Diffusion Tensor Imaging as a Probe of Cartilage Integrity after Knee Injury

描述（由申请方提供）：创伤后骨关节炎（PTOA）是前交叉韧带（ACL）断裂后相对常见的并发症。在美国，每年有超过10万例ACL断裂，其中70%发生在44岁以下的体力活动受试者中。在ACL断裂后10 - 20年，无论是否进行手术干预，PTOA的患病率估计为50- 70%。手术预防PTOA的失败导致以下假设：损伤后关节的急性变化触发了导致PTOA的级联事件。在急性创伤后阶段，强烈需要能够在分子水平上识别关节病理变化的非侵入性方法。磁共振成像（MRI）已被证明有潜力检测软组织，如关节软骨的生化成分的变化。关节软骨的病理变化被认为是至关重要的，因为它的修复能力有限。期间 ACL断裂高压缩力和剪切力作用于软骨，这导致蛋白聚糖（PG）含量的损失、软骨细胞死亡和胶原网络的破坏，从而导致软骨纤维化和软骨损失。因此，胶原蛋白和PG的测量对于准确诊断ACL断裂后的软骨损伤和了解PTOA的自然病程至关重要。然而，现有的成像生物标志物未能最佳地评估PG含量和胶原结构。虽然一些MRI标记物对PG含量敏感，但T2弛豫时间和磁化转移（MT）是唯一对胶原部分敏感的MRI标记物。为了提高检测PG和胶原变化的能力，我们的研究小组引入了关节软骨的扩散张量成像（DTI）。使用DTI的关键思想是PG和胶原蛋白对水分子的运动有不同的影响。我们小组和其他人进行的研究表明，DTI通过平均扩散率（MD）对PG含量敏感，并且分数各向异性（FA）是胶原结构的生物标志物。的 本建议的首要目标是验证和显示关节软骨DTI的可行性 作为ACL断裂后软骨基质结构和成分变化的生物标志物。我们提出以下假设：（1）DTI可以检测损伤样软骨 （2）ACL断裂时，通过MD的增加和FA的减少可以检测出ACL断裂时的软骨损伤。我们将以两个目标来检验这些假设。目的1将提供机械过载损伤模型的体外验证。我们将测试DTI在检测机械过载后软骨损伤和机械性能变化方面的价值。目的2：探讨关节软骨DTI技术检测ACL非接触性断裂患者（n=11）和健康志愿者（n=11）关节软骨变化的可行性。本研究的成功完成将为PTOA的诊断提供一种新的方法，对新型DMOA的临床评价具有重要意义。拟议项目的数据将为大型纵向研究提供基础。

DESCRIPTION (provided by applicant): Posttraumatic osteoarthritis (PTOA) is a relatively common complication that follows an episode anterior cruciate ligament (ACL) rupture. In the US there are over 100,000 ACL ruptures per year, from which 70% occur in physically active subjects under 44 years of age. At 10 to 20 years after ACL rupture the prevalence of PTOA is estimated to be 50-70%, regardless if surgical intervention was performed or not. The failure of surgery to prevent PTOA lead to the hypothesis that the acute changes in the joint following injury triggers the cascade of events leading to PTOA. There is strong need for noninvasive methods that can identify pathological changes in the joint at molecular levels in the acute posttraumatic phase. Magnetic resonance imaging (MRI) has demonstrated potential to detect changes in the biochemical composition of soft tissues, such as articular cartilage. Pathological changes in articular cartilage are considered critical due to its limited ability to repair. During ACL rupture high compressive and shear forces act on the cartilage, which cause loss of proteoglycan (PG) content, chondrocyte death and disruption of the collagen network leading to cartilage fibrillation and cartilage loss. Thus, measurement of collagen and PG is critical to accurately diagnose cartilage damage following ACL rupture and understanding the natural history of PTOA. However, existing imaging biomarkers have failed to optimally assess PG content and collagen architecture. Though a few MRI markers are sensitive to PG content, T2 relaxation time and the magnetization transfer (MT) are the only MRI markers partially sensitive to collagen. To improve the ability to detect changes in PG and collagen our group introduced diffusion tensor imaging (DTI) of articular cartilage. The key idea behind the use of DTI is that PG and collagen have different effects on the motion of water molecules. Studies performed by our group and others have shown that DTI is sensitive to the PG content through mean diffusivity (MD), and that fractional anisotropy (FA) is a biomarker for collagen architecture. The overarching goal of this proposal is to validate and show feasibility of DTI of articular cartilage as a biomarker for structural and compositional changes in the cartilage matrix after ACL rupture. We propose to test the following hypotheses: (1) DTI can detect the injury- like cartilage damage induced by mechanical overloading with accuracy>80%; (2) Cartilage damage in ACL rupture can be detected by an increase in MD and a decrease in FA. We will test these hypotheses with two aims. Aim 1 will provide ex vivo validation on an injury model by mechanical overloading. We will test the value of DTI to detect cartilage damage and the change in mechanical properties after mechanical overloading. Aim 2 will provide feasibility of DTI of articular cartilage to detect changes in articular cartilage of patients after non- contact ACL rupture (n=11) and healthy volunteers (n=11). Successful completion of our proposal will establish DTI of articular cartilage as a new method for the diagnosis of PTOA, with important implication for the clinical evaluation of novel DMOAs. Data from the proposed project will provide the basis for large longitudinal studies.