Abstract:

Congenital Long-QT Syndrome (LQTS) is a genetic dis- order affecting the repolarization of the heart. The most prevalent subtypes of LQTS are LQT1-3. In this work, we aim to evaluate the differences in the T-waves of simu- lated LQT1-3 in order to identify markers in the ECG that might help to classify patients solely based on ECG mea- surements. For LQT1, mutation S277L was used to char- acterize IKs and mutation S818L in IKr for LQT2. Volt- age clamp data were used to parametrize the ion channel equations of the ten Tusscher and Panfilov model of hu- man ventricular electrophysiology. LQT3 was integrated using an existing mutant INa model. The monodomain model was used in a transmural and apico-basal heteroge- neous model of the ventricles to calculate ventricular exci- tation propagation. The forward calculation on a torso model was performed to determine body surface ECGs. Compared to the physiological case with a QT-time of 375 ms, this interval was prolonged in all LQTS (LQT1 423 ms; LQT2 394 ms; LQT3 405 ms). The T-wave ampli- tude was changed (Einthoven lead II: LQT1 108%; LQT2 91%; LQT3 103%). Also, the width of the T-wave was en- larged (full width at half maximum: LQT1 111%; LQT2 125%; LQT3 109%). At the current state of modeling and data analysis, the three LQTS have not been distinguish- able solely by ECG data.

Abstract:

Abstract Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI.

Abstract:

Numerical and patient-specific models of the human atrial anatomy and electrophysiology have a high potential to enhance our knowledge regarding pathological conditions and to increase the outcome of diagnosis and therapy. This chapter briefly describes the current state of the art in modeling of generalized human atria. Furthermore, the chapter demonstrates ways to personalize human atrial anatomy and electrophysiology based on a variety of measurement data from, e.g. late enhancement magnetic resonance imaging (MRI), patch clamp technique, intracardiac electrograms and body surface potential maps. Wherever patient data cannot be collected, patient-group specific behavior can be integrated. Some examples of the personalization process are described and the validation process is discussed together with future options for personalization, validation and application.

Abstract:

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.

Abstract:

Computational atrial models aid the understanding of pathological mechanisms and therapeutic measures in basic research. The use of biophysical models in a clinical environment requires methods to personalize the anatomy and electrophysiology (EP). Strategies for the automation of model generation and for evaluation are needed. In this manuscript, the current efforts of clinical atrial modeling in the euHeart project are summarized within the context of recent publications in this field. Model-based segmentation methods allow for the automatic generation of ready-to-simulate patient-specific anatomical models. EP models can be adapted to patient groups based on a-priori knowledge, and to the individual without significant further data acquisition. ECG and intracardiac data build the basis for excitation personalization. Information from late enhancement (LE) MRI can be used to evaluate the success of radio-frequency ablation (RFA) procedures and interactive virtual atria pave the way for RFA planning. Atrial modeling is currently in a transition from the sole use in basic research to future clinical applications. The proposed methods build the framework for model-based diagnosis and therapy evaluation and planning. Complex models allow to understand biophysical mechanisms and enable the development of simplified models for clinical applications.

Abstract:

Multiscale cardiac modeling has made great advances over the last decade. Highly detailed atrial models were created and used for the investigation of initiation and perpetuation of atrial fibrillation. The next challenge is the use of personalized atrial models in clinical practice. In this study, a framework of simple and robust tools is presented, which enables the generation and validation of patient-specific anatomical and electrophysiological atrial models. Introduction of rule-based atrial fiber orientation produced a realistic excitation sequence and a better correlation to the measured electrocardiograms. Personalization of the global conduction velocity lead to a precise match of the measured P-wave duration. The use of a virtual cohort of nine patient and volunteer models averaged out possible model-specific errors. Intra-atrial excitation conduction was personalized manually from left atrial local activation time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps in ablation lesions. A fast marching level set approach to compute atrial depolarization was extended to incorporate anisotropy and conduction velocity heterogeneities and reproduced the monodomain solution. The presented chain of tools is an important step towards the use of atrial models for the patient-specific AF diagnosis and ablation therapy planing.

Abstract:

Ventricular ectopic beats (VEBs) trigger a characteristic response of the heart called heart rate turbulence (HRT). The HRT can be used to predict sudden cardiac death in patients with a history of myocardial infarction. In this work, we present a reliable algorithm to detect and classify ectopic beats. Every electrocardiogram (ECG) is processed with innovative filtering techniques, artifact detection methods, and a robust multichannel analysis to produce accurate annotation results. For the classification task, a support vec- tor machine was used. Furthermore, a new approach to the analysis of HRT is proposed. The HRT is interpreted as the response of a second-order system to an external perturbation. The system theoretical parameters were estimated. The influence of VEB on the morphology of subsequent T waves was also analyzed. A strong influence was detected in the study with 14 patients experiencing frequent VEB. The evolution of the morphology of the T wave with every new beat was studied, and it could be concluded that an exponential shape underlies this dynamic process and was called morphological heart rate turbulence (MHRT). Parameters were defined to quantify the MHRT. The analysis of the MHRT could help to understand the influence of an ectopic beat on the repolarization processes of the heart and more accurately stratify the risk of sudden cardiac death.

