MRI OF HIV-INDUCED NEUROPATHY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project seeks to validate the chimpanzee as a valuable non-human primate animal model with which to study brain aging using safe, non-invasive imaging techniques and assessments of motor dexterity and function. The chimpanzee brain exhibits similarities to normal and perturbed (e.g., Alzheimer's) human aging. These studies seek to: 1) develop non-invasive quantitative neuroimaging-based measurements of cerebral integrity in the brains of chimpanzees, 2) compare cerebral architecture in young vs. aged adults to validate the chimpanzee as a NHP model of human aging, and 3) validate assessment of motor slowing using a task previously used in rhesus monkeys. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have the potential of being ideal tools with which to non-invasively and non-destructively evaluate longitudinal degenerative changes in this valuable NHP species through intra-subject serial scanning. We will attempt to demonstrate sensitivity and specificity of cerebral neurodegeneration in the chimpanzee and estimate the magnitude of cerebral changes that normal (and, later, HIV-positive chimps) experience during their lifetime by performing analysis of statistical power and population effects. This will be carried out using multi-modal MRI for quantifying anatomical features (gray matter neurons and white matter fiber tracts) and using PET for measuring aging changes in brain metabolism (neuronal activity), blood flow and oxygen utilization. We will also quantify age-related changes in fine motor function, including measures of manual dexterity, manual speed, and motor coordination. Assessment of these functions will be made by providing chimpanzees relative simple, yet effective, tasks. If the preliminary results obtained with this project show promise in delineating age-related trends in structural brain differences, then the longer range goal of this project will be to seek NIH (e.g., NIA, NIAID or NINDS) R01 funding to: a) expand the numbers in both the young-adult and old-adult normal cohorts sufficiently in order to reach adequate statistical power analysis, and b) assess the influence of HIV infection in accelerating these age-dependent differences and/or whether infection promotes distinct neuropathological changes and how any changes might relate to infection duration. In this second phase, we also expect to image individual animals during age progression through multiple scans across a 5 year period.