Multiple sclerosis (MS) is the most common disease of the CNS that causes neurodegeneration and demyelination. MRI can track changes in MS lesions, but how imaging monitors inflammatory cell response or myelin content is not well characterized. In this study, we use a cuprizone toxin mouse model to determine how T2 relaxation time, myelin water fraction (MWF), diffusion tensor imaging (DTI), and gRatio MRI relate to changes with microglia, astrocytes, oligodendrocytes, and myelin. Using longitudinally imaging, MRI was able to detect inflammation-mediated demyelination. T2 reflected changes in inflammation (microglia and astrocytes) while MWF and gRatio suggested demyelination.