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

血小板聚集和凝血的计算模型以及生物流体动力学问题软件的开发

• 批准号: 9805518
• 负责人: Aaron Fogelson
• 金额: $ 31万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9805518&HistoricalAwards=false
• 关键词: Computational; Modeling; Platelet; Aggregation; Coagulation

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.

Fogelson9805518 研究者对血小板聚集和凝血进行建模和计算机模拟。 这些是正常血液凝固和与血管疾病和使用心血管假体相关的危及生命的血液凝块的组成部分。 研究者及其同事继续探索和完善他们的血小板聚集模型，包括流动、运输和表面反应的影响;这些模型采用非线性偏微分方程和常微分方程的耦合系统来描述凝血和止血过程，血液的流体动力学之间的相互作用，血小板和血浆中的化学物质的运输，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，需要发展和使用最先进的数值方法来解决。这些方法包括流体-材料相互作用的浸入边界方法，与傅立叶配置谱方法相结合的高分辨率有限差分方法，处理复杂几何区域中输运的浸入界面方法，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，并得到了与流动和血栓形成方面的领先专家的合作的帮助。 该提案还涉及开发最先进的并行计算方法，用于模拟生物流体动力学流动，如聚集和凝固，并将这些计算工具纳入一个功能强大且易于使用的问题解决环境中，以便于解决各种复杂的生物流体动力学问题。 血栓形成是指在循环系统受到侵袭的情况下形成的血凝块，是心肌梗死和其他严重心血管疾病（如缺血和心绞痛）的最接近的原因。 这也是一个与血液接触假体如机械心脏瓣膜的使用相关的主要问题。 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物化学过程。 该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测影响血栓形成的位置，范围和速度的因素。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，以及血管或假体表面导致血栓形成，这超出了当前实验室技术的范围。 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体装置。 许多其他具有挑战性的生物和生物医学流动问题与模拟血栓形成的问题具有共同的特征，因此为该项目开发的最先进的并行计算方法可能广泛应用于基础科学，医疗保健和生物技术的重要问题。 为了帮助实现这一潜力，研究人员开发和传播一个易于使用的软件包，便于使用这些计算方法来建立和进行重要的生物流体动力学问题的模拟.