Quantitative Assessment of Early Metabolic and Biochemical Changes in Osteoarthritis

项目摘要 骨关节炎(OA)是世界范围内导致残疾的主要原因，但其治疗选择仍然有限，部分原因是 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 建议同时发展正电子发射断层扫描(PET)和磁共振成像(MRI) 18F-氟化钠(18F-NaF)评价软骨下骨改建作为早期软骨下骨重建的指标 骨关节炎进展及骨代谢与关节软骨生化变化的关系。这一方法将 为OA的成像提供了相当大的进步；包括早期疾病的新标记物和对 骨性关节炎的空间和时间进程。 该项目旨在开发一种使用PET/MR进行膝关节成像的新方法，提供快速、定量和 注册的代谢和生化标记物对骨性关节炎的最早变化敏感。我们的具体目标是 (1)开发并行磁共振成像技术，以实现快速、同时的双侧膝关节磁共振成像；(2)创建 一种实现精确可重复性的柔性MRI膝关节线圈的自动衰减校正方法 18F-NaF PET摄取的动态扫描；(3)研究骨与骨之间的时空关系 18F-NaF PET对膝关节退行性变的预测价值 前十字韧带(ACL)撕裂后发生骨性关节炎风险受试者的变化。 这项工作的创新之处在于发展了一种新的成像技术，用于研究OA、PET/MR、 这提供了对最早的代谢和生化变化敏感的定量和多模式信息 在骨骼和软骨中。这项工作中开发的先进方法将增强快速、定量的评估 每种成像方式中的早期疾病生物标记物。这项工作的意义在于，我们将能够 灵敏、定量跟踪最早的骨性关节炎变化，研究骨质疏松症的时空进程 疾病。这些贡献将为OA的发病机制提供新的见解，导致新的治疗靶点， 并最终采取治疗措施来阻止骨性关节炎的发生和发展。

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.