The proposed project is designed to address two important issues in neuroimaging and HIV research. The first involves the validation of volumetric neuroimaging measures through the comparison of (a) measures obtained on MRI scans of fixed brains, (b) known water-displacement volumes of these brains, (c) measures obtained on digitized images of the fixed brain slices, and (d) measures obtained through stereological analysis of the fixed brain slices. The second involves examination of the relationship between measures of cerebral atrophy (from both MRI and neuropathological examination) and neuronal counts in specific regions. Brains will be obtained from 10 HIV+ individuals with clinical diagnoses ranging from normal neurological/neuropsychological functioning to severe dementia. The brains will be formalin fixed, and water displacement volumes will be obtained. Using a technique already developed by our group, the brains will then be embedded in gelatin, scanned according to a standard MR protocol, and sliced at the same angle and thickness as the MRI scan. Volumetric measures of whole brain, total gray matter, total white matter, neocortex within each lobe, and basal ganglia will be obtained from the scans, using procedures already established in our lab. The cut surfaces of the fixed brain slices will be digitized, and volumes will be obtained from the digitized images of the slices, using procedures similar to those used for the MRI scans. The embedded slices will then be subjected to stereological analysis in order to obtain volumetric measures of whole brain, total gray matter, total white matter, neocortex within each lobe, and basal ganglia. The slices will then be fractionated for further stereological analysis, which will yield estimation of neuronal numbers in each of these brain regions. Neuronal counts will be correlated with atrophy measures in each region.
