Faculty Bibliography

The metabolism of the polyamines, putrescine, spermidine and spermine, was studied in human brain and brain tumors. Samples of brain and tumors were incubated with 3H-putrescine and the amounts of labeled polyamines were measured. The amount of putrescine conversion was found to be greater in tumors that in normal brain samples. Furthermore, the metabolism of putrescine in brain tumors was related to tumor type and appeared to correlate with the degree of malignancy. The significance of these findings with regard to positron emission tomographic scanning and therapy of patients with malignant gliomas is discussed

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

Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities

Thirteen diagnosed schizophrenics and 11 normal controls were studied with a method using the PETT III positron emission tomograph (PET) and fluorodeoxyglucose labeled with fluorine 18. Each subject also had a computed tomographic (CT) scan. For each subject, two brain levels, one through the basal ganglia and one through the semioval center, were analyzed for the mean regional metabolic glucose rate. Specifically, relationships between frontal and posterior regions were evaluated. The CT scans of matching levels were superimposed on the functional PET images to provide anatomic criteria for region of interest selection. While no whole-slice metabolic differences were apparent between groups, schizophrenics had significantly lower activity in the frontal lobes, relative to posterior regions. The medicated and drug-free groups did not differ from one another in these regards. Trait v state dependency of the phenomenon was analyzed, and several technological limitations were considered.

The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease.

Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients

In this study the positron emission tomographic (PET)-18F-2-deoxy-2-fluoro-D-glucose (FDG) technique was used to study both normal aging and senile dementia. The results derived from 15 young normal subjects (mean age, 26 +/- 5 years) and 22 elderly normal subjects (mean age, 66 +/- 7 years) failed to indicate significant metabolic changes associated with age. A group of 24 patients with senile dementia (mean age, 73 +/- 7 years) showed consistent diminutions in regional glucose use relative to the elderly normals. Across all brain regions the diminutions were 17%-24%. There were also significant correlations between the measures of glucose use and the measures of cognitive functioning. Discriminant function classification analysis results indicate that better than 80% classification accuracy can be achieved for individual PET measures. These data suggest a possible future diagnostic use of PET in senile dementia.