Temporal changes in magnetic resonance imaging in the mdx mouse

Abstract

Background Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive loss of skeletal muscle. The phenotype is much less severe in the mdx mouse model of DMD than that seen in patients with DMD. However, a “critical period” has been described for the mdx mouse, during which there is a peak in muscle weakness and degeneration/regeneration between the 2nd and 5th weeks of life. A number of studies have employed small animal magnetic resonance imaging (MRI) to examine skeletal muscle in various dystrophic models, but such studies represent a snapshot in time rather than a longitudinal view. Results The in vivo cross-sectional T2-weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease. We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles. Here we monitored an mdx mouse using MRI from 5 to 80 weeks of age. Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter. The 4.3-fold increase in percent heterogeneity at week 9 and 13 is consistent with the notion of an early critical period described for mdx mice. Conclusions Age is a significant variable in quantitative MR studies of the mdx mouse. The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology, but the preliminary findings here, albeit based on imaging only one mdx mouse over time, suggest that the changes in MRI can occur shortly after this period, when the muscles are still recovering.