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

项目摘要 骨关节炎（OA）是全球疼痛和残疾的主要原因，并因其导致生活质量下降。 疼痛从常见的任务，如步行或爬楼梯和下楼梯。OA的一个特殊挑战是 在不可逆的结构损伤发生之前的早期和可逆阶段检测疾病。 然而，目前的成像方法是以静态方式进行的，并且对关节功能的灵敏度有限 或组织对负荷的反应。有一个主要的需要，以评估联合反应，从日常负荷 任务，以及如何在OA中改变这种反应。此外，由于年龄是骨关节炎的关键风险因素， 主要影响老年人，衰老在组织变化和对负荷应力的反应中的作用是 特别的兴趣。 PET-MRI可同时评价所有关节组织中OA的多种早期标志物。特别是，[18F]NaF 摄取可以定量评估骨代谢，包括骨灌注和[18F]离子沉积到骨中， 骨基质此外，我们观察到关节负荷急剧改变了骨生理学， [18F]NaF摄取。这表明[18F]NaF摄取可能对代谢反应的增加敏感， 整个关节单元发生破坏，导致骨负荷局部增加的骨。 该项目旨在开发一种新的成像“压力测试”，基于[18 F]NaF PET-MRI，能够评估 在单个时间点，生理性关节负荷后的全关节单位功能和多个早期关节单位功能均显著降低。 OA的标志物。我们的具体目标是（1）开发一种快速，定量，剂量和时间最小化的[18 F]NaF PET-MRI方案， 通过上下楼梯运动“压力”测试评估关节功能 （2）评价 [18F]NaF PET-MRI成像用于检测和表征与年龄相关的关节功能差异， （3）评价组织对早期OA中PET-MRI测量的负荷应力的反应， 异常反应是否预示OA疾病进展。 该项目的创新之处在于开发了新型PET和MRI方法来评估整个关节 对负荷的反应和影响关节功能和未来OA的早期退行性疾病变化的评价 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， 对生理负荷的反应，以及评估这种关节反应如何随年龄和性别而演变， 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的关节检测早期关节功能障碍。 时间点，不仅研究OA的病理生理学，危险因素和表型，而且还开发有针对性的 干预措施。

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.