Computational Tool to Assess Performance of the Aortic Trauma Stent-Grafts

 描述（由申请人提供）：创伤是44岁以下人群的头号死因，33%的创伤性死亡归因于胸腔内的主动脉损伤。使用覆膜支架对创伤主动脉进行血管内重建已发展为创伤患者的一线治疗，但这些覆膜支架设计用于患有慢性退行性动脉疾病的老年患者，对于年轻患者较小且成角较多的胸主动脉不太理想。此外，患者活动增加和更年轻的心血管系统所施加的高循环负荷可能会使覆膜支架材料失效，导致终生发病率、死亡率和昂贵的再介入。该项目的目标是创建一种计算工具，可以确定创伤患者主动脉的最佳覆膜支架特性以及植入覆膜支架的长期机械性能。该工具将能够测量覆膜支架植入年轻胸主动脉时的顺应性和覆膜支架的长期耐久性（由其承受高循环疲劳载荷的能力确定）。我们建议通过三个具体目标来实现这一目标：在目标1中，我们将确定不同年轻创伤人群（<20岁、20-29岁、30-45岁）中胸主动脉的形态测量特征，这些特征对于使用来自薄层CTA扫描的全面3D动脉重建进行覆膜支架展开至关重要。在目标2中，我们将使用从每个年龄组的组织供体获得的胸主动脉壁的双轴力学特性，以及目前批准用于创伤的两种覆膜支架（戈尔C-Tag和Medtronic Valiant）的实验确定的力学特性，构建在年轻创伤患者的动脉中展开的覆膜支架的计算机模拟模型。然后，我们将使用数学建模使覆膜支架承受典型的循环生理载荷，并评估产生的应力-应变场。在目标3中，我们将确定在承受模拟体内载荷时覆膜支架与主动脉内壁的贴合性，以及通过使用应力分析和Goodman图评估的器械承受高循环疲劳载荷的能力确定的长期耐久性。将采集每个创伤人群的这些数据，以确定器械的特定特征，这些特征可能会增强每个创伤组血管内治疗的急性和长期结局。该拟定研究将为针对年轻患者人群的现有和尚未开发的血管内器械的计算机模拟比较有效性研究奠定基础，并将为创伤导向血管内器械的分析设定新标准，促进更好覆膜支架的开发。这项工作将促进申请人融入生物医学领域，并提高她独立研究事业的潜力，同时为她将来寻求独立资助开辟一个很好的利基市场。

 DESCRIPTION (provided by applicant): Trauma is the number one cause of death among people younger than 44 years of age, and 33% of all traumatic deaths are attributed to aortic injuries within the thorax. Endovascular reconstruction of traumatized aorta using stent-grafts has evolved as a first line therapy for trauma patients, but these stent-grafts were designed for elderly patients with chronic degenerative arterial diseases and are less than ideal for the smaller and more angulated thoracic aortas of young patients. In addition, the increased patient activity and high cyclic loads imposed by more dynamic younger cardiovascular systems may push stent-graft materials to failure resulting in higher morbidity, mortality and expensive reinterventions over the course of a lifetime. The goal of this project is to create a computationa tool that can determine the optimal stent-graft characteristics for the aorta of trauma patients and the mechanical behavior of the implanted stent-grafts over the long-term. This tool will be able to measure the conformability of the stent-graft when implanted in the young thoracic aorta and the long-term durability of the stent-graft as determined by its capability to withstand high-cycle fatigue loads. We propose to accomplish this by three Specific Aims: In Aim 1 we will determine the morphometric features of the thoracic aorta in different young trauma populations (<20, 20-29, 30-45 years old) that are critical for stent-graft deployment using comprehensive 3D arterial reconstructions derived from thin-section CTA scans. In Aim 2 we will build in silico models of stent-grafts deployed in the aortas of young trauma patients using biaxial mechanical properties of thoracic aortic wall obtained from tissue donors of each age group, and experimentally determined mechanical properties of two stent-grafts (GORE C-Tag and Medtronic Valiant) that are currently approved for trauma. We will then use mathematical modeling to subject the stent-grafts to typical cyclic physiologic loads and assess the resulting stress-strain fields. In Aim 3 we will determine stent-graft conformability to the inner aortic wal when subjected to simulated in vivo loads, and long-term durability as determined by the capability of the device to withstand high-cycle fatigue loads assessed by using stress analysis and Goodman diagrams. These data will be acquired for each trauma population to identify specific characteristics of the devices that may enhance the acute and long-term outcomes of endovascular treatments in each trauma group. The proposed study will lay the foundation for in silico comparative effectiveness studies for existing and yet-to-be developed endovascular devices for young patient populations and will set new standards for analysis of trauma-oriented endovascular devices, facilitating the development of better stent-grafts. This work will promote integration of the applicant into the biomedical field and enhance her potential for independent research career while carving out an excellent niche for her to pursue independent funding in the future.