Computational and Biological Approach to Flow Diversion

分流的计算和生物学方法

• 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
• 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

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 这一竞争性更新应用专注于推进颅内血流分流(FDS)领域，即 目前约占未破裂颅内动脉瘤治疗的三分之一。那里 仍然是知识上的主要差距，阻碍了这些变革性药物临床应用的扩大 到目前为止，这种装置的范围仅限于沿颈内动脉的未破裂的近端动脉瘤。 我们设想，通过我们提出的发现系统，我们将促进新的下一代 在破裂的动脉瘤和Willis环远端的动脉瘤中使用设备，并将允许定制 降低个体患者血栓栓塞症风险的方法。我们将打破这些障碍， 通过1)了解动脉瘤闭塞的关键方面，如急性和慢性脑出血的作用，扩大了实用性。 合适的纤维蛋白沉积穿过动脉瘤颈部，2)解开侧支基础的机制 闭塞(即血流动力学的影响，或侧支血管内膜生长和内皮化的影响 Ostia，或两者兼而有之)，以及3)确定导致血栓栓塞症风险升高的潜在危险因素 并发症，如血流动力学变量、装置错位、血小板功能和不良纤维蛋白 动脉瘤颈部以外的沉积，以及其他。我们建议在以下方面采用创新方法 体内血管内纤维蛋白分子成像、计算流体动力学建模和改进的动物 建模，最后在临床研究中发现生物标记物。这些方法可以改善 不仅是FD，而且是通过更好地了解两者的机制来治疗动脉瘤的其他装置 动脉瘤愈合和并发症。我们稳健和可重复的统计评估方法将 直接评估1)在动脉瘤颈部的装置中纤维蛋白沉积速度的作用有助于强健 2)肠系膜上动脉分支模拟血管再通的适宜性和有效性 被FDs覆盖的小穿孔血管，以及3)生物和影像数据与延迟 FD治疗后的缺血事件。这一假设驱动的、多学科的、 多模式、临床-翻译研究将提供对以下方面的深入理解： FDs在动脉瘤愈合中的作用，也是装置相关并发症的发展。这些 这些发现可以为临床医生提供指导，使用当前的技术来优化结果并将 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 将允许神经干预者在设备选择方面做出更明智的决定，从而改善 病人护理。