Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort

Objective The aim of this study was to describe Duchenne muscular dystrophy (DMD) disease progression in the lower extremity muscles over 12 months using quantitative magnetic resonance (MR) biomarkers, collected across three sites in a large cohort. Methods A total of 109 ambulatory boys with DMD (8.7 ± 2.0 years; range, 5.0–12.9) completed baseline and 1‐year follow‐up quantitative MR imaging (transverse relaxation time constant; MRI‐T2), MR spectroscopy (fat fraction and 1H2O T2), and 6‐minute walk test (6MWT) measurements. A subset of boys completed additional measurements after 3 or 6 months. Results MRI‐T2 and fat fraction increased significantly over 12 months in all age groups, including in 5‐ to 6.9‐year‐old boys. Significant increases in vastus lateralis (VL) fat fraction were observed in 3 and 6 months. Even in boys whose 6MWT performance improved or remained stable over 1 year, significant increases in MRI‐T2 and fat fraction were found. Of all the muscles examined, the VL and biceps femoris long head were the most responsive to disease progression in boys with DMD. Interpretation MR biomarkers are responsive to disease progression in 5‐ to 12.9‐year‐old boys with DMD and able to detect subclinical disease progression in DMD, even within short (3–6 months) time periods. The measured sensitivity of MR biomarkers in this multicenter study may be critically important to future clinical trials, allowing for smaller sample sizes and/or shorter study windows in this fatal rare disease. Ann Neurol 2016;79:535–547