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对未破裂脑动脉瘤患者的护理。这些动脉瘤约占人口的2%，可能会自发破裂，造成毁灭性的后果。微创治疗的最新进展使许多患者避免了开颅手术。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。最近开发的一种技术，称为腔内血流转移，在治疗大动脉瘤或巨型动脉瘤方面显示出显著的前景，而其他任何技术都无法很好地治疗这些动脉瘤。尽管在小范围的治疗患者中取得了令人鼓舞的结果，但关于这些新设备的许多重要问题仍未得到解答。首先，从业者没有关于如何选择设备尺寸或设备数量以实现动脉瘤治愈的具体信息；添加“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”设备将是重要的一步。其次，这些分流剂导致动脉瘤治愈的实际原因尚不清楚；提高我们对它们实际功能的了解不仅可以帮助个别患者，还可以加快改进设备的开发。第三，许多使用这些设备治疗的患者在治疗后出现了意想不到的、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分流器，要么同时在动脉瘤中使用线圈治疗；增加线圈疗法会增加成本和风险，因此了解这些罕见但破坏性破裂背后的原因将改善患者护理。最后，所有使用这些设备治疗的患者都需要长期使用血液稀释药物治疗；对设备进行改进以避免这种需要将降低总体风险。本提案中概述的实验包括基于计算机模拟治疗前后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个重要问题，并以安全和永久地治疗脑动脉瘤为长期目标。

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.