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

Abstract Background: Imaging biomarkers of progressive MS are needed. Quantitative gradient recalled echo (qGRE) MRI technique allows evaluation of tissue damage associated with microstructural damage in multiple sclerosis (MS). Objective: To evaluate qGRE-derived R2t* as an imaging biomarker of MS disease progression as compared to atrophy and lesion burden. Methods: Twenty-three non-relapsing progressive MS (PMS), twenty-two relapsing-remitting MS (RRMS) and eighteen healthy control participants were imaged with qGRE at 3T. PMS subjects were imaged and neurologically assessed every nine months over five sessions. In each imaging session, lesion burden, atrophy and R2t* in cortical grey matter (GM), deep GM, normal-appearing white matter (NAWM) were measured. Results: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression showed significantly faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group. Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. Conclusion: Clinical impairment and progression correlated with accumulating R2t*-defined microstructural tissue damage in deep GM and NAWM. qGRE-derived R2t* is a potential imaging biomarker of MS progression.