Multinuclear MRI to Assess Joint Homeostasis after Knee Injury

多核 MRI 评估膝关节损伤后的关节稳态

• 批准号: 10390153
• 负责人: Guillaume MADELIN
• 金额: $ 70.64万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390153
• 关键词: 3-Dimensional; Acute; Age; Age-Years; Biological; Biological Markers; Biomechanics; Body mass index; Cartilage; Catabolism; Clinical; Collagen; Complication; Consensus; Data; Degenerative polyarthritis; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Enrollment; Event; Evolution; Extensor; Failure; Female; Fingerprint; Functional disorder; Goals; Homeostasis; Image; Incidence; Inflammation; Inflammatory; Injury; Institution; Interleukin-6; Interleukins; Joint repair; Joints; Knee; Knee Injuries; Knowledge; Link; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measures; Methods; Modeling; Molecular; Monitor; Motion; Operative Surgical Procedures; Orthopedics; Patient Recruitments; Patient-Focused Outcomes; Patients; Play; Population; Prevalence; Preventive treatment; Proteoglycan; Proteolysis; Protons; Relaxation; Reproducibility; Research; Risk; Role; Sampling; Scanning; Severities; Side; Signal Transduction; Sodium; Structure; Synovial Fluid; Testing; Time; Treatment Efficacy; United States; Walking; Water; Weight-Bearing state; anterior cruciate ligament injury; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; articular cartilage; base; biobank; biomechanical test; cohort; contrast enhanced; density; disability; efficacy study; follow-up; healing; imaging biomarker; imaging modality; inflammatory marker; insight; joint injury; kinematics; knee replacement arthroplasty; male; meniscus injury; novel; predictive marker; predictive modeling; prevent; prognostic; quantitative imaging; recruit; response; therapeutic target; tool

Project Summary Post-traumatic osteoarthritis (PTOA) is a common complication that follows an episode anterior cruciate ligament (ACL) rupture. In the United States, there are over 100,000 ACL ruptures per year, 70% of which occur in physically active subjects under 40 years of age. The prevalence of PTOA is estimated to be in the 50-70% range 10 to 20 years after injury, whether surgical intervention was performed or not. The failure of surgery to prevent PTOA leads to the hypothesis that the acute biological and biomechanical changes in the joint directly following injury trigger a cascade of events leading to PTOA. However, little is known about how these early biological and biomechanical changes are linked to the subsequent joint damage. To assess the loss of joint homeostasis after injury, we propose to optimize and use a novel multinuclear magnetic resonance imaging (MRI) method recently developed by our team, which is based on the simultaneous acquisition of proton (1H) and sodium (23Na) MR fingerprinting (MRF). Simultaneous 1H/23Na MRF will allow us to characterize knee cartilage integrity using both proton (structural information from relaxation times, water content) and sodium (proteoglycan content from sodium concentration and relaxation times) quantitative data. In this study, a complete panel of soluble synovial fluid (SF) biological markers of inflammation and proteolysis, of biomechanical markers (weight-bearing activities, extensor strength), and of quantitative imaging markers such as 1H/23Na MRF, diffusion tensor imaging (DTI), contrast-enhanced (CE) MRI, and T1rho MRI, will be acquired longitudinally on patients with ACL injury. The goal of this study is therefore to develop a predictive model of progression to PTOA using a combination of all these imaging, biological, and biomechanical markers acquired just after ACL injury, and over time after joint repair. This prognostic combination of biomarkers will help identify therapeutic targets and monitor the efficacy of intervention in the development of preventive treatments of PTOA. Two patient cohorts will be recruited: a short-term cohort will be tested at baseline (post-injury), 1-2-year and 3-5-year follow-ups, and a long-term cohort, which is already being being studied in our institution with clinical MRI and SF biomarkers, will be tested at 3-5-year and 6-8-year post-injury follow-ups. In aim 1, we will optimize simultaneous 1H/23Na MRF sequence for its application to knee cartilage imaging. In Aim 2, we will identify imaging, biomechanical and imaging markers, measured at baseline and 1.5 years to predict 3-year progression. In Aim 3, we will identify a set of few biomarkers for prediction of both short-term (3-5 years) and long-term (6-8 years) changes in joint homeostasis.

项目概要 创伤后骨关节炎 (PTOA) 是前十字韧带发作后的常见并发症 （ACL）断裂。在美国，每年有超过 100,000 例 ACL 断裂，其中 70% 发生在 40岁以下体力活跃的受试者。 PTOA 的患病率估计在 50-70% 范围内 受伤后10至20年，无论是否进行手术干预。手术失败无法预防 PTOA 得出这样的假设：关节的急性生物和生物力学变化直接发生在 损伤会引发一系列事件，导致 PTOA。然而，人们对这些早期的生物学和 生物力学的变化与随后的关节损伤有关。评估术后关节稳态的丧失 损伤，我们最近建议优化和使用一种新型的多核磁共振成像（MRI）方法 由我们团队开发，基于同时采集质子（1H）和钠（23Na）MR 指纹识别（MRF）。同时 1H/23Na MRF 将使我们能够使用以下方法来表征膝关节软骨的完整性： 质子（松弛时间、水含量的结构信息）和钠（蛋白聚糖含量 钠浓度和弛豫时间）定量数据。在这项研究中，一组完整的可溶性滑膜 炎症和蛋白水解、生物力学标记（负重活动、 伸肌强度），以及定量成像标记，例如 1H/23Na MRF、扩散张量成像 (DTI)、 将对 ACL 损伤的患者纵向采集对比增强 (CE) MRI 和 T1rho MRI。目标 因此，本研究的目的是结合所有这些因素来开发一个进展为 PTOA 的预测模型 ACL 损伤后以及关节修复后随时间推移采集的影像、生物和生物力学标记。这 生物标志物的预后组合将有助于确定治疗靶点并监测干预效果 PTOA 预防性治疗的开发。将招募两个患者队列：一个是短期队列 将在基线（受伤后）、1-2 年和 3-5 年随访以及长期队列中进行测试，该队列已经 我们的机构正在使用临床 MRI 和 SF 生物标志物进行研究，将在 3-5 年和 6-8 年进行测试 伤后随访。在目标 1 中，我们将优化同步 1H/23Na MRF 序列，以将其应用于膝关节 软骨成像。在目标 2 中，我们将识别在基线时测量的成像、生物力学和成像标记 1.5 年预测 3 年进展。在目标 3 中，我们将确定一组用于预测的生物标志物 关节稳态的短期（3-5 年）和长期（6-8 年）变化。