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.

项目总结。糖尿病已被确认为美国的一种流行病，其危害 这些影响对肌肉骨骼系统有广泛的影响。糖尿病患者的风险增加 肌腱损伤以及肌腱受限的关节活动度，这被认为是 足底溃疡的发展和下肢的丧失。尽管与糖尿病相关的潜在严重后遗症 肌腱并发症，缺乏非侵入性的工具在体内评估肌腱，特别是在较小的水平 肌腱建筑的。基于磁共振的扩散张量成像(DTI)有可能成为 应用于肌腱微结构的非侵入性评估。DTI利用水的方向和自由 分子在纤维束中的迁移率来表征组织的微观结构。肌腱传统上一直非常 然而，很难用DTI成像，然而，新改进的DTI脉冲序列允许应用 这项技术将肌腱组织。 此奖学金申请的长期目标是优化肌腱从损伤和代谢中的愈合 在基础科学和临床研究方法之间架起一座桥梁。作为迈向这一目标的一步，这项提议 将DTI与直接检测人体肌腱组织进行比较，并将DTI应用于临床人群 提高我们对糖尿病相关肌腱健康变化的认识。这 这一目标将使用体外和体内相结合的方法来实现。AIM 1使用阿喀琉斯 从接受截肢手术的个体采集的肌腱标本。对DTI指标进行比较 直接测量肌腱的微观结构特性，以提高我们解释DTI指标的能力。这个 用DTI对肌腱进行体外成像，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，以量化晚期糖基化终末产物的积累，以及 拉伸机械试验。AIM 2利用DTI来量化体内跟腱的微结构特性 肌腱识别与糖尿病相关的变化对肌腱健康有影响。DTI指数将在一组 有糖尿病的人与没有糖尿病的人相比。 拟议的研究结果将把肌腱评估的基础科学方法与 新出现的无创性成像方法评估肌腱微结构以及改善我们的 了解糖尿病相关肌腱微结构的改变。这一创新的方法将有助于 确定可作为肌腱损伤和疾病的成像生物标志物的参数，以供未来临床使用 介入研究。