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

改善颅内动脉瘤血管内治疗的效果：结合增材制造、计算机建模和形状记忆聚合物

• 批准号: 10685325
• 负责人: Chung-Hao Lee
• 金额: $ 66.03万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-23 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685325
• 关键词: 3-Dimensional; 3D Print; Accounting; Acute; Affect; American; Aneurysm; Animals; Arteries; Biomechanics; Brain; Brain Aneurysms; Brain Injuries; Brain hemorrhage; Calibration; Catheters; Cause of Death; Circulation; Classification; Clinical; Clinical Treatment; Collaborations; Complex; Data; Development; Devices; Dilatation - action; Effectiveness; Elastases; Elements; Evaluation Studies; Expenditure; Gel; Geometry; Goals; Hospitals; Implant; In Vitro; Incidence; Indiana; Individual; Intracranial Aneurysm; Left; Liquid substance; Mechanics; Medicine; Memory; Methods; Modeling; Morphology; Neck; New Zealand; Oklahoma; Oryctolagus cuniculus; Patients; Performance; Polymers; Porosity; Premature Mortality; Preventive; Printing; Process; Property; Protocols documentation; Recovery; Recurrence; Reporting; Research; Research Personnel; Residual state; Retreatment; Rupture; Ruptured Aneurysm; Sampling; Science; Shapes; Stroke; Structure; Subarachnoid Hemorrhage; System; Techniques; Testing; Therapeutic Embolization; Tissues; Treatment outcome; United States; Universities; Urethane; compare effectiveness; design; disability; experience; experimental study; fabrication; hemodynamics; improved; improved outcome; in silico; in vivo; iterative design; manufacture; manufacturing process; mechanical properties; microdevice; minimally invasive; mortality; nervous system disorder; neurosurgery; novel; prevent; prophylactic; thrombogenesis; translational medicine

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.

项目摘要/摘要 亚蛛网膜下腔出血（SAH）是一种破坏性的急性神经系统疾病，仍然是 过早死亡。 SAH最多是由颅内动脉瘤（ICA）的偶然破裂引起的。死亡率 在事件发生的第一周内，动脉瘤破裂的速率可达到40％。即使动脉瘤是 及时治疗中度至重度脑损伤的机会为20-35％。血管内线圈 栓塞是ICA的当前金色标准，微创疗法。但是，新兴的临床 线圈栓塞的挑战是不令人满意的动脉瘤复发率：〜44％到最初的5 - 6年 线圈疗法（其中超过50％需要重新治疗）和次优完全闭塞，尤其是针对 用复杂的3D几何形状处理宽领的ICA和/或动脉瘤。那需要耐用的 处理针对患者特异性动脉瘤和内神经瘤循环和 提供持久的完整闭塞。我们对该项目的研究目标是：1）设计和制造 个性化的栓塞设备，用于使用增材制造和合并 实验/生物力学方法，以及2）提供整体生物力学和血液动力学比较 在我们的设备和其他选定的血管内栓塞技术之间。该建议建立在 组装的初步数据，并利用Lee博士在组织生物力学和silico的经验 与聚合物科学和添加剂制造研究人员合作建模 俄克拉荷马州，印第安纳大学临床医生的临床和神经外科专业知识 - 医学和微设备 和普渡大学的成型专家。具体而言，我们建议设计，开发和评估患者特定的SMP 使用基于3D打印的聚合物制造的栓塞设备。我们的栓塞设备被指定为目标 个性化动脉瘤填充并最大化持久的完全闭塞速度。接下来，通过视野 流环测试床和体内小动物研究，我们个性化的效率和动脉瘤阻塞 与临床黄金标准以及其他三个 当代栓塞方法。该项目的终点将是用于ICA栓塞的尖端解决方案， 它使用基于整体生物力学和血液动力学分析的动脉瘤的基本信息 - 允许个人优化的动脉瘤填充以实现立即和长期的完全闭塞并减少 动脉瘤复发。总的来说，我们的发展将成为实现我们长期的逻辑第一步 通过支持个性化的预防性来推动转化医学中最新艺术的术语目标 对未破裂的ICA的管理并减少了动脉瘤破裂引起的出血性中风。

项目成果

An investigation of how specimen dimensions affect biaxial mechanical characterizations with CellScale BioTester and constitutive modeling of porcine tricuspid valve leaflets

使用 CellScale BioTester 和猪三尖瓣小叶的本构模型研究样本尺寸如何影响双轴机械特性

• DOI: 10.1016/j.jbiomech.2023.111829
• 发表时间: 2023
• 期刊: Journal of Biomechanics
• 影响因子: 2.4
• 作者: Laurence, Devin W.;Wang, Shuodao;Xiao, Rui;Qian, Jin;Mir, Arshid;Burkhart, Harold M.;Holzapfel, Gerhard A.;Lee, Chung-Hao
• 通讯作者: Lee, Chung-Hao

MetaNO: How to Transfer Your Knowledge on Learning Hidden Physics.

MetaNO：如何转移您学习隐藏物理的知识。

• DOI: 10.1016/j.cma.2023.116280
• 发表时间: 2023
• 期刊: Computer methods in applied mechanics and engineering
• 影响因子: 7.2
• 作者: Zhang,Lu;You,Huaiqian;Gao,Tian;Yu,Mo;Lee,Chung-Hao;Yu,Yue
• 通讯作者: Yu,Yue

Linking the region-specific tissue microstructure to the biaxial mechanical properties of the porcine left anterior descending artery.

• DOI: 10.1016/j.actbio.2022.07.036
• 发表时间: 2022-09-15
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Pineda-Castillo, Sergio A.;Aparicio-Ruiz, Santiago;Burns, Madison M.;Laurence, Devin W.;Bradshaw, Elizabeth;Gu, Tingting;Holzapfel, Gerhard A.;Lee, Chung-Hao
• 通讯作者: Lee, Chung-Hao