Computational modeling is an important tool to advance our knowledge on cardiac diseases and their underlying mechanisms. Computational models of conduction in cardiac tissues require identification of parameters. Our knowledge on these parameters is limited, especially for diseased tissues. Here, we assessed and quantified parameters for computational modeling of conduction in cardiac tissues. We used a rabbit model of myocardial infarction (MI) and an imaging-based approach to derive the parameters. Left ventricular tissue samples were obtained from fixed control hearts (animals: 5) and infarcted hearts (animals: 6) within 200 μm (region 1), 250-750 μm (region 2) and 1,000-1,250 μm (region 3) of the MI border. We assessed extracellular space, fibroblasts, smooth muscle cells, nuclei and gap junctions by a multi-label staining protocol. With confocal microscopy we acquired three-dimensional (3D) image stacks with a voxel size of 200 × 200 × 200 nm. Image segmentation yielded 3D reconstructions of tissue microstructure, which were used to numerically derive extracellular conductivity tensors. Volume fractions of myocyte, extracellular, interlaminar cleft, vessel and fibroblast domains in control were (in %) 65.03 ± 3.60, 24.68 ± 3.05, 3.95 ± 4.84, 7.71 ± 2.15, and 2.48 ± 1.11, respectively. Volume fractions in regions 1 and 2 were different for myocyte, myofibroblast, vessel, and extracellular domains. Fibrosis, defined as increase in fibrotic tissue constituents, was (in %) 21.21 ± 1.73, 16.90 ± 9.86, and 3.58 ± 8.64 in MI regions 1, 2, and 3, respectively. For control tissues, image-based computation of longitudinal, transverse and normal extracellular conductivity yielded (in S/m) 0.36 ± 0.11, 0.17 ± 0.07, and 0.1 ± 0.06, respectively. Conductivities were markedly increased in regions 1 (+75, +171, and +100%), 2 (+53, +165, and +80%), and 3 (+42, +141, and +60%). Volume fractions of the extracellular space including interlaminar clefts strongly correlated with conductivities in control and MI hearts. Our study provides novel quantitative data for computational modeling of conduction in normal and MI hearts. Notably, our study introduces comprehensive statistical information on tissue composition and extracellular conductivities on a microscopic scale in the MI border zone. We suggest that the presented data fill a significant gap in modeling parameters and extend our foundation for computational modeling of cardiac conduction.
Radiofrequency ablation has become a first-line approach for curative therapy of many cardiac arrhythmias. Various existing catheter designs provide high spatial resolution to identify the best spot for performing ablation and to assess lesion formation. However, creation of transmural and nonconducting ablation lesions requires usage of catheters with larger electrodes and improved thermal conductivity, leading to reduced spatial sensitivity. As trade-off, an ablation catheter with integrated mini electrodes was introduced. The additional diagnostic benefit of this catheter is still not clear. In order to solve this issue, we implemented a computational setup with different ablation scenarios. Our in silico results show that peak-to-peak amplitudes of unipolar electrograms from mini electrodes are more suitable to differentiate ablated and nonablated tissue compared to electrograms from the distal ablation electrode. However, in orthogonal mapping position, no significant difference was observed between distal electrode and mini electrodes electrograms in the ablation scenarios. In conclusion, catheters with mini electrodes bring about additional benefit to distinguish ablated tissue from nonablated tissue in parallel position with high spatial resolution. It is feasible to detect conduction gaps in linear lesions with this catheter by evaluating electrogram data from mini electrodes.
Computer simulations and imaging of human physiology and anatomy are effectively used for diagnostics and medical treatments and are thus a focus of scientific research. Suitable representation of data is a critical aspect to achieve best results. Therefore, we developed an interactive visualization scheme especially for the representation of cardiac arrhythmias based on a conventional mobile device and virtual reality (VR) goggles (Google Cardboard and Samsung Gear VR) in combination with a game engine. The aim of this paper is to raise awareness for this new technique, evaluate its potential and pro- pose a general workflow for such a visualization environment. The use of a conventional mobile device in combination with VR goggles creates a portable and low-cost system, equipped with enough processing power and pixel density for many types of applications. The user can interact with the data through head movement or a secondary controller. As current game engines support a wide range of additional input methods and controllers, the interaction method can be customized to fit the target audience. To evaluate this method, we conducted a survey with eight typical phenomena from the field of cardiac arrhythmias. The participants were asked to rate different performance aspects on a scale from one (very bad) to five (very good). All participants (N=27) rated the performance as fluent (median=5). Furthermore, most participants (70%) ranked the overall impression as very good (median=5). On the long run, the system can be used for education and presentations as well as improved planning and guidance of medical procedures.
Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intrac- ardiac electrograms (IEGMs) provide real-time informa- tion regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and inter- pretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenom- ena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was com- pared to an existing one and to clinical measurements of ve patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogo- nal catheter orientation, the presence of a second necrotic core in the near- eld of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.
J. Greiner. Simulation of intracardiac electrograms around acute point-shaped and complex ablation lesions. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2015
Radiofrequency ablation is a widely used treatment for many types of cardiac arrhythmias. However, complications and arrhythmia recurrence still arise frequently. An essential criterion for a favorable therapy outcome is the creation of transmural lesion lines with the absence of gaps. Intracardiac electrograms provide real-time information regarding the state of the cardiac tissue surrounding the catheter tip. Therefore, intracardiac electrograms may have the potential to offer beneficial contributions for the therapy success. Formation and interpretation of intracardiac electrograms is complex and yet not fully understood. Computational models try to bridge this gap by reconstructing underlying mechanism and phenomena. The clear separation of causalities and the possibility to vary parameters provide valuable knowledge. In this thesis, an existing computational model for point- shaped acute ablation scars was refined. Hereby, electrophysiological parameters were varied. Four parametersets of isotropic and anisotropic excitation propagation were investigated. Clinical measurements from five patients undergoing radiofrequency ablation to treat atrial fibrillation were compared to the computed intracardiac electrograms. Compared to the existing model, the refinements were able to improve congruence with clinical measurements. Subsequently, complex ablation scars were simulated for a parameterset with isotropic excitation propagation. The presence of a necrotic core in the near field of an acute ablation had minor impact on the computed intracardiac electrograms. Further research may lead to robust markers for gapless and transmural lesions in the intracardiac electrogram.