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 微创经导管栓塞是介入放射学中常见的非手术治疗方法 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。他们有不同的 材料（即，PVA和三丙烯酰明胶），可根据需要选择各种尺寸（50 - 1200 µm） 用于治疗从动静脉畸形到多血管肿瘤的各种疾病， 尺寸对于局部靶向栓塞是至关重要的 它们在体内的移动和积累依赖于尺寸。市售微球的局限性包括 有被冲走的危险，在X射线上没有内在的射线不透性，以及缺乏治疗方法。尽管 相似形态的微球栓塞剂，它们的物理和机械性能由于 它们的化学成分和制造工艺的差异，这反过来又影响微球和 组织相互作用和临床结果。尚未开发系统平台来研究相关性 这些特性和栓塞结果之间的关系。更重要的是，临床医生没有技术来估计 栓塞的轨迹，因此在栓塞治疗中存在显著的不确定性。微球 输送到不需要的血管将导致偏离目标的栓塞和对健康组织的损伤。的精确 即使对于有经验的医生，预测颗粒流行为和颗粒-血管分布也是困难的 因为这本质上是一个流体驱动的传输问题，还没有被系统地研究， 验证.在这个提议中，我们将首次开发一种双向交互的生物材料-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，以及3）预测微球在体内的轨迹及其在微球中的聚集。 最大限度地提高栓塞成功率，实现个性化治疗。在目标1中，我们将开发微球 其具有可控的尺寸和可调的性质以用于有效的栓塞。在目标2中，我们将开发计算 流体动力学（CFD）模型与生物材料设计相结合，以最大限度地将栓子输送到所需位置 地点最后，在目标3中，我们将使用体外血管系统和自适应神经网络来证明预测能力。 使用患者特定物理模型的框架。这项研究的成功完成表明， 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 管腔横截面内的栓塞（当前实践）或在知情注射下完全输送， 追踪导管这项试点研究将为进一步指导大型动物研究中的体内试验奠定基础 使用临床相关模型（猪肝模型）。我们设想这项创新技术可以应用于 液体栓塞剂，并且还被广泛地散布到各种血管病症的治疗中， 如前列腺增生、肝肿瘤和纤维瘤，用于转化为患者特异性治疗。