Computational and Biological Approach to Flow Diversion

描述（由申请人提供）：本研究项目的长期目标是改善未破裂脑动脉瘤患者的护理。这些动脉瘤，存在于约2%的人口，可能会发生自发性破裂的破坏性后果。微创治疗的最新进展使许多患者避免了开放性脑手术。不幸的是，这些较新的治疗方法往往导致动脉瘤闭合不完全，需要额外的治疗。最近开发的一种称为腔内血流导向的技术在治疗大型或巨型动脉瘤方面显示出了显著的前景，这些动脉瘤无法用任何其他技术进行良好治疗。尽管小系列治疗患者的结果令人鼓舞，但有关这些新器械的许多重要问题仍未得到解答。首先，医生没有关于如何选择器械尺寸或器械数量以实现动脉瘤治愈的具体信息;添加"不必要的"器械会增加患者的风险，因此了解特定患者的"理想"器械将是向前迈出的重要一步。其次，这些血流导向装置导致动脉瘤治愈的实际原因仍然未知;提高我们对它们实际功能的了解不仅可以帮助个体患者，还可以加快改进器械的开发。第三，用这些装置治疗的许多患者在治疗后遭受了意外的并且通常是致命的动脉瘤破裂，这使得许多从业者要么完全避免使用血流导向器，要么同时在动脉瘤中使用弹簧圈治疗;增加线圈治疗增加了成本和风险，因此，了解这些罕见但破坏性的破裂背后的原因将改善患者护理。最后，使用这些器械治疗的所有患者都需要使用血液稀释药物进行长期治疗;对器械进行改进以避免这种需求将降低总体风险。该提案中概述的实验包括治疗前后基于计算机的动脉瘤流动模拟的最新进展，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个重要问题，长期目标是安全和永久地治愈脑动脉瘤。

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.