Symptomatic knee osteoarthritis (KOA) affects an estimated 30 million adults in the U.S. and contributes to more than $27 billion in annual healthcare costs. The discordance between pain presentation and structural damage in KOA is a crucial issue that hampers both effective clinical management and development of disease-modifying therapies. This is in part related to different pain phenotypes (nociceptive, nociplastic and neuropathic-like) underlying the chronic pain experience in KOA. Structural pathology thought to contribute to nociceptive pain in KOA include MRI-detected bone marrow lesions (BML), effusion/synovitis, meniscal root tears and extrusion, and CT-detected intra-articular mineralization. In contrast, in patients with “neuropathic-like” and/or “nociplastic” pain, those joint alterations are less likely to explain pain. The first aim investigates the relationship between knee imaging biomarkers (MRI, CT) and pain phenotypes (nociceptive vs. neuropathic-like or nociplastic). The second aim investigates the relation between pain phenotypes and imaging biomarkers to persistent pain, 6 months post knee replacement. In the third aim, I will attempt to identify the relation of co-existing knee imaging biomarkers (on MRI and CT) to pain phenotypes. This proposal brings multiple disciplines and fields of expertise (rheumatology, radiology, pain, psychology and neuroscience) to advance our knowledge on the relationship between structural damage and pain phenotypes in KOA. This funding opportunity is critical to help me transition toward independent research and R01 funding. I will have protected time for this project and a highly supportive academic environment. I will have access to leading experts in the fields outlined above, in addition to formal coursework and career development series through Harvard Medical School, Harvard T.H. Chan School of Public Health and the Massachusetts General Hospital. As a musculoskeletal radiologist with strong research background in imaging biomarkers of KOA, this proposal will provide me with training in advanced epidemiology and biostatistics, pain research and assessment tools, as well as expertise in conducting clinical investigations of imaging biomarkers of chronic KOA pain. Successful completion of these aims may lead towards improved clinical trial designs targeting the “right therapies to the right patient” based on underlying pain phenotypes, and selection of appropriate structural outcomes related to those phenotypes. Ultimately, this work will enhance the success of identifying promising treatments for millions of people living with KOA.