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; 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 创伤后骨关节炎（PTOA）是一个常见的并发症，遵循发作前交叉韧带 （ACL）破裂。在美国，每年有100,000多个ACL破裂，其中70％发生在 40岁以下的身体活跃受试者。 PTOA的患病率估计为50-70％ 受伤后10到20年，是否进行了手术干预。手术未能防止 PTOA导致以下假设：关节的急性生物力学和生物力学变化直接随后 伤害引发了一系列导致PTOA的事件。但是，关于这些早期生物学和如何了解 生物力学变化与随后的关节损伤有关。评估关节稳态后的丧失 伤害，我们建议最近优化和使用新型的多核磁共振成像（MRI）方法 由我们的团队开发，该团队基于对质子（1H）和钠（23NA）MR的简单收购 填充（MRF）。同时1H/23NA MRF将使我们能够使用膝盖软骨完整性来使用 质子（放松时间，水含量的结构信息）和钠（来自蛋白聚糖的含量 钠浓度和松弛时间）定量数据。在这项研究中，完整的固体滑膜面板 流体（SF）旋转和蛋白水解的生物学标志物，生物力学标记（重量活性， 扩展强度），以及定量成像标记，例如1H/23NA MRF，扩散张量成像（DTI）， 对比增强（CE）MRI和T1RHO MRI，将纵向获得ACL损伤患者。目标 因此，这项研究是为了使用所有这些组合开发出向PTOA的预测模型 成像，生物力学和生物力学标记物在ACL损伤后以及关节修复后随着时间的推移而获得。这 生物标志物的预后组合将有助于确定治疗靶标并监测干预的效率 在开发PTOA的预防性治疗中。将招募两个患者队列：一个短期队列 将在基线（伤.后），1 - 2年和3 - 5年的随访以及长期同类中进行测试， 正在研究我们机构的临床MRI和SF生物标志物，将在3 - 5年和6 - 8年进行测试 受伤后的后续行动。在AIM 1中，我们将优化相当1H/23NA MRF序列的膝盖 软骨成像。在AIM 2中，我们将确定成像，生物力学和成像标记，以基线测量 和1。5年来预测3年的进展。在AIM 3中，我们将确定一组少数生物标志物来预测 联合体内平衡的短期（3 - 5年）和长期（6 - 8年）变化。