In Vivo MRI of Endogenous Remyelination in a Nonhuman Primate Model of Multiple Sclerosis

Abstract

Remyelination is crucial for recovery from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral MS lesions, we investigated whether remyelination can be detected and characterized noninvasively. In 6 animals followed with multisequence 7-tesla MRI, 36 focal lesions, classified as demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in 5 of 6 marmosets and 51% of lesions. Radiological-pathological comparison showed high sensitivity (88%) and specificity (90%) for detecting remyelination by in vivo MRI. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents and translation to clinical practice.