The Buffalo Neuroimaging Analysis Center (BNAC) has been a key center in pursuing a more complete picture of multiple sclerosis disease progression than what has been previously available. A major discovery has been the presence of microscopic diffuse damage in both normal-appearing gray matter and normal-appearing white matter compartments. The quantitative analysis of water diffusion provides a sensitive and extremely rapid surrogate measure of this damage. The BNAC has developed a fully automated and highly reproducible technique capable of quantitative measurement of a variety of diffusion parameters. This method produces diffusion indices such as mean diffusivity, entropy, fractional anisotropy, and tractography metrics.