Multiple sclerosis (MS) is being increasingly recognized as a complex neurodegenerative disorder of the brain and spinal cord that involves autoimmune mechanisms that target both white and gray matter elements. The disease is characterized by demyelination, gliosis, axonal dysfunction, and, ultimately, neuronal loss. The vast majority of individuals destined to have confirmed MS later in their lives will already exhibit disseminated plaque lesions, as revealed by conventional MRI techniques, at the time of their first inflammatory demyelinating event. New and revised diagnostic criteria have enabled us to expedite the confirmation of MS, with substantial implications for early intervention with disease-modifying treatment.[2-4] However, the ability to accurately image both neurodegeneration and its prevention in MS would greatly facilitate the systematic evaluation of novel therapeutics and their efficacy over time.