NORMAL METABOLISM AND ANATOMY OF BASAL FOREBRAIN IN MAN

Mount Sinai School Of Medicine Of Nyu, New York NY

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Abstract

DESCRIPTION (Adapted from applicant's abstract): A large data set of high-resolution coregistered PET/MRI images will be used to develop anatomical and image-processing methods to study the basal forebrain. Seventy rigorously screened healthy adults (5 men and 5 women in each decade from ages 20-90) were imaged while performing a serial verbal learning task. Thirty additional individuals will be imaged to increase statistical power. Scans were obtained with a GE 2048 head-dedicated scanner (4.5-mm resolution in plane, 2.5-3.5M counts) using 18F-deoxyglucose as the tracer. Coronal MRI images (1.2mm thick slices) were coregistered to the PET images. The investigator will focus on the striatum, pallidum and substantia innominata, with special attention to the ventral striatum (nucleus accumbens, striatal bridges into the substantia innominata) and ventral pallidum because they have been less studied (relative to the dorsal caudate and putamen) with MRI in man. A new 3D landmark-morphing method, thin-plate splines, will align and size all images to the same coordinates. The investigator will develop an atlas of basal forebrain anatomical landmarks and variance images for aligning subjects to uniform coordinates. He will test the hypothesis of greater age-related shrinkage and metabolic decrease in areas linked to motor cortex (posterior and dorsal putamen and globus pallidus) than areas linked to the limbic system (e.g., ventral striatum and pallidum). He will extend current correlational methods for understanding the topography of frontal-basal forebrain connectivity and evaluate the similarities between known nonhuman primate topography and human metabolic correlational pattern. Reciprocal compensatory size relationships between basal forebrain structures in the dorsal striatal (putamen to globus pallidus) and ventral (nucleus accumbens to ventral pallidum) systems will be explored to test the hypothesis that individuals with smaller striatal areas will show greater size or functional activity in the structures to which these areas send inhibitory projections. Lastly, the investigator will test realistic phantoms of the basal forebrain to provide accurate empirical measures of PET resolution and examine coronal postmortem cresyl violet and Weigert-stained brain slices to develop coronal slice location coordinates and assess their variation.