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Detecting Degenerative Changes in Myotonic Murine Models of Duchenne Muscular Dystrophy Using High-Frequency Ultrasound

Imaging Program, Lawson Health Research Institute, London, Ontario, Canada (N.A., T.-Y.L.); Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada (N.A., M.B., T.D.Z., A.F., T.-Y.L.); Departments of Medical Biophysics (N.A., T.-Y.L.) and Medical Imaging (A.F., T.-Y.L.), University of Western Ontario, London, Ontario, Canada; Department of Radiology, London Health Sciences Center, London, Ontario, Canada (A.F., T.-Y.L.); and Department of Diagnostic Radiology; Medical University of Innsbruck, Innsbruck, Austria (T.D.Z.).

Address correspondence to Ting-Yim Lee, PhD, Imaging Research Laboratories, Robarts Research Institute, 100 Perth Dr, London, ON N6A 5K9, Canada. E-mail: tlee{at}imaging.robarts.ca

Objective. Ultrasound imaging is an economical and noninvasive technique for studying musculoskeletal diseases such as Duchenne muscular dystrophy (DMD). Duchenne muscular dystrophy results from the loss of the cytoskeletal protein dystrophin. This in turn increases muscle susceptibility to injury, resulting in myofiber membrane leakage, inflammation, and degeneration. The purpose of this study was to detect dystrophic changes in muscle noninvasively. High-frequency ultrasound (HFU; 40 MHz) was used to obtain a resolution of 80 µm, which is not achievable with lower-frequency clinical scanners. Methods. Using HFU, we were able to visualize musculoskeletal abnormalities as hyperechoic lesions within the dystrophic muscle. To validate the imaging findings, fiducial markers were placed in close proximity to lesions under HFU guidance. The nature of the lesion was then investigated histologically. This was repeated in the lower limbs of 10 mdx (mutated dystrophin gene) mice, a transgenic murine model of DMD. Results. The abnormalities in the dystrophic muscle consisted of large influxes of leukocytic infiltrates, fibrotic scars, and calcified lesions. Conclusions. Although macrophages and fibrosis are commonly noted in DMD, to our knowledge, the presence of intramuscular calcific necrosis in dystrophic muscle has not been reported. This novel dystrophic feature of muscle degeneration may be useful in longitudinal studies of murine DMD and regenerative studies.

Key Words: calcification • disease progression • Duchenne muscular dystrophy • high-frequency ultrasound

Abbreviations: DMD, Duchenne muscular dystrophy • H&E, hematoxylin-eosin • HFU, high-frequency ultrasound