strong methionine uptake on PET helped steer the diagnosis in favor of cancerous infiltration even before the CSF cytology became positive for malignancy
AD  - Wallace-Kettering Neuroscience Institute, Wright State University, Kettering Medical Center, OH 45429, USA
UR  - PM:11804281
ER  - 

TY  - JOUR
T1  - Positron emission tomography (11)C-methionine and survival in patients with low-grade gliomas
A1  - Ribom,D.
A1  - Eriksson,A.
A1  - Hartman,M.
A1  - Engler,H.
A1  - Nilsson,A.
A1  - Langstrom,B.
A1  - Bolander,H.
A1  - Bergstrom,M.
A1  - Smits,A.
Y1  - 2001/09/15/
N1  - UI - 21610175
SP  - 1541
EP  - 1549
JF  - Cancer
VL  - 92
IS  - 6
N2  - BACKGROUND: Considerable numbers of patients with low-grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the (11)C-methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2. METHODS: The authors identified 89 patients with histologically confirmed low-grade gliomas in whom an (11)C-methionine positron emission tomography (PET) scan had been performed as part of the diagnostic tumor investigation from 1983 to 1998. Clinical data were collected, and the PET scans were re-evaluated according to a fixed protocol. The (11)C-methionine uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analyses. RESULTS: At the end of the study, 49 patients (55.1%) had died. The median overall survival was 5.7 years. Low methionine uptake was significantly favorable in the multivariate survival analysis (P = 0.04) along with oligodendroglioma (P = 0.003). In the histologic subgroups, (11)C-methionine uptake was an important survival factor among patients with astrocytomas (P = 0.05) and oligodendrogliomas (P = 0.03). Tumor resection was a favorable prognostic factor in patients with high methionine uptake (P = 0.01) but not in patients with low uptake. CONCLUSIONS: Baseline (11)C-methionine PET is a prognostic indicator in patients with low-grade gliomas. The results imply that PET is a valuable tool in the clinical management of these patients and may assist in the selection of patients for therapy
AD  - Department of Neuroscience, Neurology, University Hospital, Uppsala, Sweden. dan.ribom@neurologi.uu.se
UR  - PM:11745233
ER  - 

TY  - JOUR
T1  - Emission computer assisted tomography with single-photon and positron annihilation photon emitters
A1  - Budinger,T.F.
A1  - Derenzo,S.E.
A1  - Gullberg,G.T.
A1  - Greenberg,W.L.
A1  - Huesman,R.H.
Y1  - 1977/01//
N1  - UI - 78242672
SP  - 131
EP  - 145
JA  - J Comput.Assist.Tomogr.
VL  - 1
IS  - 1
N2  - Computed transverse section emission tomography using 99mTc with the Anger camera is compared to positron annihilation coincident detection using a ring of crystals and 68Ga. The single-photon system has a line spread function (LSF) of 9 mm full width at half maximum (FWHM) at the collimator and gives a transverse section reconstruction LSF of 11 mm FWHM with 144 views. The positron ring has a LSF of 6 mm at the center with a transverse section reconstruction LSF of 7.5 mm FWHM. Correction for uniformity of detector response and accurate center of rotation determination is essential in both techniques. The signal-to-noise ratio in a reconstruction is diminished by a factor of 1.2 x (number of resolution elements)1/4 over that expected from the average number of events per resolution element. Attenuation compensation causes more noise to appear in the center than the edge for both modes and an average increase in uncertainty of 30%. The effects of attenuation result in more loss of data for positron coincidence imaging than for single-photon imaging even at energies of 80 keV. For a 20-cm cylinder imaged in transverse section, only 20% of the positron annihilation events are not scattered; however, at 140 keV, 40% of the photons are not scattered. The relative crystal efficiency gives single-photon imaging an advantage of 5. On the other hand, the solid angle advantage of positron photon coincidence imaging is about 100 for the comparisons of this paper. Taking these factors into account, we find positron-computed section imaging has a tenfold increase in sensitivity over multiple-view imaging with the scintillation camera, which gives multiple sections but requires camera or patient rotation
UR  - PM:615887
ER  - 

TY  - BOOK
T1  - The theory and practice of 3D PET
A1  - Bendriem,B.
A1  - Townsend,D.W.
Y1  - 1998///
CY  - Dordrecht
PB  - Kluwer Academic Publishers
ER  - 

TY  - JOUR
T1  - Fast implementation of the single scatter simulation algorithm and its use in iterative image reconstruction of PET data
A1  - Werling,A.
A1  - Bublitz,O.
A1  - Doll,J.
A1  - Adam,L.E.
A1  - Brix,G.
Y1  - 2002/08/21/
N1  - UI - 22210671
SP  - 2947
EP  - 2960
JA  - Phys.Med Biol.
VL  - 47
IS  - 16
N2  - In positron emission tomography (PET), scatter correction is usually performed prior to image reconstruction using a more or less exact model of the scatter processes. These models require estimates of the true activity and object density distributions of the imaged object. The problem is that these estimates are computed from measured data and, therefore, already contain scattered events. The purpose of this work was to overcome this problem by incorporating scatter characteristics directly into the process of iterative image reconstruction. This could be achieved by an optimized implementation of the single scatter simulation (SSS) algorithm, which results in a significant speed-up of the scatter estimation procedure. The scatter simulation was then included in the forward projection step of maximum likelihood image reconstruction. The results demonstrate that this approach leads to a more exact estimation of the scatter component which cannot be obtained by a simple sequential data processing strategy
AD  - German Cancer Research Center, Heidelberg. Alexander.Werling@web.de
UR  - PM:12222858
ER  - 

TY  - JOUR
T1  - Iterative versus filtered backprojection reconstruction for statistical parametric mapping of PET activation measurements: a comparative case study
A1  - Reinders,A.A.
A1  - Paans,A.M.
A1  - de Jong,B.M.
A1  - den Boer,J.A.
A1  - Willemsen,A.T.
Y1  - 2002/01//
N1  - UI - 21635688
SP  - 175
EP  - 181
JF  - Neuroimage
VL  - 15
IS  - 1
N2  - The significance of task-induced cerebral blood flow responses, assessed using statistical parametric mapping, depends, among other things, on the signal-to-noise ratio (SNR) of these responses. Generally, positron emission tomography sinograms of H(2)(15)O activation studies are reconstructed using filtered backprojection (FBP). Alternatively, the acquired data can be reconstructed using an iterative reconstruction procedure. It has been demonstrated that the application of iterative reconstruction methods improves image SNR as compared with FBP. The aim of this study was to compare FBP with iterative reconstruction, to assess the statistical power of H(2)(15)O-PET activation studies using statistical parametric mapping. For this case study, PET data originating from a bimanual motor task were reconstructed using both FBP and maximum likelihood expectation maximization (ML-EM), an iterative algorithm. Both resulting data sets were statistically analyzed using statistical parametric mapping. It was found, with this dataset, that the statistical analysis of the iteratively reconstructed data confirm the a priori expected physiological response. In addition, increased Z scores were obtained in the iteratively reconstructed data. In particular, for the expected task-related response, activation of the posterior border of the left angular gyrus, the Z score increased from 3.00 to 3.96. Furthermore, the number of statistically significant clusters doubled while their volume increased by more than 50%. In conclusion, iterative reconstruction has the potential to increase the statistical power in H(2)(15)O-PET activation studies as compared with FBP reconstruction
AD  - Department of Biological Psychiatry, Groningen University Hospital, 9700 RB Groningen, The Netherlands. a.a.t.s.reinders@pet.azg.nl
UR  - PM:11771986
ER  - 

TY  - JOUR
T1  - Comparison of 3-D reconstruction with 3D-OSEM and with FORE+OSEM for PET
A1  - Liu,X.
A1  - Comtat,C.
A1  - Michel,C.
A1  - Kinahan,P.
A1  - Defrise,M.
A1  - Townsend,D.
Y1  - 2001/08//
N1  - UI - 21403935
SP  - 804
EP  - 814
JA  - IEEE Trans.Med Imaging
VL  - 20
IS  - 8
N2  - The combination of Fourier rebinning (FORE) and the ordered subsets expectation-maximization (OSEM), a fast statistical algorithm, appears as a promising alternative to the fully three-dimensional (3-D) iterative approach for clinical positron emission tomography (PET) data. In this paper, we evaluated the properties of FORE+OSEM and compared it with fully 3-D OSEM using both simulations and data acquired by commercial scanners. The aim is to determine to what extent the speed advantage of FORE+OSEM is paid for by a possible degradation of image quality in the case of noisy clinical PET data. A forward- and back-projection pair based on a line integral model was used in two-dimensional OSEM and 3-D OSEM (3D-OSEM) instead of a system matrix. Different variants of both approaches have been studied with simulations in terms of contrast-noise tradeoff. Two variants--FORE+OSEM with attenuation weighting (AW) [FORE+OSEM(AW)] and 3D-OSEM with attenuation-normalization weighting (ANSP) and a shifted-Poisson (SP) model [3D-OSEM(ANSP)]--were compared with measured phantom data and patient data. Based on the results from both simulations and measured data, we conclude that: 1) both attenuation (-normalization) weighting and the SP model improve the image quality but slow down the convergence and 2) despite its approximate nature, FORE+OSEM does not show apparent image degradation compared with 3D-OSEM for data with a noise level typical of a whole-body FDG scan
AD  - Division of Nuclear Medicine, Vrije Universiteit Brussel, Belgium
UR  - PM:11513031
ER  - 

TY  - JOUR
T1  - Iterative reconstruction algorithms in nuclear medicine
A1  - Vandenberghe,S.
A1  - D'Asseler,Y.
A1  - Van de Walle,R.
A1  - Kauppinen,T.
A1  - Koole,M.
A1  - Bouwens,L.
A1  - Van Laere,K.
A1  - Lemahieu,I.
A1  - Dierckx,R.A.
Y1  - 2001/03//
N1  - UI - 21065655
SP  - 105
EP  - 111
JA  - Comput.Med Imaging Graph.
VL  - 25
IS  - 2
N2  - Iterative reconstruction algorithms produce accurate images without streak artifacts as in filtered backprojection. They allow improved incorporation of important corrections for image degrading effects, such as attenuation, scatter and depth-dependent resolution. Only some corrections, which are important for accurate reconstruction in positron emission tomography and single photon emission computed tomography, can be applied to the data before filtered backprojection. The main limitation for introducing iterative algorithms in nuclear medicine has been computation time, which is much longer for iterative techniques than for filtered backprojection. Modern algorithms make use of acceleration techniques to speed up the reconstruction. These acceleration techniques and the development in computer processors have introduced iterative reconstruction in daily nuclear medicine routine. We give an overview of the most important iterative techniques and discuss the different corrections that can be incorporated to improve the image quality
AD  - MEDISIP, ELIS, Ghent University, Sint-Pietersnieuwstraat 41 B-9000, Ghent, Belgium. stefan.vandenburghe@rug.ac.be
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Vandenberghe-Iterative-reconstruction.pdf
ER  - 

TY  - JOUR
T1  - Parametric image reconstruction using spectral analysis of PET projection data
A1  - Meikle,S.R.
A1  - Matthews,J.C.
A1  - Cunningham,V.J.
A1  - Bailey,D.L.
A1  - Livieratos,L.
A1  - Jones,T.
A1  - Price,P.
Y1  - 1998/03//
N1  - UI - 98194338
SP  - 651
EP  - 666
JA  - Phys.Med Biol.
VL  - 43
IS  - 3
N2  - Spectral analysis is a general modelling approach that enables calculation of parametric images from reconstructed tracer kinetic data independent of an assumed compartmental structure. We investigated the validity of applying spectral analysis directly to projection data motivated by the advantages that: (i) the number of reconstructions is reduced by an order of magnitude and (ii) iterative reconstruction becomes practical which may improve signal-to-noise ratio (SNR). A dynamic software phantom with typical 2-[11C]thymidine kinetics was used to compare projection-based and image-based methods and to assess bias-variance trade-offs using iterative expectation maximization (EM) reconstruction. We found that the two approaches are not exactly equivalent due to properties of the non-negative least-squares algorithm. However, the differences are small (< 5%) and mainly affect parameters related to early and late time points on the impulse response function (K1 and, to a lesser extent, VD). The optimal number of EM iteration was 15-30 with up to a two-fold improvement in SNR over filtered back projection. We conclude that projection-based spectral analysis with EM reconstruction yields accurate parametric images with high SNR and has potential application to a wide range of positron emission tomography ligands
AD  - MRC Cyclotron Unit, Hammersmith Hospital, Royal Postgraduate Medical School, London, UK. steve@nucmed.rpa.cs.nsw.gov.au
UR  - PM:9533143
ER  - 

TY  - JOUR
T1  - Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals
A1  - Brix,G.
A1  - Doll,J.
A1  - Bellemann,M.E.
A1  - Trojan,H.
A1  - Haberkorn,U.
A1  - Schmidlin,P.
A1  - Ostertag,H.
Y1  - 1997/07//
N1  - UI - 97362038
SP  - 779
EP  - 786
JA  - Eur.J Nucl Med
VL  - 24
IS  - 7
N2  - The purpose of this work was to improve of the spatial resolution of a whole-body positron emission tomography (PET) system for experimental studies of small animals by incorporation of scanner characteristics into the process of iterative image reconstruction. The image-forming characteristics of the PET camera were characterized by a spatially variant line-spread function (LSF), which was determined from 49 activated copper-64 line sources positioned over a field of view (FOV) of 21.0 cm. This information was used to model the image degradation process. During the course of iterative image reconstruction, the forward projection of the estimated image was blurred with the LSF at each iteration step before the estimated projections were compared with the measured projections. The imaging characteristics of the high-resolution algorithm were investigated in phantom experiments. Moreover, imaging studies of a rat and two nude mice were performed to evaluate the imaging properties of our approach in vivo. The spatial resolution of the scanner perpendicular to the direction of projection could be approximated by a one-dimensional Gaussian-shaped LSF with a full-width at half-maximum increasing from 6.5 mm at the centre to 6.7 mm at a radial distance of 10.5 cm. The incorporation of this blurring kernel into the iteration formula resulted in a significantly improved spatial resolution of about 3.9 mm over the examined FOV. As demonstrated by the phantom and the animal experiments, the high-resolution algorithm not only led to a better contrast resolution in the reconstructed emission scans but also improved the accuracy for quantitating activity concentrations in small tissue structures without leading to an amplification of image noise or image mottle. The presented data-handling strategy incorporates the image restoration step directly into the process of algebraic image reconstruction and obviates the need for ill-conditioned "deconvolution" procedures to be performed on the projections or on the reconstructed image. In our experience, the proposed algorithm is of special interest in experimental studies of small animals
AD  - Research Program "Radiological Diagnostics and Therapy", German Cancer Research Center (DKFZ), Heidelberg, Germany
UR  - PM:9211765
ER  - 

TY  - JOUR
T1  - Linear least squares compartmental-model-independent parameter identification in PET
A1  - Thie,J.A.
A1  - Smith,G.T.
A1  - Hubner,K.F.
Y1  - 1997/02//
N1  - UI - 97196383
SP  - 11
EP  - 16
JA  - IEEE Trans.Med Imaging
VL  - 16
IS  - 1
N2  - A simplified approach involving linear-regression straight-line parameter fitting of dynamic scan data is developed for both specific and nonspecific models. Where compartmental-model topologies apply, the measured activity may be expressed in terms of: its integrals, plasma activity and plasma integrals--all in a linear expression with macroparameters as coefficients. Multiple linear regression, as in spreadsheet software, determines parameters for best data fits. Positron emission tomography (PET)-acquired gray-matter images in a dynamic scan are analyzed: both by this method and by traditional iterative nonlinear least squares. Both patient and simulated data were used. Regression and traditional methods are in expected agreement. Monte-Carlo simulations evaluate parameter standard deviations, due to data noise, and much smaller noise-induced biases. Unique straight-line graphical displays permit visualizing data influences on various macroparameters as changes in slopes. Advantages of regression fitting are: simplicity, speed, ease of implementation in spreadsheet software, avoiding risks of convergence failures or false solutions in iterative least squares, and providing various visualizations of the uptake process by straight line graphical displays. Multiparameter model-independent analyses on lesser understood systems is also made possible
AD  - Department of Nuclear Engineering, University of Tennessee, Knoxville 37996, USA
UR  - PM:9050404
ER  - 

TY  - JOUR
T1  - Automated iterative three-dimensional registration of positron emission tomography images
A1  - Hoh,C.K.
A1  - Dahlbom,M.
A1  - Harris,G.
A1  - Choi,Y.
A1  - Hawkins,R.A.
A1  - Phelps,M.E.
A1  - Maddahi,J.
Y1  - 1993/11//
N1  - UI - 94045970
SP  - 2009
EP  - 2018
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 34
IS  - 11
N2  - Two types of image similarity measures, the sum of absolute differences (SAD) and the stochastic sign change (SSC), were compared for three-dimensional registration of images from PET. To test the accuracy of both registration methods, 30 FDG brain studies, 40 13N-ammonia cardiac studies and 20 FDG liver tumor studies (where each image set contained 15 image planes, 128 x 128 pixels per plane) were made into worse case conditions by creating image sets of low counts and extreme defects. These images were then registered to the reference images that had been moved in three dimensions into a random set of known translations, rotations and normalization factors (x, y, z, theta, rho, sigma, nf). Neither method required any external fiduciary markers or operator interventions to register a set of images. The optimization of the image similarity (using the SAD or SSC) was performed with the simplex method and registration was completed within 10 min of computation time on a low-end workstation. Overall, the SAD method had an average inplane (x, y) registration error of 0.5 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.5 +/- 0.4 degrees, an out-of-plane rotational error of 1.1 +/- 1.2 degrees and a normalization factor error of 0.015 +/- 0.016. The SSC method had an average inplane (x, y) registration error of 0.6 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.7 +/- 0.5 degrees, an out-of-plane rotational error of 1.0 +/- 1.2 degrees and a normalization factor error of 0.014 +/- 0.014. This study demonstrates that either the SAD or SSC method for measuring image similarity, combined with the simplex method for function optimization, are accurate methods for registration of a wide variety of PET images including low count studies and those with marked interval changes in the pattern of count distribution
AD  - Department of Molecular and Medical Pharmacology, University of California, Los Angeles
UR  - PM:8229252
ER  - 

TY  - JOUR
T1  - Kinetics of neutral amino acid transport across the blood-brain barrier
A1  - Smith,Q.R.
A1  - Momma,S.
A1  - Aoyagi,M.
A1  - Rapoport,S.I.
Y1  - 1987/11//
N1  - UI - 88035038
SP  - 1651
EP  - 1658
JA  - J Neurochem.
VL  - 49
IS  - 5
N2  - Neutral amino acid (NAA) transport across the blood-brain barrier was examined in pentobarbital-anesthetized rats with an in situ brain perfusion technique. Fourteen of 16 plasma NAAs showed measurable affinity for the cerebrovascular NAA transport system. Values of the transport constants (Vmax, Km, KD) were determined for seven large NAAs from saturation studies, whereas Km values for five small NAAs were estimated from inhibition studies. These data, together with our previous work, provide a complete set of constants for prediction of NAA influx from plasma. Among the NAAs, Vmax varied at least fivefold and Km varied approximately 700 fold. The apparent affinity (1/Km) of each NAA was related linearly (r = 0.910) to the octanol/water partition coefficient, a measure of NAA side-chain hydrophobicity. Predicted influx values from transport constants and average plasma concentrations agree well with values measured using plasma perfusate. These results provide accurate new estimates of the kinetic constants that determine NAA transport across the blood-brain barrier. Furthermore, they suggest that affinity of a L-alpha-amino acid for the transport system is determined primarily by side-chain hydrophobicity
AD  - Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland 20892
UR  - PM:3668544
ER  - 

TY  - JOUR
T1  - Performance evaluation of the microPET R4 PET scanner for rodents
A1  - Knoess,C.
A1  - Siegel,S.
A1  - Smith,A.
A1  - Newport,D.
A1  - Richerzhagen,N.
A1  - Winkeler,A.
A1  - Jacobs,A.
A1  - Goble,R.N.
A1  - Graf,R.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 2003/01/21/
N1  - UI - 0
SP  - 737
EP  - 747
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - The microPET R4 scanner is a dedicated positron emission tomograph (PET) for studies of rodents. A number of scanner parameters such as spatial resolution, sensitivity, scatter, and count rate performance were determined in this work, which showed that the microPET R4 is a suitable PET scanner for small animals like mice and rats. In the center of the field of view (FOV) a maximal sensitivity of 43.66 cps/kBq for a centered point source was calculated from a measurement with a germanium-68 line source within an energy widow of 250-750 keV. A spatial resolution of 1.85 mm full-width at half-maximum (FWHM) in the axial direction and 1.66 mm FWHM in the transaxial direction was measured in the center with a 1-mm-diameter sodium-22 point source. Within the inner 20 mm of the FOV the volumetric resolution is better than 15.6 micro l, corresponding to a linear resolution of less than 2.5 mm in all three dimensions. Images of a high-resolution phantom and from mice and rat studies illustrate the good performance of the scanner. A maximal noise equivalent count rate (NECR) was reached at 174 kcps for a mouse phantom and at 93 kcps for a rat phantom (energy window 250-750 keV). Scatter fractions were measured between 0.30 and 0.42 for an energy window of 250-750 keV and phantom diameters similar to mice and rats. A comparison with the microPET P4 model for primates illustrates the gain in sensitivity due to a smaller detector ring diameter but also the changes in NECR
AD  - Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, 50931 Cologne, Germany, knoess@pet.mpin-koeln.mpg.de
UR  - PM:12536244
ER  - 

TY  - JOUR
T1  - Advances in animal PET scanners
A1  - Del Guerra,A.
A1  - Belcari,N.
Y1  - 2002/03//
N1  - UI - 22068195
SP  - 35
EP  - 47
JA  - Q.J Nucl Med
VL  - 46
IS  - 1
N2  - Nowadays, a growing number of research groups shows a great interest for the application of PET and SPECT techniques to the development of new drugs. Preliminary studies on small animals require high performance dedicated scanners with a higher spatial resolution and sensitivity than those of clinical systems. In this paper the potential applications of such innovative instruments are shown together with a brief review of the dedicated PET and SPECT tomographs developed worldwide. Most of the scanners have been built as research prototypes. Only two are commercially available: micro-PET(R), designed and developed at UCLA, Los Angeles as a research prototype, and now produced and distributed by Concorde Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd. (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform both PET and SPECT studies, has been developed at the University of Ferrara. The technical characteristics and performance of this scanner are described. Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now under study in various international research centers. The advantages of this new generation of animal scanners will be briefly outlined
AD  - Department of Physics, University of Pisa and INFN, Section of Pisa, Pisa, Italy. delguerra@pi.infn.it
UR  - PM:12072844
ER  - 

TY  - JOUR
T1  - The ECAT HRRT: NEMA NEC evaluation of the HRRT system, the new high-resolution research tomograph
A1  - Eriksson,L.
A1  - Wienhard,K.
A1  - Eriksson,M.
A1  - Casey,M.E.
A1  - Knoess,C.
A1  - Bruckbauer,T.
A1  - Hamill,J.
A1  - Schmand,M.
A1  - Gremillion,T.
A1  - Lenox,M.
A1  - Conti,M.
A1  - Bendriem,B.
A1  - Heiss,W.D.
A1  - Nutt,R.
Y1  - 2002///
N1  - Journal
SP  - 2085
EP  - 2088
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 5
N2  - The ECAT HRRT (high-resolution research tomograph) is a three- dimensional (3-D)-only dedicated brain positron emission tomograph (PET) with LSO and GSO scintillators. The system is based on eight panels of detectors. The HRRT's imaging performance has previously been tested with phantoms and FDG scans performed in animal and human brains that showed significantly improved spatial resolution, below 2.5 mm for animal studies and below 3 mm for brain studies. The NEC count rate performance has been evaluated based on the NU 2-2001 protocol. The results show a peak NEC approximately 30% higher than the performance of the Ecat HR+, this in spite of a more shallow detector for the HRRT, only 15 mm relative to the 30 mm for the HR+. However, peak NEC as derived from the 70-cm line source phantom is not optimized for the performance of dedicated brain scanner. NEC data derived with a 20-cm diameter, 20-cm long phantoms show a peak NEC more than 60% higher than for the HR+. The reasons for the high performance are due to several factors, the large axial coverage, the short timing window of 6 ns, and the low detector dead time, all factors that imply the use of fast LSO and GSO scintillators
UR  - ISI:000179177300009
ER  - 

TY  - JOUR
T1  - NEMA count-rate evaluation of the first and second generation of the Ecat Exact and Ecat Exact HR family of scanners
A1  - Eriksson,L.
A1  - Wienhard,K.
A1  - Eriksson,M.
A1  - Casey,M.E.
A1  - Knoess,C.
A1  - Bruckbauer,T.
A1  - Hamill,J.
A1  - Mulnix,T.
A1  - Vollmar,S.
A1  - Bendriem,B.
A1  - Heiss,W.D.
A1  - Nutt,R.
Y1  - 2002///
N1  - Journal
SP  - 640
EP  - 643
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 3
N2  - The first and second generation of the Exact and Exact HR family of scanners has been evaluated in terms of noise equivalent count rate (NEC) and count-rate capabilities. The new National Electrical Manufacturers Association standard was used for the evaluation. In spite of improved electronics and improved count-rate capabilities, the peak NEC was found to be fairly constant between the generations. The results are discussed in terms of the different electronic solutions for the two generations and its implications on system dead time and NEC count-rate capability
UR  - ISI:000178670800005
ER  - 

TY  - JOUR
T1  - PET tomograph designed for five minute routine whole body studies
A1  - Nahmias,C.
A1  - Nutt,R.
A1  - Hichwa,R.D.
A1  - Czernin,J.
A1  - Melcher,C.
A1  - Schmand,M.
A1  - Andreaco,M.
A1  - Eriksson,L.
A1  - Casey,M.
A1  - Moyers,C.
A1  - Michel,C.
A1  - Bruckbauer,T.
A1  - Conti,M.
A1  - Bendriem,B.
A1  - Hamill,J.
Y1  - 2002///
N1  - Journal
SP  - 36
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 43
IS  - 5
UR  - ISI:000175560800037
ER  - 

TY  - JOUR
T1  - Physical characteristics of the ECAT EXACT3D positron tomograph
A1  - Spinks,T.J.
A1  - Jones,T.
A1  - Bloomfield,P.M.
A1  - Bailey,D.L.
A1  - Miller,M.
A1  - Hogg,D.
A1  - Jones,W.F.
A1  - Vaigneur,K.
A1  - Reed,J.
A1  - Young,J.
A1  - Newport,D.
A1  - Moyers,C.
A1  - Casey,M.E.
A1  - Nutt,R.
Y1  - 2000///
N1  - Journal
SP  - 2601
EP  - 2618
JF  - Physics in Medicine and Biology
VL  - 45
IS  - 9
N2  - The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven Cs-137 point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (>300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8+/-0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using O-15-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding
UR  - ISI:000089438900017
ER  - 

TY  - JOUR
T1  - MicroPET: A high resolution PET scanner for imaging small animals
A1  - Cherry,S.R.
A1  - Shao,Y.
A1  - Silverman,R.W.
A1  - Meadors,K.
A1  - Siegel,S.
A1  - Chatziioannou,A.
A1  - Young,J.W.
A1  - Jones,W.F.
A1  - Moyers,J.C.
A1  - Newport,D.
A1  - Boutefnouchet,A.
A1  - Farquhar,T.H.
A1  - Andreaco,M.
A1  - Paulus,M.J.
A1  - Binkley,D.M.
A1  - Nutt,R.
A1  - Phelps,M.E.
Y1  - 1997///
N1  - Journal
SP  - 1161
EP  - 1166
JF  - IEEE Transactions on Nuclear Science
VL  - 44
IS  - 3
N2  - MicroPET is a high resolution positron emission tomography (PET) scanner designed for imaging small laboratory animals. It consists of a ring of 30 position-sensitive scintillation detectors, each with an 8 x 8 array of small lutetium oxyorthosilicate (LSO) crystals coupled via optical fibers to a multi-channel photomultiplier tube. The detectors have an intrinsic resolution averaging 1.68 mm, an energy resolution between 15 and 25% and 2.4 ns timing resolution at 511 keV. The detector ring diameter of microPET is 17.2 cm with an imaging field of view of 112 mm transaxially by 18 mm axially. The scanner has no septa and operates exclusively in 3D mode. Reconstructed image resolution 1 cm from the center of the scanner is 2.0 mm and virtually isotropic, yielding a volume resolution of 8 mm(3). For comparison, the volume resolution of state-of-the-art clinical PET systems is in the range of 50 - 75 mm(3). Initial images of phantoms have been acquired and are reported. A computer controlled bed is under construction and will incorporate a small wobble motion to improve spatial sampling. This is projected to further enhance spatial resolution. MicroPET is the first PET scanner to incorporate the new scintillator LSO and to our knowledge is the highest resolution multi-ring PET scanner currently in existence
UR  - ISI:A1997XF30000011
ER  - 

TY  - JOUR
T1  - HIGH-RESOLUTION TIME-OF-FLIGHT POSITRON EMISSION TOMOGRAPH
A1  - Ishii,K.
A1  - ORIHARA,H.
A1  - Matsuzawa,T.
A1  - Binkley,D.M.
A1  - Nutt,R.
Y1  - 1990///
N1  - Journal
SP  - 3755
EP  - 3762
JF  - Review of Scientific Instruments
VL  - 61
IS  - 12
UR  - ISI:A1990EL89300018
ER  - 

TY  - JOUR
T1  - A MULTICRYSTAL 2-DIMENSIONAL BGO DETECTOR SYSTEM FOR POSITRON EMISSION TOMOGRAPHY
A1  - Casey,M.E.
A1  - Nutt,R.
Y1  - 1986///
N1  - Journal
SP  - 460
EP  - 463
JF  - IEEE Transactions on Nuclear Science
VL  - 33
IS  - 1
UR  - ISI:A1986A073500105
ER  - 

TY  - JOUR
T1  - PET imaging using a triple-head gamma camera
A1  - Kuikka,J.T.
A1  - Sohlberg,A.
A1  - Husso-Saastamoinen,M.
Y1  - 2002/09//
N1  - UI - 22375487
SP  - 328
EP  - 331
JA  - Clin.Physiol Funct.Imaging
VL  - 22
IS  - 5
N2  - Interest in clinical fluorodeoxyglucose (FDG) imaging with multiple-head gamma cameras is growing. To improve sensitivity, triple-head coincidence imaging has been proposed. We report our initial experiences with a triple-head coincidence gamma camera with 19 mm sodium iodide crystal thickness. Several positron emission tomography-image quality parameters were evaluated using a Carlson and line source phantom. The system sensitivity with two-dimensional axial shields was 830 cps kBq-1 ml-1 and maximum noise equivalent count rate 1900 cps for an 18F-activity of 50 MBq. The imaging resolution was in central axial 7.0 mm and in central transaxial 7.6 mm, respectively. The average scatter fraction in scattered media was 29%. Clinical brain, heart and whole body images studies with [18F]FDG were acquired and they show good correlation with the phantom image quality. As a conclusion, triple-head coincidence gamma camera provides relatively high-count rate imaging with good contrast and resolution
AD  - Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. jkuikka@uku.fi
UR  - PM:12487005
ER  - 

TY  - JOUR
T1  - Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses
A1  - Pitman,A.G.
A1  - Hicks,R.J.
A1  - Binns,D.S.
A1  - Ware,R.E.
A1  - Kalff,V.
A1  - McKenzie,A.F.
A1  - Ball,D.L.
A1  - MacManus,M.P.
Y1  - 2002/02//
N1  - UI - 21890693
SP  - 114
EP  - 121
JA  - Br.J Radiol.
VL  - 75
IS  - 890
N2  - The purpose of this study was to document the accuracy of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) with sodium iodide detectors in characterizing indeterminate lung nodules or masses and in identifying additional extra-lesional findings. 50 consecutive patients without a confident diagnosis of malignancy on CT underwent (18)FDG PET with and without attenuation correction. The diagnosis of malignancy was made using visual diagnostic criteria, and tumour-to-blood pool ratios were calculated. The final diagnosis was established by surgery, biopsy or long-term follow-up. Any additional findings made at PET were recorded and similarly verified. Using blinded visual diagnostic criteria for the differentiation of malignant from benign nodules, sodium iodide PET achieved a sensitivity of 91% (30 of 33 cases), a specificity of 88% (15 of 17 cases), a positive predictive value for malignancy of 94% (30 of 32 cases) and a negative predictive value of 83% (15 of 18 cases). False positives occurred with active tuberculosis and sarcoidosis. False negatives were a 3 cm bronchoalveolar carcinoma, a 1.3 cm sarcoma metastasis and a 1 cm carcinoma. Use of tumour-to-blood pool ratios did not improve performance. PET suggested the presence of nodal or distant metastases in 13 of 33 patients with a malignant pulmonary lesion. These PET findings were confirmed in 11 patients. These results indicate that sodium iodide PET is an accurate tool for the characterization of indeterminate pulmonary masses or nodules and simultaneously provides non-invasive staging information that can alter patient management in up to one-third of such patients. Performance of sodium iodide PET is comparable with reported results for PET scanners using other detector materials
AD  - Department of Diagnostic Imaging, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
UR  - PM:11893634
ER  - 

TY  - JOUR
T1  - Comparison of FDG PET and positron coincidence detection imaging using a dual-head gamma camera with 5/8-inch NaI(Tl) crystals in patients with suspected body malignancies
A1  - Boren,E.L.,Jr.
A1  - Delbeke,D.
A1  - Patton,J.A.
A1  - Sandler,M.P.
Y1  - 1999/04//
N1  - UI - 99216405
SP  - 379
EP  - 387
JA  - Eur.J Nucl Med
VL  - 26
IS  - 4
N2  - The purpose of this study was to compare the diagnostic accuracy of fluorine-18 fluorodeoxyglucose (FDG) images obtained with (a) a dual-head coincidence gamma camera (DHC) equipped with 5/8-inch-thick NaI(Tl) crystals and parallel slit collimators and (b) a dedicated positron emission tomograph (PET) in a series of 28 patients with known or suspected malignancies. Twenty-eight patients with known or suspected malignancies underwent whole-body FDG PET imaging (Siemens, ECAT 933) after injection of approximately 10 mCi of 18F-FDG. FDG DHC images were then acquired for 30 min over the regions of interest using a dual-head gamma camera (VariCam, Elscint). The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton, and Compton/photopeak coincidence events. FDG PET imaging found 45 lesions ranging in size from 1 cm to 7 cm in 28 patients. FDG DHC imaging detected 35/45 (78%) of these lesions. Among the ten lesions not seen with FDG DHC imaging, eight were less than 1.5 cm in size, and two were located centrally within the abdomen suffering from marked attenuation effects. The lesions were classified into three categories: thorax (n=24), liver (n=12), and extrahepatic abdominal (n=9). FDG DHC imaging identified 100% of lesions above 1.5 cm in the thorax group and 78% of those below 1.5 cm, for an overall total of 83%. FDG DHC imaging identified 100% of lesions above 1.5 cm, in the liver and 43% of lesions below 1.5 cm, for an overall total of 67%. FDG DHC imaging identified 78% of lesions above 1.5 cm in the extrahepatic abdominal group. There were no lesions below 1.5 cm in this group. FDG coincidence imaging using a dual-head gamma camera detected 90% of lesions greater than 1.5 cm. These data suggest that DHC imaging can be used clinically in well-defined diagnostic situations to differentiate benign from malignant lesions
AD  - Section of Nuclear Medicine, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tenn. 37232-2675, USA
UR  - PM:10199944
ER  - 

TY  - JOUR
T1  - A multislice positron emission computed tomograph (PETT IV) yielding transverse and longitudinal images
A1  - Ter Pogossian,M.M.
A1  - Mullani,N.A.
A1  - Hood,J.
A1  - Higgins,C.S.
A1  - Currie,C.M.
Y1  - 1978/08//
N1  - UI - 78203111
SP  - 477
EP  - 484
JF  - Radiology
VL  - 128
IS  - 2
N2  - We designed, built, and tested a positron emission tomograph (PETT IV) capable of providing seven slices of the human body simultaneously. PETT IV utilizes a moving hexagonal array of 48 scintillation detectors placed around the subject. Each detector consists of a cylindrical activated sodium iodide crystal optically coupled to two photomultiplier tubes. The multislice capability is achieved by comparing the light outputs of the two photomultiplier tubes in each detector. The images are displayed either as transverse or as longitudinal tomographic sections. This system provides high sensitivity and resolution, and permits rapid and accurate three-dimensional imaging of the head and body
UR  - PM:663264
ER  - 

TY  - JOUR
T1  - Determination of the attenuation map in emission tomography
A1  - Zaidi,H.
A1  - Hasegawa,B.
Y1  - 2003/02//
N1  - UI - 22459121
SP  - 291
EP  - 315
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 2
N2  - Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmissionless and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images-namely, accurate coregistration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed
AD  - Division of Nuclear Medicine, Geneva University Hospital, Geneva, Switzerland. Department of Radiology, University of California, San Francisco, San Francisco, California
UR  - PM:12571222
ER  - 

TY  - JOUR
T1  - Evaluation of (18)F-FA-4 and (11)C-pipzA-4 as Radioligands for the In Vivo Evaluation of the High-Affinity Choline Uptake System
A1  - Gilissen,C.
A1  - De Groot,T.J.
A1  - Bronfman,F.
A1  - Van Leuven,F.
A1  - Verbruggen,A.M.
A1  - Bormans,G.M.
Y1  - 2003/02//
N1  - limiting step of acetylcholine synthesis
SP  - 269
EP  - 275
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 2
N2  - 4,4'-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system. We have evaluated 4-[1-hydroxy-2-(4-(18)F-fluoromethylpiperidin-1-yl)ethyl]-4'-[1-hydroxy-2- (4-methylpiperidin-1-yl)ethyl]biphenyl ((18)F-FA-4) and 4-[1-hydroxy-2-(4-(11)C-methylpiperazin-1-yl)ethyl]-4'-[1-hydroxy-2-(4-met hylpiperidin-1-yl)ethyl]biphenyl ((11)C-pipzA-4), an (18)F- and a (11)C-labeled derivative of A-4 as potential in vivo tracers for the HACU system. METHODS: The biodistribution of both compounds was determined in mice, and the intracerebral distribution was visualized by ex vivo and in vitro autoradiography. The in vitro affinity of the compounds was determined by a displacement study with (3)H-HC-3 on mice brain slices. RESULTS: In mice, both tracers show a high and persistent brain uptake. In vitro autoradiography shows binding to the striatum, whereas ex vivo autoradiography shows homogeneous binding throughout the brain. FA-4 and pipzA-4 inhibited the (3)H-HC-3 binding with a 50% inhibitory concentration of 57 nmol/L and 320 nmol/L, respectively. CONCLUSION: The evaluated compounds have affinity for HACU and show high uptake in the brain. In vitro binding of the compounds to the striatum cannot be inhibited by the presence of HC-3, whereas binding of HC-3 was inhibited by the presence of both FA-4 and pipzA-4, suggesting allosteric binding
AD  - Laboratory of Radiopharmaceutical Chemistry, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium. Experimental Genetics Group, Department of Human Genetics, KULeuven-Campus Gasthuisberg, Leuven, Belgium
UR  - PM:12571220
ER  - 

TY  - JOUR
T1  - Radiosynthesis of ML03, a novel positron emission tomography biomarker for targeting epidermal growth factor receptor via the labeling synthon: [11C]acryloyl chloride
A1  - Ben David,I.
A1  - Rozen,Y.
A1  - Ortu,G.
A1  - Mishani,E.
Y1  - 2003/02//
N1  - UI - 22461095
SP  - 209
EP  - 217
JA  - Appl.Radiat.Isot.
VL  - 58
IS  - 2
N2  - An automated procedure for the radiosynthesis of the labeling synthon [11C]acryloyl chloride was developed and applied for labeling several N-acryl amides with carbon-11. [11C]-6-acrylamido-4-(3,4-dichloro-6-fluoroanilino)quinazoline (ML03), a novel PET biomarker targeting the epidermal growth factor receptor tyrosine kinase (EGFr-TK) in cancer, was successfully prepared using this labeled synthon in a fully automated manner. Two other potential anticancer drugs were also labeled using the developed methodology. The potency of ML03 to inhibit autophosphorylation of EGFr-TK was evaluated by an ELISA assay indicating a low IC(50) of 0.037nM
AD  - Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, 91120, Jerusalem, Israel
UR  - PM:12573320
ER  - 

TY  - JOUR
T1  - Brain Uptake of the Acid Metabolites of F-18-Labeled WAY 100635 Analogs
A1  - Carson,R.E.
A1  - Wu,Y.
A1  - Lang,L.
A1  - Ma,Y.
A1  - Der,M.G.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
Y1  - 2003/02//
N1  - UI - 0
SP  - 249
EP  - 260
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 2
N2  - The 5-HT ligands [ F]FPWAY and [ F]FCWAY are metabolized to [ F]fluorobenzoic acid (FB) and [ F]fluorocyclohexanecarboxylic acid (FC), respectively. To quantify the penetration of these acids into the brain, dynamic positron emission tomography studies were performed in rhesus monkeys with [ F]FB and [ F]FC. High-performance liquid chromatography analysis of arterial blood samples showed no metabolites for [ F]FB, whereas [ F]FC was rapidly metabolized to [ F]fluoride. A model with one tissue compartment and vascular radioactivity was used to analyze gray matter time-activity curves. For [ F]FC, an additional term was added to account for [ F]fluoride skull spillover into the brain; this term accounted for 70% to 90% of the measured radioactivity concentration at 90 minutes. For [ F]FB, mean gray matter parameters were as follows:, 10 +/- 3 &mgr;L. min. mL; distribution volume, 0.052 +/- 0.006 (mL/mL). For [ F]FC, the values were as follows:, 15 +/- 4 &mgr;L. min. mL;, 0.29 +/- 0.06 mL/mL. The values were consistent with a physiologic model that included brain-to-blood pH difference and the plasma free fraction of the acid. Simulations based on [ F]FCWAY human data showed that [ F]FC uptake produces significant biases in estimates in regions with low specific binding. These results can be used to correct the tissue [ F]FCWAY time-activity data for brain uptake of [ F]FC using the measured [ F]FC input function.(1A) (1) (1)
UR  - PM:12571456
ER  - 

TY  - JOUR
T1  - Generalized sensory stimulation of conscious rats increases labeling of oxidative pathways of glucose metabolism when the brain glucose-oxygen uptake ratio rises
A1  - Dienel,G.A.
A1  - Wang,R.Y.
A1  - Cruz,N.F.
Y1  - 2002/12//
N1  - UI - 22356100
SP  - 1490
EP  - 1502
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 12
N2  - Interpretation of functional metabolic brain images requires understanding of metabolic shifts in working brain. Because the disproportionately higher uptake of glucose compared with oxygen ("aerobic glycolysis") during sensory stimulation is not fully explained by changes in levels of lactate or glycogen, metabolic labeling by [6-14C]glucose was used to evaluate utilization of glucose during brief brain activation. Increased labeling of tricarboxylic acid cycle-derived amino acids, mainly glutamate but also gamma-aminobutyric acid, reflects a rise in oxidative metabolism during aerobic glycolysis. The size of the glutamate, lactate, alanine, and aspartate pools changed during stimulation. Brain lactate was derived from blood-borne glucose and its specific activity was twice that of alanine, revealing pyruvate compartmentation. Glycogen labeling doubled during recovery compared with rest and activation; only 4% to 8% of the total 14C was recovered in lactate plus glycogen. Restoration of glycogen levels was slow, and diversion of glucose from oxidative pathways to restore its level could cause a prolonged reduction of the global O2/glucose uptake ratio. The rise in the brain glucose-oxygen uptake ratio during activation does not simply reflect an upward shift of glycolysis under aerobic conditions; instead, it involves altered fluxes into various (oxidative and biosynthetic) pathways with different time courses
AD  - Department of Neurology, Slot 500, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Shorey Building, Room 7S/15, Little Rock, AR 72205 U.S.A. dienelgeralda@uams.edu
UR  - PM:12468893
ER  - 

TY  - JOUR
T1  - Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease
A1  - Sultzer,D.L.
A1  - Brown,C.V.
A1  - Mandelkern,M.A.
A1  - Mahler,M.E.
A1  - Mendez,M.F.
A1  - Chen,S.T.
A1  - Cummings,J.L.
Y1  - 2003/02//
N1  - UI - 22449973
SP  - 341
EP  - 349
JA  - Am.J Psychiatry
VL  - 160
IS  - 2
N2  - OBJECTIVE: Delusional thoughts are common in patients with Alzheimer's disease and contribute prominently to morbidity. The pathophysiologic underpinnings for delusions in Alzheimer's disease are not well understood. In this study the authors examined the relationship between delusional thoughts and regional cortical metabolism in patients with Alzheimer's disease. METHOD: Twenty-five patients with probable Alzheimer's disease were included. None was taking psychotropic medication. Severity of delusions and other neuropsychiatric symptoms was assessed by using a semistructured interview and the Neurobehavioral Rating Scale just before the imaging procedure. [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure resting cerebral glucose metabolic rates in the cortical lobes and in anatomically defined subregions of the frontal and temporal cortexes. RESULTS: A linear regression model, controlling for the effects of cognitive deficits, revealed a significant relationship between severity of delusional thought and the metabolic rates in three frontal regions: the right superior dorsolateral frontal cortex (Brodmann's area 8), the right inferior frontal pole (Brodmann's area 10), and the right lateral orbitofrontal region (Brodmann's area 47). Bivariate partial correlation analysis indicated that severity of delusions was associated with hypometabolism in additional prefrontal and anterior cingulate regions. Robust relationships with metabolism in regions of the temporal cortex were not apparent. CONCLUSIONS: Dysmetabolism in specific regions of the right prefrontal cortex may be associated with delusional thought in Alzheimer's disease. Delusions appear to reflect the pathophysiologic state of particular cortical regions. Activity across distributed neuronal networks and the specific content of delusional thoughts may modulate these relationships
UR  - PM:12562582
ER  - 

TY  - JOUR
T1  - Correlation of Hippocampal Glucose Oxidation Capacity and Interictal FDG-PET in Temporal Lobe Epilepsy
A1  - Vielhaber,S.
A1  - Von Oertzen,J.H.
A1  - Kudin,A.F.
A1  - Schoenfeld,A.
A1  - Menzel,C.
A1  - Biersack,H.J.
A1  - Kral,T.
A1  - Elger,C.E.
A1  - Kunz,W.S.
Y1  - 2003/02//
N1  - UI - 0
SP  - 193
EP  - 199
JF  - Epilepsia
VL  - 44
IS  - 2
N2  - PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60-90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. METHODS: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-&mgr;m-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. RESULTS: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. CONCLUSIONS: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism
AD  - Department of Neurology II, University of Magdeburg Medical Center, Magdeburg; Departments of Nuclear Medicine, and Neurosurgery, University of Bonn, Bonn; and Department of Nuclear Medicine, University of Frankfurt, Germany
UR  - PM:12558573
ER  - 

TY  - JOUR
T1  - Age and severity of nigrostriatal damage at onset of Parkinson's disease
A1  - Fuente-Fernandez,R.
A1  - Lim,A.S.
A1  - Sossi,V.
A1  - Adam,M.J.
A1  - Ruth,T.J.
A1  - Calne,D.B.
A1  - Stoessl,A.J.
A1  - Lee,C.S.
Y1  - 2003/02//
N1  - UI - 22342844
SP  - 152
EP  - 158
JF  - Synapse
VL  - 47
IS  - 2
N2  - The clinical evolution of Parkinson's disease (PD) is known to be partly dependent on the age of onset. For example, motor complications associated with chronic dopaminomimetic treatment occur more often in younger patients. However, few attempts have been made to characterize the functional pathological differences underlying this age effect. We investigated the relationship between age and severity of nigrostriatal damage at onset of PD. Twenty patients with early PD (symptom duration </=5 years) with onset before age 50 (n = 10) and with onset after age 50 (n = 10) were studied. The two groups were compared with respect to severity of nigrostriatal damage as evaluated by positron emission tomography (PET) scanning with 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ), and d-threo-[(11)C]methylphenidate ([(11)C]MP). We found no significant differences between younger- and older-onset PD patients with regard to any of the three presynaptic markers. For putamen, the P-values corresponding to the different PET measurements ranged from P = 0.34 ([(18)F]-dopa) to P = 0.79 ([(11)C]DTBZ). However, after adjusting for treatment and PD duration, regression analysis showed that [(18)F]-dopa uptake correlated positively with age of onset (r = 0.59; P = 0.010). No correlation was found between [(11)C]DTBZ and [(11)C]MP binding potentials and age of onset (P = 0.26 and P = 0.90, respectively). These data suggest that age-of-onset-dependent differences in clinical evolution are not likely to reflect early differences in nigrostriatal pathology in PD. Age-related differences in [(18)F]-dopa uptake may be related to changes in dopamine turnover. Synapse 47:152-158, 2003
AD  - Pacific Parkinson's Research Centre, and TRIUMF, University of British Columbia, Vancouver, B.C., Canada V6T 2B5
UR  - PM:12454953
ER  - 

TY  - JOUR
T1  - Dopamine release in human ventral striatum and expectation of reward
A1  - Fuente-Fernandez,R.
A1  - Phillips,A.G.
A1  - Zamburlini,M.
A1  - Sossi,V.
A1  - Calne,D.B.
A1  - Ruth,T.J.
A1  - Stoessl,A.J.
Y1  - 2002/11/15/
N1  - UI - 22316470
SP  - 359
EP  - 363
JA  - Behav.Brain Res.
VL  - 136
IS  - 2
N2  - Using the ability of [11C]raclopride to compete with dopamine for D(2)/D(3) receptors, we investigated by positron emission tomography the effect of placebo (saline) injection on dopamine release in the ventral striatum of patients with Parkinson's disease. We found evidence for placebo-induced dopamine release of similar magnitude to that reported in healthy volunteers after amphetamine administration. However, in contrast to the dorsal striatum, there were no differences in [11C]raclopride binding potential changes between patients who experienced the reward (those who reported placebo-induced clinical benefit) and those who did not. We conclude that the release of dopamine in the ventral striatum (nucleus accumbens) is related to the expectation of reward and not to the reward itself. These observations have potential implications for the treatment of drug addiction
AD  - Pacific Parkinson's Research Centre, Vancouver Hospital and Health Sciences Center, University of British Columbia, Purdy Pavilion, 2221 Westbrook Mall, Vancouver, BC, Canada V6T 2B5
UR  - PM:12429397
ER  - 

TY  - JOUR
T1  - In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers
A1  - Podruchny,T.A.
A1  - Connolly,C.
A1  - Bokde,A.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
A1  - Kiesewetter,D.O.
A1  - Sunderland,T.
A1  - Carson,R.E.
A1  - Cohen,R.M.
Y1  - 2003/04//
N1  - UI - 22444994
SP  - 39
EP  - 44
JF  - Synapse
VL  - 48
IS  - 1
N2  - The precise effects of normal aging on the cholinergic system are unknown, as both in vitro and PET studies have shown conflicting results. In vivo determination of muscarinic receptor distribution and density has been hampered by both poor subtype selectivity and/or blood-brain barrier permeability of known ligands. Previous in vitro and in vivo work with the F-18 labeled muscarinic agonist, 3-(3- (3-[(18)F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-m ethylpyridine ((18)FP-TZTP) suggested the use of (18)FP-TZTP to selectively quantify M2 receptors in humans. In this study, we used (18)FP-TZTP to infer M2 receptor avidity in the brains of 15 healthy younger subjects (mean age = 28.3 +/- 5.5 years) and 20 healthy older subjects (mean age = 62.1 +/- 7.7 years). Corrections for subject motion during the 120-min acquisition and partial voluming (PVC) were performed. A one-tissue compartment model was used to estimate the volumes of distribution (V(T)) of (18)FP-TZTP. Within both groups of subjects, volumes of distribution (K(1)/k(2)) in cortical, subcortical, and cerebellar areas were consistent with M2 receptor topography. Compared to younger subjects older subjects had significantly higher means and standard deviations for the volumes of distribution of (18)FP-TZTP throughout much of the cerebellum, cortex, and subcortex (Global Gray V(T) = 742 +/- 163 in older subjects and 645 +/- 74 in younger subjects, P < 0.03). Across all subjects (18)FP-TZTP, regional, and Global Gray distribution volumes were significantly correlated to age (Global Gray V(T,) r = 0.41, P < 0.01). A lower concentration of acetylcholine in the synapse of some older subjects is one possible explanation for the data. Synapse 48:39-44, 2003. Published 2003 Wiley-Liss, Inc
AD  - Geriatric Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
UR  - PM:12557271
ER  - 

TY  - JOUR
T1  - Graphical analysis of 2-[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain
A1  - Chefer,S.I.
A1  - London,E.D.
A1  - Koren,A.O.
A1  - Pavlova,O.A.
A1  - Kurian,V.
A1  - Kimes,A.S.
A1  - Horti,A.G.
A1  - Mukhin,A.G.
Y1  - 2003/04//
N1  - UI - 22444992
SP  - 25
EP  - 34
JF  - Synapse
VL  - 48
IS  - 1
N2  - External imaging of nicotinic acetylcholine receptors (nAChRs) using techniques such as PET would help to clarify the roles of these receptors in the physiology and pathology of brain function. Here we report the results of quantitative PET studies of cerebral nAChRs with 2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) in rhesus monkeys. Data from dynamic PET scans were analyzed using graphical methods. Binding potential (BP) values of 2.0, 0.4, 0.3, and 0.03 observed in the thalamus (Th), cortex (Cx), striatum (Str), and cerebellum (Cb), respectively, were consistent with the pattern of alpha(4)beta(2) nAChR distribution in monkey brain. The high value of 2-[(18)F]FA-specific binding in the rhesus monkey Th and low level of that in Cb compared with nonspecific accumulation of radioactivity in these structures allowed use of Cb as a reference region for calculation of BP and volume of distribution of specific binding (VDsb) in Th by graphical methods, both with and without the plasma input function. In contrast, estimation of 2-[(18)F]FA specific binding in low-receptor-density regions such as Cx and Str required assessment of nondisplaceable volume of distribution (VDnd) in a separate study and measurement of nonmetabolized radioligand concentrations in the plasma. For accurate quantitation of 2-[(18)F]FA-specific binding by graphical analysis, PET studies should last up to 7 h due to the slow kinetics of 2-[(18)F]FA brain distribution. Further, to avoid substantial underestimation in measured BP values the doses of administered 2-[(18)F]FA should not exceed 0.1 nmol/kg body weight. The findings suggest that 2-[(18)F]FA is a promising ligand for quantitation of nAChRs in human brain. Synapse 48:25-34, 2003. Published 2003 Wiley-Liss, Inc
AD  - Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224
UR  - PM:12557269
ER  - 

TY  - JOUR
T1  - Visualization of alpha5 subunit of GABAA/benzodiazepine receptor by 11C Ro15-4513 using positron emission tomography
A1  - Maeda,J.
A1  - Suhara,T.
A1  - Kawabe,K.
A1  - Okauchi,T.
A1  - Obayashi,S.
A1  - Hojo,J.
A1  - Suzuki,K.
Y1  - 2003/03//
N1  - UI - 22382117
SP  - 200
EP  - 208
JF  - Synapse
VL  - 47
IS  - 3
N2  - Although [(11)C]Ro15-4513 and [(11)C]flumazenil both bind to the central benzodiazepine (BZ) receptors, the distributions of the two ligands are not identical in vivo. Moreover, the in vivo pharmacological properties of [(11)C]Ro15-4513 have not been thoroughly examined. In the present study, we examined the pharmacological profile of [(11)C]Ro15-4513 binding in the monkey brain using positron emission tomography (PET). [(11)C]Ro15-4513 showed relatively high accumulation in the anterior cingulate cortex, hippocampus, and insular cortex, with the lowest uptake being observed in the pons. Accumulation in the cerebral cortex was significantly diminished by the BZ antagonist flumazenil (0.1 mg/kg, i.v.), but not that in the pons. Using the pons as a reference region, the specific binding of [(11)C]Ro15-4513 in most of the cerebral cortex including the limbic regions clearly revealed two different affinity sites. On the other hand, specific binding in the occipital cortex and cerebellum showed only a low affinity site. Zolpidem with affinity for alpha1, alpha2, and alpha3 subunits of GABA(A)/BZ receptor fully inhibited [(11)C]Ro15-4513 binding in the occipital cortex and cerebellum, while only about 23% of the binding was blocked in the anterior cingulate cortex. Diazepam with affinity for alpha1, alpha2, alpha3, and alpha5 subunits inhibited the binding in all brain regions. Since Ro15-4513 has relatively high affinity for the alpha5 subunit in vitro, these in vivo bindings of [(11)C]Ro15-4513 can be interpreted as the relatively high accumulation in the fronto-temporal limbic regions representing binding to the GABA(A)/BZ receptor alpha5 subunit
AD  - Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan
UR  - PM:12494402
ER  - 

TY  - JOUR
T1  - Positron emission tomography imaging of the serotonin transporter in the pig brain using [11C](+)-McN5652 and S-([18F]fluoromethyl)-(+)-McN5652
A1  - Brust,P.
A1  - Zessin,J.
A1  - Kuwabara,H.
A1  - Pawelke,B.
A1  - Kretzschmar,M.
A1  - Hinz,R.
A1  - Bergman,J.
A1  - Eskola,O.
A1  - Solin,O.
A1  - Steinbach,J.
A1  - Johannsen,B.
Y1  - 2003/02//
N1  - UI - 22342843
SP  - 143
EP  - 151
JF  - Synapse
VL  - 47
IS  - 2
N2  - S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-FMe-McN5652) has recently been synthesized as a new potential radiotracer for positron emission tomography (PET) imaging of the 5-HT transporter. It is an analog of [(11)C](+)McN5652, which has been used in clinical PET studies for 5-HT transporter imaging. This article describes the comparison of these two radiotracers in pigs with respect to their in vivo binding characteristics. PET images revealed that the highest accumulation of both radiotracers was found in the ventral midbrain, thalamus, olfactory lobe, and pons which is consistent with the known density of 5-HT transporters. The specific binding was determined by subtracting the values of the inactive (-) enantiomers or of the occipital cortex from those obtained with [(11)C](+)McN5652 or [(18)F](+)-FMe-McN5652 in the time period between 75 and 115 min after radiotracer injection. The specific binding of the (18)F-labeled derivative was about 40% higher than that of the (11)C-labeled derivative. A strong inhibition of the specific binding was observed for both radiotracers after pretreatment with the selective 5-HT uptake inhibitor citalopram. [(18)F](+)-FMe-McN5652 showed faster kinetics than [(11)C](+)McN5652. It reached the binding equilibrium during a study length of 120 min, which was not the case for [(11)C](+)McN5652. It is concluded that [(18)F](+)-FMe-McN5652 is suitable for 5-HT transporter imaging with PET. Synapse 47:143-151, 2003
AD  - Institut fur Interdisziplinare Isotopenforschung, 04318 Leipzig, Germany
UR  - PM:12454952
ER  - 

TY  - JOUR
T1  - [11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats
A1  - Ginovart,N.
A1  - Wilson,A.A.
A1  - Meyer,J.H.
A1  - Hussey,D.
A1  - Houle,S.
Y1  - 2003/02//
N1  - UI - 22342841
SP  - 123
EP  - 133
JF  - Synapse
VL  - 47
IS  - 2
N2  - The in vivo pharmacological profile of [(11)C]-DASB, a new radioligand developed for in vivo imaging of the serotonin transporter (SERT), was evaluated in the cat brain using positron emission tomography (PET). The in vivo distribution of [(11)C]-DASB binding was consistent with the known distribution of SERT sites in the cat brain in vitro with high uptakes of radioactivity in the midbrain and thalamus, intermediate levels in striatum, and modest to low levels of radioactivity in the neocortex and cerebellum, respectively. [(11)C]-DASB binding potential (BP) values ranged from about 0.2 in the neocortex to 2.2 in the midbrain. Radioligand binding in all brain regions except cerebellum was markedly reduced following pretreatment with fluoxetine and citalopram, but was unaffected by pretreatment with GBR12909, maprotiline, and haloperidol, indicating specificity of [(11)C]-DASB binding to the SERT. Two cats were each examined using PET and [(11)C]-DASB in a longitudinal fashion (from 30 min and up to 24 days) following a single i.v. dose of: 1) fluoxetine, and 2) citalopram at different dosages. Both drugs induced similar degrees of SERT occupancy at 30 min postinjection ( approximately 90%). A comparison of citalopram and fluoxetine pharmacokinetics in the same animal and at the same dosage (1 mg/kg) showed that citalopram SERT occupancy and plasma half-lives were 9 times and 14 times shorter, respectively, than those of fluoxetine and norfluoxetine. In addition, studies performed after injection of the monoamine oxidase inhibitor tranylcypromine suggested that high levels of synaptic serotonin may compete with [(11)C]-DASB for binding on the SERT. These studies indicate that [(11)C]-DASB is a suitable PET radioligand for measuring drug occupancy of the SERT in vivo and has potential for monitoring in vivo changes in serotonin levels. Synapse 47:123-133, 2003
AD  - PET Centre, Centre for Addiction and Mental Health and University of Toronto, Toronto, Ontario M5T 1R8, Canada
UR  - PM:12454950
ER  - 

TY  - JOUR
T1  - Functional MR imaging in assessment of language dominance in epileptic patients
A1  - Sabbah,P.
A1  - Chassoux,F.
A1  - Leveque,C.
A1  - Landre,E.
A1  - Baudoin-Chial,S.
A1  - Devaux,B.
A1  - Mann,M.
A1  - Godon-Hardy,S.
A1  - Nioche,C.
A1  - Ait-Ameur,A.
Y1  - 2003/02//
SP  - 460
EP  - 467
JF  - Neuroimage
VL  - 18
IS  - 2
N2  - The value of functional MR Imaging (fMRI) in assessing language lateralization in epileptic patients candidate for surgical treatment is increasingly recognized. However few data are available for left-handed patients. Moreover determining factors for atypical dominance in patients investigated with contemporary imaging have not been reported. We studied 20 patients (14 males, 6 females; 9 right handed, 11 left handed) aged from 9 to 48 years, investigated for intractable partial epilepsy. Epileptic focus location was temporal in 14 cases, extratemporal in 6, and lateralized in the left hemisphere in 11/20. Hemispheric dominance for language was evaluated by both Wada test and fMRI using a silent word generation paradigm in all patients. Furthermore, a postictal speech test was performed in 15 patients. An fMRI language lateralization index was calculated from the number of activated pixels (Student's t test, P P < 0.05) but was not correlated with age at epilepsy onset, early brain injury (before 6 years), and lobar localization of epileptogenic focus. However the lack of a significant relationship between these factors and atypical language lateralization may be related to the small sample size
UR  - http://www.sciencedirect.com/science/article/B6WNP-47TFDNK-15/1/5f55e4caa79a1891e80347a110b000bb
ER  - 

TY  - JOUR
T1  - Early diagnosis of alzheimer's disease: contribution of structural neuroimaging
A1  - Chetelat,Gael
A1  - Baron,Jean Claude
Y1  - 2003/02//
SP  - 525
EP  - 541
JF  - Neuroimage
VL  - 18
IS  - 2
N2  - To accurately predict the development of Alzheimer's disease (AD) at its predementia stage would be a major breakthrough from both therapeutic and research standpoints. In this review, our focus is on markers obtained with structural imaging--especially magnetic resonance imaging (MRI)--and on studies of subjects at risk of developing AD. Among the latter, amnestic mild cognitive impairment (MCI) is currently the most commonly accepted reference, and therefore is specially targeted in this review. MCI refers to patients with significant but isolated memory impairment relative to subjects of identical age. Consistent with established histopathological data, structural imaging studies comparing patients with early probable AD to healthy aged subjects have shown that the most specific and sensitive features of AD at this stage are hippocampal and entorhinal cortex atrophy, especially when combined with a reduced volume of the temporal neocortex. MCI patients have significant hippocampal atrophy when compared to aged normal controls. When comparing patients with probable AD to MCI subjects, hippocampal region atrophy significantly extends to the neighboring temporal association neocortex. However, only longitudinal studies of MCI subjects are suited to assess (in a retrospective way) the predictive value of initial atrophy measurements for progression to AD. Few such studies have been published so far and for the most they were based on small samples. Furthermore, the comparison among studies is clouded by differences in both populations studied and MRI methodology used. Nevertheless, comparing the initial MRI data of at-risk subjects who convert to AD at follow-up to those of nonconverters suggests that a reduced association temporal neocortex volume combined with hippocampal or anterior cingulate cortex atrophy may be the best predictor of progression to AD. These data, although still preliminary, are consistent with postmortem studies describing the hierarchical progression of tau lesions in normal aging and early stages of AD, such that damage to the medial temporal lobe and association cortex would account for the memory and nonmemory cognitive impairments, respectively, the combination of which is required to operationally define probable AD. Future research in this field should capitalize on thorough methodology for brain structure delineation, and combine atrophy measurements to cognitive and/or functional imaging data
UR  - http://www.sciencedirect.com/science/article/B6WNP-47TFDNK-H/1/1609e174649575d457ff343e147836cd
ER  - 

TY  - JOUR
T1  - Template-Based Method for Multiple Volumes of Interest of Human Brain PET Images
A1  - Yasuno,Fumihiko
A1  - Hasnine,Akter Haque
A1  - Suhara,Tetsuya
A1  - Ichimiya,Tetsuya
A1  - Sudo,Yasuhiko
A1  - Inoue,Makoto
A1  - Takano,Akihiro
A1  - Ou,Tan
A1  - Ando,Tomomichi
A1  - Toyama,Hinako
Y1  - 2002/07//
SP  - 577
EP  - 586
JF  - Neuroimage
VL  - 16
IS  - 1
N2  - Specific region-based analysis for the quantification of brain imaging is very time-consuming work and subject to errors in both accuracy and reproducibility. In this study, we assessed a two-step template-based method for defining volumes of interest (VOIs). The first step was the spatial transformation of the VOI template from a model MRI to an individual MRI with SPM99. The second step was to refine the transformed VOI to the individual gray matter of MRI using the intensity characteristics of this image with our developed software running on a PC type of computer. The reliability of the values of the final refined VOIs was investigated by comparing them to those of manually drawn VOIs. The template-based method was found to be both accurate and robust and can be used as a reliable alternative for the manual determination of VOIs
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Yasuno-PET-Template-VOIs.pdf
ER  - 

TY  - JOUR
T1  - Genetic basis of the human epilepsies
A1  - Gardiner,R.M.
Y1  - 1999/09//
N1  - UI - 99443180
SP  - 91
EP  - 95
JA  - Epilepsy Res.
VL  - 36
IS  - 2-3
N2  - Genetic factors contribute to aetiology in up to 40% of patients with epilepsy. Over 100 single gene Mendelian disorders include epilepsy as one component of what is usually a complex neurological phenotype, but the majority of idiopathic or primary epilepsies display a 'complex' non-Mendelian pattern of inheritance. There have been significant recent advances in understanding the genetic basis of inherited epilepsies at a molecular level. Epilepsy genes fall into several distinct categories including those in which mutations cause abnormal brain development, progressive neurodegeneration, disturbed energy metabolism and abnormal function of ion channels. Ion channel genes involved include those encoding neuronal nicotinic acetylcholine receptor subunits and voltage-gated potassium and sodium channels
AD  - Department of Paediatrics, Royal Free and University College Medical School, University College London, The Rayne Institute, UK
UR  - PM:10515157
ER  - 

TY  - JOUR
T1  - Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy
A1  - Avery,R.A.
A1  - Spencer,S.S.
A1  - Spanaki,M.V.
A1  - Corsi,M.
A1  - Seibyl,J.P.
A1  - Zubal,I.G.
Y1  - 1999/08//
N1  - UI - 99367367
SP  - 830
EP  - 836
JA  - Eur.J Nucl Med
VL  - 26
IS  - 8
N2  - Single-photon emission tomography (SPET) brain imaging in epilepsy has become an increasingly important noninvasive tool in localizing the epileptogenic site. Ictal SPET demonstrates the highest localization sensitivity as compared with postictal and interictal SPET. While ictal SPET consistently reveals hyperperfusion at the epileptogenic site, postictal SPET reveals either hyper- or hypoperfusion depending on the timing of radiopharmaceutical injection. Much discussion in the literature exists about exactly when the transition from hyper- to hypoperfusion occurs at the epileptogenic site in postictal SPET. The systematic examination of two clinical variables - time of injection from seizure onset and offset - was useful in understanding postictal perfusion changes. Twenty-seven patients with medically refractory epilepsy receiving postictal and interictal SPET scans were studied. Quantitative SPET difference imaging was used to evaluate perfusion changes in relationship to injection time. Perfusion changes were found to reflect the time of injection in relation to seizure onset, but to be somewhat independent of seizure offset. Thus, the majority of patients (8/12, 67%) receiving postictal injections within 100 s after seizure onset demonstrated hyperperfusion, while all patients (15/15, 100%) receiving postictal injections more than 100 s after seizure onset showed hypoperfusion. The explanation of this phenomenon is unknown but the findings appear to parallel known changes in cerebral lactate levels
AD  - Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, Box 208042, New Haven, CT 06520-8042, USA
UR  - PM:10436195
ER  - 

TY  - JOUR
T1  - Hippocampal volume and glucose metabolism in temporal lobe epileptic foci
A1  - Theodore,W.H.
A1  - Gaillard,W.D.
A1  - De Carli,C.
A1  - Bhatia,S.
A1  - Hatta,J.
Y1  - 2001/01//
N1  - UI - 21142316
SP  - 130
EP  - 132
JF  - Epilepsia
VL  - 42
IS  - 1
N2  - PURPOSE: Reports conflict on the relation of glucose metabolism to hippocampal volume in temporal lobe foci. Previous studies usually have used side-side ratios rather than regional metabolic rates. METHODS: We measured hippocampal volume and glucose metabolism in 37 patients with temporal epileptogenic zones identified by ictal video-EEG telemetry. Metabolic rates were normalized to global brain mean. RESULTS: Both 18-fluoro-2-deoxyglucose-PET and volumetric MRI lateralized the epileptic focus determined by ictal video-EEG. There were significant correlations between left-right metabolic asymmetry and hippocampal formation volume left-right ratios. Comparisons between normalized metabolism and hippocampal formation volume, ignoring the side of the epileptic focus, showed significant relations between left hippocampal volume and left inferior lateral temporal metabolism, right hippocampus and right inferior mesial temporal, and left hippocampus and left inferior mesial temporal metabolism. In contrast, when normalized metabolism was compared with hippocampal volume in the epileptic focus, no relation was found. CONCLUSIONS: Our study suggests that the relation between hippocampal volume and glucose metabolism breaks down in epileptic foci and that hypometabolism is not dependent on neuronal loss. It is consistent with data suggesting that hypometabolism is an independent predictor of surgical outcome
AD  - Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Bldg. 10, Room 5N-250, Bethesda, MD 20892-1408, USA. theodore@codon.nih.gov
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Theodore-Hippocampus-Volume.pdf
ER  - 

TY  - JOUR
T1  - Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures
A1  - Theodore,W.H.
A1  - Bhatia,S.
A1  - Hatta,J.
A1  - Fazilat,S.
A1  - DeCarli,C.
A1  - Bookheimer,S.Y.
A1  - Gaillard,W.D.
Y1  - 1999/01/01/
N1  - UI - 99118833
SP  - 132
EP  - 136
JF  - Neurology
VL  - 52
IS  - 1
N2  - BACKGROUND: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. OBJECTIVE: To determine whether epilepsy duration is related to HF atrophy. Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. RESULTS: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures
AD  - Clinical Epilepsy Section, Epilepsy Research Branch, NINDS, NIH, Bethesda, MD 20892, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Theodore-Hippocampus-Seizures.pdf
ER  - 

TY  - JOUR
T1  - Neuroimaging and the progression of epilepsy
A1  - Theodore,W.H.
A1  - Gaillard,W.D.
Y1  - 2002///
N1  - UI - 22139321
SP  - 305
EP  - 313
JA  - Prog.Brain Res.
VL  - 135
N2  - Several lines of evidence can be used to try to answer the question of whether epilepsy is a progressive disease, and whether persistent seizures, or the underlying process itself, cause neuronal injury. The results of clinical studies have been inconclusive. Neuroimaging studies offer a quantitative approach. In patients with temporal lobe epilepsy, structural magnetic resonance imaging (MRI) has shown volume reductions ipsilateral to the epileptic focus in hippocampal and extrahippocampal regions; the former, in cross-sectional studies, increase with increasing epilepsy duration. Other factors associated with increasing hippocampal atrophy include a history of complex or prolonged febrile seizures, and generalized tonic-clonic seizure number. Positron emission tomography (PET) has shown supporting results. However, these studies have been cross-sectional rather than longitudinal. Preliminary results from prospective imaging studies using fluorodeoxyglucose PET and volumetric MRI show that patients with more recent seizure onset are less likely to have hypometabolism or volume loss than those with a long history of epilepsy. Alternate interpretations of these data include a possible progressive effect of epilepsy, or a tendency for patients with structural or functional findings at seizure onset to be more likely to develop uncontrolled epilepsy. In addition to the human studies that have been performed, parallel investigations in animal models using some of the same imaging techniques may help to unravel the factors associated with neuronal injury due to seizures, and aid in interpreting results of clinical studies
AD  - Clinical Epilepsy Section, National Institutes of Health, Building 10, Room 5N-250, Bethesda, MD 20892, USA. theodorw@ninds.nih.gov
UR  - PM:12143351
ER  - 

TY  - JOUR
T1  - Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study
A1  - Gaillard,W.D.
A1  - Kopylev,L.
A1  - Weinstein,S.
A1  - Conry,J.
A1  - Pearl,P.L.
A1  - Spanaki,M.V.
A1  - Fazilat,S.
A1  - Fazilat,S.
A1  - Venzina,L.G.
A1  - Dubovsky,E.
A1  - Theodore,W.H.
Y1  - 2002/03/12/
N1  - UI - 21886695
SP  - 717
EP  - 722
JF  - Neurology
VL  - 58
IS  - 5
N2  - OBJECTIVE: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time. METHODS: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal. RESULTS: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus. CONCLUSIONS: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset
AD  - Department of Neurology, Children's National Medical Center, The George Washington University School of Medicine, Washington, DC 20010, USA. gaillardw@ninds.nih.gov
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Gaillard-Incidence-PET.pdf
ER  - 

TY  - JOUR
T1  - Activation of language cortex with automatic speech tasks
A1  - Bookheimer,S.Y.
A1  - Zeffiro,T.A.
A1  - Blaxton,T.A.
A1  - Gaillard,P.W.
A1  - Theodore,W.H.
Y1  - 2000/10/24/
N1  - UI - 20521172
SP  - 1151
EP  - 1157
JF  - Neurology
VL  - 55
IS  - 8
N2  - OBJECTIVE: To identify automatic speech tasks that reliably demonstrate increased regional cerebral blood flow (rCBF) in Broca's and Wernicke's areas of the cortex using PET. BACKGROUND: Localizing language with direct cortical stimulation mapping requires that patients have a stable baseline on tests that engage eloquent cortex. For dysphasic patients or younger children, automatic speech tasks such as counting are often used in lieu of more complex language tests. Evidence from both lesion and neuroimaging studies suggests that these tasks may not adequately engage language cortices. In this study, we examined rCBF during automatic oromotor and speech tasks of varying complexity to identify those eliciting increased CBF in Broca's and Wernicke's areas. METHODS: Eight normal volunteers underwent PET during rest, tongue movements, and three automatic speech tasks: repeating a phoneme sequence, repeating the months of the year, and reciting a memorized prose passage. Images were averaged across subjects and compared across tasks for regional localization and laterality. RESULTS: Whereas all activation tasks produced increased relative CBF in brain regions that correlated with articulation and auditory processing, only the two tasks that used real words (versus phonemes) showed left-lateralized rCBF increases in posterior superior temporal lobe (Wernicke's area), and only the prose repetition task produced left lateralized activity in Broca's area. CONCLUSIONS: Whereas automatic speech typically does not engage language cortex, repeating a memorized prose passage showed unambiguous activation in both Broca's and Wernicke's areas. These results caution against the use of common automatic speech tasks for mapping eloquent cortex and suggest an alternative task for those with poor language abilities or acquired dysphasia who cannot perform standardized language tests reliably
AD  - Epilepsy Research Branch, NINDS, National Institutes of Health, Bethesda, MD, USA. sbook@loni.ucla.edu
UR  - PM:11071493
ER  - 

TY  - JOUR
T1  - The utility of a 3-dimensional, large-field-of-view, sodium iodide crystal--based PET scanner in the presurgical evaluation of partial epilepsy
A1  - O'Brien,T.J.
A1  - Hicks,R.J.
A1  - Ware,R.
A1  - Binns,D.S.
A1  - Murphy,M.
A1  - Cook,M.J.
Y1  - 2001/08//
SP  - 1158
EP  - 1165
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 42
IS  - 8
N2  - (18)F-FDG PET is an accurate and reliable technique for localizing medically refractory temporal lobe epilepsy, but widespread use has been hindered by limited reimbursement in many countries because of the high cost of traditional PET equipment and radioisotopes. Additionally, the place of FDG PET as a cost-effective tool for presurgical evaluation of epilepsy has been questioned because of limited data showing that FDG PET provides localization information incremental to that provided by more established techniques, particularly MRI and ictal electroencephalography (EEG). Three-dimensional (3D), large-field-of-view, sodium iodide crystal-based scanners have lower equipment and running costs and better multiplanar resolution than traditional 2-dimensional bismuth germinate (BGO) systems but have not yet been validated for evaluation of epilepsy. Our purpose was to investigate the localization rate, accuracy, and prognostic value of FDG PET images acquired on a 3D, large-field-of-view, sodium iodide crystal-based PET scanner in the presurgical evaluation of intractable partial epilepsy. We also wanted to establish the incremental value of FDG PET over established MRI and ictal EEG techniques. METHODS: Fifty-five patients who were surgical candidates because of medically refractory partial epilepsy were examined. For most of these patients, the lesions had not been clearly localized on conventional assessment. The FDG PET scans were reviewed independently by 2 reviewers who were unaware of the patients' clinical details, ictal EEG findings, and volumetric MRI results, and the FDG PET results were correlated with those of MRI and EEG and with postsurgical outcome. RESULTS: Forty-two patients (76%) had localizing FDG PET images (37 temporal, 5 extratemporal). The ictal EEG recordings were localizing in 66%, and the MRI findings were localizing in 27% (which increased to 35% after the MRI findings were reviewed again after PET). Concordance between the site of the PET localizations and the site of the MRI or EEG localizations was 100%. The PET images were localizing in 63% and 69% of patients with nonlocalizing ictal EEG and MRI findings, respectively. Twenty-one of 24 patients who subsequently underwent epilepsy surgery had localizing FDG PET images; of these 21 patients, 18 (86%) had a class I outcome. Multiple regression analysis showed the FDG PET results to be predictive of postsurgical outcome independently of the MRI findings. CONCLUSION: For intractable partial epilepsy, FDG PET using a 3D, large-field-of-view, sodium iodide crystal-based scanner provided clinically useful localizing information that was at least as accurate as the results reported for traditional BGO-based scanners. The PET images provided prognostically significant localization information incremental to that provided by volumetric MRI and ictal EEG, particularly if 1 of these studies was nonlocalizing
AD  - Australian Center for Clinical Neuropharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia
UR  - PM:11483674
ER  - 

TY  - JOUR
T1  - Neuroradiological assessment of brain structure and function and its implication in the pathogenesis of West syndrome
A1  - Juhasz,C.
A1  - Chugani,H.T.
A1  - Muzik,O.
A1  - Chugani,D.C.
Y1  - 2001/11//
N1  - UI - 21558042
SP  - 488
EP  - 495
JA  - Brain Dev.
VL  - 23
IS  - 7
N2  - Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have contributed significantly to our understanding of West syndrome. Cortical dysplastic lesions are the most common abnormalities seen with MRI in infants with spasms, but other structural lesions are also detected occasionally. An underlying cortical dysplasia may not be apparent until myelination has advanced in the brain and poor gray-white matter differentiation becomes observable. Many cortical dysplastic lesions can only be detected using PET scanning of glucose metabolism or gamma-aminobutyric acid(A) (GABA(A)) receptor binding. The MRI and PET findings, together with neurophysiological observations, strongly suggest that infantile spasms are initiated as cortical epileptic discharges that, during a 'critical' developmental period, may undergo secondary generalization in an age-dependent mechanism to emerge as spasms. The onset of spasms often coincides with the functional maturation of cerebral cortex. Based on data from glucose metabolism PET scanning as well as electrophysiological and neurochemical findings on infants with spasms, we have postulated that the offending lesion is a focal or diffuse cortical abnormality which, at a critical stage of maturation, causes abnormal functional interactions with brainstem raphe nuclei which project widely throughout the brain. Raphe-cortical projections could mediate the hypsarrhythmic changes seen on EEG. The prominent serotonergic raphe-striatal pathway and descending spinal pathways may be responsible for secondary generalization of the cortical discharges to result in the relatively symmetric spasms. It is likely that additional factors (e.g. genetic) play a role in the manifestation of the age-specific electroclinical features of West syndrome. Recently developed PET tracers can be used to detect epileptogenic brain regions and also to investigate developmental abnormalities of serotonergic (using the tracer alpha[(11)C]methyl-L-tryptophan) and GABAergic (using [(11)C]flumazenil) neurotransmitter systems. These systems are implicated in epileptogenesis, and their involvement in the pathophysiology of West syndrome can be further addressed by future functional neuroimaging studies
AD  - Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI 48201, USA
UR  - PM:11701243
ER  - 

TY  - JOUR
T1  - Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome
A1  - Juhasz,C.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Shah,A.
A1  - Shah,J.
A1  - Watson,C.
A1  - Canady,A.
A1  - Chugani,H.T.
Y1  - 2001/06/26/
SP  - 1650
EP  - 1658
JF  - Neurology
VL  - 56
IS  - 12
N2  - BACKGROUND: Cortical areas showing abnormal glucose metabolism and [(11)C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control. OBJECTIVE: To analyze whether the extent of cortex showing 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery. METHODS: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 +/- 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores. RESULTS: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found. CONCLUSIONS: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed
AD  - Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI 48201, USA
UR  - PM:11425929
ER  - 

TY  - JOUR
T1  - Postnatal maturation of human GABAA receptors measured with positron emission tomography
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Juhasz,C.
A1  - Janisse,J.J.
A1  - Ager,J.
A1  - Chugani,H.T.
Y1  - 2001/05//
N1  - UI - 21256455
SP  - 618
EP  - 626
JA  - Ann.Neurol
VL  - 49
IS  - 5
N2  - During brain development in nonhuman primates, there are large changes in GABAA receptor binding and subunit expression. An understanding of human GABAA receptor ontogeny is highly relevant in elucidating the pathophysiology of neurodevelopmental disorders in which GABAergic mechanisms play a role as well as in understanding differences that occur during development in the pharmacology of drugs acting on this system. We have measured age-related changes in the brain distribution of the GABAA receptor complex in vivo using positron emission tomography (PET) in epileptic children under evaluation for surgical treatment. PET imaging was performed using the tracer [11C]flumazenil (FMZ), a ligand that binds to alpha subunits of the GABAA receptor. FMZ binding was quantified using a two-compartment model yielding values for the volume of distribution (VD) of the tracer in tissue. All brain regions studied showed the highest value for FMZ VD at the youngest age measured (2 years), and the values then decreased exponentially with age. Medial temporal lobe structures, primary visual cortex, and thalamus showed larger differences between values for age 2 years and adults (approximately 50% decrease) than did basal ganglia, cerebellum, and other cortical regions (25-40% decreases). Furthermore, subcortical regions reached adult values earlier (14-17.5 years) than did cortical regions (18-22 years). The ontogeny data of FMZ VD from children may contribute to understanding regional differences in synaptic plasticity as well as improve rational therapeutic use of drugs acting at the GABAA receptor in the pediatric population
AD  - Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201, USA. dchugani@pet.wayne.edu
UR  - PM:11357952
ER  - 

TY  - JOUR
T1  - Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy
A1  - Juhasz,C.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Watson,C.
A1  - Shah,J.
A1  - Shah,A.
A1  - Chugani,H.T.
Y1  - 2000/09/26/
SP  - 825
EP  - 835
JF  - Neurology
VL  - 55
IS  - 6
N2  - OBJECTIVE: To analyze the clinical utility of [11C]flumazenil (FMZ) PET to detect perilesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to MRI, 2-deoxy-2-[18F]fluoro-d-glucose (FDG) PET, and electrocorticographic (ECoG) findings as well as clinical characteristics of the epilepsy in epileptic patients with brain lesion. BACKGROUND: The success of resective surgery in patients with medically intractable epilepsy and brain lesion depends not only on removal of the lesion itself but also on the reliable presurgical delineation of the epileptic cortex that commonly extends beyond it. PET could provide a noninvasive identification of such epileptogenic areas. METHODS: Seventeen patients underwent high resolution MRI, FDG and FMZ PET, and presurgical EEG evaluation, including chronic intracranial ECoG monitoring or intraoperative ECoG. Regional cortical FDG/FMZ PET abnormalities were defined on partial volume-corrected PET images using an objective method based on a semiautomated definition of areas with abnormal asymmetry. Structural lesions were defined on coregistered MRI. The marked PET abnormalities visualized on three-dimensional cortical surface were compared with each other, to the extent of MRI-defined lesion, as well as to ECoG findings. RESULTS: The mean surface extent of FMZ PET abnormalities was significantly larger than the corresponding structural lesions, but it was significantly smaller than areas of glucose hypometabolism. The size of perilesional FDG PET abnormalities showed a correlation with the lifetime number of seizures (r = 0.93, p = 0.001). The extent of perilesional FMZ PET abnormalities was independent of the seizure number and showed an excellent correspondence with spiking cortex, the resection of which resulted in seizure-free outcome in all but one operated patient. Remote FMZ PET abnormalities (n = 6) were associated with early age at seizure onset (p = 0.048) and appeared in ipsilateral synaptically connected regions from the lesion area. CONCLUSIONS: Three-dimensional surface-rendered FMZ PET is able to delineate perilesional epileptic cortex, and it may be especially useful to localize such areas in patients with extensive perilesional glucose hypometabolism associated with a large number of seizures. Remote FMZ PET abnormalities in patients with early onset and long duration of epilepsy might represent secondary epileptogenesis, but this requires further study
AD  - Departments of Pediatrics, Children's Hospital of Michigan, Detroit, MI 48201, USA
UR  - PM:10994004
ER  - 

TY  - JOUR
T1  - Evidence for coupling between glucose metabolism and glutamate cycling using FDG PET and 1H magnetic resonance spectroscopy in patients with epilepsy
A1  - Pfund,Z.
A1  - Chugani,D.C.
A1  - Juhasz,C.
A1  - Muzik,O.
A1  - Chugani,H.T.
A1  - Wilds,I.B.
A1  - Seraji-Bozorgzad,N.
A1  - Moore,G.J.
Y1  - 2000/05//
N1  - UI - 20284771
SP  - 871
EP  - 878
JA  - J Cereb.Blood Flow Metab
VL  - 20
IS  - 5
N2  - The purpose of this study was to examine the relation between glucose metabolism and glutamate concentration in the human brain, in both the normal and diseased state. Regional values of glucose metabolism measured with 2-deoxy-2[F-18]fluoro-D-glucose positron emission tomography (FDG PET) studies and single-voxel proton magnetic resonance spectroscopy (1H MRS) measurements of the glutamate/ glutamine/gamma-aminobutyric acid (Glx) tissue concentration were determined in multiple brain regions in 11 patients (5 girls and 6 boys, mean age 7.5 years) with medically intractable partial epilepsy. FDG PET and 1H MRS studies were performed in the interictal state in seven patients and in the ictal/periictal state in four patients. Regions of interest were identified in epileptic cortex (determined by intracranial and/or scalp electroencephalography) and in contralateral normal brain regions. Lower glucose metabolism and lower Glx concentrations were found in the epileptic focus than in the contralateral normal cortex in all seven patients examined in the interictal state, whereas higher glucose metabolism and higher Glx concentrations were observed in the epileptic focus in the four patients who had ictal/periictal studies. Significant correlations were found between the values of cerebral glucose utilization and Glx concentration in epileptic brain region, in nonepileptic brain regions, and in epileptic and nonepileptic regions combined. These results demonstrate a significant relation between glucose metabolism and glutamate/glutamine concentration in normal and epileptic cerebral cortex. This relation is maintained in both the interictal and ictal states
AD  - Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, USA
UR  - PM:10826538
ER  - 

TY  - JOUR
T1  - Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex
A1  - Asano,E.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Shen,C.
A1  - Juhasz,C.
A1  - Janisse,J.
A1  - Ager,J.
A1  - Canady,A.
A1  - Shah,J.R.
A1  - Shah,A.K.
A1  - Watson,C.
A1  - Chugani,H.T.
Y1  - 2000/05/23/
N1  - UI - 20284139
SP  - 1976
EP  - 1984
JF  - Neurology
VL  - 54
IS  - 10
N2  - OBJECTIVE: Using interictal alpha-[11C]methyl-l-tryptophan ([11C]AMT) PET scan, the authors have undertaken a quantitative analysis of all tubers visible on MRI or 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET, to determine the relationship between [11C]AMT uptake and epileptic activity on EEG. BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, often associated with cortical tubers and intractable epilepsy. The authors have shown previously that [11C]AMT PET scans show high tracer uptake in some epileptogenic tubers and low uptake in the remaining tubers. METHODS: Eighteen children, age 7 months to 16 years, were studied. Patients underwent video-EEG monitoring, PET scans of [11C]AMT and [18F]FDG, and T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. [11C]AMT uptake values were measured in 258 cortical tubers delineated with coregistered MRI or [18F]FDG scans. Uptake ratios were calculated between the [11C]AMT uptake in tubers and those for normal cortex (tuber/normal cortex). Using the region of epileptiform activity, the authors performed receiver operator characteristics (ROC) analysis and determined the optimal uptake ratio for detecting presumed epileptogenic tubers. RESULTS: Tuber uptake ratios ranged from 0.6 to 2.0. Tuber uptake ratios in the epileptic lobes were higher than those in the nonepileptic lobes (p < 0.0001). All 15 patients with focal seizure activity showed one or more lesions with uptake ratio above 0.98 in the epileptic lobe. ROC analysis showed that a tuber uptake ratio of 0.98 resulted in a specificity of 0.91. CONCLUSIONS: Cortical tubers with [11C]AMT uptake greater than or equal to normal cortex are significantly related to epileptiform activity in that lobe. Together, interictal [11C]AMT PET and FLAIR MRI improve the detection of potentially epileptogenic tubers in patients with TSC being evaluated for epilepsy surgery
AD  - Department of Pediatrics, Children's Hospital of Michigan and Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI 48201, USA
UR  - PM:10822440
ER  - 

TY  - JOUR
T1  - MR imaging and positron emission tomography of cortical heterotopia
A1  - Bairamian,D.
A1  - Di Chiro,G.
A1  - Theodore,W.H.
A1  - Holmes,M.D.
A1  - Dorwart,R.H.
A1  - Larson,S.M.
Y1  - 1985/11//
N1  - UI - 86034868
SP  - 1137
EP  - 1139
JA  - J Comput.Assist.Tomogr.
VL  - 9
IS  - 6
N2  - Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18F-2-deoxyglucose
UR  - PM:3877084
ER  - 

TY  - JOUR
T1  - PET, CT, and MRI imaging in neuronal migration anomalies in epileptic patients
A1  - Falconer,J.
A1  - Wada,J.A.
A1  - Martin,W.
A1  - Li,D.
Y1  - 1990///
SP  - 35
EP  - 39
JA  - Can.J Neurol Sci.
VL  - 17
ER  - 

TY  - JOUR
T1  - Cerebral glucose utilization during sleep in Landau-Kleffner syndrome: a PET study
A1  - Maquet,P.
A1  - Hirsch,E.
A1  - Dive,D.
A1  - Salmon,E.
A1  - Marescaux,C.
A1  - Franck,G.
Y1  - 1990/11//
N1  - UI - 91059855
SP  - 778
EP  - 783
JF  - Epilepsia
VL  - 31
IS  - 6
N2  - Three right-handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia-epilepsy (Landau-Kleffner syndrome) were studied during drug-induced, electroencephalographically (EEG)-monitored sleep by positron-emission tomography (PET) and the [18F]fluorodeoxyglucose (FDG) method. Our data demonstrate that in Landau-Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right-sided, left-sided, or bilateral. In the two first patients, EEG recordings showed continuous spike-and-wave discharges during sleep and a right-greater-than-left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS)
AD  - Department of Neurology, CHU Sart Tilman, Liege, Belgium
UR  - PM:1700954
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus
A1  - Franck,G.
A1  - Sadzot,B.
A1  - Salmon,E.
A1  - Depresseux,J.C.
A1  - Grisar,T.
A1  - Peters,J.M.
A1  - Guillaume,M.
A1  - Quaglia,L.
A1  - Delfiore,G.
A1  - Lamotte,D.
Y1  - 1986///
N1  - UI - 86211626
SP  - 935
EP  - 948
JA  - Adv.Neurol
VL  - 44
N2  - Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus
UR  - PM:3085438
ER  - 

TY  - JOUR
T1  - Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy
A1  - Hajek,M.
A1  - Wieser,H.G.
A1  - Khan,N.
A1  - Antonini,A.
A1  - Schrott,P.R.
A1  - Maguire,P.
A1  - Beer,H.F.
A1  - Leenders,K.L.
Y1  - 1994/11//
N1  - UI - 95060003
SP  - 2125
EP  - 2132
JF  - Neurology
VL  - 44
IS  - 11
N2  - We have studied 25 patients with interictal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after selective surgery for temporal lobe epilepsy (TLE). Based on the findings of the presurgical evaluation, including ictal intracranial EEGs, histopathologic findings, and the postoperative outcome, we classified the patients in three subgroups: (1) patients with TLE of lateral temporal origin (n = 5), (2) patients with mesiobasal limbic TLE associated with mesial gliosis (n = 14), and (3) patients with mesiobasal limbic TLE and small mesial tumors (n = 6). Postoperatively, patients with mesiobasal limbic TLE and mesial gliosis and five of six patients with mesiobasal limbic TLE and mesial tumors were seizure-free; the remaining sixth patient had one generalized seizure. Patients with TLE of lateral temporal origin had more than 90% reduction of seizure frequency. The main postoperative metabolic findings were as follows: (1) marked increase of regional cerebral metabolic rate of glucose (rCMRglu), both in the ipsilateral and, significantly, in the contralateral hemisphere in patients with mesiobasal limbic TLE and mesial gliosis-the changes of brain metabolism were characteristic for patients with the syndrome of "mesial temporal lobe epilepsy" (MTLE); (2) decrease of rCMRglu values in the contralateral mesiobasal temporal lobe (TL) cortex in all patient groups--the reduction of rCMRglu in homologous brain structures contralateral to the operated side provides evidence for stronger interhemispheric connections between both mesial TL structures than were hitherto supposed; and (3) a trend toward a normalization of rCMRglu values in the ipsilateral temporal neocortex 12 months after surgery in patients with MTLE syndrome
AD  - Neurological Department, University Hospital, Zurich, Switzerland
UR  - PM:7969971
ER  - 

TY  - JOUR
T1  - Histamine H1 receptors in complex partial seizures
A1  - Iinuma,K.
A1  - Yokoyama,H.
A1  - Otsuki,T.
A1  - Yanai,K.
A1  - Watanabe,T.
A1  - Ido,T.
A1  - Itoh,M.
Y1  - 1993/01/23/
N1  - UI - 93125016
SP  - 238
JF  - Lancet
VL  - 341
IS  - 8839
UR  - PM:8093514
ER  - 

TY  - JOUR
T1  - Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy
A1  - Olson,D.M.
A1  - Chugani,H.T.
A1  - Shewmon,D.A.
A1  - Phelps,M.E.
A1  - Peacock,W.J.
Y1  - 1990/11//
SP  - 731
EP  - 739
JF  - Epilepsia
VL  - 31
IS  - 6
N2  - The relationship between focal disturbances of glucose utilization demonstrated by positron emission tomography (PET) and electrophysiologic abnormalities defined by intraoperative electrocorticography (ECoG) was studied in eight children (aged 13 months to 12 years) who underwent cortical resection because of intractable seizures. None of the children had pure temporal lobe epilepsy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were normal in four of the eight children. The scalp electroencephalogram (EEG) showed lateralized interictal epileptiform abnormalities in all eight and lateralized ictal onset in five of eight. In seven children, interictal PET showed focal hypometabolism; the eighth child had focal, ictal hypermetabolism. ECoG at the time of surgery showed epileptiform spiking, slowing, and/or suppression of normal background activity that in every case corresponded to the focus on PET scan. The ECoG findings support the notion that in children with epilepsy focal metabolic abnormalities on PET correspond to electrophysiologically abnormal areas of cortex, which are presumably also the epileptogenic regions. Such areas can appear normal on anatomic imaging studies (CT and MRI). When ictal scalp EEG data are ambiguous or contradictory, PET provides a less invasive means than chronic grid or depth electrode recording for evaluating whether a localized epileptogenic area exists
AD  - Department of Neurology, UCLA School of Medicine 90024
UR  - PM:2245803
ER  - 

TY  - JOUR
T1  - Ipsilateral and contralateral thalamic hypometabolism as a predictor of outcome after temporal lobectomy for seizures
A1  - Newberg,A.B.
A1  - Alavi,A.
A1  - Berlin,J.
A1  - Mozley,P.D.
A1  - O'Connor,M.
A1  - Sperling,M.
Y1  - 2000/12//
SP  - 1964
EP  - 1968
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 41
IS  - 12
N2  - FDG PET is often used to help localize the seizure focus before surgery in patients with medically refractory temporal lobe epilepsy. However, the ability of certain patterns of metabolic landscape to predict postsurgical seizure outcome has not been well characterized. The purpose of this retrospective study was to determine whether FDG PET abnormalities elsewhere in the brain, in combination with those in the temporal lobes, can be used to predict seizure outcome after surgery. METHODS: Eighty patients with refractory temporal lobe seizures were imaged with PET after intravenous administration of 115 microCi/kg FDG. Images were interpreted without knowledge of clinical information by an experienced reviewer to determine seizure focus and regional metabolic changes in the brain. Metabolic activity scores were assigned for cortical and subcortical structures using the following criteria: 4 = normal activity, 3 = mildly decreased activity, 2 = moderately decreased activity, 1 = severely decreased activity, and 0 = no activity. A laterality index for each region was calculated using the equation 100 x [right - left]/[1/2 x (right + left)]. Seizure focus localization was based on the laterality of temporal lobe metabolic activity and was compared with that determined by scalp and depth electrodes and MRI results. Comparisons were made between asymmetries in metabolic activity in various brain structures and postoperative seizure frequency. Postoperative outcome was determined on the basis of cessation (complete disappearance of seizures) or continuation of seizure activity, regardless of frequency, compared with the preoperative state. RESULTS: All 64 patients who were free of seizures postoperatively had either no thalamic asymmetry or reduced metabolism on the side from which the temporal lobe was removed. In contrast, 5 of 16 patients (31%) with postoperative seizures of any frequency had hypometabolism in the thalamus contralateral to that of the removed temporal lobe. All 5 patients with reverse thalamic asymmetry had postoperative seizures. Patients with thalamic hypometabolism ipsilateral to the removed temporal lobe also had an increased risk of postoperative seizures, but this risk was not as high as in patients with the contralateral abnormality. In these patients, the temporal lobe (which appeared hypometabolic on PET) was determined to be the site of the seizure on the basis of information besides that provided by PET before surgery. CONCLUSION: This study indicated that, in patients with temporal lobe epilepsy, thalamic metabolic asymmetry, particularly in the reverse direction to that of the temporal lobe asymmetry, was associated with a poor postsurgical outcome compared with no or matched asymmetry. This determination may be important in evaluating patients for, and selecting optimal candidates for, surgical intervention
AD  - Department of Radiology, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia 19104, USA
UR  - PM:11138679
ER  - 

TY  - JOUR
T1  - Subcortical metabolic alterations in partial epilepsy
A1  - Sperling,M.R.
A1  - Gur,R.C.
A1  - Alavi,A.
A1  - Gur,R.E.
A1  - Resnick,S.
A1  - O'Connor,M.J.
A1  - Reivich,M.
Y1  - 1990/03//
N1  - UI - 90200951
SP  - 145
EP  - 155
JF  - Epilepsia
VL  - 31
IS  - 2
N2  - The function of subcortical nuclei in partial epilepsy was investigated using positron emission tomography (PET) to measure metabolism in the basal ganglia and thalamus. Sixteen patients undergoing surgical evaluation were studied with 18F-fluorodeoxyglucose (FDG) interictally and had intensive extracranial and intracranial electrophysiologic evaluations. Eight patients had left temporal lobe seizure foci, six had right temporal lobe foci, and two had right posterotemporal or parietal foci. The PET data were analyzed visually and quantitatively, using a multivariate analysis of variance on the quantitative data. Hypometabolism of subcortical nuclei was present ipsilateral to the cortical seizure focus. Cortical hypometabolism was noted focally in the temporal lobe in patients with left temporal lobe seizure foci, whereas patients with right temporal lobe seizure foci had diffuse hemispheric hypometabolism. We postulate that the subcortical hypometabolism is secondary to decreased efferent activity from temporal lobe structures, in particular amygdala and hippocampus, to subcortical nuclei. Diminished subcortical activity may then lead to defective regulation of cortical excitability in the temporal lobe, increasing the likelihood of seizure development and spread
AD  - Cerebrovascular Research Center, University of Pennsylvania, Philadelphia
UR  - PM:2108014
ER  - 

TY  - JOUR
T1  - Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans
A1  - Hilker,R.
A1  - Voges,J.
A1  - Ghaemi,M.
A1  - Lehrke,R.
A1  - Rudolf,J.
A1  - Koulousakis,A.
A1  - Herholz,K.
A1  - Wienhard,K.
A1  - Sturm,V.
A1  - Heiss,W.D.
Y1  - 2003/01//
N1  - UI - 22406153
SP  - 41
EP  - 48
JA  - Mov Disord.
VL  - 18
IS  - 1
N2  - Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment option in advanced Parkinson's disease (PD). Recent animal studies showed an increase of neuronal firing in dopaminergic neurons under effective STN-DBS. Increased striatal dopamine levels may also contribute to the stimulation's mechanism of action in humans. We investigated the striatal dopamine release in 6 patients with advanced PD under effective bilateral STN-DBS with positron emission tomography (PET) of the reversible dopamine-D2/3-receptor ligand [(11)C]raclopride (RACLO). Although STN-DBS proved to be a highly effective treatment in these subjects, we found no significant difference of the striatal RACLO binding between the STN-DBS-on and -off condition. The changes of radioligand binding did not correlate with the patients' improvement in clinical rating scales or with the stimulation amplitudes. Therefore, our PET data in living parkinsonian humans do not provide evidence for an increased striatal dopamine concentration under effective STN-DBS. We conclude that the modulation of dopaminergic activity does not seem to play a crucial role for the stimulation's mechanisms of action in parkinsonian humans
AD  - Department of Neurology, University Hospital, Cologne, Germany
UR  - PM:12518299
ER  - 

TY  - JOUR
T1  - Monosymptomatic resting tremor and Parkinson's disease: a multitracer positron emission tomographic study
A1  - Ghaemi,M.
A1  - Raethjen,J.
A1  - Hilker,R.
A1  - Rudolf,J.
A1  - Sobesky,J.
A1  - Deuschl,G.
A1  - Heiss,W.D.
Y1  - 2002/07//
N1  - UI - 22199477
SP  - 782
EP  - 788
JA  - Mov Disord.
VL  - 17
IS  - 4
N2  - We sought to elucidate the relationship between monosymptomatic resting tremor (mRT) and Parkinson's disease (PD). We studied eight mRT patients (mean Hoehn and Yahr [H&Y], 1.1 +/- 0.4), eight patients with PD (mean H&Y, 1.5 +/- 0.8), who showed all three classic parkinsonian symptoms, and seven age-matched healthy subjects. Subjects underwent cerebral magnetic resonance imaging (MRI) and multitracer positron emission tomography (PET) with 6-[(18)F]fluoro-L-dopa (F-dopa), [(18)F]fluorodeoxyglucose (FDG), and [(11)C]raclopride (RACLO). PD and mRT patients did not show significant differences in F-dopa-, RACLO-, or FDG-PET scans. In F-dopa- and RACLO-PET, significant differences between the pooled patient data and control subjects were found for the following regions: anterior and posterior putamen ipsilateral and contralateral to the more affected body side, and ipsilateral and contralateral putaminal gradients of the K(i) values. Furthermore, we found a difference for the normalized glucose values of the whole cerebellum between the control group (0.94 +/- 0.06) and PD patients (1.01 +/- 0.04; P < 0.05) but not for the mRT group (0.97 +/- 0.03). Our findings indicate that monosymptomatic resting tremor represents a phenotype of Parkinson's disease, with a nearly identical striatal dopaminergic deficit and postsynaptic D2-receptor upregulation in both patient groups. We suggest that the cerebellar metabolic hyperactivity in PD is closer related to akinesia and rigidity rather than to tremor
AD  - Klinik fur Neurologie der Universitat zu Koln, Koln, Germany
UR  - PM:12210876
ER  - 

TY  - JOUR
T1  - ANIMAL+INSECT: Improved cortical structure segmentation
A1  - Collins,D.L.
A1  - Zijdenbos,A.P.
A1  - Baare,W.F.C.
A1  - Evans,A.C.
Y1  - 1999///
N1  - Book in series
SP  - 210
EP  - 223
JF  - Information Processing in Medical Imaging, Proceedings
VL  - 1613
N2  - An algorithm for improved automatic segmentation of gross anatomical structures of the human brain is presented that merges the output of a tissue classification process with gross anatomical region masks, automatically defined by non-linear registration of a given data set with a probabilistic anatomical atlas. Experiments with 20 real MRI volumes demonstrate that the method is reliable, robust and accurate. Manually and automatically defined labels of specific gyri of the frontal lobe are similar, with a Kappa index of 0.657
UR  - ISI:000170515200016
ER  - 

TY  - JOUR
T1  - A 305-MEMBER MRI-BASED STEREOTAXIC ATLAS FOR CBF ACTIVATION STUDIES
A1  - Evans,A.C.
A1  - Collins,D.L.
Y1  - 1993///
N1  - Journal
SP  - 70
EP  - 71
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 5
UR  - ISI:A1993LB13800277
ER  - 

TY  - JOUR
T1  - EVALUATION OF ELASTIC MATCHING SYSTEM FOR ANATOMIC (CT, MR) AND FUNCTIONAL (PET) CEREBRAL IMAGES
A1  - Dann,R.
A1  - HOFORD,J.
A1  - KOVACIC,S.
A1  - Reivich,M.
A1  - Bajcsy,R.
Y1  - 1989///
N1  - Journal
SP  - 603
EP  - 611
JF  - Journal of Computer Assisted Tomography
VL  - 13
IS  - 4
UR  - ISI:A1989AG41700009
ER  - 

TY  - JOUR
T1  - A COMPUTERIZED SYSTEM FOR THE ELASTIC MATCHING OF DEFORMED RADIOGRAPHIC IMAGES TO IDEALIZED ATLAS IMAGES
A1  - Bajcsy,R.
A1  - LIEBERSON,R.
A1  - Reivich,M.
Y1  - 1983///
N1  - Journal
SP  - 618
EP  - 625
JF  - Journal of Computer Assisted Tomography
VL  - 7
IS  - 4
UR  - ISI:A1983QZ40500007
ER  - 

TY  - JOUR
T1  - Cerebral cortical localization: application and validation of the proportional grid system in MR imaging
A1  - Steinmetz,H.
A1  - Furst,G.
A1  - Freund,H.J.
Y1  - 1989/01//
N1  - UI - 89093583
SP  - 10
EP  - 19
JA  - J Comput.Assist.Tomogr.
VL  - 13
IS  - 1
N2  - The Talairach stereotactic proportional grid method for telencephalic localization was applied to magnetic resonance imaging of 30 brain hemispheres of healthy adult volunteers. Using sagittal images, outlines of the following characteristic principal sulci were identified on the brain surface to validate the method: callosal sulcus, parietooccipital sulcus, marginal sulcus, superomedial portion of central and postcentral sulcus, and posterior sylvian fissure. The maximal variation zones of sulcus location obtained by superimposition of the individual grid data on a standard proportional grid were similar to those originally reported by Talairach from pneumoencephalographic studies. However, the central sulcus, which was only studied postmortem by Talairach, was located 0.5-1 cm more posteriorly in the present study. Magnetic resonance also provided more detailed data on the considerable variation of the terminal parts of the sylvian fissure and on the well-known left-right asymmetries. The left sylvian fissure extended farther posteriorly in 11 of 15 brains. With the exception of this posterior perisylvian region, the proportional grid proved to be valid for indirect cerebral cortical localization in the regions studied
AD  - Department of Neurology, University of Dusseldorf, F.R.G
UR  - PM:2642922
ER  - 

TY  - JOUR
T1  - Very High-Resolution Morphometry Using Mass-Preserving Deformations and HAMMER Elastic Registration
A1  - Shen,D.
A1  - Davatzikos,C.
Y1  - 2003/01//
N1  - UI - 22396356
SP  - 28
EP  - 41
JF  - Neuroimage
VL  - 18
IS  - 1
N2  - This article presents a very high-resolution voxel-based morphometric method, by using a mass-preserving deformation mechanism and a fully automated spatial normalization approach, referred to as HAMMER. By using a hierarchical attribute-based deformation strategy, HAMMER partly overcomes limitations of several existing spatial normalization methods, and it achieves a level of accuracy that makes possible morphometric measurements of spatial specificity close to the voxel dimensions. The proposed method is validated by a series of experiments, with both simulated and real brain images
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Shen-HAMMER.pdf
ER  - 

TY  - JOUR
T1  - In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile
A1  - Agdeppa,E.D.
A1  - Kepe,V.
A1  - Petri,A.
A1  - Satyamurthy,N.
A1  - Liu,J.
A1  - Huang,S.-C.
A1  - Small,G.W.
A1  - Cole,G.M.
A1  - Barrio,J.R.
Y1  - 2003/03/31/
SP  - 723
EP  - 730
JF  - Neuroscience
VL  - 117
IS  - 3
N2  - Epidemiological studies have suggested that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of Alzheimer's disease (AD). The possible neuroprotection by NSAIDs in AD is generally attributed to anti-inflammatory activity. An additional mode of drug action may involve anti-aggregation of [beta]-amyloid (A[beta]) peptides by commonly used NSAIDs. We utilized in vitro competition assays, autoradiography, and fluorescence microscopy with AD brain specimens to demonstrate concentration-dependent decreases in the binding of the in vivo molecular imaging probe, 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP), against (S)-naproxen and (R)- and (S)-ibuprofen (but not diclofenac) to A[beta] fibrils and ex vivo A[beta] senile plaques. Conversely, in vitro amyloid dyes Congo Red and Thioflavine T were demonstrated in the same experiments not to bind to the FDDNP binding site. FDDNP and the NSAIDs that share the same binding site also exhibit anti-aggregation effects on A[beta] peptides, suggesting that the shared binding site on A[beta] fibrils and plaques may be a site of anti-aggregation drug action.Our results indicate for the first time the binding of select NSAIDs to plaques, specifically to the binding site of the molecular imaging probe [18F]FDDNP. Our understanding of the molecular requirements of FDDNP binding may help in the optimization of the A[beta] anti-aggregation potency of experimental drugs. [18F]FDDNP has been used to image plaques in vivo with positron emission tomography (PET), and investigations into the influence of A[beta] anti-aggregation on the risk-reduction effects of NSAIDs on AD could utilize [18F]FDDNP and PET in determining the occupancy rate of NSAIDs and experimental drugs in plaques in the living brain of AD patients
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Agdeppa-FDDNP-Ibuprofen.pdf
ER  - 

TY  - JOUR
T1  - Tracer-kinetic models for measuring cerebral blood flow using externally detected radiotracers
A1  - Larson,K.B.
A1  - Markham,J.
A1  - Raichle,M.E.
Y1  - 1987/08//
N1  - UI - 87280421
SP  - 443
EP  - 463
JA  - J Cereb.Blood Flow Metab
VL  - 7
IS  - 4
N2  - All tracer-kinetic models currently employed with positron-emission tomography (PET) are based on compartmental assumptions. Our first indication that a compartmental model might suffer from severe limitations in certain circumstances when used with PET occurred when we implemented the Kety tissue-autoradiography technique for measuring CBF and observed that the resulting CBF estimates, rather than remaining constant (to within predictable statistical uncertainty) as expected, fell with increasing scan duration T when T greater than 1 min. After ruling out other explanations, we concluded that a one-compartment model does not possess sufficient realism for adequately describing the movement of labeled water in brain. This article recounts our search for more realistic substitute models. We give our derivations and results for the residue-detection impulse responses for unit capillary-tissue systems of our two candidate distributed-parameter models. In a sequence of trials beginning with the simplest, we tested four progressively more detailed candidate models against data from appropriate residue-detection experiments. In these, we generated high-temporal-resolution counting-rate data reflecting the history of radiolabeled-water uptake and washout in the brains of rhesus monkeys. We describe our treatment of the data to yield model-independent empirical values of CBF and of other parameters. By substituting these into our trial-model functions, we were able to make direct comparisons of the model predictions with the experimental dynamic counting-rate histories, confirming that our reservations concerning the one-compartment model were well founded and obliging us to reject two others. We conclude that a two-barrier distributed-parameter model has the potential of serving as a substitute for the Kety model in PET measurements of CBF in patients, especially when scan durations for T greater than 1 min are desired
UR  - PM:3611204
ER  - 

TY  - JOUR
T1  - Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals
A1  - Dishino,D.D.
A1  - Welch,M.J.
A1  - Kilbourn,M.R.
A1  - Raichle,M.E.
Y1  - 1983/11//
N1  - UI - 84035332
SP  - 1030
EP  - 1038
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 24
IS  - 11
N2  - The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log Poct (partition coefficient for octanol/water) values of these compounds range from --0.7 to greater than 4.0. A parabolic relationship was found between the log Poct value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log Poct values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral blood flow of 100 ml X min-1 X hg-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log Poct value of between 0.9 and 2.5
UR  - PM:6605416
ER  - 

TY  - JOUR
T1  - Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis
A1  - Herscovitch,P.
A1  - Markham,J.
A1  - Raichle,M.E.
Y1  - 1983/09//
N1  - UI - 83293597
SP  - 782
EP  - 789
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 24
IS  - 9
N2  - The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia of the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship
UR  - PM:6604139
ER  - 

TY  - JOUR
T1  - Average blood flow and oxygen uptake in the human brain during resting wakefulness: a critical appraisal of the Kety-Schmidt technique
A1  - Madsen,P.L.
A1  - Holm,S.
A1  - Herning,M.
A1  - Lassen,N.A.
Y1  - 1993/07//
N1  - UI - 93301016
SP  - 646
EP  - 655
JA  - J Cereb.Blood Flow Metab
VL  - 13
IS  - 4
N2  - The Kety-Schmidt technique can be regarded as the reference method for measurement of global average cerebral blood flow (average CBF) and global average cerebral metabolic rate of oxygen (average CMRO2). However, in the practical application of the method, diffusion equilibrium for inert gas tracer between the brain and its venous blood is not reached. As a consequence, normal values for CBF and CMRO2 of 54 ml 100 g-1 min-1 and 3.5 ml 100 g-1 min-1 obtained with the Kety-Schmidt technique are an overestimation of the true values. Using the Kety-Schmidt technique we have performed 57 measurements of CBF and CMRO2 during EEG-verified wakeful rest in young normal adults. In order to estimate the equilibrium values for CBF and CMRO2, a simple computer-based simulation model was employed to quantitate the systematic overestimation caused by incomplete tracer equilibrium. When correcting the measured data, we find that the true average values for CBF and CMRO2 in the healthy young adult are approximately 46 ml 100 g-1 min-1 and approximately 3.0 ml 100 g-1 min-1. Previous studies have suggested that some of the variation in CMRO2 values could be ascribed to differences in cerebral venous anatomy. However in the present study, no correlation between CMRO2 and cerebral venous anatomy as imaged by magnetic resonance angiography could be established. Our data show that the interindividual variation of CMRO2 is 11% (coefficient of variation)
AD  - Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital, Copenhagen, Denmark
UR  - PM:8314918
ER  - 

TY  - JOUR
T1  - A system for cerebral blood flow measurement using an H215O autoradiographic method and positron emission tomography
A1  - Kanno,I.
A1  - Iida,H.
A1  - Miura,S.
A1  - Murakami,M.
A1  - Takahashi,K.
A1  - Sasaki,H.
A1  - Inugami,A.
A1  - Shishido,F.
A1  - Uemura,K.
Y1  - 1987/04//
N1  - UI - 87166227
SP  - 143
EP  - 153
JA  - J Cereb.Blood Flow Metab
VL  - 7
IS  - 2
N2  - A system for CBF measurement using an H215O autoradiographic method and positron emission tomography (PET) has been designed and installed as a clinical tool. Following an intravenous injection of H215O, a radioactivity accumulation in the brain tissue for 60 s and a continuous record of radioactivity in arterial blood were measured by a high counting speed PET device and a beta-ray detector, respectively, and CBF was calculated by a table-lookup procedure. First, this method was compared with the C15O2 inhalation steady-state method on 17 cerebrovascular disease patients and four normal subjects. The two values for CBF agreed with each other when H215O autoradiographic method was applied by correction for the dispersion in the measured arterial radioactivity-time curve. However, without the correction, the CBF by the H215O autoradiographic method revealed substantial overestimation by 30.6 +/- 17.5%. A reduced gray/white ratio of CBF was also observed in the H215O autoradiographic method. Second, simulation was performed in order to determine optimal accumulation time by PET scan; the result was that errors due to dispersion and time mismatch became critical as the accumulation time was shortened to less than 60 s
UR  - PM:3558497
ER  - 

TY  - JOUR
T1  - Remote effects in MCA territory ischemic infarction: a study of regional cerebral blood flow and oxygen metabolism using positron computed tomography and 15O labeled gases
A1  - Shishido,F.
A1  - Uemura,K.
A1  - Inugami,A.
A1  - Ogawa,T.
A1  - Yamaguchi,T.
A1  - Kanno,I.
A1  - Murakami,M.
A1  - Tagawa,K.
A1  - Yasui,N.
Y1  - 1987/03//
N1  - UI - 88017132
SP  - 36
EP  - 41
JA  - Radiat.Med
VL  - 5
IS  - 2
N2  - Using positron computed tomography (PCT) and the 15O labeled gas steady-state inhalation technique, regional cerebral blood flow (rCBF), cerebral oxygen consumption (rCMRO2), and oxygen extraction fraction (rOEF) can be measured quantitatively in humans. We quantitatively examined the relationship between focal ischemic lesions and intact regions as detected by X-ray CT in such areas as the territory of the contralateral middle cerebral artery (MCA), thalami, pons, and cerebellar hemispheres. Twenty-three PCT measurements in 13 patients with unilateral ischemic infarction in the MCA territory as detected by X-ray CT were performed. Remote effects from cerebral infarction of the MCA territory were observed in the contralateral MCA territory, ipsilateral thalamus, brainstem, and contralateral cerebellar hemisphere. Slight depression of rCBF and rCMRO2 was also observed in the contralateral thalamus and ipsilateral cerebral hemisphere; rOEF was normal in these areas. Though the depression of rCBF and rCMRO2 due to remote effects was detected in all periods, it was mildly observed 0 to 6 days after onset. The reduction of rCBF and rCMRO2 due to remote effects was less than the morphological as well as the functional threshold. The phenomenon is probably caused by neuronal deactivation, and the regions with depressed blood flow and metabolism may be in a "resting" state
AD  - Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, Japan
UR  - PM:3498974
ER  - 

TY  - JOUR
T1  - Two methods for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations
A1  - Kanno,I.
A1  - Lassen,N.A.
Y1  - 1979/02//
N1  - UI - 79130860
SP  - 71
EP  - 76
JA  - J Comput.Assist.Tomogr.
VL  - 3
IS  - 1
N2  - Two methods are described for calculation of regional cerebral blood flow from completed tomographic data of radioactive inert gas distribution in a slice of brain tissue. It is assumed that the tomographic picture gives the average inert gas concentration in each pixel over data collection periods of 30 to 60 sec. In the early picture method a single picture taken during maximum inert gas concentration (by intaarterial injection or by inhalation) is analyzed. In the sequence of pictures method the alterations in local inert gas concentration are followed over time. The proposed methods are implemented using synthetic data of xenon-133 emission computed tomography and some of the difficulties likely to be encountered in practice are stressed
UR  - PM:422795
ER  - 

TY  - JOUR
T1  - Cerebral blood flow using PET measurements of fluoromethane kinetics
A1  - Holden,J.E.
A1  - Gatley,S.J.
A1  - Hichwa,R.D.
A1  - Ip,W.R.
A1  - Shaughnessy,W.J.
A1  - Nickles,R.J.
A1  - Polcyn,R.E.
Y1  - 1981/12//
N1  - UI - 82077314
SP  - 1084
EP  - 1088
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 22
IS  - 12
UR  - PM:6975809
ER  - 

TY  - JOUR
T1  - Examination of assumptions for local cerebral blood flow studies in PET
A1  - Koeppe,R.A.
A1  - Hutchins,G.D.
A1  - Rothley,J.M.
A1  - Hichwa,R.D.
Y1  - 1987/11//
N1  - UI - 88035229
SP  - 1695
EP  - 1703
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 28
IS  - 11
N2  - Two common assumptions made in most positron emission tomography (PET) cerebral blood flow techniques have been examined in detail. These are (1) that the blood-borne radioactivity component in the measured PET data is negligible, and (2) that differences in arrival time of the arterial bolus across the brain cause insignificant biases in the estimated cerebral blood flow (CBF) values. Biases in CBF values due to partial failure of these assumptions have been predicted by computer simulation studies and also quantitated for both dynamic and single scan PET methods using H2 15O. Both computer simulations and measured PET data indicate that these assumptions can sometimes cause significant errors in the estimated flow values. The magnitude of these errors depends on the PET technique used (dynamic or static) and on the interval of data included in the flow calculations. The bias caused when these assumptions fail can be considerably reduced by omitting approximately 40 sec of data immediately following tracer administration from the CBF calculations
AD  - Cyclotron/P.E.T. Facility, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0552
UR  - PM:3499491
ER  - 

TY  - JOUR
T1  - Epilepsy surgery improves regional glucose metabolism on PET scan. A case report
A1  - Dasheiff,R.M.
A1  - Rosenbek,J.
A1  - Matthews,C.
A1  - Nickles,R.J.
A1  - Koeppe,R.A.
A1  - Hutchins,G.D.
A1  - Ramirez,L.
A1  - Dickinson,L.V.
Y1  - 1987/06//
N1  - UI - 87282502
SP  - 283
EP  - 288
JA  - J Neurol
VL  - 234
IS  - 5
N2  - A patient with medically intractable complex partial epilepsy was evaluated for epilepsy surgery by electro-encephalograph recording with depth electrodes and 18F-fluorodeoxyglucose positron emission tomography (PET). A small calcified arteriovenous malformation was excised from the left parietal lobe, and the patient became seizure free. Baseline and language stimulation PET scans were obtained preoperatively and 10 months postoperatively. There was a significant increase in glucose metabolism of the left temporal lobe postoperatively, which we interpret as evidence of improved neuronal function. We suggest that this case represents evidence for a functional, and reversible, inhibition of neuronal metabolism by epileptic activity
UR  - PM:3497232
ER  - 

TY  - JOUR
T1  - The effect of nimodipine on the evolution of human cerebral infarction studied by PET
A1  - Hakim,A.M.
A1  - Evans,A.C.
A1  - Berger,L.
A1  - Kuwabara,H.
A1  - Worsley,K.
A1  - Marchal,G.
A1  - Biel,C.
A1  - Pokrupa,R.
A1  - Diksic,M.
A1  - Meyer,E.
Y1  - 1989/08//
N1  - UI - 89292070
SP  - 523
EP  - 534
JA  - J Cereb.Blood Flow Metab
VL  - 9
IS  - 4
N2  - Fourteen patients were studied by positron emission tomography (PET) within 48 h of onset of a hemispheric ischemic stroke and again 7 days later. After the first set of PET scans, the patients were randomized to receive either nimodipine (n = 7) or a carrier solution (n = 7) by intravenous infusion. The infusions were maintained until the end of the second PET studies. CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), CMRO2, and CMRglc were measured each time. These metabolic and perfusion measurements were performed by standard methods. A surface map of each metabolic and perfusion measurement in the cortical mantle was generated by interpolating between the available slices. The various surface maps representing the physiological characteristics determined in the same or subsequent studies were aligned so that all data sets could be analyzed identically using an array of square regions of interest (ROIs). The functional status of each ROI was recorded at the two intervals following the cerebrovascular accident to characterize the evolution of the infarct, penumbra, and normal brain regions. We presumed the ischemic penumbra to be cortical regions in the proximity of the infarct and perfused at CBF values between 12 and 18 ml/100 g/min on the first PET scan, while densely ischemic regions had CBF of less than 12 nl/100 g/min and normally perfused brain greater than 18 ml/100 g/min. In the densely ischemic zone, CBF increased more in the nimodipine-treated group than in the carrier group. As well, in this region nimodipine reversed the decline in CMRO2 noted in the carrier group, the difference in the changes being significant. In the penumbra zone, comparable trends were noted in OER and CMRO2 but the difference in the changes between the two groups did not reach statistical significance. Changes in CMRglc and CBV were comparable between the two groups in both cortical regions
AD  - McConnell Brain Imaging Centre, Montreal Neurological Institute, Quebec, Canada
UR  - PM:2661584
ER  - 

TY  - JOUR
T1  - Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET
A1  - Meyer,E.
Y1  - 1989/06//
N1  - UI - 89293317
SP  - 1069
EP  - 1078
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 30
IS  - 6
N2  - The difference in tracer arrival times between the radial artery and the brain following i.v. injection of 15O-labeled water plus the difference in dispersion of the tracer bolus between these two sites have to be accounted for in order to quantify cerebral blood flow by the autoradiographic approach and positron emission tomography (PET). We describe a method that simultaneously corrects for these two effects by means of a four-parameter fit to the dynamically acquired data. Unlike with other methods, where the two corrections are performed sequentially, no additional measurement of the dispersion time constant is required. We have validated and tested the method by means of simulations and application to data from six human studies. The mean dispersion time constant of 4.0 +/- 1.2 sec, estimated by the new method for the six studies, is in fair agreement with estimates of 3 to 5 sec derived from cardiac PET
AD  - McConnell Brain Imaging Centre, Montreal Neurological Institute, Quebec, Canada
UR  - PM:2786948
ER  - 

TY  - JOUR
T1  - Permeability of capillaries in various organs as determined by use of the indicator diffusion method
A1  - Crone,C.
Y1  - 1963///
SP  - 292
EP  - 305
JA  - Acta Physiol.Scand.
VL  - 58
ER  - 

TY  - JOUR
T1  - Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors
A1  - Ericson,K.
A1  - Lilja,A.
A1  - Bergstrom,M.
A1  - Collins,V.P.
A1  - Eriksson,L.
A1  - Ehrin,E.
A1  - von Holst,H.
A1  - Lundqvist,H.
A1  - Langsrom,B.B.
A1  - Mosskin,M.
Y1  - 1985/07//
SP  - 683
EP  - 689
JA  - J Comput.Assist.Tomogr.
VL  - 9
IS  - 4
N2  - Sixteen patients with supratentorial tumors were examined with positron emission tomography (PET) using [( 11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA as well as CT. There were nine astrocytomas (grade II), three oligoastrocytomas (grade II), two anaplastic astrocytomas (grade III), and two meningiomas. Six patients with low-grade astrocytomas and all three patients with oligoastrocytomas had an accumulation of [11C]methionine varying from slightly to intensely increased as compared with normal brain tissue. There was a markedly increased uptake of methionine in the anaplastic astrocytomas. Three of the low-grade astrocytomas had a decreased uptake of [11C]methionine in at least part of the tumor as compared with normal brain tissue. Contrast enhancement on CT or uptake of [68Ga]EDTA was not a prerequisite for increased accumulation of methionine. Uptake of [11C]glucose was lower than or equal to that of normal brain tissue in the low-grade tumors and also in one of the two anaplastic astrocytomas and in the bulk of the other. In each individual case the methionine uptake tended to be higher--or less decreased--than the glucose uptake. In the low-grade tumors the uptake of methionine and that of glucose were often different, occasionally markedly different, as far as the tumoral-peritumoral areas involved. These differences were even more remarkable in the two anaplastic astrocytomas. An increased uptake of methionine was often seen in areas appearing normal on CT. It appears that PET with [11C]glucose has limitations with regard to delineation of the low-grade astrocytomas, whereas PET with [11C]methionine usually better reflects the extent of these tumors and, to a lesser degree, the extent of the high-grade neoplasms. The results of PET with [68Ga]EDTA were similar to those with postcontrast CT in most patients. The two meningiomas exhibited a high uptake of all tracers used for PET as well as a marked contrast enhancement on CT. The extent of the meningiomas judged by PET with the various tracers correlated well with the extent assessed by postcontrast CT
UR  - PM:3926834
ER  - 

TY  - JOUR
T1  - Pharmacokinetics of 11C-labelled BCNU and SarCNU in gliomas studied by PET
A1  - Mitsuki,S.
A1  - Diksic,M.
A1  - Conway,T.
A1  - Yamamoto,Y.L.
A1  - Villemure,J.G.
A1  - Feindel,W.
Y1  - 1991/02//
N1  - UI - 91217715
SP  - 47
EP  - 55
JA  - J Neurooncol.
VL  - 10
IS  - 1
N2  - This paper describes the study of the pharmacodynamics of two 11C-labelled nitrosoureas, 1,3-bis-(2-chloroethyl) nitrosourea (BNCU) and sarcosinamide chloroethylnitrosourea (SarCNU), both labelled in the carbonyl position. Distribution of the radioactivity as measured by positron emission tomography was compared to the distribution of radioactivity observed after injection of 68Ga-EDTA, this being used as an indicator of the blood-brain barrier integrity around the brain tumor. Data suggest that the new nitrosourea, SarCNU, most likely enters brain tissue by different mechanism(s) than BCNU, which enters by diffusion. Data also indicate that use of SarCNU may result in a better tumor to brain ratio than BCNU
AD  - McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Quebec, Canada
UR  - PM:1902507
ER  - 

TY  - JOUR
T1  - Quantitation of blood-brain barrier permeability by positron emission tomography
A1  - Webb,S.
A1  - Ott,R.J.
A1  - Cherry,S.R.
Y1  - 1989/12//
N1  - UI - 90139259
SP  - 1767
EP  - 1771
JA  - Phys.Med Biol.
VL  - 34
IS  - 12
AD  - Joint Department of Physics, Institute of Cancer Research, Sutton, Surrey, UK
UR  - PM:2515552
ER  - 

TY  - JOUR
T1  - Quantitative assessment of blood-brain barrier permeability in multiple sclerosis using 68-Ga-EDTA and positron emission tomography
A1  - Pozzilli,C.
A1  - Bernardi,S.
A1  - Mansi,L.
A1  - Picozzi,P.
A1  - Iannotti,F.
A1  - Alfano,B.
A1  - Bozzao,L.
A1  - Lenzi,G.L.
A1  - Salvatore,M.
A1  - Conforti,P.
Y1  - 1988/08//
N1  - UI - 89110311
SP  - 1058
EP  - 1062
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 51
IS  - 8
N2  - Fifteen patients with definite multiple sclerosis were examined with high volume delayed (HVD) CT scan and positron emission tomography (PET) using 68-Ga-EDTA as a tracer. The passage of 68-Ga-EDTA across the blood-brain barrier (BBB) was measured by using multiple graphical analysis. This method permits the simultaneous calculation of a blood to brain influx constant Ki (ml/g-1 min-1) and of the plasma volume Vp (ml/g-1). Focal areas of abnormal CT enhancement and pathological accumulation of 68-Ga-EDTA were visualised in four patients who were all examined during a clinical exacerbation of the disease. The mean Ki value measured in these areas was 12.5, SD 3.4 indicating a moderate but significant increase of BBB permeability compared with the value found in normal tissue (3.2, SD 0.9). No parallel increase in Vp values was found in these pathological areas. Quantitative data obtained with PET seems to provide further insight into the study of BBB function in multiple sclerosis
AD  - Department of Neurological Sciences, University of Rome La Sapienza, Italy
UR  - PM:3145963
ER  - 

TY  - JOUR
T1  - Simplified, noninvasive PET measurement of blood-brain barrier permeability
A1  - Iannotti,F.
A1  - Fieschi,C.
A1  - Alfano,B.
A1  - Picozzi,P.
A1  - Mansi,L.
A1  - Pozzilli,C.
A1  - Punzo,A.
A1  - Del Vecchio,G.
A1  - Lenzi,G.L.
A1  - Salvatore,M.
Y1  - 1987/05//
N1  - UI - 87195610
SP  - 390
EP  - 397
JA  - J Comput.Assist.Tomogr.
VL  - 11
IS  - 3
N2  - Blood-brain barrier (BBB) permeability to [68Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the [68Ga]EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes
UR  - PM:3106433
ER  - 

TY  - JOUR
T1  - Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography
A1  - Schlageter,N.L.
A1  - Carson,R.E.
A1  - Rapoport,S.I.
Y1  - 1987/02//
N1  - UI - 87109535
SP  - 1
EP  - 8
JA  - J Cereb.Blood Flow Metab
VL  - 7
IS  - 1
N2  - Positron emission tomography with [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA) was used to examine the integrity of the blood-brain barrier (BBB) in five patients with dementia of the Alzheimer type and in five healthy age-matched controls. Within a scanning time of 90 min, there was no evidence that measurable intravascular tracer entered the brain in either the dementia or the control group. An upper limit for the cerebrovascular permeability-surface area product of [68Ga]EDTA was estimated as 2 X 10(-6) s-1 in both groups. The results provide no evidence for breakdown of the BBB in patients with dementia of the Alzheimer type
UR  - PM:3100543
ER  - 

TY  - JOUR
T1  - Measurement of blood-brain barrier permeability with positron emission tomography and [68Ga]EDTA
A1  - Kessler,R.M.
A1  - Goble,J.C.
A1  - Bird,J.H.
A1  - Girton,M.E.
A1  - Doppman,J.L.
A1  - Rapoport,S.I.
A1  - Barranger,J.A.
Y1  - 1984/09//
N1  - UI - 84289720
SP  - 323
EP  - 328
JA  - J Cereb.Blood Flow Metab
VL  - 4
IS  - 3
N2  - Positron emission tomography (PET) was employed to examine time-dependent changes in blood-brain barrier (BBB) permeability to [68Ga]ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product (PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to [68Ga]EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions
UR  - PM:6432806
ER  - 

TY  - CHAP
T1  - The blood brain barrier
A1  - Pardridge,W.M.
Y1  - 2002///
SP  - 119
EP  - 139
VL  - 2
T2  - Cerebral blood flow and metabolism
A2  - Edvinsson,L.
A2  - Krause,D.N.
IS  - 7
CY  - Philadelphia, Pa.
PB  - Lippincott Williams & Wilkins
ER  - 

TY  - CHAP
T1  - Blood-brain-cerebrospinal fluid barriers
A1  - Betz,A.L.
A1  - Goldstein,G.W.
A1  - Katzman,R.
Y1  - 2003///
SP  - 681
EP  - 699
T2  - Basic neurochemistry
A2  - Siegel,G.J.
A2  - Agranoff,B.W.
A2  - Albers,R.W.
A2  - Molinoff,P.W.
IS  - 32
CY  - New York, NY
PB  - Raven Press
ER  - 

TY  - JOUR
T1  - Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[18F]Fluoro-dopa on the Relation Between the 18F-Fluorodopa Tissue Input Uptake Rate Constant Kocc and the [18F]Fluorodopa Plasma Input Uptake Rate Constant Ki
A1  - Sossi,V.
A1  - Holden,J.E.
A1  - Fuente-Fernandez,R.
A1  - Ruth,T.J.
A1  - Stoessl,A.J.
Y1  - 2003/03//
N1  - UI - 22508241
SP  - 301
EP  - 309
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 3
N2  - Parkinson disease is characterized by the loss of dopaminergic neurons, thus decreasing the system's ability to produce and store dopamine (DA). Such ability is often investigated using F-fluorodopa (FD) positron emission tomography. A commonly used model to investigate the DA synthesis and storage rate is the modified Patlak graphical approach. This approach allows for both plasma and tissue input functions, yielding the respective uptake rate constants K and K. This method requires the presence of an irreversible compartment and the absence of any nontrapped tracer metabolite. In the case of K, this last assumption is violated by the presence of the FD metabolite 3- -methyl-[ F]fluoro-dopa (3OMFD), which makes the K evaluation susceptible to a downward bias. It was found that both K and K are influenced by DA loss and thus are not pure measures of DA synthesis and storage. In the case of K, the presence of 3OMFD exacerbates the effect of DA egress, thus introducing a disease-dependent bias in the K determination. These findings imply that K and K provide different assessments of disease severity and that, as disease progresses, K and especially K become more related to DA storage capacity and less to the DA synthesis rate.(i) (occ) (occ) (occ) (i) (occ) (occ) (occ) (i) (occ) (i) (occ)
UR  - PM:12621305
ER  - 

TY  - JOUR
T1  - Noninvasive quantification of rCBF using positron emission tomography
A1  - Watabe,H.
A1  - Itoh,M.
A1  - Cunningham,V.
A1  - Lammertsma,A.A.
A1  - Bloomfield,P.
A1  - Mejia,M.
A1  - Fujiwara,T.
A1  - Jones,A.K.P.
A1  - Jones,T.
A1  - Nakamura,T.
Y1  - 1996///
N1  - Journal
SP  - 311
EP  - 319
JF  - Journal of Cerebral Blood Flow and Metabolism
VL  - 16
IS  - 2
N2  - This study proposes a new method for the pixel-by-pixel quantification of regional CBF (rCBF) with positron emission tomography and (H2O)-O-15 by using a reference tissue region. No arterial blood is required. Simulation studies revealed that the calculation of rCBF was fairly stable provided that the frame time was relatively short compared with total scan time. In practice, calculated CBF images correlated significantly with those obtained with the dynamic/integral method. Because the method accurately detects changes in CBF, it is particularly suitable for brain activation studies
UR  - ISI:A1996TW39300017
ER  - 

TY  - JOUR
T1  - Whole-body distribution and dosimetry of O-(2-[(18)F]fluoroethyl)-l-tyrosine
A1  - Pauleit,D.
A1  - Floeth,F.
A1  - Herzog,H.
A1  - Hamacher,K.
A1  - Tellmann,L.
A1  - Muller,H.W.
A1  - Coenen,H.H.
A1  - Langen,K.J.
Y1  - 2003/02/15/
N1  - UI - 0
SP  - 519
EP  - 524
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - The whole-body distribution of O-(2-[(18)F]fluoroethyl)- l-tyrosine (FET) was studied in seven patients with brain tumours by positron emission tomography (PET). Based on the IMEDOSE and MIRDOSE procedures, radiation absorbed doses were estimated from whole-body PET scans acquired approximately 70 and 200 min after i.v. injection of 400 MBq FET. After injection of FET, the peak of radioactivity in the blood was observed after 1.5 min, and a plateau of nearly constant radioactivity was reached at 20 min. The whole-body distribution of FET showed the highest activities in the urinary tract. All other organs exhibited only moderate FET uptake (SUV </=1.6) which remained constant between early and late PET scans. No increased uptake was seen in the bone, the biliary tract or the pancreas. Twenty-two percent of the injected activity was excreted 5 h p.i. (approx. 5.3% ID/h). The highest absorbed dose was found for the urinary bladder wall. The effective dose according to ICRP 60 was 16.5 micro Sv/MBq for adults, which would lead to an effective dose of 6.1 mSv in a PET study using 370 MBq FET
AD  - Clinic of Nuclear Medicine, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
UR  - PM:12589478
ER  - 

TY  - JOUR
T1  - 86Y-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (SMT487)-a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion
A1  - Jamar,F.
A1  - Barone,R.
A1  - Mathieu,I.
A1  - Walrand,S.
A1  - Labar,D.
A1  - Carlier,P.
A1  - De Camps,J.
A1  - Schran,H.
A1  - Chen,T.
A1  - Smith,M.C.
A1  - Bouterfa,H.
A1  - Valkema,R.
A1  - Krenning,E.P.
A1  - Kvols,L.K.
A1  - Pauwels,S.
Y1  - 2003/02/12/
N1  - UI - 0
JA  - Eur.J Nucl Med Mol.Imaging
N2  - The pharmacokinetics and dosimetry of (86)Y-DOTA(0)- d-Phe(1)-Tyr(3)-octreotide ((86)Y-SMT487) were evaluated in a phase I positron emission tomography (PET) study of 24 patients with somatostatin receptor-positive neuroendocrine tumours. The effect of amino acid (AA) co-infusion on renal and tumour uptake was assessed in a cross-over randomised setting. Five regimens were tested: no infusion, 4-h infusion of 120 g mixed AA (26.4 g l-lysine + l-arginine), 4 h l-lysine (50 g), 10 h 240 g mixed AA (52.8 g l-lysine + l-arginine) and 4 h Lys-Arg (25 g each). Comparisons were performed on an intra-patient basis. Infusions of AA started 0.5 h prior to injection of (86)Y-SMT487 and PET scans were obtained at 4, 24 and 48 h p.i. Absorbed doses to tissues were computed using the MIRD3 method. (86)Y-SMT487 displayed rapid plasma clearance and exclusive renal excretion; uptake was noted in kidneys, tumours, spleen and, to a lesser extent, liver. The 4-h mixed AA co-infusion significantly ( P<0.05) reduced (86)Y-SMT487 renal uptake by a mean of 21%. This protective effect was significant on the dosimetry data (3.3+/-1.3 vs 4.4+/-1.0 mGy/MBq; P<0.05) and was further enhanced upon prolonging the infusion to 10 h (2.1+/-0.4 vs 1.7+/-0.2 mGy/MBq; P<0.05). Infusion of Lys-Arg but not of l-lysine was more effective in reducing renal uptake than mixed AA. Infusion of AA did not result in reduced tumour uptake. The amount of (90)Y-SMT487 (maximum allowed dose: MAD) that would result in a 23-Gy cut-off dose to kidneys was calculated for each study: MAD was higher with mixed AA co-infusion by a mean of 46% (10-114%, P<0.05 vs no infusion). In comparison with 4 h mixed AA, the MAD was higher by a mean of 23% (9-37%; P<0.05) with prolonged infusion and by a mean of 16% (2-28%; P<0.05) with Lys-Arg. We conclude that infusion of large amounts of AA reduces renal exposure during peptide-based radiotherapy and allows higher absorbed doses to tumours. The prolongation of the infusion from 4 to 10 h further enhances the protective effect on the kidneys
AD  - Centre of Nuclear Medicine and Laboratory of Positron Emission Tomography, University of Louvain Medical School, Brussels and Louvain-la-Neuve, UCL 54.30, Avenue Hippocrate, 54, 1200, Brussels, Belgium
UR  - PM:12582815
ER  - 

TY  - JOUR
T1  - Synthesis, structure-activity relationship, and evaluation of SR141716 analogues: development of central cannabinoid receptor ligands with lower lipophilicity
A1  - Katoch-Rouse,R.
A1  - Pavlova,O.A.
A1  - Caulder,T.
A1  - Hoffman,A.F.
A1  - Mukhin,A.G.
A1  - Horti,A.G.
Y1  - 2003/02/13/
N1  - UI - 22459087
SP  - 642
EP  - 645
JA  - J Med Chem.
VL  - 46
IS  - 4
N2  - Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented
AD  - Neuroimaging Research Branch and Cellular Neurophysiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA
UR  - PM:12570386
ER  - 

TY  - JOUR
T1  - What's your favorite PET story?
A1  - Bryan,R.N.
Y1  - 1998/03//
N1  - Coexistence of necrosis and recurrent tumor, comment on Ricci et al.
SP  - 590
JA  - AJNR Am.J Neuroradiol.
VL  - 19
IS  - 3
UR  - PM:9541326
ER  - 

TY  - JOUR
T1  - Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful?
A1  - Forsyth,P.A.
A1  - Kelly,P.J.
A1  - Cascino,T.L.
A1  - Scheithauer,B.W.
A1  - Shaw,E.G.
A1  - Dinapoli,R.P.
A1  - Atkinson,E.J.
Y1  - 1995/03//
N1  - UI - 95165211
SP  - 436
EP  - 444
JA  - J Neurosurg
VL  - 82
IS  - 3
N2  - Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of 3 or 4 (p = 0.005). In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates
AD  - Department of Neurology, Mayo Clinic, Rochester, Minnesota
UR  - PM:7861222
ER  - 

TY  - JOUR
T1  - Histological observations on the regrowth of malignant gliomas after radiotherapy and chemotherapy
A1  - Schiffer,D.
A1  - Giordana,M.T.
A1  - Soffietti,R.
A1  - Sciolla,R.
Y1  - 1982///
N1  - UI - 83123021
SP  - 291
EP  - 299
JA  - Acta Neuropathol.(Berl)
VL  - 58
IS  - 4
N2  - The reproliferation of glioblastomas after radiation and chemotherapy has been studied in 25 tumors by means of whole mount histological preparations. The tumors have been subdivided into four groups according to the radiation dose and the distance from the end of radiation. After 4,000 rad vessel proliferations and mitoses stop, while vessel degenerations and astrocytes with deformed nuclei appear. Six months after 6,000 rad have been delivered, repopulation phenomena are clearly evident and are mainly represented by mitoses both in parenchyma and in the vessel walls, circumscribed necroses with pseudopalisadings, proliferations of formerly degenerated vessels, etc. The brain adjacent to tumor (BAT) has a great importance since it is one of the reproliferating sites, even though it may be unrecognizable for the occurrence of radiation damages
UR  - PM:6297227
ER  - 

TY  - JOUR
T1  - Magnetic resonance imaging and 11C-N-methylspiperone/positron emission tomography studies in a patient with the interval form of carbon monoxide poisoning
A1  - Yoshii,F.
A1  - Kozuma,R.
A1  - Takahashi,W.
A1  - Haida,M.
A1  - Takagi,S.
A1  - Shinohara,Y.
Y1  - 1998/09/18/
SP  - 87
EP  - 91
JA  - J Neurol Sci.
VL  - 160
IS  - 1
N2  - Magnetic resonance (MR) and (11)C-N-methylspiperone ((11)C-NMSP)/positron emission tomography (PET) imagings were repeatedly performed in a 50-year-old man with the interval form of carbon monoxide (CO) poisoning. In MR images obtained when delayed neuropsychiatric symptoms developed (two months after poisoning), the inner segments of the bilateral globus pallidus appeared as high signal intensities in the T1-weighted and low signal intensities in the T2-weighted images, suggesting prior focal hemorrhage in these areas. A PET study with (11)C-NMSP performed at that time showed an increase in dopamine D2 receptor binding in the caudate and putamen. Treatment with bromocriptine was very effective and five months after the poisoning, MR and (11)C-NMSP/PET images showed improvement, concomitantly with the disappearance of the neuropsychiatric symptoms
AD  - Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
UR  - PM:9804123
ER  - 

TY  - JOUR
T1  - Detection of primary tumor in paraneoplastic cerebellar degeneration by FDG-PET
A1  - Shinohara,Y.
A1  - Ohnuki,Y.
A1  - Yoshii,F.
A1  - Takahashi,W.
A1  - Onoe,K.
A1  - Takagi,S.
Y1  - 1998/05//
N1  - UI - 98244767
SP  - 684
JA  - Ann.Neurol
VL  - 43
IS  - 5
UR  - PM:9585368
ER  - 

TY  - JOUR
T1  - Neuroimaging in patients with seizures of probable frontal lobe origin
A1  - Swartz,B.E.
A1  - Halgren,E.
A1  - Delgado-Escueta,A.V.
A1  - Mandelkern,M.
A1  - Gee,M.
A1  - Quinones,N.
A1  - Blahd,W.H.
A1  - Repchan,J.
Y1  - 1989/09//
N1  - UI - 90005314
SP  - 547
EP  - 558
JF  - Epilepsia
VL  - 30
IS  - 5
N2  - Twenty-two patients whose electroclinical ictal characteristics suggested frontal lobe seizure foci were studied. Computed tomography (CT) scans showed abnormalities in only 32% of patients whereas magnetic resonance imaging was informative in 45%. 18FDG-Positron emission tomography (PET) scanning revealed decreased metabolism in 64% of the group. The areas of hypometabolism were focal, regional, or hemispheric. Focal frontal hypometabolism was significantly correlated with the electroclinical (semiologic) ictal localization. Therefore, FDG-PET scanning is a sensitive and specific technique for investigating patients with seizures of probable frontal lobe origins
AD  - VA Southwest Regional Program, West Los Angeles VA Medical Center (Wadsworth), CA 90073
UR  - PM:2507301
ER  - 

TY  - JOUR
T1  - Identification of frontal lobe epileptic foci in children using positron emission tomography
A1  - Da Silva,E.A.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Chugani,H.T.
Y1  - 1997/11//
N1  - UI - 98239524
SP  - 1198
EP  - 1208
JF  - Epilepsia
VL  - 38
IS  - 11
N2  - PURPOSE: Presurgical evaluation for intractable frontal lobe epilepsy (FLE) is difficult and invasive, partly because anatomic neuroimaging studies with computed tomography (CT) and magnetic resonance imaging (MRI) typically do not show a discrete lesion. In adult patients with FLE, functional neuroimaging of glucose metabolism with positron emission tomography (PET) is less sensitive in detecting focal metabolic abnormalities than in temporal lobe epilepsy (TLE). Comparable data on children with FLE are not available. METHODS: We used high-resolution PET scanning of glucose metabolism to evaluate 13 children (age 17 months to 17 years; mean age 9.5 years) with intractable FLE being considered for surgical treatment. Only children with normal CT and MRI scans were included. RESULTS: Hypometabolism including the frontal lobe was evident in 12 of the 13 children, was unilateral in 11 of 13, and was restricted to the frontal lobe in 8 of 13. One child showed bilateral frontal cortex hypometabolism and another had an ictal PET scan demonstrating unilateral frontal cortex hypermetabolism surrounded by hypometabolism. Additional hypometabolic areas outside the frontal cortex were observed in 5 children in parietal and/or temporal cortex. Localization of seizure onset on scalp EEG was available in 10 children and corresponded to the location of frontal lobe PET abnormality in 8. However, in 4 of the 10 children, the extent of hypometabolism exceeded the epileptogenic region indicated by ictal EEG. In 2 of the 13 children, the abnormality evident on EEG was more extensive than that evident on PET. In the remaining 3 children for whom only interictal EEG data were available, the PET foci did not correspond in location to the interictal EEG abnormalities. In 11 of the 13 children, the presumed region of seizure onset in the frontal lobe, as based on analysis of seizure semiology, corresponded to the locations of frontal lobe glucose metabolism abnormalities. CONCLUSIONS: Although high-resolution PET appears to be very sensitive in localizing frontal lobe glucose metabolic abnormalities in children with intractable FLE and normal CT/MRI scans, the significance of extrafrontal metabolic disturbances requires further study; these may represent additional epileptogenic areas, effects of diaschisis, seizure propagation sites, or secondary epileptogenic foci
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA
UR  - PM:9579921
ER  - 

TY  - JOUR
T1  - A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours
A1  - Sasaki,M.
A1  - Kuwabara,Y.
A1  - Yoshida,T.
A1  - Nakagawa,M.
A1  - Fukumura,T.
A1  - Mihara,F.
A1  - Morioka,T.
A1  - Fukui,M.
A1  - Masuda,K.
Y1  - 1998/09//
SP  - 1261
EP  - 1269
JA  - Eur.J Nucl Med
VL  - 25
IS  - 9
N2  - Thallium-201, carbon-11 methionine (MET) and fluorine-18 fluorodeoxyglucose (FDG) have all been used to assess brain tumours. The aim of this study was to determine which of these tracers are of use for evaluating the histological grade and the extent of astrocytoma. 201Tl single-photon emission tomography (SPET), MET positron emission tomography (PET) and FDG PET were all performed in 23 patients (13 men, 10 women) with newly diagnosed astrocytic tumours [seven with astrocytoma (grade II), ten with anaplastic astrocytoma (grade III) and six with glioblastoma (grade IV)]. The 201Tl uptake of the tumours was evaluated by a lesion-to-normal region count ratio. Both MET and FDG uptake of the tumours was evaluated by a semiquantitative analysis using the standardized uptake value. 201Tl uptake was found to increase in rank order with histological grade and was significantly different among the three groups (grade II: 1.51+/-0.36; grade III: 2.58+/-1.50; grade IV: 7. 65+/-3.84). MET uptake in grade II (1.49+/-0.44) was also significantly lower than that in both grade III (3.29+/-1.44) and grade IV (3.20+/-0.92). FDG uptake was not significantly different among the three groups (grade II: 2.90+/-0.45; grade III: 3.86+/-1. 56; grade IV: 3.57+/-0.83). No significant correlation was observed between 201Tl uptake and either MET uptake or FDG uptake. In most patients, the extent of the increased MET uptake was the largest while that of the increased FDG uptake was the smallest. In patients with positive 201Tl uptake, the extent of the 201Tl uptake was equal to or smaller than that of gadolinium enhancement. For evaluation of histological grade of astrocytic tumours. 201Tl is therefore considered to be useful though the 201Tl uptake in some grade III astrocytomas was not different from that in grade II astrocytomas. MET was found to be highly useful for detecting astrocytomas, for differentiating between benign and malignant astrocytomas, and for evaluating the extent of astrocytomas; however, it was not sufficiently useful permit evaluation of the histological grade. FDG was not found to be useful either for evaluating the histological grade or for differentiating between benign and malignant astrocytomas
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:9724375
ER  - 

TY  - JOUR
T1  - Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism in metastatic brain tumors: FDG PET study
A1  - Yamamoto,T.
A1  - Nishizawa,S.
A1  - Maruyama,I.
A1  - Yoshida,M.
A1  - Tsuchida,T.
A1  - Waki,A.
A1  - Fujibayashi,Y.
A1  - Kubota,T.
A1  - Yonekura,Y.
A1  - Itoh,H.
Y1  - 2001/04//
N1  - UI - 21340934
SP  - 103
EP  - 109
JA  - Ann.Nucl Med
VL  - 15
IS  - 2
N2  - Hyperacute changes in the expression of glycolysis-associate gene products as well as FDG uptake in tumor cells after high-dose irradiation reflect response of the cells to noxious intervention and may be a potential indicator of the outcome of treatment. To understand acute effects on the kinetics of glucose metabolism of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data in patients with metastatic brain tumors receiving stereotactic radiosurgery. MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate constants of glucose metabolism (K1*- k3*) were determined in a total of 13 tumors by a non-linear least squares fitting method for dynamic PET and arterial blood sampling data. Rate constants after radiosurgery were compared with those before radiosurgery. Changes in the rate constants induced by the therapy were also correlated with changes in tumor size evaluated by CT and/or MRI 6 months later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change in the membrane transport rates indicated by K1* and k2*. Although increases in the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly different from that before the therapy (0.024 +/- 0.012). The reduction in the tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration of the phosphorylation process was demonstrated in vivo in metastatic brain tumors as early as 4 hours after stereotactic radiosurgery, as shown experimentally in vitro in a previous report. The phenomenon may be a sensitive indicator of cell damage
AD  - Department of Radiology, Fukui Medical University, Yoshida-gun, Japan. toruy@fmsrsa.fukui-med.ac.jp
UR  - PM:11448067
ER  - 

TY  - JOUR
T1  - Construction of a standard reference for PET studies of methionine accumulation using a computerised brain atlas
A1  - Romanowski,C.A.
A1  - Leslie,D.F.
A1  - Thurfjell,L.
A1  - Ericson,K.
A1  - Stone-Elander,S.
Y1  - 1997/06//
N1  - UI - 97368701
SP  - 389
EP  - 393
JF  - Neuroradiology
VL  - 39
IS  - 6
N2  - Positron emission tomography (PET) is valuable for assessing the biochemistry and physiology of the human brain. A computerised brain atlas has been developed which allows demonstration of anatomical regions of PET images and manipulation of these images into a standardised anatomical space. Once the images are in this standardised three-dimensional space it is possible to make comparisons between individuals and groups of individuals. We describe the use of this atlas in the generation of a set of mean reference images using methionine PET images of normal volunteers
AD  - Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Romanowski-methionine-atlas.pdf
ER  - 

TY  - JOUR
T1  - Positron emission tomography using 18F-fluorodeoxyglucose in patients with stereotactically irradiated brain metastases
A1  - Ericson,K.
A1  - Kihlstrom,L.
A1  - Mogard,J.
A1  - Karlsson,B.
A1  - Lindquist,C.
A1  - Widen,L.
A1  - Collins,V.P.
A1  - Stone-Elander,S.
Y1  - 1996///
N1  - UI - 97185123
SP  - 214
EP  - 224
JA  - Stereotact.Funct.Neurosurg
VL  - 66 Suppl 1
N2  - Thirty-one patients with intracranial metastases were examined with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as a tracer. The PET study was prompted by growth of the tumor in spite of therapy, or regrowth after an initially favorable response. Increased accumulation of FDG was seen in 14 patients (group 1) and decreased in 17 (group 2). Patients in group 1 had verified tumor growth in 9 of 14 cases. The median survival after radiosurgery was 12.3 months. One patient in this group is still alive after open surgery of a recurrent metastasis. Six patients in group 2 are still alive. The median survival after radiosurgery was 19.9 months. Verified radiation reaction/necrosis was found in 5/17 and viable tumor tissue in 2. The survival time in group 2 was significantly longer than in group 1. PET is superior to computed tomography and magnetic resonance imaging in the differentiation between recurrence and radiation reaction/necrosis. However, temporary radiation effects may mask remaining tumor tissue, and repeat PET studies may sometimes be necessary
AD  - Department of Neuroradiology, Karolinska Hospital, Stockholm, Sweden
UR  - PM:9032864
ER  - 

TY  - JOUR
T1  - Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo
A1  - Tjuvajev,J.G.
A1  - Chen,S.H.
A1  - Joshi,A.
A1  - Joshi,R.
A1  - Guo,Z.S.
A1  - Balatoni,J.
A1  - Ballon,D.
A1  - Koutcher,J.
A1  - Finn,R.
A1  - Woo,S.L.
A1  - Blasberg,R.G.
Y1  - 1999/10/15/
N1  - UI - 20005688
SP  - 5186
EP  - 5193
JA  - Cancer Res.
VL  - 59
IS  - 20
N2  - The feasibility of noninvasive imaging of adenoviral-mediated herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression was assessed in a well-studied animal model of metastatic colon carcinoma of the liver. Tumors were produced in syngeneic BALB/c mice by intrahepatic injection of colon carcinoma cells (MCA-26). Seven days later, three different doses (3 x 10(8), 1 x 10(8), and 3 x 10(7) plaque-forming units (pfu) of the recombinant adenoviral vector ADV. Rous sarcoma virus (RSV)-tk bearing the HSV1-tk gene were administered by intratumoral injection in separate groups of mice. Two control groups of tumor-bearing mice received intratumoral injections of the control adenoviral vector dl-312 or buffer alone, respectively. T2-weighted magnetic resonance (MR) images of mice were obtained before administering the virus and provided an anatomical reference of hepatic tumor localization. Eighteen h after the virus injection, one group of animals was given i.v. injections of 300 microCi of no-carrier-added 5-[131I]-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera. In some animals, the tumors were sampled and processed for histology and quantitative autoradiography (QAR). The gamma camera images demonstrated highly specific localization of [131I]FIAU-derived radioactivity to the area of ADV.RSV-tk-injected tumors in the liver, which was confirmed by coregistering the gamma camera and T2-weighted MR images. There was no accumulation of [131I]FIAU-derived radioactivity in tumors that were injected with the control vector or injection solution alone. A more precise distribution of radioactivity in the area of transfected tumor was obtained by histological and QAR comparisons. A heterogeneous pattern of radioactivity distribution in transfected tumors was observed. A punctate pattern of radioactivity distribution was observed in peritumoral liver tissue in animals given injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals given injections of 3 x 10(7) pfu nor in control animals. A QAR-microscopic comparison showed that the punctate areas of radioactivity colocalized with cholangial ducts. The level of [131I]FIAU-derived radioactivity accumulation (HSV1-tk expression) in the transfected tumors was viral dose-dependent. The viral dose-dependency of radioactivity accumulation was more pronounced in peritumoral liver, which was confirmed by reverse transcription-PCR analysis. A separate group of tumor-bearing animals received different doses of ADV.RSV-tk vector followed by treatment with ganciclovir (GCV), 10 mg/kg i.p. b.i.d. for 6 days. The ADV.RSV-tk transfected tumors significantly regressed with GCV treatment; the control tumors continued to grow. During the GCV treatment, the levels of liver transaminases (ALT and AST) were significantly increased in animals that received injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals that received injections of 3 x 10(7) pfu and in control animals. The observed liver toxicity confirms the results of gamma camera and QAR imaging, which demonstrated an unwanted spread of ADV.RSV-tk vector and HSV1-tk expression in peritumoral and remote liver tissue at higher doses. These and our previous results indicate that noninvasive imaging of adenoviral-mediated HSV1-tk gene expression is feasible for monitoring cancer gene therapy in patients
AD  - Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
UR  - PM:10537296
ER  - 

TY  - JOUR
T1  - 11C-tyrosine position emission tomography and 1H magnetic resonance spectroscopy of the response of brain gliomas to radiotherapy
A1  - Heesters,M.A.
A1  - Go,K.G.
A1  - Kamman,R.L.
A1  - Mooyaart,E.L.
A1  - Meertens,H.
A1  - Paans,A.M.
A1  - Pruim,J.
Y1  - 1998/02//
N1  - UI - 98203023
SP  - 103
EP  - 108
JF  - Neuroradiology
VL  - 40
IS  - 2
N2  - We monitored 10 patients with unresected (9) or partially resected (1) supratentorial gliomas with 11C-tyrosine position emission tomography (TYR-PET) before and after radiotherapy. TYR-PET tumour volumes were measured using a threshold technique. In seven patients the tumour volume decreased after radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients the tumour protein synthesis rate (PSR) was calculated using a dynamic study protocol in combination with a PATLAK analysis. There were no changes in PSR after radiotherapy, but the PSR was calculated on the remaining tumour volume using the same threshold technique as before therapy, i.e. the decrease in tumour volume was not taken into account. In eight patients the PET data were compared with magnetic resonance spectroscopic imaging (1H-MRSI) performed simultaneously. Although there was no statistically significant correlation between TYR-PET volume changes and 1H-MRSI choline level we observed a simultaneous decrease in volume and choline in four patients
AD  - Department of Radiotherapy, Academisch Ziekenhuis Groningen, The Netherlands
UR  - PM:9541920
ER  - 

TY  - JOUR
T1  - In-beam PET measurements of beta+ radioactivity induced by proton beams
A1  - Parodi,K.
A1  - Enghardt,W.
A1  - Haberer,T.
Y1  - 2002/01/07/
N1  - UI - 21672704
SP  - 21
EP  - 36
JA  - Phys.Med Biol.
VL  - 47
IS  - 1
N2  - Our first in-beam PET measurements of the beta+ activation induced by proton irradiation are presented. Monoenergetic proton beams in the energy and intensity range suited for the treatment of deep-seated tumours were delivered by the synchrotron of the Gesellschaft fur Schwerionenforschung Darmstadt (GSI). They were stopped in PMMA blocks placed in the centre of the field of view of the positron camera that is installed in the heavy ion tumour treatment facility at GSI. The beta+ activity signal was found to be three times larger than that produced by carbon ions at the same range and applied physical dose. The reconstructed spatial beta+ activity distributions were analysed and compared with the production of positron emitters predicted by a calculation based on experimental cross-sections and on the proton flux given by the FLUKA Monte Carlo code. The shape of the depth-activity profiles was well reproduced by the model and the correlation with the proton range and the depth-dose distributions was carefully investigated. Despite the non-trivial range determination from the beta+ activity distribution in the proton case, our experimental investigation supports the feasibility of an in situ proton therapy monitoring by means of in-beam PET, as already clinically implemented for the monitoring of carbon ion therapy at GSI Darmstadt
AD  - Forschungszentrum Rossendorf, Dresden, Germany
UR  - PM:11814225
ER  - 

TY  - JOUR
T1  - The application of PET to quality assurance of heavy-ion tumor therapy
A1  - Enghardt,W.
A1  - Debus,J.
A1  - Haberer,T.
A1  - Hasch,B.G.
A1  - Hinz,R.
A1  - Jakel,O.
A1  - Kramer,M.
A1  - Lauckner,K.
A1  - Pawelke,J.
Y1  - 1999/06//
N1  - UI - 99322697
SP  - 33
EP  - 36
JA  - Strahlenther.Onkol.
VL  - 175 Suppl 2
N2  - At the new heavy ion tumor therapy facility of the Gesellschaft fur Schwerionenforschung at Darmstadt positron emission tomography (PET) has been implemented for in-beam and in-situ therapy control, i.e. during the tumor irradiation. The components necessary for this dedicated PET-imaging and their integration into the framework of therapy planning and quality assurance of heavy ion cancer treatments are presented. Results of the first application of this PET-method to patient treatments are reported
AD  - Forschungszentrum Rossendorf, Institut fur Kern- und Hadronenphysik, Dresden. W.Enghardt@fz-rossendorf.de
UR  - PM:10394393
ER  - 

TY  - JOUR
T1  - Localization of medullary thyroid carcinoma metastasis in a multiple endocrine neoplasia type 2A patient by 6-[18F]-fluorodopamine positron emission tomography
A1  - Gourgiotis,L.
A1  - Sarlis,N.J.
A1  - Reynolds,J.C.
A1  - VanWaes,C.
A1  - Merino,M.J.
A1  - Pacak,K.
Y1  - 2003/02//
SP  - 637
EP  - 641
JA  - J Clin.Endocrinol.Metab
VL  - 88
IS  - 2
N2  - 6-[(18)F]fluorodopamine, a substrate for the norepinephrine transporter, has been used as a tumor-seeking tracer in positron emission tomography (PET) to localize pheochromocytomas and other chromaffin tumors. Here, we report the case of a 42-yr-old woman with multiple endocrine neoplasia type 2A, in whom biopsy-proven recurrent medullary thyroid cancer (MTC) was detected by 6-[(18)F]fluorodopamine PET scanning. The patient had previously undergone bilateral adrenalectomy for pheochromocytoma, total thyroidectomy, and extirpation of a parapharyngeal MTC metastatic deposit. An increase in plasma calcitonin 5 yr after her initial presentation was further investigated, leading to the discovery of a mass in the left parapharyngeal space. Levels of serum and urine catecholamines and metanephrines were normal. To exclude a hormonally silent pheochromocytoma metastasis, 6-[(18)F]fluorodopamine PET was performed. The study showed a focus of radionuclide accumulation corresponding to the parapharyngeal mass. After resection of the latter, pathology confirmed metastatic MTC. To our knowledge, this is the first case of metastatic, histologically proven MTC, which was unequivocally detected by 6-[(18)F]fluorodopamine PET scanning. Because norepinephrine transporter systems have been previously found in MTC, it is conceivable that 6-[(18)F]fluorodopamine PET scanning can be used for the diagnostic localization of this tumor and its metastatic deposits because total and early resection is beneficial to the outcome of the patient
AD  - Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892,USA
UR  - PM:12574193
ER  - 

TY  - JOUR
T1  - Diagnostic localization of malignant bladder pheochromocytoma using 6-18F fluorodopamine positron emission tomography
A1  - Hwang,J.J.
A1  - Uchio,E.M.
A1  - Patel,S.V.
A1  - Linehan,W.M.
A1  - Walther,M.M.
A1  - Pacak,K.
Y1  - 2003/01//
N1  - UI - 22366184
SP  - 274
EP  - 275
JA  - J Urol.
VL  - 169
IS  - 1
AD  - Urologic Oncology Branch, National Cancer Institute/NIH, Bethesda, MD, USA
UR  - PM:12478157
ER  - 

TY  - JOUR
T1  - Diagnostic localization of pheochromocytoma: the coming of age of positron emission tomography
A1  - Pacak,K.
A1  - Eisenhofer,G.
A1  - Carrasquillo,J.A.
A1  - Chen,C.C.
A1  - Whatley,M.
A1  - Goldstein,D.S.
Y1  - 2002/09//
SP  - 170
EP  - 176
JA  - Ann.N Y.Acad.Sci.
VL  - 970
N2  - Pheochromocytoma is a rare but clinically important tumor of catecholamine-secreting chromaffin cells. This tumor constitutes a surgically curable cause of hypertension. Therefore, correct localization of pheochromocytoma is essential for effective management of this tumor. Several conventional and nuclear imaging modalities are currently available to localize pheochromocytoma. Computed tomography (CT) and magnetic resonance imaging (MRI) have good sensitivity but poor specificity for detecting pheochromocytoma, and nuclear imaging approaches such as (131)I-metaiodobenzylguanidine scintigraphy or [(111)In]-DTPA-D-Phe-pentetreotide (Octreoscan) have limited sensitivity. However, specificity of (131)I-metaiodobenzylguanidine scintigraphy is very good and this means of imaging provides a method for confirming that a tumor is a pheochromocytoma and rules out metastatic disease. Recently, we introduced a new imaging method, 6-[(18)F]fluorodopamine positron emission tomography, that can be used successfully for the detection of solitary and metastatic pheochromocytomas. Our preliminary data suggest that this method is superior to other nuclear imaging methods including metaiodobenzylguanidine and octreotide scintigraphy. In this report we provide an update regarding nuclear imaging of primary and metastatic pheochromocytoma, particularly using 6-[(18)F]fluorodopamine positron emission tomographic scanning
AD  - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development/NIH, Building 10, Room 9D42, 10 Center Drive MSC 1583, Bethesda, MD 20892, USA. karel@mail.nih.gov
UR  - PM:12381552
ER  - 

TY  - JOUR
T1  - Imaging of pheochromocytoma in 2 dogs using p-[18F] fluorobenzylguanidine
A1  - Berry,C.R.
A1  - DeGrado,T.R.
A1  - Nutter,F.
A1  - Garg,P.K.
A1  - Breitschwerdt,E.B.
A1  - Spaulding,K.
A1  - Concannon,K.D.
A1  - Zalutsky,M.R.
A1  - Coleman,R.E.
Y1  - 2002/03//
N1  - UI - 21951512
SP  - 183
EP  - 186
JA  - Vet.Radiol.Ultrasound
VL  - 43
IS  - 2
N2  - p-[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been developed as a positron emission tomography (PET) imaging radiopharmaceutical. Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The extent of the pheochromocytoma was well documented in both dogs on the PET study. The standardized uptake values within the pheochromocytomas were greater than 25 by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG study was normal. Surgical exploration and adrenal biopsy confirmed the [15F]PFBG imaging findings in both dogs. In each dog, there was rapid blood-pool clearance (within 10 min after intravenous administration of the [18F]PFBG), with high uptake specific within the myocardium and adrenal medulla. The results indicate that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in differentiating adrenal masses
AD  - Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, College of Veterinary Medicine, Raleigh 27606, USA
UR  - PM:11954815
ER  - 

TY  - JOUR
T1  - Metastases of predominantly dopamine-secreting phaeochromocytoma that did not accumulate meta-iodobenzylguanidine: imaging with whole body positron emission tomography using 18F-labelled deoxyglucose
A1  - Taniguchi,K.
A1  - Ishizu,K.
A1  - Torizuka,T.
A1  - Hasegawa,S.
A1  - Okawada,T.
A1  - Ozawa,T.
A1  - Iino,K.
A1  - Taniguchi,M.
A1  - Ikematsu,Y.
A1  - Nishiwaki,Y.
A1  - Kida,H.
A1  - Waki,S.
A1  - Uchimura,M.
Y1  - 2001/11//
N1  - UI - 21836758
SP  - 866
EP  - 870
JA  - Eur.J Surg.
VL  - 167
IS  - 11
AD  - Department of Surgery, Hamamatsu Medical Center, Shizuoka, Japan. kmtani@bekkoame.ne.jp
UR  - PM:11848244
ER  - 

TY  - JOUR
T1  - Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.
A1  - Hoegerle,S.
A1  - Nitzsche,E.
A1  - Altehoefer,C.
A1  - Ghanem,N.
A1  - Manz,T.
A1  - Brink,I.
A1  - Reincke,M.
A1  - Moser,E.
A1  - Neumann,H.P.
Y1  - 2002/02//
N1  - UI - 21677174
SP  - 507
EP  - 512
JF  - Radiology
VL  - 222
IS  - 2
N2  - PURPOSE: To evaluate fluorine 18 ((18)F) dihydroxyphenylalanine (DOPA) whole-body positron emission tomography (PET) as a biochemical imaging approach for detection of pheochromocytomas. MATERIALS AND METHODS: (18)F DOPA PET and magnetic resonance (MR) imaging were performed in 14 consecutive patients suspected of having pheochromocytomas (five sporadic, nine with von Hippel-Lindau disease); metaiodobenzylguanidine (MIBG) scintigraphy was performed in 12 of these patients. The individual imaging findings were assessed in consensus by specialists in nuclear medicine and radiologists blinded to the results of the other methods. The findings of the functional imaging methods were compared with those of MR imaging, the reference standard. Histologic verification could be obtained in eight patients with nine tumors. RESULTS: Seventeen pheochromocytomas (11 solitary, three bifocal; 14 adrenal, three extraadrenal) were detected with MR imaging. (18)F DOPA PET and MR imaging had concordant results in all 17 tumors. In contrast, MIBG scintigraphy had false-negative results in four patients with three adrenal tumors smaller than 2 cm and one extraadrenal tumor with a diameter of 3.6 cm. On the basis of these data, sensitivities of 100% for (18)F DOPA PET and of 71% for MIBG scintigraphy were calculated. Specificity was 100% for both procedures. CONCLUSION: (18)F DOPA PET is highly sensitive and specific for detection of pheochromocytomas and has potential as the functional imaging method of the future
AD  - Divisions of Nuclear Medicine, Department of Radiology, Albert-Ludwigs University, Freiburg, Germany. hoegerle@ukl.uni-freiburg.de
UR  - PM:11818620
ER  - 

TY  - JOUR
T1  - Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET
A1  - Shulkin,B.L.
A1  - Thompson,N.W.
A1  - Shapiro,B.
A1  - Francis,I.R.
A1  - Sisson,J.C.
Y1  - 1999/07//
N1  - UI - 99334189
SP  - 35
EP  - 41
JF  - Radiology
VL  - 212
IS  - 1
N2  - PURPOSE: To assess the sensitivity of positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in pheochromocytomas and, secondarily, to compare images obtained with FDG PET to those obtained with metaiodobenzylguanidine (MIBG) scintigraphy. MATERIALS AND METHODS: Twenty-nine patients with one or more known or subsequently proved pheochromocytomas underwent FDG PET (35 scans) and MIBG scintigraphy (35 scans). Tumor uptake of FDG was quantified on positive PET scans. RESULTS: Tumor uptake of FDG was detected in 22 of 29 patients. Most benign (seven of 12 patients) and most malignant (15 of 17 patients) pheochromocytomas and their metastases avidly concentrated FDG. In four patients whose pheochromocytomas failed to accumulate MIBG, uptake of FDG in the tumors was intense. For the majority of the 16 patients whose tumors concentrated both agents, however, ratings for MIBG images compared to FDG PET images for delineation of the tumor in comparison to background and normal organ accumulation were superior for nine patients (56%) and as good or better for 14 (88%). CONCLUSION: Most pheochromocytomas accumulate FDG. Uptake is found in a greater percentage of malignant than benign pheochromocytomas. FDG PET is especially useful in defining the distribution of those pheochromocytomas that fail to concentrate MIBG
AD  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA. bshulkin@umich.edu
UR  - PM:10405717
ER  - 

TY  - JOUR
T1  - Malignant pheochromocytoma of the anterior mediastinum: PET findings with [18F]FDG and 82Rb
A1  - Neumann,D.R.
A1  - Basile,K.E.
A1  - Bravo,E.L.
A1  - Chen,E.Q.
A1  - Go,R.T.
Y1  - 1996/03//
N1  - UI - 96184308
SP  - 312
EP  - 316
JA  - J Comput.Assist.Tomogr.
VL  - 20
IS  - 2
N2  - A case of a malignant pheochromocytoma arising from the anterior mediastinum is presented. We report the use of positron emission tomography with 82Rb and [18F]fluorodeoxyglucose to successfully image this neoplasm
AD  - Department of Nuclear Medicine, Division of Radiology, Cleveland Clinic Foundation, OH 44195-5074, USA
UR  - PM:8606245
ER  - 

TY  - JOUR
T1  - Validation of 4-[fluorine-18]fluoro-3-iodobenzylguanidine as a positron-emitting analog of MIBG
A1  - Vaidyanathan,G.
A1  - Affleck,D.J.
A1  - Zalutsky,M.R.
Y1  - 1995/04//
N1  - UI - 95213811
SP  - 644
EP  - 650
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 36
IS  - 4
N2  - This study evaluates the potential utility of 4-[18F]fluoro-3-iodobenzylguanidine ([18F]FIBG) as an MIBG analog. METHODS: In vitro assays of tracer binding were carried out using the SK-N-SH human neuroblastoma cell line in a paired-label format to compare [18F]FIBG directly with no-carrier-added [125I]MIBG. To ascertain whether [18F]FIBG, like MIBG, is taken up by the uptake-1 mechanism, the effects of desipramine, norepinephrine, and carrier MIBG and FIBG on cell binding were determined. Preincubation with ouabain and incubation at 4 degrees C was used to evaluate the energy-dependence of [18F]FIBG uptake by SK-N-SH cells. The tissue distribution of [18F]FIBG in mice was compared with no-carrier-added [125I]MIBG in a paired-label study. RESULTS: In paired-label binding studies, the percent binding of [18F]FIBG to neuroblastoma cells remained constant over a three-log activity range and the level was somewhat higher than that of no-carrier-added [125I]MIBG. Binding was blocked by desipramine, norepinephrine, carrier MIBG and FIBG, ouabain and by incubating at 4 degrees C, suggesting that [18F]FIBG is taken up by the uptake-1 mechanism. Radiation dosimetry calculations suggest that higher doses of [18F]FIBG, unlike [124I]MIBG, could be administered to patients. CONCLUSION: These in vitro and in vivo evaluations show that [18F]FIBG is an excellent analog of MIBG, suggesting that [18F]FIBG should be further evaluated for use in PET imaging of neuroendocrine tumors and cardiac abnormalities
AD  - Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA
UR  - PM:7699460
ER  - 

TY  - JOUR
T1  - Genes and parkinsonism
A1  - Hardy,John
A1  - Cookson,Mark R.
A1  - Singleton,Andrew
Y1  - 2003/04/01/
SP  - 221
EP  - 228
JA  - The Lancet Neurology
VL  - 2
IS  - 4
N2  - Genetic studies in families with mendelian inheritance of Parkinson's disease (PD) have reported the cloning of several disease-associated genes. These studies of rare familial forms of the disease have cast doubt on our understanding of the role of genetics in typical PD and have complicated the classification of the disorder. However, this genetic information might help us to construct a hypothesis for the pathogenetic processes that underlie PD. In this review we describe the molecular genetics of PD as currently understood to help explain the pathways that underlie neurodegeneration
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Hardy-Genes-Parkinsonism.pdf
ER  - 

TY  - JOUR
T1  - Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise
A1  - Madsen,P.L.
A1  - Sperling,B.K.
A1  - Warming,T.
A1  - Schmidt,J.F.
A1  - Secher,N.H.
A1  - Wildschiodtz,G.
A1  - Holm,S.
A1  - Lassen,N.A.
Y1  - 1993/01//
N1  - UI - 93186583
SP  - 245
EP  - 250
JA  - J Appl.Physiol
VL  - 74
IS  - 1
N2  - Results obtained by the 133Xe clearance method with external detectors and by transcranial Doppler sonography (TCD) suggest that dynamic exercise causes an increase of global average cerebral blood flow (CBF). These data are contradicted by earlier data obtained during less-well-defined conditions. To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity in the middle cerebral artery (MCA Vmean). For values of CBF and MCA Vmean a correction for an observed small drop in arterial PCO2 was carried out. Baseline values for global CBF and CMRO2 were 50.7 and 3.63 ml.100 g-1.min-1, respectively. The same values were found during dynamic exercise, whereas a 22% (P < 0.0001) increase in MCA Vmean was observed. Hence, the exercise-induced increase in MCA Vmean is not a reflection of a proportional increase in CBF
AD  - Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital, Copenhagen NV, Denmark
UR  - PM:8444699
ER  - 

TY  - JOUR
T1  - Normal average value of cerebral blood flow in younger adults is 50 ml/100 g/min
A1  - Lassen,N.A.
Y1  - 1985/09//
N1  - UI - 85289556
SP  - 347
EP  - 349
JA  - J Cereb.Blood Flow Metab
VL  - 5
IS  - 3
UR  - PM:4030914
ER  - 

TY  - CHAP
T1  - Changes in arterial gas tension
A1  - Hurn,P.D.
A1  - Traystman,R.J.
Y1  - 2002///
SP  - 384
EP  - 394
VL  - 2
T2  - Cerebral blood flow and metabolism
A2  - Edvinsson,L.
A2  - Krause,D.N.
IS  - 24
CY  - Philadelphia, Pa.
PB  - Lippincott Williams & Wilkins
ER  - 

TY  - JOUR
T1  - A decrease in regional cerebral blood volume and hematocrit in crossed cerebellar diaschisis
A1  - Yamauchi,H.
A1  - Fukuyama,H.
A1  - Nagahama,Y.
A1  - Okazawa,H.
A1  - Konishi,J.
Y1  - 1999/07//
N1  - UI - 99319109
SP  - 1429
EP  - 1431
JF  - Stroke
VL  - 30
IS  - 7
N2  - BACKGROUND AND PURPOSE: The pathophysiology of crossed cerebellar diaschisis (CCD) remains to be elucidated. In CCD, the metabolic suppression resulting from deafferentation may cause vasoconstriction, which may result in a decrease in cerebral blood volume (CBV) and may differentially affect the flows of red blood cells and of plasma. The purpose of this study was to investigate whether CCD decreases the total CBV (cerebral red blood cell volume [CRCV] plus cerebral plasma volume [CPV]) and, if so, whether CCD differentially affects the CRCV and CPV, resulting in a change in hematocrit. METHODS: We used positron emission tomography to study 7 patients with a unilateral supratentorial infarct and CCD. The distributions of CRCV and CPV were assessed by using 15O-labeled carbon monoxide and 62Cu-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The CRCV, CPV, and calculated hematocrit values were compared between the cerebellar hemispheres. RESULTS: In the cerebellar cortex contralateral to the supratentorial infarct, the values of CRCV, CPV, and total CBV were significantly decreased compared with those in the ipsilateral cerebellar cortex. The CRCV was decreased to a greater degree than the CPV, and the value of the hematocrit was decreased in the contralateral cerebellar cortex. CONCLUSIONS: CCD may decrease the total CBV, which may reflect vasoconstriction caused by decreased metabolism due to deafferentation. In addition, the more pronounced decrease in CRCV than in CPV may result in a decrease in hematocrit in CCD
AD  - Department of Neurology, Brain Pathophysiology Faculty of Medicine, Kyoto University, Japan. ymuc@kuhp.kyoto-u.ac.jp
UR  - PM:10390318
ER  - 

TY  - JOUR
T1  - Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age
A1  - Leenders,K.L.
A1  - Perani,D.
A1  - Lammertsma,A.A.
A1  - Heather,J.D.
A1  - Buckingham,P.
A1  - Healy,M.J.
A1  - Gibbs,J.M.
A1  - Wise,R.J.
A1  - Hatazawa,J.
A1  - Herold,S.
Y1  - 1990/02//
N1  - UI - 90149620
SP  - 27
EP  - 47
JF  - Brain
VL  - 113 ( Pt 1)
N2  - Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:2302536
ER  - 

TY  - JOUR
T1  - Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography
A1  - Takada,H.
A1  - Nagata,K.
A1  - Hirata,Y.
A1  - Satoh,Y.
A1  - Watahiki,Y.
A1  - Sugawara,J.
A1  - Yokoyama,E.
A1  - Kondoh,Y.
A1  - Shishido,F.
A1  - Inugami,A.
Y1  - 1992///
N1  - UI - 92396313
SP  - 128
EP  - 131
JA  - Neurol Res.
VL  - 14
IS  - 2 Suppl
N2  - Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere
AD  - Department of Neurology, Research Institute for Brain and Blood Vessels, Akita, Japan
UR  - PM:1355868
ER  - 

TY  - JOUR
T1  - Association of age with regional cerebral oxygen utilization: a positron emission tomography study
A1  - Burns,A.
A1  - Tyrrell,P.
Y1  - 1992/09//
N1  - UI - 93034649
SP  - 316
EP  - 320
JF  - Age and Ageing
JA  - Age Ageing
VL  - 21
IS  - 5
N2  - Positron emission tomography scans were performed on 14 normal subjects over the age of 50. Cerebral metabolic rate for oxygen (CMRO2) was assessed in a number of cortical and subcortical regions. There was a trend for a decrease in CMRO2 with age but this was significant only in the parietal lobe. There was a suggestion that the age/CMRO2 correlation became less strong with advancing age. CMRO2 in the occipital lobe, subcortical regions and cerebellum was not related to age. The relationship between CMRO2 and age is discussed
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London
UR  - PM:1414666
ER  - 

TY  - JOUR
T1  - The continuous inhalation of oxygen-15 for assessing regional oxygen extraction in the brain of man
A1  - Jones,T.
A1  - Chesler,D.A.
A1  - Ter Pogossian,M.M.
Y1  - 1976/04//
N1  - UI - 76233109
SP  - 339
EP  - 343
JA  - Br.J Radiol.
VL  - 49
IS  - 580
N2  - A non-invasive steady-state method for studying the regional accumulation of oxygen in the brain by continuously inhaling Oxygen-15 has been investigated. Oxygen respiration by tissue results in the formation of water of metabolism which may be considered as the "exhaust product" of respiration. In turn the steady-state distribution of this product may be related to that of oxygen utilization. It has been found in monkeys that an appreciable component of the signal, recorded over the head during the inhalation of 15O2, is attributable to the local production of 15O-labelled water of metabolism. In man the distribution of radioactivity recorded over the head during 15O2 inhalation clearly relates to active cerebral tissue. Theoretically the respiration product is linearly dependent on the oxygen extraction ratio of the tissue, and at normal cerebral perfusion it is less sensitive to changes in blood flow. At low rates of perfusion a more linear dependence on flow is shown. The dual dependence on blood flow and oxygen extraction limits the interpretation of the cerebral distribution obtained with this technique. Means for obtaining more definitive measurements with this approach are discussed
UR  - PM:820399
ER  - 

TY  - JOUR
T1  - Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue
A1  - Madsen,P.L.
A1  - Cruz,N.F.
A1  - Sokoloff,L.
A1  - Dienel,G.A.
Y1  - 1999/04//
N1  - UI - 99211366
SP  - 393
EP  - 400
JA  - J Cereb.Blood Flow Metab
VL  - 19
IS  - 4
N2  - Functional activation stimulates CMRglc more than CMRO2 and raises lactate levels in brain. This has been interpreted as evidence that brain work is supported mainly by energy derived from anaerobic glycolysis. To determine if lactate production accounts for the "excess" glucose consumption, cerebral arteriovenous differences were measured in conscious rats before, during, and 15 minutes after sensory stimulation; the brains were rapidly frozen in situ immediately after completion of blood sampling and assayed for metabolite levels. The molar O2/glucose uptake ratio fell from 6.1+/-1.1 (mean+/-SD) before stimulation to 5.0+/-1.1 during activation (P<0.01); lactate efflux from brain to blood was detectable at rest but not during stimulation. By 15 minutes after activation, O2 and lactate arteriovenous differences normalized, whereas that for glucose fell, causing the O2/glucose ratio to rise above preactivation levels to 7.7+/-2.6 (P<0.01). Brain glucose levels remained stable through all stages of activity. Brain lactate levels nearly doubled during stimulation but normalized within 15 minutes of recovery. Brain glycogen content fell during activation and declined further during recovery. These results indicate that brain glucose metabolism is not in a steady state during and shortly after activation. Furthermore, efflux from and increased content of lactate in the brain tissue accounted for less than 54% of the "excess" glucose used during stimulation, indicating that a shift to anaerobic glycolysis does not fully explain the disproportionately greater increases in CMRglc above that of CMRO2 in functionally activated brain. These results also suggest that the apparent dissociation between glucose utilization and O2 consumption during functional activation reflects only a temporal displacement; during activation, glycolysis increases more than oxidative metabolism, leading to accumulation of products in intermediary metabolic pools that are subsequently consumed and oxidized during recovery
AD  - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20902, USA
UR  - PM:10197509
ER  - 

TY  - JOUR
T1  - Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo
A1  - Gjedde,A.
A1  - Marrett,S.
Y1  - 2001/12//
N1  - UI - 21601855
SP  - 1384
EP  - 1392
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 12
N2  - The regulation of brain energy metabolism during neuronal activation is poorly understood. Specifically, the extent to which oxidative metabolism rather than glycolysis supplies the additional ATP necessary to sustain neuronal activation is in doubt. A recent hypothesis claims that astrocytes generate lactate with the muscle-type lactate dehydrogenase (LDH) isozyme LD 5. Lactate from astrocytes then undergoes oxidation in neurons after reconversion to pyruvate by the LDH subtype LD 1. On the basis of this hypothesis, the authors predicted that the time course of an excitatory increase of the oxidative metabolism of brain tissue must depend on the degree to which astrocytes provide neurons with pyruvate in the form of lactate. From the known properties of the LDH subtypes, the authors predicted two time courses for the changes of oxygen consumption in response to neuronal stimulation: one reflecting the properties of the neuronal LDH subtype LD 1, and the other reflecting the astrocytic LDH subtype LD 5. Measuring oxygen consumption (CMR O2 ) with positron emission tomography, the authors demonstrated increased CMR O2 during sustained stimulation of visual cortex with a complex stimulus. The CMR O2 increased 20.5% after 3 minutes and 27.5% after 8 minutes of stimulation, consistent with a steady-state oxygen-glucose metabolism ratio of 5.3, which is closest to the index predicted for the LD 1 subtype. The index is equal to the oxygen-glucose metabolism ratio of 5.5 calculated at baseline, indicating that pyruvate is converted to lactate in a cellular compartment with an LDH reaction closest to that of LD 1, whether at rest or during stimulation of the visual cortex with the current stimulus. The findings are consistent with a claim that neurons increase their oxidative metabolism in parallel with an increase of pyruvate, the latter generated by neuronal rather than astrocytic glycolysis
AD  - McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
UR  - PM:11740199
ER  - 

