Multi-Vendor Multi-Site Novel Accelerated MRI Relaxometry

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PROJECT SUMMARY/ABSTRACT This urgent competitive revision responds to NIAMS Notice of Special Interest (NOSI) NOT-AR-23-015. The parent study (NIAMS R01 AR077452) aims to develop novel quantitative MRI techniques (accelerated MR T1ρ and T2 mapping) to evaluate cartilage compositional changes and early degeneration in patients after anterior cruciate ligament reconstruction (ACLR), a population at high risk of developing post-traumatic osteoarthritis (PTOA). In this study, we aim to explore the mechanisms in musculoskeletal (MSK) pain and identify novel imaging (knee and brain) markers for pain after ACL injury and surgery, and at early PTOA. The proposed study will significantly expand the scope of the parent study from only focusing on structural changes (‘disease’) to one evaluating patient symptoms (‘illness’, in particular pain) in OA. With a novel multi-modal approach that includes advanced knee and brain MRI, our group will, for the first time, investigate central neural system (CNS) alterations in pain post orthopaedic injury/surgery, and in early PTOA. The study outcomes will provide critical preliminary data to formulate specific hypotheses for MSK pain, and will develop novel imaging techniques that can be utilized for future large-scale studies of pain mechanisms following orthopaedic injury/surgery and in OA/PTOA, an under-investigated area with pressing clinical needs. As such, the proposed study is aligned with the NOSI Goal A: Generate supporting evidence towards a future innovative study or new scientific direction in pain research in musculoskeletal diseases, in the areas of interest of novel pain imaging technologies. OA affects 30+ million people in the US and 300+ million people worldwide. It presents tremendous health and socioeconomic burdens with health care costs and work loss. Pain is the major factor that significantly impairs quality of life, leads to disability, and prompts patients for clinical visits and eventually total joint arthroplasty for OA. Opioid prescriptions for severe OA/PTOA pain and pain after orthopaedic injury are common, which constitutes a significant contribution to the national opioid crisis due to its high prevalence. A better understanding of the mechanisms of post-injury/surgery and OA/PTOA pains and identifying biomarkers that are associated with or predict MSK pain, the gap the proposed study aims to fill, will provide useful guidance on developing novel therapeutic targets for pain relief in OA and other MSK disorders. The proposed study presents a significant and timely expansion of the parent study. It will leverage the resources from the parent study and provide a unique opportunity to investigate relationship between joint structural damages, CNS alternations, and pain in a novel early OA model (PTOA, after orthopaedic injury and surgery). The study outcomes will provide valuable insights to MSK pain mechanisms, help identify new treatment targets for pain relief in this huge patient population, and eventually help with providing scientific solutions to battle against the ever- increasing opioid epidemic in the US.