Improved Discretization Methods for Modeling Wavefront Conduction in Nonuniform Cardiac Tissue

研究组织结构和膜兴奋性恢复在心脏心律失常中的相对作用已被证明是极具挑战性的。 波前传播的计算机模型对研究很重要，因为它允许分离效应，并提供了一些在给定的实验装置中无法监测或控制的参数。然而，由于传统数值方法的局限性，这些计算机模型要么忽略了，要么大大简化了结构和几何非均匀性对活化过程的影响。因此，大多数由它们衍生的膜发生机制通常是基于假设均匀材料特性的组织中膜特性的不均匀性的影响。对于心脏的宏观模型有更大的预测能力，他们必须能够纳入疾病引起的组织结构的影响，对传导和潜在的时间过程。 这个建议的目标是开发改进的离散化方案，在空间变化的材料和膜性能的区域中鲁棒modelingconduction。这些目标将通过创建一个统一的melltherhatical和computationalframework模拟，将允许不同的数值方法进行直接比较。模拟系统BIDOSIM将使用一个基于模块的范例，由此可以创建一个单一的“太阳-时间环境”。 这种方法将允许任何一个组成部分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自己的专业领域（即模型描述，数值积分方法，并行化），而无需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法的使用，包括四边形和三角形网格，以离散感兴趣的计算域。这两种方法的速度，精度和能力将使用显式和隐式时间步进算法进行检查。 为了确保spatialdiscretization方法能够适应跨膜离子通量动态模型的任何进步，将在一系列生理条件下评估最先进的动力学模型，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那些。 这样的适应将允许显著更少的网格点，并且使得能够更好地区分伪像与真实行为。 将通过外部用户群体的反馈加强整个软件包的开发，并通过与国家能力自评中心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。

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.