Quantitative Assessment of Early Metabolic and Biochemical Changes in Osteoarthritis

项目摘要 骨关节炎（OA）是全球残疾的主要原因，但其治疗选择仍然有限，部分原因是 这是由于缺乏非侵入性技术来量化疾病进展和对治疗的反应。我们 建议开发同步正电子发射断层扫描（PET）和磁共振成像（MRI） (PET/MR）使用18F-氟化钠（18F-NaF）评估软骨下骨重建作为早期骨损伤的标志物。 骨关节炎进展和骨代谢与关节软骨生化变化的关系。这种方法将 为OA的成像提供了相当大的进步;包括早期疾病的新标志物和对 OA的时空进展。 该项目旨在开发一种使用PET/MR进行膝关节成像的新方法， 登记了对OA最早期变化敏感的代谢和生化标志物。我们的具体目标是 (1)开发并行MR成像技术，用于快速和同步的双侧膝关节MRI;（2）创建 用于柔性MRI膝关节线圈的自动衰减校正方法，以实现精确和可再现 18F-NaF PET摄取的动态扫描;和（3）研究骨之间的时空关系 重建和邻近软骨变化，并评估18F-NaF PET是否可以预测退行性膝关节 前交叉韧带（ACL）撕裂后有发生OA风险的受试者的变化。 这项工作的创新之处在于开发了一种新的成像技术，用于研究OA，PET/MR， 它提供了对最早期代谢和生化变化敏感的定量和多模态信息 在骨骼和软骨中。在这项工作中开发的先进方法将提高快速，定量评估 每种成像模式中的早期疾病生物标志物。这项工作的意义在于，我们将能够 敏感和定量地跟踪OA的最早变化，并研究OA的时空进展， 疾病这些贡献将为OA发病机制提供新的见解，从而找到新的治疗靶点， 以及最终阻止OA发作和进展的治疗。

Project Summary Osteoarthritis (OA) is the leading cause of disability worldwide, yet its treatment options remain limited, in part due to the lack of non-invasive techniques to quantify disease progression and response to therapies. We propose to develop simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET/MR) using 18F-sodium fluoride (18F-NaF) to assess subchondral bone remodeling as a marker of early OA progression and relate bone metabolism to biochemical changes in articular cartilage. This approach will provide a considerable advance for imaging of OA; including new markers of early disease and insights into the spatial and temporal progression of OA. This project aims to develop a new approach to knee imaging using PET/MR, providing fast, quantitative and registered metabolic and biochemical markers sensitive to the earliest changes in OA. Our specific aims are (1) to develop parallel MR imaging techniques for fast and simultaneous bilateral knee MRI; (2) to create an automated attenuation correction method for flexible MRI knee coils to achieve accurate and reproducible dynamic scans of 18F-NaF PET uptake; and (3) to study the spatiotemporal relationships between bone remodeling and adjacent cartilage changes and evaluate if 18F-NaF PET can predict degenerative knee changes in subjects at risk of developing OA following anterior cruciate ligament (ACL) tears. The innovation of this work lies in the development of a novel imaging technique for studying OA, PET/MR, that offers quantitative and multimodal information sensitive to the earliest metabolic and biochemical changes in bone and cartilage. Advanced methods developed in this work will enhance fast, quantitative assessment of early disease biomarkers within each imaging modality. The significance of this work is that we will be able to sensitively and quantitatively track the earliest changes of OA, and study the spatiotemporal progression of disease. These contributions will provide new insights into OA pathogenesis, leading to new treatment targets, and ultimately therapies to arrest the onset and progression of OA.