Assessment of Skeletal Muscle Damage in Mice using Diffusion Tensor MRI

Abstract

Diagnosis of acute muscle strains is still typically made based on physical exam and patient history, but muscle injuries can be detected with magnetic resonance imaging (MRI). Conventionally, muscle strains are revealed best by T2-weighted MRI, which optimizes contrast between edema and muscular tissue. PURPOSE: To determine if variables calculated from diffusion tensor imaging (DTI) would serve as an earlier and more sensitive marker of damage after a muscle strain injury in dystrophic (mdx) and control mice. We hypothesize that DTI biomarkers will provide a more informative assessment of muscle injury, and these measures will further elucidate the increased susceptibility to injury of the mdx model. METHODS: Unilateral injury to the tibialis anterior muscle (TA) was induced by 15 maximal lengthening contractions in mdx mice (n=3) and control mice (n=3). High resolution T1 and T2-weighted structural MRI (100μm × 100μm × 750 μm) including T2 mapping and spin echo DTI (150μm × 150μm × 750 μm × 12 directions) were acquired on a 7T MRI system. T2 and diffusion tensor parameters (ie apparent diffusion coefficient [ADC], fractional anisotropy [FA], axial and radial diffusivity [AD and RD]) were calculated at each pixel location. TA imaging was compared to functional changes and HE staining and immunofluorescent labeling of TA cross-sections. RESULTS: Injury was confirmed by a significant loss of isometric torque (85% in mdx vs. 42% in controls). Parameter values were calculated as the percent increase in relation to the contralateral, uninjured TA of each animal. Greater increase in ADC, AD, and RD of the injured muscle was present in the mdx mice vs. controls when compared at proximal, medial, and distal locations of the muscle. These changes were paralleled by decreases in FA. On average, changes in DTI parameters were 1.8× greater in the mdx mice vs. controls. In comparison, changes in T2 did not indicate clear differences between mdx and controls. CONCLUSIONS: These data suggest that DTI may be a better indicator of muscle injury, even at early time points where the MR signal changes are dominated by local edema. Supported by grants from the Muscular Dystrophy association (MDA, grant 4278) and NIH-NIAMS (K01AR053235) to RML