Magnetic resonance imaging (MRI) methods thought to assess myelin and axon integrity are improving the understanding of white matter diseases like multiple sclerosis (MS). This thesis improved the understanding of how microstructural tissue changes caused by various pathologies influence MRI metrics by developing and applying MRI methods in a longitudinal study using the cuprizone mouse model of MS. In vivo and ex vivo MRI measurments (T1 and T2 relaxometry, diffusion tensor imaging, and quantitative magnetization transfer imaging) were correlated with tissue measurements taken from electron microscopy images of control and cuprizone fed mice at weeks 2 and 3 of cuprizone feeding. Significant Spearman correlations included mean diffusivity vs. myelinated axon fraction (ρ=0.84), ex vivo T2 vs. myelinated axon fraction (ρ=0.68), and normalized T2-weighted signal vs. myelinated axon fraction (ρ =-0.80). Multiparametric MRI studies show promise in bridging the gap between damage detected in images and clinical status associated with MS. / May 2016