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

Abstract

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.

Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy

“…4D–E). In agreement with a recent publication [18], we found that the IDEAL-CPMG sequence detected modest increases in the thigh muscles AFF in the six and seven year-old subjects whose 6MWD improved over year (Fig. 4D).…”

MicroRNA-29 overexpression by adeno-associated virus suppresses fibrosis and restores muscle function in combination with micro-dystrophin

“…Replacement of intact muscle with significant accumulation of fibrosis can affect muscle function (25,26). GAS muscle from mdx/utrn +/-mice treated with scAAVrh.74.…”

Upper arm and cardiac magnetic resonance imaging in Duchenne muscular dystrophy

“…Natural history studies are needed to better understand the relation between the disease progression in skeletal muscles of the upper and lower limbs and in heart of patients, which is not yet clearly understood. MRI biomarkers of muscle fat percentage are responsive to disease progression in the lower limb and forearm muscles of patients with DMD 4, 23, 24. Moreover, muscle fat percentage changes were detected in the lower limb muscles of younger patients who were functionally stable or showed improvement in the functional outcome measures over 1 year 23, 25.…”

“…MRI biomarkers of muscle fat percentage are responsive to disease progression in the lower limb and forearm muscles of patients with DMD 4, 23, 24. Moreover, muscle fat percentage changes were detected in the lower limb muscles of younger patients who were functionally stable or showed improvement in the functional outcome measures over 1 year 23, 25. Imaging fatty replacement in the myocardium may be a noncontrast method of assessing the disease state of the myocardium in individuals with DMD.…”