In Vivo MRI Characterization of an Animal Model of Osteochondrosis

描述(由申请人提供)：骨软骨症是一种重要的发育性疾病，是晚年退行性关节疾病的常见原因。在临床疾病发生的年龄之前，猪和马的骨软骨病的好发部位已经得到了广泛的研究。这些研究表明，供应骨骺(生长)软骨的软骨管血管的损伤会导致受影响部位的缺血性坏死区。这些病变很容易形成裂隙，特别是当病变位于生物力学负荷较高的部位时。裂隙穿过坏死的软骨区域到达关节表面，形成软骨性或骨关节软骨瓣(骨软骨症/剥离性骨软骨病)，导致持续性疼痛，最终导致残疾。在人类中，骨软骨症/剥脱性骨软骨炎/强迫症只有在患者经历疼痛和残疾的慢性期才被诊断和研究。这些研究中唯一可用的组织来源是在手术中移除的软骨或骨关节蒂皮瓣，这几乎没有提供关于疾病发病机制的信息。有两个迫切的需求需要提高我们理解和治疗骨软骨症和其他一系列重要的骨科发育疾病的能力，在这些疾病中，生长软骨的血液供应被怀疑在病变的发病机制中发挥了作用，或者是它们没有反应。 去接受治疗。首先，关键是我们开发新的体内成像技术来可视化软骨管血管，并表征发生在缺血软骨中的基质变化(蛋白多糖和胶原含量降低)。其次，我们需要人类疾病的动物模型来研究其发病机制，评估现有治疗方法的有效性，并确定诊断这种疾病的新方法，并提供准确的预后信息。我们团队最近验证了MRI技术，该技术能够在体内成像骨骺/生长软骨中的软骨管血管，而不需要使用造影剂，并且具有足够的清晰度来评估它们在发育性骨科疾病中的作用。在拟议的研究中，我们将通过手术横断供应股骨远端脆弱区域的血管来建立手术诱导的山羊骨软骨症模型，并将利用我们最新开发的磁共振技术在体内跟踪骨软骨病的软骨和骨损伤的进展。在最后一次活体MRI研究结束时，我们将在关节镜下对病变进行评估，并采集股骨胫骨关节用于ex Viv MRI研究和组织学评估。

DESCRIPTION (provided by applicant): Osteochondrosis is an important developmental disease that is a common cause of degenerative joint disease later in life. Predilection sites of osteochondrosis have been studied extensively in pigs and horses, prior to the age at which clinical disease occurs. These studies have demonstrated that damage to cartilage canal blood vessels supplying epiphyseal (growth) cartilage results in areas of ischemic necrosis of the affected sites. These lesions are vulnerable to the formation of a cleft, particularly if the lesios are located in sites of high biomechanical loading. The cleft passes through the area of necrotic cartilage to the articular surface, forming a cartilaginous or osteocartilaginous flap (osteochondrosis/itis dissecans) and resulting in persistent pain and, eventually, disability. In humans, osteochondrosis/osteochondritis dissecans/OCD has been diagnosed and studied only in the chronic stages at a point where the patient is experiencing pain and disability. The only source of tissue available in these studies is the cartilaginous or osteocartilaginous flap removed at surgery, which provides little information regarding the pathogenesis of the disease. Two urgent needs exist for advancing our ability to understand and treat osteochondrosis and a range of other important developmental orthopaedic diseases in which blood supply to growth cartilage is suspected to play a role in the pathogenesis of lesions or in their failure to respond to therapy. First, it is critical that we develop novel in vivo imaging techniques to visualize cartilage canal blood vessels and to characterize the matrix changes (decreased proteoglycan and collagen content) occurring in the ischemic cartilage. Second, we require an animal model of the human disease in order to investigate its pathogenesis, evaluate the efficacy of current therapies, and identify new approaches to diagnosis the condition and to provide accurate prognostic information. Our group recently has validated MRI techniques that are capable of imaging cartilage canal blood vessels in epiphyseal/growth cartilage in vivo without the use of a contrast agent and with sufficient clarity to assess their role in developmental orthopaedic disease. In the proposed studies, we will develop a surgically induced goat model of osteochondrosis by surgically transecting vessels supplying a vulnerable area of the distal femur and will utilize our newly developed MRI technology to follow the progression of the cartilage and bone lesions of osteochondrosis in vivo. At the conclusion of the last in vivo MRI study, we will arthroscopically evaluate the lesions and harvest the femorotibial joints for ex viv MRI studies and histological evaluation.