Non-invasive assessment of ligament healing in vivo

描述（由申请人提供）：该项目的总体目标是系统地完善和验证我们的新型磁共振成像协议，用于非侵入性测量愈合软组织的生物力学特性。这种转化工具将有利于临床前和临床试验，以评估新兴的韧带和肌腱修复技术。在本研究中，我们将重点关注前十字韧带 (ACL) 作为韧带损伤的模型。我们已经证明，韧带尺寸（即组织数量）和信号强度（即组织质量）的磁共振 (MR) 成像测量与 ACL 的生物力学特性相关，并且韧带尺寸和信号强度的结合进一步改善了这些预测。不幸的是，信号强度取决于图像采集参数，因此取决于协议、磁铁，因此取决于机构。然而，T2* 弛豫时间是 MR 组织特性，与组织中的胶原蛋白组织相关，不依赖于采集。我们现在有初步证据表明愈合韧带内的 T2* 松弛时间可以提供对结构特性的更可靠的估计。下一步是完善和验证这种基于 T2* MR 的预测方法，用于韧带愈合的纵向研究。在目标 1 中，我们将按照两种修复策略获得愈合中 ACL 的体积和 T2* 的 MR 测量值。这些测量值将在横截面研究的早期增殖、中期和晚期重塑阶段收集，以检查模型预测这些愈合阶段的生物力学特性的稳健程度，并在必要时将时间效应纳入模型中。在目标 2 中，我们将对基于 MR 的方法进行纵向研究，以验证其区分已知会产生愈合差异的两种修复策略的实用性，并确定在愈合早期阶段获得的扫描是否可以预测长期生物力学特性。这一发现非常有价值，因为它将缩短临床前和临床韧带愈合研究的周期时间。该项目将利用 我们完善的生物增强 ACL 修复临床前模型。在本研究中，我们基于 MR 的多重回归预测模型将在目标 1 中进行细化，并在目标 2 中进行验证。主要结果指标包括 MR 参数（T2* 弛豫时间、信号强度、体积）和愈合 ACL 的结构特性（失效负载、线性刚度）。次要结果包括 ACL 材料特性（失效应力、切线模量）和膝关节松弛度。研究完成后，我们将完善基于 MR 的预测模型，验证其在手术修复研究中的用途，并准备使用 MR 技术作为 ACL 修复和重建临床试验的主要结果指标。

DESCRIPTION (provided by applicant): The overall objective of this project is to systematically refine and validate our novel magnetic resonance imaging protocol for the non-invasive measurement of the biomechanical properties of healing soft tissues. This translational tool will be advantageous for pre-clinical and clinical trials to evaluate up-and-coming technologies for ligament and tendon repair. For this study we will focus on the anterior cruciate ligament (ACL) as a model of ligament injury. We have shown that magnetic resonance (MR) imaging measurements of ligament size (i.e., amount of tissue) and signal intensity (i.e., quality of tissue) correlate to the biomechanical properties of the ACL, and that the combination of ligament size and signal intensity further improved these predictions. Unfortunately, signal intensity is dependent on image acquisition parameters thus protocol, magnet, and hence institution dependent. However, T2* relaxation time is an MR tissue property that correlates to collagen organization in tissues that is not as acquisition dependent. We now have preliminary evidence to show that T2* relaxation times within a healing ligament provides a more reliable estimate of the structural properties. The next step is to refine and validate this T2* MR-based prediction method for use in longitudinal studies of ligament healing. In Aim 1, we will obtain MR-measures of volume and T2* of the healing ACL following two repair strategies. These measures will be collected in the early proliferative, middle and later remodeling stages of healing in a cross sectional study to examine how robustly the model predicts the biomechanical properties across these stages of healing, and to incorporate time effects into the model if necessary. In Aim 2, we will perform a longitudinal study of our MR-based approach to validate its utility for discriminating between two repair strategies known to produce differences in healing and to determine if scans obtained in the early stages of healing will predict the longer-term biomechanical properties. This finding would be very valuable as it would reduce the cycle time of both pre-clinical and clinical ligament healing studies. The project will take advantage of our well established pre-clinical model of bio-enhanced ACL repair. In this study, our MR based multi-regression prediction model will be refined in Aim 1 and validated in Aim 2. Primary outcome measures include the MR parameters (T2* relaxation time, signal intensity, volume) and the structural properties (failure load, linear stiffness) of the healing ACL. Secondary outcomes include the ACL material properties (failure stress, tangent modulus) and knee laxity. At study completion we will have refined our MR- based prediction models, validated its use for surgical repair studies, and be poised to use the MR technique as a primary outcome measure in clinical trials of ACL repair and reconstruction.