MRI-based white matter microstructural and neurochemical alterations in multiple sclerosis: a systematic review

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder characterized by focal and diffuse white matter (WM) abnormalities that may extend beyond lesions visible on conventional magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) provide complementary information regarding WM microstructural integrity and neurochemical alterations. This systematic review aimed to evaluate WM microstructural and neurochemical alterations in MS and examine the reported associations between DTI-derived diffusion metrics and MRS-derived metabolic markers. A systematic literature search was conducted for studies published from January 2002 to 2026 that evaluated MS using DTI and MRS. Data on study characteristics, clinical phenotype, diffusion metrics, MRS-derived metabolites, and DTI–MRS associations were extracted. Owing to the limited number of eligible studies and substantial heterogeneity in MRI protocols, diffusion parameters, MRS measures, and reported correlations, quantitative meta-analysis was not performed. Findings were synthesized narratively. Two studies met the eligibility criteria. Both evaluated normal-appearing WM using DTI and MRS. Reduced fractional anisotropy and increased diffusivity, including apparent diffusion coefficient and mean diffusivity, indicated altered WM microstructural integrity. MRS demonstrated alterations in N-acetylaspartate, choline, creatine, and related metabolite ratios. Significant associations between diffusion and metabolic measures were reported. DTI and MRS demonstrate complementary WM microstructural and neurochemical alterations in MS. Further studies using standardized multimodal MRI protocols and larger clinically characterized populations are needed to validate these associations.