Computational and Biological Approach to Flow Diversion

项目摘要 这种竞争性的更新应用程序的重点是推进颅内流量的快速发展领域 分流，其中，在不到5年的时间跨度，已增长到包括高达三分之一的颅内 动脉瘤治疗在美国我们将解决临床相关的，持续的知识差距，包括1） Flow Diverter有效性的主要作用机制是什么，2）异常的基础是什么，但 毁灭性并发症，包括同侧、脑实质内出血和自发性动脉瘤 破裂，以及3）这些器械的哪些设计特征可以增强以优化结局？我们 翻译，假设驱动的方法从计算/体外工作（计算流体 动力学和体外生物反应器研究）到兔模型中的体内实验，最后到临床研究。 我们的统计学稳健评价将直接解决1）壁贴壁在动脉瘤愈合中的作用， 并发症风险，2）血流导向装置植入引起的下游血流动力学紊乱， 与自发性出血的风险，和3）分流与其他因素的相对影响， 包括血栓形成和内皮化。从这种竞争性的更新中发现， 将直接适用于使用当前获批器械治疗患者的临床医生和管理患者 在血流导向治疗后，以优化结局并最大限度地减少并发症，以及 工程师和科学家专注于开发理想化的未来设备，即使是那些具有患者特异性的设备， 个性化特征。

PROJECT SUMMARY This competitive renewal application focuses on advancing the rapidly-evolving field of intracranial flow diversion, which, over the span of less than 5 years, has grown to encompass up to one-third of intracranial aneurysm treatments in the US. We will address clinically-relevant, ongoing gaps in knowledge, including 1) what constitutes the primary mechanism of action of flow diverter efficacy, 2) what underlies the unusual, but devastating complications, including ipsilateral, intraparenchymal hemorrhage and spontaneous aneurysm rupture, and 3) what design features of these devices can be enhanced to optimize outcomes? Our translational, hypothesis-driven methodology traverses from computational/in vitro work (computational fluid dynamics and in vitro bioreactor studies) to in vivo experiments in a rabbit model and, finally, to clinical studies. Our statistically robust evaluations will directly address 1) the role of wall apposition in aneurysm healing and risk for complication, 2) downstream hemodynamic derangements caused by flow diverter implantation vis-à- vis risk for spontaneous hemorrhage, and 3) the relative impact of diversion of flow versus other factors, including thrombus formation and endothelialization, in healing. The discoveries from this competitive renewal will be directly applicable to clinicians treating patients with currently-approved devices and managing patients following flow diversion treatment in order to optimize outcomes and minimize complications, as well as to engineers and scientists focused on developing idealized, future devices, even those with patient-specific, individualized features.