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 T-2, diffusion tensor, and high resolution anatomical images were acquired, and compared to behavioral, histological, and electrophysiological data. Increase in muscle T-2 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 T-2 and atrophy in the medial gastrocnemius at 10 weeks. Changes in T-2 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. (C) 2008 Elsevier Inc. All rights reserved.