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.

项目摘要 摘要创伤后骨关节炎(PTOA)是前交叉韧带损伤后的常见并发症。 (前交叉韧带)破裂。在美国，每年有超过100,000例前交叉韧带断裂，其中70%发生在 40岁以下的体力活动受试者。PTOA的患病率估计在50%到70%之间。 伤后10~20年，无论是否进行手术干预。未能通过手术预防 PTOA导致了以下假说：关节的急性生物和生物力学变化 受伤会引发一系列事件，导致创伤后应激障碍。然而，人们对这些早期的生物和 生物力学变化与随后的关节损伤有关。评估术后关节动态平衡的丧失 最近，我们建议优化和使用一种新的多核磁共振成像(MRI)方法 由我们团队开发，基于同时获取质子(1H)和钠(23Na)MR fi打印(MRF)。同步的~1H/~(23)Na磁共振成像将使我们能够使用 质子(来自松弛时间、水含量的结构信息)和钠(来自 钠浓度和松弛时间)定量数据。在这项研究中，一组完整的可溶滑膜 fluid(SF)生物标记物的fl氨化和蛋白分解，生物力学标记物(承重活动， 伸肌强度)，以及诸如1H/23Na MRF、扩散张量成像(DTI)等定量成像标记物， 对于前交叉韧带损伤的患者，将进行纵向增强(CE)MRI和T1rho MRI检查。目标是 因此，这项研究的目的是利用所有这些因素的组合来开发PTOA进展的预测模型 在前交叉韧带损伤后不久，随着时间的推移，关节修复后获得的成像、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和监测干预的EFfi死亡率 在PTOA预防性治疗的发展中。将招募两个患者队列：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，这已经是 我们机构正在研究临床MRI和SF生物标记物，将在3-5年和6-8年进行测试 受伤后的随访。在目标1中，我们将优化同时进行的1H/23Na磁流变液序列，以便将其应用于膝关节 软骨成像。在目标2中，我们将确定在基线上测量的成像、生物力学和成像标记 用1.5年的时间来预测3年的进展。在目标3中，我们将确定一组少数生物标志物来预测 关节稳态的短期(3-5年)和长期(6-8年)变化。