Multi-Vendor Multi-Site Novel Accelerated MRI Relaxometry

项目摘要/摘要 这一紧急竞争性修订响应了NIAMS特殊利益通知(NOT-AR-23-015)。这个 Parent Study(NIAMS R01AR077452)旨在开发新的定量磁共振技术(加速MR T1ρ 和T2标测)来评估患者前路手术后软骨成分的变化和早期退变 十字韧带重建术(ACLR)，创伤后骨关节炎的高危人群 (PTOA)。在这项研究中，我们的目的是探索肌肉骨骼(MSK)疼痛的机制，并识别新的 前交叉韧带损伤和手术后以及PTOA早期疼痛的影像(膝盖和脑)标志物。建议数 这项研究将显著扩大母公司研究的范围，使其从只关注结构变化(疾病) 一个人评估患者的症状(‘疾病’，特别是疼痛)。采用一种新颖的多模式方法， 包括先进的膝关节和脑MRI，我们小组将首次研究中枢神经系统(CNS) 骨科损伤/手术后疼痛的变化，以及早期PTOA。研究结果将提供关键的 初步数据，以制定MSK疼痛的具体假设，并将开发新的成像技术， 可用于未来对骨科损伤/手术后疼痛机制的大规模研究 OA/PTOA，这是一个研究不足、临床需求迫切的领域。因此，拟议的研究与 NOSI目标A：为未来的创新研究或新的科学方向提供支持证据 肌肉骨骼疾病中的疼痛研究，在新的疼痛成像技术感兴趣的领域。 美国有3000多万人受到影响，全球有3亿多人受到影响。它展现了巨大的健康和 医疗费用和失业带来的社会经济负担。疼痛是显著损害人体健康的主要因素 生活质量，导致残疾，并促使患者进行临床检查，最终进行全关节置换术 骨关节炎。阿片类药物处方用于治疗严重的骨性关节炎/PTOA疼痛和骨科损伤后的疼痛，这是常见的 由于阿片类药物的高流行率，这是对国家阿片类药物危机的重大贡献。更好的 了解损伤/手术后和OA/PTOA疼痛的机制，并确定 与MSK疼痛相关或预测MSK疼痛，这项拟议的研究旨在填补这一空白，将为 开发新的治疗靶点，用于缓解骨性关节炎和其他MSK疾病的疼痛。这项拟议的研究报告 家长研究的重大和及时的扩展。它将利用来自家长研究的资源，并 提供了一个独特的机会来研究关节结构损伤、中枢神经系统改变和 一种新的早期骨性关节炎模型中的疼痛(PTOA，骨科损伤和手术后)。研究结果将提供 对MSK疼痛机制的有价值的见解，有助于确定缓解疼痛的新治疗目标 巨大的患者群体，并最终帮助提供科学的解决方案来对抗前所未有的 阿片类药物在美国日益流行。

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.