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

弥散张量成像作为膝关节损伤后软骨完整性的探针

• 批准号: 8772192
• 负责人: Jenny T. Bencardino
• 金额: $ 22.37万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8772192
• 关键词: Acute; Age; Age-Years; Anisotropy; Anterior Cruciate Ligament; Architecture; Biochemical; Biological Markers; Body mass index; Cartilage; Cartilage Matrix; Cessation of life; Chondrocytes; Clinical; Clinical Trials; Collagen; Collagen Type II; Complication; Data; Degenerative polyarthritis; Detection; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Event; Failure; Feasibility Studies; Goals; Histology; Image; Injury; Joints; Knee Injuries; Lead; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Mechanics; Methods; Modeling; Molecular; Motion; Natural History; Noise; Operative Surgical Procedures; Pathologic Processes; Patients; Pharmaceutical Preparations; Phase; Physiologic pulse; Prevalence; Property; Proteoglycan; Radial; Reference Standards; Relaxation; Sampling; Scanning; Signal Transduction; Simulate; Staging; Structure; Techniques; Testing; Time; Validation; Water; Work; aged; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; articular cartilage; base; healthy volunteer; improved; in vivo; injured; insight; joint destruction; nanoindentation; novel; osteochondral tissue; prevent; public health relevance; repaired; research clinical testing; research study; soft tissue; tool; volunteer

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.

描述（由申请人提供）：创伤后骨关节炎（PTOA）是一种相对常见的并发症，发生在前交叉韧带（ACL）断裂后。在美国，每年有超过10万例ACL断裂，其中70%发生在44岁以下的体力活动者中。在前交叉韧带破裂后的10 - 20年，无论是否进行手术干预，pta的患病率估计为50-70%。手术预防上睑下垂的失败导致了一种假设，即损伤后关节的急性变化触发了一系列导致上睑下垂的事件。迫切需要一种非侵入性的方法，可以在分子水平上识别急性创伤后阶段关节的病理变化。磁共振成像（MRI）已经证明了检测软组织生化成分变化的潜力，如关节软骨。关节软骨的病理改变被认为是关键的，因为它的修复能力有限。在