Imaging of Joint Response to Physiological Stress with Age, Sex and in Osteoarthritis

年龄、性别和骨关节炎对生理应激的联合反应的成像

• 批准号: 10444984
• 负责人: Feliks Kogan
• 金额: $ 39.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444984
• 关键词: Acute; Affect; Age; Aging; Area; Bilateral; Biomechanics; Bone Matrix; Cartilage; Chondrocytes; Clinical/Radiologic; Degenerative Disorder; Degenerative polyarthritis; Deposition; Detection; Development; Diagnostic Imaging; Disease; Disease Progression; Dose; Elderly; Environment; Evaluation; Exercise stress test; Functional disorder; Future; Gender; Human; Hybrids; Image; Image Analysis; Imaging technology; Incidence; Injections; Intervention; Ions; Joints; Kinetics; Knee; Knee Injuries; Knee Osteoarthritis; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measurement; Measures; Meniscus structure of joint; Metabolic; Methods; Modeling; Morphology; Motion; Musculoskeletal; Nature; Obesity; Orthopedics; Pain; Pathogenesis; Patients; Perfusion; Phenotype; Physiological; Physiology; Play; Positron-Emission Tomography; Productivity; Protocols documentation; Quality of life; Recording of previous events; Research; Risk; Risk Factors; Role; Scanning; Severities; Societies; Sodium Fluoride; Stress; Stress Tests; Structure; System; Techniques; Time; Tissues; Translations; Walking; Work; base; bone; bone metabolism; clinical translation; clinically translatable; cost; disability; imaging facilities; imaging modality; innovation; interest; joint function; joint loading; kinetic model; knee pain; mineralization; novel; radiological imaging; radiotracer; response; sex; soft tissue; tool; uptake

PROJECT SUMMARY Osteoarthritis (OA) is a leading cause of pain and disability worldwide and results in a reduced quality of life due to pain from common tasks such as walking or climbing and descending stairs. A particular challenge of OA is detection of disease at an early and reversible stage before irreversible structural damage has occurred. However, current imaging methods are performed in a static fashion and have limited sensitivity to joint function or the tissue response to loading. There is a major need to evaluate the joint response from everyday loading tasks, and how this response is altered in OA. Further, as age is a key risk factor of osteoarthritis, which predominantly affects older adults, the role of aging in tissue changes and response to loading stress is of particular interest. PET-MRI offers simultaneous evaluation of multiple early markers of OA in all joint tissues. In particular, [18F]NaF uptake can quantitatively evaluate bone metabolism, including bone perfusion and deposition of [18F] ions into the bone matrix. Further, we have observed that joint loading acutely alters the bone physiology affecting [18F]NaF uptake. This suggests that [18F]NaF uptake may be sensitive to increases in the metabolic response of bone where there is breakdown of the whole-joint unit that results in focal increases in bone loading. This project aims to develop a novel imaging “stress test”, based on [18F]NaF PET-MRI, that is able to evaluate at a single time point, both the function of the whole-joint unit after physiological joint loading and multiple early markers of OA. Our Specific Aims are to (1) develop a rapid, quantitative, dose- and time-minimized [18F]NaF PET-MRI protocol to evaluate joint function from a stair ascent/descent exercise “stress” test ; (2) evaluate [18F]NaF PET-MRI imaging to detect and characterize differences in joint function associated with age and between sexes; and (3) evaluate tissue response to loading stresses measured with PET-MRI in early OA and whether abnormal response is predictive of OA disease progression. The innovation of this project is the development of novel PET and MRI methods to assess the whole-joint response to loading and evaluation of early degenerative disease changes affecting joint function and future OA progression. The significance of this work is an imaging method that is able to rapidly assess joint function in response to physiological loads, and evaluation of how this joint response evolves with age and between genders, as well as the role of altered joint physiology in OA. This may allow us to detect early joint dysfunction at a single time point, to not only study OA pathophysiology, risk factors, and phenotypes, but also to develop targeted interventions.

项目摘要 骨关节炎（OA）是全球疼痛和残疾的主要原因，导致应有的生活质量降低 诸如步行或攀爬和下降楼梯等常见任务的痛苦。 OA的一个特殊挑战是 在发生不可逆的结构损害之前，在早期且可逆的阶段发现疾病。 但是，当前的成像方法是以静态方式进行的，对关节功能的敏感性有限 或组织对负载的反应。每天加载的关节响应都需要评估关节响应 任务，以及如何在OA中改变此响应。此外，由于年龄是骨关节炎的关键危险因素，这是 主要影响老年人，衰老在组织变化中的作用和对负荷压力的反应是 特别的兴趣。 PET-MRI可简单评估所有关节组织中OA的多个早期标记。特别是[18f] naf 摄取可以定量评估骨代谢，包括骨灌注和[18f]离子沉积 骨基质。此外，我们已经观察到关节载荷急性改变了影响的骨生理 [18f] NAF摄取。这表明[18F] NAF摄取可能对增加 整个关节单元崩溃的骨骼会导致骨负荷的局灶性增加。 该项目旨在基于[18F] NAF PET-MRI开发一种新型的“压力测试”，能够评估 在一个时间点，物理关节加载后整个关节单元的功能和多个早期的功能 OA的标记。我们的具体目的是（1）开发快速，定量，剂量和时间最少的[18F] NAF PET-MRI方案 评估楼梯上升/下降运动“压力”测试的联合功能 ; （2）评估 [18F] NAF PET-MRI成像以检测和表征与年龄和年龄相关的关节功能差异 性别之间； （3）评估在OA早期用PET-MRI测量的组织对负载应力的反应 异常反应是否可以预测OA疾病进展。 该项目的创新是开发新颖的宠物和MRI方法来评估整个关节 对影响关节功能和未来OA的早期退行性疾病变化的负载和评估的反应 进展。这项工作的意义是一种成像方法，能够快速评估关节功能 对身体负荷的反应，以及对这种联合反应随着年龄和性别之间的发展的评估， 以及改变关节生理学在OA中的作用。这可能使我们能够在一个单一检测到早期关节功能障碍 时间点，不仅要研究OA病理生理学，危险因素和表型，还可以发展有针对性的 干预措施。