In Vivo MRI Characterization of an Animal Model of Osteochondrosis

描述（由申请人提供）：骨软骨病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。骨软骨病的好发部位已在猪和马中进行了广泛的研究，在临床疾病发生的年龄之前。这些研究表明，供应骨骺（生长）软骨的软骨管血管的损伤导致受影响部位的缺血性坏死区域。这些病变很容易形成裂隙，特别是如果病变位于高生物力学负荷的部位。裂隙穿过坏死软骨区域到达关节面，形成软骨或骨软骨瓣（剥脱性骨软骨病/炎），并导致持续疼痛，最终导致残疾。在人类中，骨软骨病/剥脱性骨软骨炎/强迫症仅在患者经历疼痛和残疾的慢性阶段被诊断和研究。这些研究中唯一可用的组织来源是手术切除的软骨或骨软骨瓣，其提供的关于疾病发病机制的信息很少。对于提高我们理解和治疗骨软骨病和一系列其他重要的发育性骨科疾病的能力，存在两个迫切的需求，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起作用，或者在它们的反应失败中起作用 接受治疗首先，至关重要的是，我们开发新的体内成像技术来可视化软骨管血管和表征缺血软骨中发生的基质变化（蛋白聚糖和胶原蛋白含量降低）。其次，我们需要一个人类疾病的动物模型，以研究其发病机制，评估目前的治疗方法的疗效，并确定新的方法来诊断病情，并提供准确的预后信息。我们的小组最近已经验证了MRI技术，能够在体内对骺/生长软骨中的软骨管血管进行成像，而无需使用造影剂，并且具有足够的清晰度来评估其在发育性骨科疾病中的作用。在拟议的研究中，我们将通过手术切断供应股骨远端脆弱区域的血管来开发手术诱导的山羊骨软骨病模型，并将利用我们新开发的MRI技术来跟踪体内骨软骨病的软骨和骨病变的进展。在最后一项体内MRI研究结束时，我们将在关节镜下评价病变并采集股胫关节用于体外MRI研究和组织学评价。

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.