Assessing Multiple Sclerosis Therapies Using Diffusion MRI and Experimental Autoimmune Encephalomyelitis Mice

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Although multiple disease modifying agents are available to manage the relapse of MS, therapeutic strategies able to stop MS progression are in urgent demand. With promising compounds for MS on the horizon, novel neuroimaging modalities providing quantitative assessment of CNS integrity are needed to noninvasively monitor the treatment efficacy. Conventional MRI has revolutionized the diagnosis of MS. Nevertheless, they are hardly quantitative and lack specificity differentiating complicated pathologies. Diffusion tensor imaging (DTI) has shown promise to differentiate axon from myelin pathologies through changes in axial diffusivity and radial diffusivity. However, the accuracy in interpreting DTI findings is confounded by the presence of inflammation, tissue loss, crossing fibers, and cerebrospinal fluid contamination. A novel diffusion basis spectrum imaging (DBSI) has been developed to remove the confounders allowing quantitative assessment of axonal injury, demyelination, and inflammation in MS. In this work, both DTI and DBSI were applied to evaluate MS therapies in EAE mice. Mouse CNS white matter was assessed using DTI/DBSI derived metrics and histological markers. The axial and radial diffusivity derived from both methods characterized axon and myelin integrity reflected by histology, respectively. DBSI-derived directional diffusivity demonstrated an improved correlation to corresponding histological results over that derived from DTI. More importantly, the extent of inflammation detected by DBSI also accurately reflected white matter cellularity exhibiting a linear correlation with histological cell marker. Results suggested that the biomarkers derived from DBSI could ultimately prove useful in MS drug development and evaluation