In Vivo MRI Characterization of an Animal Model of Osteochondrosis

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.