TY  - JOUR
T1  - Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients
A1  - Blomqvist,G.
A1  - Alvarsson,M.
A1  - Grill,V.
A1  - Von Heijne,G.
A1  - Ingvar,M.
A1  - Thorell,J.O.
A1  - Stone-Elander,S.
A1  - Widen,L.
A1  - Ekberg,K.
Y1  - 2002/07//
N1  - UI - 22062573
SP  - E20
EP  - E28
JA  - Am.J Physiol Endocrinol.Metab
VL  - 283
IS  - 1
N2  - Using R-beta-[1-(11)C]hydroxybutyrate and positron emission tomography, we studied the effect of acute hyperketonemia (range 0.7-1.7 micromol/ml) on cerebral ketone body utilization in six nondiabetic subjects and six insulin-dependent diabetes mellitus (IDDM) patients with average metabolic control (HbA(1c) = 8.1 +/- 1.7%). An infusion of unlabeled R-beta-hydroxybutyrate was started 1 h before the bolus injection of R-beta-[1-(11)C]hydroxybutyrate. The time course of the radioactivity in the brain was measured during 10 min. For both groups, the utilization rate of ketone bodies was found to increase nearly proportionally with the plasma concentration of ketone bodies (1.0 +/- 0.3 micromol/ml for nondiabetic subjects and 1.3 +/- 0.3 micromol/ml for IDDM patients). No transport of ketone bodies from the brain could be detected. This result, together with a recent study of the tissue concentration of R-beta-hydroxybutyrate in the brain by magnetic resonance spectroscopy, indicate that, also at acute hyperketonemia, the rate-limiting step for ketone body utilization is the transport into the brain. No significant difference in transport and utilization of ketone bodies could be detected between the nondiabetic subjects and the IDDM patients
AD  - Uppsala University PET Centre, University Hospital Uppsala, S-75185 Uppsala, Sweden. gunnar.blomqvist@pet.uu.se
UR  - PM:12067838
ER  - 

TY  - JOUR
T1  - Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia
A1  - Hasselbalch,S.G.
A1  - Madsen,P.L.
A1  - Hageman,L.P.
A1  - Olsen,K.S.
A1  - Justesen,N.
A1  - Holm,S.
A1  - Paulson,O.B.
Y1  - 1996/05//
N1  - UI - 96226470
SP  - E746
EP  - E751
JA  - Am.J Physiol
VL  - 270
IS  - 5 Pt 1
N2  - During starvation, brain energy metabolism in humans changes toward oxidation of ketone bodies. To investigate if this shift is directly coupled to circulating blood concentrations of ketone bodies, we measured global cerebral blood flow (CBF) and global cerebral carbohydrate metabolism with the Kety-Schmidt technique before and during intravenous infusion with ketone bodies. During acute hyperketonemia (mean beta-hydroxybutyrate blood concentration 2.16 mM), cerebral uptake of ketones increased from 1.11 to 5.60 mumol.100 g-1.min-1, counterbalanced by an equivalent reduction of the cerebral glucose metabolism from 25.8 to 17.2 mumol.100 g-1.min-1, with the net result being an unchanged cerebral uptake of carbohydrates. In accordance with this, global cerebral oxygen metabolism was not significantly altered (144 vs. 135 mumol.100 g-1.min-1). The unchanged global cerebral metabolic activity was accompanied by a 39% increase in CBF from 51.0 to 70.9 ml.100 g-1.min-1. Regional analysis of the glucose metabolism by positron emission tomography-[18F]fluoro-2-deoxy-D-glucose indicated that mesencephalon does not oxidize ketone bodies to the same extent as the rest of the brain. It was concluded that the immediate oxidation of ketone bodies induced a decrease in cerebral glucose uptake in spite of an adequate glucose supply to the brain. Furthermore, acute hyperketonemia caused a resetting of the coupling between CBF and metabolism that could not be explained by alterations in arterial CO2 tension or pH
AD  - Department of Neurology, Rigshospitalet, Copenhagen, Denmark
UR  - PM:8967461
ER  - 

TY  - JOUR
T1  - Use of R-beta-[1-11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans
A1  - Blomqvist,G.
A1  - Thorell,J.O.
A1  - Ingvar,M.
A1  - Grill,V.
A1  - Widen,L.
A1  - Stone-Elander,S.
Y1  - 1995/11//
N1  - UI - 96088635
SP  - E948
EP  - E959
JA  - Am.J Physiol
VL  - 269
IS  - 5 Pt 1
N2  - A method for determining regional cerebral utilization of ketone bodies in humans is described. After a bolus injection of R-beta-[1-11C]hydroxybutyrate, the time course of the tracer in the brain was measured with positron emission tomography in five healthy volunteers. The regional cerebral blood flow was measured separately. The tracer uptake in the brain could be well described by a single rate constant, indicating that the concentration of unmetabolized ketone bodies in the brain is very low and that transport across the blood-brain barrier is the rate-limiting step. At an average plasma concentration of beta-hydroxybutyrate of 0.043 mumol/ml, the utilization rate was estimated to be 0.48 nmol.ml-1.min-1. In accordance with previous animal studies, the utilization rate was found to increase almost linearly with increasing plasma concentration of beta-hydroxybutyrate. Furthermore, the utilization was higher in gray than in white matter. Finally, the ratio between the utilization in the basal ganglia and the brain as a whole was lower for ketone bodies than for glucose
AD  - Department of Clinical Neuroscience, Karolinska Pharmacy, Stockholm, Sweden
UR  - PM:7491948
ER  - 

TY  - JOUR
T1  - Brain metabolism during short-term starvation in humans
A1  - Hasselbalch,S.G.
A1  - Knudsen,G.M.
A1  - Jakobsen,J.
A1  - Hageman,L.P.
A1  - Holm,S.
A1  - Paulson,O.B.
Y1  - 1994/01//
N1  - UI - 94086638
SP  - 125
EP  - 131
JA  - J Cereb.Blood Flow Metab
VL  - 14
IS  - 1
N2  - During prolonged starvation, brain energy requirements are covered in part by the metabolism of ketone bodies. It is unknown whether short-term starvation of a few days' duration may lead to reduced brain glucose metabolism due to the change toward ketone body consumption. In the present study we measured the cerebral metabolism of glucose and ketone bodies in nine healthy volunteers before and after 3.5 days of starvation. Regional glucose metabolism was measured by dynamic positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. The mean value of K1* in gray and white matter increased by 12% (p < 0.05), whereas k2* and k3* were unchanged compared with control values. Regional glucose metabolism in cortical gray matter was reduced by 26% from 0.294 +/- 0.054 to 0.217 +/- 0.040 mumol g-1 min-1 (p < 0.001). White matter glucose metabolism decreased by 27% (p < 0.02). The decrease was uniform in gray and white matter with regional decreases ranging from 24 to 30%. A determination using Fick's principle confirmed the reduction in glucose metabolism yielding a decrease of 24% from 0.307 +/- 0.050 to 0.233 +/- 0.073 mumol g-1 min-1 (p < 0.05), whereas CBF did not change (0.57 +/- 0.07 vs. 0.57 +/- 0.06 ml g-1 min-1). The global net uptake of beta-hydroxybutyrate increased 13-fold from 0.012 +/- 0.024 to 0.155 +/- 0.140 mumol g-1 min-1 (p < 0.05). Net uptake of acetoacetate and net efflux of lactate and pyruvate did not change significantly during starvation. The present study shows that the human brain adapts to the changes in energy supply as early as 3 days following initiation of starvation, at which time ketone bodies account for approximately one-fourth of the cerebral energy requirements
AD  - Department of Neurology, Rigshospitalet, University Hospital, University of Copenhagen, Denmark
UR  - PM:8263048
ER  - 

TY  - JOUR
T1  - Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography
A1  - Stange,K.
A1  - Greitz,D.
A1  - Ingvar,M.
A1  - Hindmarsh,T.
A1  - Sollevi,A.
Y1  - 1997/06//
N1  - UI - 97351755
SP  - 117
EP  - 122
JA  - Acta Physiol Scand.
VL  - 160
IS  - 2
N2  - Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 micrograms kg-1 min-1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2-3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus [15O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 +/- 0.2 kPa, mean +/- s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 +/- 66 mL min-1, equivalent to about 64 +/- 5 mL 100 g-1 min-1. The cerebral blood flow measured by positron emission tomography technique, was 59 +/- 4 mL 100 g-1 min-1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 +/- 7 micrograms kg-1 min-1.) the cerebral blood flow, measured by magnetic resonance imaging was 60 +/- 5 mL 100 g-1 min-1. The end tidal CO2 level was slightly lower (0.2 +/- 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans
AD  - Department of Anaesthesiology and Intensive Care, Karolinska Hospital, Stockholm, Sweden
UR  - PM:9208037
ER  - 

TY  - JOUR
T1  - The effects of scopolamine on changes in regional cerebral blood flow during classical conditioning of the human eyeblink response
A1  - Bahro,M.
A1  - Molchan,S.E.
A1  - Sunderland,T.
A1  - Herscovitch,P.
A1  - Schreurs,B.G.
Y1  - 1999/05//
N1  - UI - 99276665
SP  - 187
EP  - 195
JF  - Neuropsychobiology
VL  - 39
IS  - 4
N2  - We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age +/- SEM: 26.7 +/- 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H215O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 +/- 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system
AD  - Geriatric Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Bahro@csi.com
UR  - PM:10343183
ER  - 

TY  - JOUR
T1  - Regulation of cerebral blood flow response to somatosensory stimulation through the cholinergic system: a positron emission tomography study in unanesthetized monkeys
A1  - Tsukada,H.
A1  - Kakiuchi,T.
A1  - Ando,I.
A1  - Shizuno,H.
A1  - Nakanishi,S.
A1  - Ouchi,Y.
Y1  - 1997/02/21/
N1  - UI - 97224041
SP  - 10
EP  - 17
JA  - Brain Res.
VL  - 749
IS  - 1
N2  - The effects of scopolamine, a muscarinic cholinergic receptor antagonist and physostigmine, a cholinesterase inhibitor, on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation of the forepaw were studied in the brain of unanesthetized monkeys using 15O-labeled water and high resolution positron emission tomography. Before scopolamine administration, vibrotactile stimulation produced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Intravenous administration of scopolamine at doses ranging from 1 to 500 microg/kg resulted in a dose-dependent reduction of the rCBF response. The rCBF response abolished by scopolamine (50 microg/kg) was recovered by administration of physostigmine (10 microg/kg). On the other hand, the regional cerebral metabolic rate of glucose (rCMRglc) response, measured with [18F]-2-fluoro-2-deoxy-D-glucose, to the same stimulation was unchanged by administration of either scopolamine and/or physostigmine. These results suggested that cholinergic mechanisms might be involved in regulation of the coupling between neuronal activity and rCBF response, not between the activity and rCMRglc response
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita, Shizuoka, Japan. tsukada@crl.hpk.co.jp
UR  - PM:9070622
ER  - 

TY  - JOUR
T1  - The metabolic brain pattern of young subjects given scopolamine
A1  - Cohen,R.M.
A1  - Gross,M.
A1  - Semple,W.E.
A1  - Nordahl,T.E.
A1  - Sunderland,T.
Y1  - 1994///
N1  - UI - 95113030
SP  - 133
EP  - 143
JA  - Exp.Brain Res.
VL  - 100
IS  - 1
N2  - The effect of an intravenous dose of 0.5 mg of scopolamine on the functional brain activity of normal subjects performing auditory discrimination (CPT) was determined in two independent positron emission tomography studies with [18F] 2-fluoro-deoxyglucose. In the first preliminary study, the most significant effect found was a reduction in the functional activity of the thalamus. In the second "hypothesis-testing" study, an equally prominent effect on thalamic functional activity was seen. Because the second study was performed on a high-resolution scanner with improved methodology, we re-examined scopolamine's effects on those brain regions established as determinants of CPT. Of the regions affected, the reduction in cingulate and the increase in basal ganglia metabolic rates were the most notable. We concluded that scopolamine's effects on the functions of thalamic, cingulate and basal ganglia are the likely causes of scopolamine's well-described attention-altering properties. Alterations in these same brain structures could be responsible for scopolamine's effects on other cognitive functions, e.g., memory. Alternatively, scopolamine's effects on other brain structures such as the hippocampus and frontal cortex could underlie scopolamine's effects on these other cognitive functions. Studies of scopolamine's regional metabolic effects in subjects performing these other cognitive tasks at more than a single dose and at more than one post-drug time are needed to discriminate between these two possibilities
AD  - Clinical Brain Imaging Section, NIMH, Bethesda, MD 20892-1000
UR  - PM:7813641
ER  - 

TY  - JOUR
T1  - In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography
A1  - Frey,K.A.
A1  - Koeppe,R.A.
A1  - Mulholland,G.K.
A1  - Jewett,D.
A1  - Hichwa,R.
A1  - Ehrenkaufer,R.L.
A1  - Carey,J.E.
A1  - Wieland,D.M.
A1  - Kuhl,D.E.
A1  - Agranoff,B.W.
Y1  - 1992/01//
N1  - UI - 92078316
SP  - 147
EP  - 154
JA  - J Cereb.Blood Flow Metab
VL  - 12
IS  - 1
N2  - Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands
AD  - Division of Nuclear Medicine, University of Michigan, Ann Arbor
UR  - PM:1727135
ER  - 

TY  - JOUR
T1  - Quantitative in vivo receptor binding. IV: Detection of muscarinic receptor down-regulation by equilibrium and by tracer kinetic methods
A1  - Frey,K.A.
A1  - Ciliax,B.
A1  - Agranoff,B.W.
Y1  - 1991/09//
N1  - UI - 92149699
SP  - 1017
EP  - 1023
JA  - Neurochem.Res.
VL  - 16
IS  - 9
N2  - Newly-developed methods for estimation of in vivo binding to neurotransmitter receptors should enable the detection and quantification of physiologic or pathologic changes in receptor numbers. In the present study, both equilibrium and kinetic experimental strategies for in vivo muscarinic receptor determination were applied to the detection of receptor changes induced by chronic inhibition of acetylcholinesterase in the rat. Following one week of treatment, in vitro receptor autoradiography utilizing [3H]scopolamine revealed significant losses of muscarinic binding in the cerebral cortex, hippocampus, striatum and in cranial nerve motor nuclei. The in vivo distribution of [3H]scopolamine, following infusion to approach equilibrium binding in the brain, revealed reductions in binding which paralleled the pattern and magnitude of changes detected in vitro. A simplified tracer kinetic estimation following bolus injection of the ligand also detected substantial reductions in forebrain muscarinic receptor binding. These results indicate the feasibility of detecting receptor changes underlying neuropathologic conditions in vivo, and suggest that either equilibrium or kinetic experimental approaches may be extended to clinical research applications with the use of positron or single-photon emission tomography
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor 48109
UR  - PM:1784328
ER  - 

TY  - JOUR
T1  - Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine
A1  - Dewey,S.L.
A1  - MacGregor,R.R.
A1  - Brodie,J.D.
A1  - Bendriem,B.
A1  - King,P.T.
A1  - Volkow,N.D.
A1  - Schlyer,D.J.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Gatley,S.J.
Y1  - 1990///
N1  - UI - 90260763
SP  - 213
EP  - 223
JF  - Synapse
VL  - 5
IS  - 3
N2  - The muscarinic cholinergic system has been mapped in vivo in human and baboon brain using [N-11C-methyl]-benztropine and high resolution positron emission tomography (PET). [N-11C-methyl]-benztropine uptake was observed in frontal, parietal, occipital, and temporal cortices as well as in subcortical structures including the corpus striatum and thalamus. Uptake continued to increase in baboon and human brain in all areas over an 80 minute experimental period with the exception of the cerebellum where the accumulation of radioactivity began to decrease by 25 minutes postinjection. The ratio of incorporation of [N-11C-methyl]-benztropine between corpus striatum/cerebellum was 1.53 and 1.46 in humans and baboons, respectively, at 60 minutes. Blocking studies in baboons using the muscarinic cholinergic antagonists scopolamine and benztropine and the muscarinic cholinergic agonist pilocarpine combined with blocking studies in humans using benztropine indicate that the binding of this compound is specific for the muscarinic cholinergic system. Pretreatment with the potent dopamine reuptake blocker nomifensine produced no effect on the incorporation of radioactivity in any baboon brain region examined. Analysis of labelled plasma metabolites indicates that in humans, the rate of metabolism of [N-11C-methyl]-benztropine is slow (83.0% unchanged at 30 minutes postinjection) differing quite dramatically from the rate of metabolism observed in baboons (43.4% unchanged at 30 minutes postinjection). These data combined with postmortem studies in humans and primates demonstrate that [N-11C-methyl]-benztropine is a suitable muscarinic cholinergic ligand for use in humans and baboons with PET
AD  - Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973
UR  - PM:2343375
ER  - 

TY  - JOUR
T1  - Quantitative in vivo receptor binding III: Tracer kinetic modeling of muscarinic cholinergic receptor binding
A1  - Frey,K.A.
A1  - Hichwa,R.D.
A1  - Ehrenkaufer,R.L.
A1  - Agranoff,B.W.
Y1  - 1985/10//
SP  - 6711
EP  - 6715
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 82
IS  - 19
N2  - A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term "free receptor density" is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of [3H]scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period. In this instance, specific tracer binding may be accurately determined by measuring tissue ligand concentration at a single time point after bolus intravenous injection, providing that regional cerebral blood flow is known. This derivation has potential clinical application, because it will permit construction of quantitative pictorial maps of regional free receptor densities in the human brain by means of positron emission tomographic imaging
UR  - PM:3876561
ER  - 

TY  - JOUR
T1  - The binding of 2-(4'-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component
A1  - Klunk,W.E.
A1  - Wang,Y.
A1  - Huang,G.F.
A1  - Debnath,M.L.
A1  - Holt,D.P.
A1  - Shao,L.
A1  - Hamilton,R.L.
A1  - Ikonomovic,M.D.
A1  - Dekosky,S.T.
A1  - Mathis,C.A.
Y1  - 2003/03/15/
N1  - UI - 22544666
SP  - 2086
EP  - 2092
JA  - J Neurosci.
VL  - 23
IS  - 6
N2  - 2-(4'-methylaminophenyl)benzothiazole (BTA-1) is an uncharged derivative of thioflavin-T that has high affinity for Abeta fibrils and shows very good brain entry and clearance. In this study, we asked whether BTA-1, at concentrations typical of those achieved during positron emission tomography (PET) studies, could specifically bind to amyloid deposits in the complex milieu of human brain or whether amyloid binding was overshadowed by nonspecific binding, found even in brains that did not contain amyloid deposits. We quantitatively assessed [3H]BTA-1 binding to crude homogenates of postmortem brain obtained from nine Alzheimer's disease (AD) subjects, eight controls, and six subjects with non-AD dementia. BTA-1 binding was >10-fold higher in AD brain, and the majority (94%) of the binding was specific (displaceable). High-affinity [3H]BTA-1 was observed only in AD brain gray matter and was not present in control brain gray matter, AD brain white matter, or cerebellum. The K(d) of [3H]BTA-1 for binding to AD brain (5.8 +/- 0.90 nm) was very similar to the K(d) for binding to synthetic Abeta fibrils. In addition, the K(i) of various BTA analogs for inhibition of [3H]BTA-1 binding to AD brain homogenates was very similar to their K(i) for inhibition of [3H]BTA-1 binding to synthetic Abeta fibrils. Nanomolar concentrations of [3H]BTA-1 did not appear to bind to neurofibrillary tangles. Finally, BTA-1 did not appear to bind significantly to common neuroreceptors or transporter sites. These data suggest that the binding of BTA-1 to AD brain is dominated by a specific interaction with Abeta amyloid deposits
AD  - Laboratory of Molecular Neuropharmacology, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. klunkwe@msx.upmc.edu
UR  - PM:12657667
ER  - 

TY  - JOUR
T1  - Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes
A1  - Koehne,G.
A1  - Doubrovin,M.
A1  - Doubrovina,E.
A1  - Zanzonico,P.
A1  - Gallardo,H.F.
A1  - Ivanova,A.
A1  - Balatoni,J.
A1  - Teruya-Feldstein,J.
A1  - Heller,G.
A1  - May,C.
A1  - Ponomarev,V.
A1  - Ruan,S.
A1  - Finn,R.
A1  - Blasberg,R.G.
A1  - Bornmann,W.
A1  - Riviere,I.
A1  - Sadelain,M.
A1  - O'Reilly,R.J.
A1  - Larson,S.M.
A1  - Gelovani Tjuvajev,J.G.
Y1  - 2003/03/24/
N1  - UI - 0
JA  - Nat.Biotechnol.
N2  - New technologies are needed to characterize the migration, survival, and function of antigen-specific T cells in vivo. Here, we demonstrate that Epstein-Barr virus (EBV)-specific T cells transduced with vectors encoding herpes simplex virus-1 thymidine kinase (HSV-TK) selectively accumulate radiolabeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU). After adoptive transfer, HSV-TK(+) T cells labeled in vitro or in vivo with [(131)I]FIAU or [(124)I]FIAU can be noninvasively tracked in SCID mice bearing human tumor xenografts by serial images obtained by scintigraphy or positron emission tomography (PET), respectively. These T cells selectively accumulate in EBV(+) tumors expressing the T cells' restricting HLA allele but not in EBV(-) or HLA-mismatched tumors. The concentrations of transduced T cells detected in tumors and tissues are closely correlated with the concentrations of label retained at each site. Radiolabeled transduced T cells retain their capacity to eliminate targeted tumors selectively. This technique for imaging the migration of ex vivo-transduced antigen-specific T cells in vivo is informative, nontoxic, and potentially applicable to humans
AD  - [1] Allogeneic Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. [2] Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. [3] These three authors contributed equally to this work
UR  - PM:12652311
ER  - 

TY  - JOUR
T1  - Optical bioluminescence and positron emission tomography imaging of a novel fusion reporter gene in tumor xenografts of living mice
A1  - Ray,P.
A1  - Wu,A.M.
A1  - Gambhir,S.S.
Y1  - 2003/03/15/
N1  - UI - 22535369
SP  - 1160
EP  - 1165
JA  - Cancer Res.
VL  - 63
IS  - 6
N2  - Noninvasive imaging of reporter gene expression using various imaging modalitiesis playing an increasingly important role in defining molecular events in the field of cancer biology, cell biology, and gene therapy. In this study, a novel reporter vector was constructed encoding a fusion protein comprised of a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) (tk), a positron emission tomography (PET) reporter gene, and renilla luciferase (rl), a bioluminescence optical reporter gene joined by a 20 amino acid long spacer sequence. We validated the activity of the two enzymes encoded by the fusion protein (tk(20)rl) in cell culture. Then, tumors stably expressing the tk(20)rl fusion gene were imaged both by microPET and optically using a cooled charge coupled device camera in xenograft-bearing living mice. Using a single fusion reporter (PET/optical) gene should accelerate the validation of reporter gene approaches developed in cell culture for translation into preclinical and clinical models
AD  - Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Gefen School of Medicine, University of California, Los Angeles, California 90095, USA
UR  - PM:12649169
ER  - 

TY  - JOUR
T1  - Relationship between trait anxiety, brain activity and natural killer cell activity in cancer patients: a preliminary PET study
A1  - Tashiro,M.
A1  - Itoh,M.
A1  - Kubota,K.
A1  - Kumano,H.
A1  - Masud,M.M.
A1  - Moser,E.
A1  - Arai,H.
A1  - Sasaki,H.
Y1  - 2001/11//
N1  - UI - 21612777
SP  - 541
EP  - 546
JA  - Psychooncology.
VL  - 10
IS  - 6
N2  - The purpose of this study is to examine the relationship between psychological factors, regional brain activity and natural killer cell activity (NKA). Eight patients with malignant diseases were studied by FDG-PET under a resting condition. NKA and degree of anxiety and depression were measured using Taylor's manifest anxiety scale (MAS) and Zung's self-rating depression scale (SDS). Linear correlation of NKA and psychological measures to the regional brain metabolism in cancer patients was examined using statistical parametric mapping (SPM). Positive linear correlation between NKA and regional metabolic rate ratios was identified in the visual association cortex, anterior cingulate gyrus (CG) and sensorimotor area, and negative correlation was identified in the inferolateral prefrontal cortex (ILPFC), prefrontal cortex (PFC), orbitofrontal cortex (OFC) and anterior temporal cortex. Positive linear correlation to the MAS score was identified in the visual association cortex, anterior CG, primary sensorimotor area and the posterior parietal cortex, and negative correlation was detected in the ILPFC, PFC, OFC and anterior temporal cortex. The NKA and MAS scores positively correlated with each other (p<0.001). The result might serve as supporting data for a hypothesis that psycho-immune interaction is also mediated by the cerebral cortex and limbic system
AD  - Division of Nuclear Medicine, Cyclotron and Radioisotope Centre, Tohoku University, Sendai, Japan. mtashiro@mail.cc.tohoku.ac.jp
UR  - PM:11747066
ER  - 

TY  - JOUR
T1  - The cerebral neurobiology of anxiety, anxiety displacement, and anxiety denial
A1  - Gottschalk,L.A.
A1  - Fronczek,J.
A1  - Abel,L.
A1  - Buchsbaum,M.S.
A1  - Fallon,J.H.
Y1  - 2001/01//
SP  - 17
EP  - 24
JA  - Psychother.Psychosom.
VL  - 70
IS  - 1
N2  - BACKGROUND: Previous studies examining the relationship of anxiety scores, derived from the content analysis of speech of normal individuals, have revealed that the anxiety scores occurring in the dreams associated with rapid eye movement (REM) sleep are significantly correlated with localized cerebral glucose metabolic rates assessed by positron emission tomography (PET) scanning. These significant intercorrelations occur in different cerebral areas when the anxiety scores are obtained from mental experiences reported during non-REM sleep or during wakeful silent mentation. OBJECTIVE: The purpose of the present study was to examine the intercorrelations found between anxiety attributed to the self, anxiety-displacement, and anxiety denial measured from computerized content analysis of 5-min verbal reports of subjective thoughts and feelings obtained from wakeful normal subjects and localized cerebral glucose metabolic rates during PET scanning. METHODS: The subjects were 10 wakeful young males. Their anxiety scores were derived from computerized content analysis of 5-min reports they gave of their subjective thoughts, feelings and fantasies during a 30-min period following an intravenous injection of F D-deoxyglucose (FDG). The subjects were moved 32--45 min after this injection to obtain a PET scan, which records all of the localized cerebral glucose metabolic rates during the 30 min following the FDG injection. RESULTS: Significant intercorrelations of localized cerebral glucose metabolic rates with the scores of self-anxiety, anxiety displacement, and anxiety-denial were found in dissimilar cerebral locations depending on the type of anxiety involved. The significant correlations occurred in brain regions known to be associated with the functions of emotions, cognition, memory, and vision. CONCLUSIONS: Specific combinations of cerebral areas, based on glucose metabolic rates, appear to distinguish and be associated with different verbal expressions of anxiety. Replication of this preliminary research will be carried out
AD  - The Brain Imaging Center, Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine, CA 92697, USA. lgottsch@uci.edu
UR  - PM:11150934
ER  - 

TY  - JOUR
T1  - Cingulate function in depression: a potential predictor of treatment response
A1  - Mayberg,H.S.
A1  - Brannan,S.K.
A1  - Mahurin,R.K.
A1  - Jerabek,P.A.
A1  - Brickman,J.S.
A1  - Tekell,J.L.
A1  - Silva,J.A.
A1  - McGinnis,S.
A1  - Glass,T.G.
A1  - Martin,C.C.
A1  - Fox,P.T.
Y1  - 1997/03/03/
N1  - UI - 97285875
SP  - 1057
EP  - 1061
JF  - Neuroreport
VL  - 8
IS  - 4
N2  - The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed
AD  - Research Imaging Center, University of Texas Health Science Center at San Antonio 78284-6240, USA
UR  - PM:9141092
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism during pharmacologic studies: test-retest under placebo conditions
A1  - Schmidt,M.E.
A1  - Ernst,M.
A1  - Matochik,J.A.
A1  - Maisog,J.M.
A1  - Pan,B.S.
A1  - Zametkin,A.J.
A1  - Potter,W.Z.
Y1  - 1996/07//
SP  - 1142
EP  - 1149
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 37
IS  - 7
N2  - The reliability of serial [18F]fluorodeoxyglucose (FDG) PET scans for psychopharmacologic studies was tested by using placebo infusions. METHODS: FDG scans were obtained before and after a 30 min placebo infusion (n = 10; Group 1) or after each of two bolus infusions with placebo (n = 8; Group 2). Subjects performed a continuous performance task (CPT) during each scan. Cardiovascular measures and ratings of anxiety were obtained in all subjects. Samples for determination of plasma norepinephrine (NE) were taken at multiple time points in Group 1. RESULTS: A slight increase in apparent global metabolism occurred between scans in both Groups 1 and 2. A few regions significantly increased in both groups. While an apparent increase in sympathetic activity occurred during the placebo infusion, neither NE levels, anxiety ratings nor cardiovascular measures correlated with global or regional FD6 uptake. CONCLUSION: Test-retest differences of global and regional glucose metabolism were highly consistent across two experimental designs. While increases in cerebral glucose metabolism appeared to occur during the second scan, differences between scans were small. This method may offer advantages for selected psychopharmacologic studies
AD  - Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
UR  - PM:8965185
ER  - 

TY  - JOUR
T1  - The effect of anxiety and hostility in silent mentation on localized cerebral glucose metabolism
A1  - Gottschalk,L.A.
A1  - Buchsbaum,M.S.
A1  - Gillin,J.C.
A1  - Wu,J.
A1  - Reynolds,C.A.
A1  - Herrera,D.B.
Y1  - 1992/01//
N1  - UI - 92209233
SP  - 52
EP  - 59
JA  - Compr.Psychiatry
VL  - 33
IS  - 1
N2  - Ten normal, wakeful, young (average age, 25.3 +/- 6.6 years) male subjects received positron emission tomographic (PET) scans 45 to 120 minutes after an infusion of D-[18 F]deoxyglucose in order to assess localized cerebral glucose metabolic rates during silent visual and other sensory imagery and cognitive mentation. The typescripts of the verbal reports, limited to 5 minutes, of this type of mentation (including free-associations to all the silent mental events), were blindly content-analyzed to provide objective measures of various kinds of anxiety and hostility. Many significant positive and negative correlations were found in medial cortical, lateral cortical, and subcortical gray matter, and white matter areas between the magnitude of the anxiety and hostility aroused in the silent mental processes and localized cerebral glucose metabolic rates. Clearly, energy consumption in the brain, as judged from localized glucose metabolic rates, is highly influenced by the quality and quantity of emotionally tinged private reveries and mental events occurring spontaneously within human subjects. Brain areas involved with the processing of language, sensation, cognition, memory, and emotional reactions appear to be involved especially in these significant correlations. The implications of such findings in the neurosciences and behavioral sciences are discussed
AD  - Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine 92717
UR  - PM:1555410
ER  - 

TY  - JOUR
T1  - Anxiety levels in dreams: relation to localized cerebral glucose metabolic rate
A1  - Gottschalk,L.A.
A1  - Buchsbaum,M.S.
A1  - Gillin,J.C.
A1  - Wu,J.C.
A1  - Reynolds,C.A.
A1  - Herrera,D.B.
Y1  - 1991/01/04/
N1  - UI - 91208546
SP  - 107
EP  - 110
JA  - Brain Res.
VL  - 538
IS  - 1
N2  - Ten normal male subjects were injected with D-[18F]deoxyglucose during REM sleep, and 32-45 min later they were aroused and reported their dreams as well as free associations to these dreams. Nonparametric correlations between the anxiety scores derived from the typescripts of these verbal reports by the Gottschalk-Gleser content analysis method and localized cerebral glucose metabolic rates obtained from PET scans revealed significant positive correlations in lateral parietal and medial frontal cortex and negative correlations in adjacent white matter
AD  - Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine 92717
UR  - PM:2018922
ER  - 

TY  - JOUR
T1  - Anxiety and cerebral cortical metabolism in normal persons
A1  - Giordani,B.
A1  - Boivin,M.J.
A1  - Berent,S.
A1  - Betley,A.T.
A1  - Koeppe,R.A.
A1  - Rothley,J.M.
A1  - Modell,J.G.
A1  - Hichwa,R.D.
A1  - Kuhl,D.E.
Y1  - 1990/04//
N1  - UI - 90311505
SP  - 49
EP  - 60
JA  - Psychiatry Res.
VL  - 35
IS  - 1
N2  - The State-Trait Anxiety Inventory (STAI) was administered to 43 normal volunteers immediately before and after a positron emission tomography (PET) procedure with [18F]-2-fluoro-2-deoxy-D-glucose (18F-FDG). High trait-anxious individuals had significantly higher state (situational) anxiety associated with the PET scan procedure than did low trait-anxious persons. State anxiety decreased significantly for all respondents following the PET scan procedure. No significant relationships between global or regional cortical metabolic rates and state anxiety were observed. The direct cortical metabolic effects of heightened anxiety in the scan setting, should they exist, are likely obscured in the normal variance of the 18F-FDG method
AD  - University of Michigan, Ann Arbor
UR  - PM:2367610
ER  - 

TY  - JOUR
T1  - Selective reductions in prefrontal glucose metabolism in murderers
A1  - Raine,A.
A1  - Buchsbaum,M.S.
A1  - Stanley,J.
A1  - Lottenberg,S.
A1  - Abel,L.
A1  - Stoddard,J.
Y1  - 1994/09/15/
N1  - UI - 95101839
SP  - 365
EP  - 373
JA  - Biol.Psychiatry
VL  - 36
IS  - 6
N2  - This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community
AD  - Department of Psychology, University of Southern California, Los Angeles 90089-1061
UR  - PM:7803597
ER  - 

TY  - JOUR
T1  - Effect of attention on frontal distribution of delta activity and cerebral metabolic rate in schizophrenia
A1  - Guich,S.M.
A1  - Buchsbaum,M.S.
A1  - Burgwald,L.
A1  - Wu,J.
A1  - Haier,R.
A1  - Asarnow,R.
A1  - Nuechterlein,K.
A1  - Potkin,S.
Y1  - 1989/11//
N1  - UI - 91120446
SP  - 439
EP  - 448
JA  - Schizophr.Res.
VL  - 2
IS  - 6
N2  - 15 patients with schizophrenia and nine normal volunteers had 32 channel topographic EEG recorded for spectral analysis during the uptake of 18-F-deoxyglucose (FDG) for positron emission tomography (PET). Both patients and controls performed the Continuous Performance Test, a visual vigilance task, during FDG uptake. EEG was also obtained during an initial pre-FDG resting period. Each EEG epoch was individually inspected for eye movement artifacts. Analysis confirmed increased delta activity in the frontal region of patients with schizophrenia in comparison to normal controls, and a significant correlation between increased frontal delta and relative reduction in frontal lobe metabolism among patients with schizophrenia. This finding of increased delta is consistent with PET, blood flow and topographic EEG studies of schizophrenia, suggesting reduced frontal activity
AD  - Department of Cognitive Sciences, University of California Irvine 92717
UR  - PM:2487185
ER  - 

TY  - JOUR
T1  - Estrogen use and brain metabolic change in older adults. A preliminary report
A1  - Rasgon,N.L.
A1  - Small,G.W.
A1  - Siddarth,P.
A1  - Miller,K.
A1  - Ercoli,L.M.
A1  - Bookheimer,S.Y.
A1  - Lavretsky,H.
A1  - Huang,S.C.
A1  - Barrio,J.R.
A1  - Phelps,M.E.
Y1  - 2001/07/01/
N1  - UI - 21366264
SP  - 11
EP  - 18
JA  - Psychiatry Res.
VL  - 107
IS  - 1
N2  - Because estrogen may influence brain blood flow and metabolism in older adults, we used positron emission tomography to evaluate cerebral glucose metabolic change in post-menopausal women and men. Women estrogen users (n=4), women non-users (n=8) and men (n=10) were scanned at baseline and two years later. Analyses focused on glucose metabolism in lateral temporal, inferior parietal and posterior cingulate brain regions, previously reported to decline in non-demented older persons. No metabolic differences in cerebral regions of interest were found among groups at baseline. At follow-up, women estrogen users showed significantly increased glucose metabolism in the lateral temporal region, whereas women non-users and men exhibited no significant metabolic change in this region. These findings suggest that estrogen use may protect against regional cerebral metabolic decline in postmenopausal women
AD  - Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, the Neuropsychiatric Institute, Los Angeles, CA 90095, USA. nrasgon@mednet.ucla.edu
UR  - PM:11472860
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic rates in normal human females versus normal males
A1  - Baxter,L.R.,Jr.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Selin,C.E.
A1  - Guze,B.H.
A1  - Fairbanks,L.
Y1  - 1987/07//
N1  - UI - 87318289
SP  - 237
EP  - 245
JA  - Psychiatry Res.
VL  - 21
IS  - 3
N2  - Sex-related differences have been reported for some brain neuroanatomical structures and several measures of brain function. We studied the cerebral glucose metabolic rates of normal men (n = 7) and women (n = 7) with positron emission tomography and the fluorodeoxyglucose method. Women were studied between days 5 and 15 of the menstrual cycle. Women had whole brain glucose metabolic rates that were 19% higher than those of men. All neuroanatomical structures surveyed showed significant female greater than male rates, with no particular regions being outstanding. The higher cerebral glucose metabolic rates we observed in women may have been related to the effects of the high estrogen levels that can obtain in the phase of the menstrual cycle during which we tested our female subjects
UR  - PM:3498176
ER  - 

TY  - JOUR
T1  - Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Gur,R.C.
A1  - Wong,C.
A1  - Felder,C.
A1  - Gatley,S.J.
A1  - Ding,Y.S.
A1  - Hitzemann,R.
A1  - Pappas,N.
Y1  - 2000/01//
SP  - 75
EP  - 80
JA  - Am.J Psychiatry
VL  - 157
IS  - 1
N2  - OBJECTIVE: Despite the well-documented loss of brain dopamine activity with age, little is known about its functional consequences in healthy individuals. This study investigates the relationship between measures of brain dopamine D(2) receptors (molecules that transmit dopamine signals) and regional brain glucose metabolism (a marker of brain function) in healthy individuals. METHOD: Thirty-seven healthy volunteers aged 24-86 years underwent positron emission tomography scans after injection of [(11)C]raclopride to assess dopamine D(2) receptors and [(18)]fluorodeoxyglucose to assess regional brain glucose metabolism. Two methods used to assess the correlations between metabolism and dopamine D(2) receptors-pixel-by-pixel correlations and correlations in preselected regions of interest-were then compared. RESULTS: D(2) receptors as well as frontal and cingulate metabolism declined with age. Regardless of the method used, significant correlations between metabolism and D(2) receptors were found in the frontal cortex (Brodmann's areas 6, 7, 8, 9, 10, 11, 44, 45, 47), anterior cingulate gyrus (areas 24, 32), temporal cortex (area 21), and caudate. These correlations remained significant after removing age effects (partial correlation). CONCLUSIONS: These results provide the first link between age-related declines in brain dopamine activity and frontal and cingulate metabolism, which supports the need to investigate the therapeutic utility of interventions that enhance dopamine function in the elderly. The fact that correlations remained significant after removing age effects suggests that dopamine may influence frontal, cingulate, and temporal metabolism regardless of age
AD  - Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY 11973, USA. volkow@bnl.gov
UR  - PM:10618016
ER  - 

TY  - JOUR
T1  - Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age
A1  - Loessner,A.
A1  - Alavi,A.
A1  - Lewandrowski,K.U.
A1  - Mozley,D.
A1  - Souder,E.
A1  - Gur,R.E.
Y1  - 1995/07//
N1  - UI - 95311023
SP  - 1141
EP  - 1149
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 36
IS  - 7
N2  - The main objective of this study was to determine patterns of regional brain metabolic activity utilizing high-resolution PET in normal healthy volunteers and variations in different age groups. METHODS: High-resolution [18F]FDG PET images of the entire brain were obtained in 120 healthy normal volunteers (64 men, 56 women), age range from 19 to 79 yr. Each anatomic region was assessed using a qualitative rating scale with a score ranging from 1 to 6 (1 = definitely normal and 6 = definitely abnormal). Local metabolic activity was also estimated as showing increased (+) or decreased (-) compared to normal (0) states. RESULTS: The most consistent finding in normal aging was decreased cortical metabolism, particularly in the frontal lobes. Temporal, parietal and occipital lobe metabolism varied considerably among subjects within the same age group as well as over decades. Basal ganglia, hippocampal area, thalami, cerebellum, posterior cingulate gyrus and visual cortex remained metabolically unchanged with advancing age. CONCLUSION: These data indicate that qualitative interpretation of FDG-PET images allows accurate assessment of regional metabolic activity of the brain in normal subjects similar to those described with quantitative techniques. Adequate knowledge of normal variations and changes related to normal aging is necessary for optimal assessment of pathologic states
AD  - Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, USA
UR  - PM:7790936
ER  - 

TY  - JOUR
T1  - Regional brain function in schizophrenia. I. A positron emission tomography study
A1  - Gur,R.E.
A1  - Resnick,S.M.
A1  - Alavi,A.
A1  - Gur,R.C.
A1  - Caroff,S.
A1  - Dann,R.
A1  - Silver,F.L.
A1  - Saykin,A.J.
A1  - Chawluk,J.B.
A1  - Kushner,M.
Y1  - 1987/02//
N1  - UI - 87127333
SP  - 119
EP  - 125
JA  - Arch Gen.Psychiatry
VL  - 44
IS  - 2
N2  - Local cerebral glucose metabolism was determined with 18-F-fluorodeoxyglucose using positron emission tomography in a sample of 12 unmedicated schizophrenics and 12 matched normal controls. The data were analyzed for absolute metabolic rates and region/whole-brain ratios using the cortical-subcortical, antero-posterior, and laterality dimensions. Lobar areas within cortical regions were also compared. Across groups, subcortical metabolism was higher than cortical metabolism. Patients had lower metabolism, cortically and subcortically, and a steeper subcortical to cortical gradient. Patients with higher scores on the Brief Psychiatric Rating Scale had higher absolute metabolism and higher left relative to right hemispheric metabolism than did patients with lesser severity. The results did not show "hypofrontality" in schizophrenia. These findings provide some support for cerebral dysfunction in schizophrenia and indicate the need for further examination of the cortical-subcortical dimension
UR  - PM:3492982
ER  - 

TY  - JOUR
T1  - Combined positron emission tomography and magnetic resonance imaging for the planning of stereotactic brain biopsies in children: experience in 9 cases
A1  - Pirotte,B.
A1  - Goldman,S.
A1  - Salzberg,S.
A1  - Wikler,D.
A1  - David,P.
A1  - Vandesteene,A.
A1  - Van Bogaert,P.
A1  - Salmon,I.
A1  - Brotchi,J.
A1  - Levivier,M.
Y1  - 2003/03//
N1  - UI - 22489697
SP  - 146
EP  - 155
JA  - Pediatr.Neurosurg
VL  - 38
IS  - 3
N2  - Because brain tumors can be histologically heterogeneous, stereotactic brain biopsies (SBB) may lead to inaccurate diagnosis or grading. Positron emission tomography (PET) has been used in pediatric neuro-oncology to help in the understanding and management of brain neoplasms. We combined PET and magnetic resonance (MR) imaging in the planning of SBB in 9 children (5 males and 4 females, aged 2-14 years) with infiltrative, ill-defined brain lesions. Tracers used for PET were (18)F-2-fluoro-2-deoxy-D-glucose in 4 cases, (11)C-methionine in 2 cases and both tracers in 3 cases. Biopsy targets were selected in hypermetabolic areas. PET-guided SBB provided accurate histological diagnosis in all patients and allowed a reduction of the number of trajectories in lesions located in functional areas. It also helped in better understanding and management of complex cases. This preliminary series suggests that combining PET and MR imaging in the planning of SBB in children (1) improves the diagnostic yield of SBB in infiltrative, ill-defined brain lesions, (2) makes it possible to reduce the sampling in high-risk/functional areas and (3) improves the quality of therapeutic management of pediatric brain tumors. Copyright 2003 S. Karger AG, Basel
AD  - Department of Neurosurgery, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium
UR  - PM:12601239
ER  - 

TY  - JOUR
T1  - Brain function in the vegetative state
A1  - Laureys,S.
A1  - Antoine,S.
A1  - Boly,M.
A1  - Elincx,S.
A1  - Faymonville,M.E.
A1  - Berre,J.
A1  - Sadzot,B.
A1  - Ferring,M.
A1  - De,Tiege,X
A1  - Van Bogaert,P.
A1  - Hansen,I.
A1  - Damas,P.
A1  - Mavroudakis,N.
A1  - Lambermont,B.
A1  - Del Fiore,G.
A1  - Aerts,J.
A1  - Degueldre,C.
A1  - Phillips,C.
A1  - Franck,G.
A1  - Vincent,J.L.
A1  - Lamy,M.
A1  - Luxen,A.
A1  - Moonen,G.
A1  - Goldman,S.
A1  - Maquet,P.
Y1  - 2002/12//
N1  - UI - 22422165
SP  - 177
EP  - 185
JA  - Acta Neurol Belg.
VL  - 102
IS  - 4
N2  - Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction
AD  - Cyclotron Research Center, Department of Neurology, CHU Sart Tilman, University of Liege, Liege, Belgium. steven.laureys@ulg.ac.be
UR  - PM:12534245
ER  - 

TY  - JOUR
T1  - The integration of metabolic imaging in stereotactic procedures including radiosurgery: a review
A1  - Levivier,M.
A1  - Wikler,D.,Jr.
A1  - Massager,N.
A1  - David,P.
A1  - Devriendt,D.
A1  - Lorenzoni,J.
A1  - Pirotte,B.
A1  - Desmedt,F.
A1  - Simon S Jr
A1  - Goldman,S.
A1  - Van Houtte,P.
A1  - Brotchi,J.
Y1  - 2002/12//
N1  - UI - 22394780
SP  - 542
EP  - 550
JA  - J Neurosurg
VL  - 97
IS  - 5 Suppl
N2  - OBJECT: The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). METHODS: Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography-guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. CONCLUSIONS: Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors
AD  - Centre Gamma Knife, Universite Libre de Bruxelle, Departmente de Neurochirurgie, PET-Cyclotron Biomedical, Hopital Erasme, Bruxelle, Belgique. Marc.Levivier@ulb.ac.be
UR  - PM:12507094
ER  - 

TY  - JOUR
T1  - Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory
A1  - Yasuno,F.
A1  - Suhara,T.
A1  - Nakayama,T.
A1  - Ichimiya,T.
A1  - Okubo,Y.
A1  - Takano,A.
A1  - Ando,T.
A1  - Inoue,M.
A1  - Maeda,J.
A1  - Suzuki,K.
Y1  - 2003/02//
SP  - 334
EP  - 340
JA  - Am.J Psychiatry
VL  - 160
IS  - 2
N2  - OBJECTIVE: Recent studies have indicated that the serotonergic (5-HT) system plays important roles in memory function. However, the specific relationship between 5-HT(1A) receptors and memory function is not clear in the human brain. To clarify this relationship, the authors determined the availability of 5-HT(1A) receptors in the human brain and the relationship between regional receptor binding and memory function. METHOD: Using positron emission tomography (PET) with [(11)C]WAY-100635, the authors examined 5-HT(1A) receptors and assessed their relationship with memory function. The 5-HT(1A )agonist tandospirone was then administered to investigate the effect of 5-HT(1A) receptor stimulation on cognitive function and neuroendocrinological response. RESULTS: There was a significant negative correlation between explicit memory function and 5-HT(1A) receptor binding localized in the bilateral hippocampus where the postsynaptic 5-HT(1A) receptors are enriched. Furthermore, the administration of tandospirone dose-dependently impaired explicit verbal memory, while other cognitive functions showed no significant changes. The change in memory function paralleled those of body temperature and secretion of growth hormone, which were reported to be induced by the stimulation of postsynaptic 5-HT(1A) receptors. CONCLUSIONS: Postsynaptic 5-HT(1A )receptors localized in the hippocampal formation have a negative influence on explicit memory function, which raises the possibility that the antagonistic effect of postsynaptic 5-HT(1A) receptors in the hippocampus leads to improvement of human memory function. Drugs that work as antagonists on postsynaptic 5-HT(1A) receptors may be favorable for improved control of memory impairment
AD  - Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan
UR  - PM:12562581
ER  - 

TY  - JOUR
T1  - A positron-emitter labeled glycine(B) site antagonist, [(11)C]L-703,717, preferentially binds to a cerebellar NMDA receptor subtype consisting of GluR epsilon3 subunit in vivo, but not in vitro
A1  - Haradahira,T.
A1  - Okauchi,T.
A1  - Maeda,J.
A1  - Zhang,M.R.
A1  - Kida,T.
A1  - Kawabe,K.
A1  - Mishina,M.
A1  - Watanabe,Y.
A1  - Suzuki,K.
A1  - Suhara,T.
Y1  - 2002/02//
SP  - 131
EP  - 133
JF  - Synapse
VL  - 43
IS  - 2
N2  - In previous studies, we have found that [(11)C]L-703,717, a positron-emitter labeled antagonist for the glycine-binding site of NMDA receptors, only localizes in rodent cerebellum under in vivo conditions. In order to understand the unusual cerebellar localization, we have examined the binding of [(11)C]L-703,717 to a cerebellar-specific NMDA receptor subtype consisting of GLuRepsilon3 subunit, by comparing its autoradiographic distributions between GluRepsilon3-deficient and wild-type mice. Ex vivo [(11)C]L-703,717 binding to wild-type mice showed a highly specific localization of radioactivity in the cerebellum, whereas that to the GluRepsilon3-deficient mice showed no specific localization of radioactivity in any of the brain regions. In contrast to the ex vivo binding, in vitro [(11)C]L-703,717 binding displayed a similar binding characteristic between GluRepsilon3-deficient and wild-type mice with highly specific localizations in the hippocampus and cerebral cortex. Therefore, the present study clearly demonstrated that [(11)C]L-703,717 preferentially binds to a cerebellar NMDA receptor subtype consisting of GluRepsilon3 subunit in vivo, but not in vitro
AD  - Division of Medical Imaging, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan
UR  - PM:11754492
ER  - 

TY  - JOUR
T1  - Neuroanatomical correlates of a lactate-induced anxiety attack
A1  - Reiman,E.M.
A1  - Raichle,M.E.
A1  - Robins,E.
A1  - Mintun,M.A.
A1  - Fusselman,M.J.
A1  - Fox,P.T.
A1  - Price,J.L.
A1  - Hackman,K.A.
Y1  - 1989/06//
N1  - UI - 89272490
SP  - 493
EP  - 500
JA  - Arch Gen.Psychiatry
VL  - 46
IS  - 6
N2  - Positron emission tomographic measurements of regional blood flow were used to assess local neuronal activity in patients with panic disorder and in normal control subjects before and during the infusion of sodium lactate. A new technique for the analysis of positron emission tomographic data was employed to identify significant changes in regional blood flow associated with lactate infusion in the panicking patients, nonpanicking patients, and controls. Lactate-induced panic was associated with significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis. Lactate infusion was not associated with significant changes in regional blood flow in the nonpanicking patients or control subjects. Thus, the identified regions seemed to be involved in an anxiety attack
AD  - Department of Psychiatry, Mallinckrodt Institute of Radiology, St. Louis, MO 63110
UR  - PM:2786401
ER  - 

TY  - JOUR
T1  - Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images
A1  - Fox,P.T.
A1  - Mintun,M.A.
A1  - Reiman,E.M.
A1  - Raichle,M.E.
Y1  - 1988/10//
N1  - UI - 88331147
SP  - 642
EP  - 653
JA  - J Cereb.Blood Flow Metab
VL  - 8
IS  - 5
N2  - Intersubject averaging and change-distribution analysis of subtracted positron emission tomographic (PET) images were developed and tested. The purpose of these techniques is to increase the sensitivity and objectivity of functional mapping of the human brain with PET. To permit image averaging, all primary tomographic images were converted to anatomically standardized three-dimensional images using stereotactic anatomical localization and interslice interpolation. Image noise, measured in control-minus-control subtractions, was strongly suppressed by averaging. Signal-to-noise ratio, measured in stimulus-minus-control subtractions (hand vibration minus eyes-closed rest), rose steadily with averaging, confirming the accuracy of our method of anatomical standardization. Distribution analysis of CBF change images (outlier detection by gamma-2 statistic) was assessed as an omnibus test for state-dependent changes in regional neuronal activity. Sensitivity in detecting the somatosensory response rose steadily with averaging, increasing from 50% in individual images to 100% when three or more images were averaged. Specificity was 100% at all averaging levels. Although described here as a technique for functional brain mapping with H2(15O) CBF images, image averaging, and change-distribution analysis are more generally applicable techniques, not limited to a single purpose or tracer
AD  - Department of Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, Missouri
UR  - PM:3262113
ER  - 

TY  - BOOK
T1  - Handbook of Functional Neuroimaging of Cognition
A1  - Cabeza,R.
A1  - Kingstone,A.
Y1  - 2001///
PB  - MIT Press
ER  - 

TY  - JOUR
T1  - Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects
A1  - Tsuchida,T.
A1  - Sadato,N.
A1  - Nishizawa,S.
A1  - Yonekura,Y.
A1  - Itoh,H.
Y1  - 2002/02//
N1  - UI - 21923334
SP  - 248
EP  - 250
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 29
IS  - 2
N2  - The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc(real)). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc(sim)) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC(real)) and simulated input function (AUC(IFsim)) and percent error between CMRGlc(real) and CMRGlc(sim) were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165+/-69 vs 100+/-9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%+/-1.3% vs 3.5%+/-2.2% in AUC, P=0.0015; 18.2%+/-2.2% vs 2.9%+/-1.9% in CMRGlc in grey matter, P=0.0028; 24.0%+/-4.6% vs 3.4%+/-2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions
AD  - Department of Radiology, Fukui Medical University, Matsuoka, Japan. tsucchy@fmsrsa.fukui-med.ac.jp
UR  - PM:11926388
ER  - 

TY  - JOUR
T1  - Targeting alzheimer amyloid plaques in vivo
A1  - Wengenack,T.M.
A1  - Curran,G.L.
A1  - Poduslo,J.F.
Y1  - 2000/08//
N1  - UI - 20392307
SP  - 868
EP  - 872
JA  - Nat.Biotechnol.
VL  - 18
IS  - 8
N2  - The only definitive diagnosis for Alzheimer disease (AD) at present is postmortem observation of neuritic plaques and neurofibrillary tangles in brain sections. Radiolabeled amyloid-beta peptide (Abeta), which has been shown to label neuritic plaques in vitro, therefore could provide a diagnostic tool if it also labels neuritic plaques in vivo following intravenous injection. In this study, we show that the permeability of Abeta at the blood-brain barrier can be increased by at least twofold through covalent modification with the naturally occurring polyamine, putrescine. We also show that, following intravenous injection, radiolabeled, putrescine-modified Abeta labels amyloid deposits in vivo in a transgenic mouse model of AD, as well as in vitro in human AD brain sections. This technology, when applied to humans, may be used to detect plaques in vivo, allowing early diagnosis of the disease and therapeutic intervention before cognitive decline occurs
AD  - Molecular Neurobiology Laboratory, Departments of Neurology Biochemistry/Molecular Biology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
UR  - PM:10932157
ER  - 

TY  - JOUR
T1  - Fluorine-18 labeled mouse bone marrow-derived dendritic cells can be detected in vivo by high resolution projection imaging
A1  - Olasz,E.B.
A1  - Lang,L.
A1  - Seidel,J.
A1  - Green,M.V.
A1  - Eckelman,W.C.
A1  - Katz,S.I.
Y1  - 2002/02/01/
N1  - UI - 21652925
SP  - 137
EP  - 148
JA  - J Immunol.Methods
VL  - 260
IS  - 1-2
N2  - Immunization with ex vivo generated dendritic cells has become a focus for many clinical applications. The optimal site of injection and the migration pattern of these cells remain to be elucidated. We therefore developed a novel method for labeling mouse bone marrow-derived dendritic cells (BMDC) with the positron emitting radioisotope F-18 using N-succinimidyl-4-[F-18]fluorobenzoate, which covalently binds to the lysine residues of cell surface proteins. When we determined the stability of F-18 labeled BMDC, we found that at 4 h only 44+/-10% of the initial cell-bound activity was retained at 37 degrees C, whereas considerably more (91+/-3%) was retained at 4 degrees C. Labeled cells did not exhibit any significant alteration in cell viability or phenotype as determined by trypan blue exclusion and FACS analysis 24 h after radiolabeling. Furthermore, F-18-labeled BMDC stimulated allogeneic T cells in a mixed leukocyte reaction as potently as did sham-treated BMDC and migrated towards secondary lymphoid tissue chemokine (SLC) in a chemotaxis assay in vitro with the same efficiency as sham-treated BMDC. Migration of F-18-labeled BMDC was studied after footpad injection by (1) ex vivo counting of dissected tissues using a gamma counter and (2) in vivo by imaging mice with PiPET, a 2-mm resolution positron projection imager. After 4 h, the ratio between measured activity in draining vs. contralateral (D/C) lymph nodes (LN) was 166+/-96 (n=7) in the case of live cell injections, whereas if we injected heat-killed F-18-labeled BMDC or F-18-labeled macrophages the D/C ratios were 17+/-2 (n=2) and 14+/-4 (n=2), respectively. Injection of cell-free activity in the form of F-18-labeled 4-fluorobenzoic acid resulted in a D/C ratio of 7+/-2 (n=3), suggesting that the activity measured in the draining lymph node was associated with migrated F-18-labeled BMDC. When F-18-labeled live cells were injected into the footpad, 0.18+/-0.04% (n=7) of footpad activity was found in the draining LN within 4 h, whereas none was found in the contralateral LN. Quantitative assessment of cell migration by PET projection imaging of mice confirmed the ex-vivo counting results. These studies indicate that PET imaging offers a new approach for in vivo studies of dendritic cell biodistribution and migration
AD  - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 12N238, 10 Center Drive, MSC 1908, Bethesda, MD 20892-1908, USA
UR  - PM:11792384
ER  - 

TY  - JOUR
T1  - Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F]dopa PET
A1  - Morrish,P.K.
A1  - Rakshi,J.S.
A1  - Bailey,D.L.
A1  - Sawle,G.V.
A1  - Brooks,D.J.
Y1  - 1998/03//
N1  - UI - 98186370
SP  - 314
EP  - 319
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 64
IS  - 3
N2  - OBJECTIVES: To measure the rate of progression in striatal [18F]dopa metabolism in a large group (n=32) of patients with Parkinson's disease, to estimate the average duration of preclinical period, and to examine the influence of the PET method on the assessment of rate of progression and preclinical period. METHODS: Thirty two patients with Parkinson's disease (mean age 58 (SD 13) years, mean duration 39 (SD 33) months) were assessed with [18F]dopa PET and UPDRS scoring on two occasions a mean of 18 (SD 6) months apart. PET data were sampled with separate caudate and putamen and total striatal regions of interest, and both graphical (Ki) and ratio methods of analysis. RESULTS: The mean annual rate of deterioration in [18F]dopa uptake varied according to structure and method of analysis, with putamen Ki showing the most rapid mean rate of progression (4.7% of normal mean per year). The group showed a significant deterioration (p<0.0004, paired two tailed t test) in UPDRS and in the putamen (p=0.008) and total striatal (p=0.012) [18F]dopa uptake measured using a graphical analysis, but no significant change in caudate or putamen uptake measured by a ratio approach. A study of sensitivity confirmed that putamen Ki was the most sensitive measure of disease progression, caudate ratio the least. Symptom onset in Parkinson's disease was estimated at a mean putamen [18F]dopa uptake (Ki) of 75% of normal and a mean caudate [18F]dopa uptake (Ki) of 91% of normal. CONCLUSIONS: Estimation of mean rate of progression varies according to the sensitivity of a functional imaging method to clinical severity. Sensitivity and reproducibility of method must be considered when designing studies of disease progression and neuroprotection. The mean preclinical period in Parkinson's disease is unlikely to be longer than seven years
AD  - MRC Cyclotron Unit Hammersmith Hospital, London, UK. morrishpk@cardiff.ac.uk
UR  - PM:9527140
ER  - 

TY  - JOUR
T1  - Two behavioral states studied in a single PET/FDG procedure: theory, method, and preliminary results
A1  - Chang,J.Y.
A1  - Duara,R.
A1  - Barker,W.
A1  - Apicella,A.
A1  - Finn,R.
Y1  - 1987/05//
N1  - UI - 87197642
SP  - 852
EP  - 860
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 28
IS  - 5
N2  - We have developed a method that allows two sets of regional cerebral metabolic rates of glucose (rCMRglc) to be obtained in a single extended procedure using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). This is an adaptation of the deoxyglucose method, with the addition of a second injection of FDG immediately after completion of the first scan, then followed 30 min later by a second scan. A model has been developed to allow for correction of measured tracer concentration in the second scan by subtracting the predicted remnant from the first scan. The possible applications of this method in studying behavior-metabolism relationships are demonstrated. The preliminary results show 6%-12% changes in rCMRglc values for appropriate brain regions when the behavioral state is altered, but show 0%-5% change in rCMRglc values when the behavioral state is unchanged. The method can contribute significantly to the understanding of behavior-metabolism relationships by allowing the noninvasive study of two behavioral states in a single PET procedure
UR  - PM:3494830
ER  - 

TY  - JOUR
T1  - Neuroimaging findings in a suprasellar granular cell tumor
A1  - Wilkinson,M.D.
A1  - Fulham,M.J.
A1  - Besser,M.
Y1  - 2003/01//
N1  - UI - 22431925
SP  - 26
EP  - 29
JA  - J Comput.Assist.Tomogr.
VL  - 27
IS  - 1
N2  - A 27-year-old woman presented with a history of amenorrhea, visual disturbance, and diabetes insipidus. Magnetic resonance imaging showed a large enhancing suprasellar mass with associated edema involving the left striatum. The lesion was hypometabolic on fluorodeoxyglucose-positron emission tomography. At surgery, a subtotal resection of a vascular tumor that appeared to arise from the posterior pituitary and hypothalamus was carried out. Pathologic examination revealed a granular cell tumor. We report the preoperative neuroimaging findings in this rare posterior pituitary stalk tumor
AD  - Department of Positron Emission Tomography, Royal Prince Alfred Hospital, Sydney, Australia
UR  - PM:12544238
ER  - 

TY  - JOUR
T1  - Serendipitous detection of Cushing's disease by FDG positron emission tomography and a review of the literature
A1  - Komori,T.
A1  - Martin,W.H.
A1  - Graber,A.L.
A1  - Delbeke,D.
Y1  - 2002/03//
N1  - UI - 21840968
SP  - 176
EP  - 178
JA  - Clin.Nucl Med
VL  - 27
IS  - 3
N2  - A 70-year-old woman was referred for F-18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging of the brain to evaluate progressive dementia and neuropsychiatric symptoms. Although she had a history of hypertension and diabetes mellitus, she did not exhibit phenotypic features of Cushing's disease. The FDG-PET images revealed marked FDG uptake in the pituitary gland but no evidence of degenerative dementia. Two macroadenomas were confirmed by magnetic resonance imaging. Endocrinologic evaluation revealed Cushing's disease. After surgical resection of the tumors, the patient's symptoms decreased markedly
AD  - Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2675, USA. rad031@poh.osaka-med.ac.jp
UR  - PM:11852303
ER  - 

TY  - JOUR
T1  - Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone
A1  - Lucignani,G.
A1  - Losa,M.
A1  - Moresco,R.M.
A1  - Del Sole,A.
A1  - Matarrese,M.
A1  - Bettinardi,V.
A1  - Mortini,P.
A1  - Giovanelli,M.
A1  - Fazio,F.
Y1  - 1997/09//
N1  - UI - 97430068
SP  - 1149
EP  - 1155
JA  - Eur.J Nucl Med
VL  - 24
IS  - 9
N2  - The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods
AD  - INB-CNR, Department of Nuclear Medicine, H.S. Raffaele, Milan, Italy
UR  - PM:9283109
ER  - 

TY  - JOUR
T1  - Positron emission tomography of pituitary macroadenomas: hormone production and effects of therapies
A1  - Francavilla,T.L.
A1  - Miletich,R.S.
A1  - DeMichele,D.
A1  - Patronas,N.J.
A1  - Oldfield,E.H.
A1  - Weintraub,B.D.
A1  - Di Chiro,G.
Y1  - 1991/06//
N1  - UI - 91296077
SP  - 826
EP  - 833
JF  - Neurosurgery
VL  - 28
IS  - 6
N2  - Positron emission tomography with [18F]fluorodeoxyglucose (FDG) was carried out in 24 patients with pituitary macroadenomas (32 studies) to assess the glucose utilization of these tumors in vivo. The adenoma metabolic index, which is the ratio of FDG uptake of tumor to a whole brain slice, was calculated. Comparisons were made between tumor uptake of FDG and hormone secretion and response to therapies. In each positron emission tomography study, the macroadenoma could be easily identified visually as an area of increased FDG uptake near the region of the sella. FDG uptakes were highest for nonfunctional adenomas, and the prolactin, growth hormone, and thyroid-stimulating hormone-producing groups displayed similar levels of glucose metabolism. The adenoma metabolic index for all tumors averaged 1.3, ranging from 0.3 for a thyroid-stimulating hormone adenoma to 3.5 for a nonfunctional tumor. Tumors did not exhibit metabolic rates that could characterize the type of hormone produced. Recurrent macroadenomas displayed metabolism similar to tumors not operated on, whereas irradiated adenomas showed lower glucose uptake than nonirradiated tumors. Drug therapy with bromocriptine or the long-acting somatostatin analogue octreotide also decreased the glucose utilization of the tumor. There was no correlation between the amount of hormone produced and the adenoma metabolic index when a group of tumors was analyzed. Patients scanned more than once, however, demonstrated changes in hormone levels that changed or did not change in parallel with tumor metabolism. Thus, positron emission tomography offers the potential capability for predicting and defining the growth of pituitary adenomas. This may be of particular value when plasma hormone assays and conventional imaging techniques prove inadequate for monitoring patient response to therapy
AD  - Neuroimaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
UR  - PM:2067604
ER  - 

TY  - JOUR
T1  - PET as a tool in the clinical evaluation of pituitary adenomas
A1  - Bergstrom,M.
A1  - Muhr,C.
A1  - Lundberg,P.O.
A1  - Langstrom,B.
Y1  - 1991/04//
N1  - UI - 91193800
SP  - 610
EP  - 615
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 32
IS  - 4
N2  - Positron emission tomography (PET) was used in over 400 examinations in patients with pituitary adenoma. It was demonstrated that PET with carbon-11-methionine can give valuable complementary information in the diagnosis of this tumor due to PET's ability to adequately depict viable tumor tissue in contrast to fibrosis, cysts and necrosis. Furthermore, PET with dopamine D2 receptor ligands can characterize the degree of receptor binding and thus give information as to the prerequisites for dopamine agonist treatment. Most important is the very high sensitivity given by PET with carbon-11-methionine in the evaluation of treatment effects. It is concluded that when properly used PET can be fully justified in the clinical handling of patients with pituitary adenomas and other intracranial tumors
AD  - Department of Neurology, Uppsala University PET Center, Sweden
UR  - PM:2013801
ER  - 

TY  - JOUR
T1  - PET studies with L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F-fluorodeoxyglucose in prolactinomas in relation to bromocryptine treatment
A1  - Daemen,B.J.
A1  - Zwertbroek,R.
A1  - Elsinga,P.H.
A1  - Paans,A.M.
A1  - Doorenbos,H.
A1  - Vaalburg,W.
Y1  - 1991///
N1  - UI - 92008040
SP  - 453
EP  - 460
JA  - Eur.J Nucl Med
VL  - 18
IS  - 7
N2  - Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F-fluorodeoxyglucose (18FDG). Using L-[1-11C]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocriptine. At 18 h after bromocriptine intervention, L-[1-11C]tyrosine uptake into tumour was reduced with 28% (P less than 0.07). A correlation analysis of the bromocriptine-induced decrease in L-[1-11C]tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocriptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with 18FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with L-[methyl-11C]methionine. The tumour-imaging potential of L-[methyl-11C]methionine and L-[1-11C]tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for L-[1-11C]tyrosine as compared to L-[methyl-11C]methionine. L-[1-11C]tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas
AD  - Department of Nuclear Medicine, University Hospital, Groningen, The Netherlands
UR  - PM:1915472
ER  - 

TY  - JOUR
T1  - Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study
A1  - Bergstrom,M.
A1  - Muhr,C.
A1  - Lundberg,P.O.
A1  - Bergstrom,K.
A1  - Gee,A.D.
A1  - Fasth,K.J.
A1  - Langstrom,B.
Y1  - 1987/09//
N1  - UI - 88008524
SP  - 815
EP  - 819
JA  - J Comput.Assist.Tomogr.
VL  - 11
IS  - 5
N2  - Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-[11C]methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells
AD  - Department of Neurology, University Hospital, Uppsala, Sweden
UR  - PM:3498743
ER  - 

TY  - JOUR
T1  - Amino acid distribution and metabolism in pituitary adenomas using positron emission tomography with D-[11C]methionine and L-[11C]methionine
A1  - Bergstrom,M.
A1  - Muhr,C.
A1  - Lundberg,P.O.
A1  - Bergstrom,K.
A1  - Lundqvist,H.
A1  - Antoni,G.
A1  - Fasth,K.J.
A1  - Langstrom,B.
Y1  - 1987/05//
N1  - UI - 87195609
SP  - 384
EP  - 389
JA  - J Comput.Assist.Tomogr.
VL  - 11
IS  - 3
N2  - Four patients with hormonally inactive pituitary adenomas were examined with positron emission tomography (PET) after injection, during different examinations, of L-[methyl-11C]methionine and D-[methyl-11C]methionine, respectively. After the rapid distribution phase, the enantiomer L-[11C]methionine, which is metabolically active, showed a considerable continuous irreversible trapping attributed to amino acid metabolism. The stereoisomer D-[11C]methionine, which does not participate in protein synthesis, showed a rapid distribution within the whole adenoma tissue, with a distribution space on the order of 100%. A minimal irreversible trapping was observed which could be explained by technical factors. It is concluded that PET using the two enantiomers allows a separation of passive distribution and metabolism, and that L-[11C]methionine can be used for in vivo quantitative studies of amino acid metabolism of pituitary adenomas
UR  - PM:3494753
ER  - 

TY  - JOUR
T1  - Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone
A1  - Muhr,C.
A1  - Bergstrom,M.
A1  - Lundberg,P.O.
A1  - Bergstrom,K.
A1  - Hartvig,P.
A1  - Lundqvist,H.
A1  - Antoni,G.
A1  - Langstrom,B.
Y1  - 1986/03//
SP  - 175
EP  - 180
JA  - J Comput.Assist.Tomogr.
VL  - 10
IS  - 2
N2  - Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment
UR  - PM:3485123
ER  - 

TY  - JOUR
T1  - In vivo measurement of dopamine receptors in pituitary adenomas using positron emission tomography
A1  - Muhr,C.
A1  - Bergstrom,M.
A1  - Lundberg,P.O.
A1  - Bergstrom,K.
A1  - Langstrom,B.
Y1  - 1986///
N1  - UI - 92238222
SP  - 406
EP  - 408
JA  - Acta Radiol.Suppl
VL  - 369
N2  - Patients with pituitary adenomas were examined with positron emission tomography (PET) with the administration of the 11C-labelled dopamine-D2 antagonists N-methylspiperone and raclopride. The studies were repeated after protection of the D2-receptors with Haloperidol to enable a separation of specific and unspecific receptor binding. The receptor binding was evaluated by visual inspection and with the application of a kinetic model. The results showed marked specific dopamine-D2 receptor binding in the prolactinomas and minimal or no such binding in the hormonally inactive adenomas. The two tracers 11C-raclopride and 11C-N-methylspiperone showed qualitatively the same result although raclopride resulted in a higher tumor to normal brain ratio. In conclusion, PET is a valuable complement to other radiologic techniques like computed tomography and magnetic resonance imaging in the evaluation of pituitary adenomas. An assessment of the dopamine-D2 receptors in the adenomas has a direct influence on the choice of treatment because adenomas with high amounts of receptors are in most cases effectively treated with dopamine agonists like bromocriptine
AD  - Department of Neurology, University Hospital, Uppsala, Sweden
UR  - PM:2980511
ER  - 

TY  - JOUR
T1  - Tremor in Parkinson's disease and serotonergic dysfunction: An (11)C-WAY 100635 PET study
A1  - Doder,M.
A1  - Rabiner,E.A.
A1  - Turjanski,N.
A1  - Lees,A.J.
A1  - Brooks,D.J.
Y1  - 2003/02/25/
N1  - UI - 22489610
SP  - 601
EP  - 605
JF  - Neurology
VL  - 60
IS  - 4
N2  - BACKGROUND: The pathophysiologic mechanisms underlying parkinsonian tremor remain unclear. The response to dopaminergic treatment is variable and nondopaminergic mechanisms may play a role in tremor generation. Midbrain raphe 5-HT(1A) binding provides a functional measure of serotonergic system integrity. With PET, the aim of this study was to examine regional cerebral (11)C-WAY 100635 binding to 5-HT(1A) receptors in patients with PD and to correlate it with severity of tremor. METHODS: (11)C-WAY 100635 PET was performed on 23 patients with PD and eight age-matched healthy volunteers. Brain 5-HT(1A) receptor binding was computed using compartmental modeling with a cerebellar reference tissue input function. RESULTS: The authors found mean 27% reduction in the midbrain raphe 5-HT(1A) binding potential in patients with PD compared to healthy volunteers (p < 0.001). They also showed that Unified Parkinson's Disease Rating Scale composite tremor scores, but not rigidity or bradykinesia, correlate with 5-HT(1A) binding in the raphe (p < 0.01). CONCLUSIONS: These findings support previous indirect evidence that serotonergic neurotransmission is decreased in PD in vivo. The authors hypothesize that the reduction in raphe 5-HT(1A) binding represents receptor dysfunction or loss of cell bodies due to Lewy body degeneration in PD, or both. An association between 5-HT(1A) receptor availability in the raphe and severity of parkinsonian tremor was also found
AD  - Division of Neuroscience and MRC Clinical Sciences Centre (Drs. Doder, Rabiner, Turjanski, and Brooks), Faculty of Medicine, Imperial College
UR  - PM:12601099
ER  - 

TY  - JOUR
T1  - Plasticity of the nigropallidal pathway in Parkinson's disease
A1  - Whone,A.L.
A1  - Moore,R.Y.
A1  - Piccini,P.P.
A1  - Brooks,D.J.
Y1  - 2003/02//
N1  - UI - 22444020
SP  - 206
EP  - 213
JA  - Ann.Neurol
VL  - 53
IS  - 2
N2  - The degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this (18)F-dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased (18)F-dopa uptake in the GPi is seen in early PD which then is lost in advanced PD. Our early PD cases show an absence of significant clinical progression in the face of a continuing loss of nigrostriatal projections. This indicates a compensatory neuronal plasticity that we now show to involve the nigropallidal dopamine pathway to the GPi but not to the external segment of the globus pallidus (GPe). Enhanced function of the dopamine projection to the GPi serves, we propose, to maintain a more normal pattern of pallidal output to ventral thalamus and motor cortex in early PD, whereas loss of this adaptive pathway in advanced disease may be a pivotal step in the progression of the disease
AD  - Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. alan.whone@csc.mrc.ac.uk
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Whone-pallidal-FDOPA.pdf
ER  - 

TY  - JOUR
T1  - Intravenous Nicotine Reduces Cerebral Glucose Metabolism: A Preliminary Study
A1  - Stapleton,J.M.
A1  - Gilson,S.F.
A1  - Wong,D.F.
A1  - Villemagne,V.L.
A1  - Dannals,R.F.
A1  - Grayson,R.F.
A1  - Henningfield,J.E.
A1  - London,E.D.
Y1  - 2003/04//
N1  - UI - 0
SP  - 765
EP  - 772
JF  - Neuropsychopharmacology
VL  - 28
IS  - 4
N2  - Nicotine is self-administered by smoking tobacco products, and enhances positive mood (at least in smokers). Since most drugs of abuse decrease regional cerebral metabolic rate(s) for glucose (rCMRglc) in human subjects, we posited that administration of nicotine would similarly reduce rCMRglc. Positron emission tomography (PET) with [F-18]fluorodeoxyglucose was used to assess the effects of intravenous nicotine (1.5 mg) on cerebral glucose metabolism in six healthy male volunteers (21-38 years of age). Two PET assays (placebo and nicotine) were performed, and subjective self-reports of mood and feeling state were collected. Data were analyzed using analysis of variance. Nicotine reduced global glucose metabolism (by 9.51% of placebo control), with reductions in most of the 30 individual regions tested. Nine regions had bilateral effects that reached statistical significance (p&&#60;0.05, uncorrected for the number of regions tested), although the statistical model used did not separate these effects from a global effect. The subjects reported both positive and negative effects of nicotine on mood/feeling state. The widespread decreases in cerebral metabolism are consistent with the many effects of nicotine on cognition and mood. The findings indicate that nicotine resembles other drugs of abuse in reducing brain metabolism, perhaps by a common mechanism.Neuropsychopharmacology (2003) 28, 765-772. doi:10.1038/sj.npp.1300106
UR  - PM:12655323
ER  - 

TY  - JOUR
T1  - Brain glucose metabolic changes associated with neuropsychological improvements after 4 months of treatment in patients with obsessive-compulsive disorder
A1  - Kang,D.H.
A1  - Kwon,J.S.
A1  - Kim,J.J.
A1  - Youn,T.
A1  - Park,H.J.
A1  - Kim,M.S.
A1  - Lee,D.S.
A1  - Lee,M.C.
Y1  - 2003/04//
N1  - UI - 22548682
SP  - 291
EP  - 297
JA  - Acta Psychiatr.Scand.
VL  - 107
IS  - 4
N2  - OBJECTIVE: The study was designed to elucidate regional brain metabolic changes according to a treatment and their relationship with neuropsychological performance changes in obsessive-compulsive disorder (OCD). METHOD: Cerebral glucose metabolic rates were repeatedly measured before and after treatment in 10 patients with OCD using [18F]-2-fluoro-deoxyglucose positron emission tomography (PET). They were compared on a voxel-basis, and the correlations were counted between the regional metabolic changes and the degree to improvement on the neuropsychological assessments. RESULTS: After treatment, the patients showed significant (P < 0.005, two-tailed) regional metabolic changes in multiple brain areas involving frontal-subcortical circuits and parietal-cerebellar networks. Especially, the metabolic changes of the putamen, the cerebellum, and the hippocampus were significantly correlated with the improvement of the immediate- and delayed-recall scores of the Rey-Osterrieth Complex Figure Test (RCFT). CONCLUSION: These results suggest a possibility that metabolic changes of frontal-subcortical and parietal-cerebellar circuit changes may underlie cognitive improvements in patients with OCD
AD  - Department of Psychiatry, Department of Nuclear Medicine, BK 21 Human Life Science, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea and Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea
UR  - PM:12662252
ER  - 

TY  - JOUR
T1  - Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation
A1  - Lorenz,J.
A1  - Minoshima,S.
A1  - Casey,K.L.
Y1  - 2003/05/01/
SP  - 1079
JF  - Brain
VL  - 126
IS  - 5
N2  - Frontal lobe activity during pain is generally linked to attentional processing. We addressed the question of whether bottom-up' processing and top-down' modulation of nociceptive information dissociate anatomically within the frontal lobe by using PET scanning during painful thermal stimulation of normal and capsaicin-treated skin. We showed recently that pain following normally non-painful heat stimuli on chemically irritated skin (heat allodynia) uniquely engages extensive areas of the bilateral dorsolateral prefrontal (DLPFC), ventral/orbitofrontal (VOFC) and perigenual anterior cingulate (ACC) cortices. Here, we applied principal component analysis (PCA) and multiple regression analysis to study the covariance structure of the volumes of interest (VOI) activated specifically during heat allodynia in 14 male healthy subjects and evaluated the relationship of these VOI to ratings of pain intensity and affect. Results yielded a primary principal component (PC) that correlated positively with intensity and unpleasantness and accounted for activity in the medial thalamus, bilateral anterior insula, ventral striatum, perigenual ACC and bilateral VOFC. Activities in the right and left DLPFC loaded on separate PC and correlated negatively with perceived intensity and unpleasantness. The inter-regional correlation of midbrain and medial thalamic activity was significantly reduced during high left DLPFC activity, suggesting that its negative correlation with pain affect may result from dampening of the effective connectivity of the midbrain-medial thalamic pathway. In contrast, right DLPFC activity was associated with a weakened relationship of the anterior insula with both pain intensity and affect. We propose that the DLPFC exerts active control on pain perception by modulating corticosubcortical and corticocortical pathways
UR  - http://brain.oupjournals.org/cgi/content/abstract/126/5/1079
ER  - 

TY  - JOUR
T1  - Progressive striatal and cortical dopamine receptor dysfunction in Huntington's disease: a PET study
A1  - Pavese,Nicola
A1  - Andrews,Thomasin C.
A1  - Brooks,David J.
A1  - Ho,Aileen K.
A1  - Rosser,Anne E.
A1  - Barker,Roger A.
A1  - Robbins,Trevor W.
A1  - Sahakian,Barbara J.
A1  - Dunnett,Stephen B.
A1  - Piccini,Paola
Y1  - 2003/05/01/
SP  - 1127
JF  - Brain
VL  - 126
IS  - 5
N2  - We have studied the progression of striatal and extrastriatal post-synaptic dopaminergic changes in a group of 12 patients with Huntington's disease using serial 11C-raclopride PET, a specific marker of D2 dopamine receptor binding. All patients had two 11C-raclopride PET scans 29.2 {+/-} 12.8 months apart, and six of them had a third scan 13.2 {+/-} 3.9 months later. We found a mean annual 4.8% loss of striatal 11C-raclopride binding potential (BP) between the first and second scans, and a 5.2% loss between the second and third scans. Statistical Parametric Mapping (SPM) localized significant baseline reductions in 11C-raclopride BP in both striatal and extrastriatal areas, including amygdala, temporal and frontal cortex in Huntington's disease compared with normal subjects matched for age and sex. When the 11C-raclopride scans performed 29 months after the baseline scans were considered, SPM revealed further significant striatal, frontal and temporal reductions in 11C-raclopride BP in Huntington's disease. Cross-sectional Unified Huntington's Disease Rating Scale (UHDRS) scores correlated with 11C-raclopride binding, but there was no correlation between individual changes in UHDRS motor scores and changes in striatal binding. Performance on all neuropsychological measures deteriorated with time but only the accuracy score of the one-touch Tower of London test correlated significantly with striatal and putamen D2 binding. In summary, serial 11C-raclopride PET demonstrates a linear progression of striatal loss of D2 receptors in early clinically affected Huntington's disease patients over 3 years. SPM also revealed a progressive loss of temporal and frontal D2 binding. Changes over time in clinical scores and in neuropsychological assessments, except for measures of planning, did not correlate with striatal D2 binding. This probably reflects both contributions from other affected brain structures and high variance in these measures
UR  - http://brain.oupjournals.org/cgi/content/abstract/126/5/1127
ER  - 

TY  - JOUR
T1  - The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease: a positron emission tomography study
A1  - Nakajima,T.
A1  - Nimura,T.
A1  - Yamaguchi,K.
A1  - Ando,T.
A1  - Itoh,M.
A1  - Yoshimoto,T.
A1  - Shirane,R.
Y1  - 2003/01//
SP  - 57
EP  - 63
JA  - J Neurosurg
VL  - 98
IS  - 1
N2  - OBJECT: The aim of this study was to estimate the impact of stereotactic pallidal surgery on the binding potential of dopamine D2 receptors in patients with advanced Parkinson disease (PD). METHODS: Six patients with advanced PD (three men and three women; mean age 56.7 +/- 9.8 years, Hoehn and Yahr stage 3.3 +/- 1.1/3.9 +/- 1.2 [on/off scores], mean +/- standard deviation) underwent stereotactic pallidal surgery. One underwent right posteroventral pallidotomy (PVP), one received left PVP, three were treated with deep brain stimulation (DBS) of the left globus pallidus internus (GPi), and one with bilateral DBS of the GPi. The binding potential of the dopamine D2 receptors of these patients was determined before and after surgery by using positron emission tomography scanning with 11C-nemonapride and it was compared with the value in eight healthy volunteers. The authors also examined whether changes in the D2 receptor binding potential were correlated with the clinical outcome. The clinical symptoms, especially those in the off state, were significantly improved after surgery. Preoperatively, the D2 receptor binding potential in the putamen was elevated by 27% (p < 0.01) and that in the thalamus was 29% lower than that in controls (p < 0.01). The D2 receptor binding potential in the putamen and thalamus returned to control levels after surgery. The preoperative level of the D2 receptor binding potential in the anterior cingulate cortex was comparable to that of controls, but it declined significantly after surgery, whereas the D2 receptor binding potential in other regions of both hemispheres showed no significant changes after surgery. Although the D2 receptor binding potential did not correlate with the Hoehn and Yahr stage, the Schwab and England score, or the Unified PD Rating Scale (UPDRS) score, a positive correlation was seen between the percent improvement rate of the total UPDRS score in the off state and the percentage change of the D2 receptor binding potential in the putamen (r = 0.773, p = 0.0417 according to the Pearson linear correlation). CONCLUSIONS: The altered dopamine D2 receptor binding potential in the putamen might play a crucial role in clinical improvement after PVP or DBS of the GPi in advanced PD
AD  - Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan
UR  - PM:12546353
ER  - 

TY  - JOUR
T1  - An imaging study of parkinsonism among African-Caribbean and Indian London communities
A1  - Hu,M.T.
A1  - Chaudhuri,K.R.
A1  - Jarosz,J.
A1  - Yaguez,L.
A1  - Brooks,D.J.
Y1  - 2002/11//
SP  - 1321
EP  - 1328
JA  - Mov Disord.
VL  - 17
IS  - 6
N2  - We previously reported on 131 parkinsonian patients of African-Caribbean and Indian origin attending movement disorders clinics in six London Hospitals, of whom approximately 20% manifested atypical parkinsonism with a late-onset, akinetic-rigid predominant syndrome, postural instability and minimal resting tremor refractory to levodopa therapy and dopamine agonists (see Hu et al., Neurology 2000;54[Suppl.3]: A188 and Hu et al., Mov Disord 2000;15[Suppl.3]:S212). To better elucidate the phenotype of these atypical patients (18)FDG/(18)F-dopa positron emission tomography (PET) were performed in a subgroup to look for cortical and striatal metabolic changes suggestive of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or dementia with Lewy bodies. Magnetic resonance imaging (MRI) rating of cerebral vascular lesion load, putaminal atrophy, and neuropsychological testing were also performed. Discriminant function analysis of (18)F-dopa/(18)FDG striatal metabolism in 43 patients failed to separate atypical ethnic minority from typical Caucasian Parkinson's disease (PD) patients. Additionally, atypical Indian and African-Caribbean patients did not show cortical reductions in glucose metabolism suggestive of PSP, CBD, or DLB. Cerebral vascular lesion load rated in these patients did not differ between atypical and typical PD groups, and none of the atypical patients had MRI changes suggestive of MSA or PSP. Our results suggest the atypical parkinsonian phenotype seen in African-Caribbean and Indian patients represents a levodopa-refractory form of PD separate from MSA or PSP in most patients
AD  - Movement Disorders Unit, Department of Neurology, Guy's, King's and St Thomas' School of Medicine and the Institute of Psychiatry, King's College London, London, United Kingdom. micheleh@foresthill32.fsnet.co.uk
UR  - PM:12465076
ER  - 

TY  - JOUR
T1  - Pallidal stimulation for parkinsonism: improved brain activation during sequence learning
A1  - Fukuda,M.
A1  - Ghilardi,M.F.
A1  - Carbon,M.
A1  - Dhawan,V.
A1  - Ma,Y.
A1  - Feigin,A.
A1  - Mentis,M.J.
A1  - Ghez,C.
A1  - Eidelberg,D.
Y1  - 2002/08//
SP  - 144
EP  - 152
JA  - Ann.Neurol
VL  - 52
IS  - 2
N2  - We used (15)O-labeled water and positron emission tomography to assess the effect of deep brain stimulation of the internal globus pallidus on motor sequence learning in Parkinson's disease. Seven right-handed patients were scanned on and off stimulation while they were performing a motor sequence learning task and a kinematically matched motor execution reference task. The scans were performed after a 12-hour medication washout. Stimulation parameters were adjusted for maximal motor improvement; experimental task parameters were held constant across stimulation conditions. Internal globus pallidus stimulation improved motor ratings by 37% (p < 0.01). During the sequence learning task, stimulation improved performance as measured by several correct anticipatory movements (p < 0.01) and by verbal report (p < 0.001). Concurrent positron emission tomography imaging during learning demonstrated significant (p < 0.01) increases in brain activation with stimulation in the left dorsolateral prefrontal cortex, bilaterally in premotor cortex, and in posterior parietal and occipital association areas. Stimulation did not affect the activity of these regions during the performance of the motor execution reference task. These findings suggest that internal globus pallidus deep brain stimulation can enhance the activity of prefrontal cortico-striato-pallidothalamic loops and related transcortical pathways. Improved sequence learning with stimulation may be directly related to these functional changes
AD  - Center for Neurosciences, North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA
UR  - PM:12210783
ER  - 

TY  - JOUR
T1  - Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET
A1  - Singer,H.S.
A1  - Szymanski,S.
A1  - Giuliano,J.
A1  - Yokoi,F.
A1  - Dogan,A.S.
A1  - Brasic,J.R.
A1  - Zhou,Y.
A1  - Grace,A.A.
A1  - Wong,D.F.
Y1  - 2002/08//
SP  - 1329
EP  - 1336
JA  - Am.J Psychiatry
VL  - 159
IS  - 8
N2  - OBJECTIVE: Dopaminergic abnormalities in frontal-subcortical circuits have been hypothesized as the underlying pathophysiologic mechanism in Tourette's syndrome. The objective of this study was to test the hypothesis that presynaptic dopamine release from the striatum is abnormal in adults with Tourette's syndrome. METHOD: Seven adults with Tourette's syndrome and five age-matched comparison subjects each received two positron emission tomography (PET) scans with high specific activity [11C]raclopride. The first scan followed an intravenous injection of saline; the second followed an intravenous injection of amphetamine. The relative dopamine release was estimated as the percentage difference in binding potential between the postsaline and postamphetamine scans. RESULTS: Binding potential determined after the initial [11C]raclopride scan did not significantly differ between Tourette's syndrome and comparison subjects. After amphetamine challenge, the mean value of intrasynaptic dopamine in the putamen (as determined by true equilibrium bolus estimation) increased by 21% in the subjects with Tourette's syndrome and did not change in the comparison subjects; the mean values increased by 16.9% and decreased by 1.8%, respectively, when measured by the constrained method. Dopamine release in the caudate region was not significantly different in the Tourette's syndrome and comparison subjects. CONCLUSIONS: Greater putamen dopamine release was seen in adults with Tourette's syndrome than in comparison subjects after a pharmacologic challenge with amphetamine. These results suggest that the underlying pathobiology in Tourette's syndrome is a phasic dysfunction of dopamine transmission
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
UR  - PM:12153825
ER  - 

TY  - JOUR
T1  - Relationships among the metabolic patterns that correlate with mnemonic, visuospatial, and mood symptoms in Parkinson's disease
A1  - Mentis,M.J.
A1  - McIntosh,A.R.
A1  - Perrine,K.
A1  - Dhawan,V.
A1  - Berlin,B.
A1  - Feigin,A.
A1  - Edwards,C.
A1  - Mattis,P.
A1  - Eidelberg,D.
Y1  - 2002/05//
SP  - 746
EP  - 754
JA  - Am.J Psychiatry
VL  - 159
IS  - 5
N2  - OBJECTIVE: A multivariate analysis of baseline brain metabolism was used to investigate the relationships among pathophysiological mechanisms responsible for cognitive dysfunction and dysphoria in nondemented patients with Parkinson's disease. METHOD: Using [(18)F]fluorodeoxyglucose positron emission tomography and neuropsychological tests, the authors studied 15 nondemented patients who had Parkinson's disease without major depression (DSM-III-R). Their mean age was 59.2 years (SD=9.2), the mean rating of Parkinson's disease stage (Hoehn and Yahr scale) was 3.3 (SD=0.9), and all had Mini-Mental State Examination scores of 24 or higher. To identify specific regional patterns of brain metabolism associated with abnormal cognitive and mood functioning, the data were analyzed by using brain-behavior partial least squares. This multivariate voxel-based analysis allowed detection of significant topographic patterns of metabolic activity and quantification of the extent to which each topographic pattern correlated with scores on mnemonic, visuospatial, and dysphoric tests. RESULTS: Two significant, independent topographic patterns were identified. Pattern 1 included parieto-occipito-temporal and medial temporal brain regions, and pattern 2 included the lateral frontal and anterior limbic cortex. Patterns 1 and 2 exhibited a double dissociation in their behavioral correlates: pattern 1 correlated with both visuospatial and mnemonic functioning but not with dysphoria; pattern 2 correlated with dysphoria but not with the cognitive measures. CONCLUSIONS: The authors used the independence of topographic patterns and the size of correlations between topographic patterns and behavior to infer relationships among the pathophysiological processes responsible for the correlations. The finding that mildly abnormal mnemonic and visuospatial functioning correlated with the same topographic pattern suggests that a common pathophysiology underlies this marker of cognition in Parkinson's disease. By contrast, the independence of the two topographic patterns supports the notion that different mechanisms underlie cognitive and dysphoric symptoms in nondemented patients with Parkinson's disease
AD  - Center for Neuroscience, North Shore-Long Island Jewish research Institute, Manhasset, NY, USA. marcjm@optonline.net
UR  - PM:11986127
ER  - 

TY  - JOUR
T1  - Novel observations with FDOPA-PET imaging after early nigrostriatal damage
A1  - Yee,R.E.
A1  - Irwin,I.
A1  - Milonas,C.
A1  - Stout,D.B.
A1  - Huang,S.C.
A1  - Shoghi-Jadid,K.
A1  - Satyamurthy,N.
A1  - DeLanney,L.E.
A1  - Togasaki,D.M.
A1  - Farahani,K.F.
A1  - Delfani,K.
A1  - Janson,A.M.
A1  - Phelps,M.E.
A1  - Langston,J.W.
A1  - Barrio,J.R.
Y1  - 2001/09//
SP  - 838
EP  - 848
JA  - Mov Disord.
VL  - 16
IS  - 5
N2  - Striatal 6-[18F]fluoro-L-DOPA (FDOPA) kinetic rate constants were measured by positron emission tomography (PET) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated squirrel monkeys. After scanning, stereological counts of dopaminergic neurons were done in substantia nigra, and dopamine (DA) and metabolite concentrations were determined in the caudate, putamen, and substantia nigra. Graded doses of MPTP produced animals with mild to moderate reductions (10-35%) in dopaminergic neurons, where the percent of cell loss was proportional to the amount of MPTP given. Striatal DA and metabolite concentrations were relatively unchanged in animals given 1.0 and 1.5 mg/kg of MPTP, but were significantly reduced after 2.0 mg/kg of MPTP. All animals injected with a single dose of MPTP showed no overt signs of parkinsonism. In contrast, DA and metabolite concentrations in the substantia nigra were significantly reduced for all MPTP-treated animals. Reduction of dopaminergic indices in the substantia nigra did not parallel reductions in the striatum, indicating differential sensitivity of the nigrostriatal pathway to the neurotoxic effects of MPTP. The percent change in FDOPA uptake (Ki) and decarboyxlation (k3) after MPTP showed significant positive correlations to striatal DA levels, but not to the number of dopaminergic neurons. This suggests that FDOPA is a good index of striatal DA levels
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-6948, USA
UR  - PM:11746613
ER  - 

TY  - JOUR
T1  - Striatal and pontocerebellar hypoperfusion in Hallervorden-Spatz syndrome
A1  - Castelnau,P.
A1  - Zilbovicius,M.
A1  - Ribeiro,M.J.
A1  - Hertz-Pannier,L.
A1  - Ogier,H.
A1  - Evrard,P.
Y1  - 2001/08//
N1  - UI - 21436305
SP  - 170
EP  - 174
JA  - Pediatr.Neurol
VL  - 25
IS  - 2
N2  - Hallervorden-Spatz syndrome is a group of rare and severe disorders marked by extrapyramidal symptoms and iron accumulation in the globi pallidi, usually visible by magnetic resonance imaging. To assist in determining the functional correlates of these structural abnormalities, positron emission tomography was used to measure regional cerebral blood flows and dopaminergic function in a patient with Hallervorden-Spatz syndrome that manifested as progressive generalized dystonia, optic atrophy, and bilateral pallidal "eye of the tiger" sign. Voxel-by-voxel analysis of positron emission tomography images revealed no pallidal abnormalities but demonstrated significant hypoperfusion of the head of the right caudate nucleus, pons, and cerebellar vermis. Dopaminergic function of the basal ganglia, which was assessed based on visual- analysis of fixation of 18F-labeled fluoro-levodopa, was normal. These data suggest that Hallervorden-Spatz syndrome pathogenesis is not confined to the globi pallidi, and these data also may help to generate new pathogenic hypothesis
AD  - Pediatric Neurology Service, Robert Debre Hospital, Paris, France
UR  - PM:11551749
ER  - 

TY  - JOUR
T1  - The role of language areas in motor control dysfunction in Parkinson's disease
A1  - Albani,G.
A1  - Kunig,G.
A1  - Soelch,C.M.
A1  - Mauro,A.
A1  - Priano,L.
A1  - Martignoni,E.
A1  - Leenders,K.L.
Y1  - 2001/02//
N1  - UI - 21379307
SP  - 43
EP  - 44
JA  - Neurol Sci.
VL  - 22
IS  - 1
N2  - We evaluated the differences in motor control organization between parkinsonian patients with (seven cases) and without (ten cases) gait disorder. We used positron emission tomography (O15-H2O-PET) to measure regional cerebral blood flow as a correlate for local neuronal activation. This has been assessed during repetitive joystick movements of the right hand, externally triggered using a metronome as an auditory cue. In patients with Parkinson's disease (PD) without gait disorder, the contralateral supplementary motor cortex and the bilateral cerebellum were activated, while in PD patients with gait disorder the contralateral Broca's area, the contralateral sensory motor cortex and the homolateral cerebellum were activated. Our results suggest that PD patients with gait disorder creates an internal verbal cue in order to control the output of the movement of joystick, supplying the loss of control of the supplementary motor cortex that is activated in patients without gait disorder
AD  - Department of Neurology, IRCCS, Istituto Auxologico Italiano, Piancavallo, Italy
UR  - PM:11487193
ER  - 

TY  - JOUR
T1  - Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-L-dopa
A1  - Poyot,T.
A1  - Conde,F.
A1  - Gregoire,M.C.
A1  - Frouin,V.
A1  - Coulon,C.
A1  - Fuseau,C.
A1  - Hinnen,F.
A1  - Dolle,F.
A1  - Hantraye,P.
A1  - Bottlaender,M.
Y1  - 2001/07//
SP  - 782
EP  - 792
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 7
N2  - Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B'max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B'max = 26 and 36 pmol/mL) and reserpine-treated animals (B'max = 338 and 483 pmol/mL). In vivo 11C-PE2I B'max values correlated with 18F-Dopa Ki values and in vitro 125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies
AD  - URA CEA CNRS 2210 and Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, Direction des Sciences du Vivant, CEA, Orsay Cedex, France
UR  - PM:11435790
ER  - 

TY  - JOUR
T1  - Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts
A1  - Cumming,P.
A1  - Danielsen,E.H.
A1  - Vafaee,M.
A1  - Falborg,L.
A1  - Steffensen,E.
A1  - Sorensen,J.C.
A1  - Gillings,N.
A1  - Bender,D.
A1  - Marthi,K.
A1  - Andersen,F.
A1  - Munk,O.
A1  - Smith,D.
A1  - Moller,A.
A1  - Gjedde,A.
Y1  - 2001/05//
SP  - 309
EP  - 315
JA  - Acta Neurol Scand.
VL  - 103
IS  - 5
N2  - As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Gottingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum
AD  - PET Center, Arhus General Hospital, Norrebrogade 44, Arhus, Denmark. paul@pet.auh.dk
UR  - PM:11328207
ER  - 

TY  - JOUR
T1  - Motor imagery in normal subjects and Parkinson's disease patients: an H215O PET study
A1  - Samuel,M.
A1  - Ceballos-Baumann,A.O.
A1  - Boecker,H.
A1  - Brooks,D.J.
Y1  - 2001/03/26/
N1  - UI - 21171189
SP  - 821
EP  - 828
JF  - Neuroreport
VL  - 12
IS  - 4
N2  - Motor imagery paradigms can be used to investigate motor preparation. We used positron emission tomography to compare regional cerebral blood flow (rCBF) in patients with Parkinson's disease and normal controls under three conditions: rest, motor imagery and motor execution. In controls, imagery activated bilateral dorsolateral and mesial frontal cortex, inferior parietal cortex and precuneus. Motor execution additionally activated primary motor cortex (p < 0.001). Between-group, for imagery there was relative reduction in dorsolateral and mesial frontal activation in the patient group (p<0.01). For execution, there was impaired activation of right dorsolateral frontal cortex and basal ganglia (p<0.01). Our results support the notion that underfunctioning of mesial frontal and dorsolateral prefrontal cortex may underlie motor preparation in Parkinson's disease but also suggest that akinesia may occur in the absence of impaired mesial frontal cortex activation
AD  - MRC Clinical Sciences Centre, Imperial College School of Science, Technology and Medicine, Hammersmith Hospital, London, UK
UR  - PM:11277590
ER  - 

TY  - JOUR
T1  - Functional correlates of pallidal stimulation for Parkinson's disease
A1  - Fukuda,M.
A1  - Mentis,M.
A1  - Ghilardi,M.F.
A1  - Dhawan,V.
A1  - Antonini,A.
A1  - Hammerstad,J.
A1  - Lozano,A.M.
A1  - Lang,A.
A1  - Lyons,K.
A1  - Koller,W.
A1  - Ghez,C.
A1  - Eidelberg,D.
Y1  - 2001/02//
N1  - UI - 21115249
SP  - 155
EP  - 164
JA  - Ann.Neurol
VL  - 49
IS  - 2
N2  - We measured regional cerebral blood flow with H2 15O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right-handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication-free state. Internal globus pallidus deep brain stimulation improved off-state United Parkinson's Disease Rating Scale motor ratings (37%, p < 0.002) and reduced timing errors (movement onset time, 55%, p < 0.01) as well as spatial errors (10%, p < 0.02). Concurrent regional cerebral blood flow recordings revealed a significant enhancement of motor activation responses in the left sensorimotor cortex (Brodmann area [BA] 4), bilaterally in the supplementary motor area (BA 6), and in the right anterior cingulate cortex (BA 24/32). Significant correlations were evident between the improvement in motor performance and the regional cerebral blood flow changes mediated by stimulation. With internal globus pallidus deep brain stimulation, improved movement initiation correlated with regional cerebral blood flow increases in the left sensorimotor cortex and ventrolateral thalamus and in the contralateral cerebellum. By contrast, improved spatial accuracy correlated with regional cerebral blood flow increases in both cerebellar hemispheres and in the left sensorimotor cortex. These results suggest that internal globus pallidus deep brain stimulation may selectively improve different aspects of motor performance. Multiple, overlapping neural pathways may be modulated by this intervention
AD  - Center for Neurosciences, North Shore-Long Island Jewish Research Institute, Manhasset, New York, USA
UR  - PM:11220735
ER  - 

TY  - JOUR
T1  - FDG- and Dopa-PET in postencephalitic parkinsonism
A1  - Ghaemi,M.
A1  - Rudolf,J.
A1  - Schmulling,S.
A1  - Bamborschke,S.
A1  - Heiss,W.D.
Y1  - 2000///
N1  - UI - 21017666
SP  - 1289
EP  - 1295
JA  - J Neural Transm.
VL  - 107
IS  - 11
N2  - We report a case of a 74-year old woman who following an acute virus encephalitis developed an akinetic-rigid Parkinson syndrome with tremor, hypokinesia, hypomimia, rigidity and cogwheel phenomenon in all four extremities, brady-dysdiadochokinesia as well as myoclonic jerks of the arms. Many of the clinical features of this postencephalitic parkinsonism (PEP) suggested the diagnosis of sporadic encephalitis lethargica, first described by von Economo 1917. Cerebral spinal fluid showed signs of a viral encephalitis, and a positive influenza A IgA-antibody titer (1:>160) in the viral serologic screen was found. Positron emission tomography (PET) showed an altered pattern of glucose- and dopa-metabolism clearly different from findings in idiopathic Parkinson syndrome (IPS). The acute lack of inhibitory input from the substantia nigra pars compacta to the striatum could explain the different metabolic patterns in our case in comparison to IPS patients. Our findings indicate that PEP may also be caused by influenza A and furthermore that PET clearly distinguishes PEP from IPS
AD  - Klinik fur Neurologie, Universitat Koln, Federal Republic of Germany
UR  - PM:11145004
ER  - 

TY  - JOUR
T1  - Motor and cognitive improvements in patients with Huntington's disease after neural transplantation
A1  - Bachoud-Levi,A.C.
A1  - Remy,P.
A1  - Nguyen,J.P.
A1  - Brugieres,P.
A1  - Lefaucheur,J.P.
A1  - Bourdet,C.
A1  - Baudic,S.
A1  - Gaura,V.
A1  - Maison,P.
A1  - Haddad,B.
A1  - Boisse,M.F.
A1  - Grandmougin,T.
A1  - Jeny,R.
A1  - Bartolomeo,P.
A1  - Dalla,Barba G.
A1  - Degos,J.D.
A1  - Lisovoski,F.
A1  - Ergis,A.M.
A1  - Pailhous,E.
A1  - Cesaro,P.
A1  - Hantraye,P.
A1  - Peschanski,M.
Y1  - 2000/12/09/
N1  - UI - 21012990
SP  - 1975
EP  - 1979
JF  - Lancet
VL  - 356
IS  - 9246
N2  - BACKGROUND: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease. METHODS: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease
AD  - INSERM U 421/IM3 and CHU Henri Mondor-AP/HP, Creteil, France
UR  - PM:11130527
ER  - 

TY  - JOUR
T1  - Voxel-based distribution of metabolic impairment in corticobasal degeneration
A1  - Garraux,G.
A1  - Salmon,E.
A1  - Peigneux,P.
A1  - Kreisler,A.
A1  - Degueldre,C.
A1  - Lemaire,C.
A1  - Destee,A.
A1  - Franck,G.
Y1  - 2000/09//
N1  - UI - 20462721
SP  - 894
EP  - 904
JA  - Mov Disord.
VL  - 15
IS  - 5
N2  - This report emphasizes the precise topographic distribution of cerebral metabolic impairment in corticobasal degeneration (CBD) and the pathophysiological differences between CBD and progressive supranuclear palsy (PSP). Statistical parametric mapping (SPM96) analysis of 18FDG positron emission tomography (PET) data was performed in 22 patients with CBD compared with 46 healthy subjects (HS) and 21 patients with PSP who were studied at rest. A statistical threshold of p <0.001 was fixed, further corrected for multiple or independent comparisons (p <0.05). In comparison with HS, the metabolic impairment in CBD was asymmetrically distributed in the putamen, thalamus, precentral (Brodmann's area, BA 4), lateral premotor (BA 6/44) and supplementary motor areas (SMA, BA 6), dorsolateral prefrontal (8/9/46) cortex, and the anterior part of the inferior parietal lobe (BA 40) including the intraparietal sulcus (BA 7/40). A similar hypometabolic pattern was observed for most individual analyses. When PSP was compared with CBD, metabolic impairment predominated in the midbrain, anterior cingulate (BA 24/32), and orbitofrontal regions (BA 10). The reverse contrast showed more posterior involvement in CBD (BA 6 and 5/7/40) including SMA. Our data suggest that multiple components of neural networks related to both movement execution and production of skilled movements are functionally disturbed in CBD compared with both HS and PSP
AD  - Cyclotron Research Center, Department of Neurology, University of Liege, Belgium
UR  - PM:11009197
ER  - 

TY  - JOUR
T1  - Paroxysmal dystonic choreoathetosis: clinical features and investigation of pathophysiology in a large family
A1  - Jarman,P.R.
A1  - Bhatia,K.P.
A1  - Davie,C.
A1  - Heales,S.J.
A1  - Turjanski,N.
A1  - Taylor-Robinson,S.D.
A1  - Marsden,C.D.
A1  - Wood,N.W.
Y1  - 2000/07//
N1  - UI - 20382318
SP  - 648
EP  - 657
JA  - Mov Disord.
VL  - 15
IS  - 4
N2  - Paroxysmal dystonic choreoathetosis (PDC) is an unusual hyperkinetic movement disorder characterized by attacks of chorea, dystonia, and ballism with onset in childhood. We report a large British family with dominantly inherited PDC linked to chromosome 2q and describe the clinical features in 20 affected family members. Attacks were precipitated by a variety of factors, including caffeine, alcohol, or emotion, and could be relieved by short periods of sleep in most subjects. The clinical features in the family are compared with those of 11 other PDC families in the literature and a core phenotype for PDC suggested. CSF monoamine metabolites measured at baseline and during an attack in one subject were found to increase during the attack. Magnetic resonance spectroscopy of brain and basal ganglia performed both during and between attacks was normal. Positron emission tomography using the D2 receptor ligand, 11C-raclopride, showed no abnormalities
AD  - Department of Clinical Neurology, Institute of Neurology, London, UK
UR  - PM:10928574
ER  - 

TY  - JOUR
T1  - Acute effects of thalamotomy and pallidotomy on regional cerebral metabolism, evaluated by PET
A1  - Henselmans,J.M.
A1  - de Jong,B.M.
A1  - Pruim,J.
A1  - Staal,M.J.
A1  - Rutgers,A.W.
A1  - Haaxma,R.
Y1  - 2000/06//
N1  - UI - 20277988
SP  - 84
EP  - 90
JA  - Clin.Neurol Neurosurg
VL  - 102
IS  - 2
N2  - The subacute effect of thalamotomy and pallidotomy on regional cerebral metabolism was studied by means of Positron Emission Tomography (PET). In this way we aimed to identify the pattern of functional deafferentiation following a specific lesion in the basal ganglia. The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake at 1-2 weeks after operation was compared with the uptake before operation. Analysis of the changes was done by statistical parametric mapping (SPM). Thalamotomy resulted in a reduction of FDG uptake in predominantly the lateral prefrontal- and the parietal cortex, whereas pallidotomy affected only uptake in the (pre)frontal cortex. The absence of change in the primary sensory-motor cortex after either surgical procedure may suggest that, in man, the motor portions of the thalamus exert a predominantly indirect influence on the human motor cortex
AD  - Department of Neurology, University Hospital Groningen, PO Box 30. 001, 9700 RB, Groningen, The Netherlands
UR  - PM:10817894
ER  - 

TY  - JOUR
T1  - The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers
A1  - Danielsen,E.H.
A1  - Cumming,P.
A1  - Andersen,F.
A1  - Bender,D.
A1  - Brevig,T.
A1  - Falborg,L.
A1  - Gee,A.
A1  - Gillings,N.M.
A1  - Hansen,S.B.
A1  - Hermansen,F.
A1  - Johansen,J.
A1  - Johansen,T.E.
A1  - Dahl-Jorgensen,A.
A1  - Jorgensen,H.A.
A1  - Meyer,M.
A1  - Munk,O.
A1  - Pedersen,E.B.
A1  - Poulsen,P.H.
A1  - Rodell,A.B.
A1  - Sakoh,M.
A1  - Simonsen,C.Z.
A1  - Smith,D.F.
A1  - Sorensen,J.C.
A1  - Ostergard,L.
A1  - Zimmer,J.
A1  - Gjedde,A.
Y1  - 2000/03//
SP  - 247
EP  - 259
JA  - Cell Transplant.
VL  - 9
IS  - 2
N2  - A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Gottingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum
AD  - PET-Center, Aarhus University Hospital, Denmark. erik@pet.auh.dk
UR  - PM:10811397
ER  - 

TY  - JOUR
T1  - Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography
A1  - Kunig,G.
A1  - Leenders,K.L.
A1  - Sanchez-Pernaute,R.
A1  - Antonini,A.
A1  - Vontobel,P.
A1  - Verhagen,A.
A1  - Gunther,I.
Y1  - 2000/05//
N1  - UI - 20263086
SP  - 644
EP  - 648
JA  - Ann.Neurol
VL  - 47
IS  - 5
N2  - We used positron emission tomography and [11C]flumazenil to analyze the benzodiazepine receptor binding in symptomatic and asymptomatic carriers of the Huntington's disease gene. We found an inverse relationship between [11C]flumazenil and [11C]raclopride binding in the putamen of symptomatic patients, and interpret this result as GABA receptor upregulation
AD  - PSI, Paul Scherrer Institut, PET Program, Villigen, Switzerland
UR  - PM:10805336
ER  - 

TY  - JOUR
T1  - Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study
A1  - Rinne,J.O.
A1  - Portin,R.
A1  - Ruottinen,H.
A1  - Nurmi,E.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
Y1  - 2000/04//
SP  - 470
EP  - 475
JA  - Arch Neurol
VL  - 57
IS  - 4
N2  - OBJECTIVE: To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). DESIGN: We studied 28 patients with PD and 16 age-matched healthy control subjects using [18F] fluorodopa (fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. RESULTS: [18F] Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P<.001), the caudate nucleus (to 61% of the control mean; P<.001), and the frontal cortex (to 45% of the control mean; P<.001) in patients with PD compared with controls. There was no significant association between the degree of overall cognitive impairment of patients and [18F] fluorodopa uptake values. The influx constant (Ki(occ)) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The Ki(occ) in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [18F] fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the Ki(occ) value and any of the cognitive tests. The severity of the motor symptoms of PD and [18F]fluorodopa uptake showed a negative correlation in the putamen (r = -0.38; P = .04), and in the caudate nucleus a similar trend was seen (r = -0.36; P = .06). CONCLUSIONS: Reduced [18F]fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized
AD  - Department of Neurology, University of Turku, Finland. juha.rinne@pet.tyks.fi
UR  - PM:10768619
ER  - 

TY  - JOUR
T1  - Cerebellar activation during ataxic gait in olivopontocerebellar atrophy: a PET study
A1  - Mishina,M.
A1  - Senda,M.
A1  - Ishii,K.
A1  - Ohyama,M.
A1  - Kitamura,S.
A1  - Katayama,Y.
Y1  - 1999/12//
N1  - UI - 20055713
SP  - 369
EP  - 376
JA  - Acta Neurol Scand.
VL  - 100
IS  - 6
N2  - OBJECTIVE: To investigate the possible abnormal regional brain metabolism during ataxic gait in olivopontocerebellar atrophy (OPCA), and to evaluate the response of the cerebellar subregions to instability during bipedal gait. MATERIAL AND METHODS: On 9 patients with OPCA in early phase and on 10 age-matched normal subjects, we performed positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) under two different conditions: supine resting and 30 min treadmill walking. RESULTS: Both in normals and in patients with OPCA, the FDG uptake in the walking state (Uwalk) was significantly greater than that in the resting state (Urest) in the pyramis, declive-folium-tuber and culmen of the cerebellar vermis, and in the thalamus. In the patients, the Uwalk was also significantly greater than the Urest in the posterior lobe of cerebellar hemisphere and in the pons and midbrain. In the pyramis, the activation ratio (= Uwalk/Urest) of the patients was significantly lower than that of the normals. CONCLUSIONS: We considered that these findings reflect the pathophysiology of ataxic gait in OPCA patients and the compensatory mechanism for the instability during ataxic gait
AD  - Second Department of Internal Medicine, Nippon Medical School, Japan
UR  - PM:10589796
ER  - 

TY  - JOUR
T1  - A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity
A1  - Ceballos-Baumann,A.O.
A1  - Boecker,H.
A1  - Bartenstein,P.
A1  - von,Falkenhayn,I
A1  - Riescher,H.
A1  - Conrad,B.
A1  - Moringlane,J.R.
A1  - Alesch,F.
Y1  - 1999/08//
N1  - UI - 99376036
SP  - 997
EP  - 1003
JA  - Arch Neurol
VL  - 56
IS  - 8
N2  - BACKGROUND: Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE: To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS: Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS: All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION: Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease
AD  - Department of Neurology, Technische Universitat Munchen, Munich, Germany. a.ceballos@lrz.tu-muenchen.de
UR  - PM:10448806
ER  - 

TY  - JOUR
T1  - Leads for the development of neuroprotective treatment in Parkinson's disease and brain imaging methods for estimating treatment efficacy
A1  - Stoof,J.C.
A1  - Winogrodzka,A.
A1  - van Muiswinkel,F.L.
A1  - Wolters,E.C.
A1  - Voorn,P.
A1  - Groenewegen,H.J.
A1  - Booij,J.
A1  - Drukarch,B.
Y1  - 1999/06/30/
SP  - 75
EP  - 86
JA  - Eur.J Pharmacol.
VL  - 375
IS  - 1-3
N2  - Patients suffering from Parkinson's disease display severe and progressive deficits in motor behavior, predominantly as a consequence of the degeneration of dopaminergic neurons, located in the mesencephalon and projecting to striatal regions. The cause of Parkinson's disease is still an enigma. Consequently, the pharmacotherapy of Parkinson's disease consists of symptomatic treatment, with in particular L-dihydroxyphenylalanine (L-DOPA) and/or dopamine receptor agonists. These induce a dramatic initial improvement. However, serious problems gradually develop during long-term treatment. Therefore, a more rational, c.q. causal treatment is needed which requires the introduction of compounds ameliorating the disease process itself. The development of such compounds necessitates (1) more information on the etiopathogenesis, i.e., the cascade of events that ultimately leads to degeneration of the dopaminergic neurons, and (2) brain imaging methods, to estimate the extent of the degeneration of the dopaminergic neurons in the living patient. This is not only important for the early diagnosis, but will also allow to monitor the effectiveness of alleged neuroprotective compounds on a longitudinal base. In this paper, etiopathogenic mechanisms are highlighted along the line of the oxidative stress hypothesis and within this framework, attention is mainly focused on the putative role of glutathione, dopamine auto-oxidation and phase II biotransformation enzymes. Especially, drugs able to increase the activity of phase II biotransformation enzymes seem to elicit a broad-spectrum (neuro)protective response and look very promising leads for the development of neuroprotective treatment strategies in Parkinson's disease. New developments in brain imaging methods (single photon emission computed tomography (SPECT) and positron emission tomography (PET)) to visualize the integrity of the striatal dopaminergic neurons in humans are highlighted as well. Especially, the introduction of radioligands that bind selectively to the dopamine transporter seems to be a significant step forward for the early diagnosis of Parkinson's disease. Performing these brain imaging studies with fixed time intervals does not only create the possibility to follow the degeneration rate of the dopaminergic neurons in Parkinson's disease but also provides the opportunity to estimate therapeutic effects of putative neuroprotective agents in the individual patient
AD  - Department of Neurology, Research Institute for Neurosciences, Vrije Universiteit, Amsterdam, The Netherlands. jc.stoof.neurol@med.vu.nl
UR  - PM:10443566
ER  - 

TY  - JOUR
T1  - Bilateral contemporaneous posteroventral pallidotomy for the treatment of Parkinson's disease: neuropsychological and neurological side effects. Report of four cases and review of the literature
A1  - Ghika,J.
A1  - Ghika-Schmid,F.
A1  - Fankhauser,H.
A1  - Assal,G.
A1  - Vingerhoets,F.
A1  - Albanese,A.
A1  - Bogousslavsky,J.
A1  - Favre,J.
Y1  - 1999/08//
SP  - 313
EP  - 321
JA  - J Neurosurg
VL  - 91
IS  - 2
N2  - The authors report the underestimated cognitive, mood, and behavioral complications in patients who have undergone bilateral contemporaneous pallidotomy, as seen in their early experience with functional neurosurgery for Parkinson's disease (PD) that is accompanied by severe motor fluctuations before pallidal stimulation. Four patients, not suffering from dementia, with advanced (Hoehn and Yahr Stages III-IV), medically untreatable PD featuring severe "on-off" fluctuations underwent bilateral contemporaneous posteroventral pallidotomy (PVP). All patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) protocol without positron emission tomography scans but with additional neuropsychological cognitive, mood, and behavior testing. For the first 3 to 6 months postoperatively, all patients showed a mean improvement of motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS), in the best "on" (21%) and worst "off" (40%) UPDRS III motor subscale, a mean 30% improvement in the UPDRS II activities of daily living (ADL) subscore, and 60% on the UPDRS IV complications of treatment subscale. Dyskinesia disappeared almost completely, and the mean daily duration of the off time was reduced by an average of 60%. Despite these good results in the CAPIT scores, one patient experienced a partially regressive corticobulbar syndrome with dysphagia, dysarthria, and increased drooling. No emotional lability was found in this patient, but he did demonstrate severe bilateral postoperative pretarsal blepharospasm (apraxia of eyelid opening), which interfered with walking and which required treatment with high-dose subcutaneous injections of botulinum toxin. No patient showed visual field defects or hemiparesis, but postoperative depression, changes in personality, behavior, and executive functions were seen in two individuals. Postoperative abulia was reported by the family of one patient, who lost his preoperative aggressiveness and drive in terms of ADL, speech, business, family life, and hobbies, and became more sleepy and fatigued. One patient reported postoperative mental automatisms, such as compulsive mental counting, and circular thoughts and reasoning during off phases; postoperative depression was found in two patients. However, none of the patients demonstrated these symptoms during intraoperative microelectrode stimulation. These findings are compatible with previous reports on bilateral pallidal lesions. A progressive lowering of UPDRS subscores was seen after 12 months, consistent with the progression of the disease. Bilateral simultaneous pallidotomy may be followed by emotional, behavioral, and cognitive deficits such as depression, obsessive-compulsive disorders, and loss of psychic autoactivation-abulia, as well as disabling corticobulbar dysfunction and apraxia of eyelid opening, in addition to previously described motor and visual field deficits, which make this surgery undesirable even though significant improvement in motor deficits can be achieved
AD  - Division Autonome de Neuropsychologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. joseph.ghika@chuv.hospvd.ch
UR  - PM:10433321
ER  - 

TY  - JOUR
T1  - Decreased striatal monoaminergic terminals in multiple system atrophy detected with positron emission tomography
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Little,R.
A1  - Kluin,K.J.
A1  - Heumann,M.
A1  - Martorello,S.
A1  - Johanns,J.
Y1  - 1999/06//
N1  - UI - 99287514
SP  - 769
EP  - 777
JA  - Ann.Neurol
VL  - 45
IS  - 6
N2  - We examined the density of striatal presynaptic monoaminergic terminals, using a ligand for the type 2 vesicular monoamine transporter, (+)-[11C]dihydrotetrabenazine, with positron emission tomography in 7 normal control subjects, 8 multiple system atrophy (MSA) patients with predominantly parkinsonian features (MSA-P), 8 MSA patients with principally cerebellar dysfunction (MSA-C), and 6 sporadic olivopontocerebellar atrophy (sOPCA) patients. The findings were correlated with the results of neurological evaluations and magnetic resonance imaging studies. Specific binding was significantly reduced in the putamen of all patient groups in the order MSA-P < MSA-C < sOPCA, compared with controls. Mean blood-to-brain ligand transport (K1) was significantly decreased in the putamen of all patient groups and in the cerebellar hemispheres of MSA-C and sOPCA but not MSA-P groups, compared with controls. Significant negative correlations were found between striatal binding and the intensity of parkinsonian features and between cerebellar K1 and the intensity of cerebellar dysfunction. The results suggest fundamental differences between MSA-P and MSA-C groups reflecting differential severity of degeneration of nigrostriatal and cerebellar systems in these two forms of MSA. The findings also show that some sOPCA patients have subclinical nigrostriatal dysfunction and are at risk of developing MSA with disease progression
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109-0316, USA
UR  - PM:10360769
ER  - 

TY  - JOUR
T1  - Parkinsonism, pyramidal signs, polyneuropathy, and cognitive decline after long-term occupational solvent exposure
A1  - Hageman,G.
A1  - van der,Hoek J.
A1  - van Hout,M.
A1  - van der,Laan G.
A1  - Steur,E.J.
A1  - de Bruin,W.
A1  - Herholz,K.
Y1  - 1999/03//
N1  - UI - 99254897
SP  - 198
EP  - 206
JA  - J Neurol
VL  - 246
IS  - 3
N2  - It is well known that exposure to manganese, solvents, or carbon monoxide in an occupational setting may lead to central nervous system damage and parkinsonism. The most important solvents in this respect are methanol, toluene, carbon disulfide, and n-hexane. We describe three patients who had been exposed to various solvents for more than 20 years (25, 34, and 46 years). They presented with parkinsonism, pyramidal signs, mild cognitive decline, and unresponsiveness to levodopa. Two patients had a predominantly axonal and sensory polyneuropathy of the lower legs with fasciculations in one of them. Parkinsonian features were progressive, even after the patients had stopped work. We present clinical data, neuropsychological findings, and results of brain computed tomography or magnetic resonance imaging, electroneuromyography, evoked potentials, single photon emission computed tomography, and positron-emission tomography. There is growing evidence that various organic solvents give rise to a parkinsonism syndrome with pyramidal features in susceptible individuals
AD  - Department of Neurology, Medical Spectrum Twente, Hospital Enschede, The Netherlands
UR  - PM:10323318
ER  - 

TY  - JOUR
T1  - Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson's disease: compartment analysis for beta-CFT binding with positron emission tomography
A1  - Ouchi,Y.
A1  - Yoshikawa,E.
A1  - Okada,H.
A1  - Futatsubashi,M.
A1  - Sekine,Y.
A1  - Iyo,M.
A1  - Sakamoto,M.
Y1  - 1999/05//
SP  - 601
EP  - 610
JA  - Ann.Neurol
VL  - 45
IS  - 5
N2  - We investigated changes in the kinetics in the binding of the dopamine transporter probe 2-beta-carbomethoxy-3beta-(4-[11C]fluorophenyl)tropane (beta-CFT) in living brain by compartmental analysis, using positron emission tomography in unmedicated patients with Parkinson's disease (PD) (Hoehn and Yahr stages I-II). With dynamic positron emission tomographic data from 90-minute acquisitions and metabolite-corrected arterial input functions, binding potentials (k3/k4) were calculated by using estimated rate constants (K1 - k4). In this analysis, the magnitude of the distribution volume (K1/k2) measured in the cerebellum, in which specific binding is negligible, was used as a constrained value for fitting in binding regions. Statistics showed that k3/k4 values in the striatum, the orbitofrontal cortex, and the amygdala were significantly lower in PD patients than in normal controls, whereas there were no differences in K1/k2 ratios and structural volumes between the groups. Correlation analysis showed that the putaminal and orbitofrontal binding levels were correlated positively with motor and mentation scores, respectively, of the Unified Parkinson's Disease Rating Scale. These results indicated that not only the striatal but also the orbitofrontal and amygdalar presynaptic dopaminergic functions were altered in early PD. The reductions in these mesocortical/mesolimbic functions might contribute to the mental and behavioral impairment observed in PD
AD  - Positron Medical Center, Hamamatsu Medical Center, Hamakita, Japan
UR  - PM:10319882
ER  - 

TY  - JOUR
T1  - 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in type IV 3-methylglutaconic aciduria: clinical and MRI correlations
A1  - Al Essa,M.
A1  - Bakheet,S.
A1  - Al Shamsan,L.
A1  - Patay,Z.
A1  - Powe,J.
A1  - Ozand,P.T.
Y1  - 1999/01//
N1  - UI - 99180286
SP  - 24
EP  - 29
JA  - Brain Dev.
VL  - 21
IS  - 1
N2  - The clinical, 18fluorodeoxyglucose positron emission tomography (18FDG PET) and the magnetic resonance imaging (MRI) brain scan characteristics of four patients diagnosed to have 3-methylglutaconic aciduria were reviewed retrospectively. The disease has a characteristic clinical pattern. The initial presentations were developmental delay, hypotonia, and severe failure to thrive. Later, progressive encephalopathy with rigidity and quadriparesis were observed, followed by severe dystonia and choreoathetosis. Finally, the patients became severely demented and bedridden. The 18FDG PET scans showed progressive disease, explaining the neurological status. It could be classified into three stages. Stage I: absent 18FDG uptake in the heads of the caudate, mild decreased thalamic and cerebellar metabolism. Stage II: absent uptake in the anterior half and posterior quarter of the putamina, mild-moderate decreased uptake in the cerebral cortex more prominently in the parieto-temporal lobes. Progressive decreased thalamic and cerebellar uptake. Stage III: absent uptake in the putamina and severe decreased cortical uptake consistent with brain atrophy and further decrease uptake in the cerebellum. The presence of both structural and functional changes in the brain, demonstrated by the combined use of MRI and 18FDG PET scan, with good clinical correlation, make the two techniques complementary in the imaging evaluation of 3-methylglutaconic aciduria
AD  - Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
UR  - PM:10082249
ER  - 

TY  - JOUR
T1  - PET imaging of the pre-synaptic dopamine uptake sites in rapid-onset dystonia-parkinsonism (RDP)
A1  - Brashear,A.
A1  - Mulholland,G.K.
A1  - Zheng,Q.H.
A1  - Farlow,M.R.
A1  - Siemers,E.R.
A1  - Hutchins,G.D.
Y1  - 1999/01//
SP  - 132
EP  - 137
JA  - Mov Disord.
VL  - 14
IS  - 1
N2  - BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement disorder characterized by abrupt onset over hours to days of bradykinesia, postural instability, dysphagia, dysarthria, and severe dystonic spasms with decreased levels of the dopamine metabolite, homovanillic acid (HVA), in cerebrospinal fluid (CSF). METHODS: We imaged the dopamine re-uptake system with [O-methyl-11C]beta-CFT ([11C]beta-CFT) in three severely affected individuals with RDP and four patients with idiopathic Parkinson's disease (IPD). Results were compared with those of age-matched normal volunteers. RESULTS: Positron emission tomography images from those patients with IPD demonstrated a dramatic reduction in the volume of distribution of [11C]beta-CFT whereas patients with RDP showed slightly elevated values. CONCLUSIONS: The data suggest that patients with RDP do not have a decrease in the number of dopamine re-uptake sites. Our findings suggest that, unlike the situation in IPD, low CSF HVA concentrations seen in RDP patients are not the result of degeneration of striatal dopamine terminals or loss of dopamine re-uptake sites
AD  - Department of Neurology, Indiana University School of Medicine, Indianapolis 46202-5250, USA
UR  - PM:9918356
ER  - 

TY  - JOUR
T1  - High presynaptic dopaminergic activity in children with Tourette's disorder
A1  - Ernst,M.
A1  - Zametkin,A.J.
A1  - Jons,P.H.
A1  - Matochik,J.A.
A1  - Pascualvaca,D.
A1  - Cohen,R.M.
Y1  - 1999/01//
N1  - UI - 99109299
SP  - 86
EP  - 94
JA  - J Am.Acad.Child Adolesc.Psychiatry
VL  - 38
IS  - 1
N2  - OBJECTIVE: Tourette's disorder is characterized by chronic fluctuating motor and vocal tics. Despite extensive investigation of the neuropathophysiology of the disorder by a wide array of methodologies, its neurobiochemical substrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia. METHOD: This study examined the integrity of presynaptic dopaminergic function in children with Tourette's disorder, using positron emission tomography and the tracer [18F]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). RESULTS: Subjects with Tourette's disorder showed higher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08). CONCLUSION: These findings provide evidence of dopaminergic dysfunction in children with Tourette's disorder which affects both cell nuclei and nerve terminals. Based on the known regulation of DOPA decarboxylase activity by post- and presynaptic receptors, and by extracellular dopamine concentration, abnormal activity in this enzyme may reflect deficits in a variety of functional elements of the dopamine system. The precise mechanism underlying an up-regulation of DOPA decarboxylase activity needs to be identified in future studies
AD  - Laboratory of Cerebral Metabolism, National Institute of Mental Health, NIH, Bethesda, MD 20892-4030, USA
UR  - PM:9893421
ER  - 

TY  - JOUR
T1  - Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428
A1  - McCann,U.D.
A1  - Wong,D.F.
A1  - Yokoi,F.
A1  - Villemagne,V.
A1  - Dannals,R.F.
A1  - Ricaurte,G.A.
Y1  - 1998/10/15/
SP  - 8417
EP  - 8422
JA  - J Neurosci.
VL  - 18
IS  - 20
N2  - Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has recently been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [11C]WIN-35,428, a DA transporter (DAT) ligand. The present studies determined whether living humans with a history of methamphetamine or methcathinone abuse showed evidence of lasting decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson's disease (PD). On average, subjects had abstained from amphetamine use for approximately 3 years. Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%, respectively). Larger decreases in DAT density were evident in patients with PD (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor methcathinone users showed clinical signs of parkinsonism. Persistent reductions of DAT density in methamphetamine and methcathinone users are suggestive of loss of DAT or loss of DA terminals and raise the possibility that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in which brain DA neurons have been implicated
AD  - Unit on Anxiety Disorders, Biological Psychiatry Branch, National Institute of Mental Health, Intramural Research Program, Bethesda, Maryland 20892, USA
UR  - PM:9763484
ER  - 

TY  - JOUR
T1  - Activation positron emission tomography scanning in dystonia
A1  - Ceballos-Baumann,A.O.
A1  - Brooks,D.J.
Y1  - 1998///
N1  - UI - 98423485
SP  - 135
EP  - 152
JA  - Adv.Neurol
VL  - 78
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:9750911
ER  - 

TY  - JOUR
T1  - Functional brain networks in DYT1 dystonia
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Antonini,A.
A1  - Kazumata,K.
A1  - Nakamura,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - DeLeon,D.
A1  - Bressman,S.B.
A1  - Fahn,S.
Y1  - 1998/09//
N1  - UI - 98420024
SP  - 303
EP  - 312
JA  - Ann.Neurol
VL  - 44
IS  - 3
N2  - Early-onset idiopathic torsion dystonia (ITD) is an autosomal dominant hyperkinetic movement disorder with incomplete penetrance, associated with a 3 base-pair deletion in the DYT1 gene on chromosome 9q34. To determine the metabolic substrates of brain dysfunction in DYT1 dystonia, we scanned 7 nonmanifesting and 10 affected DYT1 carriers and 14 normal volunteers with [18F]fluorodeoxyglucose and positron emission tomography. We found that DYT1 dystonia is mediated by the expression of two independent regional metabolic covariance patterns. The first pattern, identified in an analysis of nonmanifesting gene carriers was designated movement free (MF). This abnormal pattern was characterized by increased metabolic activity in the lentiform nuclei, cerebellum, and supplementary motor areas. The MF pattern was present in DYT1 carriers with and without clinical manifestations and persisted in DYT1 dystonia patients in whom involuntary movements were suppressed by sleep. The second pattern, identified in an analysis of affected gene carriers with sustained contractions at rest, was designated movement related (MR). This pattern was characterized by increased metabolic activity in the midbrain, cerebellum, and thalamus. The expression of the MR pattern was increased in waking DYT1 patients with sustained dystonia, compared with DYT1 carriers who were unaffected or who had dystonia only on action, as well as normal controls. MR subject scores declined significantly with sleep in affected DYT1 patients but not in normal controls. These findings indicate the penetrance of the DYT1 gene is considerably greater than previously assumed. ITD is mediated through the interaction of functional brain networks relating separately to gene status and to abnormal movement
AD  - Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA
UR  - PM:9749595
ER  - 

TY  - JOUR
T1  - A novel MPTP primate model of Parkinson's disease: neurochemical and clinical changes
A1  - Eberling,J.L.
A1  - Jagust,W.J.
A1  - Taylor,S.
A1  - Bringas,J.
A1  - Pivirotto,P.
A1  - VanBrocklin,H.F.
A1  - Bankiewicz,K.S.
Y1  - 1998/09/14/
N1  - UI - 98405975
SP  - 259
EP  - 262
JA  - Brain Res.
VL  - 805
IS  - 1-2
N2  - Positron emission tomography (PET) and the dopamine (DA) metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate the relationship between DA metabolism and the clinical stage of parkinsonism monkeys following either unilateral ICA MPTP infusion or unilateral ICA MPTP infusion and subsequent varying sequential systemic doses of MPTP. Clinical stage corresponded to PET measures of striatal DA metabolism, showing the usefulness of the overlesioned hemiparkinsonian monkey as a stable model of various stages of Parkinson's disease (PD)
AD  - Center for Functional Imaging, 55-121, Lawrence Berkeley National Laboratory, University of California, 1 Cyclotron Road, Berkeley, CA 94720, USA
UR  - PM:9733979
ER  - 

TY  - JOUR
T1  - Brain muscarinic receptors in progressive supranuclear palsy and Parkinson's disease: a positron emission tomographic study
A1  - Asahina,M.
A1  - Suhara,T.
A1  - Shinotoh,H.
A1  - Inoue,O.
A1  - Suzuki,K.
A1  - Hattori,T.
Y1  - 1998/08//
SP  - 155
EP  - 163
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 65
IS  - 2
N2  - OBJECTIVES: To assess muscarinic acetylcholine receptors (mAChRs) in the brains of patients with progressive supranuclear palsy and Parkinson's disease, and to correlate the cholinergic system with cognitive function in progressive supranuclear palsy and Parkinson's disease. METHODS: Positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB) was used to measure mAChRs in the brain of seven patients with progressive supranuclear palsy, 12 patients with Parkinson's disease, and eight healthy controls. All of the patients with progressive supranuclear palsy were demented. The Parkinson's disease group consisted of 11 non-demented patients and one demented patient. The mini mental state examination (MMSE) was used to assess the severity of cognitive dysfunction in all of the subjects. The modified Wisconsin card sorting test (WCST) was used to evaluate frontal cognitive function in the non-demented patients with Parkinson's disease and controls. RESULTS: The mean K3 value, an index of mAChR binding, was significantly higher for the frontal cortex in the patients with Parkinson's disease than in the controls (p<0.01). By contrast, the patients with progressive supranuclear palsy had no significant changes in the K3 values of any cerebral cortical regions. The mean score of the MMSE in the progressive supranuclear palsy group was significantly lower than that in the control group. Although there was no difference between the Parkinson's disease and control groups in the MMSE, the non-demented patients with Parkinson's disease showed significant frontal lobe dysfunction in the WCST. CONCLUSIONS: The increased mAChR binding in the frontal cortex of the patients with Parkinson's disease may reflect denervation hypersensitivity caused by loss of the ascending cholinergic input to that region from the basal forebrain and may be related to frontal lobe dysfunction in Parkinson's disease. The cerebral cortical cholinergic system may not have a major role in cognitive dysfunction in progressive supranuclear palsy
AD  - Division of Clinical Research and Radiation Health, National Institute of Radiological Science, Chiba, Japan. masatoasahina@msn.com
UR  - PM:9703164
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and metabolism in multiple system atrophy of the Shy-Drager syndrome type: a PET study
A1  - Ogawa,M.
A1  - Fukuyama,H.
A1  - Harada,K.
A1  - Kimura,J.
Y1  - 1998/06/30/
N1  - UI - 98368070
SP  - 173
EP  - 179
JA  - J Neurol Sci.
VL  - 158
IS  - 2
N2  - To investigate the role of the autonomic nervous system in cerebral blood flow (CBF) and metabolism, CBF and oxygen metabolism in patients with multiple system atrophy of the Shy-Drager syndrome type were examined. Seven patients with Shy-Drager syndrome were imaged using positron emission tomography and 15O-labeled gases. There was excellent local coupling between CBF and the cerebral metabolic rate of oxygen in the resting state. Elevation of blood pressure induced by leg raising increased CBF. The inhalation of CO2 also increased CBF in the Shy-Drager patients. These results showed that autoregulation is impaired in Shy-Drager syndrome, but local metabolic-flow coupling in the resting state and the CBF response to CO2 inhalation are spared. We conclude that the autonomic nervous system plays an important role in autoregulation, but not in local metabolic-flow coupling in the resting state. We suggest that metabolic mechanisms may mediate resting metabolic-flow coupling
AD  - Department of Neurology, Faculty of Medicine, Kyoto University, Japan
UR  - PM:9702688
ER  - 

TY  - JOUR
T1  - 6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys
A1  - Doudet,D.J.
A1  - Chan,G.L.
A1  - Holden,J.E.
A1  - McGeer,E.G.
A1  - Aigner,T.A.
A1  - Wyatt,R.J.
A1  - Ruth,T.J.
Y1  - 1998/07//
SP  - 225
EP  - 232
JF  - Synapse
VL  - 29
IS  - 3
N2  - This report describes a method to assess, in vivo, the turnover of dopamine (DA) and describes its application to the evaluation of DA function in normal monkeys and monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lesions of the DA nigro-striatal pathway. Using positron emission tomography with the tracer of presynaptic DA function, 6-[18F]fluoro-L-DOPA (FDOPA), and an extension of the graphical method of analysis, we measured the striatal FDOPA uptake rate constant, Ki, and the rate of reversibility of FDOPA trapping k(loss) in normal and MPTP-treated monkeys, either neurologically normal or displaying a parkinsonian symptomatology. An index of effective DA turnover was defined as the ratio of k(loss)/Ki. Compared to normal controls, Ki was decreased and k(loss) was increased in the MPTP-lesioned monkeys. The index of DA turnover was significantly increased in the monkeys displaying a parkinsonian symptomatology as compared to the controls and the neurologically normal MPTP-treated monkeys. The DA turnover index was also significantly increased in the neurologically normal MPTP-lesioned animals compared to normals. This suggests that an increase in DA turnover develops early in the disease process and may be one of the compensatory mechanisms partly responsible for the delay in the development of the clinical manifestations in Parkinson's disease
AD  - Department of Medicine, Kinsmen Laboratory of Neurological Research and TRIUMF, University of British Columbia, Vancouver, Canada. ddoudet@interchange.ubc.ca
UR  - PM:9635892
ER  - 

TY  - JOUR
T1  - Increased activation of frontal areas during arm movement in idiopathic torsion dystonia
A1  - Playford,E.D.
A1  - Passingham,R.E.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1998/03//
N1  - UI - 98198752
SP  - 309
EP  - 318
JA  - Mov Disord.
VL  - 13
IS  - 2
N2  - Most positron emission tomography (PET) studies of regional cerebral function in idiopathic torsion dystonia (ITD) have failed to show abnormalities, but there have been few studies of the changes in regional cerebral blood flow (rCBF) that occur during movement in dystonia. Using PET, we have studied six patients with familial generalized ITD both at rest and while moving a joystick with the right hand. The patterns of CBF change obtained were compared with those in six age-matched control subjects. In the dystonia group, free selection of movement was associated with relative increases in rCBF above that observed in control subjects in the left premotor area, the supplementary motor area (SMA), the anterior cingulate cortex, and the left dorsolateral prefrontal area. Subcortical increases were observed within the cerebellum and the putamen. There was a relative decrease in flow through the contralateral primary sensorimotor cortex. These findings contrast with those reported in patients with Parkinson's disease undertaking the same task in which the activity in the SMA and putamen was decreased. We suggest that arm dystonia in ITD is associated with overactivity of the premotor areas, including the SMA, and that this results from release of the thalamus from the normal inhibitory influence of the globus pallidus internal segment. Other abnormalities of basal ganglia control of brain stem centers may be involved in axial dystonia
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:9539346
ER  - 

TY  - JOUR
T1  - Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism
A1  - Dethy,S.
A1  - Van Blercom,N.
A1  - Damhaut,P.
A1  - Wikler,D.
A1  - Hildebrand,J.
A1  - Goldman,S.
Y1  - 1998/03//
SP  - 275
EP  - 280
JA  - Mov Disord.
VL  - 13
IS  - 2
N2  - We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L-dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L-dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L-dopa-responsive patients. Our FDG-PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L-dopa responsiveness
AD  - PET/Biomedical Cyclotron Unit and Service de Neurologie, ULB-Hopital Erasme, Brussels, Belgium
UR  - PM:9539341
ER  - 

TY  - JOUR
T1  - Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET
A1  - Antonini,A.
A1  - Kazumata,K.
A1  - Feigin,A.
A1  - Mandel,F.
A1  - Dhawan,V.
A1  - Margouleff,C.
A1  - Eidelberg,D.
Y1  - 1998/03//
SP  - 268
EP  - 274
JA  - Mov Disord.
VL  - 13
IS  - 2
N2  - The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders (APD) is complicated by the presence of signs and symptoms common to both forms of parkinsonism. Metabolic brain imaging with [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be a useful adjunct in differentiating APD from IPD. To explore this possibility, we studied 48 parkinsonian patients suspected as having possible APD because of a deteriorating response to dopaminergic treatment, the development of autonomic dysfunction, or both. A group of 56 patients with likely IPD served as control subjects. We used quantitative FDG/PET to measure regional rates of cerebral glucose use in IPD and APD patients. We used discriminant analysis to categorize IPD and APD patients based on their regional metabolic data. We found that a linear combination of caudate, lentiform, and thalamic values accurately discriminated APD from IPD patients (p < 0.0001). Significant metabolic abnormalities were present in the striatum and the thalamus of 36 of 48 (75%) APD patients. Our findings show that measurements of regional glucose metabolism can be used to discriminate patients with suspected APD from their counterparts with classic IPD. FDG/PET may be a useful adjunct to the clinical examination in the differential diagnosis of parkinsonism
AD  - Movement Disorders Center, Department of Neurology, North Shore University Hospital, Manhasset, New York 11030, USA
UR  - PM:9539340
ER  - 

TY  - JOUR
T1  - In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants
A1  - Brownell,A.L.
A1  - Livni,E.
A1  - Galpern,W.
A1  - Isacson,O.
Y1  - 1998/03//
N1  - UI - 98165382
SP  - 387
EP  - 390
JA  - Ann.Neurol
VL  - 43
IS  - 3
N2  - Positron emission tomography (PET) and carbon-11-labeled 2B-carbomethoxy-3B-(4-fluorophenyl)tropane (11C-CFT or 11-WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non-DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C-CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation
AD  - Neuroregeneration Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA, USA
UR  - PM:9506557
ER  - 

TY  - JOUR
T1  - [11C]raclopride-PET studies of the Huntington's disease rate of progression: relevance of the trinucleotide repeat length
A1  - Antonini,A.
A1  - Leenders,K.L.
A1  - Eidelberg,D.
Y1  - 1998/02//
N1  - UI - 98143601
SP  - 253
EP  - 255
JA  - Ann.Neurol
VL  - 43
IS  - 2
N2  - We used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nonetheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD
AD  - Movement Disorders Center, Department of Neurology, North Shore University Hospital, Manhasset, NY, USA
UR  - PM:9485067
ER  - 

TY  - JOUR
T1  - PET and the investigation of dementia in the parkinsonian patient
A1  - Turjanski,N.
A1  - Brooks,D.J.
Y1  - 1997///
N1  - UI - 98130903
SP  - 37
EP  - 48
JA  - J Neural Transm.Suppl
VL  - 51
N2  - Parkinsonism and dementia are present in a number of neurodegenerative conditions. They may be a manifestation of isolated brain stem (Parkinson's disease) or diffuse Lewy body disease (DLBD), or be secondary to combined Lewy body and Alzheimer's disease (AD) pathologies. Positron emission tomography (PET) studies show a resting pattern of fronto-temporo-parietal hypometabolism in both, AD and in parkinsonism-dementia (PD-dementia) patients, even when only isolated brain stem Lewy body disease is found at pathology. We have studied three patients fulfilling clinical criteria for diagnosis of DLBD. Their 18F-fluorodeoxyglucose (FDG) PET results showed an AD pattern of fronto-temporo-parietal hypometabolism, though these patients had only mild cognitive dysfunction. Parkinsonism associated with apraxia is observed in corticobasal degeneration (CBD) while impairment of frontal functions, such as planning and sorting, is seen in patients with progressive supranuclear palsy (PSP). PET studies in CBD patients have shown an asymmetric hypometabolism of cortex and thalamus contralateral to the affected limbs, while in PSP patients there is a global metabolic reduction most pronounced in frontal areas and the basal ganglia. These results suggest that metabolic PET studies can help to distinguish PD-dementia, PSP and CBD, but are unable to distinguish PD-dementia from AD. Further studies with post-mortem confirmation are required to establish if DLBD is associated with a distinctive pattern of resting hypometabolism
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:9470127
ER  - 

TY  - JOUR
T1  - Pretreatment and posttreatment positron emission tomographic scan imaging in a 20-year-old patient with Wilson's disease
A1  - Cordato,D.J.
A1  - Fulham,M.J.
A1  - Yiannikas,C.
Y1  - 1998/01//
N1  - UI - 98112723
SP  - 162
EP  - 166
JA  - Mov Disord.
VL  - 13
IS  - 1
N2  - Wilson's disease is an autosomal-recessive inherited disorder that results in predominantly hepatic and neurologic manifestations. Neurologic abnormalities include tremor, ataxia, bradykinesia, rigidity, chorea, and dystonia. We report the clinical, radiologic, and serial FDG PET findings in a 20-year-old woman who presented with an asymmetric upper limb tremor caused by Wilson's disease. Reduced striatal and cerebral cortical glucose metabolism was demonstrated on a FDG PET study performed before the commencement of D-penicillamine therapy. After 6 months of treatment, the patient had shown only minimal clinical improvement, despite an increase in striatal and cerebral cortical glucose metabolism on a repeat FDG PET study. After 14 months of treatment, however, a moderate clinical improvement was noted and there was further increase in glucose metabolism on FDG PET
AD  - Department of Neurology, Concord Hospital, Sydney, Australia
UR  - PM:9452344
ER  - 

TY  - JOUR
T1  - Alterations in opioid receptor binding in Parkinson's disease patients with levodopa-induced dyskinesias
A1  - Piccini,P.
A1  - Weeks,R.A.
A1  - Brooks,D.J.
Y1  - 1997/11//
N1  - UI - 98052464
SP  - 720
EP  - 726
JA  - Ann.Neurol
VL  - 42
IS  - 5
N2  - Levodopa-induced dyskinesias remain a major challenge in the therapeutic management of Parkinson's disease (PD). Their etiology is unknown although dysfunction of striatal opioid transmission has been implicated in experimental models of PD. To determine whether the opioid system is involved in human dyskinetic PD, we measured in vivo opioid receptor binding in PD patients with and without levodopa-induced dyskinesias, using positron emission tomography (PET) and the opioid receptor ligand [11C]diprenorphine. Striatal and thalamic/occipital uptake ratios were calculated using a region of interest (ROI) approach. In addition, we used statistical parametric mapping (SPM) and images reflecting the volume of distribution of [11C]diprenorphine to assess changes in cerebral receptor binding on a voxel-by-voxel basis. By using the ROI approach, we found significantly reduced striatal and thalamic opioid binding in dyskinetic, but not in nondyskinetic, PD patients. The SPM approach confirmed reduced availability in these areas and, in addition, showed decreased cingulate and increased prefrontal opioid receptor binding in the dyskinetic patients. Our findings confirm that altered opioid transmission is part of the pathophysiology of levodopa-induced dyskinesias in PD and support further investigation into the role of opioid agents in the management of these involuntary movements
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:9392571
ER  - 

TY  - JOUR
T1  - Differentiating between multiple system atrophy and Parkinson's disease by positron emission tomography with 18F-dopa and 18F-FDG
A1  - Otsuka,M.
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Hosokawa,S.
A1  - Sasaki,M.
A1  - Yoshida,T.
A1  - Fukumura,T.
A1  - Kato,M.
A1  - Masuda,K.
Y1  - 1997/08//
SP  - 251
EP  - 257
JA  - Ann.Nucl Med
VL  - 11
IS  - 3
N2  - Both the striatal 18F-dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]fluorodopa (FD) and [18F]fluorodeoxyglucose (FDG) in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson's disease (PD). Five of the 9 MSA patients were diagnosed as having olivopontocerebellar atrophy, whereas 2 had striatonigral degeneration and 2 demonstrated Shy-Drager syndrome. The FD uptake ratios to the occipital cortex in the MSA patients at 120 min after the administration of FD were 2.07 +/- 0.31 (mean +/- SD) and 1.96 +/- 0.29 in the caudate and the putamen, respectively, and decreased compared to those in the controls (2.72 +/- 0.11, 2.71 +/- 0.10). The same ratios in the PD patients were 2.07 +/- 0.36 and 1.74 +/- 0.24, respectively, which also decreased, but the decreased uptake in the putamen was more prominent. The caudate-putamen index (CPI)(%), which was calculated by a formula based on the difference in the uptakes in the caudate and putamen divided by the caudate uptake, indicated 5.6 +/- 4.6 in the MSA patients and 14.8 +/- 5.4 in the PD patients. The CPI for all PD patients was more than 7.0, which was the mean + 2SD for the controls, but the CPI for 3 MSA patients was more than 7.0 (accuracy: 88%). The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal and the temporal cortical glucose metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in the MSA patients decreased significantly in comparison to those in the controls. But, as the glucose metabolic rates in such regions of each patient overlapped in the two groups, the accuracy of the FDG study for differentiation was lower than that of the FD study. The putaminal glucose metabolic rates, for example, in 3 PD patients were less than 6.8 (mg/min/100 ml), which was the mean-2SD for the controls, while those in 3 MSA patients were more than 6.8 (accuracy: 75%). In addition, the combination of these two methods slightly improved the accuracy. The glucose metabolism is useful for evaluating the regional metabolic activity of the brain, and the FD study, which is specific to the dopamine system, seems to be more useful for differentiating between MSA and PD
AD  - Department of Radiology, Kyushu University, Beppu, Japan
UR  - PM:9310175
ER  - 

TY  - JOUR
T1  - 11C-diprenorphine binding in Huntington's disease: a comparison of region of interest analysis with statistical parametric mapping
A1  - Weeks,R.A.
A1  - Cunningham,V.J.
A1  - Piccini,P.
A1  - Waters,S.
A1  - Harding,A.E.
A1  - Brooks,D.J.
Y1  - 1997/09//
SP  - 943
EP  - 949
JA  - J Cereb.Blood Flow Metab
VL  - 17
IS  - 9
N2  - We compare region of interest (ROI) analytical approaches with statistical parametric mapping (SPM) of 11C-diprenorphine positron emission tomography findings in five patients with Huntington's disease (HD) and nine age-matched controls. The ROI were placed on caudate, putamen, and an occipital reference area. Ratios of striatal-occipital uptake from averaged static images centered at 60 minutes showed a mean 20% reduction in caudate (P = 0.034) and 15% reduction in putamen (P = 0.095) receptor binding in the HD patients. Dynamic data from caudate and putamen ROI, together with a plasma tracer input function, were analyzed using spectral analysis to give regional impulse response functions. Regional data at 60 minutes after impulse showed a mean 29% decrease in caudate (P = 0.006) and 23% decrease in putamen (P = 0.029) opioid binding in the HD cohort. Parametric images of tracer binding also were produced with spectral analysis on a voxel basis. The images of the unit impulse response function at 60 minutes showed a mean 31% decrease in caudate (P = 0.005) and a 26% decrease in putamen binding (P = 0.011) in HD. The voxel-based parametric images were transformed into standard stereotactic space, and a between-group comparison (patient versus controls) was performed with SPM. This approach revealed symmetrical decreases in caudate (peak 40% decrease, z score = 4.38) and putamen opioid binding (peak 24% decrease, z score = 4.686) with additional nonhypothesized changes in cingulate, prefrontal, and thalamic areas. The significance and precision of changes measured with spectral analysis applied to dynamic data sets were superior to ROI-based ratio analysis on static images. The SPM replicated the striatal reductions in opioid binding in HD and detected additional nonpredicted changes. This study suggests that SPM is a valid alternative to conventional ROI analytical approaches for determining binding changes with positron emission tomography and may have advantages over region-based analyses in exploratory studies
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:9307607
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in corticobasal degeneration: comparison with progressive supranuclear palsy and normal controls
A1  - Nagahama,Y.
A1  - Fukuyama,H.
A1  - Turjanski,N.
A1  - Kennedy,A.
A1  - Yamauchi,H.
A1  - Ouchi,Y.
A1  - Kimura,J.
A1  - Brooks,D.J.
A1  - Shibasaki,H.
Y1  - 1997/09//
N1  - UI - 98017544
SP  - 691
EP  - 696
JA  - Mov Disord.
VL  - 12
IS  - 5
N2  - The regional metabolic rate of glucose was estimated using 18F-labeled 2-deoxyglucose and positron-emission tomography (PET) in eight patients with corticobasal degeneration (CBD). Measures of cerebral glucose metabolism in these patients were compared with those for nine age-matched normal controls and eight patients with progressive supranuclear palsy (PSP). Compared with that in the normal controls, the CBD patients showed significantly reduced cerebral glucose metabolism in the contralateral hemisphere to the clinically most affected side in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex, as well as in the corpus striatum and the thalamus. In comparison with that in PSP, in CBD the glucose metabolism in the contralateral hemisphere was significantly decreased in the inferior parietal, sensorimotor, lateral temporal cortex, and the corpus striatum. These results confirm the marked asymmetric cerebral involvement in CBD and suggest that there are significant differences between CBD and PSP in the cerebral metabolism in some cerebral regions such as the inferior parietal cortex and sensorimotor cortex, which might reflect the differences in their clinical characteristics
AD  - Department of Neurology, Faculty of Medicine, Kyoto University, Japan
UR  - PM:9380049
ER  - 

TY  - JOUR
T1  - Biological imaging and the molecular basis of dopaminergic diseases
A1  - Barrio,J.R.
A1  - Huang,S.C.
A1  - Phelps,M.E.
Y1  - 1997/08/01/
SP  - 341
EP  - 348
JA  - Biochem.Pharmacol.
VL  - 54
IS  - 3
N2  - The development and validation of preclinical biological probes of nigrostriatal dysfunction are part of the next frontier for battling diseases involving dopamine deficiency. In this work, the quantitative relationship relationship between radiofluorinated L-DOPA, [e.g., L-3,4-dihydroxy-6-[18F]fluorophenylalanine (6-[18F]fluoro-L-DOPA, FDOPA)] kinetics measured with positron emission tomography and central dopamine biochemistry is discussed. A hypothesis of a possible "non-linearity" of FDOPA kinetics with dopaminergic cell losses is presented to explain apparent discrepancies in post-mortem biochemical and histological determinations in Parkinson's disease. Similar observations have been made in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed monkeys and human subjects where the FDOPA uptake constantly fell within normal values unless severe nigral damage had occurred. The limitations of FDOPA, and other biological probes, for examining the asymptomatic phase of dopaminergic diseases and the future direction of research are discussed
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, U.S.A. jbarrio@mail.nuc.ucla.edu
UR  - PM:9278092
ER  - 

TY  - JOUR
T1  - Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms
A1  - Davis,K.D.
A1  - Taub,E.
A1  - Houle,S.
A1  - Lang,A.E.
A1  - Dostrovsky,J.O.
A1  - Tasker,R.R.
A1  - Lozano,A.M.
Y1  - 1997/06//
N1  - UI - 97319592
SP  - 671
EP  - 674
JA  - Nat.Med
VL  - 3
IS  - 6
N2  - Studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in monkeys suggest that excessive inhibitory outflow from the internal segment of the globus pallidus (GPi) suppresses the motor thalamus, which reduces activation of the cerebral cortex motor system, resulting in the slowness and poverty of movement of Parkinson's disease (PD). This hypothesis is supported by reports of high rates of spontaneous neuronal discharges and hypermetabolism in GPi (ref. 4-7) and impaired activation of the supplementary motor area (SMA) and dorsolateral prefrontal regions in PD patients. Furthermore, lesion or chronic high-frequency electrical (likely inactivating) stimulation of GPi (ref. 10-14) is associated with marked improvements in akinesia and rigidity, and the impaired activation of SMA is reversed when the akinesia is treated with dopamine agonists. To test whether improvement in motor function with pallidal surgery can be attributed to increased activity in premotor cortical regions, we assessed the changes in regional cerebral blood flow (rCBF) and parkinsonian symptoms during disruption of GPi activity with high-frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsilateral premotor cortical areas during GPi stimulation, which improved rigidity and bradykinesia. These results suggest that disrupting the excessive inhibitory output of the basal ganglia reverses parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement
AD  - Department of Surgery, University of Toronto/Toronto Hospital (Western Division), Ontario, Canada
UR  - PM:9176495
ER  - 

TY  - JOUR
T1  - Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism in progressive supranuclear palsy
A1  - Yamauchi,H.
A1  - Fukuyama,H.
A1  - Nagahama,Y.
A1  - Katsumi,Y.
A1  - Dong,Y.
A1  - Konishi,J.
A1  - Kimura,J.
Y1  - 1997/05//
SP  - 606
EP  - 614
JA  - Ann.Neurol
VL  - 41
IS  - 5
N2  - Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease
AD  - Department of Neurology, Faculty of Medicine, Kyoto University, Japan
UR  - PM:9153522
ER  - 

TY  - JOUR
T1  - 6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates
A1  - Jordan,S.
A1  - Eberling,J.L.
A1  - Bankiewicz,K.S.
A1  - Rosenberg,D.
A1  - Coxson,P.G.
A1  - VanBrocklin,H.F.
A1  - O'Neil,J.P.
A1  - Emborg,M.E.
A1  - Jagust,W.J.
Y1  - 1997/03/07/
SP  - 264
EP  - 276
JA  - Brain Res.
VL  - 750
IS  - 1-2
N2  - The tracer 6-[18F]fluoro-L-m-tyrosine (FMT) was studied with regard to its biochemistry and kinetics, as well as its utility in evaluating brain dopaminergic function in primates before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment using positron emission tomography (PET). Plasma analysis of FMT and its F18-labeled metabolites 6-fluoro-3-hydroxyphenylacetic acid (FPAC) and 6-fluoro-3-hydroxyphenylethylamine (FMA) during PET scanning enabled kinetic analysis of FMT uptake. A separate study examined brain FMT metabolism in MPTP-naive monkeys euthanized 60 or 120 min after FMT injection. Almost 60% of total plasma F-18 activity was associated with FPAC and FMA 120 min after FMT injection. The FMT signal accumulated preferentially in dopaminergic areas such as caudate and putamen. This bilateral FMT signal was disrupted after unilateral intracarotid artery (ICA) MPTP infusion which reduced ipsilateral striatal activity. A three compartment three kinetic rate constant model for FMT uptake revealed reduced FMT decarboxylation (k3) in ipsilateral caudate and putamen after unilateral MPTP although a further decrease was not evident after intravenous MPTP. FPAC was the major F-18 species in all brain regions except in cerebellum where FMT was predominant 60 min post-mortem. FPAC was most concentrated in dopaminergic areas whereas lower levels occurred in areas containing few dopamine terminals. These data demonstrate preferential FMT metabolism and F-18 retention in dopaminergic tissue and support the use of FMT to evaluate normal and abnormal dopaminergic function
AD  - Center for Functional Imaging, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA
UR  - PM:9098552
ER  - 

TY  - JOUR
T1  - Sympathetic cardioneuropathy in dysautonomias
A1  - Goldstein,D.S.
A1  - Holmes,C.
A1  - Cannon,R.O.,III
A1  - Eisenhofer,G.
A1  - Kopin,I.J.
Y1  - 1997/03/06/
SP  - 696
EP  - 702
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 336
IS  - 10
N2  - BACKGROUND: The classification of dysautonomias has been confusing, and the pathophysiology obscure. We examined sympathetic innervation of the heart in patients with acquired, idiopathic dysautonomias using thoracic positron-emission tomography and assessments of the entry rate of the sympathetic neurotransmitter norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover). We related the laboratory findings to signs of sympathetic neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure responses associated with the Valsalva maneuver), central neural degeneration, and responsiveness to treatment with levodopa-carbidopa (Sinemet). METHODS: Cardiac scans were obtained after intravenous administration of 6-[18F]fluorodopamine in 26 patients with dysautonomia. Fourteen had sympathetic neurocirculatory failure--three with no signs of central neurodegeneration (pure autonomic failure), two with parkinsonism responsive to treatment with levodopa-carbidopa, and nine with central neurodegeneration unresponsive to treatment with levodopa-carbidopa (the Shy-Drager syndrome). The rates of cardiac norepinephrine spillover were estimated on the basis of concentrations of intravenously infused [3H]norepinephrine during catheterization of the right side of the heart. RESULTS: Patients with pure autonomic failure or parkinsonism and sympathetic neurocirculatory failure had no myocardial 6-[18F]fluorodopamine-derived radioactivity or cardiac norepinephrine spillover, indicating loss of myocardial sympathetic-nerve terminals, whereas patients with the Shy-Drager syndrome had increased levels of 6-[18F]fluorodopamine-derived radioactivity, indicating intact sympathetic terminals and absent nerve traffic. Patients with dysautonomia who did not have sympathetic neurocirculatory failure had normal levels of 6-[18F]fluorodopamine-derived radioactivity in myocardium and normal rates of cardiac norepinephrine spillover. CONCLUSIONS: The results of 6-[18F]fluorodopamine positron-emission tomography and neurochemical analyses support a new clinical pathophysiologic classification of dysautonomias, based on the occurrence of sympathetic neurocirculatory failure, signs of central neurodegeneration, and responsiveness to levodopa-carbidopa
AD  - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1424, USA
UR  - PM:9041100
ER  - 

TY  - JOUR
T1  - Effects of catechol-O-methyltransferase inhibition on the rates of uptake and reversibility of 6-fluoro-L-Dopa trapping in MPTP-induced parkinsonism in monkeys
A1  - Doudet,D.J.
A1  - Chan,G.L.
A1  - Holden,J.E.
A1  - Morrison,K.S.
A1  - Wyatt,R.J.
A1  - Ruth,T.J.
Y1  - 1997/03//
SP  - 363
EP  - 371
JF  - Neuropharmacology
VL  - 36
IS  - 3
N2  - The uptake rate constant and the loss rate constant that expresses the reversibility of the uptake process of 6-[18F]fluoro-L-Dopa (FDOPA) were measured by positron emission tomography in the striatum of normal rhesus monkeys and in monkeys with unilateral lesions of the dopaminergic nigro-striatal pathway, induced by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Ro 40-7592, tolcapone. After pretreatment with tolcapone, there was a very significant increase in plasma FDOPA throughout the course of the study, accompanied by a significant decrease in its main metabolite, 3-O-methylfluorodopa. Tolcapone did not induce a significant change in the uptake rate constant in either the normal or the MPTP-treated striatum. However, after tolcapone pretreatment, there was a significant decrease in the loss rate constant in the MPTP-treated striatum (25%) and a smaller, non-significant decrease in the normal striatum (13%). It is concluded that the COMT inhibitor tolcapone exhibits clear peripheral and central activity. As compared to peripheral COMT inhibitors, this central effect may help preserve and stabilize the synaptic levels of DA and, thus, further improve the effects of L-DOPA therapy in parkinsonian patients
AD  - Department of Medicine, University of British Columbia, Vancouver, Canada. ddoudet@interchange.ubc.ca
UR  - PM:9175615
ER  - 

TY  - JOUR
T1  - Differential effects of levodopa on dopaminergic function in early and advanced Parkinson's disease
A1  - Torstenson,R.
A1  - Hartvig,P.
A1  - Langstrom,B.
A1  - Westerberg,G.
A1  - Tedroff,J.
Y1  - 1997/03//
N1  - UI - 97219054
SP  - 334
EP  - 340
JA  - Ann.Neurol
VL  - 41
IS  - 3
N2  - The effect of levodopa on L-[11C]DOPA influx rate was evaluated in patients with early and advanced Parkinson's disease (PD) by using positron emission tomography (PET). The patients were scanned both drug-free and after a subsequent therapeutic levodopa infusion. Regional analysis of striatal L-[11C]DOPA influx rate showed a correlation to the degenerative loss of nerve terminals reported at postmortem analysis in PD. Levodopa induced markedly differential effects on the striatal L-[11C]DOPA influx rate in early and advanced patients. In patients with mild PD, levodopa infusion decreased L-[11C]DOPA influx, whereas in patients with advanced PD, levodopa induced significant upregulation of L-[11C]DOPA influx. These changes were confined to the putamen and were, in both patient categories, most prominent in the dorsal part of the region. The present investigation demonstrates a marked shift in the modulatory action of levodopa with the advancement of PD and suggests the induction of positive feedback in advanced PD. These findings could help explain the less graded clinical response to levodopa in advanced PD and would thus have importance for the understanding of the pathogenesis underlying motor fluctuations
AD  - Uppsala University PET Centre, Sweden
UR  - PM:9066354
ER  - 

TY  - JOUR
T1  - Dopaminergic function in familial Parkinson's disease: a clinical and 18F-dopa positron emission tomography study
A1  - Piccini,P.
A1  - Morrish,P.K.
A1  - Turjanski,N.
A1  - Sawle,G.V.
A1  - Burn,D.J.
A1  - Weeks,R.A.
A1  - Mark,M.H.
A1  - Maraganore,D.M.
A1  - Lees,A.J.
A1  - Brooks,D.J.
Y1  - 1997/02//
N1  - UI - 97180853
SP  - 222
EP  - 229
JA  - Ann.Neurol
VL  - 41
IS  - 2
N2  - There is increasing evidence for familial aggregation in Parkinson's disease (PD). It is possible that some asymptomatic relatives of PD patients have subclinical nigral Lewy body pathology and their identification could help determine the true prevalence of the disease. We used 18F-dopa positron emission tomography to investigate nigrostriatal dopaminergic terminal function in asymptomatic members of 7 unrelated kindreds in which at least 2 members had parkinsonism. Eight (25%) of the 32 asymptomatic relatives showed abnormal putamen 18F-dopa uptake (2.5 standard deviations below the normal mean). When discriminant function analysis was applied, all of these 8 subjects plus another 3 were classified with high probability as having PD. On neurological examination, 5 of the 32 relatives scanned had an isolated mild postural tremor and 2 of these 5 had reduced putamen uptake. Our findings provide further support for a role of inheritance in the etiology of PD and suggest that the penetrance for nigrostriatal dopaminergic dysfunction in familial clusters of PD is higher than the prevalence of clinical parkinsonism reported in epidemiological surveys
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:9029071
ER  - 

TY  - JOUR
T1  - Contributions of positron emission tomography to elucidating the pathogenesis of idiopathic parkinsonism and dopa responsive dystonia
A1  - Calne,D.B.
A1  - Fuente-Fernandez,R.
A1  - Kishore,A.
Y1  - 1997///
N1  - UI - 97191685
SP  - 47
EP  - 52
JA  - J Neural Transm.Suppl
VL  - 50
N2  - The metabolic mapping of brain activity, using PET, confirms the conventional wisdom of neurophysiology. In studies of pathophysiology, PET has yielded evidence that has generated new hypotheses. Progression of the lesion detectable with fluorodopa, in human subjects exposed to MPTP, raises the possibility of a transient environmental event being a cause of progressive neurodegeneration. Studies with fluorodopa in Idiopathic Parkinsonism indicate that the rate of loss of neurons is faster initially, and then tends to approach the normal age-related decline. In dopa responsive dystonia, the finding of normal fluorodopa PET led to the prediction that the lesion would be functional rather than anatomical; this has been confirmed by the identification of a defect in dopamine synthesis in this disorder. Filally, new PET ligands show promise for future studies designed to unravel the pathogenesis of diseases involving the basal ganglia
AD  - Department of Medicine, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada
UR  - PM:9120424
ER  - 

TY  - JOUR
T1  - Stereotactic thalamotomy in tremor-dominant Parkinson's disease: an H2(15)O PET motor activation study
A1  - Boecker,H.
A1  - Wills,A.J.
A1  - Ceballos-Baumann,A.
A1  - Samuel,M.
A1  - Thomas,D.G.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1997/01//
N1  - UI - 97158513
SP  - 108
EP  - 111
JA  - Ann.Neurol
VL  - 41
IS  - 1
N2  - Stereotactic thalamotomy is an effective treatment for severe drug-resistant tremor. The thalamus, however, facilitates motor activity, and thalamotomy would be predicted to inhibit movement-associated cortical activation. Two tremulous parkinsonian patients were studied with H2(15)O positron emission tomography before and after left ventralis intermedius thalamotomy. Subjects were scanned at rest and during performance of externally paced joystick movements in freely selected directions with the right hand. Thalamotomy relieved tremor but, as predicted, led to decreased activation of the left sensorimotor cortex, lateral premotor cortex, and parietal area 7 on hand movement
AD  - Medical Research Council (MRC) Cyclotron Unit, Hammersmith Hospitals, London, UK
UR  - PM:9005873
ER  - 

TY  - JOUR
T1  - Long-term changes of striatal dopamine D2 receptors in patients with Parkinson's disease: a study with positron emission tomography and [11C]raclopride
A1  - Antonini,A.
A1  - Schwarz,J.
A1  - Oertel,W.H.
A1  - Pogarell,O.
A1  - Leenders,K.L.
Y1  - 1997/01//
N1  - UI - 97144225
SP  - 33
EP  - 38
JA  - Mov Disord.
VL  - 12
IS  - 1
N2  - We used [11C]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. After 3-5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at "off" had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3-4 months after therapy began and that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long-term downregulation of striatal dopamine D2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons
AD  - PET Department, Paul Scherrer Institute, Villigen, Switzerland
UR  - PM:8990051
ER  - 

TY  - JOUR
T1  - Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging
A1  - Frey,K.A.
A1  - Koeppe,R.A.
A1  - Kilbourn,M.R.
A1  - Vander Borght,T.M.
A1  - Albin,R.L.
A1  - Gilman,S.
A1  - Kuhl,D.E.
Y1  - 1996/12//
SP  - 873
EP  - 884
JA  - Ann.Neurol
VL  - 40
IS  - 6
N2  - We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification
AD  - Department of Internal Medicine (Division of Nuclear Medicine), University of Michigan, Ann Arbor, USA
UR  - PM:9007092
ER  - 

TY  - JOUR
T1  - Glucose metabolism in the cortical and subcortical brain structures in multiple system atrophy and Parkinson's disease: a positron emission tomographic study
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Kuwabara,Y.
A1  - Hosokawa,S.
A1  - Sasaki,M.
A1  - Yoshida,T.
A1  - Fukumura,T.
A1  - Kato,M.
A1  - Masuda,K.
Y1  - 1996/12//
N1  - UI - 97147202
SP  - 77
EP  - 83
JA  - J Neurol Sci.
VL  - 144
IS  - 1-2
N2  - The brain glucose metabolism was studied by PET with 18F-FDG in 11 patients with multiple system atrophy (MSA) and 12 patients with idiopathic Parkinson's disease (PD). Seven of the 11 MSA patients were diagnosed as having olivopontocerebellar atrophy, two had striatonigral degeneration, while two demonstrated Shy-Drager syndrome. The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal, temporal and parietal cortical glucose metabolic rates and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolic rates in the MSA patients decreased significantly from the controls. The atrophy of the cerebellum and the brainstem in the MSA patients were scored by MRI. The cerebellar and brainstem glucose metabolism in the MSA patients decreased as the atrophy score in such regions advanced in each group; however, some patients with no atrophy showed a decreased glucose metabolism. Although the cerebellar and the brainstem glucose metabolism decreased in all MSA patients, such a decrease was not observed in the SND patients. The decrease in the glucose metabolism for the non-cortical regions in the MSA patients seems to be due to a diffuse depletion of the neurons not restricted to the nigrostriatal neurons. Deafferentation to the cerebral cortices seems to result in a decreased cortical metabolism. The differences in the glucose metabolism between MSA and PD as assessed by PET may be caused by the pathophysiological differences between MSA and PD, and such differences therefore appear to be useful when making a differential diagnosis between MSA and PD. The relative sparing of the brainstem and cerebellar glucose metabolism is considered to be a feature of patients with SND
AD  - Department of Radiology, Kyushu University, Beppu, Japan
UR  - PM:8994107
ER  - 

TY  - JOUR
T1  - Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis
A1  - Galardi,G.
A1  - Perani,D.
A1  - Grassi,F.
A1  - Bressi,S.
A1  - Amadio,S.
A1  - Antoni,M.
A1  - Comi,G.C.
A1  - Canal,N.
A1  - Fazio,F.
Y1  - 1996/09//
N1  - UI - 97054761
SP  - 172
EP  - 176
JA  - Acta Neurol Scand.
VL  - 94
IS  - 3
N2  - The basal ganglia are thought to be involved in the primary dystonias, largely because of the repeated demonstration of neuropathological changes in these nuclei in the secondary dystonias. A hyperactivity of a network involving basal ganglia has been suggested in experimental animal dystonia. To test this hypothesis in humans, we studied the functional correlates of primary cervical dystonia using [18F]FDG and PET. MATERIAL AND METHODS: Regional cerebral glucose metabolism (rCMRglc) was measured in 10 patients with idiopathic torticollis (6 drug-free and 4 drug-naive) and in 15 normal controls, using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). RESULTS: A significant hypermetabolism in the basal ganglia, thalamus, premotor-motor cortex and cerebellum in the patients compared with normal controls was found. The patients were correctly assigned to their clinical category by a discriminant function analysis with a total accuracy of 96%. CONCLUSION: The results support the hypothesis that a dysfunction of a subcortical-cortical motor network may play a role in the pathogenesis of focal dystonia, in agreement with the experimental dystonia models
AD  - Scientific Institute H San Raffaele, Milan, Italy
UR  - PM:8899050
ER  - 

TY  - JOUR
T1  - Postencephalitic stereotyped involuntary movements responsive to L-Dopa
A1  - Picard,F.
A1  - Saint-Martin,A.
A1  - Salmon,E.
A1  - Hirsch,E.
A1  - Marescaux,C.
Y1  - 1996/09//
N1  - UI - 97020045
SP  - 567
EP  - 570
JA  - Mov Disord.
VL  - 11
IS  - 5
N2  - In 1954, at the age of 5 years, our patient had an encephalitic syndrome associated with a prolonged lethargic state. After this episode, he developed a severe parkinsonian syndrome that, after a few years, was associated with axial dystonia and stereotyped abnormal movements of the upper limbs. This complex and progressive extrapyramidal syndrome had many similarities to the encephalitis lethargica as described by von Economo. Results of cerebral computed tomography and magnetic resonance imaging were normal. Fluorodopa positron emission tomography showed a significant bilateral reduction of tracer accumulation in both putamen, similar to that observed in patients with idiopathic Parkinson's disease. However, in this patient, treatment with L-Dopa suppressed all akinetic, dystonic and dyskinetic symptoms. The effectiveness of L-Dopa was abolished by administration of a D2 antagonist and was fully reproduced by a D2 agonist. In conclusion, this patient presented a complex postencephalitic, extrapyramidal syndrome, with akinetic symptoms and involuntary movements. These symptoms appeared to be related to a limited lesion of the dopaminergic neurons of the zona compacta of the substantia nigra
AD  - Service de Neurologie, Neuropsychologie et Explorations Fonctionnelles des Epilepsies, Hopitaux Universitaires de Strasbourg, France
UR  - PM:8866499
ER  - 

TY  - JOUR
T1  - The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease
A1  - Hume,S.P.
A1  - Lammertsma,A.A.
A1  - Myers,R.
A1  - Rajeswaran,S.
A1  - Bloomfield,P.M.
A1  - Ashworth,S.
A1  - Fricker,R.A.
A1  - Torres,E.M.
A1  - Watson,I.
A1  - Jones,T.
Y1  - 1996/08//
SP  - 103
EP  - 112
JA  - J Neurosci.Methods
VL  - 67
IS  - 2
N2  - The use of a recently commissioned small-diameter, high-resolution positron emission tomography (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using cerebellum as a reference tissue, compartmental modelling was used to obtain individual estimates of striatal binding potential (defined as the ratio of rate constants to and from the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH 23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of variation in control, anaesthetized rats were of the order of 10%. Using two models of human disease, namely striatal injection of ibotenic acid to produce postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease, marked reductions in binding potential were observed for the corresponding pre- or postsynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factor such as spill over and partial volume negate absolute quantification of tissue radioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques
AD  - Cyclotron Unit, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
UR  - PM:8872875
ER  - 

TY  - JOUR
T1  - Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington's disease
A1  - Weeks,R.A.
A1  - Piccini,P.
A1  - Harding,A.E.
A1  - Brooks,D.J.
Y1  - 1996/07//
N1  - UI - 96295937
SP  - 49
EP  - 54
JA  - Ann.Neurol
VL  - 40
IS  - 1
N2  - We have investigated striatal dopamine D1 and D2 receptor binding in asymptomatic subjects from Huntington's disease (HD) families using positron emission tomography. Nineteen adult subjects at risk of developing HD were scanned with 11C-SCH 23390 and 11C-raclopride to calculate the D1 and D2 receptor binding potential, respectively. Eight of the 19 were shown to have the HD mutation; of these, 4 subjects had significant reductions in striatal dopamine receptor binding. Abnormalities were more common in older subjects and were not correlated with the size of the HD mutation. There was a strong coefficient of correlation between individual levels of striatal D1 and D2 binding in subjects with the mutation. Of 6 other cases with a 50% risk of carrying the HD gene, 1 showed subclinical loss of caudate and putamen D2 binding. Our study suggests that both striatal D1 and D2 dopamine receptors are lost in parallel from both caudate and putamen in presymptomatic HD and that dopamine receptor binding provides a sensitive means of detecting subclinical striatal dysfunction
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:8687191
ER  - 

TY  - JOUR
T1  - Secondary parkinsonism due to focal substantia nigra lesions: a PET study with [18F]FDG and [18F]fluorodopa
A1  - Boecker,H.
A1  - Weindl,A.
A1  - Leenders,K.
A1  - Antonini,A.
A1  - Kuwert,T.
A1  - Kruggel,F.
A1  - Grafin von Einsiedel,H.
A1  - Conrad,B.
Y1  - 1996/06//
SP  - 387
EP  - 392
JA  - Acta Neurol Scand.
VL  - 93
IS  - 6
N2  - We present a 71 year old woman with predominantly right sided parkinsonism of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [18F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [18F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idiopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions
AD  - Department of Neurology, Technical University of Munich, Klinikum rechts der Isar, Germany
UR  - PM:8836298
ER  - 

TY  - JOUR
T1  - Neurological impairment and recovery in Wilson's disease: evidence from PET and MRI
A1  - Schlaug,G.
A1  - Hefter,H.
A1  - Engelbrecht,V.
A1  - Kuwert,T.
A1  - Arnold,S.
A1  - Stocklin,G.
A1  - Seitz,R.J.
Y1  - 1996/03//
SP  - 129
EP  - 139
JA  - J Neurol Sci.
VL  - 136
IS  - 1-2
N2  - We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilson's disease (WD). The rCMRGlc was determined in the basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly (r = -0.80) with the reduction of striatal rCMRGlc. Clinical scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients
AD  - Department of Neurology, Heinrich-Heine-University Dusseldorf, Germany
UR  - PM:8815159
ER  - 

TY  - JOUR
T1  - Early differential diagnosis of Parkinson's disease with 18F-fluorodeoxyglucose and positron emission tomography
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Ishikawa,T.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Chaly,T.
A1  - Belakhlef,A.
A1  - Mandel,F.
A1  - Przedborski,S.
A1  - Fahn,S.
Y1  - 1995/11//
SP  - 1995
EP  - 2004
JF  - Neurology
VL  - 45
IS  - 11
N2  - Early-stage Parkinson's disease (EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a characteristic pattern of regional metabolic asymmetry. To identify this pattern, we studied 10 EPD (Hoehn and Yahr stage I) patients (mean age 61.1 +/- 11.1 years) using 18F-FDG and PET to calculate regional metabolic rates for glucose. The scaled subprofile model (SSM) was applied to metabolic asymmetry measurements for the combined group of EPD patients and normal subjects to identify a specific covariation pattern that discriminated EPD patients from normal subjects. To determine whether this pattern could be used diagnostically, we studied a subsequent group of five presumptive EPD patients (mean age 50.9 +/- 18.3), five normal subjects (mean age 44.6 +/- 15.3), and nine patients with atypical drug-resistant early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0). In each member of this prospective cohort, we calculated the expression of the EPD-related covariation pattern (subject scores) on a case-by-case basis. We also studied 11 of the EPD patients, five patients with APD, and 10 normal subjects with 18F-fluorodopa (FDOPA) and PET to measure presynaptic nigrostriatal dopaminergic function, and we assessed the accuracy of differential diagnosis with both PET methods using discrimination analysis. SSM analysis disclosed a significant topographic contrast profile characterized by covariate basal ganglia and thalamic asymmetries. Subject scores for this profile accurately discriminated EPD patients from normal subjects and APD patients (p < 0.0001). Group assignments into the normal or parkinsonian categories with FDG/PET were comparable to those achieved with FDOPA/PET, although APD and EPD patients were not differentiable by the latter method. Metabolic brain imaging with FDG/PET may be useful in the differential diagnosis of EPD
AD  - Department of Neurology, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030, USA
UR  - PM:7501148
ER  - 

TY  - JOUR
T1  - Neurological Wilson's disease studied with magnetic resonance imaging and with positron emission tomography using dopaminergic markers
A1  - Westermark,K.
A1  - Tedroff,J.
A1  - Thuomas,K.A.
A1  - Hartvig,P.
A1  - Langstrom,B.
A1  - Andersson,Y.
A1  - Hornfeldt,K.
A1  - Aquilonius,S.M.
Y1  - 1995/09//
N1  - UI - 96064332
SP  - 596
EP  - 603
JA  - Mov Disord.
VL  - 10
IS  - 5
N2  - Four patients with neurological Wilson's disease were investigated using magnetic resonance imaging (MRI) and positron emission tomography (PET). All patients had dystonia as their major clinical manifestation but also had dysarthria and at the presentation of the disease had choreoathetoid movements in at least one limb. A multitracer approach with PET was used to visualize various aspects of dopaminergic function; [11C]-(+)-nomifensine (NMF), [11C]raclopride (RAC) and [11C]-L-DOPA (one patient). Correlation analysis of RAC and NMF binding as well as putamen/caudate uptake ratios showed corresponding reductions. The patient investigated with [11C]-L-DOPA had a normal striatal uptake. Generally, structural changes as shown by MRI corresponded to reductions both in NMF and RAC binding. There was no evident correspondence between PET findings and the severity of clinical symptoms seen in the individual patient. In two patients with discrete neurological impairment at the time of investigation, PET showed serious presynaptic dopaminergic lesions in the putamen. Our data suggest that the striatal degeneration seen in Wilson's disease comprises a complex pathology involving both afferent and efferent projections. The discrete neurological impairment seen in some patients with gross striatal pathology might be due to concomitant lesions in functionally counteracting basal ganglia circuits
AD  - Department of Internal Medicine, University Hospital Uppsala, Sweden
UR  - PM:8552111
ER  - 

TY  - JOUR
T1  - Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease
A1  - Freeman,T.B.
A1  - Olanow,C.W.
A1  - Hauser,R.A.
A1  - Nauert,G.M.
A1  - Smith,D.A.
A1  - Borlongan,C.V.
A1  - Sanberg,P.R.
A1  - Holt,D.A.
A1  - Kordower,J.H.
A1  - Vingerhoets,F.J.
Y1  - 1995/09//
N1  - UI - 95398408
SP  - 379
EP  - 388
JA  - Ann.Neurol
VL  - 38
IS  - 3
N2  - We performed fetal nigral transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the "off" state, Schwab-England disability score during the "off" state, percent "off" time, and percent "on" time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following fetal tissue transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD
AD  - Department of Surgery, University of South Florida, Tampa, USA
UR  - PM:7668823
ER  - 

TY  - JOUR
T1  - Positron emission tomography with 4-[18F]fluoro-L-m-tyrosine in MPTP-induced hemiparkinsonian monkeys
A1  - Hayase,N.
A1  - Tomiyoshi,K.
A1  - Watanabe,K.
A1  - Horikoshi,S.
A1  - Shibasaki,T.
A1  - Ohye,C.
Y1  - 1995/08//
N1  - UI - 96089314
SP  - 119
EP  - 123
JA  - Ann.Nucl Med
VL  - 9
IS  - 3
N2  - PET imaging studies with 4-[18F]fluoro-L-m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism
AD  - Department of Neurosurgery and Nuclear Medicine, Gunma University School of Medicine, Japan
UR  - PM:8534583
ER  - 

TY  - JOUR
T1  - Benzodiazepine receptor binding in cerebellar degenerations studied with positron emission tomography
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Lohman,M.
A1  - St Laurent,R.T.
Y1  - 1995/08//
N1  - UI - 95382635
SP  - 176
EP  - 185
JA  - Ann.Neurol
VL  - 38
IS  - 2
N2  - We used positron emission tomography with [11C]flumazenil to study gamma-aminobutyric acid type A/benzodiazepine receptor binding quantitatively in the cerebral hemispheres, basal ganglia, thalamus, cerebellum, and brainstem of 72 subjects, including 14 with multiple system atrophy of the ataxic (olivopontocerebellar atrophy) type, 5 with multiple system atrophy of the extrapyramidal/autonomic (Shy-Drager syndrome) type, 18 with sporadic olivopontocerebellar atrophy, 15 with dominantly inherited olivopontocerebellar atrophy, and 20 normal control subjects with similar age and sex distributions. In comparison with data obtained from the normal control subjects, we found significantly decreased ligand influx in the cerebellum and brainstem of multiple system atrophy patients of the olivopontocerebellar atrophy type and in patients with sporadic olivopontocerebellar atrophy, but not in patients with multiple system atrophy of the Shy-Drager syndrome type. Despite these differences in ligand influx, benzodiazepine binding was largely preserved in the cerebral hemispheres, basal ganglia, thalamus, cerebellum, and brainstem in patients with multiple system atrophy of both types as well as those with sporadic or dominantly inherited olivopontocerebellar atrophy as compared with normal control subjects. The finding of relative preservation of benzodiazepine receptors indicates that these sites are available for pharmacological therapy in these disorders
AD  - Department of Neurology, University of Michigan, Ann Arbor, USA
UR  - PM:7654065
ER  - 

