Cortical pathology in multiple sclerosis detected by the T1/T2-weighted ratio from routine magnetic resonance imaging.

Abstract

In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1- and T2-weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0-3.5) and 80 age- and sex-matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2-weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Patients showed lower T1/T2-weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2-weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2-weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. The T1/T2-weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519-529.