Correlations between postmortem quantitative MRI parameters and demyelination, axonal loss and gliosis in multiple sclerosis: A systematic review and meta-analysis.

Abstract

Magnetic resonance imaging (MRI) is frequently used to monitor disease progression in multiple sclerosis (MS). This study aims to systematically evaluate the correlation between MRI measures and histopathological changes, including demyelination, axonal loss, and gliosis, in the central nervous system of MS patients. We systematically reviewed post-mortem histological studies evaluating myelin density, axonal loss, and gliosis using quantitative imaging in MS. Relevant studies were identified through searches in PubMed, EMBASE, and Web of Science. A total of 38 studies involving 1782 regions of interest from 229 subjects were included. Pooled random-effects models were used to calculate the correlation between demyelination, axonal loss, gliosis, and various MRI parameters, including magnetization transfer ratio (MTR), T1 and T2 relaxation times, myelin water fraction (MWF), proton density (PD), and diffusivities. Pair-wise analyses compared results between lesioned and non-lesioned tissues. Our results demonstrated moderate to strong correlations between MRI parameters and myelin density in MS, with correlation coefficients: T1 (0.72), T2 (0.72), MTR (-0.73), FA (-0.73), RD (0.70), MD (0.70), MWF (-0.82), and PD (0.73). Interestingly, stronger correlations were found in lesioned tissues compared to non-lesioned tissues (P < 0.001). Moderate correlations were found between MRI parameters and axonal loss and gliosis. Our study reveals significant correlations between MRI techniques and histological assessments of myelin, axonal damage, and gliosis in MS. MRI metrics exhibited a more robust association with demyelination in lesioned areas than in non-lesioned brain tissue, highlighting the pronounced degree of myelin degradation in MS lesions. Further investigation is warranted to corroborate these results and refine MRI-based monitoring of MS pathology.