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High‐Frequency Ultrasound to Grade Disease Progression in Murine Models of Duchenne Muscular Dystrophy
Authors:Nabeel Ahmad MSc  Mike Bygrave BSc  Rethy Chhem MD  PhD  Lisa Hoffman PhD  Ian Welch DVM  Robert Grange PhD  Aaron Fenster PhD  David Hill PhD  Ting-Yim Lee PhD
Affiliation:1. Imaging Program, Lawson Health Research Institute, London, Ontario, Canada;2. Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada;3. Department of Radiology, London Health Sciences Center, London, Ontario, Canada;4. Department of Animal Care and Veterinary Services, University of Western Ontario, London, Ontario, Canada;5. Virginia Polytechnic Institute and State University, Blacksburg, Virginia USA;6. Departments of Medical Biophysics, University of Western Ontario, London, Ontario, Canada;7. Department of Medical Imaging, University of Western Ontario, London, Ontario, Canada
Abstract: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.
Keywords:calcification  disease progression  Duchenne muscular dystrophy  high-frequency ultrasound
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