Abstract:

Ventricular wall deformation is widely assumed to have an impact on the morphology of the T-wave that can be measured on the body surface. This study aims at quantifying these effects based on an in silico approach. To this end, we used a hybrid, static-dynamic approach: action potential propagation and repolarization were simulated on an electrophysiologically detailed but static 3-D heart model while the forward calculation accounted for ventricular deformation and the associated movement of the electrical sources (thus, it was dynamic). The displacement vectors that describe the ventricular motion were extracted from cinematographic and tagged MRI data using an elastic registration procedure. To probe to what extent the T-wave changes depend on the synchrony/asynchrony of mechanical relaxation and electrical repolarization, we created three electrophysiological configurations, each with a unique QT time: a setup with physiological QT time, a setup with pathologically short QT time (SQT), and pathologically long QT time (LQT), respectively. For all three electrophysiological configurations, a reduction of the T-wave amplitude was observed when the dynamic model was used for the forward calculations. The largest amplitude changes and the lowest correlation coefficients between the static and dynamic model were observed for the SQT setup, followed by the physiological QT and LQT setups.

Abstract:

In this paper, we present an efficient method to estimate changes in forward-calculated body surface potential maps (BSPMs) caused by variations in tissue conductivities. For blood, skeletal muscle, lungs, and fat, the influence of conductivity variations was analyzed using the principal component analysis (PCA). For each single tissue, we obtained the first PCA eigenvector from seven sample simulations with conductivities between ±75% of the default value. We showed that this eigenvector was sufficient to estimate the signal over the whole conductivity range of ±75%. By aligning the origins of the different PCA coordinate systems and superimposing the single tissue effects, it was possible to estimate the BSPM for combined conductivity variations in all four tissues. Furthermore, the method can be used to easily calculate confidence intervals for the signal, i.e., the minimal and maximal possible amplitudes for given conductivity uncertainties. In addition to that, it was possible to determine the most probable conductivity values for a given BSPM signal. This was achieved by probing hundreds of different conductivity combinations with a numerical optimization scheme. In conclusion, our method allows to efficiently predict forward-calculated BSPMs over a wide range of conductivity values from few sample simulations.

Abstract:

The impact of transmural infarctions of the left ventricle on the cardiac mechanical dynamics is evaluated for all 17 AHA segments in a computer model. The simulation framework consists of two parts: an electrophysiological model and an elastomechanical model of the ventricles. The electrophysiological model is used to simulate the electrophysiological processes on cellular level, excitation propagation and the tension development. It is linked to the elastomechanical model, which is based on nonlinear finite element analysis for continuum mechanics. Altogether, 18 simulations of the contraction of the ventricles were performed, 17 with an infarction in the respective AHA segment and one simulation for the control case. For each simulation, the mechanical dynamics as well as the wall thickening of the infarct region were analyzed and compared to the corresponding region of the control case. The simulation revealed details of the impact of the myocardial infarction on wall thickening as well as on the velocity of the infarct region for most of the AHA segments

Abstract:

Atrial myofiber orientation is complex and has multiple discrete layers and bundles. A novel robust semi-automatic method to incorporate atrial anisotropy and heterogeneities into patient-specific models is introduced. The user needs to provide 22 distinct seed-points from which a network of auxiliary lines is constructed. These are used to define fiber orientation and myocardial bundles. The method was applied to 14 patient-specific volumetric models derived from CT, MRI and photographic data. Initial electrophysiological simulations show a significant influence of anisotropy and heterogeneity on the excitation pattern and P-wave duration (20.7% shortening). Fiber modeling results show good overall correspondence with anatomical data. Minor modeling errors are observed if more than four pulmonary veins exist in the model. The method is an important step towards creating realistic patient-specific atrial models for clinical applications.

Abstract:

Atrial fibre architecture has complex patterns of bundles and layers and is known to impact on atrial electrophysiology, especially in fast-conducting bundles like Crista Terminalis, Bachmanns bundle and pectinate muscles. Based on a priori knowledge of atrial fibre structure, we incorporated rule-based fibre orientation in seven volumetric models of human atria using a semi-automatic approach. We were able to introduce multiple layers of myofibres and regional heterogeneities of ion channels in the models. We evaluated the influence of complete atrial fibre architecture on multiple modelling scales. First, we simulated atrial excitation in the isotropic and anisotropic models using the model of Courtemanche et al. in combination with the monodomain approach. Second, we computed body surface potentials from the simulated transmembrane voltages and compared these to measured ECGs from the respective patients. Temporal behaviour of the atrial excitation sequences was significantly altered in the anisotropic models compared to the sequences in the isotropic models. Complete atrial activation was achieved approximately 20% faster in the anisotropic models mostly due to fast conducting myofibre bundles. Electrophysiological heterogeneities influenced right atrial transmembrane voltage distribution over time due to a less negative action potential plateau in Crista Terminalis cells. P-wave duration was significantly shorted by the introduction of atrial anisotropy and the error to measured P-wave duration was reduced. Furthermore, a pattern change in body surface potential distribution over time was observed. The anisotropic patterns showed a better match to the measurements. Thus, the modelling error by using generalised fibre architecture for patient-specific models was smaller than by using isotropic models. The results highlight the necessity to incorporate atrial anisotropy in personalised models to produce more realistic simulations. The semi-automatic approach allows the use of these models for future clinical applications.

Abstract:

Tikhonov methods usually lead to solutions of low amplitude that are distributed around zero. When reconstructing transmembrane voltages (TMVs) in the myocardium, the signal is therefore often not in the physiological range of between around -80mV and 10mV. In this article, we propose an adjusted Tikhonov method that reconstructs TMVs in the correct range, given an estimate of one polarized node in the heart and an estimated set of nodes that have depolarized in the preceding time step. It is shown that when feeding the reconstructed TMVs into a simple cellular automaton recursively, and when using the computed excitation propagation as a prior for the Tikhonov method, it is possible to reconstruct the excitation propagation throughout the ventricular myocardium. The method requires an estimate of the region of initial activation.

Abstract:

This work is focused on different aspects within the loop of multiscale modeling:On the cellular level, effects of adrenergic regulation and the Long-QT syndrome have been investigated.On the organ level, a model for the excitation conduction system was developed and the role of electrophysiological heterogeneities was analyzed.On the torso level a dynamic model of a deforming heart was created and the effects of tissue conductivities on the solution of the forward problem were evaluated.