LAUSR

Duchenne muscular dystrophy (DMD) is characterized by a progressive replacement of muscle by fat and fibrous tissue, muscle weakness, and loss of functional abilities. Impaired vasodilatory and blood flow responses to muscle activation have also been observed in DMD and associated with mislocalization of neuronal nitric oxide synthase mu (nNOSμ) from the sarcolemma. The objective of this study was to determine whether the post-contractile blood oxygen level-dependent (BOLD) MRI response is impaired in DMD and correlated with established markers of disease severity in DMD, including MRI muscle fat fraction (FF) and clinical functional measures. Young boys with DMD (n=16, 5-14 years) and unaffected controls (n=16, 5-14 years) were evaluated using post-contractile BOLD, FF, and functional assessments. The BOLD response was measured following five brief (2 s) maximal voluntary dorsiflexion contractions, each separated by one minute of rest. FF from the anterior compartment lower leg muscles were quantified via chemical shift encoded imaging. Functional abilities were assessed using the 10m walk/run and the 6-minute walk distance (6MWD). The peak BOLD response in the tibialis anterior and extensor digitorum longus were reduced (P<0.001) in DMD compared to controls. Furthermore, the anterior compartment peak BOLD response correlated with function (6MWD ρ=0.87, P<0.0001; 10 m walk/run time ρ=-0.78, P<0.001) and FF (ρ =-0.52, P=0.05). The reduced post-contractile BOLD response in DMD may reflect impaired microvascular function. The relationship observed between the post-contractile peak BOLD response and functional measures and FF suggests that the BOLD response is altered with disease severity in DMD.