Simultaneous Imaging of Tissue Biochemistry and Metabolism associated with Biomechanics in Patella Femoral Joint Osteoarthritis

髌股关节骨关节炎与生物力学相关的组织生物化学和代谢的同步成像

• 批准号: 10443016
• 负责人: Sharmila Majumdar
• 金额: $ 70.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443016
• 关键词: Adult; Biochemistry; Biomechanics; Blood Vessels; Bone remodeling; Cartilage; Collagen; Complex; Cross-Sectional Studies; Data; Degenerative polyarthritis; Disease; Disease Progression; Enzymes; Etiology; Evaluation; Extracellular Matrix; Functional disorder; Gait; Gait abnormality; Goals; Image; Incidence; Individual; Investigation; Joints; Knee Osteoarthritis; Knee bone; Light; Longitudinal Studies; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Mediation; Metabolic; Metabolism; Modality; Modeling; Morphology; Musculoskeletal; Outcome; Pain; Pathogenesis; Pattern; Peptide Hydrolases; Persons; Positron-Emission Tomography; Process; Proteoglycan; Protons; Questionnaires; Relaxation; Resolution; Risk Factors; Role; Shapes; Source; Standardization; System; Thick; Time; Tissue imaging; Variant; Work; base; bone; cartilage degradation; disability; feature extraction; follow-up; imaging biomarker; imaging study; inhibitor; joint biomechanics; joint loading; knee pain; radiological imaging; soft tissue; subchondral bone; substantia spongiosa; tomography; treatment strategy; uptake

ABSTRACT Knee osteoarthritis (OA) is the leading cause of disability in adults, with a substantial fiscal impact. Furthermore, patellofemoral joint OA is a major source of pain and dysfunction. A hypothetical model for OA pathogenesis has been proposed whereby repetitive joint loading causes an initial increase in bone remodeling, which is associated with increased vascular invasion of the deep layers of cartilage. Emerging Proton Emission Tomography and Magnetic Resonance Imaging simultaneous systems (PET-MRI) offer an exciting new modality to simultaneously acquire numerous functional measures as well as high-resolution morphology to study this complex phenomenon. Joint loading is integral to OA progression yet currently, very little is known regarding the biomechanical factors associated with PFJOA progression. Therefore, our overall goal is to: (i) identify cross- sectional and longitudinal local patterns of cartilage and bone interactions unique to PFJOA, and (ii) determine the mediation effects of gait biomechanics and bone morphology on PFJOA progression. We will conduct a longitudinal cohort study investigating 100 people with isolated PFJOA, followed for 2 time points. Simultaneous PET-MRI and gait biomechanics will be collected for all subjects at baseline and 2-year follow-up. Aim 1: To study the cross-sectional relationships between bone and cartilage imaging biomarkers and to investigate how the patterns of interactions are mediated by gait biomechanics and bone morphology. Hypothesis 1: Elevated SUV in subjects with PFJOA will be colocalized with prolongation of T1ρ and T2 relaxation times. Complex bone-cartilage interactions mediated by change in loading as a result of abnormal gait biomechanics and bone morphology will show non-colocalized associations between bone and cartilage. Aim 2: To study the longitudinal relationships between bone and cartilage imaging biomarkers and to investigate how the patterns of interactions are mediated by gait biomechanics and morphology: Hypothesis 2: Early changes in bone metabolic activity (SUV) are a precursor to cartilage compositional changes (T1ρ and T2). Subjects with specific abnormal gait biomechanics and bone shape features will show accelerated compositional changes. Aim 3: To determine the ability of bone-cartilage interactions to predict longitudinal trajectories of structural and symptomatic PFJOA progression. Hypothesis 3: Both colocalized and non-colocalized bone-cartilage interaction patterns mediated by joint biomechanics and bone shape will be significant predictors of structural and symptomatic PJOA progression. Cross-sectional and longitudinal evaluations of cartilage composition and bone remodeling mediated by gait biomechanics as likely contributors to PFJOA progression, are vital to determine the individual and combined effects of the disease.

摘要 膝关节骨关节炎（OA）是成人残疾的主要原因，具有重大的财政影响。此外，委员会认为， 髌股关节OA是疼痛和功能障碍的主要来源。OA发病机制的假设模型有 因此，反复的关节负荷会导致骨重建的初始增加，这与 软骨深层的血管入侵增加。新兴的质子发射断层扫描和 磁共振成像同步系统（PET-MRI）提供了一种令人兴奋的新模式， 获得许多功能措施以及高分辨率形态学研究这个复杂的 现象关节负荷是骨性关节炎进展的组成部分，但目前，关于骨关节炎的进展知之甚少。 与PFJOA进展相关的生物力学因素。因此，我们的总体目标是：（一）确定交叉- PFJOA特有的软骨和骨相互作用的截面和纵向局部模式，以及（ii）确定 步态生物力学和骨形态对PFJOA进展的中介作用。我们将进行 纵向队列研究，调查100例孤立性PFJOA患者，随访2个时间点。同时 将在基线和2年随访时收集所有受试者的PET-MRI和步态生物力学。目标1： 研究骨和软骨成像生物标志物之间的横截面关系， 研究步态生物力学和骨形态如何介导相互作用的模式。 假设1：PFJOA受试者的SUV升高将与T1ρ和T2弛豫延长共定位 次异常步态导致的负荷变化介导的复杂骨-软骨相互作用 生物力学和骨形态将显示骨和软骨之间的非共定位关联。 目的2：研究骨和软骨成像生物标志物之间的纵向关系， 研究如何通过步态生物力学和形态学介导相互作用的模式： 假设2：骨代谢活性（SUV）的早期变化是软骨成分变化的前兆 (T1ρ和T2）。具有特定异常步态生物力学和骨形状特征的受试者将显示加速的 成分变化目的3：确定骨-软骨相互作用预测 结构性和症状性PFJOA进展的纵向轨迹。假设3：两者共域 由关节生物力学和骨形状介导的非共域骨-软骨相互作用模式将被 结构性和症状性PJOA进展的重要预测因素。横断面和纵向 评估软骨成分和步态生物力学介导的骨重塑可能是贡献者 PFJOA进展，是至关重要的，以确定疾病的个体和综合影响。