Diabetes-related Tendon Changes: Integrating Ex Vivo and In Vivo Approaches

糖尿病相关的肌腱变化：体外和体内方法的结合

• 批准号: 9908852
• 负责人: Jennifer Zellers
• 金额: $ 6.12万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2021-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908852
• 关键词: Advanced Glycosylation End Products; Amputation; Anisotropy; Ankle; Architecture; Asses; Basic Science; Biochemical; Biological Markers; Characteristics; Clinical; Clinical Research; Collagen; Collagen Fiber; Development; Diabetes Mellitus; Diagnostic Imaging; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Epidemic; Event; Fascicle; Fellowship; Fiber; Foot Deformities; Foot Ulcer; Freedom; Functional disorder; Funding; Future; Goals; Health; Human; Image; Imaging Device; Impairment; Individual; Injury; Institution; Intervention; Intervention Studies; Joints; Lead; Length; Link; Lower Extremity; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Mentorship; Metabolic Diseases; Methods; Musculoskeletal; Musculoskeletal System; Orthopedics; Outcome; Pain; Physiologic pulse; Plantar Ulcers; Population; Property; Radial; Research Personnel; Risk; Severities; Specimen; Structure; Techniques; Tendinopathy; Tendon Injuries; Tendon structure; Testing; Time; Tissues; Training; United States; Water; achilles tendon; base; career; density; early detection biomarkers; ex vivo imaging; foot; glycemic control; healing; imaging biomarker; imaging modality; improved; in vivo; indexing; innovation; insight; joint mobilization; limb amputation; non-invasive imaging; polarized light; soft tissue; success; tool

PROJECT SUMMARY. Diabetes has been identified as an epidemic in the United States and its deleterious effects have broad implications for the musculoskeletal system. Individuals with diabetes are at increased risk of tendon injury as well as tendon-limited joint mobility, which has been suggested to be an inciting factor in the development of plantar ulcers and lower limb loss. Despite the potentially severe sequelae of diabetes-related tendon complications, there is a lack of non-invasive tools to assess tendon in vivo particularly at smaller levels of tendon architecture. Magnetic resonance-based diffusion tensor imaging (DTI) has the potential of being applied to tendon to non-invasively assess tendon microstructure. DTI uses the direction and freedom of water molecule mobility in fiber tracts to characterize tissue microstructure. Tendon has traditionally been very difficult to image with DTI, however, a newly-improved DTI pulse sequence has allowed for the application of this technique to tendon tissue. The long-term goal of this fellowship application is to optimize tendon healing from injury and metabolic disease by bridging basic science and clinical research approaches. As a step toward that goal, this proposal compares DTI to direct testing of human tendon tissue and applies DTI to a clinical population of individuals with and without diabetes to improve our understanding of diabetes-related changes to tendon health. This objective will be accomplished using a combination of ex vivo and in vivo approaches. Aim 1 uses Achilles tendon specimens collected from individuals undergoing lower extremity amputation. DTI indices are compared to direct measurement of tendon microstructural properties to improve our ability to interpret DTI indices. The tendon is imaged ex vivo with DTI and then analyzed using quantitative polarized light imaging to measure collagen alignment, biochemical analysis to quantify accumulation of advanced glycation endproducts, and tensile mechanical testing. Aim 2 leverages DTI to quantify in vivo microstructural properties of the Achilles tendon to identify diabetes-related changes to tendon health. DTI indices will be compared in a group of individuals with compared to individuals without diabetes. The outcome of the proposed study will bridge basic science approaches of tendon assessment with emerging non-invasive imaging methods of assessing tendon microstructure as well as improve our understanding of diabetes-related alterations in tendon microstructure. This innovative approach will help identify parameters that could serve as imaging biomarkers of tendon injury and disease for future clinical, interventional studies.

项目摘要。糖尿病已被确定为美国的流行病及其有害的 影响对肌肉骨骼系统具有广泛的影响。患有糖尿病的人的风险增加 肌腱损伤以及肌腱受限的关节迁移率，这被认为是刺激因素 足底溃疡和下肢损失的发展。尽管可能存在与糖尿病有关的后遗症 肌腱并发症，缺乏非侵入性工具来在体内评估肌腱，尤其是在较小的水平上 肌腱建筑。基于磁共振的扩散张量成像（DTI）具有存在的潜力 应用于肌腱无创地评估肌腱微观结构。 DTI使用水的方向和自由 纤维区域中的分子迁移率以表征组织微观结构。传统上，肌腱非常 然而，很难与DTI进行映像，新改良的DTI脉冲序列已允许应用 这项技术用于肌腱组织。 该奖学金应用的长期目标是优化受伤和代谢的肌腱愈合 通过弥合基础科学和临床研究方法来疾病。作为朝着这个目标的一步，这一建议 将DTI与直接测试人肌腱组织进行比较，并将DTI应用于个体的临床人群 有和没有糖尿病，以提高我们对肌腱健康与糖尿病相关的变化的理解。这 将使用离体和体内方法的组合来实现目标。 AIM 1使用阿喀琉斯 从接受下肢截肢的个体收集的肌腱标本。比较DTI指数 直接测量肌腱微结构特性，以提高我们解释DTI指数的能力。这 用DTI对肌腱进行离体成像，然后使用定量偏振光成像进行分析以测量 胶原蛋白比对，生化分析以量化晚期糖基化最终产物的积累和 拉伸机械测试。 AIM 2利用DTI量化阿喀琉斯的体内微结构特性 肌腱可以鉴定肌腱健康的与糖尿病有关的变化。 DTI指数将在一组中进行比较 与没有糖尿病的人相比。 拟议研究的结果将与 新兴的评估肌腱微结构的非侵入性成像方法以及改善我们的 了解肌腱微结构中与糖尿病相关的改变。这种创新的方法将有助于 确定可以用作肌腱损伤和疾病的生物标志物的参数 介入研究。