Imaging post-traumatic osteoarthritis 10-years after ACL reconstruction: a multicenter cohort study with quantitative MRI

项目概要/摘要 前交叉韧带（ACL）损伤已被证实是创伤后骨关节炎的高危因素 （PTOA）发展尽管ACL重建（ACLR）。然而，我们对PTOA发展的理解 ACLR后，提供早期诊断和预后的可靠“标志物”（风险因素）仍然是有限的， 缺乏ACLR后PTOA的长期研究主要使用射线照片来评估结构损伤， 其仅提供限于在疾病晚期发生的骨变化的信息。既往MRI ACLR后的研究主要限于短期/中期随访。软组织的长期退化， 它们彼此之间的关系以及与ACLR后患者症状和结局的关系在很大程度上是未知的。 在这项研究中，我们的目标是填补这一空白，并提出增加形态和定量MRI（qMRI）的新的 ACLR后10年时来自多中心骨科结局网络（MOON）的嵌套队列。国家卫生研究院 一项受资助的MOON研究旨在随访ACLR患者术后，以确定其临床结局 包括PTOA发生和进展的风险因素。MOON队列在世界上是独一无二的， >3500名参与者，在2年、6年和10年随访率超过80%。MOON集团发布了 广泛研究患者报告结局指标（PROM）风险因素的多变量建模，以及 罕见结局（移植物失败、感染、全膝关节置换术）。此外，一个新的嵌套队列（n=425）， 在MOON队列中启动，该队列由年轻活跃患者组成， 评价包括X线片、物理和仪器松弛检查以及功能测试。在这 在这项研究中，我们将在这个嵌套队列中加入最先进的qMRI，以评估软骨（厚度和基质 组成T1 r和T2）、骨（3D形状建模）、肌肉（体积和脂肪浸润）和其他OA相关 病变这项研究的首要目标是描述长期结构损伤和关节软骨 ACLR后的退行性变，了解其模式及其与患者结局的关系，并确定可改变的 术前和术后早期时间点ACLR后10年PTOA的预测因素。此外，委员会认为， 10年时的MRI测量，如软骨T1 r和T2，也将作为未来的潜在预测指标。 PTOA发生（对于10年时未发生PTOA的患者）、ACLR移植物或对侧失败 ACL，并在ACLR后20年MOON时间点进行额外的关节镜手术。 拟议的研究将利用NIH资助的MOON赠款的资源，这是一个独特的，第一次 有机会全面评价膝关节结构损伤及其与患者的相互关系 在一个前瞻性、充分表征和密切监测的队列中，ACLR后10年的结局。通过识别 ACLR后10年时相对于基线和术后早期的结构损伤的可修改预测因素 点，这项研究可以直接影响改善病人的管理和治疗，以及铅 进一步开展关于确定的可改变风险因素的RCT，以减少和预防ACLR后的PTOA。

PROJECT SUMMARY/ABSTRACT Anterior Cruciate Ligament (ACL) injury is a proven high-risk factor for post-traumatic osteoarthritis (PTOA) development despite ACL reconstruction (ACLR). However, our understanding of PTOA development after ACLR is limited, and reliable “markers” (risk factors) that provide early diagnosis and prognosis are still lacking. Long-term studies of PTOA after ACLR primarily used radiographs for evaluating structural damage, which only provided information limited to bone changes that occur at late stages of the disease. Previous MRI studies after ACLR are primarily limited to short/mid-term follow up. The long-term degeneration of soft tissue, their relationship to each other, and to patient symptoms and outcomes after ACLR are largely unknown. In this study, we aim to fill this gap and propose to add morphologic and quantitative MRI (qMRI) to the novel nested cohort from the Multicenter Orthopaedic Outcomes Network (MOON) at 10 years after ACLR. The NIH funded MOON study was designed to follow ACLR patients after surgery to determine their clinical outcomes including risk factors for the initiation and progression of PTOA. The MOON cohort is unique in the world with >3500 participants and greater than 80% follow-up at 2, 6, and 10 years. The MOON group has published extensively on multivariable modeling on risk factors for patient reported outcomes measures (PROMs), and infrequent outcomes (graft failure, infection, total knee arthroplasty). Further, a novel nested cohort (n=425) was initiated within the MOON cohort which consists of young active patients with a comprehensive research evaluation including radiographs, physical and instrumented laxity examination, and functional testing. In this study, we will add state-of-the-art qMRI to this nested cohort to evaluate cartilage (thickness and matrix composition T1r and T2), bone (3D shape modeling), muscle (volume and fatty infiltration), and other OA-related lesions. The overarching goal of the study is to characterize long-term structural damage and articular cartilage degeneration after ACLR, understand their patterns and relationship to patient outcomes, and identify modifiable predictors for PTOA at 10 years after ACLR from pre-operative and early postoperative time points. Furthermore, the MRI measures, such as cartilage T1r and T2, at 10 years will also serve as potential predictors for future PTOA development (for those who do not develop PTOA at 10 years), failure of the ACLR graft or contralateral ACL, and additional arthroscopic surgery at the 20 years post-ACLR MOON time point. The proposed study will leverage resources from the NIH funded MOON grant, and this is a unique, first ever, opportunity to comprehensively evaluate the knee structural damage and their interrelationship with patient outcomes at 10 years after ACLR in a prospective, well characterized and closely monitored cohort. By identifying modifiable predictors of structural damage at 10 years after ACLR from baseline and early postoperative time points, this study can have immediate impact on improving patient management and treatment, as well as lead to further RCT on identified modifiable risk factors to reduce and prevent PTOA following ACLR.