Magnetic Resonance Imaging and Spectroscopy Assessment of Lower Extremity Skeletal Muscles in Boys with Duchenne Muscular Dystrophy: A Multicenter Cross Sectional Study

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that (H2OT2)-H-1 derived using H-1-MRS and MRI-T-2 will be sensitive to muscle involvement at a young age (5-7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls. Methods: MR data were acquired from 123 boys with DMD (ages 5-14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children's Hospital of Philadelphia). T-2-weighted multi-slice spin echo (SE) axial images and single voxel H-1-MRS were acquired from the lower leg and thigh to measure lipid fraction and (H2OT2)-H-1. Results: MRI-T-2, (H2OT2)-H-1, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T-2, (H2OT2)-H-1 and lipid fraction and vastus lateralis MRI-T-2 and (H2OT2)-H-1. In the boys with DMD, MRI-T-2 and lipid fraction were greater (p<0.05) in the oldest age group (11-14 years) than the youngest age group (5-6.9 years), while (H2OT2)-H-1 was lower in the oldest age group compared to the young age group. Discussion: Overall, MR measures of T-2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T-2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T-2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.