Magnetic resonance imaging of mouse skeletal muscle to measure denervation atrophy

We assessed the potential of different MRI measures to detect and quantify skeletal muscle changes with denervation in two mouse models of denervation/neurogenic atrophy. Acute complete denervation and chronic partial denervation were examined in calf muscles after sciatic nerve axotomy and in transgenic SOD1^G93A mice, respectively. Serial T₂, diffusion tensor, and high resolution anatomical images were acquired, and compared to behavioral, histological, and electrophysiological data. Increase in muscle T₂ signal was first detected after sciatic nerve axotomy. Progressive muscle atrophy could be monitored with MRI-based volume measurements, which correlated strongly with postmortem muscle mass measurements. Significant increase in muscle fractional anisotropy and decreases in secondary and tertiary eigenvalues obtained from diffusion tensor imaging (DTI) were observed after denervation. In SOD1^G93A animals, muscle denervation was detected by elevated muscle T₂ and atrophy in the medial gastrocnemius at 10 weeks. Changes in T₂ and muscle volume were first observed in medial gastrocnemius and later in other calf muscles. Alterations in secondary and tertiary eigenvalues obtained from DTI were first observed in tibialis anterior and medial gastrocnemius muscles at age 12 weeks. We propose that MRI of skeletal muscle is a sensitive surrogate outcome measure of denervation atrophy in animal models of neuromuscular disorders, with potential applicability in preclinical therapeutic screening studies in rodents.