Abstract

Objective: We studied diffusor tensor imaging (DTI) and quantitative susceptibility mapping (QSM) dynamics in response to inflammation, demyelination and atrophy, in rodent brain. Our goal was to map changes in DTI, QSM and volumetric outcomes, through acute and chronic phases of a demyelinating disease. Background: The Thieler’s Murine Encephalomyelitis Virus (TMEV) model is an immune-mediated chronic disease of the central nervous system initiated by an intracerebral injection of virus, which is characterized by demyelination, brain atrophy and iron accumulation, and motor impairment, similar to MS. DTI and QSM are emerging imaging techniques in revealing pathological changes of multiple sclerosis (MS), but have not been characterized in the study of the TMEV. Design/Methods: Animals (6 TMEV and 6 saline intracerebrally injected) were clinically monitored every 4 weeks for 36 weeks, starting at one month post induction (PI). In addition, every 4 weeks PI, the animals were MRI scanned on a 9.4T small animal Bruker scanner. A multi-modal voxel-wise automated atlas approach segmented brain scans into: basal ganglia, cerebellum, corpus callosum, cortex, hippocampus and thalamus to extract region specific MRI measures. Results: After a phase of growth driven volume increase, all TMEV brain segments exhibited a significant volume decrease between 10 wks to 18wks PI, and this was associated with an increase in clinical disability scores. DTI-derived fractional anisotropy (FA) was significantly elevated in the acute phase up to 10wks PI. Furthermore, brain atrophy and clinical score elevation was associated with (at 10wk to 18 wks PI) abnormal changes in QSM in 4 of the 6 segmented regions. Conclusions: Early DTI FA changes are associated with acute inflammation and early demyelination in the TMEV model of MS. Chronic demyelination and axonal loss phase of TMEV was associated with development of brain atrophy and abnormal susceptibility on QSM. Study Supported by: N/A Disclosure: Dr. Pol has nothing to disclose. Dr. Modica has nothing to disclose. Dr. Schweser has received research support from SynchroPET. Dr. Sudyn has nothing to disclose. Dr. Bertolino has nothing to disclose. Dr. Preda has nothing to disclose. Dr. Dwyer has received personal compensation for activities with Claret Medical and EMD Serono. Dr. Dwyer has received research support from Novartis. Dr. Hagemeier has nothing to disclose. Dr. Siebert has nothing to disclose. Dr. Zivadinov has received personal compensation for activities with EMD Serono, Genzyme, Novartis, for speaking and consultant fees. Dr. Zivadinov has received personal compensation in an editorial capacity for BioMed Research International, BMC Medicine, BMC Neurology, Clinical CNS Drugs, Conf Pap Neurosci, Journal of Alzheimer9s Disease, Vein and Lymphatics, and Word J Surg Proc. Dr. Zivadinov has received research support from Biogen Idec, Claret Medical, Genzyme, Intekrin-Coherus, Novartis, and Teva Pharmaceuticals.