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.

项目总结/摘要 蛛网膜下腔出血（SAH）是一种严重的急性神经系统疾病， 过早死亡蛛网膜下腔出血大多数是由颅内动脉瘤（伊卡）意外破裂引起的。死亡 在发病的第一周内，动脉瘤破裂率可高达40%。即使动脉瘤 如果及时治疗，中度至重度脑损伤的几率为20- 35%。血管内弹簧圈 栓塞是目前ICA的金标准，微创治疗;然而， 弹簧圈栓塞的挑战是动脉瘤复发率不令人满意：初次栓塞后5-6年约为44%。 弹簧圈治疗（其中超过50%需要再次治疗）和次优完全闭塞，特别是对于 治疗具有复杂3D几何形状的宽颈ICA和/或动脉瘤。因此，需要一种持久的 治疗未破裂ICA的器械，针对患者特定动脉瘤和颅内循环， 提供持久的完全闭塞。本计画之研究目标为：1）设计与制作 用于使用增材制造和组合制造治疗囊状分叉IAC的个性化栓塞装置 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 我们的器械和其他选定的血管内栓塞技术之间的差异。该提案建立在 收集初步数据，并利用李博士在组织生物力学和计算机模拟方面的经验， 建模，与聚合物科学和增材制造研究人员在大学的合作， 俄克拉荷马州，印第安纳州大学医学院临床医生的临床和神经外科专业知识，以及微型器械 也是普渡大学的导管专家具体而言，我们建议设计，开发和评估患者特异性SMP 使用基于3D打印的聚合物制造的栓塞装置。我们的栓塞装置专门针对 个性化的动脉瘤填充和最大限度地提高长期完全闭塞率。接下来，通过体外 流动回路试验台和体内小动物研究，我们的个性化的疗效和动脉瘤闭塞 栓塞器械将与临床金标准以及其他三种 现代栓塞方法。该项目的终点将是伊卡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基本信息 - 允许个体优化的动脉瘤填充，以实现即刻和长期完全闭塞，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目标的合乎逻辑的第一步， 长期目标是通过促进个性化，预防性和治疗性的转化医学， 管理未破裂的ICA并减少动脉瘤破裂引起的出血性卒中。

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