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High-Frequency Ultrasound to Grade Disease Progression in Murine Models of Duchenne Muscular Dystrophy

Imaging Program, Lawson Health Research Institute, London, Ontario, Canada (N.A., L.H., D.H., T.-Y.L.); Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada (N.A., M.B., L.H., A.F., T.-Y.L.); Department of Radiology, London Health Sciences Center, London, Ontario, Canada (N.A., R.C., A.F., T.-Y.L.); Virginia Polytechnic Institute and State University, Blacksburg, Virginia USA (R.G.); and Departments of Animal Care and Veterinary Services (I.W.), Medical Biophysics (A.F., T.-Y.L.), and Medical Imaging (A.F., T.-Y.L.), University of Western Ontario, London, Ontario, Canada.

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. This study used high-frequency ultrasound (HFU) imaging to assess muscle damage noninvasively in a longitudinal study of 2 transgenic murine models of Duchenne muscular dystrophy (DMD): mdx, which has mutated cytoskeletal protein dystrophin; and udx, which has mutated dystrophin and lacks another cytoskeleton protein, utrophin. The mdx group was further subdivided into exercised and nonexercised subgroups to assess exercise-induced damage. Methods. Muscle damage was assessed with HFU imaging (40 MHz) at biweekly intervals for 16 weeks. The assessment was based on the number of hyperechoic lesions, the lesion diameter, and muscle disorganization, giving a combined grade according to a 5-point scale. Results. High-frequency ultrasound discriminated the severity of muscle damage between wild-type and transgenic models of DMD and between mdx and udx models. Qualitative comparisons of 3-dimensional HFU images with serial histologic sections of the skeletal muscle showed the ability of ultrasound to accurately depict changes seen in the muscle architecture in vivo. Conclusions. High-frequency ultrasound images soft tissue in mice at high contrast and spatial resolution, thereby showing that this microimaging modality has the capability to assess architectural changes in muscle fibers due to myotonic dystrophy–related diseases such as DMD.

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

Abbreviations: DMD, Duchenne muscular dystrophy • Ex, exercised • H&E, hematoxylin-eosin • HFU, high-frequency ultrasound • NE, nonexercised • wt, wild-type