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：
10540708
负责人：
Juan R Cebral
金额：
$ 62.51万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-15 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10540708
关键词：
3-Dimensional Acceleration Achievement Acute Address Adverse event Aftercare Aneurysm Animal Model Arteries Biological Blood Vessels Blood specimen Brain Aneurysms Circle of Willis Clinical Clinical Research Complex Complication Computer Models Data Deposition Device Designs Device Safety Device or Instrument Development Devices Distal Endothelium Engineering Evaluation Event Fibrin Fibrinogen Funding Future Generations Growth Hemorrhage Image Interdisciplinary Study Internal carotid artery structure Intracranial Aneurysm Ischemia Knowledge Legal patent Liquid substance Modeling Monitor Morphology Neck Oryctolagus cuniculus Outcome Parents Patient Care Patients Perforation Physiologic pulse Platelet Activation Proteins Reproducibility Research Personnel Research Proposals Risk Risk Factors Role Ruptured Aneurysm Safety Side Statistical Methods Stroke Superior Mesenteric Artery Branch Superior mesenteric artery structure System Technology Testing Thrombin Thrombosis Tissue Engineering Translational Research Work biomarker discovery cell motility circulating microRNA clinical application clinical implementation clinical translation density follow-up healing hemodynamics implantation improved improved outcome in silico in vitro Model in vivo individual patient innovation microRNA biomarkers molecular imaging multidisciplinary multimodality next generation novel patient variability platelet function point of care prevent repository response stent thrombosis therapeutic target thrombotic complications tool translational research program

项目摘要

PROJECT SUMMARY This competitive renewal application focuses on advancing the field of intracranial flow diversion (FDs), that currently constitutes approximately one-third of the treatment of unruptured intracranial aneurysms. There remain key gaps in the knowledge that hinder expansion of the clinical application of these transformational devices, which to date are limited in scope to unruptured, proximal aneurysms along the internal carotid artery. We envision that, with our proposed discovery system, we will facilitate application of novel, next-generation devices in ruptured aneurysms and in aneurysms distal to the Circle of Willis, and will allow customization of approaches to minimize thromboembolic risk in individual patients. We will break down these barriers to expanded utility by 1) understanding of key aspects of aneurysm occlusion, such as the role of acute and appropriate fibrin deposition across the aneurysm neck, 2) unraveling the mechanisms underlying side branch occlusion (i.e. the impact of hemodynamic, or neointimal growth and endothelizalization across the side branch ostia, or both), and 3) identifying the potential risk factors that cause elevated risk of thromboembolic complications, such as hemodynamical variable, device malapposition, platelet function, and untoward fibrin deposition beyond the neck of the aneurysm, among others. We propose to employ innovative approaches in in vivo intravascular fibrin molecular imaging, computational fluid dynamics modeling, and improved animal modeling, and finally biomarker discovery in clinical studies. These approaches can improve the outcome of not only FD, but other devices in treating aneurysms by better understanding of the mechanisms of both aneurysm healing and complications. Our robust and reproducible methods of statistical evaluations will directly assess 1) the role of fibrin deposition rapidity in the device at the neck of the aneurysm aids robust aneurysm, 2) the suitability and validity of the superior mesenteric artery branches to simulate the patency of the small perforating vessels covered by FDs, and 3) correlate biological and imaging data with delayed ischemic events following FD therapy.The discoveries from this hypothesis-driven, multidisciplinary, multimodality, clinical-translational research will provide a robust understanding of not only the mechanism of action of FDs in aneurysm healing, but also the development of device-related complications. These discoveries can provide guidance to clinicians using current technologies to optimize outcomes and minimize complications, as well as investigators and engineers to develop improved devices. Ultimately, this information will allow neurointerventionalists to make better informed decisions on device choice, leading to improved patient care.

项目摘要这种竞争性更新应用的重点是推进颅内流动转移（FDS）的领域，该领域是目前，构成了未破裂的颅内动脉瘤的三分之一。那里在妨碍这些转化的临床应用扩展的知识中，仍然是关键差距迄今为止，其范围限制的装置沿颈内动脉近端动脉瘤限制。我们设想，借助我们提出的发现系统，我们将促进新颖的下一代应用在威利斯圆圈远端的动脉瘤和动脉瘤中破裂的设备，将允许自定义减少个别患者血栓栓塞风险的方法。我们将把这些障碍分解为通过1）了解动脉瘤阻塞的关键方面，例如急性和在整个动脉瘤颈上的适当纤维蛋白沉积，2）揭开侧面分支的机制闭塞（即血液动力学或新内膜生长和内皮化的影响 OSTIA，或两者兼而有之3）识别导致血栓栓塞风险升高的潜在风险因素并发症，例如血液动力学变量，设备不正确，血小板功能和不愉快的纤维蛋白在动脉瘤等脖子之外的沉积。我们建议采用创新的方法体内血管内纤维蛋白分子成像，计算流体动力学建模和改善的动物建模，最后是临床研究中的生物标志物发现。这些方法可以改善不仅FD，而且通过更好地理解两者的机制来治疗动脉瘤的其他设备动脉瘤愈合和并发症。我们的统计评估的强大而可重复的方法将直接评估1）纤维蛋白沉积快速速度在动脉瘤颈部的设备中的作用有帮助动脉瘤，2）上肠系膜分支的适用性和有效性，以模拟 FD覆盖的小型穿孔容器，以及3）将生物学和成像数据与延迟相关联 FD治疗后的缺血事件。从这个假设驱动的多学科的发现，多模式性，临床翻译研究将不仅提供对机制的强烈理解 FD在动脉瘤愈合中的作用，也是与设备相关并发症的发展。这些发现可以使用当前技术为临床医生提供指导，以优化结果并最小化并发症以及研究人员和工程师开发改进的设备。最终，这些信息将允许神经介入主义者对设备选择做出更好的明智决定，从而改善病人护理。