Cartilage, Bone and Marrow Interactions in Knee OA

描述（由申请人提供）：骨关节炎（OA）影响超过5000万美国人，对美国经济和医疗保健系统产生重大影响。目前，这种使人衰弱的疾病还没有治愈的方法，有效的治疗方法充其量是集中在症状缓解上。传统的MR技术已经显示出通过软骨体积或表面颤动来识别更细微的形态学改变的希望。然而，即使是这些更创新的传统技术在预测膝关节OA进展方面也不一致。因此，对早期识别危险人群的可靠、客观、无创、定量的影像学标志物有很高的需求。这项资助申请的长期目标是通过对膝关节软骨、小梁骨和骨髓的定量评估，开发一种更有效的方法来识别膝关节OA进展风险较高的个体。高分辨率、多核[钠（23Na）和质子（1H）]磁共振成像方法、超高场系统（7T）下新的图像后处理和可视化方法将对OA病理的客观评估产生重大影响。许多危险因素如关节错位、肥胖、创伤、半月板异常或十字韧带撕裂、生化、生物力学、遗传和环境因素可加重骨关节炎。具体来说，我们将使用新型的钠和质子微mri、图像处理和可视化技术，包括模糊距离变换（FDT）、数字拓扑分析（DTA）和张量分析。我们将以纵向方式获取年龄和性别匹配的OA受试者的高分辨率钠和质子MRI，以确定基线综合风险概况是否可以预测30个月内严重膝关节OA进展的风险人群。最后，我们将在基线检查中确定哪些相互作用（软骨-骨、骨髓或软骨-骨髓或三者的结合等）能更好地预测30个月内严重膝关节炎进展的潜在危险因素。这些研究一旦在人类膝关节中得到发展和验证，将不仅对OA的早期诊断产生深远的影响，而且可能在早期识别风险人群。我们预计，软骨、骨和骨髓之间的定量相互作用及其联合相互作用可能有助于设计膝关节OA进展的风险概况，而不是单独的方法。我们计划通过分包的外部合作来解决OA患者软骨、骨骼和骨髓之间的密切相互作用（Punam Saha博士，爱荷华大学电气与计算机工程与放射学系）。拨款申请的重点与NIBIB/NIAMS （NIH）生物工程研究拨款（BRG）计划的使命一致。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) affects over 50 million Americans and has a substantial impact on the US economy and the health care system. Currently, there is no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. The conventional MR techniques have shown promise for the identification of more subtle morphologic alterations as determined by cartilage volume, or surface fibrillation. However, even the more innovative of these conventional techniques have not been consistent in predicting the knee OA progression. Therefore, there is a high demand for reliable, objective, non-invasive and quantitative imaging markers that identifies the risk population at early stage. The long-term objective of this grant application is to develop a more effective means of identifying individuals at higher risk for knee OA progression via quantitative knee joint assessment of cartilage, trabecular bone and bone marrow. High- resolution, multi-nuclear [sodium (23Na) and proton (1H)] MR imaging approaches, novel image post- processing and visualization methods at ultra-high field system (7T) will significantly impact the objective assessment of OA pathology. OA may be aggravated by many risk factors such as joint malalignment, obesity, trauma, meniscal abnormalities or cruciate ligament tears, biochemical, biomechanical, genetic, and environmental. Specifically, we will use novel sodium and proton micro-MRI, image-processing and visualization technologies employing fuzzy distance transform (FDT), digital topological analysis (DTA) and tensor analysis. We will acquire high resolution sodium and proton MRI of age-and gender matched OA subjects in a longitudinal fashion to determine whether baseline combined risk profile can predict risk population for severe knee OA progression over 30 months period. Finally, we will identify which interactions (cartilage-bone, bone-marrow or cartilage-marrow or combination of all three etc) at baseline exam will better predict the potential risk factor for severe knee OA progression over 30 months period. Once developed and validated in human knee joint, these studies will profoundly affect not only to diagnose OA in its earliest stages but also possibly identifies the risk population at early stage. We anticipate that the quantitative interactions among the cartilage, bone and marrow and their combined interactions may be useful to design a risk profile for knee OA progression rather than individual approach. We plan to address these close interactions between cartilage, bone and marrow in OA patients with external collaboration through subcontract (Dr. Punam Saha, Department of Electrical & Computer Engineering and Radiology, University of Iowa). The focus of the grant application is consistent with the mission of the NIBIB/NIAMS (NIH) bioengineering research grant (BRG) program. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) affects ~6% of the US adult population and ~12-13% of those aged 60 and over. It has a substantial negative impact on the economy and the health care system. The current R01 proposal will develop a more effective means of identifying individuals at higher risk for OA progression via quantitative assessment of whole knee joint via ultra high field (7T) MRI system.