MRI of Tendon Structure and Metabolism

肌腱结构和代谢的 MRI

• 批准号: 10592920
• 负责人: David A Reiter
• 金额: $ 18.19万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592920
• 关键词: Activities of Daily Living; Acute; Affect; Anatomy; Animal Experiments; Animals; Biological; Biological Process; Biomechanics; Cells; Chemical Shift Imaging; Chemicals; Chronic; Complex; Contralateral; Coupled; Development; Dialysis procedure; Energy Metabolism; Evaluation; Exercise; Exhibits; Extracellular Matrix; Frequencies; Functional Imaging; Glycolysis; Homeostasis; Human; Image; Individual; Joints; Lower Extremity; Magic; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Maps; Measurement; Measures; Mechanics; Metabolic; Metabolism; Methodology; Methods; Molecular; Musculoskeletal; Oxygen Consumption; Pain; Pathogenesis; Pathologic; Patients; Production; Property; Rattus; Research; Resolution; Sampling; Specialist; Structure; Tendinopathy; Tendon structure; Time; Tissues; Translating; Upper Extremity; Work; achilles tendon; anaerobic glycolysis; clinical decision-making; detection sensitivity; effective therapy; experimental study; healing; human imaging; imaging biomarker; imaging study; improved; in vivo; in vivo evaluation; indexing; mechanical properties; metabolic abnormality assessment; novel; repaired; response; simulation; treatment strategy

PROJECT SUMMARY / ABSTRACT The objective of this proposal is to establish magnetic resonance imaging (MRI) for assessment of extracellular matrix (ECM) damage and cellular energy metabolism in human tendon. Tendinopathies are painful conditions effecting joints in upper and lower extremities, comprise 30% of referrals to musculoskeletal specialists, and remain challenging to treat. Tendinopathy is associated with accumulated damage to the ECM from chronic and repetitive overloading and exhibits complex and multifactorial pathogenesis altering both mechanical and cell biological function. The maintenance and repair (homeostasis) of tendon ECM is regulated by force- sensitive tendon cells that are coupled to local tissue loads through the ECM. Dysregulated ECM homeostasis can be related to extensive structural damage and diminished cellular response to environmental forces. Evaluation of tendinopathy in humans is limited by a lack of non-invasive approaches to assess both ECM (structure) and cellular response (function). Recent applications of ultrashort echo time (UTE) MRI have demonstrated exciting potential for providing quantitative indices of tendon properties that are sensitive to pathological changes. We have recently identified tendon ECM molecules and metabolites based on 1H NMR chemical shift assignments using high resolution magic angle spinning (HRMAS). We have also developed a novel in vivo UTE MRI approach in human tendon for accurate quantification of these chemical shift resonances showing correspondence with 1H NMR spectra, allowing for direct imaging quantification of matrix molecules and metabolites. Our team has recently developed a novel pipeline combining in vivo animal tendon-loading with ex vivo HRMAS NMR for directly studying load-induced metabolic activity in rat tendon. We are poised to combine detailed tissue explant, animal, and human experiments to establish new chemical shift-based measurements of ECM structure and functional imaging of load-induced tendon metabolism. In Aim 1, we will validate UTE MRI chemical shift markers of ECM damage and metabolism in tendinopathy using animal studies, human explant tissue, phantoms, and numerical simulations. In Aim 2, we will establish in- human UTE-derived chemical shift mapping of load-induced anaerobic metabolism in tendinopathy. This work will establish new MRI methods for in-human imaging studies to quantitatively investigate the interaction between ECM damage, in vivo loading, and tendon biological function, to be applied to subsequent studies of tendinopathy.

项目总结/摘要 本提案的目的是建立磁共振成像（MRI）评估细胞外 基质（ECM）损伤和细胞能量代谢的人肌腱。肌腱病是一种痛苦的疾病 影响上肢和下肢关节，占肌肉骨骼专家转诊的30%， 肌腱病与慢性炎症对ECM的累积损伤有关。 和重复性超负荷，并表现出复杂和多因素的发病机制， 细胞生物学功能肌腱ECM的维持和修复（稳态）受力的调节， 通过ECM与局部组织负荷偶联的敏感肌腱细胞。ECM稳态失调 可能与广泛的结构损伤和细胞对环境力的反应减弱有关。 由于缺乏非侵入性的方法来评估ECM， （结构）和细胞反应（功能）。超短回波时间（UTE）MRI的最新应用 证明了令人兴奋的潜力，提供定量指标的肌腱性能是敏感的， 病理变化我们最近根据1H NMR鉴定了肌腱ECM分子和代谢物 使用高分辨率魔角旋转（HRMAS）进行化学位移归属。我们还开发了一个 一种新的人体肌腱体内UTE MRI方法，用于准确定量这些化学位移 显示与1H NMR光谱对应的共振，允许基质的直接成像定量 分子和代谢物。我们的团队最近开发了一种新的管道， 用离体HRMAS NMR进行肌腱负载，用于直接研究大鼠肌腱中负载诱导的代谢活性。 我们准备将联合收割机结合详细的组织外植体、动物和人体实验， 基于移位的ECM结构测量和负荷诱导的肌腱代谢的功能成像。在Aim中 1，我们将验证UTE MRI化学位移标记物的ECM损伤和代谢的肌腱病变，使用 动物研究、人体外植体组织、模型和数值模拟。在目标2中，我们将建立- 肌腱病中负荷诱导无氧代谢人类UTE衍生化学位移图谱这项工作 将建立新的MRI方法用于人体成像研究，以定量研究相互作用 ECM损伤，体内负荷和肌腱生物学功能之间的关系，将应用于后续的研究， 肌腱病