TY  - JOUR
T1  - Hemiatrophy, juvenile-onset exertional alternating leg paresis, hypotonia, and hemidystonia and adult-onset hemiparkinsonism: the spectrum of hemiparkinsonism-hemiatrophy syndrome
A1  - Lang,A.E.
Y1  - 1995/07//
SP  - 489
EP  - 495
JA  - Mov Disord.
VL  - 10
IS  - 4
N2  - A 45-year-old woman with a history of probable perinatal craniocerebral trauma resulting in mild asymptomatic right hemiatrophy developed right leg weakness and hypotonia alternating with dystonia only after prolonged exertion at age 12. At age 27, she developed right-sided parkinsonism. Exertional paresis and dystonia and parkinsonism responded completely to levodopa; however, she developed a progressive reduction in the duration of action of levodopa over the first 4 years of treatment. Investigations including computed tomography, magnetic resonance imaging, [18F]fluorodopa, and [18F]fluorodeoxyglucose positron emission tomography scans suggested a static lesion involving the left substantia nigra. This unusual exertion-induced weakness and hypotonia alternating with hypertonia and dystonia has not been reported previously. The role of dopamine deficiency in dystonia and the role of levodopa in the development of fluctuations in Parkinson's disease are discussed. Review of the literature, including this patient, emphasizes the heterogeneity of the syndrome of hemiparkinsonism-hemiatrophy
AD  - Morton and Gloria Shulman Movement Disorders Centre, Toronto Hospital, Ontario, Canada
UR  - PM:7565831
ER  - 

TY  - JOUR
T1  - Pallidotomy increases activity of motor association cortex in Parkinson's disease: a positron emission tomographic study
A1  - Grafton,S.T.
A1  - Waters,C.
A1  - Sutton,J.
A1  - Lew,M.F.
A1  - Couldwell,W.
Y1  - 1995/06//
N1  - UI - 95297771
SP  - 776
EP  - 783
JA  - Ann.Neurol
VL  - 37
IS  - 6
N2  - Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas
AD  - Department of Neurology, University of Southern California, Los Angeles 90033-4606, USA
UR  - PM:7778851
ER  - 

TY  - JOUR
T1  - Hypersensitivity of cortical muscarinic receptors in Parkinson's disease demonstrated by PET
A1  - Asahina,M.
A1  - Shinotoh,H.
A1  - Hirayama,K.
A1  - Suhara,T.
A1  - Shishido,F.
A1  - Inoue,O.
A1  - Tateno,Y.
Y1  - 1995/06//
N1  - UI - 96012344
SP  - 437
EP  - 443
JA  - Acta Neurol Scand.
VL  - 91
IS  - 6
N2  - The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease (PD). We measured mAChR binding in the brain of eight patients with PD and eight, age-matched, healthy controls by positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB). PD patients were not demented according to DSM III criteria but showed significant frontal lobe dysfunction in the Modified Wisconsin Card Sorting Test. A mean K3 value, which is an index of mAChR binding calculated by a graphical method, was 20% higher in the frontal cortex of PD patients than controls (p < 0.05). Hypersensitivity of mAChRs in the frontal cortex of PD patients may be a response to a loss of ascending cholinergic input to that region, and may relate to frontal lobe dysfunction in PD
AD  - Department of Neurology, Chiba University, Japan
UR  - PM:7572037
ER  - 

TY  - JOUR
T1  - Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy
A1  - Rinne,J.O.
A1  - Burn,D.J.
A1  - Mathias,C.J.
A1  - Quinn,N.P.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1995/05//
SP  - 568
EP  - 573
JA  - Ann.Neurol
VL  - 37
IS  - 5
N2  - Ten patients with sporadic olivopontocerebellar atrophy and autonomic failure were studied with positron emission tomography. Subjects underwent both an [11C]diprenorphine and an [18F]fluorodopa scan. The mean caudate-occipital uptake ratio for [11C]diprenorphine was significantly reduced to 88% and the putamen-occipital uptake ratio to 85% of the control values. Individually, 4 of the 10 patients had significantly reduced opioid binding in the putamen. Mean putamen [18F]fluorodopa uptake was significantly diminished (to 71% of the control mean); individually 7 patients had significantly reduced uptake. There was a significant positive correlation between putamen-occipital uptake ratios for [11C]diprenorphine and putamen uptake of [18F]fluorodopa. Our results suggest that subclinical nigrostriatal dysfunction is present in the majority of patients with sporadic olivopontocerebellar atrophy, in accordance with it being part of the spectrum of multiple system atrophy
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:7755350
ER  - 

TY  - JOUR
T1  - n-Hexane-induced parkinsonism: pathogenetic hypotheses
A1  - Pezzoli,G.
A1  - Antonini,A.
A1  - Barbieri,S.
A1  - Canesi,M.
A1  - Perbellini,L.
A1  - Zecchinelli,A.
A1  - Mariani,C.B.
A1  - Bonetti,A.
A1  - Leenders,K.L.
Y1  - 1995/05//
N1  - UI - 95379873
SP  - 279
EP  - 282
JA  - Mov Disord.
VL  - 10
IS  - 3
N2  - n-Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by-products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n-hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease
AD  - Institute of Clinical Neurology, University of Milan, Italy
UR  - PM:7651443
ER  - 

TY  - JOUR
T1  - Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease
A1  - Kordower,J.H.
A1  - Freeman,T.B.
A1  - Snow,B.J.
A1  - Vingerhoets,F.J.
A1  - Mufson,E.J.
A1  - Sanberg,P.R.
A1  - Hauser,R.A.
A1  - Smith,D.A.
A1  - Nauert,G.M.
A1  - Perl,D.P.
Y1  - 1995/04/27/
N1  - UI - 95214677
SP  - 1118
EP  - 1124
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 332
IS  - 17
N2  - BACKGROUND. Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum. METHODS. We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 6 1/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods. RESULTS. After transplantation, the patient had sustained improvement in motor function and a progressive increase in fluorodopa uptake in the putamen on PET scanning. On examination of the brain, each of the large grafts appeared to be viable. Each was integrated into the host striatum and contained dense clusters of dopaminergic neurons. Processes from these neurons had grown out of the grafts and provided extensive dopaminergic reinnervation to the striatum in a patch-matrix pattern. Ungrafted regions of the putamen showed sparse dopaminergic innervation. We could not identify any sprouting of host dopaminergic processes. CONCLUSIONS. Grafts of fetal mesencephalic tissue can survive for a long period in the human brain and restore dopaminergic innervation to the striatum in patients with Parkinson's disease. In the patient we studied, clinical improvement and enhanced fluorodopa with uptake on PET scanning were associated the survival of the grafts and dopaminergic reinnervation of the striatum
AD  - Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA
UR  - PM:7700284
ER  - 

TY  - JOUR
T1  - Clinical/metabolic correlations in multiple system atrophy. A fludeoxyglucose F 18 positron emission tomographic study
A1  - Perani,D.
A1  - Bressi,S.
A1  - Testa,D.
A1  - Grassi,F.
A1  - Cortelli,P.
A1  - Gentrini,S.
A1  - Savoiardo,M.
A1  - Caraceni,T.
A1  - Fazio,F.
Y1  - 1995/02//
SP  - 179
EP  - 185
JA  - Arch Neurol
VL  - 52
IS  - 2
N2  - OBJECTIVE: To evaluate the regional cerebral metabolic involvement; the relationships among regional brain metabolism, clinical features, and quantitative measures of disease severity; and the patterns of brain involvement that can be related to the different types of onset: striatonigral degeneration vs olivopontocerebellar atrophy. DESIGN: Fludeoxyglucose F 18 positron emission tomography (PET) studies performed in patients with multiple system atrophy (MSA) were evaluated for their clinical features at the onset of the disease and at the time of the PET study. CASES: Seventeen patients diagnosed as having probable MSA and 10 age-matched controls. RESULTS: The hypometabolism in the putamen-pallidum complex and in the cerebellum was the best discriminant for disease classification. The efficacy of levodopa treatment was positively correlated with the metabolic activity of the putamen-pallidum complex. The patients with olivopontocerebellar atrophy type (N = 8) had a prevalent hypometabolism in the cerebellum, while the patients with striatonigral degeneration type (N = 9) had a prevalent impairment in the pallidum-putamen complex. We demonstrated a negative correlation between (1) severity of parkinsonism and metabolic values of putamen and caudate; (2) severity of cerebellar signs and metabolism in the cerebellum; and (3) autonomic dysfunction and metabolic activity in the thalamus, frontal, and temporal regions, bilaterally. CONCLUSIONS: These findings support the selective metabolic reduction in the putamen and cerebellum as a marker of MSA. The clinical/metabolic correlations, demonstrating the expected dependence of extrapyramidal and cerebellar signs by dysfunction of basal ganglia and cerebellum, also support a possible involvement of central nervous system structures in autonomic control
AD  - Institute of Neuroscience and Bioimaging, National Council of Research, Milan, Italy
UR  - PM:7848128
ER  - 

TY  - JOUR
T1  - Selective putaminal excitotoxic lesions in non-human primates model the movement disorder of Huntington disease
A1  - Burns,L.H.
A1  - Pakzaban,P.
A1  - Deacon,T.W.
A1  - Brownell,A.L.
A1  - Tatter,S.B.
A1  - Jenkins,B.G.
A1  - Isacson,O.
Y1  - 1995/02//
SP  - 1007
EP  - 1017
JF  - Neuroscience
VL  - 64
IS  - 4
N2  - While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease
AD  - Neuroregeneration Laboratory, McLean Hospital, Belmont, MA 02178, USA
UR  - PM:7753372
ER  - 

TY  - JOUR
T1  - Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions
A1  - Vingerhoets,F.J.
A1  - Snow,B.J.
A1  - Tetrud,J.W.
A1  - Langston,J.W.
A1  - Schulzer,M.
A1  - Calne,D.B.
Y1  - 1994/11//
SP  - 765
EP  - 770
JA  - Ann.Neurol
VL  - 36
IS  - 5
N2  - Transient exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome resembling idiopathic parkinsonism (IP). While IP inevitably progresses, the long-term evolution of MPTP-parkinsonism is unknown. Fluorodopa positron emission tomography (FD-PET) is a reliable tool for assessing nigrostriatal dopaminergic function. We performed FD-PET and clinical assessments on two occasions, 7 years apart, on 10 human subjects exposed to MPTP (age at the first scan, 32.7 +/- 6.9 yr [mean +/- SD], and on 10 normal individuals (age, 53 +/- 16 yr). At the time of their first scan, 5 of the subjects exposed to MPTP were clinically normal and 5 had limited signs of parkinsonism; 5 had new clinical deficits 7 years later. In the subjects exposed to MPTP, the PET index [(striatal-occipital)/occipital ratio] dropped by 2.3% per year from 0.70 +/- 0.10 (mean +/- SD) to 0.58 +/- 0.10 (p < 0.001). This was significantly faster than normal aging (p < 0.01) and similar to the progression observed in IP (p = 0.06). The findings suggest that short-term exposure to MPTP leads to a protracted decline in nigrostriatal dopaminergic function more rapid than occurs in normal aging and similar to IP progression. This is the first evidence that transient exposure to a toxin can cause progressive nigral pathology. At present, the mechanism leading to this progression is unknown. Our findings support the hypothesis that some neurodegenerative disorders may result from transient exposure to an environmental agent
AD  - Department of Medicine, Vancouver Hospital, British Columbia, Canada
UR  - PM:7979223
ER  - 

TY  - JOUR
T1  - Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism
A1  - Vingerhoets,F.J.
A1  - Snow,B.J.
A1  - Lee,C.S.
A1  - Schulzer,M.
A1  - Mak,E.
A1  - Calne,D.B.
Y1  - 1994/11//
N1  - UI - 95069944
SP  - 759
EP  - 764
JA  - Ann.Neurol
VL  - 36
IS  - 5
N2  - Previous estimates of the rate of progression of the nigral pathology underlying idiopathic parkinsonism (IP) have been derived mainly from pathological studies that have an inherent selection bias. Fluorodopa positron emission tomography (PET) is a reliable tool for assessing nigrostriatal dopaminergic function in vivo. We performed fluorodopa PET on two occasions, 7 years apart, on 16 patients with IP (age at the time of the first scan, 51 +/- 14 yr [mean +/- SD]) and 10 normal controls (age, 54 +/- 16 yr). For the patients with IP, the average duration of symptoms from the time of diagnosis to the first scan was 4.5 years (range, 1-12 yr); their PET index (striatal-occipital)/occipital ratio, dropped by 1.7% per year, from 0.49 +/- 0.08 to 0.43 +/- 0.08 (p < 0.001). The normals' ratio decreased by 0.3% per year from 0.77 +/- 0.05 to 0.75 +/- 0.10 (p = 0.33). The ratios in the IP group progressed significantly faster than the controls (p = 0.036). The rate of decline in IP represents 7.8% per decade, expressed as a fraction of the normals' initial mean value at 54 years of age. These results also permit power analysis for the design of future studies assessing the effect of treatment on the underlying pathology in IP
AD  - Neurodegenerative Disorders Centre, University Hospital, University of British Columbia, Vancouver, Canada
UR  - PM:7979222
ER  - 

TY  - JOUR
T1  - Dopamine D2 receptor binding and cerebral glucose metabolism recover after D-penicillamine-therapy in Wilson's disease
A1  - Schlaug,G.
A1  - Hefter,H.
A1  - Nebeling,B.
A1  - Engelbrecht,V.
A1  - Weiss,P.
A1  - Stocklin,G.
A1  - Seitz,R.J.
Y1  - 1994/10//
SP  - 577
EP  - 584
JA  - J Neurol
VL  - 241
IS  - 10
N2  - Regional cerebral glucose metabolism (rCMRGlc) and dopamine D2 receptor binding were measured in a 31-year-old, severely affected, untreated patient with Wilson's disease of 3 years' duration using positron emission tomography and 18F-deoxyglucose and 18F-methylspiperone ([18F]MSP), respectively. There was a severe reduction of striatal and extrastriatal rCMRGlc as well as of striatal [18F]MSP accumulation rate. After 1 year of treatment with D-penicillamine, striatal and extrastriatal rCMRGlc and striatal [18F]MSP accumulation rate reached almost normal levels. It is hypothesized that recovery of motor functions due to copper trapping therapy was associated with an increase in basal ganglia activity and a re-expression or upregulation of dopamine D2 receptors
AD  - Department of Neurology, Heinrich Heine University, Dusseldorf, Germany
UR  - PM:7836960
ER  - 

TY  - JOUR
T1  - The metabolic topography of parkinsonism
A1  - Eidelberg,D.
A1  - Moeller,J.R.
A1  - Dhawan,V.
A1  - Spetsieris,P.
A1  - Takikawa,S.
A1  - Ishikawa,T.
A1  - Chaly,T.
A1  - Robeson,W.
A1  - Margouleff,D.
A1  - Przedborski,S.
Y1  - 1994/09//
SP  - 783
EP  - 801
JA  - J Cereb.Blood Flow Metab
VL  - 14
IS  - 5
N2  - We used [18F]fluorodeoxyglucose/positron emission tomography (18F-FDG/PET) and a statistical model of regional covariation to study brain topographic organization in parkinsonism. We studied 22 patients with Parkinson's disease (PD), 20 age-matched normal volunteers, and 10 age- and severity-matched patients with presumed striatonigral degeneration (SND). We used FDG/PET to calculate global, regional, and normalized metabolic rates for glucose (GMR, rCMRglc, rCMRglc/GMR). Metabolic parameters in the three groups were compared using an analysis of variance, with a correction for multiple comparisons, and discriminant analysis. The scaled subprofile model (SSM) was applied to the combined rCMRglc dataset to identify topographic covariance profiles that distinguish PD patients from SND patients and normals. GMR, rCMRglc, and rCMRglc/GMR were normal in PD; caudate and lentiform rCMRglc/GMR was reduced in the SND group (p < 0.01). SSM analysis of the combined group of patients and normals revealed a significant topographic profile characterized by increased metabolic activity in the lentiform nucleus and thalamus associated with decreased activity in the lateral frontal, paracentral, inferior parietal, and parietooccipital areas. Individual subject scores for this profile were significantly elevated in PD patients compared with normals and SND patients (p < 0.001) and discriminated the three groups. In the PD group, subject scores for this factor correlated with individual subject Hoehn and Yahr (H & Y) scores (p < 0.02), and with quantitative rigidity (p < 0.01) and bradykinesia (p < 0.03) ratings, but not with tremor ratings. SSM analysis of right-left metabolic asymmetries yielded a topographic contrast profile that accurately discriminated mildly affected PD patients (H & Y Stage I) from normals. Our findings demonstrate that abnormal topographic covariance profiles exist in parkinsonism. These profiles have potential clinical application as neuroimaging markers in parkinsonism
AD  - Department of Neurology, North Shore University Hospital/Cornell University Medical College, Manhasset
UR  - PM:8063874
ER  - 

TY  - JOUR
T1  - Discordant twins with Parkinson's disease: positron emission tomography and early signs of impaired cognitive circuits
A1  - Holthoff,V.A.
A1  - Vieregge,P.
A1  - Kessler,J.
A1  - Pietrzyk,U.
A1  - Herholz,K.
A1  - Bonner,J.
A1  - Wagner,R.
A1  - Wienhard,K.
A1  - Pawlik,G.
A1  - Heiss,W.D.
Y1  - 1994/08//
N1  - UI - 94330687
SP  - 176
EP  - 182
JA  - Ann.Neurol
VL  - 36
IS  - 2
N2  - We evaluated 7 pairs of twins (2 monozygotic and 5 dizygotic) discordant for Parkinson's disease (PD), of whom the cotwins showed no signs of motor impairment on neurological examination. All subjects underwent positron emission tomographic measurements of cerebral glucose metabolism and dopaminergic, nigrostriatal function following injection of 2-[18F]fluoro-2-deoxy-D-glucose and L-6-[18F]fluorodopa ([18F]dopa), respectively, as well as testing for anterograde, verbal episodic, and semantic memory performance. Statistical analysis demonstrated significant reduction of striatal [18F]dopa uptake not only in the twin patients with PD but also in all of the cotwins, who showed significantly (p < 0.05) impaired [18F]dopa metabolism in at least one of the striatal measures including caudate, putaminal, and the rostrocaudal putaminal gradient of [18F]dopa uptake. Compared with age-matched controls, regional glucose metabolism was unchanged in all the twins. Neuropsychological testing showed significant (p < 0.05) impairment in verbal memory processing in the twin patients with PD and in 6 of the cotwins. Semantic memory skills were affected in 2 twin patients only. A significant correlation was found between scores obtained in Buschke's Selective Reminding Test and striatal [18F]dopa uptake, further substantiating the role of dopaminergic pathways in memory processing. The present study is the first to reveal not only significant disturbance of nigrostriatal dopaminergic function in verbal episodic memory that is known to be affected in PD. Larger studies with a longitudinal design will be necessary to answer the question of whether cognitive changes found in the cotwin group are signs of incipient PD
AD  - Max-Planck-Institut fur neurologische Forschung, Cologne, Germany
UR  - PM:8053653
ER  - 

TY  - JOUR
T1  - Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Lohman,M.
A1  - St Laurent,R.T.
Y1  - 1994/08//
SP  - 166
EP  - 175
JA  - Ann.Neurol
VL  - 36
IS  - 2
N2  - We used positron emission tomography with [18F]fluorodeoxyglucose to study local cerebral metabolic rates for glucose (ICMRglc) in patients with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA) in comparison with normal control subjects. IN MSA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In sOPCA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In dOPCA, absolute lCMRglc was significantly decreased in the brainstem and cerebellum but not in the other structures. Examination of lCMRglc normalized to the cerebral cortex in comparison with normal controls revealed in MSA significant decreases in the brainstem, cerebellum, and putamen but, in both sOPCA and dOPCA, significant decreases only in the brainstem and cerebellum. The findings indicate that these three disorders all show a marked decrease of lCMRglc in the brainstem and cerebellum but differ in the degree of hypometabolism in forebrain and cerebral cortical structures. The results are consistent with the possibility that, in many cases, sOPCA will evolve into MSA. Moreover, positron emission tomography may provide helpful diagnostic information in these neurodegenerative diseases
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0316
UR  - PM:8053652
ER  - 

TY  - JOUR
T1  - Olivopontocerebellar atrophy studied by positron emission tomography and magnetic resonance imaging
A1  - Yamaguchi,S.
A1  - Fukuyama,H.
A1  - Ogawa,M.
A1  - Yamauchi,H.
A1  - Harada,K.
A1  - Nakamura,S.
A1  - Kimura,J.
Y1  - 1994/08//
N1  - UI - 95054190
SP  - 56
EP  - 61
JA  - J Neurol Sci.
VL  - 125
IS  - 1
N2  - We examined 9 patients with olivopontocerebellar atrophy (OPCA) using positron emission tomography and magnetic resonance imaging (MRI). Regional cerebral blood flow and oxygen metabolism were compared with the findings in 10 normal age-matched volunteers. The volumes of the basis pontis and the cerebellar hemispheres were quantitated by MRI to assess the relationship between morphological changes of the pons or cerebellum and the cerebellar circulation and metabolism. In the patients with OPCA, cerebellar hemispheric blood flow and oxygen metabolism were significantly lower than in the normal volunteers. Pontine volume showed a significant correlation with the cerebellar blood flow and the metabolic rate of oxygen. In contrast, the cerebellar hemispheric volume showed no correlation with either of these parameters. Our results suggest that the disruption of pontocerebellar pathway may contribute to the reduction of both blood flow and oxygen metabolism in the cerebellum of OPCA and that detection of cerebellar circulatory impairment without marked cerebellar atrophy by neuroimaging may be suggestive of OPCA
AD  - Department of Neurology, Faculty of Medicine, Kyoto University, Japan
UR  - PM:7964889
ER  - 

TY  - JOUR
T1  - Parkinsonism caused by petroleum waste ingestion
A1  - Tetrud,J.W.
A1  - Langston,J.W.
A1  - Irwin,I.
A1  - Snow,B.
Y1  - 1994/06//
N1  - UI - 94268677
SP  - 1051
EP  - 1054
JF  - Neurology
VL  - 44
IS  - 6
N2  - A 20-year-old laborer developed moderate parkinsonism 1 week after accidentally ingesting a petroleum waste mixture. Parkinsonism persisted for 3 months and then began to improve, although subtle signs remained 29 months after exposure. 6-Fluorodopa-labeled positron emission tomography (6-FD PET) performed 3 months postexposure revealed a striatal dopamine rate constant level of 0.170 ml/striatum/min, nearly 3 SD below the mean for age-matched controls. However, subsequent PETs demonstrated 6-FD PET rate constants not significantly different than controls. Although the causative agent has not yet been identified, this case suggests that compounds capable of causing parkinsonism may exist in commonly used petroleum products
AD  - Parkinson's Institute, Sunnyvale, CA 94089-1605
UR  - PM:8208398
ER  - 

TY  - JOUR
T1  - Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT
A1  - Wullner,U.
A1  - Pakzaban,P.
A1  - Brownell,A.L.
A1  - Hantraye,P.
A1  - Burns,L.
A1  - Shoup,T.
A1  - Elmaleh,D.
A1  - Petto,A.J.
A1  - Spealman,R.D.
A1  - Brownell,G.L.
Y1  - 1994/04//
SP  - 305
EP  - 309
JA  - Exp.Neurol
VL  - 126
IS  - 2
N2  - We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease
AD  - Neuroregeneration Laboratories, McLean Hospital, Belmont, Massachusetts
UR  - PM:7925829
ER  - 

TY  - JOUR
T1  - Separating Parkinson's disease from normality. Discriminant function analysis of fluorodopa F 18 positron emission tomography data
A1  - Sawle,G.V.
A1  - Playford,E.D.
A1  - Burn,D.J.
A1  - Cunningham,V.J.
A1  - Brooks,D.J.
Y1  - 1994/03//
N1  - UI - 94175797
SP  - 237
EP  - 243
JA  - Arch Neurol
VL  - 51
IS  - 3
N2  - OBJECTIVE: To explore the relationship between normal and parkinsonian fluorodopa F 18 (18F-6-L-fluorodopa [18F-dopa]) uptake data to identify clinically normal subjects who may have preclinical Parkinson's disease. DESIGN: A statistical comparison of striatal fluorodopa F 18 positron emission tomography scan data from patients with Parkinson's disease and normal controls. SETTING: Positron emission tomography unit within a postgraduate teaching hospital. MAIN OUTCOME MEASURES: Discriminant function analysis used to compare the pattern of striatal (left and right caudate and putamen) fluorodopa F 18 uptake in normal subjects and patients with Parkinson's disease. RESULTS: The discriminant score that best separates patients with Parkinson's disease from normal controls is a function of the lowest putamen influx constant minus a function of the caudate influx constant values. Borderline low normal subjects have slightly low fluorodopa F 18 uptake throughout the striatum, whereas patients with early Parkinson's disease have low fluorodopa F 18 uptake in one putamen with preserved uptake in the caudate (for normal subjects, subtracting the caudate influx constants from a function of the lowest putamen value lowers the discriminant score, although it remains positive; for patients, subtracting a larger caudate value from a function of the putamen uptake value leads to a negative score). One control subject had a borderline low discriminant score, compatible with focal nigral pathological changes as expected in preclinical Parkinson's disease. A repeated scan taken 3 years later showed a marked reduction in fluorodopa F 18 uptake, suggesting progressive nigral dysfunction. CONCLUSION: Normal and parkinsonian fluorodopa F 18 uptake data differ both in the overall level of tracer uptake and in its spatial distribution. Subjects whose overall striatal fluorodopa F 18 uptake falls at the borderline of normal and parkinsonian values are likely to be normal if they have uniformly low uptake, but may have early or preclinical Parkinson's disease if uptake into putamen is very much lower than uptake into caudate
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:8129633
ER  - 

TY  - JOUR
T1  - Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography
A1  - Shinotoh,H.
A1  - Asahina,M.
A1  - Inoue,O.
A1  - Suhara,T.
A1  - Hirayama,K.
A1  - Tateno,Y.
Y1  - 1994///
N1  - UI - 96129622
SP  - 35
EP  - 46
JA  - J Neural Transm.Park Dis.Dement.Sect.
VL  - 7
IS  - 1
N2  - The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([11C]NMPB). [11C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n = 5) or 400 mg of L-dopa with 57 mg of benserazide (n = 2) on the binding parameter of mAChRs (K3). There was a mean 28% inhibition of K3 values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K3 was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET
AD  - Department of Neurology, School of Medicine, Chiba University, Japan
UR  - PM:8579768
ER  - 

TY  - JOUR
T1  - Dopamine D1 receptor number--a sensitive PET marker for early brain degeneration in Huntington's disease
A1  - Sedvall,G.
A1  - Karlsson,P.
A1  - Lundin,A.
A1  - Anvret,M.
A1  - Suhara,T.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 1994///
N1  - UI - 94227103
SP  - 249
EP  - 255
JA  - Eur.Arch Psychiatry Clin.Neurosci.
VL  - 243
IS  - 5
N2  - D1-dopamine receptor binding in the brain was determined by positron emission tomography (PET) in five patients with Huntington's disease, in one asymptomatic gene carrier and in five control subjects. [11C] SCH 23390 was used as the radioligand. Brain morphology was recorded by MRI. The patients who all had a mild to moderate functional impairment showed an almost 50% reduction of putamen volume as well as D1-dopamine receptor density as compared to the controls. The total D1-dopamine receptor number in the putamen was reduced by 75% in the patient group. A similar reduction was found for the caudate nucleus. The asymptomatic gene carrier had volume and density values in the lower range of the control subjects. In the frontal neocortex there also tended to be a reduced D1-dopamine receptor binding in the symptomatic patients. The results indicate that [11C] SCH 23390 binding in combination with MRI can be used as a sensitive marker for early brain degeneration in Huntington's disease. This marker may be useful to monitor the pathophysiological effect of the disease gene and also to follow therapeutic interventions aiming at preventing the degenerative process
AD  - Department of Clinical Neuroscience, Karolinska Hospital and Institute, Stockholm, Sweden
UR  - PM:8172940
ER  - 

TY  - JOUR
T1  - PET- and MRI-based assessment of glucose utilization, dopamine receptor binding, and hemodynamic changes after lesions to the caudate-putamen in primates
A1  - Brownell,A.L.
A1  - Hantraye,P.
A1  - Wullner,U.
A1  - Hamberg,L.
A1  - Shoup,T.
A1  - Elmaleh,D.R.
A1  - Frim,D.M.
A1  - Madras,B.K.
A1  - Brownell,G.L.
A1  - Rosen,B.R.
Y1  - 1994/01//
SP  - 41
EP  - 51
JA  - Exp.Neurol
VL  - 125
IS  - 1
N2  - In vivo physiological changes associated with striatal pathology were determined by measurement of glucose utilization, binding to D1 receptors and dopamine reuptake sites, regional blood flow, and behavior before and after unilateral quinolinate infusions into caudate-putamen in three nonhuman primates (Macaca fascicularis and Macaca mulatta). Following the quinolinate lesion, symptoms similar to those of Huntington's disease could be induced by dopamine agonist treatment. In addition, all animals showed a long-term decrease in glucose utilization in the caudate by [19F]fluoro-2-deoxy-D-glucose positron emission tomography (PET). At 4-6 weeks following the lesion the average decrease in glucose utilization in the caudate-putamen was between 40 and 50% of the prelesion values in primates with large lesions. Corresponding caudate-putamen regional blood volume in these animals showed a 61 and 74% decrease as studied by magnetic resonance imaging with somewhat smaller changes observed in an index of cerebral blood flow. The caudate-putamen uptake rate constants for D1 receptors reflected neuronal loss and decreased by an average 40 and 48%, as determined by 11C-labeled Schering compound (SCH 39 166) and PET. Dopamine reuptake sites and fibers assessed by the 11C-labeled cocaine analog, WIN 35 428 compound, and PET showed a temporary decrease in areas with mild neuronal loss and a long-term decrease in striatal regions with severe destruction. These results, which were consistent with behavioral changes and neuropathology seen at postmortem examination, can be related to in vivo physiological studies of Huntington's disease patients
AD  - Department of Radiology, Massachusetts General Hospital, Boston 02114
UR  - PM:7905836
ER  - 

TY  - JOUR
T1  - Metabolic and cognitive changes in hereditary ataxia
A1  - Matthew,E.
A1  - Nordahl,T.
A1  - Schut,L.
A1  - King,A.C.
A1  - Cohen,R.
Y1  - 1993/11//
N1  - UI - 94103828
SP  - 134
EP  - 140
JA  - J Neurol Sci.
VL  - 119
IS  - 2
N2  - Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were studied with [18F]-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance imaging (MRI), cognitive testing and scored neurological examination, and compared with normal controls. The neurological examination, MRI and cognitive tests showed no significant differences between at risk and normal control subjects. Mild cognitive deficits were seen in affected subjects; the degree of cognitive change appeared to relate to the severity of the illness. MRI demonstrated cerebellar and brainstem atrophy in all affected subjects. PET studies showed higher global metabolic rates (mean [SD]) in at risk subjects (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g). Normalized (region/global average) regional metabolic rates were reduced in cerebellar hemispheres and vermis, and in frontal and prefrontal areas of affected subjects in comparison to at risk and normal control subjects. These findings indicate that functional changes in some forms of autosomal dominant hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to involve other parts of the neuraxis
AD  - Clinical Brain Imaging Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
UR  - PM:8277326
ER  - 

TY  - JOUR
T1  - Positron emission tomographic studies of dopa-responsive dystonia and early-onset idiopathic parkinsonism
A1  - Snow,B.J.
A1  - Nygaard,T.G.
A1  - Takahashi,H.
A1  - Calne,D.B.
Y1  - 1993/11//
N1  - UI - 94058146
SP  - 733
EP  - 738
JA  - Ann.Neurol
VL  - 34
IS  - 5
N2  - There are two major syndromes presenting in the early decades of life with dystonia and parkinsonism: dopa-responsive dystonia (DRD) and early-onset idiopathic parkinsonism (EOIP). DRD presents predominantly in childhood with prominent dystonia and lesser degrees of parkinsonism. EOIP presents before age 40 with parkinsonism (often with associated dystonia). Both disorders are exquisitely sensitive to levodopa, although the long-term prognosis in each appears to be different. Some have suggested, however, that DRD is a form of EOIP. We performed positron emission tomography with 6-fluoro-dopa in 10 patients with DRD and 18 patients with EOIP to study the integrity of their nigrostriatal dopaminergic systems. In DRD, we found normal striatal FD uptake. In contrast, patients with EOIP had reduced striatal FD uptake. We conclude that the patho-physiologies of DRD and EOIP are distinct. Although both disorders presumably represent a deficiency of striatal dopamine, the results suggest that in DRD dopa uptake, decarboxylation, and storage mechanisms are intact. This may explain the sustained response of DRD to low doses of levodopa. 6-Fluoro-dopa positron emission tomography distinguishes DRD from EOIP
AD  - Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada
UR  - PM:8239569
ER  - 

TY  - JOUR
T1  - Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer's disease
A1  - Schapiro,M.B.
A1  - Pietrini,P.
A1  - Grady,C.L.
A1  - Ball,M.J.
A1  - DeCarli,C.
A1  - Kumar,A.
A1  - Kaye,J.A.
A1  - Haxby,J.V.
Y1  - 1993/08//
N1  - UI - 93353195
SP  - 859
EP  - 864
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 56
IS  - 8
N2  - Reduction in the regional cerebral metabolic rate for glucose (rCMRglc) in the parietal and temporal regions has been shown in Alzheimer's disease (AD). The specificity of these findings for this disease state is uncertain. We repeatedly measured rCMRglc with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in the resting state in a 68 year old man with slowly progressive dementia who, during life, was initially diagnosed as having dementia of the Alzheimer type, then Parkinson disease with dementia, but was found to have only Parkinson's disease at necropsy. Metabolic ratios (rCMRglc/mean grey CMRglc) were significantly (p < 0.05) reduced in parietal and temporal regions, as well as in the prefrontal and premotor areas. This pattern was similar in regional distribution and magnitude of the defect to that seen in patients with probable AD. These results suggest that reductions of glucose metabolism in association neocortex in AD are not specific to the disease process, but may be related to the dementia state
AD  - Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892
UR  - PM:8350100
ER  - 

TY  - JOUR
T1  - Positron emission tomography measures of benzodiazepine receptors in Huntington's disease
A1  - Holthoff,V.A.
A1  - Koeppe,R.A.
A1  - Frey,K.A.
A1  - Penney,J.B.
A1  - Markel,D.S.
A1  - Kuhl,D.E.
A1  - Young,A.B.
Y1  - 1993/07//
N1  - UI - 93297907
SP  - 76
EP  - 81
JA  - Ann.Neurol
VL  - 34
IS  - 1
N2  - We performed positron emission tomographic (PET) measurements of the regional distribution volume of benzodiazepine receptors and regional glucose metabolism in 6 drug-free patients with early Huntington's disease following injection of [11C]flumazenil, a nonsubtype selective central benzodiazepine receptor antagonist, and 18F-2-fluoro-2-deoxy-D-glucose, respectively. Flumazenil data were analyzed with a recently developed two-compartment, two-parameter tracer kinetic model. Benzodiazepine receptor density is related to distribution volume for flumazenil. In comparison with a group of healthy volunteers, benzodiazepine receptor density was significantly decreased in the caudate nucleus. Glucose metabolism was significantly reduced not only in the caudate nucleus but also in the putamen and thalamus. The changes in benzodiazepine receptor density observed in the caudate nucleus are commensurate with data obtained in postmortem autoradiographic studies of receptor density. Based on such postmortem studies we also anticipated changes in putamen and thalamic benzodiazepine receptor density. However, relatively little is known on receptor changes in early Huntington's disease, because the autoradiographic data available were obtained mostly in patients with advanced disease. The decreased glucose metabolism in the caudate and putamen agrees well with previously published results of PET studies, whereas metabolic impairment of the thalamus has not yet been described in Huntington's disease. The present study suggests that regional metabolism and gamma-aminobutyric acid (GABA)-benzodiazepine receptor changes in subcortical structures of patients with early Huntington's disease do not occur with the same time course: Caudate benzodiazepine receptor density is already severely impaired when other subcortical structures reveal only minor abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Internal Medicine, University of Michigan Medical School, Ann Arbor
UR  - PM:8390806
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism and dopamine D2 receptor analysis in a patient with hemiparkinsonism-hemiatrophy syndrome
A1  - Przedborski,S.
A1  - Goldman,S.
A1  - Levivier,M.
A1  - Giladi,N.
A1  - Bidaut,L.M.
A1  - Hildebrand,J.
A1  - Stanus,E.
A1  - Labar,D.
A1  - Luxen,A.
Y1  - 1993/07//
SP  - 391
EP  - 395
JA  - Mov Disord.
VL  - 8
IS  - 3
N2  - We report findings on brain glucose metabolism and dopamine D2 receptors generated by positron emission tomography (PET) in a 67-year-old woman with right hemiparkinsonism-hemiatrophy syndrome (HP-HA). PET with [18F]-fluorodeoxyglucose (FDG) showed marked glucose metabolism asymmetry. There were significant reductions in glucose uptake at the level of the basal ganglia and, to lesser extent, in the fronto-parietal cortex contralateral to the clinically involved side. These changes were different from those found in a patient with hemi-Parkinson's disease who was scanned under similar conditions. Because the patient with HP-HA had only minimal response to levodopa therapy, we evaluated post-synaptic dopaminergic structures using PET with [18F]-fluoroethylspiperone (FESP). No striatal binding asymmetry was found in FESP/PET, which suggests a sparing of striatal dopamine D2 receptors. The changes in FDG uptake which we found were in brain areas relevant to the clinical features of HP-HA syndrome. In addition, our study provides evidence that FDG/PET may help to differentiate HP-HA syndrome from hemi-Parkinson's disease. In most instances, since HP-HA is associated with a more benign clinical course than Parkinson's disease, this distinction is of clinical important
AD  - Department of Neurology, Universite Libre de Bruxelles-Hopital Erasme, Brussels, Belgium
UR  - PM:8341311
ER  - 

TY  - JOUR
T1  - Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]Fdopa) in humans
A1  - Cumming,P.
A1  - Leger,G.C.
A1  - Kuwabara,H.
A1  - Gjedde,A.
Y1  - 1993/07//
N1  - UI - 93301018
SP  - 668
EP  - 675
JA  - J Cereb.Blood Flow Metab
VL  - 13
IS  - 4
N2  - Like native DOPA, [18F]-6-fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) is subject to methylation and decarboxylation. To determine the rates of formation and elimination of [18F]FDOPA metabolites, plasma from human subjects undergoing positron emission tomographic (PET) studies was analyzed by high-performance liquid chromatography (HPLC). In addition to the principal metabolite O-methyl-[18F]FDOPA (OMe[18F]FDOPA), two decarboxylated metabolites were detected in plasma from carbidopa pretreated subjects. The concentrations of each metabolite during 90 min following tracer injection could be described as a function of the concentration of [18F]FDOPA, and two rate constants; k0, the rate of formation, and k-1, the rate of clearance. Plasma metabolite time series generated from total plasma activity curves and measured rate constants were in close agreement with the actual concentrations determined by HPLC fractionation. Population means for k0 (0.011 +/- 0.002 min-1) and k-1 (0.010 +/- 0.003 min-1) were used to generate "simulated" plasma curves. The measured and generated plasma curves were used as inputs for estimation of partition and decarboxylation coefficients of [18F]FDOPA in brain. The use of generated input functions from normal population means of transfer coefficients did not introduce a systematic error into the estimate of the enzyme activity. However, the high variability of these estimates in patients precludes the use of this technique as an alterative to individual HPLC measurements
AD  - Positron Imaging Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute, Canada
UR  - PM:8314919
ER  - 

TY  - JOUR
T1  - Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study
A1  - Shinotoh,H.
A1  - Inoue,O.
A1  - Hirayama,K.
A1  - Aotsuka,A.
A1  - Asahina,M.
A1  - Suhara,T.
A1  - Yamazaki,T.
A1  - Tateno,Y.
Y1  - 1993/05//
N1  - UI - 93280588
SP  - 467
EP  - 472
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 56
IS  - 5
N2  - Striatal dopamine D1 receptors were investigated in 11 patients with Parkinson's disease (PD), five patients with striatonigral degeneration (SND) and six age-matched controls by positron emission tomography and carbon-11 labelled SCH23390. The SND patients showed mean 12%, 21%, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen, and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients. The results may explain the different therapeutic responses to levadopa between SND and PD patients, and this technique might prove useful for their differentiation
AD  - Department of Neurology, School of Medicine, Chiba University, Japan
UR  - PM:8505636
ER  - 

TY  - JOUR
T1  - Comparison of somatosensory evoked potentials with striatal glucose consumption measured by positron emission tomography in the early diagnosis of Huntington's disease
A1  - Kuwert,T.
A1  - Noth,J.
A1  - Scholz,D.
A1  - Schwarz,M.
A1  - Lange,H.W.
A1  - Topper,R.
A1  - Herzog,H.
A1  - Aulich,A.
A1  - Feinendegen,L.E.
Y1  - 1993///
N1  - UI - 93125610
SP  - 98
EP  - 106
JA  - Mov Disord.
VL  - 8
IS  - 1
N2  - Both somatosensory evoked potentials (SEP) and striatal glucose consumption (rCMRGlc) measured by positron emission tomography (PET) have been reported to be abnormal early in the course of Huntington's disease (HD). To compare their diagnostic value, SEP and rCMRGlc were measured in a group of 18 first degree off-spring of HD families: 6 had manifest HD with chorea and the remaining 12 individuals were chorea-free subjects at risk for HD. In five patients with manifest disease, both SEP and striatal rCMRGlc were significantly abnormal, defined in SEP as having either a bilaterally absent frontal N30 amplitude or a reduction of the parietal N20/P25 amplitude below 1 microV on at least one side; in PET as exhibiting a reduction of the cerebellar ratio (CR) of both caudate and lentiform rCMRGlc below the 99% confidence limits of these variables determined in 20 normal volunteers. The remaining patient with manifest HD had questionably abnormal SEP and significantly reduced indices of striatal rCMRGlc. The five persons at risk for HD who had normal SEP also had normal striatal rCMRGlc; those three at-risk patients with abnormal SEP also had a reduction of the CR of both caudate and lentiform rCMRGlc. Of the remaining four individuals at risk for HD who had questionably abnormal SEP, three had CR values of striatal rCMRGlc in the normal range and one a reduction of the CR of lentiform rCMRGlc. In at-risk patients, the SEP diagnosis correlated significantly with caudate (r = -0.8; p < 0.002) and lentiform (r = -0.76; p < 0.005) rCMRGlc. These data indicate a parallel deterioration of SEP and striatal rCMRGlc early in the course of HD even before the development of chorea
AD  - Institute of Medicine, Research Center Julich, Germany
UR  - PM:8419813
ER  - 

TY  - JOUR
T1  - Striatal [11C]-N-methyl-spiperone binding in patients with focal dystonia (torticollis) using positron emission tomography
A1  - Leenders,K.
A1  - Hartvig,P.
A1  - Forsgren,L.
A1  - Holmgren,G.
A1  - Almay,B.
A1  - Eckernas,S.A.
A1  - Lundqvist,H.
A1  - Langstrom,B.
Y1  - 1993///
N1  - UI - 93326266
SP  - 79
EP  - 87
JA  - J Neural Transm.Park Dis.Dement.Sect.
VL  - 5
IS  - 2
N2  - Specific binding of [11C]-N-methyl-spiperone to striatal dopamine D2 receptors was assessed using positron emission tomography (PET) in 6 patients with adult-onset focal dystonia (predominantly spasmodic torticollis) and in 5 healthy subjects. No significant difference in average specific striatal tracer uptake between patients and healthy subjects was found. However, in the 5 patients showing lateralisation of clinical signs a trend to higher striatal tracer uptake in the contralateral hemisphere was observed
AD  - Paul Scherrer Institute, Villigen, Switzerland
UR  - PM:8101445
ER  - 

TY  - JOUR
T1  - Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine
A1  - Jenkins,I.H.
A1  - Fernandez,W.
A1  - Playford,E.D.
A1  - Lees,A.J.
A1  - Frackowiak,R.S.
A1  - Passingham,R.E.
A1  - Brooks,D.J.
Y1  - 1992/12//
N1  - UI - 93111699
SP  - 749
EP  - 757
JA  - Ann.Neurol
VL  - 32
IS  - 6
N2  - Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:1471865
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in Parkinson's disease with and without dementia
A1  - Peppard,R.F.
A1  - Martin,W.R.
A1  - Carr,G.D.
A1  - Grochowski,E.
A1  - Schulzer,M.
A1  - Guttman,M.
A1  - McGeer,P.L.
A1  - Phillips,A.G.
A1  - Tsui,J.K.
A1  - Calne,D.B.
Y1  - 1992/12//
N1  - UI - 93080474
SP  - 1262
EP  - 1268
JA  - Arch Neurol
VL  - 49
IS  - 12
N2  - Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions
AD  - Department of Medicine, University of British Columbia, Vancouver, Canada
UR  - PM:1449406
ER  - 

TY  - JOUR
T1  - Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
A1  - Widner,H.
A1  - Tetrud,J.
A1  - Rehncrona,S.
A1  - Snow,B.
A1  - Brundin,P.
A1  - Gustavii,B.
A1  - Bjorklund,A.
A1  - Lindvall,O.
A1  - Langston,J.W.
Y1  - 1992/11/26/
SP  - 1556
EP  - 1563
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 327
IS  - 22
N2  - BACKGROUND. Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism. METHODS. We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation. RESULTS. Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications. CONCLUSIONS. Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease
AD  - Department of Neurology, University Hospital, Lund, Sweden
UR  - PM:1435882
ER  - 

TY  - JOUR
T1  - Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia
A1  - Nygaard,T.G.
A1  - Takahashi,H.
A1  - Heiman,G.A.
A1  - Snow,B.J.
A1  - Fahn,S.
A1  - Calne,D.B.
Y1  - 1992/11//
N1  - UI - 93080289
SP  - 603
EP  - 608
JA  - Ann.Neurol
VL  - 32
IS  - 5
N2  - Dopa-responsive dystonia (DRD) is one form of childhood-onset idiopathic torsion dystonia. Adult-onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women and 1 man, unaffected by dystonia, developed tremor-onset parkinsonism after age 50 years. The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response. This contrasts to the typical long-term treatment complications observed in patients with Parkinson's disease. We assessed nigrostriatal dopaminergic function in the proband, with typical DRD, and the 2 women with parkinsonism using 6-[18F]fluoro-L-dopa positron emission tomography. All 3 had normal striatal 6-[18F]fluoro-L-dopa uptake. These observations provide compelling evidence that "benign" adult-onset parkinsonism may be an expression of the disease in some members of families with DRD and does not support consideration of the DRD gene as a risk factor for development of Parkinson's disease. There may be considerable clinical heterogeneity in DRD depending on the age at onset
AD  - Department of Neurology, Columbia-Presbyterian Medical Center, New York, NY 10032
UR  - PM:1449240
ER  - 

TY  - JOUR
T1  - Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease
A1  - Grafton,S.T.
A1  - Mazziotta,J.C.
A1  - Pahl,J.J.
A1  - George-Hyslop,P.
A1  - Haines,J.L.
A1  - Gusella,J.
A1  - Hoffman,J.M.
A1  - Baxter,L.R.
A1  - Phelps,M.E.
Y1  - 1992/11//
N1  - UI - 93074519
SP  - 1161
EP  - 1167
JA  - Arch Neurol
VL  - 49
IS  - 11
N2  - OBJECTIVE--To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN--Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING--Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS--Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS--None. OUTCOME MEASURES--Onset of chorea and imaging results. RESULTS--The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS--The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism
AD  - Department of Neurology, University of Southern California, School of Medicine, Los Angeles 90033-4606
UR  - PM:1444883
ER  - 

TY  - JOUR
T1  - Thalamocortical diaschisis: positron emission tomography in humans
A1  - Baron,J.C.
A1  - Levasseur,M.
A1  - Mazoyer,B.
A1  - Legault-Demare,F.
A1  - Mauguiere,F.
A1  - Pappata,S.
A1  - Jedynak,P.
A1  - Derome,P.
A1  - Cambier,J.
A1  - Tran-Dinh,S.
Y1  - 1992/10//
N1  - UI - 93057597
SP  - 935
EP  - 942
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 55
IS  - 10
N2  - To investigate further the relations between cortical energy metabolism and neuropsychological impairment after unilateral thalamic lesion, 55 patients underwent positron emission tomography studies of either cortical oxygen consumption or glucose utilisation, including eight repeat studies, at times ranging from 4 days to 98 months after the onset of the lesion [stroke (n = 44) or stereotaxic VL-Vim thalamotomy performed for movement disorders (n = 11)]. Patients with thalamotomy were also studied preoperatively and the surgery induced a significant fall in cortical metabolism on both sides (more so ipsilaterally); post-operatively the magnitude of the ipsilateral cortex hypometabolism was positively correlated to the severity of global neuropsychological impairment; similar but less significant findings were obtained for the ipsilateral/contralateral cortical metabolic asymmetry. With respect to the whole patient sample, the cortical metabolic asymmetry was initially pronounced, with subsequent monoexponential recovery, in the cognitively impaired study group, but it was only mild and showed no meaningful trend for recovery in the cognitively unaffected study group; yet even soon (< 3 months) after thalamic lesion there was a noticeable overlap of individual asymmetry values among the two study groups. These results lend further support to the view that the neuropsychological impairment that frequently follows unilateral thalamic lesions is reflected in a depression of synaptic activity in both the overlying and the contralateral cerebral cortices. For individual patients, this study also illustrates the potentially misleading nature of the measured cortical metabolic asymmetry with respect to neuropsychological status, especially at late times after lesion, in part because side to side metabolic ratios do not reflect bilateral changes
AD  - INSERM U 320, Caen, France
UR  - PM:1431957
ER  - 

TY  - JOUR
T1  - Increased striatal 18F-dopa uptake and normal glucose metabolism in idiopathic dystonia syndrome
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Shima,F.
A1  - Kuwabara,Y.
A1  - Sasaki,M.
A1  - Fukumura,T.
A1  - Kato,M.
A1  - Masuda,K.
A1  - Goto,I.
Y1  - 1992/09//
N1  - UI - 93057628
SP  - 195
EP  - 199
JA  - J Neurol Sci.
VL  - 111
IS  - 2
N2  - Striatal 18F-Dopa uptake and glucose metabolism were studied by positron emission tomography with 6-L-[18F]fluorodopa and [18F]fluorodeoxyglucose, respectively, in 8 patients with idiopathic dystonia. Patients with abnormal findings on the brain CT and MRI were excluded from this study. The clinical diagnosis consisted of torsion dystonia in 3 patients, focal dystonia limited in the arm in 3 and cervical dystonia (spasmodic torticollis) in 2. The 18F-Dopa uptake, corrected by nonspecific retention in the cerebellum, at 120 min post-administration was evaluated, and increased 18F-Dopa uptake in the putamen and in the caudate head was observed in the patients with idiopathic dystonia compared to the normal controls. The striatal glucose metabolism in the patients with idiopathic dystonia showed no difference with the normal controls. These findings suggest that pathogenetic mechanism of idiopathic dystonia involves increased presynaptic activity of the dopaminergic system in the striatum
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:1431986
ER  - 

TY  - JOUR
T1  - Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities
A1  - Foster,N.L.
A1  - Gilman,S.
A1  - Berent,S.
A1  - Sima,A.A.
A1  - D'Amato,C.
A1  - Koeppe,R.A.
A1  - Hicks,S.P.
Y1  - 1992/08//
SP  - 707
EP  - 713
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 55
IS  - 8
N2  - In studies of cerebral glucose metabolism utilising positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose, patients with the clinical picture of progressive supranuclear palsy (PSP) have shown predominantly frontal glucose hypometabolism. This is presumed to represent deafferentation of cerebral cortical from subcortical structures. In these studies, however, the diagnosis of PSP has not been verified by pathological examination. Necropsy examinations were performed in three patients with the clinical features of PSP in whom PET had demonstrated predominantly frontal hypometabolism. In two of these patients the diagnosis of PSP was confirmed pathologically, and no morphological abnormalities were found in the cerebral cortex. The third patient had extensive cortical and subcortical neuronal loss and gliosis without neurofibrillary tangles, consistent with the diagnosis of progressive subcortical gliosis (PSG). Even in retrospect no unique clinical neurological abnormality or finding on laboratory investigation could be identified that distinguished this latter patient from those with pathologically confirmed PSP. We conclude that PSG and PSP may be indistinguishable during life, and necropsy confirmation is needed for definite diagnosis
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0316
UR  - PM:1527543
ER  - 

TY  - JOUR
T1  - Hemi-parkinsonism in multiple system atrophy: a PET and MRI study
A1  - Kume,A.
A1  - Shiratori,M.
A1  - Takahashi,A.
A1  - Kato,T.
A1  - Ito,K.
A1  - Tadokoro,M.
A1  - Sakuma,S.
Y1  - 1992/07//
N1  - UI - 92373265
SP  - 37
EP  - 45
JA  - J Neurol Sci.
VL  - 110
IS  - 1-2
N2  - We selected 6 patients presenting with hemi-parkinsonism from a total of 20 patients with probable multiple system atrophy (MSA) and studied their nigrostriatal lesions using magnetic resonance (MR) imaging and positron emission tomography (PET) with 18F-labeled 2-deoxy-2-fluoro-D-glucose (FDG). T2 weighted MR images demonstrated a decreased signal intensity in the putamen of all patients. This decreased signal was more intense in the nucleus contralateral to the affected body side in 5 patients. A decreased signal in the substantia nigra was found, expanding more on the contralateral side in 3 patients. T1-weighted images showed that the contralateral putamen was smaller in size than the ipsilateral. These findings indicated that the iron deposit and the neuronal cell loss in the degenerative process were more remarkable in the contralateral nuclei. FDG uptake in 5 patients had likewise declined more in the contralateral than in the ipsilateral putamen. The study shows that these patients have the nigrostriatal lesions as described in previous reports on MSA and that an asymmetric lesion relating to clinical signs is present in the nigrostriatal system. When a patient presents with hemi-parkinsonism alone, MR imaging and PET/FDG are useful for the clinical diagnosis of MSA
AD  - Department of Neurology, Nagoya University School of Medicine, Japan
UR  - PM:1506867
ER  - 

TY  - JOUR
T1  - Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography
A1  - Brooks,D.J.
A1  - Ibanez,V.
A1  - Sawle,G.V.
A1  - Playford,E.D.
A1  - Quinn,N.
A1  - Mathias,C.J.
A1  - Lees,A.J.
A1  - Marsden,C.D.
A1  - Bannister,R.
A1  - Frackowiak,R.S.
Y1  - 1992/02//
SP  - 184
EP  - 192
JA  - Ann.Neurol
VL  - 31
IS  - 2
N2  - Equilibrium striatal: cerebellar 11C-raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L-dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean striatal: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and a fluctuating response to L-dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L-dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:1575457
ER  - 

TY  - JOUR
T1  - Transplantation of fetal dopamine neurons in Parkinson's disease: PET [18F]6-L-fluorodopa studies in two patients with putaminal implants
A1  - Sawle,G.V.
A1  - Bloomfield,P.M.
A1  - Bjorklund,A.
A1  - Brooks,D.J.
A1  - Brundin,P.
A1  - Leenders,K.L.
A1  - Lindvall,O.
A1  - Marsden,C.D.
A1  - Rehncrona,S.
A1  - Widner,H.
Y1  - 1992/02//
N1  - UI - 92246461
SP  - 166
EP  - 173
JA  - Ann.Neurol
VL  - 31
IS  - 2
N2  - Two patients with Parkinson's disease who underwent implantation of fetal mesencephalic tissue into the putamen were serially studied using positron emission tomography and [18F]6-L-fluorodopa ([18F]dopa). The uptake of [18F]dopa is related to the functional integrity of the presynaptic dopaminergic system. Preoperative studies revealed a marked decrease in putamen [18F]dopa uptake, with lesser involvement of the caudate. Two and 4 months, respectively, after operation, both patients demonstrated functional improvement, as described elsewhere. One patient was scanned 5, 8, and 13 months after the operation and the other was scanned 7 and 12 months after the operation. In both patients, [18F]dopa uptake increased within the operated putamen despite a progressive decrease in tracer uptake in the unoperated striatal structures. We believe that this increased uptake of [18F]dopa at the implantation site represents functional integrity within a surviving neural graft. While there has been little further clinical improvement beyond the fifth postoperative month, the uptake of [18F]dopa at the operation site in both patients has progressively increased. The kinetic data provide evidence of disease progression in the unoperated striatum, which, balanced against increasing graft function, may explain why clinical improvement reached a plateau within months after surgery
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:1575455
ER  - 

TY  - JOUR
T1  - Cerebral uptake and utilization of therapeutic [beta-11C]-L-DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor response
A1  - Tedroff,J.
A1  - Aquilonius,S.M.
A1  - Hartvig,P.
A1  - Bredberg,E.
A1  - Bjurling,P.
A1  - Langstrom,B.
Y1  - 1992/02//
N1  - UI - 92245885
SP  - 95
EP  - 102
JA  - Acta Neurol Scand.
VL  - 85
IS  - 2
N2  - Cerebral uptake and utilization of levodopa was measured in eight patients with idiopathic Parkinson's disease (PD) by [beta-11C]-L-DOPA and positron emission tomography (PET). By adding pharmacological doses of unlabelled levodopa to the radioactive solution it was possible to evaluate the clinical effect simultaneously with the cerebral kinetics of the drug. Additionally, in two of the patients with advanced PD, investigations with the dopamine re-uptake blocker [11C]-(+)-nomifensine and PET were carried out to get a measure of the density of striatal dopaminergic nerve-terminals. The brain uptake of [beta-11C]-L-DOPA was inversely correlated to the sum of large neutral amino acids in plasma. In the eight PD patients studied with [beta-11C]-L-DOPA striatal k3, which reflects the ability for striatal tissue to decarboxylate the tracer by the action of aromatic L-amino acid decarboxylase (AADC), was decreased 35% compared to healthy subjects. It was demonstrated that, in the patients with advanced PD and motor fluctuations on oral L-DOPA medication, reversal of parkinsonian symptoms occurred at very low striatal tissue dopamine concentrations. In the two very advanced patients studied with [11C]-(+)-nomifensine the striatal binding of the tracer was 50% reduced
AD  - Department of Neurology, University Hospital, Uppsala, Sweden
UR  - PM:1574995
ER  - 

TY  - JOUR
T1  - Subcortical damage and cortical dysfunction in progressive supranuclear palsy demonstrated by positron emission tomography
A1  - Karbe,H.
A1  - Grond,M.
A1  - Huber,M.
A1  - Herholz,K.
A1  - Kessler,J.
A1  - Heiss,W.D.
Y1  - 1992/02//
N1  - UI - 92202964
SP  - 98
EP  - 102
JA  - J Neurol
VL  - 239
IS  - 2
N2  - Regional cerebral glucose metabolism was studied in nine patients with progressive supranuclear palsy (PSP). (18F)-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) revealed general cerebral hypometabolism in all PSP patients in comparison with an age-matched reference group. When comparing the degree of regional metabolic deterioration, a consistent pattern of the most affected brain regions became obvious: the strongest significant alteration of cerebral glucose metabolism was observed in subcortical regions, e.g. in caudate nucleus, lentiform nucleus and upper mid-brain, which showed nerve cell loss in previous pathological studies. Less severe, but still significant hypometabolism was observed in frontal cortex. This pattern of hypometabolism was distinctly different from that typically seen in dementias of Alzheimer's type. The present data show that PET findings agree with histopathological studies: PSP is a primarily subcortical disease with secondary inactivation of cortical, especially of frontal brain regions
AD  - Universitatsklinik fur Neurologie, Koln, Federal Republic of Germany
UR  - PM:1552311
ER  - 

TY  - JOUR
T1  - Positron emission tomography in degenerative disorders of the dopaminergic system
A1  - Karbe,H.
A1  - Holthoff,V.
A1  - Huber,M.
A1  - Herholz,K.
A1  - Wienhard,K.
A1  - Wagner,R.
A1  - Heiss,W.D.
Y1  - 1992///
SP  - 121
EP  - 130
JA  - J Neural Transm.Park Dis.Dement.Sect.
VL  - 4
IS  - 2
N2  - 21 patients who had Parkinson's disease (PD), PD plus dementia of Alzheimer type (PDAT) or progressive supranuclear palsy (PSP), were studied with positron emission tomography (PET) using (18F)-2-fluoro-2-deoxy-D-glucose (FDG). In one patient with strictly unilateral PD side differences in striatal dopa uptake were studied with 6-(18F)fluoro-L-dopa (F-dopa). In patients with PD PET with FDG did not show any significant change in regional cerebral metabolic rates for glucose (rCMR(Glu)). In PDAT glucose metabolism was generally reduced, the most severe decrease was found in parietal cortex. The metabolic pattern was similar to that typically found in patients with Alzheimer's disease (AD). In the patient with strictly unilateral PD rCMR(Glu) was normal, F-dopa PET, however, revealed a distinct reduction of dopa uptake in the contralateral putamen. In PSP glucose metabolism was significantly decreased in subcortical regions (caudatum, putamen and brainstem) and in frontal cortex. Thus PET demonstrated a clear difference of metabolic pattern between PDAT and PSP
AD  - Universitatsklinik fur Neurologie, Koln, Federal Republic of Germany
UR  - PM:1571076
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease
A1  - Kuwert,T.
A1  - Hefter,H.
A1  - Scholz,D.
A1  - Milz,M.
A1  - Weiss,P.
A1  - Arendt,G.
A1  - Herzog,H.
A1  - Loken,M.
A1  - Hennerici,M.
A1  - Feinendegen,L.E.
Y1  - 1992///
SP  - 96
EP  - 101
JA  - Eur.J Nucl Med
VL  - 19
IS  - 2
N2  - Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and--to a lesser extent--cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment
AD  - Institute of Medicine, Research Center Julich, Federal Republic of Germany
UR  - PM:1563446
ER  - 

TY  - JOUR
T1  - Dopa-responsive dystonia: [18F]dopa positron emission tomography
A1  - Sawle,G.V.
A1  - Leenders,K.L.
A1  - Brooks,D.J.
A1  - Harwood,G.
A1  - Lees,A.J.
A1  - Frackowiak,R.S.
A1  - Marsden,C.D.
Y1  - 1991/07//
N1  - UI - 92027523
SP  - 24
EP  - 30
JA  - Ann.Neurol
VL  - 30
IS  - 1
N2  - The syndrome of dopa-responsive dystonia comprises a minority of patients with dystonia, yet it is of considerable diagnostic importance because patients respond dramatically to L-dopa therapy. Benefits from this treatment are lasting, and the problems associated with long-term L-dopa therapy in patients with Parkinson's disease are generally absent. It has been suggested that this condition is due to a defect in the dopamine synthetic pathway, which is bypassed when patients are treated with L-dopa. We have studied [18F]dopa uptake in 6 patients with classic dopa-responsive dystonia (5 familial patients and 1 sporadic patient), aged 18 to 66 years. Data have been analyzed according to a graphic approach, calculating an influx constant for each region studied. We have also studied a seventh, clinically atypical, patient with juvenile dystonia-parkinsonism. Similar data have been calculated for a group of 10 healthy control subjects and 10 patients with Parkinson's disease. The 6 patients with typical dopa-responsive dystonia had a modest but significant reduction in the uptake of tracer into both caudate and putamen, which indicates a defect in the decarboxylation, vesicular uptake, and storage of [18F]dopa. This argues against the proposition that dopa-responsive dystonia is due to an inherited defect of tyrosine hydroxylase alone. In the atypical patient, however, we found a greater reduction of [18F]dopa uptake into both caudate and putamen, comparable with that in patients with Parkinson's disease
AD  - MRC Cyclotron Unit, Hammersmith Hospital, Villigen, Switzerland
UR  - PM:1681782
ER  - 

TY  - JOUR
T1  - A regional covariance approach to the analysis of functional patterns in positron emission tomographic data
A1  - Moeller,J.R.
A1  - Strother,S.C.
Y1  - 1991/03//
N1  - UI - 91147446
SP  - A121
EP  - A135
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 2
N2  - This article provides a complete description of the subprofile scaling model (SSM) approach to the analysis of positron emission tomography (PET) data. The goals and assumptions underlying the development of SSM are outlined, and its strengths and weaknesses are discussed. It is demonstrated that all obtainable information about regional ratios can, in theory, be derived from the SSM regional covariance patterns. A general constraint on the ability to effectively remove global variation while identifying region-specific information about PET data sets is outlined and discussed within the SSM framework. Finally, an extension of the SSM technique to the generation of disease-specific covariance patterns is demonstrated for paraneoplastic cerebellar degeneration, the acquired immune deficiency syndrome dementia complex, and Parkinson's disease, and the importance of multidimensional descriptions of disease, such as may be obtained from PET data using SSM, is emphasized
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York
UR  - PM:1997480
ER  - 

TY  - JOUR
T1  - The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography
A1  - Snow,B.J.
A1  - Bhatt,M.
A1  - Martin,W.R.
A1  - Li,D.
A1  - Calne,D.B.
Y1  - 1991/01//
SP  - 12
EP  - 17
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 54
IS  - 1
N2  - Movement disorders, including Parkinsonism, are prominent features of neurological Wilson's disease (WD). This suggests there may be dysfunction of the nigrostriatal dopaminergic pathway. To explore this possibility, five patients were studied using positron emission tomography (PET) with 18F-6-fluorodopa (6FD), and magnetic resonance imaging (MRI). We calculated striatal 6FD uptake rate constants by a graphical method and compared the results with those of 18 normal subjects. It was found that four patients with symptoms all had abnormally low 6FD uptake, and the one asymptomatic patient had normal uptake. PET evidence for nigrostriatal dopaminergic dysfunction was present even after many years of penicillamine treatment. It is concluded that the nigrostriatal dopaminergic pathway is involved in neurological WD
AD  - Belzberg Laboratory of Clinical Neuroscience, Department of Radiology, University of British Columbia, Vancouver, Canada
UR  - PM:1901347
ER  - 

TY  - JOUR
T1  - The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease
A1  - Leenders,K.L.
A1  - Salmon,E.P.
A1  - Tyrrell,P.
A1  - Perani,D.
A1  - Brooks,D.J.
A1  - Sager,H.
A1  - Jones,T.
A1  - Marsden,C.D.
A1  - Frackowiak,R.S.
Y1  - 1990/12//
N1  - UI - 91069305
SP  - 1290
EP  - 1298
JA  - Arch Neurol
VL  - 47
IS  - 12
N2  - A group of healthy control subjects and patients with Parkinson's disease were investigated using positron emission tomography and two tracers as indicators of different specific properties of the presynaptic dopaminergic system in caudate nucleus and putamen. The first tracer, 6-L-(18F)-fluorodopa, was used as an analog of levodopa to assess its regional brain uptake, conversion into, and retention as dopamine and further metabolites. The second tracer, (11C)-nomifensine was employed as an indicator of striatal monaminergic reuptake sites that are principally dopaminergic. We have used this tracer to assess dopaminergic nerve terminal density. In patients with Parkinson's disease, striatal uptake of both tracers was decreased, putamen being significantly more affected than caudate. Side-to-side differences of uptake in putamen, but not caudate, correlated with corresponding left-right differences of scored clinical motor performance. Both 6-L(18F)-fluorodopa and (11C)-nomifensine tracer uptake in putamen was decreased on average to 40% of normal values, suggesting that a substantial part of the cellular elements of the dopaminergic nigrostriatal system is still intact in living parkinsonian patients. This is in contrast to the generally extreme depletion of endogenous dopamine in the putamen of patients found at postmortem. Our results lend support to the search for drug treatments that protect against further nigrostriatal cell loss and that could be exhibited as soon as the disease manifests clinically. If successful, a sufficient striatal nerve terminal pool would remain so that the effectiveness of levodopa as a dopamine repletor could persist
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:2123623
ER  - 

TY  - JOUR
T1  - PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease
A1  - Rinne,J.O.
A1  - Laihinen,A.
A1  - Nagren,K.
A1  - Bergman,J.
A1  - Solin,O.
A1  - Haaparanta,M.
A1  - Ruotsalainen,U.
A1  - Rinne,U.K.
Y1  - 1990/12//
N1  - UI - 91178836
SP  - 494
EP  - 499
JA  - J Neurosci.Res.
VL  - 27
IS  - 4
N2  - Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease
AD  - Department of Neurology, University of Turku, Finland
UR  - PM:1981915
ER  - 

TY  - JOUR
T1  - A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease
A1  - Grafton,S.T.
A1  - Mazziotta,J.C.
A1  - Pahl,J.J.
A1  - George-Hyslop,P.
A1  - Haines,J.L.
A1  - Gusella,J.
A1  - Hoffman,J.M.
A1  - Baxter,L.R.
A1  - Phelps,M.E.
Y1  - 1990/11//
SP  - 614
EP  - 621
JA  - Ann.Neurol
VL  - 28
IS  - 5
N2  - We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease. Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population. In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers. Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene. The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease
AD  - Department of Radiological Sciences, UCLA School of Medicine 90024
UR  - PM:1979723
ER  - 

TY  - JOUR
T1  - Cortical and subcortical glucose consumption measured by PET in patients with Huntington's disease
A1  - Kuwert,T.
A1  - Lange,H.W.
A1  - Langen,K.J.
A1  - Herzog,H.
A1  - Aulich,A.
A1  - Feinendegen,L.E.
Y1  - 1990/10//
N1  - UI - 91059180
SP  - 1405
EP  - 1423
JF  - Brain
VL  - 113 ( Pt 5)
N2  - In 23 patients with moderate to severe Huntington's disease (HD) and 21 normal volunteers, the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in the cerebellum, thalamus, striatum, and cortex using positron emission tomography and the 18F-deoxyglucose method. In contrast to previous reports, rCMRGlc was reduced not only in the striatum, but also in the cerebral cortex of patients with HD as compared with normal subjects. No significant difference between HD patients and normal subjects was found for thalamic and cerebellar rCMRGlc. To investigate the relationship between the clinical status and rCMRGlc, correlation coefficients for the clinical data were calculated for absolute values of rCMRGlc and for cerebellar ratios (CR) of rCMRGlc. The duration of chorea correlated significantly only with the absolute values of frontoparietal and temporo-occipital rCMRGlc and with the CRs of most cortical regions evaluated. The severity of chorea correlated significantly only with lentiform nucleus rCMRGlc. The severity of dementia correlated significantly only with the frontoparietal and temporo-occipital rCMRGlc, the CRs of most cortical regions, and the CR for the caudate nucleus. The degree of disability correlated significantly with the CRs of all regions evaluated except the occipital and the superior frontal cortex. It appears from this study that there is a reduction not only for the striatum but also for cortical rCMRGlc in patients with manifest HD, and that the cortical reduction of rCMRGlc contributes to the severity of clinical symptoms in these patients. This challenges the concept that dementia in HD is of purely subcortical origin
AD  - Institute of Medicine, Nuclear Research Centre, Julich, FRG
UR  - PM:2147116
ER  - 

TY  - JOUR
T1  - Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy
A1  - Brooks,D.J.
A1  - Ibanez,V.
A1  - Sawle,G.V.
A1  - Quinn,N.
A1  - Lees,A.J.
A1  - Mathias,C.J.
A1  - Bannister,R.
A1  - Marsden,C.D.
A1  - Frackowiak,R.S.
Y1  - 1990/10//
SP  - 547
EP  - 555
JA  - Ann.Neurol
VL  - 28
IS  - 4
N2  - Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:2132742
ER  - 

TY  - JOUR
T1  - Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson's disease
A1  - Mayberg,H.S.
A1  - Starkstein,S.E.
A1  - Sadzot,B.
A1  - Preziosi,T.
A1  - Andrezejewski,P.L.
A1  - Dannals,R.F.
A1  - Wagner,H.N.,Jr.
A1  - Robinson,R.G.
Y1  - 1990/07//
N1  - UI - 90328725
SP  - 57
EP  - 64
JA  - Ann.Neurol
VL  - 28
IS  - 1
N2  - Depression is a frequent finding in patients with Parkinson's disease (PD). Regional cerebral glucose metabolism was measured in depressed and nondepressed patients with PD and in age-comparable normal control subjects using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Relative metabolic activity in the caudate and orbital-inferior region of the frontal lobe was significantly lower in the depressed patients with PD as compared to both nondepressed patients and control subjects. There was a significant inverse correlation between relative glucose metabolism in the orbital-inferior area of the frontal lobe and depression scores. This study suggests that depression in PD is associated with dysfunction in the caudate and orbital-inferior area of the frontal lobe. This metabolic pattern is unlike that seen in patients with PD who have other behavioral deficits such as dementia, and suggests that disruption of basal ganglia circuits involving the inferior region of the frontal lobe may affect the regulation of mood
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD
UR  - PM:2375634
ER  - 

TY  - JOUR
T1  - Positron emission tomography in Shy-Drager syndrome
A1  - Bhatt,M.H.
A1  - Snow,B.J.
A1  - Martin,W.R.
A1  - Cooper,S.
A1  - Calne,D.B.
Y1  - 1990/07//
N1  - UI - 90328710
SP  - 101
EP  - 103
JA  - Ann.Neurol
VL  - 28
IS  - 1
N2  - We studied the nigrostriatal dopaminergic pathway in 3 patients with Shy-Drager syndrome, by using positron emission tomography and [18F]6-fluoro-L-dopa to determine whether their parkinsonism correlated with impaired functional integrity of the presynaptic nigrostriatal pathway. One patient had short duration of disease, mild parkinsonism, and a normal positron emission tomographic scan, suggesting pathological changes functionally distal to the nigrostriatal pathway. Two patients with longer duration of disease had more severe parkinsonism and reduced [18F]6-fluoro-L-dopa uptake, suggesting impaired nigrostriatal dopaminergic function with progression of Shy-Drager syndrome
AD  - Belzberg Laboratory of Clinical Neuroscience, Division of Neurology, University of British Columbia, Vancouver, Canada
UR  - PM:2375624
ER  - 

TY  - JOUR
T1  - Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations
A1  - Blin,J.
A1  - Baron,J.C.
A1  - Dubois,B.
A1  - Pillon,B.
A1  - Cambon,H.
A1  - Cambier,J.
A1  - Agid,Y.
Y1  - 1990/07//
N1  - UI - 90290374
SP  - 747
EP  - 752
JA  - Arch Neurol
VL  - 47
IS  - 7
N2  - In 41 patients with progressive supranuclear palsy (PSP) that was diagnosed on the basis of eight clinical criteria (25 patients with all eight criteria [probable PSP] and 16 with six or seven criteria [possible PSP]), we studied cerebral energy metabolism by using positron emission tomography and the fludeoxyglucose F 18 or the oxygen 15 method. Compared with age-matched controls, each of the cortical and subcortical metabolic values was significantly reduced, with a predominance in the frontal cortex, in both groups of patients with probable and possible PSP, without a difference between these two groups, suggesting similar underlying disease. The frontal metabolic value decreased with disease duration, but the relative frontal hypometabolism (expressed as the fronto-occipital metabolic ratio) was apparently already present in the early stages of the disease. The parkinsonian motor score was correlated with the caudate and thalamic metabolic values. The intellectual deterioration index was significantly correlated with both the frontal and the nonfrontal metabolic values. Finally, the frontal neuropsychological score was significantly correlated with only the fronto-occipital metabolic ratio. Hence, in PSP, a degenerative brain disease with subcortical lesions, the prominent frontal lobe-like syndrome essentially depends on the relative hypometabolism of the frontal cortex
AD  - Service Hospitalier Frederic Joliot, CEA, Departement de Biologie, Hopital d'Orsay, France
UR  - PM:2357154
ER  - 

TY  - JOUR
T1  - Normal striatal glucose consumption in two patients with benign hereditary chorea as measured by positron emission tomography
A1  - Kuwert,T.
A1  - Lange,H.W.
A1  - Langen,K.J.
A1  - Herzog,H.
A1  - Hefter,H.
A1  - Aulich,A.
A1  - Feinendegen,L.E.
Y1  - 1990/04//
N1  - UI - 90285679
SP  - 80
EP  - 84
JA  - J Neurol
VL  - 237
IS  - 2
N2  - Positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the regional cerebral metabolic rate of glucose consumption (rCMRGlc) in two patients with benign hereditary chorea (BHC) and 21 normal subjects. Relative and absolute values of cerebellar, striatal, thalamic, and cortical rCMRGlc were within normal limits for both patients with BHC, indicating that the choreic movement disorder encountered in these two patients was not caused by a decrease of energy metabolism in the striatum such as that found regularly in most patients with other forms of chorea (e.g. Huntington's and Wilson's disease)
AD  - Institute of Medicine, Nuclear Research Center, Julich, Federal Republic of Germany
UR  - PM:2141358
ER  - 

TY  - JOUR
T1  - Brain imaging as a tool in establishing a theory of brain pathology in obsessive compulsive disorder
A1  - Baxter,L.R.
Y1  - 1990/02//
N1  - UI - 90130354
SP  - 22
EP  - 25
JA  - J Clin.Psychiatry
VL  - 51 Suppl
N2  - Positron emission tomography (PET) studies using 18F-2-deoxy-2-fluoro-D-glucose (FDG) to determine glucose metabolic rates have been used recently to correlate the symptoms of obsessive compulsive disorder (OCD) with neuroanatomically localized brain dysfunctions. These studies, as well as data from other techniques and other disease states, suggest that the orbital cortex and the striatum are dysfunctional in OCD. This information can be used to construct a theory of how the symptoms of OCD and the related Gilles de la Tourette's syndrome and chronic motor tics are mediated by the central nervous system
AD  - Laboratory of Nuclear Medicine, University of California Los Angeles School of Medicine
UR  - PM:2298713
ER  - 

TY  - JOUR
T1  - D2 receptors in Huntington's disease: positron emission tomography findings and clinical correlates
A1  - Brandt,J.
A1  - Folstein,S.E.
A1  - Wong,D.F.
A1  - Links,J.
A1  - Dannals,R.F.
A1  - McDonnell-Sill,A.
A1  - Starkstein,S.
A1  - Anders,P.
A1  - Strauss,M.E.
A1  - Tune,L.E.
Y1  - 1990///
SP  - 20
EP  - 27
JA  - J Neuropsychiatry Clin.Neurosci.
VL  - 2
IS  - 1
N2  - The relationship of dopamine receptor binding in the caudate nucleus and the putamen to neurological and neuropsychological functioning was examined in 21 patients with Huntington's disease (HD) and eight individuals at risk of developing Huntington's disease. A significant reduction in relative binding of [11C]3-N-methylspiperone to the dopamine receptor was found in both the caudate and putamen of HD patients. Binding in the caudate was correlated only with tests of rapid coding and set alternation, while binding in the putamen was correlated only with duration of illness. The findings indicate that the well-described atrophic changes in the striatum of Huntington's disease patients are accompanied by receptor alterations. They also support previous animal and human studies indicating that the caudate nucleus plays a larger role in cognition than in motor functions
AD  - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
UR  - PM:1983772
ER  - 

TY  - JOUR
T1  - Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Kuwabara,Y.
A1  - Miyake,Y.
A1  - Tahara,T.
A1  - Masuda,K.
A1  - Hosokawa,S.
A1  - Goto,I.
A1  - Kato,M.
A1  - Ichimiya,A.
Y1  - 1989/11//
N1  - UI - 90359439
SP  - 111
EP  - 118
JA  - Ann.Nucl Med
VL  - 3
IS  - 3
N2  - Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometabolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:2641456
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism differs in adult and rigid juvenile forms of Huntington disease
A1  - Matthews,P.M.
A1  - Evans,A.C.
A1  - Andermann,F.
A1  - Hakim,A.M.
Y1  - 1989/11//
N1  - UI - 90104406
SP  - 353
EP  - 356
JA  - Pediatr.Neurol
VL  - 5
IS  - 6
N2  - A 7-year-old girl with the juvenile form of Huntington disease is described. She had personality changes, speech and gait disturbances, diffuse rigidity, dementia, and a well-documented family history of Huntington disease. Electroencephalography revealed bilateral epileptic foci; however, she had no seizures. Positron emission tomography using [18F]-2-fluoro-2-deoxy-D-glucose with an improved method for quantification of glucose metabolism in anatomically defined regions of interest demonstrated marked hypometabolism in the caudate nuclei and putamen, as is observed in adults with the disease. Glucose metabolism was also reduced in the posterior nuclei of the thalamus. Adults with Huntington disease have consistently demonstrated normal or increased rates of thalamic glucose metabolism. The findings suggest that brain metabolic alterations of Huntington disease in children differ from those in adults which is consistent with the postmortem pathologic differences previously recognized
AD  - Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, Canada
UR  - PM:2532511
ER  - 

TY  - JOUR
T1  - Positron emission tomography in manganese intoxication
A1  - Wolters,E.C.
A1  - Huang,C.C.
A1  - Clark,C.
A1  - Peppard,R.F.
A1  - Okada,J.
A1  - Chu,N.S.
A1  - Adam,M.J.
A1  - Ruth,T.J.
A1  - Li,D.
A1  - Calne,D.B.
Y1  - 1989/11//
N1  - UI - 90055075
SP  - 647
EP  - 651
JA  - Ann.Neurol
VL  - 26
IS  - 5
N2  - We employed 6-fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6-fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed
AD  - Belzberg Laboratory of Clinical Neuroscience, UBC Health Sciences Centre Hospital, Vancouver, Canada
UR  - PM:2510588
ER  - 

TY  - JOUR
T1  - Positron tomography demonstrates frontal lobe hypometabolism in progressive supranuclear palsy
A1  - Goffinet,A.M.
A1  - De Volder,A.G.
A1  - Gillain,C.
A1  - Rectem,D.
A1  - Bol,A.
A1  - Michel,C.
A1  - Cogneau,M.
A1  - Labar,D.
A1  - Laterre,C.
Y1  - 1989/02//
SP  - 131
EP  - 139
JA  - Ann.Neurol
VL  - 25
IS  - 2
N2  - A regional analysis of cerebral glucose metabolism was carried out in 9 patients with progressive supranuclear palsy by using positron emission tomography with fluorodeoxyglucose as the tracer. A consistent metabolic map of frontal hypometabolism was found in 7 patients. Brain metabolism was normal in 1 subject and diffusely decreased in another. In the 7 patients with selective hypofrontality, motor and premotor areas were severely hypometabolic, while heteromodal association cortex and paralimbic regions were comparatively less affected. Although this pattern of frontal alterations, probably due to disconnection, appeared consistent with the clinical features of the disease, it proved difficult to correlate the metabolic maps with neuropsychological disturbances
AD  - Positron Tomography Laboratory, University of Louvain, Louvain-la-Neuve, Belgium
UR  - PM:2784043
ER  - 

TY  - JOUR
T1  - Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography
A1  - Rosenthal,G.
A1  - Gilman,S.
A1  - Koeppe,R.A.
A1  - Kluin,K.J.
A1  - Markel,D.S.
A1  - Junck,L.
A1  - Gebarski,S.S.
Y1  - 1988/09//
N1  - UI - 89149014
SP  - 414
EP  - 419
JA  - Ann.Neurol
VL  - 24
IS  - 3
N2  - We compared the severity of motor dysfunction with local cerebral metabolic rates for glucose (lCMRGlc) and the degree of tissue atrophy in 30 patients with olivopontocerebellar atrophy (OPCA). We devised a scale to quantitate the degree of ataxia in the neurological examinations. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Tissue atrophy was assessed by visual rating of computed tomographic scans. PET studies revealed marked hypometabolism in the cerebellar vermis, cerebellar hemispheres, and brainstem of OPCA patients compared with 30 control subjects. A significant correlation was found between severity of motor impairment and lCMRGlc within the cerebellar vermis, both cerebellar hemispheres, and the brainstem. A significant but weaker relationship was noted between the degree of tissue atrophy in these regions and clinical severity. Partial correlation analysis revealed that motor dysfunction in OPCA correlated more strongly with lCMRGlc than with the amount of tissue atrophy. These results suggest that the clinical manifestations of OPCA are more closely related to the metabolic state of the tissue than to the structural changes in the cerebellum
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109
UR  - PM:3265863
ER  - 

TY  - JOUR
T1  - Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography
A1  - Foster,N.L.
A1  - Gilman,S.
A1  - Berent,S.
A1  - Morin,E.M.
A1  - Brown,M.B.
A1  - Koeppe,R.A.
Y1  - 1988/09//
SP  - 399
EP  - 406
JA  - Ann.Neurol
VL  - 24
IS  - 3
N2  - Progressive supranuclear palsy (PSP) is characterized by supranuclear palsy of gaze, axial dystonia, bradykinesia, rigidity, and a progressive dementia. Pathological changes in this disorder are generally restricted to subcortical structures, yet the type and range of cognitive deficits suggest the involvement of many cerebral regions. We examined the extent of functional impairment to cerebral cortical and subcortical structures as measured by the level of glucose metabolic activity at rest. Fourteen patients with PSP were compared to 21 normal volunteers of similar age using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose metabolism was reduced in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum in the patients with PSP as compared to the normal subjects. Analysis of individual brain regions revealed significant declines in cerebral glucose utilization in most regions throughout the cerebral cortex, particularly those in the superior half of the frontal lobe. Declines in the most affected regions of cerebral cortex were greater than those in any single subcortical structure. Although using conventional neuropathological techniques the cerebral cortex appears to be unaffected in PSP, significant and pervasive functional impairments in both cortical and subcortical structures are present. These observations help to account for the constellation of cognitive symptoms in individual patients with PSP and the difficulty encountered in identifying a characteristic psychometric profile for this group of patients
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109-0316
UR  - PM:3265862
ER  - 

TY  - JOUR
T1  - Effect of D-penicillamine treatment on brain metabolism in Wilson's disease: a case study
A1  - De Volder,A.
A1  - Sindic,C.J.
A1  - Goffinet,A.M.
Y1  - 1988/07//
N1  - UI - 89080743
SP  - 947
EP  - 949
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 51
IS  - 7
N2  - Sequential measurements of brain glucose metabolism were carried out in a patient with Wilson's disease, before and after successful treatment with D-penicillamine. They demonstrate an evolution of regional metabolism consistent with clinical improvement. The first study showed marked hypometabolism in the putamen on both sides. The second analysis showed bilateral improvement, with predominant residual deficits in the right putamen, while clinical symptoms of striatal dysfunction persisted on the left side. This observation suggests that positron emission tomography is able to follow the neurological evolution in cases of Wilson's disease
AD  - Positron Tomography Laboratory, University of Louvain, Louvain-la-Neuve, Belgium
UR  - PM:3264567
ER  - 

TY  - JOUR
T1  - Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings
A1  - Kluin,K.J.
A1  - Gilman,S.
A1  - Markel,D.S.
A1  - Koeppe,R.A.
A1  - Rosenthal,G.
A1  - Junck,L.
Y1  - 1988/06//
SP  - 547
EP  - 554
JA  - Ann.Neurol
VL  - 23
IS  - 6
N2  - We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem
AD  - Department of Physical Medicine, University of Michigan, Ann Arbor 48109-0316
UR  - PM:3261572
ER  - 

TY  - JOUR
T1  - Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function
A1  - Berent,S.
A1  - Giordani,B.
A1  - Lehtinen,S.
A1  - Markel,D.
A1  - Penney,J.B.
A1  - Buchtel,H.A.
A1  - Starosta-Rubinstein,S.
A1  - Hichwa,R.
A1  - Young,A.B.
Y1  - 1988/06//
N1  - UI - 88308453
SP  - 541
EP  - 546
JA  - Ann.Neurol
VL  - 23
IS  - 6
N2  - Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation
AD  - Department of Psychiatry, University of Michigan, Ann Arbor
UR  - PM:2970247
ER  - 

TY  - JOUR
T1  - Potent neurotoxic fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs as potential probes in models of Parkinson disease
A1  - Riachi,N.J.
A1  - Arora,P.K.
A1  - Sayre,L.M.
A1  - Harik,S.I.
Y1  - 1988/04//
SP  - 1319
EP  - 1321
JA  - J Neurochem.
VL  - 50
IS  - 4
N2  - We synthesized a number of fluorinated analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and tested their suitability as substrates for monoamine oxidase B in vitro and their dopaminergic neurotoxicity in vivo. Two of the compounds tested, 2'-F-MPTP and 2'-CF3-MPTP, were better enzyme substrates and possessed more potent neurotoxicity for nigrostriatal dopamine neurons than MPTP, especially 2'-F-MPTP. The results of the in vivo neurotoxicity experiments correlated well with the suitability of the compounds as substrates for monoamine oxidase. These findings could serve as a basis for the use of 18F-labeled analogs of MPTP for positron emission tomography studies of nonhuman primates for better understanding of the factors underlying MPTP toxicity. Furthermore, the discovery of two MPTP analogs with enhanced selective neurotoxicity to dopaminergic neurons may be an important clue in the continuing efforts to define the chemical structure-activity factors governing MPTP neurotoxic activation mechanisms
AD  - Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106
UR  - PM:3258018
ER  - 

TY  - JOUR
T1  - Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography
A1  - Gilman,S.
A1  - Markel,D.S.
A1  - Koeppe,R.A.
A1  - Junck,L.
A1  - Kluin,K.J.
A1  - Gebarski,S.S.
A1  - Hichwa,R.D.
Y1  - 1988/03//
SP  - 223
EP  - 230
JA  - Ann.Neurol
VL  - 23
IS  - 3
N2  - We studied local cerebral metabolic rates for glucose (1CMRglc) with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 30 patients with olivopontocerebellar atrophy (OPCA) and 30 age-matched control subjects without neurological disease. The diagnosis of OPCA was based on the history and physical findings and on the exclusion of other causes of cerebellar ataxia by means of laboratory investigations. Computed tomographic scans revealed some degree of atrophy of the cerebellum in most patients with OPCA, and many also had atrophy of the brainstem. PET studies in these patients revealed significant hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem in comparison with the normal control subjects. A significant relationship was found between the degree of atrophy and the level of 1CMRglc in the cerebellum and brainstem. Nevertheless, several patients had minimal atrophy and substantially reduced 1CMRglc, suggesting that atrophy does not fully account for the finding of hypometabolism. 1CMRglc was within normal limits for the thalamus and cerebral cortex. The data suggest that PET/1CMRglc may be useful as a diagnostic test in patients with the adult onset of cerebellar ataxia
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109-0316
UR  - PM:3259853
ER  - 

TY  - JOUR
T1  - Monoamine re-uptake sites in the human brain evaluated in vivo by means of 11C-nomifensine and positron emission tomography: the effects of age and Parkinson's disease
A1  - Tedroff,J.
A1  - Aquilonius,S.M.
A1  - Hartvig,P.
A1  - Lundqvist,H.
A1  - Gee,A.G.
A1  - Uhlin,J.
A1  - Langstrom,B.
Y1  - 1988/03//
N1  - UI - 88238054
SP  - 192
EP  - 201
JA  - Acta Neurol Scand.
VL  - 77
IS  - 3
N2  - Six patients with Parkinson's disease, selected to cover a range of clinical features, and 7 healthy volunteers aged 24-81 years, were examined by positron emission tomography after i.v. injection of racemic 11C-nomifensine, a catecholamine re-uptake blocking drug. After injection the radiotracer, radioactivity was rapidly distributed to the brain. The highest accumulation of radioactivity was found in areas rich in dopaminergic and noradrenergic innervation, such as the striatum and the thalamus. In regions with negligible dopaminergic and noradrenergic innervation, such as the cerebellum, radioactivity was lower and evenly distributed. In all investigated brain regions a marked age-related decline in 11C-nomifensine-derived radioactivity relative to the cerebellum was observed in the group of healthy volunteers. Parkinsonian patients did not show such a decline with age. In the group of parkinsonian patients with mainly unilateral involvement, the contralateral putamen exhibited the most pronounced decrease. Only the 3 parkinsonian patients aged 63 and younger showed markedly lower 11C-nomifensine binding in striatal areas than age-matched healthy volunteers. 11C-nomifensine seems to be a valuable tool for investigating noradrenergic and dopaminergic re-uptake sites in vivo. Further achievements will most likely be made when the active enantiomer becomes available
AD  - Department of Neurology, University Hospital, Uppsala University, Sweden
UR  - PM:3259784
ER  - 

TY  - JOUR
T1  - Brain glucose utilization in childhood Huntington's disease studied with positron emission tomography (PET)
A1  - De Volder,A.
A1  - Bol,A.
A1  - Michel,C.
A1  - Cogneau,M.
A1  - Evrard,P.
A1  - Lyon,G.
A1  - Goffinet,A.M.
Y1  - 1988///
N1  - UI - 88220708
SP  - 47
EP  - 50
JA  - Brain Dev.
VL  - 10
IS  - 1
N2  - Brain glucose metabolism was measured in two children with early-onset Huntington's disease, using positron emission tomography with fluorodeoxyglucose (FDG) as the tracer. A marked (48%) hypometabolism was found at the level of the caudate nuclei, but other areas of the brain, particularly the cerebral cortex, were not significantly affected. Despite its different clinical presentation, Huntington's disease in children is characterized by brain metabolic alterations similar to those found in adult patients
AD  - Positron Tomography Laboratory, University of Louvain, Louvain-la-Neuve, Belgium
UR  - PM:2967038
ER  - 

TY  - JOUR
T1  - MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans
A1  - Perlmutter,J.S.
A1  - Kilbourn,M.R.
A1  - Raichle,M.E.
A1  - Welch,M.J.
Y1  - 1987/10//
SP  - 1575
EP  - 1579
JF  - Neurology
VL  - 37
IS  - 10
N2  - We measured in vivo dopaminergic receptor binding using positron emission tomography and 18F-spiperone in an untreated symptomatic subject with MPTP-induced parkinsonism. Our technique determines four variables related to entry of 18F-spiperone into brain tissue and subsequent binding to receptors: (1) the combined forward-rate constant k1' (equal to the product of the maximum number of available specific binding sites, Bmax, times the association rate constant [ka] of 18F-spiperone and receptor); (2) the binding site dissociation rate constant k-1; (3) the free fraction of radioligand not specifically bound in brain tissue, f2; and (4) the regional permeability-surface-area product (PS) of the blood-brain barrier for spiperone. PS and f2 in the patient were not different from that of 10 normal volunteers, whereas the combined forward-rate constant (left caudate: k1' = 67.6 sec-1, normal = 0.140 +/- 0.056) and the dissociation rate constant (left caudate: k-1 = 0.116 sec-1, normal = 0.000339 +/- 0.000149) were evaluated. These findings provide potential new insights not only into the pathophysiology of this disease but into the clinical importance of dopamine receptor function as well
AD  - Department of Neurology and Neurological Surgery, Mallinckrodt Institute of Radiology, St. Louis, MO
UR  - PM:3498914
ER  - 

TY  - JOUR
T1  - In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography
A1  - Aquilonius,S.M.
A1  - Bergstrom,K.
A1  - Eckernas,S.A.
A1  - Hartvig,P.
A1  - Leenders,K.L.
A1  - Lundquist,H.
A1  - Antoni,G.
A1  - Gee,A.
A1  - Rimland,A.
A1  - Uhlin,J.
Y1  - 1987/10//
N1  - UI - 88073132
SP  - 283
EP  - 287
JA  - Acta Neurol Scand.
VL  - 76
IS  - 4
N2  - In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11C-nomifensine was administered i.v. in trace amounts (10-50 micrograms) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the time-course of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo
AD  - Department of Neurology, University Hospital, Uppsala, Sweden
UR  - PM:2961191
ER  - 

TY  - JOUR
T1  - Positron emission tomography in cases of chorea with different underlying diseases
A1  - Hosokawa,S.
A1  - Ichiya,Y.
A1  - Kuwabara,Y.
A1  - Ayabe,Z.
A1  - Mitsuo,K.
A1  - Goto,I.
A1  - Kato,M.
Y1  - 1987/10//
N1  - UI - 88061372
SP  - 1284
EP  - 1287
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 50
IS  - 10
N2  - Local cerebral metabolic rate for glucose (LCMRglc) was measured with positron emission tomography using the 18F-fluorodeoxy-glucose method in five patients with chorea due to different underlying diseases. Hypometabolism was observed in the striatum bilaterally in patients with Huntington's disease, choreoacanthocytosis, sporadic progressive chorea and dementia, and pseudo-Huntington form of dentato-rubro-pallido-luysian atrophy (DRPLA). The patient with hemichorea showed hypometabolism in the striatum on the contralateral side to the chorea. The patient with pseudo-Huntington form of DRPLA showed a diffusely decreased LCMRglc in other structures including the cerebral cortex, thalamus and cerebellum. These findings indicated that dysfunction of the striatum is relevant to the genesis of chorea in all these patients, even though the extent of dysfunction in other structures is different in each case
AD  - Department of Neurophysiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:2960785
ER  - 

TY  - JOUR
T1  - Normal caudate glucose metabolism in persons at risk for Huntington's disease
A1  - Young,A.B.
A1  - Penney,J.B.
A1  - Starosta-Rubinstein,S.
A1  - Markel,D.
A1  - Berent,S.
A1  - Rothley,J.
A1  - Betley,A.
A1  - Hichwa,R.
Y1  - 1987/03//
N1  - UI - 87156101
SP  - 254
EP  - 257
JA  - Arch Neurol
VL  - 44
IS  - 3
N2  - Glucose metabolism was examined by positron emission tomographic scanning with F-2-fluoro-2-deoxy-D-glucose in 29 persons at risk for Huntington's disease (HD), 28 age-matched controls, nine patients with stage I, and eight patients with stage II symptomatic HD. Absolute caudate metabolic rates and normalized indexes of caudate metabolism for at-risk persons were normal compared with controls. No at-risk person had caudate indexes outside two SDs of the controls' mean. Caudate metabolism in the earliest HD cases was significantly reduced compared with controls and at-risk persons, but within the 99% confidence levels of both groups. Stage II patients had caudate measures that were significantly depressed compared with those of stage I HD patients. Measurement of caudate glucose hypometabolism is unlikely to be sufficiently sensitive to serve as a presymptomatic marker of heterozygote status, although it will provide a sensitive marker for progressive caudate dysfunction in HD
UR  - PM:2950844
ER  - 

TY  - JOUR
T1  - Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Pahl,J.J.
A1  - Huang,S.C.
A1  - Baxter,L.R.
A1  - Riege,W.H.
A1  - Hoffman,J.M.
A1  - Kuhl,D.E.
A1  - Lanto,A.B.
A1  - Wapenski,J.A.
Y1  - 1987/02/12/
N1  - UI - 87115663
SP  - 357
EP  - 362
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 316
IS  - 7
N2  - Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder
UR  - PM:2949152
ER  - 

TY  - JOUR
T1  - PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline
A1  - Young,A.B.
A1  - Penney,J.B.
A1  - Starosta-Rubinstein,S.
A1  - Markel,D.S.
A1  - Berent,S.
A1  - Giordani,B.
A1  - Ehrenkaufer,R.
A1  - Jewett,D.
A1  - Hichwa,R.
Y1  - 1986/09//
N1  - UI - 87024405
SP  - 296
EP  - 303
JA  - Ann.Neurol
VL  - 20
IS  - 3
N2  - Fifteen drug-free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18F-2-fluoro-2-deoxyglucose (18F-FDG) uptake. All patients had abnormal indices of caudate metabolism on PET scanning, whereas in patients with early disease indices of putamen metabolism and CT measures of caudate atrophy were normal. Indices of caudate metabolism correlated highly with the patients' overall functional capacity (r = 0.906; p less than 0.001) and bradykinesia/rigidity (r = -0.692; p less than 0.01). Indices of putamen metabolism correlated highly with motor functions: chorea (r = -0.841; p less than 0.01), oculomotor abnormalities (r = -0.849; p less than 0.01), and fine motor coordination (r = -0.866; p less than 0.01). Indices of thalamic metabolism correlated positively with dystonia (r = 0.559; p less than 0.05). The data suggest that PET scanning with 18F-FDG is a sensitive measure of brain dysfunction in Huntington's disease and that basal ganglia metabolism is highly correlated with the overall functional capacity of individual patients and with the degree of their motor abnormalities
UR  - PM:2945510
ER  - 

TY  - JOUR
T1  - Changes in regional cerebral blood flow and oxygen metabolism following ventrolateral thalamotomy in Parkinson syndrome as revealed by positron emission tomography
A1  - Katayama,Y.
A1  - Tsubokawa,T.
A1  - Tsukiyama,T.
A1  - Hirayama,T.
Y1  - 1986///
N1  - UI - 87024565
SP  - 76
EP  - 85
JA  - Appl.Neurophysiol.
VL  - 49
IS  - 1-2
N2  - A case with unilateral symptoms of Parkinson syndrome is presented in which interesting changes in the topographic patterns of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were observed by positron emission tomography. This case was associated with severe tremor at rest exclusively in the left extremities. The parietal CBF and CMRO2 for the affected hemisphere were apparently lower than those for the nonaffected hemisphere preoperatively. After thalamotomy involving the right nucleus ventralis lateralis, including the ventralis intermedius, concomitant with complete disappearance of the tremor, the parietal CBF and CMRO2 for the affected side increased and even exceeded those for the nonaffected side
UR  - PM:3490222
ER  - 

TY  - JOUR
T1  - Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography
A1  - Leenders,K.L.
A1  - Frackowiak,R.S.
A1  - Quinn,N.
A1  - Marsden,C.D.
Y1  - 1986///
SP  - 69
EP  - 77
JA  - Mov Disord.
VL  - 1
IS  - 1
N2  - A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilisation, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilisation paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[18F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:2973559
ER  - 

TY  - JOUR
T1  - Cerebral metabolism of glucose in benign hereditary chorea
A1  - Suchowersky,O.
A1  - Hayden,M.R.
A1  - Martin,W.R.
A1  - Stoessl,A.J.
A1  - Hildebrand,A.M.
A1  - Pate,B.D.
Y1  - 1986///
N1  - UI - 89056936
SP  - 33
EP  - 44
JA  - Mov Disord.
VL  - 1
IS  - 1
N2  - Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using 18F-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC
AD  - Department of Medical Genetics, University of British Columbia, Vancouver, Canada
UR  - PM:2973557
ER  - 

TY  - JOUR
T1  - Local cerebral glucose utilisation in treated and untreated patients with Parkinson's disease
A1  - Rougemont,D.
A1  - Baron,J.C.
A1  - Collard,P.
A1  - Bustany,P.
A1  - Comar,D.
A1  - Agid,Y.
Y1  - 1984/08//
N1  - UI - 84291454
SP  - 824
EP  - 830
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 47
IS  - 8
N2  - Using the 18f-fluoro-2-deoxy-d-glucose technique and positron emission tomography (PET), the local cerebral glucose utilisation (1CMRGlc) was measured in four non-demented patients with early-onset, bilateral Parkinson's disease characterised by the predominance of akinesia. The study was done twice, first in the untreated condition, and then after levodopa had been resumed. Despite a marked clinical improvement, we found no alteration in 1CMRGlc between the first and second studies in any of the brain structure analysed. Compared to control values, 1CMRGlc in the basal ganglia was moderately increased in both studies. These essentially negative findings agree with most previous human or animal studies, and indicate that the functional alterations in the central dopaminergic systems of patients with Parkinson's disease have metabolic correlates that are too small to be demonstrated by current PET devices
UR  - PM:6332176
ER  - 

TY  - JOUR
T1  - Reduced striatal glucose consumption and prolonged reaction time are early features in Huntington's disease
A1  - Garnett,E.S.
A1  - Firnau,G.
A1  - Nahmias,C.
A1  - Carbotte,R.
A1  - Bartolucci,G.
Y1  - 1984/08//
N1  - UI - 85008804
SP  - 231
EP  - 237
JA  - J Neurol Sci.
VL  - 65
IS  - 2
N2  - Striatal glucose consumption was measured by positron emission tomography in 4 male patients, aged 16-27, suffering from Huntington's disease and in 3 age-matched control subjects. Symptoms had been present for 3 years or less; they were mainly psychiatric. Two of the patients had no chorea although the time taken to initiate a movement was prolonged and there was some reduction in the speed at which movements could be executed. Caudate atrophy was absent or minimal by CAT scan yet striatal glucose consumption was markedly reduced in all of the patients. It is suggested that striatal glucose consumption is largely determined by the functional integrity of spiny neurones in the striatum
UR  - PM:6237177
ER  - 

TY  - JOUR
T1  - Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
A1  - Markham,C.H.
A1  - Metter,E.J.
A1  - Riege,W.H.
A1  - Winter,J.
Y1  - 1982/11//
SP  - 425
EP  - 434
JA  - Ann.Neurol
VL  - 12
IS  - 5
N2  - Patterns of local cerebral glucose utilization were measured with positron emission, computed tomography using the 18F-fluorodeoxyglucose method in 13 patients with Huntington's disease (HD), 15 subjects at risk for HD, and 40 normal control subjects. These data were compared with computed tomographic measures of cerebral atrophy, with age, and with duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to patients with senile dementia, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results suggest the possibility that the caudate may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for HD
UR  - PM:6217782
ER  - 

TY  - JOUR
T1  - The correlation between cerebral glucose metabolism and benzodiazepine receptor density in the acute vegetative state
A1  - Rudolf,J.
A1  - Sobesky,J.
A1  - Ghaemi,M.
A1  - Heiss,W.D.
Y1  - 2002/11//
SP  - 671
EP  - 677
JA  - Eur.J Neurol
VL  - 9
IS  - 6
N2  - This paper compares the results of parallel positron emission tomography (PET) studies of regional cerebral glucose metabolism with the radiotracer 18F-fluorodeoxyglucose (FDG) and benzodiazepine receptor (BZR) density by PET using the BZR ligand 11C-flumazenil (FMZ), a tracer of neuronal integrity, in nine patients with acute vegetative state (AVS, duration <1 month). Overall glucose utilization was significantly reduced in AVS in comparison with age-matched controls (global metabolic rate for glucose 26 micromol/100 g/min in AVS vs. 31 micromol/100 g/min in controls). FMZ-PET demonstrated a considerable reduction of BZR binding sites in all cortical regions that grossly corresponded to the extent of reduction of cerebral glucose metabolism assessed with FDG-PET, whilst the cerebellum was spared from neuronal loss. In controls, cortical relative flumazenil binding was not lower than five times the average white matter activity, whilst in AVS, nearly all values were below this threshold. There was no relevant overlap of the data of relative flumazenil binding between both groups. The comparison of FDG- and FMZ-PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but irreversible structural brain damage
AD  - Klinik fur Neurologie der Universitat zu Koln, and Max-Planck-Institut fur Neurologische Forschung, Koln, Germany
UR  - PM:12453084
ER  - 

TY  - JOUR
T1  - Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography
A1  - Klee,B.
A1  - Law,I.
A1  - Hojgaard,L.
A1  - Kosteljanetz,M.
Y1  - 2002/11//
N1  - UI - 22341310
SP  - 657
EP  - 662
JA  - Eur.J Neurol
VL  - 9
IS  - 6
N2  - Identification of the unknown primary tumours in patients presenting with cerebral metastasis is a continued diagnostic challenge. Despite extensive and lengthy diagnostic work-up, the primary tumours will remain obscure in a significant proportion of the patients. The aim of this study was to evaluate the use of whole-body 18-F-fluorodeoxyglucose positron emission tomography (18FDG PET) scanning in this pursuit. Sixteen patients aged 34-74 years, with histologically confirmed metastatic brain tumours, were included in the study. Whole-body 18FDG PET identified pulmonary foci of probable primary tumours in all patients. Subsequent confirmation of tumour tissue was determined either by direct histological verification or indirectly by the observation of lesion appearance or lesion growth on structural imaging. This could only be obtained in eight of 16 patients, all defined as true positive. Of the remaining eight, a biopsy could not be sampled from seven patients, because of death or limited follow-up investigations, and one patient had pulmonary malignant melanoma metastases. Whole-body 18FDG PET scanning is a sensitive tool in the search for unknown primary tumours of patients with confirmed cerebral metastases allowing early and focused histological confirmation from suspicious lesions
AD  - PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, The National University Hospital, Tigshospitalet, Denmark
UR  - PM:12453082
ER  - 

TY  - JOUR
T1  - Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography
A1  - Farde,L.
A1  - Ehrin,E.
A1  - Eriksson,L.
A1  - Greitz,T.
A1  - Hall,H.
A1  - Hedstrom,C.G.
A1  - Litton,J.E.
A1  - Sedvall,G.
Y1  - 1985/06//
N1  - UI - 85216592
SP  - 3863
EP  - 3867
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 82
IS  - 11
N2  - Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders
UR  - PM:3873656
ER  - 

TY  - JOUR
T1  - Preparation of 11C-labelled SCH 23390 for the in vivo study of dopamine D-1 receptors using positron emission tomography
A1  - Halldin,C.
A1  - Stone-Elander,S.
A1  - Farde,L.
A1  - Ehrin,E.
A1  - Fasth,K.J.
A1  - Langstrom,B.
A1  - Sedvall,G.
Y1  - 1986///
N1  - UI - 87108530
SP  - 1039
EP  - 1043
JA  - Int.J Rad.Appl.Instrum.[A]
VL  - 37
IS  - 10
N2  - The dopamine D-1 receptor antagonist, SCH 23390 ((R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol), was labelled by alkylation of the desmethyl compound SCH 24518 ((R)-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7- ol) with [11C]methyl iodide. A multivariate optimization method, Simplex, was employed to obtain the optimal radiochemical yield. Both straight-phase and reversed-phase preparative HPLC were investigated in the purification of [11C]SCH 23390. Reaction in acetone with subsequent straight-phase LC separation resulted in 80% radiochemical yield, based on [11C]methyl iodide, with a total synthesis time of 35-40 min and a radiochemical purity greater than 99%. The average specific activity was on the order of 11.1 GBq/mmol. The 11C-labelled SCH 23390 was used to visualize the dopamine D-1 receptor-rich areas of a monkey brain by positron emission tomography. The data obtained showed a rapid distribution of radioactivity into the brain and a conspicuous accumulation of [11C]SCH 23390 in the striatum
UR  - PM:3027000
ER  - 

TY  - JOUR
T1  - Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET
A1  - Farde,L.
A1  - Hall,H.
A1  - Ehrin,E.
A1  - Sedvall,G.
Y1  - 1986/01/17/
N1  - UI - 86096767
SP  - 258
EP  - 261
JF  - Science
VL  - 231
IS  - 4735
N2  - D2 dopamine receptors in the putamen of living human subjects were characterized by using the selective, high-affinity D2 dopamine receptor antagonist carbon-11-labeled raclopride and positron emission tomography. Experiments in four healthy men demonstrated saturability of [11C]raclopride binding to an apparently homogeneous population of sites with Hill coefficients close to unity. In the normal putamen, maximum binding ranged from 12 to 17 picomoles per cubic centimeter and dissociation constants from 3.4 to 4.7 nanomolar. Maximum binding for human putamen at autopsy was 15 picomoles per cubic centimeter. Studies of [11C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients
UR  - PM:2867601
ER  - 

TY  - JOUR
T1  - Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs
A1  - Farde,L.
A1  - Wiesel,F.A.
A1  - Halldin,C.
A1  - Sedvall,G.
Y1  - 1988/01//
SP  - 71
EP  - 76
JA  - Arch Gen.Psychiatry
VL  - 45
IS  - 1
N2  - Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline
AD  - Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden
UR  - PM:2892477
ER  - 

TY  - JOUR
T1  - Stereoselective binding of 11C-raclopride in living human brain--a search for extrastriatal central D2-dopamine receptors by PET
A1  - Farde,L.
A1  - Pauli,S.
A1  - Hall,H.
A1  - Eriksson,L.
A1  - Halldin,C.
A1  - Hogberg,T.
A1  - Nilsson,L.
A1  - Sjogren,I.
A1  - Stone-Elander,S.
Y1  - 1988///
N1  - UI - 88234820
SP  - 471
EP  - 478
JA  - Psychopharmacology (Berl)
VL  - 94
IS  - 4
N2  - The selective D2-dopamine receptor antagonist raclopride and its pharmacologically inactive (R)-enantiomer FLB472 were labelled with 11C and used in a study with positron emission tomography to examine the stereoselectivity of 11C-raclopride binding to central D2-dopamine receptors in three healthy men. After the injection of 11C-raclopride, there was a high accumulation of radioactivity in the dopamine-rich basal ganglia, whereas after the injection of 11C-FLB472 there was no such accumulation of radioactivity. Thus, the binding of 11C-raclopride is stereoselective. Distribution ratios [radioactivity in a brain region/"free" (not protein-bound) radioactivity in plasma] were calculated for the two enantiomers to study regional differences in the accumulation of radioactivity. The distribution ratios in white matter were similar for the two enantiomers. In the putamen, a three to four-fold higher distribution ratio was found for 11C-raclopride than for 11C-FLB472, reflecting the presence of specific binding of 11C-raclopride binding to D2-dopamine receptors in the basal ganglia. In the temporal and frontal cortices the distribution ratios were, however, only a few per cent higher for 11C-raclopride than for 11C-FLB472, indicating that if D2-dopamine receptors are present in the human neocortex, then their density is indeed very low
AD  - Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden
UR  - PM:3131792
ER  - 

TY  - JOUR
T1  - D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics
A1  - Farde,L.
A1  - Wiesel,F.A.
A1  - Nordstrom,A.L.
A1  - Sedvall,G.
Y1  - 1989///
N1  - UI - 90047427
SP  - S28
EP  - S31
JA  - Psychopharmacology (Berl)
VL  - 99 Suppl
N2  - Using positron emission tomography and the selective ligands 11C-SCH23390 and 11C-raclopride, central D1- and D2-dopamine receptor occupancy was determined in schizophrenic patients treated with clinical doses of classical and atypical neuroleptics. Treatment with ten chemically distinct classical neuroleptics resulted in a 65-89% occupancy of D2-dopamine receptors. This finding represents strong support for the hypothesis that the mechanism of action of antipsychotic drugs is indeed related to a substantial degree of D2-dopamine receptor occupancy. In two patients treated with the atypical neuroleptic clozapine, 300 mg b.i.d. and 150 mg b.i.d., the D2-dopamine receptor occupancy was 65 and 40%, respectively. D1-dopamine receptor occupancy was determined in six antipsychotic drug-treated patients. No D1-dopamine receptor occupancy was found in patients treated with sulpiride and perphenazine, compounds known to be selective D2-dopamine receptor antagonists. The highest D1-dopamine receptor occupancy, 42%, was found in the patient treated with clozapine 150 mg b.i.d. The effects of the atypical neuroleptic clozapine may be related to a combined effect on both D1- and D2-dopamine receptors
AD  - Department of Psychiatry and Psychology, Karolinska Institutet, Stockholm, Sweden
UR  - PM:2573104
ER  - 

TY  - JOUR
T1  - Maps of receptor binding parameters in the human brain--a kinetic analysis of PET measurements
A1  - Blomqvist,G.
A1  - Pauli,S.
A1  - Farde,L.
A1  - Eriksson,L.
A1  - Persson,A.
A1  - Halldin,C.
Y1  - 1990///
N1  - UI - 90276502
SP  - 257
EP  - 265
JA  - Eur.J Nucl Med
VL  - 16
IS  - 4-6
N2  - A kinetic method is described for the estimation of neuroreceptor density as well as the rate constants for association and dissociation of rapidly equilibrating radioligands. The method is exemplified by positron emission tomographic measurements of the human brain using 11C-raclopride, a D 2 dopamine receptor antagonist, and 11C-Ro 15-1788, a benzodiazepine receptor antagonist. Using a linear non iterative algorithm, regional binding characteristics were calculated and displayed pixel by pixel in brain maps. Data from repeated experiments on the same subject with different amounts of the unlabeled ligand were utilized. The binding characteristics were determined according to a two step procedure in which the time course of the free radioligand concentration was estimated from a reference region considered to be free of specific receptor binding sites. Alternative methods to determine the concentration of free radioligand are discussed
AD  - Department of Clinical Neurophysiology, Karolinska Pharmacy, Karolinska Institute and Hospital, Stockholm, Sweden
UR  - PM:2112470
ER  - 

TY  - JOUR
T1  - D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride
A1  - Farde,L.
A1  - Wiesel,F.A.
A1  - Stone-Elander,S.
A1  - Halldin,C.
A1  - Nordstrom,A.L.
A1  - Hall,H.
A1  - Sedvall,G.
Y1  - 1990/03//
SP  - 213
EP  - 219
JA  - Arch Gen.Psychiatry
VL  - 47
IS  - 3
N2  - Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and [11C]raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus
AD  - Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden
UR  - PM:1968328
ER  - 

TY  - JOUR
T1  - Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics
A1  - Wong,D.F.
A1  - Wagner,H.N.,Jr.
A1  - Tune,L.E.
A1  - Dannals,R.F.
A1  - Pearlson,G.D.
A1  - Links,J.M.
A1  - Tamminga,C.A.
A1  - Broussolle,E.P.
A1  - Ravert,H.T.
A1  - Wilson,A.A.
Y1  - 1986/12/19/
N1  - UI - 87069955
SP  - 1558
EP  - 1563
JF  - Science
VL  - 234
IS  - 4783
N2  - In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density
UR  - PM:2878495
ER  - 

TY  - JOUR
T1  - Effects of endogenous dopamine on kinetics of [3H]N-methylspiperone and [3H]raclopride binding in the rat brain
A1  - Young,L.T.
A1  - Wong,D.F.
A1  - Goldman,S.
A1  - Minkin,E.
A1  - Chen,C.
A1  - Matsumura,K.
A1  - Scheffel,U.
A1  - Wagner,H.N.,Jr.
Y1  - 1991/11//
SP  - 188
EP  - 194
JF  - Synapse
VL  - 9
IS  - 3
N2  - Competition by endogenous dopamine with the binding of D2 dopamine receptor ligands may be important in the interpretation of positron emission tomography (PET) neuroreceptor studies. PET studies with N-methylspiperone (NMSP) have revealed increased D2 dopamine receptors in schizophrenia, whereas studies with raclopride (RAC) have not detected such differences. This may be due, at least in part, to differences in competition with endogenous dopamine for ligand binding. To determine effects of endogenous dopamine on in vivo receptor binding, adult male rats were preinjected with amphetamine and reserpine prior to [3H]NMSP or [3H]RAC. Striatal to cerebellar ratios of ligand binding were determined. To approximate the conditions of a PET study, a kinetic model was employed to examine effects of pharmacologically increasing brain dopamine levels (amphetamine pretreatment) on PET ligand binding. In these experiments, tail veins and arteries were cannulated and kinetic parameters determined from normalized integral plots in rats treated with amphetamine prior to radioligand injection. Both [3H]NMSP (43.5%) and [3H]RAC (41.5%) binding were significantly decreased after amphetamine pretreatment, whereas after reserpine pretreatment [3H]RAC binding was increased (52.7%). Kinetic studies revealed a marked resistance of [3H]NMSP to competition with endogenous dopamine released by amphetamine. In contrast, kinetic parameters of [3H]RAC were markedly reduced at all time intervals. This suggests significant differences in competition with endogenous dopamine by [3H]NMSP and [3H]RAC, determined kinetically. These findings may have important implications for the interpretation of PET neuroreceptor studies
AD  - Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205
UR  - PM:1776131
ER  - 

TY  - JOUR
T1  - Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone
A1  - Tune,L.E.
A1  - Wong,D.F.
A1  - Pearlson,G.
A1  - Strauss,M.
A1  - Young,T.
A1  - Shaya,E.K.
A1  - Dannals,R.F.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Sapp,J.
Y1  - 1993/12//
SP  - 219
EP  - 237
JA  - Psychiatry Res.
VL  - 49
IS  - 3
N2  - Positron emission tomography (PET) with 11C-N-methylspiperone as the radioligand was carried out in 25 chronic schizophrenic patients to determine dopamine D2 receptor density estimates in the corpus striatum. The sample included 18 neuroleptic-naive and 7 neuroleptic-free patients. Dopamine D2 receptor density estimates (Bmax) were obtained using a two-scan/four-compartment model. The Bmax estimates for the entire group (33.39 +/- 3.43 pmole/g) were significantly elevated when compared with estimates for the control group (Bmax = 15.63 +/- 2.38). The Bmax values for the entire group of schizophrenic patients showed a significant decline as a function of age. The Bmax values were significantly related to duration of illness (y = 13.2 + 10.3795x - 0.7931x2; r = 0.48). Thirteen patients and seven control subjects were added to our original publication sample (Wong et al., 1986c). The patients' Bmax values, when adjusted for age and sex effects, were significantly different compared with those of control subjects. Clinical data from the entire group were compared with published data from other research groups that have estimated dopamine D2 receptor density using different radioligands and different methods of data analysis. Comparisons of the clinical characteristics of the published studies show significant differences in patient populations, suggesting that discrepancies among published studies may reflect, in part, heterogeneity among groups of schizophrenic patients. The D2 receptor abnormality described in this study may be a late manifestation of disease, and the implications of this observation are discussed
AD  - Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD
UR  - PM:7909948
ER  - 

TY  - JOUR
T1  - In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder
A1  - Pearlson,G.D.
A1  - Wong,D.F.
A1  - Tune,L.E.
A1  - Ross,C.A.
A1  - Chase,G.A.
A1  - Links,J.M.
A1  - Dannals,R.F.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Wagner,H.N.,Jr.
Y1  - 1995/06//
SP  - 471
EP  - 477
JA  - Arch Gen.Psychiatry
VL  - 52
IS  - 6
N2  - BACKGROUND: A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM-III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax. RESULTS: Diagnostic groups differed in Bmax by analysis of variance (P < .0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r = .63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms. CONCLUSIONS: We conclude that, like schizophrenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia
AD  - Department of Psychiatry, Johns Hopkins University, Baltimore, Md, USA
UR  - PM:7771917
ER  - 

TY  - JOUR
T1  - Positron emission tomography in male violent offenders with schizophrenia
A1  - Wong,M.T.
A1  - Fenwick,P.B.
A1  - Lumsden,J.
A1  - Fenton,G.W.
A1  - Maisey,M.N.
A1  - Lewis,P.
A1  - Badawi,R.
Y1  - 1997/02/07/
N1  - UI - 97258284
SP  - 111
EP  - 123
JA  - Psychiatry Res.
VL  - 68
IS  - 2-3
N2  - The FDG PET brain scans from 31 offenders with schizophrenia and schizoaffective disorder from a maximum security mental hospital were compared with those of normal controls (N = 6) in terms of relative FDG uptake in a range of regions covering frontal and temporal regions. The patient sample was divided into those who had a history of repetitive violent offending (RVO, N = 17) and those without a repetitive violent history (NRVO, N = 14) according to the violence rating of their pre-admission convictions. Reduced FDG uptake was noted at both the right and left anterior inferior temporal (R and L AIT) regions in NRVOs but only at LAIT in RVOs. NRVOs had significantly lower FDG uptake at RAIT than RVOs. The findings suggest that metabolic changes at AIT may be related to different patterns of violent offending in patients with schizophrenia
AD  - Section of Clinical Neurophysiology, Institute of Psychiatry, London, UK. mtw@cortex.mhri.edu.au
UR  - PM:9104758
ER  - 

TY  - JOUR
T1  - 11C-SCH 39166, a selective ligand for visualization of dopamine-D1 receptor binding in the monkey brain using PET
A1  - Sedvall,G.
A1  - Farde,L.
A1  - Barnett,A.
A1  - Hall,H.
A1  - Halldin,C.
Y1  - 1991///
N1  - UI - 91227398
SP  - 150
EP  - 153
JA  - Psychopharmacology (Berl)
VL  - 103
IS  - 2
N2  - The new selective D1-dopamine receptor antagonist SCH 39166 was labelled with the positron emitting isotope 11C and used as ligand for visualization of dopamine-D1 receptor binding in Cynomolgus monkeys by PET. After intravenous administration of the ligand a marked uptake of radioactivity was recorded in the D1-dopamine receptor-rich striatum and neocortex but not in the dopamine receptor-poor cerebellum. The uptake of radioactivity in striatum and neocortex was markedly displaced after the intravenous injection of a high dose of the D1-dopamine receptor antagonist SCH 23390 but not after the 5-HT2 receptor antagonist ketanserine. 11C-SCH 39166 should be a useful tool to explore D1-dopamine receptor characteristics in the living human brain by PET
AD  - Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden
UR  - PM:1674157
ER  - 

TY  - JOUR
T1  - [11C]Ro 15-4513, a ligand for visualization of benzodiazepine receptor binding. Preparation, autoradiography and positron emission tomography
A1  - Halldin,C.
A1  - Farde,L.
A1  - Litton,J.E.
A1  - Hall,H.
A1  - Sedvall,G.
Y1  - 1992///
SP  - 16
EP  - 22
JA  - Psychopharmacology (Berl)
VL  - 108
IS  - 1-2
N2  - Ro 15-4513, a partial inverse agonist at the benzodiazepine (BZ) receptor site was labelled with 11C and used for in vitro autoradiography on human post mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. The total radiochemical yield of [11C]Ro 15-4513 was 30-40% with an overall synthesis time of 40 min. The specific radioactivity was about 1000 Ci/mmol at end of synthesis. In vitro autoradiography showed that [11C]Ro 15-4513 bound specifically predominantly in the neocortex of the human brain. Specific binding was also demonstrated in the basal ganglia and the cerebellar cortex. Flumazenil (Ro 15-1788) and clonazepam inhibited the binding in cerebral regions, but a significant proportion in the cerebellum was not inhibited by these agents. This proportion may represent alpha 6-containing BZ receptors. PET examination of [11C]Ro 15-4513 binding in Cynomolgus monkeys demonstrated high uptake of radioactivity in neocortex. The uptake of radioactivity was markedly displaced by high doses of Ro 15-4513 or clonazepam. [11C]Ro 15-4513 should be a useful ligand to examine BZ receptor characteristics in the living human brain by PET
AD  - Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden
UR  - PM:1329130
ER  - 

TY  - JOUR
T1  - High Levels of Serotonin Transporter Occupancy With Low-Dose Clomipramine in Comparative Occupancy Study With Fluvoxamine Using Positron Emission Tomography
A1  - Suhara,Tetsuya
A1  - Takano,Akihiro
A1  - Sudo,Yasuhiko
A1  - Ichimiya,Tetsuya
A1  - Inoue,Makoto
A1  - Yasuno,Fumihiko
A1  - Ikoma,Yoko
A1  - Okubo,Yoshiro
Y1  - 2003/04/01/
SP  - 386
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 60
IS  - 4
N2  - Context Serotonin transporters (5-HTT) are regarded as one of the major therapeutic targets of antidepressants. However, there have only been a few studies about 5-HTT occupancy, and in particular, data concerning classical antidepressants are still limited. Objective To investigate the relationship between 5-HTT occupancy and a wide range of antidepressant dosing protocols. Design, Setting, and Participants Antidepressant occupancies of 5-HTT were measured using positron emission tomography (PET) with [11C](+)McN5652. Twenty-seven healthy volunteers were measured with and without pretreatment with single low doses of antidepressants, and long-term doses were evaluated in 10 patients. Scan data were collected between December 12, 1995, and August 7, 2002, and data were analyzed during the 2001-2002 period at the National Institute of Radiological Sciences (Chiba, Japan). Intervention Four different doses of clomipramine hydrochloride (5-50 mg) and 3 different doses of fluvoxamine maleate (12.5-50 mg) were used for single administration. Long-term doses were 20 to 250 mg per day for clomipramine hydrochloride, and 25 to 200 mg per day for fluvoxamine maleate. Main Outcome Measure Occupancies in the thalamus were calculated using the individual baseline of [11C](+)McN5652 for single-dose studies and 2 long-term-dose studies, and the mean value of healthy volunteers as the baseline for 8 long-term-dose studies. The average data from inactive enantiomers [11C](-)McN5652 were used for the estimation of nonspecific binding. Results Occupancy of 5-HTT increased in a curvilinear manner. Even 10 mg of clomipramine hydrochloride showed approximately 80% occupancy, which was comparable with that of 50 mg of fluvoxamine maleate. Estimated median effective dose (ED50) of clomipramine hydrochloride was 2.67 mg for oral dose and 1.42 ng/mL for plasma concentration; those of fluvoxamine maleate were 18.6 mg and 4.19 ng/mL, respectively. Conclusions Clinical doses of clomipramine and fluvoxamine occupied approximately 80% of 5-HTT, and dose escalation would have minimal effect on 5-HTT blockade. Ten milligrams of clomipramine hydrochloride was enough to occupy 80% of 5-HTT in vivo
UR  - http://archpsyc.ama-assn.org/cgi/content/abstract/60/4/386
ER  - 

TY  - JOUR
T1  - [18F] beta-CIT-FP is superior to [11C] beta-CIT-FP for quantitation of the dopamine transporter
A1  - Lundkvist,C.
A1  - Halldin,C.
A1  - Ginovart,N.
A1  - Swahn,C.G.
A1  - Farde,L.
Y1  - 1997/10//
N1  - UI - 98013817
SP  - 621
EP  - 627
JA  - Nucl Med Biol.
VL  - 24
IS  - 7
N2  - beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane] is a cocaine analogue with high affinity for the dopamine transporter. Positron emission tomography (PET) studies with [O-methyl-11C] beta-CIT-FP ([11C] beta-CIT-FP) has shown that equilibrium conditions were approached but, however, not reached at the end of measurement. Moreover, metabolite studies of [11C] beta-CIT-FP in monkey plasma demonstrated a lipophilic-labelled metabolite that may enter the brain. We therefore labelled beta-CIT-FP with fluorine-18 in a position that may avoid the formation of labelled lipophilic metabolites. The more long-lived radionuclide (18F) was used to allow for measurements over longer time. [N-fluoropropyl- 18F] beta-CIT-FP ([18F] beta-CIT-FP) was prepared by N-alkylation of nor-beta-CIT with [18F]fluoropropyl bromide. PET studies were performed in cynomolgus monkeys. [18F] beta-CIT-FP entered the brain rapidly. There was a high concentration of radioactivity in the striatum and much lower in the thalamus, neocortex, and cerebellum. The striatum-to-cerebellum ratio was about 5 at time of transient equilibrium, which occurred after 60 to 100 min. After pretreatment with GBR 12909, radioactivity in the striatum was markedly reduced, thus indicating specific [18F] beta-CIT-FP binding to the dopamine transporter. The fraction of unchanged [18F] beta-CIT-FP determined by HPLC was 10-15% after 140 min. No lipophilic labelled metabolites were detected. The absence of measurable lipophilic labelled metabolites and the occurrence of transient equilibrium within the time of the PET measurement indicate that [18F] beta-CIT-FP is superior to [11C] beta-CIT-FP as a PET radioligand for quantification of the dopamine transporter in the human brain
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
UR  - PM:9352532
ER  - 

TY  - JOUR
T1  - 18F-labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters
A1  - Goodman,Mark M.
A1  - Kilts,Clinton D.
A1  - Keil,Robert
A1  - Shi,Bing
A1  - Martarello,Laurent
A1  - Xing,Dongxia
A1  - Votaw,John
A1  - Ely,Timothy D.
A1  - Lambert,Philip
A1  - Owens,Michael J.
Y1  - 2000/01//
SP  - 1
EP  - 12
JA  - Nuclear Medicine and Biology
VL  - 27
IS  - 1
N2  - Fluorine-18 labeled 2[beta]-carbomethoxy-3[beta]-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (FECNT) was synthesized in the development of a dopamine transporter (DAT) imaging ligand for positron emission tomography (PET). The methods of radiolabeling and ligand synthesis of FECNT, and the results of the in vitro characterization and in vivo tissue distribution in rats and in vivo PET imaging in rhesus monkeys of [18F]FECNT are described. Fluorine-18 was introduced into 2[beta]-carbomethoxy-3[beta]-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (4) by preparation of 1-[18F]fluoro-2-tosyloxyethane (2) followed by alkylation of 2[beta]-carbomethoxy-3[beta]-(4-chlorophenyl)nortropane (3) in 21% radiochemical yield (decay corrected to end of bombardment [EOB]). Competition binding in cells stably expressing the transfected human DAT serotonin transporter (SERT) and norepinephrine transporter (NET) labeled by [3H]WIN 35428, [3H]citalopram, and [3H]nisoxetine, respectively, indicated the following order of DAT affinity: GBR 12909 > CIT >> 2[beta]-carbomethoxy-3[beta]-(4-chlorophenyl)-8-(3-fluoropropyl)nortropane (FPCT) > FECNT. The affinity of FECNT for SERT and NET was 25- and 156-fold lower, respectively, than for DAT. Blocking studies were performed in rats with a series of transporter-specific agents and demonstrated that the brain uptake of [18F]FECNT was selective and specific for DAT-rich regions. PET brain imaging studies in monkeys demonstrated high [18F]FECNT uptake in the caudate and putamen that resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 10.5 at 60 min. [18F]FECNT uptake in the caudate/putamen peaked in less than 75 min and exhibited higher caudate- and putamen-to-cerebellum ratios at transient equilibrium than reported for 11C-WIN 35,428, [11C]CIT/RTI-55, or [18F] [beta]-CIT-FP. Analysis of monkey arterial plasma samples using high performance liquid chromatography determined that there was no detectable formation of lipophilic radiolabeled metabolites capable of entering the brain. In equilibrium displacement experiments with CIT in rhesus monkeys, radioactivity in the putamen was displaced with an average half-time of 10.2 min. These results indicate that [18F]FECNT is a radioligand that is superior to 11C-WIN 35,428, [11C]CIT/RTI-55, [18F][beta]-CIT-FP, and [18F]FPCT for mapping brain DAT in humans using PET
UR  - http://www.sciencedirect.com/science/article/B6T9Y-3YJYDT7-1/2/a028c2079744e77ed1d015ce9197a5d6
ER  - 

TY  - JOUR
T1  - Interaction of isoflurane with the dopamine transporter
A1  - Votaw,J.
A1  - Byas-Smith,M.
A1  - Hua,J.
A1  - Voll,R.
A1  - Martarello,L.
A1  - Levey,A.I.
A1  - Bowman,F.D.
A1  - Goodman,M.
Y1  - 2003/02//
N1  - UI - 22437783
SP  - 404
EP  - 411
JF  - Anesthesiology
VL  - 98
IS  - 2
N2  - BACKGROUND: Isoflurane administration is known to increase extracellular dopamine (DA) concentration. Because the dopamine transporter (DAT) is a key regulator of DA, it is likely affected by isoflurane. This study investigates the hypothesis that isoflurane inhibits DA reuptake by causing DAT to be trafficked into the cell. METHODS: Rhesus monkeys were scanned with positron emission tomography (PET) using [18F]FECNT (a highly specific DAT ligand) while anesthetized with 1% isoflurane. The isoflurane was increased to 2%, and the animals were rescanned. Uptake was analyzed with the tissue reference method using the cerebellum as the reference tissue to determine the binding potential in the putamen. Immunohistochemistry and Western blot analyses were performed in rats to determine if isoflurane administration would change the total amount of DAT. Rats breathed air plus 2% isoflurane for 30 min, and then striatal DAT assays were rapidly performed. immunocytochemistry experiments were performed using human embryonic kidney (HEK) cells stably transfected with human DAT. The cells were exposed to 4% isoflurane for 1 h while the location of DAT was observed with fluorescent confocal microscopy. RESULTS: The [18F]FECNT binding potential in rhesus monkeys decreased by 63 +/- 6% (SEM, n = 5) when isoflurane was increased from 1 to 2% as compared with no significant change (0.7 +/- 2.5%; SEM, n = 5) when the isoflurane concentration was not changed (P < 0.001). No difference in DAT staining between isoflurane-treated and control rats was apparent from visual inspection, and quantitative Western blot analyses showed no significant change in total DAT protein. After isoflurane treatment, focal puncta of intense fluorescence was visible inside the HEK cells. CONCLUSIONS: The experiments indicate that DAT is trafficked into the cell by isoflurane without changing the total amount of DAT in the striatum. The PET data are consistent with this finding, provided that intracellular DAT acquires a conformation that has low affinity for [18F]FECNT. Thus, [18F]FECNT appears to be an excellent agent for measuring plasma membrane-expressed DAT and evaluating DAT trafficking
AD  - Department of Radiology, Emory University School of Medicine, Atlanta, Georgia, USA. Votaw@commander.eushc.org
UR  - PM:12552200
ER  - 

TY  - JOUR
T1  - Self-administration of cocaine and the cocaine analog RTI-113: relationship to dopamine transporter occupancy determined by PET neuroimaging in rhesus monkeys
A1  - Wilcox,K.M.
A1  - Lindsey,K.P.
A1  - Votaw,J.R.
A1  - Goodman,M.M.
A1  - Martarello,L.
A1  - Carroll,F.I.
A1  - Howell,L.L.
Y1  - 2002/01//
SP  - 78
EP  - 85
JF  - Synapse
VL  - 43
IS  - 1
N2  - Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. The present study examined the reinforcing effects of 3beta-(4-chlorophenyl)tropane-2beta-carboxylic acid phenyl ester (RTI-113), a long-acting, selective, high-affinity dopamine uptake inhibitor. Additionally, the effects of RTI-113 pretreatment on cocaine self-administration were determined. Monkeys were trained to respond under a second-order schedule for intravenous cocaine administration (0.10 or 0.17 mg/kg/infusion). When responding was stable, cocaine (0.0030-1.0 mg/kg/infusion) and RTI-113 (0.010-0.30 mg/kg/infusion) were substituted for the cocaine training dose. Cocaine and RTI-113 were equipotent for their reinforcing effects. However, cocaine maintained higher response rates in two of the three monkeys tested. When administered as a pretreatment, RTI-113 (0.10-0.30 mg/kg) dose-dependently reduced responding maintained by two doses of cocaine. Drug effects on behavior were related to dopamine transporter (DAT) occupancy in monkey striatum during neuroimaging with positron emission tomography. DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 65-76% and 94-99% for doses of cocaine and RTI-113 that maintained maximum response rates, respectively. DAT occupancy did not differ markedly across RTI-113 pretreatment doses and ranged between 72-84%. The results suggest that the pharmacokinetic profile of RTI-113 (i.e., long-acting) may influence its ability to maintain self-administration, and therefore its abuse liability. Additionally, high DAT occupancy is required for RTI-113 to reduce cocaine-maintained responding
AD  - Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322, USA. kwilcox@rmy.emory.edu
UR  - PM:11746736
ER  - 

TY  - JOUR
T1  - Ketamine alters the availability of striatal dopamine transporter as measured by [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the monkey brain
A1  - Tsukada,H.
A1  - Nishiyama,S.
A1  - Kakiuchi,T.
A1  - Ohba,H.
A1  - Sato,K.
A1  - Harada,N.
Y1  - 2001/12/15/
N1  - UI - 21613015
SP  - 273
EP  - 280
JF  - Synapse
VL  - 42
IS  - 4
N2  - The effects of ketamine anesthesia on the binding of [(11)C]-labeled cocaine analogs, [(11)C]beta-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) and [(11)C]beta-CIT-FE (N-(2-fluoroethyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane), to the striatal dopamine transporter (DAT) were evaluated in the monkey brain using positron emission tomography (PET). We sequentially measured the kinetics of these labeled compounds in the brains of five young-adult male rhesus monkeys (Macaca mulatta) in the conscious state, followed by those under ketamine anesthesia with continuous infusion (3 and 10 mg/kg/h). After intravenous injection, [(11)C]beta-CFT and [(11)C]beta-CIT-FE were predominantly accumulated in the striatum in both conscious and ketamine-anesthetized states. In the conscious state, the striatal uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE continuously increased with time up to 91 min after injection. Continuous infusion of ketamine-induced higher levels of uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE into the brain in a dose-dependent manner as compared with conscious state, and kinetic analysis with metabolite-corrected arterial input function indicated that the binding potentials (BP = k(3)/k(4)) of both compounds were elevated by ketamine. Not only [(11)C]beta-CIT-FE but also [(11)C]beta-CFT reached the equilibrium state of specific binding in the striatum within 40-50 min after injection. The present results demonstrated that ketamine significantly alters the DAT availability as measured with [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the brain
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
UR  - PM:11746726
ER  - 

TY  - JOUR
T1  - Elevated striatal dopamine transporter in a drug naive patient with Tourette syndrome and attention deficit/ hyperactivity disorder: positive effect of methylphenidate
A1  - Krause,K.H.
A1  - Dresel,S.
A1  - Krause,J.
A1  - Kung,H.F.
A1  - Tatsch,K.
A1  - Lochmuller,H.
Y1  - 2002/08//
N1  - UI - 22306330
SP  - 1116
EP  - 1118
JA  - J Neurol
VL  - 249
IS  - 8
UR  - PM:12420715
ER  - 

TY  - JOUR
T1  - Microscopic kinetics and structure-function analysis in the vesicular acetylcholine transporter
A1  - Bravo,Dawn
A1  - Parsons,Stanley M.
Y1  - 2002/11//
SP  - 285
EP  - 289
JF  - Neurochemistry International
VL  - 41
IS  - 5
N2  - The vesicular acetylcholine transporter (VAChT) resides in synaptic vesicles of cholinergic nerve terminals. It carries out vesicular storage of ACh. The amount of ACh stored determines, along with other factors, the amount of ACh released. Knowledge of the structure-function relationship in VAChT might enable pharmacological regulation of ACh storage and release at the level of VAChT. To this end, a quantitative model for the individual steps in the overall transport cycle of VAChT has been developed. Because of the particular values of the microscopic rate constants in the model, structure-function analysis of VAChT can be misleading. Attempts to devise a pro-storage strategy to increase ACh release from cholinergic nerve terminals should take into account the microscopic kinetics of this transporter
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Bravo-vesicular-acetylcholine-transporter.pdf
ER  - 

TY  - JOUR
T1  - Central challenges facing the national clinical research enterprise
A1  - Sung,N.S.
A1  - Crowley,W.F.,Jr.
A1  - Genel,M.
A1  - Salber,P.
A1  - Sandy,L.
A1  - Sherwood,L.M.
A1  - Johnson,S.B.
A1  - Catanese,V.
A1  - Tilson,H.
A1  - Getz,K.
A1  - Larson,E.L.
A1  - Scheinberg,D.
A1  - Reece,E.A.
A1  - Slavkin,H.
A1  - Dobs,A.
A1  - Grebb,J.
A1  - Martinez,R.A.
A1  - Korn,A.
A1  - Rimoin,D.
Y1  - 2003/03/12/
N1  - UI - 22521471
SP  - 1278
EP  - 1287
JF  - JAMA
VL  - 289
IS  - 10
N2  - Medical scientists and public health policy makers are increasingly concerned that the scientific discoveries of the past generation are failing to be translated efficiently into tangible human benefit. This concern has generated several initiatives, including the Clinical Research Roundtable at the Institute of Medicine, which first convened in June 2000. Representatives from a diverse group of stakeholders in the nation's clinical research enterprise have collaborated to address the issues it faces. The context of clinical research is increasingly encumbered by high costs, slow results, lack of funding, regulatory burdens, fragmented infrastructure, incompatible databases, and a shortage of qualified investigators and willing participants. These factors have contributed to 2 major obstacles, or translational blocks: impeding the translation of basic science discoveries into clinical studies and of clinical studies into medical practice and health decision making in systems of care. Considering data from across the entire health care system, it has become clear that these 2 translational blocks can be removed only by the collaborative efforts of multiple system stakeholders. The goal of this article is to articulate the 4 central challenges facing clinical research at present--public participation, information systems, workforce training, and funding; to make recommendations about how they might be addressed by particular stakeholders; and to invite a broader, participatory dialogue with a view to improving the overall performance of the US clinical research enterprise
AD  - Burroughs Wellcome Fund, PO Box 13901, 21 T. W. Alexander Dr, Research Triangle Park, NC 27709, USA. nsung@bwfund.org
UR  - PM:12633190
ER  - 

TY  - JOUR
T1  - An imaging co-registration system using novel non-invasive and non-radioactive external markers
A1  - Wu,T.H.
A1  - Wang,J.K.
A1  - Lee,J.J.
A1  - Liu,R.S.
A1  - Guo,W.Y.
Y1  - 2003/04/12/
N1  - UI - 0
JA  - Eur.J Nucl Med Mol.Imaging
N2  - We present a system of image co-registration and its validation in phantom and volunteer studies. The system co-registered images via six novel non-invasive and non-radioactive external markers. The fiducial markers were attached with sponge bases on the skin surface of the phantom and the volunteers in a non-collinear and non-coplanar array. The subjects were scanned with a 1.5-T magnetic resonance (MR) imager using 2D spin-echo T1-weighted (SE) and 3D spoiled gradient recalled pulse sequences (SPGR) and with a positron emission tomography (PET) scanner for transmission imaging (TI) and emission imaging (EI). The sponge bases created radiolucent gaps with good contrast between the fiducial markers and skin surface. They made the markers visible with clear edge boundaries on both PET and MR images. The images to be registered were rescaled, interpolated, reformatted and followed by point-to-point registration for coordinate determination and the estimation of geometrical transformation and fiducial registration errors (FREs) via the fiducial markers. The images formed four matched pairs of inter-modality (SE-TI, SPGR-TI, SE-EI and SPGR-EI) and two pairs of intra-modality (SE-SPGR, TI-EI) imaging for direct co-registration. The parameters for direct co-registration of SE-TI and SPRG-TI were subsequently used as a bridge and applied for indirect co-registration of SE with EI (SE-EI(TI)) and SPGR with EI (SPGR-EI(TI)), respectively. The overall FREs of the phantom were, respectively, 1.50 mm for inter-modality and 1.10 mm for intra-modality direct co-registration. Those of volunteers were, respectively, 1.79 mm for inter-modality and 1.21 mm for intra-modality direct co-registration. For indirect co-registration, the overall FREs of the phantom were 2.53 mm (SE-EI(TI)) and 2.28 (SPGR-EI(TI)) mm; those of volunteers were 2.84 mm (SE-EI(TI)) and 2.81 mm (SPGR-EI(TI)). The errors of direct co-registration were smaller than those of indirect co-registration; the errors of phantom studies, MR-EI and SPGR-PET were smaller than those of the volunteer studies, MR-TI and SE-PET, respectively (all P<0.01, paired-difference test). In conclusion, motion artefacts, imaging blurring and spatial resolution of imaging remained the key factors affecting the accuracy of co-registration. High-accuracy indirect co-registration is provided by using non-invasive and non-radioactive external fiducial markers. The errors were less than 3 mm for both phantom and volunteer studies. The system is applicable for imaging co-registration of inter-modality non-dual imaging, inter-modality multi-tracer imaging and intra-modality multiple parameter images in clinical practice
AD  - Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ROC
UR  - PM:12692690
ER  - 

TY  - JOUR
T1  - Methyl-[(11)C]- l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma
A1  - Kracht,L.W.
A1  - Friese,M.
A1  - Herholz,K.
A1  - Schroeder,R.
A1  - Bauer,B.
A1  - Jacobs,A.
A1  - Heiss,W.D.
Y1  - 2003/04/12/
N1  - UI - 0
SP  - 868
EP  - 873
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 6
N2  - Positron emission tomography (PET) using methyl-[(11)C]- l-methionine ([(11)C]MET) is a useful tool in the diagnosis of brain tumours. The main mechanism of [(11)C]MET uptake is probably increased transport via the L-transporter system located in the endothelial cell membrane. We used [(11)C]MET-PET and microvessel count in glioma specimens to investigate whether the increased amino acid uptake is related to angiogenesis. Twenty-one patients with newly diagnosed and histologically confirmed glioma were investigated with [(11)C]MET-PET before open surgery. [(11)C]MET uptake was determined within an 8-mm region of interest in the area of the tumour showing the highest uptake, and the ratio to uptake in the corresponding contralateral region was calculated. To measure angiogenesis, immunostaining with factor VIII antibody was applied to sections from tumour tissue, and highlighted microvessels were counted in the area of highest vascularisation. In the entire patient group, a positive correlation was found between microvessel count and [(11)C]MET uptake (Spearman: r=0.89, P<0.001). This correlation was also significant in subgroups of patients [patients with grade II and III astrocytomas (Spearman: r=0.77, P<0.01) and patients with glioblastoma (Spearman: r=0.64, P<0.05)]. Angiogenesis, as assessed by microvessel count, and increased amino acid uptake, as assessed by [(11)C]MET-PET, are closely related events in gliomas. [(11)C]MET-PET offers a direct measure of amino acid transport and an indirect measure of microvessel density. [(11)C]MET-PET might be a useful tool to select potential responders to anti-angiogenic therapy and to monitor patients during such therapy
AD  - Max-Planck-Institut fur neurologische Forschung, Gleueler Strasse 50, 50931, Cologne, Germany
UR  - PM:12692687
ER  - 

TY  - JOUR
T1  - Evaluation or treatment effects in brain abscess with positron emission tomography: comparison of Fluorine-18-Fluorodeoxyglucose and Carbon-11-Methionine
A1  - Tsuyuguchi,N.
A1  - Sunada,I.
A1  - Ohata,K.
A1  - Takami,T.
A1  - Nishio,A.
A1  - Hara,M.
A1  - Kawabe,J.
A1  - Okamura,T.
A1  - Ochi,H.
Y1  - 2003/02//
N1  - UI - 22576872
SP  - 47
EP  - 51
JA  - Ann.Nucl Med
VL  - 17
IS  - 1
N2  - Positron emission tomography (PET) imaging is in common use preoperatively to clinically evaluate patients who present with central nervous system mass lesions. The usefulness of PET is also recognized as a method to detect intracranial tumorous lesions. A number of papers reportthat some inflammatory processes also showed the uptake of Fluorine-18-Fluorodeoxyglucose (FDG) and Carbon-11-Methionine (Met) tracers. We performed two PET studies before and after treatment in 4 patients with brain abscess. PET showed the uptake of both tracers to thebrain abscess before treatment. The area showing an increased uptake of Met corresponded closely to the enhanced area on both CT and MR images. FDG-PET visually showed an uptake of FDG in a small area corresponding to an enhanced lesion within the CT and MR images. After treatment the area of lesions became small on enhancement CT or MRI and both PET studies showed reduced lesion and decreased uptake. The mechanism of Met uptake in the inflammatory area may be related to the higher metabolic rate and the active transport of amino acids as well as disruption of the blood brain barrier. Furthermore, it appears that the mechanism of FDG uptake is also related to a higher metabolic rate and, in addition, is related to the increased density of inflammatory cells. PET studies, more directly, reflect the degree of inflammatory response in brain abscess than enhancement CT or MRI. Therefore, PET is useful in detecting the inflammatory lesion and assessing the clinical effects of antibiotics treatment on brain abscesses
AD  - Department of Neurosurgery, Osaka City University Medical School, Abeno, Japan. nao@med.osaka-cu.ac.jp
UR  - PM:12691130
ER  - 

TY  - JOUR
T1  - Neocortical Temporal FDG-PET Hypometabolism Correlates with Temporal Lobe Atrophy in Hippocampal Sclerosis Associated with Microscopic Cortical Dysplasia
A1  - Diehl,B.
A1  - LaPresto,E.
A1  - Najm,I.
A1  - Raja,S.
A1  - Rona,S.
A1  - Babb,T.
A1  - Ying,Z.
A1  - Bingaman,W.
A1  - Luders,H.O.
A1  - Ruggieri,P.
Y1  - 2003/04//
N1  - UI - 22568328
SP  - 559
EP  - 564
JF  - Epilepsia
VL  - 44
IS  - 4
N2  - PURPOSE: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. METHODS: Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. RESULTS: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. CONCLUSIONS: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD
AD  - Departments of Neurology, Neurosurgery, Neurosciences, Molecular and Functional Imaging, and Radiology, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A
UR  - PM:12681005
ER  - 

TY  - JOUR
T1  - Evaluation of the Binding Characteristics of [5-(11)C-methoxy]Donepezil in the Rat Brain for In Vivo Visualization of Acetylcholinesterase
A1  - Funaki,Y.
A1  - Kato,M.
A1  - Iwata,R.
A1  - Sakurai,E.
A1  - Sakurai,E.
A1  - Tashiro,M.
A1  - Ido,T.
A1  - Yanai,K.
Y1  - 2003/02//
N1  - UI - 22573214
SP  - 105
EP  - 112
JA  - J Pharmacol.Sci.
VL  - 91
IS  - 2
N2  - Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [(11)C]donepezil. [5-(11)C-methoxy]Donepezil was synthesized by O-methylation using [(11)C]methyl triflate. The binding of [(11)C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [(11)C]donepezil to AChE in the rat brain. The IC(50) value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the B(max) and K(d) of [(11)C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [(11)C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-(11)C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography
AD  - Cyclotron and Radioisotope Center, Tohoku University
UR  - PM:12686754
ER  - 

TY  - JOUR
T1  - A functional neuroanatomy of tics in Tourette syndrome
A1  - Stern,E.
A1  - Silbersweig,D.A.
A1  - Chee,K.Y.
A1  - Holmes,A.
A1  - Robertson,M.M.
A1  - Trimble,M.
A1  - Frith,C.D.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 2000/08//
SP  - 741
EP  - 748
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 57
IS  - 8
N2  - BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748
AD  - Functional Neuroimaging Laboratory, Department of Psychiatry, Box 140, Room 1304, Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021, USA
UR  - PM:10920461
ER  - 

TY  - JOUR
T1  - D2 receptor binding in dopa-responsive dystonia
A1  - Kunig,G.
A1  - Leenders,K.L.
A1  - Antonini,A.
A1  - Vontobel,P.
A1  - Weindl,A.
A1  - Meinck,H.M.
Y1  - 1998/11//
SP  - 758
EP  - 762
JA  - Ann.Neurol
VL  - 44
IS  - 5
N2  - We have studied dopamine D2 receptor binding by [11C]raclopride positron emission tomography in 14 patients with dopa-responsive dystonia (DRD). Data were compared with 16 levodopa-treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [11C]raclopride binding index in the putamen and caudate nucleus of DRD patients compared with controls as well as a significant elevation in the caudate nucleus compared with PD patients. The increase of [11C]raclopride binding may be interpreted either as reduced tracer displacement by endogenous dopamine, or as an alteration of the receptor features due to chronic dopamine deficiency. The difference in [11C]raclopride binding in DRD and PD patients in the caudate nucleus suggests that this structure may be of pathophysiological relevance in the presentation of the clinical features of both diseases
AD  - PET Program, Paul Scherrer Institute, Villigen, Germany
UR  - PM:9818931
ER  - 

TY  - JOUR
T1  - Reversible chorea in primary antiphospholipid syndrome
A1  - Sunden-Cullberg,J.
A1  - Tedroff,J.
A1  - Aquilonius,S.M.
Y1  - 1998/01//
N1  - UI - 98112719
SP  - 147
EP  - 149
JA  - Mov Disord.
VL  - 13
IS  - 1
N2  - A 20-year-old woman with acute chorea induced by primary antiphospholipid syndrome was studied by using fluorodeoxyglucose and positron emission tomography (PET). PET sessions were conducted during an episode of severe chorea and after recovery. The symptoms predominantly affected the right side of her face and body, and PET demonstrated a corresponding increase in lentiform and caudate nucleus metabolism prevailing on the left side. After recovery, PET showed normal values in the regions previously studied. This study adds further evidence to support the theory that acute choreas are somehow the result of striatal hypermetabolism
AD  - Department of Neurology, University Hospital, Uppsala, Sweden
UR  - PM:9452340
ER  - 

TY  - JOUR
T1  - Cerebral hypoperfusion and hypometabolism with altered striatal signal intensity in chorea-acanthocytosis: a combined PET and MRI study
A1  - Tanaka,M.
A1  - Hirai,S.
A1  - Kondo,S.
A1  - Sun,X.
A1  - Nakagawa,T.
A1  - Tanaka,S.
A1  - Hayashi,K.
A1  - Okamoto,K.
Y1  - 1998/01//
N1  - UI - 98112713
SP  - 100
EP  - 107
JA  - Mov Disord.
VL  - 13
IS  - 1
N2  - We studied cerebral perfusion and oxygen metabolism in three patients with chorea-acanthocytosis using positron-emission tomography and oxygen-15 labeled O2 and CO2. High-field magnetic resonance imaging also was performed. Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were significantly reduced in the caudate and putamen when compared with seven control subjects. Mild but significant reductions of rCBF (lower than the normal control values -2 SD) were found in the bilateral frontal, left temporal and parietal, and bilateral thalamic areas; rCMRO2 was reduced in the bilateral frontal and left temporal areas. Magnetic resonance imaging showed increased signal intensity accompanied by scattered bright spots in the caudate head and putamen on T2-weighted images; decreased signal intensity was shown at these sites on T1-weighted images. These findings were not observed in 10 neurologically normal volunteers and are rare in the common hyperkinetic form of Huntington's disease. Reduced cerebral perfusion and oxygen metabolism seem to be related to the intellectual and personality changes that occur in chorea-acanthocytosis. Combined positron-emission tomography and magnetic resonance imaging studies may improve diagnostic accuracy in patients with chorea-acanthocytosis and related disorders
AD  - Department of Neurology, Gumma University, Faculty of Medicine, Maebashi, Japan
UR  - PM:9452334
ER  - 

TY  - JOUR
T1  - Decreased [18F]spiperone binding in putamen in idiopathic focal dystonia
A1  - Perlmutter,J.S.
A1  - Stambuk,M.K.
A1  - Markham,J.
A1  - Black,K.J.
A1  - McGee-Minnich,L.
A1  - Jankovic,J.
A1  - Moerlein,S.M.
Y1  - 1997/01/15/
SP  - 843
EP  - 850
JA  - J Neurosci.
VL  - 17
IS  - 2
N2  - In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [18F]spiperone in arterial blood. A stereotactic method of localization, independent of the appearance of the images, was used to identify the putamen in all of the PET images. We analyzed the PET and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the radioligand. An index of binding called the combined forward rate constant was decreased by 29% in dystonics, as compared with normals (p < 0.05). There were no significant differences between dystonics and normals in regional blood flow, blood volume, nonspecific binding, permeability-surface area product of [18F]spiperone or the dissociation rate constant. These findings are consistent with a decrease of dopamine D2-like binding in putamen and are the first demonstration of a receptor abnormality in idiopathic dystonia. These results have important implications for the pathophysiology of dystonia as well as for function of the basal ganglia
AD  - Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
UR  - PM:8987805
ER  - 

TY  - JOUR
T1  - The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study
A1  - Boecker,H.
A1  - Wills,A.J.
A1  - Ceballos-Baumann,A.
A1  - Samuel,M.
A1  - Thompson,P.D.
A1  - Findley,L.J.
A1  - Brooks,D.J.
Y1  - 1996/05//
N1  - UI - 96202578
SP  - 650
EP  - 658
JA  - Ann.Neurol
VL  - 39
IS  - 5
N2  - We used H2 15O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol-responsive essential tremor and 6 age-matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 +/- 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 +/- 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol-associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol-induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei
AD  - Medical Research Council (MRC) Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:8619551
ER  - 

TY  - JOUR
T1  - A positron emission tomography study of primary orthostatic tremor
A1  - Wills,A.J.
A1  - Thompson,P.D.
A1  - Findley,L.J.
A1  - Brooks,D.J.
Y1  - 1996/03//
N1  - UI - 96173685
SP  - 747
EP  - 752
JF  - Neurology
VL  - 46
IS  - 3
N2  - Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:8618676
ER  - 

TY  - JOUR
T1  - Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism
A1  - Grond,M.
A1  - Pawlik,G.
A1  - Walter,H.
A1  - Lesch,O.M.
A1  - Heiss,W.D.
Y1  - 1995/09/29/
SP  - 173
EP  - 179
JA  - Psychiatry Res.
VL  - 61
IS  - 3
N2  - In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce
AD  - Max-Planck-Institut fur neurologische Forschung, Cologne, Germany
UR  - PM:8545501
ER  - 

TY  - JOUR
T1  - Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia
A1  - Ceballos-Baumann,A.O.
A1  - Passingham,R.E.
A1  - Warner,T.
A1  - Playford,E.D.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1995/03//
N1  - UI - 95209274
SP  - 363
EP  - 372
JA  - Ann.Neurol
VL  - 37
IS  - 3
N2  - Regional cerebral blood flow was measured using H2(15)O and positron emission tomography in a group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striatofrontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients
AD  - Medical Research Council (MRC) Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:7695236
ER  - 

TY  - JOUR
T1  - Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study
A1  - Wills,A.J.
A1  - Jenkins,I.H.
A1  - Thompson,P.D.
A1  - Findley,L.J.
A1  - Brooks,D.J.
Y1  - 1994/10//
N1  - UI - 95030960
SP  - 636
EP  - 642
JA  - Ann.Neurol
VL  - 36
IS  - 4
N2  - There has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We used positron emission tomography with radioactive water (H2(15)O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30-40%) but no increased olivary activity was evident. Essential tremor during arm extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:7944296
ER  - 

TY  - JOUR
T1  - Different patterns of [18F]dopa uptake in siblings with hereditary dentato-rubro-pallido-luysian atrophy
A1  - Minami,T.
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Nomura,A.
A1  - Ueda,K.
Y1  - 1994/07//
N1  - UI - 95117795
SP  - 335
EP  - 338
JA  - Brain Dev.
VL  - 16
IS  - 4
N2  - Striatal glucose metabolism and [18F]dopa uptake were studied by positron emission tomography (PET) in two siblings with hereditary dentato-rubro-pallido-luysian atrophy (HDRPLA). The regional cerebral metabolic rate of glucose showed marked decreases in the cerebellum and brainstem in both cases. The elder brother, who had trunk titubation and intention tremor of extremities, showed decreased [18F]dopa uptake in the striatum. On the other hand, the younger brother, who had spontaneous myoclonus of the right shoulder and flank, showed increased [18F]dopa uptake in the striatum. These findings suggested that the wide variety of clinical symptoms of HDRPLA observed within a single family is closely related to the various neuronal dysfunctions at the neurotransmitter level
AD  - Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:7818032
ER  - 

TY  - JOUR
T1  - Biochemical and fluorodopa positron emission tomographic findings in an asymptomatic carrier of the gene for dopa-responsive dystonia
A1  - Takahashi,H.
A1  - Levine,R.A.
A1  - Galloway,M.P.
A1  - Snow,B.J.
A1  - Calne,D.B.
A1  - Nygaard,T.G.
Y1  - 1994/03//
N1  - UI - 94168439
SP  - 354
EP  - 356
JA  - Ann.Neurol
VL  - 35
IS  - 3
N2  - We report cerebrospinal fluid monoamine metabolite analyses and 6-[18F]fluoro-1-dopa positron emission tomography (FD-PET) from an asymptomatic carrier of the gene for dopa-responsive dystonia. Cerebrospinal fluid homovanillic acid, tetrahydrobiopterin, and neopterin concentrations were reduced in this man and in his affected children. His FD-PET was normal, as we have previously found in dopa-responsive dystonia. Neurological function and FD-PET may be normal despite marked abnormality in dopamine metabolism
AD  - Neurodegenerative Disorder Center, University of British Columbia, Vancouver, Canada
UR  - PM:8122887
ER  - 

TY  - JOUR
T1  - A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections
A1  - Jenkins,I.H.
A1  - Bain,P.G.
A1  - Colebatch,J.G.
A1  - Thompson,P.D.
A1  - Findley,L.J.
A1  - Frackowiak,R.S.
A1  - Marsden,C.D.
A1  - Brooks,D.J.
Y1  - 1993/07//
N1  - UI - 93297909
SP  - 82
EP  - 90
JA  - Ann.Neurol
VL  - 34
IS  - 1
N2  - The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor
AD  - Medical Research Council (MRC) Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
UR  - PM:8517685
ER  - 

TY  - JOUR
T1  - Reversible striatal hypermetabolism in a case of Sydenham's chorea
A1  - Goldman,S.
A1  - Amrom,D.
A1  - Szliwowski,H.B.
A1  - Detemmerman,D.
A1  - Goldman,S.
A1  - Bidaut,L.M.
A1  - Stanus,E.
A1  - Luxen,A.
Y1  - 1993/07//
N1  - UI - 93341526
SP  - 355
EP  - 358
JA  - Mov Disord.
VL  - 8
IS  - 3
N2  - We studied a 10-year-old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction
AD  - PET/Biomedical Cyclotron Unit, Universite Libre de Bruxelles-Hopital Erasme, Belgium
UR  - PM:8341301
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism and striatal 18F-dopa uptake by PET in cases of chorea with or without dementia
A1  - Otsuka,M.
A1  - Ichiya,Y.
A1  - Kuwabara,Y.
A1  - Hosokawa,S.
A1  - Sasaki,M.
A1  - Fukumura,T.
A1  - Masuda,K.
A1  - Goto,I.
A1  - Kato,M.
Y1  - 1993/04//
SP  - 153
EP  - 157
JA  - J Neurol Sci.
VL  - 115
IS  - 2
N2  - Cerebral glucose metabolism was studied by positron emission tomography with [18F]fluorodeoxyglucose in 12 patients with chorea due to different underlying diseases. The striatal 18F-dopa uptake was also studied with 6-L-[18F]fluorodopa in 6 of them. Five of them were diagnosed as Huntington's disease two were as 'sporadic progressive chorea and dementia' with characteristic symptoms and signs of Huntington's disease but no family histories, two were as choreoacanthocytosis, and two had hemichorea caused by suspected vascular lesions in the contralateral striatum revealed by MRI. Caudate and putaminal glucose metabolism decreased in chorea compared to the controls. Hemichorea showed decreased glucose metabolism only in the contralateral striatum. Moreover the glucose metabolism decreased in demented each 7 patients in the frontal, temporal and parietal cortices as well as in the striatum. The caudate and putaminal 18F-dopa uptake in patients with chorea showed no difference with that in the controls. The pathogenetic mechanism of chorea may involve decreased glucose metabolism and normal presynaptic dopaminergic activity in the striatum, and that of the demented state in chorea may also involve an additional decrease of the glucose metabolism in the frontal, temporal and parietal cortices
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:8482976
ER  - 

TY  - JOUR
T1  - Glucose metabolism in the brain of patients with essential tremor
A1  - Hallett,M.
A1  - Dubinsky,R.M.
Y1  - 1993/01//
N1  - UI - 93163798
SP  - 45
EP  - 48
JA  - J Neurol Sci.
VL  - 114
IS  - 1
N2  - Using positron emission tomography with [18F]fluoro-2-deoxyglucose, we determined the regional cerebral metabolic rate of glucose utilization at rest in 8 medication-free patients with essential tremor and in 10 normal subjects. Taking the metabolic values of regions of interest as ratios to the mean hemispheric metabolism, the patients showed significant glucose hypermetabolism of the medulla and thalami, but not of the cerebellar cortex. This study lends support to earlier suggestions that circuits involving the inferior olivary nuclei in the medulla and the thalmus are involved in the generation of essential tremor
AD  - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
UR  - PM:8433096
ER  - 

TY  - JOUR
T1  - Crossed cerebellar diaschisis accompanied by hemiataxia: a PET study
A1  - Tanaka,M.
A1  - Kondo,S.
A1  - Hirai,S.
A1  - Ishiguro,K.
A1  - Ishihara,T.
A1  - Morimatsu,M.
Y1  - 1992/02//
N1  - UI - 92166835
SP  - 121
EP  - 125
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 55
IS  - 2
N2  - To study crossed cerebellar diaschisis (CCD), cerebellar blood flow and oxygen metabolism were measured with positron emission tomography (PET) in 12 patients who showed a minimal degree of hemiparesis due to single unilateral supratentorial lesion. Six patients presenting with mild to moderate cerebellar type hemiataxia showed CCD, that is, decreased blood flow and oxygen metabolism in the cerebellar hemisphere contralateral to the side of supratentorial lesion. Hemiataxia and reduced cerebellar blood flow and metabolism occurred in the ipsilateral side. Lesions were located in the thalamus in four patients and the parietal lobe and internal capsule in one each. The other six patients did not exhibit ataxia, and oxygen metabolism was not reduced in the contralateral cerebellar hemisphere. In two of these cases, however, reduced cerebellar perfusion was observed in the contralateral cerebellar hemisphere. These findings indicate that CCD occurs with hemiataxia and suggest that it results not only from disruption of the corticopontocerebellar pathway but also of the dentatorubrothalamic pathway. CCD associated with hemiataxia, demonstrated in patients with thalamic lesions, was presumed to result from retrograde deactivation of the cerebellar hemisphere via the dentatorubrothalamic pathway
AD  - Gunma University School of Medicine, Maebashi, Japan
UR  - PM:1538216
ER  - 

TY  - JOUR
T1  - Selective D1- and D2-dopamine receptor blockade both induces akathisia in humans--a PET study with [11C]SCH 23390 and [11C]raclopride
A1  - Farde,L.
Y1  - 1992///
SP  - 23
EP  - 29
JA  - Psychopharmacology (Berl)
VL  - 107
IS  - 1
N2  - Pharmacological effects were recorded and time course for receptor binding in brain was followed by positron emission tomography after IV injection of the selective D1-dopamine receptor antagonist SCH 23390 in four healthy subjects in doses of 310-810 micrograms. Akathisia, the syndrome of motor restlessness, appeared after the three highest doses. The akathisia was transient and occurred only when [11C]SCH 23390 binding in the basal ganglia was at a high level with a central D1-dopamine receptor occupancy of 45-59%. The D2-dopamine receptor antagonist [11C]raclopride was injected IV into 20 healthy subjects and 13 schizophrenic patients. Akathisia appeared in 14 healthy subjects and 7 patients and coincided with maximal [11C]raclopride binding in the basal ganglia. The findings for [11C]raclopride and [11C]SCH 23390 are the first demonstration of a relationship between time courses for radioligand binding in the human brain and simultaneously induced pharmacological effects
AD  - Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden
UR  - PM:1534178
ER  - 

TY  - JOUR
T1  - Uncoupling of blood flow and oxygen metabolism in the cerebellum in type 3 Gaucher disease
A1  - Yoshikawa,H.
A1  - Fueki,N.
A1  - Sasaki,M.
A1  - Sakuragawa,N.
Y1  - 1991/05//
N1  - UI - 92026758
SP  - 190
EP  - 192
JA  - Brain Dev.
VL  - 13
IS  - 3
N2  - Cerebral blood flow and oxygen metabolism were measured in a fourteen-year-old girl with type 3 Gaucher disease by using positron emission tomography (PET). Cranial CT and MRI showed only mild brain atrophy. PET demonstrated uncoupling of cerebral blood flow and oxygen metabolism, that is, a mild increase of cerebral blood flow and a reduction of oxygen extraction fraction and cerebral metabolic rate of oxygen only in the cerebellum. Although the mechanism is unknown, the above finding may reflect the underlying pathogenesis of the disorder. PET seems to be more sensitive than CT and MRI in detecting some functional abnormalities in the affected structures. However, further investigations must be done before concluding that this finding is unique to type 3 Gaucher disease
AD  - Division of Child Neurology, National Center Hospital for Neurology and Psychiatry, Tokyo, Japan
UR  - PM:1928613
ER  - 

TY  - JOUR
T1  - Clinical and positron emission tomographic studies in the 'extrapyramidal syndrome' of dementia of the Alzheimer type
A1  - Tyrrell,P.J.
A1  - Sawle,G.V.
A1  - Ibanez,V.
A1  - Bloomfield,P.M.
A1  - Leenders,K.L.
A1  - Frackowiak,R.S.
A1  - Rossor,M.N.
Y1  - 1990/12//
N1  - UI - 91069309
SP  - 1318
EP  - 1323
JA  - Arch Neurol
VL  - 47
IS  - 12
N2  - Extrapyramidal signs, particularly rigidity and tremor, have been reported in a proportion of patients with dementia of the Alzheimer type. To test the hypothesis that these extrapyramidal signs are similar clinically and neurochemically to the extrapyramidal signs of Parkinson's disease, a group of 20 patients satisfying clinical criteria for probable Alzheimer's disease were studied and assessed clinically for the presence of rigidity, tremor, and bradykinesia. In those patients with extrapyramidal signs, qualitative differences were observed between the signs in these patients and in subjects with Parkinson's disease. Fifteen of 20 patients underwent fluoro-18-dopa scans, which showed no significant difference in fluoro-18-dopa uptake into the caudate and putamen between normal subjects and the rigid and nonrigid patients with Alzheimer's disease, in contrast to the marked reduction in fluoro-18-dopa uptake into the putamen that is observed in Parkinson's disease. This provides clinical and in vivo neurochemical support for the hypothesis that extranigral factors may be involved in the pathogenesis of rigidity in Alzheimer's disease
AD  - Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:2252449
ER  - 

TY  - JOUR
T1  - Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels
A1  - Teitelbaum,J.S.
A1  - Zatorre,R.J.
A1  - Carpenter,S.
A1  - Gendron,D.
A1  - Evans,A.C.
A1  - Gjedde,A.
A1  - Cashman,N.R.
Y1  - 1990/06/21/
SP  - 1781
EP  - 1787
JF  - The New England Journal of Medicine
JA  - N Engl J Med
VL  - 322
IS  - 25
N2  - In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
UR  - PM:1971710
ER  - 

TY  - JOUR
T1  - PET determination of regional cerebral glucose metabolism in alcohol-dependent men and healthy controls using 11C-glucose
A1  - Wik,G.
A1  - Borg,S.
A1  - Sjogren,I.
A1  - Wiesel,F.A.
A1  - Blomqvist,G.
A1  - Borg,J.
A1  - Greitz,T.
A1  - Nyback,H.
A1  - Sedvall,G.
A1  - Stone-Elander,S.
Y1  - 1988/08//
N1  - UI - 89131792
SP  - 234
EP  - 241
JA  - Acta Psychiatr.Scand.
VL  - 78
IS  - 2
N2  - Regional brain glucose metabolism was determined in 9 male alcohol-dependent inpatients and 12 male healthy controls. All the patients were socially impaired by the alcohol abuse. All the subjects had abstained from alcohol and drugs for more than four weeks before entering the study. Brain glucose metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Regions of interest were drawn on displayed computed tomographic (CT) images of the brain. Regions were transferred to corresponding PET slices, allowing the determination of regional glucose metabolism. In the healthy volunteers there was a reduction in glucose metabolism with age. In 11 of the 19 brain regions examined, the alcoholics had a 20% to 30% lower glucose metabolism than the controls. This was true for both cortical and subcortical structures. The distribution of relative regional metabolic rates indicated that parietal cortical areas were most affected. Atrophic changes as shown by CT were not correlated to the reduced metabolism in the alcohol-dependent patients
AD  - Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden
UR  - PM:2851920
ER  - 

TY  - JOUR
T1  - Positron emission tomography in cases of chorea with different underlying disease
A1  - Lang,A.E.
A1  - Garnett,E.S.
Y1  - 1988/07//
N1  - UI - 89080731
SP  - 1010
EP  - 1011
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 51
IS  - 7
UR  - PM:3264566
ER  - 

TY  - JOUR
T1  - Positron emission tomographic studies of regional cerebral glucose metabolism in idiopathic dystonia
A1  - Chase,T.N.
A1  - Tamminga,C.A.
A1  - Burrows,H.
Y1  - 1988///
N1  - UI - 88291959
SP  - 237
EP  - 241
JA  - Adv.Neurol
VL  - 50
AD  - Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland
UR  - PM:3261115
ER  - 

TY  - JOUR
T1  - Cerebral metabolic activity in idiopathic dystonia studied with positron emission tomography
A1  - Gilman,S.
A1  - Junck,L.
A1  - Young,A.B.
A1  - Hichwa,R.D.
A1  - Markel,D.S.
A1  - Koeppe,R.A.
A1  - Ehrenkaufer,R.L.
Y1  - 1988///
N1  - UI - 88291958
SP  - 231
EP  - 236
JA  - Adv.Neurol
VL  - 50
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109
UR  - PM:3261114
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in SLE chorea: further evidence that striatal hypometabolism is not a correlate of chorea
A1  - Guttman,M.
A1  - Lang,A.E.
A1  - Garnett,E.S.
A1  - Nahmias,C.
A1  - Firnau,G.
A1  - Tyndel,F.J.
A1  - Gordon,A.S.
Y1  - 1987///
N1  - UI - 89070569
SP  - 201
EP  - 210
JA  - Mov Disord.
VL  - 2
IS  - 3
N2  - The pathophysiology of chorea in systemic lupus erythematosus (SLE) is uncertain. Pathologic examination has not identified a specific location for the causative lesion(s) and immunologic mechanisms have been suggested in its etiology. In other choreic disorders, such as Huntington's disease and benign hereditary chorea, glucose hypometabolism in the striatum has been demonstrated by positron computed tomography (PCT) using [18F]deoxyglucose. With this technique we have studied four patients with chorea secondary to SLE. In these patients the regional distribution of cerebral glucose metabolism was normal. In particular, striatal glucose metabolism was within the normal range, even though the ratio of striatal to cortical glucose metabolism was increased. Our results show that striatal hypometabolism, as seen in other disorders manifesting chorea, is not the PCT correlate of the dyskinesia
UR  - PM:3509775
ER  - 

TY  - JOUR
T1  - Pure hemidystonia with basal ganglion abnormalities on positron emission tomography
A1  - Perlmutter,J.S.
A1  - Raichle,M.E.
Y1  - 1984/03//
N1  - UI - 84201628
SP  - 228
EP  - 233
JA  - Ann.Neurol
VL  - 15
IS  - 3
N2  - We present a patient with hemidystonia and an abnormality of the contralateral basal ganglion seen only with positron emission tomography. A 50-year-old sinistral man suffered minor trauma to the right side of his head and neck. Within 20 minutes he developed paroxysmal intermittent dystonic posturing of his right face, forearm, hand, and foot, with weaker contractions of the left foot, lasting several seconds and recurring every few minutes. Neurological findings between spells were normal. The following were also normal: electrolyte, calcium, magnesium, and arterial blood gas levels, and findings of drug screen, cerebrospinal fluid examination, electroencephalography with nasopharyngeal leads, computed tomographic scanning (initially and four weeks later), and cerebral angiography. Positron emission tomographic scanning revealed abnormalities in the left basal ganglion region, including decreased oxygen metabolism, decreased oxygen extraction, increased blood volume, and increased blood flow
UR  - PM:6609680
ER  - 

TY  - JOUR
T1  - Consolidation of common parameters from multiple fits in dynamic PET data analysis
A1  - Huesman,R.H.
A1  - Coxson,P.G.
Y1  - 1997/10//
N1  - UI - 98034484
SP  - 675
EP  - 683
JA  - IEEE Trans.Med Imaging
VL  - 16
IS  - 5
N2  - In dynamic positron emission tomography (PET) data analysis, regions of interest (ROI's) are analyzed by fitting a parametric model to the time-activity curve acquired after a radio-labeled tracer has been introduced into the patient's bloodstream. This procedure can be carried out for multiple ROI's and/or multiple injections of the same or a different radiopharmaceutical. The approach presented here takes advantage of prior knowledge that some of the parameters of those multiple fits are the same. Reduction of the total number of parameters to be estimated results in smaller statistical uncertainty for all parameter estimates, especially those common to multiple fits
UR  - PM:9368123
ER  - 

TY  - JOUR
T1  - Spectral analysis of dynamic PET studies
A1  - Cunningham,V.J.
A1  - Jones,T.
Y1  - 1993/01//
N1  - UI - 93107227
SP  - 15
EP  - 23
JA  - J Cereb.Blood Flow Metab
VL  - 13
IS  - 1
N2  - We describe a new technique for the analysis of dynamic positron emission tomography (PET) studies in humans, where data consist of the time courses of label in tissue regions of interest and in arterial blood, following the administration of radiolabelled tracers. The technique produces a simple spectrum of the kinetic components which relate the tissue's response to the blood activity curve. From this summary of the kinetic components, the tissue's unit impulse response can be derived. The convolution of the arterial input function with the derived unit impulse response function gives the curve of best fit to the observed tissue data. The analysis makes no a priori assumptions regarding the number of compartments or components required to describe the time course of label in the tissue. Rather, it is based on a general linear model, presented here in a formulation compatible with its solution using standard computer algorithms. Its application is illustrated with reference to cerebral blood flow, glucose utilization, and ligand binding. The interpretation of the spectra, and of the tissue unit impulse response functions, are discussed in terms of vascular components, unidirectional clearance of tracer by the tissue, and reversible and irreversible phenomena. The significance of the number of components which can be identified within a given datum set is also discussed. The technique facilitates the interpretation of dynamic PET data and simplifies comparisons between regions and between subjects
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:8417003
ER  - 

TY  - JOUR
T1  - Simultaneous estimation of physiological parameters and the input function--in vivo PET data
A1  - Wong,K.P.
A1  - Feng,D.
A1  - Meikle,S.R.
A1  - Fulham,M.J.
Y1  - 2001/03//
N1  - UI - 21193489
SP  - 67
EP  - 76
JA  - IEEE Trans.Inf.Technol.Biomed.
VL  - 5
IS  - 1
N2  - Dynamic imaging with positron emission tomography (PET) is widely used for the in vivo measurement of regional cerebral metabolic rate for glucose (rCMRGlc) with [18F]fluorodeoxy-D-glucose (FDG) and is used for the clinical evaluation of neurological disease. However, in addition to the acquisition of dynamic images, continuous arterial blood sampling is the conventional method to obtain the tracer time-activity curve in blood (or plasma) for the numeric estimation of rCMRGlc in mg glucose/100-g tissue/min. The insertion of arterial lines and the subsequent collection and processing of multiple blood samples are impractical for clinical PET studies because it is invasive, has the remote, but real potential for producing limb ischemia, and it exposes personnel to additional radiation and risks associated with handling blood. In this paper, based on our previously proposed method for extracting kinetic parameters from dynamic PET images, we developed a modified version (post-estimation method) to improve the numerical identifiability of the parameter estimates when we deal with data obtained from clinical studies. We applied both methods to dynamic neurologic FDG PET studies in three adults. We found that the input function and parameter estimates obtained with our noninvasive methods agreed well with those estimated from the gold standard method of arterial blood sampling and that rCMRGlc estimates were highly correlated (r = 0.973). More importantly, no significant difference was found between rCMRGlc estimated by our methods and the gold standard method (P > 0.16). We suggest that our proposed noninvasive methods may offer an advance over existing methods
AD  - Department of Electronic and Information Engineering, The Hong Kong Polytechnic University, Hong Kong. kpong@cs.usyd.edu.au
UR  - PM:11300218
ER  - 

TY  - JOUR
T1  - Mild cognitive impairment: Can FDG-PET predict who is to rapidly convert to Alzheimer's disease?
A1  - Chetelat,G.
A1  - Desgranges,B.
A1  - de,la Sayette,V
A1  - Viader,F.
A1  - Eustache,F.
A1  - Baron,J.C.
Y1  - 2003/04/22/
N1  - UI - 22593670
SP  - 1374
EP  - 1377
JF  - Neurology
VL  - 60
IS  - 8
N2  - Patients with mild cognitive impairment (MCI) were assessed, and a metabolic profile associated with conversion to AD at 18-month follow- up was sought. As compared with nonconverters (n = 10), converters (n = 7) had lower fluorodeoxyglucose uptake in the right temporoparietal cortex (p = 0.02, corrected for cluster size), without individual overlap. Awaiting replication in an independent sample, these findings suggest that among patients with MCI, fluorodeoxyglucose PET may accurately identify rapid converters
AD  - INSERM EO 218 (Drs. Chetelat, Desgranges, de la Sayette, Viader, and Eustache), University of Caen, Cyceron PET Center, France
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Chetelat-MCI-PET.pdf
ER  - 

TY  - JOUR
T1  - Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy
A1  - Schaafsma,A.
A1  - de Jong,B.M.
A1  - Bams,J.L.
A1  - Haaxma-Reiche,H.
A1  - Pruim,J.
A1  - Zijlstra,J.G.
Y1  - 2003/06/15/
SP  - 23
EP  - 30
JF  - Journal of the Neurological Sciences
VL  - 210
IS  - 1-2
N2  - Positron emission tomography (PET) was used for the study of regional cerebral perfusion and metabolism in eight patients with severe post-hypoxic encephalopathy, caused by cardiac arrest and resulting in a coma lasting for at least 24 h. Using this method, we aimed to identify regional vulnerability, which was hypothesized to provide (i) insight in pathogenic mechanisms and (ii) early prognostic parameters. On day 1 post-resuscitation, 18-Fluor deoxyglucose ([F18]-FDG) indicated a marked decrease of cerebral metabolic activity. Gray matter glucose consumption was 54% of normal values, whereas white matter uptake was 70% of normal. Regional differences followed a pattern of neuronal density rather than specific patterns of functionally or biochemically defined regions or of vascular territories. In contrast to [F18]-FDG, the distribution of 15-oxygen labeled water ([O-15]-water) showed a better demarcation between gray and white matter, whereas focal deficit was not observed. In some patients, hyperperfusion relative to regional glucose consumption was observed in the occipital poles and basal ganglia. This suggests loss of vascular tone, i.e. vascular paralysis, in the basilar artery territory. CT and MRI scanning did not show any major change with respect to the hypoxic injury. In the small group studied, all patients had a poor outcome. The comparison between survivors and nonsurvivors did not reveal obvious differences in PET data, suggesting that this technique does not provide major prognostic clues adding to the prognostic information derived from serial neurological assessment in the restricted patient group characterized by prolonged coma
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Schaafsma-hypoxic-encephalopathy.pdf
ER  - 

TY  - JOUR
T1  - 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337
A1  - Wells,P.
A1  - Aboagye,E.
A1  - Gunn,R.N.
A1  - Osman,S.
A1  - Boddy,A.V.
A1  - Taylor,G.A.
A1  - Rafi,I.
A1  - Hughes,A.N.
A1  - Calvert,A.H.
A1  - Price,P.M.
A1  - Newell,D.R.
Y1  - 2003/05/07/
N1  - UI - 22620067
SP  - 675
EP  - 682
JA  - J Natl.Cancer Inst.
VL  - 95
IS  - 9
N2  - BACKGROUND: Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans. METHODS: Five patients with advanced gastrointestinal cancer were PET scanned both before and 1 hour after oral administration of the TS inhibitor AG337 (THYMITAQ [nolatrexed]); seven control patients were scanned twice but not treated with AG337. Thymidine salvage kinetics were measured in vivo using 2-[11C]thymidine PET and spectral analysis to obtain the standardized uptake values (SUV), the area under the time-activity curve (AUC), and the fractional retention of thymidine (FRT). Changes in PET parameters between scans in the AG337-treated and control groups were compared using the Mann-Whitney U test. The relationship between AG337 exposure and AG337-induced changes in tumor FRT and in plasma deoxyuridine levels (a conventional pharmacodynamic systemic measure of TS inhibition) was examined using Spearman's regression analysis. Statistical tests were two-sided. RESULTS: The between-scan change in FRT in patients treated with AG337 (38% increase, 95% confidence interval [CI] = 8% to 68%) was higher than that in control patients (3% increase, 95% CI = -11% to 17%) (P =.028). The level of AG337-induced increase in both 2-[11C]thymidine FRT and plasma deoxyuridine levels was statistically significantly correlated with AG337 exposure (r = 1.00, P =.01 for both). CONCLUSIONS: AG337 administration was associated with increased tumor tracer retention that was consistent with tumor cell uptake of exogenous 2-[11C]thymidine as a result of TS inhibition. 2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest
AD  - Imperial College School of Medicine, Hammersmith Hospital, London, UK
UR  - PM:12734319
ER  - 

TY  - JOUR
T1  - Endogenous dopamine release after pharmacological challenges in Parkinson's disease
A1  - Piccini,P.
A1  - Pavese,N.
A1  - Brooks,D.J.
Y1  - 2003/05//
N1  - UI - 22615152
SP  - 647
EP  - 653
JA  - Ann.Neurol
VL  - 53
IS  - 5
N2  - Using (11)C-raclopride positron emission tomography after methamphetamine challenge, we have evaluated regional brain changes in synaptic dopamine (DA) levels in six volunteers and six advanced Parkinson's disease (PD) patients. The pharmacological challenge induced significant release of endogenous DA in putamen not only in the normal subjects, as reflected by a 25.2% reduction in (11)C-raclopride binding potential as compared with placebo, but also in the PD patients (6.8%). In individual PD patients, we found a correlation between putamen DA release and DA storage, as measured by (18)F-dopa uptake. Localization of significant changes in (11)C-raclopride binding after methamphetamine at a voxel level with statistical parametric mapping identified striatal and prefrontal DA release in both cohorts. Statistical comparisons between normal subjects and PD confirmed significantly reduced DA release in striatal areas in PD, but normal levels of prefrontal DA release. In conclusion, significant endogenous DA release can still be induced by pharmacological challenges in the putamen of advanced PD patients, and this release correlates with residual DA storage capacity. Our data also show that the capacity to release normal DA levels in prefrontal areas after a pharmacological challenge is preserved in severe stages of the disease. Ann Neurol 2003
AD  - MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Piccini-dopamine-release.pdf
ER  - 

TY  - JOUR
T1  - Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice
A1  - De,A.
A1  - Lewis,X.Z.
A1  - Gambhir,S.S.
Y1  - 2003/05//
N1  - UI - 22605573
SP  - 681
EP  - 691
JA  - Mol.Ther.
VL  - 7
IS  - 5
N2  - Lentiviral-mediated gene delivery holds significant promise for sustained gene expression within living systems. Vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 1-based lentiviral vectors can be used to introduce transgenes in a broad spectrum of dividing as well as nondividing cells. In the current study, we construct a lentiviral vector carrying two reporter genes separated by an internal ribosomal entry site and utilize that virus in delivering both genes into neuroblastoma cells in cell culture and into cells implanted in living mice. We utilize two reporter genes, a mutant herpes simplex virus type 1 (HSV1) sr39tk as a reporter gene compatible with positron emission tomography (PET) and a bioluminescent optical reporter gene, firefly luciferase (Fluc), to image expression in living mice by an optical charge-coupled device (CCD) camera. By using this lentivirus, neuroblastoma (N2a) cells are stably transfected and a high correlation (R(2) = 0.91) between expressions of the two reporter genes in cell culture is established. Imaging of both reporter genes using microPET and optical CCD camera in living mice is feasible, with the optical approach being more sensitive, and a high correlation (R(2) = 0.86) between gene expressions is again observed in lentiviral-infected N2a tumor xenografts. Indirect imaging of HSV1-sr39tk suicide gene therapy utilizing Fluc is also feasible and can be detected with increased sensitivity by using the optical CCD. These preliminary results validate the use of lentiviral vectors carrying reporter genes for multimodality imaging of gene expression and should have many applications, including imaging of xenografts, metastasis, and cell trafficking as well as noninvasive monitoring of lentiviral-mediated gene delivery and expression
AD  - The Crump Institute for Molecular Imaging, 90095-1770, Los Angeles, California, USA
UR  - PM:12718911
ER  - 

