In Vivo Cartilage Mechanics and Degeneration After ACL Deficiency

描述（由申请人提供）：美国每年估计发生40万例前交叉韧带（ACL）损伤。ACL损伤的影响包括不稳定、疼痛、半月板损伤和早发性骨关节炎（OA）风险增加。ACL重建通常用于恢复膝关节功能，但最近的研究质疑其与非手术治疗相比缓解OA发展的能力。特别是，超过50%的ACL重建患者在手术后10年内存在晚期OA体征。因此，无论ACL是手术治疗还是非手术治疗，退行性变化仍然是一个问题。 ACL损伤后加速关节退变的确切机制尚不清楚。这些信息对于改善ACL损伤的临床治疗至关重要。尽管有许多因素可能起作用，但ACL损伤后关节运动学的改变被认为是OA发生和进展的关键因素。然而，缺乏体内数据 在动态活动例如行走期间软骨接触应变。更重要的是，描述体内软骨负荷改变与早期软骨损伤之间关系的数据有限。 ACL损伤患者软骨形态和成分的变化。 因此，本建议的目的是研究ACL损伤后发生的早期机械，成分和形态学变化。我们的假设是，在ACL缺陷的患者中，软骨接触应变升高的区域在软骨中经历显著的成分变化。此外，这些组成变化之后，在软骨负荷增加的相同区域中，病灶软骨厚度将发生变化。为了实现我们的目标，我们将研究急性、孤立、单侧ACL缺陷的受试者，并在一年随访时再次测试相同的受试者。将通过将基于3D MR的关节模型与在跑步机步态期间采集的高速双平面放射摄影图像相结合来评价肱骨接触应变。将使用T1-rho成像测量软骨组成的变化，T1-rho成像是一种对蛋白聚糖耗竭敏感的技术，是OA进展的早期指标。使用MR成像、3D建模技术和数值优化的组合，接触应变升高的区域将与软骨厚度分布的变化相关。这些新的数据将提供有价值的信息的机制，有助于ACL缺陷后的软骨退变。这些信息对于改善ACL损伤患者的临床管理至关重要，并可能为OA的发病机制提供重要见解。

DESCRIPTION (provided by applicant): An estimated 400,000 anterior cruciate ligament (ACL) injuries occur in the United States each year. The repercussions of ACL injury include instability, pain, damage to the meniscus, and increased risk early onset osteoarthritis (OA). ACL reconstruction is commonly performed in an attempt to restore knee function, but recent studies have questioned its ability to mitigate the development of OA compared to non-operative treatment. In particular, signs of advanced OA are present in more than 50% of ACL reconstruction patients within 10 years of surgery. Thus, regardless of whether the ACL is treated surgically or non-surgically, degenerative changes remain a concern. The precise mechanisms for accelerated joint degeneration after ACL injury are not well understood. This information is crucial to improving the clinical management of ACL injuries. Although many factors likely contribute, altered joint kinematics following ACL injury have been thought to be a crucial factor in the initiation and progression of OA. However, there is a lack of data on in vivo cartilage contact strains during dynamic activities such as walking. Even more importantly, there is limited data characterizing the relationship between altered in vivo cartilage loading and early changes in cartilage morphology and composition in patients with ACL injury. Therefore, the objective of this proposal is to study early mechanical, compositional, and morphologic changes that occur following ACL injury. Our hypothesis is that, in patients with ACL deficiency, regions of elevated cartilage contact strains experience significant compositional changes in cartilage. Moreover, these compositional changes will be followed by changes in focal cartilage thickness in the same regions of increased cartilage loading. To carry out our objective, we will study subjects with acute, isolated, unilateral ACL deficiency and test the same subjects again at one year follow-up. Cartilage contact strains will be evaluated by combining 3D MR-based joint models with high-speed biplanar radiographic images acquired during treadmill gait. Changes in cartilage composition will be measured using T1-rho imaging, a technique sensitive to proteoglycan depletion, which is an early indicator of OA progression. Regions of elevated contact strains will be related to changes in the distribution of cartilage thickness using a combination of MR imaging, 3D modeling techniques, and numerical optimization. These novel data will provide valuable information on the mechanisms contributing to cartilage degeneration after ACL deficiency. Such information is essential to improving the clinical management of patients with ACL injury and potentially provides important insight into the mechanisms contributing to OA.