Improving outcomes in endovascular treatment of intracranial aneurysms: Combining additive manufacturing, in-silico modeling, and shape memory polymers

项目摘要/摘要 蛛网膜下腔出血(SAH)是一种毁灭性的急性神经系统疾病，至今仍是 过早死亡。蛛网膜下腔出血多由颅内动脉瘤(ICA)偶发破裂引起。死亡 在发病的第一周内，动脉瘤破裂的比率可高达40%。即使动脉瘤是 如果及时治疗，出现中到重度脑损伤的几率为20%-35%。血管内线圈 栓塞术是目前ICAS的金标准微创治疗方法；然而，新兴的临床 弹簧圈栓塞术的挑战是不能令人满意的动脉瘤复发率：初次栓塞后5-6年复发率约为44% 弹簧圈治疗(其中50%以上需要重新治疗)，以及次优完全闭塞，特别是 治疗具有复杂3D几何结构的宽颈颈内动脉和/或动脉瘤。因此，需要一种持久的 治疗针对患者特定动脉瘤和动脉瘤内循环的未破裂ICA的设备和 提供持久的完全遮挡。本课题的研究目标是：1)设计和制造 使用添加剂制造和组合的个人化栓塞器治疗球状、分叉型IAC 实验/生物力学方法，以及2)提供整体生物力学和血流动力学比较 我们的设备和其他精选的血管内栓塞术之间存在着很大的差距。这项建议建立在 收集初步数据，并利用Lee博士在组织生物力学和硅技术方面的经验 建模，与宾夕法尼亚大学聚合物科学和添加剂制造研究人员合作 印第安纳大学临床医生的临床和神经外科专业知识-医学和微型设备 普渡大学的导管专家。具体地说，我们建议设计、开发和评估患者特定的SMP 栓塞器使用基于3D打印的聚合物制造。我们的栓塞器被指定为 个性化的动脉瘤填充，最大限度地提高长期完全闭塞率。接下来，通过体外培养 流动环试验台和体内小动物研究，我们的个性化的动脉瘤闭塞的疗效 将对照临床黄金标准以及其他三种标准对栓塞器进行系统评估 现代的栓塞法。该项目的终点将是ICA栓塞术的尖端解决方案， 它使用基于整体生物力学和血液动力学分析的关于动脉瘤的基本信息 -允许针对个体进行优化的动脉瘤填充，以实现即时和长期完全闭塞并减少 动脉瘤复发。总体而言，我们的发展将是实现我们长期- 学期目标是通过促进个性化、预防性的发展来促进转化医学的最新发展 处理未破裂的ICA，减少动脉瘤破裂导致的出血性卒中。

Project Summary/Abstract Subarachnoid hemorrhage (SAH) is a devasting acute neurological disease that remains a major cause of premature mortality. SAH is most caused by incidental rupture of an intracranial aneurysm (ICA). The mortality rate of aneurysm rupture can reach as high as 40% within the first week of incidence. Even if the aneurysm is treated in a timely manner, the chance of moderate to severe brain damage is 20-35%. Endovascular coil embolization is the current gold-standard, minimally invasive therapy of ICAs; however, emerging clinical challenges of coil embolization are unsatisfactory aneurysm recurrence rates: ~44% by 5-6 years after the initial coil therapy (of which more than 50% requiring re-treatment), and suboptimal complete occlusion, especially for treating wide-necked ICAs and/or aneurysms with a complex 3D geometry. Thus, there is a need for a durable device to treat unruptured ICAs that targets patient-specific aneurysms and intra-aneurysmal circulation and provides long-lasting complete occlusion. Our research objectives of this project are to: 1) design and fabricate personalized embolic devices for treating saccular, bifurcated IACs using additive manufacturing and a combined experimental/biomechanical approach, and 2) provide a holistic biomechanical and hemodynamic comparison between our device and other selected endovascular embolic techniques. This proposal builds upon the assembled preliminary data, and leverages Dr. Lee’s experience with tissue biomechanics and in-silico modeling, in collaboration with polymer science and additive manufacturing researchers at the University of Oklahoma, clinical and neurosurgical expertise of clinicians at Indiana University – Medicine, and micro-device and catheter expert at Purdue. Specifically, we propose to design, develop, and evaluate patient-specific SMP embolic devices using 3D printing-based polymer fabrication. Our embolic devices are designated to target personalized aneurysm filling and maximize the rate of long-lasting complete occlusion. Next, through in-vitro flow loop testbed and in-vivo small animal studies, the efficacy and aneurysm occlusion of our personalized embolic devices will be systematically evaluated in comparison to the clinical gold standard as well as three other contemporary embolic methods. The endpoint of this project will be a cutting-edge solution for ICA embolization, that uses fundamental information on aneurysms based on holistic biomechanical and hemodynamic analyses – allowing individual-optimized aneurysm filling to achieve immediate & long-term complete occlusion and reduce aneurysm recurrence. Collectively, our developments will serve as a logical first step toward attaining our long- term goal to advance the state of the art in translational medicine by facilitating personalized, preventive management of unruptured ICAs and reduce aneurysm rupture-induced hemorrhagic strokes.