Multiple sclerosis: improved identification of disease-relevant changes in gray and white matter by using...

To evaluate the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis (MS).

All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age- and sex-matched control subjects imaged at 7 T. The candidate MR imaging biomarkers were correlated with Extended Disability Status Scale (EDSS), time since CIS diagnosis, time since MS diagnosis, and age.

QS maps aided identification of significant, voxel-level increases in iron deposition in subcortical gray matter (GM) of patients with MS compared with control subjects. These voxel-level increases were not observed on R2* maps. Region-of-interest analysis of mean R2* and QS in subcortical GM demonstrated that R2* (R ≥ 0.39, P < .01) and QS (R ≥ 0.44, P < .01) were strongly correlated with EDSS. In white matter (WM), the volume of total WM damage (defined by a z score of less than -2.0 criterion, indicating demyelination) on QS maps correlated significantly with EDSS (R = 0.46, P = .02). Voxelwise QS also supported a significant contribution of age to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide more robust measures of MS disease severity compared with non-age-adjusted scores.

Using QS and R2* mapping, evidence of both significant increases in iron deposition in subcortical GM and myelin degeneration along the WM skeleton of patients with MS was identified. Both effects correlated strongly with EDSS.