Axon injury and loss, demyelination, and inflammation are the primary pathologies in multiple sclerosis (MS). However, the roles that these individual pathological processes play in MS progression are still ill defined. To investigate whole brain white matter (WM) changes, diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) were analyzed on Tract Based Spatial Statistics (TBSS) skeleton template. Both whole brain voxel-based group analysis and regional correlation analysis at the corpus callosum supported that DBSI metrics were able to quantitatively assess the white matter alterations. DBSI could be useful for quantitatively monitoring MS patient treatment and assessing neuroprotective therapies.