4 years ago

Magnetic Resonance Monitoring of Disease Progression in mdx Mice on Different Genetic Backgrounds

Genetic modifiers alter disease progression in both preclinical models and subjects with Duchenne muscular dystrophy (DMD). Using multiparametric magnetic resonance (MR) techniques, we compared the skeletal and cardiac muscles of two different dystrophic mouse models of DMD, which are on different genetic backgrounds, the C57BL/10ScSn-Dmdmdx (B10-mdx) and D2.B10-Dmdmdx (D2-mdx). The proton transverse relaxation constant (T2) using both MR imaging and spectroscopy revealed significant age-related differences in dystrophic skeletal and cardiac muscles as compared with their age-matched controls. D2-mdx muscles demonstrated an earlier and accelerated decrease in muscle T2 compared with age-matched B10-mdx muscles. Diffusion-weighted MR imaging indicated differences in the underlying muscle structure between the mouse strains. The fractional anisotropy, mean diffusion, and radial diffusion of water varied significantly between the two dystrophic strains. Muscle structural differences were confirmed by histological analyses of the gastrocnemius, revealing a decreased muscle fiber size and increased fibrosis in skeletal muscle fibers of D2-mdx mice compared with B10-mdx and control. Cardiac involvement was also detected in D2-mdx myocardium based on both decreased function and myocardial T2. These data indicate that MR parameters may be used as sensitive biomarkers to detect fibrotic tissue deposition and fiber atrophy in dystrophic strains.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017303851

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