Project Summary Changes in muscle force and stiffness underlie the control of posture and movement. These fundamental abilities are impaired in almost all movement disorders, including those resulting from stroke, cerebral palsy, musculoskeletal injury, or pain. Rehabilitation can be framed in terms of re-establishing healthy patterns of muscle force and stiffness for each patient. Consequently, a fundamental challenge in the fields of biomechanics, motor control, and physical rehabilitation has long been measuring muscle force and stiffness in health and disease, yet there are no rigorous methods for doing so noninvasively. Ultrasound shear wave elastography (SWE) was proposed as a noninvasive tool for measuring stiffness, but we have demonstrated that SWE is sensitive not only to muscle stiffness but also to force, and that these dependencies vary across muscle types. While our results call into question conclusions from many previous studies, they also suggest that SWE could be reimagined as a tool for noninvasively measuring both stiffness and force. The objective of this proposal is to evaluate this intriguing possibility, which could transform the study of human movement and guide rehabilitation protocols for numerous motor disorders. Our long-term goal is to improve treatments for musculoskeletal disorders associated with changes to muscle force or stiffness. Our central hypothesis is that muscle stiffness and force can be uniquely determined from SWE by considering the distinctive structure of muscle. Shear wave propagation is sensitive to changes in muscle stress (force normalized by cross-sectional area) and stiffness, but it remains unknown if SWE can independently measure these quantities. Aims 1 and 2 will quantify how stresses from passive lengthening and active contraction alter shear wave propagation parallel to the direction of muscle fibers, as measured by the one-dimensional ultrasound arrays currently available in clinics. Studies will be conducted in an animal model so that SWE measurements can be compared to direct measures of muscle stiffness and stress (Aim 1), before considering the complexities of several human muscles thought to have internal variations in stress (Aim 2). Finally, we will evaluate the novel technique we have developed that uses multi-directional SWE to determine muscle stress and stiffness noninvasively (Aim 3); this will occur using a combination of 3D-printed biomaterials with known mechanical properties, muscles harvested from our animal model, and human experiments to rigorously test this innovative approach and adapt it as needed to account for the unique structure of muscle. We expect that our aims will clarify precisely what is being measured by current applications of SWE to muscle and determine if a novel approach employing multidirectional SWE can be used to measure muscle force and stiffness noninvasively. Such an ability would be transformative for rehabilitation, providing quantitative as...