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: 10860577
• 负责人: Feliks Kogan
• 金额: $ 36.01万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10860577
• 关键词: Acute; Affect; Age; Area; Award; Bilateral; Cartilage; Clinical/Radiologic; Contralateral; Degenerative polyarthritis; Environment; Evaluation; Exhibits; Functional disorder; Future; Grant; Heterogeneity; Hybrids; Image; Imaging technology; Injections; Intervention; Joints; Knee; Knee Osteoarthritis; Leg; Liquid substance; Magnetic Resonance Imaging; Measures; Mechanics; Meniscus structure of joint; Metabolic; Metabolism; Methodology; Modeling; Modification; Morphology; Musculoskeletal; Orthopedics; Outcome Measure; Pain; Painless; Parents; Patellofemoral Pain Syndrome; Pathogenesis; Patients; Performance; Perfusion; Phenotype; Physiologic calcification; Physiological; Physiology; Play; Population; Productivity; Protocols documentation; Quality of life; Recording of previous events; Role; Scanning; Shapes; Signal Transduction; Sodium Fluoride; Source; Specificity; Stress; Stress Tests; Structure; System; Testing; Tissues; Walking; Work; arthropathies; bone; bone imaging; bone metabolism; cost; disability; human study; imaging facilities; imaging modality; innovation; joint injury; joint loading; kinetic model; knee pain; mechanical load; mineralization; novel; pain patient; parent grant; prevent; response; sex; stressor; tool; uptake; young adult

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.

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，这极大地限制了功能。膝盖 疼痛在OA中起着至关重要的作用。膝盖疼痛也会出现在没有OA特征的年轻患者中。在这个 人口除了对患者绩效和生活质量的影响之外，膝盖疼痛可能是未来的先兆 OA发作或进展。虽然这为治疗患者疼痛以及可能预防的早期目标提供了 未来的OA发作，疼痛表型的鉴定，尤其是膝盖疼痛中的特定疼痛来源 具有挑战性的。 MRI通常被用来识别膝盖疼痛的来源，但特异性较差，部分是由于 跨受试者出现的流体信号的异质性。此外，执行当前的成像方法 以静态的方式显示，对组织对组织对急性变化的反应评估的敏感性有限 诸如步行或雄鹿攀爬之类的关节装载活动通常是患者疼痛的压力。 PET-MRI提供了同时评估所有关节组织中OA的多个早期标记的潜力。尤其， [18F] - 氟化钠（[18F] NAF）摄取可用于研究骨代谢。 [18f] NAF摄取已显示 与tello股（PF）疼痛患者的疼痛相关。此外，我们观察到关节急性载荷 改变影响[18F] NAF摄取的骨骼生理学，这表明它可能对代谢敏感 骨骼的响应在整个关节单元中分解，从而导致骨负荷的局灶性增加。 该补充的科学前提是基于成像“应力测试”的应用 [18F] NAF PET-MRI，评估物理关节后整个关节单元的功能响应 膝盖疼痛患者的负载。我们的补充目标将扫描20个单侧PF疼痛的主题，没有 OA或[18F] NAF PET-MRI的OA或关节损伤的病史，以定量评估骨灌注的变化和 矿化[PET]以及软骨和半月板形态和微结构（T2，UTE-T2*）[MRI] [MRI] 对楼梯上升/下降“压力”测试的响应。我们假设[18F] NAF骨吸收的局灶性增加 在疼痛的膝盖中，基线楼梯上升/下降任务将更大 膝盖，暗示机械衍生的疼痛。我们将探索PF疼痛是否表现出焦距的骨负荷区域 这可能是保守干预措施的目标。我们还将探讨如何对加载的功能响应 在痛苦的膝盖中，将与年龄匹配的控制和OA人群相比。 我们的调查团队包括[18F] NAF动力学建模，成像技术和骨生理学专家， 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，包括领导 具有混合PET-MRI系统和高级动态成像和分析功能的成像中心，一起 领先的临床放射学和骨科部门。该项目的创新是评估 对机械负荷作为研究疼痛机械源的非侵入性工具的联合反应。