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: 10025170
• 负责人: Jennifer Zellers
• 金额: $ 6.53万
• 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/10025170
• 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 效应对肌肉骨骼系统具有广泛的影响。糖尿病患者的风险增加 肌腱损伤以及肌腱限制关节活动度，这被认为是肌腱损伤的诱发因素 足底溃疡和下肢丧失的发展。尽管糖尿病相关的潜在严重后遗症 肌腱并发症，缺乏非侵入性工具来评估体内肌腱，特别是在较小水平上 肌腱结构。基于磁共振的扩散张量成像（DTI）有潜力 应用于肌腱以非侵入性评估肌腱微观结构。 DTI 利用水的方向和自由度 纤维束中的分子流动性来表征组织微观结构。肌腱传统上非常 很难用 DTI 成像，但是，新改进的 DTI 脉冲序列允许应用 此技术适用于肌腱组织。 该奖学金申请的长期目标是优化肌腱的损伤和代谢愈合 通过连接基础科学和临床研究方法来研究疾病。作为实现这一目标的一步，本提案 将 DTI 与人体肌腱组织的直接测试进行比较，并将 DTI 应用于临床个体群体 患有和不患有糖尿病的人，以提高我们对糖尿病相关的肌腱健康变化的了解。这 将使用离体和体内方法的组合来实现目标。目标 1 使用阿喀琉斯 从接受下肢截肢的个体采集的肌腱标本。 DTI指数比较 直接测量肌腱微观结构特性，以提高我们解释 DTI 指数的能力。这 使用 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 胶原蛋白排列、生化分析以量化高级糖基化终产物的积累，以及 拉伸机械测试。目标 2 利用 DTI 量化跟腱的体内微观结构特性 肌腱来识别与糖尿病相关的肌腱健康变化。 DTI 指数将在一组中进行比较 患有糖尿病的人与没有糖尿病的人相比。 拟议研究的结果将把肌腱评估的基础科学方法与 评估肌腱微观结构的新兴非侵入性成像方法以及改善我们的 了解糖尿病相关的肌腱微结构变化。这种创新方法将有助于 确定可作为未来临床肌腱损伤和疾病的成像生物标志物的参数， 介入研究。