Neuromuscular disorders, including Duchenne's Muscular Dystrophy and Pompe disease, are progressive and often result in significant disability and sometimes death. Encouragingly, novel enzyme replacement and ge- netic therapies are becoming available, but they are associated with detrimental side effects and assessing their efficacy remains a challenge. Current methods used to assess muscle health are subjective, non-quantitative, and focus on muscle quantity and strength; however, measuring muscle quantity can over-estimate the amount of functional muscle, and muscle strength tests are affected by patient cooperation, pain, and co-morbidities. There is an urgent and unmet clinical need for a low-cost, non-invasive biomarker to accurately assess muscle health, monitor disease progression, and determine treatment response. Ultrasonic shear wave elasticity (SWE) imaging methods estimate the biomechanical properties of soft tissues, and these methods have demonstrated promise in the characterization of healthy and diseased muscle; however, commercially- available SWE methods are limited to estimating material parameters from a 2D imaging plane, and measure- ment variability and challenges with fiber alignment have limited clinical adoption. We have developed a 3D- SWE imaging system and advanced reconstruction algorithms with which we have obtained preliminary in vivo data that demonstrate, for the first time, the complex 3D shearwave behaviors generated by SWE excitations in vivo in skeletal muscles, and have observed significant differences between patients with myopathy that are consistent with clinical strength metrics. We have developed reconstruction algorithms that leverage the 3D-nature of these data to estimate multiple independent material properties, including: the longitudinal and transverse shear moduli, the shear anisotropy, the tensile anisotropy, and the viscosity along and across the muscle fibers. We hypothesize that the more complete material characterization afforded by these measurements will provide improved biomarkers of muscle health. We now propose to optimize the se- quencing and minimize the 3D data acquisition time; to automate and validate our parameter reconstruction al- gorithms; and to quantify the parameter measurement accuracy and precision in calibrated elasticity phantoms. Finally, we propose a pilot clinical study in which we will quantify and compare 3D-SWE muscle parameters in vivo in patients with myopathy and muscular dystrophy and in healthy controls, evaluate the repeatability of these measurements, and assess their correlation with clinical measures of muscle health. Successful com- pletion of this project will provide non-invasive quantitative biomarkers of muscle health on a low-cost portable platform, enabling frequent measurement and longitudinal monitoring of disease progression and treatment response which will facilitate personalized and optimized neuromuscular disease man- agement.