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Previous MRI studies in MS have retrospectively analyzed normal-appearing brain tissue in locations where typical MS lesions ultimately appeared, finding pre-lesional changes in several MRI metrics. However, studies have not been entirely consistent and the development of a prototypical MS lesion cannot as yet be prospectively predicted. The primary objective of this projectis to validate the preactive lesion hypothesis in MS by identifying the spatiotemporal imaging signature of white matter destined to undergo acute, focal inflammation and demyelination-specifically, one that will allow reliable, prospective detection of nascent lesions before they appear on conventional (non-quantitative) imaging. The specific aim is to acquire a longitudinal set of quantitative MRI metrics in MS patients and perform a multivariate spatiotemporal analysis of pre-lesional, normal-appearing white matter, seeking spatially clustered interval changes that presage the appearance of a typical MS plaque.