TY  - JOUR
T1  - The use of PET and knockout mice in the drug discovery process
A1  - Eckelman,W.C.
Y1  - 2003/05/01/
N1  - UI - 22592789
SP  - 404
EP  - 410
JA  - Drug Discov.Today
VL  - 8
IS  - 9
N2  - Although [15O]H(2)O, 2-[18F]fluoro-2-deoxyglucose (FDG) and other radioligands for low-density receptors and enzymes have been used in drug discovery and drug development, the impact on the pharmaceutical industry, to date, has been anecdotal. As new chemical entities are developed, radiotracers that aid in characterizing these drugs need to be developed rapidly to have an impact on the development process. The combined use of positron emission tomography (PET) and gene-manipulated animal models to validate radioligands quickly holds great promise for accelerating the discovery process
AD  - Warren G. Magnuson Clinical Center, National Institutes of Health, 10 Center Drive, 1C495, 20892, Bethesda, MD, USA
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Eckelman-PET-drugs.pdf
ER  - 

TY  - JOUR
T1  - Regional brain uptake of the muscarinic ligand, [(18)F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice
A1  - Jagoda,E.M.
A1  - Kiesewetter,D.O.
A1  - Shimoji,K.
A1  - Ravasi,L.
A1  - Yamada,M.
A1  - Gomeza,J.
A1  - Wess,J.
A1  - Eckelman,W.C.
Y1  - 2003/04//
N1  - UI - 22555374
SP  - 653
EP  - 661
JF  - Neuropharmacology
VL  - 44
IS  - 5
N2  - A muscarinic receptor radioligand, 3-(3-(3-fluoropropyl)thio) -1,2,5,thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (fP-TZTP) radiolabeled with the positron emitting radionuclide (18)F ([(18)F]FP-TZTP) displayed regional brain distribution consistent with M2 receptor densities in rat brain. The purpose of the present study is to further elucidate the subtype selectivity of [(18)F]FP-TZTP using genetically engineered mice which lacked functional M1, M2, M3, or M4 muscarinic receptors. Using ex vivo autoradiography, the regional brain localization of [(18)F]FP-TZTP in M2 knockout (M2 KO) was significantly decreased (51.3 to 61.4%; P<0.01) when compared to the wild-type (WT) mice in amygdala, brain stem, caudate putamen, cerebellum, cortex, hippocampus, hypothalamus, superior colliculus, and thalamus. In similar studies with M1KO, M3KO and M4KO compared to their WT mice, [(18)F]FP-TZTP uptakes in the same brain regions were not significantly decreased at P<0.01. However, in amygdala and hippocampus small decreases of 19.5% and 22.7%, respectively, were observed for M1KO vs WT mice at P<0.05. Given the fact that large decreases in [(18)F]FP-TZTP brain uptakes were seen only in M2 KO vs. WT mice, we conclude that [(18)F]FP-TZTP preferentially labels M2 receptors in vivo
AD  - PET Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, 20892, Bethesda, MD, USA
UR  - PM:12668051
ER  - 

TY  - JOUR
T1  - PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy
A1  - Toczek,M.T.
A1  - Carson,R.E.
A1  - Lang,L.
A1  - Ma,Y.
A1  - Spanaki,M.V.
A1  - Der,M.G.
A1  - Fazilat,S.
A1  - Kopylev,L.
A1  - Herscovitch,P.
A1  - Eckelman,W.C.
A1  - Theodore,W.H.
Y1  - 2003/03/11/
N1  - UI - 22516571
SP  - 749
EP  - 756
JF  - Neurology
VL  - 60
IS  - 5
N2  - BACKGROUND: Activation of central serotonin (5-HT)1A receptors, found in high density in brainstem raphe, hippocampus, and temporal neocortex, exerts an anticonvulsant effect in various experimental seizure models. To test the hypothesis that 5-HT1A receptor binding is reduced in human epileptic foci, PET imaging was performed using the radioligand [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyr idyl)cyclohexanecarboxamide ([18F]FCWAY), a selective 5-HT1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls. METHODS: MRI and PET were performed using [15O]water and [18F]FCWAY in 10 controls and in 12 patients with temporal lobe epilepsy confirmed on ictal video-EEG; patients also underwent [18F]fluorodeoxyglucose PET. Using quantitative PET image analysis, regional values were obtained for [18F]FCWAY volume of distribution (V), cerebral blood flow (CBF), and glucose cerebral metabolic rate (CMRglc). Hippocampal volume (HV) was also measured with MRI. [18F]FCWAY V PET and MR measures were compared within patients and controls using paired t-tests; grouped comparisons were made with two sample t-tests. RESULTS: Lower [18F]FCWAY V was found ipsilateral than contralateral to the epileptic focus in inferior medial (IMT) and lateral (ILT) temporal regions of patients (ILT 47.4 +/- 6.1 vs 61.8 +/- 6.1, p < 0.01; IMT 52 +/- 4.6 vs 67.0 +/- 6.0, p < 0.01). [18F]FCWAY V was 29% lower in raphe and 34% lower in the ipsilateral thalamic region of patients than controls. In ILT, mean [18F]FCWAY V asymmetry index (AI) was significantly greater than mean CBF and mean CMRglc AI. Mean [18F]FCWAY V AI in IMT was greater than mean HV AI, but the difference was not significant. CONCLUSION: These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci
AD  - Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, Warren Grant Magnuson Clinical Center, NIH, Bethesda, MD 20892-1408, USA
UR  - PM:12629228
ER  - 

TY  - JOUR
T1  - Biodistribution and radiation dosimetry of (18)f-fluoro-a-85380 in healthy volunteers
A1  - Bottlaender,M.
A1  - Valette,H.
A1  - Roumenov,D.
A1  - Dolle,F.
A1  - Coulon,C.
A1  - Ottaviani,M.
A1  - Hinnen,F.
A1  - Ricard,M.
Y1  - 2003/04//
N1  - UI - 22566226
SP  - 596
EP  - 601
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 4
N2  - This study reports on the biodistribution and radiation dosimetry of 2-(18)F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ((18)F-fluoro-A-85380), a promising radioligand for the imaging of central nicotinic acetylcholine receptors (nAChRs). METHODS: Whole-body scans were performed in 3 healthy male volunteers up to 2 h after intravenous injection of 137-238 MBq (18)F-fluoro-A-85380. Transmission scans (3 min per step, 8 or 9 steps according to the height of the subject) in 2-dimensional mode were used for subsequent correction of attenuation of emission scans. Emission scans (1 min per step) were acquired over 2 h. Venous blood samples were taken up to 2 h after injection of the radiotracer. Urine was freely collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, stomach, bladder, kidneys, and liver were fitted to a monoexponential model, as an uptake phase followed by a monoexponential washout, or to a biexponential model to generate time-activity curves. Using the MIRD method, ten source organs were considered in estimating radiation absorbed doses for organs of the body. RESULTS: Injection of (18)F-fluoro-A-85380 was clinically well tolerated and blood and urine pharmacologic parameters did not change significantly. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the bladder, kidneys, and liver. Slow uptake was seen in the brain. The liver received the highest absorbed dose. The average effective dose of (18)F-fluoro-A-85380 was estimated to be 0.0194 mSv/MBq. CONCLUSION: The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient
AD  - Service Hospitalier Frederic Joliot, Department of Medical Research, Division of Life Sciences, French Atomic Agency, Orsay, France. Service de Physique, Institut Gustave Roussy, Villejuif, France
UR  - PM:12679405
ER  - 

TY  - JOUR
T1  - Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [11C]Befloxatone
A1  - Bottlaender,M.
A1  - Dolle,F.
A1  - Guenther,I.
A1  - Roumenov,D.
A1  - Fuseau,C.
A1  - Bramoulle,Y.
A1  - Curet,O.
A1  - Jegham,J.
A1  - Pinquier,J.L.
A1  - George,P.
A1  - Valette,H.
Y1  - 2003/05//
N1  - UI - 22590606
SP  - 467
EP  - 473
JA  - J Pharmacol.Exp.Ther.
VL  - 305
IS  - 2
N2  - Befloxatone is a competitive and reversible inhibitor of monoamine oxidase-A (MAOI-A). The aim of the study was to characterize the in vivo properties of [(11)C]befloxatone and to validate its use as a ligand for the study of MAO-A by positron emission tomography (PET). PET studies were performed in baboons after i.v. injection of [(11)C]befloxatone (551 +/- 70 MBq, i.e.14.9 +/- 1.9 mCi). [(11)C]Befloxatone enters rapidly in the brain with a maximum uptake at 30 min. Brain concentration of the tracer is high in thalamus, striatum, pons and cortical structures (1.5-1.8% of injected dose per 100 ml of tissue), and lower in cerebellum (1.07% injected dose/100 ml). Nonsaturable uptake, obtained after a pretreatment with a high dose of nonlabeled befloxatone (0.4 mg/kg), is very low and represents only 3% of the total uptake. Brain uptake of [(11)C]befloxatone is not altered by a pretreatment of a high dose with lazabemide (0.5 mg/kg i.v.), a selective MAOI-B but is completely blocked by a pretreatment with moclobemide (MAOI-A; 10 mg/kg). This confirms, in vivo, the selectivity of befloxatone for type A MAO. [(11)C]Befloxatone brain radioactivity was displaced by administration of unlabeled befloxatone (30 min after the tracer injection). The displacement of the tracer from its binding sites is dose-dependent, with an ID(50) of 0.02 mg/kg for all studied structures. These results indicate that [(11)C]befloxatone will be an excellent probe for the study of MAO-A in humans using PET
AD  - 4, place du general Leclerc, 91401 Orsay, France. bottlaen@shfj.cea.fr
UR  - PM:12606609
ER  - 

TY  - JOUR
T1  - Measurement of the Global Lumped Constant for 2-Deoxy-2-[18F]Fluoro-D-Glucose in Normal Human Brain Using [15O]Water and 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography Imaging: A Method with Validation Based on Multiple Methodologies
A1  - Wu,Hsiao Ming
A1  - Bergsneider,Marvin
A1  - Glenn,Tom C.
A1  - Yeh,Eric
A1  - Hovda,David A.
A1  - Phelps,Michael E.
A1  - Huang,Sung Cheng
Y1  - 2003///
SP  - 32
EP  - 41
JA  - Molecular Imaging & Biology
VL  - 5
IS  - 1
N2  - PURPOSE: This study aims to determine a lumped constant (LC) value that can be applied to the 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography (FDG-PET) study to yield a physiological value of cerebral metabolic rate of glucose (CMRglc) in normal brain.PROCEDURES: We developed a more robust method for determining the global FDG LC. Dynamic FDG and H215O PET studied were acquired in 18 normal subjects. Arterial-venous difference of blood glucose level was measured.RESULTS: A global LC of 0.65 +/- 0.15 was obtained if a 3-microparameter FDG model (k4*=0)was assumed. Assumption of a 4-microparameter FDG model (k4*[ne]0) in analyzing the FDG data resulted in a higher LC value of 0.81 +/- 0.18.CONCLUSION: The value of LC used for quantitating CMRglc should match the assumption inherent to the method of data analysis. The LC results in this study agree well with recent findings in the literature
UR  - http://www.sciencedirect.com/science/article/B6X15-48KCJJM-8/2/5482fa5bb7ff21a5060f50d2df0301c4
ER  - 

TY  - JOUR
T1  - Differential modulation of subcortical target and cortex during deep brain stimulation
A1  - Haslinger,B.
A1  - Boecker,H.
A1  - Buchel,C.
A1  - Vesper,J.
A1  - Tronnier,V.M.
A1  - Pfister,R.
A1  - Alesch,F.
A1  - Moringlane,J.R.
A1  - Krauss,J.K.
A1  - Conrad,B.
A1  - Schwaiger,M.
A1  - Ceballos-Baumann,A.O.
Y1  - 2003/02//
N1  - UI - 22484101
SP  - 517
EP  - 524
JF  - Neuroimage
VL  - 18
IS  - 2
N2  - The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit
AD  - Neurologische Klinik TU-Munchen, Klinikum Rechts der Isar, Mohlstrasse 28, D-81675 Munich, Germany. b.haslinger@lrz.tu-muenchen.de
UR  - PM:12595204
ER  - 

TY  - JOUR
T1  - Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine
A1  - Deep,P.
A1  - Dagher,A.
A1  - Sadikot,A.
A1  - Gjedde,A.
A1  - Cumming,P.
Y1  - 1999/12/15/
N1  - UI - 20002994
SP  - 313
EP  - 318
JF  - Synapse
VL  - 34
IS  - 4
N2  - The efficacy of amantadine in alleviating motor symptoms of Parkinson's disease may be mediated in part by stimulation of cerebral dopa decarboxylase (DDC) activity, secondary to antagonism of N-methyl-D-aspartate (NMDA) type glutamate receptors. We tested the specific hypothesis that amantadine increases the decarboxylation rate of 6-[(18)F]fluoro-L-DOPA (FDOPA), an exogenous substrate for DDC, in healthy human brain. Radioactivity concentrations in brain tissue of neurologically normal volunteers (n = 5) injected intravenously with FDOPA ( approximately 4.5 mCi) were recorded by positron emission tomography (PET) for 120 min, first in a baseline condition, and again following three consecutive days of treatment with amantadine (100 mg/day, p.o.). Data from four telencephalic regions of interest containing appreciable DDC activity were analyzed with the tissue slope-intercept plot, using cerebellar cortex as the reference tissue, to estimate a coefficient of in situ FDOPA decarboxylation (k(3)(r), min(-1)). Mean estimates of k(3)(r) were increased following amantadine treatment in caudate nucleus (+12%), putamen (+28%), ventral striatum (+27%), and frontal cortex (+9%). For an initial confidence level of 95%, paired one-sided Student's t-tests with Bonferroni correction for multiple comparisons revealed a statistically significant drug effect in ventral striatum. Present results are consistent with stimulation of DDC activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine, and suggest that this response is an important mechanism underlying the anti-parkinsonian properties of amantadine. Nonetheless, PET studies in parkinsonian patients using higher, clinically effective doses of amantadine may reveal more pronounced enhancements of cerebral DDC activity
AD  - McConnell Brain Imaging Center, Montreal Neurological Institute, 3801 University St., Montreal, Quebec, Canada H3A 2B4. deep@pet.mni.mcgill.ca
UR  - PM:10529725
ER  - 

TY  - JOUR
T1  - The addicted human brain: insights from imaging studies
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wang,G.J.
Y1  - 2003/05//
N1  - UI - 22635566
SP  - 1444
EP  - 1451
JA  - J Clin.Invest
VL  - 111
IS  - 10
AD  - Department of Medicine, Brookhaven National Laboratory, Upton, New York, USA. Department of Psychiatry, State University of New York at Stony Brook, Stony Brook, New York, USA. Department of Chemistry, Brookhaven National Laboratory, Upton, New York, USA
UR  - PM:12750391
ER  - 

TY  - JOUR
T1  - Reproducibility of (11)C-Raclopride Binding in the Rat Brain Measured with the MicroPET R4: Effects of Scatter Correction and Tracer Specific Activity
A1  - Alexoff,D.L.
A1  - Vaska,P.
A1  - Marsteller,D.
A1  - Gerasimov,T.
A1  - Li,J.
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Taintor,N.B.
A1  - Thanos,P.K.
A1  - Volkow,N.D.
Y1  - 2003/05//
N1  - UI - 0
SP  - 815
EP  - 822
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 5
N2  - A new generation of commercial animal PET cameras may accelerate drug development by streamlining preclinical testing in laboratory animals. However, little information on the feasibility of using these machines for quantitative PET in small animals is available. Here we investigate the reproducibility of microPET imaging of (11)C-raclopride in the rat brain and the effects of tracer-specific activity and photon scatter correction on measures of D2 receptor (D2R) availability. METHODS: Sprague-Dawley rats (422 +/- 29 g; n = 7) were anesthetized with ketamine/xylazine and catheterized for tail vein injection of (11)C-raclopride. Each animal was positioned prone in the microPET, centering the head in the field of view. MicroPET data was collected for 60 min-starting at (11)C-raclopride injection-and binned into 24 time frames (6 x 10 s, 3 x 20 s, 8 x 60 s, 4 x 200 s, 3 x 600 s). In 3 studies, (11)C-raclopride was administered a second time in the same animal, with 2-4 h between injections. In a fourth animal, raclopride (1 mg/kg) was coinjected with (11)C-raclopride for the second injection. Three rats received a single dose of (11)C-raclopride. The range of doses for all studies was 6.11-18.54 MBq (165-501 micro Ci). The specific activity at injection was 4.07-48.1 GBq/ micro mol (0.11-1.3 Ci/ micro mol). Region-of-interest analysis was performed and the distribution volume ratio (DVR) was computed for striatum/cerebellum using sinograms uncorrected and corrected for scatter using a tail-fit method. RESULTS: Test-retest results showed that the (11)C-raclopride microPET DVR was reproducible (change in DVR = -8.3% +/- 4.4%). The average DVR from 6 rats injected with high specific activity (<4 nmol/kg) was 2.43 +/- 0.19 (coefficient of variation = 8%). The DVR for the blocking study was 1.23. The DVR depended on the mass of tracer (11)C-raclopride injected for doses >1.5 nmol/kg. Scatter fractions within the rat head were approximately 25%-45% resulting in an average increase of DVR of 3.5% (range, 0%-10%) after correction. CONCLUSION: This study shows that the (11)C-raclopride microPET-derived DVR is reproducible and suitable for studying D2R availability in the rat brain. MicroPET sensitivity was sufficient to determine reproducible DVRs from (11)C-raclopride injections of 9.25 MBq ( approximately 250 micro Ci). However, the effect of tracer mass on the DVR should be considered for studies using more than approximately 1-2 nmol/kg raclopride, and scatter correction has a measurable impact on the results
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York. Medical Department, Brookhaven National Laboratory, Upton, New York. Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York. Department of Applied Mathematics and Statistics, State University of New York at Stony Brook, Stony Brook, Stony Brook, New York
UR  - PM:12732684
ER  - 

TY  - JOUR
T1  - In vivo imaging of the brain cannabinoid receptor
A1  - Gifford,A.N.
A1  - Makriyannis,A.
A1  - Volkow,N.D.
A1  - Gatley,S.J.
Y1  - 2002/12//
N1  - UI - 22392869
SP  - 65
EP  - 72
JA  - Chem.Phys.Lipids
VL  - 121
IS  - 1-2
N2  - The CB1 cannabinoid receptor is expressed in the brain at levels sufficient to serve as potential target for in vivo imaging using positron emission tomography (PET) or single photon emission computed tomography methodology. To date, the most promising radioligands for the in vivo imaging of this receptor have structures based on that of the cannabinoid antagonist, SR141716A. Rodent data obtained using these in vivo radiotracers has demonstrated that both the behavioral and neurochemical effects of cannabinoids occur at very low levels of receptor occupancy. More recently, an agonist radiotracer based on the structure of aminoalkylindole cannabinoids has also been examined for in vivo labeling of CB1 receptors. Although rodent studies have indicated that in vivo imaging of CB1 receptors is feasible, at the present time this receptor has still to be successful imaged in a human PET study
AD  - Medical Department, Brookhaven National Laboratory, 11973, Upton, NY, USA
UR  - PM:12505691
ER  - 

TY  - JOUR
T1  - The orbitofrontal cortex in methamphetamine addiction: involvement in fear
A1  - Goldstein,R.Z.
A1  - Volkow,N.D.
A1  - Chang,L.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Depue,R.A.
A1  - Gur,R.C.
Y1  - 2002/12/03/
N1  - UI - 22376731
SP  - 2253
EP  - 2257
JF  - Neuroreport
VL  - 13
IS  - 17
N2  - We used Tellegen's Multidimensional Personality Questionnaire (MPQ) harm avoidance (fear) scale and the constraint superfactor as personality measures of inhibitory control and examined their association with glucose metabolism in the orbitofrontal gyrus at rest in 14 recently abstinent methamphetamine-dependent subjects and 22 comparison subjects. Higher MPQ scores were associated with higher relative orbitofrontal gyrus metabolism in the methamphetamine-dependent subjects. There was a tendency towards a negative association for the comparison subjects (test of coincidence of regression lines for the two subject groups: F = 3.3, df = 2,32; = 0.051). These results suggest that the role of the orbitofrontal cortex in inhibitory control can be manifested in stable personality predispositions and further implicate this region in the core characteristics of drug addiction
AD  - Department of Human Development, Laboratory of Neurobiology of Personality and Emotion, Cornell University, Ithaca, NY 14853, USA. rgoldstein@bnl.gov
UR  - PM:12488806
ER  - 

TY  - JOUR
T1  - Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: a preliminary study
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Maynard,L.
A1  - Fowler,J.S.
A1  - Jayne,B.
A1  - Telang,F.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Gatley,S.J.
A1  - Hitzemann,R.
A1  - Wong,C.
A1  - Pappas,N.
Y1  - 2002/12/30/
N1  - UI - 22366502
SP  - 163
EP  - 172
JA  - Psychiatry Res.
VL  - 116
IS  - 3
N2  - Imaging studies in patients with Type II alcohol dependence have revealed significant reductions in dopamine (DA) D2 receptor availability. Here we assessed the effects of alcohol detoxification in DA D2 receptors in alcoholic subjects. We evaluated 14 patients with Type II alcohol dependence tested within 6 weeks of detoxification and then re-tested 1-4 months later while alcohol free. The comparison group comprised 11 healthy controls. PET was used with [11C]raclopride to measure DA D2 receptors. Eight alcoholics and all control subjects were tested with a CTI 931 PET scanner and six alcoholics with a Siemens HR+ PET scanner. Data were analyzed separately for the studies done in the different scanners. Comparisons between early and late alcohol detoxification showed no significant changes in DA D2 receptor availability (B(max)/K(d)) for the studies done with the CTI and the HR+ scanners. Comparison with controls showed lower DA D2 receptor levels in caudate and putamen in alcoholics tested during early detoxification and in caudate during late detoxification. These studies replicate previous findings of lower striatal DA D2 receptors in alcoholics than in controls and absence of significant recovery during alcohol detoxification. These findings suggest that low DA D2 receptor availability in alcoholics is not due to alcohol withdrawal and may reflect a predisposing factor
AD  - Brookhaven National Laboratory, Upton, NY 11973, USA. volkow@bnl.gov
UR  - PM:12477600
ER  - 

TY  - JOUR
T1  - Strategy for the formation of parametric images under conditions of low injected radioactivity applied to PET studies with the irreversible monoamine oxidase A tracers [11C]clorgyline and deuterium-substituted [11C]clorgyline
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Ding,Y.S.
A1  - Franceschi,D.
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Felder,C.
A1  - Alexoff,D.
Y1  - 2002/11//
SP  - 1367
EP  - 1376
JA  - J Cereb.Blood Flow Metab
VL  - 22
IS  - 11
N2  - The construction of parametric positron emission tomography images of enzyme or receptor concentration obtained using irreversibly binding radiotracers presents problems not usually encountered with reversibly binding radiotracers. Difficulties are most apparent in brain regions having low blood flow and/or high enzyme or receptor concentration and are exacerbated with noisy data. This is especially true when minimal doses of radiotracer are administered. A comparison was recently reported of the irreversible monoamine oxidase A (MAO A) radiotracers [11C]clorgyline (CLG) and deuterium-substituted [11C]clorgyline (CLG-D) in the human brain using region of interest (ROI) analysis in which the authors observed an unexpected loss of image contrast with CLG-D compared with CLG. In order to more fully investigate patterns of binding of these irreversibly binding radiotracers, a strategy was devised to reduce noise in the generation of parametric images of the model term related to enzyme or receptor concentration. The generalized linear least squares (GLLS) method of Feng et al. (1995), a rapid linear method that is unbiased, was used for image-wide parameter estimation. Since GLLS can fail in the presence of large amounts of noise, local voxels were grouped within the image to increase the signal, and the GLLS method was combined with the standard nonlinear estimation methods when necessary. Voxels were grouped together depending on their proximity and whether they fell within a specified range of the time-integrated image. It was assumed that voxels meeting both criteria are functionally related. Simulations reflecting varying enzyme concentrations were performed to assess precision and accuracy of parameter estimates in the presence of varying amounts of noise. Using this approach, images were generated of the combination parameter lambdak3 (lambda = K1/k2, where K1 and k2 are plasma-to-tissue and tissue-to-plasma transport constants, respectively) that is related to enzyme concentration as well as images of the transport constant K1 for individual subjects. Reasonably high-quality images of both K1 and lambdak3 were obtained for CLG and CLG-D for individual subjects even with low injected doses averaging 6 mCi. While there were no differences in the K1 images, the lambdak3 images revealed the loss of contrast previously reported for CLG-D using the ROI analysis. This method should be generalizable to other tracers and should facilitate the analysis of group differences
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. jlogan@bnl.gov
UR  - PM:12439294
ER  - 

TY  - JOUR
T1  - Non-MAO A binding of clorgyline in white matter in human brain
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Franceschi,D.
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Pappas,N.
A1  - Schlyer,D.
A1  - Gatley,S.J.
A1  - Alexoff,D.
A1  - Felder,C.
A1  - Biegon,A.
A1  - Zhu,W.
Y1  - 2001/12//
SP  - 1039
EP  - 1046
JA  - J Neurochem.
VL  - 79
IS  - 5
N2  - Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. fowler@bnl.gov
UR  - PM:11739617
ER  - 

TY  - JOUR
T1  - Development of N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropargylamine (18F-fluoroclorgyline) as a potential PET radiotracer for monoamine oxidase-A
A1  - Mukherjee,J.
A1  - Yang,Z.Y.
Y1  - 1999/08//
SP  - 619
EP  - 625
JA  - Nucl Med Biol.
VL  - 26
IS  - 6
N2  - We have synthesized N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropar gylamine (18F-fluoroclorgyline) as a potential positron emission tomography (PET) radiotracer for monoamine oxidase A (MAO-A). The radiosynthesis was carried out by a 18F-fluoride-for-mesylate substitution reaction in approximately 20% radiochemical yield in specific activities of 1-2 Ci/micromol. Selectivity for MAO-A was demonstrated by the high affinity of clorgyline (IC50 = 39 nM) and lower affinity of (R)-deprenyl (IC50 > or = 100 microM) for the inhibition of 18F-fluoroclorgyline binding in vitro in rat brain membranes. The uptake of 18F-fluoroclorgyline in the rat brains was high (> 1.0% injected dose/g). The binding of 18F-fluoroclorgyline in the rat brain correlated with the distribution of MAO-A and was inhibited by preadministration of MAO-A inhibitors, clorgyline, and Ro 41-1049, whereas (R)-deprenyl, a MAO-B blocker, had no inhibitory effect. These results suggest that 18F-fluoroclorgyline is a potential PET radiotracer for MAO-A
AD  - Franklin McLean Institute, Department of Radiology, University of Chicago, Illinois, USA. jogeshwar_mukherjee@kettheath.com
UR  - PM:10587099
ER  - 

TY  - JOUR
T1  - Selective, irreversible in vivo binding of [11C]clorgyline and [11C]-L-deprenyl in mice: potential for measurement of functional monoamine oxidase activity in brain using positron emission tomography
A1  - MacGregor,R.R.
A1  - Halldin,C.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Arnett,C.D.
A1  - Langstrom,B.
A1  - Alexoff,D.
Y1  - 1985/09/01/
N1  - UI - 85307068
SP  - 3207
EP  - 3210
JA  - Biochem.Pharmacol.
VL  - 34
IS  - 17
UR  - PM:3929788
ER  - 

TY  - JOUR
T1  - Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury
A1  - Steiner,L.A.
A1  - Coles,J.P.
A1  - Czosnyka,M.
A1  - Minhas,P.S.
A1  - Fryer,T.D.
A1  - Aigbirhio,F.I.
A1  - Clark,J.C.
A1  - Smielewski,P.
A1  - Chatfield,D.A.
A1  - Donovan,T.
A1  - Pickard,J.D.
A1  - Menon,D.K.
Y1  - 2003/06/01/
SP  - 765
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 74
IS  - 6
N2  - Background: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO2) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO2, to allow assessment of oxygen supply and demand relations. Objectives: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. Methods: Using positron emission tomography, global cerebral blood flow, CMRO2, and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. Results: Low CMRO2 was associated with disturbed pressure reactivity (inverse function, R2 = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R2 = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO2 or oxygen extraction fraction. Conclusions: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome
UR  - http://jnnp.bmjjournals.com/cgi/content/abstract/74/6/765
ER  - 

TY  - JOUR
T1  - 3'-[18F]Fluoro-3'-Deoxythymidine ([18F]-FLT) as Positron Emission Tomography Tracer for Imaging Proliferation in a Murine B-Cell Lymphoma Model and in the Human Disease
A1  - Wagner,Martin
A1  - Seitz,Ulrike
A1  - Buck,Andreas
A1  - Neumaier,Bernd
A1  - Schultheiss,Stefan
A1  - Bangerter,Markus
A1  - Bommer,Martin
A1  - Leithauser,Frank
A1  - Wawra,Edgar
A1  - Munzert,Gerd
A1  - Reske,Sven N.
Y1  - 2003/05/15/
SP  - 2681
JF  - Cancer Research
JA  - Cancer Res
VL  - 63
IS  - 10
N2  - Here we describe the evaluation of 3'-[18F]fluoro-3'-deoxythymidine {[18F]-FLT} as a tracer for positron emission tomography (PET) in a murine model of B-cell lymphoma and in human malignant lymphoma. The human B-cell line DoHH2 expressed high levels of active thymidine kinase 1 (TK-1) as the key enzyme of [18F]-FLT metabolism. Immunostaining confirmed high levels of TK-1 in DoHH2 derived xenograft tumors in SCID/SCID mice. In vitro studies demonstrated a time-dependent uptake of [18F]-FLT, an efficient phosphorylation to the respective monophosphate and the incorporation of [18F]-FLT into the perchloric acid insoluble fraction in DoHH2 cells, indicating the incorporation of this tracer into the DNA. After incubation with [18F]FLT for 240 min, 12.5% {+/-} 1.0% of radioactivity applied to the medium was intracellularly trapped in DoHH2 cells. Specific accumulation of [18F]-FLT in the malignant cell clone was confirmed in biodistribution studies in SCID/SCID mice bearing DoHH2-derived tumors. The percentage of injected dose of [18F]-FLT per gram of tumor tissue correlated with the tumor-proliferation index as evaluated in BrdUrd-labeling experiments. In a pilot study of 11 patients with both indolent and aggressive lymphoma, [18F]-FLT was suitable and comparable to [18F]-FDG in the ability to detect malignant lesions by PET scan. Furthermore, we found a close correlation (r = 0.95, P < 0.005) of the [18F]-FLT standardized uptake values with the Ki67-labeling index of tissue biopsies (n = 10) in these patients. These results suggest that [18F]-FLT represents a novel tracer for PET that enables imaging of proliferation in human lymphoma in vivo
UR  - http://cancerres.aacrjournals.org/cgi/content/abstract/63/10/2681
ER  - 

TY  - JOUR
T1  - Metabolic Activation of Temozolomide Measured in Vivo Using Positron Emission Tomography
A1  - Saleem,Azeem
A1  - Brown,Gavin D.
A1  - Brady,Frank
A1  - Aboagye,Eric O.
A1  - Osman,Safiye
A1  - Luthra,Sajinder K.
A1  - Ranicar,Alex S.O.
A1  - Brock,Cathryn S.
A1  - Stevens,Malcolm F.G.
A1  - Newlands,Edward
A1  - Jones,Terry
A1  - Price,Pat
Y1  - 2003/05/15/
SP  - 2409
JF  - Cancer Research
JA  - Cancer Res
VL  - 63
IS  - 10
N2  - The purpose of this research was to quantitate and confirm the mechanism of in vivo metabolic activation of temozolomide. The secondary aims were to evaluate the tumor, normal tissue, and plasma pharmacokinetics of temozolomide in vivo, and to determine whether such pharmacokinetics resulted in tumor targeting. [11C]temozolomide kinetics were studied in men using positron emission tomography (PET). It has been postulated that temozolomide undergoes decarboxylation and ring opening in the 3-4 position to produce the highly reactive methyldiazonium ion that alkylates DNA. To investigate this, a dual radiolabeling strategy, with [11C]temozolomide separately radiolabelled in the 3-N-methyl and 4-carbonyl positions, was used. We hypothesized that 11C in the C-4 position of [4-11C-carbonyl]temozolomide would be converted to [11C]CO2 if the postulated mechanism of metabolic conversion was true resulting in lower [11C]temozolomide tumor exposure. Paired studies were performed with both forms of [11C]temozolomide in 6 patients with gliomas. Another PET scan with 11C-radiolabelled bicarbonate was performed and used to account for the metabolites of temozolomide using a data-led analytical approach. Plasma was analyzed for [11C]temozolomide and [11C]metabolites throughout the scan duration. Exhaled air was also sampled throughout the scan for [11C]CO2. The percentage ring opening of temozolomide over 90 min was also calculated to evaluate whether there was a differential in metabolic breakdown among plasma, normal tissue, and tumor. There was rapid systemic clearance of both radiolabelled forms of [11C]temozolomide over 90 min (0.2 liter/min/m2), with [11C]CO2 being the primary elimination product. Plasma [11C]CO2 was present in all of the studies with [4-11C-carbonyl]temozolomide and in half the studies with [3-N-11C-methyl]temozolomide. The mean contributions to total plasma activity by [11C]CO2 at 10 and 90 min were 12% and 28% with [4-11C-carbonyl]temozolomide, and 1% and 4% with [3-N-11C-methyl]temozolomide, respectively. There was a 5-fold increase in exhaled [11C]CO2 sampled with [4-11C-carbonyl]temozolomide compared with [3-N-11C-methyl]temozolomide (P < 0.05). A decrease in tissue exposure [area under the curve between 0 and 90 min (AUC0-90 min)] to [11C]temozolomide was also observed with [4-11C-carbonyl] temozolomide compared with [3-N-11C-methyl]temozolomide. Of potential therapeutic advantage was the higher [11C]radiotracer and [11C]temozolomide exposure (AUC0-90 min) in tumors compared with normal tissue. [11C]temozolomide ring opening over 90 min was less in plasma (20.9%; P < 0.05) compared with tumor (26.8%), gray matter (29.7%), and white matter (30.1%), with no differences (P > 0.05) between tumor and normal tissues. The significantly higher amounts of [11C]CO2 sampled in plasma and exhaled air, in addition to the lower normal tissue and tumor [11C]temozolomide AUC0-90 min observed with [4-11C-carbonyl]temozolomide, confirmed the postulated mechanism of metabolic activation of temozolomide. A higher tumor [11C]temozolomide AUC0-90 min in tumors compared with normal tissue and the tissue-directed metabolic activation of temozolomide may confer potential therapeutic advantage in the activity of this agent. This is the first report of a clinical PET study used to quantify and confirm the in vivo mechanism of metabolic activation of a drug
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Saleem - Cancer Res.pdf
ER  - 

TY  - JOUR
T1  - Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients
A1  - Hammers,Alexander
A1  - Koepp,Matthias J.
A1  - Richardson,Mark P.
A1  - Hurlemann,Rene
A1  - Brooks,David J.
A1  - Duncan,John S.
Y1  - 2003/06/01/
SP  - 1300
EP  - 1318
JF  - Brain
VL  - 126
IS  - 6
N2  - In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. {gamma}-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [11C]Flumazenil (FMZ) PET images most subtypes of GABAA receptors, present on most neurons. We investigated [11C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-Vd) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-Vd; increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Hammers-neocortical-flumazenil.pdf
ER  - 

TY  - JOUR
T1  - Extrastriatal dopamine D(2) receptors in Parkinson's disease: a longitudinal study
A1  - Kaasinen,V.
A1  - Aalto,S.
A1  - Nagren,K.
A1  - Hietala,J.
A1  - Sonninen,P.
A1  - Rinne,J.O.
Y1  - 2003/06//
N1  - UI - 22652664
SP  - 591
EP  - 601
JA  - J Neural Transm.
VL  - 110
IS  - 6
N2  - Most antiparkinsonian drugs are known to act through central dopamine D(2) receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D(2) receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of <1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D(2) receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, approximately 3 years apart, using a high-affinity extrastriatal D(2)/D(3) receptor tracer, [(11)C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D(2)-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D(2) availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D(2) receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease
AD  - Departments of Neurology
UR  - C:\Dokumente und Einstellungen\karl\Desktop\Data\TEXT\LIT\Kaasinen-extrastriatal-D2.pdf
ER  - 

TY  - JOUR
T1  - 3-O-Methyl-6-[(18)F]fluoro-l-DOPA and its evaluation in brain tumour imaging
A1  - Beuthien-Baumann,B.
A1  - Bredow,J.
A1  - Burchert,W.
A1  - Fuchtner,F.
A1  - Bergmann,R.
A1  - Alheit,H.D.
A1  - Reiss,G.
A1  - Hliscs,R.
A1  - Steinmeier,R.
A1  - Franke,W.G.
A1  - Johannsen,B.
A1  - Kotzerke,J.
Y1  - 2003/05/24/
N1  - UI - 0
SP  - 1004
EP  - 1008
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - 3- O-Methyl-6-[(18)F]fluoro- l-DOPA (OMFD) is a major metabolite of 6-[(18)F]fluoro-L-DOPA. Although synthesis of OFMD was primarily established to study the dopaminergic system, as it is an amino acid analogue, uptake in experimental tumours has been found. The aim of this study was to evaluate the applicability of OMFD for brain tumour imaging and to obtain initial estimates of whole-body biodistribution and radiation dosimetry in humans. Nineteen patients with suspected or confirmed brain tumours were investigated with OMFD and dynamic brain PET, complemented by whole-body PET in seven patients. Tracer kinetics were compared for normal brain and intracerebral lesions. Tissue accumulation was quantified with standardised uptake values (SUVs). Whole-body distribution in combination with tracer kinetics from animal experiments was used for the calculation of radiation dosimetry data. On the basis of OMFD PET, viable brain tumour was suspected in 16 patients with SUVs of 3.0+/-0.8 and a tumour to non-tumour ratio of 1.9+/-0.5. Highest tumour and normal brain uptake occurred between 15 and 30 min, with a subsequent slow decrease. Late whole-body tracer distribution was uniform without specific organ accumulation. Elimination occurred via urine. The mean radiation dose to the whole body was estimated at 0.016 mSv/MBq, with the kidneys as dose-critical organ (0.033 mGy/MBq). In conclusion, OMFD enables the visualisation of brain tumours with SUVs similar to other fluorinated amino acids. The whole-body radiation exposure from OMFD is comparable to that from FDG imaging
AD  - Klinik und Poliklinik fur Nuklearmedizin, Technische Universitat Dresden und PET Zentrum Rossendorf, Fetscherstrasse 74, 01307, Dresden, Germany
UR  - PM:12768333
ER  - 

TY  - JOUR
T1  - Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study
A1  - Drzezga,A.
A1  - Lautenschlager,N.
A1  - Siebner,H.
A1  - Riemenschneider,M.
A1  - Willoch,F.
A1  - Minoshima,S.
A1  - Schwaiger,M.
A1  - Kurz,A.
Y1  - 2003/05/23/
N1  - UI - 0
SP  - 1104
EP  - 1113
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
N2  - A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.8+/-5.8 years); these examinations included neuropsychological testing, structural cranial magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography (PET) evaluation of relative cerebral glucose metabolic rate (rCMRglc). Individual PET scans were stereotactically normalised with NEUROSTAT software (Univ. of Michigan, Ann Arbor, USA). Subsequently, statistical comparison of PET data with an age-matched healthy control population and between patient subgroups was performed using SPM 99 (Wellcome Dept. of Neuroimaging Sciences, London, UK). After 1 year, eight patients (36%) had developed probable AD (referred to as MCI(AD)), whereas 12 (55%) were still classified as having stable MCI (referred to as MCI(MCI)). Compared with the healthy control group, a reduced rCMRglc in AD-typical regions, including the temporoparietal and posterior cingulate cortex, was detected at baseline in patients with MCI(AD). Abnormalities in the posterior cingulate cortex reached significance even in comparison with the MCI(MCI) group. After 1 year, MCI(AD) patients demonstrated an additional bilateral reduction of rCMRglc in prefrontal areas, along with a further progression of the abnormalities in the parietal and posterior cingulate cortex. No such changes were observed in the MCI(MCI) group. In patients with MCI, characteristic cerebral metabolic differences can be delineated at the time of initial presentation, which helps to define prognostic subgroups. A newly emerging reduction of rCMRglc in prefrontal cortical areas is associated with the transition from MCI to AD
AD  - Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675, Munchen, Germany
UR  - PM:12764551
ER  - 

TY  - JOUR
T1  - In vivo binding of [11C]nemonapride to sigma receptors in the cortex and cerebellum
A1  - Ishiwata,K.
A1  - Senda,M.
Y1  - 1999/08//
SP  - 627
EP  - 631
JA  - Nucl Med Biol.
VL  - 26
IS  - 6
N2  - Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D2-like receptor ligand in pharmacological and neurological studies, and 11C-labeled analog ([11C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [11C]NEM binds in vivo to sigma receptors. [11C]NEM and one of six dopamine D2-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [11C]NEM was measured by a tissue dissection method. The striatal uptake of [11C]NEM was reduced by D2-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D4 receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D2-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [11C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [11C]NEM binds in vivo not only to dopamine D2-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum
AD  - Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan. ishiwata@pet.tmig.or.jp
UR  - PM:10587100
ER  - 

TY  - JOUR
T1  - The cloned dopamine D2 receptor reveals different densities for dopamine receptor antagonist ligands. Implications for human brain positron emission tomography
A1  - Seeman,P.
A1  - Guan,H.C.
A1  - Civelli,O.
A1  - Van Tol,H.H.
A1  - Sunahara,R.K.
A1  - Niznik,H.B.
Y1  - 1992/10/01/
N1  - UI - 93049880
SP  - 139
EP  - 146
JA  - Eur.J Pharmacol.
VL  - 227
IS  - 2
N2  - Since [3H]emonapride ([3H]YM-09151-2), a benzamide neuroleptic, consistently detects more dopamine D2 receptors than [3H]spiperone in the same tissue, we tested whether this property was inherent in the cloned dopamine D2 receptor. We found that the density of dopamine D2 receptors labelled by [3H]emonapride was 1.5-fold to 2-fold (mean of 1.8-fold) higher than the density of dopamine D2 receptors labelled by [3H]spiperone in cells expressing cloned dopamine D2 receptors (either the short form (from rat) or the long form (from human)), matching similar findings in anterior pituitary tissue (rat or pig) or in post-mortem human caudate nucleus tissue. The situation was similar for another benzamide, [3H]raclopride, which revealed 1.3-fold to 1.8-fold (mean of 1.5-fold) more binding sites than that for [3H]spiperone in cell membranes containing cloned dopamine D2 receptors. The apparently different dopamine D2 receptor densities revealed by these two types of 3H-ligands (i.e. [3H]spiperone and the [3H]benzamides), therefore, arise from an inherent property of the dopamine D2 receptor protein. These findings for the cloned dopamine D2 receptor, therefore, partly explain the higher dopamine D2 receptor density measured in human brain (by positron emission tomography) when using radioactive raclopride compared to results using radioactive methylspiperone.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Pharmacology, Faculty of Medicine, University of Toronto, Canada
UR  - PM:1358662
ER  - 

TY  - JOUR
T1  - Farewell to the "Shy-Drager syndrome"
A1  - Schatz,I.J.
Y1  - 1996/07/01/
N1  - UI - 96245085
SP  - 74
EP  - 75
JA  - Ann.Intern.Med
VL  - 125
IS  - 1
UR  - PM:8644992
ER  - 

TY  - JOUR
T1  - Consensus statement on the diagnosis of multiple system atrophy
A1  - Gilman,S.
A1  - Low,P.A.
A1  - Quinn,N.
A1  - Albanese,A.
A1  - Ben Shlomo,Y.
A1  - Fowler,C.J.
A1  - Kaufmann,H.
A1  - Klockgether,T.
A1  - Lang,A.E.
A1  - Lantos,P.L.
A1  - Litvan,I.
A1  - Mathias,C.J.
A1  - Oliver,E.
A1  - Robertson,D.
A1  - Schatz,I.
A1  - Wenning,G.K.
Y1  - 1999/02/01/
N1  - UI - 99237930
SP  - 94
EP  - 98
JA  - J Neurol Sci.
VL  - 163
IS  - 1
N2  - We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0316, USA. sgilman@umich.edu
UR  - PM:10223419
ER  - 

TY  - JOUR
T1  - Long term treatment and disease severity change brain responses to levodopa in Parkinson's disease
A1  - Hershey,T.
A1  - Black,K.J.
A1  - Carl,J.L.
A1  - McGee-Minnich,L.
A1  - Snyder,A.Z.
A1  - Perlmutter,J.S.
Y1  - 2003/07/01/
SP  - 844
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 74
IS  - 7
N2  - Objectives: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, but with long term treatment and disease progression, levodopa can elicit additional clinical symptoms, reflecting altered effects of levodopa in the brain. The authors examined whether long term treatment affects the brain's response to levodopa in the absence of these altered clinical responses to levodopa. Methods: Positron emission tomography (PET) measurements were used of brain-blood flow before and after an acute dose of levodopa in three groups: PD patients treated long term with levodopa without levodopa induced dyskinesias, levodopa naive PD patients, and controls. Results: It was found that the PD group treated long term responded to acute levodopa differently from controls in left sensorimotor and left ventrolateral prefrontal cortex. In both regions, the treated PD group had decreased blood flow whereas the control group had increased blood flow in response to levodopa. Levodopa naive PD patients had little or no response to levodopa in these regions. Within the treated PD group, severity of parkinsonism correlated with the degree of abnormality of the sensorimotor cortex response, but not with the prefrontal response. Conclusions: It is concluded that long term levodopa treatment and disease severity affect the physiology of dopaminergic pathways, producing altered responses to levodopa in brain regions associated with motor function
UR  - http://jnnp.bmjjournals.com/cgi/content/abstract/74/7/844
ER  - 

TY  - JOUR
T1  - Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O-H2O PET study
A1  - Kassubek,Jan
A1  - Juengling,Freimut D.
A1  - Els,Thomas
A1  - Spreer,Joachim
A1  - Herpers,Martin
A1  - Krause,Thomas
A1  - Moser,Ernst
A1  - Lucking,Carl H.
Y1  - 2003/08/15/
SP  - 85
EP  - 91
JF  - Journal of the Neurological Sciences
VL  - 212
IS  - 1-2
N2  - Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H2O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients
UR  - http://www.sciencedirect.com/science/article/B6T06-48M7W3C-1/2/8982b9978becee91fe41464510ad11e0
ER  - 

TY  - JOUR
T1  - Cortical Hypometabolism and Crossed Cerebellar Diaschisis Suggest Subcortically Induced Disconnection in CADASIL: An (18)F-FDG PET Study
A1  - Tatsch,K.
A1  - Koch,W.
A1  - Linke,R.
A1  - Poepperl,G.
A1  - Peters,N.
A1  - Holtmannspoetter,M.
A1  - Dichgans,M.
Y1  - 2003/06//
N1  - UI - 0
SP  - 862
EP  - 869
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 6
N2  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic lesions are largely confined to subcortical structures, whereas the cortex is spared. CADASIL, therefore, may serve as a model to study subcortically induced remote effects. The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection. METHODS: Eleven CADASIL patients (7 women, 4 men; mean age, 55.8 +/- 6.7 y) without cortical lesions on brain MR images underwent PET after intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according to a previously published method. For further processing, patient studies were registered to a template of a healthy control group and region-of-interest-based and voxelwise comparisons were performed. RESULTS: In CADASIL patients, mean rCMRglc was significantly reduced in all cortical and subcortical structures, compared with the values in healthy volunteers. In the subcortical gray matter, metabolic rates, given as the percentage of the mean of healthy volunteers, were 49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively. Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the frontal, parietal, temporal, and occipital lobes, respectively. On an individual level, most patients showed marked asymmetry and inhomogeneities of cortical glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed cerebellar diaschisis. CONCLUSION: This study showed that cortical glucose metabolism is significantly lower in CADASIL patients than in healthy volunteers. The observed decrease in rCMRglc may in part be explained by a reduction of cerebral blood flow and neuronal loss. In addition, our data provide evidence of remote effects secondary to the functional disruption of subcortical fiber tracts in this particular type of small-vessel disease
AD  - Department of Nuclear Medicine, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany. Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany. Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany
UR  - PM:12791811
ER  - 

TY  - JOUR
T1  - Behavioral disturbances and regional cerebral metabolism in probable Alzheimer's disease
A1  - Holthoff,V.A.
A1  - Herholz,K.
A1  - Ldecke,S.
A1  - Spirling,S.
A1  - Kalbe,E.
A1  - Lenz,O.
A1  - Zndorf,G.
A1  - Beuthien-Baumann,B.
Y1  - 2003///
SP  - 631
JA  - J.Cereb.Blood Flow Metab
VL  - 23 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Regional cerebral metabolism in unipolar depression: the relationship with clinical characteristics
A1  - Beuthien-Baumann,B.
A1  - Zndorf,G.
A1  - Ldecke,S.
A1  - Triemer,A.
A1  - Schierz,K.
A1  - Herholz,K.
A1  - Holthoff,V.A.
Y1  - 2003///
JA  - J.Cereb.Blood Flow Metab
VL  - 23 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Identification of DNA and amino acid metabolism in human gliomas by PET
A1  - Jacobs,A.H.
A1  - Dittmar,C.
A1  - Garlip,G.
A1  - Thomas,A.V.
A1  - Kracht,L.W.
A1  - Wienhard,K.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 2003///
SP  - 376
JA  - J.Cereb.Blood Flow Metab
VL  - 23 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study
A1  - Whone,A.L.
A1  - Watts,R.L.
A1  - Stoessl,A.J.
A1  - Davis,M.
A1  - Reske,S.
A1  - Nahmias,C.
A1  - Lang,A.E.
A1  - Rascol,O.
A1  - Ribeiro,M.J.
A1  - Remy,P.
A1  - Poewe,W.H.
A1  - Hauser,R.A.
A1  - Brooks,D.J.
Y1  - 2003/07//
N1  - UI - 22721298
SP  - 93
EP  - 101
JA  - Ann.Neurol.
VL  - 54
IS  - 1
N2  - Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and (18)F-dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen (18)F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06). Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, -14.1%; levodopa, -22.9%; 95% CI, 4.24-13.3), but the decrease was significantly lower with ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by (18)F-dopa PET. Ann Neurol 2003
AD  - Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
UR  - PM:12838524
ER  - 

TY  - JOUR
T1  - Phonological short-term memory networks following recovery from Landau and Kleffner syndrome
A1  - Majerus,S.
A1  - Laureys,S.
A1  - Collette,F.
A1  - Del Fiore,G.
A1  - Degueldre,C.
A1  - Luxen,A.
A1  - Van der,Linden M.
A1  - Maquet,P.
A1  - Metz-Lutz,M.N.
Y1  - 2003/07//
N1  - UI - 22695013
SP  - 133
EP  - 144
JA  - Hum.Brain Mapp.
VL  - 19
IS  - 3
N2  - Landau-Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise healthy children, together with spike-wave discharges predominating over superior temporal regions and activated by sleep. Although the outcome of language abilities is variable, a residual impairment in verbal short-term memory (STM) is frequent. This STM deficit might be related to the persistent dysfunction of those temporal lobe regions where epileptic discharges were observed during the active phase of the disorder. We tested this hypothesis by measuring brain activation during immediate serial recall of lists of 4 words, compared to single word repetition, using H(2) (15)O positron emission tomography (PET), in 3 LKS patients after recovery and in 14 healthy controls. The patients (TG, JPH, and DC) had shown abnormally increased or decreased glucose metabolism in left or right superior temporal gyrus (STG) at different stages during the active phase of their disease. At the time of this study, the patients were 6-10 years from the active phase of LKS. Results showed that Patients JPH and DC had impaired performance in the STM condition, whereas TG showed near normal performance. PET data showed that JPH and DC activated significantly less than controls left and right posterior STG. TG, having near normal STM performance, showed increased activity in the posterior part of the right STG. These data suggest that impaired verbal STM at late outcome of LKS might indeed be related to a persistent decrease of activity in those posterior superior temporal gyri that were involved in the epileptic focus during the active phase
AD  - Department of Cognitive Sciences, University of Liege, Liege, Belgium. smajerus@ulg.ac.be
UR  - PM:12811730
ER  - 

TY  - JOUR
T1  - [(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain
A1  - Halldin,C.
A1  - Erixon-Lindroth,N.
A1  - Pauli,S.
A1  - Chou,Y.H.
A1  - Okubo,Y.
A1  - Karlsson,P.
A1  - Lundkvist,C.
A1  - Olsson,H.
A1  - Guilloteau,D.
A1  - Emond,P.
A1  - Farde,L.
Y1  - 2003/06/13/
N1  - UI - 0
JA  - Eur.J.Nucl.Med.Mol.Imaging
N2  - The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2 E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [(11)C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/&mgr;mol). [(11)C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled beta-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [(11)C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [(11)C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [(11)C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm, Sweden
UR  - PM:12811422
ER  - 

TY  - JOUR
T1  - Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome
A1  - Siessmeier,T.
A1  - Nix,W.A.
A1  - Hardt,J.
A1  - Schreckenberger,M.
A1  - Egle,U.T.
A1  - Bartenstein,P.
Y1  - 2003/07//
N1  - UI - 22695447
SP  - 922
EP  - 928
JA  - J.Neurol.Neurosurg.Psychiatry
VL  - 74
IS  - 7
N2  - OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits. METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores. RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism. CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system
AD  - Department of Nuclear Medicine, Johannes Gutenberg University, Mainz, Germany Department of Neurology, Johannes Gutenberg University, Mainz Department of Psychosomatic Medicine and Psychotherapy, Johannes Gutenberg University, Mainz
UR  - PM:12810781
ER  - 

TY  - JOUR
T1  - PET visualization of microglia in multiple sclerosis patients using [11C]PK11195
A1  - Debruyne,J.C.
A1  - Versijpt,J.
A1  - Van Laere,K.J.
A1  - De Vos,F.
A1  - Keppens,J.
A1  - Strijckmans,K.
A1  - Achten,E.
A1  - Slegers,G.
A1  - Dierckx,R.A.
A1  - Korf,J.
A1  - De Reuck,J.L.
Y1  - 2003/05//
N1  - UI - 22637710
SP  - 257
EP  - 264
JA  - Eur.J.Neurol.
VL  - 10
IS  - 3
N2  - Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up-regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno-pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium-lesions was significantly increased compared with normal white matter. Uptake in T2-lesions was generally decreased, suggesting a PBR down-regulation. However, uptake values increased whenever a clinical or MR-relapse was present, suggestive for a dynamic process with a transient PBR up-regulation. During disease progression, an increase of normal-appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS
AD  - Department of Neurology, Ghent University Hospital, Ghent, Belgium. jan.debruyne@rug.ac.be
UR  - PM:12752399
ER  - 

TY  - JOUR
T1  - VMAT2 binding is elevated in dopa-responsive dystonia: Visualizing empty vesicles by PET
A1  - Fuente-Fernandez,R.
A1  - Furtado,S.
A1  - Guttman,M.
A1  - Furukawa,Y.
A1  - Lee,C.S.
A1  - Calne,D.B.
A1  - Ruth,T.J.
A1  - Stoessl,A.J.
Y1  - 2003/07//
N1  - UI - 22596048
SP  - 20
EP  - 28
JF  - Synapse
VL  - 49
IS  - 1
N2  - Dopa-responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d-threo-[(11)C]methylphenidate ([(11)C]MP) and 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), and [(11)C]raclopride were also used in the study. We found increased [(11)C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [(11)C]MP binding potential or [(18)F]-dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [(11)C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [(11)C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [(11)C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines. Synapse 49:20-28, 2003
AD  - Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, B.C., Canada
UR  - PM:12710012
ER  - 

TY  - JOUR
T1  - SCA-2 presenting as parkinsonism in an Alberta family: clinical, genetic, and PET findings
A1  - Furtado,S.
A1  - Farrer,M.
A1  - Tsuboi,Y.
A1  - Klimek,M.L.
A1  - Fuente-Fernandez,R.
A1  - Hussey,J.
A1  - Lockhart,P.
A1  - Calne,D.B.
A1  - Suchowersky,O.
A1  - Stoessl,A.J.
A1  - Wszolek,Z.K.
Y1  - 2002/11/26/
N1  - UI - 22339033
SP  - 1625
EP  - 1627
JF  - Neurology
VL  - 59
IS  - 10
N2  - The authors describe an Alberta family with levodopa-responsive parkinsonism without cerebellar abnormalities. Genetic testing showed expanded repeats for SCA-2; other mutations for parkinsonism were excluded. The expanded allele shows interruption of the CAG repeat with CAA. PET in two affected members showed reduced fluorodopa uptake in striatum and normal raclopride binding. Families with autosomal dominant, levodopa-responsive parkinsonism should be tested for the SCA-2 mutation
AD  - Movement Disorder Clinic, Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
UR  - PM:12451209
ER  - 

TY  - CHAP
T1  - Neurodegenerative disorders of the cerebellum
A1  - Gilman,S.
A1  - Heumann,M.
A1  - Junck,L.
Y1  - 2000///
SP  - 417
EP  - 455
T2  - Brain mapping: The disorders
A2  - Toga,A.W.
A2  - Mazziotta,J.C.
A2  - Frackowiak,R.S.J.
IS  - 17
CY  - San Diego
PB  - Academic Press
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - The decline of dopaminergic neurons in Parkinson's disease is nonlinear: A serial positron emission tomography study with 18- Fluorodopa
A1  - Hilker,R.
A1  - Schweitzer,K.
A1  - Ghaemi,M.
A1  - Weisenbach,S.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 2002///
N1  - Journal
SP  - 131
JF  - Movement Disorders
VL  - 17
UR  - ISI:000179489800182
ER  - 

TY  - JOUR
T1  - Comparison of FORE, OSEM and SAGE algorithms to 3DRP in 3D PET using phantom and human subject data
A1  - Krzywinski,M.
A1  - Sossi,V.
A1  - Ruth,T.J.
Y1  - 1999///
N1  - Journal
SP  - 1114
EP  - 1120
JF  - IEEE Transactions on Nuclear Science
VL  - 46
IS  - 4
N2  - Using phantom and human subject data, we have compared a number of reconstruction algorithms to the current "gold standard" method, 3D Reprojection Method (3DRP), in an effort to validate them as practical 3D reconstruction alternatives for dynamic PET scanning. The algorithms evaluated were (a) Fourier Rebinning (FORE) followed by 2D Filtered Back Projection (2D FBP), (b) FORE followed by Ordered Subsets Expectation- Maximization (OSEM) and (c) FORE followed by Space Alternating Generalized Expectation-Maximization (SAGE). The main benefits of these methods are two-fold: significantly shorter reconstruction times and improved signal-to-noise ratio at matched resolution for the iterative schemes. We demonstrate that FORE + 2D FBP can replace 3DRP with no significant impact on subsequent data analysis. In particular, distribution volume ratios (DVRs) obtained with FORE + 2D FBP differed from those obtained with 3DRP by 0.3 +/- 0.7% (n = 33) and -0.7 +/- 1.1%(n = 21) for cortical and cerebellar input functions, respectively. Both OSEM and SAGE performed well compared to 3DRP, with improved noise characteristics and DVR differences of < 3%
UR  - ISI:000082566000023
ER  - 

TY  - JOUR
T1  - Quantitative comparison of three- and two-dimensional PET with human brain studies
A1  - Sossi,V.
A1  - Oakes,T.R.
A1  - Chan,G.L.Y.
A1  - Schulzer,M.
A1  - Ruth,T.J.
Y1  - 1998///
N1  - Journal
SP  - 1714
EP  - 1719
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 39
IS  - 10
N2  - The aim of this study was to test the quantitation accuracy of three-dimensional PET in brain scanning. Methods: Three- dimensional data from 11 human subjects were tested using C-11- dihydrotetrabenazine, C-11-Schering 23390 and F-18-FDG as tracers. Two-dimensional scans were performed on the same subjects and the distribution volume, distribution volume ratio and local metabolic rate of glucose (LMRGlu) values obtained from these were used as reference. Three-dimensional data were processed as follows: iterative convolution subtraction scatter correction, detector normalization including radial and axial geometric factors, attenuation correction extracted from a two- dimensional transmission scan, Kinahan-Rogers reconstruction and region-of-interest-based sensitivity calibration. Results: No major systematic differences between the two methods were found. The agreement between the two-dimensional and three- dimensional data was within 5%. Although statistical analysis generally did not show this difference to be significant, reliability analysis indicated that comparing two-dimensional and three-dimensional data might introduce some inaccuracies. Conclusion: Three-dimensional PET yields quantitatively valid results for brain scanning
UR  - ISI:000076316200018
ER  - 

TY  - JOUR
T1  - Effect of Scatter from Radioactivity Outside of the Field-Of- View in 3D Pet
A1  - Sossi,V.
A1  - Barney,J.S.
A1  - Harrison,R.
A1  - Ruth,T.J.
Y1  - 1995///
N1  - Journal
SP  - 1157
EP  - 1161
JF  - IEEE Transactions on Nuclear Science
VL  - 42
IS  - 4
N2  - The contribution of the scattered events originating from Radioactivity Outside the tomograph Field of View (ROFOV) is treated differently by different scatter correction algorithms. Using measured data we have evaluated the amount of scatter originating from ROFOV, its axial and transaxial distribution in two energy windows for direct and a subset of oblique planes in 3D PET. Nonuniform distributions were observed with the total contribution found to be non negligible when the amount of ROFOV was comparable to the radioactivity in the Field of View (FOV)
UR  - ISI:A1995RP81900169
ER  - 

TY  - JOUR
T1  - A Database of [11C]WAY-100635 Binding to 5-HT1A Receptors in Normal Male Volunteers: Normative Data and Relationship to Methodological, Demographic, Physiological, and Behavioral Variables
A1  - Rabiner,Eugenii A.
A1  - Messa,Cristina
A1  - Sargent,Peter A.
A1  - Husted-Kjaer,Karen
A1  - Montgomery,Andrew
A1  - Lawrence,Andrew D.
A1  - Bench,Christopher J.
A1  - Gunn,Roger N.
A1  - Cowen,Phillip
A1  - Grasby,Paul M.
Y1  - 2002/03//
SP  - 620
EP  - 632
JF  - Neuroimage
VL  - 15
IS  - 3
N2  - PET studies of [11C]WAY-100635 binding are proving to be a useful tool to evaluate 5-HT1A receptor function in vivo in humans. We describe the pattern of [11C]WAY-100635 binding in 61 healthy male brains and examine its variability. For all PET scans, binding potential (BP) values for [11C]WAY-100635 in different regions were calculated using a simplified reference tissue model, with the cerebellum as reference region. Specifically we describe (1) region of interest and SPM databases of PET [11C]WAY-100635 binding, including test-retest variability; (2) the sensitivity of [11C]WAY-100635 binding to manipulations of endogenous 5-HT; and (3) correlations between [11C]WAY-100635 binding and radiochemical, demographic, physiological, and behavioral variables. The regional distribution of [11C]WAY-100635 binding in healthy human brain was similar to that reported in vitro. The test-retest variability was ~12% (range 9-16%) and was similar for all methods of regional sampling. The binding of [11C]WAY-100635 was insensitive to changes in brain 5-HT induced by tryptophan infusion and depletion. Although BP values varied greatly across subjects (range 2.9-6.8), there were no significant correlations of regional and global BP with common radiochemical, demographic, physiological, and personality variables. Specifically, in contrast with two recent small studies, we found no decline of [11C]WAY-100635 binding with age in our large cohort over the age range of 24 to 53 years. Assessment of 5-HT1A receptors in vivo using PET and [11C]WAY-100635 gives reliable measures of 5-HT1A binding. The large between-subject variability observed could not be explained by common methodological, physiological, or behavioral factors and hence the biological basis of this variability remains to be clarified
UR  - http://www.sciencedirect.com/science/article/B6WNP-457VFVM-J/2/10644db9176114be4ce109ab221cc100
ER  - 

TY  - JOUR
T1  - Abnormal Functional Connectivity in Posttraumatic Stress Disorder
A1  - Shaw,Marnie E.
A1  - Strother,Stephen C.
A1  - McFarlane,Alexander C.
A1  - Morris,Philip
A1  - Anderson,Jon
A1  - Clark,C.Richard
A1  - Egan,Gary F.
Y1  - 2002/03//
SP  - 661
EP  - 674
JF  - Neuroimage
VL  - 15
IS  - 3
N2  - This study investigated the efficacy of a combined multivariate/resampling procedure for the analysis of PET activation studies. The covariance-based multivariate analysis was used to investigate distributed brain systems in posttraumatic stress disorder (PTSD) patients and matched controls during performance of a working memory task. The results were compared to univariate results obtained in an earlier study. We also examined whether the PTSD patients demonstrated a breakdown in functional connectivity that may be associated with working memory difficulties often experienced by these patients. A resampling procedure was used specifically to test the reliability of measured between-group effects, to avoid mistaken inference on the basis of random intersubject differences. Significant and reproducible differences in network connectivity were obtained for the two groups. The functional connectivity pattern of the patient group was characterized by relatively more activation in the bilateral inferior parietal lobes and the left precentral gyrus than the control group, and less activation in the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. The resampling procedure provided direct evidence that working memory updating was abnormal in PTSD patients relative to matched controls. This work focuses on the need to identify extended brain networks (in addition to regionally specific changes) for the full characterization of brain responses in neuroimaging experiments. Our multivariate analysis explicitly measures the reliability of the patterns of functional connectivity we obtain and demonstrates the potential of such analyses for the study of brain network dysfunction in psychopathology
UR  - http://www.sciencedirect.com/science/article/B6WNP-457VFVM-P/2/debfebc62d145fbd33a02ae5644175fd
ER  - 

TY  - JOUR
T1  - Improved Parametric Image Generation Using Spatial-Temporal Analysis of Dynamic PET Studies
A1  - Zhou,Yun
A1  - Huang,Sung Cheng
A1  - Bergsneider,Marvin
A1  - Wong,Dean F.
Y1  - 2002/03//
SP  - 697
EP  - 707
JF  - Neuroimage
VL  - 15
IS  - 3
N2  - The value of parametric images that represent both spatial distribution and quantification of the physiological parameters of tracer kinetics has long been recognized. However, the inherent high noise level of pixel kinetics of dynamic PET makes it unsuitable to generate parametric images of the microparameters of tracer kinetic model by conventional weighted nonlinear least squares (WNLS) fitting. Based on the concept that both spatial and temporal information should be integrated to improve parametric image quality, a nonlinear ridge regression with spatial constraint (NLRRSC) parametric imaging algorithm was proposed in this study. For NLRRSC, a term that penalizes local spatial variation of parameters was added to the cost function of WNLS fitting. The initial estimates and spatial constraint were estimated by component representation model (CRM) with cluster analysis. A hierarchical cluster with average linkage method was used to extract components. The ridge parameter was determined by linear ridge regression theory at each iteration, and a modified Gauss-Newton algorithm was used for minimizing the cost function. Results from a computer simulation showed that the percent mean square error of estimates obtained by NLRRSC can be decreased by 60-80% compared to that of WNLS. The parametric images estimated by NLRRSC are significantly better than the ones generated by WNLS. A highly correlated linear relationship was found between the ROI values calculated from the microparametric images generated by NLRRSC and estimates from ROI kinetic fitting. NLRRSC provided a reliable estimate of glucose metabolite uptake rate with a comparable image quality compared to Patlak analysis. In conclusion, NLRRSC is a reliable and robust parametric imaging algorithm for dynamic PET studies
UR  - http://www.sciencedirect.com/science/article/B6WNP-457VFVM-V/2/f191517465df8113f4532726db2e473f
ER  - 

TY  - JOUR
T1  - A PET study of sequential finger movements of varying length in patients with Parkinson's disease
A1  - Catalan,M.J.
A1  - Ishii,K.
A1  - Honda,M.
A1  - Samii,A.
A1  - Hallett,M.
Y1  - 1999/03//
N1  - UI - 99192070
SP  - 483
EP  - 495
JF  - Brain
VL  - 122 ( Pt 3)
N2  - To study the difficulty that patients with Parkinson's disease have in performing long sequential movements, we used H2(15)O PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson's disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson's disease patients showed relative overactivity in the precuneus, premotor and parietal cortices. Increasing the complexity of movements resulted in increased rCBF in the premotor and parietal cortices of normal subjects; the Parkinson's disease patients showed greater increases in these same regions and had additional significant increases in the anterior supplementary motor area (SMA)/cingulate. Performance of self-selected movements induced significant activation of the anterior SMA/cingulate in normal subjects but not in Parkinson's disease patients. We conclude that in Parkinson's disease patients more cortical areas are recruited to perform sequential finger movements; this may be the result of increasing corticocortical activity to compensate for striatal dysfunction
AD  - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA
UR  - PM:10094257
ER  - 

TY  - JOUR
T1  - Brain imaging of 18F-fallypride in normal volunteers: Blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors
A1  - Mukherjee,J.
A1  - Christian,B.T.
A1  - Dunigan,K.A.
A1  - Shi,B.
A1  - Narayanan,T.K.
A1  - Satter,M.
A1  - Mantil,J.
Y1  - 2002/12//
N1  - UI - 22237211
SP  - 170
EP  - 188
JF  - Synapse
VL  - 46
IS  - 3
N2  - Human studies of dopamine D2/D3 receptors using (18)F-fallypride-PET in normal volunteers were performed to evaluate brain distribution in striatal and extrastriatal regions, evaluate metabolites in blood plasma, establish PET imaging protocol for this new radiotracer, evaluate graphical methods of analysis to quantitate D2/D3 receptors, and assess the ability of (18)F-fallypride to measure changes in D2/D3 receptors with aging as a model. Subjects (6; 21-63 years) had a PET scan on a Siemens HR+ scanner with (18)F-fallypride and a T1-weighted MRI scan on a 1.5T GE scanner for purposes of anatomical coregistration with PET. A 3-h PET scan with (18)F-fallypride (0.07 mCi/Kg) was carried out on each subject and repeated in 4-6 weeks. Arterial or arterialized venous blood was obtained in all subjects in order to evaluate blood activity levels and analyze metabolites in the plasma. Brain regions-of-interest were identified and drawn using PET and PET-MR coregistered images. PET data was analyzed using graphical methods in which cerebellum was used as the reference region providing distribution volume ratios (DVR) from which binding potential (BP) was derived and used as a measure of concentration of receptors. Distribution of (18)F-fallypride was consistent in all subjects studied and the rank order of receptor concentration was putamen > caudate > thalamus = pituitary > amygdala > colliculi > substantia nigra > hippocampus = temporal cortex > parietal cortex = occipital cortex = orbitofrontal cortex. For younger subjects, BP ranged from 37 for the putamen to 0.4 for orbitofrontal cortex, with a test-retest error of about 10%. Both hydrophilic and lipophilic metabolites were observed in arterial blood plasma and analyses showed approx. 30-40% of plasma radioactivity at 3 h was (18)F-fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of (18)F-fallypride. PET studies with (18)F-fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions. Synapse 46:170-188, 2002
AD  - Department of Nuclear Medicine/PET, Kettering Medical Center, Dayton, Ohio 45429
UR  - PM:12325044
ER  - 

TY  - JOUR
T1  - The elusive concept of brain connectivity
A1  - Horwitz,Barry
Y1  - 2003/06//
SP  - 466
EP  - 470
JF  - Neuroimage
VL  - 19
IS  - 2
N2  - Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution
UR  - http://www.sciencedirect.com/science/article/B6WNP-48J44GM-P/2/a63e7b52e8ff3c8972e71d87743c57df
ER  - 

TY  - JOUR
T1  - Cost-Effectiveness of PET in the Diagnosis of Alzheimer Disease
A1  - McMahon,Pamela M.
A1  - Araki,Sally S.
A1  - Sandberg,Eileen A.
A1  - Neumann,Peter J.
A1  - Gazelle,G.Scott
Y1  - 2003/06/11/
SP  - 2282020915
JF  - Radiology
N2  - PURPOSE: To evaluate the cost-effectiveness of positron emission tomography (PET) in the diagnosis of Alzheimer disease (AD) in community-dwelling patients with mild or moderate dementia who present to specialized AD centers. MATERIALS AND METHODS: A decision-analytic model was used to compare costs and quality-adjusted life years (QALYs) associated with strategies involving single photon emission computed tomography (SPECT), dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging, and PET as functional imaging adjuncts to the standard clinical work-up. Sensitivity analyses were performed to examine changes in test characteristics, health-related quality-of-life survey instruments, therapeutic effectiveness, and treatment rules. RESULTS: The use of PET to confirm the results of the standard clinical work-up cost more but yielded fewer benefits than a strategy in which dynamic susceptibility-weighted contrast-enhanced MR imaging was substituted for the typically performed structural computed tomography. This relationship remained stable in scenarios in which standard diagnostic work-up accuracy, drug treatment effectiveness, and version of the Health Utilities Index were altered. Dynamic susceptibility-weighted contrast-enhanced MR imaging cost $598,800 per QALY gained (range, $74,400 to $1.9 million per QALY), compared with the cost of the standard diagnostic work-up. Treating all patients with dementia was the dominant imaging strategy, except when side effects in patients with non-AD-related dementia were modeled. In all scenarios, SPECT yielded fewer benefits than other strategies at a higher cost. CONCLUSION: PET may have high diagnostic accuracy, but adding it to the standard diagnostic regimen at AD clinics would yield limited, if any, benefits at very high costs
UR  - http://radiology.rsnajnls.org/cgi/content/abstract/2282020915v1
ER  - 

TY  - JOUR
T1  - Imaging substance P receptors (NK1) in the living human brain using positron emission tomography
A1  - Hargreaves,R.
Y1  - 2002///
N1  - DB - MEDLINE
SP  - 18
EP  - 24
JF  - Journal of Clinical Psychiatry
VL  - 63 Suppl 11
N2  - Substance P (SP)-neurokinin-1 (NK1) receptor pathways have been implicated in the pathophysiology of emesis and depression. Autoradiographic studies in monkey and human brains have shown a high expression of NK1 receptors in regions important for the regulation of affective behaviors and the neurochemical response to stress. Furthermore, clinical studies demonstrated that treatment with the SP (NK1 receptor) antagonist (SPA) aprepitant (also known as MK-0869) significantly improves depression symptoms and reduces the incidence of chemotherapy-induced nausea and vomiting. An important objective of all neuroscience drug discovery and development programs is to establish the correlation between dose, receptor occupancy, and the observed clinical effect (the dose-response relationship). These goals can be achieved using radioactive receptor-specific tracers and dynamic noninvasive brain imaging modalities, such as positron emission tomography (PET). In the SPA program, a tracer and 2 over black square]; [1 and 2 over black square]8F]SPA-RQ was chosen for PET studies on the basis of several criteria, including high affinity for the NK1 receptor, low nonspecific binding, and good blood-brain barrier penetration. PET imaging studies in rhesus monkeys and humans confirmed these tracer features and established the usefulness of this probe for in vivo NK1 receptor occupancy studies. Subsequent PET occupancy studies in humans predicted that very high levels of central NK1 receptor occupancy (> 90%) were associated with therapeutically significant antidepressant and antiemetic effects. Future PET imaging studies will focus on quantification of NK1 receptor expression in depressed patients, both before and after successful treatment with antidepressants. [References: 19] <9>
ER  - 

TY  - JOUR
T1  - Predictors of treatment response in bipolar disorders: evidence from clinical and brain imaging studies
A1  - Ketter,T.A.
A1  - Wang,P.W.
Y1  - 2002///
N1  - DB - MEDLINE
SP  - 21
EP  - 25
JF  - Journal of Clinical Psychiatry
VL  - 63 Suppl. 3
N2  - The clinical features of bipolar disorders can be correlated with responses to medications. Patients who respond to lithium, for example, often present differently from those who respond to divalproex or carbamazepine, but the correlations are relatively modest. Brain-imaging tools, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), can relate brain function to clinical features and medication responses. For example, in depression, it appears that prefrontal cortical function is decreased while subcortical anterior paralimbic activity is increased. Preliminary evidence suggests that baseline metabolism increases and decreases in the left insula may be associated with carbamazepine and nimodipine responses, respectively, and that cerebral lithium concentrations may correlate with antimanic effects. Although it is not yet a clinical tool for bipolar disorders, brain imaging provides useful research data to understand the fundamental neurobiology of mood disorders and to more effectively target therapeutics. [References: 55] <45>
ER  - 

TY  - JOUR
T1  - Principal components of the Beck Depression Inventory and regional cerebral metabolism in unipolar and bipolar depression
A1  - Dunn,R.T.
A1  - Kimbrell,T.A.
A1  - Ketter,T.A.
A1  - Frye,M.A.
A1  - Willis,M.W.
A1  - Luckenbaugh,D.A.
A1  - Post,R.M.
Y1  - 2002/03/01/
N1  - DB - MEDLINE
JF  - Biological Psychiatry.51(5):387-99,
N2  - BACKGROUND: We determined clustering of depressive symptoms in a combined group of unipolar and patients with bipolar disorder using Principle Components Analysis of the Beck Depression Inventory. Then, comparing unipolars and bipolars, these symptom clusters were examined for interrelationships, and for relationships to regional cerebral metabolism for glucose measured by positron emission tomography. METHODS: and 2 over black square]; [1 and 2 over black square]8F]-fluoro-deoxyglucose positron emission tomography scans and Beck Depression Inventory administered to 31 unipolars and 27 bipolars, all medication-free, mildly-to-severely depressed. BDI component and total scores were correlated with global cerebral metabolism for glucose, and voxel-by-voxel with cerebral metabolism for glucose corrected for multiple comparisons. RESULTS: In both unipolars and bipolars, the psychomotor-anhedonia symptom cluster correlated with lower absolute metabolism in right insula, claustrum, anteroventral caudate/putamen, and temporal cortex, and with higher normalized metabolism in anterior cingulate. In unipolars, the negative cognitions cluster correlated with lower absolute metabolism bilaterally in frontal poles, and in right dorsolateral frontal cortex and supracallosal cingulate. CONCLUSIONS: Psychomotor-anhedonia symptoms in unipolar and bipolar depression appear to have common, largely right-sided neural substrates, and these may be fundamental to the depressive syndrome in bipolars. In unipolars, but not bipolars, negative cognitions are associated with decreased frontal metabolism. Thus, different depressive symptom clusters may have different neural substrates in unipolars, but clusters and their substrates are convergent in bipolars. <46>
ER  - 

TY  - JOUR
T1  - Greater loss of 5-HT(2A) receptors in midlife than in late life
A1  - Sheline,Y.I.
A1  - Mintun,M.A.
A1  - Moerlein,S.M.
A1  - Snyder,A.Z.
Y1  - 2002/03//
N1  - DB - MEDLINE
SP  - 430
EP  - 435
JF  - American Journal of Psychiatry
VL  - 159
N2  - OBJECTIVE: Earlier work has shown markedly lower density of serotonin 2A (5-HT(2A)) receptors in elderly subjects than in young healthy subjects. In this study the authors used positron emission tomography (PET) and [(18)F]altanserin, a ligand with high affinity for the 5-HT(2A) receptor, to examine the relationship between 5-HT(2A) receptor density and age in more detail. METHOD: The 22 subjects ranged in age from 21 to 69 years (mean=43.4, SD=13.3) and were healthy comparison subjects in a study of depression. Regions of interest were determined on magnetic resonance images and were transferred to coregistered PET data. The data were derived from dynamic PET scanning and arterial sampling with resulting plasma activity data corrected for labeled metabolites. Compartmental modeling was used to estimate the radioligand distribution volume. By comparing the distribution volume (DV) of different regions to the cerebellum distribution volume, DV(ratio)-1, which is proportional to the binding potential, was calculated. RESULTS: The decrease in 5-HT(2A) binding was not linear but on average was approximately 17% per decade from age 20. The correlations between age and 5-HT(2A) DV(ratio)-1 were significant for the global measure and for the medial gyrus rectus, anterior cingulate, posterior medial prefrontal cortex, hippocampus, and occipital cortex. Most of the fall off in receptor binding occurred up through midlife, and there was less decrease in late life. There were no decreases in regional brain volumes of corresponding magnitudes. CONCLUSIONS: 5-HT(2A) receptor binding decreases dramatically in a variety of brain regions up through midlife. <48>
ER  - 

TY  - JOUR
T1  - Quantification of 5-HT(1A) receptors in human brain using p-MPPF kinetic modelling and PET
A1  - Sanabria-Bohorquez,S.M.
A1  - Biver,F.
A1  - Damhaut,P.
A1  - Wikler,D.
A1  - Veraart,C.
A1  - Goldman,S.
Y1  - 2002/01//
N1  - DB - MEDLINE
SP  - 76
EP  - 81
JF  - European Journal of Nuclear Medicine & Molecular Imaging
VL  - 29
N2  - Serotonin-1A (5-HT(1A)) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N-(2"-pyridinyl)- p-[(18)F]fluorobenzamido] ethyl] piperazine ( p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT(1A) receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT(1A) receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT(1A) receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT(1A) receptor human studies. <52>
ER  - 

TY  - JOUR
T1  - Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study
A1  - Meyer,J.H.
A1  - Wilson,A.A.
A1  - Ginovart,N.
A1  - Goulding,V.
A1  - Hussey,D.
A1  - Hood,K.
A1  - Houle,S.
Y1  - 2001/11//
N1  - DB - MEDLINE
SP  - 1843
EP  - 1849
JF  - American Journal of Psychiatry
VL  - 158
N2  - OBJECTIVE: Selective serotonin reuptake inhibitors are commonly used to treat major depression; however, the percentage of serotonin (5-HT) transporter (5-HTT) sites occupied during clinical dosing is unknown. This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked. METHOD: Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT binding potential was measured with [(11)C]DASB and positron emission tomography, before and after 4 weeks of treatment. The binding potential is proportional to receptor density. Striatal 5-HTT binding potential was measured twice in six healthy subjects and once in 11 healthy subjects. RESULTS: A significant decrease in striatal 5-HTT binding potential was found after either treatment, compared to changes found over a 4-week period in healthy subjects. For patients treated with 20 mg/day of paroxetine (N=7), the mean proportion of 5-HTT sites occupied was 83%. For patients treated with 20 mg/day of citalopram (N=4), the mean 5-HTT occupancy was 77%. 5-HTT occupancy increased in a nonlinear relationship with serum levels of paroxetine such that a plateau of occupancy around 85% occurred for serum paroxetine levels greater than 28 microg/liter. CONCLUSIONS: During treatment with clinical doses of paroxetine or citalopram, approximately 80% of 5-HTT receptors are occupied. This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential but may be necessary for some therapeutic effects. <57>
ER  - 

TY  - JOUR
T1  - The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study
A1  - Meyer,J.H.
A1  - Kapur,S.
A1  - Eisfeld,B.
A1  - Brown,G.M.
A1  - Houle,S.
A1  - Dasilva,J.
A1  - Wilson,A.A.
A1  - Rafi-Tari,S.
A1  - Mayberg,H.S.
A1  - Kennedy,S.H.
Y1  - 2001/01//
N1  - DB - MEDLINE
SP  - 78
EP  - 85
JF  - American Journal of Psychiatry
VL  - 158
N2  - OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression. <88>
ER  - 

TY  - JOUR
T1  - Prefrontal cortical hypometabolism during low-dose interferon alpha treatment
A1  - Juengling,F.D.
A1  - Ebert,D.
A1  - Gut,O.
A1  - Engelbrecht,M.A.
A1  - Rasenack,J.
A1  - Nitzsche,E.U.
A1  - Bauer,J.
A1  - Lieb,K.
Y1  - 2000/11//
N1  - DB - MEDLINE
SP  - 383
EP  - 389
JF  - Psychopharmacology
VL  - 152
N2  - OBJECTIVE: To evaluate prospectively interferon alpha (IFN-alpha) associated effects on cerebral glucose metabolism and its correlation to neuropsychiatric symptoms during low-dose IFN-alpha-treatment. METHODS: Eleven patients treated with low-dose IFN-alpha for chronic hepatitis C were prospectively evaluated by neuropsychiatric tests and cerebral and 2 over black square]; [1 and 2 over black square]8F]deoxyglucose positron emission tomography (FDG-PET) before and in the 12th week of treatment. PET images were spatially normalized, corrected for variance in global activity and pixel-based t-statistics were calculated for each set of PET scans using SPM96 software. Pixel-cluster with P<0.001 for hypo- or hypermetabolism were displayed in parametric images. Covariance analysis with neuropsychiatric tests was calculated for each cluster. RESULTS: In week 12 of IFN-alpha treatment, significant hypometabolism with a decrease of local activity ranging from 8 to 12% was found in all patients bilaterally in the prefrontal cortex (BA 9), which correlated in a covariate analysis with changes in depression score as measured by Beck's Depression Inventory. Additionally, hypermetabolism with a maximum increase in local activity of 6-8% was seen in all patients in putamina as well as the left occipital region (BA 18). Before IFN-alpha treatment, only 1/11 patient showed depressive symptomatology. After 3 months of treatment, 6/11 patients were classified as having mild to moderate depressive symptoms (P<0.1; Wilcoxon test). CONCLUSIONS: Low-dose IFN-alpha therapy is associated with significant prefrontal hypometabolism. This hypometabolism covaried with depression score, but was even found in clinically non-depressed patients. These findings may reflect a possible predisposing factor for IFN-alpha associated neuropsychiatric syndromes and might contribute to a pathophysiological model of affective disorders, as endogenous IFN-alpha levels are elevated in a subset of psychotic patients during acute disease. <91>
ER  - 

TY  - JOUR
T1  - Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response
A1  - Mayberg,H.S.
A1  - Brannan,S.K.
A1  - Tekell,J.L.
A1  - Silva,J.A.
A1  - Mahurin,R.K.
A1  - McGinnis,S.
A1  - Jerabek,P.A.
Y1  - 2000/10/15/
N1  - DB - MEDLINE
JF  - Biological Psychiatry.48(8):830-43,
N2  - BACKGROUND: Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized. METHODS: Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment. RESULTS: Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes. CONCLUSIONS: Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse. <99>
ER  - 

TY  - JOUR
T1  - Drug action at the 5-HT(1A) receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-(11)C]WAY-100635
A1  - Rabiner,E.A.
A1  - Gunn,R.N.
A1  - Wilkins,M.R.
A1  - Sargent,P.A.
A1  - Mocaer,E.
A1  - Sedman,E.
A1  - Cowen,P.J.
A1  - Grasby,P.M.
Y1  - 2000/07//
N1  - DB - MEDLINE
SP  - 509
EP  - 513
JF  - Nuclear Medicine & Biology
VL  - 27
N2  - Serotonin(1A) (5-HT(1A)) receptors have been implicated in the pathophysiology and treatment of anxiety and depression and are a target for novel drug development. In this qualitative study, positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635 were used to assess 5-HT(1A) autoreceptor and postsynaptic receptor occupancy in man in vivo by five different compounds with nanomolar affinity for this site. Occupancy by pindolol, penbutolol, buspirone, EMD 68843, and S 15535 was compared to test-retest data from 10 healthy volunteers. All drugs, apart from buspirone, displayed occupancy at the 5-HT(1A) receptor site. Pindolol demonstrated a preferential occupancy at the autoreceptor compared to the postsynaptic receptor over a plasma range of about 10-20 ng/mL. Differential occupancy may be an important component of novel drug action. The level of autoreceptor or postsynaptic occupancy needed to achieve significant physiological effects is not known, although it is of note that none of the drugs in this study achieved occupancies beyond 60%. Overall this study demonstrates the utility of PET in aiding novel drug development. <106>
ER  - 

TY  - JOUR
T1  - A preliminary study of the effects of electroconvulsive therapy on regional brain glucose metabolism in patients with major depression
A1  - Yatham,L.N.
A1  - Clark,C.C.
A1  - Zis,A.P.
Y1  - 2000/06//
N1  - DB - MEDLINE
JF  - Journal of ECT.16(2):171-6,
N2  - Animal studies have shown that a course of electroconvulsive shock (ECS) leads to a significant reduction in glucose metabolism in rat brains 1 day after the last ECS. In humans, of the two positron emission tomography (PET) studies that assessed the effects of a course of electroconvulsive therapy (ECT) on brain glucose metabolism in depressed patients, one reported no change while the other found a trend for reduction in glucose metabolism in frontal cortical region 24 hours after last ECT. The changes in glucose metabolism detected 24 hours after the last ECS/ECT treatment might simply be due to subacute effects of a seizure. We hypothesized that the changes in brain metabolism that persist 1 week after a course of ECT are more likely to underlie the therapeutic effects of ECT. We, therefore, investigated the effects of a course of ECT on brain glucose metabolism 1 week after last ECT by using PET and and 2 over black square]; [1 and 2 over black square]8F]fluorodeoxyglucose (FDG). Six patients who met DSM-IV criteria for a diagnosis of major depressive disorder (unipolar), and were referred for ECT as the clinically indicated treatment were recruited. They underwent two PET scans, one prior to first ECT and the second a week after last ECT. The number of ECT treatments subjects received ranged from 8 to 12 with a mean of 11. Five out of six patients responded to the ECT treatment. Cerebral metabolic rates for glucose were slightly lower in most regions post treatment compared with pretreatment but the differences were not statistically significant. Similarly, there was no significant correlation between changes in regional cerebral metabolic rates for glucose (rCMRglc) and changes in Hamilton Depression Rating Scale (HAM-D 21-item) scores. Our results might suggest that rCMRglc rates are not altered 1 week after a therapeutic course of ECT in depressed patients. Further studies using new generation PET scanners, which have a higher resolution, in larger numbers of depressed patients, are clearly needed before firm conclusions can be drawn. <111>
ER  - 

TY  - JOUR
T1  - Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex
A1  - Wu,J.
A1  - Buchsbaum,M.S.
A1  - Gillin,J.C.
A1  - Tang,C.
A1  - Cadwell,S.
A1  - Wiegand,M.
A1  - Najafi,A.
A1  - Klein,E.
A1  - Hazen,K.
A1  - Bunney,W.E.,Jr.
A1  - Fallon,J.H.
A1  - Keator,D.
Y1  - 1999/08//
N1  - DB - MEDLINE
SP  - 1149
EP  - 1158
JF  - American Journal of Psychiatry
VL  - 156
N2  - OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments. <123>
ER  - 

TY  - JOUR
T1  - The interaction between mood and cognitive function studied with PET
A1  - Baker,S.C.
A1  - Frith,C.D.
A1  - Dolan,R.J.
Y1  - 1997/05//
N1  - DB - MEDLINE
SP  - 565
EP  - 578
JF  - Psychological Medicine
VL  - 27
N2  - BACKGROUND: Experimentally induced depressed mood is a suggested model for retarded depression. We describe the neural response associated with induced mood and the locus of the interaction between systems mediating mood and cognitive function. METHODS: Normal subjects performed a verbal fluency task during induced elated and depressed mood states. Regional cerebral blood flow (rCBF) was measured as an index of neural activity using Positron Emission Tomography (PET). RESULTS: In both elated and depressed mood state rCBF was increased in lateral orbitofrontal cortex, rCBF was also increased in the midbrain in elated mood. In the depressed condition rCBF was decreased in rostral medial prefrontal cortex. Verbal fluency produced an expected increase of rCBF in left dorsolateral prefrontal, inferior frontal and premotor cortex, anterior cingulate and insula cortex bilaterally, the left supramarginal gyrus posteriorly and the thalamus. Activation in the verbal fluency task was attenuated throughout the left prefrontal, premotor and cingulate cortex and thalamus in both elated and depressed mood conditions. An attenuation of anterior cingulate activation was specific to depressed mood. CONCLUSIONS: Alteration of mood is associated with activation of orbitofrontal cortex which may be critical to the experience of emotion. The mood induced modulation of verbal fluency induced activations is consistent with resting state findings of decreased function in these regions in depressed patients. The present data suggest that resting state rCBF profile may represent the modulation of spontaneous activity in this network by a core system that is dysfunctional in depression. <171>
ER  - 

TY  - JOUR
T1  - Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings
A1  - Sultzer,D.L.
A1  - Mahler,M.E.
A1  - Cummings,J.L.
A1  - Van Gorp,W.G.
A1  - Hinkin,C.H.
A1  - Brown,C.
Y1  - 1995/08//
N1  - DB - MEDLINE
SP  - 773
EP  - 780
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 52
N2  - OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. RESULTS: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia. <200>
ER  - 

TY  - JOUR
T1  - Frontal lobe dysfunction in secondary depression. [Review] [188 refs]
A1  - Mayberg,H.S.
Y1  - 1994///
N1  - DB - MEDLINE
JF  - Journal of Neuropsychiatry & Clinical Neurosciences.6(4):428-42,
N2  - Depression is common in patients with neurological disease, particularly with diseases involving the basal ganglia. Although the mechanisms of mood disorders in these patients are poorly understood, selective neural pathways affected directly and indirectly by basal ganglia injury provide a strategy for examining these patients with functional imaging techniques. Studies of regional cerebral glucose metabolism by use of positron-emission tomography are reviewed. These studies demonstrate bilateral hypometabolism of orbital-inferior prefrontal cortex and anterior temporal cortex in depressed subjects, independent of disease etiology. This pattern is similar to that seen in patients with primary unipolar depression. These findings suggest that disruption of paralimbic pathways linking frontal cortex, temporal cortex, and striatum may contribute to both primary depression and depression associated with basal ganglia disease. The findings support the evolving concept of a neuroanatomical locus for mood regulation. [References: 188] <207>
ER  - 

TY  - JOUR
T1  - Gender-related differences in regional cerebral glucose metabolism in normal volunteers
A1  - Andreason,P.J.
A1  - Zametkin,A.J.
A1  - Guo,A.C.
A1  - Baldwin,P.
A1  - Cohen,R.M.
Y1  - 1994/02//
N1  - DB - MEDLINE
SP  - 175
EP  - 183
JF  - Psychiatry Research
VL  - 51
N2  - Positron emission tomography studies have correlated changes in the cerebral metabolic rate of glucose utilization (CMRglu) with symptoms of depression, aggression, impulsivity, and hyperactivity. Psychiatric disorders in which these symptoms are manifested are disproportionately represented among the sexes. We evaluated gender differences in regional CMRglu in control subjects (21 men and 18 women) with particular interest in the global, orbital frontal, and left anterolateral prefrontal cortical (LAPFC) CMRglu. A trend was present for global CMRglu to be greater in women than in men. Regional CMRglu was lower in men than in women in the orbital frontal area. No differences were observed in the LAPFC region. <214>
ER  - 

TY  - JOUR
T1  - Left and right hemisphere contribution to recovery from neglect after right hemisphere damage--an [18F]FDG PET study of two cases
A1  - Perani,D.
A1  - Vallar,G.
A1  - Paulesu,E.
A1  - Alberoni,M.
A1  - Fazio,F.
Y1  - 1993/02//
N1  - DB - MEDLINE
SP  - 115
EP  - 125
JF  - Neuropsychologia
VL  - 31
N2  - A 2-and 2 over black square]; [1 and 2 over black square]8F]-Fluoro-2-Deoxy-D-Glucose (and 2 over black square]; [1 and 2 over black square]8F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere. <233>
ER  - 

TY  - JOUR
T1  - Neuroanatomical circuits in depression: implications for treatment mechanisms. [Review] [129 refs]
A1  - Drevets,W.C.
A1  - Raichle,M.E.
Y1  - 1992///
N1  - DB - MEDLINE
JF  - Psychopharmacology Bulletin.28(3):261-74,
N2  - We previously investigated the functional neuroanatomy of familial pure depressive disease (FPDD) using positron emission tomography (PET) measurements of regional blood flow and obtained evidence that flow is increased in the left prefrontal cortex, amygdala, and medial thalamus and is decreased in the medial caudate. These data along with other evidence suggested that circuits involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus are involved in the pathophysiology of FPDD. One of these circuits, the limbic-thalamo-cortical circuit, which includes the amygdala, the medio-dorsal thalamus, and parts of the ventral and medial prefrontal cortex, may be engaged in abnormal reverberatory activity that maintains the cognitive and emotional set of depression. Using this hypothesis as a neural model to investigate antidepressant treatment mechanisms, we review evidence that the changes in dopaminergic, serotonergic, and noradrenergic function induced by somatic antidepressant therapies may yield modulatory effects on limbic-thalamo-cortical activity. We also discuss preliminary findings of treatment-associated changes in this circuit in studies comparing PET images acquired before and during antidepressant treatment. [References: 129] <237>
ER  - 

TY  - JOUR
T1  - Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study
A1  - Laplane,D.
A1  - Levasseur,M.
A1  - Pillon,B.
A1  - Dubois,B.
A1  - Baulac,M.
A1  - Mazoyer,B.
A1  - Tran,Dinh S.
A1  - Sette,G.
A1  - Danze,F.
A1  - Baron,J.C.
Y1  - 1989/06//
N1  - DB - MEDLINE
SP  - 699
EP  - 725
JF  - Brain
VL  - 112
N2  - Eight patients are reported who shared the combination of bilateral basal ganglia lesions and a frontal lobe-like syndrome. The main features were inertia and loss of drive, with preservation of intellectual function. Some patients showed stereotyped activities with compulsive and obsessive behaviour which were sometimes highly elaborate in pattern. Extrapyramidal clinical signs were absent or mild. Brain damage, related to anoxic or toxic encephalopathy, was demonstrated by CT scans and MRI. The lesions appeared to be confined to the lentiform nuclei, particularly affecting the pallidum, although there was generalized brain atrophy in 2 cases. Positron emission tomography (PET) in 7 patients revealed hypometabolism of the prefrontal cortex relative to other parts of the brain. The PET studies suggest dysfunction of the prefrontal cortex as a result of damage to the lentiform nuclei. These clinical, anatomical and functional observations emphasize the role of the circuits linking the prefrontal associative cortex and some specific areas of the neostriatum, including the pallidum. The existence of distinct nonoverlapping circuits in the motor field or in the associative field can explain the fact that basal ganglia lesions may give rise to a clinical picture that is either purely motor, purely behavioural (as in some of our patients), or both. Similarities existed between some symptoms found in our patients and certain features of major psychiatric illnesses such as severe depression, catatonic schizophrenia, and obsessive-compulsive disorder. This raises the hypothesis that some aspects of these psychiatric disorders could be related to structural and physiological disturbances in the systems linking the frontal associative cortex and the basal ganglia. <281>
ER  - 

TY  - JOUR
T1  - The differential diagnosis of depression. Relevance of positron emission tomography studies of cerebral glucose metabolism to the bipolar-unipolar dichotomy
A1  - Schwartz,J.M.
A1  - Baxter,L.R.,Jr.
A1  - Mazziotta,J.C.
A1  - Gerner,R.H.
A1  - Phelps,M.E.
Y1  - 1987/09/11/
N1  - DB - MEDLINE
SP  - 1368
EP  - 1374
JF  - JAMA
VL  - 258
ER  - 

TY  - JOUR
T1  - Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study
A1  - Phillips,P.C.
A1  - Dhawan,V.
A1  - Strother,S.C.
A1  - Sidtis,J.J.
A1  - Evans,A.C.
A1  - Allen,J.C.
A1  - Rottenberg,D.A.
Y1  - 1987/01//
N1  - DB - MEDLINE
SP  - 59
EP  - 63
JF  - Annals of Neurology
VL  - 21
N2  - Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity. <297>
ER  - 

TY  - JOUR
T1  - Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study
A1  - Abrahams,S.
A1  - Goldstein,L.H.
A1  - Kew,J.J.
A1  - Brooks,D.J.
A1  - Lloyd,C.M.
A1  - Frith,C.D.
A1  - Leigh,P.N.
Y1  - 1996/12//
N1  - UI - 97163179
SP  - 2105
EP  - 2120
JF  - Brain
VL  - 119 ( Pt 6)
N2  - PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient selection was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments
AD  - Department of Psychology, Institute of Psychiatry, London, UK
UR  - PM:9010014
ER  - 

TY  - JOUR
T1  - Cortical motor-sensory hypometabolism in amyotrophic lateral sclerosis: a PET study
A1  - Hatazawa,J.
A1  - Brooks,R.A.
A1  - Dalakas,M.C.
A1  - Mansi,L.
A1  - Di Chiro,G.
Y1  - 1988/07//
N1  - UI - 88273768
SP  - 630
EP  - 636
JA  - J Comput.Assist.Tomogr.
VL  - 12
IS  - 4
N2  - We previously reported generalized cerebral glucose hypometabolism in amyotrophic lateral sclerosis (ALS) patients with upper motor neuron disease, using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose. The present article presents a more detailed regional analysis of the hypometabolism, including measurements of the motor-sensory cortex at higher levels than used earlier. The analysis is based on 19 PET studies of 12 patients with ALS, four of whom had only lower motor neuron involvement, and 11 studies of age-matched control subjects. A brain size correction was included to eliminate differences in metabolism related to brain size but not to pathology. The eight ALS patients with both upper and lower motor neuron disease showed generalized hypometabolism, compared with the normal control subjects, that was greatest in the motor-sensory cortex and putamen. The motor-sensory deficit was strongly correlated with length of disease, and a marked sequential reduction was seen in repeat studies on four of the patients. There was also significant right-left asymmetry in these scans. No cerebral hypometabolism was seen in the four ALS patients without upper motor neuron involvement. Although the observed motor-sensory deficit in ALS is consistent with histopathological findings, the more generalized hypometabolism and the asymmetry suggest more widespread effects
AD  - National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892
UR  - PM:3260610
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and oxygen metabolism in progressive dementia associated with amyotrophic lateral sclerosis
A1  - Tanaka,M.
A1  - Kondo,S.
A1  - Hirai,S.
A1  - Sun,X.
A1  - Yamagishi,T.
A1  - Okamoto,K.
Y1  - 1993/12/01/
N1  - UI - 94118049
SP  - 22
EP  - 28
JA  - J Neurol.Sci.
VL  - 120
IS  - 1
N2  - We examined regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) in 4 patients with progressive dementia associated with amyotrophic lateral sclerosis (ALS), in 9 patients with classical ALS without dementia, and in 13 normal controls, using positron emission tomography with oxygen-15 gas and oxygen-15 labeled carbon dioxide. The mean rCBF and rCMRO2 in the anterior cerebral hemispheres decreased significantly in patients with progressive dementia with ALS, compared to those in controls. Patients with only ALS showed very mild reductions of rCBF and rCMRO2 which were not statistically significant. These data suggest that hypoperfusion and oxygen hypometabolism in the anterior cerebral hemispheres have an etiological relationship to deterioration of intellect in patients with progressive dementia with ALS. A significant reduction in the mean rCBF was also found in the cerebellar hemispheres in progressive dementia with ALS, while a reduction of mean rCMRO2 was not significant. Remote effects analogous to crossed cerebellar diaschisis occurring bilaterally were assumed to explain the cerebellar hypoperfusion
AD  - Department of Neurology, Gunma University School of Medicine, Japan
UR  - PM:8289076
ER  - 

TY  - JOUR
T1  - A positron emission tomography study of frontal lobe function (verbal fluency) in amyotrophic lateral sclerosis
A1  - Abrahams,S.
A1  - Leigh,P.N.
A1  - Kew,J.J.
A1  - Goldstein,L.H.
A1  - Lloyd,C.M.
A1  - Brooks,D.J.
Y1  - 1995/05//
N1  - UI - 96059142
SP  - 44
EP  - 46
JA  - J Neurol.Sci.
VL  - 129 Suppl
N2  - Positron emission tomography (PET) was used to investigate the location of cerebral cortical and subcortical abnormalities in non-demented patients with amyotrophic lateral sclerosis (ALS). Involvement of the frontal lobes was investigated with a task of executive frontal lobe function (verbal fluency/word generation), using a PET activation paradigm. Two groups of ALS patients defined by the presence or absence of cognitive impairment were tested. ALS patients who had cognitive impairments showed a region of cortical and subcortical dysfunction which extended across a wide area of the frontal lobes, and included the insular cortex and thalamic nuclear complex. These findings support the notion that extra-motor involvement is relatively common in ALS and broadens concepts of selective vulnerability in ALS
AD  - Department of Psychology, Institute of Psychiatry, London, UK
UR  - PM:7595618
ER  - 

TY  - JOUR
T1  - Lowered cerebral glucose utilization in amyotrophic lateral sclerosis
A1  - Dalakas,M.C.
A1  - Hatazawa,J.
A1  - Brooks,R.A.
A1  - Di Chiro,G.
Y1  - 1987/11//
N1  - UI - 88105302
SP  - 580
EP  - 586
JA  - Ann.Neurol.
VL  - 22
IS  - 5
N2  - Regional cerebral metabolic rates for glucose (rCMRGlc) were analyzed in 19 studies of 12 patients with amyotrophic lateral sclerosis (ALS) by positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose. In the 8 ALS patients with upper motor neuron signs, the mean cortical rCMRGlc was significantly lower than in 11 age-matched control subjects (p less than 0.01). The degree of hypometabolism correlated with the duration of the clinical signs and extended throughout the cortex and basal ganglia, but not to the cerebellum. Of the 4 such patients who had repeat PET scans, 3 demonstrated significant subsequent reduction in the rCMRGlc, corresponding to the worsening of the clinical picture. In contrast, 4 ALS patients with disease confined to lower motor neurons and 3 patients with lower motor neuron disease from old paralytic poliomyelitis had normal or near-normal rCMRGlc throughout the brain. Because histological evidence shows no generalized neuronal cell loss in the cortex of ALS patients, including in some cases the primary motor regions, the demonstration of severe generalized hypometabolism in structurally normal cortex indicates that some cortical neurons exist in a state of neuronal nonfunction, rather than cell death, and that anatomoclinical correlations may be more complex. The data also indicate that ALS with upper motor neuron involvement extends beyond the corticospinal tracts and differs in cortical function from the ALS confined to lower motor neurons or the other lower motor neuron disorders
AD  - National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892
UR  - PM:3501273
ER  - 

TY  - JOUR
T1  - Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study
A1  - Ludolph,A.C.
A1  - Langen,K.J.
A1  - Regard,M.
A1  - Herzog,H.
A1  - Kemper,B.
A1  - Kuwert,T.
A1  - Bottger,I.G.
A1  - Feinendegen,L.
Y1  - 1992/02//
N1  - UI - 92245883
SP  - 81
EP  - 89
JA  - Acta Neurol.Scand.
VL  - 85
IS  - 2
N2  - In this study the regional cerebral glucose utilization and the neuropsychological performance of patients with amyotrophic lateral sclerosis (ALS) was investigated. Special attention was given to neuropsychological tests thought to mirror frontal lobe dysfunction. The regional cerebral glucose utilization was studied in 18 patients using high-resolution positron emission tomography. Clinically all patients displayed upper and lower motor neurone signs. In ALS patients glucose metabolism was significantly reduced in the frontal and in the entire cortex compared with controls; no changes were seen in the cerebellum. Comprehensive neuropsychological assessment of ALS patients compared to a pair matched control group revealed mild frontal dysfunction which in part significantly correlated with reduced glucose metabolism in the cortex and subcortical structures. We conclude that in patients with ALS, glucose consumption is decreased in parts of the brain other than the motor cortex accompanied by mild neuropsychological deficits based on the tests employed in this study
AD  - Department of Neurology, University of Munster, FRG
UR  - PM:1574993
ER  - 

TY  - JOUR
T1  - Potential amyloid-imaging agents: Binding ratios to homogenates of post-mortem AD and control brain
A1  - Klunk,W.
A1  - Debnath,M.
A1  - Holt,D.
A1  - Wang,Y.M.
A1  - Huang,G.F.
A1  - Mathis,C.
Y1  - 2002///
N1  - Journal
SP  - 1149
JF  - Neurobiology of Aging
VL  - 23
IS  - 1
UR  - ISI:000177465301128
ER  - 

TY  - JOUR
T1  - First human study with a benzothiazole amyloid-imaging agent in Alzheimer's disease and control subjects
A1  - Engler,H.
A1  - Blomqvist,G.
A1  - Bergstrom,M.
A1  - Estrada,S.
A1  - Sandell,J.
A1  - Antoni,G.
A1  - Langstrom,B.
A1  - Nordberg,A.
A1  - Barletta,J.
A1  - Klunk,W.
A1  - Debnath,M.
A1  - Holt,D.
A1  - Wang,Y.M.
A1  - Huang,G.F.
A1  - Mathis,C.
Y1  - 2002///
N1  - Journal
SP  - 1568
JF  - Neurobiology of Aging
VL  - 23
IS  - 1
UR  - ISI:000177465301540
ER  - 

TY  - JOUR
T1  - Labeled glucose analogs in the genomic era
A1  - Gatley,S.J.
Y1  - 2003/07//
N1  - UI - 22727352
SP  - 1082
EP  - 1086
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 7
AD  - Brookhaven National Laboratory, Upton, New York
UR  - PM:12843225
ER  - 

TY  - JOUR
T1  - Differential Features of Metabolic Abnormalities Between Medial and Lateral Temporal Lobe Epilepsy: Quantitative Analysis of (18)F-FDG PET Using SPM
A1  - Kim,Y.K.
A1  - Lee,D.S.
A1  - Lee,S.K.
A1  - Kim,S.K.
A1  - Chung,C.K.
A1  - Chang,K.H.
A1  - Choi,K.Y.
A1  - Chung,J.K.
A1  - Lee,M.C.
Y1  - 2003/07//
N1  - UI - 0
SP  - 1006
EP  - 1012
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 7
N2  - Because limited resection could yield an equally good surgical outcome as standard anterior resection in temporal lobe epilepsy (TLE), the differentiation of medial from lateral TLE is important. We tried to find the differential features in metabolic abnormalities between medial and lateral TLE groups using quantitative analysis including statistical parametric mapping (SPM). METHODS: We examined 113 (18)F-FDG PET scans of TLE patients who had surgically and pathologically proven lesions and a good surgical outcome (78 medial TLE, 35 lateral TLE). Each scan was compared with those of 22 healthy control subjects to detect hypometabolic regions using a t test of the SPM method and interhemispheric asymmetry using 2-group, 2-condition analysis on SPM. Group analysis was performed between medial and lateral TLE using mirrored PET images. The sensitivity was defined as the detection rate of hypometabolism in the ipsilateral temporal lobes, and the specificity was defined as the nondetection rate in the contralateral lobes. The extent of the hypometabolism was calculated as the number of significant voxels, and the severity was calculated by the asymmetry index (ASI), in the medial or lateral temporal lobes on Statistical Probabilistic Anatomical Map template images. RESULTS: The hypometabolism in the temporal lobes was detected ipsilateral to the seizure focus in 76% of the TLE patients (76% in medial TLE, 77% in lateral TLE) but on the contralateral temporal lobes in 32% of the patients. After considering interhemispheric temporal asymmetry, the sensitivity was found to be 89%, and the specificity was 91% without differences between the medial and lateral TLE groups. In both medial and the lateral TLE, the hypometabolism was more prominent in the lateral cortical structures than in the medial structures. The hypometabolism in the medial temporal structures was found less frequently in the lateral TLE group, and the extent of the hypometabolism was significantly larger in the medial TLE group. ASIs of the medial temporal structure and superior temproral gyrus of lateral temporal structure were significantly higher in the medial TLE. CONCLUSION: SPM analysis of (18)F-FDG PET in TLE patients could localize accurately the seizure focus and helped in the discrimination of the medial TLE from the lateral TLE. We suggest the lateral TLE, rather than the medial TLE, should be considered when glucose metabolism is relatively preserved in the medial temporal structures
AD  - Department of Nuclear Medicine, Seoul National University, College of Medicine, Seoul, Korea. Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea. Department of Neurosurgery, Seoul National University, College of Medicine, Seoul, Korea. Department of Diagnostic Radiology, Seoul National University, College of Medicine, Seoul, Korea. Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea
UR  - PM:12843213
ER  - 

TY  - JOUR
T1  - Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible?
A1  - Tsuyuguchi,N.
A1  - Sunada,I.
A1  - Iwai,Y.
A1  - Yamanaka,K.
A1  - Tanaka,K.
A1  - Takami,T.
A1  - Otsuka,Y.
A1  - Sakamoto,S.
A1  - Ohata,K.
A1  - Goto,T.
A1  - Hara,M.
Y1  - 2003/05//
N1  - UI - 22629166
SP  - 1056
EP  - 1064
JA  - J Neurosurg.
VL  - 98
IS  - 5
N2  - OBJECT: In this study the authors examined how to differentiate radiation necrosis from recurrent metastatic brain tumor following stereotactic radiosurgery by using positron emission tomography (PET) with L-[methyl-11C]methionine (MET). METHODS: In 21 adult patients with suspected recurrent metastatic brain tumor or radiation injury, MET-PET scans were obtained. These patients had previously undergone stereotactic radiosurgery and subsequent contrast-enhanced magnetic resonance (MR) examinations before nuclear medicine imaging. Positron emission tomography images were obtained as a static scan of 10 minutes performed 20 minutes after injection of 370 MBq of MET. On MET-PET scans, the portion of the tumor with the highest accumulation of MET was selected as the region of interest (ROI), and the ratio of tumor tissue to normal tissue (T/N) was defined as the mean counts of radioisotope per pixel in the tumor divided by the mean counts per pixel in normal gray matter. The standardized uptake value (SUV) was calculated using the same ROI in the tumor. The accuracy of the MET-PET scan was evaluated by correlating findings with results of subsequent histological analysis (11 cases) or, in cases in which surgery or biopsy was not performed, with subsequent clinical course and MR imaging findings (10 cases). Histological examinations performed in 11 cases showed viable tumor cells with necrosis in nine and necrosis with no viable tumor cells in two. Another 10 cases were characterized as radiation necrosis because the patients exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR images after 5 months. The mean T/N was 1.15 in the radiation necrosis group (12 cases) and 1.62 in the tumor recurrence group (nine cases). The mean SUV was 1.78 in the necrosis group and 2.5 in the recurrence group. There were statistically significant differences between the recurrence and necrosis groups in T/N and SUV. Furthermore, the borderline T/N value was 1,42 according to a 2 x 2 factorial table (high T/N or low T/N, recurrence or necrosis). From this result, the sensitivity and specificity of MET-PET scanning in detecting tumor recurrence were determined to be 77.8 and 100%, respectively. CONCLUSIONS: The use of MET-PET scanning is a sensitive and accurate technique for differentiating between metastatic brain tumor recurrence and radiation necrosis following stereotactic radiosurgery. This study reveals important information for creating strategies to treat postradiation reactions
AD  - Department of Neurosurgery, Osaka City University Graduate School of Medicine, Abeno, Osaka, Japan. nao@med.osaka-cu.ac.jp
UR  - PM:12744366
ER  - 

TY  - JOUR
T1  - Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain
A1  - Tzourio-Mazoyer,N.
A1  - Landeau,B.
A1  - Papathanassiou,D.
A1  - Crivello,F.
A1  - Etard,O.
A1  - Delcroix,N.
A1  - Mazoyer,B.
A1  - Joliot,M.
Y1  - 2002/01//
SP  - 273
EP  - 289
JF  - Neuroimage
VL  - 15
IS  - 1
N2  - An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps
UR  - http://www.sciencedirect.com/science/article/B6WNP-4575RNN-1F/2/3d7eadc4477a1a64629325332495df1d
ER  - 

TY  - JOUR
T1  - Measuring drug-related receptor occupancy with positron emission tomography
A1  - Passchier,Jan
A1  - Gee,Antony
A1  - Willemsen,Antoon
A1  - Vaalburg,Willem
A1  - van Waarde,Aren
Y1  - 2002/07//
SP  - 278
EP  - 286
JA  - Methods
VL  - 27
IS  - 3
UR  - http://www.sciencedirect.com/science/article/B6WN5-46HNPXK-C/2/74ae9965514d4f95c5d384f0fa913364
ER  - 

TY  - JOUR
T1  - Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease
A1  - Kemppainen,N.
A1  - Laine,M.
A1  - Laakso,M.P.
A1  - Kaasinen,V.
A1  - Nagren,K.
A1  - Vahlberg,T.
A1  - Kurki,T.
A1  - Rinne,J.O.
Y1  - 2003/07//
N1  - UI - 0
SP  - 149
EP  - 154
JA  - Eur.J Neurosci.
VL  - 18
IS  - 1
N2  - Post mortem studies have revealed a loss of dopamine D2 receptors in the temporal lobes in Alzheimer's disease (AD). Moreover, the role of hippocampal D2 receptors on memory performance has been suggested in experimental studies. However, there are no previous in vivo studies on extrastriatal D2 receptors in AD. Our aim was to examine in vivo whether hippocampal or temporal cortical dopamine D2 receptors are affected in AD and whether D2 receptor availability is associated with the memory dysfunction seen in AD. Fourteen patients with probable AD and 11 age- and sex-matched controls were studied with positron emission tomography using a dopamine D2/D3 receptor antagonist [11C]FLB 457. The D2 receptor binding potentials (BPs) were measured in extrastriatal brain regions and a neuropsychological investigation was performed on the patients with AD. In AD, the D2 receptor availability was reduced in the hippocampus: by 34% (P = 0.03) in the right hippocampus and by 14% (P = 0.78) in the left hippocampus as compared with controls. Multiple linear regression analysis showed that the BP in the right hippocampus had a significant positive association with verbal memory performance (Wechsler Memory Scale - Revised) (P = 0.001) and picture naming (the Boston Naming Test) (P = 0.002). Our findings suggest a role for temporal lobe D2 receptors in the memory and naming performance in AD, and suggest that studies to evaluate the efficiency of dopaminergic medication on patients with early AD might be warranted
AD  - Department of Neurology and Turku PET Centre, PO Box 52, University of Turku, FIN-20521 Turku, Finland Department of Psychology, Abo Akademi University, Turku, Finland Department of Neurology and Clinical Radiology, Kuopio University Hospital, Kuopio, Finland Turku PET Centre, Radiochemistry Laboratory, Turku, Finland Department of Biostatistics, University of Turku, Turku, Finland Department of Clinical Radiology, Turku University Central Hospital, Turku, Finland
UR  - PM:12859348
ER  - 

TY  - JOUR
T1  - Kinetics of the uptake and distribution of the dopamine D(2,3) agonist (R)-N-[1-(11)C]n-propylnorapomorphine in brain of healthy and MPTP-treated Gottingen miniature pigs
A1  - Cumming,P.
A1  - Gillings,N.M.
A1  - Jensen,S.B.
A1  - Bjarkam,C.
A1  - Gjedde,A.
Y1  - 2003/07//
N1  - UI - 22716863
SP  - 547
EP  - 553
JA  - Nucl Med Biol.
VL  - 30
IS  - 5
N2  - The binding of radioligand agonists to dopamine receptors in living brain can be informative about the abundance of receptors which are coupled to intracellular second messenger systems. Therefore, we developed a radiosynthesis for the dopamine D(2,3) partial agonist (R)-N- [1-(11)C]n-propylnorapomorphine ([(11)C]NPA). The uptake of this tracer in brain of anesthetized Gottingen miniature pigs was recorded by positron emission tomography (PET) and analyzed by compartmental analysis using the metabolite-corrected arterial input, and using reference tissue methods. [(11)C]NPA had a blood-brain unidirectional clearance of approximately 0.35 ml g(-1) min(-1) and an apparent distribution volume of 6 ml g(-1) in cerebellum. The ligand had a binding potential of 1.5 in striatum, comparable to that reported previously for the receptor antagonist [(11)C]raclopride in the same strain of animals. Significant binding was detected in the hypophysis, thalamus, and medial forebrain bundle. The binding in striatum was of comparable magnitude in normal pigs and in pigs with a documented 50% dopamine depletion produced by MPTP-intoxication. Deep brain stimulation of the subthalamus was without conspicuous effect on the binding of [(11)C]NPA in vivo. Results of this preliminary study indicate that this tracer meets many requirements for assaying dopamine agonist binding sites by PET
AD  - PET Center, Arhus University Hospitals, Norrebrogade 44, and Centre for Functionally Integrated Neuroscience, Aarhus, Denmark
UR  - PM:12831994
ER  - 

TY  - JOUR
T1  - The competition between endogenous dopamine and radioligands for specific binding to dopamine receptors
A1  - Cumming,P.
A1  - Wong,D.F.
A1  - Dannals,R.F.
A1  - Gillings,N.
A1  - Hilton,J.
A1  - Scheffel,U.
A1  - Gjedde,A.
Y1  - 2002/06//
SP  - 440
EP  - 450
JA  - Ann.N Y.Acad.Sci.
VL  - 965
N2  - The ternary complex model of G-protein-linkage to receptors holds that agonists increase the affinity of the receptors for the G protein. Consequently, an agonist can exert the greatest inhibition of the binding of radioligands which are also agonists. We hypothesized that competition from endogenous dopamine in striatum of living mice should thus have a greater effect on the binding of the D(2,3) agonist N-[(3)H]propylnorapomorphine ([(3)H]NPA), than on the binding of the D(2,3) antagonist [(11)C]raclopride in living brain. The binding potential (p(B(0))), defined as the ratio of bound-to-unbound ligand after reserpine treatment, was measured in mouse striatum for [(11)C]raclopride (p(B(0))(RAC)(C)) = 8.5, and for [(3)H]NPA(p(B(0))(NPA)) = 5.3. Relative to these baseline values after dopamine depletion, saline-treatment decreased the p(B) of [(3)H]NPA by one-half, while the p(B) of [(11)C]raclopride declined by only one-third. Amphetamine decreased the p(B) of [(3)H]NPA to a greater extent than that of [(11)C]raclopride. The apparent inhibition constant of endogenous dopamine depended on the dopamine occupancy and declined to a value 1.66 times greater for [(3)H]NPA than for [(11)C]raclopride at its highest occupancies. Thus, the agonist binding was more sensitive than antagonist binding to competition from endogenous dopamine. Dopamine agonist ligands may be especially useful for PET studies of dopamine receptor occupancy by endogenous synaptic dopamine. Analysis of the effect of dopamine occupancy on the inhibition of agonist indicated a limited supply of G protein, with a maximum ternary complex fraction of 40% of maximum antagonist binding capacity
AD  - PET Center, Arhus University Hospitals, Arhus, Denmark. paul@pet.auh.dk
UR  - PM:12105119
ER  - 

TY  - JOUR
T1  - (-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors
A1  - Hwang,D.R.
A1  - Kegeles,L.S.
A1  - Laruelle,M.
Y1  - 2000/08//
SP  - 533
EP  - 539
JA  - Nucl Med Biol.
VL  - 27
IS  - 6
N2  - Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [(11)C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[(11)C]NPA was prepared by reacting norapomorphine with [(11)C]propionyl chloride and a lithium aluminum hydride reduction. [(11)C]Propionyl chloride was prepared by reacting [(11)C]CO(2) with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[(11)C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700+/-1900 mCi/micromol ( N=7; ranged 110-5200 mCi/micromol at EOS). Rodent biodistribution studies showed high uptake of [(11)C](-)-NPA in D(2) receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[(11)C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86+/-0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D(2) receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D(2) agonist. (-)-[(11)C]NPA is a promising new D(2) agonist PET tracer for probing D(2) receptors in vivo using PET
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York, USA. hwang@neuron.cpmc.columbia.edu
UR  - PM:11056366
ER  - 

TY  - JOUR
T1  - Synthesis and in vivo distribution in the rat of a dopamine agonist: N-([11C]methyl)norapomorphine
A1  - Zijlstra,S.
A1  - van der,Worp H.
A1  - Wiegman,T.
A1  - Visser,G.M.
A1  - Korf,J.
A1  - Vaalburg,W.
Y1  - 1993/01//
N1  - UI - 93214632
SP  - 7
EP  - 12
JA  - Nucl Med Biol.
VL  - 20
IS  - 1
N2  - A method for the rapid production and purification of 10,11-dihydroxy-N-([11C]methyl)norapomorphine ([11C]APO), a dopamine agonist (DA), is described. The potency of this ligand for studying the D2-receptors was examined. The label was introduced by N-methylation of norapomorphine hydrobromide with no-carrier-added (n.c.a) [11C]CH3I, produced from cyclotron-produced [11C]carbon dioxide. In 60 min (EOB) a radiochemical yield of 15% (corrected for decay) was achieved, based on [11C]CH3I. The specific activity ranged from 5 to 11 GBq/mumol. The distribution, after intravenous injection, was studied in rats. The radioactivity level in the striatum was higher than in the cerebellum and frontal cortex and was decreased after D2-blockade. The highest uptake ratio (1.47) was found at 30 min after injection. Dopamine depletion with reserpine did increase the striatum/cerebellum ratio at a low dosage of [11C]APO (10 nmol/kg). High uptakes of [11C]apomorphine were found in the lungs, liver and kidneys
AD  - PET Center, University Hospital, Groningen, The Netherlands
UR  - PM:8096418
ER  - 

TY  - JOUR
T1  - Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemodynamic impairment revisited
A1  - Derdeyn,C.P.
A1  - Videen,T.O.
A1  - Yundt,K.D.
A1  - Fritsch,S.M.
A1  - Carpenter,D.A.
A1  - Grubb,R.L.
A1  - Powers,W.J.
Y1  - 2002/03//
N1  - UI - 21861510
SP  - 595
EP  - 607
JF  - Brain
VL  - 125
IS  - Pt 3
N2  - The presence or degree of haemodynamic impairment due to occlusive cerebrovascular disease is often inferred from measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and the cerebral rate for oxygen metabolism (CMRO2). However, the relationship of these variables, in particular CBV, to regional cerebral haemodynamics is not clearly established in humans with subacute or chronic disease. In the present study, we investigated the relationship of CBV to OEF, CBF and CMRO2, and to subsequent stroke risk in patients with unilateral carotid artery occlusion, in order to define better the associated haemodynamic and metabolic changes. We reviewed data from 81 patients with symptomatic carotid occlusion enrolled in a prospective study of haemodynamic factors and stroke risk. Measurements of CBV, CBF, OEF and CMRO2 were made on entry using PET. Patients were divided into groups by hemispheric ratios and absolute ipsilateral values of OEF and CBV, based on comparison with normal controls. Haemodynamic and metabolic values, risk factors and stroke risk were compared between groups. Based on hemispheric ratios, 45 patients had increased ipsilateral OEF; CBV was increased in 19 of these 45 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 19 patients and the remaining 26 patients with increased OEF and normal or reduced CBV. Thirteen ipsilateral strokes occurred during follow-up, and 10 of the 13 occurred in the 19 patients with increased OEF and CBV (log rank P < 0.0001). Thirty-two of the 68 patients with complete quantitative PET data had increased OEF by absolute ipsilateral values. CBV was increased in 20 of the 32 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 20 patients and the remaining 12 patients with increased OEF and normal CBV. Seven of the nine ipsilateral strokes that occurred in the 68 patients occurred in those 20 patients with increased OEF and increased CBV (log rank P = 0.003). The higher risk of ischaemic stroke in patients with increased OEF and CBV suggests that their degree of haemodynamic compromise is more severe than those with increased OEF and normal CBV. In patients with chronic carotid occlusion and increased OEF, increased CBV may indicate pronounced vasodilation due to exhausted autoregulatory vasodilation. The physiological explanation for the measurement of normal CBV in patients with increased OEF is less certain and may reflect preserved autoregulatory capacity
AD  - Neuroradiology Section, Division of Radiological Sciences, Mallinckrodt Institute of Radiology, St Louis, Missouri 63110, USA. derdeync@mir.wustl.edu
UR  - PM:11872616
ER  - 

TY  - JOUR
T1  - Acetazolamide reactivity on 123I-IMP single photon emission computed tomography in patients with major cerebral artery occlusive disease: correlation with positron emission tomography parameters
A1  - Hirano,T.
A1  - Minematsu,K.
A1  - Hasegawa,Y.
A1  - Tanaka,Y.
A1  - Hayashida,K.
A1  - Yamaguchi,T.
Y1  - 1994/09//
N1  - UI - 94342434
SP  - 763
EP  - 770
JA  - J Cereb.Blood Flow Metab
VL  - 14
IS  - 5
N2  - Single photon emission computed tomography (SPECT) with acetazolamide challenge has increasingly been used for evaluating hemodynamic reserve in stroke patients. The accuracy of this test, however, has not been validated with positron emission tomography (PET). In 14 patients who had occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA) with minimal or no infarction on computed tomography (CT) and magnetic resonance imaging (MRI), we compared acetazolamide reactivity on SPECT with N-isopropyl-p-[123I]-iodoamphetamine to hemodynamic parameters determined with gas inhalation labeled 15O steady-state PET studies. The asymmetry index (AI)--i.e., the percentage of the activity rate of the ischemic MCA territory versus the contralateral one, was determined by SPECT. Acetazolamide reactivity expressed as delta AI, or change in AI after acetazolamide challenge, was significantly lower in seven patients than -8.4%, the lower limit of the 95% confidence interval for the normal reactivity. Values of ipsilateral CBF, cerebral blood volume (CBV)/CBF, and oxygen extraction fraction (OEF) and contralateral OEF were significantly different between patients with normal and reduced acetazolamide reactivity. Values of delta AI were correlated with OEF (r = -0.87; p < 0.001) and CBV/CBF (r = -0.56; p < 0.05). All patients with OEF > 0.52, the mean + 2 SD calculated from five normal volunteers, also had reduced acetazolamide reactivity, while the patients with normal OEF values had normal reactivity. The present study has demonstrated that SPECT studies with an acetazolamide challenge can detect the Stage II hemodynamic failure
AD  - Department of Medicine, National Cardiovascular Center, Osaka, Japan
UR  - PM:8063872
ER  - 

TY  - JOUR
T1  - PET evaluation of cerebral hemodynamics in occlusive cerebrovascular disease pre- and postsurgery
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Sasaki,M.
A1  - Yoshida,T.
A1  - Fukumura,T.
A1  - Masuda,K.
A1  - Fujii,K.
A1  - Fukui,M.
Y1  - 1998/05//
N1  - UI - 98252244
SP  - 760
EP  - 765
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 39
IS  - 5
N2  - We studied cerebral blood flow (CBF), oxygen extraction fraction (OEF), transit time (TT) and hemodynamic reserve capacity using acetazolamide (ACZ) in both the pre- and postoperative states, and evaluated the effect of surgery on the cerebral hemodynamics. METHODS: Twelve patients with a unilateral occlusive cerebral artery were studied. Among them, seven patients had extracranial-intracranial (EC-IC) bypass surgery, while the remaining five patients had carotid endarterectomies. The CBF was measured using the (15)O-water bolus injection method in a resting state, 5 and 20 min after intravenous ACZ (1 g), while the OEF and TT were measured by the (15)O steady state method. The values of these parameters were obtained by regions of interest set over the cerebral hemisphere on both sides, and which then were compared between the pre- and postoperative states using the paired Student's t-test. RESULTS: The t values were 1.36 (CBF at rest), 2.97 (CBF at 5 min after intravenous ACZ), 1.40 (CBF at 20 min after intravenous ACZ), 2.00 (OEF) and -0.86 (TT) on the surgical side, and -0.16, 0.21, 0.22, -0.47 and 0.61 on the nonsurgical side, respectively. The t values of the ACZ response (% increase in CBF) were 3.07 (5 min after intravenous ACZ) and 0.72 (20 min) on the surgical side, and 1.03 and 0.90 on the nonsurgical side, respectively. A significant change was observed only in the CBF studies 5 min after intravenous ACZ. CONCLUSION: PET can demonstrate significant cerebral hemodynamic change after surgery, especially in CBF measurement 5 min after intravenous ACZ, and may therefore be useful for evaluating cerebral hemodynamics pre- and postsurgery
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:9591570
ER  - 

TY  - JOUR
T1  - Cerebral hemodynamics and metabolism in moyamoya disease--a positron emission tomography study
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Sasaki,M.
A1  - Yoshida,T.
A1  - Masuda,K.
A1  - Ikezaki,K.
A1  - Matsushima,T.
A1  - Fukui,M.
Y1  - 1997/10//
N1  - UI - 98073876
SP  - S74
EP  - S78
JA  - Clin.Neurol.Neurosurg.
VL  - 99 Suppl 2
N2  - We studied the cerebral blood flow (CBF), cerebrovascular response to hypercapnia, oxygen extraction fraction (OEF), metabolic rate for oxygen (CMRO2), blood volume (CBV) and transit time (TT: CBV/CBF) in Moyamoya disease using positron emission tomography (PET). The subjects consisted of 23 patients with Moyamoya disease, including eight pediatric and 15 adult patients. Among them, ten patients were examined both before and after surgery. The pediatric patients showed a marked increase in the CBV and a prolonged TT, especially in the striatum. The adult patients also showed a prolonged TT, but it was less prominent than that observed in pediatric patients, while the CBF remained at the level of the normal controls. The cerebrovascular response to hypercapnia was markedly impaired in both the pediatric and adult patients, which thus indicates a decrease in the hemodynamic reserve capacity. After surgery, the CBV, TT and cerebrovascular response to hypercapnia all improved, mainly in the temporal cortex where extracranial-intracranial (EC-IC) bypass surgery had been performed. In the striatum, the CBV also decreased, while the TT was shortened after surgery. A PET study was thus found to be useful for evaluating the cerebral hemodynamics in Moyamoya disease and monitoring the effect of surgery
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:9409411
ER  - 

TY  - JOUR
T1  - Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage
A1  - Hayashi,T.
A1  - Suzuki,A.
A1  - Hatazawa,J.
A1  - Kanno,I.
A1  - Shirane,R.
A1  - Yoshimoto,T.
A1  - Yasui,N.
Y1  - 2000/12//
N1  - UI - 21003932
SP  - 1014
EP  - 1018
JA  - J Neurosurg.
VL  - 93
IS  - 6
N2  - OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH
AD  - Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita, Japan. hayashi@nsg.med.tohoku.ac.jp
UR  - PM:11117843
ER  - 

TY  - JOUR
T1  - Influence of the normalization template on the outcome of statistical parametric mapping of PET scans
A1  - Gispert,J.D.
A1  - Pascau,J.
A1  - Reig,S.
A1  - Martinez-Lazaro,R.
A1  - Molina,V.
A1  - Garcia-Barreno,P.
A1  - Desco,M.
Y1  - 2003/07//
SP  - 601
EP  - 612
JF  - Neuroimage
VL  - 19
IS  - 3
N2  - Spatial normalization is an essential preprocessing step in statistical parametric mapping (SPM)-based analysis of PET scans. The standard template provided with the SPM99 software package was originally constructed using 15O-H2O PET scans and is commonly applied regardless of the tracer actually used in the scans being analyzed. This work studies the effect of using three different normalization templates in the outcome of the statistical analysis of PET scans: (1) the standard SPM99 PET template; (2) an 18F-FDG PET template, constructed by averaging PET scans previously normalized to the standard template; and (3) an MRI-aided 18F-FDG PET template, constructed by averaging PET scans normalized according to the deformation parameters obtained from MRI scans. A strictly anatomical MRI normalization of each PET was used as a reference, under the rationale that a normalization based only upon MRI should provide higher spatial accuracy. The potential bias involved in the normalization process was estimated in a clinical SPM study comparing schizophrenic patients with control subjects. For each between-group comparison, three SPM maps were obtained, one for each template. To evaluate the influence of the template, these SPM maps were compared to the reference SPM map achieved using the anatomical normalization. SPMs obtained by MRI-aided normalization showed the highest spatial specificity, and also higher sensitivity when compared to the standard normalization using the SPM99 15O-H2O template. These results show that the use of the standard template under inappropriate conditions (different tracer or mental state) may lead to inconsistent interpretations of the statistical analysis
UR  - http://www.sciencedirect.com/science/article/B6WNP-48N2TP4-1/2/fc7d99ff8d68cf28b42f7b47421b5f78
ER  - 

TY  - JOUR
T1  - A novel method for noninvasive detection of neuromodulatory changes in specific neurotransmitter systems
A1  - Alpert,Nathaniel M.
A1  - Badgaiyan,Rajendra D.
A1  - Livni,Elijahu
A1  - Fischman,Alan J.
Y1  - 2003/07//
SP  - 1049
EP  - 1060
JF  - Neuroimage
VL  - 19
IS  - 3
N2  - Over the last decade, it has become possible to study theories of cognition using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These methods yield statistical parametric maps of changes in cerebral blood flow (CBF) elicited by cognitive tasks. A limitation of these studies is that they provide no information about the underlying neurochemistry. However, it is possible to extend the concept of activation studies to include measurements targeting neurotransmitters and specific receptor populations. Cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level. The increased neurotransmitter level can be used to alter the kinetics of specifically bound radioligands. We describe a new approach to the design and analysis of neuromodulation experiments. This approach uses PET, a single-scan session design, and a linear extension of the simplified reference region model (LSSRM) that accounts for changes in ligand binding induced by cognitive tasks or drug challenge. In the LSSRM, an "activation" parameter is included that represents the presence or absence of change in apparent dissociation rate. Activation of the neurotransmitter is detected statistically when the activation parameter is shown to violate the null hypothesis. Simulation was used to explore the properties of the LSSRM with regard to model identifiability, effect of statistical noise, and confounding effects of CBF-related changes. Simulation predicted that it is possible to detect and map neuromodulatory changes in single-subject designs. A human study was conducted to confirm the predictions of simulation using 11C-raclopride and a motor planning task. Parametric images of transport, binding potential, areas of significant dopamine release, and statistical parameters were computed. Examination of the kinetics of activation demonstrated that maximum dopamine release occurred immediately following task initiation and then decreased with a half-time of about 3 min. This method can be extended to explore neurotransmitter involvement in other behavioral and cognitive domains
UR  - http://www.sciencedirect.com/science/article/B6WNP-48TMFPF-4/2/c6097e232d1072fc70df4c81acec7a77
ER  - 

TY  - JOUR
T1  - Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task
A1  - Bolla,K.I.
A1  - Eldreth,D.A.
A1  - London,E.D.
A1  - Kiehl,K.A.
A1  - Mouratidis,M.
A1  - Contoreggi,C.
A1  - Matochik,J.A.
A1  - Kurian,V.
A1  - Cadet,J.L.
A1  - Kimes,A.S.
Y1  - 2003/07//
SP  - 1085
EP  - 1094
JF  - Neuroimage
VL  - 19
IS  - 3
N2  - Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with 15O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence
UR  - http://www.sciencedirect.com/science/article/B6WNP-48J44GM-B/2/04ab7f14b2dcc3f4be17e8255a44b84c
ER  - 

TY  - JOUR
T1  - Posterior probability maps and SPMs
A1  - Friston,K.J.
A1  - Penny,W.
Y1  - 2003/07//
SP  - 1240
EP  - 1249
JF  - Neuroimage
VL  - 19
IS  - 3
N2  - This technical note describes the construction of posterior probability maps that enable conditional or Bayesian inferences about regionally specific effects in neuroimaging. Posterior probability maps are images of the probability or confidence that an activation exceeds some specified threshold, given the data. Posterior probability maps (PPMs) represent a complementary alternative to statistical parametric maps (SPMs) that are used to make classical inferences. However, a key problem in Bayesian inference is the specification of appropriate priors. This problem can be finessed using empirical Bayes in which prior variances are estimated from the data, under some simple assumptions about their form. Empirical Bayes requires a hierarchical observation model, in which higher levels can be regarded as providing prior constraints on lower levels. In neuroimaging, observations of the same effect over voxels provide a natural, two-level hierarchy that enables an empirical Bayesian approach. In this note we present a brief motivation and the operational details of a simple empirical Bayesian method for computing posterior probability maps. We then compare Bayesian and classical inference through the equivalent PPMs and SPMs testing for the same effect in the same data
UR  - http://www.sciencedirect.com/science/article/B6WNP-48TKG6N-1/2/fd663897eee48211f9949d6e9bdbcb2b
ER  - 

TY  - JOUR
T1  - Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
A1  - Caspi,Avshalom
A1  - Sugden,Karen
A1  - Moffitt,Terrie E.
A1  - Taylor,Alan
A1  - Craig,Ian W.
A1  - Harrington,HonaLee
A1  - McClay,Joseph
A1  - Mill,Jonathan
A1  - Martin,Judy
A1  - Braithwaite,Antony
A1  - Poulton,Richie
Y1  - 2003/07/18/
SP  - 386
JF  - Science
VL  - 301
IS  - 5631
N2  - In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup
UR  - http://www.sciencemag.org/cgi/content/abstract/301/5631/386
ER  - 

TY  - JOUR
T1  - Topographical analysis of glucose metabolism, as measured with positron emission tomography, in dementia of the Alzheimer type: use of linear histograms
A1  - McNamara,D.
A1  - Horwitz,B.
A1  - Grady,C.L.
A1  - Rapoport,S.I.
Y1  - 1987/09//
N1  - UI - 88006597
SP  - 89
EP  - 97
JA  - Int.J Neurosci.
VL  - 36
IS  - 1-2
N2  - A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease
AD  - Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892
UR  - PM:3498701
ER  - 

TY  - JOUR
T1  - Regional hypometabolism related to language disturbance in Alzheimer's disease
A1  - Hirono,N.
A1  - Mori,E.
A1  - Ishii,K.
A1  - Ikejiri,Y.
A1  - Imamura,T.
A1  - Shimomura,T.
A1  - Ikeda,M.
A1  - Yamashita,H.
A1  - Takatsuki,Y.
A1  - Sasaki,M.
Y1  - 1998/03//
N1  - UI - 98185484
SP  - 68
EP  - 73
JA  - Dement.Geriatr.Cogn Disord.
VL  - 9
IS  - 2
N2  - To elucidate the nature of language disturbance in Alzheimer's disease (AD) and the cerebral area involved in it, we studied 65 AD patients with the Western Aphasia Battery (WAB) and with 18F-fluorodeoxyglucose and positron emission tomography. Partial correlations were evaluated between the Aphasia Quotient of WAB and regional cerebral glucose metabolism normalized by the mean metabolic rate in the bilateral primary sensorimotor areas after controlling age, sex, education and severity of illness. Language disturbance in AD is accounted for by deficits in the semantic processing of language and is related to glucose hypometabolism in the inferior temporal gyrus and inferior parietal lobule, especially in the dominant side. These results offer further evidence suggesting that the lexico-semantic processing system is mediated in these regions
AD  - Department of Clinical Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Japan. hirono@hiabcd.go.jp
UR  - PM:9524796
ER  - 

TY  - JOUR
T1  - Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18
A1  - Gonzalez,R.G.
A1  - Fischman,A.J.
A1  - Guimaraes,A.R.
A1  - Carr,C.A.
A1  - Stern,C.E.
A1  - Halpern,E.F.
A1  - Growdon,J.H.
A1  - Rosen,B.R.
Y1  - 1995/10//
N1  - UI - 96112312
SP  - 1763
EP  - 1770
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 16
IS  - 9
N2  - PURPOSE: To determine whether magnetic susceptibility functional MR imaging of cerebral blood volumes provides information similar to fludeoxyglucose F 18 positron emission tomography (PET) brain images in patients undergoing evaluation for dementia. METHODS: Ten subjects were studied with both PET and functional MR. Clinical diagnoses included probable Alzheimer disease (n = 5), possible Alzheimer disease (n = 1), Pick disease (n = 2), and primary progressive aphasia (n = 2). The studies were quantitatively evaluated by coregistration of PET and functional MR images followed by regression analyses of corresponding regions of interest. Qualitatively, each brain was categorized into eight regions, and each was classified as normal or abnormal by visual inspection. RESULTS: Correlation coefficients between registered functional MR and PET images were excellent (mean, r = 0.58) in most of the cerebrum. Significant correlations were observed in 72 of 74 brain sections. Qualitatively, 16 brain regions were judged to be abnormal by both MR imaging and PET; 46 regions were normal by both; 10 regions were abnormal by PET only; and 8 regions were abnormal only by functional MR. The concordance between functional MR and PET was 78%, which was highly significant. CONCLUSION: Cerebral blood volumes images derived from magnetic susceptibility (functional MR) provide information similar to fludeoxyglucose F 18 PET images in demented patients undergoing evaluation for dementia
AD  - Massachusetts General Hospital NMR Center, Charlestown, MA 02129, USA
UR  - PM:8693972
ER  - 

TY  - JOUR
T1  - Slowly progressive aphasia followed by Alzheimer's dementia: a case report
A1  - De Oliveira,S.A.
A1  - Castro,M.J.
A1  - Bittencourt,P.R.
Y1  - 1989/03//
N1  - UI - 89350567
SP  - 72
EP  - 75
JA  - Arq Neuropsiquiatr.
VL  - 47
IS  - 1
N2  - Slowly progressive aphasia has been found in 8 published cases, 2 of whom progressed over a period of years to generalized dementia. Positron emission tomography demonstrated decreased glucose metabolism in the left perisylvian region in 2 cases. We describe a patient who had slowly progressive aphasia and developed generalized Alzheimer's dementia 7 years after presentation. There was no clinical or laboratory evidence of concomitant disease. Computerized tomography showed generalized atrophy more marked on the left perisylvian region late in the disease, when EEG showed generalized slowing more marked on the same area. Slowly progressive aphasia of old age should be considered a separate entity until further studies elucidate its relation to Alzheimer's dementia
AD  - Unidade de Neurologia Clinica, Hospital Nossa Senhora das Gracas, Curitiba, Brasil
UR  - PM:2788403
ER  - 

TY  - JOUR
T1  - Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: a promising alternative to nuclear medicine
A1  - Harris,G.J.
A1  - Lewis,R.F.
A1  - Satlin,A.
A1  - English,C.D.
A1  - Scott,T.M.
A1  - Yurgelun-Todd,D.A.
A1  - Renshaw,P.F.
Y1  - 1998/10//
N1  - UI - 99017483
SP  - 1727
EP  - 1732
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 19
IS  - 9
N2  - BACKGROUND AND PURPOSE: The goal of our study was to evaluate the sensitivity and specificity for Alzheimer disease of semiquantitative dynamic susceptibility contrast (DSC) MR imaging as compared with results of qualitative single-photon emission computed tomography (SPECT) in the same patients and with previously published semiquantitative SPECT results. METHODS: Fifty subjects were studied: 19 patients with probable Alzheimer disease with moderate cognitive impairment, eight mildly impaired patients with possible or probable Alzheimer disease, 18 group-matched elderly healthy comparison subjects, and five elderly comparison patients with psychiatric diagnoses. Relative values of temporoparietal regional cerebral blood volume (rCBV) were measured as a percentage of cerebellar rCBV, and group classification was assessed with logistic regression. The DSC MR imaging results were compared with SPECT scans in these same subjects and with previously published semiquantitative SPECT data. RESULTS: Temporoparietal rCBV ratios were reduced 20% bilaterally in the patients with Alzheimer disease. Using left and right temporoparietal rCBV as index measures, sensitivity was 95% in moderately affected patients with Alzheimer disease and 88% in patients with mild cases. Specificity was 96% in healthy comparison subjects and in psychiatric comparison subjects. Sensitivity with DSC MR imaging was considerably better than with visual clinical readings of SPECT scans (74% in moderate and 50% in mild Alzheimer disease cases), and was similar to previous published SPECT temporoparietal measurements (90%). Specificity with SPECT was 100% visually and 87% based on previous temporoparietal measurements. CONCLUSIONS: DSC MR imaging of rCBV is promising as a safe, potentially lower-cost alternative to nuclear medicine imaging for the evaluation of patients with dementia
AD  - Radiology Computer Aided Diagnostic Laboratory, Massachusetts General Hospital, Boston 02114, USA
UR  - PM:9802497
ER  - 

TY  - JOUR
T1  - Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy
A1  - Hodges,J.R.
A1  - Patterson,K.
A1  - Oxbury,S.
A1  - Funnell,E.
Y1  - 1992/12//
N1  - UI - 93136986
SP  - 1783
EP  - 1806
JF  - Brain
VL  - 115 ( Pt 6)
N2  - We report five patients with a stereotyped clinical syndrome characterized by fluent dysphasia with severe anomia, reduced vocabulary and prominent impairment of single-word comprehension, progressing to a stage of virtually complete dissolution of the semantic components of language. A marked reduction in the ability to generate exemplars from restricted semantic categories (e.g. animals, vehicles, etc.) was a consistent and early feature. Tests of semantic memory demonstrated a radically impoverished knowledge about a range of living and man-made items. In contrast, phonology and grammar of spoken language were largely preserved, as was comprehension of complex syntactic commands. Reading showed a pattern of surface dyslexia. Autobiographical and day-to-day (episodic) memory were relatively retained. Non-verbal memory, perceptual and visuospatial abilities were also strikingly preserved. In some cases, behavioural and personality changes may supervene; one patient developed features of the Kluver-Bucy Syndrome. Radiological investigations have shown marked focal temporal atrophy in all five patients, and functional imaging by single positron emission tomography and positron emission tomography (one case) have implicated the dominant temporal lobe in all five. In the older literature, such cases would have been subsumed under the rubric of Pick's disease. Others have been included in series with progressive aphasia. We propose the term semantic dementia, first coined by Snowden et al. (1989), to designate this clinical syndrome
AD  - University of Cambridge Clinical School, Addenbrooke's Hospital, UK
UR  - PM:1486461
ER  - 

TY  - JOUR
T1  - Is benzodiazepine-induced amnesia due to deactivation of the left prefrontal cortex?
A1  - Bagary,M.
A1  - Fluck,E.
A1  - File,S.E.
A1  - Joyce,E.
A1  - Lockwood,G.
A1  - Grasby,P.
Y1  - 2000/06//
N1  - UI - 20378279
SP  - 292
EP  - 299
JA  - Psychopharmacology (Berl)
VL  - 150
IS  - 3
N2  - The amnesic properties of benzodiazepines result from an impairment in explicit (conscious) acquisition of new material. RATIONALE: Explicit encoding of new material has consistently resulted in an increase in regional cerebral blood flow (rCBF) in the left prefrontal cortex, as measured by positron emission tomography (PET). OBJECTIVE: PET was used to determine whether an amnesic dose of midazolam (0.075 mg/kg) attenuated activation in this area during explicit memory encoding. METHODS: A second condition (condition A) used a task to control for the automatic processing that occurs during explicit learning (condition E). RESULTS: The subjects who received midazolam (n=7) recognised significantly fewer words than those who received placebo (n=8), but were not impaired with regard to automatic processing. rCBF was significantly increased in the left prefrontal cortex during explicit encoding of word lists in all subjects and in the temporal lobe and parieto-occipital regions during automatic processing. rCBF was significantly decreased in the prefrontal, superior temporal and parieto-occipital regions following midazolam. The midazolam-induced deactivation in the prefrontal cortex did not affect rCBF activations induced by the explicit memory condition (E-A). CONCLUSIONS: These results suggest that a specific interaction with prefrontal cortex activation does not underlie the amnesic effect of midazolam. However, it remains possible that a threshold level of prefrontal rCBF is necessary for encoding and that, after midazolam, this was not reached
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:10923757
ER  - 

TY  - JOUR
T1  - Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome
A1  - Joyce,E.M.
A1  - Rio,D.E.
A1  - Ruttimann,U.E.
A1  - Rohrbaugh,J.W.
A1  - Martin,P.R.
A1  - Rawlings,R.R.
A1  - Eckardt,M.J.
Y1  - 1994/12//
N1  - UI - 95312583
SP  - 225
EP  - 239
JA  - Psychiatry Res
VL  - 54
IS  - 3
N2  - Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [18F]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency
AD  - Academic Department of Psychiatry, Charing Cross and Westminster Medical School, London, UK
UR  - PM:7792327
ER  - 

TY  - JOUR
T1  - Severe global amnesia presenting as Wernicke-Korsakoff syndrome but resulting from atypical lesions
A1  - Welch,L.W.
A1  - Nimmerrichter,A.
A1  - Kessler,R.
A1  - King,D.
A1  - Hoehn,R.
A1  - Margolin,R.
A1  - Martin,P.R.
Y1  - 1996/03//
N1  - UI - 96243424
SP  - 421
EP  - 425
JA  - Psychol.Med
VL  - 26
IS  - 2
N2  - A female alcoholic presented with Wernicke's encephalopathy subsequent to administration of diazepam and glucose (without thiamine) for treatment of withdrawal seizures. Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted. Magnetic resonance imaging (MRI) revealed infarction of the right temporal lobe with hippocampal atrophy, but no lesions of thalamus or atrophy of mammillary bodies. Positron emission tomography (PET) confirmed decreased cerebral metabolic rates for glucose (CMRglu) in the right temporal lobe corresponding to MRI findings, but also significant metabolic asymmetry of dorsal thalamus, i.e. reduced CMRglu in left versus right. This patient is unique in that neuroradiological findings revealed intact mammillary bodies and suggest asymmetrical dysfunctions (structural right temporal and functional left diencephalic) to produce her profound amnesia
AD  - Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN 37232-2647, USA
UR  - PM:8685298
ER  - 

TY  - JOUR
T1  - Alteration of regional cerebral glucose metabolic rate in non-Korsakoff chronic alcoholism
A1  - Sachs,H.
A1  - Russell,J.A.
A1  - Christman,D.R.
A1  - Cook,B.
Y1  - 1987/12//
N1  - UI - 88049010
SP  - 1242
EP  - 1251
JA  - Arch Neurol
VL  - 44
IS  - 12
N2  - That chronic alcoholism yields devastating effects to the central nervous systems of its victims is well known, but the actual physiologic mechanisms underlying that deterioration have yet to be completely identified. What is also known is that many chronic alcoholics seem to recover brain function after a protracted period of abstinence, but the actual mechanisms of that restoration are also not well understood. Using positron emission tomography with the tracer 11C-2-deoxy-D-glucose as a probe to measure regional cerebral metabolic rate of glucose (RCMRGlu), we compared the magnitudes of glucose consumption in 44 brain regions between a group of newly abstinent chronic alcoholics without Korsakoff's psychosis and a control group of normal nonalcoholic subjects whose range of age was that of the alcoholic group. We found that RCMRGlu measurements in the brains of alcoholics were significantly lower than in the brains of the control group, and that there were many fewer significant interregional correlations in the brains of the alcoholics than in the brains of the control group. We also found no significant correlation between age and global metabolic rate of glucose in either group. However, even though the number of alcoholic subjects was too few to allow a reliable statistical comparison, the measurements suggest that chronic alcoholics over the age of 50 years suffer a greater decrease of RCMRGlu values than do their counterparts under the age of 50 years. While resting in a bland environment, neither alcoholic nor control subjects were found to have significant differences in RCMRGlu values between their brain hemispheres. In contrast to this similarity, normal dextrous subjects responded to a nonverbal auditory stimulus by increasing the metabolic rate of glucose in their right hemispheres while eight of nine chronic alcoholics did not. The results of this pilot study point to arguments that the alcoholic brain metabolizes glucose at a lower rate than do normal brains, that there are fewer region-to-region functional relationships in the alcoholic brain than in the normal brain, and that alcoholics may be impaired in right hemispheric processing. In subsequent investigations, we will measure the metabolic changes that follow abstinence, if any, by tracking subjects throughout an interval of rehabilitation. Also, we intend to test the findings of this study by measuring greater numbers of alcoholic subjects to separate the consequences of measurement variability, age, and chance from the underlying biologic processes that seem to be affected by chronic alcoholism
AD  - Department of Neurology, State University of New York at Stony Brook
UR  - PM:3314816
ER  - 

TY  - JOUR
T1  - Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances
A1  - Kopelman,M.D.
A1  - Reed,L.J.
A1  - Marsden,P.
A1  - MAYES,A.R.
A1  - Jaldow,E.
A1  - Laing,H.
A1  - Isaac,C.
Y1  - 2001///
N1  - UI - 21612481
SP  - 423
EP  - 432
JA  - Neurocase.
VL  - 7
IS  - 5
N2  - A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered
AD  - Neuropsychiatry and Memory Disorders Clinic, University Department of Psychiatry and Psychology, King's College, St Thomas's Campus, London SE1 7EH, UK. michael.kopelman@kcl.a.cuk
UR  - PM:11744784
ER  - 

TY  - JOUR
T1  - PET findings and neuropsychological deficits in a case of Fahr's disease
A1  - Hempel,A.
A1  - Henze,M.
A1  - Berghoff,C.
A1  - Garcia,N.
A1  - Ody,R.
A1  - Schroder,J.
Y1  - 2001/11/30/
N1  - UI - 21605342
SP  - 133
EP  - 140
JA  - Psychiatry Res
VL  - 108
IS  - 2
N2  - In a case of Fahr's disease with frontal lobe type dementia and hyperkinetic-hypotone syndrome, functional changes were investigated using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) as a tracer. Computed tomography showed bilateral calcifications in the putamen and globus pallidus consistent with the diagnosis of Fahr's disease and a frontally pronounced brain atrophy. In contrast, reduced glucose uptake in PET was not only confined to the areas mentioned above, but extended to the temporal and parietal cortices, bilaterally. These functional changes corresponded to the neuropsychological deficits observed, i.e. disturbed selective attention and cognitive flexibility, verbal perseverations, and declarative memory deficits. It is suggested that functional changes may precede cerebral atrophy in Fahr's disease and may reflect deficits in functional circuits, which involve both the basal ganglia and the frontal, parietal, and temporal lobes
AD  - Department of Psychiatry, University of Heidelberg, Vossstr. 2, D-69115 Heidelberg, Germany. albrecht_hempel@med.uni-heidelberg.de
UR  - PM:11738547
ER  - 

TY  - JOUR
T1  - Bilateral orbitomedial leucotomy for obsessive-compulsive disorder: a single-case study using positron emission tomography
A1  - Sachdev,P.
A1  - Trollor,J.
A1  - Walker,A.
A1  - Wen,W.
A1  - Fulham,M.
A1  - Smith,J.S.
A1  - Matheson,J.
Y1  - 2001/10//
N1  - UI - 21435613
SP  - 684
EP  - 690
JA  - Aust.N Z.J Psychiatry
VL  - 35
IS  - 5
N2  - OBJECTIVE: The objective of this report is to correlate the clinical outcome of neurosurgery for obsessive-compulsive disorder (OCD) with regional cerebral glucose metabolic changes. CLINICAL PICTURE: The patient was a 37-year-old female patient with severe and intractable OCD. TREATMENT: The patient was treated with bilateral stereotactic lesions in the frontal white matter superior to the orbito-medial cortex. OUTCOME: She had a remarkable improvement in her obsessive-compulsive symptoms, which was sustained up to 3 years of follow up. A positron emission tomography (PET) scan performed 18 days after surgery demonstrated an obvious reduction of metabolism in the caudate head, anterior cingulate and orbital, medial and lateral prefrontal cortices and the thalamus. At 1 year postsurgery, metabolic rate was still reduced in the anterior cingulate gyrus, caudate and thalamus compared with preoperative baseline. The patient demonstrated no long-term cognitive effects of the surgery. CONCLUSIONS: This case supports some of the cortical-subcortical circuit dysfunction models of OCD and argues for the further evaluation of neurosurgery for the treatment of a severe and intractable disorder
AD  - Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. p.sachdev@unsw.edu.au
UR  - PM:11551286
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of a chronic pain patient successfully treated with somatosensory thalamic stimulation
A1  - Kupers,R.C.
A1  - Gybels,J.M.
A1  - Gjedde,A.
Y1  - 2000/09//
N1  - UI - 20420253
SP  - 295
EP  - 302
JF  - Pain
VL  - 87
IS  - 3
N2  - Previous neuroimaging studies suggested that the neuronal network underlying the perception of chronic pain may differ from that underlying acute pain. To further map the neural network associated with chronic pain, we used positron emission tomography (PET) to determine significant regional cerebral blood flow (rCBF) changes in a patient with chronic facial pain. The patient is implanted with a chronic stimulation electrode in the left ventroposterior medial thalamic nucleus with which he can completely suppress his chronic pain. The patient was scanned in the following conditions: before thalamic stimulation (pain, no stimulation), during thalamic stimulation (no pain, stimulation) and after successful thalamic stimulation (no pain, no stimulation). Comparing baseline scans during pain with scans taken after stimulation, when the patient had become pain-free, revealed significant rCBF increases in the prefrontal (Brodmann areas (BA) 9, 10, 11 and 47) and anterior insular cortices, hypothalamus and periaqueductal gray associated with the presence of chronic pain. No significant rCBF changes occurred in thalamus, primary and secondary somatosensory cortex and anterior cingulate cortex, BA 24'. Significant rCBF decreases were observed in the substantia nigra/nucleus ruber and in the anterior pulvinar nucleus. During thalamic stimulation, blood flow significantly increased in the amygdala and anterior insular cortex. These data further support that there are important differences in the cerebral processing of acute and chronic pain
AD  - PET Center, Aarhus University Hospital, Norrebrogade 44, DK-8000, Aarhus, Denmark. ron@pet.auh.dk
UR  - PM:10963909
ER  - 

TY  - JOUR
T1  - Neuropsychological and neuroimaging correlates in corticobasal degeneration
A1  - Frasson,E.
A1  - Moretto,G.
A1  - Beltramello,A.
A1  - Smania,N.
A1  - Pampanin,M.
A1  - Stegagno,C.
A1  - Tanel,R.
A1  - Rizzuto,N.
Y1  - 1998/10//
N1  - UI - 20386585
SP  - 321
EP  - 328
JA  - Ital.J Neurol Sci.
VL  - 19
IS  - 5
N2  - The aim of this study was to correlate neuropsychological and neuroimaging findings in corticobasal degeneration (CBD). Three patients with clinical criteria for CBD were examined by means of neuropsychological tests, brain magnetic resonance imaging (MRI), and flow and metabolism neuroimaging techniques. Neuropsychological assessment revealed impairment in executive functions, manual dexterity and motor programming with significant asymmetry between upper limbs. Ideomotor and oral apraxia were also detected, and memory deficits were observed in one patient. MRI revealed cortical dilation of the frontal and peri-rolandic regions, symmetrical in one case and asymmetrical in the other two cases. An increased T2 signal intensity in the posterolateral putamen and substantia nigra ipsilateral to the cortical atrophy was observed in one patient. Asymmetries of both frontal and parietal cortices and basal ganglia were detected in all three patients by 18-fluorodeoxyglucose positron emission tomography; temporal region hypometabolism was associated in one patient. These cortical and subcortical asymmetries were observed in two patients by single photon emission tomography with the tracer technetium Tc 99m hexamethyl propylenamine oxime; cortical asymmetry was observed in only one patient. The results showed that functional neuroimaging findings correlated well with neuropsychological aspects in CBD. Neuroimaging and neuropsychological correlations may contribute toward understanding anatomical and functional abnormalities associated with this neurodegenerative disorder
AD  - Department of Neurological and Visual Sciences, Policlinico Borgo Roma, Verona, Italy
UR  - PM:10933454
ER  - 

TY  - JOUR
T1  - Functional anatomical study of psychogenic amnesia
A1  - Yasuno,F.
A1  - Nishikawa,T.
A1  - Nakagawa,Y.
A1  - Ikejiri,Y.
A1  - Tokunaga,H.
A1  - Mizuta,I.
A1  - Shinozaki,K.
A1  - Hashikawa,K.
A1  - Sugita,Y.
A1  - Nishimura,T.
A1  - Takeda,M.
Y1  - 2000/07/10/
N1  - UI - 20351681
SP  - 43
EP  - 57
JA  - Psychiatry Res
VL  - 99
IS  - 1
N2  - Psychogenic amnesia is characterized by an inability to recall information already stored in the patient's memory. It is usually related to a stressful or traumatic event that cannot be explained by manifest brain damage. To examine the underlying functional disturbance of brain areas in this condition, we performed a positron emission tomography (PET) activation study on a psychogenic amnesic patient and on 12 normal control subjects. A task requiring explicit retrograde memory of faces was compared with a control task. To assess functional modifications associated with the processes of recovery, a second PET study was performed on the patient 12 months after onset. During the task, activation of the right anterior medial temporal region including the amygdala was increased in the psychogenic amnesic patient. Activation of the bilateral hippocampal regions increased only in the control subjects. During recovery, the right anterior medial temporal region became less active while the right hippocampal region became more active. Activation levels also differed in the anterior cingulate cortex, prefrontal cortex and some other cortical regions between control subjects and the patient. These findings suggest that the changes in these limbic and limbic-cortical functions are related to symptoms of the psychogenic amnesia
AD  - Department of Neuropsychiatry, Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. yasuno@nirs.go.jp
UR  - PM:10891648
ER  - 

TY  - JOUR
T1  - Adult-onset Hallervorden-Spatz syndrome presenting as cortical dementia
A1  - Cooper,G.E.
A1  - Rizzo,M.
A1  - Jones,R.D.
Y1  - 2000/04//
N1  - UI - 20306924
SP  - 120
EP  - 126
JA  - Alzheimer Dis.Assoc.Disord.
VL  - 14
IS  - 2
N2  - The authors examined behavioral and pathophysiologic substrates in a patient with adult-onset Hallervorden-Spatz syndrome who presented with insidious cognitive decline but no motor impairment. The authors combined longitudinal case history and serial neuropsychologic testing with functional neuroimaging (positron emission tomography), structural neuroimaging (magnetic resonance imaging), and brain tissue analyses. Serial assessments of a 29-year-old woman showed progressive dementia. Marked cognitive and behavioral deficits were seen on neuropsychologic testing, corresponding to striking cortical abnormalities on positron emission tomography, magnetic resonance imaging, and histopathologic studies. Typical motor manifestations of the disorder did not emerge until the patient was 34 years old, 5 years after the onset of cognitive symptoms. Hallervorden-Spatz syndrome should be considered in the differential diagnosis of progressive cortical dementia in a young adult, even in the absence of motor dysfunction
AD  - Department of Neurology, University of Iowa, Iowa City 52242, USA
UR  - PM:10850751
ER  - 

TY  - JOUR
T1  - Neuroimaging and behavioral correlates of recovery from mnestic block syndrome and other cognitive deteriorations
A1  - Markowitsch,H.J.
A1  - Kessler,J.
A1  - Weber-Luxenburger,G.
A1  - Van,der,V
A1  - Albers,M.
A1  - Heiss,W.D.
Y1  - 2000/01//
N1  - UI - 20108336
SP  - 60
EP  - 66
JA  - Neuropsychiatry Neuropsychol.Behav.Neurol
VL  - 13
IS  - 1
N2  - OBJECTIVE: We conducted a follow-up study on a patient with enduring psychic shock-induced cognitive impairment to study by neuropsychological and functional imaging methods the degree of his recovery process on the brain and cognitive levels. BACKGROUND: Based on the assumption that trauma and stress conditions can alter the functions of the nervous systems, we report on a patient whom we studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. METHODS: We report on a patient studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were used for neural and detailed neuropsychological testing for cognitive deficits. RESULTS: The patient initially manifested severe intellectual decline, including severe anterograde and retrograde amnesia. His symptoms were correlated with major, although selective, reductions in his brain metabolism (2-3 SD below those of controls). Presently, he shows a normal brain metabolism and has regained parts of his memory and many of his other intellectual capabilities. Nevertheless, he still has long-term memory impairments. CONCLUSIONS: This case demonstrates a close relation between brain metabolism and cognitive performance, with major deficits of both at 2 months and major recovery of both at 12 months after a shocking event. It can serve as an example for possible stress-related deteriorations in certain brain regions, which can be partly corrected by psychotherapeutic interventions, passing time, and favorable environmental conditions
AD  - Department of Physiological Psychology, University of Bielefeld, Germany. hjmarkowitsch@post.uni-bielefeld.de
UR  - PM:10645738
ER  - 

TY  - JOUR
T1  - Cerebral oxygen metabolism in newborns
A1  - Altman,D.I.
A1  - Perlman,J.M.
A1  - Volpe,J.J.
A1  - Powers,W.J.
Y1  - 1993/07//
N1  - UI - 93295832
SP  - 99
EP  - 104
JF  - Pediatrics
VL  - 92
IS  - 1
N2  - OBJECTIVE. A better understanding of the developmental changes in brain energy metabolism that occur in human neonates is critically important for designing rational treatment strategies that ensure an adequate supply of nutrients to the brain and minimize deleterious side effects of therapeutic interventions in sick newborns. METHODS. Cerebral metabolic rate for oxygen (CMRO2) was measured with positron emission tomography in 11 sick newborns of different gestational ages. RESULTS. In five preterm infants, mean hemispheric CMRO2 was 0.06 to 0.54 mL 100 g-1 min-1. Two of these preterm infants with virtually absent CMRO2 (0.06 mL 100 g-1 min-1) had minimal or no evidence of parenchymal brain injury detected in the newborn period. In six term infants, mean hemispheric CMRO2 was 0.0 to 1.3 mL 100 g-1 min-1. Two with no neurological disease had mean hemispheric CMRO2 of 0.4 and 0.7 mL 100 g-1 min-1 and were normal at 6 and 7 months, respectively. CONCLUSIONS. CMRO2 in four newborns who had minimal or no detectable brain injury was considerably below the threshold for brain viability in adults of 1.3 mL 100 g-1 min-1. This indicates that energy requirements in fetal and newborn brain are minimal or can be met by nonoxidative metabolism
AD  - Department of Neurology, Washington University School of Medicine, St Louis, MO 63110
UR  - PM:8516092
ER  - 

TY  - JOUR
T1  - Cerebral blood flow requirement for brain viability in newborn infants is lower than in adults
A1  - Altman,D.I.
A1  - Powers,W.J.
A1  - Perlman,J.M.
A1  - Herscovitch,P.
A1  - Volpe,S.L.
A1  - Volpe,J.J.
Y1  - 1988/08//
N1  - UI - 89024524
SP  - 218
EP  - 226
JA  - Ann.Neurol
VL  - 24
IS  - 2
N2  - Measurements of regional cerebral blood flow (CBF) with positron emission tomography in adult humans with cerebrovascular disease have demonstrated consistently that values below 10 ml/(100 gm.min) occur only in infarcted brain. Although experimental data suggest that the newborn brain may be more resistant to ischemic injury than the adult brain, the minimum CBF necessary to sustain neuronal viability in newborn infants is unknown. We have measured CBF with positron emission tomography in 16 preterm and 14 term newborn infants and have determined the relationship between CBF and subsequent brain function as assessed by neurological examination and developmental assessment. The range of mean CBF in the preterm infants was 4.9 to 23 ml/(100 gm.min) and the range of mean CBF in the term infants was 9.0 to 73 ml/(100 gm.min). Five preterm infants and one term infant with mean CBF less than 10 ml/(100 gm.min) survived. Three of these 5 preterm infants, with mean CBF of 4.9, 5.2, and 9.3 ml/(100 gm.min), respectively, have normal neurological examinations and Bayley Scales of 80 or greater at 6, 6, and 24 months of age, respectively. One (mean CBF 6.9) has normal cognitive development (Bayley 103) and a mild spastic diplegia at age 19 months, and one infant (mean CBF 6.2) has a left hemiparesis and a Binet IQ score of 70 at age 33 months. The term infant, with a mean CBF of 9.0 ml/(100 gm.min), was developing normally when he died of sepsis at age 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Pediatrics, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110
UR  - PM:3263081
ER  - 

TY  - JOUR
T1  - Positron emission tomography in the asphyxiated term newborn: parasagittal impairment of cerebral blood flow
A1  - Volpe,J.J.
A1  - Herscovitch,P.
A1  - Perlman,J.M.
A1  - Kreusser,K.L.
A1  - Raichle,M.E.
Y1  - 1985/03//
N1  - UI - 85197716
SP  - 287
EP  - 296
JA  - Ann.Neurol
VL  - 17
IS  - 3
N2  - Hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the term newborn is the most common recognized cause of the subsequent motor deficits often grouped under the rubric "cerebral palsy." In order to provide insight into the basic nature and pathogenesis of the brain injury in such infants, we studied regional cerebral blood flow (CBF) by positron emission tomography (PET) in 17 asphyxiated term infants during the acute period of illness. A consistent and apparently unifying abnormality was observed, namely, a relative decrease in CBF to parasagittal regions, generally symmetrical and more marked posteriorly than anteriorly. Thus, parasagittal values for CBF were generally 25 to 50% lower than those for the sylvian cortex; in the normal or near normal infant, parasagittal values are only approximately 10% lower than those for the sylvian cortex. (Additional normal findings for regional CBF were 50% higher flows to the cerebral cortex than to the cerebral white matter and flows to the basal ganglia and thalamus at least as high as those to the cerebral cortex). That the relative deficit in CBF to parasagittal regions reflects tissue injury was indicated by the close topographic correlation on technetium brain scans in 3 patients of increased tissue uptake of radionuclide and the CBF abnormality. Moreover, the single patient studied at postmortem examination exhibited parasagittal ischemic cerebral injury that correlated well with the PET abnormality of regional CBF. The topography of the PET abnormality, i.e., the cerebrovascular watershed regions, suggests that the brain injury is basically ischemic and that the pathogenesis relates to impaired cerebral perfusion, perhaps secondary to systemic hypotension occurring in association with the perinatal asphyxia. Experimental data support this formulation
UR  - PM:3873209
ER  - 

TY  - JOUR
T1  - Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement
A1  - Volpe,J.J.
A1  - Herscovitch,P.
A1  - Perlman,J.M.
A1  - Raichle,M.E.
Y1  - 1983/11//
N1  - UI - 84041247
SP  - 589
EP  - 601
JF  - Pediatrics
VL  - 72
IS  - 5
N2  - Of all patients with intraventricular hemorrhage, those with hemorrhagic intracerebral involvement exhibit the highest rates of mortality and neurologic morbidity and, indeed, account for the vast majority of all neurologic impairment in infants with intraventricular hemorrhage. Insight into the basic nature of the critical cerebral involvement requires determination of regional cerebral blood flow, previously not possible. Positron emission tomography (PET) now provides the capability of measuring regional cerebral blood flow with high resolution and little risk. In this study, we utilized PET in six premature infants (920 to 1,200 g) with major intraventricular hemorrhage and hemorrhagic intracerebral involvement to measure regional cerebral blood flow during the acute period (5 to 17 days of age). Cerebral blood flow was determined after intravenous injection of H2O, labeled with the positron-emitting isotope, 15O (oxygen 15). Findings were similar and dramatic in all six infants. In the area of hemorrhagic intracerebral involvement, little or no cerebral blood flow was detected. However, in addition, surprisingly, a marked two- to fourfold reduction in cerebral blood flow was observed throughout the affected hemisphere, well posterior and lateral to the intracerebral hematoma, including cerebral white matter and, to a lesser extent, frontal, temporal, and parietal cortex. In the one infant studied a second time, ie, at 3 months of age, the extent and severity of the decreased cerebral blood flows in the affected hemisphere were similar to those observed on the study during the neonatal period. At the three autopsies, the affected left hemisphere showed extensive infarction, corroborating the PET scans. These observations, the first demonstration of the use of PET in the determination of regional cerebral blood flow in the newborn, show marked impairments in regional cerebral blood flow in the hemisphere containing an apparently restricted intracerebral hematoma, indicating that the hemorrhagic intracerebral involvement is only a component of a much larger lesion, ischemic in basic nature, ie, an infarction. This large ischemic lesion explains the poor neurologic outcome in infants with intraventricular hemorrhage and hemorrhagic intracerebral involvement
UR  - PM:6605514
ER  - 

TY  - CHAP
T1  - Depression
A1  - Mayberg,H.S.
Y1  - 2000///
SP  - 485
EP  - 507
T2  - Brain mapping: The disorders
A2  - Toga,A.W.
A2  - Mazziotta,J.C.
A2  - Frackowiak,R.S.J.
IS  - 19
CY  - San Diego
PB  - Academic Press
Y2  - -32676///
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow and metabolism in patients with transient global amnesia: a positron emission tomography study
A1  - Fujii,K.
A1  - Sadoshima,S.
A1  - Ishitsuka,T.
A1  - Kusuda,K.
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Fujishima,M.
Y1  - 1989/05//
N1  - UI - 89279371
SP  - 622
EP  - 630
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 52
IS  - 5
N2  - In four patients who experienced transient global amnesia (TGA), clinical features and neuroradiological findings including positron emission tomography (PET) were studied within three months of the episodes, and compared with those in seven cases with cerebral transient ischaemic attacks (TIA). None of TGA patients had a previous history or significant risk factors for the cerebrovascular diseases. Their electroencephalogram, brain CT and angiogram for the head and neck were almost normal. PET study showed better preserved cerebral blood flow and oxygen metabolism in each area of the brain in patients with TGA compared with those with TIA in whom focal reductions of flow and metabolism were evident. These observations suggest that TGA is caused by reversible circulatory and/or metabolic disturbance, of which mechanism might be different from that in TIA
AD  - Second Department of Internal Medicine, Kyushu University, Fukuoka City, Japan
UR  - PM:2786552
ER  - 

TY  - JOUR
T1  - Characterization of a synthetic anionic vector for oligonucleotide delivery using in vivo whole body dynamic imaging
A1  - Tavitian,B.
A1  - Marzabal,S.
A1  - Boutet,V.
A1  - Kuhnast,B.
A1  - Terrazzino,S.
A1  - Moynier,M.
A1  - Dolle,F.
A1  - Deverre,J.R.
A1  - Thierry,A.R.
Y1  - 2002/04//
N1  - UI - 22029278
SP  - 367
EP  - 376
JA  - Pharm.Res
VL  - 19
IS  - 4
N2  - PURPOSE: To compare the pharmacokinetics and bioavailability of an oligonucleotide delivered in a free form or using cationic or anionic synthetic carrier systems. METHODS: Whole body dynamic quantitative imaging and metabolism of a HIV antisense oligonucleotide intravenously administered either free or incorporated into synthetic carriers were compared in baboons. using non invasive positron emission tomography and an enzyme-based competitive hybridization assay, respectively. RESULTS: In its free form, the oligonucleotide showed high liver and kidney concentration, rapid plasmatic degradation and elimination from the body. Use of a cationic vector slightly protected the oligonucleotide against degradation and enhanced uptake by the reticulo-endothelial system. In contrast, the anionic vector dramatically enhanced the uptake in several organs, including the lungs, spleen and brain, with a prolonged accumulation of radioactivity in the brain. Using this vector, intact oligonucleotide was detected in plasma for up to two hours after injection. and the T 1/2beta and distribution volume increased by 4- and 7-fold, respectively. No evidence of toxicity was found after a single dose administration. CONCLUSIONS: The anionic vector improves significantly the bioavailability and the pharmacokinetics of the oligonucleotide, and is a promising delivery system for in vivo administration of therapeutic nucleic acids
AD  - INSERM M 0103, CEA-SHFJ, Orsay, France. tavitian@shfj.cea.fr
UR  - PM:12033366
ER  - 

TY  - JOUR
T1  - Functional disconnection between the prefrontal and parietal cortices during working memory processing in schizophrenia: a[15(O)]H2O PET study
A1  - Kim,J.J.
A1  - Kwon,J.S.
A1  - Park,H.J.
A1  - Youn,T.
A1  - Kang,do H.
A1  - Kim,M.S.
A1  - Lee,D.S.
A1  - Lee,M.C.
Y1  - 2003/05//
N1  - UI - 22612191
SP  - 919
EP  - 923
JA  - Am J Psychiatry
VL  - 160
IS  - 5
N2  - OBJECTIVE: The prefrontal-parietal circuits have been reported to play an important role in working memory. The purpose of this study was to use direct neuroimaging to address whether interregional correlation in the prefrontal-parietal circuits is impaired in schizophrenia. METHOD: [(15)O]H(2)O positron emission tomography was used to compare regional blood flow changes in 12 schizophrenic and 12 healthy comparison subjects during the n-back sequential-picture working memory task. Interregional correlation was assessed by correlating the regional activation of the lateral prefrontal area with that of other activated areas in each subject group. RESULTS: Dorsolateral prefrontal activation was observed around the right superior frontal sulcus in the healthy subjects, and ventrolateral prefrontal activation below the right inferior frontal sulcus was observed in the schizophrenic patients. Activation in the right lateral prefrontal cortex was significantly correlated with activation in the bilateral inferior parietal region in the healthy subjects but was not correlated with any regional activation in the patients. CONCLUSIONS: The findings suggest prefrontal-parietal functional disconnection, particularly prefrontal dissociation and abnormal prefrontal-parietal interaction, during working memory processing in schizophrenia
AD  - Department of Psychiatry and Nuclear Medicine, College of Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongno-gu, Seoul, Korea 110-744
UR  - PM:12727696
ER  - 

TY  - JOUR
T1  - Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis
A1  - Davidson,L.L.
A1  - Heinrichs,R.W.
Y1  - 2003/02/15/
N1  - UI - 22600873
SP  - 69
EP  - 87
JA  - Psychiatry Res
VL  - 122
IS  - 2
N2  - Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies of the frontal and temporal lobes in schizophrenia patients and healthy controls have proliferated over the past 2 decades, but there have been relatively few attempts to quantify the evidence. In this meta-analytic review, 155 studies on frontal and temporal lobe neurobiology were synthesized, reflecting results from 4043 schizophrenia patients and 3977 normal controls. Cohen's d was used to quantify case-control differences, and moderator variable analysis indexed the relation of sample and imaging characteristics to the magnitude of these differences. Frontal metabolic and blood flow deficiencies in conjunction with cognitive activation tasks ("hypofrontality") emerged as the strongest body of evidence, demonstrating abnormalities that distinguish approximately half of schizophrenia patients from healthy people. Most case-control comparisons with structural and functional imaging yield small and in many cases unstable findings. Technical scanning parameters like slice thickness and magnet strength did not vary with case-control differences consistently across the meta-analyses. However, patient sample characteristics including sample size, handedness and gender composition emerged frequently as moderators of brain-imaging effect sizes
AD  - Department of Psychology, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3. larad@yorku.ca
UR  - PM:12714172
ER  - 

TY  - JOUR
T1  - Neuroreceptor imaging in psychiatric disorders
A1  - Frankle,W.G.
A1  - Laruelle,M.
Y1  - 2002/11//
SP  - 437
EP  - 446
JA  - Ann.Nucl Med
VL  - 16
IS  - 7
N2  - Molecular imaging, the study of receptors, transporters and enzymes, as well as other cellular processes, has grown in recent years to be one of the most active neuroimaging areas. The application of single photon emission tomography (SPECT) and positron emission tomography (PET) techniques to the study of psychiatric illness has lead to increased understanding of disease processes as well as validated, in vivo, theories of illness etiology. Within the field of psychiatry these techniques have been applied most widely to the study of schizophrenia. Studies within schizophrenia are largely limited to either the dopamine or serotonin system. This is due in large part to the availability of suitable radiotracers as well as the current theories on the etiology of the illness. Two basic study designs are used when studying schizophrenia using molecular imaging and make up the majority of studies reviewed in this manuscript. The first type, termed "clinical studies," compares the findings from PET and SPECT studies in those with schizophrenia to normal controls in an attempt to understand the pathophysiology of the illness. The second study design, termed "occupancy studies," uses these techniques to enhance the understanding of the mechanism of action of the medications used in treating this illness. This review will focus on the findings of molecular imaging studies in schizophrenia, focusing, for the most part, on the serotonin and dopamine systems. Emphasis will be placed on how these findings and techniques are currently being used to inform the development of novel treatments for schizophrenia
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York 10032, USA. wf2004@columbia.edu
UR  - PM:12508833
ER  - 

TY  - JOUR
T1  - Neuroanatomy and neurophysiology in schizophrenia
A1  - Kasai,K.
A1  - Iwanami,A.
A1  - Yamasue,H.
A1  - Kuroki,N.
A1  - Nakagome,K.
A1  - Fukuda,M.
Y1  - 2002/06//
N1  - UI - 22063679
SP  - 93
EP  - 110
JA  - Neurosci.Res
VL  - 43
IS  - 2
N2  - Schizophrenia is a major mental disorder, characterized by their set of symptoms, including hallucinatory-delusional symptoms, thought disorder, emotional flattening, and social withdrawal. Since 1980s, advances in neuroimaging and neurophysiological techniques have provided tremendous merits for investigations into schizophrenia as a brain disorder. In this article, we first overviewed neuroanatomical studies using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), and postmortem brains, followed by neurophysiological studies using event-related potentials (ERPs) and magnetoencephalography (MEG), in patients with schizophrenia. Evidences from these studies suggest that schizophrenia is a chronic brain disorder, structurally and functionally affecting various cortical and subcortical regions involved in cognitive, emotional, and motivational aspects of human behavior. Second, we reviewed recent investigations into neurobiological basis for schizophrenic symptoms (auditory hallucinations and thought disorder) using these indices as well as hemodynamic assessments such as positron emission tomography (PET) and functional MRI (f-MRI). Finally, we addressed the issue of the heterogeneity of schizophrenia from the neurobiological perspective, in relation to the neuroanatomical and neurophysiological measures
AD  - Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. kasaik-tky@umin.ac.jp
UR  - PM:12067745
ER  - 

TY  - JOUR
T1  - Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635
A1  - Tauscher,J.
A1  - Kapur,S.
A1  - Verhoeff,N.P.
A1  - Hussey,D.F.
A1  - Daskalakis,Z.J.
A1  - Tauscher-Wisniewski,S.
A1  - Wilson,A.A.
A1  - Houle,S.
A1  - Kasper,S.
A1  - Zipursky,R.B.
Y1  - 2002/06//
SP  - 514
EP  - 520
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 59
IS  - 6
N2  - BACKGROUND: Results of postmortem studies show an elevation in serotonin-1A (5-hydroxytryptamine-1A [5-HT(1A)]) receptor density in the prefrontal and temporal cortices of patients with schizophrenia. This study examined 5-HT(1A) receptors in vivo in patients with schizophrenia using positron emission tomography and [carbonyl-(11)C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyrid inyl)cyclohexane carboxamide ([(11)C]WAY-100635). METHODS: The 5-HT(1A) binding potential of 14 antipsychotic drug-naive patients with a DSM-IV diagnosis of schizophrenia was compared with that of 14 age-matched healthy controls. Positron emission tomography data were analyzed using 9 cortical regions of interest, which were delineated on a coregistered magnetic resonance image and transferred to the positron emission tomographic image, with the cerebellum as the reference region for a simplified reference tissue model. We also performed a voxel-wise comparison using statistical parametric mapping. RESULTS: The region of interest-based analysis revealed a significant mean +/- SD cortical 5-HT(1A) receptor binding potential increase of 7.1% +/- 6.4% in patients with schizophrenia (F = 2.975; P =.02); local differences were +20% in the left medial temporal cortex (F = 9.339;P =.005) and +13% in the right medio temporal cortex (F = 4.453; P =.045). There were no significant differences in regional tracer delivery or cerebellar [(11)C]WAY-100635 uptake. The voxel-based analysis also confirmed a group difference in the left medial temporal cortex. CONCLUSIONS: The biological significance of elevated 5-HT(1A) receptor density in schizophrenia remains unclear. Given the location of 5-HT(1A) receptors on pyramidal cells, this elevation may reflect an abnormal glutamatergic network. Our finding needs to be viewed in light of preclinical evidence supporting a role for 5-HT(1A) receptors in mediating antipsychotic action and extrapyramidal adverse effects of drugs
AD  - PET Centre, Toronto, Ontario. johannes.tauscher@akh-wien.ac.at
UR  - PM:12044193
ER  - 

TY  - JOUR
T1  - Prefrontal dopamine D1 receptors and working memory in schizophrenia
A1  - Abi-Dargham,A.
A1  - Mawlawi,O.
A1  - Lombardo,I.
A1  - Gil,R.
A1  - Martinez,D.
A1  - Huang,Y.
A1  - Hwang,D.R.
A1  - Keilp,J.
A1  - Kochan,L.
A1  - Van Heertum,R.
A1  - Gorman,J.M.
A1  - Laruelle,M.
Y1  - 2002/05/01/
SP  - 3708
EP  - 3719
JA  - J Neurosci.
VL  - 22
IS  - 9
N2  - Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for working memory processing. The defective ability of patients with schizophrenia at working memory tasks is a core feature of this illness. It has been postulated that this impairment relates to a deficiency in mesocortical DA function. In this study, D1 receptor availability was measured with positron emission tomography and the selective D1 receptor antagonist [11C]NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [11C]NNC 112 binding potential (BP) was significantly elevated in the DLPFC of patients with schizophrenia (1.63 +/- 0.39 ml/gm) compared with control subjects (1.27 +/- 0.44 ml/gm; p = 0.02). In patients with schizophrenia, increased DLPFC [11C]NNC 112 BP was a strong predictor of poor performance at the n-back task, a test of working memory. These findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, New York 10032, USA. aa324@columbia.edu
UR  - PM:11978847
ER  - 

TY  - JOUR
T1  - Age and regional cerebral blood flow in schizophrenia: age effects in anterior cingulate, frontal, and parietal cortex
A1  - Schultz,S.K.
A1  - O'Leary,D.S.
A1  - Boles Ponto,L.L.
A1  - Arndt,S.
A1  - Magnotta,V.
A1  - Watkins,G.L.
A1  - Hichwa,R.D.
A1  - Andreasen,N.C.
Y1  - 2002///
N1  - UI - 21881815
SP  - 19
EP  - 24
JA  - J Neuropsychiatry Clin.Neurosci.
VL  - 14
IS  - 1
N2  - Positron emission tomography ([(15)O] water PET) was used to examine the relationship between age and regional cerebral blood flow (rCBF) in schizophrenia. Forty-nine unmedicated male patients, ages 20-51, underwent imaging during an eyes-closed resting condition. Negative correlations were observed between age and rCBF in the anterior cingulate, as well as in frontal (Brodmann area 8) and parietal cortex (area 40) bilaterally. The observation of reduced rCBF in the anterior cingulate with increased age is consistent with previous findings in healthy subjects. In contrast, the reduced flow observed in the frontal and parietal regions may be unique to schizophrenia
AD  - Department of Radiology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1000, USA. Susan-schultz@uiowa.edu
UR  - PM:11884650
ER  - 

TY  - JOUR
T1  - Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder
A1  - Buchsbaum,M.S.
A1  - Nenadic,I.
A1  - Hazlett,E.A.
A1  - Spiegel-Cohen,J.
A1  - Fleischman,M.B.
A1  - Akhavan,A.
A1  - Silverman,J.M.
A1  - Siever,L.J.
Y1  - 2002/03/01/
N1  - UI - 21843975
SP  - 141
EP  - 150
JA  - Schizophr.Res
VL  - 54
IS  - 1-2
N2  - In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients
AD  - Neuroscience PET Laboratory, Department of Psychiatry, Mt. Sinai School of Medicine, Box 1505, One Gustave L. Levy Place, New York, NY 10029-6574, USA. monte.buchsbaum@mssm.edu
UR  - PM:11853988
ER  - 

TY  - JOUR
T1  - Sensorimotor gating deficits and hypofrontality in schizophrenia
A1  - Hazlett,E.A.
A1  - Buchsbaum,M.S.
Y1  - 2001/09/01/
N1  - UI - 21423639
SP  - D1069
EP  - D1072
JA  - Front Biosci.
VL  - 6
N2  - Patients with schizophrenia exhibit (a) deficient sensorimotor gating as indexed by impaired prepulse inhibition (PPI) of the startle eyeblink reflex suggesting abnormal automatic information processing and (b) abnormal attentional modulation of PPI suggesting impaired controlled information processing. Here we test the hypothesis of deficient attentional modulation of PPI in schizophrenia as a defect in the interrelationship between frontal lobe functions of planning and executive action and posterior function of processing of sensory stimulation using positron emission tomography (PET). Consistent with the literature, our findings indicate that unmedicated schizophrenia patients exhibit lower frontal/occipital ratios (termed "hypofrontality") compared with healthy controls (n=15 in each group) during a standard tone-length-judgment (attention-to-prepulse) task. Moreover, better attentional modulation of PPI was associated with higher frontal/occipital ratios in the control, but not the patient group. These findings extend animal models to humans by demonstrating the importance of frontal and occipital lobe coordination in the modulation of PPI
AD  - Department of Psychiatry, Box 1505, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA. erin.hazlett@mssm.edu
UR  - PM:11532605
ER  - 

