Pathological Signatures of White Matter Lesions in Multiple Sclerosis versus Stroke: A Synthetic MRI Study

Purpose To evaluate whether quantitative synthetic MRI (SyMRI) parameters can differentiate non-specific white matter lesions (nsWMLs) in patients with multiple sclerosis (MS) and ischemic stroke, and to assess differences in normal-appearing white matter (NAWM) between these groups. Methods Thirty MS patients and nineteen ischemic stroke patients underwent standardized MRI including SyMRI. Three lesion categories were analyzed: typical MS lesions (MSL), non-specific lesions in MS (nsWML-MS), and non-specific lesions in stroke (nsWML-S). SyMRI-derived parameters (R1, R2, proton density, and myelin content) were extracted from each region of interest (ROI), and one ROI was placed in NAWM per patient. Group differences were evaluated using non-parametric tests. Logistic regression models, both unadjusted and age-adjusted, assessed predictors of MS diagnosis. Results Typical MS lesions showed lower myelin content and R1 and higher proton density than nsWML-MS (all p < 0.0001). Compared with nsWML-S, nsWML-MS demonstrated lower myelin content and higher proton density (p < 0.05), while R1 and R2 values did not differ. NAWM differences between MS and stroke emerged only after age adjustment. Age alone discriminated MS from stroke (AUC 0.83), with modest improvement when NAWM measures were added (AUC 0.86). Conclusion SyMRI captures both lesion-specific and diffuse NAWM differences between MS and stroke. Age strongly influences quantitative white matter measures, and adjusting for age reveals subtle NAWM pathology in MS. SyMRI may support differential diagnosis in patients with ambiguous white matter lesions.