Faculty Bibliography

The method of centroids is an approach to the analysis of three-dimensional whole-brain positron emission tomography (PET) metabolic images. It utilizes the brain's geometric centroid and metabolic centroid so as to objectively characterize the central tendency of the distribution of metabolic activity in the brain. The method characterizes the three-dimensional PET metabolic image in terms of four parameters: the coordinates of the metabolic centroid and the mean metabolic rate of the whole brain. These parameters are not sensitive to spatially uniform random noise or to the position of the subject's head within a uniform PET camera field of view. The method has been applied to 40 normal subjects, 22 schizophrenics who were treated with neuroleptics, and 20 schizophrenics who were neuroleptic-free. The mean metabolic centroid of the normal subjects was found to be superior to the mean geometric centroid of the brain. The mean metabolic centroid of chronic schizophrenics is lower and more posterior to the mean geometric centroid than is that of normals. This difference is greater in medicated than in unmedicated schizophrenics. The posterior and downward displacement of the mean metabolic centroid is consistent with the concepts of hypofrontality, hyperactivity of subcortical structures, and neuroleptic effect in schizophrenics

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

An indirect approach to the relationship among drug dose, plasma level, and the competition between a labeled neuroleptic drug [18F]N-methylspiroperidol (18F-NMS) for binding sites in striatal tissue in normal and schizophrenic subjects is described. The slope of the line plotting the ratio of activity in the striatum (As) to activity in the cerebellum (Ac) versus time up to 5 hr postinjection of 18F-NMS is taken as a marker of site occupancy. An inverse relation between labeled competitor uptake and drug plasma level has been demonstrated for the classes of antipsychotic drug studied. Striatal uptake studies showed a progressive increase in all subjects following drug withdrawal up to 156 hr postwithdrawal. Uptake and clearance of 18F-NMS in cerebellar tissue was not appreciably affected by antipsychotic medication or drug withdrawal

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

The metabolic patterns of correlation among brain images obtained during resting conditions and during an eye tracking task were investigated in 12 controls and 18 chronic schizophrenics using positron emission tomography (PET) and deoxy[11C]glucose. Analyses of the interaction between brain regions revealed highly significant differences between groups under both test conditions. Schizophrenics showed lower correlations between anterior and posterior areas and between thalamus and cortical areas than the normals and less change between the baseline and the task than the normals. The schizophrenic subjects showed derangements in the pattern of interactions among brain areas, both under baseline and under activation as compared to the control group

This study examines the effect of different behavioral conditions on patterns of correlation between regional cerebral metabolic rates for glucose. Cerebral glucose metabolism was determined with positron emission tomography and (11C)-deoxyglucose in 29 normal subjects between the ages of 23 and 55. Seventeen subjects were studied in an unstimulated (resting) condition and 12 subjects during a phoneme monitoring language stimulation. Partial correlation coefficients, controlling for whole brain glucose metabolism, were calculated for pairs of metabolic rates in 14 cortical and 2 subcortical regions. Both stimulated and unstimulated subjects showed statistically significant correlations between left and right hemisphere homologs. The stimulated subjects also showed significant within-hemisphere correlations between left but not right hemisphere regions. These included left perisylvian regions classically associated with language functions (left inferior frontal, left superior temporal and left transverse temporal cortical regions) as well as other regions. Significant correlations between left regions and a right superior temporal region were also found. In general, these findings show a pattern of cross-hemisphere symmetry at rest and of hemisphere asymmetry during stimulation. Moreover, the asymmetry observed during stimulation appears to be superimposed upon a pattern of cross-hemisphere symmetry similar to that observed in the unstimulated state

Serial PET measurements of [1-11C]putrescine ([11C]PUT) uptake and glucose metabolic rate (GMR) using [1-11C]2-deoxy-D-glucose ([11C]2DG) were made on eight human subjects with a radiological and, in most cases, pathological diagnosis of primary or metastatic brain tumor. Blood-to-brain influx constants (Ki) were calculated for [11C]PUT. Tumor uptake of 11C after [11C]PUT injection was unidirectional peaking at 15 min. The mean +/- s.d. Kis for [11C]PUT for tumor and normal brain tissue were 0.78 +/- 0.045 and 0.024 +/- 0.007 ml cc-1 min-1, respectively (average of ratio, 3.11) whereas the ratio of GMR for tumor and normal brain tissue was 1.2 +/- 0.5. The mean Ki for four active, high grade astrocytomas was 0.098 +/- 0.030 in contrast to 0.027 +/- 0.008 ml cc-1 min-1 for two patients with low grade astrocytoma. Active high grade astrocytomas also showed marked CT contrast enhancement and regional glucose hypermetabolism. In one subject with brain metastases, both [11C]PUT and GMR correlated with a declining clinical picture in repeated studies over a 4-mo period. PET studies with [11C]PUT provide a better signal:noise ratio than GMR measurements, are useful for locating small glycolytically hypometabolic tumors and, when used in longitudinal studies in a single subject, appear to provide an index of degree of malignancy