TY  - JOUR
T1  - Effect of schizophrenia on frontotemporal activity during word encoding and recognition: a PET cerebral blood flow study
A1  - Ragland,J.D.
A1  - Gur,R.C.
A1  - Raz,J.
A1  - Schroeder,L.
A1  - Kohler,C.G.
A1  - Smith,R.J.
A1  - Alavi,A.
A1  - Gur,R.E.
Y1  - 2001/07//
N1  - UI - 21324079
SP  - 1114
EP  - 1125
JA  - Am J Psychiatry
VL  - 158
IS  - 7
N2  - OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval
AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-4283, USA. ragland@bblmail.psycha.upenn.edu
UR  - PM:11431234
ER  - 

TY  - JOUR
T1  - No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopride and [(11)C]FLB 457
A1  - Talvik,M.
A1  - Nordstrom,A.L.
A1  - Nyberg,S.
A1  - Olsson,H.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 2001/06//
N1  - UI - 21278153
SP  - 926
EP  - 930
JA  - Am J Psychiatry
VL  - 158
IS  - 6
N2  - OBJECTIVE: The authors' goal was to test the hypothesis of extrastriatal D(2) receptor selectivity as the mechanism of action of clozapine. METHOD: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D(2) receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [(11)C]raclopride was used for determination of D(2) receptor occupancy in the striatum. The radioligand [(11)C]FLB 457 was chosen for determination of D(2) receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex. RESULTS: In patients treated with haloperidol the D(2) receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D(2) receptor occupancy was relatively low in both the striatum and the extrastriatal regions. CONCLUSIONS: The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine
AD  - Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. mirjam.talvik@nvso.sll.se
UR  - PM:11384901
ER  - 

TY  - JOUR
T1  - D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study
A1  - Gefvert,O.
A1  - Lundberg,T.
A1  - Wieselgren,I.M.
A1  - Bergstrom,M.
A1  - Langstrom,B.
A1  - Wiesel,F.
A1  - Lindstrom,L.
Y1  - 2001/04//
N1  - UI - 21213714
SP  - 105
EP  - 110
JA  - Eur.Neuropsychopharmacol.
VL  - 11
IS  - 2
N2  - OBJECTIVE: Quetiapine is a novel antipsychotic agent with many atypical features, including low D(2) and higher 5HT(2A) affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D(2) and 5HT(2A) receptors in schizophrenic patients. METHODS: Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D(2) and 5HT(2A) occupancies were determined using [(11)C] raclopride and [(11)C] N-methylspiperone as ligands, respectively, and PET imaging. RESULTS: Mean D(2) receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study. CONCLUSIONS: In clinically effective doses, quetiapine induced low occupancy at D(2) receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses
AD  - Department of Psychiatric Research, Central Hospital, S-721 89, Vasteras, Sweden. ola.gefvert@ltvastmanland.se
UR  - PM:11313155
ER  - 

TY  - JOUR
T1  - Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography
A1  - Okubo,Y.
A1  - Suhara,T.
A1  - Suzuki,K.
A1  - Kobayashi,K.
A1  - Inoue,O.
A1  - Terasaki,O.
A1  - Someya,Y.
A1  - Sassa,T.
A1  - Sudo,Y.
A1  - Matsushima,E.
A1  - Iyo,M.
A1  - Tateno,Y.
A1  - Toru,M.
Y1  - 2000///
N1  - UI - 20350586
SP  - 2455
EP  - 2464
JA  - Life Sci.
VL  - 66
IS  - 25
N2  - Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia
AD  - Department of Neurobehavioral Medicine, Graduate School of Tokyo Medical and Dental University, Japan. okubo.psyc@med.tmd.ac.jp
UR  - PM:10894088
ER  - 

TY  - JOUR
T1  - A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy
A1  - Kapur,S.
A1  - Zipursky,R.
A1  - Jones,C.
A1  - Shammi,C.S.
A1  - Remington,G.
A1  - Seeman,P.
Y1  - 2000/06//
SP  - 553
EP  - 559
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 57
IS  - 6
N2  - BACKGROUND: Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. METHODS: Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose. RESULTS: Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours. CONCLUSIONS: Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion
AD  - Department of Psychiatry, University of Toronto, Ontario. kapur@clarke-inst.on.ca
UR  - PM:10839333
ER  - 

TY  - JOUR
T1  - Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: A PET study using [(18)F]setoperone
A1  - Ngan,E.T.
A1  - Yatham,L.N.
A1  - Ruth,T.J.
A1  - Liddle,P.F.
Y1  - 2000/06//
N1  - UI - 20292759
SP  - 1016
EP  - 1018
JA  - Am J Psychiatry
VL  - 157
IS  - 6
N2  - OBJECTIVE: The authors compared serotonin receptor binding in patients with schizophrenia and healthy comparison subjects. METHOD: They used positron emission tomography with [(18)F]setoperone to examine six patients with schizophrenia who had never been given neuroleptics and seven age-matched subjects who did not have schizophrenia. RESULTS: A nondirected voxel-based analysis of the subjects' entire search volume found that serotonin 2A binding potential in the frontal cortex index was significantly smaller (by 16.3%) in patients with schizophrenia than in healthy subjects. CONCLUSIONS: The authors conclude that the decrease in serotonin receptor densities previously reported in postmortem studies of subjects with schizophrenia are present at the onset of the illness, before exposure to neuroleptics
AD  - Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. ngan@unixg.ubc.ca
UR  - PM:10831488
ER  - 

TY  - JOUR
T1  - Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography
A1  - Laakso,A.
A1  - Vilkman,H.
A1  - Alakare,B.
A1  - Haaparanta,M.
A1  - Bergman,J.
A1  - Solin,O.
A1  - Peurasaari,J.
A1  - Rakkolainen,V.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 2000/02//
N1  - UI - 20137702
SP  - 269
EP  - 271
JA  - Am J Psychiatry
VL  - 157
IS  - 2
N2  - OBJECTIVE: Recent in vivo imaging studies indicate a dysregulated presynaptic function of the striatal dopaminergic system in patients with schizophrenia. To further explore the basis of this phenomenon, the authors studied brain dopamine transporter binding in vivo in patients with first-episode, never-medicated schizophrenia. METHOD: Nine patients with schizophrenia and nine healthy matched comparison subjects were recruited. Striatal dopamine transporter binding was measured with positron emission tomography and a specific dopamine transporter ligand, [(18)F]CFT, a radiolabeled form of 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane. RESULTS: Average caudate and putamen dopamine transporter binding potentials were almost identical in the patients and comparison subjects, but the patients lacked the right-left asymmetry of the caudate dopamine transporter binding seen in the comparison group. CONCLUSIONS: Average striatal dopamine transporter density is unaltered in neuroleptic-naive patients with schizophrenia. However, patients lack asymmetry in caudate dopamine transporter binding, which conforms with disrupted brain lateralization in this disorder
AD  - Department of Psychiatry, University of Turku, Finland
UR  - PM:10671399
ER  - 

TY  - JOUR
T1  - Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum
A1  - Hazlett,E.A.
A1  - Buchsbaum,M.S.
A1  - Byne,W.
A1  - Wei,T.C.
A1  - Spiegel-Cohen,J.
A1  - Geneve,C.
A1  - Kinderlehrer,R.
A1  - Haznedar,M.M.
A1  - Shihabuddin,L.
A1  - Siever,L.J.
Y1  - 1999/08//
N1  - UI - 99378753
SP  - 1190
EP  - 1199
JA  - Am J Psychiatry
VL  - 156
IS  - 8
N2  - OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia
AD  - Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. hazlett@msvax.mssm.edu
UR  - PM:10450259
ER  - 

TY  - JOUR
T1  - Frontal lobe psychopathology: mania, depression, confabulation, catatonia, perseveration, obsessive compulsions, and schizophrenia
A1  - Joseph,R.
Y1  - 1999///
N1  - UI - 99348899
SP  - 138
EP  - 172
JA  - Psychiatry
VL  - 62
IS  - 2
N2  - The frontal lobes can be subdivided into major functional neuroanatomical domains, which, when injured, surgically destroyed, or reduced in activity or volume, give rise to signature pathological and psychiatric symptomology. A review of case reports and over 50 years of research, including magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography scans, indicates that apathy, "blunted" schizophrenia, major depression, and aphasic-perseverative disturbance of speech and thought are associated with left lateral as well as bilateral frontal (and striatal) abnormalities. Impulsiveness, confabulatory verbosity, grandiosity, increased sexuality, and mania are associated with right frontal (as well as bilateral) disturbances. Gegenhalten, catatonia, and disturbances of "will" are indicative of medial frontal injuries. Disinhibitory states and obsessive-compulsive perseverative abnormalities are more frequently observed with orbital frontal lobe dysfunction, including frontal-striatal disturbances. These associations, however, are not always clear-cut as patients with the same diagnosis may demonstrate different symptoms that may be due to an additional abnormality in a different region of the brain. Moreover, as the frontal subdivisions are richly interconnected, and as frontal lobe abnormalities are not always discrete or well localized, a wide array of seemingly divergent waxing and waning symptoms may be manifest, sometimes simultaneously, including manic depression and what has been referred to as the "frontal lobe personality."
AD  - Brain Research Laboratory, San Jose, CA 95126, USA
UR  - PM:10420428
ER  - 

TY  - JOUR
T1  - Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients
A1  - Nyberg,S.
A1  - Eriksson,B.
A1  - Oxenstierna,G.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 1999/06//
N1  - UI - 99288397
SP  - 869
EP  - 875
JA  - Am J Psychiatry
VL  - 156
IS  - 6
N2  - OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range = 79%-85%), 5-HT2A receptor occupancy was 95% (range = 86%-109%), and six patients had developed extrapyramidal side effects. After dose reduction to 3 mg/day, D2 receptor occupancy was 72% (range = 53%-78%), and 5-HT2A receptor occupancy was 83% (range = 65%-112%). Three patients had extrapyramidal side effects at this time. CONCLUSIONS: Treatment with risperidone, 6 mg/day, is likely to induce unnecessarily high D2 receptor occupancy, with a consequent risk of extrapyramidal side effects. High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely. The authors previously suggested an optimal interval for D2 receptor occupancy of 70%-80%. To achieve this, resperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. svante.nyberg@neuro.ks.se
UR  - PM:10360125
ER  - 

TY  - JOUR
T1  - D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET
A1  - Remington,G.
A1  - Kapur,S.
Y1  - 1999///
N1  - UI - 99270508
SP  - 15
EP  - 19
JA  - J Clin.Psychiatry
VL  - 60 Suppl 10
N2  - The advent of a number of new antipsychotics has been paralleled by efforts to better delineate their mechanisms of action and, in doing so, further our understanding of schizophrenia and its pathophysiology. Technological advances, such as positron emission tomography (PET), have proven to be powerful tools in this process, allowing us to evaluate in vivo models based primarily on in vitro evidence. Combined serotonin-2/dopamine-2 (5-HT2/D2) antagonism represents one such model, and we now have PET evidence available that can be extrapolated to our understanding and clinical use of both conventional and novel antipsychotics
AD  - Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada. gr@sig.clarke-inst.on.ca
UR  - PM:10340683
ER  - 

TY  - JOUR
T1  - Visualizing fronto-striatal circuitry and neuroleptic effects in schizophrenia
A1  - Buchsbaum,M.S.
A1  - Hazlett,E.A.
A1  - Haznedar,M.M.
A1  - Spiegel-Cohen,J.
A1  - Wei,T.C.
Y1  - 1999///
N1  - UI - 99239848
SP  - 129
EP  - 137
JA  - Acta Psychiatr.Scand.Suppl
VL  - 395
N2  - Disturbances in fronto-striatal circuitry have been postulated to be important in schizophrenia. Positron emission tomography typically shows decreased metabolic rates in these areas relative to other brain areas in schizophrenia. After treatment with typical neuroleptics, striatal metabolic rates are increased, but other brain areas tend not to show significant changes. Atypical neuroleptics less markedly affect striatal metabolic rates, but show wider cortical effects. In order to examine fronto-striatal circuitry, a technique for visualizing the correlations between metabolic rates in all brain areas was applied in 33 controls and 27 unmedicated schizophrenic patients. Correlation images revealed strong fronto-striatal connections in controls, but weak fronto-striatal links in schizophrenic patients. Changes in striatal circuits, also reflected in recent anatomical studies, may be important for understanding antipsychotic effects
AD  - Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029-6574, USA
UR  - PM:10225342
ER  - 

TY  - JOUR
T1  - Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia
A1  - Kapur,S.
A1  - Zipursky,R.B.
A1  - Remington,G.
Y1  - 1999/02//
N1  - UI - 99142671
SP  - 286
EP  - 293
JA  - Am J Psychiatry
VL  - 156
IS  - 2
N2  - OBJECTIVE: Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens. METHOD: Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of [11C]raclopride and [18F]setoperone, respectively, and positron emission tomography imaging. RESULTS: Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine. CONCLUSIONS: Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects
AD  - The Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, ON, Canada. kapur@clarke-inst.on.ca
UR  - PM:9989565
ER  - 

TY  - JOUR
T1  - Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia
A1  - Hietala,J.
A1  - Syvalahti,E.
A1  - Vilkman,H.
A1  - Vuorio,K.
A1  - Rakkolainen,V.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Kuoppamaki,M.
A1  - Eronen,E.
A1  - Ruotsalainen,U.
A1  - Salokangas,R.K.
Y1  - 1999/01/04/
N1  - UI - 99143385
SP  - 41
EP  - 50
JA  - Schizophr.Res
VL  - 35
IS  - 1
N2  - We have previously reported aberrations in the striatal presynaptic dopamine function in neuroleptic-naive schizophrenic patients compared to healthy controls (Hietala, J., Syvalahti, E., Vuorio, K. et al., 1995. Lancet 346, 1130-1131). In this extended study we explore whether the altered presynaptic dopamine function correlates with the clinical symptomatology in schizophrenia. Striatal dopamine synthesis capacity (6-[18F]fluorodopa (FDOPA) uptake, Ki values) was studied with positron emission tomography in 10 neuroleptic-naive schizophrenic patients and 13 healthy controls. The clinical symptomatology was characterized with the Positive and Negative Symptom Scale (PANSS). The patients had an increased FDOPA uptake in striatum and lacked the asymmetry in caudate FDOPA uptake (p = 0.0005), confirming our earlier results. Left striatal FDOPA uptake (Ki) values correlated negatively with depressive symptoms in a highly significant manner. On the other hand, paranoid symptomatology correlated positively with right putamen FDOPA uptake at a trend level (rho = 0.73, p < 0.02). The lack of asymmetry in caudate Ki values did not associate with any dimension of psychopathology. The major finding in this study is that depressive symptoms in neuroleptic-naive first-admission schizophrenia are associated with low presynaptic dopamine function. This link appears to be hemisphere-related and may have drug-treatment implications, e.g., in prediction of response to D2 receptor blocking antipsychotic drugs. A possible connection between paranoid symptomatology and subcortical hyperdopaminergia is suggested, but this remains to be further verified
AD  - Department of Psychiatry, Turku University Central Hospital, Finland. jahi@utu.fi
UR  - PM:9988840
ER  - 

TY  - JOUR
T1  - Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects
A1  - Lewis,R.
A1  - Kapur,S.
A1  - Jones,C.
A1  - Dasilva,J.
A1  - Brown,G.M.
A1  - Wilson,A.A.
A1  - Houle,S.
A1  - Zipursky,R.B.
Y1  - 1999/01//
N1  - UI - 99107318
SP  - 72
EP  - 78
JA  - Am J Psychiatry
VL  - 156
IS  - 1
N2  - OBJECTIVE: Several postmortem studies have reported a decreased density of serotonin 5-HT2 receptors in the prefrontal cortex in schizophrenia. The purpose of this study was to investigate this in patients with schizophrenia by means of [18F]setoperone and positron emission tomography (PET) imaging. METHOD: Thirteen neuroleptic-free patients with schizophrenia, 10 of whom were also neuroleptic-naive, were compared with a group of 26 normal subjects in the same age range. The density of 5-HT2 receptors was assessed with the use of [18F]setoperone and PET in standardized cortical regions of interest. RESULTS: Increasing age was associated with similar declines in 5-HT2 receptors in all cortical regions in the patient group and in the normal comparison group. After control for the effect of age, there was no statistically significant difference between the patients and the comparison subjects in 5-HT2 receptor density in any of the cortical regions. CONCLUSIONS: This study failed to find the decrease in 5-HT2 receptors reported in postmortem studies of schizophrenia. The study had the power to detect a decrease of 25% or more in 5-HT2 receptors, which was anticipated on the basis of the previous postmortem studies. Thus, a primary serotonergic abnormality in schizophrenia, if one exists, is either small or unlikely to be at the level of the 5-HT2 receptors. This finding does not rule out a therapeutic role for 5-HT2 antagonists in schizophrenia, but it does suggest that the therapeutic contribution is likely to be an indirect one
AD  - The Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, ON, Canada
UR  - PM:9892300
ER  - 

TY  - JOUR
T1  - Functional hypofrontality and working memory dysfunction in schizophrenia
A1  - Carter,C.S.
A1  - Perlstein,W.
A1  - Ganguli,R.
A1  - Brar,J.
A1  - Mintun,M.
A1  - Cohen,J.D.
Y1  - 1998/09//
N1  - UI - 98403626
SP  - 1285
EP  - 1287
JA  - Am J Psychiatry
VL  - 155
IS  - 9
N2  - OBJECTIVE: Hypofrontality is a common but not invariable finding in schizophrenia. Inconsistencies in the literature may reflect, in part, the fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functional demands on this region. METHOD: The authors studied eight patients with schizophrenia and eight matched comparison subjects using [(15)O]H2O positron emission tomography and the "N-back" task, which activates the prefrontal cortex as a function of working memory load in normal subjects. RESULTS: Under low-working-memory-load conditions, the accuracy of both groups in the N-back task was equal, but when the memory load increased, the patients' performance deteriorated more than did that of the comparison subjects. The regional cerebral blood flow response to increased working memory load was significantly reduced in the patients' right dorsolateral prefrontal cortex. CONCLUSIONS: These results confirm the importance of using tasks that tap specific cognitive functions, linked to specific neural systems, in studies of brain-behavior relationships in schizophrenia. Hypofrontality is reliably demonstrated in schizophrenia during tasks that engage working memory functions of the prefrontal cortex
AD  - Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, PA 15213, USA. cscarter+@pitt.edu
UR  - PM:9734557
ER  - 

TY  - JOUR
T1  - Prefrontal cortex activity in people with schizophrenia and control subjects. Evidence from positron emission tomography for remission of 'hypofrontality' with recovery from acute schizophrenia
A1  - Spence,S.A.
A1  - Hirsch,S.R.
A1  - Brooks,D.J.
A1  - Grasby,P.M.
Y1  - 1998/04//
N1  - UI - 98381122
SP  - 316
EP  - 323
JA  - Br.J Psychiatry
VL  - 172
N2  - BACKGROUND: Hypo-activation of the left dorsolateral prefrontal cortex is inconsistently found in neuroimaging studies of schizophrenia. As the left dorsolateral prefrontal cortex is involved in the generation of action, disordered function in this region may be implicated in schizophrenic symptomatology. METHOD: We used H2 15O positron emission tomography to study dorsolateral prefrontal cortical function in men with schizophrenia (n = 13) and male control subjects (n = 6) performing joystick movements on two occasions, 4-6 weeks apart. The patients were initially in relapse. To clarify dorsolateral prefrontal cortical function we also scanned another group of control subjects (n = 5) performing mouth movements. RESULTS: The control subjects performing hand or mouth movements activated the left dorsolateral prefrontal cortex to a maximum when the movements were self-selected. The men with relapsed schizophrenia exhibited left dorsolateral prefrontal cortical hypoactivation, which remitted with symptomatic improvement. CONCLUSIONS: Hypofrontality in these patients is a dynamic phenomenon across time, possibly related to current symptomatology. The most appropriate question about the presence of hypofrontality in schizophrenia may be when, rather than whether, it will occur
AD  - Imperial College School of Medicine, MRC Cyclotron Unit, London. sean@wren.rpms.ac.uk
UR  - PM:9715333
ER  - 

TY  - JOUR
T1  - Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: a positron emission tomography study
A1  - Ragland,J.D.
A1  - Gur,R.C.
A1  - Glahn,D.C.
A1  - Censits,D.M.
A1  - Smith,R.J.
A1  - Lazarev,M.G.
A1  - Alavi,A.
A1  - Gur,R.E.
Y1  - 1998/07//
N1  - UI - 98338784
SP  - 399
EP  - 413
JF  - Neuropsychology
VL  - 12
IS  - 3
N2  - Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 15O-water measures of rCBF. Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals
AD  - Department of Psychiatry, University of Pennsylvania health Systems, Philadelphia, USA. ragland@bblmail.psycha.upenn.edu
UR  - PM:9673996
ER  - 

TY  - JOUR
T1  - 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation
A1  - Kapur,S.
A1  - Zipursky,R.B.
A1  - Remington,G.
A1  - Jones,C.
A1  - Dasilva,J.
A1  - Wilson,A.A.
A1  - Houle,S.
Y1  - 1998/07//
N1  - UI - 98324043
SP  - 921
EP  - 928
JA  - Am J Psychiatry
VL  - 155
IS  - 7
N2  - OBJECTIVE: Olanzapine is a new atypical antipsychotic recently introduced for the treatment of schizophrenia. The purpose of this study was to investigate olanzapine's binding to the serotonin 5-HT2 and dopamine D2 receptors in schizophrenic patients being treated with clinically relevant doses. METHOD: Twelve patients with schizophrenia were randomly assigned to 5, 10, 15, or 20 mg/day of olanzapine in a prospective fashion. Three other subjects taking 30-40 mg/day were also included. Once steady-state plasma levels were achieved, dopamine D2 and serotonin 5-HT2 receptors were assessed by using [11C]raclopride and [18F]setoperone positron emission tomography imaging, respectively. Ratings of clinical status, extrapyramidal side effects, and prolactin levels were also obtained. RESULTS: Olanzapine induced near saturation of the 5-HT2 receptors, even at 5 mg/day. Its D2 occupancy increased with dose: patients taking 5-20 mg/day showed 43%-80% D2 occupancy, while patients taking 30-40 mg/day showed 83%-88%. CONCLUSIONS: Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses. However, its D2 occupancy is higher than that of clozapine and similar to that of risperidone. In the usual clinical dose range of 10-20 mg/day, its occupancy varies from 71% to 80%, and this restricted range may explain its freedom from extrapyramidal side effects and prolactin elevation. However, doses of 30 mg/day and higher are associated with more than 80% D2 occupancy and may have a higher likelihood of prolactin elevation and extrapyramidal side effects
AD  - Schizophrenia Division, Clarke Institute of Psychiatry, Toronto, Ont., Canada. kapur@clarke-inst.on.ca
UR  - PM:9659858
ER  - 

TY  - JOUR
T1  - Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients
A1  - Trichard,C.
A1  - Paillere-Martinot,M.L.
A1  - Attar-Levy,D.
A1  - Recassens,C.
A1  - Monnet,F.
A1  - Martinot,J.L.
Y1  - 1998/04//
N1  - UI - 98207624
SP  - 505
EP  - 508
JA  - Am J Psychiatry
VL  - 155
IS  - 4
N2  - OBJECTIVE: This study examined the binding to cortical serotonin 5-HT2A receptors of conventional doses of the typical neuroleptic chlorpromazine in comparison with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific dopamine D2-D3 blocker. METHOD: Seventeen schizophrenic patients treated with chlorpromazine (75-700 mg/day), four treated with clozapine (200-600 mg/day), and five treated with amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A binding was estimated by reference to the values for 14 antipsychotic-free schizophrenic subjects with the use of positron emission tomography and [18F]setoperone, a high-affinity radioligand for cortical 5-HT2A receptors. RESULTS: A dose-dependent decrease in the number of available cortical binding sites for [18F] setoperone was demonstrated in the chlorpromazine group; for the highest dose, there was a virtual lack of sites available for binding. A very low percentage of available binding sites was also observed in the clozapine-treated patients at all doses. This suggests a high level of 5-HT2A blockade with both clozapine and high doses of chlorpromazine. No significant binding of amisulpride to 5-HT2A receptors was detected. CONCLUSIONS: A high level of 5-HT2A receptor blockade does not appear specific to clozapine in comparison with high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT2A blockade itself
AD  - Institut National de la Sante et de la Recherche Medicale, Service Hospitalier Frederic Joliot, Paris, France
UR  - PM:9545996
ER  - 

TY  - JOUR
T1  - Positron emission tomography finding of a high striatal D2 receptor occupancy in olanzapine-treated patients
A1  - Nordstrom,A.L.
A1  - Nyberg,S.
A1  - Olsson,H.
A1  - Farde,L.
Y1  - 1998/03//
N1  - UI - 98169047
SP  - 283
EP  - 284
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 55
IS  - 3
UR  - PM:9510228
ER  - 

TY  - JOUR
T1  - The relationship between risperidone plasma levels and dopamine D2 occupancy: a positron emission tomographic study
A1  - Remington,G.
A1  - Kapur,S.
A1  - Zipursky,R.
Y1  - 1998/02//
N1  - UI - 98132190
SP  - 82
EP  - 83
JA  - J Clin.Psychopharmacol.
VL  - 18
IS  - 1
UR  - PM:9472848
ER  - 

TY  - JOUR
T1  - Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method
A1  - Breier,A.
A1  - Su,T.P.
A1  - Saunders,R.
A1  - Carson,R.E.
A1  - Kolachana,B.S.
A1  - de Bartolomeis,A.
A1  - Weinberger,D.R.
A1  - Weisenfeld,N.
A1  - Malhotra,A.K.
A1  - Eckelman,W.C.
A1  - Pickar,D.
Y1  - 1997/03/18/
N1  - UI - 97225994
SP  - 2569
EP  - 2574
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 94
IS  - 6
N2  - A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [11C]raclopride specific binding (mean +/- SEM): -22.3% (+/-2.7) vs. -15.5% (+/-1.8),P = 0.04, respectively. Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamine concentrations was substantially greater than controls. These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia
AD  - Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. alan_breier@nih.gov
UR  - PM:9122236
ER  - 

TY  - JOUR
T1  - Presynaptic dopaminergic function in the striatum of schizophrenic patients
A1  - Dao-Castellana,M.H.
A1  - Paillere-Martinot,M.L.
A1  - Hantraye,P.
A1  - Attar-Levy,D.
A1  - Remy,P.
A1  - Crouzel,C.
A1  - Artiges,E.
A1  - Feline,A.
A1  - Syrota,A.
A1  - Martinot,J.L.
Y1  - 1997/02/07/
N1  - UI - 97215459
SP  - 167
EP  - 174
JA  - Schizophr.Res
VL  - 23
IS  - 2
N2  - The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased 18F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The 18F-fluoro-L-DOPA (18F-DOPA) uptake rate constant Ki was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean Ki was found. The variability of the 18F-DOPA uptake values was higher in the caudate (p < 0.01) and in the putamen (p < 0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function
AD  - Service Hospitalier Frederic Joliot, CEA, INSERM U 334, Orsay, France
UR  - PM:9061812
ER  - 

TY  - JOUR
T1  - Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients
A1  - Hietala,J.
A1  - Syvalahti,E.
A1  - Vuorio,K.
A1  - Rakkolainen,V.
A1  - Bergman,J.
A1  - Haaparanta,M.
A1  - Solin,O.
A1  - Kuoppamaki,M.
A1  - Kirvela,O.
A1  - Ruotsalainen,U.
A1  - .
Y1  - 1995/10/28/
N1  - UI - 96036427
SP  - 1130
EP  - 1131
JF  - Lancet
VL  - 346
IS  - 8983
N2  - Presynaptic dopamine function (6-[18F]-fluorodopa uptake) in the brains of seven neuroleptic-naive first-admission schizophrenic patients and eight healthy controls was studied with positron emission tomography. The fluorodopa influx constant (Ki) in putamen was higher in the patients than in controls (average mean: 0.0149 vs 0.0129, p = 0.034). The changes in caudate were smaller but significantly lateralised to the left caudate. There was one catatonic schizophrenic patient in our sample. This patient had lower striatal Ki than any control. Alterations in striatal presynaptic dopamine function may constitute a part of disrupted neural circuits that predispose to schizophrenic psychosis
AD  - Department of Pharmacology, University of Turku, Finland
UR  - PM:7475604
ER  - 

TY  - JOUR
T1  - D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients
A1  - Nordstrom,A.L.
A1  - Farde,L.
A1  - Nyberg,S.
A1  - Karlsson,P.
A1  - Halldin,C.
A1  - Sedvall,G.
Y1  - 1995/10//
SP  - 1444
EP  - 1449
JA  - Am J Psychiatry
VL  - 152
IS  - 10
N2  - OBJECTIVE: Central D1, D2, and 5-HT2 receptor occupancy in schizophrenic patients treated with clozapine was determined and related to clozapine serum concentrations. METHOD: Seventeen patients treated with clozapine (125-600 mg/day) were examined with positron emission tomography (PET) and one to three of the following selective radioligands: [11C]SCH23390 (N = 11), [11C]raclopride (N = 16), and [11C]N-methylspiperone (N = 5). Clozapine concentration in serum was determined by gas chromatography/mass spectrometry. RESULTS: D2 receptor occupancy (20%-67%) was lower than that previously determined in patients treated with classical neuroleptics (70%-90%). D1 receptor occupancy (36%-59%) was higher than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in clozapine serum concentration (105-2121 ng/ml) at the time of PET examination, D2 receptor occupancy was low in all patients and was not described by the curvilinear relationship between serum drug concentration and receptor occupancy that has been demonstrated for classical antipsychotics. CONCLUSIONS: The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extrapyramidal side effects. The combination of relatively high D1, low D2, and very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum concentrations have not been unequivocally shown to predict clinical effects. In this study, concentration did not predict degree of occupancy in brain. Thus, careful clinical titration cannot be replaced by monitoring of drug concentrations for optimization of clozapine treatment in individual patients
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:7573582
ER  - 

TY  - JOUR
T1  - Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task
A1  - Frith,C.D.
A1  - Friston,K.J.
A1  - Herold,S.
A1  - Silbersweig,D.
A1  - Fletcher,P.
A1  - Cahill,C.
A1  - Dolan,R.J.
A1  - Frackowiak,R.S.
A1  - Liddle,P.F.
Y1  - 1995/09//
N1  - UI - 96092850
SP  - 343
EP  - 349
JA  - Br.J Psychiatry
VL  - 167
IS  - 3
N2  - BACKGROUND. This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD. Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS. In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION. These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex
AD  - Institute of Neurology, London
UR  - PM:7496643
ER  - 

TY  - JOUR
T1  - No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-methylspiperone
A1  - Nordstrom,A.L.
A1  - Farde,L.
A1  - Eriksson,L.
A1  - Halldin,C.
Y1  - 1995/08/08/
N1  - UI - 96048662
SP  - 67
EP  - 83
JA  - Psychiatry Res
VL  - 61
IS  - 2
N2  - The dopamine hypothesis of schizophrenia received strong support when a two- to three-fold elevation of D2 receptor densities was demonstrated by positron emission tomography (PET) and [11C]N-methylspiperone ([11C]NMSP). In the present study, the reproducibility of this finding was examined by application of a similar method in seven normal comparison subjects and seven neuroleptic-naive schizophrenic patients examined by PET before and after administration of haloperidol, 7.5 mg. After haloperidol, the specific binding of [11C]NMSP was reduced by 80-90%, resulting in a signal-to-noise ratio that was unfavorably low for reliable quantification. No significant difference was found between normal subjects and patients in a descriptive analysis of the time-activity curves or in a nonequilibrium graphical determination of D2 receptor densities in the basal ganglia. The results are consistent with those of a previous quantitative PET study of [11C]raclopride binding, which showed normal densities of D2 receptors in the striatum of neuroleptic-naive schizophrenic patients
AD  - Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
UR  - PM:7480390
ER  - 

TY  - JOUR
T1  - Clozapine effects on glucose metabolic rate in striatum and frontal cortex
A1  - Potkin,S.G.
A1  - Buchsbaum,M.S.
A1  - Jin,Y.
A1  - Tang,C.
A1  - Telford,J.
A1  - Friedman,G.
A1  - Lottenberg,S.
A1  - Najafi,A.
A1  - Gulasekaram,B.
A1  - Costa,J.
A1  - .
Y1  - 1994/09//
N1  - UI - 95050392
SP  - 63
EP  - 66
JA  - J Clin.Psychiatry
VL  - 55 Suppl B
N2  - Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, Orange 92668
UR  - PM:7961576
ER  - 

TY  - JOUR
T1  - [No hypofrontality in schizophrenia demonstrated by positron emission tomography]
A1  - Biver,F.
A1  - Delvenne,V.
A1  - Goldman,S.
A1  - Luxen,A.
A1  - De,Maertelaer,V
A1  - Lotstra,F.
A1  - Mendlewicz,J.
Y1  - 1992/09//
N1  - UI - 94303430
SP  - 261
EP  - 278
JA  - Acta Psychiatr.Belg.
VL  - 92
IS  - 5
N2  - We studied cerebral glucose metabolism, using Positron Emission Tomography (PET) and (F-18) fluorodeoxyglucose, in 15 young schizophrenic patients compare to 15 age-matched healthy volunteers. The PET investigation was made in a quiet room with a dimly light. Each subject remained in a supine resting state with eyes closed. Results failed to demonstrate any differences in glucose utilization between schizophrenic patients and control subjects, as far as absolute or relative, left and right values are concerned. Besides, variability of metabolic values was significantly higher in schizophrenics than in controls
AD  - Service de Psychiatrie, Cliniques Universitaires de Bruxelles, Hopital, Erasme
UR  - PM:1345405
ER  - 

TY  - JOUR
T1  - Toward a brain map of auditory hallucinations
A1  - Cleghorn,J.M.
A1  - Franco,S.
A1  - Szechtman,B.
A1  - Kaplan,R.D.
A1  - Szechtman,H.
A1  - Brown,G.M.
A1  - Nahmias,C.
A1  - Garnett,E.S.
Y1  - 1992/08//
N1  - UI - 92343904
SP  - 1062
EP  - 1069
JA  - Am J Psychiatry
VL  - 149
IS  - 8
N2  - OBJECTIVE: This study asks whether auditory hallucinations are reflected in a distinctive metabolic map of the brain. METHOD: Regional brain metabolism was measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM-III schizophrenic patients who experienced auditory hallucinations during glucose uptake and 10 who did not. All patients were free of neuroleptics and 19 had never been treated with neuroleptics. Nine patients were reexamined after 1 year to assess effects of neuroleptic treatment. RESULTS: Compared with the patients who did not experience hallucinations, the patients who did experience hallucinations had significantly lower relative metabolism in auditory and Wernicke's regions and a trend toward higher metabolism in the right hemisphere homologue of Broca's region. Hallucination scores correlated positively and significantly with relative metabolism in the striatum and anterior cingulate regions. Neuroleptic treatment resulted in a significant increase in striatal metabolism and a reduced frontal-parietal ratio, which was significantly correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory hallucinations involve language regions of the cortex in a pattern similar to that seen in normal subjects listening to their own voices but different in that left prefrontal regions are not activated. The striatum plays a critical role in auditory hallucinations
AD  - Department of Psychiatry, McMaster University, Hamilton, Ont., Canada
UR  - PM:1353314
ER  - 

TY  - JOUR
T1  - Regional brain glucose metabolism: correlations to biochemical measures and anxiety in patients with schizophrenia
A1  - Wik,G.
A1  - Wiesel,F.A.
Y1  - 1991/10//
N1  - published erratum appears in Psychiatry Res 1992 May;45(1):65
SP  - 101
EP  - 114
JA  - Psychiatry Res
VL  - 40
IS  - 2
N2  - Regional brain glucose metabolism in 20 patients with schizophrenia (DSM-III) was investigated by positron emission tomography (PET) with uniformly labeled 11C-glucose as the tracer. Monoamine metabolites were analyzed in cerebrospinal fluid (CSF) and serum, and prolactin was analyzed in serum. Intensity of anxiety was rated directly after the PET study. Ten healthy volunteers served as controls. In the patients, weak positive and negative relationships were found between homovanillic acid in CSF and prolactin in serum, respectively, and regional metabolic rates. In all subjects, positive correlations were found between the level of anxiety and the regional glucose metabolism. In the controls, positive correlations were found between anxiety and the frontal/parietal ratios of the left hemisphere, whereas anxiety scores of the patients correlated negatively to relative metabolic rates of the right medial frontal cortex and the left thalamus. These observations may indicate alterations in the neuronal systems participating in the initiation of anxiety and arousal in schizophrenia
AD  - Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden
UR  - PM:1722339
ER  - 

TY  - JOUR
T1  - Striatal D2 dopaminergic receptors assessed with positron emission tomography and [76Br]bromospiperone in untreated schizophrenic patients
A1  - Martinot,J.L.
A1  - Peron-Magnan,P.
A1  - Huret,J.D.
A1  - Mazoyer,B.
A1  - Baron,J.C.
A1  - Boulenger,J.P.
A1  - Loc'h,C.
A1  - Maziere,B.
A1  - Caillard,V.
A1  - Loo,H.
A1  - .
Y1  - 1990/01//
N1  - UI - 90087135
SP  - 44
EP  - 50
JA  - Am J Psychiatry
VL  - 147
IS  - 1
N2  - Striatal D2 dopaminergic receptors of 12 drug-free schizophrenic patients and 12 normal subjects were investigated with positron emission tomography and [76Br]bromospiperone. Patients were classified according to DSM-III criteria, and their clinical symptoms were rated according to Andreasen's negative and positive symptom scales. The ratio of striatal to cerebellar radioactivity was taken as an index of striatal D2 dopamine receptor density. There was no significant difference between the control subjects and the overall schizophrenic group and no significant relationship between this index and the symptom ratings. However, state-dependent variables could partly account for the striatal D2 receptor density variability
AD  - Service Hospitalier Frederic Joliot, Departement de Biologie, Commissariat a l'Energie Atomique, Orsay, France
UR  - PM:2293788
ER  - 

TY  - JOUR
T1  - Low frontal glucose utilization in chronic schizophrenia: a replication study
A1  - Wolkin,A.
A1  - Angrist,B.
A1  - Wolf,A.
A1  - Brodie,J.D.
A1  - Wolkin,B.
A1  - Jaeger,J.
A1  - Cancro,R.
A1  - Rotrosen,J.
Y1  - 1988/02//
N1  - UI - 88131338
SP  - 251
EP  - 253
JA  - Am J Psychiatry
VL  - 145
IS  - 2
N2  - Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy
AD  - Department of Psychiatry, New York University School of Medicine, New York City
UR  - PM:3257653
ER  - 

TY  - JOUR
T1  - Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia
A1  - Weinberger,D.R.
A1  - Berman,K.F.
Y1  - 1988///
N1  - UI - 89072596
SP  - 157
EP  - 168
JA  - Schizophr.Bull.
VL  - 14
IS  - 2
N2  - Cerebral metabolic hypofrontality in schizophrenia is a controversial research finding. In this article we discuss some of the issues that fuel this controversy, and we speculate on the neural mechanisms that may be responsible for the finding. Most regional cerebral blood flow (rCBF) studies using radioactive xenon have found hypofrontality; the results of positron emission tomography (PET) studies have been less consistent. Several technical factors are discussed that might contribute to the inconsistencies, including airway artifacts with xenon, limitations of tomography in studying the cortex, and approaches to data analysis. The possibility that hypofrontality is a result of medication is also critically examined. The medication factor is still unclear, but most studies of patients before and after neuroleptic medication find that cerebral metabolism goes up, not down, after treatment. The role of patient behavior and experience during an rCBF or PET procedure is an important variable that has not been adequately controlled in most studies. We suggest that this has been the most important variable in interpreting cerebral metabolic data in schizophrenia. Studies of patients examined during a behavior that normally activates prefrontal cortex have consistently found hypofrontality. One theoretical mechanism that could account for hypofrontality as well as many clinical and research findings in schizophrenia is dysfunction of dopaminergic neural transmission at the level of the prefrontal cortex
AD  - Clinical Brain Disorders Branch, NIMH, Neuropsychiatric Research Hospital at St. Elizabeths, Washington, DC 20032
UR  - PM:3059465
ER  - 

TY  - JOUR
T1  - Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography
A1  - Wolkin,A.
A1  - Angrist,B.
A1  - Wolf,A.
A1  - Brodie,J.
A1  - Wolkin,B.
A1  - Jaeger,J.
A1  - Cancro,R.
A1  - Rotrosen,J.
Y1  - 1987///
N1  - UI - 87261663
SP  - 241
EP  - 246
JA  - Psychopharmacology (Berl)
VL  - 92
IS  - 2
N2  - The effects of d-amphetamine (0.5 mg/kg PO) on regional cerebral glucose utilization were measured with Positron Emission Tomography (PET). Subjects included ten chronic schizophrenics and six controls who received amphetamine, and six chronic schizophrenics and nine controls who received placebo or no treatment. Amphetamine decreased glucose metabolism in all regions studied (frontal, temporal, and striatal) in normal and schizophrenic subjects. The metabolic effects of amphetamine were correlated with plasma level of the drug. Cortical atrophy was associated with a blunted metabolic response
UR  - PM:3110848
ER  - 

TY  - JOUR
T1  - PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride
A1  - Farde,L.
A1  - Halldin,C.
A1  - Stone-Elander,S.
A1  - Sedvall,G.
Y1  - 1987///
SP  - 278
EP  - 284
JA  - Psychopharmacology (Berl)
VL  - 92
IS  - 3
N2  - Tracer doses of 11C-SCH 23390 and 11C-raclopride, selective D1-dopamine and D2-dopamine receptor antagonists, respectively, were injected intravenously into three healthy male volunteers and two drug-treated schizophrenic patients. Regional radioactivity in brain and plasma was followed during 1 h by positron emission tomography (PET). After injection of both ligands a high accumulation of radioactivity was observed in the dopamine-rich caudate putamen. Experiments with 11C-SCH 23390, but not 11C-raclopride, showed a conspicuous accumulation of radioactivity also in the neocortex. None of the ligands accumulated in the dopamine-poor cerebellum. Specific binding of 11C-raclopride in the putamen was reduced by more than 80% in schizophrenic patients treated with antipsychotic doses of sulpiride or cis(Z)-flupentixol decanoate. 11C-SCH 23390 binding was slightly reduced in both the cortex and the putamen after treatment with cis(Z)-flupentixol decanoate but not after sulpiride. The results indicate that clinical antipsychotic drug treatment with sulpiride and cis(Z)-flupentixol decanoate causes a substantial blockade of D2-dopamine receptors in the basal ganglia but has only a minor effect on D1-dopamine receptors
UR  - PM:2957716
ER  - 

TY  - JOUR
T1  - Brain metabolism in patients with schizophrenia before and after acute neuroleptic administration
A1  - Volkow,N.D.
A1  - Brodie,J.D.
A1  - Wolf,A.P.
A1  - Angrist,B.
A1  - Russell,J.
A1  - Cancro,R.
Y1  - 1986/10//
N1  - UI - 87059906
SP  - 1199
EP  - 1202
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 49
IS  - 10
N2  - Positron emission tomography (PET) with 11C-2-deoxyglucose (11DG) was used to compare regional brain metabolism in four patients with chronic schizophrenia who had no history of psychotropic medication and in 12 normal controls. Patients had a second PET scan after an injection of thiothixene to evaluate the effects of acute neuroleptics on glucose metabolism. The patients showed higher glucose metabolic values than the normals and did not show the metabolic hypofrontality reported in chronic medicated patients with schizophrenia. Administration of the neuroleptic did not have a significant effect in the metabolic pattern of the patients. These results give support to the hypothesis that prolonged medication may contribute to the metabolic hypofrontal pattern seen in patients with schizophrenia
UR  - PM:3491182
ER  - 

TY  - JOUR
T1  - Brain organization in schizophrenia
A1  - Volkow,N.D.
A1  - Brodie,J.D.
A1  - Wolf,A.P.
A1  - Gomez-Mont,F.
A1  - Cancro,R.
A1  - Van Gelder,P.
A1  - Russell,J.A.
A1  - Overall,J.
Y1  - 1986/08//
N1  - UI - 86278492
SP  - 441
EP  - 446
JA  - J Cereb.Blood Flow Metab
VL  - 6
IS  - 4
N2  - Brain metabolism was measured with positron emission tomography and [11C]deoxyglucose during baseline and during a visual task in 12 normal subjects and 18 schizophrenic patients. Global measures of metabolism for 11 brain regions were transformed into relative values by dividing them by the metabolic value for whole brain. Factor analysis was accomplished on the matrix of intercorrelations among the relative regional values for the normal and for the schizophrenic patients under baseline and under the task. Four factors that revealed independently varying metabolism in frontal, occipital, left-versus-right hemisphere, and subcortical structures were obtained. The frontal and subcortical factors discriminated between normal subjects and schizophrenic patients, whereas the occipital factor discriminated between baseline and task. Although activity in these individual regions varied significantly, it was the pattern of differences in regional metabolic activity that best discriminated between diagnostic groups and testing conditions
UR  - PM:3488322
ER  - 

TY  - JOUR
T1  - In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and [76Br]bromospiperone
A1  - Maziere,B.
A1  - Loc'h,C.
A1  - Baron,J.C.
A1  - Sgouropoulos,P.
A1  - Duquesnoy,N.
A1  - D'Antona,R.
A1  - Cambon,H.
Y1  - 1985/08/27/
N1  - UI - 86055973
SP  - 267
EP  - 272
JA  - Eur.J Pharmacol.
VL  - 114
IS  - 3
N2  - The brain regional distribution and kinetics of [76Br]bromospiperone, a derivative of a neuroleptic (spiperone) labeled with the positron emitter bromine-76, were studied by time-of-flight tomography after i.v. injection in man. In a control subject the kinetic distribution study showed an accumulation of radioactivity which reached a maximum 3 h postinjection in the frontal cortex and cerebellum regions and 4-5 h postinjection in the basal ganglia. Thereafter the striatal activity remained essentially constant over a period of 25 h. In a group of 13 control subjects, the mean value for the striatum-to-cerebellum ratio, at 4.5 h postinjection, was 1.84 (S.D. 0.21). In two schizophrenics treated with high doses of haloperidol, this ratio was found to be only 1.22. These data indicate that radiolabeled bromospiperone is very suitable for human pharmacological or pathological investigations of the central dopaminergic system
UR  - PM:3877639
ER  - 

TY  - JOUR
T1  - PET studies of glucose metabolism in patients with schizophrenia
A1  - Widen,L.
A1  - Blomqvist,G.
A1  - Greitz,T.
A1  - Litton,J.E.
A1  - Bergstrom,M.
A1  - Ehrin,E.
A1  - Ericson,K.
A1  - Eriksson,L.
A1  - Ingvar,D.H.
A1  - Johansson,L.
A1  - Nilsson,J.L.
A1  - Stone-Elander,S.
A1  - Sedvall,G.
A1  - Wiesel,F.
A1  - Wiik,G.
Y1  - 1983/05//
N1  - UI - 83279598
SP  - 550
EP  - 552
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 4
IS  - 3
N2  - The hypothesis of abnormal patterns of metabolism in schizophrenia was examined in a series of six young patients with psychotic symptoms satisfying the research diagnostic criteria. After intravenous injection of 11C-glucose obtained through a photosynthetic process, the regional activity of 11C in brain was measured with a four-ring positron camera. Regions of interest were obtained from computed tomographic images. Each patient underwent a second positron emission tomographic examinations after 4-5 weeks of treatment with a neuroleptic drug. No evidence of a hypofrontal pattern was found, but after treatment there was a reduced frontal uptake on the left side compared with temporal regions. The left-right asymmetry in the lentiform nucleus was reduced after treatment
UR  - PM:6136180
ER  - 

TY  - JOUR
T1  - Subthalamic deep brain stimulation does not induce striatal dopamine release in Parkinson's disease
A1  - Strafella,A.P.
A1  - Sadikot,A.F.
A1  - Dagher,A.
Y1  - 2003/07/01/
N1  - UI - 22708878
SP  - 1287
EP  - 1289
JF  - Neuroreport
VL  - 14
IS  - 9
N2  - Deep brain stimulation of the subthalamic nucleus (STN) is an increasingly prevalent treatment for advanced Parkinson's disease (PD). Its main mechanism of action is thought to be a reduction in the inhibitory outflow from basal ganglia to cerebral cortex. However, recent animal experiments have led to the suggestion that high frequency stimulation of the STN also acts by promoting dopamine release. We tested this hypothesis by performing [11C]raclopride PET on and off stimulation in six patients with PD and implanted STN stimulators. There was no difference in tracer binding in the striatum between the two testing conditions. We conclude that high frequency stimulation of the STN does not act by increasing dopamine release
UR  - PM:12824777
ER  - 

TY  - JOUR
T1  - Cerebral blood flow changes induced by subthalamic stimulation in Parkinson's disease
A1  - Strafella,A.P.
A1  - Dagher,A.
A1  - Sadikot,A.F.
Y1  - 2003/03/25/
N1  - UI - 22542127
SP  - 1039
EP  - 1042
JF  - Neurology
VL  - 60
IS  - 6
N2  - The authors used PET to show that the abnormal pattern of cerebral blood flow (CBF) activation described in PD is normalized by electrical stimulation of subthalamic nucleus. Improvement in bradykinesia correlated with increase in CBF due to stimulation in the supplementary motor area and anterior cingulate cortex. Compared to unilateral stimulation, bilateral stimulation induced a greater extent of activation in bilateral cortical areas and additional bilateral activation of globus pallidus
AD  - Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
UR  - PM:12654980
ER  - 

TY  - JOUR
T1  - Dysfunctional cortico-cerebellar circuits cause 'cognitive dysmetria' in schizophrenia
A1  - Wiser,A.K.
A1  - Andreasen,N.C.
A1  - O'Leary,D.S.
A1  - Watkins,G.L.
A1  - Boles Ponto,L.L.
A1  - Hichwa,R.D.
Y1  - 1998/06/01/
N1  - UI - 98328559
SP  - 1895
EP  - 1899
JF  - Neuroreport
VL  - 9
IS  - 8
N2  - We examined regional cerebral blood flow (rCBF) during a long-term recognition memory task for words in schizophrenic patients and in healthy subjects using positron emission tomography (PET). The task was designed so that performance scores were similar in the patient and control subjects. This memory retrieval task did not increase rCBF in the patients' prefrontal cortex, precuneus and cerebellum as much as it did in the control group. These results point to a dysfunctional corticocerebellar circuit leading to poorly coordinated mental activity ('cognitive dysmetria'), which could explain the broad range of schizophrenic symptoms. In addition, other brain areas were more activated by the task in the patient group than in the control group and may form a compensatory network performing the memory retrieval task by assisting or replacing the dysfunctional cortico-cerebellar circuit
AD  - Mental Health Clinical Research Center, University of Iowa, College of Medicine, Iowa City 52242-1057, USA
UR  - PM:9665622
ER  - 

TY  - JOUR
T1  - Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort
A1  - Abi-Dargham,A.
A1  - Gil,R.
A1  - Krystal,J.
A1  - Baldwin,R.M.
A1  - Seibyl,J.P.
A1  - Bowers,M.
A1  - van Dyck,C.H.
A1  - Charney,D.S.
A1  - Innis,R.B.
A1  - Laruelle,M.
Y1  - 1998/06//
N1  - UI - 98282906
SP  - 761
EP  - 767
JA  - Am J Psychiatry
VL  - 155
IS  - 6
N2  - OBJECTIVE: The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects. METHOD: Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM. RESULTS: No differences were observed between patients with schizophrenia and the comparison group in D2 receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms. CONCLUSIONS: In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia
AD  - Department of Psychiatry, Yale University, New Haven, Conn., USA. aadar@neuron.cpmc.columbia.edu
UR  - PM:9619147
ER  - 

TY  - JOUR
T1  - Increased dopamine transmission in schizophrenia: relationship to illness phases
A1  - Laruelle,M.
A1  - Abi-Dargham,A.
A1  - Gil,R.
A1  - Kegeles,L.
A1  - Innis,R.
Y1  - 1999/07/01/
N1  - UI - 99322778
SP  - 56
EP  - 72
JA  - Biol.Psychiatry
VL  - 46
IS  - 1
N2  - BACKGROUND: Abnormalities of dopamine function in schizophrenia are suggested by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyperdopaminergic state in schizophrenia has been difficult to demonstrate, given the difficulty to measure dopamine transmission in the living human brain. Such evidence has recently emerged. Three studies reported an increase in dopamine transmission following acute amphetamine challenge in patients with schizophrenia compared to matched healthy control subjects, thus demonstrating a dysregulation of dopamine in schizophrenia. In all studies, a large variance was observed within the schizophrenic group in the magnitude of this finding, and clinical predictors of this effect could not be identified. METHODS: In this paper, we combined previously published and newly acquired data to obtain sufficient power to address this question. RESULTS: The most important findings derived from this extended data set are: 1) dysregulation of dopamine function revealed by the amphetamine challenge is present at onset of illness and in patients never previously exposed to neuroleptic medications; 2) this dysregulation was observed in patients experiencing an episode of illness exacerbation, but not in patients studied during a remission phase. CONCLUSIONS: A hyperdopaminergic state is present in schizophrenia during the initial episode and subsequent relapses, but not in periods of remission. This finding has important consequences for the development of new treatment strategies for the remission phase
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA
UR  - PM:10394474
ER  - 

TY  - JOUR
T1  - Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET
A1  - Lindstrom,L.H.
A1  - Gefvert,O.
A1  - Hagberg,G.
A1  - Lundberg,T.
A1  - Bergstrom,M.
A1  - Hartvig,P.
A1  - Langstrom,B.
Y1  - 1999/09/01/
N1  - UI - 99401640
SP  - 681
EP  - 688
JA  - Biol.Psychiatry
VL  - 46
IS  - 5
N2  - BACKGROUND: The aim of the present study was to investigate dopamine synthesis in the brain of drug-free schizophrenic patients, not only in the striatum but also in extrastriatal areas like the prefrontal cortex, brain areas that for a long time has been in focus of interest in the pathophysiology of schizophrenia. METHODS: PET was performed in 12 drug-free (10 drug-naive) psychotic schizophrenic patients and 10 healthy volunteers matched for age and gender using 11C-labelled L-DOPA as the tracer. The time-radioactivity curve from occipital cortex (located within Brodman area 17 and 18) was used as input function to calculate L-DOPA influx rate, Ki images, that were matched to a common brain atlas. A significant overall increase of the Ki values was found in the schizophrenic group as compared with healthy controls. RESULTS: In particular, significantly higher Ki were found in the schizophrenic patients compared to the controls in the caudate nucleus, putamen and in parts of medial prefrontal cortex (Brod 24). The Ki value reflect an increased utilization of L-DOPA, presumably due to increased activity of the amino acid decarboxylate enzyme. CONCLUSIONS: The results indicate that the synthesis of dopamine is elevated within the striatum and parts of medial prefrontal cortex in schizophrenia
AD  - Department of Psychiatric Research, University of Uppsala, Vasteras Central Hospital, Sweden
UR  - PM:10472420
ER  - 

TY  - JOUR
T1  - FDG-PET for clinical use. Results of the 3rd German Interdisciplinary Consensus Conference, "Onko-PET III", 21 July and 19 September 2000
A1  - Reske,S.N.
A1  - Kotzerke,J.
Y1  - 2001/11//
N1  - UI - 21558290
SP  - 1707
EP  - 1723
JA  - Eur.J Nucl Med
VL  - 28
IS  - 11
N2  - Positron emission tomography (PET) is the most powerful molecular imaging technique currently available for clinical use. Because deranged tumour metabolism is a common finding in many malignancies, PET is frequently used for tissue characterisation, staging and therapy control. Four previous consensus studies in Germany, performed up to 1997, have established indications for fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET in oncology, neurology and cardiology. More than 10,000 references on FDG-PET have been published in the meantime, mostly on oncological issues. Therefore, it was the aim of the present paper to provide an update on the clinical use of FDG-PET in oncology. For this purpose a systematic literature search was performed in all common medical literature databases. All hits were manually checked and abstracts, case reports, technically oriented papers and reviews were excluded from analysis. A questionnaire comprising 24 items was developed for standardised quality assessment according to evidence-based medicine (EBM) criteria. We selected 533 papers for further review by an interdisciplinary panel of 58 experts from oncology, radiology and nuclear medicine. Clinical use was judged according to the following grading scheme: 1a, established clinical use; 1b, clinical use probable; 2, useful in individual cases; 3, not yet assessable owing to missing or incomplete data; 4, clinical use rare (either as inferred from theoretical considerations or as demonstrated by published studies). Of the 533 papers selected, 122 references with 7,092 documented patients fulfilled the EBM criteria for detailed review. The results of these studies were tabulated and are available at www.nucmed-ulm.de. Clinical indications (grade 1a or 1b) were established for differentiating benign from malignant lesions in pulmonary nodules, pancreatic masses and residual masses after chemotherapy in malignant lymphoma. Staging was improved by FDG-PET in oesophageal cancer, breast cancer, head and neck cancer, lung cancer, malignant lymphoma and malignant melanoma. Effectiveness of radio- and/or chemotherapy could be better controlled in Hodgkin's disease and high-grade non-Hodgkin's lymphoma. Restaging was improved in relapsing thyroid cancer, colorectal cancer, head and neck cancer, lung cancer and malignant melanoma. In summary, the efficiency of FDG-PET was studied in several thousand patients with malignant tumours and was found to be well documented in the international high-quality peer-reviewed literature. There are clear-cut clinical indications for FDG-PET in diagnosis, staging and therapy control, and the technique can help to improve the management of many patients with cancer
AD  - Department of Nuclear Medicine, University Clinic of Ulm, Robert-Koch-Strasse 8, 89070 Ulm, Germany. sven.reske@medizin.uni-ulm.de
UR  - PM:11702115
ER  - 

TY  - JOUR
T1  - Occupancy of 5-HT1A receptors by clozapine in the primate brain: a PET study
A1  - Chou,Y.H.
A1  - Halldin,C.
A1  - Farde,L.
Y1  - 2003/03//
SP  - 234
EP  - 240
JA  - Psychopharmacology (Berl)
VL  - 166
IS  - 3
N2  - RATIONALE: The pharmacological mechanism underlying the atypical properties of the antipsychotic drug clozapine remains to be identified. The serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor subtype has been suggested to play a role in the pathophysiology of schizophrenia and is one among several central neuroreceptors for which clozapine has moderate affinity in vitro. OBJECTIVE: The aim of this positron emission tomography (PET) study was to determine 5-HT(1A) receptor occupancy in the monkey brain after IV injection of clozapine in doses that previously have been shown to give plasma concentrations representative of the 200 to 800 mg oral dose range recommended for clinical management of patients. METHODS: Each of four cynomolgus monkeys was examined three times on the same day with PET and the radioligand [carbonyl-(11)C]WAY-100635. The first measurement was performed at baseline conditions, the second after clozapine 1.5 mg/kg and the third after 6 mg/kg. Two additional monkeys were examined at baseline and after 15 mg/kg IV. Central 5-HT(1A) receptor occupancy was calculated using an equilibrium-ratio analysis. RESULTS: The occupancy ranged from 23 to 34% after 1.5 mg/kg clozapine and from 36 to 49% after 6 mg/kg in different brain regions of the four monkeys. The regional receptor occupancy values after 15 mg/kg were between 39 and 51% in the two monkeys. There was no evident difference between the frontal cortex, the temporal cortex and the raphe nucleus. CONCLUSION: The study shows that clozapine occupies 5-HT(1A) receptors in the primate brain at clinically representative plasma concentrations. The results support that the 5-HT(1A) receptor is a candidate target for the atypical drug actions of clozapine
AD  - Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Stockholm, Sweden. yuanhc@hotmail.com
UR  - PM:12589516
ER  - 

TY  - JOUR
T1  - Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB
A1  - Houle,S.
A1  - Ginovart,N.
A1  - Hussey,D.
A1  - Meyer,J.H.
A1  - Wilson,A.A.
Y1  - 2000/11//
N1  - UI - 20555399
SP  - 1719
EP  - 1722
JA  - Eur.J Nucl Med
VL  - 27
IS  - 11
N2  - Two novel radioligands, N,N-dimethyl-2-(2-amino-4-methoxyphenylthio) b enzylamine (DAPP) and (N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (DASB), were radiolabeled with carbon-11 and evaluated as in vivo probes of the serotonin transporter (SERT) using positron emission tomography (PET). Both compounds are highly selective, with nanomolar affinity for the serotonin transporter and micromolar affinity for the dopamine and norepinephrine transporters. Six volunteers were imaged twice, once with each of the two radioligands. Both ligands displayed very good brain penetration and selective retention in regions rich in serotonin reuptake sites. Both had similar brain uptake and kinetics, but the cyano analogue, [11C]DASB, had a slightly higher brain penetration in all subjects. Plasma analysis revealed that both radiotracers were rapidly metabolized to give mainly hydrophilic species as determined by reverse-phase high-performance liquid chromatography. Inhibition of specific binding to the SERT was demonstrated in three additional subjects imaged with [11C]DASB following an oral dose of the selective serotonin reuptake blocker citalopram. These preliminary studies indicate that both these substituted phenylthiobenzylamines have highly suitable characteristics for probing the serotonin reuptake system with PET in humans
AD  - Vivian Rakoff PET Centre, University of Toronto, ON, Canada
UR  - PM:11105830
ER  - 

TY  - JOUR
T1  - In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652
A1  - Parsey,R.V.
A1  - Kegeles,L.S.
A1  - Hwang,D.R.
A1  - Simpson,N.
A1  - Abi-Dargham,A.
A1  - Mawlawi,O.
A1  - Slifstein,M.
A1  - Van Heertum,R.L.
A1  - Mann,J.J.
A1  - Laruelle,M.
Y1  - 2000/09//
N1  - UI - 20448180
SP  - 1465
EP  - 1477
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 41
IS  - 9
N2  - Abnormal brain regional densities of serotonin (5-hydroxytryptamine [5-HT]) transporters have been reported in postmortem studies in several neuropsychiatric conditions, such as major depression and schizophrenia. trans-1,2,3,5,6,10-beta-Hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]- isoquinoline ([11C]McN 5652) is the first PET radioligand successfully developed to label 5-HT transporters in the living human brain. The purpose of this study was to develop an imaging protocol and analytic method to measure regional 5-HT transporter binding potential (BP) with [11C]McN 5652 in humans. METHODS: The arterial input function and brain uptake of (+)-[11C]McN 5652 and (-)-[11C]McN 5652, the active and inactive enantiomers, respectively, were measured in 6 healthy volunteers. Results: (+)-[11C]McN 5652 concentrated in brain regions rich in 5-HT transporters (midbrain, thalamus, basal ganglia, and medial temporal lobe structures), whereas the uptake of (-)-[11C]McN 5652 was more uniformly distributed. Total distribution volumes (V(T)) were derived using kinetic 2-compartment analysis and graphic analysis. V(T) derived by both methods were highly correlated. (+)-[11C]McN 5652 regional V(T) ranged from 18 +/- 2 mL/g in the cerebellum to 46 +/- 13 mL/g in the midbrain. (-)-[11C]McN 5652 regional VT ranged from 10 +/- 2 mL/g in the cerebellum to 14 +/- 3 mL/g in the thalamus. (+)-[11C]McN 5652 V(T) were higher than (-)-[11C]McN 5652 V(T) in all regions, including the cerebellum, a region devoid of 5-HT transporters. Blocking experiments were also performed in baboons with saturating doses of citalopram and in humans with nonsaturating doses of paroxetine. Cerebellar and neocortical (+)-[11C]McN 5652 V(T) were unaffected by pretreatment with 5-HT transporter blockers. In areas of high receptor concentration (midbrain, caudate, and thalamus) 5-HT transporter blockers decreased (+)-[11C]McN 5652 V(T) to the level of cerebellum (+)-[11C]McN 5652 V(T). CONCLUSION: These experiments indicate that the use of the difference between (+)- and (-)-[11C]McN 5652 V(T) to define specific binding to 5-HT transporters leads to an overestimation of specific binding. 5-HT transporter BP was derived as the difference between the regional and cerebellar (+)-[11C]McN 5652 V(T). BP values were in good agreement with the distribution of 5-HT transporters in the human brain, except for regions of relatively low 5-HT transporter concentration, such as the prefrontal cortex, where no specific binding was detected using (+)-[11C]McN 5652. (+)-[11C]McN 5652 is an appropriate radiotracer to quantify 5-HT transporters in regions with relatively high concentration of 5-HT transporters, such as the midbrain, thalamus, and basal ganglia, and should prove useful in elucidating abnormalities of 5-HT transmission in neuropsychiatric conditions
AD  - Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA
UR  - PM:10994724
ER  - 

TY  - JOUR
T1  - Personality traits and striatal dopamine synthesis capacity in healthy subjects
A1  - Laakso,A.
A1  - Wallius,E.
A1  - Kajander,J.
A1  - Bergman,J.
A1  - Eskola,O.
A1  - Solin,O.
A1  - Ilonen,T.
A1  - Salokangas,R.K.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 2003/05//
N1  - UI - 22612189
SP  - 904
EP  - 910
JA  - Am J Psychiatry
VL  - 160
IS  - 5
N2  - OBJECTIVE: Neuroimaging and genetic studies suggest that individual differences in the brain dopaminergic system contribute to the normal variability of human personality (e.g., social detachment and novelty seeking). The authors studied whether presynaptic dopamine function is also associated with personality traits. METHOD: Presynaptic dopamine synthesis capacity in the brain was measured with positron emission tomography and [(18)F]fluorodopa in 33 healthy adults, and personality traits were assessed with the Karolinska Scales of Personality. Associations were studied by using a linear regression model controlling for the effects of age and gender on both variables. RESULTS: High scores on two of the anxiety-related personality scales, somatic anxiety and muscular tension, and on one aggressivity-related scale, irritability, were significantly associated with low [(18)F]fluorodopa uptake in the caudate. No statistically significant associations were observed between [(18)F]fluorodopa uptake and the detachment scale or scales related to novelty-seeking behavior (impulsiveness and monotony avoidance). CONCLUSIONS: The results suggest a role for the dopaminergic system in the regulation of anxiety in healthy subjects. Together with previous studies, they also indicate differential involvement of various components of the dopaminergic system in normal and pathological personality traits
AD  - Department of Pharmacology and Clinical Pharmacology, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland
UR  - PM:12727694
ER  - 

TY  - JOUR
T1  - Cerebral blood flow during anticipation of public speaking in social phobia: a PET study
A1  - Tillfors,M.
A1  - Furmark,T.
A1  - Marteinsdottir,I.
A1  - Fredrikson,M.
Y1  - 2002/12/01/
N1  - UI - 22349138
SP  - 1113
EP  - 1119
JA  - Biol.Psychiatry
VL  - 52
IS  - 11
N2  - BACKGROUND: The aim was to examine the neural correlates of anxiety elicited by the anticipation of public speaking in individuals with social phobia.Positron emission tomography and (15)O-water was used to measure regional cerebral blood flow in subjects with DSM-IV defined social phobia during anxiety anticipation. Heart rate and subjective anxiety were also recorded. While being scanned, subjects were speaking alone either before or after speaking in public. To evaluate anticipatory anxiety we compared individuals speaking alone before they were speaking in front of an audience with those who did the reverse. RESULTS: Heart rate and subjective anxiety measures confirmed anticipatory anxiety in social phobics who performed their private speech before their public. This was accompanied by enhanced cerebral blood flow in the right dorsolateral prefrontal cortex, left inferior temporal cortex, and in the left amygdaloid-hippocampal region. Brain blood flow was lower in the left temporal pole and bilaterally in the cerebellum in the anticipation group. CONCLUSIONS: Brain regions with altered perfusion presumably reflect changes in neural activity associated with worry about anticipated public performance. We speculate that anticipatory anxiety in social phobics originates in an affect sensitive fear network encompassing the amygdaloid-hippocampal region, prefrontal, and temporal areas
AD  - Department of Social Sciences, Orebro University, Orebro, Sweden
UR  - PM:12460694
ER  - 

TY  - JOUR
T1  - Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652
A1  - Kent,J.M.
A1  - Coplan,J.D.
A1  - Lombardo,I.
A1  - Hwang,D.R.
A1  - Huang,Y.
A1  - Mawlawi,O.
A1  - Van Heertum,R.L.
A1  - Slifstein,M.
A1  - Abi-Dargham,A.
A1  - Gorman,J.M.
A1  - Laruelle,M.
Y1  - 2002/12//
N1  - UI - 22345184
SP  - 341
EP  - 348
JA  - Psychopharmacology (Berl)
VL  - 164
IS  - 4
N2  - RATIONALE: Although selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of anxiety and depressive disorders, the occupancy of the serotonin reuptake transporter (SERT) achieved in humans at typical clinical doses by these agents remains poorly characterized. OBJECTIVE: The purpose of this study was to determine the occupancy of the SERT achieved in vivo by the SSRI paroxetine in social phobia patients at typical antianxiety doses. METHODS: Measures of SERT availability were obtained with positron emission tomography and the SERT radiotracer [(11)C](+)-McN 5652 in five patients with social phobia before and during treatment with paroxetine at usual therapeutic doses (20-40 mg per day). RESULTS: Occupancy of the SERT by paroxetine was high in all subjects and in all regions measured after 3-6 months of continuous treatment. CONCLUSIONS: The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT
AD  - New York State Psychiatry Institute, New York, NY 10032, USA. JMK14@columbia.edu
UR  - PM:12457263
ER  - 

TY  - JOUR
T1  - rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest
A1  - Boshuisen,M.L.
A1  - Ter Horst,G.J.
A1  - Paans,A.M.
A1  - Reinders,A.A.
A1  - den Boer,J.A.
Y1  - 2002/07/15/
N1  - UI - 22109228
SP  - 126
EP  - 135
JA  - Biol.Psychiatry
VL  - 52
IS  - 2
N2  - BACKGROUND: Our goal was to identify brain structures involved in anticipatory anxiety in panic disorder (PD) patients compared to control subjects. METHODS: Seventeen PD patients and 21 healthy control subjects were studied with H(2)(15)O positron emission tomography scan, before and after a pentagastrin challenge. RESULTS: During anticipatory anxiety we found hypoactivity in the precentral gyrus, the inferior frontal gyrus, the right amygdala, and the anterior insula in PD patients compared to control subjects. Hyperactivity in patients compared to control subjects was observed in the parahippocampal gyrus, the superior temporal lobe, the hypothalamus, the anterior cingulate gyrus, and the midbrain. After the challenge, the patients showed decreases compared to the control subjects in the precentral gyrus, the inferior frontal gyrus, and the anterior insula. Regions of increased activity in the patients compared to the control subjects were the parahippocampal gyrus, the superior temporal lobe, the anterior cingulate gyrus, and the midbrain. CONCLUSIONS: The pattern of regional cerebral blood flow activations and deactivations we observed both before and after the pentagastrin challenge was the same, although different in intensity. During anticipatory anxiety more voxels were (de)activated than during rest after the challenge
AD  - Department of Psychiatry, Division of Biological Psychiatry, Graduate School of Behavioral and Cognitive Neurosciences, Groningen University Hospital, The Netherlands
UR  - PM:12114004
ER  - 

TY  - JOUR
T1  - Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study
A1  - Pissiota,A.
A1  - Frans,O.
A1  - Fernandez,M.
A1  - von Knorring,L.
A1  - Fischer,H.
A1  - Fredrikson,M.
Y1  - 2002/04//
N1  - UI - 22105813
SP  - 68
EP  - 75
JA  - Eur.Arch Psychiatry Clin.Neurosci.
VL  - 252
IS  - 2
N2  - SUMMARY: Patients with combat-related posttraumatic stress disorder (PTSD) show altered cognitive and affective processing and symptomatic responding following exposure to trauma reminders. Previous symptom provocation studies using brain imaging have involved Vietnam veterans. In this study neural correlates were investigated in patients with PTSD resulting from trauma in more recent war zones. (15)Oxygen water and positron emission tomography were used to measure regional cerebral blood flow (rCBF) in patients with war- and combat-related chronic PTSD during exposure to combat and neutral sounds. Self-reports and heart rate confirmed symptomatic responding during traumatic stimulation. The war-related condition, as compared to the neutral, increased rCBF in the right sensorimotor areas (Brodmann areas 4/6), extending into the primary sensory cortex (areas 1/2/3), and the cerebellar vermis. RCBF also increased in the right amygdala and in the periaqueductal gray matter adjacent to the pons. During provocation rCBF was lowered in the right retrosplenial cortex (areas 26/29/30 extending into area 23). Symptom provocation in PTSD promote sensorimotor, amygdaloid and midbrain activation. We conclude that perceptually induced symptom activation in PTSD is associated with an emotionally determined motor preparation and propose that subcortically initiated rather than cortically controlled memory mechanisms determine this pattern
AD  - Uppsala University, Department of Psychology, Box 1225, 75142 Uppsala, Sweden. anna.pissiota@psyk.uu.se
UR  - PM:12111339
ER  - 

TY  - JOUR
T1  - Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy
A1  - Furmark,T.
A1  - Tillfors,M.
A1  - Marteinsdottir,I.
A1  - Fischer,H.
A1  - Pissiota,A.
A1  - Langstrom,B.
A1  - Fredrikson,M.
Y1  - 2002/05//
SP  - 425
EP  - 433
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 59
IS  - 5
N2  - BACKGROUND: Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized. This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow (rCBF) in social phobia. METHODS: By means of positron emission tomography with oxygen 15-labeled water, rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task. Patients were matched for sex, age, and phobia severity, based on social anxiety questionnaire data, and randomized to citalopram medication, cognitive-behavioral group therapy, or a waiting-list control group. Scans were repeated after 9 weeks of treatment or waiting time. Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report questionnaires. Questions were readministered after 1 year. RESULTS: Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy, whereas the waiting-list group remained unchanged. Four patients in each treated group and 1 waiting-list patient were classified as responders. Within both treated groups, and in responders regardless of treatment approach, improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala, hippocampus, and the periamygdaloid, rhinal, and parahippocampal cortices. Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects, and in responders than nonresponders, particularly in the right hemisphere. The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later. CONCLUSIONS: Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala, hippocampus, and neighboring cortical areas, ie, brain regions subserving bodily defense reactions to threat
AD  - Department of Psychology, Uppsala University, Box 1225, SE-751 42 Uppsala, Sweden. tomas.furmark@psyk.uu.se
UR  - PM:11982446
ER  - 

TY  - JOUR
T1  - Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography
A1  - Gordon,C.M.
A1  - Dougherty,D.D.
A1  - Fischman,A.J.
A1  - Emans,S.J.
A1  - Grace,E.
A1  - Lamm,R.
A1  - Alpert,N.M.
A1  - Majzoub,J.A.
A1  - Rauch,S.L.
Y1  - 2001/07//
N1  - UI - 21338646
SP  - 51
EP  - 57
JA  - J Pediatr.
VL  - 139
IS  - 1
N2  - OBJECTIVE: To delineate functional brain abnormalities associated with anorexia nervosa (AN). STUDY DESIGN: Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were performed on 8 female patients with AN and 8 healthy female control subjects during exposure to 3 types of stimuli: high-calorie foods, low-calorie foods, and non-food items. Heart rate and internal state analog scale scores were also obtained. Stereotactic transformation and statistical parametric mapping techniques were used to analyze imaging data. RESULTS: During the high-calorie condition, control subjects reported a significant desire to eat, whereas subjects with AN reported elevated anxiety and exhibited increases in heart rate. Patients with AN had elevated bilateral medial temporal lobe rCBF compared with control subjects. Planned comparisons for group-by-condition interactions demonstrated greater activation within left occipital cortex and right temporo-occipital cortex for the high-calorie versus low-calorie contrast in patients with AN compared with control subjects. CONCLUSIONS: Our finding of elevated rCBF within bilateral medial temporal lobes is similar to published results in patients with psychotic disorders and may be related to the body image distortion common to AN. The high-calorie food phobia exhibited by patients with AN appears to be associated with exaggerated responses in visual association cortex, as has been previously observed in studies of specific phobias
AD  - Divisions of Adolescent/Young Adult Medicine and Endocrinology, Children's Hospital, Boston, Massachusetts, USA
UR  - PM:11445794
ER  - 

TY  - JOUR
T1  - No difference in brain activation during cognitive performance between ecstasy (3,4-methylenedioxymethamphetamine) users and control subjects: a [H2(15)O]-positron emission tomography study
A1  - Gamma,A.
A1  - Buck,A.
A1  - Berthold,T.
A1  - Vollenweider,F.X.
Y1  - 2001/02//
N1  - UI - 21040733
SP  - 66
EP  - 71
JA  - J Clin.Psychopharmacol.
VL  - 21
IS  - 1
N2  - The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use
AD  - Research Unit, University Hospital of Psychiatry, Zurich, Switzerland. gamma@bli.unizh.ch
UR  - PM:11199950
ER  - 

TY  - JOUR
T1  - Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria
A1  - Drevets,W.C.
A1  - Gautier,C.
A1  - Price,J.C.
A1  - Kupfer,D.J.
A1  - Kinahan,P.E.
A1  - Grace,A.A.
A1  - Price,J.L.
A1  - Mathis,C.A.
Y1  - 2001/01/15/
N1  - UI - 21093236
SP  - 81
EP  - 96
JA  - Biol.Psychiatry
VL  - 49
IS  - 2
N2  - BACKGROUND: Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior; however, understanding the relationship between subjective emotional experience and ventral striatal dopamine (DA) release has awaited human studies. Using positron emission tomography (PET), we correlated the change in endogenous dopamine concentrations following dextroamphetamine (AMPH) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions. METHODS: We obtained PET measures of [(11)C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection (0.3 mg/kg IV) in seven healthy subjects. The change in [(11)C]raclopride binding potential (DeltaBP) induced by AMPH pretreatment and the correlation between DeltaBP and the euphoric response to AMPH were compared between the anteroventral striatum (AVS; comprised of accumbens area, ventromedial caudate, and anteroventral putamen) and the dorsal caudate (DCA) using an MRI-based region of interest analysis of the PET data. RESULTS: The mean DeltaBP was greater in the AVS than in the DCA (p <.05). The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS (r = -.95; p <.001), but not in the DCA (r =.30, ns). Post hoc assessments showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS (r =.80; p [uncorrected] <.05) and that similar relationships may exist between DeltaBP and emotion ratings in the ventral putamen (as were found in the AVS). CONCLUSIONS: The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans. The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH
AD  - University of Pittsburgh School of Medicine, Department of Psychiatry, Medical Center, PET Facility Room B-938 PUH, 200 Lothrop Street, Pittsburgh, PA 15213, USA
UR  - PM:11164755
ER  - 

TY  - JOUR
T1  - Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET
A1  - Weiner,S.M.
A1  - Otte,A.
A1  - Schumacher,M.
A1  - Klein,R.
A1  - Gutfleisch,J.
A1  - Brink,I.
A1  - Otto,P.
A1  - Nitzsche,E.U.
A1  - Moser,E.
A1  - Peter,H.H.
Y1  - 2000/05//
N1  - UI - 20247002
SP  - 377
EP  - 385
JA  - Ann.Rheum.Dis.
VL  - 59
IS  - 5
N2  - OBJECTIVE: To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE). METHODS: Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months. RESULTS: PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles. CONCLUSIONS: PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease
AD  - Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Medizinische Klinik, Hugstetter Strasse 55, 79106 Freiburg, Germany
UR  - PM:10784521
ER  - 

TY  - JOUR
T1  - Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates
A1  - Ginovart,N.
A1  - Farde,L.
A1  - Halldin,C.
A1  - Swahn,C.G.
Y1  - 1999/02//
N1  - UI - 99146618
SP  - 154
EP  - 162
JF  - Synapse
VL  - 31
IS  - 2
N2  - Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. nathalie@cermep.fr
UR  - PM:10024013
ER  - 

TY  - JOUR
T1  - Brain correlates of an unexpected panic attack: a human positron emission tomographic study
A1  - Fischer,H.
A1  - Andersson,J.L.
A1  - Furmark,T.
A1  - Fredrikson,M.
Y1  - 1998/07/24/
N1  - UI - 98383475
SP  - 137
EP  - 140
JA  - Neurosci.Lett.
VL  - 251
IS  - 2
N2  - Previous brain imaging studies on symptom provocation in panic anxiety have used either drug-infusions or sensory related stimulation to induce panic attacks. We here report positron emission tomographic measurements of regional cerebral blood flow (rCBF) during an unexpected panic attack in a healthy female volunteer participating in a fear conditioning study. During a first but not a second run with electric shock presentations the woman unexpectedly experienced a panic attack that fulfilled the DSM-IV criteria. Panic was associated with decreased rCBF in the right orbitofrontal (Brodmann area 11), prelimbic (area 25), anterior cingulate (area 32) and anterior temporal cortices (area 15). These findings suggest that neural activity in brain regions previously associated with symptom provocation in specific phobics and subjects with posttraumatic stress disorder also are involved during panic in healthy individuals
AD  - Department of Psychology, Uppsala University, Sweden. hakan.fischer@psyk.uu.se
UR  - PM:9718993
ER  - 

TY  - JOUR
T1  - The application of positron emission tomography to the study of normal and pathologic emotions
A1  - Reiman,E.M.
Y1  - 1997///
N1  - UI - 98090368
SP  - 4
EP  - 12
JA  - J Clin.Psychiatry
VL  - 58 Suppl 16
N2  - This report reviews six studies in which positron emission tomography (PET) was used to investigate the neuroanatomic correlates of emotion, anxiety, and anxiety disorders. PET was used to study brain regions that participate in film- and recall-generated discrete emotions (happiness, sadness, and disgust), picture-generated positive and negative emotions, and normal anticipatory anxiety; participate in the predisposition to, elicitation of, and treatment of panic attacks; participate in social phobic anxiety; and participate in specific phobic anxiety. Results of these investigations suggest that thalamic and medial prefrontal regions may participate in aspects of normal emotion unrelated to its type, valence, or stimulus; that modality-specific sensory association areas and anterior temporal lobe regions appear to participate in the evaluation procedure that invests exteroceptive sensory information with emotional significance; that anterior insular regions appear to participate in the evaluation procedure that invests potentially distressing cognitive and interoceptive sensory information with negative emotional significance; and that anterior cingulate, cerebellar vermis, midbrain, and other brain regions appear to participate in the elaboration of normal and pathologic forms of anxiety. As a complement to other research strategies, PET promises to help determine how multiple brain regions and the mental operations to which they are related work in concert to produce emotions and how they conspire to produce emotional disorders
AD  - Department of Psychiatry, University of Arizona, Good Samaritan Regional Medical Center, Phoenix 85006, USA
UR  - PM:9430503
ER  - 

TY  - JOUR
T1  - Cerebral glucose utilization is reduced in second test session
A1  - Stapleton,J.M.
A1  - Morgan,M.J.
A1  - Liu,X.
A1  - Yung,B.C.
A1  - Phillips,R.L.
A1  - Wong,D.F.
A1  - Shaya,E.K.
A1  - Dannals,R.F.
A1  - London,E.D.
Y1  - 1997/06//
N1  - UI - 97379928
SP  - 704
EP  - 712
JA  - J Cereb.Blood Flow Metab
VL  - 17
IS  - 6
N2  - Cerebral glucose utilization was higher during the first positron emission tomography (PET) session than during the second session, as assayed using the PET [18F]fluorodeoxyglucose method in male human volunteers. This difference was due largely to data from subjects with low-trait anxiety, since subjects with high anxiety showed similar metabolism in both PET sessions. High-anxiety subjects showed greater right/ left ratios of cerebral metabolism than low-anxiety subjects, particularly during the second PET session. These findings suggest that the level of anxiety may be an important variable to consider in PET studies using multiple sessions
AD  - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA
UR  - PM:9236727
ER  - 

TY  - JOUR
T1  - Brain hypometabolism of glucose in bulimia nervosa
A1  - Delvenne,V.
A1  - Goldman,S.
A1  - Simon,Y.
A1  - De,Maertelaer,V
A1  - Lotstra,F.
Y1  - 1997/05//
N1  - UI - 97283965
SP  - 313
EP  - 320
JA  - Int.J Eat.Disord.
VL  - 21
IS  - 4
N2  - OBJECTIVE: A cerebral function lateralization has been described in bulimic patients in positron emission tomography (PET) studies realized during a specific cognitive task. The purpose of this study was to evaluate, at rest, brain glucose metabolism in patients with bulimia nervosa. METHOD: PET with (18-F)-fluorodeoxyglucose was used to evaluate cerebral glucose metabolism in 11 normal-weight bulimic girls compared to 11 age- and sex-matched healthy volunteers. Patients were diagnosed following DSM-IV and were off psychoactive medication. RESULTS: In comparison with control subjects, bulimic patients showed global and regional absolute hypometabolism of glucose. In relative values, only parietal cortex metabolism was significantly lower in bulimic patients. No correlation was found within groups for absolute or relative cerebral glucose metabolic rates (rCMRglu) and body mass index (BMI), anxiety scores, or Hamilton scores of depression. DISCUSSION: Since previous studies have demonstrated similar disturbances in anorectic patients, we hypothesized that these observations could be a consequence of neurobiological perturbations following nutritional deficiencies or a particular cerebral dysfunction in eating disorders
AD  - Department of Psychiatry, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium
UR  - PM:9138041
ER  - 

TY  - JOUR
T1  - Relationship between psychostimulant-induced "high" and dopamine transporter occupancy
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Gatley,S.J.
A1  - Ding,Y.S.
A1  - Logan,J.
A1  - Dewey,S.L.
A1  - Hitzemann,R.
A1  - Lieberman,J.
Y1  - 1996/09/17/
N1  - UI - 96413656
SP  - 10388
EP  - 10392
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 93
IS  - 19
N2  - The ability of cocaine to inhibit the dopamine transporter (DAT) appears to be crucial for its reinforcing properties. The potential use of drugs that produce long-lasting inhibition of the DAT as a mean of preventing the "high" and reducing drug-seeking behavior has become a major strategy in medication development. However, neither the relation between the high and DAT inhibition nor the ability to block the high by prior DAT blockade have ever been demonstrated. To evaluate if DAT could prevent the high induced by methylphenidate (MP), a drug which like cocaine inhibits the DAT, we compared the responses in eight non-drug-abusing subjects between the first and the second of two MP doses (0.375 mg/kg, i.v.) given 60 min apart. At 60 min the high from MP has returned to baseline, but 75-80% of the drug remains in brain. Positron-emission tomography and [11C]d-threo-MP were used to estimate DAT occupancies at different times after MP. DAT inhibition by MP did not block or attenuate the high from a second dose of MP given 60 min later, despite a 80% residual transporter occupancy from the first dose. Furthermore some subjects did not perceive a high after single or repeated administration despite significant DAT blockade. These results indicate that DAT occupancy is not sufficient to account for the high, and that for DAT inhibitors to be therapeutically effective, occupancies > 80% may be required
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8816810
ER  - 

TY  - JOUR
T1  - Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers
A1  - Benkelfat,C.
A1  - Bradwejn,J.
A1  - Meyer,E.
A1  - Ellenbogen,M.
A1  - Milot,S.
A1  - Gjedde,A.
A1  - Evans,A.
Y1  - 1995/08//
SP  - 1180
EP  - 1184
JA  - Am J Psychiatry
VL  - 152
IS  - 8
N2  - OBJECTIVE: The authors tested the prediction of temporal cortex activation during experimentally induced anxiety by using positron emission tomography and the [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF) changes in normal volunteers challenged with a bolus injection of cholecystokinin tetrapeptide (CCK4). METHOD: Eight right-handed healthy subjects (five male, three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans separated by 15-minute intervals; each scan followed an intravenous bolus injection of either saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once, as the first or second bolus, in a random-order, placebo-controlled, double-blind fashion. Two of the three placebo conditions were nominally identical, and the remaining placebo was used to control for anticipatory anxiety. Magnetic resonance imaging scans were obtained for subsequent anatomical correlation of blood flow changes. RESULTS: CCK4, but not placebo, elicited a marked anxiogenic response, reflected by robust increases in subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated with 1) robust and bilateral increases in extracerebral blood flow in the vicinity of the superficial temporal artery territory and 2) CBF increases in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and the cerebellar vermis. CONCLUSIONS: Some of the temporopolar cortex CBF activation peaks previously reported in humans in association with drug- and non-drug-induced anxiety, as well as the increase in regional CBF in the claustrum-insular-amygdala region, may be of vascular and/or muscular origin
AD  - McConnell Brain Imaging Center, Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
UR  - PM:7625467
ER  - 

TY  - JOUR
T1  - Functional neuroanatomy of visually elicited simple phobic fear: additional data and theoretical analysis
A1  - Fredrikson,M.
A1  - Wik,G.
A1  - Annas,P.
A1  - Ericson,K.
A1  - Stone-Elander,S.
Y1  - 1995/01//
N1  - UI - 95183683
SP  - 43
EP  - 48
JF  - Psychophysiology
VL  - 32
IS  - 1
N2  - We investigated central nervous system correlates of simple phobic fear. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli. Diazepam (0.1 mg/kg body weight i.v.) or placebo was administered under double-blind conditions after initial PET scans. The PET scans were then repeated. The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation. Phobic as compared to neutral stimulation elevated the regional to whole brain (relative) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus, prefrontal, orbitofrontal, temporopolar, and posterior cingulate cortex. Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices. The observed rCBF pattern replicates our previous findings in snake phobics (M. Fredrikson et al. [1993] Psychophysiology, 30, 127-131; G. Wik et al. [1993] Psychiatry Research (Neuroimaging), 50, 15-24) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas
AD  - Department of Psychiatry and Psychology, Karolinska Institute and Hospital, Stockholm, Sweden
UR  - PM:7878168
ER  - 

TY  - JOUR
T1  - Functional anatomy of obsessive-compulsive phenomena
A1  - McGuire,P.K.
A1  - Bench,C.J.
A1  - Frith,C.D.
A1  - Marks,I.M.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 1994/04//
N1  - UI - 94313325
SP  - 459
EP  - 468
JA  - Br.J Psychiatry
VL  - 164
IS  - 4
N2  - Regional cerebral blood flow was measured with H2 15O positron emission tomography in four patients with obsessive-compulsive disorder. Patients were scanned on 12 occasions in the same session, with each scan paired with brief exposure to one of a hierarchy of contaminants that elicited increasingly intense urges to ritualise. The relationship between symptom intensity and regional cerebral blood flow (rCBF; an index of neural activity) was subsequently examined in the group and in individual patients. The group showed significant positive correlations between symptom intensity and blood flow in the right inferior frontal gyrus, caudate nucleus, putamen, globus pallidus and thalamus, and the left hippocampus and posterior cingulate gyrus. Negative correlations were evident in the right superior prefrontal cortex, and the temporoparietal junction, particularly on the right side. The pattern in single subjects was broadly similar, although individual differences in neural response were also observed. A graded relationship between symptom intensity and regional brain activity can thus be identified in obsessive-compulsive disorder. It is hypothesised that the increases in rCBF in the orbitofrontal cortex, neostriatum, global pallidus and thalamus were related to urges to perform compulsive movements, while those in the hippocampus and posterior cingulate cortex corresponded to the anxiety that accompanied them
AD  - Institute of Psychiatry, De Crespigny Park, London
UR  - PM:8038933
ER  - 

TY  - JOUR
T1  - An acute effect of triazolam on muscarinic cholinergic receptor binding in the human brain measured by positron emission tomography
A1  - Suhara,T.
A1  - Inoue,O.
A1  - Kobayashi,K.
A1  - Satoh,T.
A1  - Tateno,Y.
Y1  - 1994/01//
N1  - UI - 95166983
SP  - 311
EP  - 317
JA  - Psychopharmacology (Berl)
VL  - 113
IS  - 3-4
N2  - An acute effect of triazolam, a potent benzodiazepine agonist, on cholinergic receptor binding in the human brain was measured by PET (positron emission tomography) using [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a potent muscarinic cholinergic receptor antagonist. Two PET scans were performed in each subject: (1) control scan; (2) after oral administration of 0.5 mg triazolam or placebo. The previously discussed amnestic effect of triazolam was measured by immediate and delayed recall of meaningful and meaningless syllables. A compartment model employing the radioactivity in the cerebellum as an input function was used for the quantification of receptor binding. The binding parameter, k3, was decreased after triazolam administration in all measured regions, whereas no change was observed after placebo treatment. The reduction compared to the control study varied from 8.6 +/- 3.7% in the temporal cortex to 16.3 +/- 6.3% in the thalamus. Triazolam administration impaired both immediate and delayed recall of syllables, whereas placebo administration had no effects. Benzodiazepine agonists are reported to decrease the cortical acetylcholine release. The decrease of acetylcholine release in the synaptic cleft might be the explanation for the decreased binding of [11C]NMPB
AD  - Division of Clinical Research, National Institute of Radiological Sciences, Chiba-shi, Japan
UR  - PM:7862838
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions
A1  - Bench,C.J.
A1  - Friston,K.J.
A1  - Brown,R.G.
A1  - Frackowiak,R.S.
A1  - Dolan,R.J.
Y1  - 1993/08//
N1  - UI - 94052458
SP  - 579
EP  - 590
JA  - Psychol.Med
VL  - 23
IS  - 3
N2  - We have previously reported focal abnormalities of regional cerebral blood flow (rCBF) in a group of 33 patients with major depression. This report, on an extended sample of 40 patients who demonstrated identical regional deficits to those previously described, examines the relationships between depressive symptoms and patterns of rCBF. Patients' symptom ratings were subjected to factor analysis, producing a three-factor solution. The scores for these three factors, which corresponded to recognizable dimensions of depressive illness, were then correlated with rCBF. The first factor had high loadings for anxiety and correlated positively with rCBF in the posterior cingulate cortex and inferior parietal lobule bilaterally. The second factor had high loadings for psychomotor retardation and depressed mood and correlated negatively with rCBF in the left dorsolateral prefrontal cortex and left angular gyrus. The third factor had a high loading for cognitive performance and correlated positively with rCBF in the left medial prefrontal cortex. These data indicate that symptomatic specificity may be ascribed to regional functional deficits in major depressive illness
AD  - Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
UR  - PM:7901863
ER  - 

TY  - JOUR
T1  - Neural correlates of self-induced dysphoria
A1  - Pardo,J.V.
A1  - Pardo,P.J.
A1  - Raichle,M.E.
Y1  - 1993/05//
N1  - UI - 93243452
SP  - 713
EP  - 719
JA  - Am J Psychiatry
VL  - 150
IS  - 5
N2  - OBJECTIVE: The authors explored the question of whether acute, transient changes in mood are reflected in activation of discrete neuronal systems in the human brain. METHOD: Using positron emission tomography, they measured the regional cerebral blood flow (CBF) of seven psychiatrically healthy subjects under two conditions. During the control condition the subjects were resting with their eyes closed. During the active condition, with their eyes still closed, they were asked to imagine or recall a situation that would make them feel very sad. They were explicitly asked to experience sadness and to avoid any feelings of anger or anxiety. RESULTS: There were significant differences in regional CBF measured during the control condition and during the active condition, particularly in the inferior and orbitofrontal cortices. Women showed bilateral inferior and orbitofrontal activation, but men displayed predominantly left-sided activation in these areas. CONCLUSIONS: The authors conclude that the inferior and orbitofrontal cortices play an important role in normal emotional cognitive processes
AD  - Department of Psychiatry, Washington University Medical Center, St. Louis
UR  - PM:8480815
ER  - 

TY  - JOUR
T1  - A functional cerebral response to frightening visual stimulation
A1  - Wik,G.
A1  - Fredrikson,M.
A1  - Ericson,K.
A1  - Eriksson,L.
A1  - Stone-Elander,S.
A1  - Greitz,T.
Y1  - 1993/04//
N1  - UI - 93288770
SP  - 15
EP  - 24
JA  - Psychiatry Res
VL  - 50
IS  - 1
N2  - The defense reaction, a fundamental reflex in the human behavioral response to threat, is characterized by anxiety and increased activity of the sympathetic nervous system. To study changes in regional cerebral blood flow (rCBF) related to the defense reaction, volunteers with snake phobia were investigated with positron emission tomography. The relative rCBF during phobogenic visual stimulation was increased in the secondary visual cortex but reduced in the hippocampus, orbitofrontal, prefrontal, temporopolar, and posterior cingulate cortex compared with that observed during neutral visual stimulation. The relative rCBF under aversive stimulation was intermediate between phobic and neutral stimulation. The rCBF patterns observed are suggested to represent a functional cerebral correlate to the visually elicited defense reaction and its associated emotions
AD  - Department of Psychiatry and Psychology, Karolinska Institute and Hospital, Stockholm, Sweden
UR  - PM:8511220
ER  - 

TY  - JOUR
T1  - Decreased cerebral response to inhibitory neurotransmission in alcoholics
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Hitzemann,R.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Pappas,N.
A1  - Biegon,A.
A1  - Dewey,S.L.
Y1  - 1993/03//
N1  - UI - 93167371
SP  - 417
EP  - 422
JA  - Am J Psychiatry
VL  - 150
IS  - 3
N2  - OBJECTIVE: Changes in gamma-aminobutyric acid (GABA)-benzodiazepine receptor function have been implicated in alcohol tolerance, withdrawal, and dependence. The purpose of this study was to investigate whether recently detoxified alcoholic subjects had abnormalities in brain GABA-benzodiazepine receptor function. METHOD: The effect of 30 micrograms/kg of lorazepam on regional brain glucose metabolism was studied in 12 normal subjects and 10 alcoholic subjects with the use of positron emission tomography and [18F]fluorodeoxyglucose. RESULTS: Lorazepam decreased whole brain glucose metabolism in both the normal subjects (13% change) and the alcoholic subjects (10% change), and the response was correlated with the concentration of lorazepam in plasma. Whereas the normal and alcoholic subjects showed similar responses to lorazepam in occipital and cerebellar metabolism, the alcoholic subjects showed significantly less of a response than the comparison subjects in the thalamus, basal ganglia, and orbitofrontal cortex. The rate of response in the orbitofrontal cortex was significantly correlated with cerebellar metabolism at baseline. CONCLUSIONS: The alcoholic subjects had a blunted response to lorazepam that was specific to certain brain regions. The association between cerebellar metabolism and response to lorazepam suggests that the cerebellum may contribute to the decreased sensitivity to lorazepam which was seen in the alcoholic subjects
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973
UR  - PM:8382010
ER  - 

TY  - JOUR
T1  - PET in generalized anxiety disorder
A1  - Wu,J.C.
A1  - Buchsbaum,M.S.
A1  - Hershey,T.G.
A1  - Hazlett,E.
A1  - Sicotte,N.
A1  - Johnson,J.C.
Y1  - 1991/06/15/
N1  - UI - 91363487
SP  - 1181
EP  - 1199
JA  - Biol.Psychiatry
VL  - 29
IS  - 12
N2  - Positron emission tomography (PET) measurements of cerebral glucose use were made in 18 patients with generalized anxiety disorder (GAD) during a passive viewing task off medication, and an active vigilance viewing task before and after medication or placebo treatment. In the passive viewing task, patients with GAD were compared with 15 normal controls. A significant difference in pattern of absolute brain metabolism was found. Patients showed lower absolute metabolic rates in basal ganglia and white matter. Relative metabolism was increased in the left inferior area 17 in the occipital lobe, right posterior temporal lobe, and the right precentral frontal gyrus. Significant left-right asymmetry of the parahippocampal gyri was not found in patients with GAD. An active vigilance task resulted in activation of relative basal ganglia metabolism in patients. Benzodiazepine therapy resulted in decreases in absolute metabolic rates for cortical surface, limbic system, and basal ganglia and was not associated with normalization of patterns of glucose metabolism. Change in anxiety scores was significantly correlated with change in limbic system and basal ganglia for the placebo group. The normal-anxious difference in the basal ganglia and the change seen in this region after benzodiazepine treatment are suggestive of a role in anxiety for this structure
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine 92717
UR  - PM:1888800
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic differences in patients with panic disorder
A1  - Nordahl,T.E.
A1  - Semple,W.E.
A1  - Gross,M.
A1  - Mellman,T.A.
A1  - Stein,M.B.
A1  - Goyer,P.
A1  - King,A.C.
A1  - Uhde,T.W.
A1  - Cohen,R.M.
Y1  - 1990/08//
N1  - UI - 90380223
SP  - 261
EP  - 272
JF  - Neuropsychopharmacology
VL  - 3
IS  - 4
N2  - Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder [Nature 310:683 (1984)] were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al. [Nature; Am J Psychiatry 143:469 (1986)], we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task
AD  - Section on Clinical Brain Imaging, Laboratory of Cerebral Metabolism, NIMH, Bethesda, Maryland
UR  - PM:2400544
ER  - 

TY  - JOUR
T1  - Neuroanatomical correlates of anticipatory anxiety
A1  - Reiman,E.M.
A1  - Fusselman,M.J.
A1  - Fox,P.T.
A1  - Raichle,M.E.
Y1  - 1989/02/24/
N1  - published erratum appears in Science 1992 Jun 19;256(5064):1696
SP  - 1071
EP  - 1074
JF  - Science
VL  - 243
IS  - 4894 Pt 1
N2  - Positron emission tomographic measurements of regional blood flow, a marker of local neuronal activity, were used to investigate the neuroanatomical correlates of a normal emotion. Healthy volunteers were studied before, during, and after anticipation of a painful electric shock. During anticipatory anxiety, there were significant blood flow increases in bilateral temporal poles, the same regions recently implicated in a lactate-induced anxiety attack in patients with panic disorder. Thus, the temporal poles seem to be involved in normal and pathological forms of human anxiety
AD  - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
UR  - PM:2784226
ER  - 

TY  - JOUR
T1  - Reproducibility of cerebral glucose metabolic measurements in resting human subjects
A1  - Bartlett,E.J.
A1  - Brodie,J.D.
A1  - Wolf,A.P.
A1  - Christman,D.R.
A1  - Laska,E.
A1  - Meissner,M.
Y1  - 1988/08//
N1  - UI - 88273343
SP  - 502
EP  - 512
JA  - J Cereb.Blood Flow Metab
VL  - 8
IS  - 4
N2  - Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no more than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at run 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low intrasubject variability and high stability over a 24-h period
AD  - Department of Psychiatry, NYU Medical Center, NY 10016
UR  - PM:3260593
ER  - 

TY  - JOUR
T1  - The effect of diazepam sedation on cerebral glucose metabolism in Alzheimer's disease as measured using positron emission tomography
A1  - Foster,N.L.
A1  - VanDerSpek,A.F.
A1  - Aldrich,M.S.
A1  - Berent,S.
A1  - Hichwa,R.H.
A1  - Sackellares,J.C.
A1  - Gilman,S.
A1  - Agranoff,B.W.
Y1  - 1987/08//
N1  - UI - 87280417
SP  - 415
EP  - 420
JA  - J Cereb.Blood Flow Metab
VL  - 7
IS  - 4
N2  - The effect of sedation induced by intravenous diazepam on cerebral glucose metabolic activity was examined with [18F]2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in five patients with probable Alzheimer's disease. Each subject was studied on 2 separate days: on one occasion at rest with eyes patched and ears open, and on the second when sedated with intravenous diazepam titrated to maintain stage II sleep by clinical and EEG criteria. Similar patterns of glucose uptake were observed in both the presence and the absence of sedation, but overall glucose utilization was depressed an average of 20% and was closely correlated with the amount of diazepam administered prior to the injection of FDG. The predominant temporoparietal hypometabolism and relative sparing of frontal metabolism observed in this disease are therefore not explained by differences in anxiety or activity level in this patient group. Utilization of diazepam sedation for PET study appears to be safe and may permit the study of patients otherwise unable to cooperate with FDG-PET procedures
UR  - PM:3497161
ER  - 

TY  - JOUR
T1  - Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder
A1  - Buchsbaum,M.S.
A1  - Wu,J.
A1  - Haier,R.
A1  - Hazlett,E.
A1  - Ball,R.
A1  - Katz,M.
A1  - Sokolski,K.
A1  - Lagunas-Solar,M.
A1  - Langer,D.
Y1  - 1987/06/22/
N1  - UI - 87227962
SP  - 2393
EP  - 2400
JA  - Life Sci.
VL  - 40
IS  - 25
N2  - Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with 18F-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate
UR  - PM:2884547
ER  - 

TY  - JOUR
T1  - Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls
A1  - Baxter,L.R.,Jr.
A1  - Phelps,M.E.
A1  - Mazziotta,J.C.
A1  - Guze,B.H.
A1  - Schwartz,J.M.
A1  - Selin,C.E.
Y1  - 1987/03//
N1  - [published erratum appears in Arch Gen Psychiatry 1987 Sep;44(9):800] [see comments]
SP  - 211
EP  - 218
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 44
IS  - 3
N2  - We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states
UR  - PM:3493749
ER  - 

TY  - JOUR
T1  - Trazodone treatment response in obsessive-compulsive disorder--correlated with shifts in glucose metabolism in the caudate nuclei
A1  - Baxter,L.R.,Jr.
A1  - Thompson,J.M.
A1  - Schwartz,J.M.
A1  - Guze,B.H.
A1  - Phelps,M.E.
A1  - Mazziotta,J.C.
A1  - Selin,C.E.
A1  - Moss,L.
Y1  - 1987///
N1  - UI - 88097934
SP  - 114
EP  - 122
JF  - Psychopathology
VL  - 20 Suppl 1
N2  - Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is difficult to treat. The effects of trazodone hydrochloride treatment were studied, both with and without the addition of a monoamine oxidase inhibitor, in OCD patients. Changes in symptoms correlated with changes in local cerebral metabolic rates for glucose (LCMRGlc), as measured by positron emission tomography and the 18F-fluorodeoxyglucose method. All patients whose OCD responded favorably to drug treatment showed a relative increase in glucose metabolism in the heads of the caudate nuclei compared with the metabolic rate in the ipsilateral hemisphere as a whole (ratio LCMRGlc caudate/LCMRGlc hemisphere). Patients who did not respond to treatment did not show an increase in this ratio, and the difference between responders and nonresponders was significant (p less than 0.03). Changes in the ratio LCMRGlc caudate/LCMRGlc hemisphere correlated with changes on OCD and depression rating scales
AD  - Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine
UR  - PM:3501130
ER  - 

TY  - JOUR
T1  - The application of positron emission tomography to the study of panic disorder
A1  - Reiman,E.M.
A1  - Raichle,M.E.
A1  - Robins,E.
A1  - Butler,F.K.
A1  - Herscovitch,P.
A1  - Fox,P.
A1  - Perlmutter,J.
Y1  - 1986/04//
N1  - UI - 86156366
SP  - 469
EP  - 477
JA  - Am J Psychiatry
VL  - 143
IS  - 4
N2  - Positron emission tomography was used to study eight patients with panic disorder who were vulnerable to lactate-induced panic, eight patients with panic disorder who were not vulnerable to lactate-induced panic, and 25 normal control subjects. Patients who were vulnerable to lactate-induced panic had several abnormalities in the resting, nonpanic state: an abnormal hemispheric asymmetry of parahippocampal blood flow, blood volume, and oxygen metabolism; abnormally high whole brain metabolism; and abnormal susceptibility to episodic hyperventilation. A hypothetical model for the neurobiology of panic disorder, involving the abnormal parahippocampal region and its afferent and efferent connections, is proposed
UR  - PM:3485385
ER  - 

TY  - JOUR
T1  - Human brain-immune relationships: a PET study
A1  - Wik,G.
A1  - Lekander,M.
A1  - Fredrikson,M.
Y1  - 1998/09//
N1  - UI - 98443163
SP  - 242
EP  - 246
JA  - Brain Behav.Immun.
VL  - 12
IS  - 3
N2  - To study brain-immune relations, we correlated positron emission tomographic (PET) measures of regional cerebral blood flow (rCBF) with immune measures in 10 female volunteers. The natural killer (NK) activity correlated negatively with activity bilaterally in the secondary sensory cortex, whereas the Concanavalin A (Con A) response correlated positively with rCBF bilaterally in secondary visual, motor, and sensory cortices, the thalamus, the putamen, and the left hippocampus. Although representing preliminary data from a small number of subjects, these observations provide further support for the presence of interactions between the brain and the immune system
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:9769159
ER  - 

TY  - JOUR
T1  - Evidence of altered cerebral blood-flow relationships in acute phobia
A1  - Wik,G.
A1  - Fredrikson,M.
A1  - Fischer,H.
Y1  - 1997/10//
N1  - UI - 98056070
SP  - 253
EP  - 263
JA  - Int.J Neurosci.
VL  - 91
IS  - 3-4
N2  - Functional cerebral guiding and integrating systems may be revealed by analyzing the covariation of regional cerebral blood flow (rCBF). Positron emission tomography (PET) was used to measure absolute rCBF in 14 volunteers with specific phobia and 6 nonphobic controls, when exposed to videos containing phobia-relevant and neutral scenes. A fear reaction and increased covariation between absolute rCBFs was observed during phobia-relevant as compared to neutral stimulation in phobics only. In controls fear was not elicited and rCBF covariation was not influenced by stimulus condition, being similar to the pattern observed in phobics during neutral stimulation. We suggest the rCBF correlative pattern during phobic fear to reflect fear-related activation of distinct neuronal pathways that involves the amygdala, the thalamus, and the striatum. We theorize that these pathways are activated also by uncontrolled emotions in diverse conditions, like posttraumatic stress disorder, panic disorder, and schizophrenia
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:9394231
ER  - 

TY  - JOUR
T1  - Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder
A1  - Nuttin,B.J.
A1  - Gabriels,L.A.
A1  - Cosyns,P.R.
A1  - Meyerson,B.A.
A1  - Andreewitch,S.
A1  - Sunaert,S.G.
A1  - Maes,A.F.
A1  - Dupont,P.J.
A1  - Gybels,J.M.
A1  - Gielen,F.
A1  - Demeulemeester,H.G.
Y1  - 2003/06//
N1  - UI - 22649190
SP  - 1263
EP  - 1272
JF  - Neurosurgery
VL  - 52
IS  - 6
N2  - OBJECTIVE: Because of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODS: We stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTS: The psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 +/- 8.0) than in the postoperative stimulator-off condition (mean, 32.3 +/- 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSION: These observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography
AD  - Department of Neurosurgery, Laboratory of Experimental Neurosurgery and Neuroanatomy, Catholic University of Leuven, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. bart.nuttin@uz.kuleuven.ac.be
UR  - PM:12762871
ER  - 

TY  - JOUR
T1  - Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression
A1  - Saxena,S.
A1  - Brody,A.L.
A1  - Ho,M.L.
A1  - Zohrabi,N.
A1  - Maidment,K.M.
A1  - Baxter,L.R.,Jr.
Y1  - 2003/03//
SP  - 522
EP  - 532
JA  - Am J Psychiatry
VL  - 160
IS  - 3
N2  - OBJECTIVE: Serotonin reuptake inhibitor (SRI) medications are effective in the treatment of both major depressive disorder and obsessive-compulsive disorder (OCD), but it is unknown whether the neural substrates of treatment response for the two disorders are the same or different. The authors sought to identify pretreatment cerebral glucose metabolic markers of responsiveness to SRI treatment in patients with OCD versus major depressive disorder and to determine whether the pretreatment patterns associated with improvement of OCD symptoms were the same as or different from those associated with improvement of major depressive disorder symptoms. METHOD: [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure cerebral glucose metabolism in 27 patients with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent OCD and major depressive disorder, who were all then treated with 30-60 mg/day of paroxetine for 8-12 weeks. Correlations were calculated between pretreatment regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms, depressive symptoms, and overall functioning. RESULTS: While improvement of OCD symptoms was significantly correlated with higher pretreatment glucose metabolism in the right caudate nucleus (partial r=-0.53), improvement of major depressive disorder symptoms was significantly correlated with lower pretreatment metabolism in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91). CONCLUSIONS: These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment
AD  - Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. ssaxena@mednet.ucla.edu
UR  - PM:12611834
ER  - 

TY  - JOUR
T1  - Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder
A1  - Kwon,J.S.
A1  - Kim,J.J.
A1  - Lee,D.W.
A1  - Lee,J.S.
A1  - Lee,D.S.
A1  - Kim,M.S.
A1  - Lyoo,I.K.
A1  - Cho,M.J.
A1  - Lee,M.C.
Y1  - 2003/01/20/
N1  - UI - 22478311
SP  - 37
EP  - 47
JA  - Psychiatry Res
VL  - 122
IS  - 1
N2  - Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD
AD  - BK 21 Human Life Sciences, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea
UR  - PM:12589881
ER  - 

TY  - JOUR
T1  - Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study
A1  - Rauch,S.L.
A1  - Shin,L.M.
A1  - Dougherty,D.D.
A1  - Alpert,N.M.
A1  - Fischman,A.J.
A1  - Jenike,M.A.
Y1  - 2002/11//
N1  - UI - 22319532
SP  - 782
EP  - 791
JF  - Neuropsychopharmacology
VL  - 27
IS  - 5
N2  - The purpose of this study was to identify neuroimaging predictors of medication response in contamination-related obsessive compulsive disorder (OCD). Prior studies of OCD had indicated that glucose metabolic rates within orbitofrontal cortex (OFC) were inversely correlated with subsequent response to serotonergic reuptake inhibitors (SRIs) and that glucose metabolic rates within posterior cingulate cortex (PCC) were positively correlated with subsequent response to cingulotomy. Nine subjects with contamination-related OCD underwent a 12-week open trial of treatment with the SRI fluvoxamine. Percent change in Yale-Brown Obsessive Compulsive Scale score, from pre- to post-treatment, served as the index of treatment response. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) were obtained prior to treatment, in the context of a symptom provocation paradigm. Statistical parametric mapping was used to identify brain loci where pre-treatment rCBF was significantly correlated with subsequent treatment response. Consistent with a priori hypotheses, lower rCBF values in OFC and higher rCBF values in PCC predicted better treatment response. This same pattern of associations was present regardless of whether the imaging data were acquired during a provoked or neutral state. These findings are consistent with prior studies of OCD, indicating that PET indices of brain activity within OFC are inversely correlated with subsequent response to SRIs. In addition, similar to findings regarding cingulotomy for OCD, indices of activity within PCC appear to be positively correlated with response to fluvoxamine as well. Finally, this pattern is sufficiently robust as to be relatively independent of symptomatic state at the time of tracer uptake
AD  - Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rauch@psych.mgh.harvard.edu
UR  - PM:12431852
ER  - 

TY  - JOUR
T1  - Obsessive-compulsive disorder secondary to brain dysgerminoma in an adolescent boy: a positron emission tomography case report
A1  - Gamazo-Garran,P.
A1  - Soutullo,C.A.
A1  - Ortuno,F.
Y1  - 2002///
N1  - UI - 22315166
SP  - 259
EP  - 263
JA  - J Child Adolesc.Psychopharmacol.
VL  - 12
IS  - 3
N2  - The neuroanatomical model involved in the pathophysiology of obsessive-compulsive disorder (OCD) postulates a hyperactivation of orbitofrontal, limbic, and basal ganglia circuits. We report a case of OCD secondary to brain dysgerminoma affecting this circuit in an adolescent who responded to citalopram. The patient is a 16-year-old-boy with a midline germinal tumor (dysgerminoma) affecting the caudate nuclei; left lenticular, right internal capsule's genu; and bilateral involvement of the interventricular septum close to the interventricular foramina. He had OCD symptoms and elevated tumor markers when he had a tumor relapse, and fluorodeoxyglucose positron emission tomography showed caudate nuclei involvement. He responded to citalopram that had to be titrated gradually to 80 mg/day
AD  - Department of Psychiatry and Medical Psychology, Clinica Universitaria, University of Navarra College of Medicine, Pamplona, Spain
UR  - PM:12427300
ER  - 

TY  - JOUR
T1  - Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression
A1  - Saxena,S.
A1  - Brody,A.L.
A1  - Ho,M.L.
A1  - Alborzian,S.
A1  - Maidment,K.M.
A1  - Zohrabi,N.
A1  - Ho,M.K.
A1  - Huang,S.C.
A1  - Wu,H.M.
A1  - Baxter,L.R.,Jr.
Y1  - 2002/03//
N1  - UI - 21868545
SP  - 250
EP  - 261
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 59
IS  - 3
N2  - BACKGROUND: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS: We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. RESULTS: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbitofrontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in nondepressed OCD patients but with an increase in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement
AD  - Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 300 UCLA Medical Plaza, Room 2229, Los Angeles, CA 90095, USA. ssaxena@mednet.ucla.edu
UR  - PM:11879163
ER  - 

TY  - JOUR
T1  - Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder
A1  - Rauch,S.L.
A1  - Dougherty,D.D.
A1  - Cosgrove,G.R.
A1  - Cassem,E.H.
A1  - Alpert,N.M.
A1  - Price,B.H.
A1  - Nierenberg,A.A.
A1  - Mayberg,H.S.
A1  - Baer,L.
A1  - Jenike,M.A.
A1  - Fischman,A.J.
Y1  - 2001/11/01/
N1  - UI - 21560174
SP  - 659
EP  - 667
JA  - Biol.Psychiatry
VL  - 50
IS  - 9
N2  - BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value
AD  - Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
UR  - PM:11704072
ER  - 

TY  - JOUR
T1  - FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder
A1  - Brody,A.L.
A1  - Saxena,S.
A1  - Schwartz,J.M.
A1  - Stoessel,P.W.
A1  - Maidment,K.
A1  - Phelps,M.E.
A1  - Baxter,L.R.,Jr.
Y1  - 1998/11/09/
N1  - UI - 99085959
SP  - 1
EP  - 6
JA  - Psychiatry Res
VL  - 84
IS  - 1
N2  - In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication
AD  - UCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA. abrody@ucla.edu
UR  - PM:9870412
ER  - 

TY  - JOUR
T1  - Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorders
A1  - Nordahl,T.E.
A1  - Stein,M.B.
A1  - Benkelfat,C.
A1  - Semple,W.E.
A1  - Andreason,P.
A1  - Zametkin,A.
A1  - Uhde,T.W.
A1  - Cohen,R.M.
Y1  - 1998/11/15/
N1  - UI - 99039005
SP  - 998
EP  - 1006
JA  - Biol.Psychiatry
VL  - 44
IS  - 10
N2  - BACKGROUND: Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients. METHODS: An independent group of panic disorder patients placed on imipramine was studied with positron-emission tomography, testing for evidence of normalization versus persistence of the abnormal rCMRglc ratios. Differences in orbital frontal rCMRglc values between the imipramine-treated and the previously reported unmedicated panic disorder patients were tested examining for evidence that the differences would resemble those noted in obsessive-compulsive disorder (OCD) patients treated with clomipramine. RESULTS: We found the same abnormally low L/R hippocampal and posterior inferior prefrontal rCMRglc ratios in the imipramine-treated panic disorder patients. In addition, we found posterior orbital frontal rCMRglc decreases in the imipramine-treated panic disorder patients compared with the unmedicated panic disorder patients. CONCLUSIONS: These abnormal asymmetries found in unmedicated panic disorder patients and now in imipramine-treated panic disorder patients may reflect a trait abnormality. The orbital frontal rCMRglc differences between the imipramine-treated and unmedicated patients are similar to changes noted in OCD patients treated with clomipramine and may reflect direct or indirect effects of imipramine treatment in panic disorder patients
AD  - Department of Psychiatry, UC Davis Medical Center, Sacramento, California, USA
UR  - PM:9821564
ER  - 

TY  - JOUR
T1  - Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning
A1  - Rauch,S.L.
A1  - Savage,C.R.
A1  - Alpert,N.M.
A1  - Dougherty,D.
A1  - Kendrick,A.
A1  - Curran,T.
A1  - Brown,H.D.
A1  - Manzo,P.
A1  - Fischman,A.J.
A1  - Jenike,M.A.
Y1  - 1997///
N1  - UI - 98108759
SP  - 568
EP  - 573
JA  - J Neuropsychiatry Clin.Neurosci.
VL  - 9
IS  - 4
N2  - Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder (OCD) to that of matched control subjects while they performed an implicit learning task. Although patients and control subjects evidenced comparable learning, imaging data from control subjects indicated bilateral inferior striatal activation, whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation. The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder. Furthermore, when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems, they instead appear to access brain regions normally associated with explicit (conscious) information processing
AD  - Massachusetts General Hospital, Charlestown 02129, USA
UR  - PM:9447498
ER  - 

TY  - JOUR
T1  - A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals
A1  - Cottraux,J.
A1  - Gerard,D.
A1  - Cinotti,L.
A1  - Froment,J.C.
A1  - Deiber,M.P.
A1  - Le Bars,D.
A1  - Galy,G.
A1  - Millet,P.
A1  - Labbe,C.
A1  - Lavenne,F.
A1  - Bouvard,M.
A1  - Mauguiere,F.
Y1  - 1996/03/29/
N1  - UI - 96300598
SP  - 101
EP  - 112
JA  - Psychiatry Res
VL  - 60
IS  - 2-3
N2  - Ten nondepressed patients with obsessive-compulsive disorder (OCD) who were characterized by predominant checking rituals were compared with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral blood flow levels (rCBF) were measured with positron emission tomography (H2 15O) across four conditions: rest, auditory stimulation with idiosyncratic normal or abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest. Order of neutral and obsessive stimulation was randomized. Higher subjective responses to obsessive than to neutral stimulation were found in both groups; subjective response was higher in OCD patients when obsessive stimulation was presented first. A four-way analysis of variance (group x stimulation order x hemisphere x condition [neutral or obsessive stimulation]) was performed on stimulation minus rest normalized rCBF values. Control subjects had significantly higher rCBF in the thalamus and putamen. A trend toward higher rCBF in OCD patients was found in the superior temporal regions. When neutral stimulation was presented first, rCBF was significantly higher in the caudate region of control subjects. Obsessive stimulation was associated with higher rCBF than neutral stimulation in orbitofrontal regions in both groups of subjects. Under obsessive stimulation, superior temporal and orbitofrontal activities were correlated in OCD patients but not in control subjects. Our study suggests specific abnormalities of information processing in the basal ganglia and temporal structures of compulsive checkers
AD  - Department of Psychiatry, Hopital Neurologique, Lyon, France
UR  - PM:8723300
ER  - 

TY  - JOUR
T1  - Individual differences in cerebral metabolic patterns during pharmacotherapy in obsessive-compulsive disorder: a multiple regression/discriminant analysis of positron emission tomographic data
A1  - Azari,N.P.
A1  - Pietrini,P.
A1  - Horwitz,B.
A1  - Pettigrew,K.D.
A1  - Leonard,H.L.
A1  - Rapoport,J.L.
A1  - Schapiro,M.B.
A1  - Swedo,S.E.
Y1  - 1993/12/01/
N1  - UI - 94122279
SP  - 798
EP  - 809
JA  - Biol.Psychiatry
VL  - 34
IS  - 11
N2  - A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD
AD  - Laboratory of Neurosciences, National Institute of Aging/NIH, Bethesda, MD 20892
UR  - PM:8292684
ER  - 

TY  - JOUR
T1  - Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study
A1  - Martinot,J.L.
A1  - Allilaire,J.F.
A1  - Mazoyer,B.M.
A1  - Hantouche,E.
A1  - Huret,J.D.
A1  - Legaut-Demare,F.
A1  - Deslauriers,A.G.
A1  - Hardy,P.
A1  - Pappata,S.
A1  - Baron,J.C.
A1  - .
Y1  - 1990/09//
N1  - UI - 91063142
SP  - 233
EP  - 242
JA  - Acta Psychiatr.Scand.
VL  - 82
IS  - 3
N2  - The authors compared 16 nondepressed obsessive-compulsive patients (OCS) with 8 normal controls (NC) of similar age for resting-state regional cerebral glucose metabolic rates (rCMRglu) using positron emission tomography with the fluorodeoxyglucose method. OCS were rated for clinical data, and a neuropsychological battery was administered to 14 patients on the day of the scan. Absolute rCMRglu for whole cortex, and normalized prefrontal lateral cortex metabolic rates, were both significantly lower in OCS than in NC. No significant difference between treated (n = 10) and drug-free (n = 6) OCS was found for those variables. OCS were significantly impaired in the neuropsychological tasks assessing memory and attention. The rCMRglu for prefrontal lateral cortex were negatively correlated to Stroop-test subscores. This "frontal-oriented" task assessed the ability of OCS to inhibit immediate but inappropriate responses. These results suggest, in OCS, a modification of the general activating systems of cortical function and a relationship between the lateral prefrontal rCMRglu decrease and a selective attention deficit
AD  - Department of Frederic Joliot, Atomic Energy Commission, Orsay, France
UR  - PM:2248050
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder
A1  - Baxter,L.R.,Jr.
A1  - Schwartz,J.M.
A1  - Mazziotta,J.C.
A1  - Phelps,M.E.
A1  - Pahl,J.J.
A1  - Guze,B.H.
A1  - Fairbanks,L.
Y1  - 1988/12//
N1  - UI - 89060450
SP  - 1560
EP  - 1563
JA  - Am J Psychiatry
VL  - 145
IS  - 12
N2  - The authors compared 10 nondepressed patients with obsessive-compulsive disorder with 10 normal control subjects of the same sex and similar age for cerebral glucose metabolic rates obtained using positron emission tomography. Obsessive-compulsive patients showed significantly elevated metabolic rates in the whole cerebral hemispheres, heads of the caudate nuclei, orbital gyri, and the orbital gyri relative to the ipsilateral hemisphere (the orbital-hemisphere ratio). These results are similar to those the authors reported previously for another group of obsessive-compulsive patients and normal control subjects
AD  - Department of Radiological Sciences, University of California, Los Angeles
UR  - PM:3264118
ER  - 

TY  - JOUR
T1  - Increased left posterior parietal-temporal cortex activation after D-fenfluramine in women with panic disorder
A1  - Meyer,J.H.
A1  - Swinson,R.
A1  - Kennedy,S.H.
A1  - Houle,S.
A1  - Brown,G.M.
Y1  - 2000/05/15/
N1  - UI - 20283983
SP  - 133
EP  - 143
JA  - Psychiatry Res
VL  - 98
IS  - 3
N2  - It is unclear whether the functional changes found in panic disorder reflect disturbed physiology of particular neurotransmitters. One method of investigating altered neurotransmission is to assess regional brain activations in response to agonist challenges. D-Fenfluramine is a medication that induces neuronal release of serotonin. Using 15OH(2)O and positron emission tomography (PET), measurements of regional cerebral blood flow (rCBF) were done at t=-20, -5, +20 and +35 relative to the IV D-fenfluramine injection (t=0) in nine panic-disordered and 18 healthy subjects. Subjects were otherwise healthy, right-handed, non-smoking and not taking psychotropic medication. 15OH(2)O PET scans were assessed with Statistical Parametric Mapping using individual global cerebral blood flow as a covariate. Comparisons of the (baseline) first two scans between healthy and panic-disordered subjects showed a decreased rCBF in the left posterior parietal-superior temporal cortex in the patient group. Fenfluramine-induced increases as defined by the last two scans minus the first two scans were compared between groups and a significantly greater increase in the same left posterior parietal-superior temporal region was found in panic-disordered subjects. Consistent with this finding, differences between the last two scans (post-fenfluramine) of the healthy and panic-disordered subjects showed an increased rCBF in the left superior temporal cortex in panic-disordered subjects. Functional pathology in the left parietal-superior temporal cortex in panic disorder may be related to abnormal modulation by serotonin
AD  - The Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Clarke Division, 250 College Street, M5T 1R8, Toronto, Ontario, Canada. jmeyer@clark-inst.on.ca
UR  - PM:10821996
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in women with panic disorder
A1  - Bisaga,A.
A1  - Katz,J.L.
A1  - Antonini,A.
A1  - Wright,C.E.
A1  - Margouleff,C.
A1  - Gorman,J.M.
A1  - Eidelberg,D.
Y1  - 1998/09//
N1  - UI - 98403608
SP  - 1178
EP  - 1183
JA  - Am J Psychiatry
VL  - 155
IS  - 9
N2  - OBJECTIVE: This study was undertaken to clarify earlier inconsistent findings in brain metabolic topography in panic disorder patients at rest. METHOD: Positron emission tomography (PET) with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in six female patients with a DSM-III-R diagnosis of panic disorder and in six healthy female volunteers. All patients with panic disorder were medication free and were sensitive to lactate infusion. RESULTS: A significant increase in glucose metabolism was found in the left hippocampus and parahippocampal area of the panic disorder subjects in comparison with that found in the healthy subjects. In addition, a significant decrease in metabolism was found in the right inferior parietal and right superior temporal brain regions of the panic disorder subjects in comparison with that of the normal subjects. There was no significant correlation between scores for the severity of panic disorder or for the severity of lactate-induced panic attack and the quantified PET abnormality. CONCLUSIONS: These data provide further support for the hypothesis of an abnormal brain metabolism in the hippocampal and parahippocampal area in individuals with panic disorder and also suggest other areas of aberrant brain metabolism in this disorder
AD  - Department of Psychiatry, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA
UR  - PM:9734539
ER  - 

TY  - JOUR
T1  - Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse
A1  - Bremner,J.D.
A1  - Vythilingam,M.
A1  - Vermetten,E.
A1  - Southwick,S.M.
A1  - McGlashan,T.
A1  - Staib,L.H.
A1  - Soufer,R.
A1  - Charney,D.S.
Y1  - 2003/05/15/
N1  - UI - 22627481
SP  - 879
EP  - 889
JA  - Biol.Psychiatry
VL  - 53
IS  - 10
N2  - BACKGROUND: Animal studies have shown that early stressors result in lasting changes in structure and function of brain areas involved in memory, including hippocampus and frontal cortex. Patients with childhood abuse-related posttraumatic stress disorder (PTSD) have alterations in both declarative and nondeclarative memory function, and imaging studies in PTSD have demonstrated changes in function during stimulation of trauma-specific memories in hippocampus, medial prefrontal cortex, and cingulate. The purpose of this study was to assess neural correlates of emotionally valenced declarative memory in women with early childhood sexual abuse and PTSD. METHODS: Women with early childhood sexual abuse-related PTSD (n = 10) and women without abuse or PTSD (n = 11) underwent positron emission tomographic (PET) measurement of cerebral blood flow during a control condition and during retrieval of neutral (e.g., "metal-iron") and emotionally valenced (e.g., "rape-mutilate") word pairs. RESULTS: During retrieval of emotionally valenced word pairs, PTSD patients showed greater decreases in blood flow in an extensive area, which included orbitofrontal cortex, anterior cingulate, and medial prefrontal cortex (Brodmann's areas 25, 32, 9), left hippocampus, and fusiform gyrus/inferior temporal gyrus, with increased activation in posterior cingulate, left inferior parietal cortex, left middle frontal gyrus, and visual association and motor cortex. There were no differences in patterns of brain activation during retrieval of neutral word pairs between patients and control subjects. CONCLUSIONS: These findings are consistent with dysfunction of specific brain areas involved in memory and emotion in PTSD. Regions implicated in this study of emotionally valenced declarative memory are similar to those from prior imaging studies in PTSD using trauma-specific stimuli for symptom provocation, adding further supportive evidence for a dysfunctional network of brain areas involved in memory, including hippocampus, medial prefrontal cortex, and cingulate, in PTSD
AD  - Department of Psychiatry and Behavioral Sciences, Emory Center for Positron Emission Tomography, Emory University School of Medicine, Atlanta, Georgia 30306, USA
UR  - PM:12742675
ER  - 

TY  - JOUR
T1  - MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder
A1  - Bremner,J.D.
A1  - Vythilingam,M.
A1  - Vermetten,E.
A1  - Southwick,S.M.
A1  - McGlashan,T.
A1  - Nazeer,A.
A1  - Khan,S.
A1  - Vaccarino,L.V.
A1  - Soufer,R.
A1  - Garg,P.K.
A1  - Ng,C.K.
A1  - Staib,L.H.
A1  - Duncan,J.S.
A1  - Charney,D.S.
Y1  - 2003/05//
N1  - UI - 22612192
SP  - 924
EP  - 932
JA  - Am J Psychiatry
VL  - 160
IS  - 5
N2  - OBJECTIVE: Animal studies have suggested that early stress is associated with alterations in the hippocampus, a brain area that plays a critical role in learning and memory. The purpose of this study was to measure both hippocampal structure and function in women with and without early childhood sexual abuse and the diagnosis of posttraumatic stress disorder (PTSD). METHOD: Thirty-three women participated in this study, including women with early childhood sexual abuse and PTSD (N=10), women with abuse without PTSD (N=12), and women without abuse or PTSD (N=11). Hippocampal volume was measured with magnetic resonance imaging in all subjects, and hippocampal function during the performance of hippocampal-based verbal declarative memory tasks was measured by using positron emission tomography in abused women with and without PTSD. RESULTS: A failure of hippocampal activation and 16% smaller volume of the hippocampus were seen in women with abuse and PTSD compared to women with abuse without PTSD. Women with abuse and PTSD had a 19% smaller hippocampal volume relative to women without abuse or PTSD. CONCLUSIONS: These results are consistent with deficits in hippocampal function and structure in abuse-related PTSD
AD  - Department of Psychiatry and Behavioral Sciences, Emory Clinical Neuroscience Research Unit, Emory University School of Medicine, 1256 Briarcliff Road, Atlanta, GA 30306, USA. jdbremn@emory.edu
UR  - PM:12727697
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder
A1  - Osuch,E.A.
A1  - Benson,B.
A1  - Geraci,M.
A1  - Podell,D.
A1  - Herscovitch,P.
A1  - McCann,U.D.
A1  - Post,R.M.
Y1  - 2001/08/15/
N1  - UI - 21413456
SP  - 246
EP  - 253
JA  - Biol.Psychiatry
VL  - 50
IS  - 4
N2  - BACKGROUND: Nuclear imaging studies have examined cerebral blood flow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. METHODS: Subjects with varying traumatic histories and longstanding PTSD were studied using [15O]-H2O positron emission tomography with an auditory script of their traumatic event. Eight subjects had three resting scans followed by their script and additional scans. Heart rate responses as well as the presence of flashbacks and their intensity were recorded. rCBF was correlated with flashback intensity in each subject's scan. Combined analysis of all subjects' data yielded common regions related to the flashback experience. RESULTS: rCBF correlated directly with flashback intensity in the brainstem, lingula, bilateral insula, right putamen and left hippocampal and perihippocampal, somatosensory and cerebellar regions. Inverse correlations with rCBF were found in bilateral dorsolateral prefrontal, right fusiform and right medial temporal cortices. CONCLUSIONS: This study correlated flashback intensity and rCBF in a group of patients with chronic PTSD suggesting involvement of brainstem, and areas associated with motor control, complex visual/spatial cues and memory
AD  - Uniformed Services University of the Health Sciences, Maryland, USA
UR  - PM:11522258
ER  - 

TY  - JOUR
T1  - Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder
A1  - Bremner,J.D.
A1  - Narayan,M.
A1  - Staib,L.H.
A1  - Southwick,S.M.
A1  - McGlashan,T.
A1  - Charney,D.S.
Y1  - 1999/11//
N1  - UI - 20019172
SP  - 1787
EP  - 1795
JA  - Am J Psychiatry
VL  - 156
IS  - 11
N2  - OBJECTIVE: Childhood sexual abuse is very common in our society, but little is known about the long-term effects of abuse on brain function. The purpose of this study was to measure neural correlates of memories of childhood abuse in sexually abused women with and without the diagnosis of posttraumatic stress disorder (PTSD). METHOD: Twenty-two women with a history of childhood sexual abuse underwent injection of [15O]H2O, followed by positron emission tomography imaging of the brain while they listened to neutral and traumatic (personalized childhood sexual abuse events) scripts. Brain blood flow during exposure to traumatic and neutral scripts was compared for sexually abused women with and without PTSD. RESULTS: Memories of childhood sexual abuse were associated with greater increases in blood flow in portions of anterior prefrontal cortex (superior and middle frontal gyri-areas 6 and 9), posterior cingulate (area 31), and motor cortex in sexually abused women with PTSD than in sexually abused women without PTSD. Abuse memories were associated with alterations in blood flow in medial prefrontal cortex, with decreased blood flow in subcallosal gyrus (area 25), and a failure of activation in anterior cingulate (area 32). There was also decreased blood flow in right hippocampus, fusiform/inferior temporal gyrus, supramarginal gyrus, and visual association cortex in women with PTSD relative to women without PTSD. CONCLUSIONS: These findings implicate dysfunction of medial prefrontal cortex (subcallosal gyrus and anterior cingulate), hippocampus, and visual association cortex in pathological memories of childhood abuse in women with PTSD. Increased activation in posterior cingulate and motor cortex was seen in women with PTSD. Dysfunction in these brain areas may underlie PTSD symptoms provoked by traumatic reminders in subjects with PTSD
AD  - Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Conn., USA
UR  - PM:10553744
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation
A1  - Shin,L.M.
A1  - McNally,R.J.
A1  - Kosslyn,S.M.
A1  - Thompson,W.L.
A1  - Rauch,S.L.
A1  - Alpert,N.M.
A1  - Metzger,L.J.
A1  - Lasko,N.B.
A1  - Orr,S.P.
A1  - Pitman,R.K.
Y1  - 1999/04//
N1  - UI - 99216744
SP  - 575
EP  - 584
JA  - Am J Psychiatry
VL  - 156
IS  - 4
N2  - OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus
AD  - Department of Psychiatry, Massachusetts General Hospital, Boston, USA. Ishin01@emerald.tufts.edu
UR  - PM:10200737
ER  - 

TY  - JOUR
T1  - Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories
A1  - Semple,W.E.
A1  - Goyer,P.F.
A1  - McCormick,R.
A1  - Compton-Toth,B.
A1  - Morris,E.
A1  - Donovan,B.
A1  - Muswick,G.
A1  - Nelson,D.
A1  - Garnett,M.L.
A1  - Sharkoff,J.
A1  - Leisure,G.
A1  - Miraldi,F.
A1  - Schulz,S.C.
Y1  - 1996/05/31/
N1  - UI - 96390160
SP  - 17
EP  - 28
JA  - Psychiatry Res
VL  - 67
IS  - 1
N2  - Performance on an attentional task was assessed in posttraumatic stress disorder patients with substance abuse histories (PTSD-SA). Positron emission tomography (PET) was used to measure concurrent regional cerebral blood flow (rCBF). Eight male PTSD-SA patients and eight normal subjects each received three serial PET scans with 15O-labeled water under the following conditions: (1) resting, (2) auditory continuous performance task (ACPT1), and (3) repeat auditory task (ACPT2). PTSD-SA patients made more errors of commission on the ACPT than normal subjects. Examination of right frontal and parietal cortex ACPT task substrates revealed decreased parietal blood flow in PTSD-SA, which may represent a pathophysiology for poor attentional task performance in PTSD-SA. Attentional problems may underlie other symptomatology in PTSD
AD  - Cleveland Veterans Administration Medical Center (11B), Brecksville, OH 44141, USA
UR  - PM:8797239
ER  - 

TY  - JOUR
T1  - Alcohol intoxication induces greater reductions in brain metabolism in male than in female subjects
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Franceschi,D.
A1  - Wong,C.T.
A1  - Pappas,N.R.
A1  - Netusil,N.
A1  - Zhu,W.
A1  - Felder,C.
A1  - Ma,Y.
Y1  - 2003/06//
N1  - UI - 22707169
SP  - 909
EP  - 917
JA  - Alcohol Clin.Exp.Res
VL  - 27
IS  - 6
N2  - BACKGROUND: The mechanisms underlying the gender differences in alcohol drinking behavior and alcohol's effects are poorly understood and may reflect gender differences in brain neurochemistry. Alcohol decreases glucose metabolism in the human brain in a pattern that is consistent with its facilitation of GABAergic neurotransmission. We compared the regional changes in brain glucose metabolism during alcohol intoxication between female and male subjects. METHODS: Ten female and 10 male healthy controls were scanned with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose twice: 40 min after placebo (diet soda) or alcohol (0.75 g/kg mixed with diet soda). RESULTS: Alcohol significantly and consistently decreased whole-brain metabolism. The magnitude of these changes was significantly larger in male (-25 +/- 6%) than in female (-14 +/- 11%; p < 0.005) subjects. Half of the female subjects had reductions in metabolism during intoxication that were significantly lower than those in male subjects. This blunted response in the female subjects was not due to differences in alcohol concentration in plasma, because these did not differ between the genders. In contrast, the self-reports for the perception of intoxication were significantly greater in female than in male subjects. The cognitive deterioration during alcohol intoxication, although not significant, tended to be worse in female subjects. CONCLUSIONS: This study shows a markedly blunted sensitivity to the effects of acute alcohol on brain glucose metabolism in female subjects that may reflect gender differences in alcohol's modulation of GABAergic neurotransmission. The greater behavioral effects of alcohol in female subjects despite the blunted metabolic responses could reflect other effects of alcohol, for which the regional metabolic signal may be hidden within the large decrements in metabolism that occur during alcohol intoxication
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gjwang@bnl.gov
UR  - PM:12824811
ER  - 

TY  - JOUR
T1  - Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex
A1  - Volkow,N.D.
A1  - Chang,L.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Ding,Y.S.
A1  - Sedler,M.
A1  - Logan,J.
A1  - Franceschi,D.
A1  - Gatley,J.
A1  - Hitzemann,R.
A1  - Gifford,A.
A1  - Wong,C.
A1  - Pappas,N.
Y1  - 2001/12//
N1  - UI - 21585152
SP  - 2015
EP  - 2021
JA  - Am J Psychiatry
VL  - 158
IS  - 12
N2  - OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. volkow@bnl.gov
UR  - PM:11729018
ER  - 

TY  - JOUR
T1  - Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence
A1  - Volkow,N.D.
A1  - Chang,L.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Franceschi,D.
A1  - Sedler,M.
A1  - Gatley,S.J.
A1  - Miller,E.
A1  - Hitzemann,R.
A1  - Ding,Y.S.
A1  - Logan,J.
Y1  - 2001/12/01/
SP  - 9414
EP  - 9418
JA  - J Neurosci.
VL  - 21
IS  - 23
N2  - Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals
AD  - Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov
UR  - PM:11717374
ER  - 

TY  - JOUR
T1  - Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers
A1  - Volkow,N.D.
A1  - Chang,L.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Franceschi,D.
A1  - Sedler,M.J.
A1  - Gatley,S.J.
A1  - Hitzemann,R.
A1  - Ding,Y.S.
A1  - Wong,C.
A1  - Logan,J.
Y1  - 2001/03//
SP  - 383
EP  - 389
JA  - Am J Psychiatry
VL  - 158
IS  - 3
N2  - OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions
AD  - Department of Psychiatry, State University of New York at Stony Brook, USA. volkow@bnl.gov
UR  - PM:11229978
ER  - 

TY  - JOUR
T1  - Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers
A1  - Volkow,N.D.
A1  - Chang,L.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Leonido-Yee,M.
A1  - Franceschi,D.
A1  - Sedler,M.J.
A1  - Gatley,S.J.
A1  - Hitzemann,R.
A1  - Ding,Y.S.
A1  - Logan,J.
A1  - Wong,C.
A1  - Miller,E.N.
Y1  - 2001/03//
N1  - UI - 21152307
SP  - 377
EP  - 382
JA  - Am J Psychiatry
VL  - 158
IS  - 3
N2  - OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain
AD  - Department of Psychiatry, State University of New York at Stony Brook, USA. volkow@bnl.gov
UR  - PM:11229977
ER  - 

TY  - JOUR
T1  - Smoking a single cigarette does not produce a measurable reduction in brain MAO B in non-smokers
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Franceschi,D.
A1  - Logan,J.
A1  - Pappas,N.
A1  - Shea,C.
A1  - MacGregor,R.R.
A1  - Garza,V.
Y1  - 1999/12//
N1  - UI - 20524500
SP  - 325
EP  - 329
JA  - Nicotine.Tob.Res
VL  - 1
IS  - 4
N2  - Positron emission tomography (PET) studies with [11C]L-deprenyl-D2 have shown that brain monoamine oxidase (MAO) B is 40% lower in smokers than in non-smokers. Here we investigated whether MAO B inhibition can be detected after smoking a single cigarette. Eight normal healthy non-smokers (35 +/- 11 years) received two PET studies 2 h apart with [11C]L-deprenyl-D2, one at baseline and the second 5-10 min after the subject had smoked a single cigarette. Plasma nicotine and expired carbon monoxide (CO) were measured prior to smoking and 10 min after smoking completion as an index of tobacco smoke exposure. A three-compartment model was used to calculate lambda k3, a model term which is proportional to MAO B activity and which is derived from the time course of carbon-11 in the brain and the time course of the radiotracer in the plasma and K1, the plasma-to-brain transfer constant (for [11C]L-deprenyl-D2) which is related to brain blood flow. Subjects experienced difficulty inhaling and became dizzy and/or nauseous after smoking. Plasma nicotine averaged 11.6 +/- 5.5 ng/ml and expired CO averaged 8 +/- 10 ppm after smoking. The average lambda k3 and K1 for 11 different brain regions did not differ significantly between baseline and smoking. These results indicate that the reduction in MAO B in smokers probably occurs gradually and requires chronic tobacco smoke exposure
AD  - Brookhaven National Laboratory, Upton, NY 11973, USA. fowler@bnl.gov
UR  - PM:11072429
ER  - 

TY  - JOUR
T1  - Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fischman,M.W.
A1  - Foltin,R.
A1  - Fowler,J.S.
A1  - Franceschi,D.
A1  - Franceschi,M.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - Wong,C.
A1  - Ding,Y.S.
A1  - Hitzemann,R.
A1  - Pappas,N.
Y1  - 2000/08/11/
N1  - UI - 20437140
SP  - 1507
EP  - 1515
JA  - Life Sci.
VL  - 67
IS  - 12
N2  - The route of administration influences the reinforcing effects of cocaine. Here we assessed whether there were differences in the efficacy of cocaine to block the dopamine transporters (major target for cocaine's reinforcing effects), as a function of route of administration. Positron emission tomography and [11C]cocaine, a dopamine transporter radioligand, were used to compare the levels of dopamine transporter blockade induced by intravenous, smoked and intranasal cocaine in 32 current cocaine abusers. In parallel, the temporal course for the self-reports of "high" were obtained. Cocaine significantly blocked dopamine transporters. The levels of blockade were comparable across all routes of administration and a dose effect was observed for intravenous and intranasal cocaine but not for smoked cocaine. For equivalent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self reports of "high" than intranasal cocaine and showed a trend for a greater effect than intravenous cocaine. The time to reach peak subjective was significantly faster for smoked (1.4+/-0.5 min) than for intravenous cocaine (3.1+/-0.9 min), which was faster than intranasal cocaine (14.6+/-8 min). Differences in the reinforcing effects of cocaine as a function of the route of administration are not due to differences in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the speed of cocaine's delivery into the brain on its reinforcing effects
AD  - Medical Department, Upton, NY 11973, USA. volkow@bnl.gov
UR  - PM:10983846
ER  - 

TY  - JOUR
T1  - Comparative studies of epibatidine derivatives [18F]NFEP and [18F]N-methyl-NFEP: kinetics, nicotine effect, and toxicity
A1  - Ding,Y.S.
A1  - Molina,P.E.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Volkow,N.D.
A1  - Kuhar,M.J.
A1  - Carroll,F.I.
Y1  - 1999/01//
SP  - 139
EP  - 148
JA  - Nucl Med Biol.
VL  - 26
IS  - 1
N2  - We have previously shown that [18F]norchlorofluoroepibatidine ([18F]NFEP) would be an ideal radiotracer for positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChR); however, its high toxicity is a limiting factor for human studies. We, therefore, synthesized its N-methyl derivative ([18F]N-Me-NFEP) and carried out comparative studies. The distribution volumes for different brain regions were higher for [18F]N-Me-NFEP than those for [18F]NFEP (average: 52.5+/-0.9 vs. 36.4+/-0.7 for thalamus), though the distribution volume (DV) ratios were similar (3.93+/-0.27 vs. 3.65+/-0.19 for thalamus to cerebellum). Treatment with nicotine reduced the binding of both radiotracers. Toxicology studies in awake rats showed that N-methyl-NFEP has a lower mortality (0 vs. 30%) and smaller effect on plasma catecholamines than NFEP at a dose of 1.5 microg/kg. However, marked alterations in cardiorespiratory parameters were observed after injection of N-methyl-NFEP (0.5 microg/kg, IV) to an awake dog. Our results suggest that although the binding characteristics of [18F]NFEP and [18F]N-Me-NFEP appear to be ideally suited for PET imaging studies of the human brain, their relatively small safety margin will limit their use in humans
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. ding@bnl.gov
UR  - PM:10096514
ER  - 

TY  - JOUR
T1  - Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: implications in addiction
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Hitzemann,R.
A1  - Angrist,B.
A1  - Gatley,S.J.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Pappas,N.
Y1  - 1999/01//
SP  - 19
EP  - 26
JA  - Am J Psychiatry
VL  - 156
IS  - 1
N2  - OBJECTIVE: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. METHOD: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. RESULTS: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. CONCLUSIONS: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov
UR  - PM:9892293
ER  - 

TY  - JOUR
T1  - Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high"
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Gatley,S.J.
A1  - Logan,J.
A1  - Ding,Y.S.
A1  - Dewey,S.L.
A1  - Hitzemann,R.
A1  - Gifford,A.N.
A1  - Pappas,N.R.
Y1  - 1999/01//
SP  - 14
EP  - 20
JA  - J Pharmacol.Exp.Ther.
VL  - 288
IS  - 1
N2  - The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Using positron emission tomography (PET), we previously showed that intravenous cocaine induced a significant level of DAT blockade, which was associated with the intensity for self-reports of "high" in cocaine abusers. In this study, we measured DAT occupancies after intravenous methylphenidate and assessed whether they also were associated with the "high". Occupation of DAT by intravenous MP was measured with PET using [11C]cocaine, as a DAT ligand, in eight normal control subjects tested with different methylphenidate doses. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was used as measure of DAT availability. In parallel, self-reports of "high" were measured. Methylphenidate produced a dose-dependent blockade of DAT with an estimated ED50 of 0.075 mg/kg. DAT occupancies were significantly correlated with the "high" (p <.03). However, four of the eight subjects, despite having significant levels of DAT blockade, did not perceive the "high". Methylphenidate is as effective as cocaine in blocking DAT in the human brain (cocaine ED50 = 0.13 mg/kg), and DAT blockade, as for cocaine, was also associated with the "high". However, the fact that there were subjects who despite significant DAT blockade did not experience the "high" suggests that DAT blockade, although necessary, is not sufficient to produce the "high"
AD  - Brookhaven National Laboratory, Upton, New York, USA
UR  - PM:9862747
ER  - 

TY  - JOUR
T1  - Regional cerebral metabolism in female alcoholics of moderate severity does not differ from that of controls
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Pappas,N.R.
A1  - Wong,C.T.
A1  - Pascani,K.
A1  - Felder,C.A.
A1  - Hitzemann,R.J.
Y1  - 1998/11//
N1  - UI - 99050971
SP  - 1850
EP  - 1854
JA  - Alcohol Clin.Exp.Res
VL  - 22
IS  - 8
N2  - It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [18F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:9835307
ER  - 

TY  - JOUR
T1  - Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain
A1  - Ding,Y.S.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Dewey,S.L.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - Pappas,N.
Y1  - 1997/05//
N1  - UI - 97325585
SP  - 71
EP  - 78
JA  - Psychopharmacology (Berl)
VL  - 131
IS  - 1
N2  - Methylphenidate (Ritalin) is the most commonly prescribed psychoactive medication for children in the US where it is used for the treatment of attention deficit hyperactivity disorder. Methylphenidate is marketed as a racemic mixture of the d-threo and l-threo enantiomers. It is believed that the d enantiomer is responsible for the therapeutic effect of methylphenidate. In this study we labeled the individual enantiomers with carbon-11 and compared their binding and pharmacokinetics in the human and baboon brain. Microdialysis studies in the rat were performed to compare their potency in elevating striatal dopamine concentration. Positron emission tomographic (PET) studies with [11C]d-threo-methylphenidate ([11C]d-threo-MP) demonstrated highest regional uptake in basal ganglia. In contrast, [11C]l-threo-methylphenidate ([11C]l-threo-MP) displayed similar uptakes in all brain regions. The ratios of distribution volumes at the steady-state for the basal ganglia to cerebellum (DVBG/DVCB) ranged from 2.2 to 3.3 for [11C]d-threo-MP in baboon and human, and only 1.1 for [11C]l-threo-MP. Pretreatment with unlabeled methylphenidate (0.5 mg/kg) or GBR12909 (1.5 mg/kg) markedly reduced the striatal but not the cerebellar uptake of [11C]d-threo-MP, whereas there was no effect on DVBG/DVCB for [11C]l-threo-MP. In the rat, d-threo-MP increased extracellular dopamine concentration by 650% whereas l-threo-MP did not affect dopamine levels. These results indicate that pharmacological specificity of MP resides entirely in the d-threo isomer and directly show that binding of the l-isomer in human brain is mostly nonspecific
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. ding@simbrain.chm.bnl.gov
UR  - PM:9181638
ER  - 

TY  - JOUR
T1  - Model for estimating dopamine transporter occupancy and subsequent increases in synaptic dopamine using positron emission tomography and carbon-11-labeled cocaine
A1  - Gatley,S.J.
A1  - Volkow,N.D.
A1  - Gifford,A.N.
A1  - Ding,Y.S.
A1  - Logan,J.
A1  - Wang,G.J.
Y1  - 1997/01/10/
N1  - UI - 97119239
SP  - 43
EP  - 52
JA  - Biochem.Pharmacol.
VL  - 53
IS  - 1
N2  - Although increases in dopamine secondary to the inhibition of the dopamine transporter appear to underlie the reinforcing properties of cocaine, there is presently no model that relates the elevation of synaptic dopamine to the transporter occupancy by cocaine. We propose such a model based on positron emission tomographic (PET) measurements of the brain concentration of cocaine and the assumption of rapid equilibrium between free cocaine and cocaine bound to the dopamine transporter. A euphorigenic dose of cocaine (about 40 mg) is predicted to occupy 80-90% of the transporters, while a perceptible dose (about 5 mg) occupies about 40% of the transporters. If reuptake of dopamine is reduced in proportion to the fraction of transporters occupied by cocaine, our model indicates that synaptic dopamine rises supra-linearly with occupancy, so that 5 and 40 mg doses of cocaine give about 2- and 10-fold increases, respectively. A consequence is that a given dose of cocaine produces a similar degree of elevation of dopamine regardless of the prior level of occupation of the transporters by cocaine. This prediction is supported by recent PET/neuropsychological studies in our laboratory where dopamine transporter occupancy was measured after giving methylphenidate intravenously to volunteers; similarly intense "highs" were reported whether the initial occupancy was zero or 75-85%. It could also explain why attempts to block the psychostimulant-induced "high" by pretreating subjects with drugs that block the dopamine transporter have been unsuccessful, and why the use of methylphenidate to treat cocaine addicts led to increased cocaine consumption
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8960062
ER  - 

TY  - JOUR
T1  - Decreases in dopamine receptors but not in dopamine transporters in alcoholics
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Hitzemann,R.
A1  - Ding,Y.S.
A1  - Pappas,N.
A1  - Shea,C.
A1  - Piscani,K.
Y1  - 1996/12//
N1  - 95-6 (Raclopride)
SP  - 1594
EP  - 1598
JA  - Alcohol Clin.Exp.Res
VL  - 20
IS  - 9
N2  - It has been hypothesized that ethanol's actions on the dopamine (DA) system may participate in addiction. The purpose of this study was to evaluate the DA system in the brain of alcoholics. We evaluated 10 alcoholics and 17 nonalcoholics using positron emission tomography and [11C]raclopride to measure DA D2 receptors. In addition, in 5 of the alcoholics and 16 of the nonalcoholics, we also measured DA transporters with [11C]d-threo methylphenidate. The ratio of the distribution volumes in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was used as model parameter of DA D2 receptor and transporter availability. Dopamine D2 receptor availability (Bmax/Kd) was significantly lower in alcoholics (2.1 +/- 0.5) than in nonalcoholics (2.7 +/- 0.6) (p < 0.05) and was not correlated with days since last alcohol use. Alcoholics showed DA transporter values similar to those in nonalcoholics. The ratio of DA D2 receptor to transporter availability was significantly higher in nonalcoholics (1.4 +/- 0.1) than in alcoholics (1.1 +/- 0.1) (p < 0.005). Alcoholics showed significant reductions in D2 receptors (postsynaptic marker) but not in DA transporter availability (presynaptic marker) when compared with nonalcoholics. Because D2 receptors in striatum are mainly localized in gamma-aminobutyric acid (GABA) cells these results provide evidence of GABAergic involvement in the dopaminergic abnormalities seen in alcoholics
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8986209
ER  - 

TY  - JOUR
T1  - Distribution volume ratios without blood sampling from graphical analysis of PET data
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Ding,Y.S.
A1  - Alexoff,D.L.
Y1  - 1996/09//
SP  - 834
EP  - 840
JA  - J Cereb.Blood Flow Metab
VL  - 16
IS  - 5
N2  - The distribution volume ratio (DVR), which is a linear function of receptor availability, is widely used as a model parameter in imaging studies. The DVR corresponds to the ratio of the DV of a receptor-containing region to a nonreceptor region and generally requires the measurement of an arterial input function. Here we propose a graphical method for determining the DVR that does not require blood sampling. This method uses data from a nonreceptor region with an average tissue-to-plasma efflux constant k2 to approximate the plasma integral. Data from positron emission tomography studies with [11C]raclopride (n = 20) and [11C]d-threo-methylphenidate ([11C]dMP) (n = 8) in which plasma data were taken and used to compare results from two graphical methods, one that uses plasma data and one that does not. k2 was 0.163 and 0.051 min-1 for [11C]raclopride and [11C]dMP, respectively. Results from both methods were very similar, and the average percentage difference between the methods was -0.11% for [11C]raclopride and 0.46% for [11C]dMP for DVR of basal ganglia (BG) to cerebellum (CB). Good agreement between the two methods was also achieved for DVR images created by both methods. This technique provides an alternative method of analysis not requiring blood sampling that gives equivalent results for the two ligands studied. It requires initial studies with blood sampling to determine the average kinetic constant and to test applicability. In some cases, it may be possible to neglect the k2 term if the BG/CB ratio becomes reasonably constant for a sufficiently long period of time over the course of the experiment
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8784228
ER  - 

TY  - JOUR
T1  - Cocaine uptake is decreased in the brain of detoxified cocaine abusers
A1  - Volkow,N.D.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Logan,J.
A1  - Hitzemannn,R.
A1  - Gatley,S.J.
A1  - MacGregor,R.R.
A1  - Wolf,A.P.
Y1  - 1996/03//
N1  - UI - 97020320
SP  - 159
EP  - 168
JF  - Neuropsychopharmacology
VL  - 14
IS  - 3
N2  - Binding of [11C]cocaine in brain was measured with positron emission tomography in 12 detoxified cocaine abusers and in 20 controls to evaluate if there were changes in cocaine binding and in dopamine (DA) transporter availability associated with chronic cocaine use. Nine controls and 10 cocaine abusers had an additional scan with [18F]N-methylspiroperidol to measure dopamine D2 receptors. Cocaine abusers had significantly lower uptake of [11C]cocaine in brain (6.2 +/- 1% dose/cc tissues) than controls (7.7 +/- 2%). The distribution volumes (DV) for [11C]cocaine were reduced in basal ganglia (BG), cortex, thalamus, and cerebellum (CB) of cocaine abusers. However there were no differences in the ratio of the DV in BG to that in CB, which is an estimate of DA transporter availability. Values for DA D2 receptor availability were decreased in cocaine abusers and did not correlate with estimates of dopamine transporter availability. In summary, detoxified cocaine abusers showed decreased uptake of cocaine in brain but did not show changes in DA transporter availability
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8866699
ER  - 

TY  - JOUR
T1  - Cocaine addiction: hypothesis derived from imaging studies with PET
A1  - Volkow,N.D.
A1  - Ding,Y.S.
A1  - Fowler,J.S.
A1  - Wang,G.J.
Y1  - 1996///
SP  - 55
EP  - 71
JA  - J Addict.Dis.
VL  - 15
IS  - 4
N2  - Analysis of the behavior of cocaine in the human brain with Positron Emission Tomography reveals that it is not only its affinity for the dopamine transporter that gives it its unique properties but also its fast pharmacokinetics. Its very fast uptake and clearance from the brain contrast with that of methylphenidate, another drug that inhibits the DA transporter. Methylephenidate clears from the brain at a much slower rate and is less addictive than cocaine. We postulate that periodic and frequent stimulation of the dopaminergic system secondary to chronic use of cocaine favors activation of a circuit that involves the orbitofrontal cortex, cingulate gyrus, thalamus and striatum. This circuit is abnormal in cocaine abusers and we postulate that is activation by cocaine perpetuates the compulsive administration of the drug and is perceived by the cocaine abuser as a intense desire resulting in the loss of control over the drive to take more cocaine
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
UR  - PM:8943582
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism in violent psychiatric patients: a preliminary study
A1  - Volkow,N.D.
A1  - Tancredi,L.R.
A1  - Grant,C.
A1  - Gillespie,H.
A1  - Valentine,A.
A1  - Mullani,N.
A1  - Wang,G.J.
A1  - Hollister,L.
Y1  - 1995/11/10/
N1  - UI - 96353319
SP  - 243
EP  - 253
JA  - Psychiatry Res
VL  - 61
IS  - 4
N2  - Positron emission tomography with 18F-deoxyglucose was used to evaluate regional brain glucose metabolism in eight normal subjects and eight psychiatric patients with a history of repetitive violent behavior. Seven of the patients showed widespread areas of low brain metabolism. Although the location of the abnormal regions varied among patients, they showed significantly lower relative metabolic values in medial temporal and prefrontal cortices than did normal comparison subjects. These regions have been implicated as substrates for aggression and impulsivity, and their dysfunction may have contributed to the patients' violent behavior
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. volkow@brain.med.bnl.gov
UR  - PM:8748468
ER  - 

TY  - JOUR
T1  - Serotonin 5-HT2 receptor availability in chronic cocaine abusers
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Schlyer,D.
A1  - MacGregor,R.R.
A1  - Hitzemann,R.J.
A1  - Gjedde,A.
A1  - Wolf,A.P.
Y1  - 1995/03/10/
N1  - UI - 96112125
SP  - L299
EP  - L303
JA  - Life Sci.
VL  - 56
IS  - 16
N2  - Serotonin 5-HT2 receptor availability was evaluated in chronic cocaine abusers (n = 19) using positron emission tomography and F-18 N-methylspiperone and was compared to control subjects (n =19). 5-HT2 Receptor availability was measured in frontal, occipital, cingulate and orbitofrontal cortices using the ratio of the distribution volume in the region of interest to that in the cerebellum which is a function of Bmax/Kd. 5-HT2 Receptor availability was significantly higher in cingulate and orbitofrontal cortices than in other frontal regions or occipital cortex. The values were not different in normal subjects and cocaine abusers. These results did not show any changes in 5-HT2 receptor availability in cocaine abusers as compared to the control subjects
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:8614247
ER  - 

TY  - JOUR
T1  - Comparison of two pet radioligands for imaging extrastriatal dopamine transporters in human brain
A1  - Wang,G.J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Ding,Y.S.
A1  - Logan,J.
A1  - Gatley,S.J.
A1  - MacGregor,R.R.
A1  - Wolf,A.P.
Y1  - 1995///
N1  - UI - 96004824
SP  - L187
EP  - L191
JA  - Life Sci.
VL  - 57
IS  - 14
N2  - We compared the sensitivity of two dopamine transporter (DAT) ligands ([C-11]cocaine and [C-11]d-threo-methylphenidate) for measurement of extrastriatal DAT availability using positron emission tomography (PET) on separated groups of 10 age matched male volunteers (age range, 21-49 years). DAT availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd'+ 1). DAT availability measured with [C-11]d-threo-methylphenidate was highest in basal ganglia, followed by thalamus > temporal insula, cingulate > orbitofrontal, frontal and occipital cortices. A similar ranking order for DAT availability was obtained with [C-11]cocaine. Specific binding (Bmax'/Kd') of [C-11]cocaine in thalamus was 25-33% that of basal ganglia and [C-11]d-threo-methylphenidate in thalamus was 11-13% that of basal ganglia. The regional measures with [C-11]cocaine were significantly correlated with those of [C-11]d-threo-methylphenidate (p < or = 0.0001). These results document extrastriatal binding in human brain with two different DAT ligands
AD  - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:7564877
ER  - 

TY  - JOUR
T1  - Effects of blood flow on [11C]raclopride binding in the brain: model simulations and kinetic analysis of PET data
A1  - Logan,J.
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Dewey,S.L.
A1  - MacGregor,R.
A1  - Schlyer,D.
A1  - Gatley,S.J.
A1  - Pappas,N.
A1  - King,P.
A1  - .
Y1  - 1994/11//
N1  - UI - 95014823
SP  - 995
EP  - 1010
JA  - J Cereb.Blood Flow Metab
VL  - 14
IS  - 6
N2  - To assess the stability of different measures of receptor occupancy from [11C]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor-ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which PCO2 was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or PCO2) may cause changes in DV, and these effects need to be considered when evaluating experimental results
UR  - PM:7929663
ER  - 

TY  - JOUR
T1  - Decreased dopamine transporters with age in health human subjects
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wang,G.J.
A1  - Logan,J.
A1  - Schlyer,D.
A1  - MacGregor,R.
A1  - Hitzemann,R.
A1  - Wolf,A.P.
Y1  - 1994/08//
N1  - UI - 94330696
SP  - 237
EP  - 239
JA  - Ann.Neurol
VL  - 36
IS  - 2
N2  - The effects of aging on brain dopamine transporters was evaluated in 26 healthy male volunteers (age range, 21-63 years) using positron emission tomography and [11C]cocaine. The ratio of the distribution volume for [11C]cocaine in basal ganglia to that in cerebellum was used as a model parameter for dopamine transporter availability and showed a significant negative correlation with age (r = 0.65, p < 0.0005). This results document an age-related decline in dopamine transporters in healthy individuals
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973
UR  - PM:8053661
ER  - 

TY  - JOUR
T1  - Studies with differentially labeled [11C]cocaine, [11C]norcocaine, [11C]benzoylecgonine, and [11C]- and 4'-[18F]fluorococaine to probe the extent to which [11C]cocaine metabolites contribute to PET images of the baboon brain
A1  - Gatley,S.J.
A1  - Yu,D.W.
A1  - Fowler,J.S.
A1  - MacGregor,R.R.
A1  - Schlyer,D.J.
A1  - Dewey,S.L.
A1  - Wolf,A.P.
A1  - Martin,T.
A1  - Shea,C.E.
A1  - Volkow,N.D.
Y1  - 1994/03//
N1  - UI - 94157554
SP  - 1154
EP  - 1162
JA  - J Neurochem.
VL  - 62
IS  - 3
N2  - The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-methyl-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3I, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methyl-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methyl-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4'-[N-methyl-11CH3]fluorococaine and 4'-[18F]fluorococaine (prepared by nucleophilic aromatic substitution from [18F]fluoride- and 4'-nitrococaine) were compared with [N-methyl-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4'-fluorococaine were equipotent at the dopamine reuptake site, but that 4'-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973
UR  - PM:8113802
ER  - 

TY  - JOUR
T1  - Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications
A1  - Smith,G.S.
A1  - de Leon,M.J.
A1  - George,A.E.
A1  - Kluger,A.
A1  - Volkow,N.D.
A1  - McRae,T.
A1  - Golomb,J.
A1  - Ferris,S.H.
A1  - Reisberg,B.
A1  - Ciaravino,J.
A1  - .
Y1  - 1992/11//
N1  - UI - 93074517
SP  - 1142
EP  - 1150
JA  - Arch Neurol
VL  - 49
IS  - 11
N2  - Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD
AD  - Department of Psychiatry, University School of Medicine, NY 10016
UR  - PM:1444881
ER  - 

TY  - JOUR
T1  - Decreased brain metabolism in neurologically intact healthy alcoholics
A1  - Volkow,N.D.
A1  - Hitzemann,R.
A1  - Wang,G.J.
A1  - Fowler,J.S.
A1  - Burr,G.
A1  - Pascani,K.
A1  - Dewey,S.L.
A1  - Wolf,A.P.
Y1  - 1992/08//
N1  - UI - 92343896
SP  - 1016
EP  - 1022
JA  - Am J Psychiatry
VL  - 149
IS  - 8
N2  - OBJECTIVE: The extent to which cerebral dysfunction in alcoholics is related to the direct effects of alcohol in the brain rather than to indirect mechanisms and/or alcohol withdrawal remains unclear. The purpose of this study was to evaluate whether healthy alcoholics with no evidence of alcohol-associated complications showed changes in brain glucose metabolism. METHOD: Positron emission tomography and [18F]-fluorodeoxyglucose were used to measure regional brain metabolism. The study group consisted of 22 normal, healthy, right-handed volunteers and 22 neurologically intact, healthy, right-handed alcoholics tested 6 to 32 days after alcohol discontinuation. RESULTS: Alcoholics showed significantly lower whole brain metabolism than normal control subjects. Normalization of regional metabolic values to the whole brain metabolic rate revealed that the left parietal and right frontal cortices were the most affected regions. Although the whole brain metabolic rate was correlated with the amount of time since alcohol discontinuation, the "normalized" decreases in left parietal and right frontal glucose metabolism were not. CONCLUSIONS: These findings support the contribution of the direct effect of alcohol as well as alcohol withdrawal on the changes in regional brain metabolism seen in alcoholics. They also provide evidence of cerebral changes in neurologically intact healthy alcoholics
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973
UR  - PM:1636801
ER  - 

TY  - JOUR
T1  - Changes in brain glucose metabolism in cocaine dependence and withdrawal
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Hitzemann,R.
A1  - Dewey,S.
A1  - Bendriem,B.
A1  - Alpert,R.
A1  - Hoff,A.
Y1  - 1991/05//
N1  - UI - 91206610
SP  - 621
EP  - 626
JA  - Am J Psychiatry
VL  - 148
IS  - 5
N2  - OBJECTIVE: The authors investigated changes in brain function associated with cocaine dependence and withdrawal to provide clues regarding the processes that lead to the uncontrollable self-administration of cocaine. METHOD: They measured regional brain metabolism with [18F]-fluorodeoxyglucose (FDG) and positron emission tomography in 15 outpatients with the diagnosis of cocaine abuse and 17 normal comparison subjects. Ten of the patients were studied less than 1 week after they had last had cocaine, and five were studied 2-4 weeks after withdrawal. RESULTS: Patients studied within 1 week of cocaine withdrawal but not those studied within 2-4 weeks of cocaine withdrawal had higher levels of global brain metabolism as well as higher levels of regional brain metabolism in the basal ganglia and orbitofrontal cortex than did normal subjects, probably as a consequence of less brain dopamine activity. There was also a significant relationship between the number of days since cocaine withdrawal and regional brain glucose metabolism in the orbitofrontal cortex and in the basal ganglia, and the correlations between cocaine craving and metabolic activity were significant in the prefrontal cortex and the orbitofrontal cortex. CONCLUSIONS: Although the time-dependent fall in metabolic activity suggests that the higher metabolic activity observed less than a week after cocaine withdrawal may represent a nonspecific expression of drug withdrawal, the selectivity of changes in glucose metabolism for the basal ganglia and for the orbitofrontal cortex suggests that the regional metabolic changes seen in cocaine abusers during detoxification are related to changes in brain dopamine activity
AD  - Medical Department Brookhaven National Laboratory, Upton, NY 11973
UR  - PM:2018164
ER  - 

TY  - JOUR
T1  - Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)
A1  - Dewey,S.L.
A1  - Volkow,N.D.
A1  - Logan,J.
A1  - MacGregor,R.R.
A1  - Fowler,J.S.
A1  - Schlyer,D.J.
A1  - Bendriem,B.
Y1  - 1990/12//
N1  - UI - 91178845
SP  - 569
EP  - 575
JA  - J Neurosci.Res
VL  - 27
IS  - 4
N2  - Muscarinic cholinergic M1 and M2 receptors in young and aged adult male volunteers were studied using [N-11C-methyl]-benztropine, a specific muscarinic cholinergic receptor ligand, and high resolution positron emission tomography (PET). A regionally specific pattern of decreased binding was observed in aged volunteers. Using two separate methods of data analysis, thalamic, hippocampal and cerebellar regions showed no decreases in the apparent specific binding of [N-11C-methyl]-benztropine while frontal, parietal, temporal and occipital cortices as well as the corpus striatum showed age related changes in binding that declined (in 82 yrs old subject) to about 50% of the value obtained from the youngest volunteer (19 yrs). These data suggest that regions high in muscarinic receptor density, the corpus striatum and the cortical mantle, show a greater rate of decline than those areas that have a relatively low number of muscarinic receptors. Furthermore, this study demonstrates the usefulness of PET and [N-11C-methyl]-benztropine for assessing age related regional changes in muscarinic cholinergic receptor binding in the living human brain
AD  - Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973
UR  - PM:2079718
ER  - 

TY  - JOUR
T1  - Effects of chronic cocaine abuse on postsynaptic dopamine receptors
A1  - Volkow,N.D.
A1  - Fowler,J.S.
A1  - Wolf,A.P.
A1  - Schlyer,D.
A1  - Shiue,C.Y.
A1  - Alpert,R.
A1  - Dewey,S.L.
A1  - Logan,J.
A1  - Bendriem,B.
A1  - Christman,D.
A1  - .
Y1  - 1990/06//
N1  - UI - 90261768
SP  - 719
EP  - 724
JA  - Am J Psychiatry
VL  - 147
IS  - 6
N2  - To assess the effects of chronic cocaine intoxication on dopamine receptors in human subjects, the authors evaluated [18F]N-methylspiroperidol binding using positron emission tomography in 10 cocaine abusers and 10 normal control subjects. Cocaine abusers who had been detoxified for 1 week or less showed significantly lower values for uptake of [18F]N-methylspiroperidol in striatum than the normal subjects, whereas the cocaine abusers who had been detoxified for 1 month showed values comparable to those obtained from normal subjects. The authors conclude that postsynaptic dopamine receptor availability decreases with chronic cocaine abuse but may recover after a drug-free interval
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000
UR  - PM:2343913
ER  - 

TY  - JOUR
T1  - Acute effects of ethanol on regional brain glucose metabolism and transport
A1  - Volkow,N.D.
A1  - Hitzemann,R.
A1  - Wolf,A.P.
A1  - Logan,J.
A1  - Fowler,J.S.
A1  - Christman,D.
A1  - Dewey,S.L.
A1  - Schlyer,D.
A1  - Burr,G.
A1  - Vitkun,S.
A1  - .
Y1  - 1990/04//
N1  - UI - 90311504
SP  - 39
EP  - 48
JA  - Psychiatry Res
VL  - 35
IS  - 1
N2  - To evaluate the effects of ethanol in the human brain, we tested six normal subjects and six alcoholics using positron emission tomography and 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) under baseline conditions and 24 hours later after ethanol administration (1 g/kg). Ethanol inhibited cortical and cerebellar glucose metabolism with relative sparing of the basal ganglia and corpus callosum. This inhibition was more pronounced in the alcoholics than in the controls. Measurement of the constants for glucose transport and utilization showed that decreased glucose metabolism was due to a reduction in glucose phosphorylation and not to a change of glucose transport into the tissue. The pattern of regional metabolic inhibition by alcohol paralleled the distribution of benzodiazepine receptors in the human brain
AD  - Medical Department, Brookhaven National Laboratory, Upton, NY 11973
UR  - PM:2164230
ER  - 

TY  - JOUR
T1  - Cerebral blood flow in chronic cocaine users: a study with positron emission tomography
A1  - Volkow,N.D.
A1  - Mullani,N.
A1  - Gould,K.L.
A1  - Adler,S.
A1  - Krajewski,K.
Y1  - 1988/05//
N1  - UI - 89001786
SP  - 641
EP  - 648
JA  - Br.J Psychiatry
VL  - 152
N2  - Occurrence of cerebrovascular accidents has been associated with cocaine abuse. We investigated the relative distribution of cerebral blood flow (CBF) in groups of chronic cocaine users, and of normal controls. Relative CBF was measured using positron emission tomography and 15 oxygen-labelled water. The cocaine users showed areas of deranged CBF as evidenced by patchy regions of defective isotope accumulation throughout their brain. The chronic cocaine users showed decreased relative CBF in the prefrontal cortex when compared with normal subjects. The repeated scans of some cocaine users, after 10 days of cocaine withdrawal, continued to show decreased relative CBF of the prefrontal cortex. We hypothesise that some of the widespread defects in CBF in the cocaine users could reflect the effects of vasospasm in cerebral arteries exposed chronically to the sympathomimetic actions of cocaine
AD  - Department of Psychiatry, University of Texas Health Science Center, Houston
UR  - PM:3262397
ER  - 

TY  - JOUR
T1  - Effects of acute alcohol intoxication on cerebral blood flow measured with PET
A1  - Volkow,N.D.
A1  - Mullani,N.
A1  - Gould,L.
A1  - Adler,S.S.
A1  - Guynn,R.W.
A1  - Overall,J.E.
A1  - Dewey,S.
Y1  - 1988/05//
N1  - UI - 88304308
SP  - 201
EP  - 209
JA  - Psychiatry Res
VL  - 24
IS  - 2
N2  - Regional distribution of cerebral blood flow was assessed in a group of 13 normal social drinkers under baseline conditions and after acute alcohol intoxication. Blood flow measurements were done using 15O-labeled water and positron emission tomography (PET). Each subject underwent two control sessions under baseline conditions and two sessions after alcohol. Seven of the subjects were given 0.5 g/kg of alcohol and six were given 1 g/kg of alcohol p.o. The first and second post-alcohol scans were done 40 and 60 min after alcohol ingestion. The studies revealed that both the high and the low doses of alcohol reduced blood flow to the cerebellum. This effect was significant only for the high doses of alcohol, which also increased blood flow to the right temporal and the prefrontal cortex. The decrease in blood flow of the cerebellum could account for the muscular incoordination induced by alcohol
AD  - Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston
UR  - PM:3261427
ER  - 

TY  - JOUR
T1  - Cerebral involvement in systemic lupus erythematosus
A1  - Volkow,N.D.
A1  - Warner,N.
A1  - McIntyre,R.
A1  - Valentine,A.
A1  - Kulkarni,M.
A1  - Mullani,N.
A1  - Gould,L.
Y1  - 1988///
N1  - UI - 88281232
SP  - 91
EP  - 98
JA  - Am J Physiol Imaging
VL  - 3
IS  - 2
N2  - Four patients with central nervous system lupus erythematosus (SLE), were studied with nuclear magnetic resonance imaging (NMRI) and positron emission tomography (PET) to assess cerebral blood flow and glucose metabolism. The NMRI showed brain atrophy and demyelinating defects. The PET scan showed cerebral blood flow and metabolic abnormalities that improved in one patient after neuropsychiatric recovery. These preliminary findings demonstrate cerebral derangements in patients with SLE cerebritis
AD  - Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston 77030
UR  - PM:3260788
ER  - 

TY  - JOUR
T1  - Neural substrates of violent behaviour. A preliminary study with positron emission tomography
A1  - Volkow,N.D.
A1  - Tancredi,L.
Y1  - 1987/11//
N1  - UI - 88184280
SP  - 668
EP  - 673
JA  - Br.J Psychiatry
VL  - 151
N2  - Brain function was evaluated in four psychiatric patients with a history of repetitive purposeless violent behaviour, using EEG, CT scan, and positron emission tomography (PET). Three patients showed spiking activity in left temporal regions, and two showed CT scan abnormalities characterised by generalised cortical atrophy. The PET scans for the four cases showed evidence of blood flow and metabolic abnormalities in the left temporal lobe. Two patients also had derangement in the frontal cortex. The patients showing the largest defects with the PET scans were those whose CT scans were reported as normal. This paper shows the utility of PET in investigating possible brain derangements that could lead to violent behaviour
AD  - University of Texas Health Science Center, Houston 77225
UR  - PM:3502251
ER  - 

TY  - JOUR
T1  - Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men
A1  - Leyton,M.
A1  - Boileau,I.
A1  - Benkelfat,C.
A1  - Diksic,M.
A1  - Baker,G.
A1  - Dagher,A.
Y1  - 2002/12//
N1  - UI - 22352584
SP  - 1027
EP  - 1035
JF  - Neuropsychopharmacology
VL  - 27
IS  - 6
N2  - Eight healthy men underwent two positron emission tomography (PET) [11C]raclopride scans, one following placebo, the second following d-amphetamine (0.30 mg/kg, p.o.). PET data were analyzed using: (1) brain parametric maps to statistically generate regions of significant change; and (2) a priori identified regions of interest (ROI) manually drawn on each individual's co-registered magnetic resonance (MR) images. Compared with placebo, d-amphetamine decreased [11C]raclopride binding potential (BP) with significant effects in ventral but not dorsal striatum. Change in BP in the statistically generated cluster correlated with self-reported drug-induced 'drug wanting' (r = 0.83, p =.01) and the personality trait of Novelty Seeking-Exploratory Excitability (r = 0.79, p =.02). The same associations were seen in the manually drawn ROI in ventral striatum but not in dorsal putamen or caudate. Changes in extracellular dopamine (DA) did not correlate with mood. Mesolimbic DA might mediate interest in obtaining reward rather than reward, per se. Individual differences in amphetamine-induced DA release might be related to predispositions to drug and novelty seeking
AD  - Department of Psychiatry, McGill University, Montreal, Quebec, Canada. marco.leyton@mcgill.ca
UR  - PM:12464459
ER  - 

TY  - JOUR
T1  - Effects of amphetamine and evoked dopamine release on [11C]raclopride binding in anesthetized cats
A1  - Ginovart,N.
A1  - Hassoun,W.
A1  - Le Cavorsin,M.
A1  - Veyre,L.
A1  - Le Bars,D.
A1  - Leviel,V.
Y1  - 2002/07//
N1  - UI - 22058656
SP  - 72
EP  - 84
JF  - Neuropsychopharmacology
VL  - 27
IS  - 1
N2  - The effects of halothane and ketamine anesthesia on [11C]raclopride binding were assessed in the cat striatum at basal conditions and after drug- or depolarization-induced dopamine (DA) release using Positron Emission Tomography. At baseline, Scatchard analyses revealed that the higher [11C]raclopride binding found under halothane anesthesia was mainly attributable to a higher radioligand apparent affinity. Decreased [11C]raclopride binding was demonstrated following amphetamine under ketamine but not under halothane anesthesia. Under ketamine anesthesia transient DA overflows induced by direct stimulations of DA neurons through an intracerebral electrode induced transient changes in [11C]raclopride binding with a remarkable spatiotemporal accuracy. No effect was observed under halothane anesthesia. The failure to detect competition between DA and [11C]raclopride for binding on D(2)-receptors under halothane anesthesia might reflect, as already reported for other brain receptor systems, a halothane-promoted conversion of D(2)-receptors to a state of lower affinity for DA. It is suggested that the affinity state of receptors is a factor to be considered in in vivo ligand-activation studies
AD  - CERMEP Cyclotron Unit, 59 Boulevard Pinel, 69003 Lyon, France. nginovart@camhpet.on.ca
UR  - PM:12062908
ER  - 

TY  - JOUR
T1  - A PET study of D(1)-like dopamine receptor ligand binding during altered endogenous dopamine levels in the primate brain
A1  - Chou,Y.H.
A1  - Karlsson,P.
A1  - Halldin,C.
A1  - Olsson,H.
A1  - Farde,L.
Y1  - 1999/09//
SP  - 220
EP  - 227
JA  - Psychopharmacology (Berl)
VL  - 146
IS  - 2
N2  - RATIONALE: Several positron emission tomography (PET) studies have shown that radioligand binding to D(2)-like dopamine receptors competes with endogenous dopamine. OBJECTIVE: The purpose of this PET study was to examine the effect of amphetamine and reserpine on D(1)-like dopamine receptor binding. METHODS: Three Cynomolgus monkeys were examined with the radioligands [(11)C]SCH 23390 or [(11)C]NNC 112 at baseline condition and after pretreatment with amphetamine (2 mg/kg IV). The B/F values (binding potential) in the striatum and the neocortex were calculated at transient equilibrium. In two monkeys, the effect of the long-lasting dopamine depletion after reserpine (1 mg/kg IV) was followed by a repeated Scatchard procedure in up to 77 days after drug administration. The Scatchard analysis was based on two PET measurements with high and low specific radioactivity and allowed the calculation of D(1)-like dopamine receptor density (B(max)) and apparent affinity (K(D)(app)). RESULTS: The effect of amphetamine on the B/F values was between -14 and 6%. These changes can be considered as within the range of the test-retest reliability. Thus, there was no evident effect of amphetamine-induced dopamine release on D(1)-like dopamine receptor binding. Five hours after reserpine administration, there was no change in B(max) or K(D)(app). At 3, 23, and 28 days after reserpine administration, the Scatchard analyses indicated a 13-20% reduction in B(max) without any evident change in K(D)(app) in both the striatum and the neocortex. CONCLUSIONS: The lack of evident effects of amphetamine and reserpine on D(1)-like dopamine receptor binding is markedly different from the 20% amphetamine-induced decrease and 50% reserpine-induced increase that has been consistently reported for D(2)-like dopamine receptor binding. The data indicated that D(1)-like dopamine receptor occupancy of endogenous dopamine is low at physiological condition. It is thus unlikely that D(1)-like dopamine receptor radioligands can be used to measure changes in the concentration of endogenous dopamine
AD  - Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm, Sweden. yuanhc@psyk.ks.se
UR  - PM:10525759
ER  - 

TY  - JOUR
T1  - GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans
A1  - Villemagne,V.L.
A1  - Wong,D.F.
A1  - Yokoi,F.
A1  - Stephane,M.
A1  - Rice,K.C.
A1  - Matecka,D.
A1  - Clough,D.J.
A1  - Dannals,R.F.
A1  - Rothman,R.B.
Y1  - 1999/09/15/
SP  - 268
EP  - 273
JF  - Synapse
VL  - 33
IS  - 4
N2  - Major neurochemical effects of methamphetamine include release of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) via a carrier-mediated exchange mechanism. Preclinical research supports the hypothesis that elevations of mesolimbic DA mediate the addictive and reinforcing effects of methamphetamine and amphetamine. This hypothesis has not been adequately tested in humans. Previous in vivo rodent microdialysis demonstrated that the high affinity DA uptake inhibitor, GBR12909, attenuates cocaine- and amphetamine-induced increases in mesolimbic DA. The present study determined the ability of GBR12909 to attenuate amphetamine-induced increases in striatal DA as measured by [(11)C]raclopride continuous infusion positron emission tomography (PET) scans in two Papio anubis baboons. [(11)C]Raclopride was given in a continuous infusion paradigm resulting in a flat volume of distribution vs. time for up to 45 min postinjection. At that time, a 1.5 mg/kg amphetamine i.v. bolus was administered which caused a significant (30.3%) reduction in the volume of distribution (V(3)"). The percent reduction in the volume of distribution and, hence, a measure of the intrasynaptic DA release ranged between 22-41%. GBR12909 (1 mg/kg, slow i.v. infusion) was administered 90 min before the administration of the radiotracer. The comparison of the volume of distribution before and after administration of GBR12909 showed that GBR12909 inhibited amphetamine-induced DA release by 74%. These experiments suggest that GBR12909 is an important prototypical medication to test the hypothesis that stimulant-induced euphoria is mediated by DA and, if the DA hypothesis is correct, a potential treatment agent for cocaine and methamphetamine abuse. Furthermore, this quantitative approach demonstrates a way of testing various treatment medications, including other forms of GBR12909 such as a decanoate derivative
AD  - Departments of Radiology and Environmental Health Sciences, Divisions of Nuclear Medicine and Radiation Health Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0807, USA
UR  - PM:10421707
ER  - 

TY  - JOUR
T1  - Intravenous dextroamphetamine and brain glucose metabolism
A1  - Ernst,M.
A1  - Zametkin,A.J.
A1  - Matochik,J.
A1  - Schmidt,M.
A1  - Jons,P.H.
A1  - Liebenauer,L.L.
A1  - Hardy,K.K.
A1  - Cohen,R.M.
Y1  - 1997/12//
N1  - UI - 98059816
SP  - 391
EP  - 401
JF  - Neuropsychopharmacology
VL  - 17
IS  - 6
N2  - This study reports the effects of intravenous dextroamphetamine on cerebral glucose metabolism assayed by positron emission tomography (PET) and [fluorine-18]fluorodeoxyglucose (FDG) in 13 healthy adults during the performance of a continuous visual attention task. Two FDG PET scans were performed within a single experimental session. The first scan was preceded by the injection of placebo and the second scan by the injection of 0.15 mg/kg dextroamphetamine. Global and normalized regional glucose metabolic rates (rCMRglc) were examined as a function of pharmacological challenge and subjective experience. Subcortical, limbic, frontal, and cerebellar rCMRglc significantly increased after dextroamphetamine, whereas rCMRglc of the temporal cortex significantly decreased. Physiological and self-report measures of subjective states showed the expected alterations. These rCMRglc changes reflect both the direct pharmacological effect of dextroamphetamine on monoaminergic neurotransmitter systems as well as enhancement of the activation of the neural network mediating the performance of the continuous attention task
AD  - Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
UR  - PM:9397427
ER  - 

