SignificancePutative imaging biomarkers for myelin in MS have been correlated with pathological evidence of myelin loss in the context of a complex pathological environment. However, they have not been shown to improve dynamically with myelin repair because of limited therapies available that can induce that repair. Using MRI analysis from the double-blind, placebo-controlled remyelination ReBUILD trial we provide the first direct, biologically validated imaging-based evidence of medically induced myelin repair. MRI-derived myelin water fraction (MWF) values increase in normal-appearing white matter of the corpus-callosum with the administration of a tool remyelinating compound (clemastine). Furthermore, significant myelin repair occurs outside of lesions—focusing attention for repair beyond the lesion and setting corpus-callosum MWF as a standard for clinical programs investigating remyelinating therapies.