Establishing the Relationship Between Muscle Quality and Joint Loading for Individuals with Transtibial Amputation - ABSTRACT The loss of function following an amputation is profound and life altering. To date, interventions to improve long term functional abilities and limit detrimental secondary injuries (e.g. osteoarthritis) have not been effective. While multifactorial, the effect of altered muscle quality, specifically of the quadriceps, on functional outcomes for individuals with transtibial amputation is poorly understood. Work by our group in other conditions shows that muscle quality changes after injury and is directly related to loss of function, including protracted strength deficits. My long-term career goal is to combine my background in bioengineering with the skills developed through this F32 training grant to develop novel therapeutic strategies and devices to improve function and quality of life for individuals with lower limb loss. This training award will allow me to 1) assess the muscle quality of the thigh of the intact and residual limbs with novel magnetic resonance imaging sequences, 2) predict the relationship between thigh muscle quality and muscle strength, and finally 3) characterize the relationship between muscle quality, muscle strength, and knee joint loading for individuals with transtibial amputation. Muscle quality will be assessed using novel magnetic resonance imaging techniques including T1rho mapping and diffusion tensor imaging. These techniques will provide new insights on the muscle tissue morphology, including any increases in fibrotic tissue or decreases in pennation angle and fiber tract length, that affect the muscle's overall ability to function properly and efficiently. To evaluate muscle strength and mobility, participants will complete maximum voluntary isometric knee flexion and validated surveys targeting self-reported mobility. Finally, joint contact forces of the intact limb will be assessed through a computational musculoskeletal model. Through the work proposed for this NRSA F32, I will refine and gain skills critical for a successful career as an independent translational researcher seeking to collaborate with clinician scientists. Training will include skills development in medical imaging acquisition and analysis, clinically relevant strength assessment, instrumented motion analysis, musculoskeletal modeling, clinical research management, and statistical analysis. Including in the training plan are accessory career development activities including related course work (e.g. biomechanics, statistics, medical imaging), grant writing workshops, opportunities for research dissemination, and mentorship that will all be key components to developing a well-rounded skill set for a future academic career. My selected sponsor, institution, and mentors will provide the perfect environment for encouraging success.