Magnetic Resonance Imaging and Spectroscopy Biomarkers in Hereditary Muscle Diseases

Statement of problem: Clinical research in hereditary muscle disease is limited by the absence of quantitative and objective biomarkers and outcome measures that track disease severity. A growing body of literature supports the use of magnetic resonance imaging (MRI) as a potential biomarker of disease in skeletal muscle. The work presented seeks to examine the viability of magnetic resonance-based biomarkers in muscular dystrophy. Methods: We conducted a systematic review of publications reporting MRI findings in skeletal muscle in muscular dystrophy and congenital myopathy populations. We subsequently performed an observational study of whole-body MRI in people with type 1 facioscapulohumeral muscular dystrophy (FSHD) to characterize the frequency and severity of muscle involvement in this population. We then used a multivoxel magnetic resonance spectroscopy (MRS) protocol to obtain metabolite concentration profiles of skeletal muscle in people with FSHD. These profiles were compared to those of healthy volunteers. The associations between MRI/MRS measurements and clinical strength and function were examined using linear regression models. Results: A systematic review of the literature on MRI in hereditary myopathies showed widely variable methods of analysis and reporting. However, distinctive patterns of muscle involvement can be identified in some diseases. Whole-body MRI was used to characterize muscle involvement and sparing in FSHD. MRS further identified differences in muscle metabolite concentrations in people with FSHD compared to healthy controls. Both MRI and MRS measurements showed a significant association with strength in specific muscle groups. Conclusions: MRI and MRS can be used to identify patterns of disease and assess disease severity in the muscular dystrophies. Longitudinal studies are needed to develop imaging techniques as biomarkers for use in clinical trials and observational studies