Faculty Bibliography

Glucocorticoids are known to play a role in the regulation of peripheral glucose mobilization and metabolism. Although several animal studies have shown that hippocampal glucose metabolism is reduced acutely and chronically by the action of corticosterone and that excess glucocorticoids are harmful to hippocampal neurons, little is known about the central effects of glucocorticoids in the human. In this study we examined the brain glucose utilization (CMRglu) response to hydrocortisone (cortisol) in seven normal elderly and eight Alzheimer's disease (AD) patients. On 2 separate days, immediately after the administration of a bolus of either 35 mg hydrocortisone or placebo, we administered 2-deoxy-2-[18F]fluoro-D-glucose. After a 35-min radiotracer uptake period, positron emission tomography (PET) images were collected. PET CMRglu images were analyzed using two methods: an image transformation that allowed analyses across cases on a voxel by voxel basis, and an anatomically based region of interest method that used coregistered magnetic resonance imaging scans. Both image analysis methods yielded similar results, identifying relative to placebo, a specific hippocampal CMRglu reduction in response to the hydrocortisone challenge that was restricted to the normal group. The region of interest technique showed CMRglu reductions of 16% and 12% in the right and left hippocampi, respectively. Blood collected during the PET scans showed, for the normal group, a rise in plasma glucose levels, starting approximately 25 min after hydrocortisone administration. The AD group did not show this effect. Baseline cortisol was elevated in the AD group, but the clearance of hydrocortisone was not different between the groups. In conclusion, these data show that among normal individuals in the presence of a pharmacological dose of cortisol, the glucose utilization of the hippocampus is specifically reduced, and serum glucose levels increase. Based in part on other studies, we offer the interpretation that glucocorticoid-mediated regulation of glucose transport is altered in AD, and this may underlie both the hippocampal insensitivity to cortisol and the failure in these patients to mount a peripheral glucose response. As our findings could reflect an altered state of the AD patients, we interpret our results as preliminary with respect to evidence for metabolic abnormalities in AD. The results suggest the continued study of the hydrocortisone challenge as a test of hippocampal responsivity

We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy (HA) in a research clinic population of 130 normal elderly, 72 nondemented patients with very mild memory and cognitive impairments (MCI), 73 mild Alzheimer's disease (AD) patients, and 130 patients with moderate to severe AD. HA was found in 29% of the normal elderly group and its frequency of occurrence was strongly related to increasing age. For normal elderly 60-75 years of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age. Among the three groups of impaired patients, the frequencies of HA ranged from 78% in the MCI patients to 96% in the advanced AD group. Unlike the normal elderly group, the percentages were not related to age. In both the normal elderly group and MCI group disproportionately more males than females had HA. After controlling for learning and the effects of generalized brain changes as reflected in ventricular size, only in the normal group was HA associated with reduced delayed verbal recall performance. Follow-up examinations for 15 individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded clinical and neuropathologic diagnoses of AD in all cases. The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments. Further longitudinal and neuropathologic work is required to validate the relationship between hippocampal formation atrophy and AD

OBJECTIVE: A method for segmenting MR images of the breast was applied to determine fatty and fibroglandular tissue volumes in breasts of women in different age groups. The results were compared with subjective assessments of breast density from X-ray mammograms in the same patients. MATERIALS AND METHODS: Two experienced mammographers assessed the percentage of fat in the breasts of 40 women who were 20-83 years old. MR images were obtained on a 1.0-T scanner equipped with a bilateral receive-only breast coil. Images were acquired using a three-dimensional T1-weighted gradient-echo sequence with a 1.25 x 1.4 x 2.5 mm resolution. On average, breast parenchyma appeared in 30 images in each breast. Image segmentation was based on a semiautomated, two-compartmental (fatty and fibroglandular tissue) model that accounts for partial volume effects. To validate the accuracy of the MR imaging segmentation technique, we performed a phantom study using an identical imaging sequence. RESULTS: The accuracy of the MR imaging segmentation of the phantom was of the order of 2%. In our subjects, fat content was 42.5% +/- 30.3% (mean +/- SD) on mammography versus 66.5% +/- 18% on MR images. Although we found a significant correlation (r = .63) between the two techniques, mammography poorly differentiated breasts containing less than 45% fat. When our analysis included only dense breasts (i.e., those containing less than 75% fat on MR images), the correlation coefficient decreased to .34. The largest discrepancies between mammography and MR imaging occurred in breasts that had 60-80% fat as measured on MR imaging. CONCLUSION: Fatty and fibroglandular tissue can be differentiated on MR images of the breast with high precision and accuracy, therefore allowing assessment of breast density. The conclusions of researchers who used mammographic density patterns should be reassessed

The properties of permanent magnets composed of uniformly magnetized wedges are presented in this paper. The magnets are fully open structures capable of generating strong fields exceeding the remanence of the material