Aneurysm Sac Growth as the Etiology of Recurrence in Coiled Cerebral Aneurysms

描述（由申请人提供）：脑动脉瘤是脑内动脉的囊状扩张。如果不及时治疗，有些可能会破裂，导致死亡或损害。血管内弹簧圈栓塞术是一种最近越来越流行的治疗方法。在这里，动脉瘤囊通过导管进入并填充弹簧圈，这应该会诱导动脉瘤内凝块的形成。弹簧圈凝块将阻止血液进入，从而保护动脉瘤免于破裂和出血。但在一些患者中，在手术后的几个月到几年内，血液会重新进入囊内，这是一种称为复发的并发症。10-30%接受弹簧圈治疗的患者可能会复发。复发的原因知之甚少。重要的是要了解导致复发的原因，因为这是应对这一挑战和减少其发生率的第一步。这也将显著影响动脉瘤患者的干预策略。该项目的总体目标是揭示复发的机制。传统的想法认为复发的发生是因为线圈质量压缩了自身（即，随着时间的推移，囊内的体积减小），为血液重新进入囊内腾出空间。尽管这似乎是合理的，但通过采用严格的三维图像分析技术对飞行员群体进行的初步研究表明并非如此。本研究的主要假设是复发的机制是动脉瘤囊本身的生长，而不一定是弹簧圈压实。本项目的具体目标#1是在25例弹簧圈栓塞动脉瘤复发患者的统计学把握度人群中检验该假设。将利用三维图像处理和计算分析工具对旋转血管造影扫描的动脉瘤囊和弹簧圈质量体积进行准确重建和估计，以评估复发受试者中是否存在囊生长。此外，确定是否有一些可衡量的 动脉瘤形态或治疗过程的度量可以作为复发的风险因素。申请人的小组已经开发了用于将患者特异性动脉瘤的三维形态严格量化为尺寸和形状度量的计算形态测量工具。具体目标#2是比较来自目标#1的复发倾向群体与对照群体（即，未显示复发的盘绕动脉瘤），其大小和位置匹配。目标是确定哪些（如果有的话）患者特异性可测量指标可以作为复发的预后指标。识别复发的风险因素可能有助于识别和避免这种安全有效的手术中容易发生这种主要并发症的患者。如果目标1中的结果与复发与囊生长相关的假设一致，则动脉瘤生长的患者不适合进行该手术。因此，拟议项目可能会对动脉瘤患者的临床管理产生重大影响。 公共卫生相关性：脑动脉瘤越来越多地通过放置栓塞弹簧圈来治疗，这将阻止血液进入动脉瘤。一种常见的并发症是血液重新进入动脉瘤，称为复发。该项目旨在了解复发的原因，并开发使用三维计算分析方法预测哪些患者可能倾向于复发的方法。

DESCRIPTION (provided by applicant): Cerebral aneurysms are sac-like expansions of arteries in the brain. If left untreated, some may rupture causing death or impairment. Endovascular coiling is a recent and increasingly popular method of treatment. Here the aneurysm sac is accessed by a catheter and filled with coils, which should induce formation of a clot inside the aneurysm. The coil-clot mass will disallow entry of blood and hence protect the aneurysm from rupture and bleeding. But in some patients, within months to years of the procedure, blood is noted to re-enter the sac, a complication called recurrence. Recurrence can occur in 10-30% of patients treated with coils. The causes of recurrence are poorly understood. It is important to understand what causes recurrence because that is the first step in addressing this challenge and reducing its incidence. It will also significantly impact intervention strategie for aneurysm patients. The overall goal of this project is to shed light on the mechanisms underlying recurrence. Conventional thinking holds that recurrence occurs because the coil mass compacts itself (i.e., reduces in size) inside the sac over time, making room for blood to re-enter it. Plausible as this may seem, preliminary studies performed by employing rigorous three-dimensional image analysis techniques with a pilot population suggest otherwise. The primary hypothesis of this study is that the mechanism for recurrence is the growth of the aneurysm sac itself, not necessarily coil compaction Specific aim #1 of the project is to test the hypothesis in a statistically powered population of 25 coil-embolized aneurysm patients presenting with recurrence. Three dimensional image processing and computational analysis tools will be leveraged for accurate reconstructions and estimations of the aneurysm sac and coil mass volumes from rotational angiography scans in order to assess whether sac growth exists in recurrence subjects. Further, it would be quite beneficial to identify if some measurable metrics of aneurysm morphology or treatment procedure ay serve as risk factors for recurrence. The applicants' group has developed computational morphometric tools for rigorously quantifying the three-dimensional morphology of patient- specific aneurysms into size and shape metrics. Specific aim #2 is to compare metrics of morphology and procedure between the recurrence-prone population from aim #1 with a control population (i.e., coiled aneurysms that do not show recurrence) that is size and location-matched. The goal is to ascertain which, if any, of the patient-specific measurable metrics may serve as prognostic indicators of recurrence. Identifying risk factors of recurrence may help identify and avoid patients prone to this major complication from this otherwise safe and effective procedure. If the results in aim #1 are consistent with proposed hypothesis that recurrence is associated with sac growth, patients with growing aneurysms are not suitable candidates for this procedure. The proposed project therefore can significantly impact clinical management of aneurysm patients. PUBLIC HEALTH RELEVANCE: Cerebral aneurysms are increasingly treated by placement of embolization coils that will block blood from entering them. One common complication is the re-entry of blood into the aneurysm, called recurrence. This project aims to understand the cause of recurrence and develop ways to predict which patients may be prone to it using three-dimensional computational analysis methods.