Abstract:

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.

Abstract:

Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation. In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential alternans. To assess the models ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate action potential and restitution properties, as well as the initiation of reentrant circuits.

Abstract:

VERTRAUEN IN DIE / IN DER WISSENSCHAFT?Streitgespräche in den Wissenschaftlichen Sitzungen der Versammlung der Akademiemitglieder am 30. November 2012 und am 14. Juni 2013

Abstract:

Cardiac computer modeling can help to gain a deeper insight into the physiological processes of the heart. In this work we present a new electromechanical modeling framework which allows to simulate the contraction of the atria in a model of the whole heart with realistic bound- ary conditions. For the active tension development (TD) we used a model, which was originally developed to describe the TD of the ventricles. However, TD in the atria differs significantly from that of the ventricles. On that account, we adapted the TD model to the measurement data of the atria. The modeling framework allows to obtain a realistic motion of the atria during the contraction cycle.

Abstract:

A new method to predict changes in a lead-field matrix induced by conductivity variations of a single body tissue is proposed. The approach is based on the princi- ple component analysis (PCA) with three initial lead-field matrices transformed to vectors as input. For each tissue blood, lungs, muscles and fat a PCA was carried out. Further, for each tissue the default conductivity value and the conductivity varied by ±50 % were used to calculate the sample lead-field matrices. The results of the PCAs in- dicate that for every tissue the first principle component suffices to predict the conductivity-induced changes in the samples. With an interpolation of the scores we addition- ally show that the prediction is not bound to the sample ma- trices but moreover every matrix within each conductivity range is possibly estimated and conclusively predicted.

Abstract:

Complex fractionated atrial electrograms (CFAE) are a target for catheter ablation as they coincide with areas of slow conduction. In this study we simulated different vol- ume fractions of diffuse and patchy fibrosis up to 50 %. Catheter signals for different electrode spacings were cal- culated and characteristic features were compared to a clinical database of CFAE-signals. A linear slowing of global conduction velocities was found independent of the type of fibrosis. For patchy fibrosis, electrograms displayed fractionation, which was not seen for diffuse fibrosis of the same degree. In comparison to clinical data, simulated electrograms showed up to 10 zero crossings per electro- gram, which was also seen for clinical EGMs with medium fractionation (class 2 of 3). For both, clinical (84 %) and simulated (88 %) signals, a significant difference in ampli- tude is present between fractionated and non-fractionated signals.

Abstract:

Creating transmural ablation scars in a reliable way is a key issue in improvement of therapeutical pro- cedures for cardiac arrhythmias. About one third of the patients has to undergo several procedures till arrhythmic episodes are successfully treated. Morphological features of intracardiac electrograms might contribute to evaluate scar transmurality during the ablation procedure. We an- alyzed intracardiac signals before, during and after point- wise ablation in patients with atrial flutter. Unipolar elec- trograms of the distal electrode showed a relative decrease in amplitude of the second extremum of up to 99 % with a mean of 84±20.6 % after the endpoint of ablation.

Abstract:

Intracardiac electrograms are the key in under- standing, interpretation and treatment of cardiac arrhythmias. However, electrogram morphologies are strongly variable due to catheter position, orientation and contact. Simulations of intracardiac electrograms can improve comprehension and quantification of influencing parameters and therefore reduce misinterpretations. In this study simulated intracardiac electro- grams are analyzed regarding tilt angles of the catheter relative to the propagation direction, electrode tissue distances as well as clinical filter settings. Catheter signals are computed on a realistic 3D catheter geometry using bidomain simulations of cardiac electrophysiology. Thereby high conductivities of the catheter electrodes are taken into account. For validation, simulated electrograms are compared with in vivo electrograms recorded during an EP-study with direct annotation of catheter orientation and tissue contact. Good agreement was reached regarding timing and signal width of simulated and measured electrograms. Correlation was 0.92±0.07 for bipolar, 0.92±0.05 for unipolar distal and 0.80 ± 0.12 for unipolar proximal electrograms for different catheter orientations and locations.

Abstract:

Abstract. Atrial fibrillation (AF) is the most common cardiac arrhyth- mia. Patient-specific computational modeling of the atria can provide a better understanding about mechanisms underlying the arrhythmia and will potentially be used for model-based ablation therapy evaluation and planning. Electrical excitation spreads from the left to the right atrium at discrete locations. The location of the muscular bridges cannot be determined from image data. In the present study, left atrial activation sources were manually identified in local activation time maps of 4 AF patients. This information was used to adjust rule-based placed intera- trial bridges in anatomical atrial models of the patients. Sinus rhythm simulations showed a better qualitative agreement to the measured left atrial activation patterns after the adjustment of the bridges. For one patient, the simulated body surface potential (BSP) pattern after the adjustment correlated better to measured BSP maps. The results show that the fusion of intracardiac electrical measurements of early left atrial activation can be used to refine patient atria models with information of the myocardial structure which cannot be imaged. In future, such personalized atrial models may be used to support EP interventions.

