In Vivo Knee Motion and ACL Biomechanics During Dynamic Activities

摘要：ACL术后10年，超过50%的患者存在OA的影像学证据 重建然而，ACL重建后早发性OA的病因尚不清楚。而 以前的工作已经证明了重建后关节运动的变化，但尚不清楚这些变化是如何发生的。 运动涉及软骨对体内负荷的局部机械响应的变化。该信息可以 对于理解OA的发病至关重要，因为软骨的机械反应会影响软骨 体内平衡根据这一机制，我们的试验数据表明，测量的高软骨应变区域 在ACL损伤和重建的患者中， OA的特点。重要的是，这些退行性变化早在重建后18个月就观察到了。 因此，在本提案中，我们的总体假设是， ACL损伤和重建后软骨对负荷的影响可以预测长期软骨 退化具体地说，我们假设，在软骨区域经历升高的应变， 负荷，早期退变将通过改变的组成和减少的软骨厚度来反映。因此我们 将在四个时间点测量局部软骨应变、成分和厚度：ACL损伤后， 重建，以及术后3个月，1年和2年。在每个时间点， 将使用高速双平面放射照相术和MR成像来测量体内过程中的局部软骨应变。 加载中为了评估软骨退变，我们将使用MRI来测量特定部位的成分变化， （使用T1rho和T2弛豫时间）和软骨厚度。此外，我们的分析将考虑相关的 生物学变量，如年龄、性别和BMI，以及临床因素，如移植物放置特征， 半月板损伤除了机械因素外，生物因素如关节炎症和润滑 也可能在ACL重建后的软骨退化中起作用。因此，滑液和血清 以测量炎症介质和代谢生物标志物。利用这些数据，我们将开发一个 ACL重建后软骨退化的预测模型，利用机械和生物学 因素，以及其他人口统计学和临床特征，以预测软骨健康的下降。 此外，这一全面的数据集将用于开发临床表型，以识别那些高血压患者。 ACL重建后软骨退化的风险。重要的是，这些表型的发展将 使靶向治疗方法集中在外科手术，药物靶点，和非 药物干预，如物理治疗或减肥，以防止软骨退化。 因此，我们的研究结果将阐明软骨局部机械反应的改变对 ACL重建后的退行性变，并改善高风险患者的识别和治疗， 软骨退化

Abstract: Radiographic evidence of OA is present in more than 50% of patients 10 years after ACL reconstruction. However, the etiology of early onset OA after ACL reconstruction is not well understood. While previous work has demonstrated changes in joint motion following reconstruction, it is unclear how these altered motions relate to changes in the local mechanical response of cartilage to in vivo loading. This information may be critical to understanding the onset of OA, as the mechanical response of cartilage affects cartilage homeostasis. In line with this mechanism, our pilot data indicates that regions of high cartilage strain measured in patients with ACL injury and reconstruction are susceptible to decreased cartilage thickness, a characteristic feature of OA. Importantly, these degenerative changes are observed as early as 18 months post-reconstruction. Therefore, in this proposal our overall hypothesis is that site-specific changes in the mechanical response of cartilage to loading following ACL injury and reconstruction are predictive of long-term cartilage degeneration. Specifically, we hypothesize that in regions of cartilage experiencing elevated strain during loading, early degeneration will be reflected by altered composition and decreased cartilage thickness. Thus, we will measure localized cartilage strain, composition, and thickness at four time-points: after ACL injury but prior to reconstruction, as well as at 3 months, 1 year, and 2 years after surgery. At each time point, a combination of high-speed biplanar radiography and MR imaging will be used to measure local cartilage strains during in vivo loading. To assess cartilage degeneration, we will use MRI to measure site-specific changes in composition (using T1rho and T2 relaxation times) and cartilage thickness. Additionally, our analyses will account for relevant biological variables such as age, sex, and BMI, and clinical factors such as graft placement characteristics and meniscus injuries. In addition to mechanical factors, biological factors such as joint inflammation and lubrication may also play a role in cartilage degeneration after ACL reconstruction. Therefore, synovial fluid and serum will be collected to measure inflammatory mediators and metabolic biomarkers. Using this data, we will develop a predictive model of cartilage degeneration after ACL reconstruction that utilizes both mechanical and biological factors, as well as other demographic and clinical characteristics, to predict declines in cartilage health. Furthermore, this comprehensive dataset will be used to develop clinical phenotypes to identify those at high risk for cartilage degradation after ACL reconstruction. Importantly, the development of these phenotypes will enable targeted treatment approaches focusing on surgical procedures, pharmaceutical targets, and non- pharmacological interventions such as physical therapy or weight loss in preventing cartilage degeneration. Therefore, our findings will both elucidate the role of alterations in the local mechanical response of cartilage on degeneration after ACL reconstruction and improve the identification and treatment of patients at high risk for cartilage degeneration.