Computational and Biological Approach to Flow Diversion

分流的计算和生物学方法

• 批准号: 9284516
• 负责人: Juan R Cebral
• 金额: $ 47.1万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 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/9284516
• 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; Hemorrhage; In Vitro; Interdisciplinary Study; Intracranial Aneurysm; Investigation; 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; Vascular remodeling; Work; cell growth; clinically relevant; design; efficacy evaluation; experimental study; healing; hemodynamics; implantation; improved; in vivo; individual patient; individualized medicine; multidisciplinary; multimodality; outcome prediction; pre-clinical; pressure; programs; prospective; response; simulation; tool; translational research program; treatment planning; virtual

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.

项目概要 这一具有竞争力的更新应用程序专注于推动快速发展的颅内血流领域 转移，在不到 5 年的时间里，已发展到涵盖颅内转移的三分之一 美国的动脉瘤治疗。我们将解决临床相关的、持续存在的知识差距，包括 1) 分流器功效的主要作用机制是什么，2) 不寻常的现象背后是什么，但是 毁灭性的并发症，包括同侧实质内出血和自发性动脉瘤 破裂，以及 3）可以增强这些设备的哪些设计功能以优化结果？我们的 翻译性的、假设驱动的方法论贯穿于计算/体外工作（计算流体 动力学和体外生物反应器研究）到兔子模型的体内实验，最后是临床研究。 我们统计上稳健的评估将直接解决 1) 壁并置在动脉瘤愈合中的作用和 并发症的风险，2) 因植入分流器而引起的下游血流动力学紊乱 自发性出血的风险，以及 3) 血流改道与其他因素的相对影响， 包括愈合过程中的血栓形成和内皮化。这次竞争性更新的发现 将直接适用于临床医生使用当前批准的设备治疗患者和管理患者 进行血流改道治疗后，以优化结果并最大限度地减少并发症，并 工程师和科学家专注于开发理想化的未来设备，甚至是那些针对特定患者、 个性化特征。