Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis

Background Multiple sclerosis (MS) is a chronic disease affecting the human central nervous system (CNS) and leading to neurologic disability. Although conventional MRI techniques can readily detect focal white matter (WM) lesions, it remains challenging to quantify tissue damage in normal-appearing gray matter (GM) and WM. Purpose To demonstrate that a new MRI biomarker, R2t*, can provide quantitative analysis of tissue damage across the brain in MS patients in a single scan. Study Type Prospective. Subjects Forty-four MS patients and 19 healthy controls (HC). Field Strength/Sequence 3T, quantitative gradient-recalled-echo (qGRE), Magnetization-prepared rapid gradient-echo, fluid-attenuated inversion recovery. Assessment Severity of tissue damage was assessed by reduced R2t*. Tissue atrophy was assessed by cortical thickness and cervical spinal cord cross-sectional area (CSA). Multiple Sclerosis Functional Composite was used for clinical assessment. Results R2t* in cortical GM was more sensitive to MS damage than cortical atrophy. Using more than two standard deviations (SD) reduction versus age-matched HC as the cutoff, 48% of MS patients showed lower R2t*, versus only 9% with lower cortical thickness. Significant correlations between severities of tissue injury were identified among 1) upper cervical cord and several cortical regions, including motor cortex (P < 0.001), and 2) adjacent regions of GM and subcortical WM (P < 0.001). R2t*-defined tissue cellular damage in cortical GM was greater relative to adjacent WM. Reductions in cortical R2t* correlated with cognitive impairment (P < 0.01). Motor-related clinical signs correlated most with cervical cord CSA (P < 0.001). Data Conclusion Reductions in R2t* within cortical GM was more sensitive to tissue damage than atrophy, potentially allowing a reduced sample size in clinical trials. R2t* together with structural morphometry suggested topographic patterns of regions showing correlated tissue damage throughout the brain and the cervical spinal cord of MS patients. Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:487-498.