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: 10792426
• 负责人: Sharmila Majumdar
• 金额: $ 5.13万
• 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/10792426
• 关键词: Acceleration; Adult; Artificial Intelligence; Biochemistry; Biomechanics; Biomedical Engineering; Blood Vessels; Bone remodeling; Cartilage; Complex; Cross-Sectional Studies; Data; Degenerative polyarthritis; Disease; Disease Progression; Doctor of Philosophy; Engineering; Environment; Etiology; Femur; Functional disorder; Gait; Gait abnormality; Goals; Health; Image; Incidence; Invaded; Investigation; Joints; Knee Osteoarthritis; Knee bone; Longitudinal Studies; Longitudinal cohort study; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Mediating; Mediation; Metabolic; Metabolism; Modality; Modeling; Modification; Morphology; Musculoskeletal; Outcome; Pain; Parents; Pathogenesis; Patients; Pattern; Persons; Prevention; Process; Productivity; Protons; Questionnaires; Rehabilitation therapy; Relaxation; Research; Research Project Grants; Resolution; Risk Factors; Role; Scientist; Shapes; Source; Standardization; System; Technology; Thick; Time; Tissue imaging; Training; Variant; Work; advanced disease; bone; cartilage degradation; cohort; combat; disability; doctoral student; feature extraction; follow-up; imaging biomarker; imaging study; innovation; interest; joint biomechanics; joint loading; knee pain; radiological imaging; soft tissue; subchondral bone; substantia spongiosa; tomography; treatment strategy; uptake

ABSTRACT The overall goal of this Supplement to Promote Diversity in Health-Related Research is to provide training and support to a promising aspiring scientist (Mr. Hector Carbajal Mendez, PhD student in Bioengineering) in an innovative and productive research environment. Mr. Carbajal Mendez is a brilliant engineer with interests in using IMU’s to better understand joint loading. This interest directly align with my labs focus on joint health in subjects with knee osteoarthritis (OA). Specifically, 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.

摘要 这一补充的总体目标，以促进健康相关研究的多样性是提供 培训和支持一位有前途、有抱负的科学家（Hector Carbajal Mendez先生， 生物工程）在一个创新和富有成效的研究环境。卡巴哈尔·门德斯先生是一位 有兴趣使用IMU的工程师，以更好地了解联合加载。这种兴趣直接与 我的实验室专注于膝关节骨关节炎（OA）受试者的关节健康。具体而言，髌股关节OA 是疼痛和功能障碍的主要来源。已经提出了OA发病机制的假设模型， 重复的关节负荷导致骨重建的初始增加，这与血管生成增加有关。 软骨深层的侵入。新兴的质子发射断层扫描和磁共振 同步成像系统（PET-MRI）提供了一种令人兴奋的新模式，可以同时采集大量 功能测量以及高分辨率形态学来研究这种复杂的现象。联合载荷是 然而，目前对与骨关节炎进展相关的生物力学因素知之甚少， PFJOA进展。因此，我们的总体目标是：（i）确定横向和纵向的局部模式 PFJOA特有的软骨和骨相互作用，以及（ii）确定步态生物力学的中介作用 和骨形态对PFJOA进展的影响我们将进行一项纵向队列研究，调查100名 孤立性PFJOA患者，随访2个时间点。同时进行PET-MRI和步态生物力学测试， 在基线和2年随访时收集所有受试者的数据。目的1：研究横截面关系 骨和软骨成像生物标志物之间的关系，并研究相互作用的模式是如何 由步态生物力学和骨形态学介导。 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。