TY  - JOUR
T1  - Recovery of striatal dopamine function after acute amphetamine- and methamphetamine-induced neurotoxicity in the vervet monkey
A1  - Melega,W.P.
A1  - Raleigh,M.J.
A1  - Stout,D.B.
A1  - Lacan,G.
A1  - Huang,S.C.
A1  - Phelps,M.E.
Y1  - 1997/08/22/
SP  - 113
EP  - 120
JA  - Brain Res
VL  - 766
IS  - 1-2
N2  - In six vervet monkeys, presynaptic striatal dopamine function was assessed longitudinally by [18F]fluoro-L-DOPA (FDOPA)-positron emission tomography (PET) after administration (2 x 2 mg/kg, i.m., 4 h apart) of either amphetamine (Amp), n = 3, or methamphetamine (MeAmp), n = 3. At 1-2 weeks postdrug, both Amp and MeAmp exposure effected similar decreases (60-70%) in the FDOPA influx rate constant (FDOPA Ki), an index of striatal dopamine synthesis capacity. Subsequent studies in these subjects showed that FDOPA Ki values were decreased by 45-67% at 3-6 weeks, by 25% at 10-12 weeks and by 16% in one Amp-treated subject at 32 weeks. Biochemical analysis showed that striatal dopamine concentrations were decreased by 75% at 3-4 weeks and by 55% at 10-12 weeks. These results indicate that in vervet monkey striatum, an acute Amp or MeAmp drug dosage produces extensive striatal dopamine system neurotoxicity. However, these effects were reversible; observed time-dependent recovery in both FDOPA Ki and dopamine concentrations indicates that neurochemical plasticity remains active in the adult primate striatum. At 3-4 and 10-12 weeks postdrug, the concurrent characterization of the striatal FDOPA Ki and dopamine concentrations for individual subjects showed that Ki decreases between 24 and 67% corresponded to dopamine depletions of 55-85%. These relatively larger postdrug decrements in steady-state striatal dopamine concentrations suggest that compensatory increases in dopamine synthesis capacity develop in the partially lesioned striatum. In contrast to the dopamine depletion in striatum, substantia nigra concentrations remained unchanged from referent values at both 3-4 and 10-12 weeks postdrug. Thus, the integrity of the substantia nigra could not be inferred from decreases in the striatal FDOPA Ki parameter. This disparity between striatum and substantia nigra reactivity to systemic administration of amphetamines suggests that each has unique dopamine system regulatory mechanisms
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1735, USA. bmelega@v401.nuc.ucla.edu
UR  - PM:9359594
ER  - 

TY  - JOUR
T1  - Kinetic modeling of [11C]raclopride: combined PET-microdialysis studies
A1  - Endres,C.J.
A1  - Kolachana,B.S.
A1  - Saunders,R.C.
A1  - Su,T.
A1  - Weinberger,D.
A1  - Breier,A.
A1  - Eckelman,W.C.
A1  - Carson,R.E.
Y1  - 1997/09//
N1  - UI - 97452816
SP  - 932
EP  - 942
JA  - J Cereb.Blood Flow Metab
VL  - 17
IS  - 9
N2  - The in vivo binding of D2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [11C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse
AD  - Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
UR  - PM:9307606
ER  - 

TY  - JOUR
T1  - Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion
A1  - Carson,R.E.
A1  - Breier,A.
A1  - de Bartolomeis,A.
A1  - Saunders,R.C.
A1  - Su,T.P.
A1  - Schmall,B.
A1  - Der,M.G.
A1  - Pickar,D.
A1  - Eckelman,W.C.
Y1  - 1997/04//
N1  - UI - 97288248
SP  - 437
EP  - 447
JA  - J Cereb.Blood Flow Metab
VL  - 17
IS  - 4
N2  - Positron emission tomography and single-photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [11C]raclopride by paired bolus injections and with [123I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [11C]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (VT). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. VT values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control VT values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [11C]raclopride study using the B/I method
AD  - Positron Emission Tomography Department, National Institutes of Health, National Institutes of Mental Health, Bethesda, Maryland 20892-1180, USA
UR  - PM:9143226
ER  - 

TY  - JOUR
T1  - Ethological and 6-[18F]fluoro-L-DOPA-PET profiles of long-term vulnerability to chronic amphetamine
A1  - Melega,W.P.
A1  - Raleigh,M.J.
A1  - Stout,D.B.
A1  - Huang,S.C.
A1  - Phelps,M.E.
Y1  - 1997/03//
SP  - 259
EP  - 268
JA  - Behav.Brain Res
VL  - 84
IS  - 1-2
N2  - A chronic 10-day amphetamine (Amp) protocol was used to induce significant long-term decrements of the striatal [18F]fluoro-L-DOPA influx rate constant (FDOPA Ki) in the vervet monkey. Longitudinal FDOPA-positron emission tomography (PET) assessment in Amp-treated subjects subsequently revealed a gradual recovery of striatal dopamine function: FDOPA Ki values were decreased by approximately 70% at 1 month, approximately 45% at 6 months, approximately 20% at 12 months and were similar to pre-Amp values at 24 months. Motoric and social behavioral measures were obtained on all subjects within a species-typical group setting. Behavioral observations were conducted during both basal and stressor-challenge conditions, the latter being created by placing a potential intruder-animal in an individual cage adjacent to the subject's group enclosure. During basal conditions, post-Amp stereotypies were present at 2 weeks and locomotor behaviors were increased throughout 1 month; both alterations occurred while FDOPA Ki values were significantly decreased. Social behaviors were also significantly affected; affiliative behavior was decreased up to 6 months while aggressive behavior was increased for 12 months. However, a different pattern of behavioral changes emerged under stressor-challenge conditions. Motoric and social changes were of greater magnitude and persisted longer than in basal settings while aggressive behavior remained elevated at 24 months. These results indicate that chronic Amp-induced decreases in FDOPA Ki values and behavioral alterations are reversible. Changes in striatal dopamine function as indexed with FDOPA-PET are not correlated with post-Amp alterations in behaviors and moreover, expression of those behaviors is context-dependent
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1735, USA. bmelega@v401.nuc.ucla.edu
UR  - PM:9079790
ER  - 

TY  - JOUR
T1  - Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study
A1  - Mattay,V.S.
A1  - Berman,K.F.
A1  - Ostrem,J.L.
A1  - Esposito,G.
A1  - Van Horn,J.D.
A1  - Bigelow,L.B.
A1  - Weinberger,D.R.
Y1  - 1996/08/01/
N1  - UI - 96335663
SP  - 4816
EP  - 4822
JA  - J Neurosci.
VL  - 16
IS  - 15
N2  - Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine
AD  - Clinical Brain Disorders Branch, Intramural Research Porgram, National Institute of Mental Health, National Institutes of Health Neuroscience Center at Saint Elizabeth's, Washington, DC 20032, USA
UR  - PM:8764668
ER  - 

TY  - JOUR
T1  - Effect of dopaminergic drugs on the in vivo binding of [3H]WIN 35,428 to central dopamine transporters
A1  - Scheffel,U.
A1  - Steinert,C.
A1  - Kim,S.E.
A1  - Ehlers,M.D.
A1  - Boja,J.W.
A1  - Kuhar,M.J.
Y1  - 1996/06//
SP  - 61
EP  - 69
JF  - Synapse
VL  - 23
IS  - 2
N2  - [11C]WIN 35,428 (also designated [11C]CFT) is now being used in several positron emission tomography (PET) centers to image dopamine (DA) transporter sites in the mammalian brain. Whether and to what extent in vivo WIN 35,428 binding is influenced by intra- and extrasynaptic dopamine levels are largely unknown. The purpose of the present study was to evaluate the effects of various drugs, known to affect DA levels and release, on the binding of [3H]WIN 35,428 to central DA transporters in the mouse brain. D-Amphetamine, which releases DA from neurons and blocks the DA transporter directly, inhibited striatal [3H]WIN 35,428 binding in dose-dependent manner. Similarly, alpha-methyl-DL-p-tyrosine, an inhibitor of tyrosine hydroxylase, blocked [3H]WIN 35,428 binding, possibly via competitive inhibition by the metabolite p-hydroxyamphetamine. Specific binding of [3H]WIN 35,428 was insensitive to changes in synaptic DA levels caused by pretreatment of the animals with high doses of D2 receptor agonists (apomorphine, bromocriptine), antagonists (haloperidol) or the inhibitor of dopaminergic neuron firing gamma-butyrolactone (GBL). High doses (> 50 mg/kg) of L-DOPA (in combination with benserazide), however, reduced [3H]WIN 35,428 binding significantly, yet for a relatively short time (approximately 2.5 h). Chronic treatment with L-deprenyl elicited no changes in in vivo [3H]WIN 35,428 accumulation in the striatum. Neurotoxic damage of DA neurons caused by administration of high doses of amphetamine was detected in the striatum by a significant reduction in [3H]WIN 35,428 binding 7 days after cessation of amphetamine treatment. Thus, [3H]WIN 35,428 binding was only affected by neurotoxic loss of neurons, by administration of uptake inhibitors, or by some treatments which significantly elevate DA levels. Compounds which inhibit DA release or deplete DA acutely do not increase [3H]WIN 35,428 binding, suggesting that normal or "resting" levels of DA are not sufficient to alter [3H]WIN 35,428 binding in vivo. These findings are important for our understanding of the function and regulation of the DA transporter, as well as the in vivo binding of the radioligand [3H/11 C]WIN 35,428. Moreover, they will be important for the interpretation of PET studies in which [11C]WIN 35,428 is used to assess the integrity of dopaminergic neurons
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
UR  - PM:8723710
ER  - 

TY  - JOUR
T1  - In vivo striatal binding of the D1 antagonist SCH 23390 is not modified by changes in dopaminergic transmission
A1  - Thibaut,F.
A1  - Vaugeois,J.M.
A1  - Bonnet,J.J.
A1  - Costentin,J.
Y1  - 1996/03//
N1  - UI - 96377360
SP  - 267
EP  - 272
JF  - Neuropharmacology
VL  - 35
IS  - 3
N2  - The in vivo striatal binding of [3H]SCH 23390, an antagonist of the D1 dopamine receptors, was investigated in mice submitted to pretreatment to either decrease (gammabutyrolactone 750 mg/kg, i.p.) or, increase (3,4-dihydroxyphenylalanine (L-DOPA) 200 mg/kg i.p. plus dexamphetamine 4 mg/kg, s.c.) dopaminergic transmission. Such conditions failed to modify [3H]SCH 23390 binding. However, we observed that dopamine (at concentrations > or = 1 microM), reduced the in vitro binding of [3H]SCH 23390 in membrane fractions. These results suggest that modifications in dopamine neurotransmission do not alter the in vivo quantification of D1 receptors with [3H]SCH 23390, for example, in studies that use positron emission tomography
AD  - Unite de Neuropsychopharmacologie Experimentale, Saint Etienne du Rouvray, France
UR  - PM:8783200
ER  - 

TY  - JOUR
T1  - Positron Emission Tomography Studies of Potential Mechanisms Underlying Phencyclidine-Induced Alterations in Striatal Dopamine
A1  - Schiffer,W.K.
A1  - Logan,J.
A1  - Dewey,S.L.
Y1  - 2003/07/23/
N1  - UI - 0
JF  - Neuropsychopharmacology
VL  - epub
N2  - Positron emission tomography (PET), in combination with (11)C-raclopride, was used to examine the effects of phencyclidine (PCP) on dopamine (DA) in the primate striatum. In addition, we explored the hypotheses that GABAergic pathways as well as molecular targets beyond the N-methyl-D-aspartate (NMDA) receptor complex (ie dopamine transporter proteins, DAT) contribute to PCP's effects. In the first series of experiments, (11)C-raclopride was administered at baseline and 30 min following intravenous PCP administration. In the second series of studies, gamma-vinyl GABA (GVG) was used to assess whether enhanced GABAergic tone altered NMDA antagonist-induced changes in DA. Animals received an initial PET scan followed by pretreatment with GVG (300 mg/kg), then PCP 30 min prior to a second scan. Finally, we explored the possible contributions of DAT blockade to PCP-induced increases in DA. By examining (11)C-cocaine binding a paradigm in which PCP was coadministered with the radiotracer, we assessed the direct competition between these two compounds for the DAT. At 0.1, 0.5, and 1.0 mg/kg, PCP decreased (11)C-raclopride binding by 2.1, 14.9+/-2.2 and 8.18+/-1.1%, respectively. These effects were completely attenuated by GVG (3.38+/-3.1% decrease in (11)C-raclopride binding). Finally, PCP (0.5 mg/kg) decreased (11)C-cocaine binding by 25.5+/-4.3%, while at 1.0 mg/kg this decrease was 13.5%, consistent with a competitive interaction at the DAT. These results suggest that PCP may be exerting some direct effects through the DAT and that GABA partially modulates NMDA-antagonist-induced increases in striatal DA.Neuropsychopharmacology advance online publication, 23 July 2003; doi:10.1038/sj.npp.1300258
AD  - [1] 1SUNY Stony Brook, Department of Neurobiology and Behavior, Stony Brook, NY, USA [2] 2Brookhaven National Laboratory, Chemistry Department, Upton, NY, USA
UR  - PM:12888780
ER  - 

TY  - JOUR
T1  - Bupropion occupancy of the dopamine transporter is low during clinical treatment
A1  - Meyer,J.H.
A1  - Goulding,V.S.
A1  - Wilson,A.A.
A1  - Hussey,D.
A1  - Christensen,B.K.
A1  - Houle,S.
Y1  - 2002/08//
SP  - 102
EP  - 105
JA  - Psychopharmacology (Berl)
VL  - 163
IS  - 1
N2  - RATIONALE: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design. RESULTS: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion
AD  - Department of Psychiatry, PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. jmeyer@camhpet.on.ca
UR  - PM:12185406
ER  - 

TY  - JOUR
T1  - Age-related changes in the striatal dopaminergic system in the living brain: a multiparametric PET study in conscious monkeys
A1  - Harada,N.
A1  - Nishiyama,S.
A1  - Satoh,K.
A1  - Fukumoto,D.
A1  - Kakiuchi,T.
A1  - Tsukada,H.
Y1  - 2002/07//
SP  - 38
EP  - 45
JF  - Synapse
VL  - 45
IS  - 1
N2  - In the present study, age-related changes in the striatal dopaminergic system were examined in the living brains of conscious young (6.2 +/- 1.5 years old) and aged (20.2 +/- 2.6 years old) monkeys (Macaca mulatta) using positron emission tomography (PET). L-[beta-(11)C]DOPA and [(11)C]beta-CFT were applied to determine dopamine presynaptic functions such as synthesis rate and transporter (DAT) availability, respectively. Striatal dopamine D(1)- (D(1)R) and D(2)-like receptor (D(2)R) binding were measured with [(11)C]SCH23390 and [(11)C]raclopride, respectively. Although the markers of presynaptic terminals showed parallel age-related declines, the reduction of dopamine synthesis rate measured with L-[beta-(11)C]DOPA was slightly smaller than that of DAT determined with [(11)C]beta-CFT. The binding of [(11)C]raclopride to D(2)R in vivo was significantly reduced with aging, while that of [(11)C]SCH23390 to D(1)R showed no such marked age-related reduction. When the DAT inhibitor GBR12909 (0.5 and 5 mg/kg) was administered, DAT availability, dopamine synthesis, and D(2)R binding were significantly decreased in a dose-dependent manner in both age groups; however, the degrees of the decreases in these parameters were significantly higher in young rather than in aged animals. Dopamine concentration in the striatal extracellular fluid (ECF), as measured by microdialysis, was increased by administration of GBR12909 in a dose-dependent manner and the degree of the increase in dopamine level decreased with age. These results demonstrate that age-related changes of dopamine neuronal functions were not limited to the resting condition but were also seen in the functional responses to the neurotransmitter modulation
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434-8601, Japan
UR  - PM:12112412
ER  - 

TY  - JOUR
T1  - Cocaine-induced brain activation determined by positron emission tomography neuroimaging in conscious rhesus monkeys
A1  - Howell,L.L.
A1  - Hoffman,J.M.
A1  - Votaw,J.R.
A1  - Landrum,A.M.
A1  - Wilcox,K.M.
A1  - Lindsey,K.P.
Y1  - 2002/01//
N1  - UI - 21851426
SP  - 154
EP  - 160
JA  - Psychopharmacology (Berl)
VL  - 159
IS  - 2
N2  - RATIONALE: Cerebral blood flow can provide a useful dependent measure to characterize cocaine-induced changes in brain function. The acute effects of cocaine administration on cerebral blood flow may have direct relevance to the etiology of cocaine addiction. OBJECTIVES: The present study used positron emission tomography (PET) neuroimaging techniques to characterize the acute effects of cocaine administration on cerebral blood flow in conscious rhesus monkeys. METHODS: Functional changes in cerebral blood flow were determined in four drug-naive subjects with the positron-emitting tracer 15O water following acute i.v. administration of cocaine (0.3 and 1.0 mg/kg). Specific attention was devoted to the development of an effective and comfortable head restraint device to use in the imaging of conscious monkeys. Experimental sessions comprised eight consecutive i.v. injections of 15O water at 10-min intervals. PET scans of 90 s duration occurred 10 s after each injection. RESULTS: Repeated baseline determinations of cerebral blood flow prior to drug administration were reliable. Cocaine had significant, dose-related effects on cerebral blood flow at 5 min postinjection that diminished relative to control (saline) conditions by 15 min postinjection. Brain activation maps normalized to global flow showed prominent cocaine-induced activation of prefrontal cortex localized primarily to dorsolateral regions. Importantly, cocaine-induced brain activation was blocked by pretreatment with the selective serotonin uptake inhibitor, alaproclate (3.0 and 10.0 mg/kg). The results document a distinct pattern of cocaine-induced brain activation that is sensitive to pharmacological manipulation. CONCLUSION: The pattern of brain activation induced by acute administration of cocaine may provide a useful means to evaluate medication effectiveness for treating cocaine addiction
AD  - Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322, USA. leonard@rmy.emory.edu
UR  - PM:11862343
ER  - 

TY  - JOUR
T1  - Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration
A1  - Morgan,D.
A1  - Grant,K.A.
A1  - Gage,H.D.
A1  - Mach,R.H.
A1  - Kaplan,J.R.
A1  - Prioleau,O.
A1  - Nader,S.H.
A1  - Buchheimer,N.
A1  - Ehrenkaufer,R.L.
A1  - Nader,M.A.
Y1  - 2002/02//
N1  - UI - 21676861
SP  - 169
EP  - 174
JA  - Nat.Neurosci.
VL  - 5
IS  - 2
N2  - Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction
AD  - Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA
UR  - PM:11802171
ER  - 

TY  - JOUR
T1  - Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter
A1  - Gu,X.H.
A1  - Zong,R.
A1  - Kula,N.S.
A1  - Baldessarini,R.J.
A1  - Neumeyer,J.L.
Y1  - 2001/12/03/
SP  - 3049
EP  - 3053
JA  - Bioorg.Med Chem.Lett.
VL  - 11
IS  - 23
N2  - A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of beta-CIT (19), the fluoroethyl ester of beta-CIT (20), the N-fluoropropyl derivative of beta-CBT (12), and the fluoropropyl ester of beta-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of (18)F-labeled PET imaging agents for the DAT
AD  - Medicinal Chemistry Laboratory, Alcohol and Drug Abuse Research Center, Belmont, MA 02478-9106, USA
UR  - PM:11714608
ER  - 

TY  - JOUR
T1  - Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET
A1  - Sekine,Y.
A1  - Iyo,M.
A1  - Ouchi,Y.
A1  - Matsunaga,T.
A1  - Tsukada,H.
A1  - Okada,H.
A1  - Yoshikawa,E.
A1  - Futatsubashi,M.
A1  - Takei,N.
A1  - Mori,N.
Y1  - 2001/08//
SP  - 1206
EP  - 1214
JA  - Am J Psychiatry
VL  - 158
IS  - 8
N2  - OBJECTIVE: A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics. METHOD: PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score. RESULTS: The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. CONCLUSIONS: These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density
AD  - Department of Psychiatry and Neurology, Hamamatsu School of Medicine, 3600 Handa-cho Hamamatsu, 431-3192 Shizuoka, Japan. ysekine@hama-med.ac.jp
UR  - PM:11481152
ER  - 

TY  - JOUR
T1  - An apparatus and behavioral training protocol to conduct positron emission tomography (PET) neuroimaging in conscious rhesus monkeys
A1  - Howell,L.L.
A1  - Hoffman,J.M.
A1  - Votaw,J.R.
A1  - Landrum,A.M.
A1  - Jordan,J.F.
Y1  - 2001/04/30/
N1  - UI - 21225789
SP  - 161
EP  - 169
JA  - J Neurosci.Methods
VL  - 106
IS  - 2
N2  - Nonhuman primates offer a unique resource in neuroimaging research, providing the opportunity to manipulate appropriate biological and behavioral variables under well-controlled experimental conditions in an animal model that is closely related to humans, both functionally and neuroanatomically. The present report describes the development and standardization of PET neuroimaging protocols in conscious rhesus monkeys and their application to characterize the acute effects of cocaine on cerebral blood flow. Specific attention was devoted to the development of an effective and comfortable head restraint device to be used in the imaging of conscious monkeys. The restraint device was designed to attach to a standard primate chair to facilitate frequent immobilization. Subjects received extensive behavioral training prior to neuroimaging in order to ensure their comfort and minimize potential stress associated with the imaging protocols. Functional changes in cerebral blood flow were characterized in three subjects with the positron-emitting tracer 15O water following acute i.v. administration of cocaine. Regions of interest were defined on MRI scans with a high degree of accuracy. Cocaine caused pronounced increases in cerebral blood flow at 5 min postinjection that diminished markedly within 25 min. The results document the feasibility to conduct PET neuroimaging studies of cerebral blood flow in conscious nonhuman primates. Extension of the methodology to include brain activation during behavioral studies could contribute significantly to the growing discipline of behavioral neuroscience
AD  - Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322, USA. leonard@rmy.emory.edu
UR  - PM:11325436
ER  - 

TY  - JOUR
T1  - Neural activity related to drug craving in cocaine addiction
A1  - Kilts,C.D.
A1  - Schweitzer,J.B.
A1  - Quinn,C.K.
A1  - Gross,R.E.
A1  - Faber,T.L.
A1  - Muhammad,F.
A1  - Ely,T.D.
A1  - Hoffman,J.M.
A1  - Drexler,K.P.
Y1  - 2001/04//
N1  - UI - 21191565
SP  - 334
EP  - 341
JF  - Archives of General Psychiatry
JA  - Arch Gen Psychiatry
VL  - 58
IS  - 4
N2  - BACKGROUND: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. METHODS: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition. RESULTS: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites. CONCLUSIONS: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex)
AD  - Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1639 Pierce Dr, Suite 4000, PO Drawer AF, Atlanta, GA 30322, USA. sdpcdk@emory.edu
UR  - PM:11296093
ER  - 

TY  - JOUR
T1  - Neural activity related to anger in cocaine-dependent men: a possible link to violence and relapse
A1  - Drexler,K.
A1  - Schweitzer,J.B.
A1  - Quinn,C.K.
A1  - Gross,R.
A1  - Ely,T.D.
A1  - Muhammad,F.
A1  - Kilts,C.D.
Y1  - 2000///
N1  - UI - 21028924
SP  - 331
EP  - 339
JA  - Am J Addict.
VL  - 9
IS  - 4
N2  - This study examined the neural correlates of cue-induced anger in cocaine-dependent men in an initial investigation of possible neurobiological explanations for the putative association between cocaine addiction and violence. We used positron emission tomography (PET) to localize alterations in regional cerebral blood flow (rCBF) during mental imagery of a personal anger-associated scene and of an emotionally neutral scene in ten cocaine-dependent men. Compared to the emotionally neutral imagery control condition, anger was associated with marked decreases in rCBF in multiple areas of the frontal cortex (particularly the right inferior frontal gyrus), left posterior insula, left fusiform gyrus, and midbrain. Conversely, this same inferior frontal area was activated by anger imagery in nicotine-dependent men. Anger was also associated with increases in rCBF in the right fusiform gyrus, right and left middle occipital gyri, left post-central gyrus, left medial frontal gyrus, left cuneus, and in the left anterior cingulate gyrus. The study showed that cue-induced anger in cocaine-dependent men was associated with decreased activity in frontal cortical areas involved in response monitoring and inhibition. The lack of this association in nicotine-dependent men suggests a possible deficit in anger regulation associated with cocaine dependence and a possible link between cocaine dependence, violence, and relapse
AD  - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga., USA. karen.drexler@med.va.gov
UR  - PM:11155786
ER  - 

TY  - JOUR
T1  - Cholinergic neuronal modulation alters dopamine D2 receptor availability in vivo by regulating receptor affinity induced by facilitated synaptic dopamine turnover: positron emission tomography studies with microdialysis in the conscious monkey brain
A1  - Tsukada,H.
A1  - Harada,N.
A1  - Nishiyama,S.
A1  - Ohba,H.
A1  - Kakiuchi,T.
Y1  - 2000/09/15/
SP  - 7067
EP  - 7073
JA  - J Neurosci.
VL  - 20
IS  - 18
N2  - To evaluate the cholinergic and dopaminergic neuronal interaction in the striatum, the effects of scopolamine, a muscarinic cholinergic antagonist, on the striatal dopaminergic system were evaluated multi-parametrically in the conscious monkey brain using high-resolution positron emission tomography in combination with microdialysis. l-3,4-Dihydroxyphenylalanine (l-[beta-(11)C]DOPA) and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane ([beta-(11)C]CFT) were used to measure dopamine synthesis rate and dopamine transporter (DAT) availability, respectively. For assessment of dopamine D(2) receptor binding in vivo, [(11)C]raclopride was applied because this labeled compound, which has relatively low affinity to dopamine D(2) receptors, was hypothesized to be sensitive to the striatal synaptic dopamine concentration. Systemic administration of scopolamine at doses of 10 and 100 microg/kg dose-dependently increased both dopamine synthesis and DAT availability as measured by l-[beta-(11)C]DOPA and [beta-(11)C]CFT, respectively. Scopolamine decreased the binding of [(11)C]raclopride in a dose-dependent manner. Scopolamine induced no significant changes in dopamine concentration in the striatal extracellular fluid (ECF) as determined by microdialysis. However, scopolamine dose-dependently facilitated the striatal ECF dopamine induced by the DAT inhibitor GBR12909 at a dose of 0.5 mg/kg. Scatchard plot analysis in vivo of [(11)C]raclopride revealed that scopolamine reduced the apparent affinity of dopamine D(2) receptors. These results suggested that the inhibition of muscarinic cholinergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability, resulting in no significant changes in apparent "static" ECF dopamine level but showing a decrease in [(11)C]raclopride binding in vivo attributable to the reduction of affinity of dopamine D(2) receptors
AD  - Central Research Laboratory, Hamamatsu Photonics K. K., Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
UR  - PM:10995853
ER  - 

TY  - JOUR
T1  - 2Beta-carbomethoxy-3beta-(4- and 2-[18F]fluoromethylphenyl)tropanes: specific probes for in vivo quantification of central dopamine transporter sites
A1  - Stout,D.
A1  - Petric,A.
A1  - Satyamurthy,N.
A1  - Nguyen,Q.
A1  - Huang,S.C.
A1  - Namavari,M.
A1  - Barrio,J.R.
Y1  - 1999/11//
SP  - 897
EP  - 903
JA  - Nucl Med Biol.
VL  - 26
IS  - 8
N2  - Dopamine reuptake transporter binding kinetics of 2beta-carbomethoxy-3beta-(4-[18F]fluoromethylphenyl)tropane (p-FWIN) and 2beta-carbomethoxy-3beta-(2-[18F]fluoromethylphenyl)tropane (o-FWIN) were determined in vervet monkeys using positron emission tomography (PET). Ligand localization was rapid and specific to the striatum with kinetic estimates comparable with those of 11C-labeled WIN 35,428 (CWIN). Binding was more specific with p-FWIN than with CWIN or o-FWIN. The relatively longer half-life of the 18F radiolabel enabled longer acquisition times with p-FWIN, resulting in less variability in the kinetic estimates
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-6948, USA
UR  - PM:10708303
ER  - 

TY  - JOUR
T1  - Long-term methamphetamine-induced decreases of [(11)C]WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey
A1  - Melega,W.P.
A1  - Lacan,G.
A1  - DeSalles,A.A.
A1  - Phelps,M.E.
Y1  - 2000/03/15/
SP  - 243
EP  - 249
JF  - Synapse
VL  - 35
IS  - 4
N2  - The effects of glial cell line-derived neurotrophic factor (GDNF) pretreatment on methamphetamine (METH)-induced striatal dopamine system deficits in the vervet monkey were characterized with [(11)C]WIN 35,428 (WIN)-positron emission tomography (PET). WIN, a cocaine analog that binds to the dopamine transporter (DAT), was used to provide an index of striatal dopamine terminal integrity. In two subjects, GDNF (200 microg/40 microl) was injected into the caudate and putamen unilaterally vs. saline contralaterally. After 1-2 weeks, + and -GDNF striatal WIN-PET binding values were equivalent as calculated by multiple time graphic analysis, suggestive of an absence of unilateral DAT up-regulation. Three other subjects (n = 3) received GDNF injections into the caudate and putamen unilaterally and one week later, were administered METH HCl (2 x 2 mg/kg; i.m., 24 hours apart; a neurotoxic dosage for this species). At 1 week post-METH, WIN-PET studies showed that mean WIN binding was decreased by 72% in the +GDNF and by 92% in the -GDNF striatum relative to pre-drug assessment values. Thus, GDNF pretreatment reduced the extent of METH-induced decreases in WIN binding. Subsequent WIN-PET studies (1.5-9-month range) showed a protracted recovery of WIN binding in each striatum, indicative of long-term but partially reversible METH neurotoxicity. Further, at each time point, WIN binding remained relatively higher in the +GDNF vs. -GDNF striatum. These results provide further evidence that the adult non-human primate brain remains responsive to exogenously administered GDNF and that this pharmacotherapy approach can counteract aspects of neurotoxic actions associated with methamphetamine
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles CA 90095-1735, USA. wmelega@mednet.ucla.edu
UR  - PM:10657033
ER  - 

TY  - JOUR
T1  - A selective radiobrominated cocaine analogue for imaging of dopamine uptake sites: pharmacological evaluation and PET experiments
A1  - Helfenbein,J.
A1  - Loc'h,C.
A1  - Bottlaender,M.
A1  - Emond,P.
A1  - Coulon,C.
A1  - Ottaviani,M.
A1  - Fuseau,C.
A1  - Chalon,S.
A1  - Guenther,I.
A1  - Besnard,J.C.
A1  - Frangin,Y.
A1  - Guilloteau,D.
A1  - Maziere,B.
Y1  - 1999///
SP  - 2715
EP  - 2726
JA  - Life Sci.
VL  - 65
IS  - 25
N2  - (E)-N-(3-bromoprop-2-enyl)-2beta-carbomethoxy-3beta-4'-tolyl -nortropane or PE2Br, an analogue of cocaine was labelled with the positron emitter 76Br (T1/2=16 h) for pharmacological evaluation in the rat and PET investigation in the monkey. [76Br]PE2Br was obtained by electrophilic substitution from the tributylstannyl precursor with radiochemical yield of 80%. In vivo biodistribution studies of [76Br]PE2Br (20 MBq/nmol) in rats showed a high uptake in the striatum (2.2% ID/g tissue at 15 min p.i.). The striatum to cerebellum radioactivity ratio was 6 at 1 hour p.i. Striatal uptake of [76Br]PE2Br was almost completely prevented by pretreatment with GBR 12909, but citalopram and maprotiline had no effect, confirming the selectivity of the radioligand for the dopamine transporter. PET imaging of the biodistribution of [76Br]PE2Br in the baboon demonstrated rapid and high uptake in the brain (5% ID at 3 min p.i.). The striatal radioactivity concentration reached a plateau at 20 min p.i. (7% ID/100 mL). The uptake in the cortex and cerebellum was very low. A significantly higher uptake in the thalamus was observed. At 1h p.i., the striatum to cerebellum ratio and thalamus to cerebellum ratio were 8 and 1.9 respectively. In competition experiments the radioactivity in the striatum and the thalamus was displaced by 5 mg/kgof cocaine and 5 mg/kg of GBR 12909, but citalopram and maprotiline had no effect. These results showed that [76Br]PE2Br is in vivo a potent and selective radioligand suitable for PET imagingof the dopamine transporter
AD  - INSERM U316 Laboratoire de Biophysique Medicale et Pharmaceutique, Tours, France
UR  - PM:10622281
ER  - 

TY  - JOUR
T1  - Isoflurane anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain
A1  - Tsukada,H.
A1  - Nishiyama,S.
A1  - Kakiuchi,T.
A1  - Ohba,H.
A1  - Sato,K.
A1  - Harada,N.
A1  - Nakanishi,S.
Y1  - 1999/12/04/
SP  - 85
EP  - 96
JA  - Brain Res
VL  - 849
IS  - 1-2
N2  - The effects of the dopamine transporter (DAT) inhibitors cocaine and GBR12909 on DAT and dopamine D(2) receptors were evaluated in the brains under awake and isoflurane-anesthetized monkeys using high-resolution positron emission tomography (PET) in combination with microdialysis. The striatal DAT availability and dopamine D(2) receptor binding were assayed with [11C]beta-CFT (WIN35,428) and [11C]raclopride, respectively. Cocaine or GBR12909 at a dose of 2 mg/kg was administered intravenously 30 min prior to the injection of labeled compounds. In the awake state, the in vivo binding of [11C]beta-CFT to DAT was significantly decreased by administration of cocaine or GBR12909 at a dose of 2 mg/kg. In contrast, [11C]raclopride binding to dopamine D(2) receptors was decreased only by GBR12909. Under isoflurane anesthesia, dopamine concentration in the striatal extracellular fluid (ECF), as measured by microdialysis, was markedly increased by cocaine or GBR12909 compared to the awake state. Isoflurane anesthesia more markedly enhanced the binding of [11C]beta-CFT in the saline-injected animals, and the degrees of reduction by cocaine and GBR12909 were more marked than those observed in the awake state. Under isoflurane anesthesia, the binding of [11C]raclopride was reduced not only by GBR12909 but also by cocaine which did not affect the binding in the awake state. Taken together, these observations indicated that isoflurane anesthesia enhanced not only the direct inhibitory effects of cocaine and GBR12909 on DAT, but also their indirect effects on dopamine D(2) receptors
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Japan. tsukada@crl.hpk.co.jp
UR  - PM:10592290
ER  - 

TY  - JOUR
T1  - Synthesis of 3beta-(4-[18F]fluoromethylphenyl)- and 3beta-(2-[18F] fluoromethylphenyl)tropane-2beta-carboxylic acid methyl esters: new ligands for mapping brain dopamine transporter with positron emission tomography
A1  - Petric,A.
A1  - Barrio,J.R.
A1  - Namavari,M.
A1  - Huang,S.C.
A1  - Satyamurthy,N.
Y1  - 1999/07//
N1  - UI - 99400170
SP  - 529
EP  - 535
JA  - Nucl Med Biol.
VL  - 26
IS  - 5
N2  - The synthesis of two new dopamine transporter ligands, 3beta-(4-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester and 3beta-(2-fluoromethylphenyl)tropane-2beta-carboxylic acid methyl ester, and their spectral characterization are described. The precursors for these ligands were prepared by TiCl4 catalyzed chloromethylation of 3beta-phenyltropane-2beta-carboxylic acid methyl ester followed by separation of the isomeric product mixture of 2- and 4-chloromethylphenyltropane derivatives. Reaction of the chloromethyl analogs with no-carrier-added [18F]fluoride ion followed by high performance liquid chromatography purification provided the corresponding [18F]fluoromethyltropanes, in good radiochemical yields, useful for imaging the brain dopamine transporter system in vivo with positron emission tomography
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-6948, USA
UR  - PM:10473191
ER  - 

TY  - JOUR
T1  - PET examination of three potent cocaine derivatives as specific radioligands for the serotonin transporter
A1  - Helfenbein,J.
A1  - Sandell,J.
A1  - Halldin,C.
A1  - Chalon,S.
A1  - Emond,P.
A1  - Okubo,Y.
A1  - Chou,Y.H.
A1  - Frangin,Y.
A1  - Douziech,L.
A1  - Gareau,L.
A1  - Swahn,C.G.
A1  - Besnard,J.C.
A1  - Farde,L.
A1  - Guilloteau,D.
Y1  - 1999/07//
SP  - 491
EP  - 499
JA  - Nucl Med Biol.
VL  - 26
IS  - 5
N2  - Several positron emission tomography (PET) radioligands based on the aryl tropane structure have been used for studies on monoamine reuptake sites. RTI-364, RTI-330, and RTI-357 (3-beta-(4'-n-propyl-,4'-iso-propyl-, and 4'-iso-propenyl-phenyl)nortropane-2-beta-carboxylic acid methyl ester) are three recently synthesized cocaine analogues with higher affinity for the serotonin (5-HTT) than the dopamine transporter (DAT). Unlabelled RTI-364 and RTI-330 were prepared in a two-step synthesis. The key step was the addition of the appropriate propyl Grignard reagent to anhydroecgonine methyl ester. RTI-357 was prepared in a three-step synthesis with a palladium-catalyzed coupling reaction of beta-CIT and isopropenylzinc bromide as key step. Hydrolysis of the ester functions gave the carboxylic acid analogues of RTI-364, RTI-330, and RTI-357, which were labelled with 11C using [11C]methyl iodide in dimethyl formamide (DMF) and tetrabutylammonium hydroxide (TBAH) as base. All three compounds entered the monkey brain in a high degree (approximately 5-10%). There was a low uptake of [11C]RTI-364 in serotonin-rich brain areas, whereas [11C]RTI-330 and [11C]RTI-357 showed a marked uptake of radioactivity in the thalamus and the brainstem, regions known to contain serotonin transporters. Transient equilibrium was reached at 15 and 40 min for [11C]RTI-330 and [11C]RTI-357, respectively. After pretreatment with citalopram, the ratio of radioactivity in the thalamus and the brainstem to the cerebellum were markedly reduced for [11C]RTI-357 but not for [11C]RTI-330. The results indicate that [11C]RTI-357 is a potential PET radioligand for quantitation of the serotonin reuptake site
AD  - INSERM U316 Universite Francois Rabelais, Tours, France
UR  - PM:10473187
ER  - 

TY  - JOUR
T1  - Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria
A1  - Bartzokis,G.
A1  - Beckson,M.
A1  - Newton,T.
A1  - Mandelkern,M.
A1  - Mintz,J.
A1  - Foster,J.A.
A1  - Ling,W.
A1  - Bridge,T.P.
Y1  - 1999/06//
N1  - UI - 99259411
SP  - 582
EP  - 590
JF  - Neuropsychopharmacology
VL  - 20
IS  - 6
N2  - To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence
AD  - Psychiatry Service, Little Rock VA Medical Center, AR 72114, USA
UR  - PM:10327427
ER  - 

TY  - JOUR
T1  - Doses of GBR12909 that suppress cocaine self-administration in non-human primates substantially occupy dopamine transporters as measured by [11C] WIN35,428 PET scans
A1  - Villemagne,V.L.
A1  - Rothman,R.B.
A1  - Yokoi,F.
A1  - Rice,K.C.
A1  - Matecka,D.
A1  - Dannals,R.F.
A1  - Wong,D.F.
Y1  - 1999/04//
N1  - UI - 99202520
SP  - 44
EP  - 50
JF  - Synapse
VL  - 32
IS  - 1
N2  - GBR12909 (GBR) is a high-affinity, selective, and long-acting inhibitor of dopamine (DA) uptake that produces a persistent and noncompetitive blockade of DA transporters and substantially reduces cocaine-induced increases in extracellular DA in the nucleus accumbens of rats. Prior studies showed that intravenous infusion of GBR to Rhesus monkeys selectively reduced (1 mg/kg) and eliminated (3 mg/kg) cocaine self-administration. This study tested the hypothesis that doses of GBR that reduce cocaine self-administration in nonhuman primates produce significant occupation of DA transporters. DA transporters were quantitated in two baboons using [11C]WIN35,428 and positron emission tomography (PET). Each baboon underwent paired control/blocked PET scans (performed on three separate study days, 3-4 weeks apart). On the first scan the baboon received saline (3 ml/kg) 90 minutes before the injection of the radiotracer. GBR (1 mg/kg i.v.) was infused 90 minutes before the second [11C]WIN 35,428 study. The same experimental design was repeated with GBR doses of 3 and 10 mg/kg, respectively. Doses of 1 (n = 2), 3 mg/kg (n = 2), and 10 mg/kg (n = 2) reduced binding potential by 26, 53, and 72%, respectively. GBR was well tolerated in all baboons. These results demonstrate that doses of GBR that suppress cocaine self-administration in nonhuman primates also produce high occupancy of the DA transporter. These data strongly suggest that occupancy for the DA transporter by GBR explains its ability to attenuate cocaine-induced increases in extracellular DA and to suppress cocaine self-administration. Moreover, these data suggest that experimental human studies of orally administered GBR to test the DA hypothesis of cocaine addiction should use doses that produce at least 70% occupancy of the DA transporter
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0807, USA
UR  - PM:10188637
ER  - 

TY  - JOUR
T1  - Dizocilpine and reduced body temperature do not prevent methamphetamine-induced neurotoxicity in the vervet monkey
A1  - Melega,W.P.
A1  - Lacan,G.
A1  - Harvey,D.C.
A1  - Huang,S.C.
A1  - Phelps,M.E.
Y1  - 1998/12/11/
N1  - UI - 99091269
SP  - 17
EP  - 20
JA  - Neurosci.Lett.
VL  - 258
IS  - 1
N2  - [11C]WIN 35,428 (WIN), a cocaine analog that binds to the dopamine transporter (DAT), and positron emission tomography (PET) were used to evaluate the potential neuroprotective effects of dizocilpine (MK-801) on methamphetamine (MeAmp) induced neurotoxicity in the striatal dopamine system of the vervet monkey. MK-801 (1 mg/kg, i.m.) was administered 30 min prior to a neurotoxic MeAmp dosage for this species (2 x 2 mg/kg, 4 h apart); control subjects received MeAmp. MK-801 treated subjects were anesthetized by the drug for 6-8 h; throughout that period, a 2-3 degrees C decrease in body temperature was measured. At 1-2 weeks post-MeAmp, decreases of approximately 75% in striatal WIN binding were observed for both MK-801/MeAmp and MeAmp subjects. Thus, in this non-human primate species, the combination of MK-801 pretreatment and reduced body temperature did not provide protection from the MeAmp-induced loss of DAT. Further, the absence of an elevated body temperature during the acute MeAmp exposure period indicated that hyperthermia, per se, was not a necessary concomitant of the MeAmp neurotoxicity profile as has been previously demonstrated in rodents. These results provide evidence that different regulatory factors maintain the integrity of the rodent and primate striatal dopamine systems
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1735, USA. wmelega@mednet.ucla.edu
UR  - PM:9876041
ER  - 

TY  - JOUR
T1  - Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals
A1  - Hume,S.P.
A1  - Gunn,R.N.
A1  - Jones,T.
Y1  - 1998/02//
SP  - 173
EP  - 176
JA  - Eur.J Nucl Med
VL  - 25
IS  - 2
N2  - With the stated aim of scanning small regions of interest in mice, several high-resolution positron emission tomographic (PET) systems are presently under development. Some, however, have low sensitivity and require high doses of radioactivity to achieve count statistics adequate to reconstruct small volumes. Using in vivo dissociation constants for three carbon-11 labelled ligands previously measured in rat brain, the present paper utilises simple saturation kinetics to estimate the limits on radioactivity and specific activity, to minimise the degree of receptor occupancy and achieve maximal specific binding of the radioligand. The extent of the problem is exemplified by considering a high-affinity ligand (dissociation constant in vitro approximately 0.1 nM; in vivo approximately 5 nmol/kg i.v. injected dose), where routinely produced levels of specific activity ( approximately 100 MBq/nmol) would limit the activity injected into mice to approximately 0.1 MBq for a 1% receptor occupancy. If, as is feasible, the new generation of high resolution PET systems requires an injected activity >10 MBq, then a >100-fold increase in specific activity would be needed for tracer kinetics to hold. The paper highlights the need to consider realistically achievable goals if high-resolution PET is to be accepted as a viable methodology to acquire pharmacologically and physiologically accurate ligand-receptor binding data in mice
AD  - PET Methodology Group, MRC Cyclotron Unit, Hammersmith Hospital, London, W12 0NN, UK
UR  - PM:9473266
ER  - 

TY  - JOUR
T1  - Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable to those recreationally abused by humans: evidence from [11C]WIN-35,428 positron emission tomography studies and direct in vitro determinations
A1  - Villemagne,V.
A1  - Yuan,J.
A1  - Wong,D.F.
A1  - Dannals,R.F.
A1  - Hatzidimitriou,G.
A1  - Mathews,W.B.
A1  - Ravert,H.T.
A1  - Musachio,J.
A1  - McCann,U.D.
A1  - Ricaurte,G.A.
Y1  - 1998/01/01/
SP  - 419
EP  - 427
JA  - J Neurosci.
VL  - 18
IS  - 1
N2  - The present study sought to determine whether doses of methamphetamine in the range of those used recreationally by humans produce brain dopamine (DA) neurotoxicity in baboons and to ascertain whether positron emission tomography (PET) imaging with the DA transporter (DAT) ligand [11C]WIN-35,428 ([11C]2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane) could be used to detect methamphetamine-induced DAT loss in living primates. Baboons were treated with saline (n = 3) or one of three doses of methamphetamine [0.5 mg/kg (n = 2); 1 mg/kg (n = 2); and 2 mg/kg (n = 3)], each of which was given intramuscularly four times at 2 hr intervals. PET studies were performed before and 2-3 weeks after methamphetamine treatment. After the final PET studies, animals were killed for direct neurochemical determination of brain DA axonal markers. PET-derived binding potential values, used to index striatal DAT density, were significantly decreased after methamphetamine, with larger decreases occurring after higher methamphetamine doses. Reductions in striatal DAT documented by PET were associated with decreases in DA, dihydroxyphenylacetic acid, and specific [3H]WIN-35,428 and [3H]DTBZ binding determined in vitro. Decreases in DAT detected with PET were highly correlated with decreases in specific [3H]WIN-35,428 binding determined in vitro in the caudate of the same animal (r = 0.77; p = 0.042). These results indicate that methamphetamine, at doses used by some humans, produces long-term reductions in brain DA axonal markers in baboons, and that it is possible to detect methamphetamine-induced DAT loss in living nonhuman primates by means of PET
AD  - Department of Radiology, Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
UR  - PM:9412518
ER  - 

TY  - JOUR
T1  - Decreasing striatal 6-FDOPA uptake with increasing duration of cocaine withdrawal
A1  - Wu,J.C.
A1  - Bell,K.
A1  - Najafi,A.
A1  - Widmark,C.
A1  - Keator,D.
A1  - Tang,C.
A1  - Klein,E.
A1  - Bunney,B.G.
A1  - Fallon,J.
A1  - Bunney,W.E.
Y1  - 1997/12//
N1  - UI - 98059817
SP  - 402
EP  - 409
JF  - Neuropsychopharmacology
VL  - 17
IS  - 6
N2  - It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects. Middle abstinence cocaine addicts (n = 5, off cocaine 11-30 days) had significantly lower striatal 6-FDOPA uptake compared to normal controls or early abstinence cocaine addicts (n = 6, off cocaine 1-10 days). The cocaine-dependent subjects (n = 11) showed a significant negative correlation between days off cocaine and striatal 6-FDOPA uptake. The results suggest that during abstinence from cocaine there is a delayed decrease in dopamine terminal activity in the striatum
AD  - Department of Psychiatry, University of California, Irvine College of Medicine, USA
UR  - PM:9397428
ER  - 

TY  - JOUR
T1  - PET study of competition between intravenous cocaine and [11C]raclopride at dopamine receptors in human subjects
A1  - Schlaepfer,T.E.
A1  - Pearlson,G.D.
A1  - Wong,D.F.
A1  - Marenco,S.
A1  - Dannals,R.F.
Y1  - 1997/09//
N1  - UI - 97432279
SP  - 1209
EP  - 1213
JA  - Am J Psychiatry
VL  - 154
IS  - 9
N2  - OBJECTIVE: Animal data suggest that the strong euphoriant effects of cocaine are related to the drug's enhancement of available dopamine at the synaptic cleft. The authors' goal was to determine whether this mechanism is the same in humans because the development of putative pharmacological agents for treatment of cocaine dependence depends on this knowledge. METHOD: Positron emission tomography with [11C]raclopride was used to examine the effects of the intravenous administration of 48 mg of cocaine (a typical "street" dose) on the occupancy of dopamine 2 receptors in the putamen of 11 self-identified intravenous drug abusers. RESULTS: All 11 subjects reported subjective stimulation and euphoria in response to cocaine administration. Radioligand occupancy at dopamine receptors was decreased significantly after cocaine administration, suggesting that higher dopamine concentrations were competing at the receptor site. CONCLUSIONS: These results support the concept of dopamine system involvement in human cocaine abuse
AD  - Department of Psychiatry, Johns Hopkins Medical Institutions, Baltimore, USA. schlaepf@welchlink.welch.jhu.edu
UR  - PM:9286178
ER  - 

TY  - JOUR
T1  - In vitro and in vivo characterisation of nor-beta-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain
A1  - Bergstrom,K.A.
A1  - Halldin,C.
A1  - Hall,H.
A1  - Lundkvist,C.
A1  - Ginovart,N.
A1  - Swahn,C.G.
A1  - Farde,L.
Y1  - 1997/06//
SP  - 596
EP  - 601
JA  - Eur.J Nucl Med
VL  - 24
IS  - 6
N2  - Radiolabelled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane (nor-beta-CIT) is a des-methyl analogue of beta-CIT, which in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter than beta-CIT (IC50=4.2 nM). Nor-beta-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-beta-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [125I]nor-beta-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 microM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [11C]nor-beta-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [11C]nor-beta-CIT were 20%-40% higher than those previously obtained with [11C]beta-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-beta-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain
AD  - Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm, Sweden
UR  - PM:9169564
ER  - 

TY  - JOUR
T1  - D2 dopamine receptor polymorphism and brain regional glucose metabolism
A1  - Noble,E.P.
A1  - Gottschalk,L.A.
A1  - Fallon,J.H.
A1  - Ritchie,T.L.
A1  - Wu,J.C.
Y1  - 1997/04/18/
N1  - UI - 97275955
SP  - 162
EP  - 166
JA  - Am J Med Genet.
VL  - 74
IS  - 2
N2  - Positron emission tomography (PET) studies have shown decreased glucose metabolism in brain regions of detoxified alcoholics and cocaine abusers. However, it is not clear whether this decrease is due to chronic drug abuse or a pre-existing condition. Molecular genetic studies have found an association of the D2 dopamine receptor (DRD2) A1 allele with alcoholism and drug abuse. Moreover, reduced central dopaminergic function has been suggested in subjects who carry the A1 allele (A1+) compared with those who do not (A1-). In the present study, using 18F-deoxyglucose, regional glucose metabolism was determined in healthy nonalcohol/nondrug-abusing subjects with the A1+ or A1- allele. The mean relative glucose metabolic rate (GMR) was significantly lower in the A1+ than the A1- group in many brain regions, including the putamen, nucleus accumbens, frontal and temporal gyri and medial prefrontal, occipito-temporal and orbital cortices. Decreased relative GMR in the A1+ group was also found in Broca's area, anterior insula, hippocampus, and substantia nigra. A few brain areas, however, showed increased relative GMR in the A1+ group. Since polymorphism of the DRD2 gene is commonly observed in humans, the importance of differentiating A1+ and A1- alleles subjects in PET studies is suggested
AD  - Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles 90024-1759, USA
UR  - PM:9129716
ER  - 

TY  - JOUR
T1  - Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine
A1  - Melon,P.G.
A1  - Boyd,C.J.
A1  - McVey,S.
A1  - Mangner,T.J.
A1  - Wieland,D.M.
A1  - Schwaiger,M.
Y1  - 1997/03//
SP  - 451
EP  - 456
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 38
IS  - 3
N2  - Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog 11C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. METHODS: Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional 11C-hydroxyephedrine uptake and blood flow, as assessed with 13N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. RESULTS: Active chronic cocaine users showed small areas of abnormal blood flow and 11C-hydroxyephedrine retention in the heart in comparison with normal volunteers. The extent of abnormalities expressed as a percent of the total polar map area averaged 2.0% +/- 2.6% and 2.5% +/- 2.7% for blood flow and 11C-hydroxyephedrine uptake, respectively. Myocardial 11C-hydroxyephedrine retention was significantly reduced by 22% in active cocaine users (0.109 +/- 0.017 min-1), as compared to normal controls (0.140 +/- 0.027 min-1). CONCLUSION: PET imaging with 11C-hydroxyephedrine permits quantitative assessment of cardiac norepinephrine transporter function in active chronic cocaine users. The results of this study suggest prolonged reduction of norepinephrine uptake and storage capacity in the cardiac sympathetic nerve terminals which may reflect the effect of repetitive elevation of norepinephrine levels induced by cocaine exposure
AD  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA
UR  - PM:9074537
ER  - 

TY  - JOUR
T1  - Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study
A1  - Nakamura,H.
A1  - Hishinuma,T.
A1  - Tomioka,Y.
A1  - Ishiwata,S.
A1  - Ido,T.
A1  - Iwata,R.
A1  - Funaki,Y.
A1  - Itoh,M.
A1  - Fujiwara,T.
A1  - Yanai,K.
A1  - Sato,M.
A1  - Numachi,Y.
A1  - Yoshida,S.
A1  - Mizugaki,M.
Y1  - 1997/02//
N1  - UI - 97332301
SP  - 165
EP  - 169
JA  - Nucl Med Biol.
VL  - 24
IS  - 2
N2  - Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization
AD  - Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan
UR  - PM:9190247
ER  - 

TY  - JOUR
T1  - Effects of binge pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain: an in vivo study using positron emission tomography
A1  - Tsukada,H.
A1  - Kreuter,J.
A1  - Maggos,C.E.
A1  - Unterwald,E.M.
A1  - Kakiuchi,T.
A1  - Nishiyama,S.
A1  - Futatsubashi,M.
A1  - Kreek,M.J.
Y1  - 1996/12/01/
N1  - UI - 97081141
SP  - 7670
EP  - 7677
JA  - J Neurosci.
VL  - 16
IS  - 23
N2  - The aim of the present study was to determine the effect of "binge" pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain. Male Sprague Dawley rats were injected three times at 1 hr intervals with saline or cocaine (15 mg/kg) each day for 2, 7, or 14 d. The in vivo binding of [11C]SCH23390 (dopamine D1 receptor antagonist) and [11C]N-methylspiperone (NMSP; dopamine D2 receptor antagonist) in the striatal region was measured by a high-resolution positron emission tomography at 1 and 3.5 hr, respectively, after the last cocaine or saline injection. Acute (2 d) binge cocaine administration did not change the in vivo binding potential of [11C]SCH23390 or the binding of [11C]NMSP in the striatum. After 7 d of binge cocaine administration, a significant decrease in the binding potential of [11C]SCH23390 was observed, whereas no change in the binding of [11C]NMSP was found. After 14 d of binge cocaine administration, the in vivo binding was significantly reduced for both [11C]SCH23390 and [11C]NMSP. Separate saturation experiments indicated that the observed alterations of in vivo binding were attributable mainly to apparent alterations in the affinity and not the number of binding sites. These results suggest that both dopamine D1 and D2 receptors may have altered physiologically available binding sites after binge pattern cocaine administration
AD  - Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan
UR  - PM:8922423
ER  - 

TY  - JOUR
T1  - Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving
A1  - Zubieta,J.K.
A1  - Gorelick,D.A.
A1  - Stauffer,R.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 1996/11//
N1  - UI - 97054452
SP  - 1225
EP  - 1229
JA  - Nat.Med
VL  - 2
IS  - 11
N2  - The endogenous opioid system has been recently implicated in the reinforcing actions of cocaine and other addictive drugs. In this study we examined mu opioid receptor binding in ten cocaine-dependent men and seven nonaddicted controls using positron emission tomography and [11C] carfentanil. Mu opioid binding was increased in several brain regions of the cocaine addicts studied 1-4 days after their last use of cocaine. Binding was positively correlated with the severity of cocaine craving experienced at the time. The upregulation of mu opioid receptor binding persisted after 4 weeks of monitored cocaine abstinence. These findings demonstrate for the first time the involvement of the endogenous opioid system in cocaine dependence and cocaine craving in living human subjects
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
UR  - PM:8898749
ER  - 

TY  - JOUR
T1  - Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo
A1  - Wong,D.F.
A1  - Harris,J.C.
A1  - Naidu,S.
A1  - Yokoi,F.
A1  - Marenco,S.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Yaster,M.
A1  - Evans,A.
A1  - Rousset,O.
A1  - Bryan,R.N.
A1  - Gjedde,A.
A1  - Kuhar,M.J.
A1  - Breese,G.R.
Y1  - 1996/05/28/
SP  - 5539
EP  - 5543
JA  - Proc.Natl.Acad.Sci.U.S.A
VL  - 93
IS  - 11
N2  - Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders
AD  - Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
UR  - PM:8643611
ER  - 

TY  - JOUR
T1  - [11C]beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography
A1  - Halldin,C.
A1  - Farde,L.
A1  - Lundkvist,C.
A1  - Ginovart,N.
A1  - Nakashima,Y.
A1  - Karlsson,P.
A1  - Swahn,C.G.
Y1  - 1996/04//
N1  - UI - 97020655
SP  - 386
EP  - 390
JF  - Synapse
VL  - 22
IS  - 4
N2  - The cocaine analogue beta-CIT-FE (N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) was labeled with 11C for positron emission tomography (PET) studies of the dopamine transporter. After intravenous administration to a cynomolgus monkey, [11C]beta-CIT-FE accumulated in the striatum with a striatum-to-cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific [11C]beta-CIT-FE binding in the striatum was obtained within 30-50 min. The radioactivity ratios of the thalamus to the cerebellum and the neocortex to the cerebellum were about 2 and 1.5, respectively. In displacement and pretreatment experiments, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT or the dopamine transporter inhibitor GBR 12909, indicating that striatal radioactivity following injection of [11C]beta-CIT-FE represents reversible binding to dopamine transporter sites. After displacement or pretreatment with cocaine there was a marked effect not only in the striatum but also in the thalamus and neocortex. [11C]beta-CIT-FE has potential as a useful PET radioligand for quantitation of the dopamine transporter in the primate brain in vivo
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:8867033
ER  - 

TY  - JOUR
T1  - In vivo evaluation of [11C]- and [18F]-labelled cocaine analogues as potential dopamine transporter ligands for positron emission tomography
A1  - Wilson,A.A.
A1  - DaSilva,J.N.
A1  - Houle,S.
Y1  - 1996/02//
SP  - 141
EP  - 146
JA  - Nucl Med Biol.
VL  - 23
IS  - 2
N2  - Four analogues of the potent dopamine transporter ligand, WIN 35,428, were radiolabelled with 11C and 18F at the 2-beta-carboxy position for evaluation as potential ligands for imaging dopamine uptake sites by positron emission tomography (PET) namely, methyl (1R-2-exo-3-exo)-8- methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate (RTI-32), its 4-chlorophenyl analogue (RTI-31), 2'-fluoroethyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2 - carboxylate (FETT) and its 4-chlorophenyl analogue (FECT). Upon intravenous injection in rats, all four radiotracers displayed preferential accumulation of radioactivity in regions known to contain high concentrations of dopamine uptake sites. Competition studies with two of the analogues, [11C]RTI-32 and [18F]FETT, demonstrated that, for both radiotracers, binding was saturable and displayed the appropriate pharmacology as potential PET ligands for imaging the dopamine transporter. Striatum to cerebellar ratios for [11C]RTI-32 (at 90 min post-injection) and [18F]FETT (at 120 min post-injection) were 27 and 21, respectively
AD  - Pet Centre, Clarke Institute of Psychiatry, Toronto, On, Canada
UR  - PM:8868286
ER  - 

TY  - JOUR
T1  - Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging
A1  - Meltzer,P.C.
A1  - Liang,A.Y.
A1  - Brownell,A.L.
A1  - Elmaleh,D.R.
A1  - Madras,B.K.
Y1  - 1993/04/02/
N1  - UI - 93217956
SP  - 855
EP  - 862
JA  - J Med Chem.
VL  - 36
IS  - 7
N2  - It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3 beta-(3,4- dichlorophenyl)tropane-2 beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated
AD  - Organix Inc., Woburn, Massachusetts 01801
UR  - PM:8464040
ER  - 

TY  - JOUR
T1  - Synthesis of carbon-11 labeled iodinated cocaine derivatives and their distribution in baboon brain measured using positron emission tomography
A1  - Yu,D.W.
A1  - Gatley,S.J.
A1  - Wolf,A.P.
A1  - MacGregor,R.R.
A1  - Dewey,S.L.
A1  - Fowler,J.S.
A1  - Schlyer,D.J.
Y1  - 1992/06/12/
N1  - UI - 92309307
SP  - 2178
EP  - 2183
JA  - J Med Chem.
VL  - 35
IS  - 12
N2  - Three iodine-substituted derivatives of cocaine, methyl esters of 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-8-methyl-[1R-(exo,exo)]-8- azabicyclo[3.2.1]octane-2 carboxylic acid (2a-c), were synthesized and subjected to N-demethylation to give the corresponding noriodococaines 3-[(2'-,3'-, and 4'-iodobenzoyl)oxy]-[1R-(exo,exo)]-8- azabicyclo[3.2.1]-octane-2-carboxylic acid (3a-c). These were remethylated with [11C]CH3I to give the [N-11C-methyl]iodococaines 4a-c which were examined in baboon brain in vivo using positron emission tomography (PET). Compared to [N-11C]cocaine itself the regional distributions were changed from a highly specific localization in the corpus striatum to more diffuse patterns which included the cerebellum and cortex. Peak brain uptakes and clearance kinetics were also changed. [N-11C]-o-Iodococaine (4a) had a peak uptake in the striatum at 4-5 min after injection of only 17% that of cocaine in the same animal. The peak uptake of [N-11C]-p-iodococaine (4c) was 60% of that of [N-11C]cocaine and a clearance half-time of approximately 55 min, twice that of [N-11C]cocaine. [N-11C]-m-Iodococaine (4b) displayed half the uptake of [N-11C]cocaine, buts its clearance was similar to that of the parent molecule. The fractions of unmetabolized tracer in blood plasma at 1-30 min were higher for 4a-c than for [N-11C]cocaine. Plasma protein binding experiments showed 10%, 0.3%, 1.6%, and 6% as the free fraction for cocaine and o-, m-, and p-iodococaines respectively, consistent with the low brain uptake observed for the ortho isomer, and implicated alpha 1-acid glycoprotein as responsible for the low free fraction of o-iodococaine. The potencies of 2a-c to displace tritiated cocaine from striatal membranes were p-iodo approximately cocaine greater than m-iodo approximately o-iodo
AD  - Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973
UR  - PM:1613745
ER  - 

TY  - JOUR
T1  - Program for PET image alignment: effects on calculated differences in cerebral metabolic rates for glucose
A1  - Phillips,R.L.
A1  - London,E.D.
A1  - Links,J.M.
A1  - Cascella,N.G.
Y1  - 1990/12//
N1  - UI - 91093789
SP  - 2052
EP  - 2057
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 31
IS  - 12
N2  - A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states
AD  - NIDA Addiction Research Center, Baltimore, MD 21224
UR  - PM:2266408
ER  - 

TY  - JOUR
T1  - The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers
A1  - Pohjalainen,T.
A1  - Rinne,J.O.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Anttila,K.
A1  - Syvalahti,E.K.
A1  - Hietala,J.
Y1  - 1998/05//
N1  - UI - 98336772
SP  - 256
EP  - 260
JA  - Mol.Psychiatry
VL  - 3
IS  - 3
N2  - Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D2 receptor density in vivo in human striatum. Low D2 receptor binding in vivo has been found to associate with alcohol/substance dependence. It has been suggested that the A1 allele of human D2 receptor gene might be associated to a specific type of alcoholism and possibly to a reduced D2 receptor density in vitro. We have determined D2 dopamine receptor-binding density (Bmax), affinity (Kd) and availability (Bmax/Kd) in 54 healthy Finnish volunteers using PET and [11C]raclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D2 receptor characteristics in vivo. A statistically significant reduction in D2 receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent Kd between the two groups. In conclusion, the association between the A1 allele and low D2 receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers
AD  - Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland
UR  - PM:9672901
ER  - 

TY  - JOUR
T1  - Sex differences in the striatal dopamine D2 receptor binding characteristics in vivo
A1  - Pohjalainen,T.
A1  - Rinne,J.O.
A1  - Nagren,K.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 1998/06//
N1  - UI - 98282907
SP  - 768
EP  - 773
JA  - Am J Psychiatry
VL  - 155
IS  - 6
N2  - OBJECTIVE: The authors investigated whether striatal dopamine D2 receptor binding characteristics in vivo are similar in men and women and whether there are sex-related differences in the decline in D2 receptor density due to aging. METHOD: Striatal D2 receptor density (Bmax), affinity (Kd), and binding potential (Bmax/Kd) were measured with positron emission tomography and [11C]raclopride in 54 healthy subjects (33 men and 21 women). RESULTS: Women had generally lower D2 receptor affinity than men, and this difference was statistically significant in the left striatum. Bmax and Bmax/Kd tended to decline with age twice as fast in men as in women, but the difference did not reach statistical significance. CONCLUSIONS: These results confirm the age-related reduction of D2 receptor density and binding potential in both sexes in vivo. The lower D2 receptor affinity suggests an increased endogenous striatal dopamine concentration in women. This may have implications for the differential vulnerability of men and women to psychiatric disorders like schizophrenia and alcohol and substance dependence
AD  - Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland
UR  - PM:9619148
ER  - 

TY  - JOUR
T1  - Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography
A1  - Tiihonen,J.
A1  - Vilkman,H.
A1  - Rasanen,P.
A1  - Ryynanen,O.P.
A1  - Hakko,H.
A1  - Bergman,J.
A1  - Hamalainen,T.
A1  - Laakso,A.
A1  - Haaparanta-Solin,M.
A1  - Solin,O.
A1  - Kuoppamaki,M.
A1  - Syvalahti,E.
A1  - Hietala,J.
Y1  - 1998/03//
SP  - 156
EP  - 161
JA  - Mol.Psychiatry
VL  - 3
IS  - 2
N2  - Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoholics. Markedly low FDOPA uptake (Ki) was observed in the left caudate of two alcoholic patients, but the mean striatal uptake values of the patient group were higher than those of the control group. The greatest difference was observed in the mean FDOPA intake in the left putamen, which was 28% higher in the patient group (t = 3.00, P = 0.008, d.f. = 16, independent samples t-test), and in the right caudate (difference 36%, t = 2.87, P = 0.01). The elevated FDOPA uptake in putamen and caudate correlated with poor Wisconsin Card Sorting Test (WCST) performance (error %) among alcoholics (correlation coefficients from 0.49 to 0.56), which suggests that the magnitude of presynaptic dopamine function alteration correlates with the degree of disability to modify one's behavior. The results do not give support to the hypothesis of generally decreased striatal dopamine turnover in type 1 alcoholism, but on the contrary indicate an increased presynaptic dopamine function. This may represent a compensatory mechanism to low postsynaptic DA function. The low presynaptic DA function observed in the left caudate of two patients suggests that type 1 alcoholism may be a heterogeneous disorder
AD  - Department of Forensic Psychiatry, University of Kuopio, Finland
UR  - PM:9577840
ER  - 

TY  - JOUR
T1  - Effects of m-chlorophenylpiperazine on regional brain glucose utilization: a positron emission tomographic comparison of alcoholic and control subjects
A1  - Hommer,D.
A1  - Andreasen,P.
A1  - Rio,D.
A1  - Williams,W.
A1  - Ruttimann,U.
A1  - Momenan,R.
A1  - Zametkin,A.
A1  - Rawlings,R.
A1  - Linnoila,M.
Y1  - 1997/04/15/
SP  - 2796
EP  - 2806
JA  - J Neurosci.
VL  - 17
IS  - 8
N2  - m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[18F]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method. Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics
AD  - Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1256, USA
UR  - PM:9092601
ER  - 

TY  - JOUR
T1  - Positron emission tomographic imaging of serotonin activation effects on prefrontal cortex in healthy volunteers
A1  - Mann,J.J.
A1  - Malone,K.M.
A1  - Diehl,D.J.
A1  - Perel,J.
A1  - Nichols,T.E.
A1  - Mintun,M.A.
Y1  - 1996/05//
SP  - 418
EP  - 426
JA  - J Cereb.Blood Flow Metab
VL  - 16
IS  - 3
N2  - Serotonergic system abnormalities have been implicated in major depression, suicide, violence, alcoholism, and other psychopathologies. The prolactin response to fenfluramine has been widely used as a neuroendocrine probe to study brain serotonin responsivity. We have extended this methodology by using the positron emission tomography (PET) 18F-fluorodeoxyglucose (18FDG) method to examine the fenfluramine-induced changes in regional cerebral glucose metabolism (rCMRglu), an indicator of changes in regional neuronal activity. We report results on 16 healthy controls, each of whom underwent two PET studies. One group of six subjects had a placebo on day 1 and a single 60 mg oral dose of fenfluramine on day 2. The second group, of 10 subjects, was tested on two consecutive occasions without drug or placebo. Data were analyzed for significant rCMRglu changes on day 2 vs day 1 using the statistical parametric mapping method (p < 0.01). Subjects who did not receive drugs showed no statistically significant areas of rCMRglu increase or decrease on day 2 versus day 1. In contrast, the group that received fenfluramine showed significant fenfluramine-induced responses. Areas of rCMRglu increases involved mainly the left prefrontal and left temperoparietal cortex. Within the prefrontal cortex, two major areas of rCMRglu increase included, first, an area centered on the anterior cingulate and, second, an area in the lateral prefrontal cortex involving principally the inferior, middle, and superior frontal gyri. Some decreases in rCMRglu were observed, principally in the right hemisphere. This PET-fenfluramine paradigm is a potentially useful method for studying abnormalities of serotonin function in the prefrontal cortex
AD  - Department of Neuroscience, New York Psychiatric Institute, New York, USA
UR  - PM:8621746
ER  - 

TY  - JOUR
T1  - Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence
A1  - Hietala,J.
A1  - West,C.
A1  - Syvalahti,E.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Sonninen,P.
A1  - Ruotsalainen,U.
Y1  - 1994/11//
N1  - UI - 95199498
SP  - 285
EP  - 290
JA  - Psychopharmacology (Berl)
VL  - 116
IS  - 3
N2  - Striatal D2 dopamine receptor characteristics of nine male patients with alcohol dependence abstinent for 1-68 weeks and eight healthy male volunteers were studied in vivo with positron emission tomography. The selective D2 receptor ligand [11C]raclopride and equilibrium model was used for D2 receptor density (Bmax) and affinity (Kd) measurements. A trend for a decreased striatal D2 receptor density and for reduced D2 receptor affinity was observed in patients with alcohol dependence. These parameters were not statistically significantly different between alcoholics and controls, but the ratio between D2 receptor density and affinity (Bmax/Kd or the striatum/cerebellum ratio from the high specific activity scan) was highly significantly lower in alcoholics than that of controls. In conclusion, the low D2 dopamine receptor Bmax/Kd ratio (striatum/cerebellum ratio) indicates that specific aspects of striatal [11C]raclopride binding in vivo are deviant in alcoholics compared to controls. The result is compatible with a reduced avidity of striatal dopamine D2 receptors in alcoholics, which is in line with the idea that D2 dopaminergic mechanisms are involved in the biology of alcohol dependence in man
AD  - Department of Pharmacology, University of Turku, Finland
UR  - PM:7892418
ER  - 

TY  - JOUR
T1  - Marchiafava-Bignami disease with dementia: severe cerebral metabolic depression revealed by PET
A1  - Pappata,S.
A1  - Chabriat,H.
A1  - Levasseur,M.
A1  - Legault-Demare,F.
A1  - Baron,J.C.
Y1  - 1994///
N1  - UI - 95200503
SP  - 131
EP  - 137
JA  - J Neural Transm.Park Dis.Dement.Sect.
VL  - 8
IS  - 1-2
N2  - The Cerebral Metabolic Rate of Glucose (CMRGlu) was measured with positron emission tomography and 18F-FDG in a patient with Marchiafava-Bignami Disease (MBD)-related dementia. Despite MRI evidence of lesions essentially limited to the corpus callosum (CC), but consistent with the cognitive pattern of cortical dementia, the CMRGlu was markedly reduced in the frontal and temporo-parieto-occipital association cortices. Disruption of cortico-cortical networks crossing the CC presumably contributed to, but may not in and by itself explain, the severity of the clinical-metabolic findings in this patient. An additional role could be played by microscopic white matter lesions and/or neocortical neuronal loss, which have been occasionally observed in post-mortem studies of MBD patients
AD  - Service Hospitalier Frederic Joliot (SHFJ), CEA, DRIPP, Orsay, France
UR  - PM:7893375
ER  - 

TY  - JOUR
T1  - PET analysis of [11C]flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls
A1  - Litton,J.E.
A1  - Neiman,J.
A1  - Pauli,S.
A1  - Farde,L.
A1  - Hindmarsh,T.
A1  - Halldin,C.
A1  - Sedvall,G.
Y1  - 1993/04//
N1  - UI - 93288769
SP  - 1
EP  - 13
JA  - Psychiatry Res
VL  - 50
IS  - 1
N2  - Benzodiazepine (BZ) receptor binding in the brain was determined in five chronic alcohol-dependent men and in five healthy male control subjects using [11C]flumazenil (Ro 15-1788) and positron emission tomography (PET). Magnetic resonance imaging was used to evaluate brain anatomy and pathology, and to define regions of interest in the brain. [11C]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400-3400 Ci/mmol) and the second with low (approximately 1 Ci/mmol) specific radioactivity. Radioactivity in the pons was taken as an estimate of free and nonspecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dCb(t)/dt) was equal to zero. The values were used in a Scatchard analysis for determination of the maximum density of binding sites (Bmax) and the equilibrium binding constant (Kd). The mean values of Bmax and Kd were about the same in the two groups, but the Bmax variance for the alcoholics was significantly greater for all regions of interest as compared with the healthy volunteers. The results may indicate that chronic alcohol consumption has multiple effects on the BZ receptor complex
AD  - Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden
UR  - PM:8390063
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose utilization in chronic organic mental disorders associated with alcoholism
A1  - Martin,P.R.
A1  - Rio,D.
A1  - Adinoff,B.
A1  - Johnson,J.L.
A1  - Bisserbe,J.C.
A1  - Rawlings,R.R.
A1  - Rohrbaugh,J.W.
A1  - Stapleton,J.M.
A1  - Eckardt,M.J.
Y1  - 1992///
N1  - UI - 92330497
SP  - 159
EP  - 167
JA  - J Neuropsychiatry Clin.Neurosci.
VL  - 4
IS  - 2
N2  - Localized cerebral utilization rates for glucose (CMRglu) were determined in 10 detoxified patients with alcoholic organic mental disorders and in 7 age-equivalent normal volunteers using [18F]2-fluoro-2-deoxyglucose positron emission tomography. Although gray and white matter CMRglu were not significantly different, normalized CMRglu was increased in the left cerebellar and parietal cortical regions and decreased in the right posterior white matter and anterior temporal regions of alcoholic patients, and the pattern of regional CMRglu differed between the two groups. The results suggest functional disruption of right-sided and frontal brain regions and hyperactivity of cerebellar-cortical connections in alcoholic chronic organic mental disorders
AD  - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
UR  - PM:1627977
ER  - 

TY  - JOUR
T1  - Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography
A1  - Gilman,S.
A1  - Adams,K.
A1  - Koeppe,R.A.
A1  - Berent,S.
A1  - Kluin,K.J.
A1  - Modell,J.G.
A1  - Kroll,P.
A1  - Brunberg,J.A.
Y1  - 1990/12//
N1  - UI - 91136158
SP  - 775
EP  - 785
JA  - Ann.Neurol
VL  - 28
IS  - 6
N2  - Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109-0316
UR  - PM:2285264
ER  - 

TY  - JOUR
T1  - Local cerebral glucose utilisation in chronic alcoholics: a positron tomographic study
A1  - Samson,Y.
A1  - Baron,J.C.
A1  - Feline,A.
A1  - Bories,J.
A1  - Crouzel,C.
Y1  - 1986/10//
N1  - UI - 87059900
SP  - 1165
EP  - 1170
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 49
IS  - 10
N2  - Using positron tomography, a study of regional cerebral glucose utilisation was performed prospectively in a highly selected group of six neurologically unaffected primary chronic alcoholics. In this group, neuropsychological, behavioural and CT scan anomalies were comparable with those previously reported in more extensive studies. With respect to age-matched control values, cerebral metabolic rate was not significantly modified in the selected cortical, subcortical and cerebellar regions of interest. However, the metabolic regional distribution index, which reflects the distribution pattern of glucose utilisation, was selectively and significantly decreased in the medio-frontal area, pointing to a limbic metabolic dysfunction apparently linked to chronic alcoholism
UR  - PM:3491181
ER  - 

TY  - JOUR
T1  - "Ecstasy"-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology. An 18-FDG PET study
A1  - Schreckenberger,M.
A1  - Gouzoulis-Mayfrank,E.
A1  - Sabri,O.
A1  - Arning,C.
A1  - Zimny,M.
A1  - Zeggel,T.
A1  - Wagenknecht,G.
A1  - Kaiser,H.J.
A1  - Sass,H.
A1  - Buell,U.
Y1  - 1999/12//
SP  - 1572
EP  - 1579
JA  - Eur.J Nucl Med
VL  - 26
IS  - 12
N2  - The aim of this study was to determine the acute effects of the "Ecstasy" analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a randomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose (18FDG) positron emission tomography (PET) 110-120 min after oral administration of 2 mg/kg MDE (n = 7) or placebo (n = 8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using Tl-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMRGlu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed significantly decreased rMRGlu in the bilateral frontal cortex: left frontal posterior (-7.1%, P < 0.05) and right prefrontal superior (-4.6%, P < 0.05). On the other hand, rMRGlu was significantly increased in the bilateral cerebellum (right: +10.1%, P < 0.05; left: +7.6%, P < 0.05) and in the right putamen (+6.2%, P < 0.05). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r = 0.87, P < 0.05), both the right amygdala (r = 0.90, P < 0.01) and the left posterior cingulate (r = 0.90, P < 0.01) to difficulties in abstract thinking, and the right frontal inferior (r = 0.85, P < 0.05), right anterior cingulate (r = 0.93, P < 0.01), and left anterior cingulate (r = 0.85, P < 0.05) to attentional deficits. A negative correlation was found between the left frontal operculum (Broca's area) and attentional deficits (r = -0.85, P < 0.05). The present study revealed acute neurometabolic changes under the "Ecstasy" analogue MDE, indicating a frontostriatocerebellar imbalance paralleling other psychotropic substances or various psychiatric disorders
AD  - Department of Nuclear Medicine, Aachen University of Technology, Germany
UR  - PM:10638409
ER  - 

TY  - JOUR
T1  - Neural mechanism of propofol anesthesia in severe depression: a positron emission tomographic study
A1  - Ogawa,K.
A1  - Uema,T.
A1  - Motohashi,N.
A1  - Nishikawa,M.
A1  - Takano,H.
A1  - Hiroki,M.
A1  - Imabayashi,E.
A1  - Ohnishi,T.
A1  - Inoue,T.
A1  - Takayama,Y.
A1  - Takeda,M.
A1  - Matsuda,H.
A1  - Andoh,T.
A1  - Yamada,Y.
Y1  - 2003/05//
N1  - UI - 22602014
SP  - 1101
EP  - 1111
JF  - Anesthesiology
VL  - 98
IS  - 5
N2  - BACKGROUND: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression. METHODS: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data. RESULTS: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states. CONCLUSIONS: As in earlier studies using normal subjects, pronounced suppression in rCBF in the brain stem reticular formation, the thalamus, and the parietal association cortex occurred even in severely depressed patients. However, previously reported decreases in rCBF in the basal frontal lobe were absent in depressed patients
AD  - National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. k-ogawa@pd5.so-net.ne.jp
UR  - PM:12717131
ER  - 

TY  - JOUR
T1  - Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography
A1  - Kaisti,K.K.
A1  - Metsahonkala,L.
A1  - Teras,M.
A1  - Oikonen,V.
A1  - Aalto,S.
A1  - Jaaskelainen,S.
A1  - Hinkka,S.
A1  - Scheinin,H.
Y1  - 2002/06//
N1  - UI - 22159332
SP  - 1358
EP  - 1370
JF  - Anesthesiology
VL  - 96
IS  - 6
N2  - BACKGROUND: The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis. METHODS: Using H(2)(15)O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC(50), or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 microg/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation. RESULTS: Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36-53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7-16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62-70%, with minor further effects. In the SPM analysis of the "awake to 1 MAC/EC(50)" step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices. CONCLUSIONS: Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC(50) level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases
AD  - Department of Anesthesiology and Clinical Neurophysiology, Turku University Hospital, Turku, Finland
UR  - PM:12170048
ER  - 

TY  - JOUR
T1  - Changes in reward-induced brain activation in opiate addicts
A1  - Martin-Soelch,C.
A1  - Chevalley,A.F.
A1  - Kunig,G.
A1  - Missimer,J.
A1  - Magyar,S.
A1  - Mino,A.
A1  - Schultz,W.
A1  - Leenders,K.L.
Y1  - 2001/10//
N1  - UI - 21560550
SP  - 1360
EP  - 1368
JA  - Eur.J Neurosci.
VL  - 14
IS  - 8
N2  - Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process
AD  - Paul Scherrer Institute, PET Program, CH-5232 Villigen, Switzerland. Chantal.Martin@unibas.ch
UR  - PM:11703464
ER  - 

TY  - JOUR
T1  - Correlating in vivo anaesthetic effects with ex vivo receptor density data supports a GABAergic mechanism of action for propofol, but not for isoflurane
A1  - Alkire,M.T.
A1  - Haier,R.J.
Y1  - 2001/05//
N1  - UI - 21459177
SP  - 618
EP  - 626
JA  - Br.J Anaesth.
VL  - 86
IS  - 5
N2  - If the in vivo effects of anaesthesia are mediated through a specific receptor system, then a relationship could exist between the regional changes in brain metabolism caused by a particular agent and the underlying regional distribution of the specific receptors affected by that agent. Positron emission tomography data from volunteers studied while unconscious during propofol (n=8) or isoflurane (n=5) anaesthesia were used retrospectively to explore for evidence of relationships between regional anaesthetic effects on brain glucose metabolism and known (ex vivo) regional distribution patterns of human receptor binding sites. The regional metabolic reductions caused by propofol differed significantly from those of isoflurane. Propofol's reductions negatively correlated most significantly with the regional distribution of [3H]diazepam and [3H]flunitrazepam (benzodiazepine) binding site densities (r=-0.86, P<0.0005; r=-0.79, P<0.005, respectively) and less strongly with [3H]naloxone (opioid) binding density (r=-0.69, P<0.05). Isoflurane's reductions positively correlated only with muscarinic (acetylcholine) binding density (r=0.85, P<0.05). These findings are consistent with the hypothesis that some of propofol's in vivo anaesthetic effects may be mediated through a GABAergic mechanism and suggest some of isoflurane's in vivo effects might involve antagonism of central acetylcholine functioning
AD  - Department of Anesthesiology, University of California-Irvine Medical Center, Orange 92868, USA
UR  - PM:11575335
ER  - 

TY  - JOUR
T1  - Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study
A1  - Bonhomme,V.
A1  - Fiset,P.
A1  - Meuret,P.
A1  - Backman,S.
A1  - Plourde,G.
A1  - Paus,T.
A1  - Bushnell,M.C.
A1  - Evans,A.C.
Y1  - 2001/03//
N1  - UI - 21145697
SP  - 1299
EP  - 1308
JA  - J Neurophysiol.
VL  - 85
IS  - 3
N2  - We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information. Using positron emission tomography (PET) and the H(2)(15)O bolus technique, we measured regional distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They were scanned under five different levels of propofol anesthesia. Using a computer-controlled infusion, the following plasma levels of propofol were targeted: Level W (Waking, 0 microg/ml), Level 1 (0.5 microg/ml), Level 2 (1.5 microg/ml), Level 3 (3.5 microg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off. The level of consciousness was evaluated before each scan by the response of the subject to a verbal command. At Level W, all volunteers were fully awake. They reported being slightly drowsy at Level 1, they had a slurred speech and slow response at Level 2, and they were not responding at all at Level 3. The following variations in regional CBF (rCBF) were observed. During the waking state (Level W), vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions, including the left primary somatosensory cortex and the left and right secondary somatosensory cortex. During anesthesia, propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual, parietal, and prefrontal cortical regions. At Level 1 through 3, propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex, whereas the thalamic rCBF response was abolished only at Level 3, when volunteers lost consciousness. We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus
AD  - Department of Anesthesia, McGill University, Montreal, Quebec H3A 1A2, Canada
UR  - PM:11247998
ER  - 

TY  - JOUR
T1  - Neural responses associated with cue evoked emotional states and heroin in opiate addicts
A1  - Sell,L.A.
A1  - Morris,J.S.
A1  - Bearn,J.
A1  - Frackowiak,R.S.
A1  - Friston,K.J.
A1  - Dolan,R.J.
Y1  - 2000/08/01/
N1  - UI - 20400218
SP  - 207
EP  - 216
JA  - Drug Alcohol Depend.
VL  - 60
IS  - 2
N2  - Ten male opiate addicts, who were current heroin injectors, underwent positron emission tomographic (PET) scanning during exposure to a sequence of six alternating drug related and neutral video cues, on two occasions. After the second scan, each subject received heroin or placebo using a randomised single-blind procedure. This design allowed the investigation of patterns of brain activity during a range of self-reported cue evoked emotional states, both in the presence and absence of heroin. Self-reports of 'urge to use' correlated strongly with increased regional blood flow (rCBF) in the inferior frontal and orbitofrontal cortex target regions of the mesolimbic dopaminergic system, implicated in conditioning and reward. 'Urge to use' was also associated with highly significant increased rCBF in the right pre-cuneus, an area associated with episodic memory retrieval, and in the left insula, implicated in the processing of the emotional components of stimuli. Self-reports of feeling 'high' correlated with rCBF activation in the hippocampus, an area relevant to the acquisition of stimulus-associated reinforcement
AD  - National Addiction Centre, Institute of Psychiatry, 4 Windsor Walk, SE5 8AF, London, UK
UR  - PM:10940548
ER  - 

TY  - JOUR
T1  - Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders
A1  - Ketter,T.A.
A1  - Kimbrell,T.A.
A1  - George,M.S.
A1  - Willis,M.W.
A1  - Benson,B.E.
A1  - Danielson,A.
A1  - Frye,M.A.
A1  - Herscovitch,P.
A1  - Post,R.M.
Y1  - 1999/11/15/
N1  - UI - 20045413
SP  - 1364
EP  - 1374
JA  - Biol.Psychiatry
VL  - 46
IS  - 10
N2  - BACKGROUND: Positron emission tomography (PET) studies have reported baseline (medication free) differences between mood disorder patients and healthy control subjects, but relatively little is known about relationships between baseline PET scans and treatment responses. Carbamazepine (CBZ) and to a more limited extent nimodipine (NIMO) seem useful in mood disorders. We explored whether baseline regional cerebral glucose metabolism (rCMRglu) could discriminate CBZ and NIMO responders from nonresponders and healthy control subjects. METHODS: In refractory mood disorder patients, we examined relationships between responses to these drugs, assessed by Clinical Global Impression-Improvement scores, and baseline rCMRglu, determined with fluorine-18 deoxy-glucose and PET. RESULTS: CBZ responders had baseline left insular hyper-metabolism compared to healthy control subjects and nonresponders, whereas nonresponders had widespread (including left insular) hypometabolism. Degree of CBZ response correlated with baseline paralimbic (including insula) and prefrontal hypermetabolism. In responders but not nonresponders, CBZ decreased widespread metabolism, with the degree of decrease in left insula correlating with response. In contrast, NIMO responders but not nonresponders had baseline widespread (including left insular) hypometabolism. Left prefrontal and left insular baseline hypometabolism, but not metabolic changes with treatment correlated with degree of NIMO response. CONCLUSIONS: These data suggest that baseline anterior paralimbic and prefrontal hypermetabolism may be associated with CBZ response, and hypometabolism with NIMO response. Based on these preliminary data, further exploration of relationships between baseline PET scans and treatment responses is indicated
AD  - Stanford University School of Medicine, California, USA
UR  - PM:10578451
ER  - 

TY  - JOUR
T1  - Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism
A1  - Alkire,M.T.
A1  - Pomfrett,C.J.
A1  - Haier,R.J.
A1  - Gianzero,M.V.
A1  - Chan,C.M.
A1  - Jacobsen,B.P.
A1  - Fallon,J.H.
Y1  - 1999/03//
N1  - UI - 99176556
SP  - 701
EP  - 709
JF  - Anesthesiology
VL  - 90
IS  - 3
N2  - BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism
AD  - Department of Anesthesiology, University of California-Irvine Medical Center, Orange 92668, USA. MAlkire@UCI.edu
UR  - PM:10078670
ER  - 

TY  - JOUR
T1  - Positron emission tomographic analysis of central dopamine D1 receptor binding in normal subjects treated with the atypical neuroleptic, SDZ MAR 327
A1  - Christian,B.T.
A1  - Babich,J.W.
A1  - Livni,E.
A1  - Alpert,N.M.
A1  - Bonab,A.A.
A1  - Munconi,L.
A1  - Polinski,R.
A1  - Rubin,R.H.
A1  - Fischman,A.J.
Y1  - 1998/01//
N1  - UI - 99074418
SP  - 243
EP  - 247
JA  - Int.J Mol.Med
VL  - 1
IS  - 1
N2  - SDZ MAR 327 is a new neuroleptic agent with high in vitro affinity for dopamine D1 and D2 receptors. The goal of this study was to determine the effect of time after SDZ MAR 327 administration on central dopamine D1 receptor occupancy in healthy humans. Positron emission tomography (PET) with the dopamine D1 receptor ligand, [11C] SCH 23390, was performed in 6 male volunteers (age 22-34), in both the drug naive state and at 1, 2 and 4 h after a single oral dose of SDZ MAR 327 (9 mg). The pre and post drug treatment [11C] SCH 23390 dynamic data were analyzed using two different methods, each yielding a parameter proportional to the receptor density: i) a simple regional comparison approximating the specifically bound to free fraction, B/F; and ii) a two compartment, two parameter model yielding the apparent distribution volume DV". With both methods, a metabolite corrected arterial input function was used and the vascular fraction of tissue (Vb) was fixed at a previously determined value of 4%. Method I served as a qualitative comparison of the paired studies and demonstrated little difference between the pre and post drug conditions, method II also confirmed that there was no significant change in binding of [11C] SCH 23390 in the striatum. These data indicate that SDZ MAR 327 produces little if any effect on dopamine D1 receptor binding at the dose used
AD  - Division of Nuclear Medicine of the Department of Radiology, Massachusetts General Hospital, and the Department of Radiology, Harvard Medical School, Boston, MA, USA
UR  - PM:9852226
ER  - 

TY  - JOUR
T1  - Positron emission tomography study of regional cerebral metabolism in humans during isoflurane anesthesia
A1  - Alkire,M.T.
A1  - Haier,R.J.
A1  - Shah,N.K.
A1  - Anderson,C.T.
Y1  - 1997/03//
N1  - UI - 97219020
SP  - 549
EP  - 557
JF  - Anesthesiology
VL  - 86
IS  - 3
N2  - BACKGROUND: Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET). METHODS: Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the 18fluorodeoxyglucose technique. RESULTS: Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg.100 g-1.min-1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg.100 g-1.min-1 (P < or = 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake. CONCLUSION: These data clarify that the anesthetic state evident in the living human brain during unresponsiveness induced with isoflurane is associated with a global, fairly uniform, whole-brain glucose metabolic reduction of 46 +/- 11%
AD  - Department of Anesthesiology, University of California-Irvine Medical Center, Orange 92668, USA. MAlkire@UCI.edu
UR  - PM:9066320
ER  - 

TY  - JOUR
T1  - Kinetics of 11C-labeled opiates in the brain of rhesus monkeys
A1  - Hartvig,P.
A1  - Bergstrom,K.
A1  - Lindberg,B.
A1  - Lundberg,P.O.
A1  - Lundqvist,H.
A1  - Langstrom,B.
A1  - Svard,H.
A1  - Rane,A.
Y1  - 1984/07//
N1  - UI - 84267349
SP  - 250
EP  - 255
JA  - J Pharmacol.Exp.Ther.
VL  - 230
IS  - 1
N2  - The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity
UR  - PM:6611397
ER  - 

TY  - JOUR
T1  - Mu-receptor agonism with alfentanil increases striatal dopamine D2 receptor binding in man
A1  - Hagelberg,N.
A1  - Kajander,J.K.
A1  - Nagren,K.
A1  - Hinkka,S.
A1  - Hietala,J.
A1  - Scheinin,H.
Y1  - 2002/07//
N1  - UI - 22107792
SP  - 25
EP  - 30
JF  - Synapse
VL  - 45
IS  - 1
N2  - Animal studies indicate that mu-opioids indirectly modulate neurotransmission in the nigrostriatal dopaminergic pathway. We used positron emission tomography (PET) to study the effects of alfentanil (a mu-opioid receptor agonist) on striatal dopamine D2 receptor binding in eight healthy male volunteers. D2 receptor binding was determined by using [(11)C]raclopride as radioligand. Each subject underwent two PET sessions on the same day, the first without the drug (control) and the second during alfentanil infusion. Alfentanil was administered as target-controlled infusion to maintain pseudo steady-state plasma concentration of 80 ng/ml throughout the PET session. A freeze lesion model was used for pain testing at the end of both PET sessions. A mechanical pain stimulus of 5 N was rated by the subjects using a visual analog scale. Regions of interest for the putamen, caudate nucleus, and cerebellum were drawn on MRI images and transferred to PET images. Alfentanil increased the binding potential of [(11)C]raclopride in the putamen by 6.0% (P = 0.04) and in the caudate nucleus by 7.4% (P = 0.008). Alfentanil caused a small reduction in respiratory rate (P = 0.046) and oxygen saturation (P < 0.001), and a moderate consistent increase in end-tidal CO(2) (P < 0.001). Pain scores were significantly smaller after alfentanil PET scan (median VAS 9 (0-42) vs. 23.5 (15-52), P = 0.008). These results indicate that pharmacologically relevant concentrations of alfentanil increase D2 dopamine receptor binding in the striatum in man. This increase is assumed to reflect reduced dopamine release
AD  - Department of Anesthesiology and Intensive Care, Turku University Central Hospital, Turku, Finland
UR  - PM:12112410
ER  - 

TY  - JOUR
T1  - mu-opioid receptor-mediated antinociceptive responses differ in men and women
A1  - Zubieta,J.K.
A1  - Smith,Y.R.
A1  - Bueller,J.A.
A1  - Xu,Y.
A1  - Kilbourn,M.R.
A1  - Jewett,D.M.
A1  - Meyer,C.R.
A1  - Koeppe,R.A.
A1  - Stohler,C.S.
Y1  - 2002/06/15/
N1  - UI - 22072286
SP  - 5100
EP  - 5107
JA  - J Neurosci.
VL  - 22
IS  - 12
N2  - Sex differences in the experience of clinical and experimental pain have been reported. However, the neurobiological sources underlying the variability in pain responses between sexes have not been adequately explored, especially in humans. The endogenous opioid neurotransmitters and mu-opioid receptors are centrally implicated in responses to stress, in the suppression of pain, and in the action of opiate analgesic drugs. Here we examined sex differences in the activation of the mu-opioid system in response to an intensity-controlled sustained deep-tissue pain challenge with positron emission tomography and a mu-opioid receptor-selective radiotracer. Twenty-eight young healthy volunteers (14 men and 14 women) were studied during saline control and pain conditions using a double-blind, randomized, and counterbalanced design. Women were scanned during the early follicular phase of their menstrual cycles after ovulatory cycles. Significant sex differences in the regional activation of the mu-opioid system in response to sustained pain were detected compared with saline controls. Men demonstrated larger magnitudes of mu-opioid system activation than women in the anterior thalamus, ventral basal ganglia, and amygdala. Conversely, women demonstrated reductions in the basal state of activation of the mu-opioid system during pain in the nucleus accumbens, an area previously associated with hyperalgesic responses to the blockade of opioid receptors in experimental animals. These data demonstrate that at matched levels of pain intensity, men and women during their follicular phase differ in the magnitude and direction of response of the mu-opioid system in distinct brain nuclei
AD  - Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720, USA
UR  - PM:12077205
ER  - 

TY  - JOUR
T1  - Placebo and opioid analgesia-- imaging a shared neuronal network
A1  - Petrovic,P.
A1  - Kalso,E.
A1  - Petersson,K.M.
A1  - Ingvar,M.
Y1  - 2002/03/01/
N1  - UI - 21862294
SP  - 1737
EP  - 1740
JF  - Science
VL  - 295
IS  - 5560
N2  - It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia
AD  - Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Stockholm 171 76, Sweden., Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Finland
UR  - PM:11834781
ER  - 

TY  - JOUR
T1  - [11C]Raclopride binding was reduced in vivo by sigma(1) receptor ligand SA4503 in the mouse brain, while [11C]SA4503 binding was not by raclopride
A1  - Ishiwata,K.
A1  - Kobayashi,T.
A1  - Kawamura,K.
A1  - Matsuno,K.
A1  - Senda,M.
Y1  - 2001/10//
N1  - UI - 21463489
SP  - 787
EP  - 792
JA  - Nucl Med Biol.
VL  - 28
IS  - 7
N2  - [11C]Raclopride is widely used as a representative dopamine D(2)-like receptor ligand in positron emission tomography (PET) studies, and [11C]1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride ([11C]SA4503) is a recently developed selective ligand for mapping sigma(1) receptors in the brain. The striatal uptake of [11C]raclopride in mice was reduced by co-injection of an excess amount of SA4503, in spite of the fact that raclopride had no effect on the brain uptake of [11C]SA4503 as shown in a previous study. The blocking effect of SA4503 on the striatal uptake of [11C]raclopride was dose-dependent, but disappeared by 1 h or 6 h after intraperitoneal injection of SA4503. The brain uptake of [11C]SA4503 was not affected by a dopamine transporter inhibitor GBR 12909, nor was [11C]beta-CIT-FP inhibited by SA4503. The IC(50) values of raclopride for sigma(1) and sigma(2) receptor subtypes measured in vitro were 11800 nM and 4950 nM, respectively, suggesting that the affinity was too low for [11C]raclopride to bind in vivo to sigma receptors. On the other hand, the IC(50) value of SA4503 for dopamine D(2) receptors was 470 nM, that is approximate 1/25 of the affinity of raclopride for the dopamine D(2) receptors. Therefore, possible explanations for the partial blocking effects of SA4503 on the striatal uptake of [11C]raclopride are: (1) an excess amount of SA4503 may reduce the [11C]raclopride uptake due to its low affinity for dopamine D(2) receptors, or (2) SA4503 may enhance endogenous dopamine release, which results in the competitive inhibition of the [11C]raclopride uptake. These findings support that both [11C]raclopride and [11C]SA4503 are selective in vivo ligands for dopamine D(2)-like receptors and sigma(1) receptors, respectively, in spite of the partial blocking effect of SA4503 on the striatal uptake of [11C]raclopride
AD  - Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. ishiwata@pet.tmig.or.jp
UR  - PM:11578899
ER  - 

TY  - JOUR
T1  - Functional imaging of brain responses to pain. A review and meta-analysis
A1  - Peyron,R.
A1  - Laurent,B.
A1  - Garcia-Larrea,L.
Y1  - 2000/10//
N1  - UI - 21002368
SP  - 263
EP  - 288
JA  - Neurophysiol.Clin.
VL  - 30
IS  - 5
N2  - Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated
AD  - Departement de neurologie, hopital de Bellevue, boulevard Pasteur, 42055 Saint-Etienne, France
UR  - PM:11126640
ER  - 

TY  - JOUR
T1  - Preclinical evaluation of [11C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma1 receptors in the cat brain
A1  - Kawamura,K.
A1  - Ishiwata,K.
A1  - Shimada,Y.
A1  - Kimura,Y.
A1  - Kobayashi,T.
A1  - Matsuno,K.
A1  - Homma,Y.
A1  - Senda,M.
Y1  - 2000/08//
N1  - UI - 20475866
SP  - 285
EP  - 292
JA  - Ann.Nucl Med
VL  - 14
IS  - 4
N2  - Our previous in vivo study with rats has demonstrated that 11C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) is a potential radioligand for mapping CNS sigmal receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [11C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [11C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma2 or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for signal receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [11C]SA4503 has the potential for mapping sigma1 receptor by PET
AD  - Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan. kawamura@pet.tmig.or.jp
UR  - PM:11023029
ER  - 

TY  - JOUR
T1  - Opiate receptor avidity in the thalamus is sexually dimorphic in the elderly
A1  - Cohen,R.M.
A1  - Carson,R.E.
A1  - Sunderland,T.
Y1  - 2000/11//
N1  - UI - 20473117
SP  - 226
EP  - 229
JF  - Synapse
VL  - 38
IS  - 2
N2  - Opiate receptor avidity (B(')(max)/K(D)), was measured in the subcortex of nine females (five healthy subjects, four Alzheimer patients) and 15 males (seven healthy subjects, eight Alzheimer patients), 51-75 years of age, with the opiate receptor antagonist 6-deoxy-6-beta-[(18)F]fluoronaltrexone (cyclofoxy, CF) and a positron emission tomograph. CF avidity was 27.5% less in the thalamus of healthy women compared to healthy men and 48.5% less in Alzheimer disease female patients compared to male patients
AD  - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20982-1274, USA. bob@shiloh.nimh.nih.gov
UR  - PM:11018796
ER  - 

TY  - JOUR
T1  - Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography
A1  - Smith,J.S.
A1  - Zubieta,J.K.
A1  - Price,J.C.
A1  - Flesher,J.E.
A1  - Madar,I.
A1  - Lever,J.R.
A1  - Kinter,C.M.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 1999/09//
N1  - UI - 99405752
SP  - 956
EP  - 966
JA  - J Cereb.Blood Flow Metab
VL  - 19
IS  - 9
N2  - The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
UR  - PM:10478647
ER  - 

TY  - JOUR
T1  - Positron emission tomography receptor studies in epilepsy
A1  - Duncan,J.S.
Y1  - 1999/07//
N1  - UI - 99401889
SP  - 482
EP  - 488
JA  - Rev.Neurol (Paris)
VL  - 155
IS  - 6-7
N2  - Investigations with specific PET ligands that bind to specific neuro-receptors give information on abnormalities of neurotransmission involved in the pathophysiology of the epilepsies. Data need to be interpreted in the light of optimal structural imaging. Objective voxel-based and region-based analyses, with correction of partial volume effect, are complementary. Central benzodiazepine (cBZR) and opioid receptors have been studied most. Reduced cBZR binding is commonly seen at an epileptic focus, in a more restricted distribution than an area of hypometabolism, and sometimes also in projection areas. In contrast to acquired lesions causing partial seizures, focal increases in cBZR binding have been demonstrated in malformations of cortical development and also in areas of brain that appear normal on MRI, indicating the widespread nature of the abnormalities. Focal abnormalities of cBZR are also commonly found in patients with partial seizures and normal MRI. It is not yet clear how useful these data will prove to be in presurgical evaluation. Mu- and delta-opioid receptors have been found to be increased in temporal neocortex overlying mesial temporal epileptic foci, but with different patterns of increase. Dynamic studies of the binding of 11C-diprenorphine to opioid receptors are possible using PET, and have implied the release of cerebral endogenous opioids at the time of serial absences and reflex seizures induced by reading. Other tracers, that have been applied less widely, label the enzyme monoamine oxidase type B and peripheral benzodiazepine and histamine H1 receptors
AD  - Institute of Neurology, National Hospital for Neurology & Neurosurgery, London, UK
UR  - PM:10472664
ER  - 

TY  - JOUR
T1  - Gender and age influences on human brain mu-opioid receptor binding measured by PET
A1  - Zubieta,J.K.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 1999/06//
N1  - UI - 99288393
SP  - 842
EP  - 848
JA  - Am J Psychiatry
VL  - 156
IS  - 6
N2  - OBJECTIVE: Both age and gender are being increasingly recognized as important factors influencing CNS structure and function. However, there are relatively few data on actual neurochemical differences between the sexes in human subjects or on their interaction with age. One of the central neurotransmitter systems for which sex differences have been suggested by animal models and clinical human data is the opioid. In this study the authors examined age- and gender-associated variations in mu-opioid receptor binding with positron emission tomography (PET). METHOD: Healthy human subjects were studied with PET and the radiotracer [11C]carfentanil, a selective mu-opioid agonist. Two separate subject groups were examined: one group of 24 men and 12 women was studied in a retrospective analysis of data, and a second group of 12 men and 18 women was recruited prospectively and studied with a higher-resolution scanner. RESULTS: Mu-opioid receptor binding potential (Bmax/Kd) was found to increase with age in neocortical areas and the putamen. Sex differences, with higher mu-opioid binding in women, were observed in a number of cortical and subcortical areas. Gender-by-age interactions were observed in the thalamus and the amygdala; in vivo mu-opioid binding declined in postmenopausal women to levels below those of men. CONCLUSIONS: These data imply that both age and gender are important variables to consider in the interpretation of investigations of human function in which the opioid system plays a role. Also, women's reproductive status (reproductive age versus postmenopausal) may influence the function of CNS opioid systems
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
UR  - PM:10360121
ER  - 

TY  - JOUR
T1  - Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine
A1  - Willoch,F.
A1  - Tolle,T.R.
A1  - Wester,H.J.
A1  - Munz,F.
A1  - Petzold,A.
A1  - Schwaiger,M.
A1  - Conrad,B.
A1  - Bartenstein,P.
Y1  - 1999/04//
N1  - UI - 99251700
SP  - 686
EP  - 690
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 20
IS  - 4
N2  - Using 18F-fluorodeoxyglucose and 11C-diprenorphine positron emission tomography (PET), we investigated alterations in glucose metabolism and opioid receptor binding in a patient with central poststroke pain, which developed after a small pontine hemorrhagic infarction. In comparison with normal databases, reduced 11C-diprenorphine binding was more accentuated than the hypometabolism on the lateral cortical surface contralateral to the symptoms, and a differential abnormal distribution between the tracers was seen in pain-related central structures. These results show that 11C-diprenorphine PET provides unique information for the understanding of central poststroke pain
AD  - Department of Nuclear Medicine, Technische Universitat Munchen, Germany
UR  - PM:10319982
ER  - 

TY  - JOUR
T1  - Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography
A1  - Madar,I.
A1  - Lesser,R.P.
A1  - Krauss,G.
A1  - Zubieta,J.K.
A1  - Lever,J.R.
A1  - Kinter,C.M.
A1  - Ravert,H.T.
A1  - Musachio,J.L.
A1  - Mathews,W.B.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 1997/03//
N1  - UI - 97219057
SP  - 358
EP  - 367
JA  - Ann.Neurol
VL  - 41
IS  - 3
N2  - The involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies in patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation of the opioid-receptor subtypes. The present study extends our previous observations to delta-opioid receptors by using the delta-receptor-selective antagonist [11C]methylnaltrindole ([11C]MeNTI). Paired measurements of delta- and mu-opioid receptor binding and metabolic activity were performed with PET using [11C]MeNTI and [11C]carfentanil ([11C]CFN) and [18F]fluorodeoxyglucose ([18F]FDG), respectively. Binding of [11C]MeNTI and [11C]CFN increased and [18F]FDG uptake decreased in the temporal cortex (TC) ipsilateral to the focus. Decreases in [18F]FDG uptake were more widespread regionally than were increases in opioid receptors. Increases in the delta- and mu-receptor binding showed different regional patterns. Increases in mu-receptor binding were confined to the middle aspect of the inferior TC, whereas binding of delta receptors increased in the mid-inferior TC and anterior aspect of the middle and superior TC. The increase in delta receptors suggests their anticonvulsant action, as previously shown for the delta-receptor subtype, whereas the different regional pattern of receptor alterations suggest the distinct roles of different opioid-receptor subtypes in seizure phenomena
AD  - Department of Radiology, Johns Hopkins University, Baltimore, MD 21287, USA
UR  - PM:9066357
ER  - 

TY  - JOUR
T1  - Functional neuroimaging with positron emission tomography
A1  - Henry,T.R.
Y1  - 1996/12//
N1  - UI - 97115444
SP  - 1141
EP  - 1154
JF  - Epilepsia
VL  - 37
IS  - 12
N2  - Epilepsy research using positron emission tomography (PET) has provided considerable new information about ictal and interictal dysfunctions in human epilepsy. Neuroreceptor mapping with PET ligands has revealed altered central benzodiazepine receptor and opiate receptor densities in partial epilepsies interictally, and regional increases in endogenous opioid peptide concentrations during absence seizures. Imaging of perfusion and glucose metabolism during cognitive processing has shown interictal abnormalities of regional activation in partial and generalized epilepsies. The diagnostically robust patterns of interictal glucose hypometabolism are not adequately explained by macrostructural and microstructural alterations in temporal lobe epilepsy. Current investigations of the pathophysiology of interictal hypometabolism must address ultrastructural and neurochemical factors. Clinical PET in presurgical evaluation of medically refractory epilepsies remains an active area of research, but remarkably little antiepileptic drug research has exploited PET techniques
AD  - Department of Neurology, Entory University School of Medicine, Atlanta, Georgia, USA
UR  - PM:8956845
ER  - 

TY  - JOUR
T1  - Imaging of delta opioid receptors in human brain by N1'-([11C]methyl)naltrindole and PET
A1  - Madar,I.
A1  - Lever,J.R.
A1  - Kinter,C.M.
A1  - Scheffel,U.
A1  - Ravert,H.T.
A1  - Musachio,J.L.
A1  - Mathews,W.B.
A1  - Dannals,R.F.
A1  - Frost,J.J.
Y1  - 1996/09//
N1  - UI - 97197931
SP  - 19
EP  - 28
JF  - Synapse
VL  - 24
IS  - 1
N2  - Recently, we have developed the positron emitting radiotracer N1'-([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for delta opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [11C]MeNTI for the delta opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [11C]MeNTI for delta opioid receptor in the human brain. First, the regional kinetics of [11C]MeNTI are in accordance with the density of the delta opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [11C]MeNTI correlated well (r = 0.91) with the in vitro distribution of delta opioid sites but not with mu or kappa site densities (r < or = 0.008 or r < or = 0.014, respectively). [11C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [11C]MeNTI binding. Naltrexone inhibition of [11C]MeNTI binding was most effective in delta receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of delta opioid sites. [11C]MeNTI is the first radioligand which selectively labels delta opioid receptors in vivo in the human brain following systemic administration. The availability of [11C]MeNTI will enable a receptor specific analysis of the role of [11C]MeNTI receptors in normal and abnormal human brain
AD  - Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21205-2179, USA
UR  - PM:9046073
ER  - 

TY  - JOUR
T1  - Human brain activity response to fentanyl imaged by positron emission tomography
A1  - Firestone,L.L.
A1  - Gyulai,F.
A1  - Mintun,M.
A1  - Adler,L.J.
A1  - Urso,K.
A1  - Winter,P.M.
Y1  - 1996/06//
N1  - UI - 96233539
SP  - 1247
EP  - 1251
JA  - Anesth.Analg.
VL  - 82
IS  - 6
N2  - Positron emission tomography (PET) is a noninvasive imaging technique that can be used to observe drug actions on human brain in vivo. We used 15O-water PET scanning in six volunteers to examine the effects on regional cerebral activity as reflected by regional cerebral blood flow (rCBF) of a small intravenous bolus of fentanyl. rCBF was compared between scans obtained after fentanyl or a placebo using three separate statistical criteria including a pixel-by-pixel t statistic; significance was stringently defined at P values < 0.01. Anatomic locations of regional cerebral activity changes were verified by aligning rCBF PET scans with cranial magnetic resonance images using mathematical coregistration. Fentanyl administration was associated with significant increases in rCBF consistent with regional neuronal activation in both cingulate and orbitofrontal and medial prefrontal cortices, as well as caudate nuclei. These areas are responsive to nociceptive stimuli and are involved in avoidance learning, reward and addiction, visceromotor control, maintenance of attention, and pain-related affective behavior. Significant decreases were noted in both frontal and temporal areas and the cerebellum, a distribution far less extensive than that of opiate receptors in general. These data indicate that fentanyl's effects are highly localized and specifically affect cerebral regions associated with a range of pain-related behaviors
AD  - Department of Anesthesiology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
UR  - PM:8638799
ER  - 

TY  - JOUR
T1  - Opiate receptors in idiopathic generalised epilepsy measured with [11C]diprenorphine and positron emission tomography
A1  - Prevett,M.C.
A1  - Cunningham,V.J.
A1  - Brooks,D.J.
A1  - Fish,D.R.
A1  - Duncan,J.S.
Y1  - 1994/09//
N1  - UI - 95112786
SP  - 71
EP  - 77
JA  - Epilepsy Res
VL  - 19
IS  - 1
N2  - The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:7813416
ER  - 

TY  - JOUR
T1  - Quantification of opiate receptors in two patients with mesiobasal temporal lobe epilepsy, before and after selective amygdalohippocampectomy, using positron emission tomography
A1  - Bartenstein,P.A.
A1  - Prevett,M.C.
A1  - Duncan,J.S.
A1  - Hajek,M.
A1  - Wieser,H.G.
Y1  - 1994/06//
N1  - UI - 95045354
SP  - 119
EP  - 125
JA  - Epilepsy Res
VL  - 18
IS  - 2
N2  - Using PET, reduced glucose metabolism (rCMRglu) and increased binding of the mu opiate receptor ligand 11C-carfentanil have been demonstrated in lateral temporal cortex overlying mesial temporal epileptic foci. Binding of the non-specific opiate receptor ligand 11C-diprenorphine (DPN) to lateral temporal cortex has not shown consistent asymmetries. We measured rCMRglu with 18F-FDG and binding of 11C-diprenorphine in two patients with temporal lobe epilepsy (TLE) before and 5 months after selective amygdalo-hippocampectomy (both patients were seizure-free post-operatively). Pre-operatively, in both patients rCMRglu was decreased in mesial temporal lobe (MTL) (asymmetry index AI = -9.1 and 9.0) ipsilateral to the EEG focus. A more marked reduction was seen in ipsilateral lateral temporal cortex (LTC) (AI = -32.0 and 18.9). DPN binding was reduced in MTL and LTC (AI MTL = -9.3 and 16.2; AI LTC = -8.0 and 5.5) ipsilateral to the focus, but was within 2 SD of the normal range. Post-operatively, the reduction of rCMRglu in LTC was accentuated in one patient and decreased in the other (AI = -23.1 and 45.7) while there was a further reduction of DPN binding in LTC in both patients (AI = -27.8 and 9.8). These preliminary results in only two patients are compatible with downregulation of opiate receptors in LTC after removal of the epileptic focus or post-operative neuronal dysfunction
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:7957034
ER  - 

TY  - JOUR
T1  - Quantitation of [11C]diprenorphine cerebral kinetics in man acquired by PET using presaturation, pulse-chase and tracer-only protocols
A1  - Jones,A.K.
A1  - Cunningham,V.J.
A1  - Ha-Kawa,S.K.
A1  - Fujiwara,T.
A1  - Liyii,Q.
A1  - Luthra,S.K.
A1  - Ashburner,J.
A1  - Osman,S.
A1  - Jones,T.
Y1  - 1994/03//
N1  - UI - 94328621
SP  - 123
EP  - 134
JA  - J Neurosci.Methods
VL  - 51
IS  - 2
N2  - The quantitation of regional cerebral in vivo opioid receptor rate constants using [11C]diprenorphine and positron emission tomography (PET) using 3 types of protocol (presaturation, pulse-chase naloxone displacement and tracer-only protocols) together with measurements of regional cerebral blood flow is described in normal volunteers. Arterial blood was sampled continuously for radioactivity and was corrected for metabolites and plasma/blood partition of radioactivity to provide a continuous plasma input function. A compartmental model involving 3 tissue compartments was used to describe the regional cerebral pharmacokinetics of the tracer. The compartments comprised: (1) free plus rapidly exchanging non-specifically bound ligand, (2) specifically bound, naloxone displaceable ligand, and (3) a kinetically distinguishable non-specifically bound pool. Regional estimates of fractional rate constants relating to specific binding were obtained using naloxone in a pulse-chase design of tracer displacement. Less precise estimates of these rate constraints were obtained from single-tracer-only studies, but when binding was expressed as the tissue total volume of distribution relative to plasma there was good correlation with regional values obtained from pulse-chase studies performed in the same individuals. The application of these protocols to the measurement of indices of regional-specific opioid receptor binding in the human brain is discussed
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:8051944
ER  - 

TY  - JOUR
T1  - Investigation of the opioid system in absence seizures with positron emission tomography
A1  - Bartenstein,P.A.
A1  - Duncan,J.S.
A1  - Prevett,M.C.
A1  - Cunningham,V.J.
A1  - Fish,D.R.
A1  - Jones,A.K.
A1  - Luthra,S.K.
A1  - Sawle,G.V.
A1  - Brooks,D.J.
Y1  - 1993/12//
N1  - UI - 94096001
SP  - 1295
EP  - 1302
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 56
IS  - 12
N2  - The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 minutes after injection of diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate constant (k3). These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:8270930
ER  - 

TY  - JOUR
T1  - Comparison of bolus and infusion methods for receptor quantitation: application to [18F]cyclofoxy and positron emission tomography
A1  - Carson,R.E.
A1  - Channing,M.A.
A1  - Blasberg,R.G.
A1  - Dunn,B.B.
A1  - Cohen,R.M.
A1  - Rice,K.C.
A1  - Herscovitch,P.
Y1  - 1993/01//
N1  - UI - 93107232
SP  - 24
EP  - 42
JA  - J Cereb.Blood Flow Metab
VL  - 13
IS  - 1
N2  - Positron emission tomography studies with the opiate antagonist [18F]cyclofoxy ([18F]CF) were performed in baboons. Bolus injection studies demonstrated initial uptake dependent on blood flow. The late uptake showed highest binding in caudate nuclei, amygdala, thalamus, and brainstem and the least accumulation in cerebellum. By 60 min postinjection, regional brain radioactivity cleared at the same rate as metabolite-corrected plasma, i.e., transient equilibrium was achieved. Compartmental modeling methods were applied to time-activity curves from brain and metabolite-corrected plasma. Individual rate constants were estimated with poor precision. The model estimate of the total volume of distribution (VT), representing the ratio of tissue radioactivity to metabolite-corrected plasma at equilibrium, was reliably determined. The apparent volume of distribution (Va), the concentration ratio of tissue to metabolite-corrected plasma during transient equilibrium, was compared with the fitted VT values to determine if single-scan methods could provide accurate receptor measurements. Va significantly overestimated VT and produced artificially high image contrast. These differences were predicted by compartment model theory and were caused by a plasma clearance rate that was close to the slowest tissue clearance rate. To develop a simple method to measure VT, an infusion protocol consisting of bolus plus continuous infusion (B/I) of CF was designed and applied in a separate set of studies. The Va values from the B/I studies agreed with the VT values from both B/I and bolus studies. This infusion approach can produce accurate receptor measurements and has the potential to shorten scan time and simplify the acquisition and processing of scan and blood data
AD  - Positron Emission Tomography Department, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
UR  - PM:8380178
ER  - 

TY  - JOUR
T1  - In vivo binding of N1'-([11C]methyl)naltrindole to delta-opioid receptors in mouse brain
A1  - Lever,J.R.
A1  - Scheffel,U.
A1  - Kinter,C.M.
A1  - Ravert,H.T.
A1  - Dannals,R.F.
A1  - Wagner,H.N.,Jr.
A1  - Frost,J.J.
Y1  - 1992/06/17/
N1  - UI - 93049672
SP  - 459
EP  - 460
JA  - Eur.J Pharmacol.
VL  - 216
IS  - 3
N2  - The regional distribution of N1'-([11C]methyl)naltrindole ([11C]MeNTI) in vivo in mouse brain correlates with established delta opioid receptor densities in vitro. [11C]MeNTI binding is blocked by naltrindole, a delta antagonist, but not by cyprodime, a mu antagonist, of by (+/-)-U50,488, a kappa agonist. Thus, [11C]MeNTI selectively labels central delta opioid receptors in vivo in mouse, and shows promise for positron emission tomography studies of delta sites in human brain
AD  - Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205
UR  - PM:1330587
ER  - 

TY  - JOUR
T1  - Preparation and biodistribution in mice of [11C]carfentanil: a radiopharmaceutical for studying brain mu-opioid receptors by positron emission tomography
A1  - Saji,H.
A1  - Tsutsumi,D.
A1  - Magata,Y.
A1  - Iida,Y.
A1  - Konishi,J.
A1  - Yokoyama,A.
Y1  - 1992/02//
N1  - UI - 92392690
SP  - 63
EP  - 67
JA  - Ann.Nucl Med
VL  - 6
IS  - 1
N2  - A potent mu-opioid agonist, [11C]carfentanil, was prepared by the methylation of carfentanil carboxylic acid with [11C]methyl iodide in order to study brain mu-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/mumol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of [11C]carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of [11C]carfentanil by the thalamus and striatum. These results indicate that [11C]carfentanil binds specifically to brain mu-opioid receptors
AD  - Faculty of Pharmaceutical Sciences, Kyoto University, Japan
UR  - PM:1325823
ER  - 

TY  - JOUR
T1  - Regional brain measurement of Bmax and KD with the opiate antagonist cyclofoxy: equilibrium studies in the conscious rat
A1  - Kawai,R.
A1  - Carson,R.E.
A1  - Dunn,B.
A1  - Newman,A.H.
A1  - Rice,K.C.
A1  - Blasberg,R.G.
Y1  - 1991/07//
N1  - UI - 91268158
SP  - 529
EP  - 544
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 4
N2  - Brain distribution of the opiate receptor antagonist, cyclofoxy (CF), was evaluated at equilibrium in rats. A combination of i.v. injection and constant i.v. infusion was used to administer CF over a wide dose range (2.4-450 nmol/rat). Kinetic simulations and experimental results showed that this administration schedule accomplishes "true" tissue-blood equilibrium of CF within 60 min. To estimate the receptor-ligand binding parameters, we assumed that the CF concentration at the receptor site is identical to that in plasma water at equilibrium, and can be calculated from measured blood data after corrections for radiolabeled metabolites and plasma protein binding. This assumption was supported by CSF and plasma water measurements at equilibrium. Regional KD, Bmax, and a nonspecific tissue binding equilibrium constant (Keq) were estimated by fitting the tissue and plasma water concentrations to a single receptor model; the estimated values were 1.4-2.9 nM, 15-74 pmol/g of tissue, and 5.2-8.0, respectively. They are in good agreement with previous in vitro measurements (Rothman and McLean, 1988) as well as in vivo estimates from i.v. injection experiments (Sawada et al., 1990c). The conventional method to estimate the receptor-ligand binding parameters using data from cerebellum to approximate nonspecific tissue binding was found to be unacceptable. Although cerebellum is a brain region with no opiate receptors in rats, small differences in nonspecific tissue binding in different brain regions resulted in significant overestimations of KD and Bmax with this method. Receptor-active and -inactive enantiomers [[18F](-)-CF and [3H](+)-CF)] were simultaneously administered to the same animal and the receptor-bound CF concentration could be accurately measured; this method was used to estimate Bmax from a single study in a single animal and has potential for direct application in human studies using positron emission tomography
AD  - Nuclear Medicine PET Program, NIDDK, National Institutes of Health, Bethesda, Maryland
UR  - PM:1646826
ER  - 

TY  - JOUR
T1  - In vivo distribution of opioid receptors in man in relation to the cortical projections of the medial and lateral pain systems measured with positron emission tomography
A1  - Jones,A.K.
A1  - Qi,L.Y.
A1  - Fujirawa,T.
A1  - Luthra,S.K.
A1  - Ashburner,J.
A1  - Bloomfield,P.
A1  - Cunningham,V.J.
A1  - Itoh,M.
A1  - Fukuda,H.
A1  - Jones,T.
Y1  - 1991/05/13/
N1  - UI - 91326335
SP  - 25
EP  - 28
JA  - Neurosci.Lett.
VL  - 126
IS  - 1
N2  - In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefrontal cortex) and lateral pain system (primary somatosensory cortex) in male volunteers has been quantitated using [11C]diprenorphine and positron emission tomography. High levels of opioid receptor binding were seen in the cortical projections of the medial pain system in the cingulate and prefrontal cortex as has previously been observed in post-mortem studies. However, a focal reduction of opioid receptor binding was observed and quantitated in the primary motor/sensory strip when compared to surrounding parietal cortex. This new finding suggests that the medial pain system is likely to be more susceptible to exogenous and endogenous opioid neuromodulation than the so-called lateral pain system
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, U.K
UR  - PM:1650933
ER  - 

TY  - JOUR
T1  - Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography
A1  - Sadzot,B.
A1  - Price,J.C.
A1  - Mayberg,H.S.
A1  - Douglass,K.H.
A1  - Dannals,R.F.
A1  - Lever,J.R.
A1  - Ravert,H.T.
A1  - Wilson,A.A.
A1  - Wagner,H.N.,Jr.
A1  - Feldman,M.A.
A1  - .
Y1  - 1991/03//
N1  - [published erratum appears in J Cereb Blood Flow Metab 1992 Sep;12(5):885]
SP  - 204
EP  - 219
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 2
N2  - [11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of [11C]diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of [11C]diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205
UR  - PM:1847703
ER  - 

TY  - JOUR
T1  - Kinetic analysis of transport and opioid receptor binding of [3H](-)-cyclofoxy in rat brain in vivo: implications for human studies
A1  - Sawada,Y.
A1  - Kawai,R.
A1  - McManaway,M.
A1  - Otsuki,H.
A1  - Rice,K.C.
A1  - Patlak,C.S.
A1  - Blasberg,R.G.
Y1  - 1991/03//
N1  - UI - 91147464
SP  - 183
EP  - 203
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 2
N2  - [3H]Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model (Sawada et al., 1990a) and a classical compartmental pharmacokinetic model (Wong et al., 1986a) were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied modestly in different brain structures (Keq = 3-9), whereas the binding potential (BP) varied over a much broader range (BP = 0.6-32). In vivo estimates of the opioid receptor dissociation constant were similar for different brain structures (KD = 2.1-5.2 nM), whereas the apparent receptor density (Bmax) varied between 1 (cerebellum) and 78 (thalamus) pmol/g of brain. The receptor dissociation rate constants in cerebrum (k4 = 0.08-0.16 min-1; koff = 0.16-0.23 min-1) and brain vascular permeability (PS = 1.3-3.4 ml/min/g) are sufficiently high to achieve equilibrium conditions within a reasonable period of time. Graphical analysis (Patlak and Blasberg, 1985) of the data is inappropriate due to the high tissue-loss rate constant (kb = 0.03-0.07 min-1) for CF in brain. From these findings, CF should be a very useful opioid receptor ligand for the estimation of the receptor binding parameters in human subjects using [18F]CF and positron emission tomography
AD  - Nuclear Medicine Department Clinical Center, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
UR  - PM:1847702
ER  - 

TY  - JOUR
T1  - Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro
A1  - Cunningham,V.J.
A1  - Hume,S.P.
A1  - Price,G.R.
A1  - Ahier,R.G.
A1  - Cremer,J.E.
A1  - Jones,A.K.
Y1  - 1991/01//
N1  - UI - 91072468
SP  - 1
EP  - 9
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 1
N2  - The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [3H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (Bmax), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37 degrees C, pH 7.4, in the presence and absence of naloxone, to give corresponding regional estimates of Bmax and the half-saturation constant Kd. The results showed a close correlation between in vitro and in vivo regional estimates of Bmax over a wide range. There were no significant interregional differences either in Kd in vitro or in the Kd derived from the in vivo analysis, although in vitro and in vivo estimates differed by an order of magnitude. This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, England
UR  - PM:1845764
ER  - 

TY  - JOUR
T1  - Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography
A1  - Frost,J.J.
A1  - Mayberg,H.S.
A1  - Sadzot,B.
A1  - Dannals,R.F.
A1  - Lever,J.R.
A1  - Ravert,H.T.
A1  - Wilson,A.A.
A1  - Wagner,H.N.,Jr.
A1  - Links,J.M.
Y1  - 1990/07//
N1  - UI - 90270301
SP  - 484
EP  - 492
JA  - J Cereb.Blood Flow Metab
VL  - 10
IS  - 4
N2  - The kinetics and regional distribution of [11C]carfentanil, a mu-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at approximately 40 min, whereas [11C]diprenorphine showed a linear increase until approximately 60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of mu-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-mu sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the mu sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the delta- and kappa-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace mu, delta, and kappa subtypes, will help offset these limitations
AD  - Department of Radiology (Division of Nuclear Medicine), Johns Hopkins Medical Institutions, Baltimore, Maryland
UR  - PM:2161414
ER  - 

TY  - JOUR
T1  - N-(3-[18F]fluoropropyl)-N-nordiprenorphine: synthesis and characterization of a new agent for imaging opioid receptors with positron emission tomography
A1  - Chesis,P.L.
A1  - Hwang,D.R.
A1  - Welch,M.J.
Y1  - 1990/05//
N1  - UI - 90230256
SP  - 1482
EP  - 1490
JA  - J Med Chem.
VL  - 33
IS  - 5
N2  - A series of N-fluoroalkyl (1-5) and N-alkyl (6-8) analogues of the high-affinity opioid receptor antagonist diprenorphine (9) has been synthesized and evaluated with in vitro binding assays. Three of the N-fluoroalkyl compounds were prepared with the positron-emitting radionuclide 18F (1a, 2a, 5a), and their biodistribution was determined in rats. Compounds 2a and 5a were made by using a two-step labeling procedure, [18F]fluoride displacement of an iodoalkyl triflate followed by N-alkylation, that required 2 h and proceeded in 4-6% overall radiochemical yield at the end of synthesis. The effective specific activity of compounds 2a and 5a, determined by competitive receptor binding assay, was 840-1820 Ci/mmol. Compound 1a was made by the same two-step procedure, with the bromoalkyl triflate, in 0.3-0.6% radiochemical yield at an effective specific activity of 106-264 Ci/mmol. Specificity of binding in vivo was measured as the percent injected dose/gram of striatal tissue divided by the percent injected dose/gram of cerebellar tissue. The best striatum to cerebellum ratio (3.32 +/- 0.74 at 30 min) was achieved with N-(3-[18F]-fluoropropyl)-N-nordiprenorphine (2a, [18F]FPND). The high specific binding demonstrated by this compound indicates that it may be useful for in vivo imaging of opioid receptors with positron emission tomography
AD  - Division of Radiation Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110
UR  - PM:2158564
ER  - 

TY  - JOUR
T1  - Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography
A1  - Frost,J.J.
A1  - Douglass,K.H.
A1  - Mayberg,H.S.
A1  - Dannals,R.F.
A1  - Links,J.M.
A1  - Wilson,A.A.
A1  - Ravert,H.T.
A1  - Crozier,W.C.
A1  - Wagner,H.N.,Jr.
Y1  - 1989/06//
N1  - UI - 89234279
SP  - 398
EP  - 409
JA  - J Cereb.Blood Flow Metab
VL  - 9
IS  - 3
N2  - [11C]-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of [11C]-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible
AD  - Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland
UR  - PM:2541148
ER  - 

TY  - JOUR
T1  - Radiosynthesis of an opiate receptor binding radiotracer: [11C]carfentanil
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Frost,J.J.
A1  - Wilson,A.A.
A1  - Burns,H.D.
A1  - Wagner,H.N.,Jr.
Y1  - 1985/04//
N1  - UI - 85260093
SP  - 303
EP  - 306
JA  - Int.J Appl.Radiat.Isot.
VL  - 36
IS  - 4
N2  - Carfentanil, a potent opiate receptor agonist, was labeled with 11C for in vivo studies using positron emission tomography. This synthesis was completed in approximately 30 min using iodomethane as the 11C precursor. The synthesis, purification, characterization, and determination of specific activity are presented and discussed
UR  - PM:2991142
ER  - 

TY  - JOUR
T1  - Imaging opiate receptors in the human brain by positron tomography
A1  - Frost,J.J.
A1  - Wagner,H.N.,Jr.
A1  - Dannals,R.F.
A1  - Ravert,H.T.
A1  - Links,J.M.
A1  - Wilson,A.A.
A1  - Burns,H.D.
A1  - Wong,D.F.
A1  - McPherson,R.W.
A1  - Rosenbaum,A.E.
A1  - .
Y1  - 1985/03//
N1  - UI - 85132021
SP  - 231
EP  - 236
JA  - J Comput.Assist.Tomogr.
VL  - 9
IS  - 2
N2  - Carfentanil is a potent, synthetic opiate that binds to mu opiate receptors with very high affinity (KI = 0.051 nM, 37 degrees C). In rat brain, carfentanil is 90 and 250 times more selective for mu opiate receptors compared with delta and kappa opiate receptors, respectively. Carbon-11-carfentanil was synthesized by reacting [11C]methyliodide with the carboxylic acid precursor of carfentanil. Carbon-11-carfentanil was injected intravenously in man and a baboon and the distribution of the radioactivity in the brain was monitored using positron emission tomography. High concentrations of radioactivity were observed in the basal ganglia and thalamus, intermediate concentrations in the frontal and parietal cerebral cortex, and low concentrations in the cerebellum and occipital cortex; this distribution corresponds to the known regional density of opiate receptors measured using in vitro techniques. This heterogeneous distribution could be abolished by pretreatment with naloxone (1 mg/kg), an opiate antagonist. The percent inhibition of binding by naloxone is approximately 90% in the caudate nucleus and medial thalamus for the period 30-60 min after injection; therefore, this method is associated with a high level of specific binding to opiate receptors compared with nonspecific binding sites. The ability to measure opiate receptors in vivo in man makes it possible to study a variety of neurologic and psychiatric disorders in which opiate receptors are thought to be abnormal and to study physiologic role of opiate receptors in the central nervous system
UR  - PM:2982931
ER  - 

TY  - JOUR
T1  - 3-[18F]Acetylcyclofoxy: a useful probe for the visualization of opiate receptors in living animals
A1  - Pert,C.B.
A1  - Danks,J.A.
A1  - Channing,M.A.
A1  - Eckelman,W.C.
A1  - Larson,S.M.
A1  - Bennett,J.M.
A1  - Burke,T.R.,Jr.
A1  - Rice,K.C.
Y1  - 1984/11/19/
N1  - UI - 85051859
SP  - 281
EP  - 286
JA  - FEBS Lett.
VL  - 177
IS  - 2
N2  - A fluoro-analogue of the potent narcotic antagonist, naltrexone, was synthesized and shown to bind with high affinity to opiate receptors in vitro. 3-[18F]acetylcyclofoxy was prepared via a one-step triflate displacement reaction with the positron emitting 18F ion from tetraethylammonium [18F] fluoride. 3-[18F]acetylcyclofoxy accumulation in opiate receptor rich brain regions of both rat and baboon is shown to be completely displaced by the active enantiomer of naloxone [-)-naloxone) while the identical dose of the pharmacologically inert (+)-naloxone has no detectable effect. Moreover, both rat and baboon brain showed the well documented, typical opiate receptor distribution so that basal ganglia and thalamus are clearly visible in the living baboon brain up to 95 min after intravenous injection of 3-[18F] acetylcyclofoxy. We expect that 3-[18F )acetylcyclofoxy will be a useful probe for visualizing opiate receptors in living humans
UR  - PM:6094248
ER  - 

TY  - JOUR
T1  - Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease
A1  - Hilker,R.
A1  - Voges,J.
A1  - Weisenbach,S.
A1  - Kalbe,E.
A1  - Burghaus,L.
A1  - Ghaemi,M.
A1  - Lehrke,R.
A1  - Koulousakis,A.
A1  - Herholz,K.
A1  - Sturm,V.
A1  - Heiss,W.-D.
Y1  - 2004///
SP  - 7
EP  - 16
JF  - Journal of Cerebral Blood Flow & Metabolism
JA  - J.Cereb.Blood Flow Metab.
VL  - 24
ER  - 

TY  - JOUR
T1  - PET studies of the influences of nicotine on neural systems in cigarette smokers
A1  - Rose,J.E.
A1  - Behm,F.M.
A1  - Westman,E.C.
A1  - Mathew,R.J.
A1  - London,E.D.
A1  - Hawk,T.C.
A1  - Turkington,T.G.
A1  - Coleman,R.E.
Y1  - 2003/02//
N1  - UI - 22449971
SP  - 323
EP  - 333
JA  - Am J Psychiatry
VL  - 160
IS  - 2
N2  - OBJECTIVE: The effects of acute nicotine administration and smoking on brain function were investigated in two studies, with the primary goal of identifying neural systems that mediate these effects. METHOD: In study 1, 18 healthy volunteer cigarette smokers were exposed to three conditions in a single session: 1) smoking a nicotine-containing cigarette, 2) smoking a denicotinized cigarette, or 3) receiving intravenous nicotine injections in conjunction with smoking a denicotinized cigarette. In study 2, 16 subjects smoked a nicotine-containing and denicotinized cigarette in each of two sessions 2 hours after receiving the nicotinic antagonist mecamylamine (10 mg) or placebo orally. Regional cerebral blood flow (rCBF) was assessed by using the bolus (15)O-labeled water method and positron emission tomography. Subjective measures of smoking withdrawal symptoms were also collected. RESULTS: A principal-components analysis of rCBF data pooled from the two studies identified three factors consisting of frontal, striatal, and reticular systems. The amygdala was considered as a separate region of interest. Nicotine increased normalized rCBF in the left frontal region and decreased rCBF in the left amygdala. The rCBF in the right hemisphere reticular system was related to nicotine dose in an inverted-U-shaped pattern and was strongly related to self-reported craving for cigarettes and to the addiction scale of a smoking motivation questionnaire. The effects of mecamylamine on rCBF were generally opposite to those of nicotine. CONCLUSIONS: The results indicate that nicotine influences brain regions involved in arousal and reward and suggest specific functional systems that may be linked to motivationally significant aspects of tobacco dependence
AD  - Veterans Affairs Medical Center, Durham, NC, USA. jerose@acpub.duke.edu
UR  - PM:12562580
ER  - 

TY  - JOUR
T1  - Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers
A1  - Dagher,A.
A1  - Bleicher,C.
A1  - Aston,J.A.
A1  - Gunn,R.N.
A1  - Clarke,P.B.
A1  - Cumming,P.
Y1  - 2001/10//
N1  - UI - 21525230
SP  - 48
EP  - 53
JF  - Synapse
VL  - 42
IS  - 1
N2  - Several drugs of abuse, including nicotine, are thought to exert their reinforcing effects through actions on the mesolimbic dopamine system. Animal and human studies suggest that chronic administration of addictive drugs may lead to impaired dopamine neurotransmission in the nucleus accumbens. We measured D1 receptor density in 11 smokers and 18 nonsmokers using positron emission tomography and the D1 receptor ligand [11C]SCH 23390. Ten of the smokers were scanned twice, once after overnight abstinence from cigarettes, and once while smoking at their usual rate, to account for possible acute effects of cigarette smoking on D1 receptor binding. In addition, eight control subjects were scanned twice to assess the reproducibility of the method. We used compartmental modeling to measure [11C]SCH 23390 binding potential, a measure of D1 receptor density. There were no differences in binding between abstinent and nonabstinent scans in smokers or in the two scans in controls. However, there was a significant reduction in [11C]SCH 23390 binding potential in smokers compared to nonsmokers in the striatum, most prominently in the ventral striatum. This suggests that there is a reduction in dopamine D1 receptor density in the ventral striatum of human cigarette smokers relative to nonsmokers, which implies that the postsynaptic mesolimbic dopamine system may be chronically underactive in smokers, either as an antecedent or consequence of addiction to cigarettes. Such a hypodopaminergic state may play an important role in sustaining nicotine-seeking behavior. Alternatively, an inherited reduction in dopamine receptors in the striatum may be associated with an increased risk of addictive behavior
AD  - McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada. alain@bic.mni.mcgill.ca
UR  - PM:11668590
ER  - 

TY  - JOUR
T1  - Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study
A1  - Martin-Solch,C.
A1  - Magyar,S.
A1  - Kunig,G.
A1  - Missimer,J.
A1  - Schultz,W.
A1  - Leenders,K.L.
Y1  - 2001/08//
N1  - UI - 21428192
SP  - 278
EP  - 286
JA  - Exp.Brain Res
VL  - 139
IS  - 3
N2  - Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded
AD  - PET Program, Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen, Switzerland. chantal.martin@unibas.ch
UR  - PM:11545466
ER  - 

TY  - JOUR
T1  - Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers
A1  - Domino,E.F.
A1  - Minoshima,S.
A1  - Guthrie,S.
A1  - Ohl,L.
A1  - Ni,L.
A1  - Koeppe,R.A.
A1  - Zubieta,J.K.
Y1  - 2000/12/01/
N1  - UI - 20473127
SP  - 313
EP  - 321
JF  - Synapse
VL  - 38
IS  - 3
N2  - The hypothesis for this research was that regional cerebral blood flow (rCBF) would increase following nasal nicotine administration to overnight abstinent tobacco smokers in relationship to the known brain distribution of nicotinic cholinergic receptors (nAChRs). Nine male and nine female healthy adult smokers were studied. They abstained overnight from tobacco products for 10 or more hours prior to study the next morning. Nicotine nasal spray was given in doses of 1-2.5 mg total with half in each nostril while the subject was awake and resting in a supine position. Oleoresin of pepper solution in a similar volume was used as an active placebo to control for the irritating effects of nicotine. Both substances were given single blind to the subjects. Positron emission tomography (PET) with H(2)(15)O was used to measure rCBF. The data from each subject volunteer were normalized to global activity to better assess regional brain changes. Both nasal nicotine and pepper spray produced similar increases in CBF in somesthetic area II, consistent with the irritant effects of both substances. The mean rCBF effects of nasal pepper were subtracted from those of nasal nicotine to determine the actions of nicotine alone. The latter produced increases in rCBF in the thalamus, pons, Brodman area 17 of the visual cortex, and cerebellum. Some brain areas that contain a large number of nAChRs, such as the thalamus, showed an increase in CBF. Other areas that have few nAChRs, such as the cerebellum, also showed an increase in relative CBF. The hippocampal/parahippocampal areas showed greater regional decreases (left) and lesser increases (right) in CBF that correlated with the increase in plasma arterial nicotine concentrations. The results obtained indicate complex primary and secondary effects of nicotine in which only some regional brain CBF changes correlate with the known distribution of nAChR. No gender differences were noted
AD  - Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA
UR  - PM:11020234
ER  - 

TY  - JOUR
T1  - Characterization of the nicotinic ligand 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine in vivo
A1  - Valette,H.
A1  - Bottlaender,M.
A1  - Dolle,F.
A1  - Guenther,I.
A1  - Coulon,C.
A1  - Hinnen,F.
A1  - Fuseau,C.
A1  - Ottaviani,M.
A1  - Crouzel,C.
Y1  - 1999///
SP  - L93
EP  - L97
JA  - Life Sci.
VL  - 64
IS  - 5
N2  - The biodistribution of the nicotinic acetylcholine receptor (nAChR) radioligand 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([18F]fluoro-A-85380, half-life of fluorine-18 = 110 min) in selected rat brain areas was assessed in vivo. The radiotracer showed a good penetration in the brain. The regional distribution of the radioligand was consistent with the density of nAChRs determined from previous studies in vitro. Sixty minutes post-injection, the highest uptake was observed in the thalamus, (1% I.D./g tissue), an intermediate one in the frontal cortex (0.78% I.D./g tissue), and the lowest in the cerebellum (0.5% I.D./g tissue). Pretreatment with several nAChR ligands (nicotine, cytisine, epibatidine, unlabeled fluoro-A-85380) substantially reduced uptake of the radioligand in the three cerebral areas. Pretreatment with the nAChR channel blocker mecamylamine or with the muscarinic receptor antagonist dexetimide had no appreciable effect on the uptake of fluoro-A-85380. These results support the high in vivo selectivity and specificity of fluoro-A-85380. Therefore, [18F]fluoro-A-85380 may be useful for positron emission tomography study of nAChRs in humans
AD  - CEA, Service Hospitalier Frederic Joliot, DSV/DRM, Orsay, France
UR  - PM:10072197
ER  - 

TY  - JOUR
T1  - Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography
A1  - Nordberg,A.
A1  - Lundqvist,H.
A1  - Hartvig,P.
A1  - Lilja,A.
A1  - Langstrom,B.
Y1  - 1995///
N1  - UI - 95329257
SP  - 21
EP  - 27
JA  - Alzheimer Dis.Assoc.Disord.
VL  - 9
IS  - 1
N2  - A compartment model has been developed and validated for the kinetic analysis of (S)(-)11C-nicotine binding in the brain including a compensation for the influence of regional cerebral blood flow (rCBF). The model was applied to eight patients with Alzheimer disease (AD) and three age-matched healthy volunteers who received intravenous injections of (S)(-)11C-nicotine and 11C-butanol. The uptake and time course of radioactivity in different brain regions were assessed by positron emission tomography (PET). The rate constant k2* was formulated by dividing the K2 rate constant for 11C-nicotine with the K1 rate constant for 11C-butanol and thereby minimizing the influence of CBF on the quantitated binding of 11C-nicotine. The rate constant k2* for 11C-nicotine giving a quantitative measure of binding in the brain tissue was significantly higher in the temporal and frontal cortices as well as in the hippocampus of AD brains as compared with controls, indicating deficits in specific nicotinic binding in these brain areas of AD patients. A significant and negative correlation was obtained between cognitive function (Mini-Mental State Examination) and k2* of 11C-nicotine in the temporal and frontal cortices as well as in the hippocampus. The described kinetic model allowed in vivo quantification of nicotinic receptor binding in brain, which will be of importance in the future for evaluation of diagnosis, progress of disease, as well as the therapeutic effects in the treatment of AD
AD  - Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Sweden
UR  - PM:7605618
ER  - 

TY  - JOUR
T1  - PET studies of the uptake of (S)- and (R)-[11C]nicotine in the human brain: difficulties in visualizing specific receptor binding in vivo
A1  - Nyback,H.
A1  - Halldin,C.
A1  - Ahlin,A.
A1  - Curvall,M.
A1  - Eriksson,L.
Y1  - 1994/06//
N1  - UI - 95167055
SP  - 31
EP  - 36
JA  - Psychopharmacology (Berl)
VL  - 115
IS  - 1-2
N2  - (S)- and (R)-[11C]nicotine were synthesized by methylation of (S)- and (R)-nornicotine using [11C]methyl iodide. Following their intravenous injection in tracer doses to smoking and nonsmoking healthy males the radioactivity in arterial blood showed a sharp peak at about 1 min followed by a plateau level for the remaining 50 min of recording. Uptake in the brain, as measured by positron emission tomography (PET), was rapid with a peak at 5 min followed by a steady decline towards the end of the measurement. The regional distribution of radioactivity followed essentially the distribution of gray matter with high uptake in the cortex, the thalamus and the basal ganglia and low uptake in the pons, cerebellum and white matter. Levels of the labelled natural enantiomer, (S)-[11C]nicotine, were higher than those of the synthetic enantiomer, (R)-[11C]nicotine, particularly in the smokers. The time-activity curves of (S)-[11C]nicotine uptake were not changed by co-administration of 1.0 mg of unlabelled nicotine with the labelled nicotine. Similarly administration of unlabelled nicotine at the peak of radioactivity, 6 min following (S)-[11C]nicotine, had no effect on the time-activity curves. Thus essential criteria for visualizing receptor binding with the PET technique could not be fulfilled. Calculation of kinetic constants using a two-compartment model gave values indicating that the brain uptake of [11C]nicotine is mainly determined by the cerebral blood flow, extraction of the tracer over the blood-brain barrier and unspecific binding. Thus 11C-labelled nicotine does not seem to be a suitable tracer for PET studies of nicotinic cholinergic receptors in the human brain
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:7862909
ER  - 

TY  - JOUR
T1  - Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters
A1  - Yokoi,F.
A1  - Komiyama,T.
A1  - Ito,T.
A1  - Hayashi,T.
A1  - Lio,M.
A1  - Hara,T.
Y1  - 1993/01//
N1  - UI - 93130936
SP  - 46
EP  - 52
JA  - Eur.J Nucl Med
VL  - 20
IS  - 1
N2  - Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labeled (R)nicotine. The rCBF of the same subjects was measured by PET using the C15O2 inhalation steady-state method. The distribution of 11C activity in the brain after injection of 11C-(R)nicotine was almost equivalent to the CBF image obtained with the C15O2 inhalation stead-state method. The kinetics of 11C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with 11C-(R)nicotine were higher than with C15O2 gas. The relatively long fixed distribution of 11C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H215O
AD  - Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan
UR  - PM:8420783
ER  - 

TY  - JOUR
T1  - Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography
A1  - Saji,H.
A1  - Magata,Y.
A1  - Yamada,Y.
A1  - Tajima,K.
A1  - Yonekura,Y.
A1  - Konishi,J.
A1  - Ohmomo,Y.
A1  - Yokoyama,A.
Y1  - 1992/03//
N1  - UI - 92306212
SP  - 734
EP  - 736
JA  - Chem.Pharm.Bull.(Tokyo)
VL  - 40
IS  - 3
N2  - A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S)-[11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity
AD  - Department of Radiopharmaceutical Chemistry, Kyoto University, Japan
UR  - PM:1611685
ER  - 

TY  - JOUR
T1  - Uptake and regional distribution of (+)-(R)- and (-)-(S)-N-[methyl-11C]-nicotine in the brains of rhesus monkey. An attempt to study nicotinic receptors in vivo
A1  - Nordberg,A.
A1  - Hartvig,P.
A1  - Lundqvist,H.
A1  - Antoni,G.
A1  - Ulin,J.
A1  - Langstrom,B.
Y1  - 1989///
N1  - UI - 89374734
SP  - 195
EP  - 205
JA  - J Neural Transm.Park Dis.Dement.Sect.
VL  - 1
IS  - 3
N2  - N-[methyl-11C] nicotine (11C-nicotine) was given intravenously to monkeys and the uptake and regional distribution of radioactivity was followed in the brain using positron emission tomography (PET). The 11C-radioactivity in the brain peaked within 1-2 min and then rapidly declined. Pretreatment with unlabelled nicotine (10 micrograms/kg) reduced the uptake of 11C-radioactivity to the brain by 30%. The uptake of radioactivity was higher following (+)11C-nicotine than (-)11C-nicotine. Both enantiomers were distributed in a similar manner within the brain. When animals were infused with a peripheral nicotinic blocker (trimetaphan) the uptake of radioactivity to the brain was lower following (+)11C-nicotine compared to (-)11C-nicotine. The amount of radioactivity was high in the occipital cortex, thalamus, intermediate in the frontal cortex and low in white matter in (-)11C injected monkeys while no regional difference in distribution of 11C-radioactivity was observed after injection of (+)11C-nicotine
AD  - Department of Pharmacology, University of Uppsala, Sweden
UR  - PM:2789067
ER  - 

TY  - JOUR
T1  - Positron imaging in ischemic stroke disease using compounds labeled with oxygen 15. Initial results of clinicophysiologic correlations
A1  - Ackerman,R.H.
A1  - Correia,J.A.
A1  - Alpert,N.M.
A1  - Baron,J.C.
A1  - Gouliamos,A.
A1  - Grotta,J.C.
A1  - Brownell,G.L.
A1  - Taveras,J.M.
Y1  - 1981/09//
N1  - UI - 81281134
SP  - 537
EP  - 543
JA  - Arch Neurol
VL  - 38
IS  - 9
N2  - Initial results in over 50 patients with stroke suggest that positron images made during continuous inhalation of carbon dioxide labeled with oxygen 15 and molecular oxygen labeled with oxygen 15 provide data on tissue function that may be relevant to acute stroke management. Five cases illustrate the following findings: 15O-activity patterns observed in areas of ischemic injury or infarction are what one would expect if the 15O distributions represented physiologic functions, such as cerebral blood flow and metabolism. Areas of abnormal 15O activity correlate with the clinical or computed tomographic (CT) localization of the deficit. In studies performed acutely, changes in 15O distributions anticipate alterations in CT scans and may be predictive of outcome. Data related to oxygen metabolism correlate better with tissue viability than do those reflecting cerebral blood flow
UR  - PM:6791617
ER  - 

TY  - JOUR
T1  - Regional cerebral blood flow and oxygen metabolism during migraine with and without aura
A1  - Andersson,J.L.
A1  - Muhr,C.
A1  - Lilja,A.
A1  - Valind,S.
A1  - Lundberg,P.O.
A1  - Langstrom,B.
Y1  - 1997/08//
N1  - UI - 97395771
SP  - 570
EP  - 579
JF  - Cephalalgia
VL  - 17
IS  - 5
N2  - Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO2) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6), headache (n = 10) and after treatment with sumatriptan (n = 4). Data were analysed using an ROI-based approach from 26 different anatomically defined regions, and also an exploratory approach whereby all subjects were normalized to a stereotactic brain atlas; t-maps were constructed by depicting significant changes between states. The exploratory approach revealed a region corresponding to the primary visual cortex with significant reductions in rCBF (23.1%) and rCMRO2 (22.5%), but no change in rOER during the headache phase compared to baseline. These data suggest that cerebral ischemia was not the primary cause of the attacks in these cases
AD  - Uppsala University PET Centre, Sweden
UR  - PM:9251871
ER  - 

TY  - JOUR
T1  - Simplified quantitative determination of cerebral perfusion reserve with H2(15)O PET and acetazolamide
A1  - Arigoni,M.
A1  - Kneifel,S.
A1  - Fandino,J.
A1  - Khan,N.
A1  - Burger,C.
A1  - Buck,A.
Y1  - 2000/10//
N1  - UI - 20534518
SP  - 1557
EP  - 1563
JA  - Eur.J Nucl Med
VL  - 27
IS  - 10
N2  - The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H2(15)O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H2(15)O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PRnAA) and rCBF (PRrCBF) (PRnAA=0.843 PRrCBF + 0.092, r=-0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PRnAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling
AD  - PET Center, Division of Nuclear Medicine, University Hospital, Zurich, Switzerland
UR  - PM:11083547
ER  - 

TY  - JOUR
T1  - Brainstem activation specific to migraine headache
A1  - Bahra,A.
A1  - Matharu,M.S.
A1  - Buchel,C.
A1  - Frackowiak,R.S.
A1  - Goadsby,P.J.
Y1  - 2001/03/31/
N1  - UI - 21188370
SP  - 1016
EP  - 1017
JF  - Lancet
VL  - 357
IS  - 9261
N2  - Findings from functional imaging studies have shown activation of the brainstem during migraine without aura (MWOA) and activation of the hypothalamus during cluster headache. We assessed a patient with cluster headache and migraine by positron emission tomography during an active cluster headache after he had taken 1.2 glyceryl trinitate. The patient developed a typical MWOA, during which we saw activation in the dorsal rostral brainstem. There was no activation in the region of the hypothalamus. Our findings provide evidence that migraine involves the brainstem, and show several areas involved in cluster headaches. Our data show the potential for objective distinction between primary headache syndromes with functional imaging, in disorders hitherto distinguished on clinical grounds
UR  - PM:11293599
ER  - 

TY  - JOUR
T1  - Depression of energy metabolism in distant brain structures: studies with positron emission tomography in stroke patients
A1  - Baron,J.C.
Y1  - 1989/12//
N1  - UI - 90371200
SP  - 281
EP  - 285
JA  - Semin.Neurol
VL  - 9
IS  - 4
AD  - Inserm U. Cyceron, Caen, France
UR  - PM:2701774
ER  - 

TY  - JOUR
T1  - Early [18F]FDG positron emission tomography in infants with hypoxic-ischaemic encephalopathy shows hypermetabolism during the postasphyctic period
A1  - Blennow,M.
A1  - Ingvar,M.
A1  - Lagercrantz,H.
A1  - Stone-Elander,S.
A1  - Eriksson,L.
A1  - Forssberg,H.
A1  - Ericson,K.
A1  - Flodmark,O.
Y1  - 1995/11//
N1  - UI - 96162294
SP  - 1289
EP  - 1295
JA  - Acta Paediatr.
VL  - 84
IS  - 11
N2  - Six full-term infants suffering from perinatal asphyxia and with moderate or severe hypoxic-ischaemic encephalopathy were investigated by positron emission tomography (PET). Regional cerebral metabolic rates of glucose (rCMRgl) were determined using [2-18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans at a median age of 2.5 days (range 2-5 days). Localized increases in rCMRgl were visually observed in five infants. In a subgroup of three infants, absolute values of rCMRgl in different brain regions were calculated. In all cases the results of the PET studies were in good agreement with those of the neuroradiological, neurophysiological and clinical investigations. Information indicating pathophysiological events could be extracted earlier with PET than with conventional morphological imaging techniques. We conclude that [18F]FDG-PET scans performed in critically ill, asphyxiated infants very soon after birth provide valuable information for the prediction about neurological outcome
AD  - Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden
UR  - PM:8580629
ER  - 

TY  - JOUR
T1  - Functional neuroimaging studies of motor recovery after stroke in adults: a review
A1  - Calautti,C.
A1  - Baron,J.C.
Y1  - 2003/06//
N1  - UI - 22677390
SP  - 1553
EP  - 1566
JF  - Stroke
VL  - 34
IS  - 6
N2  - BACKGROUND: The precise mechanisms of and biological basis for motor recovery after stroke in adults are still largely unknown. Reorganization of the motor system after stroke as assessed by functional neuroimaging is an intriguing but challenging new field of research. Provocative but equivocal findings have been reported to date. SUMMARY OF REVIEW: We present an overview of functional neuroimaging studies (positron emission tomography or functional MRI) of motor tasks in patients recovered or still recovering from motor deficit after stroke. After a brief account of the connectivity of motor systems and the imaging findings in normal subjects, the literature concerning stroke patients is reviewed and discussed, and a general model is proposed. CONCLUSIONS: Both cross-sectional and longitudinal studies have demonstrated that the damaged adult brain is able to reorganize to compensate for motor deficits. Rather than a complete substitution of function, the main mechanism underlying recovery of motor abilities involves enhanced activity in preexisting networks, including the disconnected motor cortex in subcortical stroke and the infarct rim after cortical stroke. Involvement of nonmotor and contralesional motor areas has been consistently reported, with the emerging notion that the greater the involvement of the ipsilesional motor network, the better is the recovery. This hypothesis is supported by the enhanced activity of the ipsilesional primary motor cortex induced by motor training and acute pharmacological interventions, in parallel with improved motor function. Further longitudinal studies assessing the relationships between such changes and actual recovery, as well as manipulating such changes by rehabilitation or pharmacological maneuvers, should provide further information on these fundamental questions. This review closes with some perspectives for future research
AD  - Department of Neurology, University of Cambridge, Cambrid, UK
UR  - PM:12738893
ER  - 

TY  - JOUR
T1  - Cerebral oxygen metabolism after aneurysmal subarachnoid hemorrhage
A1  - Carpenter,D.A.
A1  - Grubb,R.L.,Jr.
A1  - Tempel,L.W.
A1  - Powers,W.J.
Y1  - 1991/09//
N1  - UI - 91340874
SP  - 837
EP  - 844
JA  - J Cereb.Blood Flow Metab
VL  - 11
IS  - 5
N2  - Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure the regional cerebral metabolic rate for oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood flow (rCBF) 16 times in 11 patients with aneurysmal SAH. All studies were performed preoperatively; no patient had hydrocephalus or intracerebral hematoma on brain CT. Eight patients with no arteriographic vasospasm who were studied on days 1-4 post-SAH had a significant 25% reduction in global CMRO2 compared to age-matched controls, and no significant change in global OEF, suggesting a primary reduction in CMRO2 caused by SAH. Four patients studied seven times during arteriographic vasospasm had significantly increased rOEF with unchanged CMRO2 in arterial territories affected by arteriographic vasospasm compared to territories without vasospasm, indicative of cerebral ischemia without infarction. No brain regions studied with PET were infarcted on follow-up CT. We conclude that the initial aneurysm rupture produces a primary reduction in CMRO2, and that subsequent vasospasm causes ischemia
AD  - Edward Mallinckrodt Institute of Radiology, Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
UR  - PM:1874816
ER  - 

TY  - JOUR
T1  - Cortical metabolism in posterolateral thalamic stroke: PET study
A1  - Chabriat,H.
A1  - Pappata,S.
A1  - Levasseur,M.
A1  - Fiorelli,M.
A1  - Tran,Dinh S.
A1  - Baron,J.C.
Y1  - 1992/09//
N1  - UI - 93034140
SP  - 285
EP  - 290
JA  - Acta Neurol Scand.
VL  - 86
IS  - 3
N2  - In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain
AD  - Biology Department, Service Hospitalier Frederic Joliot, CEA, Caen, France
UR  - PM:1414249
ER  - 

TY  - JOUR
T1  - Experimental thromboembolic stroke studied by positron emission tomography: immediate versus delayed reperfusion by fibrinolysis
A1  - De Ley,G.
A1  - Weyne,J.
A1  - Demeester,G.
A1  - Stryckmans,K.
A1  - Goethals,P.
A1  - Van,de,V
A1  - Leusen,I.
Y1  - 1988/08//
N1  - UI - 88273346
SP  - 539
EP  - 545
JA  - J Cereb.Blood Flow Metab
VL  - 8
IS  - 4
N2  - Acute obstruction of the middle cerebral artery (MCA) was obtained by injecting a single autologous blood clot into the internal carotid artery of dogs. The technique induced very reproducible unilateral ischemic lesions in the MCA territory; hemorrhagic transformation of the lesions was often seen. The hemodynamic and metabolic effects of blood clot embolism were studied in 35 dogs with positron emission tomography (PET) and the 15O steady-state technique, and compared with a control group of seven intact animals. In the acute phase, the involved brain tissue still had a nearly normal oxygen consumption (-11%) despite the lowered tissue perfusion (-20%) caused by the vascular obstruction. The lowered oxygen availability was compensated by an increased oxygen extraction ratio (+11%). Twenty-four hours after the insult, the hemodynamic situation had barely changed, and the ischemic event had evolved into a brain infarct in which oxygen consumption was clearly lowered (-25%) and accompanied by a significant lowering (-22%) of the oxygen extraction ratio compared with the acute situation. Therapeutic thrombolysis by local administration of streptokinase (500,000 IU), starting 30 min after the insult, was not able to salvage any brain tissue or to ameliorate tissue perfusion despite angiographically confirmed clot lysis. However, when fibrinolytic therapy was started within the first 5 min after the insult, hemispheric blood flow was normalized, and most of the threatened brain tissue was salvaged, as was indicated by its normalized oxygen consumption and oxygen extraction ratio. Early fibrinolysis was accompanied by definite clinical improvement and substantial reduction in the severity of the morphological lesions that were never hemorrhagic
AD  - Laboratory of Normal and Pathological Physiology, University of Gent, Belgium
UR  - PM:3260595
ER  - 

TY  - JOUR
T1  - Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs
A1  - De Ley,G.
A1  - Eechaute,W.
A1  - Strijckmans,K.
A1  - Goethals,P.
A1  - Lemahieu,I.
A1  - Van,de,V
A1  - Weyne,J.
Y1  - 1993/03//
N1  - UI - 93190332
SP  - 400
EP  - 405
JF  - Stroke
VL  - 24
IS  - 3
N2  - BACKGROUND AND PURPOSE: Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect. METHODS: The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography. RESULTS: In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction. CONCLUSIONS: The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine
AD  - Laboratory of Normal and Pathological Physiology, University of Gent, Belgium
UR  - PM:8446977
ER  - 

TY  - JOUR
T1  - Crossed cerebellar diaschisis after middle cerebral artery infarction
A1  - De Reuck,J.
A1  - Decoo,D.
A1  - Lemahieu,I.
A1  - Strijckmans,K.
A1  - Goethals,P.
A1  - Van Maele,G.
Y1  - 1997/02//
N1  - UI - 97261534
SP  - 11
EP  - 16
JA  - Clin.Neurol Neurosurg
VL  - 99
IS  - 1
N2  - It is unclear whether crossed cerebellar diaschisis (CCD) is merely an epiphenomenon, as its clinical significance remains uncertain. We retrospectively analysed the positron emission tomographic (PET) findings in 28 patients with a chronic, stable middle cerebral artery (MCA) infarct and in 22 controls, using the steady state technique and 15O. Also, the Orgogozo scores on admission and at the time of the PET examination were compared in the patients with MCA infarction. Based on the asymmetry index and the 95% confidence limits for regional cerebellar blood flow (rCBF) and oxygen consumption (rCMRO2) in the control group, the stroke patients were subdivided in a group with (n = 8) and a group without (n = 20) CCD. The CCD group had lower values of rCMRO2 in the infarct and border areas compared to those of the non-CCD patients. The infarct location within the MCA territory was similar but the size was somewhat larger in the CCC group. The degree of neurological improvement was better in the non-CCD group. Although persistence of CCD has no real clinical significance it appears to be correlated to more severe and widespread ischaemia in the affected MCA territory and to the lack of significant clinical improvement
AD  - Department of Neurology, University Hospital, Ghent, Belgium
UR  - PM:9107461
ER  - 

TY  - JOUR
T1  - [Methyl-11C]thymidine positron emission tomography in tumoral and non-tumoral cerebral lesions
A1  - De Reuck,J.
A1  - Santens,P.
A1  - Goethals,P.
A1  - Strijckmans,K.
A1  - Lemahieu,I.
A1  - Boon,P.
A1  - Achten,E.
A1  - Lemmerling,M.
A1  - Vandekerckhove,T.
A1  - Caemaert,J.
Y1  - 1999/06//
N1  - UI - 99356361
SP  - 118
EP  - 125
JA  - Acta Neurol Belg.
VL  - 99
IS  - 2
N2  - BACKGROUND: No ideal radiopharmaceutical exists for positron emission tomography (PET) that fulfills all clinical requirements for the study of brain tumors. PURPOSE: The usefulness of a recently developed PET tracer, [methyl-11C]thymidine ([methyl-11C]TdR) is explored in brain tumors. PATIENTS AND METHODS: Twenty patients with confirmed tumoral and non-tumoral brain lesions were investigated with [methyl-11C] TdR PET. The 11C activity was visually and quantitatively assessed. In two patients, dynamic scans were performed. The PET findings were compared to those of magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and to the final diagnosis. RESULTS: Eight out of ten patients with confirmed tumoral lesions or tumor recurrence had increased 11C activity within the lesion. In ten non-tumoral lesions no increased 11C uptake was found. The dynamic PET studies showed that [methyl-11C] TdR first acts as a blood flow tracer, but that later on the uptake of 11C activity is due to labeled metabolites, crossing the blood-brain barrier. Increased tracer activity was only observed in tumoral and not in non-tumoral contrast-enhanced lesions on MRI or CT. CONCLUSIONS: [Methyl-11C] TdR is not a selective PET radiopharmaceutical for brain tumors, but can be used as a tracer for tumoral blood-brain barrier disruption
AD  - PET Center UZ/RUG, Department of Neurology, University Hospital, Gent, Belgium
UR  - PM:10427354
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism in postanoxic syndrome due to cardiac arrest
A1  - De Volder,A.G.
A1  - Michel,C.
A1  - Guerit,J.M.
A1  - Bol,A.
A1  - Georges,B.
A1  - de Barsy,T.
A1  - Laterre,C.
Y1  - 1994///
N1  - UI - 95066720
SP  - 183
EP  - 189
JA  - Acta Neurol Belg.
VL  - 94
IS  - 3
N2  - Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies
AD  - Positron Tomography Laboratory, UCL, Louvain-la-Neuve
UR  - PM:7976223
ER  - 

TY  - JOUR
T1  - Positron emission tomography studies in headache
A1  - Diener,H.C.
Y1  - 1997/11//
N1  - UI - 98102068
SP  - 622
EP  - 625
JF  - Headache
VL  - 37
IS  - 10
N2  - Positron emission tomography (PET) allows the quantitative measurement of regional cerebral flow (rCBF) in humans in quantitative terms. Gross changes in rCBF are due to variation in vessel diameter. Changes of rCBF also reflect synaptic activity (inhibition and excitation). Therefore, PET was used to monitor changes in blood flow during the aura and headache phase of a migraine attack and to investigate focal areas of increased or decreased blood flow, e.g., in the brain stem and midbrain. Hemispheric rCBF was unchanged in spontaneous migraine attacks without aura. This was true for the headache side as well as for the nonheadache side. Sumatriptan had no effects on cerebral blood flow. Regional cerebral blood flow was increased in midline brain stem structures during the headache phase, but also when the headache had been treated with sumatriptan. This persisting increased activity might reflect activity of a presumed migraine center in the brain stem. These changes are specific for migraine attacks and are not seen during attacks of cluster headache. Positron emission tomography measurements in the early phase of a migraine attack in a single subject showed flow reductions in the occipital cortex spreading forwards; an observation which would be compatible with the existence of spreading depression in humans. Our attempts to study the aura phase with PET have, to date, been unsuccessful
AD  - Department of Neurology, University of Essen, Germany
UR  - PM:9439081
ER  - 

TY  - JOUR
T1  - Evidence for transhemispheric diaschisis in unilateral stroke
A1  - Dobkin,J.A.
A1  - Levine,R.L.
A1  - Lagreze,H.L.
A1  - Dulli,D.A.
A1  - Nickles,R.J.
A1  - Rowe,B.R.
Y1  - 1989/12//
N1  - UI - 90073290
SP  - 1333
EP  - 1336
JA  - Arch Neurol
VL  - 46
IS  - 12
N2  - Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis
AD  - Department of Neurology, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705
UR  - PM:2590018
ER  - 

TY  - JOUR
T1  - Comparison of vasodilatory effect of carbon dioxide inhalation and intravenous acetazolamide on brain vasculature using positron emission tomography
A1  - Gambhir,S.
A1  - Inao,S.
A1  - Tadokoro,M.
A1  - Nishino,M.
A1  - Ito,K.
A1  - Ishigaki,T.
A1  - Kuchiwaki,H.
A1  - Yoshida,J.
Y1  - 1997/04//
N1  - UI - 97318159
SP  - 139
EP  - 144
JA  - Neurol Res
VL  - 19
IS  - 2
N2  - Carbon dioxide (CO2) and acetazolamide are increasingly being used as vasodilators to detect cerebrovascular reserve capacity in patients of chronic cerebrovascular disease. The functional cerebrovascular reserve or ability of cerebral vessels to lower their resistance in response to decrease in cerebral perfusion pressure is expressed as change in cerebral blood flow from baseline under a vasodilatory stimuli. Theoretically a vasodilator causing maximum vasodilation, and thereby expressing complete reserve capacity would be more suitable for such a purpose. We quantitatively compared the vasodilating effect of 5% CO2 inhalation and 1 g of intravenous acetazolamide by positron emission tomography. Cerebrovascular reserve was quantified in six patients with chronic cerebrovascular disease in the same sitting, using oxygen-15 labeled water (H2(15)O) positron emission tomography at rest, during 5% CO2 inhalation and after 1 g intravenous acetazolamide. A significant linear correlation in both nonlesion hemisphere (r = 0.701, p < 0.001) and in lesion hemisphere (r = 0.626, p < 0.005) was found between CO2 and acetazolamide for cerebrovascular reserve capacity. This correlation improved by considering cerebrovascular reserve per unit change in arterial carbon dioxide (r = 0.744, p < 0.001 in nonlesion hemisphere and r = 0.721, p < 0.001 in lesion hemisphere). The quantitative value of global reserve capacity was different by CO2 stimuli (5.2%) and acetazolamide (49.7%). Though a similar vasodilatory response is elicited by both vasodilators, acetazolamide seems to be more potent and therefore should be preferred to detect patients with exhausted cerebrovascular reserve capacity
AD  - Department of Radiology, Nagoya University School of Medicine, Japan
UR  - PM:9175142
ER  - 

TY  - JOUR
T1  - In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke
A1  - Gerhard,A.
A1  - Neumaier,B.
A1  - Elitok,E.
A1  - Glatting,G.
A1  - Ries,V.
A1  - Tomczak,R.
A1  - Ludolph,A.C.
A1  - Reske,S.N.
Y1  - 2000/09/11/
N1  - UI - 20460039
SP  - 2957
EP  - 2960
JF  - Neuroreport
VL  - 11
IS  - 13
N2  - Neuroprotective strategies are currently being developed for stroke patients. Although the focus is on the development of early treatment the importance of late pathogenetic events is increasingly recognized. To investigate the microglial reaction in stroke we used a marker for activated microglia, [11C]PK11195, and PET in five patients with ischemic stroke 5-53 days after infarction. In one patient serial measurements were made. We demonstrated in each individual and at each point in time that a microglial reaction takes place in the area where T1 weighted MRI (magnetic resonance imaging) shows intensity changes. We consider this PET method as a promising tool to study the late pathogenetic consequences of cerebral infarction and to evaluate neuroprotective strategies with respect to the consequences of the microglial activation
AD  - Neurologische Universitatsklink im Rehabilitationskrankenhaus Ulm, Germany
UR  - PM:11006973
ER  - 

TY  - JOUR
T1  - Comparative regional analysis of 2-fluorodeoxyglucose and methylglucose uptake in brain of four stroke patients. With special reference to the regional estimation of the lumped constant
A1  - Gjedde,A.
A1  - Wienhard,K.
A1  - Heiss,W.D.
A1  - Kloster,G.
A1  - Diemer,N.H.
A1  - Herholz,K.
A1  - Pawlik,G.
Y1  - 1985/06//
N1  - UI - 85182900
SP  - 163
EP  - 178
JA  - J Cereb.Blood Flow Metab
VL  - 5
IS  - 2
N2  - The glucose metabolic rate of the human brain can be measured with labeled deoxyglucose, using positron emission tomography, provided certain conditions are fulfilled. The original method assumed irreversible trapping of deoxyglucose metabolites in brain during the experimental period, and it further requires that a conversion factor between deoxyglucose and glucose, the "lumped constant," be known for the brain regions of interest. We examined the assumption of irreversible trapping of fluorodeoxyglucose metabolites in brain of four patients in 365 normal and 4 recently infarcted regions. The average net, steady-state rate of fluorodeoxyglucose (KD) accumulation in normal regions of the four patients was 0.025 ml g-1 min-1. We also examined the variability of the lumped constant. We first confirmed that methylglucose is not phosphorylated in the human brain. We then estimated the lumped constant from the regional distribution of labeled methylglucose in brain. The average (virtual) volume of distribution of labeled methylglucose in the normal regions was 0.46 ml g-1 and was the same in both gray and white matter structures. The average brain glucose content corresponding to this value was 1.3 mumol g-1, assuming a Michaelis constant (Kt) of 3.7 mM for glucose transport across the blood-brain barrier. The lumped constant varied insignificantly between 0.4 and 0.5 in most regions, with an overall average of 0.44. It did not vary significantly between the patients and was the same in gray and white matter structures, but was inversely related to the calculated metabolic rate. This observation indicates that metabolic rates calculated with a fixed lumped constant (e.g., 0.40) would be slightly underestimated at high metabolic rates and slightly overestimated at low metabolic rates. The average glucose metabolic rates of the 365 normal regions, in which gray matter regions prevailed by 20:1, was 32 mumol 100 g-1 min-1. The average glucose phosphorylation rate in white matter was 20 mumol 100 g-1 min-1 with a lumped constant of 0.45. In the recently infarcted areas, the lumped constants varied from 0.37 to 2.83, corresponding to glucose metabolic rates varying from 2 to 18 mumol 100 g-1 min-1. Two infarct types were identified. In one type, the phosphorylation-limited type, glucose content and the lumped constant were close to normal (1 mumol g-1 and 0.40, respectively). In the other, the transport/flow-limited type, the glucose content was low (0.2 mumol g-1), and the lumped constant in excess of unity. The evidence from the present study upholds the model of Sokoloff et al. in every detail
UR  - PM:3872872
ER  - 

TY  - JOUR
T1  - Neuroimaging in headache
A1  - Goadsby,P.J.
Y1  - 2001/05/01/
N1  - UI - 21197874
SP  - 179
EP  - 187
JA  - Microsc.Res Tech.
VL  - 53
IS  - 3
N2  - Neuroimaging of primary headache syndromes, such as cluster headache and migraine, has begun to provide a glimpse of the neuroanatomical and physiological basis of the conditions. Although these headache types have been widely described as vascular, there is now considerable imaging and clinical evidence to suggest that they are primarily driven from the brain. The shared anatomical and physiological substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography (PET) has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine, and in the hypothalamic grey in cluster headache. These areas are involved not simply as a response to first division nociceptive pain impulses but specifically in each syndrome, probably in some permissive or dysfunctional role. In a recent PET study in cluster headache, as well as brain activation, tracer pooled in the region of the major basal arteries. This is likely to be due to vasodilatation of these vessels during the acute pain-attack and represents the first convincing activation of neural vasodilator mechanisms in humans. The author takes the view that the known physiology and pathophysiology of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to place emphasis on the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Understanding this neurovascular relationship facilitates an understanding of the pain mechanisms, while characterising the CNS dysfunction will ultimately allow us to dissect out the basic pathogenesis of these disorders
AD  - Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom. peterg@ion.ucl.ac.uk
UR  - PM:11301493
ER  - 

TY  - JOUR
T1  - Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement
A1  - Hayashida,K.
A1  - Tanaka,Y.
A1  - Hirose,Y.
A1  - Kume,N.
A1  - Iwama,T.
A1  - Miyake,Y.
A1  - Ishida,Y.
A1  - Matsuura,H.
A1  - Miyake,Y.
A1  - Nishimura,T.
Y1  - 1996/12//
N1  - UI - 97158022
SP  - 1047
EP  - 1051
JA  - Nucl Med Commun.
VL  - 17
IS  - 12
N2  - The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide
AD  - Department of Radiology, National Cardiovascular Centre, Osaka University, Japan
UR  - PM:9004301
ER  - 

TY  - JOUR
T1  - PET, CT, and MR imaging in cerebrovascular disease
A1  - Heiss,W.D.
A1  - Herholz,K.
A1  - Bocher-Schwarz,H.G.
A1  - Pawlik,G.
A1  - Wienhard,K.
A1  - Steinbrich,W.
A1  - Friedmann,G.
Y1  - 1986/11//
N1  - UI - 87058303
SP  - 903
EP  - 911
JA  - J Comput.Assist.Tomogr.
VL  - 10
IS  - 6
N2  - Forty-five patients with cerebrovascular disease (single and multiple infarcts, intracerebral hemorrhages) were examined with X-ray CT, magnetic resonance (MR) imaging, and positron emission tomography (PET). In six patients with acute infarcts repeat measurements with all techniques were performed after 2 weeks. Magnetic resonance and PET were more sensitive in the detection of ischemic lesions than X-ray CT. With PET, functional disturbances could be demonstrated even in two cases where CT and MR were normal, while the latter techniques were superior in exactly localizing a lesion. Changes in lesion appearance with time were observed with all techniques, and the pathophysiologically important phenomena of hyperperfusion or hypermetabolism were documented in four infarcts with PET
UR  - PM:3491096
ER  - 

TY  - JOUR
T1  - Progressive derangement of periinfarct viable tissue in ischemic stroke
A1  - Heiss,W.D.
A1  - Huber,M.
A1  - Fink,G.R.
A1  - Herholz,K.
A1  - Pietrzyk,U.
A1  - Wagner,R.
A1  - Wienhard,K.
Y1  - 1992/03//
N1  - UI - 92193352
SP  - 193
EP  - 203
JA  - J Cereb.Blood Flow Metab
VL  - 12
IS  - 2
N2  - Sixteen patients were studied by multitracer positron emission tomography (PET) within 6-48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13-25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 +/- 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 +/- 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke
AD  - Max-Planck-Institut fur Neurologische Forschung, Cologne, Germany
UR  - PM:1548292
ER  - 

TY  - JOUR
T1  - The ischemic penumbra
A1  - Heiss,W.D.
A1  - Graf,R.
Y1  - 1994/02//
N1  - UI - 94227969
SP  - 11
EP  - 19
JA  - Curr.Opin.Neurol
VL  - 7
IS  - 1
N2  - The term ischemic penumbra, originally applied to brain tissue perfused at values between the functional and morphologic thresholds, has recently been extended to characterize ischemically affected but still viable tissue with uncertain chances for infarction or recovery. Results have accumulated supporting the concept of the ischemic penumbra as a dynamic process of impaired perfusion and metabolism eventually propagating with time from the center of ischemia to the neighboring tissue. As mediators and modulators of this process, waves of depolarization, extracellular increases in excitatory amino acids, activation of Ca++ channels, induction of immediate early genes and expression of heat-shock proteins, among others, have been discussed. The contribution of the various electrophysiologic and biochemical/molecular events to the complex cascade, eventually leading to neuronal damage, is still controversial. The demonstration of viable (penumbra) tissue by positron emission tomography up to several hours after ischemic stroke renders the rationale for therapeutic interventions. A short therapeutic window of a few hours is relevant for re-establishment of perfusion; the time-dependent propagation of the ischemic penumbra suggests an extended period for effective intervention with biochemical/molecular processes
AD  - Max-Planck-Institut fur neurologische Forschung, Koln, Federal Republic of Germany
UR  - PM:8173671
ER  - 

TY  - JOUR
T1  - Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion
A1  - Heiss,W.D.
A1  - Graf,R.
A1  - Lottgen,J.
A1  - Ohta,K.
A1  - Fujita,T.
A1  - Wagner,R.
A1  - Grond,M.
A1  - Weinhard,K.
Y1  - 1997/04//
N1  - UI - 97288243
SP  - 388
EP  - 400
JA  - J Cereb.Blood Flow Metab
VL  - 17
IS  - 4
N2  - The wider clinical acceptance of thrombolytic therapy for ischemic stroke has focused more attention on experimental models of reversible focal ischemia. Such models enable the study of the effect of ischemia of various durations and of reperfusion on the development of infarctions. We used high-resolution positron emission tomography (PET) to assess cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) before, during, and up to 24 h after middle cerebral artery occlusion (MCAO) in cats. After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened after 30 min in five, after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30-min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of reperfusion. In those cats surviving the first day, infarct size was determined on serial histologic sections. The arterial occlusion immediately reduced CBF in the MCA territory to < 40% of control, while CMRO2 was less affected, causing an increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and 120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial OEF increase had already disappeared during the later period of ischemia in those cats that died during the reperfusion period. After 30-min MCAO, the reperfusion period was characterized by a transient reactive hyperemia and fast normalization of CBF, CMRO2, and CMRglc, and no or only small infarcts in the deep nuclei were found in histology. After 60- and 120-min MCAO, the extent of hyperperfusion was related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and cortical/subcortical infarcts of varying sizes developed. A clear difference was found in the flow/metabolic pattern between surviving and dying cats: In cats dying during the observation period, extended postischemic hyperperfusion accompanied large defects in CMRO2 and CMRglc, large infarcts developed, and intracranial pressure increased fatally. In those surviving the day after MCAO, increased OEF persisted over the ischemic episode, postischemic hyperperfusion was less severe and shorter, and the perfusional and metabolic defects as well as the final infarcts were smaller. These results stress the importance of the severity of ischemia for the further course after reperfusion and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfusion was also observed
AD  - Max Planck Institute for Neurological Research, Cologue, Germany
UR  - PM:9143221
ER  - 

TY  - JOUR
T1  - Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia
A1  - Heiss,W.D.
A1  - Kessler,J.
A1  - Thiel,A.
A1  - Ghaemi,M.
A1  - Karbe,H.
Y1  - 1999/04//
N1  - UI - 99226448
SP  - 430
EP  - 438
JA  - Ann.Neurol
VL  - 45
IS  - 4
N2  - As previous functional neuroimaging studies could not settle the controversy regarding the contribution of dominant and subdominant hemisphere to recovery from poststroke aphasia, language performance was related to H2(15)O-positron emission tomographic activation patterns in 23 right-handed aphasic patients 2 and 8 weeks after stroke. In patients classified according to the site of lesion (frontal, n = 7; subcortical, n = 9; temporal, n = 7) and in 11 control subjects, flow changes caused by a word repetition task were calculated in 14 regions representing eloquent and contralateral homotopic areas. These areas were defined on coregistered magnetic resonance imaging scans and tested for significance (Bonferroni corrected t test, alpha = 0.0036). At baseline, differences in test performance were only found between the subcortical and temporal group. The extent of recovery, however, differed and was reflected in the activation. The subcortical and frontal groups improved substantially; they activated the right inferior frontal gyrus and the right superior temporal gyrus (STG) at baseline and regained left STG activation at follow-up. The temporal group improved only in word comprehension; it activated the left Broca area and supplementary motor areas at baseline and the precentral gyrus bilaterally as well as the right STG at follow-up, but could not reactivate the left STG. These differential activation patterns suggest a hierarchy within the language-related network regarding effectiveness for improvement of aphasia; ie, right hemispheric areas contribute, if left hemispheric regions are destroyed. Efficient restoration of language is usually only achieved if left temporal areas are preserved and can be reintegrated into the functional network
AD  - Max-Planck-Institut fur neurologische Forschung and Neurologische Universitatsklinik Koln, Germany
UR  - PM:10211466
ER  - 

TY  - JOUR
T1  - Postoperative hemodynamic and metabolic changes in patients with subarachnoid hemorrhage
A1  - Hino,A.
A1  - Mizukawa,N.
A1  - Tenjin,H.
A1  - Imahori,Y.
A1  - Taketomo,S.
A1  - Yano,I.
A1  - Nakahashi,H.
A1  - Hirakawa,K.
Y1  - 1989/11//
N1  - UI - 90050369
SP  - 1504
EP  - 1510
JF  - Stroke
VL  - 20
IS  - 11
N2  - Positron emission tomography was performed using an oxygen-15 gas inhalation technique to measure regional cerebral blood flow, metabolic rate for oxygen, oxygen extraction fraction, and cerebral blood volume in 13 patients with subarachnoid hemorrhage during the period of delayed vasospasm after surgery as well as in 10 volunteers as controls. Compared with the controls, the patients showed decreased hemoglobin concentration and decreased total arterial oxygen content due to postoperative hemodilution. Global reductions in the metabolic rate for oxygen and in the tissue oxygen supply were noted even in the apparently normal cortex of the patients in spite of adequate blood flow and adequate oxygen extraction fraction. In addition, regional reductions in blood flow and in perfusion reserve were seen in the cortical territory corresponding to cerebral vasospasm. Our results indicate that two processes are involved in the pathophysiology of cerebral vasospasm: 1) generalized impairment of oxygen metabolism with a reduced tissue oxygen supply, even in the apparently normal cortex, and 2) additional impairment of regional perfusion in the territory of vasospasm
AD  - Department of Neurosurgery, Kyoto Prefectural University of Medicine, Japan
UR  - PM:2815185
ER  - 

TY  - JOUR
T1  - Cerebral circulation and oxygen metabolism in childhood moyamoya disease: a perioperative positron emission tomography study
A1  - Ikezaki,K.
A1  - Matsushima,T.
A1  - Kuwabara,Y.
A1  - Suzuki,S.O.
A1  - Nomura,T.
A1  - Fukui,M.
Y1  - 1994/12//
N1  - UI - 95054436
SP  - 843
EP  - 850
JA  - J Neurosurg
VL  - 81
IS  - 6
N2  - Thirteen children with moyamoya disease who had no apparent cerebral infarction or hemorrhage were examined pre- and postoperatively by means of positron emission tomography (PET) to investigate the underlying cerebral circulation and metabolism and the effect of bypass surgery. The preoperative regional cerebral blood flow (rCBF) and mean transit time were significantly decreased and increased, respectively, in the cerebral cortex of these patients compared to control values. The regional cerebral blood volume (rCBV) and the regional oxygen extraction fraction (rOEF) had significantly increased to compensate for the reduced rCBF and perfusion pressure and also to maintain the regional cerebral metabolic rate of oxygen (rCMRO2). In the basal ganglia, rCBV elevation was more prominent than that in the cerebral cortex, although changes in rCBF, rOEF, and rCMRO2 were relatively minor. Postoperative improvements were observed predominantly near the cortex where bypass surgery had been performed and in the basal ganglia. Direct and combined indirect bypass procedures improved cerebral circulation more effectively than single indirect bypass surgery. Although the angiographic findings were not always compatible with the clinical results, the postoperative improvements on PET scans correlated with the disappearance of transient ischemic attacks. In addition to the clinical courses and angiographic findings, PET analysis was indispensable in evaluating the cerebral circulation and metabolism in childhood moyamoya disease
AD  - Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:7965114
ER  - 

TY  - JOUR
T1  - Uncoupling between CBF and oxygen metabolism in a patient with chronic subdural haematoma: case report
A1  - Ishikawa,T.
A1  - Kawamura,S.
A1  - Hadeishi,H.
A1  - Suzuki,A.
A1  - Yasui,N.
A1  - Shishido,F.
A1  - Uemura,K.
Y1  - 1992/05//
N1  - UI - 92291741
SP  - 401
EP  - 403
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 55
IS  - 5
N2  - The regional cerebral blood flow (rCBF) and oxygen metabolism of a patient with a chronic subdural haematoma were examined quantitatively, using positron emission tomography (PET). Before operation, the rCBF was decreased slightly throughout the brain, whereas the regional oxygen extraction fraction (rOEF) was increased throughout the brain, with values ranging from 0.36 to 0.60. One month after operation, the rCBF had recovered remarkably in almost all regions and rOEF had decreased to within the normal range
AD  - Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA, Japan
UR  - PM:1602314
ER  - 

TY  - JOUR
T1  - STA-MCA bypass surgery for internal carotid artery occlusion--comparative follow-up study
A1  - Ishikawa,T.
A1  - Yasui,N.
A1  - Suzuki,A.
A1  - Hadeishi,H.
A1  - Shishido,F.
A1  - Uemura,K.
Y1  - 1992/01//
N1  - UI - 92285030
SP  - 5
EP  - 9
JA  - Neurol Med Chir (Tokyo)
VL  - 32
IS  - 1
N2  - Sixty-three patients with internal carotid artery occlusion manifesting as transient ischemic attack or minor stroke received superficial temporal artery-middle cerebral artery bypass surgery and medical treatment (n = 27) or medical treatment only (n = 36). Long-term follow-up showed that there was no significant difference in the outcomes. However, positron emission tomography studies suggested that patients with misery perfusion in the chronic stage benefited from extracranial-intracranial bypass surgery
AD  - Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-Akita
UR  - PM:1375987
ER  - 

