Improved Discretization Methods for Modeling Wavefront Conduction in Nonuniform Cardiac Tissue

不均匀心脏组织中波前传导建模的改进离散化方法

• 批准号: 9974533
• 负责人: Craig Henriquez
• 金额: $ 31.36万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9974533&HistoricalAwards=false
• 关键词: Improved; Discretization; Methods; Modeling; Wavefront

Investigations into the relative roles of tissue structure and membraneExcitability recovery on creating conditions for arrhythmias in the heart have proven tobe extremely challenging. Computer models of wavefront propagation have beenimportant to the inquiry by allowing effects to be isolated and by providing access tosome of the parameters that cannot be monitored or controlled in a given experimentalsetup. Due to limitations in the traditionally employed numerical methods, however,these computer models have either ignored or greatly simplified the effects of structuraland geometrical non-uniformities on the activation process. Consequently, mostmechanisms for arrhythmogenesis derived from them are generally based on theeffects of non-uniformities of membrane properties in tissue with assumed uniformmaterial properties. For macroscopic models of the heart to have greater predictiveability they must be able to incorporate the effects of diseased-induced tissue structureinhomogeneities on conduction and potential timecourses. The objectives of this proposal are to develop improved discretization schemes for robustly modelingconduction in regions with spatially varying material and membrane properties. Theseobjectives will be accomplished by creating a unified meltherhatical and computationalframework for simulation that will allow different numerical methods to be directlycompared. The simulation system, BIDOSIM, will use a module-based paradigm fromwhich a single "sun-time environment" can be created. This approach will allow any advances made in any one component to lead directly to an advancement of the wholeprogram. This modularity will thus enable developers from different disciplines to focuson their own area of expertise (i.e model description, numerical integration methods,parallelization) without needing to simultaneously work on the other areas. BIDOSIMwill be used to evaluate the use of structured and unstructured finite volume methods,that involve quadrilateral and triangular grids, to discretize the computational domainsof interest. The speed, accuracy and ability of both types of methods will be examinedusing explicit and implicit time stepping algorithms. To ensure that the spatialdiscretization methods are able to accommodate any advances in the dynamical models of the ion fluxes across the membrane state-of-the-art kinetic models, such as the Lucfludy II ventricular and Nygren atrial models, will be evaluated over a range of physiological conditions. Finally, strategies for using spatially adaptive gridding in regions with abrupt changes in tissue properties, such as those expected in diseased myocardium, will be developed. Such adaptation will allow significantly fewer grid points and enable the ability to distinguish better artifact from true behavior. The development of the overall software package will be enhanced through feedback from an outside group of users and dissemination will be facilitated through partnerships with two national centers, NCSA and the Center for Bioelectric Field Simulation.

对组织结构和膜兴奋性恢复在造成心脏心律失常条件方面的相关作用的研究已被证明是极其具有挑战性的。波前传播的计算机模型对研究很重要，因为它允许隔离影响，并提供对在给定实验设置中无法监测或控制的某些参数的访问。然而，由于传统数值方法的局限性，这些计算机模型忽略或大大简化了结构和几何不均匀对激活过程的影响。因此，从它们衍生的大多数心律失常的机制通常是基于假定材料性质均匀的组织中膜性质的不均匀的影响。为了使心脏的宏观模型具有更大的可预测性，它们必须能够包含疾病诱导的组织结构同质性对传导和潜在时间过程的影响。这项提议的目标是开发改进的离散化方案，用于稳健地模拟具有空间变化的材料和膜特性的区域中的传导。这些目标将通过为模拟建立统一的综合和计算框架来实现，该框架将允许不同的数值方法进行直接比较。模拟系统BIDOSIM将使用基于模块的范例，从该范例可以创建单一的“太阳时间环境”。这种方法将允许在任何一个组件中取得的任何进步直接导致整个计划的进步。因此，这种模块化将使来自不同学科的开发人员能够专注于他们自己的专业领域(即模型描述、数值积分方法、并行化)，而不需要同时在其他领域工作。BIDOSIM将用于评估结构化和非结构化有限体积方法的使用，这些方法涉及四边形和三角形网格，以离散感兴趣的计算领域。将使用显式和隐式时间推进算法来检验这两种方法的速度、精度和能力。为了确保空间离散化方法能够适应跨膜离子通量动力学模型的任何进展，将在一系列生理条件下评估最先进的动力学模型，例如Lucfludy II心室和Nygren心房模型。最后，将开发在组织特性突然变化的区域中使用空间自适应网格的策略，例如在患病心肌中预期的变化。这样的适应将允许显著减少网格点，并能够区分更好的伪影和真实行为。整个软件包的开发将通过外部用户群体的反馈得到加强，并将通过与NCSA和生物电场模拟中心这两个国家中心的伙伴关系促进传播。