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: 9928547
• 负责人: Feliks Kogan
• 金额: $ 24.9万
• 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/9928547
• 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 由于缺乏量化疾病进展和对疗法反应的非侵入性技术。我们 提议开发同时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标志物 OA的进展并将骨代谢与关节软骨的生化变化相关。这种方法会 为OA成像提供了相当大的进步；包括早期疾病的新标记和洞察力 OA的空间和时间进展。 该项目旨在使用PET/MR开发一种新的膝盖成像，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）开发快速和同时双侧膝盖MRI的平行MR成像技术； （2）创建一个 灵活的MRI膝盖线圈的自动衰减校正方法，以实现准确且可重复的 18F-NAF宠物吸收的动态扫描； （3）研究骨骼之间的时空关系 重塑和邻近软骨会发生变化，并评估18F-NAF PET是否可以预测退化性膝关节 前交叉韧带（ACL）泪流后，受试者有风险的受试者的变化。 这项工作的创新在于开发用于研究OA，PET/MR的新型成像技术 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。这项工作中开发的高级方法将增强快速的定量评估 每种成像方式中的早期疾病生物标志物。这项工作的重要性是我们将能够 敏感和定量地跟踪OA的最早变化，并研究时空的进展 疾病。这些贡献将为OA发病机理提供新的见解，从而导致新的治疗目标， 并最终疗法来阻止OA的发作和进展。