Multiparameter MRI analysis of the time course of induced muscle damage and regeneration.

Abstract

To test the ability of different magnetic resonance imaging (MRI) modalities to discriminate the time course of damage and regeneration in a model of acute, toxin-induced muscle damage. We analyzed the time course of tissue and cellular changes in mouse lower limb musculature following localized injection of myotoxin by T2 , magnetization transfer (MT), and diffusion-weighted MRI. We also used T1 -weighted imaging to measure leg muscle volume. In addition, postmortem histological analysis of toxin-injected muscles was compared to uninjected controls. The damages detected by the MRI modalities are transient and recover within 3 weeks. Muscle water diffusivity and edema measured by leg volume increased within the first hours after injection of the toxin. The rate constant for volume increase was 0.65 ± 0.11 hr(-1) , larger than the increase in T2 (0.045 ± 0.013 hr(-1) ) and change in MT ratio (0.028 ± 0.021 hr(-1) ). During repair phase, the rate constants were much smaller: 0.022 ± 0.004 hr(-1) , 0.013 ± 0.0019 hr(-1) and 0.0042 ± 0.0016 hr(-1) for volume, T2 , and MT ratio, respectively. Histological analyses confirmed the underlying cellular changes that matched the progression of MR images. The kinetics of change in the MRI measurements during the progression of damage and repair shows MRI modalities can be used to distinguish these processes.