Multinuclear MRI to Assess Joint Homeostasis after Knee Injury

项目摘要 创伤后骨关节炎（PTOA）是前交叉韧带损伤后常见的并发症 (ACL)破裂在美国，每年有超过100，000例ACL断裂，其中70%发生在 40岁以下的体力活动受试者。PTOA的患病率估计在50-70%的范围内 损伤后10至20年，无论是否进行手术干预。手术不能阻止 PTOA导致以下假设： 损伤触发导致PTOA级联事件。然而，人们对这些早期生物学和 生物力学变化与随后的关节损伤有关。评估关节内稳态的丧失， 损伤，我们建议优化和使用一种新的多核磁共振成像（MRI）的方法，最近 我们的团队开发的，这是基于同时获取质子（1H）和钠（23 Na）MR 指纹打印（MRF）。同时使用1H/23 Na MRF将使我们能够表征膝关节软骨的完整性， 质子（来自弛豫时间、水含量的结构信息）和钠（来自弛豫时间、水含量的蛋白聚糖含量）两者都是 钠浓度和弛豫时间）定量数据。在这项研究中，一个完整的面板可溶性滑膜， 炎症和蛋白水解的生物标志物，生物力学标志物（负重活动， 伸肌强度）和定量成像标记物如1H/23 Na MRF，扩散张量成像（DTI）， 将对ACL损伤患者纵向采集对比增强（CE）MRI和T1 rho MRI。目标 因此，本研究的目的是结合所有这些因素，开发一种进展为PTOA的预测模型。 ACL损伤后即刻和关节修复后随时间推移获得的影像学、生物学和生物力学标记。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的有效性 在PTOA的预防性治疗的发展。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， 正在我们的机构进行临床MRI和SF生物标志物的研究，将在3-5年和6-8年时进行检测 受伤后的随访。目的1：优化1H/23 Na同步MRF序列在膝关节的应用 软骨成像在目标2中，我们将确定基线时测量的成像、生物力学和成像标记物 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 关节稳态的短期（3-5年）和长期（6-8年）变化。

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.