权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

项目总结