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

项目摘要。糖尿病在美国已被确定为一种流行病， 影响对肌肉骨骼系统具有广泛的影响。糖尿病患者的风险增加 肌腱损伤以及肌腱受限的关节活动度，这被认为是一个煽动因素， 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，特别是在较小的水平 肌腱结构。基于磁共振的扩散张量成像（DTI）具有被 应用于肌腱以非侵入性地评估肌腱微观结构。DTI利用水的方向和自由 分子在纤维束中的流动性来表征组织的微观结构。传统上，肌腱 难以用DTI成像，然而，新改进的DTI脉冲序列允许应用 将这种技术应用于肌腱组织。 这项奖学金申请的长期目标是优化肌腱愈合的损伤和代谢 疾病的桥梁基础科学和临床研究方法。作为实现这一目标的一步， 将DTI与直接测试人体肌腱组织进行比较，并将DTI应用于临床人群 有和没有糖尿病，以提高我们对糖尿病相关的肌腱健康变化的理解。这 将使用离体和体内方法的组合来实现目的。Aim 1使用Achilles 从接受下肢截肢的个体中收集的肌腱标本。比较DTI指标 直接测量肌腱的微观结构特性，以提高我们解释DTI指数的能力。的 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，生化分析以量化晚期糖基化终产物的积累，以及 拉伸力学测试目的2利用DTI量化跟腱的体内微结构特性 肌腱，以确定糖尿病相关的肌腱健康变化。DTI指数将在一组比较， 与没有糖尿病的人相比。 拟议研究的结果将桥接肌腱评估的基础科学方法， 新兴的评估肌腱微观结构的非侵入性成像方法，以及提高我们的 了解糖尿病相关的肌腱微结构改变。这种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，用于未来的临床， 干预性研究。

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.