In Vivo Cartilage Mechanics and Degeneration After ACL Deficiency

描述(由申请人提供)：据估计，美国每年发生40万例前十字韧带(ACL)损伤。前交叉韧带损伤的影响包括不稳定、疼痛、半月板损伤，以及增加早发性骨关节炎(OA)的风险。重建前交叉韧带通常是为了恢复膝关节功能，但最近的研究质疑其与非手术治疗相比是否有能力缓解骨性关节炎的发展。特别是，超过50%的前交叉韧带重建患者在手术后10年内出现了晚期骨性关节炎的迹象。因此，无论前交叉韧带是手术治疗还是非手术治疗，退行性改变仍然是一个令人担忧的问题。前交叉韧带损伤后关节加速退变的确切机制尚不清楚。这些信息对于改善前交叉韧带损伤的临床治疗至关重要。尽管许多因素可能起作用，但前交叉韧带损伤后关节运动学的改变被认为是骨关节炎发生和发展的关键因素。然而，目前还缺乏关于活体的数据。 在行走等动态活动中，软骨接触应变。更重要的是，有有限的数据来描述体内软骨负荷改变和早期之间的关系。 前交叉韧带损伤患者软骨形态和成分的变化。因此，这项建议的目的是研究前交叉韧带损伤后发生的早期机械、成分和形态变化。我们的假设是，在前交叉韧带缺乏的患者中，软骨接触应变升高的区域经历了软骨成分的显著变化。此外，在这些成分变化之后，在软骨负荷增加的相同区域，局灶性软骨厚度也会发生变化。为了实现我们的目标，我们将研究急性、孤立、单侧前交叉韧带缺乏症的受试者，并在一年的随访中再次测试相同的受试者。软骨接触应变将通过结合基于3D MR的关节模型和在跑步机步态过程中获得的高速双平面X光图像来评估。软骨成分的变化将使用T1-Rho成像来测量，这是一种对蛋白多糖耗竭敏感的技术，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。这些新的数据将为关于前交叉韧带缺乏后软骨退变的机制提供有价值的信息。这些信息对于改善前交叉韧带损伤患者的临床治疗至关重要，并潜在地为了解导致骨关节炎的机制提供了重要的见解。

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.