Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy.

INTRODUCTION/AIMS: Improved methodologies to monitor the progression of Duchenne muscular dystrophy (DMD) are needed, especially in the context of clinical trials. We report changes in muscle magnetic resonance imaging (MRI) parameters in participants with DMD, including changes in lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) and their relationship to changes in functional parameters.

METHODS

MRI data were obtained as part of a clinical study (NCT02310763) of domagrozumab, an antibody-targeting myostatin that negatively regulates skeletal muscle mass. This post hoc analysis evaluated participants with Dixon MRI data and corresponding functional data at baseline and weeks 49 and 97. Images were analyzed to evaluate changes in adductors, hamstrings, and quadriceps.

RESULTS

There was a positive correlation between increases in LMV and function. LMV changes in adductors (R = 0.51) and quadriceps (R = 0.54) showed a stronger correlation with function than LMV changes in hamstrings (R = 0.30). There was a negative correlation between MFF and MFI, respectively, and function in adductors (R = -0.57, R = -0.42), quadriceps (R = -0.59, R = -0.50), and hamstrings (R = -0.53, R = -048). Participants with preserved North Star Ambulatory Assessment scores had high total LMV (LMVtot) and low total MFI (MFItot). Low ratios of LMVtot to MFItot, or participants with small LMVtot and high MFItot, appeared to have a rapid decline in function and loss of ambulation.

DISCUSSION: These findings support the use of MRI biomarkers as potential surrogate endpoints in clinical trials of patients with DMD.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02310763.