Quantitative Susceptibility Mapping Values Quantification in Deep Gray Matter Structures for Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background/objectives: This systematic review and meta-analysis aimed to investigate the role of magnetic susceptibility (χ) in deep gray matter (DGM) structures, including the putamen (PUT), globus pallidus (GP), caudate nucleus (CN), and thalamus, in the most common types of multiple sclerosis (MS) and relapsing-remitting MS (RRMS), using quantitative susceptibility mapping (QSM).

Methods: The literature was systematically reviewed up to November 2023, adhering to PRISMA guidelines. This study was conducted using a random-effects model to calculate the standardized mean difference (SMD) in QSM values between patients with RRMS and healthy controls (HCs). Publication bias and risk of bias were also assessed.

Results: Nine studies involving 1074 RRMS patients with RRMS and 640 HCs were included in the meta-analysis. The results showed significantly higher QSM (χ) values in the PUT (SMD = 0.40, 95% confidence interval [CI] = 0.22-0.59, p = .000), GP (SMD = 0.60, 95% CI = 0.50-0.70, p = .00), and CN (SMD = 0.40, 95% CI = 0.15-0.66, p = .005) of RRMS patients compared to HCs. However, there were no significant differences in the QSM values in the thalamus between patients with RRMS and HCs (SMD = -0.33, 95% CI -0.67-0.01, p = .026). Age- and sex-based subgroup analysis demonstrated that younger patients (< 40 years) in the PUT, GP, and CN groups and larger male populations (> 25%) in the PUT and GP groups had more significant χ. Interestingly, thalamic QSM values were found to decrease in RRMS patients over 40 years of age and in higher male populations. Sex-based subgroup analysis indicated higher iron levels in the PUT and GP of RRMS patients regardless of sex. QSM values were higher in certain brain regions (PUT, GP, and CN) during the early stages (disease duration < 9.6 years) of RRMS, but lower in the thalamus during the later stages (disease duration > 9.6 years) than HCs.

Discussion/conclusion: QSM may serve as a biomarker for understanding χ value alterations such as iron dysregulation and its contribution to neurodegeneration in RRMS, especially in the basal ganglia nuclei including PUT, GP, and CN.