血流动力学作用下血栓形成的数学模型与计算仿真研究

Pathological thrombosis induced myocardial infarction (MI) and stroke are the leading causes of death for human being; thrombosis is also the main reason for malfunction of many blood-wetted medical devices, such as blood pump and stent. Clinical practice, pharmacy and medical devices development have urgent requirements on quantitative prediction of thrombosis, which makes mathematical and computational modelling of thrombosis become a trend. Based on the frame of continuum mechanics, current project aims to develop a mathematical and numerical model of thrombosis which is highly coupled with hemodynamics. The new model will improve three important mechanisms of thrombosis which haven’t been considered or are not well modeled by existing models, i.e. the von Willebrand factor (vWF) mediated platelet adhesion and aggregation, shear accumulation and shear activation of platelet and platelet migration. Applying the model, current project plans to investigate the mechanism of thrombosis in atherosclerotic vessels and its relation with MI, thrombosis and thrombus distribution in the blood pump of a ventricular assistant device, and the mechanisms of platelet accumulation and thrombosis near the joint of medical devices portions and in some aneurysms. Current project has important significance for enriching the study of thrombosis under flowing blood. The thrombosis model developed in current project can be an economic and time-saving tool for predicting thrombosis in various problems and is expected to be widely applied in studying pathogenesis of cardiovascular diseases and developing medical devices.

病理性血栓形成导致的心肌梗塞与中风是人类最主要致死原因之一；血栓也是血液浸润医疗仪器，如心脏泵、心脏支架，失效的重要原因。临床实践、药物与医疗仪器优化设计等对定量预测血栓形成提出了迫切需求，使以数学与计算仿真研究血栓成为了一种趋势。本项目拟以连续力学为框架，发展与血流动力学高度耦合的血栓形成数学与数值模型，完善现有血栓模型在描述血管性血友病因子（vWF）调节下血小板粘附与聚合、血小板应力积累与剪切激活以及血小板迁移三个重要机理环节存在的不足。利用数值模型，项目拟探索血管病理性狭窄处血栓易发机理及其与心肌梗塞的关联，心室辅助装置心脏泵内血栓形成机理与空间分布，医疗仪器部件接口处与血管瘤内血小板富集及血栓易发机理。本项目对于丰富流动血液内血栓形成机理研究有重要意义；本项目成果可为预测血栓形成提供廉价省时的研究方法与工具，在相关心脑血管疾病致病机理研究、医疗仪器优化设计等领域具有广泛应用前景。

人工器官使用过程中引起的凝血功能异常是限制其被更广泛应用的一大难题：每年20-30%的病人经历凝血异常导致的非手术内出血，15-27%发生栓塞中风，6-14%发生装置血栓，而几乎所有人工肺失效都是由血栓形成导致的。由于动物、临床试验昂贵费时，数值仿真在仪器开发中被广泛采用；但人工心脏与人工肺内部，特别是血液泵（心脏泵），流场复杂且血栓形成伴随多机制链式生化反应，一直以来流体科学家只能依赖流场分析设计泵结构，而未有模型可预测泵内血栓形成。通过理论推导、数值计算程序开发与计算仿真，构建了连续力学框架下可适用于高低剪切流动及多相流条件下的多尺度血栓形成数学模型，基于OpenFOAM的计算流体力学工具库，构建了适用于研究任意几何形状的新型血栓模型数值求解器。利用血栓模型数值求解器，仿真研究了带狭窄段直通道内血栓形成过程并与实验观察进行比较，探讨了狭窄血管内及血管瘤内血栓形成规律及其与心肌梗塞、中风的关联；研究了血小板壁面富集效应，以及其对于血栓形成的强化作用；研究了带微缝隙心脏泵内血栓形成过程，证明了由机械轴承的使用而引入的微缝隙可增加血栓风险；数值仿真研究了磁悬浮无机械轴承心脏泵血栓形成过程，证明了vWF作用下，转子凸起小叶片周围，任然易发生血栓，且以白血栓为主，表明vWF调节机制发挥了重要作用。项目不仅研究揭示了多个典型血栓形成过程的重要机理，而且所构建的血栓仿真软件可进一步与优化软件结合，建立具有工程（商业）价值的人工器官抗血栓优化设计平台。