Tissue damage detected by quantitative gradient echo MRI correlates with clinical progression in non-relapsing progressive MS

Background: Imaging biomarkers of progressive multiple sclerosis (MS) are needed. Quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) evaluates microstructural tissue damage in MS. Objective: To evaluate qGRE-derived R2t* as an imaging biomarker of MS progression compared with atrophy and lesion burden. Methods: Twenty-three non-relapsing progressive MS (PMS), 22 relapsing-remitting MS (RRMS), and 18 healthy control participants underwent standard MS physical and cognitive neurological assessments and imaging with qGRE, FLAIR, and MPRAGE at 3T. PMS subjects were tested clinically and imaged every 9 months over 45 months. Imaging measures included lesion burden, atrophy, and R2t* in cortical gray matter (GM), deep GM, and normal-appearing white matter (NAWM). Longitudinal analysis of clinical performance and imaging biomarkers in PMS subjects was conducted via linear models with subject as repeated, within-subject factor. Relationship between imaging biomarkers and clinical scores was assessed by Spearman rank correlation. Results: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression (N = 13) showed faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group (N = 10). Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. Conclusion: qGRE-derived R2t* is a potential imaging biomarker of MS progression.