Effects Of Downhill Running On Muscle MRI T2 In Young mdx Mice

Abstract

Previous studies have demonstrated that downhill treadmill running causes skeletal muscle damage that can be detected with magnetic resonance transverse relaxation time (T2) in adult dystrophic mice (mdx). However, young mdx mice (under 12 weeks of age) are characterized by a peak inflammatory phase with greater heterogeneity among muscles, potentially making it more difficult to detect T2 changes. PURPOSE: To determine whether muscle damage following downhill running can be detected in young mdx mice using proton magnetic resonance imaging (MRI) and spectroscopy (MRS). METHODS: C57BL/10ScSn-DMDmdx (mdx, n=5) and wild-type C57BL/10ScSn (controls, n=5) male mice of 6-9 weeks of age performed downhill running on a treadmill (14% grade at 8-12m/min for 45-60 min). MRI/MRS was conducted prior to and 24 hours following running in the mice hindlimbs. T2-weighted, multiple-slice, single spin-echo MR axial images were acquired (TR 2s, TE 14/40 ms, 12 slices) from the hindlimbs. MRI T2 values were calculated on a pixel-by-pixel basis for the anterior compartment (AC), posterior compartment (PC), and the deep medial region between the tibia and fibula (MC). In addition, single voxel 1H-MRS data were acquired from the soleus and gastrocnemius using stimulated echo acquisition mode (STEAM; TR 9 s, 32 TE’s exponentially spaced: 5-288 ms, 4 phase cycles) with a 4.7 T Varian/Agilent MR system. RESULTS: At baseline, T2 was elevated (p<0.05) in mdx mice (26.8±1.2ms) compared to controls (24.8±0.9 ms). Following downhill running, the mdx mice had elevated (p<0.05) T2 values compared to baseline when a composite of the compartments were compared (Pre: 26.8±1.2ms; Post: 28.8±1.4 ms). The MC was typically (80%) the most affected hindlimb region in the mdx mice. Similarly, 1H-MRS derived T2 values were increased (p=0.05) in a composite measure of the soleus and gastrocnemius after downhill running (29.8±4.2ms) in mdx compared to before downhill running (26.4±2.8ms). There were no significant changes in T2 in control mice after performing the downhill running protocol. CONCLUSIONS: Overall, our findings support the use of downhill running combined with MR T2 measures as a valuable approach for testing potential therapeutic interventions in young dystrophic mice. Funding Source: NIH (NIAMS) R01 AR070101.