This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A reliable, noninvasive biomarker for following disease progression has not been developed for evaluating both patients and mouse models of Huntington's Disease (HD). Useful biomarkers should provide insights into HD pathogenesis while monitoring progression from a presymptomatic state. Proton magnetic resonance spectroscopy (1H MRS), using high field magnets at the Center for Magnetic Resonance Research (CMRR), non-invasively measures concentrations of brain chemicals across the lifespan. Previous 1H MRS studies in the striatum, the brain region most affected in HD, revealed chemical changes early and asynchronously over the lifespan of HD mice. We propose to pilot high resolution 1H MRS protocols that will permit future longitudinal studies to follow chemical changes from presymptomatic to early disease stages in individuals at risk for HD. The potential of these translational studies will be to develop a tool for analyzing disease progression in mice and humans, while enhancing understanding of HD pathogenesis. We propose to explore the use of 1H MRS at 3T in humans for the following aims: Aim 1: To evaluate metabolite profiles in striatal (caudate and putamen) and cortical (occipital and sensorimotor) regions in gene negative controls and gene positive early stage HD subjects using 1H MRS at 3T. Aim 2: To determine the intersubject variability in metabolite concentrations from the selected 1H Magnetic Resonance Spectroscopy of Early HD brain regions in gene negative controls and gene positive early stage HD subjects.