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. The purpose of this study is to evaluate the structural and functional changes that occur within specific pathways of the brain in MS patients. These measures will be compared over time to determine the relationship between anatomical and functional changes and clinical measures of progression. Serial MRI scans will be used to measure changes in tissue integrity over a period of 3 years, at 6 month intervals. Novel structural techniques (magnetization transfer imaging (MTI), diffusion tensor imaging (DTI), atrophy measures and spectroscopy) will be used to monitor changes within specific tissue compartments and white matter pathways. (ie MTI P myelin, NAA spectroscopy P neurons, DTI P internal capsule, corpus callosum). Traditional structural measures (enhancing lesions, T2 burden) will be obtained as well for comparison. Serial functional MRI of motor and cognitive tasks will be obtained at the same time points to determine if functional disintegration is an important factor in progre ssive disability as would be predicted by the threshold theory.