Computational and Biological Approach to Flow Diversion

分流的计算和生物学方法

• 批准号: 8216809
• 负责人: Ramanathan Kadirvel
• 金额: $ 56.55万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8216809
• 关键词: Aftercare; Aneurysm; Animal Model; Anticoagulants; Arteries; Binding Proteins; Biocompatible Materials; Biological; Biological Process; Blood Vessels; Brain Aneurysms; Capsid Proteins; Case Series; Cell Proliferation; Chronic; Communities; Computer Simulation; Coupled; Coupling; Development; Devices; Dose; Endothelial Cells; Evaluation; Frequencies; Future; General Population; Goals; Healed; Histologic; Image; Implant; Individual; Interdisciplinary Study; Intracranial Aneurysm; Knowledge; Lead; Liquid substance; Marketing; Measurement; Metric; Microarray Analysis; Modeling; Modification; Molecular; Morphology; Neck; Oryctolagus cuniculus; Outcome; Parents; Patient Care; Patients; Perforating Artery; Pharmaceutical Preparations; Platinum; Population; Recurrence; Research; Research Personnel; Research Proposals; Retreatment; Risk; Role; Rupture; Ruptured Aneurysm; Safety; Series; Speed; Spontaneous Rupture; Stem cells; Stroke; Structure; System; Techniques; Therapeutic Embolization; Thrombosis; Thrombus; Time; Tissues; Translational Research; Work; brain surgery; cell motility; clinical application; clinically relevant; cost; density; healing; hemodynamics; implantation; improved; in vivo; minimally invasive; novel strategies; preclinical evaluation; primary outcome; programs; research study; response; tool; treatment planning; treatment response; virtual

DESCRIPTION (provided by applicant): The long term objective of this research program is to improve the care of patients harboring unruptured brain aneurysms. These aneurysms, present in approximately 2% of the population, may undergo spontaneous rupture with devastating consequences. Recent advances in minimally invasive treatments have allowed many patients to avoid open brain surgery. Unfortunately, these newer treatments often result in imperfect closure of the aneurysm, requiring additional treatments. A recently developed technique, called intraluminal flow diversion, has shown remarkable promise in treating even large or giant aneurysms, which are not well treated with any other technique. Notwithstanding promising results from small series of treated patients, many important questions about these new devices remain unanswered. First, practitioners have no concrete information on how to choose device size or number of devices in order to achieve aneurysm cure; addition of "unnecessary" devices increases risk to patients and thus knowledge about the "ideal" device for a given patient would be an important step forward. Second, the actual reasons behind why these flow diverters result in aneurysm cure remain unknown; advancing our knowledge of how they actually function would not only help individual patients but also speed development of improved devices. Third, a number of patients treated with these devices have suffered unexpected and usually fatal rupture of the aneurysm after treatment, which has convinced many practitioners either to avoid the use of flow diverters altogether or to use, at the same time, coil treatment in the aneurysm; adding the coil therapy increases both cost and risk, and thus understanding the reasons behind these rare but devastating ruptures would improve patient care. Finally, all patients treated with these devices require long term treatment with blood thinning medications; improvements in the device to avoid this need would decrease overall risk. The experiments outlined in this proposal include the latest advances in computer-based simulations of aneurysm flows, both before and after treatment, coupled with use of a widely-studied animal model. Study of these experimental systems will allow us to answer each of the important questions listed above, with the long term objective of safely and permanently curing brain aneurysms. PUBLIC HEALTH RELEVANCE: This research proposal will substantially improve the tools available for studying new treatments for brain aneurysms, allowing individualized treatment plans to be devised and carried out for individual patients.

描述(申请人提供)：这项研究计划的长期目标是改善对患有未破裂脑动脉瘤的患者的护理。这些动脉瘤出现在大约2%的人群中，可能会发生自发性破裂，造成毁灭性的后果。最近在微创治疗方面的进步使许多患者避免了开放的脑部手术。不幸的是，这些新的治疗方法往往导致动脉瘤不完全闭合，需要额外的治疗。最近开发的一种名为腔内分流的技术，在治疗大型或巨型动脉瘤方面显示出非凡的前景，而其他任何技术都无法很好地治疗这些动脉瘤。尽管小范围治疗的患者取得了令人振奋的结果，但关于这些新设备的许多重要问题仍然没有得到回答。首先，从业者没有关于如何选择设备大小或设备数量以实现动脉瘤治愈的具体信息；增加“不必要的”设备会增加患者的风险，因此了解特定患者的“理想”设备将是向前迈出的重要一步。其次，这些分流器导致动脉瘤治愈的真正原因尚不清楚；提高我们对它们实际功能的了解不仅有助于个别患者，还将加快改进设备的开发。第三，使用这些设备治疗的许多患者在治疗后遭遇了意想不到的、通常是致命的动脉瘤破裂，这说服了许多从业者要么完全避免使用流量分流器，要么同时在动脉瘤中使用弹簧圈治疗；增加弹簧圈治疗增加了成本和风险，因此了解这些罕见但毁灭性破裂背后的原因将改善患者的护理。最后，所有接受这些设备治疗的患者都需要使用血液稀释药物进行长期治疗；改进设备以避免这种需要将降低总体风险。这项建议中概述的实验包括在治疗前后基于计算机模拟动脉瘤流动的最新进展，以及广泛研究的动物模型的使用。对这些实验系统的研究将使我们能够回答上面列出的每一个重要问题，长期目标是安全和永久地治愈脑动脉瘤。 公共卫生相关性：这项研究提案将大大改进可用于研究脑动脉瘤新疗法的工具，允许为个别患者设计和实施个性化治疗计划。