Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy as Diagnostic and Progression Marker Using Multispectral Optoacoustic Tomography

Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) is one of the most common progressive childhood muscle diseases with an incidence of 1 in 3500 male newborns and is associated primarily with decreased life expectancy. From the age of 4-5 years manifest motor problems in everyday life, typical signs of proximal muscle weakness, with lab-chemical increase of the muscle enzyme (creatinine kinase, CK). Within a few years, relevant muscle and tendon shortening leading to joint malpositions and instability, as well as scoliosis and loss of walking around the age of 10 are formed. Supportive therapies can not curatively affect complications and progression of the disease. Pathogenetically, there is a deficiency of dystrophin, a structural protein of the sarcolemma, which is caused by mutations (usually deletions) of the dystrophin gene (Xp21.3-p21.2). The result of dystrophin deficiency is a necrosis of muscle cells that are replaced by connective tissue and adipose tissue. Clinical scores (6-minute walk test, 6MWT) and MRI studies to characterize the degenerative changes of skeletal muscle in the early stages are available for the quantitative assessment of the disease progression as well as therapy effects, the significance of which is controversially discussed. However, the highly sensitive assessment of gene therapy effects (e.g., PTC 124) will become increasingly important in the future. Sensitive, non-invasive methods for the detection of early muscle degeneration and muscle function in the course are of great clinical and scientific importance. The purpose of this first pilot study is to investigate whether the differences in skeletal muscle composition of healthy volunteers and ambulatory patients with early stage DMD can be quantified and characterized using multispectral optoacoustic tomography (MSOT). This could in the future generate a completely new, non-invasive method to develop non-invasive biomarkers of disease progression or therapy response.