MRI shows promise as a surrogate outcome measure for DMD that is capable of non-invasively detecting muscle damage in patients. Here we use magnetic resonance technologies to identify and longitudinally characterize phenotypes in the mdx model of DMD. Since mdx mice naturally show a peak of necrosis, weakness and disease at 3 to 6 weeks of age, followed by a natural recovery phase in which they show only mild skeletal muscle disease, the peak disease phase is commonly used to assess preclinical efficacy of therapeutics. We find mdx mice show significant imaging and spectroscopic alterations during this peak disease phase. Furthermore, these changes decrease as mice progress to the recovery phase. Our findings indicate non-invasive MRI and NMR spectroscopy are sensitive outcome measures that can be used to study disease and evaluate potential therapies in the mdx model of muscular dystrophy. Significant deficits in AP24534 943319-70-8 phosphocreatine and increased inorganic phosphate are also found in DMD patients. Since energy for muscle contractions comes from phosphocreatine, which is used for generation of ATP through a reversible reaction with creatine phosphokinase, the PCr:ATP ratio is reflective of the energy state of muscle. Thus, the decrease in PCr:ATP reflects a muscle bioenergetics deficit in both dystrophic 3- to 12-year-old DMD patients and 6-week-old mdx mice. Similar results have been found in ex vivo cardiac studies of mdx mice, where a decrease in PCr is found in association with a decrease in mitochondrial content of heart tissue. Consistent with heart muscle, we and others find significant mitochondrial deficits in mdx skeletal muscle. Other muscle disorders such as mitochondrial myopathies and polio paralysis show a deficit in phosphocreatine levels as well. Interestingly, we find the PCr:ATP ratio in mdx increases to a level not significantly different from wild-type by 8 to 10 weeks of age. This illustrates an improvement in energetics of dystrophic mdx skeletal muscle during the period associated with recovery. MRI of mdx muscle provides significant phenotypes at all ages examined, characterized by hyper-intense foci and a more heterogeneous appearance. Histology shows these imaging phenotypes correspond to dystrophic lesions containing a mix of inflammation with degenerating, regenerating, and hypertrophic myofibers. This is consistent with Walter et al, who find hyperintense regions are consistent with dystrophic lesions and damaged myofibers enhanced by contrast agents, and who use 1 H spectroscopy in mdx to show minimal fatty infiltration in comparison to DMD. We see foci of hyper-intense signal change over time, consistent with a dynamic disease process and with time frames established for muscle repair following crush injury. We find cross-sectional area of mdx muscle increases over time, while absolute volume of dystrophic lesions in imaging does not. Data in the literature indicate such increases in CSAmax are the result of hypertrophy and regeneration. Comparing spectroscopy and imaging results, there is a discrepancy in mdx mice. Spectroscopy shows an initial energetics deficit that is eliminated by 8–10 weeks, while imaging phenotypes improve but persist at all ages examined. Established muscle histology and function data may provide insight into these differences.