Integrated experimental and computational approach for accurate patient-specific vascular embolization

用于准确的患者特异性血管栓塞的综合实验和计算方法

• 批准号: 10724852
• 负责人: Amirhossein Arzani
• 金额: $ 19.07万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724852
• 关键词: 3D Print; Accounting; Address; Aneurysm; Animal Model; Animals; Arterial Embolization; Arteriovenous malformation; Authorization documentation; Behavior; Biocompatible Materials; Biomedical Engineering; Blood; Blood Vessels; Blood flow; Calibration; Catheters; Charge; Chemicals; Clinical; Computational Technique; Decision Making; Degenerative polyarthritis; Development; Disease; Embolism; Ensure; Evaluation; Face; Family; Family suidae; Feedback; Fibroid Tumor; Foundations; Friction; Gastrointestinal Hemorrhage; Gelatin; Geometry; Hemorrhage; Hydrophobicity; Hypervascular; In Vitro; Injections; Intervention; Interventional radiology; Investigation; Ischemia; Life; Liquid substance; Liver; Liver neoplasms; Location; Maps; Marketing; Mechanics; Medical; Microspheres; Modeling; Morphology; Movement; North Carolina; Oils; Outcome; Particle Size; Patients; Penetration; Performance; Physicians; Physiological; Pilot Projects; Positioning Attribute; Procedures; Process; Production; Property; Prostatic hypertrophy; Randomized; Recurrence; Reporting; Resistance; Risk; Roentgen Rays; Safety; Shapes; Stroke; Surface; Techniques; Technology; Testing; Therapeutic; Therapeutic Embolization; Time; Tissues; Translations; Transportation; Uncertainty; Universities; Utah; Vascular Diseases; Visualization; Work; authority; behavior prediction; blood vessel occlusion; calginat; clinical practice; clinically relevant; computational platform; design; experience; fabrication; improved; in vivo; in vivo evaluation; individual patient; individualized medicine; injured; innovation; innovative technologies; insight; malformation; manufacturing process; mechanical properties; meter; microsphere delivery; minimally invasive; next generation; particle; personalized medicine; physical model; physical property; rational design; simulation; success; treatment planning; tumor

PROJECT SUMMARY Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. One of the most commonly used embolic agents for clinical practice are microspheres. They come with different materials (i.e., PVA and trisacryl gelatin) in a variety of sizes (50 - 1200 µm), which can be strategically selected to treat various conditions ranging from arteriovenous malformations to hypervascular tumors, Accurate particle size is crucial for localized targeted embolization since the delivery of microspheres is driven by blood flow and their movement and accumulation in vivo is size-dependent. Limitations of marketed microspheres include danger of being washed away, no intrinsic radiopacity for visualization on X-ray, and lack of therapeutics. Despite the similar morphologies microspherical embolic agents, their physical and mechanical properties vary due to differences in their chemical composition and manufacturing processes, which in turn influence microsphere and tissue interactions and clinical outcomes. No systemic platform has been developed to investigate the correlation between these properties and embolic outcomes. More importantly, clinicians have no technology for estimating the trajectory of emboli and as such significant uncertainty exists in embolization treatment. Microsphere transportation to undesired vessels will cause off-target embolization and damage to healthy tissue. The precise prediction of particle-flow behavior and the particle-vessel distribution is difficult even for experienced physicians because this is essentially a fluid-driven transport problem that has not been systemically investigated and validated. In this proposal, we will develop, for the first time, a two-way interactive biomaterial-computational platform that will 1) offer rational design of multifunctional microspheres, 2) accurately guide the transcatheter location for microsphere deployment, and 3) predict microsphere in vivo trajectory and their aggregation in the vasculature to maximize embolic success for personalized therapies. In Aim 1, we will develop microspheres with controllable sizes and tunable properties for effective embolization. In Aim 2, we will develop computational fluid dynamics (CFD) models integrated with biomaterial design to maximize emboli transport to desired locations. Lastly in Aim 3, we will demonstrate predictive capability using in-vitro vasculature and adaptive framework using patient specific physical models. Successful completion of this study shows that the versatile biomaterial-computational platform can maximize the delivery of embolic microspheres under random injection of emboli within the luminal cross-section (current practice) or complete delivery under informed injection with tracking the catheter. This pilot study will set the stage for further guided in vivo testing in large animal studies using clinically relevant models (porcine liver models). We envision that this innovative technology can be applied to liquid embolic agents, and also be widely disseminated to the treatment of diverse vascular conditions, such as prostate hyperplasia, liver tumor, and fibroids, for translation to patient-specific therapy.

项目摘要 最小侵入性经导管栓塞是介入放射学中常见的非外科手术 用于故意阻塞血管，用于治疗患病或受伤的脉管系统。之一 最常用的用于临床实践的栓塞药是微球。他们有不同的 材料（即PVA和Trisacryl明胶）的各种尺寸（50-1200 µm），可以策略性地选择它们 为了治疗从动脉畸形到高血管肿瘤的各种疾病，精确的颗粒 大小对于局部靶向栓塞至关重要，因为微球的递送是由血流和 它们在体内的运动和积累依赖大小。市场微球的局限性包括 被冲走的危险，没有固有的放射性X射线可视化和缺乏治疗。尽管 相似的形态微球栓塞剂，其物理和机械性能因 它们的化学组成和制造过程的差异，进而影响微球和 组织相互作用和临床结果。尚未开发系统的平台来调查相关性 在这些属性和栓塞结果之间。更重要的是，临床医生没有估计的技术 栓子治疗中存在栓子和如此明显的不确定性的轨迹。微球 运输到不希望的血管将导致靶向栓塞和对健康组织的损害。精度 即使对于经验丰富的医生来说，也很难预测粒子流行为和粒子血管分布 因为这本质上是一个流体驱动的运输问题，尚未被系统调查，并且 经过验证。在此提案中，我们将首次发展一个双向互动生物材料计算 平台将提供1）提供多功能微球的合理设计，2）准确指导经导管 微球部署的位置，以及3）预测体内轨迹的微球及其在 脉管系统可为个性化疗法最大化栓塞成功。在AIM 1中，我们将开发微球 具有可控尺寸和可调特性，可有效栓塞。在AIM 2中，我们将开发计算 流体动力学（CFD）模型与生物材料设计集成，以最大化栓子传输到所需 位置。最后，在AIM 3中，我们将使用体外脉管系统和自适应表现出预测能力 使用患者特定物理模型的框架。这项研究的成功完成表明多功能 生物材料计算平台可以在随机注射下最大化栓塞微球的递送 在腔横截面（当前练习）或在知情注射下完成的栓塞中的栓子 跟踪导管。这项试点研究将为大型动物研究中的进一步指导体内测试奠定基础 使用临床相关模型（猪肝模型）。我们设想可以应用这种创新技术 液体栓塞剂，也被广泛传播到潜水的血管条件的治疗中， 作为前列腺增生，肝肿瘤和纤维，以转化为患者特异性治疗。