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.

项目概要 骨关节炎 (OA) 是全世界疼痛和残疾的主要原因，并导致生活质量下降 步行或爬楼梯等常见任务带来的疼痛，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。膝关节疼痛也出现在没有 OA 特征的年轻患者中。在这个 除了对患者表现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。虽然这提供了治疗患者疼痛并可能预防疼痛的早期目标 未来 OA 的发病、疼痛表型的识别，尤其是膝关节疼痛的具体疼痛源仍然存在 具有挑战性的。 MRI 最常用于尝试确定膝盖疼痛的来源，但特异性较差，部分原因是 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 以静态方式进行，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，例如步行或爬楼梯，这些活动通常是患者疼痛的压力源。 PET-MRI 具有同时评估所有关节组织中多种 OA 早期标志物的潜力。尤其， [18F]-氟化钠 ([18F]NaF) 摄取可用于研究骨代谢。 [18F]NaF 吸收已显示 与髌股（PF）疼痛患者疼痛的相关性。此外，我们观察到关节负荷急剧 改变影响 [18F]NaF 吸收的骨生理学，这表明它可能对代谢敏感 整个关节单元损坏时骨骼的反应，导致骨负荷局部增加。 本补充品的科学前提是应用成像“压力测试”，该测试基于 [18F]NaF PET-MRI，评估生理关节后全关节单元的功能反应 膝盖疼痛患者的负荷。我们的补充目标将扫描 20 名患有单侧 PF 疼痛且无症状的受试者 使用 [18F]NaF PET-MRI 定量评估骨灌注和关节损伤史 矿化 [PET] 以及软骨和半月板形态和微观结构（T2、UTE-T2*）[MRI] 对楼梯上升/下降“压力”测试的反应。我们假设 [18F]NaF 骨摄取局部增加 基线上楼梯/下楼梯后，与无痛对侧相比，疼痛膝盖的任务会更大 膝盖，提示机械性疼痛。我们将探讨 PF 疼痛是否表现出局灶性高骨负荷区域 这可能是保守干预的目标。我们还将探讨这个功能如何响应加载 将与年龄匹配的对照组以及骨关节炎人群进行比较。 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 成像中心配备混合 PET-MRI 系统和先进的动态成像和分析功能 拥有领先的临床放射科和骨科部门。本项目的创新点是评价 对机械负荷的关节反应作为研究机械疼痛来源的非侵入性工具。