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.

抽象的 本补充促进健康相关研究多样性的总体目标是提供 为一位有前途、有抱负的科学家提供培训和支持（Hector Carbajal Mendez 先生，博士生） Carbajal Mendez 先生在创新和富有成效的研究环境中是一位才华横溢的人。 对使用 IMU 更好地了解关节载荷感兴趣的工程师这种兴趣直接符合。 我的实验室专注于膝骨关节炎 (OA) 患者的关节健康，特别是髌股关节 OA。 是疼痛和功能障碍的主要根源，由此提出了 OA 发病机制的假设模型。 重复的关节负荷会导致骨重塑的最初增加，这与血管的增加有关 新兴质子发射断层扫描和磁共振侵入软骨深层。 同步成像系统 (PET-MRI) 提供了一种令人兴奋的新模式，可以同时获取大量数据 功能测量以及高分辨率形态来研究这种复杂的现象。 OA 进展不可或缺的一部分，但目前，人们对与 OA 相关的生物力学因素知之甚少 因此，我们的总体目标是：(i) 确定横截面和纵向局部模式。 PFJOA 特有的软骨和骨骼相互作用，以及 (ii) 确定步态生物力学的中介作用 我们将进行一项纵向队列研究，调查 100 名患者。 患有孤立性 PFJOA 的患者将接受 2 个时间点的同步 PET-MRI 和步态生物力学检查。 目标 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 由步态生物力学和骨骼形态介导。 假设 1：PFJOA 受试者中 SUV 升高将与 T1ρ 和 T2 弛豫延长共定位 步态异常导致的负荷变化介导复杂的骨-软骨相互作用。 生物力学和骨骼形态将显示骨骼和软骨之间的非共定位关联。 目标 2：研究骨和软骨成像生物标志物之间的纵向关系并 研究步态生物力学和形态学如何介导相互作用的模式： 假设 2：骨代谢活动 (SUV) 的早期变化是软骨成分变化的先兆 （T1ρ 和 T2）具有特定异常步态生物力学和骨骼形状特征的受试者将表现出加速。 目标 3：确定骨-软骨相互作用的预测能力。 结构性和症状性 PFJOA 进展的纵向轨迹 假设 3：两者共定位。 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 结构性和症状性 PJOA 进展的重要预测因素。