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

摘要 膝骨性关节炎(OA)是导致成年人残疾的主要原因，对经济有重大影响。此外， 膝关节骨性关节炎是疼痛和功能障碍的主要来源。一个关于骨性关节炎发病机制的假想模型 有人提出，重复的关节负荷会导致骨重建的初始增加，这与 随着软骨深层血管侵入的增加。新兴的质子发射层析成像和 磁共振成像同步系统(PET-MRI)提供了一种令人兴奋的新模式 获得大量的功能测量以及高分辨率的形态来研究这一复合体 现象。关节负荷是骨性关节炎进展过程中不可或缺的一部分，但目前对关节负荷的知之甚少。 与PFJOA进展相关的生物力学因素。因此，我们的总体目标是：(I)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。我们将进行一项 纵向队列研究调查了100名孤立性PFJOA患者，跟踪观察了2个时间点。同时进行 所有受试者在基线和2年随访时将收集PET-MRI和步态生物力学数据。目标1：实现 研究骨和软骨成像生物标记物之间的横断面关系，并 研究步态生物力学和骨骼形态是如何调节相互作用模式的。 假设1：PFJOA受试者升高的SUV将与T1、ρ和T2松弛的延长共同定位 泰晤士报。异常步态引起的负荷变化所介导的复杂的骨-软骨相互作用 生物力学和骨骼形态将显示骨和软骨之间的非共定位联系。 目的2：研究骨和软骨影像生物标志物之间的纵向关系 研究步态生物力学和形态是如何调节相互作用模式的： 假设2：早期骨代谢活动的改变(SUV)是软骨成分改变的先兆 (T1ρ和T2)。有特殊异常步态生物力学和骨骼形状特征的受试者将表现为加速 构成上的变化。目的3：确定骨-软骨相互作用预测能力 结构性和症状性PFJOA进展的纵向轨迹。假设3：两个地方都在同一地点 而由关节生物力学和骨形状介导的非共定位骨-软骨相互作用模式将是 结构性和症状性PJOA进展的重要预测因子。横截面和纵向 步态生物力学对软骨成分和骨重建的影响 对于确定疾病的个别和综合影响是至关重要的。

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.