TY  - JOUR
T1  - Hemodynamic changes during neural deactivation in human brain: a positron emission tomography study of crossed cerebellar diaschisis
A1  - Ito,H.
A1  - Kanno,I.
A1  - Shimosegawa,E.
A1  - Tamura,H.
A1  - Okane,K.
A1  - Hatazawa,J.
Y1  - 2002/06//
N1  - UI - 22121097
SP  - 249
EP  - 254
JA  - Ann.Nucl Med
VL  - 16
IS  - 4
N2  - The mechanism of crossed cerebellar diaschisis (CCD) is considered to be secondary hypoperfusion due to neural deactivation. To elucidate the hemodynamics during neural deactivation, the hemodynamics of CCD was investigated. The cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and vascular responses to hypercapnia and acetazolamide stress for CCD were measured in 20 patients with cerebrovascular disease by positron emission tomography with H2(15O), C15O, and 15O2. Vascular responses to hypercapnia and acetazolamide stress were almost the same between CCD side and unaffected side of the cerebellum, a finding that supports the idea that the mechanism of CCD is secondary hypoperfusion due to neural deactivation. The degree of decrease in CBF on the CCD side was almost the same as that in CBV, indicating that vascular blood velocity does not change during neural deactivation. The relation between CBF and CBV of the CCD and unaffected sides was CBV = 0.29 CBF0.56. On the CCD side, the degree of deerease in CMRO2 was less than that in CBF, resulting in a significantly increased OEF. The increased OEF along with the decreased CBV on the CCD side might indicate that neural deactivation primarily causes vasoconstriction rather than a reduction of oxygen metabolism
AD  - Department of Radiology and Nuclear Medicine, Akita Research Institute of Brain and Blood Vessels, Japan. hito@akita-noken.go.jp
UR  - PM:12126094
ER  - 

TY  - JOUR
T1  - Diaschisis of specific cerebellar lobules: pontine haematoma studied with high-resolution PET and MRI
A1  - Jacobs,A.
A1  - Herholz,K.
A1  - Pietrzyk,U.
A1  - Wurker,M.
A1  - Wienhard,K.
A1  - Heiss,W.D.
Y1  - 1996/02//
N1  - UI - 96361821
SP  - 131
EP  - 136
JA  - J Neurol
VL  - 243
IS  - 2
N2  - Cerebellar glucose metabolism was studied in one patient with a hemipontine haematoma in order to investigate remote metabolic effects within the cerebellar lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage, and in three normal subjects cerebellar glucose metabolisms was studied using 18F-2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography (PET). Regions of interest were placed on sagittal brain slices of co-registered magnetic resonance images for quantitative evaluation of glucose metabolism in each cerebellar lobule. Interruption of corticopontine fibres caused inactivation of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in the anterior lobe and the posterior portion of the quadrangular lobule. Damage within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g. pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine nuclei, led to ipsi- and contralateral cerebellar diaschisis within the semilunar, gracile and biventral lobules. High-resolution PET is capable of demonstrating bilateral diaschisis involving specific cerebellar lobules to a different degree that is consistent with the pontine anatomy of the cortico-ponto-cerebellar pathway and with the location of the haemorrhagic lesion
AD  - Max-Planck-Institut fur Neurologische Forschung und Klinik fur Neurologie der Universitat zu Koln, Cologne, Germany
UR  - PM:8750549
ER  - 

TY  - JOUR
T1  - Brain plasticity in poststroke aphasia: what is the contribution of the right hemisphere?
A1  - Karbe,H.
A1  - Thiel,A.
A1  - Weber-Luxenburger,G.
A1  - Herholz,K.
A1  - Kessler,J.
A1  - Heiss,W.D.
Y1  - 1998/09//
N1  - UI - 98378387
SP  - 215
EP  - 230
JA  - Brain Lang
VL  - 64
IS  - 2
N2  - The brain may use two strategies to recover from poststroke aphasia: the structural repair of primarily speech-relevant regions or the activation of compensatory areas. We studied the cortical metabolic recovery in aphasic stroke patients with positron emission tomography (PET) at rest and during word repetition. The left supplementary motor area (SMA) showed the most prominent compensatory activation in the subacute state of stroke. The restitution of the left superior temporal cortex determined the long-term prognosis of aphasia. The brain recruited right-hemispheric regions for speech processing, when the left-hemispheric centers were permanently impaired. This strategy, however, was significantly less effective than the repair of the original speech-relevant network
AD  - Department of Neurology, University Hospital, Cologne, Germany
UR  - PM:9710490
ER  - 

TY  - JOUR
T1  - Haemodynamic and metabolic changes following extra-intracranial bypass surgery
A1  - Kawamura,S.
A1  - Sayama,I.
A1  - Yasui,N.
A1  - Uemura,K.
Y1  - 1994///
N1  - UI - 94317571
SP  - 135
EP  - 139
JA  - Acta Neurochir.(Wien.)
VL  - 126
IS  - 2-4
N2  - In order to study the haemodynamic and metabolic changes following bypass surgery, the regional cerebral blood flow (rCBF), the oxygen extraction fraction (rOEF), the cerebral metabolic rate of oxygen (rCMRO2), and the cerebral blood volume (rCBV) were measured using a positron emission tomograph (PET) on 13 patients who had unilateral internal carotid artery and/or middle cerebral artery occlusion. The patients were divided into two subgroups according to pre-operative rOEF values from the arterial occlusion side: the misery perfusion group, which had high rOEF values (> or = 0.56), and the coupling perfusion group, which had normal rOEF values (0.38-0.48). A post-operative PET study was performed 1-2 months and/or 1-5 years following the surgery. Six of the misery perfusion cases showed a post-operative CBF increase, where an accompanying OEF decreased to its normal level, indicating an attenuated misery perfusion state. The CMRO2 values, however, remained low. The other 7 coupling perfusion cases had an ipsilateral CBF increase in the earlier PET study. We conclude that misery perfusion is attenuated following bypass surgery, although the procedure does not consistently improve oxygen metabolism
AD  - Department of Surgical Neurology, Research Institute for Brain and Blood Vessels, Akita, Japan
UR  - PM:8042545
ER  - 

TY  - JOUR
T1  - Effects of stroke on local cerebral metabolism and perfusion: mapping by emission computed tomography of 18FDG and 13NH3
A1  - Kuhl,D.E.
A1  - Phelps,M.E.
A1  - Kowell,A.P.
A1  - Metter,E.J.
A1  - Selin,C.
A1  - Winter,J.
Y1  - 1980/07//
N1  - UI - 80263984
SP  - 47
EP  - 60
JA  - Ann.Neurol
VL  - 8
IS  - 1
N2  - By means of emission computed tomography (ECT), we used 18F-fluorodeoxyglucose (18FDG) and 13N-ammonia (13NH3) as indicators of abnormalities in local cerebral glucose utilization (LCMRglc) and relative perfusion, respectively. The ECAT positron tomograph was used to scan normal control subject and 10 stroke patients at various times during recovery. In normal subjects, mean CMRglc was 5.28 +/- 0.76 mg per 100 gm tissue per minute (mean +/- SD; N = 8). In patients with stroke, mean CMRglc in the contralateral hemisphere was moderately decreased during the first week, profoundly depressed in irreversible coma, and normal after clinical recovery. Quantification was restricted by incomplete understanding of tracer behavior in diseased brain, but relative local distributions of 18FDG and 13NH3 trapping qualitatively reflected the increases and decreases as well as coupling and uncoupling expected for local alterations in glucose utilization and perfusion in stroke. Early after cerebrovascular occlusion there was a greater decrease in local trapping of 13NH3, than 18FDG within the infarct, probably because of increased anaerobic glycolysis. Otherwise, 18FDG was a more sensitive indicator of cerebral dysfunction than was 13NH3. Hypometabolism, due to deactivation or minimal damage, was demonstrated with the 18FDG scan in deep structures and broad zones of cerebral cortex that appeared normal on x-ray computed tomography and technetium 99m pertechnetate scans. In its present state of development, the 18FDG ECT method should aid in defining the location and extent of altered brain in studies of disordered function after stroke. With improved knowledge of tracer behaviour in diseased brain, the method has promise for mapping the response to therapeutic intervention and increasing our understanding of how the human brain responds to stroke
UR  - PM:6967712
ER  - 

TY  - JOUR
T1  - Contralateral cerebellar hypometabolism following cerebral insult: a positron emission tomographic study
A1  - Kushner,M.
A1  - Alavi,A.
A1  - Reivich,M.
A1  - Dann,R.
A1  - Burke,A.
A1  - Robinson,G.
Y1  - 1984/05//
N1  - UI - 84229908
SP  - 425
EP  - 434
JA  - Ann.Neurol
VL  - 15
IS  - 5
N2  - Positron emission tomographic studies of 16 patients with cerebral ischemia and brain tumor showed asymmetries in cerebellar metabolism not encountered in 14 normal control subjects. An asymmetry was present in 62.5% of cases. The lower metabolic rate occurred in the cerebellar hemisphere contralateral to the cerebral lesion (p less than 0.001; sign test). In all cases computed tomography showed the supratentorial lesion to be unilateral and the posterior fossa contents to be unaffected. The presence of depressed cerebellar metabolism was highly associated with involvement of the contralateral parietal lobe (p less than 0.02; phi coefficient). The presence of a cerebellar abnormality was not related to the presence of any particular sign. Serial studies showed normalization of cerebellar metabolism over time. It is likely that this effect is a result of interruption of the functional interconnections between the cerebrum and the cerebellum
UR  - PM:6329071
ER  - 

TY  - JOUR
T1  - Cerebral hemodynamic change in the child and the adult with moyamoya disease
A1  - Kuwabara,Y.
A1  - Ichiya,Y.
A1  - Otsuka,M.
A1  - Tahara,T.
A1  - Gunasekera,R.
A1  - Hasuo,K.
A1  - Masuda,K.
A1  - Matsushima,T.
A1  - Fukui,M.
Y1  - 1990/02//
N1  - UI - 90162769
SP  - 272
EP  - 277
JF  - Stroke
VL  - 21
IS  - 2
N2  - To clarify the differences in cerebral hemodynamics and metabolism between children and adults with bilateral moyamoya disease, we measured regional cerebral blood flow, regional oxygen extraction fraction, regional metabolic rate for oxygen, regional cerebral blood volume, and regional transit time using positron emission tomography in nine patients (five children and four adults) and compared the values with those in controls (four children with unilateral moyamoya disease and six normal adults). The major differences between pediatric and adult patients were in regional cerebral blood volume and regional oxygen extraction fraction. Regional cerebral blood volume was more markedly increased relative to the control value in the children than in the adults. Also, regional oxygen extraction fraction was greater than control in areas with low blood flow in the children but was never increased in the adults. However, in the adults, only regional transit time was significantly prolonged relative to the control values. The increased regional oxygen extraction fraction relative to the control value observed in children with moyamoya disease may explain why transient ischemic attacks are a common symptom in this group
AD  - Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:2305403
ER  - 

TY  - JOUR
T1  - Posthypoxic amnesia: regional cerebral glucose consumption measured by positron emission tomography
A1  - Kuwert,T.
A1  - Homberg,V.
A1  - Steinmetz,H.
A1  - Unverhau,S.
A1  - Langen,K.J.
A1  - Herzog,H.
A1  - Feinendegen,L.E.
Y1  - 1993/08//
N1  - UI - 94045728
SP  - 10
EP  - 16
JA  - J Neurol Sci.
VL  - 118
IS  - 1
N2  - Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 7 subjects suffering from chronic posthypoxic amnesia and in 12 controls. In 6 of the 7 patients regional decreases in rCMRGlc below normal limits were found involving the thalamus in 3 cases, the medial temporal cortex in 2 cases, and the caudate nucleus and cerebellum in one case each. No significant decrease in rCMRGlc was observed in any of the neocortical regions in any of the patients studied. Significant differences between group means of rCMRGlc were found only for the thalamus and the medial temporal cortex. These data suggest that posthypoxic amnesia stems from damage to the medial temporal cortex and its thalamic projection areas and not from neocortical dysfunction, confirming recent theories on the genesis of amnesia in man
AD  - Institut fur Medizin, Forschungszentrum Julich, Germany
UR  - PM:8229044
ER  - 

TY  - JOUR
T1  - Contralateral flow reduction in unilateral stroke: evidence for transhemispheric diaschisis
A1  - Lagreze,H.L.
A1  - Levine,R.L.
A1  - Pedula,K.L.
A1  - Nickles,R.J.
A1  - Sunderland,J.S.
A1  - Rowe,B.R.
Y1  - 1987/09//
N1  - UI - 87320472
SP  - 882
EP  - 886
JF  - Stroke
VL  - 18
IS  - 5
N2  - Using clinical presentation, angiography, computed tomography, and nuclear magnetic resonance imaging, 7 patients were identified who had strictly unilateral hemispheric infarction and unilateral cerebrovascular disease. In 6, cerebral blood flow measured by fluorine-18-fluoromethane inhalation and positron emission tomography was reduced in the contralateral hemisphere (p less than 0.05). Multiple regression analysis demonstrated a high correlation between contralateral flow reduction and the degree of flow impairment in the infarcted area (r = 0.941, p = 0.0014) but not with age, risk factor profile, blood pressure, PCO2, hematocrit, or duration of stroke. We conclude that transhemispheric diaschisis best explains the contralateral flow reduction seen in supratentorial ischemic stroke
UR  - PM:3498240
ER  - 

TY  - JOUR
T1  - Computerized tomography, magnetic resonance imaging, and positron emission tomography in the study of brain trauma. Preliminary observations
A1  - Langfitt,T.W.
A1  - Obrist,W.D.
A1  - Alavi,A.
A1  - Grossman,R.I.
A1  - Zimmerman,R.
A1  - Jaggi,J.
A1  - Uzzell,B.
A1  - Reivich,M.
A1  - Patton,D.R.
Y1  - 1986/05//
N1  - UI - 86198916
SP  - 760
EP  - 767
JA  - J Neurosurg
VL  - 64
IS  - 5
N2  - Results of computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), xenon-133 measurement of cerebral blood flow (CBF), and neuropsychological assessments are described in three head-injured patients. The patients were selected because they presented with intracranial hemorrhage diagnosed by CT. Two of the patients were studied acutely and again approximately 6 months later. In the acute stage, MRI was superior to CT in identifying the precise location and extent of intracranial hemorrhage and associated edema. Small subdural hematomas diagnosed on MRI were missed with CT scanning. The extent of apparent encephalomalacia in the chronic stages of injury was also better defined with MRI. Positron emission tomography showed disturbances of glucose metabolism that extended beyond the structural abnormalities demonstrated by MRI and CT; anterior temporal lobe dysfunction was particularly evident in all three patients. Regional CBF studies failed to detect a number of the abnormalities seen on MRI and CT, and even ignored the metabolic dysfunction evident on PET that should have been accompanied by changes in regional CBF. The neuropsychological studies localized frontal lesions, but did not reveal abnormalities attributable to the structural lesions and the reduced metabolism in the anterior temporal lobes
UR  - PM:3486260
ER  - 

TY  - JOUR
T1  - PET of infant in persistent vegetative state
A1  - Larsen,P.D.
A1  - Gupta,N.C.
A1  - Lefkowitz,D.M.
A1  - Van Gundy,J.C.
A1  - Hadford,D.J.
Y1  - 1993/07//
N1  - UI - 94030273
SP  - 323
EP  - 326
JA  - Pediatr.Neurol
VL  - 9
IS  - 4
N2  - This is the first report of cranial positron emission tomography findings of an infant in a persistent vegetative state. Serial positron emission tomography/2-deoxy-2[18F]fluoro-D-glucose studies demonstrated persistent global reduction of cerebral glucose metabolism, results similar to those found in adults in persistent vegetative states. Positron emission tomography may be useful in confirming this clinical diagnosis in infants
AD  - Department of Neurology, Creighton University Medical Center, Omaha, Nebraska 68131
UR  - PM:8216549
ER  - 

TY  - JOUR
T1  - Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke
A1  - Markus,R.
A1  - Donnan,G.A.
A1  - Kazui,S.
A1  - Read,S.
A1  - Hirano,T.
A1  - Scott,A.M.
A1  - O'Keefe,G.J.
A1  - Tochon-Danguy,H.J.
A1  - Sachinidis,J.I.
A1  - Reutens,D.C.
Y1  - 2002/06//
N1  - UI - 22028641
SP  - 425
EP  - 433
JF  - Neuroimage
VL  - 16
IS  - 2
N2  - Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects
AD  - Department of Medicine, The University of Melbourne, Australia
UR  - PM:12030827
ER  - 

TY  - JOUR
T1  - Children with unilateral occlusion or stenosis of the ICA associated with surrounding moyamoya vessels--"unilateral" moyamoya disease
A1  - Matsushima,T.
A1  - Inoue,T.
A1  - Natori,Y.
A1  - Fujii,K.
A1  - Fukui,M.
A1  - Hasuo,K.
A1  - Kuwabara,Y.
Y1  - 1994///
N1  - UI - 95274440
SP  - 196
EP  - 202
JA  - Acta Neurochir.(Wien.)
VL  - 131
IS  - 3-4
N2  - The clinical features of 6 children who are probable sufferers of "unilateral" Moyamoya disease are here reported. They showed angiographic findings which were compatible with those of Moyamoya disease, albeit only on one side. They did not, however, show any basic aetiologic factors. The age of onset, the clinical symptoms and the findings of electroencephalography, angiography, and positron emission tomography in these cases were also quite similar to those in the cases of Moyamoya disease except for unilateral involvement. All 6 patients underwent either direct or indirect EC-IC bypass surgery. In 3 children who received encephalo-duro-arterio-synangiosis, an indirect bypass procedure, the collateral circulation was well formed postoperatively. In the follow-up study, 2 of the 6 cases starting with a unilateral lesion developed bilateral involvement later. However, the other 4 cases persisted in showing only unilateral involvement. These 4 cases may suggest the existence of "unilateral" Moyamoya disease in the paediatric age, and it is recommended that such cases be treated similarly to those of bilateral Moyamoya disease
AD  - Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan
UR  - PM:7754820
ER  - 

TY  - JOUR
T1  - HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern
A1  - Mielke,R.
A1  - Pietrzyk,U.
A1  - Jacobs,A.
A1  - Fink,G.R.
A1  - Ichimiya,A.
A1  - Kessler,J.
A1  - Herholz,K.
A1  - Heiss,W.D.
Y1  - 1994/10//
N1  - UI - 95129570
SP  - 1052
EP  - 1060
JA  - Eur.J Nucl Med
VL  - 21
IS  - 10
N2  - Positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) and single-photon emission tomography (SPET) of 99mTc-hexamethylpropylene amine oxime (HMPAO) were performed under identical resting conditions within 3 h in 20 patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 13 normal persons. In the temporoparietal association cortex similar impairment of relative regional cerebral glucose metabolism (rCMRGl) and relative HMPAO uptake (rCBF) was found. In addition PET showed hypometabolism in the occipital association cortex. The functional pattern was condensed to a ratio of regional values of association areas divided by regional values of structures that are typically less affected by AD. In normals this ratio was significantly related to age for PET metabolic data (r = -0.66, P = 0.01). The ratio was significantly lower in AD than in VD and controls for both rCMRGl and rCBF. In AD only, the metabolic ratio was related to severity of dementia (r = 0.54, P = 0.003) and age (r = 0.64, P = 0.003). Metabolic differences between normals and AD patients were less obvious in old age. In contrast, there were no significant correlations between the perfusion ratio and severity of dementia or age. Comparing the metabolic and perfusion ratio by receiver operating characteristic curves, PET differentiated AD from normals only marginally better than SPET. Differentiation between AD and VD was much better achieved by PET. Our results suggest that both PET and SPET can distinguish AD patients from controls, whereas for differentiation between AD and VD SPET is of little value
AD  - Max-Planck-Institut fur Neurologische Forschung, Koln, Germany
UR  - PM:7828614
ER  - 

TY  - JOUR
T1  - Evolution of crossed cerebellar diaschisis in middle cerebral artery infarction
A1  - Miura,H.
A1  - Nagata,K.
A1  - Hirata,Y.
A1  - Satoh,Y.
A1  - Watahiki,Y.
A1  - Hatazawa,J.
Y1  - 1994/04//
N1  - UI - 94243113
SP  - 91
EP  - 96
JA  - J Neuroimaging
VL  - 4
IS  - 2
N2  - To elucidate the evolution of crossed cerebellar diaschisis, cerebral oxygen metabolism was measured repeatedly by positron emission tomography (PET) in 35 consecutive patients with unilateral cerebral infarction within the territory of middle cerebral artery. The crossed cerebellar diaschisis was defined as significant when the laterality ratio of cerebral oxygen metabolism between the left and right cerebellar hemispheres exceeded the control range (mean +/- 2 standard deviations) as derived from 27 age-matched normal volunteers. Significant crossed cerebellar diaschisis was observed in 31 patients (89%) on the initial PET studies. Of these 31 patients, 23 with infarcts involving the frontal sensorimotor cortex persistently had crossed cerebellar diaschisis up to 5 years after onset, whereas the diaschisis disappeared in 8 patients with smaller infarcts mainly in the frontal or parietal lobe without recovery of oxygen metabolism in the infarcted areas. These present results suggest that crossed cerebellar diaschisis can exist persistently even in the late stage in those having a lesion involving the cortical pontine-cerebellar pathways
AD  - Department of Neurology, Research Institute for Brain and Blood Vessels, Akita, Japan
UR  - PM:8186536
ER  - 

TY  - JOUR
T1  - Efficacy of direct revascularization in adult Moyamoya disease: haemodynamic evaluation by positron emission tomography
A1  - Morimoto,M.
A1  - Iwama,T.
A1  - Hashimoto,N.
A1  - Kojima,A.
A1  - Hayashida,K.
Y1  - 1999///
N1  - UI - 99281013
SP  - 377
EP  - 384
JA  - Acta Neurochir.(Wien.)
VL  - 141
IS  - 4
N2  - To evaluate the efficacy of direct cerebrovascular reconstruction to prevent intracranial bleeding from the point of view of haemodynamic status, we performed positron emission tomography (PET) studies in 5 adult patients with Moyamoya disease before and after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. Regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO2) and regional oxygen extraction fraction (rOEF) in the MCA territories and regional cerebral blood volume (rCBV) in the striatum were measured before and after STA-MCA anastomosis. Correlation between the change of these PET parameters and post-operative decreased opacification of Moyamoya vessels were analyzed. Pre-operatively, significant elevation of rCBV were observed in the basal ganglia as well as significant reduction of rCBF and elevation of rOEF with reduction of rCMRO2 in the MCA territories, indicating "misery" perfusion in the cerebral hemisphere and blood pooling in the Moyamoya vessels under increased haemodynamic stress. Post-operative PET study showed improvement of misery perfusion and reduction of rCBV in the basal ganglia. Reduction of rCBV in the basal ganglia generally compatible with decreasing Moyamoya vessels on angiographic findings. Our results suggests that direct bypass surgery could have a potential both for decreasing haemodynamic stress on Moyamoya vessels and to improve misery perfusion in the hemisphere
AD  - Department of Neurosurgery, Kyoto University Medical School, Japan
UR  - PM:10352747
ER  - 

TY  - JOUR
T1  - Cerebral blood flow and metabolism following superficial temporal artery to superior cerebellar artery bypass for vertebrobasilar occlusive disease
A1  - Ogawa,A.
A1  - Kameyama,M.
A1  - Muraishi,K.
A1  - Yoshimoto,T.
A1  - Ito,M.
A1  - Sakurai,Y.
Y1  - 1992/06//
N1  - UI - 92269015
SP  - 955
EP  - 960
JA  - J Neurosurg
VL  - 76
IS  - 6
N2  - In order to clarify the effectiveness of extracranial-intracranial bypass operations in patients with vertebrobasilar occlusive disease, the authors used positron emission tomography to investigate the cerebral blood flow (CBF) and metabolism of eight patients undergoing superficial temporal artery (STA)-superior cerebellar artery (SCA) bypass procedures. In the preoperative studies, CBF in the region of the posterior fossa was low and the oxygen extraction fraction (OEF) was high, the so-called "misery perfusion syndrome." Such changes were evident in both the posterior circulation and the anterior circulation regions. Postoperatively, there was a significant increase in CBF, a significant decrease in the OEF not only in the region of posterior circulation but also over the entire brain, and a disappearance of the uncoupling between CBF and oxygen metabolism. The STA-SCA bypass procedure is effective in improving CBF and metabolism in patients with vertebrobasilar occlusive disease
AD  - Division of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan
UR  - PM:1588429
ER  - 

TY  - JOUR
T1  - The effect of hemodynamically significant carotid artery disease on the hemodynamic status of the cerebral circulation
A1  - Powers,W.J.
A1  - Press,G.A.
A1  - Grubb,R.L.,Jr.
A1  - Gado,M.
A1  - Raichle,M.E.
Y1  - 1987/01//
N1  - UI - 87074474
SP  - 27
EP  - 34
JA  - Ann.Intern.Med
VL  - 106
IS  - 1
N2  - Although the presence of a hemodynamically significant carotid artery lesion is commonly used as an indicator of impaired cerebral circulation, the effect of such lesions on cerebral perfusion pressure and cerebral blood flow has never been determined accurately. We used positron emission tomography (PET) to study 19 patients with unilateral hemodynamically significant carotid artery disease (greater than 66% diameter reduction) and no evidence of cerebral infarction. According to PET measurements in the cerebral hemisphere distal to the lesion, 7 patients had normal cerebral hemodynamics, 8 had reduced perfusion pressure with normal blood flow, and 4 had reduced blood flow. Neither the percent stenosis nor the residual lumen diameter in the carotid artery was a reliable indicator of the hemodynamic status of the cerebral circulation. However, a significant relationship was found between the PET measurements of cerebral hemodynamics and the arteriographic circulation pattern (p = 0.006). The role of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease cannot be determined from the severity of carotid artery disease alone
UR  - PM:3491558
ER  - 

TY  - JOUR
T1  - Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease
A1  - Powers,W.J.
A1  - Grubb,R.L.,Jr.
A1  - Raichle,M.E.
Y1  - 1989/01//
N1  - UI - 89080841
SP  - 61
EP  - 67
JA  - J Neurosurg
VL  - 70
IS  - 1
N2  - The importance of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease remains uncertain. The extracranial-intracranial (EC-IC) bypass trial has been criticized for failing to identify and separately analyze those patients with chronic reduction in regional cerebral perfusion pressure (rCPP) who might be most likely to benefit from surgery. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) and blood volume (rCBV) were performed on 29 patients with symptomatic occlusion or intracranial stenosis of the carotid arterial system prior to undergoing EC-IC bypass surgery. Twenty-four patients had evidence of reduced rCPP (increased rCBV/rCBF ratio) distal to the arterial lesion. Of 21 patients who survived surgery without stroke, three suffered ipsilateral ischemic strokes during the 1st postoperative year. A nonrandomized control group of 23 nonsurgical patients' with similar clinical, arteriographic, and PET characteristics experienced no ipsilateral ischemic strokes during the 1st year following PET. Based on these results in 44 patients, the probability that successful surgery reduces the occurrence of ipsilateral ischemic stroke 1 year later was calculated. This probability ranged from 0.045 for a 50% reduction to 0.168 for a 10% reduction. Thus, there was little evidence to suggest that measurements of cerebral hemodynamics can identify a group of patients who would benefit from EC-IC bypass surgery
AD  - Division of Radiation Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
UR  - PM:2783342
ER  - 

TY  - JOUR
T1  - Positron emission tomography in minor ischemic stroke using oxygen-15 steady-state technique
A1  - Pozzilli,C.
A1  - Itoh,M.
A1  - Matsuzawa,T.
A1  - Fukuda,H.
A1  - Abe,Y.
A1  - Sato,T.
A1  - Takeda,S.
A1  - Ido,T.
Y1  - 1987/04//
N1  - UI - 87166226
SP  - 137
EP  - 142
JA  - J Cereb.Blood Flow Metab
VL  - 7
IS  - 2
N2  - A study with positron emission tomography (PET) was performed on 10 patients with ischemic stroke and mild disability. The patients underwent cerebral angiography, x-ray computed tomography (CT) scan and regional cerebral measurements of CBF, CMRO2, oxygen extraction ratio (OER), and cerebral blood volume (CBV). Only minor arterial involvement was detected by angiography. In all patients, PET images of functional defects were more extensive than the corresponding CT hypodensity, and there were statistically significant reductions in CBF, CMRO2, and CBF/CBV ratio as compared with control subjects. Half of the regions analyzed in the affected hemisphere demonstrated a disruption of the normal coupling between CBF and CMRO2 as reflected by OER values significantly higher or lower than those of the corresponding region of the contralateral hemisphere. The pathophysiological pattern of high OER combined with a reduction in CBF proportionally greater than the reduction in CMRO2 was particularly indicative of regional chronic hemodynamic compromise in these patients
UR  - PM:3494026
ER  - 

TY  - JOUR
T1  - The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke
A1  - Read,S.J.
A1  - Hirano,T.
A1  - Abbott,D.F.
A1  - Markus,R.
A1  - Sachinidis,J.I.
A1  - Tochon-Danguy,H.J.
A1  - Chan,J.G.
A1  - Egan,G.F.
A1  - Scott,A.M.
A1  - Bladin,C.F.
A1  - McKay,W.J.
A1  - Donnan,G.A.
Y1  - 2000/08//
N1  - UI - 20393568
SP  - 228
EP  - 235
JA  - Ann.Neurol
VL  - 48
IS  - 2
N2  - We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued
AD  - National Stroke Research Institute, Austin and Repatriation Medical Centre, Melbourne, Australia
UR  - PM:10939574
ER  - 

TY  - JOUR
T1  - Effect of reserpine on regional cerebral glucose metabolism in control and migraine subjects
A1  - Sachs,H.
A1  - Wolf,A.
A1  - Russell,J.A.
A1  - Christman,D.R.
Y1  - 1986/11//
N1  - UI - 87048221
SP  - 1117
EP  - 1123
JA  - Arch Neurol
VL  - 43
IS  - 11
N2  - The regional cerebral metabolic rate of glucose metabolism (RCMRGlu) in five headache and six control subjects was measured with positron emission tomography (PET) using the tracer 2-deoxy-D-[1-11C] glucose before and after the administration of reserpine. The short half-life of the carbon 11 tracer made possible a test-retest paradigm wherein each subject served as his own control in assessing the effect of reserpine on RCMRGlu. Thus, measurements were first performed with subjects at rest and subsequently at 1 1/2 hours after the parenteral administration of reserpine (rest-reserpine). In control subjects without history of migraine, reserpine did not induce headache, and, furthermore, PET measurements 1 1/2 hours after drug administration consistently showed a global increase in RCMRGlu over resting values similar to that observed in a normal control (rest-rest) group not receiving reserpine. By contrast, four of the five subjects with migraine began to experience a mild unilateral headache or visual disturbances 1 1/2 hours after reserpine, at which time PET scanning showed a 5% to 30% decline in RCMRGlu below the values that had been measured before reserpine injection, all well outside of the 99% confidence limits of normal variation separately determined on 25 control subjects (rest-rest). There was no apparent laterality, and subjects with a history of either common or classic migraine responded in a similar manner. The difference in percent change in RCMRGlu following administration of reserpine observed in these four subjects with migraine headaches was significantly different over all regions of interest as compared with all six control subjects receiving the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
UR  - PM:3490841
ER  - 

TY  - JOUR
T1  - Is positron emission tomography a useful tool for studying migraine?
A1  - Sadzot,B.
A1  - Maquet,P.
A1  - Franck,G.
Y1  - 1995///
N1  - UI - 96022412
SP  - 316
EP  - 322
JF  - Cephalalgia
VL  - 15
IS  - 4
N2  - Despite the high prevalence of migraine in the population, the pathophysiology of this condition remains poorly understood. Vascular changes have been postulated. With positron emission tomography and various radiotracers, it is possible to have a non-invasive access to a number of parameters of interest in migraine research. These are presented and discussed in this article. PET has great potential for answering some basic questions concerning the physiological or biochemical changes that can occur during and between migraine attacks. Few studies have been published, however, probably because of (i) limitations inherent to the technique and (ii) problems in study design
AD  - Department of Neurology, University of Liege, Belgium
UR  - PM:7585930
ER  - 

TY  - JOUR
T1  - Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. II. Quantitative pH mapping in patients with ischemic cerebrovascular diseases
A1  - Senda,M.
A1  - Alpert,N.M.
A1  - Mackay,B.C.
A1  - Buxton,R.B.
A1  - Correia,J.A.
A1  - Weise,S.B.
A1  - Ackerman,R.H.
A1  - Dorer,D.
A1  - Buonanno,F.S.
Y1  - 1989/12//
N1  - UI - 90062285
SP  - 859
EP  - 873
JA  - J Cereb.Blood Flow Metab
VL  - 9
IS  - 6
N2  - A practical method has been developed that, using 11CO2 and positron emission tomography (PET), computes and maps (a) "effective pH" (pHt), a weighted average of intra- and extracellular pH, and (b) "clearance" (K1), product of blood flow and 11CO2 extraction. This method, together with measurements of cerebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K1 was positively correlated with CBF (n = +0.78). The k1/CBF ratio, representing the extraction fraction ratio of 11CO2 to H2 15O, was negatively correlated with CBF (r = -0.54), suggesting that 11CO2 extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 ml/min/100 g), higher OEF (78.1%), and lower pHt (6.96) than the contralateral cortex (CBF = 41.4 ml/min/100 g, OEF = 53.3%, pHt = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 ml/min/100 g), lower OEF (32.0%), and higher pHt (7.12) than the contralateral cortex (CBF = 45.3 ml/min/100 g, OEF = 58.0%, pHt = 7.06), which suggested an increase in extracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability
AD  - Department of Radiology, Massachusetts General Hospital, Boston 02114
UR  - PM:2511212
ER  - 

TY  - JOUR
T1  - Repeated fluorodeoxyglucose positron emission tomography of the brain in infants with suspected hypoxic-ischaemic brain injury
A1  - Suhonen-Polvi,H.
A1  - Kero,P.
A1  - Korvenranta,H.
A1  - Ruotsalainen,U.
A1  - Haaparanta,M.
A1  - Bergman,J.
A1  - Simell,O.
A1  - Wegelius,U.
Y1  - 1993/09//
N1  - UI - 94039284
SP  - 759
EP  - 765
JA  - Eur.J Nucl Med
VL  - 20
IS  - 9
N2  - Positron emission tomography (PET) permits the study of cerebral metabolism in vivo. We performed repeated PET studies with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for estimation of neurological prognosis in infants with suspected hypoxic-ischaemic brain injury. Fourteen infants (gestational age 35.3 +/- 4.67 weeks) were examined during the neonatal period (at age 38.4 +/- 2.7 weeks) and again at the age of 3.5 +/- 0.7 months; one further infant was studied only once at the age of 2.5 months. All children also underwent ultrasound examinations. Electroencephalography and computed tomography or magnetic resonance imaging were performed according to their clinical condition and their neurological development has been followed. FDG accumulated most actively in the subcortical areas (thalami, brainstem and cerebellum) and the sensorimotor cortex during the neonatal period. The repeated PET study showed that the uptake of FDG was markedly high and increased in all brain sections of infants with normal development (n = 11), whereas those with delayed development (n = 4) had significantly lower values (P < or = 0.005)
AD  - Department of Pediatrics, Turku University Central Hospital, Finland
UR  - PM:8223769
ER  - 

TY  - JOUR
T1  - Tissue acid-base balance and oxygen metabolism in human cerebral infarction studied with positron emission tomography
A1  - Syrota,A.
A1  - Castaing,M.
A1  - Rougemont,D.
A1  - Berridge,M.
A1  - Baron,J.C.
A1  - Bousser,M.G.
A1  - Pocidalo,J.J.
Y1  - 1983/10//
N1  - UI - 84050948
SP  - 419
EP  - 428
JA  - Ann.Neurol
VL  - 14
IS  - 4
N2  - Nine patients who had suffered strokes were examined between 10 and 34 days after onset using positron emission tomography. DMO labeled with carbon 11 was used to evaluate brain acid-base balance, and the oxygen-15 inhalation technique was used to measure regional cerebral blood flow, the oxygen extraction fraction, and cerebral metabolic rate for oxygen. [11C]DMO concentration and oxygen metabolism variables were measured in the infarcted area and in the symmetrical region in the contralateral cerebral hemisphere. [11C]DMO concentration was found to be unchanged or slightly increased in five cases and markedly increased in four cases. The apparent increase in tissue pH can be explained by the presence of a large extracellular fluid space with a pH nearly identical to that of brain plasma, or by an increase in intracellular pH, or by both phenomena. The change in [11C]DMO concentration in the infarcted area relative to that in the normal tissue was independent of the change in blood flow. Cerebral metabolic rate for oxygen was decreased in all cases. The increase in [11C]DMO concentration in the infarcted area was linearly correlated with the decrease in the oxygen extraction fraction in the same region; that is, it was correlated with the occurrence of perfusion in excess of metabolic demand. The overabundant local perfusion could play a role in the decreased H+ content
UR  - PM:6416140
ER  - 

TY  - JOUR
T1  - Tomographic mapping of brain intracellular pH and extracellular water space in stroke patients
A1  - Syrota,A.
A1  - Samson,Y.
A1  - Boullais,C.
A1  - Wajnberg,P.
A1  - Loc'h,C.
A1  - Crouzel,C.
A1  - Maziere,B.
A1  - Soussaline,F.
A1  - Baron,J.C.
Y1  - 1985/09//
N1  - UI - 85289558
SP  - 358
EP  - 368
JA  - J Cereb.Blood Flow Metab
VL  - 5
IS  - 3
N2  - Functional images of regional intracellular pH (pHi) and of fractional volume of extracellular water (FVECW) were obtained in 10 patients with recent hemispheric infarction (between 10 and 19 days after onset of symptoms) using positron emission tomography (PET). The volume of extracellular water relative to that of total water was evaluated in each pixel of the PET scan 7-8 h after injection of 76Br. The pHi image was calculated from the data obtained after injection of [11C]5,5-dimethyl-2,4-oxazolidinedione and from the FVECW image. Regional CBF, oxygen extraction, and oxygen metabolism were also measured in the same patients. In normal hemisphere, mean +/- SD values for FVECW and pHi were 0.12 +/- 0.01 and 6.86 +/- 0.11, respectively. FVECW was increased in the infarcted area in most patients. pHi was increased in the infarct in seven patients and unchanged in three. The increase in pHi was not correlated with changes in FVECW, CBF, or CMRO2, but there was a significant correlation with the decrease in oxygen extraction fraction in the same region. Thus, the decreased H+ content in the infarcted area was correlated with the occurrence of perfusion in excess of metabolic demand. An alkaline shift in pHi enhances the glycolysis rate and could explain why the glucose metabolism is less affected than the oxygen metabolism in recent cerebral infarction. The pHi measured in the infarct could represent mainly the pHi of phagocytic cells that use aerobic glycolysis to synthesize hydrogen peroxide
UR  - PM:3875620
ER  - 

TY  - JOUR
T1  - Cerebral circulation and oxygen metabolism in moyamoya disease of ischemic type in children
A1  - Taki,W.
A1  - Yonekawa,Y.
A1  - Kobayashi,A.
A1  - Ishikawa,M.
A1  - Kikuchi,H.
A1  - Nishizawa,S.
A1  - Senda,M.
A1  - Yonekawa,Y.
A1  - Fukuyama,H.
A1  - Harada,K.
A1  - .
Y1  - 1988/10//
N1  - UI - 89208600
SP  - 259
EP  - 262
JA  - Childs Nerv.Syst.
VL  - 4
IS  - 5
N2  - Cerebral rCBF, rOEF, rCMRO2, and rCBV in moyamoya disease were studied by means of positron emmission tomography (PET), using 15O as a tracer. Steady-state methods with C15O2 and 15O2 were used to obtain the functional images of rCBF, rCMRO2, and rOEF. The 15O single-inhalation method was used to obtain the rCBV image. Five children (two boys and three girls) with mean age of 11 years and eight normal volunteers with mean age of 31 years were included in the study. The symptoms of moyamoya disease were due to cerebral ischemia, such as transient ischemic attack (TIA), reversible ischemic neurological deficit (RIND), and minor stroke. The interval between the latest ictus and PET scan ranged from 3 days to 3 years 6 months. Physiological parameters (rCBF, rCMRO2 etc.) in cerebral gray matter, cerebral white matter and basal ganglia were calculated from the single functional images. Any, low density areas appearing in X-ray-CT performed just prior to the PET study were carefully excluded from the analysis. The parameters of moyamoya disease were statistically compared with normal control parameters. Though the value of rCBF was slightly higher in moyamoya disease, this difference was not statistically significant. On the other hand, in moyamoya disease rCBV increased significantly in gray matter, white matter, and basal ganglia. The ratio of CBF to CBV is considered to be the index of perfusion pressure and reciprocal of cerebral mean transit time under the normal autoregulation of CBF. This ratio was calculated and compared with the normal value for each tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Neurosurgery, National Cardiovascular Center, Osaka, Japan
UR  - PM:3266563
ER  - 

TY  - JOUR
T1  - Cerebral circulation and metabolism in adults' moyamoya disease--PET study
A1  - Taki,W.
A1  - Yonekawa,Y.
A1  - Kobayashi,A.
A1  - Ishikawa,M.
A1  - Kikuchi,H.
A1  - Nishizawa,S.
A1  - Yonekura,Y.
A1  - Tanada,S.
A1  - Fukuyama,H.
Y1  - 1989///
N1  - UI - 90071609
SP  - 150
EP  - 154
JA  - Acta Neurochir.(Wien.)
VL  - 100
IS  - 3-4
N2  - Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral metabolic rate for oxygen (rCMRO2) and cerebral blood volume (rCBV) in nine cases of moyamoya disease in adults were studied with positron emission CT (PET) scan, using 15O steady-state methods. Three cases showed ischaemic symptoms and the other six cases showed haemorrhagic symptoms. PET scan was performed during the chronic stage. Control data were obtained from eight normal volunteers. Regional cerebral blood flow and other physiological parameters in cerebral gray matter, white matter and basal ganglia were compared with normal controls. All nine cases of Moyamoya disease showed decreased rCBF, though not significant, in cerebral gray matter, white matter and basal ganglia. Reduction of rCBF was significant in the cerebral cortex of six haemorrhagic cases. This significant decrease was considered to be due to diaschisis and also brain atrophy caused by the cerebral haemorrhage. There was a significant increase in rCBV in white matter of the both ischaemic and haemorrhagic cases. The calculated value of CBF/CBV is considered to be an index of perfusion pressure. This value was significantly decreased in all three regions, though rOEF was not significantly increased in moyamoya disease. Hence the cerebral circulation in adults with moyamoya disease appears to be characterized by a mild decrease in perfusion pressure and prolonged circulated time
AD  - Department of Neurosurgery, Kyoto University Medical School, Japan
UR  - PM:2589122
ER  - 

TY  - JOUR
T1  - Cerebello-thalamo-cerebral diaschisis: a case report
A1  - Tecco,J.M.
A1  - Wuilmart,P.
A1  - Lasseaux,L.
A1  - Wikler,D.,Jr.
A1  - Damhaut,P.
A1  - Goldman,S.
A1  - Gilles,C.
Y1  - 1998/04//
N1  - UI - 98217902
SP  - 115
EP  - 116
JA  - J Neuroimaging
VL  - 8
IS  - 2
N2  - This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG) in a 69-year-old woman who underwent resection of the left cerebellar hemisphere for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral cortical and subcortical structures was evaluated by studying the level of glucose metabolic activity at rest. Relative glucose metabolism was reduced in the prefrontal cortex contralateral to the cerebellar lesion. Contralateral thalamic metabolism was reduced significantly. The results suggest that this phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a functional depression of the cerebello-thalamo-cortical pathway
AD  - Service de Psychogeriatrie, Hopital Ambroise Pare, Mons, Belgium
UR  - PM:9557154
ER  - 

TY  - JOUR
T1  - Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation
A1  - Tuominen,S.
A1  - Juvonen,V.
A1  - Amberla,K.
A1  - Jolma,T.
A1  - Rinne,J.O.
A1  - Tuisku,S.
A1  - Kurki,T.
A1  - Marttila,R.
A1  - Poyhonen,M.
A1  - Savontaus,M.L.
A1  - Viitanen,M.
A1  - Kalimo,H.
Y1  - 2001/08//
N1  - UI - 21378791
SP  - 1767
EP  - 1774
JF  - Stroke
VL  - 32
IS  - 8
N2  - BACKGROUND AND PURPOSE: CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. METHODS: The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. RESULTS: The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. CONCLUSIONS: Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable
AD  - Department of Neurology, Turku University Hospital and University of Turku, Finland
UR  - PM:11486103
ER  - 

TY  - JOUR
T1  - Positron emission tomography in patients with a primary intracerebral hematoma
A1  - Uemura,K.
A1  - Shishido,F.
A1  - Higano,S.
A1  - Inugami,A.
A1  - Kanno,I.
A1  - Takahashi,K.
A1  - Yasui,N.
A1  - Tagawa,K.
Y1  - 1986///
N1  - UI - 92238228
SP  - 426
EP  - 428
JA  - Acta Radiol.Suppl
VL  - 369
N2  - Using positron emission tomography, the regional cerebral blood flow (CBF), oxygen extraction fraction (OEF) and oxygen consumption (CMRO2) were studied in 21 patients with hypertensive intracerebral hematomas. The study showed a very localized decrease of CBF and CMRO2 around a hematoma, and revealed in two cases (9.1%) distinct luxury perfusion around it. There was diffuse reduction of CBF with increased OEF in hematomas larger than 4.5 cm in diameter. The results suggested that surgical evacuation should be considered for hematomas with a diameter exceeding 4.5 cm
AD  - Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, Japan
UR  - PM:2980516
ER  - 

TY  - JOUR
T1  - Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction
A1  - Weiller,C.
A1  - Ramsay,S.C.
A1  - Wise,R.J.
A1  - Friston,K.J.
A1  - Frackowiak,R.S.
Y1  - 1993/02//
N1  - UI - 93167764
SP  - 181
EP  - 189
JA  - Ann.Neurol
VL  - 33
IS  - 2
N2  - We have previously shown bilateral activation of motor pathways and the recruitment of additional motor areas in studies of groups of patients with recovery from motor stroke. We have now developed a new positron emission tomographic technique to measure the changes in regional cerebral blood flow elicited during a motor task in individual patients, relative to the cerebral activation found in normal subjects. The patterns of cerebral activation in each of 8 individual patients with capsular lesions of the pyramidal tract and complete recovery from hemiplegia are described by comparison with the pattern found in a representative sample of 10 normal subjects. We found a large ventral extension of the hand field of the contralateral (sensori)motor cortex in all patients with lesions of the posterior limb of the internal capsule. Greater activation than in normal subjects was found in variable combinations of the supplementary motor areas, the insula, the frontal operculum, and the parietal cortex. Structures belonging to motor pathways ipsilateral to the recovered limb were also more activated in the patients than in normal subjects. However, additional activation of the ipsilateral (sensori)motor cortex was only found in the 4 patients who exhibited associated movements of the unaffected hand when the recovered hand performed the motor task. We conclude that recovery from motor stroke due to striatocapsular damage is associated with individually different patterns of functional reorganization of the brain. These patterns are dependent on the site of the subcortical lesion and the somatotopic organization of the pyramidal tract, both of which may determine the precise potential for recovery of limb function following this type of brain injury
AD  - Neurologische Klinik und Poliklinik, Universitatsklinikum Essen, Germany
UR  - PM:8434880
ER  - 

TY  - JOUR
T1  - Brain stem activation in spontaneous human migraine attacks
A1  - Weiller,C.
A1  - May,A.
A1  - Limmroth,V.
A1  - Juptner,M.
A1  - Kaube,H.
A1  - Schayck,R.V.
A1  - Coenen,H.H.
A1  - Diener,H.C.
Y1  - 1995/07//
N1  - UI - 96071527
SP  - 658
EP  - 660
JA  - Nat.Med
VL  - 1
IS  - 7
N2  - Evidence from animal experiments shows that the brain stem is involved in the pathophysiology of migraine. To investigate human migraine, we used positron emission tomography to examine the changes in regional cerebral blood flow as an index of neuronal activity in the human brain during spontaneous migraine attacks. During the attacks, increased blood flow was found in the cerebral hemispheres in cingulate, auditory and visual association cortices and in the brain stem. However, only the brain stem activation persisted after the injection of sumatriptan had induced complete relief from headache and phono- and photophobia. These findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control
AD  - Department of Neurology, University of Essen, Germany
UR  - PM:7585147
ER  - 

TY  - JOUR
T1  - Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts
A1  - Wise,R.J.
A1  - Rhodes,C.G.
A1  - Gibbs,J.M.
A1  - Hatazawa,J.
A1  - Palmer,T.
A1  - Frackowiak,R.S.
A1  - Jones,T.
Y1  - 1983/12//
N1  - UI - 84078384
SP  - 627
EP  - 637
JA  - Ann.Neurol
VL  - 14
IS  - 6
N2  - Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology
UR  - PM:6606390
ER  - 

TY  - JOUR
T1  - Dynamic positron emission tomography for study of cerebral hemodynamics in a cross section of the head using positron-emitting 68Ga-EDTA and 77Kr
A1  - Yamamoto,Y.L.
A1  - Thompson,C.J.
A1  - Meyer,E.
A1  - Robertson,J.S.
A1  - Feindel,W.
Y1  - 1977/01//
N1  - UI - 78242680
SP  - 43
EP  - 56
JA  - J Comput.Assist.Tomogr.
VL  - 1
IS  - 1
N2  - Dynamic positron emission tomographic studies were performed on over 120 patients with occlusive cerebrovascular disease, arteriovenous malformations, and brain tumors, using the positron section scanner, consisting of a ring of 32 scintillation detectors. The radiopharmaceuticals were nondiffusible 68Ga-EDTA for transit time and uptake studies and the diffusible tracer, 77Kr, for quantitative regional cerebral blood flow studies in every square centimeter of the cross section of the head. The results of dynamic positron emission tomography in correlation with the results from the gamma scintillation camera dynamic studies and computed tomography (CT) scans are discussed
UR  - PM:615893
ER  - 

TY  - JOUR
T1  - Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage
A1  - Zazulia,A.R.
A1  - Diringer,M.N.
A1  - Videen,T.O.
A1  - Adams,R.E.
A1  - Yundt,K.
A1  - Aiyagari,V.
A1  - Grubb,R.L.,Jr.
A1  - Powers,W.J.
Y1  - 2001/07//
N1  - UI - 21329100
SP  - 804
EP  - 810
JA  - J Cereb.Blood Flow Metab
VL  - 21
IS  - 7
N2  - A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 +/- 7.6 vs. 37.0 +/- 13.9 mL 100 g(-1) min(-1), P = 0.0004; CMRO2: 1.4 +/- 0.5 vs. 2.9 +/- 0.9 mL 100 g(-1) min(-1), P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 +/- 0.15 vs. 0.47 +/- 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 +/- 0.16 vs. 0.51 +/- 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset
AD  - Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
UR  - PM:11435792
ER  - 

TY  - JOUR
T1  - Transplantation in Parkinson's disease: PET changes correlate with the amount of grafted tissue
A1  - Cochen,V.
A1  - Ribeiro,M.J.
A1  - Nguyen,J.P.
A1  - Gurruchaga,J.M.
A1  - Villafane,G.
A1  - Loc'h,C.
A1  - Defer,G.
A1  - Samson,Y.
A1  - Peschanski,M.
A1  - Hantraye,P.
A1  - Cesaro,P.
A1  - Remy,P.
Y1  - 2003/08//
N1  - UI - 22770717
SP  - 928
EP  - 932
JA  - Mov Disord.
VL  - 18
IS  - 8
N2  - We compared the striatal uptake of [(18)F]fluorodopa with [(76)Br]-FE-CBT, a positron emission tomography (PET) ligand of the dopamine transporter (DAT), which estimates the density of dopamine nerve terminals, in 6 patients with Parkinson's disease grafted with fetal mesencephalic cells. There was no change in DAT ligand binding in the grafted putamen, despite a significant increase of [(18)F]fluorodopa uptake. This finding suggests that the clinical benefit induced by the graft is more related to increased dopaminergic activity than improved dopaminergic innervation in the host striatum and, therefore, that [(18)F]fluorodopa remains the optimal tracer to evaluate grafted PD patients. Further analysis showed that the clinical and [(18)F]fluorodopa uptake changes after the grafts were correlated with the number of ventral mesencephalae used for implantation
AD  - Unite de Recherche Associee Commissariat a l'Energie Atomique (CEA)-Centre National de la Recherche Scientifique (CNRS) 2210, Orsay, France
UR  - PM:12889084
ER  - 

TY  - JOUR
T1  - Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers
A1  - Breier,A.
A1  - Malhotra,A.K.
A1  - Pinals,D.A.
A1  - Weisenfeld,N.I.
A1  - Pickar,D.
Y1  - 1997/06//
N1  - UI - 97310341
SP  - 805
EP  - 811
JA  - Am J Psychiatry
VL  - 154
IS  - 6
N2  - OBJECTIVE: Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor, such as phencyclidine and ketamine, produce an acute psychotic state in normal individuals that resembles some symptoms of schizophrenia. The aim of this study was to determine which brain regions are involved in NMDA receptor-mediated psychosis. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in 17 healthy volunteers while an acute psychotic state was induced simultaneously by the administration of subanesthetic doses of ketamine. RESULTS: Ketamine produced focal increases in metabolic activity in the prefrontal cortex and an acute psychotic state. A change in one psychotic symptom, conceptual disorganization, was significantly related to prefrontal activation. CONCLUSIONS: These data suggest that the prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis
AD  - Experimental Therapeutics Branch, NIMH, Bethesda, MD 20892, USA
UR  - PM:9167508
ER  - 

TY  - JOUR
T1  - Determination of 18F-fluoro-2-deoxy-D-glucose rate constants in the anesthetized baboon brain with dynamic positron tomography
A1  - Miyazawa,H.
A1  - Osmont,A.
A1  - Petit-Taboue,M.C.
A1  - Tillet,I.
A1  - Travere,J.M.
A1  - Young,A.R.
A1  - Barre,L.
A1  - MacKenzie,E.T.
A1  - Baron,J.C.
Y1  - 1993/12//
N1  - UI - 94202886
SP  - 263
EP  - 272
JA  - J Neurosci.Methods
VL  - 50
IS  - 3
N2  - We have determined the rate constants (ki*) of 18F-fluorodeoxyglucose (FDG) in the unlesioned baboon brain, for use in positron emission tomography (PET) measurements of glucose utilization. In contrast to earlier reports, we used a radiosynthesis which guarantees production of FDG essentially uncontaminated by fluorodeoxymannose, and an improved determination of ki* by (1) direct measurement of the time-shift between bolus arrival in femoral arterial plasma and brain, (2) rapid initial PET frames, and (3) extended data acquisition (up to 180 min). Young adult baboons were studied under anesthesia with either phencyclidine or etomidate. The FDG time-activity curves obtained from temporal grey matter showed a consistent decline after about 80 min, indicating true product loss. Three-compartment modelling was performed for increasing fitting intervals (20-120 min) with both a 5-parameter (K1*-k4*, and vascular volume (Vo)) and a 4-parameter (K1*-k3*,Vo) model. With the latter, both the calculated FDG net clearance ((K* = K1*.k3*/(k2* + k3*)) and the fitted kinetic constants were dependent on fitting interval, i.e., they showed sustained unstability. With the former, the constant k4*, which presumably represents dephosphorylation, was overestimated and unstable for short fitting times (presumably due to heterogeneous brain compartments in the sample tissue), but stabilized at approximately 0.01 min-1 for fitting times > or = 80 min; K1*-k3* and K* were also stable after this time. These findings were identical for both anesthetic regimen. Thus, in the anesthetized baboon, the FDG ki* values can be reliably determined based on an adequate PET acquisition paradigm and with a model that incorporates k4* and > or = 80 min time-activity data
AD  - Centre Cyceron, Caen, France
UR  - PM:8152238
ER  - 

TY  - JOUR
T1  - Positron emission tomographic studies of central cholinergic nerve terminals
A1  - Widen,L.
A1  - Eriksson,L.
A1  - Ingvar,M.
A1  - Parsons,S.M.
A1  - Rogers,G.A.
A1  - Stone-Elander,S.
Y1  - 1992/02/17/
N1  - UI - 92342289
SP  - 1
EP  - 4
JA  - Neurosci.Lett.
VL  - 136
IS  - 1
N2  - The aim of this study was to develop a quantitative method for the study of cholinergic nerve terminals in vivo. An 18F-labeled analogue of vesamicol ([18F]FMV) that binds with high affinity to synaptic vesicles from Torpedo electric organ was synthesized and evaluated in vivo in rats and monkeys by positron emission tomography (PET). In rats, the tracer was rapidly cleared from the blood and highly extracted into the brain, where it was specifically and irreversibly bound. In monkeys, a specific binding of the tracer was observed in brain regions known to contain cholinergic nerve terminals. Preinjection of non-labeled vesamicol prevented the cerebral binding of [18F]FMV to a high affinity site in both species. Our results are a major step towards quantitative human in vivo studies of presynaptic cholinergic functions
AD  - Department of Clinical Neurophysiology, Karolinska Institute and Hospital, Stockholm, Sweden
UR  - PM:1321961
ER  - 

TY  - JOUR
T1  - Evaluation of F18-deoxyglucose positron emission tomography (FDG-PET) to assess the nature of neurogenic tumours
A1  - Cardona,S.
A1  - Schwarzbach,M.
A1  - Hinz,U.
A1  - Dimitrakopoulou-Strauss,A.
A1  - Attigah,N.
A1  - Mechtersheimer section
A1  - Lehnert,T.
Y1  - 2003/08//
N1  - UI - 22758436
SP  - 536
EP  - 541
JA  - Eur.J Surg.Oncol.
VL  - 29
IS  - 6
N2  - AIMS: Benign neurofibromas and malignant peripheral nerve sheath tumours (MPNST) commonly develop in patients with neurofibromatosis. Differentiation of benign from malignant tumours by conventional preoperative imaging is unreliable. FDG-PET is a non-invasive technique for biological tumour evaluation. The aim of this study was to assess the value of FDG-PET in patients with neurogenic tumours suspicious for MPNST.METHODS: Benign and malignant neurogenic soft tissue tumours were prospectively evaluated by computed tomography or magnetic resonance imaging. Three-dimensional qualitative and quantitative FDG-PET was performed. Standard uptake value (SUV) was analyzed with respect to histological diagnosis and follow-up data.RESULTS: Twenty-five neurogenic soft tissue tumours were included. FDG-PET identified all primary (n=6) and recurrent MPNST (n=7). Benign lesions (n=12) did not demonstrate high FDG uptake. The SUV was significantly higher in MPNST (median 2.9; range 1.8-12.3), than in benign tumours (median 1.1; range 0.5-1.8) (p<0.001). At a cut-off value of 1.8 SUV measured 1 h post-injection FDG-PET distinguished between MPNST and benign neurogenic tumours with 100% sensitivity and 83% specificity.CONCLUSIONS: FDG-PET allows discrimination of benign from malignant neurogenic tumours. This should be particularly useful in patients with neurofibromatosis as FDG-PET may help to avoid multiple surgical procedures for benign tumours
AD  - Section of Surgical Oncology, Department of Surgery, and Institute of Pathology, University of Heidelberg, Heidelberg, Germany
UR  - PM:12875862
ER  - 

TY  - JOUR
T1  - Neural correlates of memories of abandonment in women with and without borderline personality disorder
A1  - Schmahl,C.G.
A1  - Elzinga,B.M.
A1  - Vermetten,E.
A1  - Sanislow,C.
A1  - McGlashan,T.H.
A1  - Bremner,J.D.
Y1  - 2003/07/15/
N1  - UI - 22755842
SP  - 142
EP  - 151
JA  - Biol.Psychiatry
VL  - 54
IS  - 2
N2  - BACKGROUND: Borderline personality disorder (BPD) is a common psychiatric disorder that is often linked to early stressors. One particularly salient feature of the disorder is fear of abandonment. This pilot study was conducted to measure neural correlates of memories of abandonment in women with and without BPD. METHODS: Twenty women with a history of childhood sexual abuse underwent measurement of brain blood flow with positron emission tomography imaging while they listened to scripts describing neutral and personal abandonment events. Brain blood flow during exposure to abandonment and neutral scripts was compared among women with and without BPD. RESULTS: Memories of abandonment were associated with greater increases in blood flow in bilateral dorsolateral prefrontal cortex (middle frontal gyrus, Brodmann's areas 9 and 10) as well as right cuneus (area 19) in women with BPD than in women without BPD. Abandonment memories were associated with greater decreases in right anterior cingulate (areas 24 and 32) in women with BPD than in women without BPD. CONCLUSIONS: These findings implicate dysfunction of dorsolateral and medial prefrontal cortex including anterior cingulate, left temporal cortex, and visual association cortex in memories of abandonment in women with BPD. These brain areas may mediate symptoms of BPD
AD  - Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Freiburg, Germany
UR  - PM:12873804
ER  - 

TY  - JOUR
T1  - Positron emission tomography in female patients with Borderline personality disorder
A1  - Juengling,F.D.
A1  - Schmahl,C.
A1  - Hesslinger,B.
A1  - Ebert,D.
A1  - Bremner,J.D.
A1  - Gostomzyk,J.
A1  - Bohus,M.
A1  - Lieb,K.
Y1  - 2003/03//
N1  - UI - 22727408
SP  - 109
EP  - 115
JA  - J Psychiatr.Res
VL  - 37
IS  - 2
N2  - The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD
AD  - Department of Nuclear Medicine, PET group, University of Freiburg Medical School, Hugstetterstr. 55, D-79106, Freiburg, Germany
UR  - PM:12842164
ER  - 

TY  - JOUR
T1  - Brain Regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder
A1  - Leyton,M.
A1  - Okazawa,H.
A1  - Diksic,M.
A1  - Paris,J.
A1  - Rosa,P.
A1  - Mzengeza,S.
A1  - Young,S.N.
A1  - Blier,P.
A1  - Benkelfat,C.
Y1  - 2001/05//
N1  - UI - 21229039
SP  - 775
EP  - 782
JA  - Am J Psychiatry
VL  - 158
IS  - 5
N2  - OBJECTIVE: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is thought to be disturbed in patients exhibiting impulsive behaviors. However, until recently it has not been possible to test this hypothesis in the brains of living humans. METHOD: Unidirectional trapping of the 5-HT precursor analog alpha-[(11)C]methyl-L-tryptophan (alpha-[(11)C]MTrp) has been proposed as an index of 5-HT synthesis capacity. The authors measured brain regional alpha-[(11)C]MTrp trapping with positron emission tomography in medication-free subjects with borderline personality disorder (N=13) and a healthy comparison group (N=11). Impulsivity was assessed by using a laboratory measure of behavioral disinhibition, go/no-go commission errors. RESULTS: Compared to healthy men, the men with borderline personality disorder had significantly lower alpha-[(11)C]MTrp trapping in corticostriatal sites, including the medial frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In the women with borderline personality disorder, significantly lower alpha-[(11)C]MTrp trapping was seen in fewer regions, but in both men and women, negative correlations with impulsivity scores were identified in the medial frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum. CONCLUSIONS: Low 5-HT synthesis capacity in corticostriatal pathways may contribute to the development of impulsive behaviors in persons with borderline personality disorder
AD  - Department of Psychiatry, McGill University, Monteal, Quebec, Canada
UR  - PM:11329401
ER  - 

TY  - JOUR
T1  - A fenfluramine-activated FDG-PET study of borderline personality disorder
A1  - Soloff,P.H.
A1  - Meltzer,C.C.
A1  - Greer,P.J.
A1  - Constantine,D.
A1  - Kelly,T.M.
Y1  - 2000/03/15/
N1  - UI - 20181701
SP  - 540
EP  - 547
JA  - Biol.Psychiatry
VL  - 47
IS  - 6
N2  - BACKGROUND: Impulsive aggression in patients with personality disorders is associated with diminished levels of cerebrospinal fluid (CSF) 5-HIAA, blunted neuroendocrine responses to serotonergic agonists, and decreased glucose utilization in the prefrontal cortex. We tested the hypothesis that impulsive aggression in borderline personality disorder (BPD) may be associated with diminished serotonergic regulation in the prefrontal cortex, using positron-emission tomography (PET) neuroimaging during pharmacologic challenge with d,l fenfluramine (FEN). METHODS: A 2-day, single-blind, placebo-controlled FEN challenge study was conducted in five patients with BPD (and no Axis I MDD) and eight healthy control participants. On Day 1, 4 mCi [(18)F]-fluorodeoxyglucose (FDG) was injected 3 hours after ingestion of placebo; on Day 2, FDG was injected 3 hours after ingestion of.8 mg/kg to 60 mg of d,l fenfluramine. After 30 min, a 45-min emission scan was acquired on the Siemans/CTI 951r/31 scanner. PET data were aligned to MR images and analyzed by Statistical Parametric Mapping (SPM96). RESULTS: In response to placebo, uptake of FDG was greater in control participants than patients in large areas of the prefrontal cortex including medial and orbital regions bilaterally (BA 10-11), left superior temporal gyrus, and right insular cortex. There were no areas in which patients had greater relative regional uptake than control participants. In response to FEN, relative regional uptake of FDG (relative to placebo) was greater in control participants compared to patients in medial and orbital regions of right prefrontal cortex (BA 10), left middle and superior temporal gyri (BA 22-23), left parietal lobe (BA 40), and left caudate body. CONCLUSIONS: Patients with BPD have diminished response to serotonergic stimulation in areas of prefrontal cortex associated with regulation of impulsive behavior
AD  - Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
UR  - PM:10715360
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism in borderline personality disorder
A1  - de la Fuente,J.M.
A1  - Goldman,S.
A1  - Stanus,E.
A1  - Vizuete,C.
A1  - Morlan,I.
A1  - Bobes,J.
A1  - Mendlewicz,J.
Y1  - 1997/09//
N1  - UI - 98034565
SP  - 531
EP  - 541
JA  - J Psychiatr.Res
VL  - 31
IS  - 5
N2  - We searched for regional cerebral metabolic disturbances in patients with borderline personality disorder (BPD). Ten inpatients with BPD, no current DSM-IIIR Axis I diagnosis and free of any psychotropic substances, were compared with 15 age-matched control subjects using positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose and semiquantitative analysis of regional glucose metabolic activity. We found relative hypometabolism in patients with borderline personality disorder at the level of the premotor and prefrontal cortical areas, the anterior part of the cingulate cortex and the thalamic, caudate and lenticular nuclei. This study shows significant cerebral metabolic disturbances in patients with borderline personality disorder. These metabolic disturbances, which are similar to some of those described in other psychiatric entities, may help to understand the characteristic clinical aspects of this disorder
AD  - Department of Psychiatry, Erasme Hospital, Free University of Brussels, Belgium
UR  - PM:9368195
ER  - 

TY  - JOUR
T1  - Positron-emission tomography and personality disorders
A1  - Goyer,P.F.
A1  - Andreason,P.J.
A1  - Semple,W.E.
A1  - Clayton,A.H.
A1  - King,A.C.
A1  - Compton-Toth,B.A.
A1  - Schulz,S.C.
A1  - Cohen,R.M.
Y1  - 1994/02//
N1  - UI - 94235125
SP  - 21
EP  - 28
JF  - Neuropsychopharmacology
VL  - 10
IS  - 1
N2  - This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively
AD  - Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, Ohio
UR  - PM:8179791
ER  - 

TY  - JOUR
T1  - Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: first clinical experience
A1  - Grosu,A.L.
A1  - Lachner,R.
A1  - Wiedenmann,N.
A1  - Stark,S.
A1  - Thamm,R.
A1  - Kneschaurek,P.
A1  - Schwaiger,M.
A1  - Molls,M.
A1  - Weber,W.A.
Y1  - 2003/08/01/
N1  - UI - 22756455
SP  - 1450
EP  - 1463
JA  - Int.J Radiat.Oncol.Biol.Phys.
VL  - 56
IS  - 5
N2  - PURPOSE: (a) To implement a fully automatic method to integrate (11)C-methionine positron emission tomography (MET-PET) data into stereotactic radiation treatment planning using the commercially available BrainLAB System, by means of CT/MET-PET image fusion. (b) To validate the fully automatic CT/MET-PET image fusion technique with respect to accuracy and robustness. (c) To give a short glance at the clinical consequences for patients with brain tumors. METHODS AND MATERIALS: In 12 patients with brain tumors (9 meningeomas, 3 gliomas), CT, MRI, and MET-PET were performed for stereotactic fractionated radiation treatment planning. The CT and MET-PET investigations were performed using a relocatable mask for head fixation. Fifteen external reference markers (5 on each lateral and 5 on the frontal localizer plate) that could be identified in CT and MET-PET were applied on the stereotactic localizer frame; the marker positions were exactly defined for both investigations. The MRI/CT fusion was done completely automatically. The CT/MET-PET fusion was performed using two different methods: The gold standard was the CT/PET fusion based on the reference markers, and the test method was the automatic, intensity-based CT/PET fusion, independent of the external markers. The markers visible on CT and transmission PET were matched using a point-to-line matching algorithm. To quantify the amount of misregistration, the two fusion methods were compared by calculating the mean value of deviation between corresponding points inside a cubic volume of interest of > or =512 cm(3) defined within the cranial cavity. The gross tumor volume (CT/MRI) outlined on CT and T1-MRI with contrast medium was compared with the gross tumor volume (PET) defined in the reoriented MET-PET data sets. The clinical impact of MET-PET in tumor volume definition for stereotactic radiotherapy will be discussed. RESULTS: The fully automatic integration of MET-PET into stereotactic radiation treatment planning was successfully realized in all patients investigated. Mean deviation of the intensity-based automatic CT/PET fusion compared with the external marker-based gold standard was 2.4 mm; the standard deviation was 0.5. The algorithm's robustness was evaluated, and the discrepancy of fusion results due to different initial image alignments was determined to be below 1 mm inside the test volume of interest. In patients with meningiomas and gliomas, MET-PET was shown to deliver additional information concerning tumor extension. CONCLUSION: The precision of the automatic CT/PET image fusion was high. A mean deviation of 2.4 mm is acceptable, considering that it is approximately equal to the pixel size of the PET data sets. MET-PET improves target volume definition for stereotactic fractionated radiotherapy of meningiomas and gliomas
AD  - Department of Radiation Oncology, Technical University Munich, Munich, Germany. anca-ligia@lrz.tum.de
UR  - PM:12873691
ER  - 

TY  - JOUR
T1  - Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery
A1  - Calautti,C.
A1  - Leroy,F.
A1  - Guincestre,J.Y.
A1  - Marie,R.M.
A1  - Baron,J.C.
Y1  - 2001/12/21/
N1  - UI - 21617726
SP  - 3883
EP  - 3886
JF  - Neuroreport
VL  - 12
IS  - 18
N2  - We prospectively studied 5 patients while they were recovering from left-sided subcortical stroke affecting the cortico-spinal tract, and examined them twice with H(2)(15)O-PET over several months while performing an identical task with the affected hand. Concomitant motor recovery was assessed by measuring the number of thumb-to-index tappings performed in 15 s at each PET session. Across patients, the hemispheric activation balance tended to shift over time toward the unaffected hemisphere, but the magnitude of this shift was highly variable from patient to patient and significantly correlated with recovery. Thus, in subcortical stroke, a shift of activation balance towards the unaffected hemisphere appears associated with lesser initial recovery and, conversely, the more this physiological balance is maintained over time the better the recovery
AD  - INSERM U320 and University Hospital, Caen, France
UR  - PM:11742203
ER  - 

TY  - JOUR
T1  - Follow-up of radial arterial catheterization for positron emission tomography studies
A1  - Jons,P.H.
A1  - Ernst,M.
A1  - Hankerson,J.
A1  - Hardy,K.
A1  - Zametkin,A.J.
Y1  - 1997///
N1  - UI - 99194080
SP  - 119
EP  - 123
JA  - Hum.Brain Mapp.
VL  - 5
IS  - 2
N2  - Radial arterial catheterization is needed for repeated arterial blood samples to construct tracer input curves of positron emission tomography (PET) scans (Herscovitch [1993]: Rheum Dis Clin North Am 19:765-794). Complications resulting from such short-term catheterizations are rare. Sixteen investigators followed 106 subjects who had arterial lines placed in the context of a PET study. Abnormalities were reported in 8 of 106 (7.5%) cases. Of these eight cases, three (37.5%) were inpatients diagnosed with anorexia nervosa, a condition that may represent a risk factor. All abnormalities were benign, did not affect motor function, and did not require medical intervention
AD  - Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1384, USA. pjons@irp.nida.nih.gov
UR  - PM:10096416
ER  - 

TY  - JOUR
T1  - Brain glucose metabolism in anorexia nervosa and affective disorders: influence of weight loss or depressive symptomatology
A1  - Delvenne,V.
A1  - Goldman,S.
A1  - De,Maertelaer,V
A1  - Wikler,D.
A1  - Damhaut,P.
A1  - Lotstra,F.
Y1  - 1997/05/16/
N1  - UI - 97348508
SP  - 83
EP  - 92
JA  - Psychiatry Res
VL  - 74
IS  - 2
N2  - Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters
AD  - Department of Psychiatry, Hopital Erasme, Universite Libre de Bruxelles, Belgium
UR  - PM:9204511
ER  - 

TY  - JOUR
T1  - Brain hypometabolism of glucose in anorexia nervosa: normalization after weight gain
A1  - Delvenne,V.
A1  - Goldman,S.
A1  - De,Maertelaer,V
A1  - Simon,Y.
A1  - Luxen,A.
A1  - Lotstra,F.
Y1  - 1996/10/15/
N1  - UI - 97049339
SP  - 761
EP  - 768
JA  - Biol.Psychiatry
VL  - 40
IS  - 8
N2  - Using positron emission tomography and (18-F)-fluorodeoxyglucose, we studied cerebral glucose metabolism in 10 anorectic girls within their underweight state and after weight gain. Ten age- and sex-matched healthy volunteers were used as controls. Both groups were scanned during rest, eyes closed and with low ambient noise. In absolute values, the underweight anorectic patients, when compared to control subjects, showed a global (p = 0.002) and regional (p < or = 0.001) hypometabolism of glucose which normalized with weight gain. In relative values, no global difference could be assessed between underweight anorectic patients and controls but a trend can, nevertheless, be observed toward parietal and superior frontal cortex hypometabolism associated with a relative hypermetabolism in the caudate nuclei and in the inferior frontal cortex. After weight gain, all regions normalized for absolute and relative values, although a trend appears toward relative parietal hypometabolism and inferior frontal cortex hypermetabolism in weight gain anorectic patients. Absolute brain glucose hypometabolism might result from neuroendocrinological or morphological aspects of anorexia nervosa or might be the expression of altered neurotransmission following deficient nutritional state. As some differences exists in relative values in underweight patients and tend to persist in weight gain states, this could support a potential abnormal cerebral functioning, a different reaction to starvation within several regions of the brain or different restoration rates according to the region
AD  - Department of Psychiatry, Hopital Erasme, Universite Libre de Bruxelles, Belgium
UR  - PM:8894069
ER  - 

TY  - JOUR
T1  - Neuroimaging in anorexia nervosa
A1  - Herholz,K.
Y1  - 1996/04/16/
N1  - UI - 96323980
SP  - 105
EP  - 110
JA  - Psychiatry Res
VL  - 62
IS  - 1
N2  - Neuroimaging in anorexia nervosa has revealed morphological and functional alterations, most of which are currently interpreted as consequences of the anorectic state that are reversible, at least partially, after weight gain. Enlargement of CSF spaces, mainly of cortical sulci, is evident on CT and MRI. This reversible shrinkage of brain tissue ("pseudoatrophy") also affects the pituitary gland. A functional imaging study with positron emission tomography (PET) revealed caudate hyperactivity during the anorectic state, and several mild right-left asymmetries possibly related to alterations of mental state (vigilance, depression, etc.) have also been reported in bulimia nervosa. New aspects may be added, when techniques to image functional brain activation during specific tasks and regional receptor binding capacities are used to study anorexia nervosa
AD  - Max-Planck-Institut fur neurologische Forschung, Koln, Germany
UR  - PM:8739120
ER  - 

TY  - JOUR
T1  - Glucose metabolism in the caudate nuclei of patients with eating disorders, measured by PET
A1  - Krieg,J.C.
A1  - Holthoff,V.
A1  - Schreiber,W.
A1  - Pirke,K.M.
A1  - Herholz,K.
Y1  - 1991///
N1  - UI - 91346185
SP  - 331
EP  - 333
JA  - Eur.Arch Psychiatry Clin.Neurosci.
VL  - 240
IS  - 6
N2  - Regional cerebral glucose metabolism was measured with 18F-2-fluoro-2-deoxyglucose and positron emission tomography in nine patients with bulimia nervosa and in seven patients with anorexia nervosa. Relative caudate glucose metabolism (caudate glucose metabolism divided by global cerebral glucose metabolism) was significantly higher in anorexia nervosa than in bulimia nervosa, suggesting that caudate hyperactivity is characteristic of the anorexic state. Whether increased caudate function is a consequence of anorexic behaviour or whether it is directly involved in the pathogenesis of anorexia nervosa is an issue still to be clarified
AD  - Max Planck Institute for Psychiatry, Clinical Institute, Munich, Federal Republic of Germany
UR  - PM:1831664
ER  - 

TY  - JOUR
T1  - Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography
A1  - Wu,J.C.
A1  - Hagman,J.
A1  - Buchsbaum,M.S.
A1  - Blinder,B.
A1  - Derrfler,M.
A1  - Tai,W.Y.
A1  - Hazlett,E.
A1  - Sicotte,N.
Y1  - 1990/03//
N1  - UI - 90178496
SP  - 309
EP  - 312
JA  - Am J Psychiatry
VL  - 147
IS  - 3
N2  - Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using [18F]-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion that bulimia is a diagnostic grouping distinct from these disorders
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine 92717
UR  - PM:2309947
ER  - 

TY  - JOUR
T1  - Regional cerebral glucose metabolism in anorexia nervosa measured by positron emission tomography
A1  - Herholz,K.
A1  - Krieg,J.C.
A1  - Emrich,H.M.
A1  - Pawlik,G.
A1  - Beil,C.
A1  - Pirke,K.M.
A1  - Pahl,J.J.
A1  - Wagner,R.
A1  - Wienhard,K.
A1  - Ploog,D.
A1  - .
Y1  - 1987/01//
N1  - UI - 87076806
SP  - 43
EP  - 51
JA  - Biol.Psychiatry
VL  - 22
IS  - 1
N2  - Regional cerebral glucose metabolism was measured in five female anorectic patients, during the anorectic state and after weight gain, using the fluorodeoxyglucose method and positron emission tomography. In addition, these results were compared with those of 15 young male normals. During the anorectic state, significant caudate hypermetabolism was found bilaterally, unlike the finding in repeat measurements or in male normals. In some other brain structures (temporal cortex, lentiform nucleus, thalamus, and brainstem), significant hypermetabolism was also found during the anorectic state, but these results were not concordant for both sides and in both comparisons. There was no difference between patients after improvement and young male normals
UR  - PM:3491631
ER  - 

TY  - JOUR
T1  - Comparison of regional brain metabolism in bulimia nervosa and affective disorder assessed with positron emission tomography
A1  - Hagman,J.O.
A1  - Buchsbaum,M.S.
A1  - Wu,J.C.
A1  - Rao,S.J.
A1  - Reynolds,C.A.
A1  - Blinder,B.J.
Y1  - 1990/07//
N1  - UI - 91010245
SP  - 153
EP  - 162
JA  - J Affect.Disord.
VL  - 19
IS  - 3
N2  - Women with bulimia often present with symptoms of depression in addition to bingeing and purging behavior. Brain metabolism in eight women with bulimia nervosa was compared to that in eight women with major affective disorder and eight normal women, using positron emission tomography and 18-fluoro-2-deoxyglucose. Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lost the normal right activation in some areas, but maintained basal ganglia activity. Depressives retained right hemisphere activation, but had decreased metabolism in basal ganglia. This suggests that although women with bulimia frequently present with symptoms of depression, the pathophysiologic changes associated with bulimia differ from major effective disorder
AD  - Department of Psychiatry, University of California-Irvine 92717
UR  - PM:2145335
ER  - 

TY  - JOUR
T1  - Detecting residual cognitive function in persistent vegetative state
A1  - Owen,A.M.
A1  - Menon,D.K.
A1  - Johnsrude,I.S.
A1  - Bor,D.
A1  - Scott,S.K.
A1  - Manly,T.
A1  - Williams,E.J.
A1  - Mummery,C.
A1  - Pickard,J.D.
Y1  - 2002///
N1  - UI - 22388009
SP  - 394
EP  - 403
JA  - Neurocase.
VL  - 8
IS  - 5
N2  - Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state
AD  - MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK. adrian.owen@mrc-bu.cam.ac.uk
UR  - PM:12499414
ER  - 

TY  - JOUR
T1  - Registration of neuroimaging data: Implementation and clinical applications
A1  - Thurfjell,L.
A1  - Pagani,M.
A1  - Andersson,J.L.R.
A1  - Jonsson,C.
A1  - Lundqvist,R.
A1  - Wagner,A.
Y1  - 2000/01//
N1  - Times Cited: 3
SP  - 39
EP  - 46
JF  - Journal of Neuroimaging
VL  - 10
IS  - 1
N2  - Image registration brings images into a form in which each voxel corresponds to a predetermined anatomic entity and is necessary for comparisons of data across scans. Intrasubject registration is a matter of translating and rotating one image volume into correspondence with another. Intersubject registration is more difficult because it requires the removal of individual anatomy dependence from the data. This article describes, with the help of clinical examples, automated methods for intrasubject registration of scans within and between modalities, and intersubject registration used for registering a three-dimensional brain atlas with a patient's brain scan
AD  - Uppsala Univ, Ctr Image Anal, S-75237 Uppsala, Sweden
UR  - ISI:000084834400007
L3  - JCR: http://isi3.isilinks.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JCR&SrcApp=PRODUCT_NAME&SrcURL=http%3A//wos4.isiknowledge.com/CIW.cgi&SrcImageURL=http://isi3.isilinks.com/images/tbwos.gif&KeyRecord=1051-2284&DestApp=JCR&PointOfEntry=Impact
ER  - 

TY  - JOUR
T1  - A multivariate approach to registration of dissimilar tomographic images
A1  - Andersson,J.L.R.
A1  - Thurfjell,L.
Y1  - 1999/07//
N1  - Times Cited: 7
SP  - 718
EP  - 733
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 26
IS  - 7
N2  - We devised a method to allow for retrospective registration of tomographic images with very different information content, the main emphasis being on sets of positron emission tomography images obtained with different tracers. A multivariate cost-function based on information theory was used as an index of "goodness-of-alignment". The cost-function makes no assumptions regarding the form of the relationship between the two image sets, and is hence very general. Image volumes, with known relative spatial orientation, were simulated for tracers with different uptake patterns and the method was validated by assessing its ability to recover these known orientations. The method was able to recover the known transformations with an accuracy of about 1 mm and 1 degrees along and around all axes, even for tracer combinations with radically different uptake patterns and with large initial misalignment. With the suggested method it is feasible to retrospectively align examinations obtained with different tracers and/or modalities
AD  - Inst Neurol, Wellcome Dept Cognit Neurol, London WC1N 3BG, England
UR  - ISI:000081483100007
ER  - 

TY  - JOUR
T1  - Implementation and validation of a fully automatic system for intra- and interindividual registration of PET brain scans
A1  - Andersson,J.L.R.
A1  - Thurfjell,L.
Y1  - 1997/01//
N1  - Times Cited: 27
SP  - 136
EP  - 144
JF  - Journal of Computer Assisted Tomography
VL  - 21
IS  - 1
N2  - Purpose: Stereotactic coordinate spaces and methods to adapt subjects to that space are required when performing averaging of functional studies across subjects. Methods: A rapid and fully automatic method to perform intersubject registration and adaptation to a previously defined coordinate space has been developed and implemented. The implementation has been performed within an existing software developed to facilitate manual registration and adaptation, thus offering a versatile combination of automatic and manual tools. Furthermore, a novel measure, based on the F-statistic for intersubject (block) differences, for the assessment of intersubject goodness of fit was suggested and validated. Results: The intra- and intersubject registration was validated by its application to data from six human subjects participating in an activation study. The registration was performed both manually and automatically, and the results indicated that the automatic method performed at least as well as the manual. The block F-statistic was lower for the automatic method, and the z-scores were not significantly different for the methods. The localization of activated regions showed good agreement and differed by an average of 6 mm between the methods. Conclusion: It is concluded that the suggested method is a valuable alternative to the current manual approach
AD  - SUBFEMTOMOLE BIORECOGNIT PROJECT,UPPSALA,SWEDEN
UR  - ISI:A1997WF02100027
ER  - 

TY  - JOUR
T1  - Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study
A1  - Bergsneider,M.
A1  - Hovda,D.A.
A1  - Shalmon,E.
A1  - Kelly,D.F.
A1  - Vespa,P.M.
A1  - Martin,N.A.
A1  - Phelps,M.E.
A1  - McArthur,D.L.
A1  - Caron,M.J.
A1  - Kraus,J.F.
A1  - Becker,D.P.
Y1  - 1997/02//
N1  - UI - 97163619
SP  - 241
EP  - 251
JA  - J Neurosurg
VL  - 86
IS  - 2
N2  - Experimental traumatic brain injury studies have shown that cerebral hyperglycolysis is a pathophysiological response to injury-induced ionic and neurochemical cascades. This finding has important implications regarding cellular viability, vulnerability to secondary insults, and the functional capability of affected regions. Prior to this study, posttraumatic hyperglycolysis had not been detected in humans. The characteristics and incidence of cerebral hyperglycolysis were determined in 28 severely head injured patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). The local cerebral metabolic rate of glucose (CMRG) was calculated using a standard compartmental model. In six of the 28 patients, the global cerebral metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements of arteriovenous differences of oxygen and cerebral blood flow (xenon-133). Hyperglycolysis, defined as an increase in glucose utilization that measures two standard deviations above expected levels, was documented in all six patients in whom both FDG-PET and CMRO2 determinations were made within 8 days of injury. Five additional patients were found to have localized areas of hyperglycolysis adjacent to focal mass lesions. Within the 1st week following the injury, 56% of patients studied had presumptive evidence of hyperglycolysis. The results of this study indicate that the metabolic state of the traumatically injured brain should be defined differentially in terms of glucose and oxygen metabolism. The use of FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally following severe head injury in humans. The results of this clinical study directly complement those previously reported in experimental brain-injury studies, indicating the capability of imaging a fundamental component of cellular pathophysiology characteristic of head injury
AD  - Division of Neurosurgery, University of California at Los Angeles Brain Injury Research Center, USA
UR  - PM:9010426
ER  - 

TY  - JOUR
T1  - Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability
A1  - Bergsneider,M.
A1  - Hovda,D.A.
A1  - McArthur,D.L.
A1  - Etchepare,M.
A1  - Huang,S.C.
A1  - Sehati,N.
A1  - Satz,P.
A1  - Phelps,M.E.
A1  - Becker,D.P.
Y1  - 2001/04//
N1  - UI - 21174055
SP  - 135
EP  - 148
JA  - J Head Trauma Rehabil.
VL  - 16
IS  - 2
N2  - OBJECTIVE: Utilizing [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), we assessed the temporal pattern and the correlation of functional and metabolic recovery following human traumatic brain injury. DESIGN AND SUBJECTS: Fifty-four patients with injury severity ranging from mild to severe were studied. Thirteen of these patients underwent both an acute and delayed FDG-PET study. RESULTS: Analysis of the pooled global cerebral metabolic rate of glucose (CMRglc) values revealed that the intermediate metabolic reduction phase begins to resolve approximately one month following injury, regardless of injury severity. The correlation, in the 13 patients studied twice, between the extent of change in neurologic disability, assessed by the Disability Rating Scale (DRS), and the change in CMRglc from the early to late period was modest (r = -0.42). Potential explanations for this rather poor correlation are discussed. A review of the pertinent literature regarding the use of PET and related imaging modalities, including single photon emission tomography (SPECT) for the assessment of patients following traumatic brain injury is given. CONCLUSION: The dynamic profile of CMRglc that changes following traumatic brain injury is seemingly stereotypic across a broad range and severity of injury types. Quantitative FDG-PET cannot be used as a surrogate technique for estimating degree of global functional recovery following traumatic brain injury
AD  - Department of Surgery, Division of Neurosurgery, UCLA Brain Research Institute, Harbor-University of California at Los Angeles Medical Center, USA
UR  - PM:11275575
ER  - 

TY  - JOUR
T1  - Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury
A1  - Diringer,M.N.
A1  - Videen,T.O.
A1  - Yundt,K.
A1  - Zazulia,A.R.
A1  - Aiyagari,V.
A1  - Dacey,R.G.,Jr.
A1  - Grubb,R.L.
A1  - Powers,W.J.
Y1  - 2002/01//
SP  - 103
EP  - 108
JA  - J Neurosurg
VL  - 96
IS  - 1
N2  - OBJECT: Recently, concern has been raised that hyperventilation following severe traumatic brain injury (TBI) could lead to cerebral ischemia. In acute ischemic stroke, in which the baseline metabolic rate is normal, reduction in cerebral blood flow (CBF) below a threshold of 18 to 20 ml/100 g/min is associated with energy failure. In severe TBI, however, the metabolic rate of cerebral oxygen (CMRO2) is low. The authors previously reported that moderate hyperventilation lowered global hemispheric CBF to 25 ml/100 g/min but did not alter CMRO2. In the present study they sought to determine if hyperventilation lowers CBF below the ischemic threshold of 18 to 20 ml/100 g/ min in any brain region and if those reductions cause energy failure (defined as a fall in CMRO2). METHODS: Two groups of patients were studied. The moderate hyperventilation group (nine patients) underwent hyperventilation to PaCO2 of 30 +/- 2 mm Hg early after TBI, regardless of intracranial pressure (ICP). The severe hyperventilation group (four patients) underwent hyperventilation to PaCO2 of 25 +/- 2 mm Hg 1 to 5 days postinjury while ICP was elevated (20-30 mm Hg). The ICP, mean arterial blood pressure, and jugular venous O2 content were monitored, and cerebral perfusion pressure was maintained at 70 mm Hg or higher by using vasopressors when needed. All data are given as the mean +/- standard deviation unless specified otherwise. The moderate hyperventilation group was studied 11.2 +/- 1.6 hours (range 8-14 hours) postinjury, the admission Glasgow Coma Scale (GCS) score was 5.6 +/- 1.8, the mean age was 27 +/- 9 years, and eight of the nine patients were men. In the severe hyperventilation group, the admission GCS score was 4.3 +/- 1.5, the mean age was 31 +/- 6 years, and all patients were men. Positron emission tomography measurements of regional CBF, cerebral blood volume, CMRO2, and oxygen extraction fraction (OEF) were obtained before and during hyperventilation. In all 13 patients an automated search routine was used to identify 2.1-cm spherical nonoverlapping regions with CBF values below thresholds of 20, 15, and 10 ml/ 100 g/min during hyperventilation, and the change in CMRO2 in those regions was determined. In the regions in which CBF was less than 20 ml/100 g/min during hyperventilation, it fell from 26 +/- 6.2 to 13.7 +/- 1 ml/ 100 g/min (p < 0.0001), OEF rose from 0.31 to 0.59 (p < 0.0001), and CMRO2 was unchanged (1.12 +/- 0.29 compared with 1.14 +/- 0.03 ml/100 g/min; p = 0.8). In the regions in which CBF was less than 15 ml/100 g/min during hyperventilation, it fell from 23.3 +/- 6.6 to 11.1 +/- 1.2 ml/100 g/min (p < 0.0001), OEF rose from 0.31 to 0.63 (p < 0.0001), and CMRO2 was unchanged (0.98 +/- 0.19 compared with 0.97 +/- 0.23 ml/100 g/min; p = 0.92). In the regions in which CBF was less than 10 ml/100 g/min during hyperventilation, it fell from 18.2 +/- 4.5 to 8.1 +/- 0 ml/100 g/min (p < 0.0001), OEF rose from 0.3 to 0.71 (p < 0.0001), and CMRO2 was unchanged (0.78 +/- 0.26 compared with 0.84 +/- 0.32 ml/100 g/min; p = 0.64). CONCLUSIONS: After severe TBI, brief hyperventilation produced large reductions in CBF but not energy failure, even in regions in which CBF fell below the threshold for energy failure defined in acute ischemia. Oxygen metabolism was preserved due to the low baseline metabolic rate and compensatory increases in OEF; thus, these reductions in CBF are unlikely to cause further brain injury
AD  - Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA. diringerm@neuro.wustl.edu
UR  - PM:11794590
ER  - 

TY  - JOUR
T1  - Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study
A1  - Jansen,H.M.
A1  - van der,Naalt J.
A1  - van Zomeren,A.H.
A1  - Paans,A.M.
A1  - Veenma-van der Duin,L.
A1  - Hew,J.M.
A1  - Pruim,J.
A1  - Minderhoud,J.M.
A1  - Korf,J.
Y1  - 1996/02//
N1  - UI - 96225746
SP  - 221
EP  - 224
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 60
IS  - 2
N2  - Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury
AD  - Department of Neurology, Groningen University Hospital, The Netherlands
UR  - PM:8708661
ER  - 

TY  - JOUR
T1  - Quantitative assessment of longitudinal metabolic changes in vivo after traumatic brain injury in the adult rat using FDG-microPET
A1  - Moore,T.H.
A1  - Osteen,T.L.
A1  - Chatziioannou,T.F.
A1  - Hovda,D.A.
A1  - Cherry,T.R.
Y1  - 2000/10//
N1  - UI - 20496628
SP  - 1492
EP  - 1501
JA  - J Cereb.Blood Flow Metab
VL  - 20
IS  - 10
N2  - With the advent and emerging importance of neurobiology and its relation to behavior, scientists desire the capability to apply noninvasive, quantitative imaging of neuronal activity to small rodents. To this end, the authors' laboratory has developed microPET, a high-resolution positron emission tomography (PET) scanner that is capable of performing in vivo molecular imaging at a resolution sufficient to resolve major structures in the rat brain. The authors report in this article that, in conjunction with 2-[18F]fluoro-2-deoxyglucose (FDG), microPET provides accurate rates of cerebral glucose metabolism (59.7 to 108.5 micromol/100 g x min) in conscious adult rats as validated by within-subject autoradiographic measurements (59.5 to 136.2 micromol/100 g x min; r = 0.88; F[1,46] = 168.0; P < 0.001). By conducting repeated quantitative scanning, the authors demonstrate the sensitivity and accuracy of FDG-microPET to detect within-subject metabolic changes induced by traumatic brain injury. In addition, the authors report that longitudinal recovery from traumatic brain injury-induced metabolic depression, as measured by quantitative FDG-microPET, is significantly correlated (r = 0.65; P < 0.05) to recovery of behavioral dysfunction, as assessed by the Morris Water Maze performance of the same rats, after injury. This is the first study to demonstrate that FDG-microPET is quantitative, reproducible, and sensitive to metabolic changes, introducing a new approach to the longitudinal study of small animal models in neuroscience research
AD  - Division of Neurosurgery, University of California, Los Angeles, USA
UR  - PM:11043912
ER  - 

TY  - JOUR
T1  - Coordinated expression in chronically unconscious persons
A1  - Plum,F.
A1  - Schiff,N.
A1  - Ribary,U.
A1  - Llinas,R.
Y1  - 1998/11/29/
N1  - UI - 99071429
SP  - 1929
EP  - 1933
JA  - Philos.Trans.R.Soc.Lond B Biol.Sci.
VL  - 353
IS  - 1377
N2  - The clinically described 'persistent vegetative state' (PVS), consists of wakefulness unaccompanied by any evidence of the subject's awareness of self or environment. Past studies from our own and other laboratories have used positron emission tomography (PET) to study brain metabolism in approximately 20 such patients during wakeful periods. All those efforts identified global cerebral glucose metabolism at or below levels encountered during deep barbiturate anaesthesia. Nevertheless, the clinical literature includes rare reports of relatively isolated cognitive functions expressed by PVS patients late in their course. The observation raises the question of whether such activity reflects awareness or unconscious automatic behaviour. We employed magnetometry (MEG), PET scanning, MR imaging and 24-hour EEG recordings to evaluate three patients clinically vegetative between six months and 20 years after onset. Neither meticulous clinical examinations nor 24-hour EEG and video monitoring provided any hint of cognitive interaction in any subject. Nevertheless, patient 1 uttered single words once every 48 hours or more; patient 2 frequently expressed coordinated, non-purposeful, non-dystonic movements in arms and/or legs; and, patient 3 expressed strong emotional negativity without motor responses to noxious stimuli with occasional quieting in response to prosodic stimuli. All patients had whole-brain averaged global metabolism levels below 50% of normal. Patient 1, however, demonstrated preserved islands of increased metabolism in the posterior frontal and posterior temporal lobes, as well as MEG activations of Heschl's gyrus all located in the left hemisphere. In patient 2, selected increased metabolism was confined to the frontal poles and related subcortical structures. MRI in patient 3 demonstrated severe, bilateral post-traumatic cerebral atrophy. PET metabolism was diffusely reduced to 40% of normal but MEG evoked potentials indicated early and late sensory processing with abnormal later evoked components. The correlation of fragmentary behaviour with preserved metabolic and physiologic activity in cortical and subcortical regions known to support specific modular functions is novel. The finding demonstrates the capacity of severely damaged brains to partially express surviving modular functions without evidence of integrative processes that would be necessary to produce consciousness. We conclude that the mere expression of isolated neuropsychologic activity by isolated modules is insufficient to generate consciousness in overwhelmingly damaged brains
AD  - Cornell University Medical College, New York Presbyterian Hospital, NY 10021, USA
UR  - PM:9854265
ER  - 

TY  - JOUR
T1  - Verbal recall and recognition following traumatic brain injury: a [0-15]-water positron emission tomography study
A1  - Ricker,J.H.
A1  - Muller,R.A.
A1  - Zafonte,R.D.
A1  - Black,K.M.
A1  - Millis,S.R.
A1  - Chugani,H.
Y1  - 2001/04//
N1  - UI - 21206054
SP  - 196
EP  - 206
JA  - J Clin.Exp.Neuropsychol.
VL  - 23
IS  - 2
N2  - Although several studies exist which have examined static functional neuroimaging following traumatic brain injury (TBI), controlled cognitive activation studies of episodic memory in this population have not been published. The present investigation studied verbal recall using [O-15]-water positron emission tomography (PET) in 5 individuals who sustained severe TBI (M GCS=6.8; M years post-injury=3.18), and 4 non-injured control participants. Statistical image analysis demonstrated changes in frontoparietal regional cerebral blood flow (rCBF) in both groups, but there were interesting differences between groups and across conditions. Frontal lobe rCBF changes in TBI patients were reduced during free recall but enhanced during recognition, when compared to controls. Changes in cerebellar rCBF were observed in the control group during free recall, but not in the TBI sample. In both groups, bifrontal rCBF increases were noted on recognition tasks. The present findings provide evidence of alterations in specific substrates involved in verbal recall following brain injury
AD  - Neuropsychology and Neuroscience Laboratory, Kessler Medical Rehabilitation Research and Education Corporation, 1199 Pleasant Valley Way, West Orange, NJ 07052, USA. jricker@kmrrec.org
UR  - PM:11309673
ER  - 

TY  - JOUR
T1  - Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report
A1  - Thiel,A.
A1  - Pietrzyk,U.
A1  - Sturm,V.
A1  - Herholz,K.
A1  - Hovels,M.
A1  - Schroder,R.
Y1  - 2000/01//
N1  - UI - 20090383
SP  - 232
EP  - 234
JF  - Neurosurgery
VL  - 46
IS  - 1
N2  - OBJECTIVE AND IMPORTANCE: To demonstrate the usefulness of positron emission tomography-magnetic resonance imaging (MRI) coregistration for differentiation of radiation necrosis and recurrent tumor in stereotactic planning. CLINICAL PRESENTATION: T1-weighted MRI scans of a 43-year-old woman revealed a contrast-enhancing lesion 4 years after open removal of a recurrent, right parieto-occipital Grade II oligodendroglioma and subsequent external radiation therapy. The suspected contrast-enhancing lesion revealed only moderate tracer uptake (1.3 times the uptake in the contralateral normal cortex) in a coregistered [11C]methionine positron emission tomographic scan. Approximately 15 mm posterior and mesial to the center of the contrast-enhancing lesion, however, an area of higher tracer uptake was found (1.8 times that of the contralateral normal cortex), which exhibited only very minor contrast enhancement on MRI. TECHNIQUE: The coregistered images were used for planning stereotactic serial biopsies, from the contrast-enhancing lesion as well as from the area with higher methionine uptake. Histological examination demonstrated that the contrast-enhancing lesion with low methionine uptake was necrotic tissue, and the nonenhancing area with high methionine uptake was recurrent tumor. CONCLUSION: High-resolution positron emission tomography and modern coregistration techniques allow differentiation of contrast enhancement and methionine uptake in irradiated brain tissue within small areas. High methionine uptake is typical for recurrent tumor tissue and can be differentiated from minor tracer accumulation resulting from disruption of the blood-brain barrier or macrophage activity within the necrotic area
AD  - Max-Planck-Institute for Neurological Research, Department of Neurology, University of Cologne, Germany
UR  - PM:10626957
ER  - 

TY  - JOUR
T1  - 18-Fluorodeoxyglucose positron emission tomography in children and adolescents with traumatic brain injury
A1  - Worley,G.
A1  - Hoffman,J.M.
A1  - Paine,S.S.
A1  - Kalman,S.L.
A1  - Claerhout,S.J.
A1  - Boyko,O.B.
A1  - Kandt,R.S.
A1  - Santos,C.C.
A1  - Hanson,M.W.
A1  - Oakes,W.J.
A1  - .
Y1  - 1995/03//
N1  - UI - 95196958
SP  - 213
EP  - 220
JA  - Dev.Med Child Neurol
VL  - 37
IS  - 3
N2  - Twenty-two previously normal children and adolescents who suffered a severe, non-penetrating traumatic brain injury had PET during rehabilitation at a median of 1.5 months after the injury. Outcome was assessed at a median of 25 months after brain injury. 16 subjects had CT or MRI within 24 days of PET and 11 subjects had a second PET at the point of outcome (median 28 months after first PET). The PET score (obtained by adding the score of 15 brain regions: normal metabolism = 1; reduced = 0) was significantly associated with the clinical outcome measure. PET earlier than 12 weeks after head trauma correlated with outcome, but later PET did not. PET scores improved significantly between rehabilitation and outcome for the 11 subjects who had two PETs, but improvement was not associated with improvement in clinical condition. PET score did not add to the amount of variance explained in the last regression model for prediction of outcome when the results of contemporaneous CT/MRI and clinical condition were taken into account. The data suggest that routine PET during rehabilitation is no more useful than contemporaneous CT or MRI for prediction of outcome
AD  - Department of Pediatrics, Duke University Medical Center, Durham, NC 27710
UR  - PM:7890126
ER  - 

TY  - JOUR
T1  - Diagnostic imaging in 13 cases of Rasmussen's encephalitis: can early MRI suggest the diagnosis?
A1  - Chiapparini,L.
A1  - Granata,T.
A1  - Farina,L.
A1  - Ciceri,E.
A1  - Erbetta,A.
A1  - Ragona,F.
A1  - Freri,E.
A1  - Fusco,L.
A1  - Gobbi,G.
A1  - Capovilla,G.
A1  - Tassi,L.
A1  - Giordano,L.
A1  - Viri,M.
A1  - Dalla,Bernardina B.
A1  - Spreafico,R.
A1  - Savoiardo,M.
Y1  - 2003/03//
SP  - 171
EP  - 183
JF  - Neuroradiology
VL  - 45
IS  - 3
N2  - Rasmussen's encephalitis (RE) is a rare, progressive, chronic encephalitis characterised by drug-resistant epilepsy, progressive hemiparesis and mental impairment. It typically involves only one cerebral hemisphere, which becomes atrophic. We present neuroradiological findings in 13 children with RE. MRI was performed in all patients, fluorodeoxyglucose positron-emission tomography (PET) in three, Tc-99m hexamethylpropylenamine oxime single-photon emission computed tomography (SPECT) in two and proton MR spectroscopy ((1)HMRS) in two. MRI showed progression of the hemisphere atrophy, always prevalent in the region primarily involved (13 patients), spread of the abnormal signal in white matter (11) and cortex (10) and progression of atrophy of the head of the caudate nucleus (nine). Associated secondary changes were: atrophy of the contralateral cerebellar hemisphere (in four patients), the ipsilateral hippocampus (in five) and the brain stem (in five). The earliest CT and MRI abnormalities, seen between 1 day and 4 months after the first seizure (in 12 patients examined, nine of whom had MRI) in one cerebral hemisphere included: high signal on T2-weighted images in the cortex (seven patients) and white matter (nine), cortical atrophy usually involving the frontoinsular region, with mild or severe enlargement of the lateral ventricle (eight) and moderate atrophy of the head of the caudate nucleus (seven). Cortical swelling in the early stage of the disease was recognisable only in two patients. PET revealed hypometabolism, SPECT decreased perfusion, and (1)HMRS reduction of N-acetylaspartate in the affected hemisphere. PET and SPECT were usually performed in the late stages and did not provide specific findings. MRI thus demonstrates the progression of RE and may suggest the diagnosis in the early stages, often before the appearance of neurological deficits. Early diagnosis of RE may be crucial for selecting patients for aggressive medical therapy or major surgical interventions such as hemispherectomy
AD  - Department of Neuroradiology, Istituto Nazionale Neurologico C Besta, Via Celoria 11, 20133 Milano, Italy. l.chiapparini@doctor.com
UR  - PM:12684722
ER  - 

TY  - JOUR
T1  - (18)F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis
A1  - Fiorella,D.J.
A1  - Provenzale,J.M.
A1  - Coleman,R.E.
A1  - Crain,B.J.
A1  - Al Sugair,A.A.
Y1  - 2001/08//
N1  - UI - 21388918
SP  - 1291
EP  - 1299
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 22
IS  - 7
N2  - BACKGROUND AND PURPOSE: Rasmussen encephalitis is a chronic, progressive encephalitis that manifests as an abrupt-onset, intractable seizure disorder in previously developmentally normal children. The objectives of the current study were to characterize the (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and MR imaging findings in Rasmussen encephalitis and to test the hypotheses that data from both imaging techniques are required to establish the diagnosis and identify the affected cerebral hemisphere in some cases. METHODS: Eleven patients with Rasmussen encephalitis were identified from a review of a computer database. The MR (n = 10) and PET (n = 11) imaging data were reviewed retrospectively and conjointly. RESULTS: On MR images, nine of 10 patients manifested bilateral cerebral atrophy that predominantly involved one hemisphere. One patient had purely unilateral cerebral atrophy. We observed foci of abnormally increased T2 signal intensity in nine of 10 patients. On FDG PET images, all patients showed extensive regions of hypometabolism within the cerebral hemisphere that showed the greatest atrophy. Discrete foci of hypermetabolism, indicative of seizure activity, were observed in six patients. The FDG PET and MR imaging findings were either stable or gradually progressive in patients with multiple imaging studies (MR, n = 5; FDG PET, n = 5). CONCLUSION: Rasmussen encephalitis is characterized by diffuse, unilateral cerebral hypometabolism on FDG PET images, with corresponding regions of cerebral atrophy on MR images. Although MR imaging data alone are sufficient to suggest a diagnosis of Rasmussen encephalitis in many cases, correlation with FDG PET data increases diagnostic confidence and allows the unequivocal identification of the affected cerebral hemisphere in patients whose MR imaging findings are subtle or distributed bilaterally
AD  - Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
UR  - PM:11498416
ER  - 

TY  - JOUR
T1  - Brain organization of motor and language functions following hemispherectomy: a [(15)O]-water positron emission tomography study
A1  - Muller,R.A.
A1  - Chugani,H.T.
A1  - Muzik,O.
A1  - Mangner,T.J.
Y1  - 1998/01//
N1  - UI - 98136110
SP  - 16
EP  - 22
JA  - J Child Neurol
VL  - 13
IS  - 1
N2  - The capacity of the developing brain for compensatory reorganization after early hemispherectomy has been previously shown in neurobehavioral studies, above all with regard to language recovery. The present study examines the organization of motor and language areas by means of [(15)O]-water positron emission tomography (PET) in a 6-year-old boy who underwent right functional hemispherectomy at age 3 years. The results suggest that compensatory allocation for movement of the weak hand primarily involves the premotor, inferior frontal, and insular cortices, and the supplementary motor area in the retained hemisphere, as well as the bilateral cerebellum. Receptive language and prosodic functions primarily activated the left perisylvian cortices. However, language and motor activations were also seen in cortical and subcortical remains on the hemispherectomized side suggesting incomplete disconnection by functional hemispherectomy
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit 48201-2196, USA
UR  - PM:9477243
ER  - 

TY  - JOUR
T1  - Luxury perfusion phenomenon in acute herpes simplex virus encephalitis
A1  - Tanaka,M.
A1  - Uesugi,M.
A1  - Igeta,Y.
A1  - Kondo,S.
A1  - Sun,X.
A1  - Hirai,S.
Y1  - 1995/02//
N1  - UI - 95298476
SP  - 43
EP  - 45
JA  - Ann.Nucl Med
VL  - 9
IS  - 1
N2  - In a patient with acute herpes simplex virus (HSV) encephalitis, positron emission tomography (PET) demonstrated increased cerebral blood flow in the affected temporal lobe accompanied by reduction in the cerebral oxygen extraction fraction and the cerebral metabolic rate of oxygen, i.e., luxury perfusion. Follow-up PET studies showed reduction in cerebral perfusion until it was more closely coupled with oxygen metabolism after the resolution of the acute inflammation. These findings support previous single photon emission computed tomographic data and provide a pathophysiological background for the occurrence of hyperperfusion in HSV encephalitis. This is an interesting example of the luxury perfusion phenomenon occurring in a disease other than cerebral ischemia
AD  - Department of Neurology, Gunma University School of Medicine, Japan
UR  - PM:7779530
ER  - 

TY  - JOUR
T1  - Sequential positron emission tomographic evaluations of brain metabolism in acute herpes encephalitis
A1  - Meyer,M.A.
A1  - Hubner,K.F.
A1  - Raja,S.
A1  - Hunter,K.
A1  - Paulsen,W.A.
Y1  - 1994/04//
N1  - UI - 94243100
SP  - 104
EP  - 105
JA  - J Neuroimaging
VL  - 4
IS  - 2
N2  - This first known positron emission tomography report on metabolic changes in acute herpes simplex virus (HSV-1) encephalitis demonstrates focal hypermetabolism in areas of cerebral cortex adjacent to actively inflamed hippocampus acutely infected with HSV-1. When neuropsychiatric symptoms recurred in a previously healthy 61-year-old patient 1 month after recovering from acute HSV-1 encephalitis, repeat positron emission tomography with fluorodeoxyglucose was helpful in ruling out recurrent active infection by showing marked hypometabolism throughout the previously infected temporal lobe
AD  - University of Tennessee Medical Center, Biomedical Imaging Center, Knoxville, TN 37920
UR  - PM:8186524
ER  - 

TY  - JOUR
T1  - Rasmussen's encephalitis: neuroimaging findings in four patients
A1  - Tien,R.D.
A1  - Ashdown,B.C.
A1  - Lewis,D.V.,Jr.
A1  - Atkins,M.R.
A1  - Burger,P.C.
Y1  - 1992/06//
N1  - UI - 92271880
SP  - 1329
EP  - 1332
JA  - AJR Am J Roentgenol.
VL  - 158
IS  - 6
N2  - Rasmussen's encephalitis is a devastating disease of childhood causing progressive neurologic deficits and intractable seizure activity. Patients frequently have episodes of epilepsia partialis continua and, much less frequently, generalized status epilepticus. The seizures are intractable despite aggressive medical management. In advanced cases, hemispherectomy appears to be the only option to control the seizures. Permanent physical and mental impairments are inevitable. The cause of this disease is unknown, although pathologic specimens demonstrate nonspecific changes that are compatible with viral encephalitis. The progressive brain damage is typically so insidious in onset and gradual in course that it is difficult to make an accurate diagnosis on the basis of clinical evidence. We retrospectively evaluated the CT, xenon CT, positron emission tomographic, and MR neuroimaging findings in four young patients with pathologically suspected Rasmussen's encephalitis (three patients had CT scans, two had xenon CT scans, two had MR scans, and one had a positron emission tomogram). All studies showed abnormalities of the involved cerebral hemisphere: CT and MR revealed nonspecific atrophy, xenon CT showed decreased cerebral blood flow, and positron emission tomography revealed a hypometabolic state. Rasmussen's encephalitis is a diagnosis of exclusion; however, the information obtained from neuroimaging studies in combination with the clinical course should suggest this disorder
AD  - Department of Radiology, Duke University Medical Center, Durham, NC 27710
UR  - PM:1590136
ER  - 

TY  - JOUR
T1  - Changing patterns of glucose metabolism during the course of subacute sclerosing panencephalitis as measured with 18FDG-positron-emission tomography
A1  - Huber,M.
A1  - Pawlik,G.
A1  - Bamborschke,S.
A1  - Fink,G.R.
A1  - Karbe,H.
A1  - Schlenker,M.
A1  - Bewermeyer,H.
A1  - Heiss,W.D.
Y1  - 1992/03//
N1  - UI - 92243166
SP  - 157
EP  - 161
JA  - J Neurol
VL  - 239
IS  - 3
N2  - 18FDG-positron emission tomography performed at different stages in the course of subacute sclerosing panencephalitis revealed a changing pattern of metabolic disturbance. In clinical stage II patients the inflammation in the basal ganglia appeared to lead to neuronal excitation accompanied by hypermetabolism. Widespread cortical functional inhibition of metabolism followed. The striatal inflammation ended with necrosis and hypometabolism, with resulting functional cortical disinhibition; later, deep midbrain structures and brain stem became hypermetabolic. A patient clinically in remission showed no such changes in cerebral glucose metabolism
AD  - Neurologische Universitatsklinik, Koln, Federal Republic of Germany
UR  - PM:1573420
ER  - 

TY  - JOUR
T1  - FDG-PET in the selection of brain lesions for biopsy
A1  - Hanson,M.W.
A1  - Glantz,M.J.
A1  - Hoffman,J.M.
A1  - Friedman,A.H.
A1  - Burger,P.C.
A1  - Schold,S.C.
A1  - Coleman,R.E.
Y1  - 1991/09//
N1  - UI - 91358782
SP  - 796
EP  - 801
JA  - J Comput.Assist.Tomogr.
VL  - 15
IS  - 5
N2  - The CT-guided stereotaxic needle biopsy has become a widely used procedure in the diagnostic evaluation of intracranial lesions including tumors. Conventional CT or MR frequently defines the anatomic regions of abnormality, which may be multiple lesions or a single lesion that is heterogeneous in cellular composition owing to the topographic variation of cellular constituency or the combination of active disease, nonspecific inflammation, necrosis, and/or edema. In these cases, selection of the most appropriate site for a successful diagnostic needle biopsy can be difficult. In three patients, we have used [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the site most likely to provide a diagnostic biopsy result. In the first patient, who presented with confusion, multiple biopsies from the temporal lobe, based on MR abnormalities, revealed only reactive gliosis and edema. Repeat biopsy directed by PET revealed an anaplastic astrocytoma. In a second patient, PET allowed us to differentiate radiation effect from active metastatic breast cancer. In the third patient, who presented with a grand mal seizure, biopsy of a CT-defined hypodense region demonstrated lymphocytosis. Metabolism of FDG was normal or increased in areas of Aspergillus encephalitis at autopsy. These preliminary studies suggest a complementary role for FDG-PET and CT or MR in selected patients for defining the intracranial site most likely to yield a positive biopsy result
AD  - Department of Radiology, Duke University Medical Center, Durham, NC 27710
UR  - PM:1885797
ER  - 

TY  - JOUR
T1  - Positron emission tomography demonstrated localized luxury perfusion in subacute sclerosing panencephalitis
A1  - Yoshikawa,H.
A1  - Fueki,N.
A1  - Yoneyama,H.
A1  - Ogawa,M.
A1  - Sakuragawa,N.
Y1  - 1990/10//
N1  - UI - 91060898
SP  - 311
EP  - 315
JA  - J Child Neurol
VL  - 5
IS  - 4
N2  - Positron emission tomography (PET) was performed on two patients in different stages of subacute sclerosing panencephalitis (SSPE) and compared with the concurrent computed tomography (CT) findings and clinical status. Case 1, which was in stage II, showed luxury perfusion in the anterior half of the cerebrum and decreases of cerebral blood flow and oxygen metabolism in the right frontal watershed zone, where CT showed low density. Case 2, which was in stage III, showed marked decreases of cerebral blood flow and cerebral metabolic rate of oxygen in all regions except the occipital region. The present PET study demonstrated that SSPE showed inflammatory-destructive progression and rostral-caudal progression. Further, it was suspected that low density on CT scan, especially in the watershed zone, resulted partly from disturbances in cerebral circulation
AD  - Division of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan
UR  - PM:2246484
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis
A1  - Huber,M.
A1  - Herholz,K.
A1  - Pawlik,G.
A1  - Szelies,B.
A1  - Jurgens,R.
A1  - Heiss,W.D.
Y1  - 1989/01//
N1  - UI - 89087362
SP  - 97
EP  - 100
JA  - Arch Neurol
VL  - 46
IS  - 1
N2  - Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level
AD  - Max-Planck-Institut fur Neurologische Forschung, Cologne, West Germany
UR  - PM:2783367
ER  - 

TY  - JOUR
T1  - Impulsivity and prefrontal hypometabolism in borderline personality disorder
A1  - Soloff,Paul H.
A1  - Meltzer,Carolyn Cidis
A1  - Becker,Carl
A1  - Greer,Phil J.
A1  - Kelly,Thomas M.
A1  - Constantine,Doreen
Y1  - 2003/07/30/
SP  - 153
EP  - 163
JF  - Psychiatry Research: Neuroimaging
VL  - 123
IS  - 3
N2  - Prefrontal hypoperfusion and decreased glucose uptake in the prefrontal cortex (PFC) are found in violent criminal offenders, murderers and aggressive psychiatric patients. These abnormalities may be independent of diagnosis and associated with impulsive-aggression as a personality trait. Impulsive-aggression is a clinical characteristic of borderline personality disorder (BPD) where it is associated with assaultive and suicidal behaviors. We conducted FDG-PET studies in 13 non-depressed, impulsive female subjects with BPD and 9 healthy controls to look for abnormalities in glucose metabolism in areas of the PFC associated with regulation of impulsive behavior. Statistical Parametric Mapping-99 ( was used to analyze the PET data with Hamilton depression scores as covariate. Significant reductions in FDG uptake in BPD subjects relative to healthy controls were found bilaterally in medial orbital frontal cortex, including Brodmann's areas 9, 10 and 11. There were no significant areas of increased uptake in BPD subjects compared to control subjects. Covarying for measures of impulsivity or impulsive-aggression rendered insignificant the differences between groups. Decreased glucose uptake in medial orbital frontal cortex may be associated with diminished regulation of impulsive behavior in BPD
UR  - http://www.sciencedirect.com/science/article/B6TBW-491J4PK-2/2/7181b813d26e22c505715a9cc65493a9
ER  - 

TY  - JOUR
T1  - Measurement of the Extracellular Space in Brain Tumors Using (76)Br-Bromide and PET
A1  - Bruehlmeier,M.
A1  - Roelcke,U.
A1  - Blauenstein,P.
A1  - Missimer,J.
A1  - Schubiger,P.A.
A1  - Locher,J.T.
A1  - Pellikka,R.
A1  - Ametamey,S.M.
Y1  - 2003/08//
N1  - UI - 22784353
SP  - 1210
EP  - 1218
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 8
N2  - Brain edema significantly contributes to the clinical course of human brain tumor patients. There is evidence that an enlargement of the extracellular space (ECS) is involved in the development of brain edema. Although T2-weighted magnetic resonance (T2-MR) images represent brain edema by its increased water content, they do not differentiate ECS enlargement from increased intracellular water content. METHODS: On the basis of the known distribution of bromide in the ECS, we used (76)Br-bromide and PET to measure the regional ECS in 9 brain tumor patients. Transport rate constants and the distribution volume (DV) of (76)Br-bromide in normal brain and tumor were derived from dynamic PET scans and the measured (76)Br-bromide concentration in arterial plasma. We evaluated different models regarding their reliability in estimating the ECS. RESULTS: Assuming that the DV of (76)Br-bromide represents the ECS, robust estimates were possible for all investigated regions. In normal brain, ECS was within a narrow range-for example, occipital lobe, 19.9% +/- 3.1%-and was lower in 2 dexamethasone-treated patients compared with untreated patients. In 7 of 9 tumors, increased ECS ranged between 43.8% and 61.1%. ECS increases were confined to the tumor mass and did not extend into peritumoral edematous brain. Two patients with large hyperintense lesions according to T2-MR images showed normal ECS values within the lesion. CONCLUSION: (76)Br-Bromide PET allows a quantitative measurement of the ECS in brain edema and in normal brain. The discrepancies between lesions shown by T2-MRI and regional ECS enlargement as measured with PET challenge the concept of tumor-induced brain edema
AD  - Paul Scherrer Institute, Center for Radiopharmaceutical Science, Villigen, Switzerland. Department of Nuclear Medicine, Cantonal Hospital, Aarau, Switzerland. Department of Neurology, Cantonal Hospital, Aarau, Switzerland
UR  - PM:12902409
ER  - 

TY  - JOUR
T1  - The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker
A1  - Lockhart,A.
A1  - Davis,B.
A1  - Matthews,J.C.
A1  - Rahmoune,H.
A1  - Hong,G.
A1  - Gee,A.
A1  - Earnshaw,D.
A1  - Brown,J.
Y1  - 2003/02//
N1  - UI - 22511633
SP  - 199
EP  - 206
JA  - Nucl Med Biol.
VL  - 30
IS  - 2
N2  - The peripheral benzodiazepine receptor ligand PK11195 has been used as an in vivo marker of neuroinflammation in positron emission tomography studies in man. One of the methodological issues surrounding the use of the ligand in these studies is the highly variable kinetic behavior of [(11)C]PK11195 in plasma. We therefore undertook a study to measure the binding of [(3)H]PK11195 to whole human blood and found a low level of binding to blood cells but extensive binding to plasma proteins. Binding assays using [(3)H]PK11195 and purified human plasma proteins demonstrated a strong binding to alpha1-acid glycoprotein (AGP) and a much weaker interaction with albumin. Immunodepletion of AGP from plasma resulted in the loss of plasma [(3)H]PK11195 binding demonstrating: (i) the specificity of the interaction and (ii) that AGP is the major plasma protein to which PK11195 binds with high affinity. PK11195 was able to displace fluorescein-dexamethasone from AGP with IC(50) of <1.2 microM, consistent with a high affinity interaction. These findings are important for understanding the behavior of the ligand in positron emission tomography studies for three reasons. Firstly, AGP is an acute phase protein and its levels will vary during infection and pathological inflammatory diseases such as multiple sclerosis. This could significantly alter the free plasma concentrations of the ligand and contribute to its variable kinetic behavior. Secondly, AGP and AGP-bound ligand may contribute to the access of [(11)C]PK11195 to the brain parenchyma in diseases with blood brain barrier breakdown. Finally, local synthesis of AGP at the site of brain injury may contribute the pattern of [(11)C]PK11195 binding observed in neuroinflammatory diseases
AD  - GlaxoSmithKline, Translational Medicine and Technology, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 2GG, UK. andrew_2_lockhart@gsk.com
UR  - PM:12623120
ER  - 

TY  - JOUR
T1  - Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study
A1  - Sun,X.
A1  - Tanaka,M.
A1  - Kondo,S.
A1  - Okamoto,K.
A1  - Hirai,S.
Y1  - 1998/04//
N1  - UI - 98299349
SP  - 89
EP  - 94
JA  - Ann.Nucl Med
VL  - 12
IS  - 2
N2  - Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO2. A correlation between the decrease in rCMRO2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information
AD  - Department of Neurology, Gunma University School of Medicine, Maebashi, Japan
UR  - PM:9637279
ER  - 

TY  - JOUR
T1  - Positron emission tomography, magnetic resonance imaging and proton NMR spectroscopy of white matter in multiple sclerosis
A1  - Schiepers,C.
A1  - Van Hecke,P.
A1  - Vandenberghe,R.
A1  - Van Oostende,S.
A1  - Dupont,P.
A1  - Demaerel,P.
A1  - Bormans,G.
A1  - Carton,H.
Y1  - 1997/02//
N1  - UI - 97304057
SP  - 8
EP  - 17
JA  - Mult.Scler.
VL  - 3
IS  - 1
N2  - OBJECTIVE: To assess characteristics of MS lesions and normal appearing white matter (NAWM) with various imaging modalities. Glucose metabolism was investigated with FDG-PET, metabolite concentration with proton NMR spectroscopy, and lesion detection with routine brain MRI. METHODS: Thirteen patients were studied in a stable phase of their disease, and two during an acute episode. Nine healthy volunteers served as controls. RESULTS: Three patients had a normal brain MRI, 12 had typical lesions. MR images were registered to the PET planes. Lesions and contra-lateral control areas were analyzed, 10/15 lesions showed relative hyper-metabolism and 2 hypo-metabolism. NAA concentration was significantly decreased in both lesions and NAWM. CONCLUSION: In stable MS, most large lesions have a relatively increased glucose utilization and decreased NAA concentration. NAWM showed a significantly decreased NAA concentration compared to healthy subjects, but no difference in glucose metabolism. Active lesions in acute MS are also hyper-metabolic. This finding opens a new window on the classification of white matter lesions based on glucose utilization
AD  - Department of Nuclear Medicine, University Hospital Gasthuisberg, Leuven, Belgium
UR  - PM:9160342
ER  - 

TY  - JOUR
T1  - Cobalt-55 positron emission tomography in relapsing-progressive multiple sclerosis
A1  - Jansen,H.M.
A1  - Willemsen,A.T.
A1  - Sinnige,L.G.
A1  - Paans,A.M.
A1  - Hew,J.M.
A1  - Franssen,E.J.
A1  - Zorgdrager,A.M.
A1  - Pruim,J.
A1  - Minderhoud,J.M.
A1  - Korf,J.
Y1  - 1995/10//
N1  - UI - 96098602
SP  - 139
EP  - 145
JA  - J Neurol Sci.
VL  - 132
IS  - 2
N2  - Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the brain that can have a progressive course. However, the progression of relapsing-remitting (RR) MS into relapsing-progressive (RP) MS might represent a more fundamental change in disease activity, i.e. decay of vulnerable neurons and oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue structure is caused by a combination of demyelination and cellular loss, both of which are likely to cause disability in MS. We used the PET isotope cobalt-55 (Co) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact that Ca influx is essential in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine whether Co-PET detects any RP-MS lesions and, if so, to assess any correlation with the progression rate (PR) of the disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion frequency was assessed and correlated with the PR of the disease. Co-PET demonstrated significantly more lesions in the MS brain than in the healthy brain, both periventricular and cortical. Every single MRI lesion could be retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated significantly with PR. Our pilot study possibly suggests Co-PET as a tool in estimating disease activity in RP-MS.(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Neurology, University Hospital Groningen, Netherlands
UR  - PM:8543939
ER  - 

TY  - JOUR
T1  - Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis
A1  - Pozzilli,C.
A1  - Fieschi,C.
A1  - Perani,D.
A1  - Paulesu,E.
A1  - Comi,G.
A1  - Bastianello,S.
A1  - Bernardi,S.
A1  - Bettinardi,V.
A1  - Bozzao,L.
A1  - Canal,N.
A1  - .
Y1  - 1992/10//
N1  - UI - 93108006
SP  - 51
EP  - 57
JA  - J Neurol Sci.
VL  - 112
IS  - 1-2
N2  - Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function
AD  - Department of Neurological Sciences, University of Rome La Sapienza, Italy
UR  - PM:1469440
ER  - 

TY  - JOUR
T1  - Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis
A1  - Brooks,D.J.
A1  - Leenders,K.L.
A1  - Head,G.
A1  - Marshall,J.
A1  - Legg,N.J.
A1  - Jones,T.
Y1  - 1984/11//
N1  - UI - 85057026
SP  - 1182
EP  - 1191
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 47
IS  - 11
N2  - Regional cerebral oxygen utilisation (rCMRO2), oxygen extraction (rOER), blood flow (rCBF), and blood volume (rCBV) have been determined for fifteen patients with multiple sclerosis in remission using positron emission tomography (PET). Cerebral oxygen utilisation and blood flow were significantly reduced in both white matter and peripheral cortical grey matter in the multiple sclerosis patients compared to a group of normal controls. No evidence of regional cerebral ischaemia in the multiple sclerosis group was found. Lowest levels of cerebral oxygen utilisation were found in patients with cerebral atrophy, and in patients in whom a significant fall in present full-scale IQ from estimated pre-morbid levels had occurred. No correlation was found between rCMRO2 values and severity of locomotor dysfunction or clinical disease duration
UR  - PM:6334132
ER  - 

TY  - JOUR
T1  - Analgesia by electrostimulation of the trigeminal ganglion in patients with trigeminopathic pain: a PET activation study
A1  - Willoch,F.
A1  - Gamringer,U.
A1  - Medele,R.
A1  - Steude,U.
A1  - Tolle,T.R.
Y1  - 2003/05//
N1  - UI - 22635833
SP  - 119
EP  - 130
JF  - Pain
VL  - 103
IS  - 1-2
N2  - Electrostimulation of the trigeminal ganglion (TGES) has shown good results in treatment of trigeminopathic pain in selected patients. To map the mechanisms of TGES analgesia, we determined changes in relative regional cerebral blood flow (rCBF) in ten patients with trigeminopathic pain using positron emission tomography. The patients were scanned before stimulation (habitual pain), after short-term stimulation (1 min, stTGES) and after long-term stimulation (ltTGES). Highly significant pain alleviation was reported after ltTGES. Relative rCBF changes after stTGES, which was without significant pain relief, were attributed mainly to intrinsic TGES effects. A statistical comparison of the subtraction images of ltTGES and stTGES disclosed significant rCBF increases after ltTGES in rostral parts of anterior cingulate cortex (ACC) and neighboring orbitofrontal and medial frontal cortices. Regression analysis of rCBF changes and subjective ratings of pain revealed an inverse relationship in the ipsilateral rostral ACC, and only rCBF changes in the caudal part of the contralateral ACC were consistent with the encoding of pain. The present study provides evidence for a pain modulating role of the rostral ACC, critically important in electrostimulation-induced analgesia, and identifies the caudal ACC as a region encoding pain sensation
AD  - Department of Nuclear Medicine, Technische Universitat Munchen, Klinikum rechts der Isar, Ismaningerstrasse, 22, 81675 Munich, Germany. frode.willoch@rikshospitalet.no
UR  - PM:12749966
ER  - 

TY  - JOUR
T1  - Striatal dopamine D1 and D2 receptors in burning mouth syndrome
A1  - Hagelberg,N.
A1  - Forssell,H.
A1  - Rinne,J.O.
A1  - Scheinin,H.
A1  - Taiminen,T.
A1  - Aalto,S.
A1  - Luutonen,S.
A1  - Nagren,K.
A1  - Jaaskelainen,S.
Y1  - 2003/01//
SP  - 149
EP  - 154
JF  - Pain
VL  - 101
IS  - 1-2
N2  - Animal studies have indicated that the nigrostriatal dopaminergic system is involved in central pain modulation. In a recent positron emission tomography (PET) study, we demonstrated presynaptic dysfunction of the nigrostriatal dopaminergic pathway in burning mouth syndrome, which is a chronic pain state. The objective of the present study was to examine striatal dopamine D1 and D2 receptors in these patients. We used 11C-NNC 756 and 11C-raclopride to study D1 and D2 receptor binding in a PET study in ten burning mouth patients and 11 healthy controls. Patients underwent a structured psychiatric evaluation and an electrophysiological test for the excitability of the blink reflex. The striatal uptake of 11C-NNC 756 did not differ between patients and controls. In a voxel-level analysis, the uptake of 11C-raclopride was statistically significantly higher in the left putamen in burning mouth patients (corrected P-value 0.038 at cluster-level). In the region of interest analysis, the D1/D2 ratio was 7.7% lower in the right putamen (0.64+/-0.04 vs. 0.69+/-0.04, P=0.01) and 6.4 % lower in the left putamen (0.65+/-0.05 vs. 0.70+/-0.05, P=0.05) when compared to controls. Increased 11C-raclopride uptake and the subsequent decrease in the D1/D2 ratio may indicate a decline in endogenous dopamine levels in the putamen in burning mouth patients
AD  - Department of Anesthesiology and Intensive Care, Turku University Central Hospital, PO Box 52, FIN-20521, Turku, Finland
UR  - PM:12507709
ER  - 

TY  - JOUR
T1  - Changes in human regional cerebral blood flow following hypertonic saline induced experimental muscle pain: a positron emission tomography study
A1  - Korotkov,A.
A1  - Ljubisavljevic,M.
A1  - Thunberg,J.
A1  - Kataeva,G.
A1  - Roudas,M.
A1  - Pakhomov,S.
A1  - Radovanovic,S.
A1  - Lyskov,E.
A1  - Medvedev,S.
A1  - Johansson,H.
Y1  - 2002/12/25/
N1  - UI - 22347685
SP  - 119
EP  - 123
JA  - Neurosci.Lett.
VL  - 335
IS  - 2
N2  - A positron emission tomography imaging study was performed on 16 healthy volunteers to reveal changes in cortical activation during acute muscle pain induced by intra-muscular injection of hypertonic saline into the left triceps brachii muscle. Changes in regional cerebral blood flow (rCBF) were measured with the use of [(15)O] labelled water during 'Rest1', 'Needle' (insertion of a needle without injection), 'Rest2' and 'Pain' conditions. Differences in rCBF were found in the comparison of Pain and Needle, and Pain and Rest2 conditions, revealing activation of the contralateral insula and putamen. The results are discussed with respect to possible differences in brain processing of muscle and cutaneous noxious inputs
AD  - Center for Musculoskeletal Research, Umea University and National Institute for Working Life, Box 7654, Petrus Laestadius vag, S907 13, Umea, Sweden
UR  - PM:12459513
ER  - 

TY  - JOUR
T1  - Local sympathetic denervation in painful diabetic neuropathy
A1  - Tack,C.J.
A1  - van Gurp,P.J.
A1  - Holmes,C.
A1  - Goldstein,D.S.
Y1  - 2002/12//
N1  - UI - 22341180
SP  - 3545
EP  - 3553
JF  - Diabetes
VL  - 51
IS  - 12
N2  - This study assessed whether painful diabetic neuropathy is associated with abnormal sympathetic nervous function in the affected limbs. Nine patients with diabetes (four men, five women; age 61 +/- 7 years) and painful peripheral neuropathy of the feet, but without evidence of generalized autonomic neuropathy, underwent intravenous infusion of tritiated norepinephrine (NE) and sampling of arterial and venous blood in both feet and in one arm to quantify the rate of entry of NE into the local venous plasma (NE spillover). In the same patients, positron emission tomography (PET) scanning after intravenous injection of the sympathoneural imaging agent 6-[(18)F]fluorodopamine was used to visualize sympathetic innervation and after intravenous [(13)N]ammonia to visualize local perfusion. The results were compared with those in the feet of normal volunteers and in an unaffected foot of patients with unilateral complex regional pain syndrome (CRPS). In addition, neurochemical results obtained in painful diabetic neuropathy were compared with those obtained in diabetic control patients with painless neuropathy and diabetic control patients without neuropathy. Local arteriovenous difference in plasma NE levels (DeltaNE(AV)) and NE spillover in the arms did not differ across the groups. However, DeltaNE(AV) in the feet was significantly less in the group with painful diabetic neuropathy than in the control groups. Also NE spillover in the feet tended to be lower in painful neuropathy. DeltaNE(AV) of diabetic control patients without neuropathy (n = 6) resembled values in the control groups without diabetes, whereas patients with painless diabetic neuropathy (n = 6) had evidence suggesting partial loss of sympathetic innervation. PET scanning revealed decreased flow-corrected 6-[(18)F]fluorodopamine-derived radioactivity in patients with painful diabetic neuropathy, compared with values in normal volunteers and patients with CRPS. The results provide neurochemical and neuroimaging evidence for regionally selective sympathetic denervation in the painful feet of patients with diabetic neuropathy
AD  - Division of General Internal Medicine, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. c.tack@aig.umcn.nl
UR  - PM:12453912
ER  - 

TY  - JOUR
T1  - A unique representation of heat allodynia in the human brain
A1  - Lorenz,J.
A1  - Cross,D.
A1  - Minoshima,S.
A1  - Morrow,T.
A1  - Paulson,P.
A1  - Casey,K.
Y1  - 2002/07/18/
N1  - UI - 22151627
SP  - 383
EP  - 393
JF  - Neuron
VL  - 35
IS  - 2
N2  - Skin inflammation causes innocuous heat to become painful. This condition, called heat allodynia, is a common feature of pathological pain states. Here, we show that heat allodynia is functionally and neuroanatomically distinct from normal heat pain. We subtracted positron emission tomography scans obtained during painful heating of normal skin from scans during equally intense but normally innocuous heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to the frontal lobe during heat allodynia. The results suggest that different central pathways mediate the intensity and certain qualitative aspects of pain. In making this differentiation, the brain recognizes unique physiological features of different painful conditions, thus permitting adaptive responses to different pain states
AD  - Department Neurology, University of Michigan, Ann Arbor, MI 48109, USA
UR  - PM:12160755
ER  - 

TY  - JOUR
T1  - Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls
A1  - Derbyshire,S.W.
A1  - Jones,A.K.
A1  - Creed,F.
A1  - Starz,T.
A1  - Meltzer,C.C.
A1  - Townsend,D.W.
A1  - Peterson,A.M.
A1  - Firestone,L.
Y1  - 2002/07//
N1  - UI - 21966365
SP  - 158
EP  - 168
JF  - Neuroimage
VL  - 16
IS  - 1
N2  - Changes in regional cerebral blood flow (rCBF) have previously been demonstrated in a number of cortical and subcortical regions, including the cerebellum, midbrain, thalamus, lentiform nucleus, and the insula, prefrontal, anterior cingulate, and parietal cortices, in response to experimental noxious stimuli. Increased anterior cingulate responses in patients with chronic regional pain and depression to noxious stimulation distant from the site of clinical pain have been observed. We suggested that this may represent a generalized hyperattentional response to noxious stimuli and may apply to other types of chronic regional pain. Here these techniques are extended to a group of patients with nonspecific chronic low back pain. Thirty-two subjects, 16 chronic low back pain patients and 16 controls, were studied using positron emission tomography. Thermal stimuli, corresponding to the experience of hot, mild, and moderate pain, were delivered to the back of the subject's right hand using a thermal probe. Each subject had 12 measurements of rCBF, 4 for each stimulus. Correlation of rCBF with subjective pain experience revealed similar responses across groups in the cerebellum, midbrain (including the PAG), thalamus, insula, lentiform nucleus, and midcingulate (area 24') cortex. These regions represented the majority of activations for this study and those recorded by other imaging studies of pain. Although some small differences were observed between the groups these were not considered sufficient to suggest abnormal nociceptive processing in patients with nonspecific low back pain. (c) 2002 Elsevier Science (USA)
AD  - Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213
UR  - PM:11969326
ER  - 

TY  - JOUR
T1  - Cortical representation of the sensory dimension of pain
A1  - Hofbauer,R.K.
A1  - Rainville,P.
A1  - Duncan,G.H.
A1  - Bushnell,M.C.
Y1  - 2001/07//
N1  - UI - 21324644
SP  - 402
EP  - 411
JA  - J Neurophysiol.
VL  - 86
IS  - 1
N2  - It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3G 1Y6, Canada
UR  - PM:11431520
ER  - 

TY  - JOUR
T1  - Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study
A1  - Jaaskelainen,S.K.
A1  - Rinne,J.O.
A1  - Forssell,H.
A1  - Tenovuo,O.
A1  - Kaasinen,V.
A1  - Sonninen,P.
A1  - Bergman,J.
Y1  - 2001/02/15/
N1  - UI - 21157698
SP  - 257
EP  - 260
JF  - Pain
VL  - 90
IS  - 3
N2  - Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6-[(18)F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition
AD  - Department of Clinical Neurophysiology, Turku University Central Hospital, PL 52, FI-20 521 Turku, Finland. satu.jaaskelainen@tyks.fi
UR  - PM:11207397
ER  - 

TY  - JOUR
T1  - Cerebral responses to pain in patients suffering acute post-dental extraction pain measured by positron emission tomography (PET)
A1  - Derbyshire,S.W.
A1  - Jones,A.K.
A1  - Collins,M.
A1  - Feinmann,C.
A1  - Harris,M.
Y1  - 1999/06//
N1  - UI - 0
SP  - 103
EP  - 113
JA  - Eur.J Pain
VL  - 3
IS  - 2
N2  - Previous studies with normal volunteers have demonstrated distributed cortical responses to experimental heat pain within a network of structures. The network includes the insula, anterior cingulate, prefrontal, inferior parietal and somatosensory cortices. Patients suffering from chronic nociceptive pain following rheumatoid arthritis (RA) have shown damped central responses to experimental heat pain applied to the back of the right hand. In this study of patients with acute, left-sided, post-molar-extraction (surgical) pain, we assessed the cortical responses to experimental heat pain, applied to the back of the right hand, using positron emission tomography (PET), and compared the responses with a previously reported control group and the RA group. In response to the experimental heat pain, the surgical group indicated significantly increased regional cerebral blood flow in the prefrontal cortex [Brodman's area (BA) 44] ipsilateral to the heat stimulus. Contralateral increases were detected in the putamen and transverse temporal gyrus (BA 40/41/42) with bilateral increases in the insular cortex. Compared to the control and RA group, there were significantly reduced responses in the anterior cingulate (BA 24), pre-frontal medial, and orbito-frontal (BA 9/10/32/47) cortices. These results suggest that relatively discrete regions of the cerebral cortex are responsible for acute nociceptive processing during an acute inflammatory episode. The reduced frontal and anterior cingulate responses to the experimental heat pain (applied to the right hand) during acute inflammatory pain (left jaw) illustrates cortical modulation of nociceptive processing that may be related to non-somatotopic, bilateral, nociceptive inputs to these areas. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain
AD  - UCLA/CURE Neuroenteric Disease Program, WLA VAMC, Building 115 Room 223, Los Angeles, CA, 90073, USA
UR  - PM:10700340
ER  - 

TY  - JOUR
T1  - PET study on central processing of pain in trigeminal neuropathy
A1  - Hsieh,J.C.
A1  - Meyerson,B.A.
A1  - Ingvar,M.
Y1  - 1999/03//
N1  - UI - 0
SP  - 51
EP  - 65
JA  - Eur.J Pain
VL  - 3
IS  - 1
N2  - Recent functional brain imaging studies with positron emission tomography (PET), in painful peripheral mononeuropathy and nitroglycerin-provoked cluster headache attacks, suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC), in attributing emotional valence and attention to the pain suffering. We have investigated the central processing of painful trigeminal neuropathy (PTN) in patients treated with electric extradural precentral gyrus stimulation (PCGS). Increased regional cerebral blood flow (rCBF) was detected in the right caudal ACC [Brodmann area (BA) 24] and anterior limbic thalamus, while a decreased activity was observed in the right MPFC (BA 9/32) during the habitual-pain state, in comparison with the pain-alleviated state regardless of the inflicted side of PTN. The involvement of BA 9/32 and the anterior limbic thalamus spatially extended to the left hemisphere, but the local maxima and a significant negative correlation between the rCBF changes in the two structures were found only in the right hemisphere. The activation of the caudal BA24 further supports the theory that ACC is crucial for the suffering in chronic pain. Our study not only verifies the preferential role of the right hemisphere in the appreciation of pain suffering, but further supports that sustained chronic pain, being devoid of the motivational component of an escape response, targets the right hemisphere, particularly the BA24 of the ACC. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain
AD  - PET Cognitive Neurophysiology, Department of Clinical Neuroscience, Karolinska Hospital/Karolinska Institute, Stockholm, S-17176, Sweden
UR  - PM:10700337
ER  - 

TY  - JOUR
T1  - Cerebral blood-flow changes evoked by two levels of painful heat stimulation: a positron emission tomography study in humans
A1  - Svensson,P.
A1  - Johannsen,P.
A1  - Jensen,T.S.
A1  - Arendt-Nielsen,L.
A1  - Nielsen,J.
A1  - Stodkilde-Jorgensen,H.
A1  - Gee,A.D.
A1  - Baarsgaard,Hansen S.
A1  - Gjedde,A.
Y1  - 1998///
N1  - UI - 0
SP  - 95
EP  - 107
JA  - Eur.J Pain
VL  - 2
IS  - 2
N2  - Positron emission tomography (PET) and accumulation of H(2)(15)O as a marker of neuronal activity were used to create maps of cerebral blood-flow changes evoked by painful heat stimulation in 10 subjects. Two levels of painful tonic and phasic heat stimuli were applied with use of a newly developed contact heat thermode on the volar surface of the dominant (right) arm. The subjects participated in two separate PET sessions. Maps reflecting low and high levels of painful tonic heat were obtained in the first session, and low and high levels of painful phasic heat in the second session. The subjects scored their peak pain intensity and unpleasantness on 10-cm visual analogue scales. For each subject, PET images were aligned to nuclear magnetic resonance (NMR) images and remapped into the standardized co-ordinate system of Talairach. After normalization of the PET volumes, subtraction images were formed voxel-by-voxel and converted to a t-statistic volume. The perceived pain intensity and unpleasantness were identical with painful tonic and phasic heat stimulation. Directed searches revealed significant blood-flow increases in the contralateral primary sensorimotor cortex (MI/SI), SII, insular cortex and cingulate cortex when the low tonic heat map was subtracted from the high. A similar, but not identical, pain-processing network was observed for the maps representing the subtraction of low and high phasic heat. In this subtraction, the blood-flow increases in MSI/SI did not reach statistical significance, and significant blood flow decreases were found in the contralateral middle temporal gyrus. Finally, the location of the activation site in the cingulate cortex was different from that observed during tonic heat pain. This study has provided more evidence for the existence of a common pain-processing network engaged during the perception of different levels of toxic and phasic heat pain. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain
AD  - Center for Sensory-Motor Interaction, Aalborg University, Denmark
UR  - PM:10700305
ER  - 

TY  - JOUR
T1  - Pain-related cerebral activation is altered by a distracting cognitive task
A1  - Petrovic,P.
A1  - Petersson,K.M.
A1  - Ghatan,P.H.
A1  - Stone-Elander,S.
A1  - Ingvar,M.
Y1  - 2000/03//
N1  - UI - 20159086
SP  - 19
EP  - 30
JF  - Pain
VL  - 85
IS  - 1-2
N2  - It has previously been suggested that the activity in sensory regions of the brain can be modulated by attentional mechanisms during parallel cognitive processing. To investigate whether such attention-related modulations are present in the processing of pain, the regional cerebral blood flow was measured using [(15)O]butanol and positron emission tomography in conditions involving both pain and parallel cognitive demands. The painful stimulus consisted of the standard cold pressor test and the cognitive task was a computerised perceptual maze test. The activations during the maze test reproduced findings in previous studies of the same cognitive task. The cold pressor test evoked significant activity in the contralateral S1, and bilaterally in the somatosensory association areas (including S2), the ACC and the mid-insula. The activity in the somatosensory association areas and periaqueductal gray/midbrain were significantly modified, i.e. relatively decreased, when the subjects also were performing the maze task. The altered activity was accompanied with significantly lower ratings of pain during the cognitive task. In contrast, lateral orbitofrontal regions showed a relative increase of activity during pain combined with the maze task as compared to only pain, which suggests the possibility of the involvement of frontal cortex in modulation of regions processing pain
AD  - Section of Clinical Neurophysiology, Department of Clinical Neuroscience, Karolinska Institute/Karolinska Hospital, 171 76, Stockholm, Sweden
UR  - PM:10692599
ER  - 

TY  - JOUR
T1  - Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study
A1  - Davis,K.D.
A1  - Taub,E.
A1  - Duffner,F.
A1  - Lozano,A.M.
A1  - Tasker,R.R.
A1  - Houle,S.
A1  - Dostrovsky,J.O.
Y1  - 2000/01//
N1  - UI - 20081830
SP  - 64
EP  - 69
JA  - J Neurosurg
VL  - 92
IS  - 1
N2  - OBJECT: Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS. METHODS: The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas. CONCLUSIONS: The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain
AD  - Department of Surgery, University of Toronto, Ontario, Canada. kdavis@playfair.utoronto.ca
UR  - PM:10616084
ER  - 

TY  - JOUR
T1  - Pain intensity processing within the human brain: a bilateral, distributed mechanism
A1  - Coghill,R.C.
A1  - Sang,C.N.
A1  - Maisog,J.M.
A1  - Iadarola,M.J.
Y1  - 1999/10//
N1  - UI - 99445756
SP  - 1934
EP  - 1943
JA  - J Neurophysiol.
VL  - 82
IS  - 4
N2  - Functional imaging studies of human subjects have identified a diverse assortment of brain areas that are engaged in the processing of pain. Although many of these brain areas are highly interconnected and are engaged in multiple processing roles, each area has been typically considered in isolation. Accordingly, little attention has been given to the global functional organization of brain mechanisms mediating pain processing. In the present investigation, we have combined positron emission tomography with psychophysical assessment of graded painful stimuli to better characterize the multiregional organization of supraspinal pain processing mechanisms and to identify a brain mechanism subserving the processing of pain intensity. Multiple regression analysis revealed statistically reliable relationships between perceived pain intensity and activation of a functionally diverse group of brain regions, including those important in sensation, motor control, affect, and attention. Pain intensity-related activation occurred bilaterally in the cerebellum, putamen, thalamus, insula, anterior cingulate cortex, and secondary somatosensory cortex, contralaterally in the primary somatosensory cortex and supplementary motor area, and ipsilaterally in the ventral premotor area. These results confirm the existence of a highly distributed, bilateral supraspinal mechanism engaged in the processing of pain intensity. The conservation of pain intensity information across multiple, functionally distinct brain areas contrasts sharply with traditional views that sensory-discriminative processing of pain is confined within the somatosensory cortex and can account for the preservation of conscious awareness of pain intensity after extensive cerebral cortical lesions
AD  - Pain and Neurosensory Mechanisms Branch, National Institutes of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA
UR  - PM:10515983
ER  - 

TY  - JOUR
T1  - Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans
A1  - Paulson,P.E.
A1  - Minoshima,S.
A1  - Morrow,T.J.
A1  - Casey,K.L.
Y1  - 1998/05//
N1  - UI - 98359666
SP  - 223
EP  - 229
JF  - Pain
VL  - 76
IS  - 1-2
N2  - The purpose of the present study was to determine whether gender differences exist in the forebrain cerebral activation patterns of the brain during pain perception. Accordingly, positron emission tomography (PET) with intravenous injection of H2(15)O was used to detect increases in regional cerebral blood flow (rCBF) in normal right-handed male and female subjects as they discriminated differences in the intensity of innocuous and noxious heat stimuli applied to the left forearm. Each subject was instructed in magnitude estimation based on a scale for which 0 indicated 'no heat sensation'; 7, 'just barely painful' and 10, 'just barely tolerable'. Thermal stimuli were 40 degrees C or 50 degrees C heat, applied with a thermode as repetitive 5-s contacts to the volar forearm. Both male and female subjects rated the 40 degrees C stimuli as warm but not painful and the 50 degrees C stimuli as painful but females rated the 50 degrees C stimuli as significantly more intense than did the males (P=0.0052). Both genders showed a bilateral activation of premotor cortex in addition to the activation of a number of contralateral structures, including the posterior insula, anterior cingulate cortex and the cerebellar vermis, during heat pain. However, females had significantly greater activation of the contralateral prefrontal cortex when compared to the males by direct image subtraction. Volume of interest comparison (t-statistic) also suggested greater activation of the contralateral insula and thalamus in the females (P < 0.05). These pain-related differences in brain activation may be attributed to gender, perceived pain intensity, or to both factors
AD  - Neurology Research Laboratories, University of Michigan, VA Medical Center, Ann Arbor 48105, USA
UR  - PM:9696477
ER  - 

TY  - JOUR
T1  - Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography
A1  - Derbyshire,S.W.
A1  - Jones,A.K.
Y1  - 1998/05//
N1  - UI - 98359654
SP  - 127
EP  - 135
JF  - Pain
VL  - 76
IS  - 1-2
N2  - We have previously demonstrated the localised positron emission tomographic cerebral correlates of the experience of painful phasic heat in the normal human brain. In this study we examine whether these responses are different using a continuous, tonic heat stimulus. The regional cerebral responses to non-painful and painful thermal stimuli in 12 male subjects were studied by monitoring serial measurements of regional cerebral blood flow (rCBF) with positron emission tomography (PET) using H2(15)O. Significantly increased rCBF responses to tonic noxious stimulation compared with non-noxious stimulation were observed bilaterally in the anterior cingulate (Brodmann's area (BA) 24) cortex. Contralateral responses were observed in the lentiform nucleus and posterior insula cortex and ipsilateral responses were observed in the thalamus, cerebellum, prefrontal (BA 10) cortex and anterior insula cortex. These findings demonstrate general agreement between the main areas of cerebral activation during both phasic and tonic pain
AD  - PET Facility, University of Pittsburgh Medical Center, PA 15213, USA
UR  - PM:9696465
ER  - 

TY  - JOUR
T1  - Experimental cranial pain elicited by capsaicin: a PET study
A1  - May,A.
A1  - Kaube,H.
A1  - Buchel,C.
A1  - Eichten,C.
A1  - Rijntjes,M.
A1  - Juptner,M.
A1  - Weiller,C.
A1  - Diener,H.C.
Y1  - 1998/01//
N1  - UI - 98173497
SP  - 61
EP  - 66
JF  - Pain
VL  - 74
IS  - 1
N2  - Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache
AD  - Department of Neurology, University of Essen, Germany. amay@ion.ucl.ac.uk
UR  - PM:9514561
ER  - 

TY  - JOUR
T1  - Reduced cortical responses to noxious heat in patients with rheumatoid arthritis
A1  - Jones,A.K.
A1  - Derbyshire,S.W.
Y1  - 1997/10//
N1  - UI - 98050765
SP  - 601
EP  - 607
JA  - Ann.Rheum.Dis.
VL  - 56
IS  - 10
N2  - OBJECTIVES: To test the hypothesis that patients with chronic inflammatory pain develop adaptive cortical responses to noxious stimulation characterised by reduced anterior cingulate responses. METHODS: Positron emission tomography was used to measure changes in regional cerebral blood flow (rCBF) in response to an acute experimental pain stimulus in six patients with rheumatoid arthritis (RA) in comparison to six age and sex matched controls. A standardised and reproducible non-painful and painful phasic heat stimulus was delivered by a thermal probe to the back of the right hand during six two minute periods during which time rCBF measurements were made. The effects of non-painful heat were subtracted from those of painful heat to weight the analysis towards the non-discriminatory or 'suffering' components of pain processing. Significance maps of pain processing were generated and compared in each group and contrasted with results obtained in a group of patients with atypical facial pain (AFP) that have been previously published. RESULTS: The RA patients showed remarkably damped cortical and subcortical responses to pain compared with the control group. Significant differences between the two groups were observed in the prefrontal (BA 10) and anterior cingulate (BA 24) and cingulofrontal transition cortical (BA 32) areas. The reduced anterior cingulate responses to standardised heat pain were compared with the increased cingulate responses seen in patients with psychogenically maintained pain (AFP) who had both lower pain tolerance and mood than the RA group. CONCLUSIONS: Major cortical adaptive responses to standardised noxious heat can be measured and contrasted in patients with different types of chronic pain. The different pattern of cingulate and frontal cortical responses in the patients with inflammatory and non-nociceptive pain suggest that different mechanisms are operating, possibly at a thalamocortical level. Implications for treatment strategies for chronic pain are discussed
AD  - Human Physiology and Pain Research Laboratory, University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford
UR  - PM:9389221
ER  - 

TY  - JOUR
T1  - Cerebral processing of acute skin and muscle pain in humans
A1  - Svensson,P.
A1  - Minoshima,S.
A1  - Beydoun,A.
A1  - Morrow,T.J.
A1  - Casey,K.L.
Y1  - 1997/07//
N1  - UI - 97384782
SP  - 450
EP  - 460
JA  - J Neurophysiol.
VL  - 78
IS  - 1
N2  - The human cerebral processing of noxious input from skin and muscle was compared with the use of positron emission tomography with intravenous H2(15)O to detect changes in regional cerebral blood flow (rCBF) as an indicator of neuronal activity. During each of eight scans, 11 normal subjects rated the intensity of stimuli delivered to the nondominant (left) forearm on a scale ranging from 0 to 100 with 70 as pain threshold. Cutaneous pain was produced with a high-energy CO2 laser stimulator. Muscle pain was elicited with high-intensity intramuscular electrical stimulation. The mean ratings of perceived intensity for innocuous and noxious stimulation were 32.6 +/- 4.5 (SE) and 78.4 +/- 1.7 for cutaneous stimulation and 15.4 +/- 4.2 and 73.5 +/- 1.4 for intramuscular stimulation. The pain intensity ratings and the differences between noxious and innocuous ratings were similar for cutaneous and intramuscular stimuli (P > 0.05). After stereotactic registration, statistical pixel-by-pixel summation (Z score) and volumes-of-interest (VOI) analyses of subtraction images were performed. Significant increases in rCBF to both noxious cutaneous and intramuscular stimulation were found in the contralateral secondary somatosensory cortex (SII) and inferior parietal lobule [Brodmann area (BA) 40]. Comparable levels of rCBF increase were found in the contralateral anterior insular cortex, thalamus, and ipsilateral cerebellum. Noxious cutaneous stimulation caused significant activation in the contralateral lateral prefrontal cortex (BA 10/46) and ipsilateral premotor cortex (BA 4/6). Noxious intramuscular stimulation evoked rCBF increases in the contralateral anterior cingulate cortex (BA 24) and subsignificant responses in the contralateral primary sensorimotor cortex (MI/SI) and lenticular nucleus. These activated cerebral structures may represent those recruited early in nociceptive processing because both forms of stimuli were near pain threshold. Correlation analyses showed a negative relationship between changes in rCBF for thalamus and MI/SI for cutaneous stimulation, and positive relationships between thalamus and anterior insula for both stimulus modalities. Direct statistical comparisons between innocuous cutaneous and intramuscular stimulation with the use of Z scores and VOI analyses showed no reliable differences between these two forms of noxious stimulation, indicating a substantial overlap in brain activation pattern. The comparison of noxious cutaneous and intramuscular stimulation indicated more activation in the premotor cortex, SII, and prefrontal cortex with cutaneous stimulation, but these differences did not reach statistical significance. The similar cerebral activation patterns suggest that the perceived differences between acute skin and muscle pain are mediated by differences in the intensity and temporospatial pattern of neuronal activity within similar sets of forebrain structures
AD  - Department of Prosthetic Dentistry and Stomatognathic Physiology, Orofacial Pain Clinic, Royal Dental College, University of Aarhus, Denmark
UR  - PM:9242293
ER  - 

TY  - JOUR
T1  - Functional localization of pain perception in the human brain studied by PET
A1  - Xu,X.
A1  - Fukuyama,H.
A1  - Yazawa,S.
A1  - Mima,T.
A1  - Hanakawa,T.
A1  - Magata,Y.
A1  - Kanda,M.
A1  - Fujiwara,N.
A1  - Shindo,K.
A1  - Nagamine,T.
A1  - Shibasaki,H.
Y1  - 1997/01/20/
N1  - UI - 97235324
SP  - 555
EP  - 559
JF  - Neuroreport
VL  - 8
IS  - 2
N2  - To elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula
AD  - Department of Brain Pathophysiology, Faculty of Medicine, Kyoto University, Japan
UR  - PM:9080447
ER  - 

TY  - JOUR
T1  - Functional imaging of an illusion of pain
A1  - Craig,A.D.
A1  - Reiman,E.M.
A1  - Evans,A.
A1  - Bushnell,M.C.
Y1  - 1996/11/21/
N1  - UI - 97078749
SP  - 258
EP  - 260
JF  - Nature
VL  - 384
IS  - 6606
N2  - Touching warm and cool bars that are spatially interlaced produces a painful burning sensation resembling that caused by intense, noxious cold. We demonstrated previously that this thermal grill illusion can be explained as an unmasking phenomenon that reveals the central inhibition of pain by thermosensory integration. In order to localize this unmasking in the human brain, we have used positron emission tomography (PET) to compare the cortical activation patterns evoked by the thermal grill and by cool, warm, noxious cold and noxious heat stimuli. The thermal grill illusion produces activation in the anterior cingulate cortex, whereas its component warm and cool stimuli do not. This area is also activated by noxious heat or cold. Thus, increased activity in the anterior cingulate cortex appears to be selectively associated with the perception of thermal pain. Disruption of thermosensory and pain integration may account for the central pain syndrome that can occur after stroke damage
AD  - Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013, USA. braig@mha.chw.edu
UR  - PM:8918874
ER  - 

TY  - JOUR
T1  - Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain
A1  - Casey,K.L.
A1  - Minoshima,S.
A1  - Morrow,T.J.
A1  - Koeppe,R.A.
Y1  - 1996/07//
SP  - 571
EP  - 581
JA  - J Neurophysiol.
VL  - 76
IS  - 1
N2  - 1. We wished to determine whether there are differences in the spatial pattern and intensity of synaptic activity within the conscious human forebrain when different forms and intensities of innocuous and noxious thermal stimuli are experienced. Accordingly, positron emission tomography (PET) with intravenous injection of H2(15)O was used to detect increases in regional cerebral blood flow (rCBF) in normal humans as they discriminated differences in the intensity of noxious and innocuous thermal stimulation applied to the nondominant (left) arm. After stereotactic registration, subtraction images were formed from each subject by subtracting counts of emissions obtained during lower-intensity stimulation from those obtained during stimulation at higher intensities. A statistical summation analysis (Z score) of individual voxels was performed. In addition, volumes of interest were chosen on the basis of a priori hypotheses and the results of previously published PET studies. In both types of analysis, statistical thresholds were established with corrections for multiple comparisons. 2. Twenty-seven subjects were divided into three groups of nine subjects each for the three phases of this investigation. For studies in which repetitive contact heat stimuli were used, each subject was instructed in magnitude estimation on the basis of a scale for which 0 indicated "no heat sensation," 7 "just barely painful," and 10 "just barely tolerable." For the study of pain elicited by immersion of the hand in cold water, subjects were instructed to use a scale in which 0 represented "no pain" and 10 represented just barely tolerable pain. 3. In the warm-discrimination study, two intensities of innocuous heat (36 and 43 degrees C) were applied with a thermode as repetitive 5-s contacts to the volar forearm for a total of approximately 100 s, 8 stimuli before and 12 during each scan. Each temperature was applied on alternate scans for a total of four scans per subject. Neither stimulus was rated painful. All subjects discriminated the 43 degrees C stimulus (average rating 5.90 +/- 1.43, mean +/- SD) from the 36 degrees C stimulus (1.96 +/- 1.08, mean +/- SD; t = 13.19, P < 0.0001). Significant increases in rCBF to the 43 degrees C stimuli were found in the contralateral ventral posterior thalamus, lenticular nucleus, medial prefrontal cortex (Brodmann's areas 10 and 32), and cerebellar vermis. 4. The procedure for discriminating between noxious and innocuous heat stimuli was identical to that used for warm discrimination except that the stimulation temperatures were 40 and 50 degrees C. All subjects rated the 50 degrees C stimuli as painful (average rating 8.9 +/- 0.9, mean +/- SD) and the 40 degrees C stimuli as warm, but not painful (2.1 +/- 1.0). Significant rCBF increases to 50 degrees C stimuli were found contralaterally in the thalamus, anterior cingulate cortex, premotor cortex, and secondary somatosensory (S2) and posterior insular cortices. Significant activity also appeared within the region of the contralateral anterior insula and lenticular nucleus. The ipsilateral premotor cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis, also showed significant rCBF increases. Cerebral blood flow (CBF) increases just below the threshold for statistical significance were seen in the contralateral sensorimotor cortex [primary motor cortex (M1)/primary somatosensory cortex (S1)]. 5. For discrimination between tonic innocuous cold and tonic cold pain, the left hand was immersed to the wrist, throughout each of six scans, in water kept at an average temperature of either 20.5 +/- 1.15 degrees C (mean +/- SD) or 6.02 +/- 1.18 degrees C (mean +/- SD) on alternate scans. All subjects rated the intensity of the stimuli on a scale in which 0 indicated no pain and 10 represented barely tolerable pain. Subjects rated the 20 degrees C water immersion as painless (average rating 0.18 +/- 0.48, mean +/- SD), but gave ratings indicating i
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109, USA
UR  - PM:8836245
ER  - 

TY  - JOUR
T1  - Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging
A1  - Vogt,B.A.
A1  - Derbyshire,S.
A1  - Jones,A.K.
Y1  - 1996/07//
N1  - UI - 96325589
SP  - 1461
EP  - 1473
JA  - Eur.J Neurosci.
VL  - 8
IS  - 7
N2  - Neurosurgical and positron emission tomography (PET) human studies and animal electrophysiological studies show that part of the anterior cingulate cortex (ACC) is nociceptive. Since the contribution of the ACC to pain processing is poorly understood, this study employed PET and magnetic resonance (MR) image co-registration in grouped and individual cases to locate regions of altered relative regional cerebral blood flow (rCBF). Seven right-handed, neurologically intact males were subjects; each received neuropsychological and pain threshold testing. Subjects were scanned during infusion of H2[15O]: four randomized scans during innocuous heat stimulation to the back of the left hand and four scans during noxious but bearable heat to the same place. The averaged rCBF values during innocuous stimuli were subtracted from those during noxious stimuli and statistical parametric maps (SPMs) for the group were computed to identify regions of altered relative rCBF. Finally, single-subject PET images of elevated and reduced rCBF were co-registered with MR images and projected onto reconstructions of the medial surface of the hemisphere. The SPM analysis of the group showed one site with elevated rCBF in the midcingulate cortex and one in the perigenual cortex predominantly contralateral to the side of stimulation. There were bilateral sites of reduced rCBF in the cingulofrontal transitional cortex and in the posterior cingulate cortex (PCC). Co-registered PET and MR images for individuals showed that only one case had a single, large region of elevated rCBF, while the others had a number of smaller regions. Six cases had at least one significant elevation of rCBF in the right hemisphere that primarily involved area 24b'; five of these cases also had an elevation in area 32', while the seventh case had elevated rCBF in these areas in the left hemisphere. The rostral site of elevated rCBF in the group was at the border of areas 24/24' and areas 32/32' although most cases had a site of elevation more rostral in the perigenual cingulate cortex. The ACC site of reduced rCBF was in areas 8 and 32 and that in the PCC included much of areas 29/30 in the callosal sulcus, areas 23b and 31 on the cingulate gyral surface and parietal area 7m. The localization of relative rCBF changes suggests different roles for the cingulate cortex in pain processing: (i) elevated rCBF in area 24' may be involved in response selection like nocifensive reflex inhibition; (ii) activation of the perigenual cortex may participate in affective responses to noxious stimuli like suffering associated with pain; and (iii) reduced rCBF in areas 8 and 32 may enhance pain perception in the perigenual cortex, while that in the PCC may disengage visually guided processes
AD  - Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA
UR  - PM:8758953
ER  - 

TY  - JOUR
T1  - Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography
A1  - Derbyshire,S.W.
A1  - Jones,A.K.
A1  - Devani,P.
A1  - Friston,K.J.
A1  - Feinmann,C.
A1  - Harris,M.
A1  - Pearce,S.
A1  - Watson,J.D.
A1  - Frackowiak,R.S.
Y1  - 1994/10//
N1  - UI - 95016765
SP  - 1166
EP  - 1172
JF  - Journal of Neurology, Neurosurgery, and Psychiatry
JA  - J Neurol Neurosurg Psychiatry
VL  - 57
IS  - 10
N2  - The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:7931375
ER  - 

TY  - JOUR
T1  - Distributed processing of pain and vibration by the human brain
A1  - Coghill,R.C.
A1  - Talbot,J.D.
A1  - Evans,A.C.
A1  - Meyer,E.
A1  - Gjedde,A.
A1  - Bushnell,M.C.
A1  - Duncan,G.H.
Y1  - 1994/07//
N1  - UI - 94300330
SP  - 4095
EP  - 4108
JA  - J Neurosci.
VL  - 14
IS  - 7
N2  - Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions
AD  - Centre de Recherche en Sciences Neurologiques, Universite de Montreal, Quebec, Canada
UR  - PM:8027764
ER  - 

TY  - JOUR
T1  - Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli
A1  - Casey,K.L.
A1  - Minoshima,S.
A1  - Berger,K.L.
A1  - Koeppe,R.A.
A1  - Morrow,T.J.
A1  - Frey,K.A.
Y1  - 1994/02//
N1  - UI - 94231248
SP  - 802
EP  - 807
JA  - J Neurophysiol.
VL  - 71
IS  - 2
N2  - 1. To identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans, we performed H2 15O positron emission tomographic (PET) analyses of cerebral blood flow (CBF) on nine normal volunteers while they received repetitive noxious (50 degrees C) and innocuous (40 degrees C) 5 s heat pulses to the forearm (average resting temperature of 31.8 degrees C). Each subject rated the subjective intensity of each stimulation series according to a magnitude estimation procedure in which 0 = no heat sensation, 7 = barely painful, and 10 = barely tolerable. 2. Three scans were performed at each temperature. Mean CBF images were created for each experimental condition and oriented onto standardized stereotaxic coordinates. Subtraction images were created between conditions for each subject and averaged across subjects. Volumes of interest (VOI) were chosen, based on a priori hypotheses and the results of previously published PET studies. In addition, a separate statistical summation analysis of individual voxels was performed. Statistical thresholds were established with corrections for multiple comparisons. 3. Significant CBF increases to 50 degrees C stimuli were found in the contralateral thalamus, cingulate cortex, S2 and S1 cortex, and insula. The ipsilateral S2 cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis also showed significant CBF increases. All subjects rated the 50 degrees C stimuli as painful (average subjective rating = 8.9 +/- 0.9 SD) and the 40 degrees C stimuli as warm, but not painful (average subjective rating = 2.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)
AD  - Department of Neurology, University of Michigan, Ann Arbor 48109
UR  - PM:8176441
ER  - 

TY  - JOUR
T1  - Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy
A1  - Di Piero,V.
A1  - Jones,A.K.
A1  - Iannotti,F.
A1  - Powell,M.
A1  - Perani,D.
A1  - Lenzi,G.L.
A1  - Frackowiak,R.S.
Y1  - 1991/07//
N1  - UI - 91375742
SP  - 9
EP  - 12
JF  - Pain
VL  - 46
IS  - 1
N2  - We have studied 5 patients with unilateral, severe chronic pain due to cancer before and after percutaneous, ventrolateral cervical cordotomy to investigate the central effects of the procedure. The aim was to identify the functional anatomical correlates of abolishing unilateral nociceptive input to the brain. Patients were investigated by positron emission tomography using C15O2 to evaluate cerebral blood flow. Comparisons were made between the patients with unilateral pain before cordotomy and normal volunteers. These demonstrated significantly less blood flow in 3 out of 4 of the individual quadrants of the hemithalamus contralateral to the side of pain (P less than 0.01-0.05). These differences were abolished by cordotomy. Comparison of the patients before and after cordotomy showed a significant decrease in blood flow in the dorsal anterior quadrant of the thalamus contralateral to the side of pain (P less than 0.05) which was normalised after cordotomy. There were no significant changes in the prefrontal or primary somatosensory cortex. We conclude that chronic pain results in a decrease of synaptic activity at thalamic level either from decreased activity in neurones projecting to that region and/or attenuated local neuronal firing. We have demonstrated no secondary remote effects in cortex, indicating the importance of subcortical mechanisms in central responses to chronic pain
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, U.K
UR  - PM:1716753
ER  - 

TY  - JOUR
T1  - Cortical and subcortical localization of response to pain in man using positron emission tomography
A1  - Jones,A.K.
A1  - Brown,W.D.
A1  - Friston,K.J.
A1  - Qi,L.Y.
A1  - Frackowiak,R.S.
Y1  - 1991/04/22/
N1  - UI - 91305357
SP  - 39
EP  - 44
JA  - Proc.R.Soc.Lond B Biol.Sci.
VL  - 244
IS  - 1309
N2  - A quantitative study of the regional cerebral responses to non-painful and painful thermal stimuli in six normal volunteers has been done by monitoring serial measurements of regional blood flow measured by positron emission tomography (PET). In comparison to a baseline of warm stimulation no statistically significant changes in blood flow were seen in relation to increasing non-painful heat. However, highly significant increases in blood flow were seen in response to painful heat in comparison to non-painful heat. These changes were in the contralateral cingulate cortex, thalamus and lenticular nucleus. These findings are discussed in relation to previous physiological observations of responses to nociceptive stimuli in man and primates
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, U.K
UR  - PM:1677194
ER  - 

TY  - JOUR
T1  - 15O Radioactivity clearance is faster after intracarotid bolus injection of 15O-labeled oxyhemoglobin than after 15O-water injection
A1  - Seki,C.
A1  - Kershaw,J.
A1  - Toussaint,P.J.
A1  - Kashikura,K.
A1  - Matsuura,T.
A1  - Fujita,H.
A1  - Kanno,I.
Y1  - 2003/07//
N1  - UI - 22726865
SP  - 838
EP  - 844
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 7
N2  - The authors tested the hypothesis that the oxygen content of brain tissue is negligible by injecting an intracarotid bolus of 15O-labeled tracer into rats. Under the hypothesis, the clearance rates of 15O radioactivity from the brain after injections of both 15O-labeled water (H(2)15O) and 15O-labeled oxyhemoglobin (HbO15O) should be identical. However, the logarithmic slope of the 15O radioactivity curve after HbO15O injection (0.494 +/- 0.071 min-1) was steeper than that after H(2)15O injection (0.406 +/- 0.038 min-1) (P<0.001, n = 13), where the time range used in the comparison was between 60 and 120 seconds after the injection. A possible interpretation of this result is that nonmetabolized O15O may dwell in the brain tissue for a finite period of time before it is eventually metabolized or returned to the blood stream unaltered. These findings contradict assumptions made by models currently used to measure cerebral oxygen metabolism
AD  - Akita Laboratory, Japan Science and Technology Corporation, Akita, Japan
UR  - PM:12843787
ER  - 

TY  - JOUR
T1  - Increase in Prefrontal Cortex Serotonin(2A) Receptors Following Estrogen Treatment in Postmenopausal Women
A1  - Kugaya,A.
A1  - Epperson,C.N.
A1  - Zoghbi,S.
A1  - van Dyck,C.H.
A1  - Hou,Y.
A1  - Fujita,M.
A1  - Staley,J.K.
A1  - Garg,P.K.
A1  - Seibyl,J.P.
A1  - Innis,R.B.
Y1  - 2003/08//
N1  - UI - 22781583
SP  - 1522
EP  - 1524
JA  - Am J Psychiatry
VL  - 160
IS  - 8
N2  - OBJECTIVE: This study investigated the effect of estrogen on brain serotonin 2A (5-HT(2A)) receptors in postmenopausal women and whether there was any correlation of receptor changes with cognition and mood. METHOD: Ten postmenopausal subjects underwent positron emission tomography measurements of 5-HT(2A) receptor binding with [(18)F]deuteroaltanserin before and after estrogen replacement therapy. RESULTS: 5-HT(2A) receptor binding was significantly increased after estrogen replacement therapy in the right prefrontal cortex (right precentral gyrus [Brodmann's area 9], inferior frontal gyrus [Brodmann's area 47], medial frontal gyrus [Brodmann's area 6, 10] and the anterior cingulate cortex [Brodmann's area 32]). In the inferior frontal gyrus [Brodmann's area 44]), receptor up-regulation was correlated with change in plasma estradiol. Verbal fluency and Trail Making Test performance, but not mood, were significantly improved by estrogen without correlation with receptor changes. CONCLUSIONS: Estrogen increases 5-HT(2A) receptor binding in human prefrontal regions
UR  - PM:12900319
ER  - 

TY  - JOUR
T1  - 11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease
A1  - Ono,M.
A1  - Wilson,A.
A1  - Nobrega,J.
A1  - Westaway,D.
A1  - Verhoeff,P.
A1  - Zhuang,Z.P.
A1  - Kung,M.P.
A1  - Kung,H.F.
Y1  - 2003/08//
N1  - UI - 22782598
SP  - 565
EP  - 571
JA  - Nucl Med Biol.
VL  - 30
IS  - 6
N2  - A series of stilbene derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of the stilbenes were successfully achieved by a simple Wadsworth-Emmons reaction between diethyl (4-nitrobenzyl)phosphonate and 4-methoxybenzaldehyde. 4-N,N-dimethylamino-4'-methyoxy and the corresponding 4-N-monomethylamino-, 4'-hydroxy stilbenes showed good binding affinities towards Abeta aggregates in vitro (K(i) < 10 nM). The (11)C labeled 4-N-methylamino-4'-hydroxystilbene, [(11)C]4, was prepared by (11)C methylation of 4-amino-4'-hydroxystilbene. The [(11)C]4 displayed a moderate lipophilicity (log P = 2.36), and showed a very good brain penetration and washout from normal rat brain after an iv injection. In vitro autoradiography of transgenic AD mouse brain sections showed a high specific labeling of beta-amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [(11)C]4, N-[(11)C]methylamino-4'-hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping Abeta plaques in the brain of patients with Alzheimer's disease
AD  - Department of Radiology, University of Pennsylvania, 19104, Philadelphia, PA, USA
UR  - PM:12900282
ER  - 

TY  - JOUR
T1  - Intratumoral histologic heterogeneity of gliomas. A quantitative study
A1  - Paulus,W.
A1  - Peiffer,J.
Y1  - 1989/07/15/
N1  - UI - 89287976
SP  - 442
EP  - 447
JF  - Cancer
VL  - 64
IS  - 2
N2  - Quantitative data for intratumoral histologic heterogeneity were obtained by investigating ten small and ten large punched samples from 50 unembedded supratentorial gliomas. The 1000 samples were diagnosed according to the World Health Organization (WHO) classification and six histopathologic features associated with malignancy were evaluated (cellular density, nuclear pleomorphism, necroses, histologic architecture, vessels, and mitoses), each with defined gradations. The slides were read independently by two observers. The initially high interobserver variability (grade, 22.2%; type, 10.3%; and tumor presence/absence, 7.1%) was for the most part due to intermediate grades and types and was reduced to 1.7% after mutual review. Small samples showed lower mean grade than large samples and more often absence of tumor (7.6% versus 2.4%). Of all gliomas, 48% showed differently typed samples, 82% differently graded samples, and 62% benign and malignant grades. Intratumoral heterogeneity was higher for the necroses than for the other histopathologic features. Our results underscore the importance of extensive tissue sampling
AD  - Institute of Brain Research, University of Tuebingen, Federal Republic of Germany
UR  - PM:2736491
ER  - 

TY  - JOUR
T1  - PET quantitation: blessing and curse
A1  - Di Chiro,G.
A1  - Brooks,R.A.
Y1  - 1988/09//
N1  - UI - 88316429
SP  - 1603
EP  - 1604
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 29
IS  - 9
UR  - PM:3261788
ER  - 

TY  - JOUR
T1  - Measurement of blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume in human brain tumours and surrounding oedematous tissue
A1  - Lammertsma,A.A.
A1  - Wise,R.J.
A1  - Cox,T.C.
A1  - Thomas,D.G.
A1  - Jones,T.
Y1  - 1985/08//
N1  - UI - 87050528
SP  - 725
EP  - 734
JA  - Br.J Radiol.
VL  - 58
IS  - 692
N2  - The blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume were measured in brain tumours and the surrounding cerebral tissues. A total of 21 patients were studied. These included 10 primary tumours, eight secondary and three with unknown histology. Measurements were performed using the oxygen-15 steady state inhalation technique and positron emission tomography. Within the tumours no relation between blood flow, oxygen utilisation and blood volume was found. In all tumours oxygen supply was in excess of the oxygen demand of the tissues as reflected in oxygen extraction ratios that were lower than those of normal brain tissue. No indication of local ischaemia in peritumour oedema was found
UR  - PM:3879853
ER  - 

TY  - JOUR
T1  - Biodistribution, radiation dose estimates, and in vivo pgp modulation studies of (18)f-Paclitaxel in nonhuman primates
A1  - Kurdziel,K.A.
A1  - Kiesewetter,D.O.
A1  - Carson,R.E.
A1  - Eckelman,W.C.
A1  - Herscovitch,P.
Y1  - 2003/08//
N1  - UI - 22784369
SP  - 1330
EP  - 1339
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 8
N2  - Multidrug resistance (MDR) associated with increased expression and function of the P-glycoprotein (Pgp) efflux pump often causes chemotherapeutic failure in cancer. To provide insight into both the dynamics of the pump and the effects of MDR, we radiolabeled paclitaxel, a substrate for the Pgp pump, with (18)F to study MDR in vivo with PET. We obtained biodistribution and radiation dose estimates for (18)F-paclitaxel (FPAC) in monkeys and studied the effects of a Pgp blocker (XR9576, tariquidar) on FPAC kinetics. METHODS: Paired baseline and Pgp modulation (2 mg/kg XR9576) 4-h whole-body dynamic PET scans were obtained in 3 rhesus monkeys after injection of FPAC. Measured residence times were extrapolated to humans and radiation dose estimates were obtained using MIRDOSE3.1. The postmodulator area under the time-activity curves (AUCs) and Logan plot slopes, a measure of tracer distribution volume (equilibrium tissue-to-plasma ratio) that is inversely proportional to tracer efflux, were compared with baseline values to determine changes in FPAC distribution. RESULTS: Cumulative activities of the organs sampled accounted for 80% of the injected dose. The critical organ is gallbladder wall (0.19 mGy/MBq [0.69 rad/mCi]), followed by liver (0.14 mGy/MBq [0.52 rad/mCi]); the effective dose is 0.022 mSv/MBq (0.083 rem/mCi). XR9576 preinfusion changed the Logan plot slope for liver by +104% (P = 0.02), lung by +87% (P = 0.11), and kidney by -14% (P = 0.08). Changes in the mean AUC (normalized to the plasma AUC) were +54% (P = 0.08), +97% (P = 0.04), and -12% (P = 0.02), respectively, for liver, lung, and kidney. No significant difference was found in the metabolite-corrected plasma AUC (normalized to the injected dose) between the baseline and XR9576 modulator studies (P = 0.69). CONCLUSION: Under Radioactive Drug Research Committee guidelines, 266 MBq (7.2 mCi) FPAC can be administered to humans up to 3 times a year. The increase in FPAC accumulation in liver and lung after XR9576 is consistent with Pgp inhibition and demonstrates the potential of FPAC to evaluate MDR
AD  - PET Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland
UR  - PM:12902425
ER  - 

TY  - JOUR
T1  - Targeting of transferrin receptors in nude mice bearing A431 and LS174T xenografts with [18F]holo-transferrin: permeability and receptor dependence
A1  - Aloj,L.
A1  - Jogoda,E.
A1  - Lang,L.
A1  - Caraco,C.
A1  - Neumann,R.D.
A1  - Sung,C.
A1  - Eckelman,W.C.
Y1  - 1999/09//
N1  - UI - 99420127
SP  - 1547
EP  - 1555
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 40
IS  - 9
N2  - The goal of this study was to investigate whether 18F-labeled transferrin (Tf), which has a molecular weight (Mr) of approximately 79,000, binds to Tf receptor sites in tumors in a specific manner within the time frame commensurate with the half-life of 18F (109.7 min). We have previously shown that [18F]holo-Tf ([18F]Tf) maintains all properties of native Tf in vitro and that it can specifically target liver Tf receptor sites in vivo. METHODS: The distribution of [18F]Tf, using [18F]albumin (Alb) or [14C]Alb as a control, was studied over a 6-h period in nude mice bearing LS174T and A431 xenografts of a high- and low-permeability tumor, respectively. RESULTS: Measurements of Tf receptor concentration in the tumor extracts suggest similar binding capacities. In vivo, liver uptake values were higher for [18F]Tf than for both [18F]Alb and [14C]Alb throughout the study, indicating specific binding. In contrast, tumor Tf uptake values remained below those of the Alb tracers, and tumor-to-blood ratios of [18F]Tf in each xenograft increased in parallel with those of the Alb tracers. The permeabilities of [14C]Alb and [18F]Tf in LS174T were calculated to be 1.29+/-0.49 and 1.03+/-0.38 microL/min/g (mean +/- SD), respectively, whereas the permeabilities of the two tracers in A431 were 0.79+/-0.24 and 0.44+/-0.04 microL/min/g. Pharmacokinetic modeling of the data using these permeabilities and the high plasma and extracellular concentrations of endogenous Tf showed that the observed uptake values in the two xenografts are consistent with a non-receptor-mediated distribution. In the liver, the absence of permeability barriers yields specific [18F]Tf binding to receptors compared with the [14C]Alb control, within 5 min after injection. CONCLUSION: Receptor-mediated accumulation of [18F]Tf in tumor xenografts is impaired by rate-determining permeability and competition from endogenous Tf and is not achieved in a time frame of 6 h
AD  - Nuclear Medicine Department, Clinical Center, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA
UR  - PM:10492378
ER  - 

TY  - JOUR
T1  - Navigating the paraneoplastic neurological syndromes
A1  - Giannopoulou,C.
Y1  - 2003/03//
N1  - UI - 22604261
SP  - 333
EP  - 338
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 3
UR  - PM:12722733
ER  - 

TY  - JOUR
T1  - Logarithmic estimation of disease progression and preclinical period duration with 18F-DOPA positron emission tomography in Parkinson's disease
A1  - Hilker,R.
A1  - Schweitzer,K.
A1  - Ghaemi,M.
A1  - Weisenbach,S.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 2003///
SP  - SC202
JF  - European Journal of Neurology
JA  - Eur J Neurol
VL  - 10 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Imaging in epilepsy
A1  - Theodore,W.H.
Y1  - 2002///
SP  - 1
EP  - 9
JF  - Curr Science
VL  - 82
ER  - 

TY  - JOUR
T1  - Epilepsy and surgical mapping
A1  - Richardson,M.P.
Y1  - 2003///
N1  - UI - 22583317
SP  - 179
EP  - 192
JA  - Br.Med Bull.
VL  - 65
N2  - Drug treatment resistant epilepsy is an important public health problem. Patients with epilepsy of focal origin may have an excellent outcome following surgery that removes the source of seizures. Identification of the precise cortical region producing seizures is crucial to a good outcome; additionally, identification of eloquent cortical areas near the region to be resected is essential to prevent postoperative neurological deficit. A wide range of imaging techniques is valuable for imaging the epileptogenic zone, including high-resolution T1 MRI, T2 signal quantitation, MR spectroscopy, diffusion imaging, PET, SPECT and simultaneous EEG-fMRI. Eloquent cortex has in the past been mapped using highly invasive techniques; fMRI of motor and cognitive tasks holds great promise for future non-invasive mapping strategies
AD  - Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, UK
UR  - PM:12697625
ER  - 

TY  - JOUR
T1  - Neuropharmacological imaging in epilepsy with PET and SPECT
A1  - Henry,T.R.
A1  - Pennell,P.B.
Y1  - 1998/09//
N1  - UI - 99012460
SP  - 199
EP  - 210
JA  - Q.J Nucl Med
VL  - 42
IS  - 3
N2  - Functional neuroimaging with positron and single photon emitter-labeling has added considerably to the understanding of epileptic seizure activity and of the postictal and interictal cerebral dysfunctions that accompany many epilepsies. Some of these functional alterations cannot be studied in humans by any other technique, and in other instances the information is complementary to that provided by other techniques, some of which are invasive or even require tissue destruction. Available radiotracer imaging techniques have yet to be fully applied to several important epileptic syndromes (including the Lennox-Gastaut syndrome and other secondary generalized epilepsies), to physiological aspects of the natural history of temporal lobe epilepsy or any other commonly occurring epilepsy, and to the assessment of mechanisms of action and adverse effects of antiepileptic drugs and other epilepsy therapies. New radiotracers should be developed to permit study of specific excitatory amino acid receptors and other receptor sites that are known to be relevant to the development of epilepsy, to the onset of individual seizures, and to interictal dysfunctions
AD  - Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
UR  - PM:9796368
ER  - 

TY  - JOUR
T1  - In vivo hippocampal glucose metabolism in mesial temporal lobe epilepsy
A1  - Knowlton,R.C.
A1  - Laxer,K.D.
A1  - Klein,G.
A1  - Sawrie,S.
A1  - Ende,G.
A1  - Hawkins,R.A.
A1  - Aassar,O.S.
A1  - Soohoo,K.
A1  - Wong,S.
A1  - Barbaro,N.
Y1  - 2001/10/09/
N1  - UI - 21475986
SP  - 1184
EP  - 1190
JF  - Neurology
VL  - 57
IS  - 7
N2  - BACKGROUND: The appearance of decreased 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake in the mesial temporal region in temporal lobe epilepsy may simply reflect loss of gray matter due to hippocampal atrophy. Increased partial volume effects due to atrophic hippocampi may further increase appearance of hypometabolism. METHODS: The authors used a combination of MRI-PET coregistration, with MRI-based gray matter segmentation, and partial volume correction to improve the examination of hippocampal specific glucose uptake in FDG PET. The goal was to determine 1) if relative mesial temporal hypometabolism is an artifact of gray matter (hippocampal) atrophy, 2) whether hippocampal metabolism correlates with atrophy evaluated on MRI, and 3) if MRI-based partial volume correction influences measurement of hippocampal metabolic-volume relationships, including epilepsy lateralization. RESULTS: Findings showed that ipsilateral hippocampi of mesial temporal lobe epilepsy (MTLE) are relatively hypometabolic per unit of gray matter volume, and that hippocampal metabolism directly correlates with hippocampal volume. Specifically, partial volume corrected hippocampal metabolism correlated strongly (r = 0.613, p < 0.001) with hippocampal volume. Without partial volume correction, a weaker, but still significant, correlation was present (r = 0.482, p < 0.001). Degree of asymmetry was consistently greater and provided higher sensitivity of lateralization with partial volume vs non-partial volume corrected metabolic measurements. CONCLUSIONS: Although, decreased metabolism may occur in the absence of neuronal cell loss, hippocampal atrophy and presumed degree of neuronal cell loss appears to be a primary factor involved in the cause of decreased metabolism in epileptogenic hippocampi. Partial volume correction is recommended for optimal interpretation of hippocampal structure and function relationships
AD  - Department of Neurology, University of Alabama at Birmingham, 35294, USA. knowlton@uab.edu
UR  - PM:11591833
ER  - 

