PROJECT SUMMARY/ ABSTRACT This is a renewal for a Midcareer Investigator Award in Patient-Oriented Research (K24). The applicant, Dr. Richard Souza, is a clinician-scientist, Professor in Physical Therapy and Rehabilitation Science at the University of California, San Francisco. Throughout his career, Dr. Souza has built upon his clinical background through detailed and comprehensive studies on the influence of loading mechanics on knee and hip osteoarthritis (OA). These studies have used biomechanical methods such as motion capture systems, accelerometer-based activity monitoring, and strength assessment through dynamometry, and have characterized disease status and progression using advanced quantitative MRI metrics including T1ρ and T2 relaxation time mapping of knee and hip cartilage. Combining his background in musculoskeletal biomechanics with the world-renowned research team in the Department of Radiology and Biomedical Imaging at UCSF, Dr. Souza has been able to uncover key biomechanical variables that contribute to the earliest changes in the OA process. These efforts have resulted in a series of R01 awards on joint mechanics in OA, including a recently funded MPI R01 on bone and cartilage interaction in persons with patellofemoral joint OA (R01 AR079647). Understanding the predictive capability of lower extremity joint biomechanics to identify disease progression has been the driving force of Dr. Souza’s work. The team of investigators at UCSF in the Musculoskeletal Quantitative Imaging Research group, including Drs. Sharmila Majumdar, Thomas Link, Daehyun Yoon, Galateia Kazakia, and numerous other have built a collaborative infrastructure ripe for mentoring trainees with interest in the intersection of biomechanics and quantitative imaging. The current application requests funding (50% salary support) for 5 years to support the protected time necessary to conduct the proposed patient-oriented research and to expand opportunities for mentoring within the UCSF community. This protected time will allow Dr. Souza to continue to lead a productive research group and maintain minimal teaching and administrative responsibility at the Departmental and University levels. Dr. Souza will also obtain additional training in [18]FDG PET MR analysis and tracer kinetics, pain imaging, both peripherally and centrally, as well as participate in the Training in Clinical Research (TICR) program. There are plentiful opportunities to expand the work Dr. Souza has begun, and extremely high potential for clinical break-through in this important area of clinical research.