High-frequency ultrasound to grade disease progression in murine models of Duchenne muscular dystrophy.
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.
Ahmad
Nabeel
N
Imaging Research Laboratories, Robarts Research Institute, 100 Perth Dr, London, ON N6A 5K9, Canada.
Bygrave
Mike
M
Chhem
Rethy
R
Hoffman
Lisa
L
Welch
Ian
I
Grange
Robert
R
Fenster
Aaron
A
Hill
David
D
Lee
Ting-Yim
TY
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D016189:Dystrophin / Q000235:genetics; D017353:Gene Deletion; D021621:Imaging, Three-Dimensional; D008137:Longitudinal Studies; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D009137:Muscular Dystrophy, Animal / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010805:Physical Conditioning, Animal; D017354:Point Mutation; D014463:Ultrasonography / Q000379:methods; D049411:Utrophin / Q000235:genetics
D016189:Dystrophin; D049411:Utrophin