Computational Modeling of Platelet Aggregation and Coagulation and Development of Software for Biofluid Dynamics Problems

研究者对血小板聚集和凝血进行建模和计算模拟。它们是正常凝血和与血管疾病和使用心血管假体相关的危及生命的血凝块的组成部分。研究者及其同事继续探索和完善他们的血小板在小直径和大直径血管中的聚集模型；继续发展混凝模型，包括流动、输运和表面反应的影响；整合血小板聚集和凝血模型，形成更全面的止血和血栓形成过程模型。这些模型使用非线性偏微分方程和常微分方程的耦合系统来描述血液流体动力学之间的相互作用，血小板和血浆中化学物质的运输，形成聚集体的力学和化学，以及凝固过程的溶液相和表面结合的生物化学。这些模型提出了大量的计算挑战，需要开发和使用最先进的数值方法来解决问题。这些方法包括流体-材料相互作用的浸入边界方法，与傅里叶搭配谱方法相结合的高分辨率有限差分方法，处理复杂几何区域传输的浸入界面方法，以及并行计算。这项工作涉及计算结果和实验室实验之间的广泛比较，并借助于与流动和血栓形成方面的领先专家的合作。该提案还涉及开发最先进的并行计算方法来模拟生物流体动力学流动，如涉及聚集和凝固的流动，并将这些计算工具包括在一个功能强大且易于使用的问题解决环境中，以促进解决各种复杂的生物流体动力学问题。血栓形成是在循环系统血管内形成的血块，是大多数心脏病发作和其他严重心血管疾病（如缺血和心绞痛）的近端原因。这也是与使用接触血液的假体（如机械心脏瓣膜）相关的一个主要问题。这些血凝块形成的过程非常复杂，涉及许多动态的、有时相互竞争、有时相互加强的生物物理和生化过程。该项目的一个主要部分包括开发强大的数学和计算工具来研究这一复杂的过程，并使用这些工具来探测影响血栓形成位置、程度和速度的因素。计算建模补充了传统的实验方法，并提供了一种模拟复杂动态事件的方法，如流体、血细胞、凝血因子、血管或假体表面之间的动态相互作用，导致血栓形成，这是目前实验室技术无法达到的。这样的模拟可以为控制这一重要生物过程的基本机制提供新的见解，并最终有助于更合理地设计治疗干预和假体装置。许多其他具有挑战性的生物和生物医学流动问题具有模拟血栓形成的共同特征，因此为该项目开发的最先进的并行计算方法可能会广泛应用于基础科学，医疗保健和生物技术等重要问题。为了帮助实现这一潜力，研究人员开发并传播了一个易于使用的软件包，该软件包有助于使用这些计算方法来建立和执行重要的生物流体动力学问题的模拟。

Fogelson9805518 The investigator undertakes modeling and computationalsimulation of platelet aggregation and coagulation. These arethe components of normal blood clotting and of thelife-threatening blood clots associated with vascular disease andwith the use of cardiovascular prostheses. The investigator andcoworkers continue to explore and refine their models of plateletaggregation in small and large diameter vessels; continuedevelopment of models of coagulation including the effects offlow, transport, and surface reactions; and integrate theplatelet aggregation and coagulation models to form a morecomprehensive model of the hemostatic and thrombotic processes.These models use coupled systems of nonlinear partial andordinary differential equations to describe interactions betweenthe blood's fluid dynamics, the transport of platelets andchemicals in the blood plasma, the mechanics and chemistry ofdeveloping aggregates, and the solution-phase and surface-boundbiochemistry of the coagulation process. The models presentsubstantial computational challenges that require development anduse of state-of-the-art numerical methods for their solution.These include immersed boundary methods for fluid-materialinteractions, high-resolution finite-difference methods combinedwith Fourier-collocation spectral methods, immersed-interfacemethods for handling transport in regions of complex geometry,and parallel computation. This work involves extensivecomparisons between computational results and laboratoryexperiments and is aided by collaboration with leading experts onflow and thrombosis. The proposal is also concerned withdeveloping state-of-the-art parallel computational methods forsimulating biofluid dynamic flows like those involved inaggregation and coagulation, and with including thesecomputational tools in a powerful and easy-to-use problem solvingenvironment that facilitates solving a wide range of complexbiofluid dynamic problems. Thrombosis, which is the formation of blood clots withinvessels of the circulatory system, is the proximal cause of mostheart attacks and of other severe cardiovascular problems such asischemia and angina. It is also a major problem associated withthe use of blood-contacting prostheses such as mechanical heartvalves. The process by which these blood clots form is verycomplex and involves many dynamic, sometimes competing, sometimesmutually-reinforcing, biophysical and biochemical processes. Amajor part of this project involves developing powerfulmathematical and computational tools for studying this complexprocess, and using these tools to probe the factors that effectthe location, extent, and speed of formation of thrombi.Computational modeling complements traditional experimentalapproaches and provides a way to simulate complex dynamic events,like the dynamic interactions among fluid, blood cells, clottingfactors, and blood vessel or prosthesis surface that lead tothrombosis, that are beyond the reach of current laboratorytechniques. Such simulations can give new insights into thebasic mechanisms that control this important biological process,and can ultimately help in the more rational design oftherapeutic interventions and prosthetic devices. Many otherchallenging biological and biomedical flow problems have featuresin common with that of simulating thrombosis, and so thestate-of-the-art parallel computational methods developed forthis project potentially have wide-spread application to problemsimportant to basic science, health care, and biotechnology. Tohelp realize this potential the investigators develop anddisseminate an easy-to-use software package that facilitatesusing these computational methods to set up and carry outsimulations of important biofluid dynamics problems.