TY  - JOUR
T1  - Planned ictal FDG PET imaging for localization of extratemporal epileptic foci
A1  - Meltzer,C.C.
A1  - Adelson,P.D.
A1  - Brenner,R.P.
A1  - Crumrine,P.K.
A1  - Van Cott,A.
A1  - Schiff,D.P.
A1  - Townsend,D.W.
A1  - Scheuer,M.L.
Y1  - 2000/02//
N1  - UI - 20152975
SP  - 193
EP  - 200
JF  - Epilepsia
VL  - 41
IS  - 2
N2  - PURPOSE: This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro-2-deoxy-glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratemporal origin. METHODS: Ictal PET imaging was performed in four patients (two men and two women, ages 28-61) with continuous or very frequent (every 3-15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single-photon emission tomography (SPECT) imaging. RESULTS: Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroencephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case. CONCLUSIONS: We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures
AD  - Department of Radiology, University of Pittsburgh, Pennsylvania, USA. meltzer@radserv.arad.upmc.edu
UR  - PM:10691116
ER  - 

TY  - JOUR
T1  - In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis
A1  - Koepp,M.J.
A1  - Hand,K.S.
A1  - Labbe,C.
A1  - Richardson,M.P.
A1  - Van Paesschen,W.
A1  - Baird,V.H.
A1  - Cunningham,V.J.
A1  - Bowery,N.G.
A1  - Brooks,D.J.
A1  - Duncan,J.S.
Y1  - 1998/05//
N1  - UI - 98244755
SP  - 618
EP  - 626
JA  - Ann.Neurol
VL  - 43
IS  - 5
N2  - By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect
AD  - MRC Cyclotron Unit, Hammersmith Hospital, London, UK
UR  - PM:9585356
ER  - 

TY  - JOUR
T1  - Central benzodiazepine receptor autoradiography in hippocampal sclerosis
A1  - Hand,K.S.
A1  - Baird,V.H.
A1  - Van Paesschen,W.
A1  - Koepp,M.J.
A1  - Revesz,T.
A1  - Thom,M.
A1  - Harkness,W.F.
A1  - Duncan,J.S.
A1  - Bowery,N.G.
Y1  - 1997/09//
N1  - UI - 97459172
SP  - 358
EP  - 364
JA  - Br.J Pharmacol.
VL  - 122
IS  - 2
N2  - 1. The gamma-aminobutyric acid (GABA)A/central benzodiazepine receptor (cBZR) complex is a major inhibitory receptor in the vertebrate CNS. Binding of [11C]-flumazenil to this complex in vivo is reduced in hippocampal sclerosis (HS). It has been uncertain whether reduced cBZR binding is entirely due to neuronal loss in HS. 2. The objective of this study was to characterize abnormalities of the cBZR in HS with a correlative autoradiographic and quantitative neuropathological study. 3. Saturation autoradiographic studies were performed with [3H]-flumazenil to investigate relationships between neuronal density and receptor availability (Bmax) and affinity (Kd) in HS. Hippocampal tissue was obtained at surgery from 8 patients with intractable temporal lobe epilepsy (TLE) due to HS and autopsies of 6 neurologically normal controls. Neuronal densities were obtained by means of a 3-D counting method. 4. Bmax values for [3H]-flumazenil binding in the subiculum, CA1, CA2, CA3, hilus and dentate gyrus were all found to be significantly reduced in HS compared with controls and significant increases in affinity were observed in the subiculum, hilus and dentate gyrus. In HS, cBZR density in the CA1 region was significantly reduced (P < 0.05) to a greater extent than could be attributable to neurone loss. In other regions, Bmax was reduced in parallel with neuronal density. 5. In HS, there is a loss of cBZR in CA1 over and above loss of neurones. This finding and increases in affinity for flumazenil in subiculum, hilus and dentate gyrus imply a functional abnormality of the GABAA/cBZR complex that may have a role in the pathophysiology of epileptogenicity in HS
AD  - Department of Pharmacology, School of Pharmacy, London
UR  - PM:9313947
ER  - 

TY  - JOUR
T1  - Postsurgical outcome of patients with uncontrolled complex partial seizures and temporal lobe hypometabolism on 18FDG-positron emission tomography
A1  - Delbeke,D.
A1  - Lawrence,S.K.
A1  - Abou-Khalil,B.W.
A1  - Blumenkopf,B.
A1  - Kessler,R.M.
Y1  - 1996/05//
N1  - UI - 96315705
SP  - 261
EP  - 266
JA  - Invest Radiol.
VL  - 31
IS  - 5
N2  - RATIONAL AND OBJECTIVE. The purpose of this study is to evaluate the relation between a focus of temporal lobe hypometabolism, including comparison between mesial and lateral asymmetry on fluorine-18-labeled-deoxyglucose-positron emission tomography (18FDG-PET) and surgical outcome in patients with uncontrolled partial seizures. METHODS. Case histories, electroencephalogram (EEG) findings, radiographic findings, and surgical outcome (36 +/- 11 months of follow-up) were reviewed in 38 consecutive patients who had a interictal 18FDG-PET scan and subsequent temporal resection. RESULTS. Among the 36 patients who had a temporal lobe focus of hypometabolism (more than 15% asymmetry to contralateral side), 61% (22 of 36) became seizure-free, 33% (12 of 36) markedly improved and 6% (2 of 36) did not improve. The focus of hypometabolism on PET was in agreement with the epileptic focus on the noninvasive EEG in 30 of 36 patients and in 19 of the 22 patients who underwent an invasive EEG. The asymmetry index for the mesial temporal lobe was significantly higher in the group of patients who became seizure-free compared with the other patients. CONCLUSION. This study confirms that a focus of interictal temporal hypometabolism on PET is associated with marked improvement of seizure control after surgery in 94% (34 of 36) of the patients. Hypometabolism in the mesial temporal lobe appears to be associated with a seizure-free outcome
AD  - Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
UR  - PM:8724123
ER  - 

TY  - JOUR
T1  - The effect of carbamazepine on cerebral glucose metabolism
A1  - Theodore,W.H.
A1  - Bromfield,E.
A1  - Onorati,L.
Y1  - 1989/05//
N1  - UI - 89372746
SP  - 516
EP  - 520
JA  - Ann.Neurol
VL  - 25
IS  - 5
N2  - We used positron emission tomography with 18F-2-deoxy-D-glucose to study the effect of carbamazepine on local cerebral metabolic rate for glucose (lCMRGlc) in 9 patients with complex partial seizures. Twenty regions of interest were evaluated. Seven control patients had serial scans without a drug change. Metabolic rates were significantly (p less than 0.05) lower in patients on carbamazepine in 6 of 20 regions of interest (3 left cerebral hemisphere, 3 right). Mean lCMRGlc was 7.4 +/- 2.0 mg/min/100 in patients on carbamazepine and 8.8 +/- 2.5 in patients off carbamazepine (p less than 0.00005; cutoff level for 180 comparisons: 0.00027). The mean (+/- SEM) difference in lCMRGlc between scans was 12 +/- 2%. No significant changes in lCMRGlc on serial scans were detected in any of the 20 regions for the control group. The mean (+/- SEM) variation for control regions of interest was 1 +/- 1%. This study showed that carbamazepine depresses cerebral glucose metabolism as much as phenytoin does, but much less than phenobarbital does. The difference in effect on lCMRGlc may be related to drug mechanisms of action, as well as to effects on memory, learning, mood, and behavior
AD  - Clinical Epilepsy Section, National Institutes of Health, Bethesda, MD 20892
UR  - PM:2774494
ER  - 

TY  - JOUR
T1  - Effect of valproate on cerebral metabolism and blood flow: an 18F-2-deoxyglucose and 15O water positron emission tomography study
A1  - Gaillard,W.D.
A1  - Zeffiro,T.
A1  - Fazilat,S.
A1  - DeCarli,C.
A1  - Theodore,W.H.
Y1  - 1996/06//
N1  - UI - 96237812
SP  - 515
EP  - 521
JF  - Epilepsia
VL  - 37
IS  - 6
N2  - We compared the effect of valproate (VPA) on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF), measured with 18F-2-deoxyglucose (18FDG) and 15O water positron emission tomography (PET), in 10 normal volunteers. Mean VPA dose was 17.7 mg/kg, and mean VPA level was 82.1 mg/L (+/-16.5) for 4 weeks. VPA reduced global CMRGlc by 9.4% (9.60 +/- 0.76 vs. 8.59 +/- 1.02 mg Glc/min/100 g, p < 0.05) and regionally in all anatomic areas (p < 0.05 for 11 of 26 areas). VPA diminished global CBF by 14.9% (56.55 +/- 6.70 vs. 47.48 +/- 4.42 ml/min/100 g, p < 0.002) and regionally in all anatomic areas (p < 0.05 for 12 of 26 areas). No significant correlation was noted between VPA level and either global CMRGlc or CBF. The effect of VPA on global CMRGlc is similar to that of carbamazepine (CBZ) and phenytoin but less than that of phenobarbital, valium, or combination therapy with VPA and CBZ. VPA reduced regional CBF (rCBF) but not CMRGlc in the thalamus, an effect that may be associated with VPA's mechanism of action against generalized seizures
AD  - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
UR  - PM:8641226
ER  - 

TY  - JOUR
T1  - Positron Emission Tomography of Striatal Serotonin Transporters in Parkinson Disease
A1  - Kerenyi,Levente
A1  - Ricaurte,George A.
A1  - Schretlen,David J.
A1  - McCann,Una
A1  - Varga,Jozsef
A1  - Mathews,William B.
A1  - Ravert,Hayden T.
A1  - Dannals,Robert F.
A1  - Hilton,John
A1  - Wong,Dean F.
A1  - Szabo,Zsolt
Y1  - 2003/09/01/
SP  - 1223
EP  - 1229
JF  - Archives of Neurology
JA  - Arch.Neurol.
VL  - 60
IS  - 9
N2  - Background Little is known about serotonin neurons in Parkinson disease (PD). Objective To study the serotonin system in PD with positron emission tomography, using the serotonin transporter radioligand [11C](+)McN5652. Design and Patients We measured the density of the serotonin transporter and the density of [11C]WIN35 428-labeled dopamine transporters in the striatum of 13 adults with PD and 13 age- and sex-matched controls. To assess the effects of possible differences in blood flow or brain atrophy, we also measured regional cerebral blood flow and the size of the regions of interest for the caudate nucleus and putamen. Results Patients with PD showed reductions in the specific distribution volumes of [11C](+)McN5652 in the caudate (P<.01) and putamen (P<.01), along with the expected reductions in striatal [11C]WIN35 428 binding (P<.01). There were no reductions in regional cerebral blood flow or the sizes of the regions of interest, mitigating against potential confounding effects of blood flow, brain atrophy, or partial volume effects. Reductions in serotonin transporter binding correlated with ratings of disease staging. Conclusions These results suggest that the density of serotonin transporters, like that of dopamine transporters, is reduced in the striatum of patients with PD and that these changes are related to disease stage
UR  - http://archneur.ama-assn.org/cgi/content/abstract/60/9/1223
ER  - 

TY  - JOUR
T1  - Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment
A1  - Nestor,P.J.
A1  - Fryer,T.D.
A1  - Smielewski,P.
A1  - Hodges,J.R.
Y1  - 2003/09//
N1  - UI - 22833210
SP  - 343
EP  - 351
JA  - Ann.Neurol
VL  - 54
IS  - 3
N2  - The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction
AD  - University of Cambridge, Neurology Unit, Cambridge, United Kingdom
UR  - PM:12953266
ER  - 

TY  - JOUR
T1  - Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy
A1  - Thorngren-Jerneck,K.
A1  - Ohlsson,T.
A1  - Sandell,A.
A1  - Erlandsson,K.
A1  - Strand,S.E.
A1  - Ryding,E.
A1  - Svenningsen,N.W.
Y1  - 2001/04//
N1  - UI - 21165353
SP  - 495
EP  - 501
JA  - Pediatr.Res
VL  - 49
IS  - 4
N2  - Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-((18)F) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 microCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p < 0.01). Six infants with mild HIE had a mean (range) CMRgl of 55.5 (37.7-100.8) micromol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) micromol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 micromol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) micromol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) micromol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome
AD  - Department of Pediatrics, Lund University Hospital, S-221 85 Lund, Sweden. kristina.thorngren-jerneck@pedi.lu.se
UR  - PM:11264432
ER  - 

TY  - JOUR
T1  - Developmental changes of cerebral blood flow and oxygen metabolism in children
A1  - Takahashi,T.
A1  - Shirane,R.
A1  - Sato,S.
A1  - Yoshimoto,T.
Y1  - 1999/05//
N1  - UI - 99296040
SP  - 917
EP  - 922
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 20
IS  - 5
N2  - BACKGROUND AND PURPOSE: Normal values for cerebral blood flow (CBF) and metabolism in adults are well established, but not for children. Our goal, therefore, was to clarify functional developmental changes of the brain in children in relation to CBF and oxygen metabolism. METHODS: We measured regional CBF (rCBF), regional cerebral metabolic rate for oxygen (rCMRO2), and regional oxygen extraction fraction (rOEF), using positron emission tomography (PET). We performed 30 PET studies in 24 children ages 10 days to 16 years (nine boys, 15 girls), using a steady inhalation method with C(15)O2, (15)O2, and 15CO in order to measure rCBF, rCMRO2, and rOEF, respectively. Regions of interest were set in the primary cerebral areas (sensorimotor, visual, temporal, and parietal cortex), cerebral association areas (frontal and visual association), basal ganglia (lenticular and thalamus), and posterior fossa (brain stem and cerebellar cortex). Subjects were grouped by age (< 1, 1 to < 3, 3 to < 8, and > or = 8 years), and the absolute values of the parameters were compared with those obtained from 10 healthy adults. RESULTS: rCBF and rCMRO2 were lower in the neonatal period than in older children and adults, and increased significantly during early childhood. rCBF was higher as compared with adults, peaking around age 7, whereas rCMRO2 was relatively high, with the last area to increase being the frontal association cortex. Both rCBF and rCMRO2 reached adult values during adolescence. No difference in rCBF was observed between the basal ganglia and the primary cerebral cortex; however, it was prominent in the occipital lobe in every age bracket. No significant changes in rOEF were found during childhood. CONCLUSION: The dynamic changes of rCBF and rCMRO2 observed in children probably reflect the physiologic developmental state within anatomic areas of the brain
AD  - Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan
UR  - PM:10369366
ER  - 

TY  - JOUR
T1  - Cerebral glucose transport and metabolism in preterm human infants
A1  - Powers,W.J.
A1  - Rosenbaum,J.L.
A1  - Dence,C.S.
A1  - Markham,J.
A1  - Videen,T.O.
Y1  - 1998/06//
N1  - UI - 98289427
SP  - 632
EP  - 638
JA  - J Cereb.Blood Flow Metab
VL  - 18
IS  - 6
N2  - Few data regarding early developmental changes in cerebral (blood-to-brain) glucose transport (CTXglc) and CMRglc are available for humans. We measured CBF, CTXglc, and CMRglc with positron emission tomography at 4 to 7 days of life in six preterm human infants whose estimated gestational age was 25 to 34 weeks. The Michaelis-Menten constants Kt and Tmax were estimated from CTXglc and the calculated cerebral capillary plasma glucose concentration. Mean CMRglc was 8.8 mumol 100 g-1 min-1. The CMRglc did not correlate with plasma glucose concentration (r = .315, P = .543), whereas CTXglc showed a significant correlation with plasma glucose concentration (r = .836, P = .038). Estimation of the Michaelis-Menten constants from the best fit to the measured data produced values of Kt = 6.0 mumol mL-1 and Tmax = 32.6 mumol 100 g-1 min-1. These values for Kt in the developing human brain are similar to those that have been reported for the mature brain of adolescent and adult humans and adult nonhuman primates, indicating the affinity of the glucose transport protein for D-glucose is similar. However, Tmax is approximately one third to one half of the comparable values for mature brain, indicating a reduced number of available luminal transporters
AD  - Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA
UR  - PM:9626187
ER  - 

TY  - JOUR
T1  - Retraction
A1  - Ricaurte,G.A.
A1  - Yuan,J.
A1  - Hatzidimitriou,G.
A1  - Branden,J.Cord
A1  - McCann,U.D.
Y1  - 2003/09/12/
N1  - see also report: C:\Dokumente und Einstellungen\karl.PET\Desktop\Data\TEXT\LIT\Ricaurte-Science-retraction.pdf
SP  - 1479
JF  - Science
VL  - 301
IS  - 5639
UR  - PM:12970544
ER  - 

TY  - JOUR
T1  - MDMA ("ecstasy") and neurotoxicity
A1  - Mithoefer,M.
A1  - Jerome,L.
A1  - Doblin,R.
Y1  - 2003/06/06/
N1  - UI - 22677323
SP  - 1504
EP  - 1505
JF  - Science
VL  - 300
IS  - 5625
UR  - PM:12791964
ER  - 

TY  - CHAP
T1  - Data acquisition and image reconstruction for 3D PET
A1  - Defrise,M.
A1  - Kinahan,P.
Y1  - 1998///
SP  - 11
EP  - 53
T2  - The theory and practice of 3D PET
A2  - Bendriem,B.
A2  - Townsend,D.W.
IS  - 2
CY  - Dordrecht
PB  - Kluwer Academic Publishers
ER  - 

TY  - CHAP
T1  - Quantitative procedures in 3D PET
A1  - Bailey,D.L.
Y1  - 1998///
SP  - 55
EP  - 109
T2  - The theory and practice of 3D PET
A2  - Bendriem,B.
A2  - Townsend,D.W.
IS  - 3
CY  - Dordrecht
PB  - Kluwer Academic Publishers
ER  - 

TY  - JOUR
T1  - Performance of a brain PET camera based on anger-logic gadolinium oxyrorthosilicate detectors
A1  - Karp,J.S.
A1  - Surti,S.
A1  - Daube-Witherspoon,M.E.
A1  - Freifelder,R.
A1  - Cardi,C.A.
A1  - Adam,L.E.
A1  - Bilger,K.
A1  - Muehllehner,G.
Y1  - 2003///
N1  - J
SP  - 1340
EP  - 1349
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 44
IS  - 8
N2  - A high-sensitivity, high-resolution brain PET scanner ("G-PET") has been developed. This scanner is similar in geometry to a previous brain scanner developed at the University of Pennsylvania, the HEAD Penn-PET, but the detector technology and electronics have been improved to achieve enhanced performance. Methods: This scanner has a detector ring diameter of 42.0 cm with a patient aperture of 30.0 cm and an axial field of view of 25.6 cm. It comprises a continuous light-guide that couples 18,560 (320 x 58 array) 4 X 4 X 10 mm(3) gadolinium oxyorthosilicate (GSO) crystals to 288 (36 x 8 array) 39-mm photomultiplier tubes in a hexagonal arrangement. The scanner operates only in 3-climensional (3D) mode because there are no interplane septa. Performance measurements on the G-PET scanner were made following National Electrical Manufacturers Association NU 2-2001 procedures for most measurements, although NU 2-1994 procedures were used when these were considered more appropriate for a brain scanner (e.g., scatter fraction and counting-rate performance measurements). Results: The transverse and axial resolutions near the center are 4.0 and 5.0 mm, respectively. At a radial offset of 10 cm, these numbers deteriorate by approximately 0.5 mm. The absolute sensitivity of this scanner measured with a 70-cm long line source is 4.79 counts per second (cps)/kBq. The scatter fraction measured with a line source in a 20-cm-diameter X 19-cm-long cylinder is 39% (for a lower energy threshold of 410 keV). For the same cylinder, the peak noise equivalent counting rate is 60 kcps at an activity concentration of 7.4 kBq/mL (0.20 muCi/mL), whereas the peak true coincidence rate is 132 kcps at an activity concentration of 14 kBq/mL (0.38 muCi/mL). Images from the Hoffman brain phantom as well as F-18-FDG patient scans illustrate the high quality of images acquired on the G-PET scanner. Conclusion: The G-PET scanner attains the goal of high performance for brain imaging through the use of an Anger-logic GSO detector design with continuous optical coupling. This detector design leads to good energy resolution, which is needed in 3D imaging to minimize scatter and random coincidences
UR  - ISI:000184650900025
ER  - 

TY  - JOUR
T1  - A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals
A1  - Ziegler,S.I.
A1  - Pichler,B.J.
A1  - Boening,G.
A1  - Rafecas,M.
A1  - Pimpl,W.
A1  - Lorenz,E.
A1  - Schmitz,N.
A1  - Schwaiger,M.
Y1  - 2001///
N1  - J
SP  - 136
EP  - 143
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 28
IS  - 2
N2  - To fully utilize positron emission tomography (PET) as a non-invasive tool for tissue characterization, dedicated instrumentation is being developed which is specially suited far imaging mice and rats. Semiconductor detectors, such as avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes for the readout of scintillation crystals. Since the scintillation characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the combination of LSO and APDs seems favourable, and the goal of this study was to build a positron tomograph with LSO-APD modules to prove the feasibility of such an approach. A prototype PET scanner based on APD readout of small, individual LSO crystals was developed for tracer studies in mice and rats. The tomograph consists of two sectors (86 mm distance), each comprising three LSO-APD modules, which can be rotated for the acquisition of complete projections. In each module, small LSO crystals (3.7x3.7x 12 mm(3)) are individually coupled to one channel within matrices containing 2x8 square APDs (2.6x2.6 mm(2) sensitive area per channel). The list-made data are reconstructed with a penalized weighted least squares algorithm which includes the spatially dependent line spread function of the tomograph. Basic performance parameters were measured with phantoms and first experiments with rats and mice were conducted to introduce this methodology for biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of the total detector diameter. Image resolution was shown to be 2.4 mm within the whole reconstructed field of view. Using a lower energy threshold of 450 keV, the system sensitivity was 350 Hz/MBq for a line source in air in the centre of the field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter fraction at the centre of the field of view was 16% (450 keV threshold). The count rate was linear up to 700 coincidence counts per second. In vivo studies of anaesthetized rats and mice showed the feasibility of in vivo imaging using this PET scanner. The first LSO-APD prototype tomograph has been successfully introduced for in vivo animal imaging. APD arrays in combination with LSO crystals offer new design possibilities for positron tomographs with finely granulated detector channels
UR  - ISI:000167224700002
ER  - 

TY  - JOUR
T1  - Performance evaluation of a whole-body PET scanner using the NEMA protocol
A1  - Brix,G.
A1  - Zaers,J.
A1  - Adam,L.E.
A1  - Bellemann,M.E.
A1  - Ostertag,H.
A1  - Trojan,H.
A1  - Haberkorn,U.
A1  - Doll,J.
A1  - Oberdorfer,F.
A1  - Lorenz,W.J.
Y1  - 1997///
N1  - J
SP  - 1614
EP  - 1623
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 10
N2  - This study evaluates the performance of the newly developed high-resolution whole-body PET scanner ECAT EXACT HR+. Methods: The scanner consists of four rings of 72 bismuth germanate block detectors each, covering an axial field of view of 15.5 cm with a patient port of 56.2 cm. A single block detector is divided into an 8 x 8 matrix, giving a total of 32 rings with 576 detectors each, The dimensions of a single detector element are 4.39 x 4.05 x 30 mm(3). The scanner is equipped with extendable tungsten septa for two-dimensional two-dimensional measurements, as well as with three Ge-68 line sources for transmission scans and daily quality control, The spatial resolution, scatter fraction, count rate, sensitivity, uniformity and accuracy of the implemented correction algorithms were evaluated after the National Electrical Manufacturers Association protocol using the standard acquisition parameters, Results: The transaxial resolution in the two-dimensional mode is 4.3 mm (4.4 mm) in the center and increases to 4.7 mm (4.8 mm) tangential and to 8.3 mm (8.0 mm) radial at a distance of r = 20 cm from the center, The axial slice width measured in the two-dimensional mode varies between 4.2 and 6.6 mm FWHM over the transaxial field of view, In the three-dimensional mode the average axial resolution varies between 4.1 mm FWHM in the center and 7.8 mm at r = 20 cm. The scatter fraction is 17.1% (32.5%) for a lower energy discriminator level of 350 keV. The maximum true event count rate of 263 (345) kcps was measured at an activity concentration of 142 (26.9) kBq/ml. The total system sensitivity for true events is 5.7 (27.7) cps/Bq/ml. From the uniformity measurements, we obtained a volume variance of 3.9% (5.0%) and a system variance of 1.6% (1.7%). The implemented three-dimensional scatter correction algorithm reveals very favorable properties, whereas the three-dimensional attenuation correction yields slightly inaccurate results in low- and high-density regions. Conclusion: The ECAT EXACT HR+ has an excellent, nearly isotropic spatial resolution, which is advantageous for brain and small animal studies, While the relatively low slice sensitivity may hamper the capability for performing fast dynamic two-dimensional studies, the scanner offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging
UR  - ISI:A1997XZ76600029
ER  - 

TY  - JOUR
T1  - Three-dimensional imaging characteristics of the HEAD PENN-PET scanner
A1  - Karp,J.S.
A1  - Freifelder,R.
A1  - Geagan,M.J.
A1  - Muehllehner,G.
A1  - Kinahan,P.E.
A1  - Lewitt,R.M.
A1  - Shao,L.X.
Y1  - 1997///
N1  - J
SP  - 636
EP  - 643
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 38
IS  - 4
N2  - A volume-imaging PET scanner, without interplane septa, for brain imaging has been designed and built to achieve high performance, specifically in spatial resolution and sensitivity. The scanner is unique in its use of a single annular crystal of NaI(Tl), which allows a field of view (FOV) of 25.6 cm in both the transverse and axial directions. Data are reconstructed into an image matrix of 128(3) with (2 mm)3 voxels, using three-dimensional image reconstruction algorithms. Methods: Point-source measurements are performed to determine spatial resolution over the scanner FOV, and cylindrical phantom distributions are used to determine the sensitivity, scatter fraction and counting rate performance of the system. A three-dimensional brain phantom and F-18-FDG patient studies are used to evaluate image quality with three-dimensional reconstruction algorithms. Results: The system spatial resolution is measured to be 3.5 mm in both the transverse and axial directions, in the center of the FOV. The true sensitivity, using the standard NEMA phantom (6 liter), is 660 kcps/mu Ci/ml, after subtracting a scatter fraction of 34%. Due to deadtime effects, we measure a peak true counting rate, after scatter and randoms subtraction, of 100 kcps at 0.7 mCi for a smaller brain-sized (1.1 liter) phantom, and 70 kcps for a head-sized (2.5 liter) phantom at the same activity. A typical F-18-FDG clinical brain study requires only 2 mCi to achieve high statistics (100 million true events) with a scan time of 30 min. Conclusion: The HEAD PENN-PET scanner is based on a cost-effective design using NaI(Tl) and has been shown to achieve high performance for brain studies and pediatric whole-body studies. As a full-time three-dimensional imaging scanner with a very large axial acceptance angle, high sensitivity is achieved. The system becomes counting-rate limited as the activity is increased, but we achieve high image quality with a small injected dose. This is a significant advantage for clinical imaging, particularly for pediatric patients
UR  - ISI:A1997WR37700036
ER  - 

TY  - JOUR
T1  - ECAT ART - A continuously rotating PET camera: Performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department
A1  - Bailey,D.L.
A1  - Young,H.
A1  - Bloomfield,P.M.
A1  - Meikle,S.R.
A1  - Glass,D.
A1  - Myers,M.J.
A1  - Spinks,T.J.
A1  - Watson,C.C.
A1  - Luk,P.
A1  - Peters,A.M.
A1  - Jones,T.
Y1  - 1997///
N1  - J
SP  - 6
EP  - 15
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 24
IS  - 1
N2  - Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps . kBq(-1). ml(-1). This compares with 5800 and 40500 cps . kBq(-1). ml(-1) in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of similar to 15 kBq . ml(-1) in the cylinder. Spatial resolution is similar to 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 mu Sv . h(-1) for a typical fluorine-18 fluorodeoxyglucose (F-18-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with F-18-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging
UR  - ISI:A1997WH64700003
ER  - 

TY  - JOUR
T1  - Combined MRI-PET scanner: A Monte Carlo evaluation of the improvements in PET resolution due to the effects of a static homogeneous magnetic field
A1  - Raylman,R.R.
A1  - Hammer,B.E.
A1  - Christensen,N.L.
Y1  - 1996///
N1  - J
SP  - 2406
EP  - 2412
JF  - IEEE Transactions on Nuclear Science
VL  - 43
IS  - 4
N2  - Positron emission tomography (PET) relies upon the detection of photons resulting from the annihilation of positrons emitted by a radiopharmaceutical. The combination of images obtained with PET and magnetic resonance imaging (MRI) have begun to greatly enhance the study of many physiological processes, A combined MRI-PET scanner could alleviate much of the spatial and temporal coregistration difficulties currently encountered in utilizing images from these complementary imaging modalities. In addition, the resolution of the PET scanner could be improved by the effects of the magnetic field. In this computer study, the utilization of a strong static homogeneous magnetic field to increase PET resolution by reducing the effects of positron range and photon noncollinearity was investigated. The results reveal that significant enhancement of resolution can be attained, For example, an approximately 27% increase in resolution is predicted for a PET scanner incorporating a 10-Tesla magnetic field. Most of this gain in resolution is due to magnetic confinement of the emitted positrons, Although the magnetic field does mix some positronium states resulting in slightly less photon noncollinearity, this reduction does not significantly affect resolution, Photon noncollinearity remains as the fundamental limiting factor of large PET scanner resolution
UR  - ISI:A1996VD77800009
ER  - 

TY  - JOUR
T1  - Effect of Increased Axial-Field of View on the Performance of A Volume Pet Scanner
A1  - Karp,J.S.
A1  - Kinahan,P.E.
A1  - Muehllehner,G.
A1  - Countryman,P.
Y1  - 1993///
N1  - J
SP  - 299
EP  - 306
JF  - IEEE Transactions on Medical Imaging
VL  - 12
IS  - 2
N2  - The performance of the PENN-PET 240H scanner from UGM Medical Systems is tested and compared to the prototype PENN-PET scanner built at the University of Pennsylvania. The UGM PENN-PET scanner consists of six continuous position-sensitive NaI(Tl) detectors, which results in a 50 cm transverse field-of-view and a 12.8 cm axial field-of-view. The fine spatial sampling in the axial direction allows the data to be sorted into as many as 64 transverse planes, each 2 mm thick. A large axial acceptance angle, without interplane septa, results in a high-sensitivity and low-randoms fraction, with a low-scatter fraction due to the use of a narrow photopeak energy window. This paper emphasizes those performance measurements that illustrate the special characteristics of a volume imaging scanner and how they change as the axial length is increased
UR  - ISI:A1993LV99000018
ER  - 

TY  - JOUR
T1  - Factors Affecting Accuracy and Precision in Pet Volume Imaging
A1  - Karp,J.S.
A1  - Daube-Witherspoon,M.E.
A1  - Muehllehner,G.
Y1  - 1991///
N1  - J
SP  - A38
EP  - A44
JF  - Journal of Cerebral Blood Flow and Metabolism
VL  - 11
IS  - 2
N2  - Volume imaging positron emission tomographic (PET) scanners with no septa and a large axial acceptance angle offer several advantages over multiring PET scanners. A volume imaging scanner combines high sensitivity with fine axial sampling and spatial resolution. The fine axial sampling minimizes the partial volume effect, which affects the measured concentration of an object. Even if the size of an object is large compared to the slice spacing in a multiring scanner, significant variation in the concentration is measured as a function of the axial position of the object. With a volume imaging scanner, it is necessary to use a three-dimensional reconstruction algorithm in order to avoid variations in the axial resolution as a function of the distance from the center of the scanner. In addition, good energy resolution is needed in order to use a high energy threshold to reduce the coincident scattered radiation
UR  - ISI:A1991EZ34600027
ER  - 

TY  - JOUR
T1  - Design of a new BaF2PET module concept and preliminary evaluation results
A1  - Cleon,G.
A1  - Allemand,R.
A1  - Papillon,S.
A1  - Pinot,L.
A1  - Richard,A.
A1  - Charon,Y.
A1  - Laniece,P.
A1  - Menard,L.
A1  - Valentin,L.
A1  - Mastrippolito,R.
Y1  - 2002///
N1  - J
SP  - 139
EP  - 140
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 1
N2  - We describe a new positron emission tomography (PET) detection module using BaF2 crystals. We use the separation between the fast (0.6 ns, 220 11111) and the slow (630 ns, 310 nm) scintillation component of the barium fluoride through an ultraviolet glass filter to code the interaction localization. The timing is done on the fast component and the spectroscopy on the slow component. The photoelectric yield of BaF2 crystals (10 x 10 x 30, 8 x 8 x 30, and 6 x 6 x 30 mm(3)) coupled to 1-in-diameter photomultiplier tubes has been measured to quantify the light losses due to this geometry. As a reference, we present simulations and measurements of the efficiency of these crystals for detection of 511-keV gammas in coincidence and a measurement of the time resolution of the system
UR  - ISI:000175427300023
ER  - 

TY  - JOUR
T1  - The Super Pet 3000-e - A Pet Scanner Designed for High Count Rate Cardiac Applications
A1  - Terpogossian,M.M.
A1  - Ficke,D.C.
A1  - Beecher,D.E.
A1  - Hoffmann,G.R.
A1  - Bergmann,S.R.
Y1  - 1994///
N1  - J
SP  - 661
EP  - 669
JF  - Journal of Computer Assisted Tomography
VL  - 18
IS  - 4
N2  - Objective: Mathematical models for the delineation of regional myocardial perfusion and metabolism with PET require faithful reconstruction of arterial and myocardial time-activity curves following administration of radiotracers. High temporal resolution is often required in such measurements. Many commercially available tomographs exhibit long dead times that limit their count rate capabilities. To overcome these limitations, we developed and tested a whole-body tomographic device (Super PET 3000-E) with high count rate capabilities. The use of cesium fluoride scintillation detectors coupled with a one-to-one detector photomultiplier configuration reduces the system resolving and dead times.Materials and Methods: The Super PET 3000-E was subjected to a series of tests with phantoms to determine its resolution, sensitivity, linearity, count rate capabilities, dead time, and random coincidence contribution.Results: The system sensitivity is 136 kcounts/s/mu Ci/ml and its transverse and longitudinal resolutions are 8.5 and 10.5 mm full width at half-maximum, respectively. The system can easily record a total event rate of 2.0 Mcounts/s with minimal dead time loss and excellent linearity.Conclusion: The system fulfills its design goals and allows the very high count rate performance needed for the application of the physiological models used in our cardiac studies
UR  - ISI:A1994NW80500030
ER  - 

TY  - JOUR
T1  - Characteristics of Small Barium Fluoride (Baf2) Scintillator for High Intrinsic Resolution Time-Of-Flight Positron Emission Tomography
A1  - Wong,W.H.
A1  - Mullani,N.A.
A1  - Wardworth,G.
A1  - Hartz,R.K.
A1  - Bristow,D.
Y1  - 1984///
N1  - J
SP  - 381
EP  - 386
JF  - IEEE Transactions on Nuclear Science
VL  - 31
IS  - 1
UR  - ISI:A1984SC57700084
ER  - 

TY  - JOUR
T1  - PET instrumentation: What are the limits?
A1  - Budinger,T.F.
Y1  - 1998///
N1  - J
SP  - 247
EP  - 267
JF  - Seminars in Nuclear Medicine
VL  - 28
IS  - 3
N2  - This report has emphasized the attributes of positron emission tomography (PET) through a discussion of the historical development with attention to limitations or factors that are of importance in using and further developing this technology. As is the case for all nuclear detector developments, the factors that require consideration are spatial resolution, uniformity of resolution, sensitivity, distortions (attenuation), background noise (scatter and randoms), image volume, data acquisition capabilities (count-rate saturation), and limitations based on allowable radiation doses to the subject, forty years ago, the fact gamma-cameras could not handle the count-rates from the short half-life radionuclides that had clinical applications at that time tie, O-15, C-11, N-13) precluded their acceptance in nuclear medicine. With the advent of F-18 applications particularly with FDG in oncology, this limitation was no longer a barrier. Twenty years ago and until recently, the promise of time-of-flight PET78.79 has been stifled by the fact that the appropriately fast scintillator BaF2 had too low an efficiency (low density) to be useful in improving the signal to noise of a time-of-flight tomograph over contemporary systems. With the development of dense scintillators with high light output and high speed such as LSO30 the time-of-flight potentials are now once again worth pursuing. Twenty years ago systems that theoretically would have improved sensitivity by minimal or no septa with spherical geometric arrangements of detectors(8.21) were ignored because it appeared that scatter backgrounds would lead to a signal to noise less than 1. But in the last 5 years, cylindrical systems without septa have shown that noise effective sensitivity improvements of a factor of 4 can be realized. With time-of-flight additional improvements in sensitivity will be realized. Horizons for detector development include discovery of new scintillators, new methods of registering scintillation light,(81) deployment of larger field of view systems and methods of compensating for scatter, randoms, attenuation, and irregular sampling associated with new geometries which can encircle most of the body. The expected limit for PET is 2 mm isotropic resolution for the head and appendages including joints and breasts. Clinical realization of this resolution for the thorax and abdomen requires compensation for motion and even in this area strategies are underdevelopment which rely on the improvement in sensitivity being realized by 3D systems. Copyright (C) 1998 by W.B. Saunders Company
UR  - ISI:000075205100007
ER  - 

TY  - JOUR
T1  - A Rotating Pet Scanner Using BGO Block Detectors - Design, Performance and Applications
A1  - Townsend,D.W.
A1  - WENSVEEN,M.
A1  - Byars,L.G.
A1  - Geissbuhler,A.
A1  - TOCHONDANGUY,H.J.
A1  - CHRISTIN,A.
A1  - Defrise,M.
A1  - Bailey,D.L.
A1  - Grootoonk,S.
A1  - DONATH,A.
A1  - Nutt,R.
Y1  - 1993///
N1  - J
SP  - 1367
EP  - 1376
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 34
IS  - 8
N2  - Recent advances in fully three-dimensional reconstruction for multi-ring PET scanners have led us to explore the potential of a prototype scanner based on the rotation of two opposing arrays of BGO block detectors. The prototype contains only one-third of the number of detectors in the equivalent full ring scanner, resulting in reduced cost. With a lower energy threshold at 250 keV, the absolute efficiency of the scanner is 0.5% and the scatter fraction is 35% for a 20-cm cylinder. Transaxial and axial spatial resolution is about 6 mm. The maximum noise equivalent count rate estimated for a 15-cm diameter cylinder is 36,000 cps at a concentration of 26 kBq/ml. The minimum scan time for a F-18-fluoro-2-deoxyglucose (FDG) brain study is 55 sec. The camera has been validated for clinical applications using both FDG and Rb-82
UR  - ISI:A1993LP02300028
ER  - 

TY  - JOUR
T1  - A Deconvolution Scatter Correction for A 3-D Pet System
A1  - Mckee,B.T.A.
A1  - Gurvey,A.T.
A1  - Harvey,P.J.
A1  - Howse,D.C.
Y1  - 1992///
N1  - J
SP  - 560
EP  - 569
JF  - IEEE Transactions on Medical Imaging
VL  - 11
IS  - 4
N2  - The 3-D PET system at Queen's University provides high resolution imaging over a limited volume. With a detector sampling of 1 mm, QPET has over 10(11) lines of response, so images are reconstructed using a backproject-then-filter algorithm. In this paper we present a method to remove the scattered background from the reconstructed image by deconvolation with a point response function which includes the scatter contribution. The amplitude of the scattered response function is obtained by constraining a region of the corrected image to zero average amplitude. This method assumes that the shape of scatter distribution is shift invariant and independent of the shape of the scattering object and the distribution of the position activity. We tested the validity of these approximations for the QPET geometry using simulations. An average scatter response function for the system was obtained from these simulations and compared with results from measurements. The method was tested using experimental data from an irregularly shaped acrylic phantom. It was simple to implement and resulted in a satisfactory correction of the scattered background for our small-volume system
UR  - ISI:A1992KK63500012
ER  - 

TY  - JOUR
T1  - Image Quantification with A Large Area Multiwire Proportional Chamber Positron Camera (Mup-Pet)
A1  - Cherry,S.R.
A1  - Marsden,P.K.
A1  - Ott,R.J.
A1  - Flower,M.A.
A1  - Webb,S.
A1  - Babich,J.W.
Y1  - 1989///
N1  - J
SP  - 694
EP  - 700
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 15
IS  - 11
UR  - ISI:A1989AZ70800005
ER  - 

TY  - JOUR
T1  - The Performance of A Multiwire Proportional Chamber Positron Camera for Clinical Use
A1  - Marsden,P.K.
A1  - Ott,R.J.
A1  - Bateman,J.E.
A1  - Cherry,S.R.
A1  - Flower,M.A.
A1  - Webb,S.
Y1  - 1989///
N1  - J
SP  - 1043
EP  - 1062
JF  - Physics in Medicine and Biology
VL  - 34
IS  - 8
UR  - ISI:A1989AH75100007
ER  - 

TY  - JOUR
T1  - Treatment of Axial Data in 3-Dimensional Pet
A1  - Daube-Witherspoon,M.E.
A1  - Muehllehner,G.
Y1  - 1987///
N1  - J
SP  - 1717
EP  - 1724
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 28
IS  - 11
UR  - ISI:A1987K850000009
ER  - 

TY  - JOUR
T1  - High-Density Avalanche Chamber (Hidac) Positron Camera
A1  - Townsend,D.
A1  - Frey,P.
A1  - Jeavons,A.
A1  - Reich,G.
A1  - TOCHONDANGUY,H.J.
A1  - DONATH,A.
A1  - CHRISTIN,A.
A1  - Schaller,G.
Y1  - 1987///
N1  - J
SP  - 1554
EP  - 1562
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 28
IS  - 10
UR  - ISI:A1987K339700011
ER  - 

TY  - JOUR
T1  - Volume Measurement Invivo Using Positron Tomography
A1  - Townsend,D.
A1  - Frey,P.
A1  - DONATH,A.
A1  - Clack,R.
A1  - Schorr,B.
A1  - Jeavons,A.
Y1  - 1984///
N1  - J
SP  - 105
EP  - 112
JF  - Nuclear Instruments & Methods in Physics Research Section A-Accelerators Spectrometers Detectors and Associated Equipment
VL  - 221
IS  - 1
UR  - ISI:A1984SP57000020
ER  - 

TY  - JOUR
T1  - Imaging small animals with positron emission tomography
A1  - Schafers,K.P.
Y1  - 2003///
N1  - J
SP  - 86
EP  - 89
JF  - Nuklearmedizin-Nuclear Medicine
VL  - 42
IS  - 3
N2  - During the post few years many research centers have successfully applied their knowledge of positron emission tomography (PET) to construct PET scanners which are dedicated to image small animals such as rats and mice. Although there are many in-house built systems which are used in laboratory environments, only G few of them are commercially available at this time. This review will give an overview of dedicated animal PET systems with their technical description and main physical characteristics. Graphical analysis of spatial resolution against absolute sensitivity allows a comparison of the most important characteristics of each camera.The quadHIDAC, a PET scanner recently installed at the Department of Nuclear Medicine, University Hospital Monster, acquires images with sub-millimeter spatial resolution. A F-18-FDG whole body image of a mouse with small structures like the left ventricle of the heart clearly visualized, demonstrates its excellent spatial resolution
UR  - ISI:000183737200003
ER  - 

TY  - JOUR
T1  - Recent results of the TierPET scanner
A1  - Weber,S.
A1  - Bauer,A.
A1  - Herzog,H.
A1  - Kehren,F.
A1  - Muhlensiepen,H.
A1  - Vogelbruch,J.
A1  - Coenen,H.H.
A1  - Zilles,K.
A1  - Halling,H.
Y1  - 2000///
N1  - J
SP  - 1665
EP  - 1669
JF  - IEEE Transactions on Nuclear Science
VL  - 47
IS  - 4
N2  - At the Forschungszentrum Julich a high resolution positron emission tomograph (TierPET) for imaging small laboratory animals, especially rats, has been constructed. The scanner is based on arrays of YAP crystals. As a special feature the detector distances can be varied continuously from 16 to 58 cm. Due to the variable detector distances the performance of the scanner has to be evaluated in various configurations. Special attention was paid to dedicated data acquisition protocols and adequate applications with regard to the system sensitivity
UR  - ISI:000089576400021
ER  - 

TY  - JOUR
T1  - One-pass list-mode EM algorithm for high-resolution 3-D PET image reconstruction into large arrays
A1  - Reader,A.J.
A1  - Ally,S.
A1  - Bakatselos,F.
A1  - Manavaki,R.
A1  - Walledge,R.J.
A1  - Jeavons,A.P.
A1  - Julyan,P.J.
A1  - Zhao,S.
A1  - Hastings,D.L.
A1  - Zweit,J.
Y1  - 2002///
N1  - J
SP  - 693
EP  - 699
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 3
N2  - High-resolution three-dimensional (3-D) positron emission tomography (PET) scanners with high count rate performance, such as the quad-high density avalanche chamber (HIDAC), place new demands on image reconstruction algorithms due to the large quantities of high-precision list-mode data which are produced. Therefore, a reconstruction algorithm is required which can, in a practical time frame, reconstruct into very large image arrays (submillimeter voxels, which range over a large field of view) whilst preferably retaining the precision of the data. This work presents an algorithm which meets these demands: one-pass list-mode expectation maximization (OPL-EM) algorithm. The algorithm operates directly on list-mode data, passes through the data once only, accounts for finite resolution effects in the system model, and can also include regularization. The algorithm performs multiple image updates during its single pass through the list-mode data, corresponding to the number of subsets that the data have been split into. The algorithm has been assessed using list-mode data from a quad-HIDAC and is compared to the analytic reconstruction method 3-D reprojection (RP) with 3-D filtered backprojection
UR  - ISI:000178670800013
ER  - 

TY  - JOUR
T1  - Small-animal PET cameras
A1  - Jeavons,A.P.
Y1  - 2000///
N1  - J
SP  - 1442
EP  - 1443
JF  - Journal of Nuclear Medicine
JA  - J.Nucl.Med.
VL  - 41
IS  - 8
UR  - ISI:000089888800033
ER  - 

TY  - JOUR
T1  - A 3D HIDAC-PET camera with sub-millimetre resolution for imaging small animals
A1  - Jeavons,A.P.
A1  - Chandler,R.A.
A1  - Dettmar,C.A.R.
Y1  - 1999///
N1  - J
SP  - 468
EP  - 473
JF  - IEEE Transactions on Nuclear Science
VL  - 46
IS  - 3
N2  - A HIDAC-PET camera consisting essentially of 5 million 0.5mm gas avalanching detectors has been constructed for small-animal imaging. The particular HIDAC advantage - a high 3D spatial resolution - has been improved to 0.95mm fwhm and to 0.7mm fwhm when reconstructing with 3D-OSEM methods incorporating resolution recovery. A depth-of-interaction resolution of 2.5mm is implicit, due to the laminar construction. Scatter-corrected sensitivity, at 8.9cps/kBq (i.e. 0.9%) from a central point source, or 7.2cps/kBq (543cps/kBq/cm(3)) from a distributed (40mm diameter, 60mm long) source is now much higher than previous, and other, work. A field-of-view of 100mm (adjustable to 200mm) diameter by 210mm axially permits whole-body imaging of small animals, containing typically 4MBqs of activity, at 40kcps of which 16% are random coincidences, with a typical scatter fraction of 44%. Throughout the field-of-view there are no positional distortions and relative quantitation is uniform to +/-3.5%, but some variation of spatial resolution is found. The performance demonstrates that HIDAC technology is quite appropriate for small-animal PET cameras
UR  - ISI:000081461200004
ER  - 

TY  - JOUR
T1  - A microvolumetric blood counter/sampler for metabolic PET studies in small animals
A1  - Lapointe,D.
A1  - Cadorette,J.
A1  - Rodrigue,S.
A1  - Rouleau,D.
A1  - Lecomte,R.
Y1  - 1998///
N1  - J
SP  - 2195
EP  - 2199
JF  - IEEE Transactions on Nuclear Science
VL  - 45
IS  - 4
N2  - Quantitative metabolic imaging in small animals with positron emission tomography (PET) requires the determination of the tracer concentration in whole blood, arterial plasma and metabolites as a function of time, A blood counting and sampling system was designed to simultaneously measure the time-activity curve as microvolumes of blood are collected. The system consists of a flow-through counter made of a plastic scintillator to detect positrons and of a computer-controlled blood sampler based on the concept of bubble segmentation. The number and size of samples, the withdrawal speed and the sampling time are programmable and can be modified on-line. Samples as small as 10 mu l can be repetitively obtained from an implanted arterial catheter in the femoral vein or artery of small rats (150 g) or the jugular vein of mice (20 g). For medium sampling speed (100 mu l/min) at a constant rate, the standard deviation of the sample activity is typically less than 1%. By cutting the tubing at the bubbles at the end of the experiment, samples are made available for further processing and biochemical analysis. This apparatus has become an essential tool for quantitative animal PET studies, allowing easy, reliable sampling at a low cost
UR  - ISI:000075401600020
ER  - 

TY  - JOUR
T1  - A simple on-line arterial time-activity curve detector for [O-15]water PET studies: Part 1
A1  - Wollenweber,S.D.
A1  - Hichwa,R.D.
A1  - Ponto,L.L.B.
Y1  - 1997///
N1  - J
SP  - 1613
EP  - 1617
JF  - IEEE Transactions on Nuclear Science
VL  - 44
IS  - 4
N2  - A simple, automated on-line detector system has been fabricated and implemented to detect the arterial time-activity curve (TAG) for bolus-injection [O-15]water PET studies. This system offers two significant improvements over existing systems: a pump mechanism is not required to control arterial blood flow through the detector and dispersion correction of the time-activity curve for dispersion in external tubing is unnecessary. The [O-15] positrons emanating from blood within a thin-walled, 0.134 cm inner-diameter plastic tube are detected by a 0.5 cm wide by 1.0 cm long by 0.1 cm thick plastic scintillator mounted to a miniature PMT. Photon background is reduced to insignificant levels by a 2.0 cm thick cylindrical lead shield. Mean cerebral blood flow (mCBF) determined from an autoradiographic model and from the TAC measured by 1-second automated sampling was compared to that calculated from a TAC acquired using 5-second integrated manual samples. Improvements in timing resolution (1-sec vs. 5-sec) cause small but significant differences between the two sampling methods. Dispersion is minimized due to small tubing diameters, short lengths of tubing between the radial arterial sampling site and the detector and the presence of a 3-way valve 10 cm proximal to the detector
UR  - ISI:A1997XP91900024
ER  - 

TY  - JOUR
T1  - A simple on-line arterial time-activity curve detector for [O-15]water PET studies: Part 2
A1  - Wollenweber,S.D.
A1  - Hichwa,R.D.
A1  - Ponto,L.L.B.
Y1  - 1997///
N1  - J
SP  - 1417
EP  - 1419
JF  - IEEE Transactions on Nuclear Science
VL  - 44
IS  - 3
N2  - A simple, automated on-line detector system has been fabricated and implemented to detect the arterial time-activity curve (TAC) for bolus-injection [O-15]water PET studies. This system offers two significant improvements over existing systems: a pump mechanism is not required to control arterial blood flow through the detector and dispersion correction cg the time-activity curve for dispersion in external tubing is unnecessary. The [O-15] positrons emanating from blood within a thin-walled, 0.134 cm inner-diameter plastic tube are detected by a 0.5 cm wide by 1.0 cm long by 0.1 cm thick plastic scintillator mounted to a miniature PMT. Photon background is reduced to insignificant levels by a 2.0 cm thick cylindrical lead shield. Mean cerebral blood now (mCBF) determined from an autoradiographic model and from the TAC measured by 1-second automated sampling was compared to that calculated from a TAC acquired using 5-second integrated manual samples. Improvements in timing resolution (1-sec vs. 5-sec) cause small but significant differences between the two sampling methods. Dispersion is minimized due to small tubing diameters, short lengths of tubing between the radial arterial sampling site and the detector and the presence of a 3-way valve 10 cm proximal to the detector
UR  - ISI:A1997XF30000052
ER  - 

TY  - JOUR
T1  - Characteristics of A New Automated Blood-Sampling System for Positron Emission Tomography
A1  - Eriksson,L.
A1  - Ingvar,M.
A1  - Rosenqvist,G.
Y1  - 1995///
N1  - J
SP  - 1007
EP  - 1011
JF  - IEEE Transactions on Nuclear Science
VL  - 42
IS  - 4
N2  - A new commercially available automated blood sampling system (ABSS) for positron emission tomography has been evaluated. The system uses a single EGO crystal and detects with high efficiency the annihilation radiation from tracers, labelled with positron emitting isotopes, in arterial blood. In addition the possibilities to use the ABSS as a detector in the analysis of the plasma samples with liquid chromatography techniques under flow conditions has been explored
UR  - ISI:A1995RP81900145
ER  - 

TY  - JOUR
T1  - A fast rebinning algorithm for 3D positron emission tomography using John's equation
A1  - Defrise,M.
A1  - Liu,X.A.
Y1  - 1999///
N1  - J
SP  - 1047
EP  - 1065
JF  - Inverse Problems
VL  - 15
IS  - 4
N2  - Volume imaging in positron emission tomography (PET) requires the inversion of the three-dimensional (3D) x-ray transform. The usual solution to this problem is based on 3D filtered-backprojection (FBP), but is slow. Alternative methods have been proposed which factor the 3D data into independent 2D data sets corresponding to the 2D Radon transforms of a stack of parallel slices. Each slice is then reconstructed using 2D FBP. These so-called rebinning methods are numerically efficient but are approximate. In this paper a new exact rebinning method is derived by exploiting the fact that the 3D x-ray transform of a function is the solution to the second-order partial differential equation first studied by John. The method is proposed for two sampling schemes, one corresponding to a pair of infinite plane detectors and another one corresponding to a cylindrical multi-ring PET scanner. The new FORE-J algorithm has been implemented for this latter geometry and was compared with the approximate Fourier rebinning algorithm FORE and with another exact rebinning algorithm, FOREX. Results with simulated data demonstrate a significant improvement in accuracy compared to FORE, while the reconstruction time is doubled. Compared to FOREX, the FORE-J algorithm is slightly less accurate but more than three times faster
UR  - ISI:000082802900014
ER  - 

TY  - JOUR
T1  - A Factorization Method for the 3D X-Ray Transform
A1  - Defrise,M.
Y1  - 1995///
N1  - J
SP  - 983
EP  - 994
JF  - Inverse Problems
VL  - 11
IS  - 5
N2  - We consider the inversion of the three-dimensional (3D) x-ray transform with a limited data set containing the line integrals which have two intersections with the lateral surface of a cylindrical detector. The usual solution to this problem ids based on 3D filtered-backprojection, but this method is slow. This paper presents a new algorithm which factors the 3D reconstruction problem into a set of independent 2D radon transforms for a stack of parallel slices. Each slice is then reconstructed using standard 2D filtered-backprojection. the algorithm is based on the application of the stationary-phase approximation to the 2D Fourier transform of the data, and is an extension to three dimensions of the frequency-distance relation derived by Edholm et al for the 2D radon transform. Error estimates are also obtained
UR  - ISI:A1995RZ58600004
ER  - 

TY  - JOUR
T1  - HeinzelCluster: accelerated reconstruction for FORE and OSEM3D
A1  - Vollmar,S.
A1  - Michel,C.
A1  - Treffert,J.T.
A1  - Newport,D.F.
A1  - Casey,M.
A1  - Knoss,C.
A1  - Wienhard,K.
A1  - Liu,X.
A1  - Defrise,M.
A1  - Heiss,W.D.
Y1  - 2002///
N1  - J
SP  - 2651
EP  - 2658
JF  - Physics in Medicine and Biology
VL  - 47
IS  - 15
N2  - Using iterative three-dimensional (3D) reconstruction techniques for reconstruction of positron emission tomography (PET) is not feasible on most single-processor machines due to the excessive computing time needed, especially so for the large sinogram sizes of our high-resolution research tomograph (HRRT).In our first approach to speed up reconstruction time we transform the 3D scan into the format of a two-dimensional (2D) scan with sinograms that can be reconstructed independently using Fourier rebinning (FORE) and a fast 2D reconstruction method. On our dedicated reconstruction cluster (seven four-processor systems, Intel PIII@700 MHz, switched fast ethernet and Myrinet, Windows NT Server), we process these 2D sinograms in parallel. We have achieved a speedup >23 using 26 processors and also compared results for different communication methods (RPC, Syngo, Myrinet GM).The other approach is to parallelize OSEM3D (implementation of C Michel), which has produced the best results for HRRT data so far and is more suitable for an adequate treatment of the sinogram gaps that result from the detector geometry of the HRRT. We have implemented two levels of parallelization for our dedicated cluster (a shared memory fine-grain level on each node utilizing all four processors and a coarse-grain level allowing for 15 nodes) reducing the time for one core iteration from over 7 h to about 35 min
UR  - ISI:000177510200009
ER  - 

TY  - JOUR
T1  - Accelerated image reconstruction using ordered subsets of projection data
A1  - Hudson,H.
A1  - Larkin,R.
Y1  - 1994///
SP  - 601
EP  - 609
JA  - IEEE Trans.Med.Imaging
VL  - 13
ER  - 

TY  - JOUR
T1  - ROC analysis of ordered subset expectation maximization and filtered back projection technique for FDG-PET in lung cancer
A1  - Son,H.K.
A1  - Yun,M.J.
A1  - Jeon,T.J.
A1  - Kim,D.O.
A1  - Jung,H.J.
A1  - Lee,J.D.
A1  - Yoo,H.S.
A1  - Kim,H.J.
Y1  - 2003///
N1  - J
SP  - 37
EP  - 41
JF  - IEEE Transactions on Nuclear Science
VL  - 50
IS  - 1
N2  - The purpose of this study was to evaluate the image quality and discriminative ability of fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) images reconstructed by conventional filtered back projection (FBP) and ordered subset expectation maximization (OSEM) in patients with lung cancer. Thirty-six subjects including normal controls and lung cancer patients underwent whole body PET scan (emission 3 min, transmission 1 min) using a GE Advance Scanner after the administration of approximately 370 MBq of FDG. The raw data were then reconstructed, by conventional FBP and OSEM. The PET images were interpreted by two observers with random exposure of normal and diseased cases for transverse and coronal sections. The results were evaluated using receiver operating characteristic (ROC) curve analysis. The image quality of 36 subjects including normal controls and lung cancer patients reconstructed by OSEM was generally superior to FBP in terms of visual analysis. FBP without attenuation correction had better image contrast than OSEM, although it had poor image quality. ROC analysis indicated that for this limited set of studies OSEM with attenuation correction out-performed conventional FBP in terms of its discriminative ability of lung cancer with FDG-PET. The results indicated that OSEM provides better image quat and, superior discriminative ability than conventional FBP for diagnosis of lung cancer by whole body FDG-PET
UR  - ISI:000180945600006
ER  - 

TY  - JOUR
T1  - Estimation of image noise in PET using the bootstrap method
A1  - Dahlbom,M.
Y1  - 2002///
N1  - J
SP  - 2062
EP  - 2066
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 5
N2  - The bootstrap method applied to positron emission tomography (PET) data was evaluated as a technique to determine regional image noise in PET. To validate the method, 250 scans (5 min each) of a uniform cylinder filled with Ge-68 was acquired and reconstructed using filtered backprojection (FBP). A single 5-min list mode scan was also acquired. From the list mode data, 250 bootstrap replicates were generated by randomly drawing, with replacement, prompt and random events. In each replicate, the total numbers of prompt and random events were kept identical to the number in the original list mode data set. The 250 individual scans, and the bootstrap replicates, were reconstructed using FBP and ordered subset expectation maximization (OSEM). Mean and standard-deviation (SD) images were generated from the reconstructed images. Mean and SD were also calculated in a central region of the image sets. Visual inspection showed no appreciable difference between the SD images derived from the repeated scans and the bootstrap replicates. Profiles through the images, showed no significant difference between image sets. Using an increased number of bootstrap replicates produced less noise in the SD images. Region of interest analysis showed, that the SDs derived from the bootstrap replicates were very close to the ones derived from the repeat scans, independent of reconstruction algorithm. The results indicate that the bootstrap method can accurately estimate regional image noise in PET. This could potentially provide a method to accurately compare image noise in phantom and patient data under various imaging and processing conditions, without the need for repeat scans
UR  - ISI:000179177300005
ER  - 

TY  - JOUR
T1  - A non-parametric bootstrap approach for analysing the statistical properties of SPECT and PET images
A1  - Buvat,I.
Y1  - 2002///
N1  - J
SP  - 1761
EP  - 1775
JF  - Physics in Medicine and Biology
VL  - 47
IS  - 10
N2  - Knowledge of the statistical properties of reconstructed single photon emission computed tomography (SPECT) and positron emission tomography (PET) images would be helpful for optimizing acquisition and image processing protocols, We describe a non-parametric bootstrap approach to accurately estimate the statistical properties of SPECT or PET images whatever the noise properties in the projections and the reconstruction algorithm. Using analytical simulations and real PET data, this method is shown to accurately predict the statistical properties. including the variance and covariance, of reconstructed pixel values for both linear (filtered backprojection) and non-linear (ordered subset expectation maximization) reconstruction algorithms
UR  - ISI:000176029200011
ER  - 

TY  - JOUR
T1  - Effects of iterative reconstruction on image contrast and lesion detection in gamma camera coincidence imaging in lung and breast cancers
A1  - Paul,A.K.
A1  - Tatsumi,M.
A1  - Yutani,K.
A1  - Fujino,K.
A1  - Hashikawa,K.
A1  - Nishimura,T.
Y1  - 2002///
N1  - J
SP  - 103
EP  - 110
JF  - Nuclear Medicine Communications
VL  - 23
IS  - 1
N2  - To investigate the effects of iterative reconstruction in F-18-fluorodeoxyglucose (FDG) gamma camera coincidence imaging (GCI), image contrast and visual detection obtained by using the iterative ordered-subsets expectation maximization (OSEM) reconstruction, in a phantom and in patients with lung cancer and breast cancer, were compared with those obtained by using the conventional filtered backprojection (FBP) reconstruction. Images of a cylindrical phantom containing hot spheres of various sizes (10-38 mm) were acquired by positron emission tomography (PET) and GCI at various sphere-to-background activity ratios. Forty-one consecutive patients with biopsy-proven cancer of lung (n = 20) and breast (n = 21) underwent PET and GCI on the same day after intravenous injection of 370 MBq of FDG. GCI images reconstructed by the OSEM and the FBP were compared. FDG PET was considered as the standard of reference. In GCI phantom images, OSEM yielded better contrast and signal-to-noise ratio (SNR) than FBP over the range of sphere sizes. Attenuation correction improved both the image measures and sphere detection obtained by the OSEM in GCI. In the study involving patients, FDG PET depicted 41 primary tumours and 2.5 metastatic lymph nodes. All of the tumours >2 cm in diameter (n = 25), six of the nine tumours 1.5-2.0 cm in diameter (67%), two of seven tumours <1.5 cm in diameter (29%), and 20 metastatic lymph nodes (80%) were detected in attenuation uncorrected GCI reconstructed by the OSEM as well as the FBP. The undetected lesions in GCI were identical between the OSEM and the FBP reconstructions. OSEM yielded significantly greater tumour-to-background (T/B) ratios and lower noise than FBP in GCI (T/B ratios, 4.1 +/- 3.2 vs 3.7 +/- 2.7, P = 0.02; noise, 0.09 +/- 0.04 vs 0.14 +/- 0.05, P < 0.0001). In conclusion, OSEM yielded better image contrast and less noise than the FBP in GCI, but the lesion detection obtained by the OSEM and the FBP in attenuation uncorrected GCI in patients with lung cancer and breast cancer were similar. Phantom data suggest the potential of OSEM for improving lesion detection in GCI after attenuation correction. ((C) 2002 Lippincott Williams & Wilkins)
UR  - ISI:000172991600016
ER  - 

TY  - JOUR
T1  - Efficient scatter modelling for incorporation in maximum likelihood reconstruction
A1  - Hutton,B.F.
A1  - Baccarne,V.
Y1  - 1998///
N1  - J
SP  - 1658
EP  - 1665
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 25
IS  - 12
N2  - Definition of a simplified model of scatter which can be incorporated in maximum likelihood reconstruction for single-photon emission tomography (SPET) continues to be appealing; however, implementation must be efficient for it to be clinically applicable. In this paper an efficient algorithm for scatter estimation is described in which the spatial scatter distribution is implemented as a spatially invariant convolution for points of constant depth in tissue. The scatter estimate is weighted by a space-dependent build-up factor based on the measured attenuation in tissue, Monte Carlo simulation of a realistic thorax phantom was used to validate this approach. Further efficiency was introduced by estimating scatter once after a small number of iterations using the ordered subsets expectation maximisation (OSEM) reconstruction algorithm. The scatter estimate was incorporated as a constant term in subsequent iterations rather than modifying the scatter estimate each iteration. Monte Carlo simulation was used to demonstrate that the scatter estimate does not change significantly provided at least two iterations OSEM reconstruction, subset size 8, is used. Complete scatter-corrected reconstruction of 64 projections of 40x128 pixels was achieved in 38 min using a Sun Sparc20 computer
UR  - ISI:000077652500008
ER  - 

TY  - JOUR
T1  - Fast reconstruction of 3D PET data with accurate statistical modeling
A1  - Comtat,C.
A1  - Kinahan,P.E.
A1  - Defrise,M.
A1  - Michel,C.
A1  - Townsend,D.W.
Y1  - 1998///
N1  - J
SP  - 1083
EP  - 1089
JF  - IEEE Transactions on Nuclear Science
VL  - 45
IS  - 3
N2  - This paper presents the results of combining high sensitivity 3D PET whole-body acquisition followed by fast 2D iterative reconstruction methods based on accurate statistical models. This combination is made possible by Fourier rebinning (FORE), which accurately converts a 3D data set to a set of 2D sinograms. The combination of volume imaging with statistical reconstruction allows improvement of noise-bias trade-offs when image quality is dominated by measurement statistics. The rebinning of the acquired data into a 2D data set reduces the computation time of the reconstruction. For both penalized weighted least-squares (PWLS) and ordered-subset EM: (OSEM) reconstruction methods, the usefulness of a realistic model of the expected measurement statistics is shown when the data are pre-corrected for attenuation and random and scattered coincidences, as required for the FORE rebinning algorithm. The results presented are based on 3D simulations of whole-body scans that include the major statistical effects of PET acquisition and data correction procedures. As the PWLS method requires knowledge of the variance of the projection data, a simple model for the effect of FORE rebinning on data variance is developed
UR  - ISI:000074190800006
ER  - 

TY  - JOUR
T1  - The design and implementation of a motion correction scheme for neurological PET
A1  - Bloomfield,P.M.
A1  - Spinks,T.J.
A1  - Reed,J.
A1  - Schnorr,L.
A1  - Westrip,A.M.
A1  - Livieratos,L.
A1  - Fulton,R.
A1  - Jones,T.
Y1  - 2003///
N1  - J
SP  - 959
EP  - 978
JF  - Physics in Medicine and Biology
VL  - 48
IS  - 8
N2  - A method is described to monitor the motion of the head during neurological positron emission tomography (PET) acquisitions and to correct the data post acquisition for the recorded motion prior to image reconstruction. The technique uses an optical tracking system, Polaris(TM), to accurately monitor the position of the head during the PET acquisition. The PET data are acquired in list mode where the events are written directly to disk during acquisition. The motion tracking information is aligned to the PET data using a sequence of pseudo-random numbers, which are inserted into the time tags in the list mode event stream through the gating input interface on the tomograph. The position of the head is monitored during the transmission acquisition, and it is assumed that there is minimal head motion during this measurement. Each event, prompt and delayed, in the list mode event stream is corrected for motion and transformed into the transmission space. For a given line of response, normalization, including corrections for detector efficiency, geometry and crystal interference and dead time are applied prior to motion correction and rebinning in the sinogram.A series of phantom experiments were performed to confirm the accuracy of the method: (a) a point source located in three discrete axial positions in the tomograph field of view, 0 mm, 10 mm and 20 mm from a reference point, (b) a multi-line source phantom rotated in both discrete and gradual rotations through +/- 5degrees and +/- 15degrees, including a vertical and horizontal movement in the plane. For both phantom experiments images were reconstructed for both the fixed and motion corrected data. Measurements for resolution, full width at half maximum (FWHM) and full width at tenth maximum (FWTM), were calculated from these images and a comparison made between the fixed and motion corrected datasets. From the point source measurements, the FWHM at each axial position was 7.1 mm in the horizontal direction, and increasing from 4.7 rum at the 0 mm position, to 4.8 mm, 20 mm offset, in the vertical direction. The results from the multi-line source phantom with +/- 5degrees rotations showed a maximum degradation in FWHM, when compared with the stationary phantom, of 0.6 mm, in the horizontal direction, and 0.3 mm in the vertical direction. The corresponding values for the larger rotation, +/- 15degrees, were 0.7 mm and 1.1 mm, respectively.The performance of the method was confirmed with a Hoffman brain phantom moved continuously, and a clinical acquisition using [C-11]raclopride (normal volunteer). A visual comparison of both the motion and non-motion corrected images of the Hoffman brain phantom clearly demonstrated the efficacy of the method. A sample time-activity curve extracted from the clinical study showed irregularities prior to motion correction, which were removed after correction.A method has been developed to accurately monitor the motion of the head during a neurological PET acquisition, and correct for this motion prior to image reconstruction. The method has been demonstrated to be accurate and does not add significantly to either the acquisition or the subsequent data processing
UR  - ISI:000182759300001
ER  - 

TY  - JOUR
T1  - Correction for head movements in positron emission tomography using an optical motion-tracking system
A1  - Fulton,R.R.
A1  - Meikle,S.R.
A1  - Eberl,S.
A1  - Pfeiffer,J.
A1  - Constable,C.J.
A1  - Fulham,M.J.
Y1  - 2002///
N1  - J
SP  - 116
EP  - 123
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 1
N2  - Methods capable of correcting for head motion in all six degrees of freedom have been proposed for positron emission tomography (PET) brain imaging but not yet demonstrated in human studies. These methods rely on the accurate measurement of head motion in relation to the reconstruction coordinate frame. We present methodology for the direct calibration of an optical motion-tracking system to the reconstruction coordinate frame using paired coordinate measurements obtained simultaneously from a PET scanner and tracking system. We also describe the implementation of motion correction, based on the multiple acquisition frame method originally described by Picard and Thompson, using data provided by the motion tracking system. Effective compensation for multiple six-degree-of-freedom movements is demonstrated in dynamic PET scans of the Hoffman brain phantom and a normal volunteer. We conclude that reduced distortion and improved quantitative accuracy can be achieved with this method in PET brain studies degraded by head movements
UR  - ISI:000175427300020
ER  - 

TY  - JOUR
T1  - A hybrid 3-D reconstruction/registration algorithm for correction of head motion in emission tomography
A1  - Hutton,B.F.
A1  - Kyme,A.Z.
A1  - Lau,Y.H.
A1  - Skerrett,D.W.
A1  - Fulton,R.R.
Y1  - 2002///
N1  - J
SP  - 188
EP  - 194
JF  - IEEE Transactions on Nuclear Science
VL  - 49
IS  - 1
N2  - Even with head restraint, small head movements can occur during data acquisition in emission tomography that are sufficiently large to result in detectable artifacts in the final reconstruction. Direct measurement of motion can be cumbersome and difficult to implement, whereas previous attempts to use the measured projection data for correction have been limited to simple translation orthogonal to the projection. A fully three-dimensional (3-D) algorithm is proposed that estimates the patient orientation based on the projection of motion-corrupted data, with incorporation of motion information within subsequent ordered-subset expectation-maximization subiterations. Preliminary studies have been performed using a digital version of the Hoffman brain phantom. Movement was simulated by constructing a mixed set of projections in discrete positions of the phantom. The algorithm determined the phantom orientation that best matched each constructed projection with its corresponding measured projection. In the case of a simulated single movement in 24 of 64 projections, all misaligned projections were correctly identified. Incorporating data at the determined object orientation resulted in a reduction of mean square difference (MSD) between motion-corrected and motion-free reconstructions, compared to the MSD between uncorrected and motion-free reconstructions, by a factor of 1.9
UR  - ISI:000175427300033
ER  - 

TY  - JOUR
T1  - Implementation and performance of an optical motion tracking system for high resolution brain PET imaging
A1  - Lopresti,B.J.
A1  - Russo,A.
A1  - Jones,W.F.
A1  - Fisher,T.
A1  - Crouch,D.G.
A1  - Altenburger,D.E.
A1  - Townsend,D.W.
Y1  - 1999///
N1  - J
SP  - 2059
EP  - 2067
JF  - IEEE Transactions on Nuclear Science
VL  - 46
IS  - 6
N2  - Head motion during PET scanning is widely regarded as a source of image degradation and resolution loss. Recent improvements in the spatial resolution of state-of-the-art tomographs may be compromised by patient motion during scanning, as these high resolution data will be increasingly susceptible to smaller movements of the head. We have developed an opto-electronic motion tracking system based on commercially-available technology that is capable of very accurate real-time measurements of the position and orientation of the patient's head. These positions are transformed to the reference frame of the PET scanner, and could potentially be used to provide motion correction of list-mode emission data on an event-by-event basis
UR  - ISI:000085058700003
ER  - 

TY  - JOUR
T1  - Compounds labelled with short-lived beta(+)-emitting radionuclides and some applications in life sciences. The importance of time as a parameter
A1  - Langstrom,B.
A1  - Kihlberg,T.
A1  - Bergstrom,M.
A1  - Antoni,G.
A1  - Bjorkman,M.
A1  - Forngren,B.H.
A1  - Forngren,T.
A1  - Hartvig,P.
A1  - Markides,K.
A1  - Yngve,U.
A1  - Ogren,M.
Y1  - 1999/09//
N1  - UI - 99416376
SP  - 651
EP  - 669
JA  - Acta Chem.Scand.
VL  - 53
IS  - 9
N2  - Some examples of recent development of the synthesis of compounds labelled with short-lived beta(+)-emitting radionuclides will be discussed with an emphasis on the importance of time in selecting a synthetic strategy. Furthermore the use of such labelled compounds to monitor certain processes in areas within the field of analytical chemistry and in various applications in drug development will be presented
AD  - Uppsala University PET Centre, Sweden
UR  - PM:10486908
ER  - 

TY  - BOOK
T1  - Radiopharmaceuticals for positron emission tomography
A1  - Stcklin,G.
A1  - Pike,V.W.
Y1  - 1993///
CY  - Dordrecht
PB  - Kluwer
ER  - 

TY  - JOUR
T1  - Quantification of human brain benzodiazepine receptors using [(18)F]fluoroethylflumazenil: a first report in volunteers and epileptic patients
A1  - Leveque,P.
A1  - Sanabria-Bohorquez,S.
A1  - Bol,A.
A1  - De Volder,A.
A1  - Labar,D.
A1  - Van Rijckevorsel,K.
A1  - Gallez,B.
Y1  - 2003/09/06/
N1  - UI - 0
JA  - Eur.J Nucl Med Mol.Imaging
VL  - epub
N2  - Fluorine-18 fluoroethylflumazenil ([(18)F]FEF) is a tracer for central benzodiazepine (BZ) receptors which is proposed as an alternative to carbon-11 flumazenil for in vivo imaging using positron emission tomography (PET) in humans. In this study, [(18)F]FEF kinetic data were acquired using a 60-min two-injection protocol on three normal subjects and two patients suffering from mesiotemporal epilepsy as demonstrated by abnormal magnetic resonance imaging and [(18)F]fluorodeoxyglucose positron emission tomography. First, a tracer bolus injection was performed and [(18)F]FEF rapidly distributed in the brain according to the known BZ receptor distribution. Thirty minutes later a displacement injection of 0.01 mg/kg of unlabelled flumazenil was performed. Activity was rapidly displaced from all BZ receptor regions demonstrating the specific binding of [(18)F]FEF. No displacement was observed in the pons. Plasma input function was obtained from arterial blood sampling, and metabolite analysis was performed by high-performance liquid chromatography. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 70% of the total radioactivity in plasma corresponded to [(18)F]FEF, reaching 24% at 30 min post injection. The interactions between [(18)F]FEF and BZ receptors were described using linear compartmental models with plasma input and reference tissue approaches. Binding potential values were in agreement with the known distribution of BZ receptors in human brain. Finally, in two patients with mesiotemporal sclerosis, reduced uptake of [(18)F]FEF was clearly observed in the implicated left hippocampus
AD  - Unite de tomographie par positrons, Universite catholique de Louvain, Louvain-la-Neuve, Belgium
UR  - PM:13680197
ER  - 

TY  - JOUR
T1  - PET/CT: a new imaging technology in nuclear medicine
A1  - Schoder,H.
A1  - Erdi,Y.E.
A1  - Larson,S.M.
A1  - Yeung,H.W.
Y1  - 2003/09/05/
N1  - UI - 0
JA  - Eur.J Nucl Med Mol.Imaging
VL  - epub
N2  - This review discusses the technical background of combined PET and CT and considers the clinical applications of PET/CT imaging. Questions addressed include: Is PET/CT superior to PET imaging alone? If so, in which patient populations and in what respect? Can PET/CT imaging affect patient management? Can PET/CT be practiced economically? While much work remains to be done, the available data clearly suggest that PET/CT decreases imaging time per patient and, even for the experienced reader, significantly reduces the number of equivocal PET interpretations. PET/CT also has the ability to improve accuracy of PET image interpretation and to affect clinical decision making, thereby improving patient management. The nuclear medicine community should approach this new technology with an open mind and focus on its clinical usefulness. The decision regarding whether PET/CT should be part of the equipment in a given nuclear medicine or radiology practice largely depends on the specific patient population. It is concluded that present skepticism concerning combined PET/CT will subside once critics of this new modality have had the opportunity to clearly see on images its many advantages compared with either PET alone or conventional image fusion approaches
AD  - Department of Radiology/Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 77, NY 10021, New York, USA
UR  - PM:12961037
ER  - 

TY  - JOUR
T1  - A PET study after treatment with an anxiety-provoking agent, m-chlorophenyl-piperazine, in conscious rhesus monkeys
A1  - Takamatsu,H.
A1  - Noda,A.
A1  - Murakami,Y.
A1  - Tatsumi,M.
A1  - Ichise,R.
A1  - Nishimura,S.
Y1  - 2003/09//
N1  - UI - 22841376
SP  - 1516
EP  - 1521
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 9
N2  - Several PET studies have been performed on conscious nonhuman primates to examine brain function. However, it is unclear how anxiety or stress during PET measurements influences brain function. In the present study, we examined the effects of a well-known anxiety-provoking agent, m-chlorophenyl-piperazine (mCPP), on regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate of glucose (rCMRglc) using PET on conscious rhesus monkeys. METHODS: Male rhesus monkeys with experience undergoing PET measurements were used. Twenty and 40 min after mCPP injection (0.2, 1.0, or 5.0 mg/kg intramuscularly; n = 5), rCBF and rCMRglc were measured using an intravenous injection of (15)O-H(2)O and (18)F-FDG, respectively. Physiologic parameters, plasma cortisol, and prolactin levels were monitored during PET measurements. RESULTS: Treatment with mCPP significantly increased rCBF in both the cingulate cortex and striatum in a dose-dependent manner, and bell-shaped reductions in rCMRglc were observed for all regions examined. mCPP also significantly increased plasma cortisol and prolactin levels. Physiologic parameters were not affected by mCPP treatment. CONCLUSION: The present study demonstrates that treatment with the anxiety-provoking agent mCPP significantly affects rCBF and rCMRglc in conscious monkeys. Therefore, since the increases in hormone levels demonstrate that mCPP treatment produced anxiety or stress, these results suggest that anxiety or stress influences conscious brain function. Furthermore, the present study suggests that prevention of anxiety or stress is important when measuring conscious brain function in monkeys
AD  - Medical and Pharmacological Research Center Foundation, Inoyama-Town, Hakui-City, Ishikawa, Japan. takamatsu@mprcf.or.jp
UR  - PM:12960201
ER  - 

TY  - JOUR
T1  - 18F-Fluorothymidine radiation dosimetry in human PET imaging studies
A1  - Vesselle,H.
A1  - Grierson,J.
A1  - Peterson,L.M.
A1  - Muzi,M.
A1  - Mankoff,D.A.
A1  - Krohn,K.A.
Y1  - 2003/09//
N1  - UI - 22841371
SP  - 1482
EP  - 1488
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 9
N2  - 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET imaging agent that shows promise for studying cellular proliferation in human cancers. FLT is a nucleoside analog that enters cells and is phosphorylated by human thymidine kinase 1, but the 3' substitution prevents further incorporation into DNA. We estimated the radiation dosimetry for this tracer from data gathered in patient studies. METHODS: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images of 18 patients after intravenous injection of (18)F-FLT. Radiation-absorbed doses were calculated using the MIRD Committee methods, taking into account variations that were based on the distribution of activities observed in the individual patients. Effective dose equivalent (EDE) was calculated using International Commission on Radiological Protection Publication 60 tissue weighting factors for the standard man and woman. RESULTS: For a single bladder voiding at 6 h after (18)F-FLT injection, the (18)F-FLT EDE (mean +/- SD) was 0.028 +/- 0.012 mSv/MBq (103 +/- 43 mrem/mCi) for a standard male patient and 0.033 +/- 0.012 mSv/MBq (121 +/- 43 mrem/mCi) for a standard female patient. The organ that received the highest dose was the bladder (male, 0.179 mGy/MBq [662 mrad/mCi]; female, 0.174 mGy/MBq [646 mrad/mCi]), followed by the liver (male, 0.045 mGy/MBq [167 mrad/mCi]; female, 0.064 mGy/MBq [238 mrad/mCi]), the kidneys (male, 0.035 mGy/MBq [131 mrad/mCi]; female, 0.042 mGy/MBq [155 mrad/mCi]), and the bone marrow (male, 0.024 mGy/MBq [89 mrad/mCi]; female, 0.033 mGy/MBq [122 mrad/mCi]). CONCLUSION: Organ dose estimates for (18)F-FLT are comparable to those associated with other commonly performed nuclear medicine tests, and the potential radiation risks associated with (18)F-FLT PET imaging are within accepted limits
AD  - Department of Radiology, Division of Nuclear Medicine, University of Washington Medical Center, Seattle, Washington 98195, USA. vesselle@u.washington.edu
UR  - PM:12960196
ER  - 

TY  - JOUR
T1  - Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG
A1  - Buck,A.K.
A1  - Halter,G.
A1  - Schirrmeister,H.
A1  - Kotzerke,J.
A1  - Wurziger,I.
A1  - Glatting,G.
A1  - Mattfeldt,T.
A1  - Neumaier,B.
A1  - Reske,S.N.
A1  - Hetzel,M.
Y1  - 2003/09//
N1  - UI - 22841362
SP  - 1426
EP  - 1431
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 44
IS  - 9
N2  - Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG. METHODS: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis. RESULTS: Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions. CONCLUSION: (18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation
AD  - Department of Nuclear Medicine, University of Ulm, Ulm, Germany. andreas.buck@medizin.uni-ulm.de
UR  - PM:12960187
ER  - 

TY  - JOUR
T1  - Synthesis of 2'-deoxy-2'-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU
A1  - Mangner,T.J.
A1  - Klecker,R.W.
A1  - Anderson,L.
A1  - Shields,A.F.
Y1  - 2003/04//
N1  - UI - 22631426
SP  - 215
EP  - 224
JA  - Nucl Med Biol.
VL  - 30
IS  - 3
N2  - An efficient and reliable synthesis of 2'-deoxy-2'-[(18)F]fluoro-beta-D-arabinofuranosyl nucleosides is presented. Overall decay-corrected radiochemical yields of 35-45% of 4 analogs, FAU, FMAU, FBAU and FIAU are routinely obtained in >98% radiochemical purity and with specific activities of greater than 3 Ci/micromol (110 MBq/micromol) in a synthesis time of approximately 3 hours. When approximately 220 mCi (8.15 GBq) of starting [(18)F]fluoride is used, 25 -30 mCi (0.93 -1.11 GBq) of product (enough to image two patients sequentially) is typically obtained
AD  - Children's Hospital of Michigan, PET Center, Wayne State University, Detroit, MI 48201, USA. tmangner@pet.wayne.edu
UR  - PM:12745012
ER  - 

TY  - JOUR
T1  - Use of 5-[(76)Br]bromo-2'-fluoro-2'-deoxyuridine as a ligand for tumour proliferation: validation in an animal tumour model
A1  - Borbath,I.
A1  - Gregoire,V.
A1  - Bergstrom,M.
A1  - Laryea,D.
A1  - Langstrom,B.
A1  - Pauwels,S.
Y1  - 2002/01//
N1  - UI - 21665936
SP  - 19
EP  - 27
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 29
IS  - 1
N2  - Uncontrolled cell proliferation is one of the prominent features in cancer development. Precise tools are needed for determination of the proliferation rate before, during and after treatment, thereby permitting assessment of treatment efficacy. The purpose of this study was to validate the use of 5-[(76)Br]bromo-2'-fluoro-2'-deoxyuridine ((76)Br-BFU) as a proliferation marker in an animal tumour model. Comparison was made with 2-[(14)C]thymidine ((14)C-TdR) incorporation and the labelling index assessed by bromodeoxyuridine (BrdUrd-LI). Fibrosarcoma (NFSA)-bearing mice were used for all experiments. Gemcitabine (dFdC), a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. dFdC was injected intraperitoneally at a dose of 0.5 mg/kg or 40 mg/kg to induce partial ( approximately 50%) or complete inhibition of DNA synthesis, respectively. (76)Br-BFU (0.5-3 MBq per animal), (14)C-TdR (37-74 kBq per animal) and cold BrdUrd (60 mg/kg) were injected intraperitoneally in combination or alone. Animals were sacrificed at various times after tracer administration, and tumour and small intestine were removed for determination of radioactivity in whole tissue and the DNA fraction, as well as for LI assessment by flow cytometry. Cimetidine (6 mg/kg) was used to decrease (76)Br-BFU elimination and increase its bioavailability. The fraction of radioactivity associated with DNA increased with the time interval between tracer injection and tissue removal. At 6 h after injection, for both tracers, more than 95% of the radioactivity in the tumours was associated with the DNA fraction and an excellent correlation was observed with the LI. Similar findings were observed in the small intestine. Under all experimental conditions, (76)Br-BFU uptake was 4-10 times lower than (14)C-TdR uptake. Co-injection of cimetidine resulted in a three- to fourfold increase in (76)Br-BFU incorporation without affecting the effect of dFdC on DNA synthesis. (76)Br-BFU is a potentially good tracer for the assessment of tumour proliferation. It has all the specifications required of a PET tracer for clinical use. One limitation to its use is the necessity of co-injecting cimetidine to increase its bioavailability and hence its sensitivity for PET detection
AD  - Department of Nuclear Medicine, Catholic University of Louvain, Brussels, Belgium
UR  - PM:11807603
ER  - 

TY  - JOUR
T1  - Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression
A1  - Yaghoubi,S.
A1  - Barrio,J.R.
A1  - Dahlbom,M.
A1  - Iyer,M.
A1  - Namavari,M.
A1  - Satyamurthy,N.
A1  - Goldman,R.
A1  - Herschman,H.R.
A1  - Phelps,M.E.
A1  - Gambhir,S.S.
Y1  - 2001/08//
N1  - UI - 21376326
SP  - 1225
EP  - 1234
JF  - The Journal of Nuclear Medicine
JA  - J Nucl Med
VL  - 42
IS  - 8
N2  - 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals. Our aim was to study the kinetics, biodistribution, stability, dosimetry, and safety of [(18)F]FHBG in healthy human volunteers, preparatory to imaging patients undergoing HSV1-tk gene therapy. METHODS: [(18)F]FHBG was synthesized with a specific activity of 37,000--444,000 GBq/mmol and a radiochemical purity > 99%. Ten healthy volunteers consented to participate in the study. A transmission scan was obtained before bolus injection of 70.3--229.4 MBq [(18)F]FHBG into a hand vein, followed by dynamic PET imaging with 4 consecutive emission scans. Warmed hand-vein blood was withdrawn at various times after injection for blood time--activity measurements. Electrocardiography, blood pressure, and blood and urine pharmacologic parameters were measured before and after injection of the [(18)F]FHBG tracer (n = 5). The stability of [(18)F]FHBG in the urine was analyzed. Attenuation-corrected images were reconstructed using the ordered-subsets expectation maximization algorithm. Image region-of-interest time-activity data were used with the MIRD program to estimate absorbed radiation dosages. RESULTS: [(18)F]FHBG had rapid blood clearance; only 8.42% +/- 4.76% (mean +/- SD) of the peak blood activity remained at approximately 30 min. The average ratio of plasma activity to whole-blood activity during the study was 0.91 +/- 0.04. Penetration of [(18)F]FHBG across the blood-brain barrier was not observed. The primary routes of clearance were renal and hepatobiliary. High activities were observed in the bladder, gut, liver, and kidneys, but <0.0002% of the injected dose per gram was observed in other tissues. In the urine, 83% of activity 180 min after injection was stable [(18)F]FHBG. Blood and urine pharmacologic parameters did not change significantly after injection of the [(18)F]FHBG tracer. The bladder absorbed the highest radiation dose. CONCLUSION: [(18)F]FHBG has the desirable in vivo characteristics of stability, rapid blood clearance, low background signal, biosafety, and acceptable radiation dosimetry in humans. This study forms the foundation for using [(18)F]FHBG in applications to monitor HSV1-tk reporter gene expression
AD  - Crump Institute for Molecular Imaging, UCLA--DOE Laboratory of Structural Biology and Molecular Medicine, UCLA School of Medicine, University of California, Los Angeles, 90095-1770, USA
UR  - PM:11483684
ER  - 

TY  - JOUR
T1  - Predominant ventromedial frontopolar metabolic impairment in frontotemporal dementia
A1  - Salmon,Eric
A1  - Garraux,Gaetan
A1  - Delbeuck,Xavier
A1  - Collette,Fabienne
A1  - Kalbe,Elke
A1  - Zuendorf,Gerhard
A1  - Perani,Daniela
A1  - Fazio,Ferruccio
A1  - Herholz,Karl
Y1  - 2003/09//
SP  - 435
EP  - 440
JF  - Neuroimage
VL  - 20
IS  - 1
N2  - In a multicenter study, FDG-PET images in a population of 29 patients with frontotemporal dementia (FTD) were compared to controls with similar age from each center. A conjunction analysis led to identification of the ventromedial frontopolar cortex as the single region affected in each and every FTD patients. This precise regional metabolic impairment should be integrated with recent neuropsychological researches, such as those showing that the ventromedial frontal cortex is critically involved in decision-making processes based on personal experience, feelings of rightness or social knowledge, processes that are characteristically impaired in FTD
UR  - http://www.sciencedirect.com/science/article/B6WNP-4991PTP-G/2/c9ddedd4a385ae70e864a7785d72345b
ER  - 

TY  - JOUR
T1  - Gliomatosis cerebri evaluated by 18F-alpha-methyl tyrosine positron-emission tomography
A1  - Sato,N.
A1  - Inoue,T.
A1  - Tomiyoshi,K.
A1  - Aoki,J.
A1  - Oriuchi,N.
A1  - Takahashi,A.
A1  - Otani,T.
A1  - Kurihara,H.
A1  - Sasaki,T.
A1  - Endo,K.
Y1  - 2003/09/13/
N1  - UI - 0
JF  - Neuroradiology
VL  - epub
N2  - Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-(18)F] alpha-methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P<0.01), and between the T/N ratio of FMT and FDG in patients ( P<0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement
AD  - Department of Diagnostic Radiology, Gunma University School of Medicine, 3-39-15 Shouwa-machi, Maebashi, 371-8511, Gunma, Japan
UR  - PM:13680026
ER  - 

TY  - JOUR
T1  - Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood
A1  - Pfund,Z.
A1  - Chugani,D.C.
A1  - Muzik,O.
A1  - Juhasz,C.
A1  - Behen,M.E.
A1  - Lee,J.
A1  - Chakraborty,P.
A1  - Mangner,T.
A1  - Chugani,H.T.
Y1  - 2002/04//
N1  - UI - 22082610
SP  - 253
EP  - 260
JA  - J Child Neurol
VL  - 17
IS  - 4
N2  - Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood. Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 7 6/12 years) using alpha[11C]methyl-L-tryptophan positron emission tomography (PET). The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient. The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 7 8/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 9 11/12 years). Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally. The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks. In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity. Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group. There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042). These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood. Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder
AD  - Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA
UR  - PM:12088079
ER  - 

TY  - JOUR
T1  - 5HT2 receptors in cerebral cortex of migraineurs studied using PET and 18F-fluorosetoperone
A1  - Chabriat,H.
A1  - Tehindrazanarivelo,A.
A1  - Vera,P.
A1  - Samson,Y.
A1  - Pappata,S.
A1  - Boullais,N.
A1  - Bousser,M.G.
Y1  - 1995/04//
N1  - UI - 95368688
SP  - 104
EP  - 108
JF  - Cephalalgia
VL  - 15
IS  - 2
N2  - Since the brain 5HT2 receptors might be implicated in migraine pathogenesis, we have used positron emission tomography and 18F-fluorosetoperone, a 5HT2 specific radioligand, to investigate in vivo the cortical 5HT2 receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura (n = 5) or only migraine without aura (n = 4) were studied between attacks. Twelve unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after 18F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT2 receptors may be unaltered between attacks in migraine sufferers
AD  - Service Hospitalier Frederic Joliot, Orsay, France
UR  - PM:7641243
ER  - 

TY  - JOUR
T1  - Migraine
A1  - Ferrari,M.D.
Y1  - 1998/04/04/
N1  - UI - 98206602
SP  - 1043
EP  - 1051
JF  - Lancet
VL  - 351
IS  - 9108
AD  - Department of Neurology, Leiden University Medical Centre, Netherlands. mferrari@neurology.azl.nl
UR  - PM:9546526
ER  - 

TY  - JOUR
T1  - Dopamine D2 receptors quantified in vivo in human narcolepsy
A1  - MacFarlane,J.G.
A1  - List,S.J.
A1  - Moldofsky,H.
A1  - Firnau,G.
A1  - Chen,J.J.
A1  - Szechtman,H.
A1  - Garnett,S.
A1  - Nahmias,C.
Y1  - 1997/02/01/
N1  - UI - 97177428
SP  - 305
EP  - 310
JA  - Biol.Psychiatry
VL  - 41
IS  - 3
N2  - Assays in brain tissues from humans suffering from narcolepsy, and from genetically narcoleptic dogs have suggested that dopamine function may be disturbed in this condition. We have used the specific D2 receptor ligand N-(3-[18F]fluoropropyl)-spiperone and positron tomography to study a group of 6 well-characterized medication-free, HLA-DR2 DRW15 DW6-positive narcoleptic patients and a group of age- and sex-matched control individuals during life. We found no difference in striatal D2 receptor binding between these two groups. These results suggest that narcolepsy is not associated with alterations in D2 receptor density and affinity
AD  - Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada
UR  - PM:9024953
ER  - 

TY  - JOUR
T1  - Striatal dopamine D1 receptors in narcolepsy: a PET study with [11C]NNC 756
A1  - Rinne,J.O.
A1  - Hublin,C.
A1  - Partinen,M.
A1  - Ruottinen,H.
A1  - Nagren,K.
A1  - Lehikoinen,P.
A1  - Ruotsalainen,U.
A1  - Laihinen,A.
Y1  - 1996/12//
N1  - UI - 97218441
SP  - 262
EP  - 264
JA  - J Sleep Res
VL  - 5
IS  - 4
N2  - We investigated dopamine D1 receptors in the putamen and caudate nucleus with positron emission tomography in six patients with narcolepsy and five healthy controls using [11C]NNC 756 as ligand. The caudate-to-cerebellum and putamen-to-cerebellum ratios of [11C]NNC 756 were within normal limits in patients with narcolepsy. No evidence of increased D1 receptor binding in narcolepsy was found
AD  - Department of Neurology, University of Turku, Finland
UR  - PM:9065878
ER  - 

TY  - JOUR
T1  - The neurobiology, diagnosis, and treatment of narcolepsy
A1  - Scammell,T.E.
Y1  - 2003/02//
N1  - UI - 22444014
SP  - 154
EP  - 166
JA  - Ann.Neurol
VL  - 53
IS  - 2
N2  - Narcolepsy is a common cause of chronic sleepiness distinguished by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy and hallucinations. Recent advances provide compelling evidence that narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the neuropeptide orexin (also known as hypocretin). Because orexin promotes wakefulness and inhibits rapid eye movement sleep, its absence may permit inappropriate transitions between wakefulness and sleep. These discoveries have considerably improved our understanding of the neurobiology of sleep and should foster the development of rational treatments for a variety of sleep disorders
AD  - Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. tscammel@caregroup.harvard.edu
UR  - PM:12557281
ER  - 

TY  - JOUR
T1  - Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-{beta} ligand in transgenic mice
A1  - Bacskai,Brian J.
A1  - Hickey,Gregory A.
A1  - Skoch,Jesse
A1  - Kajdasz,Stephen T.
A1  - Wang,Yanming
A1  - Huang,Guo feng
A1  - Mathis,Chester A.
A1  - Klunk,William E.
A1  - Hyman,Bradley T.
Y1  - 2003/09/29/
SP  - 2034101100
JF  - Proceedings of the National Academy of Sciences
JA  - PNAS
VL  - epub
N2  - Edited by L. L. Iversen, University of Oxford, Oxford, United Kingdom, and approved August 13, 2003 (received for review July 2, 2003)The lack of a specific biomarker makes preclinical diagnosis of Alzheimer's disease (AD) impossible, and it precludes assessment of therapies aimed at preventing or reversing the course of the disease. The development of a tool that enables direct, quantitative detection of the amyloid-{beta} deposits found in the disease would provide an excellent biomarker. This article demonstrates the real-time biodistribution kinetics of an imaging agent in transgenic mouse models of AD. Using multiphoton microscopy, Pittsburgh compound B (PIB) was imaged with sub-{micro}m resolution in the brains of living transgenic mice during peripheral administration. PIB entered the brain quickly and labeled amyloid deposits within minutes. The nonspecific binding was cleared rapidly, whereas specific labeling was prolonged. WT mice showed rapid brain entry and clearance of PIB without any binding. These results demonstrate that the compound PIB has the properties required for a good amyloid-imaging agent in humans with or at risk for AD
UR  - http://www.pnas.org/cgi/content/abstract/2034101100v1
ER  - 

TY  - JOUR
T1  - Synthesis and evaluation of C-11-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents
A1  - Mathis,C.A.
A1  - Wang,Y.M.
A1  - Holt,D.P.
A1  - Huang,G.F.
A1  - Debnath,M.L.
A1  - Klunk,W.E.
Y1  - 2003///
N1  - J
SP  - 2740
EP  - 2754
JF  - Journal of Medicinal Chemistry
VL  - 46
IS  - 13
N2  - The synthesis and evaluation of a series of neutral analogues of thioflavin-T (termed BTA's) with high affinities for aggregated amyloid and a wide range of lipophilicities are reported. Radiolabeling with high specific activity [C-11]methyl iodide provided derivatives for in vivo evaluation. Brain entry in control mice and baboons was high for nearly all of the analogues at early times after injection, but the clearance rate of radioactivity from brain tissue varied by more than 1 order of magnitude. Upon the basis of its rapid clearance from normal mouse and baboon brain tissues, [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [C-11]6-OH-BTA-1) was selected as the lead compound for further evaluation. The radiolabeled metabolites of [C-11]6-OH-BTA-1 were polar and did not enter brain. The binding affinities of [N-methyl-H-3]6-OH-BTA-1 for homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils, were similar (K-d = 1.4 nM and 4.7 nM, respectively), but the ligand-to-Abeta peptide binding stoichiometry was similar to400-fold higher for AD brain than Abeta(1-40) fibrils. Staining of AD frontal cortex tissue sections with 6-OH-BTA-1 indicated the selective binding of the compound to amyloid plaques and cerebrovascular amyloid. The encouraging in vitro and in vivo properties of [C-11]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition
UR  - ISI:000183511500020
ER  - 

TY  - JOUR
T1  - Detection of amyloid plaques by radioligands for A beta 40 and A beta 42 - Potential imaging agents in Alzheimer's patients
A1  - Kung,M.P.
A1  - Skovronsky,D.M.
A1  - Hou,C.
A1  - Zhuang,Z.P.
A1  - Gur,T.L.
A1  - Zhang,B.
A1  - Trojanowski,J.Q.
A1  - Lee,V.M.Y.
A1  - Kung,K.F.
Y1  - 2003///
N1  - J
SP  - 15
EP  - 23
JF  - Journal of Molecular Neuroscience
VL  - 20
IS  - 1
N2  - Alzheimer's disease (AD) is linked to increased brain deposition of amyloid-beta (Abeta) peptides in senile plaques (SPs), and recent therapeutic efforts have focused on inhibiting the production or enhancing the clearance of Abeta in brain. However, it has not been possible to measure the burden of SPs or assess the effect of potential therapies on brain Abeta levels in patients. Toward that end, we have developed a novel radioligand, [I-125]TZDM, which binds Abeta fibrils with high affinity, crosses the blood-brain barrier (BBB), and labels amyloid plaques in vivo. Compared to a styrylbenzene probe, [I-125]IMSB, [I-125]TZDM showed a 10-fold greater brain penetration and labeled plaques with higher sensitivity for in vivo imaging. However, this ligand also labels white matter, which contributes to undesirable high background regions of the brain. Interestingly, parallel to their differential binding characteristics onto fibrils composed of 40 (Abeta40)- or 42 (Abeta42)-amino-acid-long forms of Abeta peptides, these radioligands displayed differential labeling of SPs in AD brain sections under our experimental conditions. It was observed that [I-125]IMSB labeled SPs containing Abeta40, amyloid angiopathy (AA), and neurofibrillary tangles, whereas [I-125]TZDM detected only SPs and Abeta42-positive AA. Since increased production and deposition of Abeta42 relative to Abeta40 may be crucial for the generation of SPs, [I-125]TZDM and related derivatives may be more attractive probes for in vivo plaque labeling. Further structural modifications of TZDM to lower the background labeling will be needed to optimize the plaque-labeling property
UR  - ISI:000182000400002
ER  - 

TY  - JOUR
T1  - Structure-activity relationship of imidazo[1,2-alpha]pyridines as ligands for detecting beta-amyloid plaques in the brain
A1  - Zhuang,Z.P.
A1  - Kung,M.P.
A1  - Wilson,A.
A1  - Lee,C.W.
A1  - Plossl,K.
A1  - Hou,C.
A1  - Holtzman,D.M.
A1  - Kung,H.F.
Y1  - 2003///
N1  - J
SP  - 237
EP  - 243
JF  - Journal of Medicinal Chemistry
VL  - 46
IS  - 2
N2  - A series of novel beta-amyloid (Abeta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-alpha]pyridine, (IMPY), and its related derivatives were prepared. An in vitro binding study with preformed Abeta aggregates showed that 16(IMPY) and its bromo derivative competed with binding of 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [I-125]7(TZDM), a known ligand for Abeta aggregates, with high binding affinities (K-i = 15 and 10 nM, respectively). In vitro autoradiography of brain sections of a transgenic mouse (Tg2576) with [I-125]16(IMPY) displayed high selective binding to amyloid-like structures, comparable to that observed by staining with thioflavin-S visualized under fluorescence. In vivo biodistribution after an intravenous injection of [I-125]16(IMPY) in normal mice showed a high initial brain uptake and fast washout, indicating a low background activity associated with this iodinated ligand. Taken together, the data suggests that [I-123]16(IMPY) may be useful for imaging Abeta aggregates in patients with Alzheimer's disease
UR  - ISI:000180307000007
ER  - 

TY  - JOUR
T1  - IMPY: an improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques
A1  - Kung,M.P.
A1  - Hou,C.
A1  - Zhuang,Z.P.
A1  - Zhang,B.
A1  - Skovronsky,D.
A1  - Trojanowski,J.Q.
A1  - Lee,V.M.Y.
A1  - Kung,H.F.
Y1  - 2002///
N1  - J
SP  - 202
EP  - 210
JF  - Brain Research
VL  - 956
IS  - 2
N2  - Development of small molecular probes for in vivo labeling and detection of beta-amyloid (Abeta) plaques in patients of Alzheimer's disease (AD) is of significant scientific interest, and it may also assist the development of drugs targeting Abeta plaques for treatment of AD. A novel probe, [I-123/I-125]IMPY, 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo [1,2-a]pyridine, was successfully prepared with an iododestannylation reaction catalyzed by hydrogen peroxide. The modified thioflavin-T derivative displayed a good binding affinity for preformed synthetic Abeta40 aggregates in solution (K-i = 15+/-5 nM) and showed selective plaque labeling on postmortem AD brain sections. Biodistribution study in normal mice after an iv injection of [I-125]IMPY exhibited excellent brain uptake (2.9% initial dose/brain at 2 min) and fast washout (0.2% initial dose/brain at 60 min). These properties are highly desirable for amyloid plaque imaging agents. In vivo plaque labeling was evaluated in a transgenic mouse model (Tg2576) engineered to produce excess amyloid plaques in the brain. Ex vivo autoradiograms of brain sections of the Tg 2576 mouse obtained at 4 h after an i.v. injection of [I-125]IMPY clearly displayed a distinct plaque labeling with a low background activity. When the same brain section was stained with a fluorescent dye, thioflavin-S, the same Abeta plaques showed prominent fluorescent labeling consistent with the results of the autoradiogram. In conclusion, these findings clearly suggest that radioiodinated IMPY demonstrates desirable characteristics for in vivo labeling of Abeta plaques and it may be useful as a molecular imaging agent to study amyloidogenesis in the brain of living AD patients. (C) 2002 Elsevier Science B.V. All rights reserved
UR  - ISI:000179621000003
ER  - 

TY  - JOUR
T1  - Discordance between cerebral oxygen and glucose metabolism, and hemodynamics in a mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode patient
A1  - Nariai,T.
A1  - Ohno,K.
A1  - Ohta,Y.
A1  - Hirakawa,K.
A1  - Ishii,K.
A1  - Senda,M.
Y1  - 2001/07//
N1  - UI - 21355518
SP  - 325
EP  - 329
JA  - J Neuroimaging
VL  - 11
IS  - 3
N2  - A patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode (MELAS) syndrome underwent serial measurement of cerebral blood flow with xenon computed tomography (Xe-CBF) while presenting with strokelike episodes accompanied by a cerebral lesion. He underwent positron emission tomography (PET) measurement of the regional cerebral blood flow (PET-CBF), metabolic rate of oxygen (CMRO2), and glucose (CMRGlu) after his symptoms and lesion disappeared. During the symptomatic period, Xe-CBF and the Xe-CBF response to acetazolamide loading were well preserved both in and outside the low-density lesion. In the PET study, decreased CMRO2 and increased PET-CBF and CMRGlu were noted in the entire brain. The strokelike episodes of patients with MELAS are more likely attributed to the failure of oxygen metabolism than to a vascular accident
AD  - Neurosurgical Section, Brain Medical Science Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. nariai.nsrg@tmd.ac.jp
UR  - PM:11462305
ER  - 

TY  - JOUR
T1  - Adenosine A(2A) receptor imaging with [C-11]KF18446 PET in the rat brain after quinolinic acid lesion: Comparison with the dopamine receptor imaging
A1  - Ishiwata,K.
A1  - Ogi,N.
A1  - Hayakawa,N.
A1  - Oda,K.
A1  - Nagaoka,T.
A1  - Toyama,H.
A1  - Suzuki,F.
A1  - Endo,K.
A1  - Tanaka,A.
A1  - Senda,M.
Y1  - 2002///
N1  - J
SP  - 467
EP  - 475
JF  - Annals of Nuclear Medicine
VL  - 16
IS  - 7
N2  - We proposed [C-11]KF18446 as a selective radioligand for mapping the adenosine A(2A) receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [ I I C] KF 18446 PET can detect the change in the striatal adenosine A2A receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [C-11]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [C-11]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [(11C)]raclopride binding to dopamine D-2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [C-11]SCH 23390 binding to dopamine D-1 receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that (C-11]KF18446 PET can detect change in the adenosine A(2A) receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum
UR  - ISI:000179724100005
ER  - 

TY  - JOUR
T1  - Preclinical studies on [C-11]MPDX for mapping adenosine A(1) receptors by positron emission tomography
A1  - Ishiwata,K.
A1  - Nariai,T.
A1  - Kimura,Y.
A1  - Oda,K.
A1  - Kawamura,K.
A1  - Ishii,K.
A1  - Senda,M.
A1  - Wakabayashi,S.
A1  - Shimada,J.
Y1  - 2002///
N1  - J
SP  - 377
EP  - 382
JF  - Annals of Nuclear Medicine
VL  - 16
IS  - 6
N2  - In previous in vivo studies with mice, rats and cats, we have demonstrated that [C-11]MPDX ([1-methyl- C-11]8-dicyclopropylmethyl-1-methyl-3-propylxanthine) is a potential radioligand for mapping adenosine A(1) receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. The radiation absorbed-dose by [C-11]MPDX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of MPDX were not found. The monkey brain was clearly visualized by PET with [C-11]MPDX. We have concluded that [C-11]MPDX is suitable for mapping adenosine A(1) receptors in the human brain by PET
UR  - ISI:000178670300002
ER  - 

TY  - JOUR
T1  - In vivo imaging of adenosine A(1) receptors in the human brain with [F-18]CPFPX and positron emission tomography
A1  - Bauer,A.
A1  - Holschbach,M.H.
A1  - Meyer,P.T.
A1  - Boy,C.
A1  - Herzog,H.
A1  - Olsson,R.A.
A1  - Coenen,H.H.
A1  - Zilles,K.
Y1  - 2003///
N1  - J
SP  - 1760
EP  - 1769
JF  - Neuroimage
VL  - 19
IS  - 4
N2  - The important roles played by the A(1) adenosine receptor (A(1)AR) in brain physiology and pathology make this receptor a target for in vivo imaging. Here we describe the distribution of A(1)ARs in the living human brain with PET, made possible for the first time by the highly potent and selective A(1)AR antagonist 8-cyclopentyl-3-(3-[F-18]fluoropropyl)-1-propylxanthine ([F-18]CPFPX). In vivo data demonstrate a rapid cerebral uptake, peaking at 2.9 +/- 0.6% injected dose/liter at 3.3 +/- 1.3 min, followed by a gradual washout. Consistent with the results of autoradiography, high receptor densities occurred in the putamen and the mediodorsal thalamus. Neocortical regions showed regional differences in [F-18]CPFPX binding, with high accumulation in temporal > occipital > parietal > frontal lobes and a lower level of binding in the sensorimotor cortex. Ligand accumulation was low in cerebellum, midbrain, and brain stem. Metabolism of [18 F]CPFPX is rapid outside the central nervous system, but the metabolites do not penetrate the blood-brain barrier. In conclusion, in vivo application of [F-18]CPFPX, a highly potent and selective PET ligand, for the first time allows the imaging of A(1)ARs in the living human brain. (C) 2003 Elsevier Science (USA). All rights reserved
UR  - ISI:000185079000045
ER  - 

TY  - JOUR
T1  - Preview of a new trial of extracranial-to-intracranial arterial anastomosis: the carotid occlusion surgery study
A1  - Adams,H.P.,Jr.
A1  - Powers,W.J.
A1  - Grubb,R.L.,Jr.
A1  - Clarke,W.R.
A1  - Woolson,R.F.
Y1  - 2001/07//
N1  - UI - 21287029
SP  - 613
EP  - 624
JA  - Neurosurg Clin.N Am
VL  - 12
IS  - 3
N2  - In 1985, the International Study of Extracranial-to-Intracranial Arterial Anastomosis demonstrated no benefit from extracranial-to-intracranial arterial bypass operations in treatment of patients with extensive cerebrovascular disease including those with occlusions of the internal carotid artery. Interest in the potential use of extracranial-to-intracranial arterial bypass operations, however, has been rekindled by evidence that some patients with occlusion of the internal carotid artery have a poor collateral circulation and a high risk for recurrent ischemic events. Other patients with adequate perfusion after occlusion have a low likelihood for recurrent stroke. Restricting surgical treatment to only those patients judged to have a high risk for recurrent stroke might improve the usefulness of the bypass operation. A new clinical trial is proposed, testing the potential usefulness of extracranial-to-intracranial arterial bypass operations for treatment of carefully selected patients with occlusion of the internal carotid artery. Several issues that are being addressed in this new trial are described in this article
AD  - Division of Cerebrovascular Diseases, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. harold-adams@uiowa.edu
UR  - PM:11390318
ER  - 

TY  - JOUR
T1  - Transcortical aphasia. Importance of the nonspeech dominant hemisphere in language repetition
A1  - Berthier,M.L.
A1  - Starkstein,S.E.
A1  - Leiguarda,R.
A1  - Ruiz,A.
A1  - Mayberg,H.S.
A1  - Wagner,H.
A1  - Price,T.R.
A1  - Robinson,R.G.
Y1  - 1991/06//
N1  - UI - 91292361
SP  - 1409
EP  - 1427
JF  - Brain
VL  - 114 ( Pt 3)
N2  - While a relative preservation of repetition in acute transcortical aphasia (TA) has usually been associated with the functional integrity of the speech dominant (left) perisylvian area, recent amytal data (Bando et al., 1986) have suggested a fundamental role of the nondominant (right) hemisphere in language repetition. The neuroradiological correlates of repetition were studied in a consecutive series of 21 patients with acute TA. A similar frequency of either perisylvian or extraperisylvian pathology was found. In 2 patients with perisylvian pathology, the injection of amytal in the hemisphere contralateral to the lesion abolished repetition. Positron emission tomography (PET) in another patient revealed marked hypometabolism over the entire left cortical mantle ipsilateral to a basal ganglia lesion, suggesting that preserved repetition was carried out by right hemisphere structures. This was confirmed in a second patient with left extraperisylvian pathology, in whom a second lesion in the right hemisphere resulted in impaired repetition. These findings suggest that the spared contralateral hemisphere may subserve residual repetition in some transcortical aphasic patients with a lesion within or outside the speech-dominant perisylvian area
AD  - Institute of Neurological Research Dr Raul Carrea, Buenos Aires, Argentina
UR  - PM:2065258
ER  - 

TY  - JOUR
T1  - Regional increases in [11C]flumazenil binding after epilepsy surgery
A1  - Savic,I.
A1  - Blomqvist,G.
A1  - Halldin,C.
A1  - Litton,J.E.
A1  - Gulyas,B.
Y1  - 1998/05//
N1  - UI - 98273611
SP  - 279
EP  - 286
JA  - Acta Neurol Scand.
VL  - 97
IS  - 5
N2  - INTRODUCTION: Animal experiments suggest that epileptic seizures alter the expression of mRNA for neuro-receptors. PET measurements with [11C]flumazenil show that patients with partial seizures have a reduced density of benzodiazepine (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for seizure activity, the so called projection areas. Recent data suggest that the degree of BZ receptor reduction in ER is correlated to seizure frequency. We therefore hypothesized that seizure activity can alter the BZ receptor binding, and that some of these changes could normalize when the seizures disappeared. METHODS: In 4 patients whose seizures were generated by mesial temporal lobe structures, BZ receptor density was measured with [11C]flumazenil PET before, and 1 year after the epilepsy surgery and cessation of seizures. By use of a computerized anatomical brain atlas the same regions were analyzed in both PET scans, and the results related to data from 7 healthy controls. RESULTS: Presurgical PET scans showed reductions in BZ receptor density in the epileptogenic region and some of its primary projection areas. Other cortical regions had normal values. Postsurgically, the calculated BZ receptor density normalized (29+/-17% increase) in several of the affected projection areas, whereas the values in other cortical regions remained unaltered. CONCLUSION: Regional reductions in BZ receptor density may be dynamic and related to seizures. The present preliminary observations encourage further studies on seizure-related changes in regional receptor binding in humans
AD  - Karolinska Institute, Dept of Neurology, Huddinge Hospital, Sweden
UR  - PM:9613555
ER  - 

TY  - JOUR
T1  - Localized cerebellar reductions in benzodiazepine receptor density in human partial epilepsy
A1  - Savic,I.
A1  - Thorell,J.O.
Y1  - 1996/07//
SP  - 656
EP  - 662
JA  - Arch Neurol
VL  - 53
IS  - 7
N2  - BACKGROUND: Previous studies suggest that the morphological substrate for cerebellar dysfunction is destruction of Purkinje cells, but disagree on whether this is caused by seizure- or drug-related toxicity. The benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbon 11 is a sensitive marker of Purkinje cells. OBJECTIVE: To investigate whether cerebellar dysfunction in partial epilepsy is related to seizures through cerebrocerebellar connections. DESIGN: Positron emission tomography with [11C] flumazenil was conducted in 5 patients with frontal lobe seizures, 12 patients with mesial temporal lobe seizures, and 7 healthy men. Eight patients also had [18F]-fluorodeoxyglucose positron emission tomography. Cerebellar regions of interest were delineated using magnetic resonance imaging and a computerized anatomical brain atlas, and the epileptogenic regions were determined with a multimethod assessment. RESULTS: Patients with frontal lobe seizures had a significantly reduced BZ receptor density in the anterior cerebellum contralateral to the seizure onset region (P < or = .001), 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterior) cerebellum (P < or = .001 for both). No significant asymmetries were found in regional glucose metabolism. CONCLUSIONS: The observed distribution of BZ receptor reductions is congruent with animal experiments showing tht frontal lobe projections to the cerebellum are crossed, whereas projections from mesial temporal loe are predominantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the gamma-aminobutyric BZ system
AD  - Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:8929173
ER  - 

TY  - JOUR
T1  - [11C]flumazenil positron emission tomography visualizes frontal epileptogenic regions
A1  - Savic,I.
A1  - Thorell,J.O.
A1  - Roland,P.
Y1  - 1995/12//
N1  - UI - 96082230
SP  - 1225
EP  - 1232
JF  - Epilepsia
VL  - 36
IS  - 12
N2  - Presently available noninvasive methods correctly localize epileptogenic regions in only approximately 50% of patients with frontal lobe epilepsy (FLE). Earlier studies have shown that temporal lobe epileptogenic regions may be identified readily by positron emission tomography (PET) measurements of regional benzodiazepine (BZD) receptor binding. We tested the specific applicability of this method in patients with FLE. Six patients with frontal partial seizures and 7 healthy men were investigated with PET and the BZD receptor ligand [11C]flumazenil. All patients had magnetic resonance (MR) brain scans. The independent assessment of seizure-onset region was based on seizure semiology, intra- and extracranial EEG and, in 4 cases, also on [18F]fluorodeoxyglucose (FDG)-PET. The epileptic focus/seizure-generating region was correctly identified by [11C]flumazenil PET in all patients. This region was characterized by a significant reduction in BZD receptor density. The area with reduced BZD receptor density was better delimited than the corresponding hypometabolic region, which was observed in 50% of patients investigated with [18F]FDG-PET. MRI was normal in 5 patients. Visualization of BZD receptors with [11C]flumazenil PET appears to be a promising approach for noninvasive identification of frontal lobe epileptogenic regions
AD  - Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
UR  - PM:7489700
ER  - 

TY  - JOUR
T1  - Markedly increased mesiotemporal lobe metabolism in a case with PLEDs: further evidence that PLEDs are a manifestation of partial status epilepticus
A1  - Handforth,A.
A1  - Cheng,J.T.
A1  - Mandelkern,M.A.
A1  - Treiman,D.M.
Y1  - 1994/07//
N1  - UI - 94364320
SP  - 876
EP  - 881
JF  - Epilepsia
VL  - 35
IS  - 4
N2  - The pathophysiologic and clinical significance of periodic lateralized epileptiform discharges (PLEDs) is unclear; whether PLEDs represent an ictal condition that should be treated remains uncertain. We performed FDG-positron emission computed tomography (FDG-PET) in a patient with PLEDs at 3 days, 18 days, and 10 weeks after onset. During left temporal PLEDs, the initial scan showed intense hypermetabolism of the left mesiotemporal region. The second scan, performed when PLEDs were resolving, displayed reduced hypermetabolism. The follow-up scan, when PLEDs had resolved, showed left temporal hypometabolism. These findings, together with clinical evidence from the literature, are compatible with the interpretation that PLEDs represent partial status epilepticus (SE); whether vigorous therapy is required to prevent neuronal damage from this focal seizure activity remains uncertain
AD  - Neurology Division, Department of Veterans Affairs Medical Center, West Los Angeles, CA 90073
UR  - PM:8082637
ER  - 

TY  - JOUR
T1  - Focal cerebral metabolic abnormality in a patient with continuous spike waves during slow-wave sleep
A1  - Park,Y.D.
A1  - Hoffman,J.M.
A1  - Radtke,R.A.
A1  - DeLong,G.R.
Y1  - 1994/04//
N1  - UI - 94275095
SP  - 139
EP  - 143
JA  - J Child Neurol
VL  - 9
IS  - 2
N2  - We report an 11-year-old boy with continuous spike-wave discharges during sleep accompanied by partial motor and atypical absence seizures, psychomotor regression, and severe behavior problems. During wakefulness, epileptiform discharges occurred over the right parietal region, suggesting that the continuous spike-wave discharges during sleep were a manifestation of secondary bilateral synchrony. Bilateral suppression of the spike-and-wave activity was observed after right-sided intracarotid amobarbital injection, further supporting the impression of secondary bilateral synchrony. The right superior temporoparietal increase in metabolic activity during continuous spike-wave discharges and noncontinuous spike-wave discharges was seen on [18F]fluorodeoxyglucose positron emission tomography and supports a right temporoparietal focus in our case. The presence of a focal abnormality suggests that surgical therapy may be effective
AD  - Department of Pediatrics (Neurology), Duke University Medical Center, Durham, NC
UR  - PM:8006363
ER  - 

TY  - JOUR
T1  - Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression
A1  - Bremner,J.D.
A1  - Vythilingam,M.
A1  - Ng,C.K.
A1  - Vermetten,E.
A1  - Nazeer,A.
A1  - Oren,D.A.
A1  - Berman,R.M.
A1  - Charney,D.S.
Y1  - 2003/06/18/
SP  - 3125
EP  - 3134
JF  - JAMA
VL  - 289
IS  - 23
N2  - CONTEXT: We previously used positron emission tomography (PET) measurement of brain metabolism with 18fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion-induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using alpha-methylparatyrosine (AMPT). OBJECTIVE: To assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, double-blind trial in which 18 patients recruited in 1997-2000 from the general community who had depression in remission while taking NRIs had PET imaging in a psychiatric research unit following AMPT and placebo administration. INTERVENTIONS: After initial medication with desipramine and follow-up until response, patients underwent active AMPT (five 1-g doses administered orally over 28 hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered similarly) catecholamine depletion challenges in randomized order of assignment, after which PET imaging was performed on day 3 of each condition. Both study conditions were performed 1 week apart. MAIN OUTCOME MEASURES: Regional brain metabolism rates in patients with and without AMPT-induced return of depressive symptoms. RESULTS: AMPT-induced return of depressive symptoms was experienced by 11 of the 18 patients and led to decreased brain metabolism in a number of cortical areas, with the greatest magnitude of effects in orbitofrontal (P =.002) and dorsolateral prefrontal (P =.03) cortex and thalamus (P =.006). Increased resting metabolism in prefrontal and limbic areas predicted vulnerability to return of depressive symptoms. CONCLUSIONS: Different neurochemical systems that mediate depression may have effects on a common brain circuitry. Baseline metabolism in successfully treated depressed patients may predict vulnerability to future episodes of depression
AD  - Department of Psychiatry, Emory Center for Positron Emission Tomography, Emory University School of Medicine, Atlanta, GA, USA. jdbremn@emory.edu
UR  - PM:12813118
ER  - 

TY  - JOUR
T1  - The functional neuroanatomy of Tourette's syndrome: an FDG PET study III: functional coupling of regional cerebral metabolic rates
A1  - Jeffries,K.J.
A1  - Schooler,C.
A1  - Schoenbach,C.
A1  - Herscovitch,P.
A1  - Chase,T.N.
A1  - Braun,A.R.
Y1  - 2002/07//
N1  - UI - 22058658
SP  - 92
EP  - 104
JF  - Neuropsychopharmacology
VL  - 27
IS  - 1
N2  - Functional coupling of regional cerebral metabolic rates for glucose measured with [18F]-Fluoro-2-deoxy-D-glucose PET was compared in 18 drug-free patients with Tourette's Syndrome (TS) and 16 age- and sex-matched control subjects. Pearson product-moment correlation matrices containing correlations between metabolic rates in regions sampled throughout the brain were generated independently for TS patients and controls and compared. Significant differences between Z-transformed correlation coefficients were used to identify group differences, and revealed that the connectivity of the ventral striatum was most severely affected in TS. Changes in the coupling of other brain areas-primary motor areas, somatosensory association areas, and insula-also appeared to differentiate TS patients and controls. Evaluation of interrelationships between cortico-striato-thalamo-cortical circuits revealed the existence of functional connections between the motor and lateral orbitofrontal circuits in both groups, however, a reversal in the pattern of these interactions differentiated TS patients and controls. In controls, activity in these circuits appeared to be negatively correlated-i.e. increased activity in one is associated with relative inactivity the other. In TS patients, on the other hand, activity in the motor and lateral orbitofrontal circuits appears to be positively coupled. These results lend further credence to the hypothesis that altered limbic-motor interactions represent a pathophysiological hallmark of this disease
AD  - Language Section, Voice Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 10, Room 5N118A, Bethesda, MD 20892, USA
UR  - PM:12062910
ER  - 

TY  - JOUR
T1  - Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids
A1  - Pardridge,W.M.
Y1  - 1998/05//
N1  - UI - 98226253
SP  - 635
EP  - 644
JA  - Neurochem.Res
VL  - 23
IS  - 5
N2  - The transport of neutral amino acids through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo, is an important control point for the overall regulation of cerebral metabolism, including protein synthesis and neurotransmitter production. The Michaelis-Menten kinetics of BBB amino acid transport have been investigated in vivo with the brain uptake index (BUI) technique, and in vitro with the isolated human brain capillary preparation. The only amino acid that is albumin-bound is tryptophan, and the majority of albumin-bound tryptophan in the plasma is available for transport through the BBB via an enhanced dissociation mechanism that operates at the surface of the brain capillary endothelium. The availability in brain of amino acids is predicted from the BBB Km values to be sharply influenced by supra-physiological concentrations of phenyalanine in the 200-500 microM range. Moreover, the measurement of cerebral protein synthesis with an internal carotid artery perfusion technique and HPLC-based measurements of aminoacyl-transfer RNA specific activities shows an inverse relationship between cerebral protein synthesis and plasma phenyalanine concentrations in the 200-500 microM range. These findings indicate the neurotoxicity of hyperphenylalninemia is not restricted to the phenylketonuria range of approximately 2000 microM, but is exerted in the supra-physiological range of 200-500 microM
AD  - Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1682, USA. wpardrid@med1.medsch.ucla.edu
UR  - PM:9566601
ER  - 

TY  - JOUR
T1  - In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization
A1  - Chugani,D.C.
A1  - Ackermann,R.F.
A1  - Phelps,M.E.
Y1  - 1988/06//
N1  - UI - 88213454
SP  - 291
EP  - 303
JA  - J Cereb.Blood Flow Metab
VL  - 8
IS  - 3
N2  - The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states
AD  - Department of Pharmacology, UCLA School of Medicine
UR  - PM:2966803
ER  - 

TY  - JOUR
T1  - Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons
A1  - Shiue,C.Y.
A1  - Vallabhahosula,S.
A1  - Wolf,A.P.
A1  - Dewey,S.L.
A1  - Fowler,J.S.
A1  - Schlyer,D.J.
A1  - Arnett,C.D.
A1  - Zhou,Y.G.
Y1  - 1997/02//
N1  - UI - 97244948
SP  - 145
EP  - 150
JA  - Nucl Med Biol.
VL  - 24
IS  - 2
N2  - No-carrier-added (NCA)[11C](+/-)-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [11C]H3I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/mumol at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [11C]ketamine may not be an ideal tracer for studying NMDA receptor with PET
AD  - Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA
UR  - PM:9089707
ER  - 

TY  - JOUR
T1  - Synthesis of halogen-substituted pyridyl and pyrimidyl derivatives of [3,2-c]pyrazolo corticosteroids: strategies for the development of glucocorticoid receptor mediated imaging agents
A1  - Hoyte,R.M.
A1  - Zhang,J.X.
A1  - Lerum,R.
A1  - Oluyemi,A.
A1  - Persaud,P.
A1  - O'Connor,C.
A1  - Labaree,D.C.
A1  - Hochberg,R.B.
Y1  - 2002/11/21/
N1  - UI - 22319267
SP  - 5397
EP  - 5405
JA  - J Med Chem.
VL  - 45
IS  - 24
N2  - Ligands for the glucocorticoid receptor labeled with high-energy isotopes are highly desired for their potential applications in nuclear medical studies of the brain where the dysregulation of this receptor system is thought to be involved in various neurodegenerative disorders. Analogues of the glucocorticoid cortivazol have previously been prepared as target compounds for labeling with high-energy isotopes. However, the phenyl rings of arylpyrazoles of this type are not sufficiently activated for nucleophilic substitution reactions that are generally required for the synthesis of radiohalogenated analogues. Since suitably substituted aromatic nitrogen heterocyclic groups are amenable to nucleophilic substitution, the goal of this study was the synthesis of pyridylpyrazolo and pyrimidylpyrazolo analogues similar to cortivazol that could be labeled with radiohalogens in the pyridine or pyrimidine rings. We describe the synthesis of several [3,2-c]pyrazolo steroids containing pyridyl, halopyridyl, and pyrimidyl substituents at the 2' position of the pyrazole ring. These compounds were tested for binding to the glucocorticoid receptor and for biological activity in glucocorticoid responsive HeLa cells grown in tissue culture. Of the pyridyl and pyrimidyl derivatives, 2'-(3-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole showed superior activity in both assays and it was used as the basis for the synthesis of several analogues that were halogenated in the pyridine ring. These halogenated compounds were all tested for their binding to the glucocorticoid receptor and for their biological activity. One, a fluorinated compound 2'-(2-fluoro-5-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole had excellent activity, considerably better than the potent glucocorticoid dexamethasone. Most importantly, fluorination was achieved using a nucleophilic exchange reaction, a method that is adaptable to radiolabeling with the positron-emitting isotope fluorine-18. Thus, considering its superior biological activity and adaptability for facile radiosynthesis, this target compound has the potential for imaging of glucocorticoid receptor containing tissues using positron emission tomography
AD  - Department of Chemistry, State University of New York, Old Westbury, New York 11568, USA
UR  - PM:12431067
ER  - 

TY  - JOUR
T1  - Oestrogen receptors in meningiomas: a correlative PET and immunohistochemical study
A1  - Moresco,R.M.
A1  - Scheithauer,B.W.
A1  - Lucignani,G.
A1  - Lombardi,D.
A1  - Rocca,A.
A1  - Losa,M.
A1  - Casati,R.
A1  - Giovanelli,M.
A1  - Fazio,F.
Y1  - 1997/07//
N1  - UI - 98000144
SP  - 606
EP  - 615
JA  - Nucl Med Commun.
VL  - 18
IS  - 7
N2  - There have been a number of indications that sex hormones can affect the rate of growth of meningiomas during pregnancy. The presence of oestrogen or progesterone receptors in meningiomas and the influence of sex hormones upon cell cultures derived from human meningiomas have been extensively investigated. The results have been controversial, with most of the discussion centring upon the presence and possible role of oestrogen receptors. The aim of the present study was to assess oestrogen receptors in human meningiomas with 16alpha[l8F]fluoro-17beta-oestradiol ([18F]FES) and positron emission tomography (PET). With this purpose in mind, we measured the regional brain uptake of [18F]FES in six patients with a neuroradiological and histological diagnosis of meningioma, comparing the in vivo PET data with the immunohistological analysis of oestrogen receptors performed on formalin-fixed, paraffin-embedded tissue obtained at surgery. Two analyses were used for the in vivo measurement of [18F]FES binding to oestrogen receptors: the ratio of tumour activity to that of normal tissue (T/NT), calculated 90 min after tracer injection, and the ratio between the equilibrium distribution volume (DV) in normal and pathological tissues, calculated by means of a graphical kinetic analysis. PET studies demonstrated a marked uptake of [18F]FES by the tumour in four of the six patients. Immunohistochemical assay using a manual staining method capable of detecting oestrogen receptors at a level of > 10 pmol mg(-1) of protein detected only sparse immunostaining in one of the six meningiomas. Distinct albeit weak immunostaining was demonstrated in five of the six meningiomas when the sensitivity of the immunohistochemical assay was increased to < 10 pmol mg(-1) of protein by use of an automated staining method (Bioteck 1000). Comparison of the in vivo and immunohistochemical results showed a correlation in five of the six patients, thus indicating the high sensitivity of [18F]FES for the in vivo evaluation of oestrogen receptor expression
AD  - INB-CNR, Department of Nuclear Medicine, University of Milan, H.S. Raffaele, Italy
UR  - PM:9342097
ER  - 

TY  - JOUR
T1  - Synthesis and organ distribution of [18F]fluoro-Org 6141 in the rat: a potential glucocorticoid receptor ligand for positron emission tomography
A1  - Visser,G.M.
A1  - Krugers,H.J.
A1  - Luurtsema,G.
A1  - van Waarde,A.
A1  - Elsinga,P.H.
A1  - deKloet,E.R.
A1  - Groen,M.B.
A1  - Bohus,B.
A1  - Go,K.G.
A1  - Paans,A.M.
A1  - .
Y1  - 1995/10//
N1  - UI - 96123934
SP  - 915
EP  - 920
JA  - Nucl Med Biol.
VL  - 22
IS  - 7
N2  - For the synthesis of [18F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18F-, the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18F activity uptake in the brain had not yet reached a maximum at this interval. Although [18F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs
AD  - PET Center and Groningen Center for Catalysis and Synthesis, Groningen, The Netherlands
UR  - PM:8547889
ER  - 

TY  - JOUR
T1  - Systemic and cerebral kinetics of 16 alpha [18F]fluoro-17 beta-estradiol: a ligand for the in vivo assessment of estrogen receptor binding parameters
A1  - Moresco,R.M.
A1  - Casati,R.
A1  - Lucignani,G.
A1  - Carpinelli,A.
A1  - Schmidt,K.
A1  - Todde,S.
A1  - Colombo,F.
A1  - Fazio,F.
Y1  - 1995/03//
N1  - UI - 95164598
SP  - 301
EP  - 311
JA  - J Cereb.Blood Flow Metab
VL  - 15
IS  - 2
N2  - Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha [18F]fluoro-17 beta-estradiol ([18F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [18F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [18F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [18F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [18F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [18F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [18F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus
AD  - Department of Nuclear Medicine, University of Milan, Institute H. San Raffaele, Italy
UR  - PM:7860663
ER  - 

TY  - JOUR
T1  - Fluorine-substituted corticosteroids: synthesis and evaluation as potential receptor-based imaging agents for positron emission tomography of the brain
A1  - Pomper,M.G.
A1  - Kochanny,M.J.
A1  - Thieme,A.M.
A1  - Carlson,K.E.
A1  - VanBrocklin,H.F.
A1  - Mathias,C.J.
A1  - Welch,M.J.
A1  - Katzenellenbogen,J.A.
Y1  - 1992/05//
N1  - UI - 92406491
SP  - 461
EP  - 480
JA  - Int.J Rad.Appl.Instrum.B
VL  - 19
IS  - 4
N2  - We have prepared eight fluorine-substituted corticosteroids representing ligands selective for Type I and Type II corticosteroid receptor subtypes as potential imaging agents for corticosteroid receptor-containing regions of the brain. Receptor binding affinity assays show that fluorine substitution for hydroxyl or hydrogen in these steroids generally results in some reduction in affinity, with the result that the absolute affinity of these fluorine-substituted ligands for receptor is less than that typical for steroid hormones that show receptor-based, target selective uptake in vivo. Five of these compounds were prepared in fluorine-18 labeled form by a simple sulfonate ester displacement reaction, and their tissue distribution was studied in the adrenalectomized rat. There is no selective accumulation nor selective retention of the Type I selective corticosteroids (18F-RU 26752, 21-[18F]fluoroprogesterone, 21-[18F]fluoro-11 beta-hydroxyprogesterone) in either the brain, or other target tissues (pituitary, kidney, liver). The Type II selective corticosteroids (18F-RU 28362, 18F-triamcinolone acetonide) show uptake into the hippocampus which can be partially blocked by a competing ligand; in target tissues outside the brain, the blocking is more complete. All of the 18F-labeled compounds show considerable defluorination, evident as high bone activity levels. These results, coupled with earlier findings in the literature, suggest that radiolabeled corticosteroid receptor ligands with both greater metabolic stability and higher receptor binding affinity and selectivity are needed for imaging corticosteroid receptors in the hippocampus
AD  - Department of Chemistry, University of Illinois, Urbana 61801
UR  - PM:1526811
ER  - 

TY  - JOUR
T1  - In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography
A1  - Learned-Coughlin,Susan M.
A1  - Bergstrom,Mats
A1  - Savitcheva,Irina
A1  - Ascher,John
A1  - Schmith,Virginia D.
A1  - Langstrom,Bengt
Y1  - 2003/10/15/
SP  - 800
EP  - 805
JF  - Biological Psychiatry
VL  - 54
IS  - 8
N2  - BackgroundConverging lines of evidence are consistent with an inhibitory effect of the antidepressant and smoking-cessation aid bupropion on dopamine and norepinephrine reuptake, but the in vivo effects of the drug at the human dopamine transporter (DAT) have not been studied to date. This study employed positron emission tomography (PET) to assess the extent and duration of DAT receptor occupancy by bupropion and its metabolites under conditions of steady-state oral dosing with bupropion sustained-release (SR) in healthy volunteers.MethodsSix healthy male volunteers received bupropion SR 150 mg daily on days 1 through 3 and 150 mg every 12 hours on day 4 through the morning of day 11. PET investigations were performed between 1 and 7 days before initiation of bupropion SR dosing, as well as 3, 12, and 24 hours after the last dose of bupropion SR on day 11.ResultsBupropion and its metabolites inhibited striatal uptake of the selective DAT-binding radioligand 11C-[beta]CIT-FE in vivo. Three hours after the last dose of bupropion SR, average DAT occupancy by bupropion and its metabolites was 26%--a level that was maintained through the last PET assessment at 24 hours after dosing.ConclusionsBupropion and its metabolites induced a low occupancy of the striatal DAT over 24 hours under conditions of steady-state oral dosing with therapeutic doses of bupropion SR. These data are consistent with the hypothesis that dopamine reuptake inhibition may be responsible in part for the therapeutic effects of the drug
UR  - http://www.sciencedirect.com/science/article/B6T4S-48BM404-8/2/46a35c8b457cb36e108aea0713d394be
ER  - 

TY  - JOUR
T1  - Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma
A1  - Voges,J.
A1  - Reszka,R.
A1  - Gossmann,A.
A1  - Dittmar,C.
A1  - Richter,R.
A1  - Garlip,G.
A1  - Kracht,L.
A1  - Coenen,H.H.
A1  - Sturm,V.
A1  - Wienhard,K.
A1  - Heiss,W.D.
A1  - Jacobs,A.H.
Y1  - 2003/10//
N1  - UI - 22881265
SP  - 479
EP  - 487
JA  - Ann.Neurol
VL  - 54
IS  - 4
N2  - In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection-enhanced delivery of an HSV-1-tk gene-bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector-distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies
AD  - Department of Stereotaxy and Functional Neurosurgery, University of Koln
UR  - PM:14520660
ER  - 

TY  - JOUR
T1  - Neurobiology of suicidal behaviour
A1  - Mann,J.J.
Y1  - 2003///
SP  - 819
EP  - 828
JA  - Nat.Rev.Neurosci.
VL  - 4
ER  - 

TY  - JOUR
T1  - Neurological sequelae of cyanide intoxication--the patterns of clinical, magnetic resonance imaging, and positron emission tomography findings
A1  - Rosenow,F.
A1  - Herholz,K.
A1  - Lanfermann,H.
A1  - Weuthen,G.
A1  - Ebner,R.
A1  - Kessler,J.
A1  - Ghaemi,M.
A1  - Heiss,W.D.
Y1  - 1995/11//
N1  - UI - 96074195
SP  - 825
EP  - 828
JA  - Ann.Neurol
VL  - 38
IS  - 5
N2  - We report 2 patients with neurological sequelae of oral cyanide intoxication who were evaluated clinically and neuropsychologically, with high-resolution magnetic resonance imaging and one of them with positron emission tomography. The clinical syndrome was characterized by extrapyramidal motor and cerebellar symptoms such as bradykinesia, hypomimia, slowed speech, anteropulsion, and marked retropulsion, but little tremor. The sensory and pyramidal motor systems were normal or relatively spared. On neuropsychological testing the intellectual capacity and memory functions were normal, whereas the speed of motor reaction and verbal fluency were reduced. Magnetic resonance imaging showed damage of the globus pallidus, putamen, substantia nigra, subthalamic nucleus, and cerebellum in both patients, whereas the sensory-motor cortex and hippocampus were relatively spared. 18F-6-Fluoro-dopa positron emission tomography revealed a symmetrical reduction of striatal dopa uptake by 42% on average that was similar in the putamen and caudate. 18F-2-Fluoro-2-deoxyglucose positron emission tomography showed a regional reduction of the glucose metabolism in the posterior putamen and temporo-parieto-occipital and cerebellar cortex
AD  - Department of Neurology, University of Cologne, Germany
UR  - PM:7486875
ER  - 

TY  - JOUR
T1  - Brain abnormalities in murderers indicated by positron emission tomography
A1  - Raine,A.
A1  - Buchsbaum,M.
A1  - LaCasse,L.
Y1  - 1997/09/15/
N1  - UI - 97430986
SP  - 495
EP  - 508
JA  - Biol.Psychiatry
VL  - 42
IS  - 6
N2  - Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI
AD  - Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA
UR  - PM:9285085
ER  - 

TY  - JOUR
T1  - Abnormal temporal lobe metabolism in violent subjects: correlation of imaging and neuropsychiatric findings
A1  - Seidenwurm,D.
A1  - Pounds,T.R.
A1  - Globus,A.
A1  - Valk,P.E.
Y1  - 1997/04//
N1  - UI - 97272312
SP  - 625
EP  - 631
JF  - American Journal of Neuroradiology
JA  - AJNR Am J Neuroradiol
VL  - 18
IS  - 4
N2  - PURPOSE: To search for metabolic correlates of clinical and electrophysiological abnormalities in violent subjects. METHODS: Seven subjects with histories of extremely violent behavior were studied with positron emission tomography (PET) with fludeoxyglucose F 18 (FDG), brain electrical area mapping, MR imaging, neuropsychiatric and neuropsychological testing, and clinical examination during medical evaluation associated with legal proceedings. Nine control subjects without evidence of organic brain disease were also studied with FDG-PET. Quantitative PET data were calculated as standardized uptake values comparing the highest occipital region with the lowest temporal region. RESULTS: Temporal lobe metabolism was decreased in the study group relative to the control subjects. Medial temporal lobe metabolism was 39% lower than that in the occipital cortex in study subjects and only 27% lower than that in control subjects. These groups differed by Mann-Whitney U test and Wilcoxon's two-sample test. Metabolic differences correlated with limbic neuropsychiatric and electrophysiological abnormalities in the violent group. CONCLUSION: In this selected population of violent subjects, FDG-PET scans showed metabolic abnormalities in the temporal lobes. These abnormalities correlated with limbic abnormalities seen at electrophysiological and neuropsychiatric evaluation
AD  - Radiological Associates of Sacramento 95814, USA
UR  - PM:9127022
ER  - 

TY  - JOUR
T1  - Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers
A1  - Jonsson,E.G.
A1  - Nothen,M.M.
A1  - Grunhage,F.
A1  - Farde,L.
A1  - Nakashima,Y.
A1  - Propping,P.
A1  - Sedvall,G.C.
Y1  - 1999/05//
N1  - UI - 99321146
SP  - 290
EP  - 296
JA  - Mol.Psychiatry
VL  - 4
IS  - 3
N2  - The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [11C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (-141C Del) and high striatal dopamine receptor density (t= 2.32, P= 0.02). In agreement with some previous studies the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t=2.58, P=0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t= 2.58, P= 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. erikj@psyk.ks.se
UR  - PM:10395223
ER  - 

TY  - BOOK
T1  - Positron Emission Tomography. Basic Science and Clinical Practice
A1  - Valk,P.E.
A1  - Bailey,D.L.
A1  - Townsend,D.W.
A1  - Maisey,M.N.
Y1  - 2003///
PB  - Springer Verlag
SN  - 1-85233-485-1
ER  - 

TY  - JOUR
T1  - Radiopharmaceutical chemistry for positron emission tomography
A1  - Elsinga,P.H.
Y1  - 2002///
N1  - J
SP  - 208
EP  - 217
JA  - Methods
VL  - 27
IS  - 3
N2  - Radiopharmaceutical chemistry includes the selection, preparation, and preclinical evaluation of radiolabeled compounds. This paper describes selection criteria for candidates for positron emission tomography (PET) investigations. Practical aspects of nucleophilic and electrophilic F-18-fluorinations and C-11-methylations are described. These aspects include production of fluorine-18 and carbon-11, workup of fluorine-18, F-18 radiochemistry, production of [C-11]methyl iodide and triflate, and C-11-methylation radiochemistry. (C) 2002 Elsevier Science (USA). All rights reserved
UR  - ISI:000178072600003
ER  - 

TY  - JOUR
T1  - Brain radioligands - State of the art and new trends
A1  - Halldin,C.
A1  - Gulyas,B.
A1  - Langer,O.
A1  - Farde,L.
Y1  - 2001///
N1  - J
SP  - 139
EP  - 152
JF  - Quarterly Journal of Nuclear Medicine
VL  - 45
IS  - 2
N2  - Non-invasive radioligand imaging methods for brain receptor studies use either short-lived positron-emitting radionuclides such as C-11 and F-18 for positron emission tomography (PET) or single photon-emitting radionuclides such as I-123 for single photon emission computed tomography (SPECT). PET and SPECT use radioligands which are injected intravenously into experimental animals, human volunteers or patients. The main applications of radioligands in brain research concern human neuropsychopharmacology and the discovery and development of novel drugs to be used in the therapy of neurological and psychiatric disorders. A basic problem in PET and SPECT brain receptor studies is the lack of useful radioligands with appropriate binding characteristics. Prerequisite criteria need to be satisfied for a radioligand to reveal target binding sites in vivo. This section will discuss these important criteria and also review recent examples in neuroreceptor radioligand development such as selective radioligands for brain monoamine transporters
UR  - ISI:000169620400003
ER  - 

TY  - JOUR
T1  - Evaluation of the Depth of Interaction (DOI) for the High Resolution Research Tomograph (HRRT) - a comparison between scanners with and without DOI
A1  - Knoess,C.
A1  - Boellaard,R.
A1  - Lenox,M.
A1  - Vollmar,S.
A1  - Casey,M.
A1  - Fluegge,G.
A1  - Lammertsma,A.A.
A1  - Wienhard,K.
A1  - Heiss,W.-D.
Y1  - 2003///
JF  - IEEE Transactions on Nuclear Science
VL  - MIC
ER  - 

TY  - JOUR
T1  - Exact Local Comparison of [11C]-L-methionine Uptake and Histopathologic Findings in 105 Specimen from Serial Stereotactic Biopsies
A1  - Kracht,L.W.
A1  - Miletic,H.
A1  - Busch,S.
A1  - Jacobs,A.
A1  - Voges,J.
A1  - Hoevels,M.
A1  - Lucht,H.
A1  - Herholz,K.
A1  - Heiss,W.-D.
Y1  - 2003///
SP  - 190
JF  - European Journal of Nuclear Medicine
JA  - Eur.J.Nucl.Med.
VL  - 30 (Suppl.2 )
ER  - 

TY  - JOUR
T1  - Predicting performance from functional imaging data: methods matter
A1  - Sidtis,John J.
A1  - Strother,Stephen C.
A1  - Rottenberg,David A.
Y1  - 2003/10//
SP  - 615
EP  - 624
JF  - Neuroimage
VL  - 20
IS  - 2
N2  - In the standard approach to functional imaging studies, brain-behavior relationships are studied by contrasting data obtained during different behavioral states. It is generally assumed that relative change yields meaningful data about relevant brain processes, and that the magnitude of the change reflects the extent of a region's involvement in the behavior being studied. The present study takes a different approach by asking the question, Can functional imaging data predict performance? Regional cerebral blood flow was measured using positron emission tomography in a group of 13 right-handed, normal volunteers during speech production and quiet baseline. A number of methodological assumptions were addressed by examining the relationships between different imaging measures derived from the same raw data and performance on the speech task. The results demonstrate that several common assumptions are not necessarily true. First, although measures based on "activated" scans alone had predictive value with respect to speech rate, measures based on contrasts between "baseline" and "activated" states did not. This was true regardless of whether the contrast was based on subtraction or covariance analyses. Second, while many regions demonstrated large signal increases during speech, speech rate could be predicted by a linear combination of data from two regions, neither of which had the highest "activation" peak, and one of which had a negative relationship with performance. The results demonstrate that contrasting experimental conditions do not necessarily isolate or enhance brain activity related to performance, and that the current assumptions about activation in functional imaging need to be reconsidered
UR  - http://www.sciencedirect.com/science/article/B6WNP-49D2CG2-6/2/0e73b7cf513e13a8ca1a994454067e2e
ER  - 

TY  - JOUR
T1  - Development of a new reporter gene system--dsRed/xanthine phosphoribosyltransferase-xanthine for molecular imaging of processes behind the intact blood-brain barrier
A1  - Doubrovin,M.
A1  - Ponomarev,V.
A1  - Serganova,I.
A1  - Soghomonian,S.
A1  - Myagawa,T.
A1  - Beresten,T.
A1  - Ageyeva,L.
A1  - Sadelain,M.
A1  - Koutcher,J.
A1  - Blasberg,R.G.
A1  - Tjuvajev,J.G.
Y1  - 2003/04//
N1  - UI - 22845195
SP  - 93
EP  - 112
JA  - Mol.Imaging
VL  - 2
IS  - 2
N2  - We report the development of a novel dual-modality fusion reporter gene system consisting of Escherichia coli xanthine phosphoribosyltransferase (XPRT) for nuclear imaging with radiolabeled xanthine and Discosoma red fluorescent protein for optical fluorescent imaging applications. The dsRed/XPRT fusion gene was successfully created and stably transduced into RG2 glioma cells, and both reporters were shown to be functional. The level of dsRed fluorescence directly correlated with XPRT enzymatic activity as measured by ribophosphorylation of [14C]-xanthine was in vitro (Ki = 0.124 +/- 0.008 vs. 0.00031 +/- 0.00005 mL/min/g in parental cell line), and [*]-xanthine octanol/water partition coefficient was 0.20 at pH = 7.4 (logP = -0.69), meeting requirements for the blood-brain barrier (BBB) penetrating tracer. In the in vivo experiment, the concentration of [14C]-xanthine in the normal brain varied from 0.20 to 0.16 + 0.05% dose/g under 0.87 + 0.24% dose/g plasma radiotracer concentration. The accumulation in vivo in the transfected flank tumor was to 2.4 +/- 0.3% dose/g, compared to 0.78 +/- 0.02% dose/g and 0.64 +/- 0.05% dose/g in the control flank tumors and intact muscle, respectively. [14C]-Xanthine appeared to be capable of specific accumulation in the transfected infiltrative brain tumor (RG2-dsRed/XPRT), which corresponded to the 585 nm fluorescent signal obtained from the adjacent cryosections. The images of endogenous gene expression with the "sensory system" have to be normalized for the transfection efficiency based on the "beacon system" image data. Such an approach requires two different "reporter genes" and two different "reporter substrates." Therefore, the novel dsRed/XPRT fusion gene can be used as a multimodality reporter system in the biological applications requiring two independent reporter genes, including the cells located behind the BBB
AD  - Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 513, New York, NY 10021, USA
UR  - PM:12964307
ER  - 

TY  - JOUR
T1  - Molecular-genetic imaging: current and future perspectives
A1  - Blasberg,R.G.
A1  - Tjuvajev,J.G.
Y1  - 2003/06//
N1  - UI - 22666823
SP  - 1620
EP  - 1629
JA  - J Clin.Invest
VL  - 111
IS  - 11
AD  - Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. blasberg@neurol.mskcc.org
UR  - PM:12782662
ER  - 

TY  - JOUR
T1  - Molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl) amino]-2-naphthyl]ethylidene) malononitrile labels prion plaques in vitro
A1  - Bresjanac,M.
A1  - Smid,L.M.
A1  - Vovko,T.D.
A1  - Petric,A.
A1  - Barrio,J.R.
A1  - Popovic,M.
Y1  - 2003/09/03/
N1  - UI - 22835870
SP  - 8029
EP  - 8033
JA  - J Neurosci.
VL  - 23
IS  - 22
N2  - The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Straussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [18F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer's disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD
AD  - Laboratory for Neuronal Plasticity and Regeneration, Institute of Pathophysiology, University of Ljubljana, SI-1000 Ljubljana, Slovenia. maja.bresjanac@mf.uni-lj.si
UR  - PM:12954864
ER  - 

TY  - JOUR
T1  - The neuropathology of primary mood disorder
A1  - Harrison,P.J.
Y1  - 2002/07//
N1  - UI - 22071583
SP  - 1428
EP  - 1449
JF  - Brain
VL  - 125
IS  - Pt 7
N2  - The biological mechanisms proposed to underlie primary mood disorder do not usually include a neuropathological component. However, a significant MRI literature attests to structural abnormalities in regions and has encouraged neuropathological investigations from which candidate histological correlates have begun to emerge. In particular, there are several reports of cytoarchitectural alterations in anterior cingulate and prefrontal cortices, characterized by a decrease in the number or density of glia. Reductions in the size and density of some neuronal populations have also been described, accompanied by alterations in indices of synaptic terminals and dendrites. This form of pathology putatively reflects aberrant neurodevelopment or impaired cellular plasticity. A separate pathological process is suggested by the excess of subcortical focal lesions seen on MRI, especially in elderly patients; these probably reflect white matter damage of vascular origin. Both types of pathology have been observed, to a greater or lesser extent, in unipolar as well as bipolar mood disorders. None of the findings appear attributable to treatment with antidepressants, mood stabilizers or electroconvulsive therapy (ECT). However, all findings remain preliminary due to a lack of unequivocal replication and the failure to control fully for other potential confounders and co-morbid conditions. There are also basic questions to be answered concerning the clinical correlates, magnitude, progression and heterogeneity of the pathology. Nevertheless, it must now be considered likely that changes in brain structure, both macroscopic and microscopic, are a feature of primary mood disorder, a fact to be taken into account when interpreting functional imaging, neuropsychological and neurochemical data. The neuropathology is postulated to contribute to the pathophysiology and dysfunction of the neural circuits which regulate mood and its associated cognitions, behaviours and somatic symptoms
AD  - Department of Psychiatry, University of Oxford, UK. paul.harrison@psych.ox.ac.uk
UR  - PM:12076995
ER  - 

TY  - JOUR
T1  - Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression
A1  - Drevets,W.C.
Y1  - 2000///
N1  - UI - 20557288
SP  - 413
EP  - 431
JA  - Prog.Brain Res
VL  - 126
N2  - Neuroimaging studies of major depression have identified neurophysiological abnormalities in multiple areas of the prefrontal cortex (PFC), the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities are mood state-dependent, and appear in regions where cerebral blood flow (CBF) increases during other normal and pathological emotional states. These neurophysiological differences between depressives and non-depressed controls may thus locate areas where physiological activity changes to mediate or respond to the emotional, behavioral and cognitive manifestations of major depressive episodes (MDE). Other abnormalities persist following symptom remission, and are found in orbital and medial PFC areas where post mortem studies demonstrate reductions in cortex volume and/or histopathological changes in primary mood disorders. These orbital and medial PFC areas have been shown by other types of evidence to modulate emotional behavior and stress responses, suggesting that dysfunction involving these regions may be involved in the pathogenesis of depressive symptoms. Finally, physiological activity is decreased during MDE in dorsal PFC areas implicated in language, selective attention, visuospatial or mnemonic processing, but these abnormalities reverse with symptom remission. These areas of 'deactivation' during the depressed state may reflect neurophysiological interactions between cognitive and emotional processing, and may relate to the subtle cognitive impairments associated with MDE
AD  - Department of Psychiatry, University of Pittsburgh Medical Center, PA 15213, USA. drevets@pet.upmc.edu
UR  - PM:11105660
ER  - 

TY  - JOUR
T1  - Neuroimaging studies of mood disorders
A1  - Drevets,W.C.
Y1  - 2000/10/15/
N1  - UI - 20520129
SP  - 813
EP  - 829
JA  - Biol.Psychiatry
VL  - 48
IS  - 8
N2  - Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in cortex volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders
AD  - Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
UR  - PM:11063977
ER  - 

TY  - JOUR
T1  - Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment
A1  - Mayberg,H.S.
Y1  - 2003///
N1  - UI - 22583318
SP  - 193
EP  - 207
JA  - Br.Med Bull.
VL  - 65
N2  - While characterization of pathogenetic mechanisms underlying major depression is a fundamental aim of neuroscience research, an equally critical clinical goal is to identify biomarkers that might improve diagnostic accuracy and guide treatment selection for individual patients. To this end, a synthesis of functional neuroimaging studies examining regional metabolic and blood flow changes in depression is presented in the context of a testable limbic-cortical network model. 'Network' dysfunction combined with active intrinsic compensatory processes is seen to explain the heterogeneity of depressive symptoms observed clinically, as well as variations in pretreatment scan patterns described experimentally. Furthermore, the synchronized modulation of these dysfunctional limbic-cortical pathways is considered critical for illness remission, regardless of treatment modality. Testing of response-specific functional relationships among regional 'nodes' within this network using multivariate approaches is discussed, with a perspective aimed at identifying biomarkers of treatment non-response, relapse risk and disease vulnerability. Characterization of adaptive and maladaptive functional interactions among these pathways is seen as a critical step towards future development of evidenced-based algorithms that will optimize the diagnosis and treatment of individual depressed patients
AD  - Department of Psychiatry and the Rotman Research Institute, University of Toronto, Ontario, Canada
UR  - PM:12697626
ER  - 

TY  - JOUR
T1  - The role of functional neuroimaging in the neuropsychology of depression
A1  - Liotti,M.
A1  - Mayberg,H.S.
Y1  - 2001/02//
N1  - UI - 21220813
SP  - 121
EP  - 136
JA  - J Clin.Exp.Neuropsychol.
VL  - 23
IS  - 1
N2  - Depressed individuals show impaired performance in tests of attention and concentration. They also exhibit PET resting state abnormalities in dorsal prefrontal cortex and anterior cingulate, regions known to be substrates of attentional processing in healthy individuals. This chapter outlines a strategy to study neuropsychological mechanisms in emotional disorders using functional imaging methods. It reviews evidence strongly implicating the dorsolateral prefrontal cortex, particularly in the right hemisphere, as a key brain structure in emotion/cognition interactions in negative mood states. It will be argued that this neocortical region is a crucial convergence zone, being the substrate of sustained attention to the external environment, and the main target of limbic-cortical influences during changes in mood state across health and disease
AD  - Research Imaging Center, and Department of Radiology, Psychiatry and Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX, USA. liotti@uthscsa.edu
UR  - PM:11320448
ER  - 

TY  - JOUR
T1  - Limbic-cortical dysregulation: a proposed model of depression
A1  - Mayberg,H.S.
Y1  - 1997///
N1  - UI - 97422759
SP  - 471
EP  - 481
JA  - J Neuropsychiatry Clin.Neurosci.
VL  - 9
IS  - 3
N2  - A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders
AD  - Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio 78284-6240, USA. mayberg@uthscsa.edu
UR  - PM:9276848
ER  - 

TY  - JOUR
T1  - Is depression a risk factor for dementia or cognitive decline? A review
A1  - Jorm,A.F.
Y1  - 2000/07//
N1  - UI - 20318598
SP  - 219
EP  - 227
JF  - Gerontology
VL  - 46
IS  - 4
N2  - BACKGROUND: It is generally accepted that depression can be associated with significant cognitive deficits and that depression can be comorbid with dementia. OBJECTIVE: This review seeks to go further and ask whether depression earlier in life can be a risk factor for subsequent dementia or for cognitive decline. METHODS: A review was made of the epidemiological evidence from case-control and prospective studies that depression is a risk factor. The literature was also reviewed in relation to six hypotheses that might explain an association: (1) depression treatments are a risk factor for dementia, (2) dementia and depression share common risk factors, (3) depression is a prodrome of dementia, (4) depression is an early reaction to cognitive decline, (5) depression affects the threshold for manifesting dementia, and (6) depression is a causal factor in dementia. RESULTS: A meta-analysis found that depression was associated with an increased risk of subsequent dementia in both case-control studies (95% CI for relative risk: 1.16-3.50) and prospective studies (95% CI: 1.08-3.20). There was little support for hypotheses 1 and 2. The other hypotheses have limited support, but warrant further research. CONCLUSION: There is sufficient evidence to take seriously the possibility that depression is a risk factor for dementia and cognitive decline. Further work is needed to examine depression as a prodrome of vascular dementia, depression as an early reaction to perceived cognitive decline, the effects of depression on the threshold for manifesting dementia, and depression as a source of hippocampal damage through a glucocorticoid cascade
AD  - NHMRC Psychiatric Epidemiology Research Centre, Australian National University, Canberra. Anthony.Jorm@anu.edu.au
UR  - PM:10859462
ER  - 

TY  - JOUR
T1  - Distinction between preclinical Alzheimer's disease and depression
A1  - Visser,P.J.
A1  - Verhey,F.R.
A1  - Ponds,R.W.
A1  - Kester,A.
A1  - Jolles,J.
Y1  - 2000/05//
N1  - UI - 20269676
SP  - 479
EP  - 484
JA  - J Am Geriatr.Soc.
VL  - 48
IS  - 5
N2  - OBJECTIVE: To assess the prevalence of depression in subjects with preclinical Alzheimer's disease (AD) and to investigate the possibility of differentiating subjects with preclinical AD and depression from subjects with depression-related cognitive impairment. DESIGN: A prospective, observational cohort study. SETTING: An outpatient memory clinic of a university-affiliated hospital. PARTICIPANTS: Nondemented subjects with cognitive impairment older than 55 years (n = 111) without neurological or somatic causes for the cognitive impairment. MEASUREMENTS: At baseline, data were collected on patient characteristics, the severity of depression, and cognitive functioning. The course of the cognitive impairment and the presence of dementia were assessed after 2 and 5 years. RESULTS: Twenty-five subjects had preclinical dementia with Alzheimer's type dementia at follow-up. Sixty percent of these subjects (n = 15) were depressed at baseline. Subjects with depression and preclinical AD had at baseline a poorer performance on the cognitive tasks and were older than the subjects with depression-related cognitive impairment. Logistic regression with backward step selection selected age and memory performance as the best predictors for Alzheimer's type dementia in the depressed subjects. The specificity of these predictors for the diagnosis of future Alzheimer's type dementia in depressed subjects was 94%, sensitivity was 90%, positive predictive value was 90%, and negative predictive value was 94%. CONCLUSIONS: Depression is common in preclinical AD. Depressed subjects with preclinical AD can be accurately differentiated from subjects with depression-related cognitive impairment by age and the severity of the memory impairment. Research that aims to investigate preclinical AD should not exclude a priori subjects with depression inasmuch as preclinical AD is often accompanied by depression
AD  - Department of Psychiatry and Neuropsychology, Institute of Brain and Behavior, University of Maastricht, The Netherlands
UR  - PM:10811539
ER  - 

TY  - JOUR
T1  - Responses of posttraumatic pericontusional cerebral blood flow and blood volume to an increase in cerebral perfusion pressure
A1  - Steiner,L.A.
A1  - Coles,J.P.
A1  - Johnston,A.J.
A1  - Czosnyka,M.
A1  - Fryer,T.D.
A1  - Smielewski,P.
A1  - Chatfield,D.A.
A1  - Salvador,R.
A1  - Aigbirhio,F.I.
A1  - Clark,J.C.
A1  - Menon,D.K.
A1  - Pickard,J.D.
Y1  - 2003/11//
N1  - UI - 22962376
SP  - 1371
EP  - 1377
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 11
N2  - SUMMARY: In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation
AD  - *Wolfson Brain Imaging Centre, the dagger University Department of Anesthesia, and double dagger Academic Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
UR  - PM:14600445
ER  - 

TY  - JOUR
T1  - A theoretical model of oxygen delivery and metabolism for physiologic interpretation of quantitative cerebral blood flow and metabolic rate of oxygen
A1  - Hayashi,T.
A1  - Watabe,H.
A1  - Kudomi,N.
A1  - Kim,K.M.
A1  - Enmi,J.
A1  - Hayashida,K.
A1  - Iida,H.
Y1  - 2003/11//
N1  - UI - 22962370
SP  - 1314
EP  - 1323
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 11
N2  - SUMMARY: The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiologic and pathophysiologic conditions remains the subject of debate. In the present study, we have developed a theoretical model for oxygen delivery and metabolism, which describes the diffusion of oxygen at the capillary-tissue interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen, allowing a variation in simple-capillary oxygen diffusibility, termed "effective oxygen diffusibility (EOD)." The model was used to simulate the relationship between CBF and CMRO2, as well as oxygen extraction fraction (OEF), when various pathophysiologic conditions were assumed involving functional activation, ischemia, hypoxia, anemia, or hypo- and hyper-capnic CBF variations. The simulations revealed that, to maintain CMRO2 constant, a variation in CBF and Hb required active change in EOD. In contrast, unless the EOD change took place, the brain allowed small but significant nonlinear change in CMRO2 directly dependent upon oxygen delivery. Application of the present model to quantitative neuroimaging of CBF and CMRO2 enables us to evaluate the biologic response at capillary level other than Hb- and flow-dependent properties of oxygen transport and may give us another insight regarding the physiologic control of oxygen delivery in the human brain
AD  - *Department of Investigative Radiology, Research Institute of National Cardiovascular Center, and the dagger Department of Radiology and Nuclear Medicine, Hospital of National Cardiovascular Center, Fujishirodai, Suita, Osaka, Japan
UR  - PM:14600439
ER  - 

TY  - JOUR
T1  - Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis
A1  - Chih,C.P.
A1  - Roberts Jr,E.L.
Y1  - 2003/11//
N1  - UI - 22962364
SP  - 1263
EP  - 1281
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 11
N2  - SUMMARY: Glucose had long been thought to fuel oxidative metabolism in active neurons until the recently proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH) challenged this view. According to the ANLSH, activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The conventional hypothesis asserts that glucose is the primary substrate for both neurons and astrocytes during neural activity and that lactate produced during activity is removed mainly after neural activity. The conventional hypothesis does not assign any particular fraction of glucose metabolism to the aerobic or anaerobic pathways. In this review, the authors discuss the theoretical background and critically review the experimental evidence regarding these two hypotheses. The authors conclude that the experimental evidence for the ANLSH is weak, and that existing evidence and theoretical considerations support the conventional hypothesis
AD  - *Geriatric Research, Education, and Clinical Center, and Research Office, Miami VA Medical Center, Miami, Florida; dagger Department of Neurology, University of Miami School of Medicine, Miami, Florida
UR  - PM:14600433
ER  - 

TY  - JOUR
T1  - Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain
A1  - Ichise,M.
A1  - Liow,J.S.
A1  - Lu,J.Q.
A1  - Takano,A.
A1  - Model,K.
A1  - Toyama,H.
A1  - Suhara,T.
A1  - Suzuki,K.
A1  - Innis,R.B.
A1  - Carson,R.E.
Y1  - 2003/09//
N1  - UI - 22853272
SP  - 1096
EP  - 1112
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 9
N2  - SUMMARY: The authors developed and applied two new linearized reference tissue models for parametric images of binding potential (BP) and relative delivery (R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTM(O)) was modified (MRTM) and used to estimate a clearance rate (k'2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k'2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k'2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTM(O) from 12-70% to 1-4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies
AD  - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. masanori.ichise@nih.gov
UR  - PM:12973026
ER  - 

TY  - JOUR
T1  - Quantification of 5-HT2A receptors in the human brain using [18F]altanserin-PET and the bolus/infusion approach
A1  - Pinborg,L.H.
A1  - Adams,K.H.
A1  - Svarer,C.
A1  - Holm,S.
A1  - Hasselbalch,S.G.
A1  - Haugbol,S.
A1  - Madsen,J.
A1  - Knudsen,G.M.
Y1  - 2003/08//
N1  - UI - 22784157
SP  - 985
EP  - 996
JA  - J Cereb.Blood Flow Metab
VL  - 23
IS  - 8
N2  - The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using [18F]altanserin-positron emission tomography (PET) and the bolus/infusion approach. A bolus/infusion ratio of 1.75 h aimed at attaining rapid steady state in blood and brain was predicted from previous bolus studies performed in our laboratory. The infusion schedule was tested in normal subjects (n = 10) using dynamic PET and frequent plasma sampling for 6 h. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 3 h. To represent free and nonspecifically bound [18F]altanserin and its radiolabeled metabolites only, cerebellum must show no displacement in 5-HT(2A) displacement studies. To validate this, saturating doses of cold ketanserin were administered and it was found that specific binding of [18F]altanserin decreased uniformly to the level of the cerebellum and no change in the cerebellar time-activity curve was found after ketanserin administration. A shorter experimental setup was tested in a second group (n = 20) including patients with neuropsychiatric disorders. Dynamic PET (five frames of 8 minutes each) and venous blood sampling at midscan time started 2 h after [18F]altanserin administration. The mean percentage rate of change per hour in the outcome parameter, DV(3)', was low (mean -0.3% h-1; range -7.3-7.2% h-1) and no correlation of DV(3)' versus time was demonstrated. It is concluded that 5-HT(2A) receptor studies can be conducted within 2 h of [18F]altanserin infusion, yielding reliable results
AD  - Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Denmark. pinborg@nru.dk
UR  - PM:12902843
ER  - 

TY  - JOUR
T1  - [11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson's disease
A1  - Kumar,Ajit
A1  - Mann,Sharanpal
A1  - Sossi,Vesna
A1  - Ruth,Thomas J.
A1  - Stoessl,A.Jon
A1  - Schulzer,Michael
A1  - Lee,Chong S.
Y1  - 2003/12/01/
SP  - 2648
EP  - 2655
JF  - Brain
VL  - 126
IS  - 12
N2  - Levodopa effectively improves motor symptoms of Parkinson's disease. However, the beneficial effects of levodopa often erode over time with the emergence of response fluctuations. Although these response changes have been recognized from the early levodopa era, their mechanisms remain poorly understood. We investigated the role of dopamine (DA) terminal loss in the development of motor fluctuations by employing PET with [11C]({+/-})dihydrotetrabenazine ([11C]DTBZ) as an in vivo marker for DA nerve terminals. Levodopa response was characterized by analysing the time-response curve to a single dose of levodopa with a finger-tapping test. PET scans were performed in 11 patients with asymmetric Parkinson's disease (age: 61.12 {+/-} 7.97 years; duration of Parkinson's disease: 10.55 {+/-} 4.53 years; mean {+/-} SD). Each patient performed finger-tapping tests for up to 5 h after taking a therapeutic dose of levodopa. Results showed significantly lower [11C]DTBZ binding potential (BP; Bmax/Kd) and baseline tapping rates on the more affected putamen and corresponding body side, respectively, than on the other (P = 0.003 for the former, P = 0.013 for the latter). Among the variables describing the time-response curve, the duration and early decay time were significantly shorter on the more affected side (P = 0.051 and P = 0.021, respectively). Latency to the onset and latency to 50% Emax (the magnitude of the levodopa response) were significantly longer on the more-affected side (P = 0.013 and P = 0.004, respectively). Emax was not significantly different between the two sides. The asymmetry (difference from the more affected to less affected side) of [11C]DTBZ BP in the putamen showed a highly significant correlation with the corresponding asymmetry of the estimated EC50 (levodopa concentration producing 50% of the maximal response; P = 0.022; r = -0.727), a marginally significant correlation with that of latency to the onset (P = 0.065; r = -0.583) and no significant correlation with that of the magnitude, duration or early decay time. This pattern of changes in levodopa response from the less affected to more affected side was similar to that from stable to fluctuating responders except for the latency to onset. These findings suggest a pathogenetic role for DA terminal loss in the development of motor fluctuations. However, the absence of a significant correlation between the early decay of levodopa response and DA terminal density suggests that DA terminal loss alone cannot account for the development of motor fluctuations. Therefore, our study suggests that both levodopa treatment and DA terminal loss contribute to the pathogenesis of motor fluctuations
UR  - http://brain.oupjournals.org/cgi/content/abstract/126/12/2648
ER  - 

TY  - JOUR
T1  - Brain acetylcholinesterase activity in dementia with Lewy bodies, Alzheimer's disease and frontotemporal dementia
A1  - Shinotoh,H.
A1  - Aotsuka,A.
A1  - Fukushi,K.
A1  - Nagatsuka,S.
A1  - Tanaka,N.
A1  - Ota,T.
A1  - Sato,K.
A1  - Shiraishi,A.
A1  - Namba,H.
A1  - Tanada,S.
A1  - Irie,T.
Y1  - 2003///
SP  - S598
JA  - J Cereb.Blood Flow Metab
VL  - 23 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Reduction of striatal D2 receptor binding in non-manifesting carriers of the DYT1 mutation
A1  - Dhawan,V.
A1  - Ma,Y.
A1  - Okulski,J.
A1  - Asanuma,K.
A1  - Chaly,T.
A1  - Carbon,M.
A1  - Eidelberg,D.
Y1  - 2003///
SP  - S643
JA  - J Cereb.Blood Flow Metab
VL  - 23 (Suppl. 1)
ER  - 

TY  - JOUR
T1  - Assessment of spatial normalization of PET ligand images using ligand-specific templates
A1  - Meyer,J.H.
A1  - Gunn,R.N.
A1  - Myers,R.
A1  - Grasby,P.M.
Y1  - 1999/05//
N1  - UI - 99263281
SP  - 545
EP  - 553
JF  - Neuroimage
VL  - 9
IS  - 5
N2  - Recent advances allow robust computation of parametric maps of ligand-receptor binding from PET data sets. Parametric maps may be statistically analyzed at the voxel level, given suitable techniques for both the spatial normalization of image data into a standard space and the application of appropriate statistical tests. The purpose of this study was to spatially normalize parametric maps of [carbonyl-11C]WAY-100635 and [11C]raclopride binding using SPM 96 and ligand-specific templates. Ligand-specific templates were created from integral images taken from healthy subjects. For this, a MRI-based spatial normalization was used: T1-weighted MRI scans were coregistered to the PET integral images, and the spatial normalization of the MRI to the SPM 96 T1 MRI template was applied to the integral images. These integral images were meaned and smoothed to form [carbonyl-11C]WAY-100635 and [11C]raclopride templates. Reliability of spatial normalization using the ligand template method and the previous MRI-based spatial normalization was investigated by using a second set of integral images taken from a different cohort: Landmark coordinates were defined on all spatially normalized integral images. Mean coordinates were found in order to produce an overall (average) landmark for each location. For each image, at each location, the distance from the landmark coordinates to the overall landmark were found. A multivariate analysis of variance was used to examine the effects of observer variance, landmark location, and the method used. Visually acceptable templates were created. While observer variance was not significant, the landmark x method interaction was significant. The ligand template method had significantly smaller distances: Among the landmark locations with this method, the mean distances between individual image landmarks and overall image landmarks ranged from 1. 1 to 4.9 mm. The ligand template method provides a reliable approach for spatial normalization of PET ligand images
AD  - MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, United Kingdom
UR  - PM:10329294
ER  - 

TY  - JOUR
T1  - A critical discussion of the role of neuroimaging in mild cognitive impairment
A1  - Wolf,H.
A1  - Jelic,V.
A1  - Gertz,H.J.
A1  - Nordberg,A.
A1  - Julin,P.
A1  - Wahlund,L.O.
Y1  - 2003///
N1  - UI - 22491168
SP  - 52
EP  - 76
JA  - Acta Neurol Scand.Suppl
VL  - 179
N2  - OBJECTIVE: In this paper, the current neuroimaging literature is reviewed with regard to characteristic findings in mild cognitive impairment (MCI). Particular attention is drawn to the possible value of neuroimaging modalities in the prediction and early diagnosis of Alzheimer's disease (AD). METHODS: First, the potential contribution of neuroimaging to an early, preclinical diagnosis of degenerative disorders is discussed at the background of our knowledge about the pathogenesis of AD. Second, relevant neuroimaging studies focusing on MCI are explored and summarized. Neuroimaging studies were found through Medline search and by systematically checking through the bibliographies of relevant articles. RESULTS: Structural volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission tomography (SPECT) are currently the most commonly used neuroimaging modalities in studies focusing on MCI. There were considerable variations in demographical and clinical characteristics across studies. However, significant hippocampal and entorhinal cortex volume reductions were consistently found in subjects with MCI as compared with cognitively unimpaired controls. While hippocampal and entorhinal cortex atrophy in subjects with MCI are also well-established risk factors for the development of AD, these measures cannot be regarded as being of high predictive value in an individual case. Evidence for other typical neuroimaging changes in MCI is still scarce. In PET and SPECT studies, reduced blood flow and/or glucose metabolism in temporoparietal association areas, posterior cingulate and hippocampus were associated with a higher risk of progressive cognitive decline in MCI. In quantitative electroencephalogram (QEEG), low beta, high theta, low alpha and slowed mean frequency were associated with development of dementia. CONCLUSIONS: Existing studies suggest that neuroimaging measures have the potential to become valuable tools in the early diagnosis of AD. To establish their value in routine use, larger studies, preferably with long prospective follow-up are needed
AD  - Karolinska Institutet, Neurotec, Division of Geriatric Medicine, Huddinge University Hospital, Sweden. wolfh@medizin.uni-leipzig.de
UR  - PM:12603252
ER  - 

TY  - JOUR
T1  - Clinical-neuropathological correlations in Alzheimer's disease and related dementias
A1  - Galasko,D.
A1  - Hansen,L.A.
A1  - Katzman,R.
A1  - Wiederholt,W.
A1  - Masliah,E.
A1  - Terry,R.
A1  - Hill,L.R.
A1  - Lessin,P.
A1  - Thal,L.J.
Y1  - 1994/09//
N1  - UI - 94361630
SP  - 888
EP  - 895
JA  - Arch Neurol
VL  - 51
IS  - 9
N2  - OBJECTIVE: To compare neurologists' initial clinical diagnoses made according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition guidelines with neuropathological diagnoses of Alzheimer's disease (AD) and related dementias. DESIGN: Consecutive autopsies in a prospective cohort study. SETTING: Community-dwelling patients with dementia referred to neurologists at an Alzheimer's Disease Research Center and satellite clinics (n = 151) and patients initially evaluated when institutionalized (n = 19). PATIENTS: Of 204 elderly patients who had an autopsy performed, 170 had received a complete dementia evaluation according to NINCDS-ADRDA guidelines. MAIN OUTCOME MEASURES: Percentage agreement between neurologists' initial clinical diagnoses and pathological findings. RESULTS: Of 137 patients clinically diagnosed as having probable or possible AD, 123 (90%) had AD neuropathological findings; this included 29 with AD accompanied by Lewy bodies, and 14 with AD and one or more infarcts. Cases of vascular and mixed dementia (AD and infarct[s]) had lower rates of agreement with pathological findings. Possible AD cases were more likely than probable AD cases to show pathological features other than AD. Clinicians predicted the presence or absence of AD pathological findings significantly better than chance. In patients with AD pathological lesions, older age of onset and male gender were significantly associated with shorter duration from disease onset to death. CONCLUSIONS: Clinicians accurately predicted AD pathological findings or their absence in most cases. Attributing other degenerative dementias to AD, misdiagnosing patients with combined AD and Lewy bodies and misjudging the vascular contribution to dementia were the major areas of inaccuracy. Formal criteria for dementia associated with non-AD lesions, Lewy bodies, and infarcts need to be developed and tested
AD  - Alzheimer's Disease Research Center, University of California-San Diego
UR  - PM:8080388
ER  - 

TY  - JOUR
T1  - The value of positron emission tomography in the clinical evaluation of dementia
A1  - Gill,S.S.
A1  - Rochon,P.A.
A1  - Guttman,M.
A1  - Laupacis,A.
Y1  - 2003/02//
N1  - UI - 22447131
SP  - 258
EP  - 264
JA  - J Am Geriatr.Soc.
VL  - 51
IS  - 2
N2  - Positron emission tomography (PET) has been promoted as a means of improving the diagnosis of Alzheimer's disease (AD), but the evidence to support its incremental value is unclear. To assess the evidence regarding the use of PET in the clinical evaluation of AD, a systematic review of the English-language literature indexed in MEDLINE (1975-January 2001), the Cochrane Library (issue 4, 2000), and health technology assessment (HTA) reports was conducted. Articles identified by this review process were graded for methodological and reporting quality using a standardized grading scheme. Sixteen original articles and seven HTA reports were identified. In general, the articles addressed: using PET to differentiate AD from normal aging or non-Alzheimer's dementias, PET imaging compared with single positron emission computed tomography imaging, using PET to predict the progression of dementia, and agreement and reliability in the interpretation of PET images. Serious problems with study design and methodology in all articles were identified. Previous HTA reports have generally recommended that PET not be used in the clinical evaluation of dementia. In conclusion, there is little evidence to support the addition of PET to the routine clinical evaluation of patients with suspected or established dementia. Suggestions for future research in this area are offered
AD  - Kunin-Lunenfeld Applied Research Unit, Baycrest Center for Geriatric Care, Toronto, Canada. gill_sudeep@hotmail.com
UR  - PM:12558725
ER  - 

TY  - JOUR
T1  - Usefulness of positron emission tomography in evaluating dementia
A1  - Rutschmann,O.T.
A1  - Matchar,D.B.
Y1  - 2002/02/27/
N1  - UI - 21856839
SP  - 985
EP  - 986
JF  - JAMA
VL  - 287
IS  - 8
UR  - PM:11866638
ER  - 

TY  - JOUR
T1  - When should functional neuroimaging techniques be used in the diagnosis and management of Alzheimer's dementia? A decision analysis.
A1  - Kulasingham,S.L.
A1  - Samsa,G.P.
A1  - Zarin,D.A.
A1  - Rutschmann,O.T.
A1  - Patwardhan,M.B.
A1  - McCrory,D.C.
A1  - Schmechel,D.E.
A1  - Matchar,D.B.
Y1  - 2003///
SP  - 542
EP  - 550
JF  - Value in Health
VL  - 6
IS  - 5
ER  - 

TY  - JOUR
T1  - Disease, level of impact, and quality of research methods. Three dimensions of clinical efficacy assessment applied to magnetic resonance imaging
A1  - Kent,D.L.
A1  - Larson,E.B.
Y1  - 1992/03//
N1  - UI - 92202032
SP  - 245
EP  - 254
JA  - Invest Radiol.
VL  - 27
IS  - 3
N2  - Assessment of the clinical efficacy of diagnostic imaging technologies frequently involves reviews of published research. Reports may be classified in three dimensions; by disease, by type of assessment, and by the quality of research methods. The disease dimension describes the condition or conditions shown by an imaging technique. The assessment dimension spans five levels: technical capacity, diagnostic accuracy, diagnostic impacts, therapeutic impacts, and patient outcome impacts. The methods quality dimension can be expressed as four levels: excellent, good, fair or poor. An important interaction exists: the level of efficacy addressed by a research project dictates which methodologic procedures are important. For example, randomization is important only when a research report addresses the levels of therapeutic and patient outcome impacts. The authors suggest that classification of studies according to the three preceding dimensions maps the breadth (across diseases), depth (across levels of clinical efficacy), and quality of the assessment of complex imaging technologies. Such a map should help participants in technology assessment define the progress they have made. The classification strategy as applied to the clinical efficacy assessment of magnetic resonance imaging (MRI) for neuroradiology is illustrated
AD  - Northwest Health Services Research and Development Field Program, VA Medical Center, Seattle, Washington 98108
UR  - PM:1551777
ER  - 

TY  - JOUR
T1  - Higher in vivo muscarinic-2 receptor distribution volumes in aging subjects with an apolipoprotein E-epsilon4 allele
A1  - Cohen,R.M.
A1  - Podruchny,T.A.
A1  - Bokde,A.L.
A1  - Carson,R.E.
A1  - Herscovitch,P.
A1  - Kiesewetter,D.O.
A1  - Eckelman,W.C.
A1  - Sunderland,T.
Y1  - 2003/09/01/
N1  - UI - 22658834
SP  - 150
EP  - 156
JF  - Synapse
VL  - 49
IS  - 3
N2  - The apolipoprotein E-epsilon4 allele confers an increased susceptibility to age-related memory problems and Alzheimer's disease. Abnormalities in the cholinergic system are also likely contributors to memory deficits associated with aging and AD. To determine the effect of the APOE-epsilon4 allele on the muscarinic component of the cholinergic system of aging subjects, 10 healthy subjects with APOE-epsilon4 alleles (APOE-epsilon4+) and 10 without (APOE-epsilon4-), ranging in age from 52 to 75 years, were tomographically scanned with the F-18-labeled muscarinic-2 (M2) selective agonist, 3-(3-(3-[(18)F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydr o-1-methylpyridine ([(18)F]FP-TZTP). The distribution volumes (V(T)) of [(18)F]FP-TZTP were determined by compartmental modeling of partial volume and free fraction corrected PET scans. Regional cerebral blood flow (rCBF) measurements with H(2) (15)O were also performed. Global Gray V(T) (840 +/- 155 ml plasma/ml tissue) was greater in APOE-epsilon4+ subjects than APOE-epsilon4- subjects (660 +/- 113 ml plasma/ml tissue, P = 0.01), and previously studied younger subjects. There were no significant differences between the groups with respect to rCBF, but within the APOE-epsilon4+ group there was a trend for subjects with the higher Global Gray V(T)s to have lower Global Gray CBFs (r = -0.65, P < 0.06). A lower concentration of acetylcholine in the synapse of APOE-epsilon4+ older individuals is a likely explanation for the greater [(18)F]FP-TZTP distribution volumes
AD  - Geriatric Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
UR  - PM:12774299
ER  - 

TY  - JOUR
T1  - Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease
A1  - Hurtig,H.I.
A1  - Trojanowski,J.Q.
A1  - Galvin,J.
A1  - Ewbank,D.
A1  - Schmidt,M.L.
A1  - Lee,V.M.
A1  - Clark,C.M.
A1  - Glosser,G.
A1  - Stern,M.B.
A1  - Gollomp,S.M.
A1  - Arnold,S.E.
Y1  - 2000/05/23/
N1  - UI - 20284128
SP  - 1916
EP  - 1921
JF  - Neurology
VL  - 54
IS  - 10
N2  - BACKGROUND: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer's pathology has been a frequent finding, recent advances in immunostaining of alpha-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD. METHODS: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for alpha-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression. RESULTS: CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites. CONCLUSION: CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer's pathology, which was present in a minority of the cases in this series
AD  - Department of Neurology, University of Pennsylvania, PA, USA. hihurtig@pahosp.com
UR  - PM:10822429
ER  - 

TY  - JOUR
T1  - Neuropharmacology and drug development
A1  - Gee,A.D.
Y1  - 2003///
N1  - UI - 22583316
SP  - 169
EP  - 177
JA  - Br.Med Bull.
VL  - 65
N2  - Positron emission tomography (PET) and allied non-invasive imaging techniques are being increasingly embraced by the pharmaceutical industry. These imaging modalities allow the assessment of novel drug action in man at a very early stage of the drug's discovery and development process; in turn, this enables earlier decision making about the developmental potential of novel and potential therapeutics. The in vivo characterisation of novel molecular targets and disease mechanisms in man is intimately connected with future developments in the diagnosis, management and treatment of human disease. The utility of non-invasive imaging modalities within the pharmaceutical industry is discussed with particular reference to the use of PET in drug discovery and development in the 21st century
AD  - Translational Medicine and Technologies, GlaxoSmithKline, Clinical Research Unit, ACCI, Addenbrookes Hospital, Cambridge, UK
UR  - PM:12697624
ER  - 

TY  - JOUR
T1  - Comparison of [(18)F]FHBG and [(14)C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection
A1  - Min,J.J.
A1  - Iyer,M.
A1  - Gambhir,S.S.
Y1  - 2003/11//
N1  - UI - 22939782
SP  - 1547
EP  - 1560
JA  - Eur.J Nucl Med Mol.Imaging
VL  - 30
IS  - 11
N2  - Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1-beta- d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells-stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [(18)F]FHBG, [(3)H]PCV, and [(14)C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [(14)C]FIAU accumulation was greater than that of [(3)H]PCV and [(18)F]FHBG in control cells and in HSV1-tk stably transfected cells ( P<0.001). After infection of C6 cells with AdCMV- HSV1-tk (1.5x10(8) pfu), [(18)F]FHBG and [(3)H]PCV accumulation was significantly greater than that of [(14)C]FIAU ( P<0.01). [(18)F]FHBG and [(3)H]PCV accumulated to a significantly greater extent than [(14)C]FIAU in C6-stb-sr39tk+ and AdCMV- HSV1-sr39tk infected C6 cells ( P<0.001). Results from the nude mice supported the results in cell culture. [(14)C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [(18)F]FHBG ( P<0.05); however, compared with [(14)C]FIAU, [(18)F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [(18)F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A-stb-tk+). [(14)C]FIAU accumulated in HSV1-tk stably expressing cells to a greater extent than either [(3)H]PCV or [(18)F]FHBG. However, the accumulation of [(3)H]PCV and [(18)F]FHBG in adenoviral infected C6 cells or hepatocytes was equivalent to or greater than that of [(14)C]FIAU. These results may be due to intracellular biochemical changes (e.g., thymidine) when cells are infected with adenovirus. For adenoviral studies, the [(18)F]FHBG/ HSV1-sr39tk combination was shown to be more sensitive than the [(14)C]FIAU/ HSV1-tk combination HSV1-tk
AD  - The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B3-399A BRI 700 Westwood Plaza, CA 90095-1770, Los Angeles, USA
UR  - PM:14579096
ER  - 

TY  - JOUR
T1  - Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study
A1  - Garcia-Larrea,L.
A1  - Peyron,R.
A1  - Mertens,P.
A1  - Gregoire,M.C.
A1  - Lavenne,F.
A1  - Le Bars,D.
A1  - Convers,P.
A1  - Mauguiere,F.
A1  - Sindou,M.
A1  - Laurent,B.
Y1  - 1999/11//
N1  - DA - 19991217
SP  - 259
EP  - 273
JF  - Pain
VL  - 83
IS  - 2
N2  - Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results
AD  - Functional Neurology Unit, UPRES-EA 1880, Claude Bernard University, and Institut Federatif de Neurosciences of Lyon (IFNL), Lyon, France. larrea@cismsun.univ-lyon.fr
UR  - PM:10534598
ER  - 

