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

项目总结 骨关节炎(OA)是世界范围内疼痛和残疾的主要原因，并导致生活质量下降。 到行走或攀登和下楼梯等常见任务带来的疼痛，这些都极大地限制了功能。膝 疼痛在骨性关节炎中起着至关重要的作用。膝关节疼痛也出现在没有骨性关节炎特征的年轻患者中。在这 在人群中，除了对患者表现和生活质量的影响外，膝关节疼痛可能是未来的先兆 骨性关节炎的发病或进展。虽然这提供了一个早期目标，既可以治疗患者的疼痛，也可以预防 膝关节疼痛残留物中疼痛表型的识别，特别是特定疼痛来源的鉴定 很有挑战性。核磁共振最常被用来试图确定膝关节疼痛的来源，但其特异性很差，部分原因是 在不同受试者之间出现的流体信号的异质性。此外，执行当前的成像方法 在静态方式下，并且对评估组织对急性变化的反应表现出有限的敏感性 关节负荷活动，如步行或爬楼梯，通常是患者疼痛的压力源。 PET-MRI提供了同时评估所有关节组织中多个骨关节炎早期标志物的潜力。特别是， [18F]-氟化钠([18F]NaF)摄取可用于研究骨代谢。[18F]氟化钠的吸收率已显示 髌股关节痛与疼痛的相关性研究。此外，我们还观察到关节载荷显著增加。 改变影响[18F]NaF摄取的骨生理，这表明它可能对代谢敏感 骨的反应，当整个关节单位破裂，导致骨负荷局灶性增加。 本补充材料的科学前提是应用成像“压力测试”，基于 [18F]NaF PET-MRI，用于评价生理性关节术后全关节单位的功能反应 负荷性膝部疼痛患者。我们的补充目标将扫描20名患有单侧PF疼痛和NO的受试者 骨性关节炎或关节损伤病史的[18F]NaF PET-MRI定量评估骨灌注量的变化和 矿化[PET]以及软骨和半月板的形态和微结构(T2，UTE-T2*)[MRI] 对楼梯上升/下降“压力”测试的反应。我们假设病灶增加了[18F]NaF的骨摄取 在基线阶梯上升/下降任务后，疼痛的膝关节将比非疼痛的对侧更大 膝盖，提示机械性疼痛。我们将探索PF疼痛是否表现出局部高骨量区域。 这可能是保守干预的目标。我们还将探讨该函数对加载的响应 膝关节疼痛的患者将与年龄匹配的对照组以及骨性关节炎患者进行比较。 我们的研究团队包括[18F]NaF动力学建模、成像技术和骨生理学方面的专家， 以及肌肉骨骼临床医生。我们的环境提供了所有必要的工具，包括领先的 配备混合PET-MRI系统以及高级动态成像和分析功能的成像中心 拥有领先的临床放射科和骨科。本项目的创新之处在于对 关节对机械负荷的反应作为研究机械性疼痛来源的无创性工具。

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, which greatly limit function. Knee pain plays a critical role in OA. Knee pain also presents in younger patients without features of OA. In this population, beyond its effects on patient performance and quality of life, knee pain may be a precursor of future OA onset or progression. While this offers an early target to both treat patient pain as well as potentially prevent future OA onset, identification of pain phenotypes and especially specific pain sources in knee pain remains challenging. MRI is most often utilized to try to identify sources of knee pain, but has poor specificity, partly due to the heterogeneity of fluid signal that appears across subjects. Further, current imaging methods are performed in a static fashion and have shown limited sensitivity to evaluation of tissue response to acute changes due to joint loading activities such as walking, or stair climbing which often are the stressor of the patient’s pain. PET-MRI offers potential to simultaneously evaluate multiple early markers of OA in all joint tissues. In particular, [18F]-sodium fluoride ([18F]NaF) uptake can be used to study bone metabolism. [18F]NaF uptake has shown correlation with pain in patellofemoral (PF) pain patients. Further, we have observed that joint loading acutely alters the bone physiology affecting [18F]NaF uptake which suggests it may be sensitive to the metabolic response of bone where there is breakdown of the whole-joint unit that results in focal increases in bone loading. The scientific premise of this supplement is the application of an imaging “stress test,” based on [18F]NaF PET-MRI, to evaluate the function response of the whole-joint unit after physiological joint loading in patients with knee pain. Our supplemental Aim will scan 20 subjects with unilateral PF pain and no history of OA or joint injury with [18F]NaF PET-MRI to quantitatively assess changes in bone perfusion and mineralization [PET] as well as cartilage and meniscus morphology and microstructure(T2, UTE-T2*) [MRI] in response to a stair ascent/descent “stress” test. We hypothesize that focal increases in [18F]NaF bone uptake after a baseline stair ascent/descent task will be larger in the painful knee compared with non-painful contralateral knee, suggestive of mechanical-derived pain. We will explore if PF pain exhibits focally high areas of bone load which may be targets for conservative interventions. We will also explore how this functional response to loading is in the painful knee will compare to age-matched controls as well as to an OA population. Our investigative team includes experts in [18F]NaF kinetic modeling, imaging technology, and bone physiology, as well as musculoskeletal clinicians. Our environment provides all the necessary tools, including a leading imaging center with a hybrid PET-MRI system and advanced dynamic imaging and analysis capabilities, together with leading clinical radiology and orthopedics departments. The innovation of this project is the evaluation of the joint response to mechanical loading as non-invasive tool to study mechanical sources of pain.