Peak width of skeletonized mean diffusivity (PSMD) as marker of widespread white matter tissue damage in multiple sclerosis

Background: Peak width of skeletonized mean diffusivity (PSMD) is a novel and fully automated, MRI biomarker, which has shown clinical relevance in cerebral small vessel diseases (SVD). We aimed here to assess PSMD levels across the brain of patients with multiple sclerosis (MS), in comparison to normal controls (NC) and patients with CADASIL, a genetically defined form of severe SVD. Methods: We assessed PSMD in relapsing-remitting (RR) MS patients (n = 47) in comparison to age-matched CADASIL patients (n = 25) and NC (n = 28). Diffusion Tensor Imaging data were acquired on 1.5T MR clinical scanner to automatically compute PSMD through “skeletonization” of WM tracts and diffusion histograms. Results: RRMS had lower WM lesion volume (LV) than CADASIL (8.6 ± 8.2 vs 24.4 ± 17.4 cm3, p < 0.001). After correction for LV, PSMD values in MS were higher than in CADASIL patients (adjusted mean values: 4.5 vs 3.9 × 10−4 mm2/s, p = 0.03) and in both patient groups were higher than in NC (2.8 ± 0.3 × 10−4 mm2/s, p < 0.001). PSMD values correlated with LV in both patient groups (r = 0.8, p < 0.001 in MS; r = 0.6, p = 0.002 in CADASIL). Conclusions: In both patient groups, PSMD was higher than in NC and closely correlated with LV, suggesting sensitivity in assessing brain tissue damage in these disorders. In MS patients, PSMD levels were higher than in CADASIL patients, despite the lower LV. This might be related to more severe normal-appearing WM abnormalities occurring in the MS brains. This novel, fully automated, MRI metric may represent a useful marker for a robust quantification of the diffuse WM tissue damage in MS.