Diagnosis of Osteochondrosis using high field MRI

项目简介/摘要Cathy Carlson博士是明尼苏达大学兽医学院终身教授，资深兽医病理学家和骨科研究员。虽然卡尔森博士是一名积极的研究合作者，但近年来，逐渐增加的服务承诺和其他责任使她无法在研究中发挥更重要的作用。在此申请中，她要求获得两年50%的工资支持，同时她将获得高场磁共振成像（MRI）领域的新知识，并将这些知识应用于开发诊断骨软骨病亚临床病变的方法。在这些研究中，她将使用具有相当专业知识的具有良好特征的骨软骨病动物模型（仔猪自发性疾病）。她的主要导师Michael Garwood博士是高场MRI技术开发领域的专家，她的指导委员会：Jutta Ellermann博士（人类骨科MRI专家，包括骨软骨病），Denis Clohisy博士（骨科外科系主任，经验丰富的骨科研究员）和Jack Lewis博士（软骨矩阵生物学和生物力学专家）。在提议的，高度创新的研究中，卡尔森博士对骨质疏松症动物模型的广泛知识和经验将与导师组最先进的高场MRI专业知识相结合，以确定幼猪完整关节中骨质疏松症的亚临床病变，这种疾病的发病率接近100%。新开发的高场核磁共振技术将用于检测和表征软骨的早期损伤。拟议研究的具体目的是：1)开发高场MRI技术，以识别和表征来自仔猪的完整和脱臼的肱骨远端和股骨远端（猪和人最常见的偏好部位）的骨软骨病亚临床病变（局部广泛的软骨坏死区域）；2)发展定量技术，表征病变的胶原蛋白和蛋白多糖成分，并与MRI结果进行比较；3)发展高场MRI技术来识别和绘制软骨管血管，并在血管灌注硫酸钡的清除标本中验证这些血管。这项职业发展奖将使卡尔森博士有专门的时间来1)获得MRI方法方面的专业知识；2)与磁成像研究中心的科学家密切互动；3)鉴定和获取适合研究的猪标本；4)协助解释MRI结果，并通过与MRI评估相同部位的平行组织学研究来修改技术；5)与一个高素质的导师小组互动，该小组的成员将为她提出的研究提供具体和全面的投入。卡尔森博士的长期职业目标是继续从事学术研究，为该项目获得并维持RO1资金，并将至少75%的精力投入到研究活动中。

DESCRIPTION (provided by applicant): Project Summary/Abstract Dr. Cathy Carlson is an experienced, ACVP-boarded veterinary pathologist and orthopaedic researcher who is a tenured full professor in the College of Veterinary Medicine at the University of Minnesota. Although Dr. Carlson is an active research collaborator, gradually increasing service commitments and other responsibilities have prevented her from having a more central role in research in recent years. In this application, she requests 50% salary support for two years while she acquires new knowledge in the area of high field magnetic resonance imaging (MRI) and applies this knowledge to the development of methods to diagnose subclinical lesions of osteochondrosis. For these studies, she will use a well-characterized animal model of osteochondrosis (spontaneous disease in young pigs) with which she has considerable expertise. She will be assisted in these studies by her primary mentor, Dr. Michael Garwood, who is an expert in the area of high field MRI technique development, and her mentoring committee: Dr. Jutta Ellermann (expert in human orthopaedic MRI, including osteochondrosis), Dr. Denis Clohisy (chair of the Department of Orthopaedic Surgery and experienced orthopaedic researcher), and Dr. Jack Lewis (cartilage matrix biology and biomechanics expert). In the proposed, highly innovative studies, the extensive knowledge and experience that Dr. Carlson has with a well-documented animal model of osteochondrosis will be combined with the state-of- the-art high field MRI expertise of the mentor group to identify subclinical lesions of osteochondrosis in intact joints of young pigs, in which the disease occurs with nearly 100% prevalence. Newly developed high field MRI techniques will be used to detect and characterize early damage to the cartilage. The specific aims of the proposed studies are to 1) Develop high-field MRI techniques to identify and characterize subclinical lesions of osteochondrosis, (locally extensive areas of cartilage necrosis), in intact and disarticulated specimens of distal humerus and distal femur (most common predilection sites in both swine and humans) from young pigs; 2) Develop quantitative techniques to characterize the collagen and proteoglycan components of the lesions for comparison with the MRI results; and 3) Develop high-field MRI techniques to identify and map cartilage canal blood vessels and validate these in cleared specimens in which the vessels have been perfused with barium sulfate. This career development award will allow Dr. Carlson the dedicated time to 1) gain expertise in MRI methodology; 2) interact closely with the scientists at the Center for Magnetic Imaging Research; 3) identify and acquire the appropriate porcine specimens for study; 4) assist in interpreting the MRI findings and modifying the techniques through parallel histological studies in the same sites as those evaluated by MRI; and 5) interact with a highly qualified mentor group, the members of which will provide both specific and global input to her proposed research. Dr. Carlson's long-term career goal is to remain in academic research, obtain and maintain RO1 funding for this project, and to devote at least 75% of her effort to research activities. PUBLIC HEALTH RELEVANCE: Project Narrative Osteochondrosis is a focal or multifocal failure in the process of endochondral ossification (conversion of growth cartilage to bone during growth and development) that predisposes the affected site to the formation of a cartilaginous/osteocartilaginous flap (osteochondritis dissecans/OCD), resulting in joint pain and dysfunction. It occurs increasingly commonly in children and young adult patients, and treatment usually includes surgical removal of the flap; however, because of the poor healing qualities of articular cartilage, the affected joint is at risk for the later development of osteoarthritis. If,as proposed in the present application, methods could be developed to diagnose the subclinical disease (prior to the formation of the flap), it is very likely that temporary lifestyle changes, designed to decrease joint trauma, would allow complete and spontaneous healing of the affected site.