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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要微创经导管栓塞是介入放射学中常见的非手术手术用于故意闭塞血管以治疗患病或受伤的脉管系统之一。临床实践中最常用的栓塞剂是微球，它们具有不同的特性。各种尺寸 (50 - 1200 µm) 的材料（即 PVA 和三丙烯酸明胶），可进行策略性选择治疗从动静脉畸形到富血管肿瘤的各种疾病，精确颗粒尺寸对于局部靶向栓塞至关重要，因为微球的输送是由血流驱动的，并且它们在体内的运动和积累取决于尺寸。市售微球的局限性包括：尽管有被冲走的危险，X射线上没有固有的射线不透性，并且缺乏治疗方法。形态相似的微球栓塞剂，其物理机械性能因它们的化学成分和制造工艺存在差异，进而影响微球和尚未开发出系统性平台来研究组织相互作用和临床结果。更重要的是，战士们没有评估这些特性和栓塞结果的技术。栓塞的轨迹，因此栓塞治疗中存在很大的不确定性。输送到不需要的血管会导致脱靶栓塞并对健康组织造成损害。即使对于经验丰富的医生来说，预测颗粒流行为和颗粒血管分布也很困难因为这本质上是一个流体驱动的运输问题，尚未得到系统的研究和在本提案中，我们将首次开发一种双向交互式生物材料计算。该平台将 1) 提供多功能微球的合理设计，2) 准确引导经导管微球部署的位置，3) 预测微球体内轨迹及其在体内的聚集脉管系统以最大限度地提高个性化治疗的栓塞成功率在目标 1 中，我们将开发微球。在目标 2 中，我们将通过计算来开发具有可控尺寸和可调节特性的有效栓塞。流体动力学 (CFD) 模型与生物材料设计相结合，可最大限度地将栓子输送至所需位置最后，在目标 3 中，我们将展示使用体外脉管系统和自适应的预测能力。使用患者特定物理模型的框架成功完成这项研究表明该框架具有多功能性。生物材料计算平台可以在随机注射下最大限度地输送栓塞微球管腔横截面内的栓子（当前实践）或在知情注射下完成交付这项试点研究将为大型动物研究中的进一步引导体内测试奠定基础。我们预计这种创新技术可以应用到临床相关模型（猪肝模型）。液体栓塞剂，并广泛传播到治疗多种血管疾病，例如如增生、肝肿瘤和前列腺肌瘤，转化为患者特异性治疗。