Multiple sclerosis: improved identification of disease-relevant changes in gray and white matter by using susceptibility-based MR imaging.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
From the Department of Physics (D.A.R., R.S.M.), Center for Functional and Metabolic Mapping, Robarts Research Institute (D.A.R., I.S., J.S.G., R.S.M.), and Department of Neurology, University Hospital (M.K.), University of Western Ontario, 1151 Richmond St North, London, ON, Canada N6A 5B7.
David A
DA
Rudko
Igor
I
Solovey
Joseph S
JS
Gati
Marcelo
M
Kremenchutzky
Ravi S
RS
Menon
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
D015415:Biomarkers; D007501:Iron