Quantitative Assessment of Early Metabolic and Biochemical Changes in Osteoarthritis

骨关节炎早期代谢和生化变化的定量评估

• 批准号: 9979846
• 负责人: Feliks Kogan
• 金额: $ 24.35万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979846
• 关键词: Affect; Aftercare; Anterior Cruciate Ligament; Area; Bilateral; Biochemical; Biochemical Markers; Biochemistry; Biological Markers; Bone Matrix; Bone remodeling; Cartilage; Cartilage Matrix; Clinical; Collaborations; Collagen; Data; Degenerative polyarthritis; Development; Diagnostic Imaging; Discipline of Nuclear Medicine; Disease; Disease Marker; Disease Progression; Early Diagnosis; Environment; Future; Geometry; Hybrids; Image; Imaging Techniques; Joints; Knee; Knee Osteoarthritis; Knowledge; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medicine; Mentors; Metabolic; Metabolic Marker; Methods; Molecular; Morphology; Operative Surgical Procedures; Orthopedics; Pathogenesis; Patients; Photons; Population; Positioning Attribute; Positron-Emission Tomography; Process; Productivity; Property; Proteoglycan; Protocols documentation; Quality of life; Relaxation; Reproducibility; Research; Resolution; Resources; Risk; Role; Scanning; Sodium Fluoride; System; Techniques; Time; Tissues; Tracer; Training; Universities; Validation; Work; anterior cruciate ligament rupture; articular cartilage; attenuation; bone; bone metabolism; cost; disability; flexibility; high risk; image reconstruction; imaging approach; imaging modality; improved; innovation; insight; joint injury; joint stress; multimodality; novel; novel imaging technique; novel marker; novel strategies; programs; response; response to injury; spatiotemporal; subchondral bone; targeted treatment; tool; uptake

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.

项目概要 骨关节炎 (OA) 是世界范围内导致残疾的主要原因，但其治疗选择在一定程度上仍然有限 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) 评估软骨下骨重塑作为早期骨重建的标志 OA 进展并将骨代谢与关节软骨的生化变化联系起来。这种方法将 为 OA 成像提供了相当大的进步；包括早期疾病的新标志物和见解 OA 的空间和时间进展。 该项目旨在开发一种使用 PET/MR 进行膝关节成像的新方法，提供快速、定量和 注册的代谢和生化标志物对 OA 的最早变化敏感。我们的具体目标是 (1) 开发用于快速、同步双侧膝关节 MRI 的并行 MR 成像技术； (2) 创建一个 柔性 MRI 膝关节线圈的自动衰减校正方法，以实现准确且可重复的效果 18F-NaF PET 摄取的动态扫描； (3)研究骨骼之间的时空关系 重塑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 前十字韧带 (ACL) 撕裂后有发生 OA 风险的受试者发生变化。 这项工作的创新在于开发了一种用于研究 OA、PET/MR、 提供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对 每种成像方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 敏感且定量地追踪 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，从而产生新的治疗目标， 以及最终阻止 OA 发生和进展的治疗方法。