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

Fogelson 9805518研究人员负责对血小板聚集和凝血进行建模和计算模拟。这些都是正常凝血和威胁生命的血栓的组成部分，这些血栓与血管疾病和心血管假体的使用有关。研究人员和同事继续探索和完善他们在小直径和大直径血管中的血小板聚集模型；继续开发凝血模型，包括流动、运输和表面反应的影响；并将血小板聚集和凝血模型结合起来，形成更全面的止血和血栓过程模型。这些模型使用非线性偏微分方程组和常微分方程组来描述血液流体动力学、血浆中血小板和化学物质的传输、聚集体形成的力学和化学以及凝血过程的溶液相和表面界面生物化学之间的相互作用。这些模型提出了巨大的计算挑战，需要开发和使用最先进的数值方法来解决它们。这些方法包括用于流体-材料相互作用的浸没边界方法，结合傅立叶配置谱方法的高分辨率有限差分法，用于处理复杂几何区域的输运的浸没界面方法，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，并得到了与流动和血栓形成方面的领先专家的合作。该建议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，如那些涉及聚集和凝聚的流动，并将这些计算工具包括在一个强大且易于使用的问题解决环境中，以促进解决广泛的复杂生物流体动力学问题。血栓形成是血液凝块侵入循环系统而形成的，是心脏病发作和其他严重心血管问题(如缺血和心绞痛)的近端原因。这也是与使用机械心脏瓣膜等接触血液的假体有关的一个主要问题。这些血块的形成过程非常复杂，涉及许多动态的、有时相互竞争、有时相互促进的生物物理和生化过程。这个项目的一个主要部分是开发强大的数学和计算工具来研究这个复杂的过程，并使用这些工具来探索影响血栓形成位置、范围和速度的因素。计算建模是对传统实验方法的补充，并提供了一种模拟复杂动态事件的方法，如导致血栓形成的流体、血细胞、凝血因子和血管或假体表面之间的动态相互作用，这是目前的实验室技术所无法达到的。这种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肢设备。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有可能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，研究人员开发和传播了一个易于使用的软件包，该软件包便于使用这些计算方法来建立和进行重要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.