Insights From Quantitative Susceptibility Mapping: An Umbrella Review of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and neurodegeneration. Conventional MRI techniques lack specificity for detecting subtle pathological changes, such as iron deposition and myelin dynamics. Quantitative susceptibility mapping (QSM), an advanced MRI method sensitive to tissue magnetic susceptibility (χ), has emerged as a promising tool for evaluating iron-related pathology and demyelination in MS. This umbrella review synthesizes evidence from systematic reviews and meta-analyses to consolidate the role of QSM in MS diagnosis, monitoring, and prognostication.

Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, Web of Science, and Embase identified seven studies (four meta-analyses, three systematic reviews) encompassing 5389 MS patients, covering publications up to January 1, 2025. Methodological quality was assessed using AMSTAR 2, revealing moderate-to-low confidence in findings.

Key results demonstrated elevated χ in deep gray matter structures-particularly the globus pallidus, putamen, and caudate nucleus-in MS patients compared to healthy controls, correlating with clinical disability (e.g., Expanded Disability Status Scale scores) and cognitive dysfunction. Thalamic χ exhibited dynamic patterns, with reduced susceptibility in advanced disease stages. QSM outperformed conventional techniques (e.g., R2*, SWI) in detecting iron deposition, differentiating lesion types (e.g., paramagnetic rim lesions), and distinguishing MS from mimics. Rim-enhancing lesions showed higher χ values linked to inflammatory activity, while white matter lesions reflected demyelination-driven susceptibility changes. Despite QSM's diagnostic and prognostic potential, methodological heterogeneity and inconsistent standardization of PRL criteria limit comparability.

This review underscores QSM's utility as a biomarker for MS pathophysiology while advocating for standardized protocols and longitudinal studies to validate its clinical translation.