From pathology to MRI and back: Clinically relevant biomarkers of multiple sclerosis lesions

Focal lesions in both white and gray matter are characteristic of multiple sclerosis (MS). Histopathological studies have helped define the main underlying pathological processes involved in lesion formation and evolution, serving as a gold standard for many years. However, histopathology suffers from an intrinsic bias resulting from over-reliance on tissue samples from late stages of the disease or atypical cases and is inadequate for routine patient assessment. Pathological-radiological correlative studies have established advanced MRI’s sensitivity to several relevant MS-pathological substrates and its practicality for assessing dynamic changes and following lesions over time. This review focuses on novel imaging techniques that serve as biomarkers of critical pathological substrates of MS lesions: the central vein, chronic inflammation, remyelination and repair, and cortical lesions. For each pathological process, we address the correlative value of MRI to MS pathology, its contribution in elucidating MS pathology in vivo, and the clinical utility of the imaging biomarker.