Quantitative MRI Assessment of Myotoxin-Induced Skeletal Muscle Damage of mdx Mice

Although magnetic resonance imaging (MRI) has been extensively applied in dystrophic muscle, longitudinal characterization of multiple quantitative MRI parameters during degeneration and regeneration remains limited. This study aimed to longitudinally characterize changes in quantitative MRI parameters in control and dystrophic mouse muscles following myotoxin-induced myonecrosis using multi-parametric MRI (mpMRI).

mpMRI was performed at 14 Tesla in mdx ^4cv mice (n = 10) and control (ctrl) mice (n = 5) following intramuscular BaCl₂ injection. Quantitative maps of T1, T2, magnetization transfer ratio (MTR), and diffusion metrics were obtained from myotoxin- and saline-injected hind-limb muscles at multiple time points.

Mean T1 values decreased, reaching minima at day 5 in ctrl (3.05 ± 0.67 s) and day 3 in mdx ^4cv (2.60 ± 0.28 s) muscles. Mean T2 values increased and peaked at day 3 in both ctrl (34.83 ± 4.73 ms) and mdx ^4cv (33.53 ± 2.98 ms) muscles. MTR values decreased, reaching lowest levels at day 5 post-injection in both ctrl (69.12% ± 6.23%) and mdx ^4cv (69.20% ± 5.83%) muscles. T1, T2, and MTR returned to near-baseline values by day 21 day. Diffusion metrics demonstrated early increases in mean and radial diffusivity with a concomitant decrease in fractional anisotropy, followed by recovery between days 5 and 7.

mpMRI revealed distinct, time-dependent changes following myotoxin injury, demonstrating the added value of mpMRI as a noninvasive approach for sensitively characterizing the temporal evolution of quantitative MRI parameters following myotoxin-induced muscle injury in both control and dystrophic mice.