Imaging Biomarkers of Knee Osteoarthritis

项目摘要 骨关节炎（OA）是一种退行性关节疾病，在美国影响超过2700万人 一个人到2030年，约有6700万人将受到OA的影响。这一庞大的受影响人口和 OA的严重后果是使健康护理系统花费巨大。OA的特点是 通过细胞外基质（ECM）成分的生化、结构和形态降解， 关节软骨ECM主要由两组大分子组成， (PG)和胶原纤维。软骨退化的早期诊断需要能够非侵入性地 在形态变化发生之前检测PG浓度和胶原完整性的变化。T1ρ和T2 弛豫时间受这些病理过程的影响，并且是最广泛使用的生物化学方法。 全世界的软骨核磁共振成像一些研究人员已经证明，T1ρ弛豫时间是 T2弛豫时间对软骨的蛋白多糖含量更敏感，而T2弛豫时间对胶原蛋白更敏感 网络的定向性和完整性以及水化。这些成像生物标志物有可能在早期发现 疾病的阶段（临床前），定量评估疾病严重程度，监测疾病进展， 可能监测OA治疗。 该提案的总体目标是开发、评估和翻译高度加速的3D-T1ρ和T2 在标准临床3 T扫描仪上进行体内膝关节OA应用的标测（每个方案均在5分钟内） 采用新颖的压缩传感（CS）和并行成像（PI）策略。加速3D- T1ρ和T2定位技术可以很容易地结合到常规的临床方案中，用于生化分析。 除了标准形态学评估外，还可评估软骨，并可作为未来的成像 用于OA的疾病修饰疗法的生物标志物。这项研究的结果将大大影响 我们的个性化治疗方案的能力，并可能防止过早OA的发展。最后， 我们打算将这些序列传播到其他学术网站，以便广泛实施， 多中心研究。

PROJECT SUMMARY Osteoarthritis (OA) is a degenerative joint disease, affecting more than 27 million people in the United States alone. By 2030 approximately 67 million people will be affected by OA. This large affected population and the severe consequent debility of OA lead to significant expenses to the health care system. OA is characterized by biochemical, structural and morphologic degradation of components of the extracellular matrix (ECM) of articular cartilage. The ECM is composed of primarily two groups of macromolecules including proteoglycan (PG) and collagen fibers. Early diagnosis of cartilage degeneration would require the ability to non-invasively detect changes in PG concentration and collagen integrity before morphological changes occur. T1ρ and T2 relaxation times are affected by these pathological processes and are the most widely used biochemical cartilage MRI sequences worldwide. Several researchers have demonstrated that the T1ρ relaxation time is more sensitive to proteoglycan content of the cartilage, while T2 relaxation time is more sensitive to collagen orientation and integrity of network and hydration. These imaging biomarkers have potential to detect early stages of the disease (pre-clinical), quantitatively assess disease severity, monitor disease progression and possibly monitor OA therapy. The overarching goal of this proposal is to develop, evaluate and translate highly accelerated 3D-T1ρ and T2 mapping (each protocol under 5 minutes) for in-vivo knee OA applications on a standard clinical 3T scanner employing novel compressed sensing (CS) and parallel imaging (PI) strategies. The proposed accelerated 3D- T1ρ and T2 mapping techniques can be easily incorporated into routine clinical protocols for biochemical assessment of cartilage in addition to standard morphological evaluation and could serve as future imaging biomarkers for disease modifying therapies for OA. The outcome of this proposed study will significantly impact our ability for personalized treatment regimens and possibly prevent the development of premature OA. Finally, we intend on disseminating the sequences to other academic sites for widespread implementation and future multicenter studies.