Background: An increasing number of pharmaceutical companies are interested in drug development for Becker muscular dystrophy, but assessing efficacy in this slowly-progressing disease is challenging. Quantitative magnetic resonance imaging (qMRI) measurement of fat fraction (FF) is highly sensitive to disease progression in the muscular dystrophies, including BMD. The aim of the ImagingNMD study is to characterize disease progression in BMD to facilitate clinical trials.
Methods:Thirty men with BMD volunteered to participate in the study and underwent quantitative whole-body Dixon imaging to generate fat fraction (FF) maps. Whole-body composite fat fraction (WB FF) was calculated as the mean of the FF of the biceps brachii, triceps brachii, deltoid, erector spinae, rectus abdominus, quadriceps, hamstrings, soleus, medial gastrocnemius, and tibialis anterior muscles. Participants completed functional testing including the North Star Assessment for Dysferlinopathies (NSAD) and Performance of Upper Limb (PUL).
Results: Considerable variability in muscle fat fraction was observed across individuals: WB FF ranged from 10% to 66%. Characteristic patterns of involvement were seen: the thighs and trunk, as well as the medial gastrocnemius and erector spinae muscles, had high average FF, while the deltoid, lower leg, and triceps brachii muscles had low average FF. WB FF was not significantly correlated with age in BMD (rho=0.41, p=0.09), but was significantly correlated with NSAD score (rho=-0.88, p<0.0001). WB FF was also significantly correlated with PUL score (-0.60, p=0.008). However, 63% of participants scored at least 40/42 on the PUL; among these participants, WB FF was 0.33 ± 0.17, indicating that substantial disease involvement is present before upper extremity function declines. Conclusions: MRI FF is strongly associated with functional performance in BMD. This data set provides information to help design clinical trials; however more participants are needed to ensure that the data set reflects the full population of men living with BMD.