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Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. Twenty-one subjects with MS underwent serial enhanced MRIs including NODDI, the key metrics of which are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.