Serial MRI of leptomeningeal inflammation in rodent experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (P1.389)

Objective: To investigate pattern of leptomeningeal contrast enhancement (LMCE) using serial MRI in experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). To explore the association of LMCE with clinical symptoms and disease progression. To characterize the relationship between MRI detected LMCE, and the underlying histologically quantified pathological correlates. Background: Leptomeningeal inflammation, as evaluated by LMCE, has been implied to be a predictive marker of cortical lesion formation in MS patients. However, the temporal pattern of LMCE in EAE myelin oligodendrocyte glycoprotein (MOG) is unknown. Design/Methods: Four C57BL/6J mice immunized with MOG peptide fragment (35–55 amino acid) and 4 saline injected animals were scanned for LMCE at pre-induction and at 1, 2 and 4 weeks post induction (PI). LMCE scan was obtained using two dimensional-fluid attenuated inversion recovery sequence after post-contrast (Gadovist®) administration on 9.4T Bruker scanner. Stage matched brain cryo-sections were assessed for measuring cellular density of Iba1 positive microphage/microglia. Results: All 4 EAE-MOG animals showed presence of LMCE and but not in the control saline mice. The peak signal intensity of LMCE was evidenced at one week PI in the meninges. The LMCE intensity decreased through 2–4-week PI, but it never returned to the baseline or saline injected normality levels. The peak of LMCE was associated with weight loss starting at 1 week PI and with clinical symptoms starting at 2 weeks PI. Histological analysis of the brain tissue showed a higher density of immune response cells in the meninges of the EAE-MOG animals, corresponding to the areas of LMCE. Conclusions: Serial MRI demonstrated that LMCE peak intensity in the meninges corresponds with the acute inflammatory phase of EAE-MOG disease progression. The peak meningeal LMCE intensity observation was followed by development of clinical disease symptoms and associated with higher inflammatory cell density. Study Supported by: N/A Disclosure: Dr. Pol has nothing to disclose. Dr. Schweser has received research support from SynchroPET. Dr. Bertolino has nothing to disclose. Dr. Preda has nothing to disclose. Dr. Svienson has nothing to disclose. Dr. Sudyn has nothing to disclose. Dr. Babek 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.