Institute of Membrane and Systems Biology , University of Leeds , Leeds LS2 9JT , UK.
Interface Focus. 2011 Feb 6;1(1):101-16. doi: 10.1098/rsfs.2010.0005. Epub 2010 Dec 3.
Reaction-diffusion computational models of cardiac electrophysiology require both dynamic excitation models that reconstruct the action potentials of myocytes as well as datasets of cardiac geometry and architecture that provide the electrical diffusion tensor D, which determines how excitation spreads through the tissue. We illustrate an experimental pipeline we have developed in our laboratories for constructing and validating such datasets. The tensor D changes with location in the myocardium, and is determined by tissue architecture. Diffusion tensor magnetic resonance imaging (DT-MRI) provides three eigenvectors e(i) and eigenvalues λ(i) at each voxel throughout the tissue that can be used to reconstruct this architecture. The primary eigenvector e(1) is a histologically validated measure of myocyte orientation (responsible for anisotropic propagation). The secondary and tertiary eigenvectors (e(2) and e(3)) specify the directions of any orthotropic structure if λ(2) is significantly greater than λ(3)-this orthotropy has been identified with sheets or cleavage planes. For simulations, the components of D are scaled in the fibre and cross-fibre directions for anisotropic simulations (or fibre, sheet and sheet normal directions for orthotropic tissues) so that simulated conduction velocities match values from optical imaging or plunge electrode experiments. The simulated pattern of propagation of action potentials in the models is partially validated by optical recordings of spatio-temporal activity on the surfaces of hearts. We also describe several techniques that enhance components of the pipeline, or that allow the pipeline to be applied to different areas of research: Q ball imaging provides evidence for multi-modal orientation distributions within a fraction of voxels, infarcts can be identified by changes in the anisotropic structure-irregularity in myocyte orientation and a decrease in fractional anisotropy, clinical imaging provides human ventricular geometry and can identify ischaemic and infarcted regions, and simulations in human geometries examine the roles of anisotropic and orthotropic architecture in the initiation of arrhythmias.
心脏电生理学的反应-扩散计算模型既需要重建心肌细胞动作电位的动态激励模型，也需要提供心脏几何形状和结构的数据集，该数据集提供电扩散张量 D，它决定了兴奋如何在组织中传播。我们展示了我们在实验室中开发的用于构建和验证此类数据集的实验流程。张量 D 随心肌位置而变化，并且由组织结构决定。扩散张量磁共振成像 (DT-MRI) 在整个组织的每个体素中提供三个特征向量 e(i) 和特征值 λ(i)，可用于重建这种结构。主特征向量 e(1) 是心肌细胞方向的组织学验证度量 (负责各向异性传播)。如果 λ(2) 明显大于 λ(3)，则次特征向量和三特征向量 (e(2) 和 e(3)) 指定任何各向异性结构的方向-这种各向异性已被鉴定为薄片或劈裂面。对于模拟，在各向异性模拟中，D 的分量按纤维和交叉纤维方向缩放 (或者对于各向异性组织，按纤维、薄片和薄片法向方向缩放)，以便模拟传导速度与光学成像或浸入电极实验的值匹配。模型中动作电位传播的模拟模式通过心脏表面时空活动的光学记录部分验证。我们还描述了几种增强管道组件的技术，或者允许管道应用于不同的研究领域：Q 球成像在几个体素内提供了多模态方向分布的证据，通过各向异性结构的变化可以识别梗塞-心肌细胞方向的不规则性和各向异性分数的降低，临床成像提供了人类心室几何形状，并可以识别缺血和梗塞区域，以及在人类几何形状中的模拟研究检查了各向异性和各向异性结构在心律失常起始中的作用。
