Faculty Bibliography

Inter-subject coregistration is a powerful neuroimaging technique that enables comparison and detection of morphological differences across groups of subjects. The present study uses digital phantoms to evaluate errors in two widely employed approaches to inter-subject coregistration of structural MR images of the brain: the manual step-wise approach and the automated method provided with the software package SPM96. Phantoms were constructed by deforming a high resolution T1-weighted MR image in which we have embedded 12 landmarks. For the manual method the accuracy ranged from 0.8 mm in quadrigeminal plate to 2.4 mm in superior central sulcus and occipital lobe. The average error was 1.5 mm. For the automated SPM96 method and the 9 parameter model, the accuracy ranged from 0.8 mm to 2.1 mm and averaged 1.1 mm. Error of the manual method correlated strongly with the distance from the center of the image (r = 0.77, slope =.020, p =.003). The linear correlation of the error obtained with the automated method with the distance was poor (r = 0.39, slope =.008, p > 0.2). The results suggest that the inferior performance of the manual method is due to its step-wise approach and to a relatively large rotational error.

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

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

Our goal was to ascertain the involvement of the temporal lobe in the preclinical (not yet diagnosable) stages of dementia of the Alzheimer's type (DAT) by using MRI-derived volumes. We assessed anatomical subdivisions of the temporal lobe on three groups of carefully screened age- and education-matched elderly individuals: 27 normal elderly (NL), 22 individuals with minimal cognitive impairment (MCI), who did not fulfill DAT criteria but were regarded at high risk for future DAT, and 27 DAT individuals. We found hippocampal volume reductions of 14% for the MCI and 22% for the DAT group compared to the NL group. Utilizing regression analyses and after accounting for gender head size-age, generalized atrophy (CSF), and other temporal lobe subvolumes, the hippocampal volume separated NL from MCI individuals, correctly classifying 74%. For NL and MCI groups combined the hippocampal volume was the only temporal lobe subvolume related to delayed recall memory performance. When contrasting MCI and DAT individuals, the fusiform gyrus volume uniquely improved the ability of the hippocampal volume to separate MCI from DAT individuals from 74 to 80%. Our cross-sectional data suggest that, within the temporal lobe, specific hippocampal volume reductions separated the group at risk for DAT from the normal group. By the time impairments are sufficient to allow a diagnosis of DAT to be made, in addition to the medial temporal lobe volume reductions, the lateral temporal lobe is also showing volume reductions, most saliently involving the fusiform gyrus

Brain activation is accompanied by local decreases in vascular deoxyhemoglobin. Theoretically, gradient-echo and spin-echo sequences show similar sensitivity to capillary deoxyhemoglobin, but spin-echo sequences should be less sensitive to venous deoxyhemoglobin. This is an important distinction in the context of cortical localization. We report herein a direct experimental comparison of a gradient-echo sequence (fast low-angle shot [FLASH]) with a spin-echo sequence (rapid acquisition with relaxation enhancement [RARE]) for functional MRI (fMRI) in seven subjects undergoing visual stimulation. A Student t test analysis was used to locate areas of significant activation, and then computerized image segmentation was performed to determine the type of activated tissue. Contrary to previous reports, both sequences proved equally sensitive to overall activation. RARE activation, however, was more specific for gray matter, as suggested by prior theoretical models

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

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