Anton J. Prassl

Generation of histo−anatomically representative models of the individual heart: tools and application

This paper presents methods to build histo-anatomically detailed individualized cardiac models. The models are based on high-resolution three-dimensional anatomical and/or diffusion tensor magnetic resonance images, combined with serial histological sectioning data, and are used to investigate individualized cardiac function. The current state of the art is reviewed, and its limitations are discussed. We assess the challenges associated with the generation of histo-anatomically representative individualized in silico models of the heart. The entire processing pipeline including image acquisition, image processing, mesh generation, model set-up and execution of computer simulations, and the underlying methods are described. The multifaceted challenges associated with these goals are highlighted, suitable solutions are proposed, and an important application of developed high-resolution structure–function models in elucidating the effect of individual structural heterogeneity upon wavefront dynamics is demonstrated.

Image-based models of cardiac structure in health and disease.

Computational approaches to investigating the electromechanics of healthy and diseased hearts are becoming essential for the comprehensive understanding of cardiac function. In this article, we first present a brief review of existing image‐based computational models of cardiac structure. We then provide a detailed explanation of a processing pipeline which we have recently developed for constructing realistic computational models of the heart from high resolution structural and diffusion tensor (DT) magnetic resonance (MR) images acquired ex vivo. The presentation of the pipeline incorporates a review of the methodologies that can be used to reconstruct models of cardiac structure. In this pipeline, the structural image is segmented to reconstruct the ventricles, normal myocardium, and infarct. A finite element mesh is generated from the segmented structural image, and fiber orientations are assigned to the elements based on DTMR data. The methods were applied to construct seven different models of healthy and diseased hearts. These models contain millions of elements, with spatial resolutions in the order of hundreds of microns, providing unprecedented detail in the representation of cardiac structure for simulation studies. Copyright

Automatically Generated, Anatomically Accurate Meshes for Cardiac Electrophysiology Problems

Significant advancements in imaging technology and the dramatic increase in computer power over the last few years broke the ground for the construction of anatomically realistic models of the heart at an unprecedented level of detail. To effectively make use of high-resolution imaging datasets for modeling purposes, the imaged objects have to be discretized. This procedure is trivial for structured grids. However, to develop generally applicable heart models, unstructured grids are much preferable. In this study, a novel image-based unstructured mesh generation technique is proposed. It uses the dual mesh of an octree applied directly to segmented 3-D image stacks. The method produces conformal, boundary-fitted, and hexahedra-dominant meshes. The algorithm operates fully automatically with no requirements for interactivity and generates accurate volume-preserving representations of arbitrarily complex geometries with smooth surfaces. The method is very well suited for cardiac electrophysiological simulations. In the myocardium, the algorithm minimizes variations in element size, whereas in the surrounding medium, the element size is grown larger with the distance to the myocardial surfaces to reduce the computational burden. The numerical feasibility of the approach is demonstrated by discretizing and solving the monodomain and bidomain equations on the generated grids for two preparations of high experimental relevance, a left ventricular wedge preparation, and a papillary muscle.

Image-based models of cardiac structure with applications in arrhythmia and defibrillation studies

The objective of this article is to present a set of methods for constructing realistic computational models of cardiac structure from high-resolution structural and diffusion tensor magnetic resonance images and to demonstrate the applicability of the models in simulation studies. The structural image is segmented to identify various regions such as normal myocardium, ventricles, and infarct. A finite element mesh is generated from the processed structural data, and fiber orientations are assigned to the elements. The Purkinje system, when visible, is modeled using linear elements that interconnect a set of manually identified points. The methods were applied to construct 2 different models; and 2 simulation studies, which demonstrate the applicability of the models in the analysis of arrhythmia and defibrillation, were performed. The models represent cardiac structure with unprecedented detail for simulation studies.

Influence of myocardial fiber/sheet orientations on left ventricular mechanical contraction:

At any point in space the material properties of the myocardium are characterized as orthotropic, that is, there are three mutually orthogonal axes along which both electrical and mechanical parameters differ. To investigate the role of spatial structural heterogeneity in an orthotropic material, electro-mechanically coupled models of the left ventricle (LV) were used. The implemented models differed in their arrangement of fibers and sheets in the myocardium, but were identical otherwise: (i) a generic homogeneous model, where a rule-based method was applied to assign fiber and sheet orientations, and (ii) a heterogeneous model, where the assignment of the orthotropic tissue structure was based on experimentally obtained fiber/sheet orientations. While both models resulted in pressure–volume loops and metrics of global mechanical function that were qualitatively and quantitatively similar and matched well with experimental data, the predicted deformations were strikingly different between these models, particularly with regard to torsion. Thus, the simulation results strongly suggest that heterogeneous structure properties play an important nonnegligible role in LV mechanics and, consequently, should be accounted for in computational models.

