In Vivo Early Detection of Cartilage Degeneration Using High Field MRI

候选人和职业发展计划。候选人在生物工程方面受过良好的培训， 强调定量磁共振成像（MRI）。她的长期科学目标是改善 通过非侵入性成像技术了解、检测和治疗严重疾病，以及 最终提高医疗质量。在短期内，凭借这一奖项，候选人的目标是 获得必要的培训，以成为一个独立的生物医学研究人员;特别是， 能够发起和进行她自己的研究计划，在定量MRI骨关节炎和膝关节损伤。 这位候选人和她的导师组建了一个独立的研究团队， 和临床相关领域，以帮助她实现这一目标。拟议的职业发展计划包括1） 保护至少75%的研究时间，2）生物学/病理学和临床方面的系统培训， 肌肉骨骼疾病通过参加课程，杂志俱乐部，研讨会，科学会议，并定期 与合作研究者的互动; 3）获得新的研究技能和专业知识的研究计划。 Research.骨关节炎（OA）是最常见的以软骨为特征的关节疾病 退化OA软骨退变的非侵入性早期检测具有越来越重要的临床意义 重要性目前的成像技术仅限于提供软骨的主要形态学变化 往往发生在OA的晚期。我们建议在高场开发先进的MRI技术 强度（3特斯拉），通过探测胶原蛋白多糖的变化来早期检测软骨退化 (PG)矩阵我们的初步数据表明，MR T1 p弛豫时间是一个有希望的候选者。 目的.拟议项目的目标是：1）进一步开发体内尖端标测技术， 3 T扫描仪，2）使用OA软骨标本建立其与胶原-PG基质的关系 探讨全膝关节置换术后软骨监测的临床意义 前交叉韧带（ACL）撕裂的膝关节纵向损伤， 创伤后OA还将尖端值与TZrelaxation时间和对比后TI relaxation进行比较 延迟钆增强MRI（dGEMRIC）。驱动假说是，在体内， 测量这些弛豫时间可以在形态学改变之前检测早期软骨退化。 观察到变化。将来，这些技术可能允许对新的外科手术和 药理学技术来治疗受损的软骨。这项研究的结果预计也将 为更好地管理ACL断裂和潜在的其他膝关节损伤提供指导和工具。 总之，该提案解决了肌肉骨骼疾病的一个重要问题， 作为培养候选人独立研究能力的工具。

Candidate and Career Development Plan. The candidate is well trained in bioengineering with an emphasis on quantitative Magnetic Resonance Imaging (MRI). Her long-term scientific goal is to improve the understanding, detection, and treatment of serious diseases through non-invasive imaging techniques, and to ultimately improve the quality of health care. In the short term, with this award, the candidate aims to obtain the necessary training in order to become an independent biomedical researcher; specifically, to be able to initiate and conduct her own research program in quantitative MRI for osteoarthritis and knee injuries. The candidate and her mentor have assembled a team of independent investigators in both basic science and clinical related fields to help her achieve this goal. The proposed career development plan includes 1) protected at least 75% research time, 2) a systematic training in biology/pathology and clinical aspects of musculoskeletal diseases by attending courses, journal clubs, seminars, scientific meetings, and regular nteractions with co-investigators; 3) a research plan for acquiring new research skills and expertise. Research. Osteoarthritis (OA) is the most common joint disease characterized by cartilage degeneration. Non-invasive early detection of cartilage degeneration in OA is of increasing clinical importance. Current imaging techniques are limited to providing primarily morphologic changes of cartilage that tend to occur at late stages of OA. We propose to develop advanced MRI techniques at a high field strength (3 Tesla) for early detection of cartilage degeneration by probing changes in collagen-proteoglycan (PG) matrix. Our preliminary data have shown MR T1p relaxation time as a promising candidate for this purpose. The objective of the proposed project is to 1) further develop in vivo Tip mapping techniques on a 3T scanner, 2) to establish its relationship with collagen-PG matrix using cartilage specimens from OA patients who undergo total knee arthroplasty; and 3) to explore its clinical significance by monitoring cartilage damage longitudinally in knees with anterior cruciate ligament (ACL) tear that are at high risk for posttraumatic OA. Tip values will also be compared with TZrelaxation time and post-contrast TI relaxation time with delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC). The driving hypothesis is that in vivo measurement of these relaxation times can detect early cartilage degeneration before morphologica changes are observed. In the future, these techniques may permit a critical evaluation of new surgical and pharmacological techniques to treat damaged cartilage. The results of this study are also anticipated to provide direction and tools for better management for ACL ruptures and potentially other knee injuries. In summary, the proposal addresses a significant issue in musculoskeletal diseases, and will serve wel as a training vehicle to establish research independency of the candidate.