Abstract

Objective: To characterize changes in demyelinated rodent brains, driven by Theiler’s Murine Encephalomyelitis Virus (TMEV), using diffusion tensor imaging (DTI). We quantified fractional anisotropy (FA) changes in white matter brain structures. Background: DTI is an emerging imaging technique for revealing pathological changes in multiple sclerosis (MS). TMEV, a mouse model of MS, is an immune-mediated chronic demyelinating disease of the central nervous system initiated by an intracerebral injection of virus. TMEV progression has not yet been characterized by DTI FA. We measured FA changes using high field MRI scanning in order to understand how different structures are affected by TMEV longitudinally. Design/Methods: Animals (6 TMEV and 6 saline intracerebrally injected, Swiss Jim Lambert mice) were clinically monitored and MRI scanned every 4 weeks for 36 weeks, starting at one month post induction (mPI). We used 9.4T small animal Bruker scanner. ANTS registration tool was used for warping images to co-register follow up scans with the first time point. Manually generated white matter structure specific label masks were applied to extract voxel-wise mean FA value. We focused on the medial corpus callosum (CC), internal capsules (IC), fimbria (Fr) and anterior commissure (AC) analysis. Results: Significant differences in effect of TMEV on different white matter structures were noted. Amongst all measured structures, Fr exhibited an earlier trend in decreased FA value when compared to saline brains starting at 6 mPI, leading to a significant difference at 8 mPI. Similarly, we found significant decrease in FA at 8mPI for IC when compared to saline brains. Conclusions: Notable differences in decrease FA measure reveal which white matter structures are more vulnerable to TMEV disease progression within the brain. Further exploration of above imaging data combined with mechanistic histological studies may reveal factors mediating white matter structures resilience. Disclosure: Dr. Cuberos has nothing to disclose. Dr. Pol has nothing to disclose. Dr. Punugu has nothing to disclose. Dr. Sudyn has nothing to disclose. Dr. Schweser has nothing to disclose. Dr. Modica has nothing to disclose. Dr. Bertolino has nothing to disclose. Dr. Preda has nothing to disclose. Dr. Dwyer has nothing to disclose. Dr. Zivadinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Claret Medical, Celgene and Novartis for speaking and consultant fees. Dr. Zivadinov has received research support from RZ received financial support for research activities from Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus and Quintiles IMS.