Computational and Biological Approach to Flow Diversion

分流的计算和生物学方法

基本信息

批准号：
9175421
负责人：
Juan R Cebral
金额：
$ 50.91万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-20 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9175421
关键词：
Address Aftercare Algorithms Aneurysm Biological Biomedical Engineering Bioreactors Brain Aneurysms Characteristics Chronic Clinic Clinical Clinical Data Clinical Research Complication Computer Simulation Coupled Coupling Device or Instrument Development Devices Distal Engineering Etiology Europe Evaluation Event Funding Future Grant Healed Hemorrhage In Vitro Interdisciplinary Study Intracranial Aneurysm Ipsilateral Knowledge Liquid substance Measures Methodology Methods MicroRNAs Modeling Optical Coherence Tomography Oryctolagus cuniculus Outcome Patient Care Patients Pharmacotherapy Phase Physiologic pulse Process RNA marker Reporting Research Research Personnel Research Proposals Risk Role Ruptured Aneurysm Safety Sales Scientist Techniques Technology Testing Thrombus Translating Translational Research Vascular remodeling Work cell growth clinically relevant design efficacy evaluation healing hemodynamics implantation improved in vivo individual patient individualized medicine multidisciplinary multimodality pre-clinical pressure programs prospective research study response simulation tool treatment planning virtual

项目摘要

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.

项目摘要这种竞争性更新应用的重点是促进颅内流动的快速发展领域在不到5年的时间里，转移已经成长为颅内三分之一美国动脉瘤治疗。我们将解决与临床上的临床相关，持续的知识差距，包括1）是什么构成流动分化效率的主要作用机理，2）是什么是不寻常的，但是毁灭性的并发症，包括同侧，核内出血和赞助动脉瘤破裂和3）可以增强这些设备的哪些设计功能以优化结果？我们的转化，假设驱动的方法学从计算/体外工作（计算流体）遍历动力学和体外生物反应器研究）在兔模型中进行体内实验，最后是临床研究。我们的统计上强大的评估将直接解决1）墙壁的作用在动脉瘤愈合中的作用并发症的风险，2）流动分化的实施引起的下游血液动力学进化 VEV危险出现出血的风险，3）流动转移与其他因素的相对影响，包括血栓形成和内皮化，在愈合中。从这种竞争更新中发现的发现将直接适用于治疗目前批准的设备并管理患者患者的临床医生遵循流量转移处理以优化结果并最大程度地减少并发症以及工程师和科学家致力于开发理想化的未来设备，甚至具有特定患者的设备，个性化功能。