Modeling the dispersion in electromechanically coupled myocardium

We present an approach to model the dispersion of fiber and sheet orientations in the myocardium. By utilizing structure parameters, an existing orthotropic and invariant-based constitutive model developed to describe the passive behavior of the myocardium is augmented. Two dispersion parameters are fitted to experimentally observed angular dispersion data of the myocardial tissue. Computations are performed on a unit myocardium tissue cube and on a slice of the left ventricle indicating that the dispersion parameter has an effect on the myocardial deformation and stress development. The use of fiber dispersions relating to a pathological myocardium had a rather big effect. The final example represents an ellipsoidal model of the left ventricle indicating the influence of fiber and sheet dispersions upon contraction over a cardiac cycle. Although only a minor shift in the pressure-volume (PV) loops between the cases with no dispersions and with fiber and sheet dispersions for a healthy myocardium was observed, a remarkably different behavior is obtained with a fiber dispersion relating to a diseased myocardium. In future simulations, this dispersion model for myocardial tissue may advantageously be used together with models of, for example, growth and remodeling of various cardiac diseases.

Image-Based Personalization of Cardiac Anatomy for Coupled Electromechanical Modeling.

Computational models of cardiac electromechanics (EM) are increasingly being applied to clinical problems, with patient-specific models being generated from high fidelity imaging and used to simulate patient physiology, pathophysiology and response to treatment. Current structured meshes are limited in their ability to fully represent the detailed anatomical data available from clinical images and capture complex and varied anatomy with limited geometric accuracy. In this paper, we review the state of the art in image-based personalization of cardiac anatomy for biophysically detailed, strongly coupled EM modeling, and present our own tools for the automatic building of anatomically and structurally accurate patient-specific models. Our method relies on using high resolution unstructured meshes for discretizing both physics, electrophysiology and mechanics, in combination with efficient, strongly scalable solvers necessary to deal with the computational load imposed by the large number of degrees of freedom of these meshes. These tools permit automated anatomical model generation and strongly coupled EM simulations at an unprecedented level of anatomical and biophysical detail.

Electroanatomical Characterization of Atrial Microfibrosis in a Histologically Detailed Computer Model

Fibrosis is thought to play an important role in the formation and maintenance of atrial fibrillation (AF). The propensity of fibrosis to increase AF vulnerability depends not only on its amount, its texture plays a crucial role as well. While the detection of fibrotic tissue patches in the atria with extracellular recordings is feasible based on the analysis of electrogram fractionation, as used in clinical practice to identify ablation targets, the classification of fibrotic texture is a more challenging problem. This study seeks to establish a method for the electroanatomical characterization of the fibrotic textures based on the analysis of electrogram fractionation. The proposed method exploits the dependence of fractionation patterns on the incidence direction of wavefronts which differs significantly as a function of texture. A histologically detailed computer model of the right atrial isthmus was developed for testing the method. A stimulation protocol was conceived which generated various incidence directions for any given recording site where electrograms were computed. A classification method is derived then for discriminating three types of fibrosis, no fibrosis (control), diffuse, and patchy fibrosis. Simulation results showed that electrogram fractionation and amplitudes and their dependence upon incidence direction allow a robust discrimination between different classes of fibrosis. Finally, to minimize the technical effort, sensitivity analysis was performed to identify a minimum number of incidence directions required for robust classification.

A Macro Finite-Element Formulation for Cardiac Electrophysiology Simulations Using Hybrid Unstructured Grids

Abstract-Electrical activity in cardiac tissue can be described by the bidomain equations whose solution for large-scale simulations still remains a computational challenge. Therefore, improvements in the discrete formulation of the problem, which decrease computational and/or memory demands are highly desirable. In this study, we propose a novel technique for computing shape functions of finite elements (FEs). The technique generates macro FEs (MFEs) based on the local decomposition of elements into tetrahedral subelements with linear shape functions. Such an approach necessitates the direct use of hybrid meshes (HMs) composed of different types of elements. MFEs are compared to classic standard FEs with respect to accuracy and RAM memory usage under different scenarios of cardiac modeling, including bidomain and monodomain simulations in 2-D and 3-D for simple and complex tissue geometries. In problems with analytical solutions, MFEs displayed the same numerical accuracy of standard linear triangular and tetrahedral elements. In propagation simulations, conduction velocity and activation times agreed very well with those computed with standard FEs. However, MFEs offer a significant decrease in memory requirements. We conclude that HMs composed of MFEs are well suited for solving problems in cardiac computational electrophysiology.

An Efficient Finite Element Approach for Modeling Fibrotic Clefts in the Heart

Advanced medical imaging technologies provide a wealth of information on cardiac anatomy and structure at a paracellular resolution, allowing to identify microstructural discontinuities which disrupt the intracellular matrix. Current state-of-the-art computer models built upon such datasets account for increasingly finer anatomical details, however, structural discontinuities at the paracellular level are typically discarded in the model generation process, owing to the significant costs which incur when using high resolutions for explicit representation. In this study, a novel discontinuous finite element (dFE) approach for discretizing the bidomain equations is presented, which accounts for fine-scale structures in a computer model without the need to increase spatial resolution. In the dFE method, this is achieved by imposing infinitely thin lines of electrical insulation along edges of finite elements which approximate the geometry of discontinuities in the intracellular matrix. Simulation results demonstrate that the dFE approach accounts for effects induced by microscopic size scale discontinuities, such as the formation of microscopic virtual electrodes, with vast computational savings as compared to high resolution continuous finite element models. Moreover, the method can be implemented in any standard continuous finite element code with minor effort.