Abstract:

Heart Rate Turbulence (HRT) is the distinctive response of the sinus rhythm of the heart to an isolated ventricular ectopic beat (VEB). The quantification of this process can be used to stratify the risk of sudden cardiac death in patients with a history of acute myocardial infarction. A sensitivity of around 30% has been achieved in different studies. However, the large number of misleading results of the method suggests that new and better risk stratifiers could be developed. In this work, Holter ECG recordings were used to analyze the morphology of the T wave during the HRT in patients with chronic heart failure. The HRT was characterized by newly introduced parameters. In ad- dition, the comparison between normal T waves before and after the VEB showed small but significant changes in mor- phology. The morphological changes of the T wave could be used for diagnostic purposes.

Abstract:

While human ether-à-go-go-related gene (hERG) mutations N588K and K897T are associated with atrial fib- rillation (AF), the underlying arrhythmogenic mechanisms are understood only incompletely. In this work, an ap- proach integrating IKr measurement data from transgenic Xenopus oocytes into established computational models of cardiac electrophysiology is presented. Parameters are es- timated using a minimization formulation, which is handled by a hybrid particle swarm optimization (PSO) and trust- region-reflective (TRR) algorithm. Cell models adapted to the mutation measurements show a significantly shorter ac- tion potential (AP) with less pronounced spike-and-dome morphology. Results of single cell simulations compare with myocytes in chronic AF.

Abstract:

Local activation time (LAT) maps help to understand the path of electrical excitation in cardiac arrhythmias. They can be generated automatically from intracardiac electrograms using various criteria provided by commercial electroanatomical mapping systems. This study compares existing criteria and a novel method based on the non-linear energy operator (NLEO) with respect to their precision and robustness.

Abstract:

Simultaneous biatrial electroanatomical mapping was performed in a 54 year old woman using two 64-electrode basket catheters. Local activation time (LAT) maps were extracted retrospectively for single atrial excitations during sinus rhythm using the non-linear energy operator (NLEO). Considering both ampltiude and frequency information, the NLEO has shown to be a reliable estimator for the LAT. This paper presents an approach for creating biatrial LAT maps using the NLEO for single atrial excitations. The varying propagation pattern of individual beats reveals the presence and location of supraventricular extrasystoles.

Abstract:

Dynamic modeling of physiological time series represents an auspicious approach in the arena of biomedical signal processing. This study illustrates a new methodology for identifying dynamic models that is based on stationary stochastic processes. The method is applied to time series extracted from the ECG. Simulations of the gained models yield physiologically plausible results.

Abstract:

The correct detection of the P wave in the electrocardiogram (ECG) is very important for the evaluation of the atrial activity. The presented algorithm fusions intracardiac measurements and ECG data to detect P waves in the ECG. With this, it is possible to detect P waves simultaneously appearing with T waves and multiple P waves between two ventricular excitations.Die korrekte Erkennung der P-Welle im Elektrokardiogramm (EKG) ist äußerst wichtig zur Erkennung von Krankheiten in den Vorhöfen des Herzens. Hier soll ein Algorithmus vorgestellt werden, der die Informationen aus einer EKG-Messung und einer intrakardialen Messung der elektrischen Aktivität in den Vorhöfen kombiniert. Damit ist es möglich sowohl von T-Wellen überdeckte P-Wellen als auch mehrere P-Wellen zwischen zwei Kammeraktivierungen zu detektieren.

Abstract:

The inverse problem of ECG is the task of cardiac source reconstruction from the measured body surface potential maps (BSPM). It is ill posed and therefore requires regularization, which is usually applied uniformly to the whole heart geometry. In order to improve the solution quality and localize potentials extrema we propose a local regularization method: the weighting is done iteratively according to the solution spatial content. The performed test showed the ability of the new method to overcome over smoothing and to better reconstruct strong solution gradients.

Abstract:

The goal of ECG imaging is the reconstruction of cardiac electrical activities from the potentials measured on the thorax sur- face. The tool can gain prominent clinical value for diagnosis and pre- interventional planning. The problem is however ill-posed, i.e. it is highly sensitive to modelling and measurement errors. In order to overcome this obstacle a regularization technique must be applied. In this paper we pro- pose a new optimization based method for simultaneous reconstruction of transmembrane voltages and epicardial potentials for localizing the origin of ventricular ectopic beats.Compared to second-order Tikhonov regularization, the new approach showed superior performance in marking activated regions and provided meaningful results where Tikhonov method failed.

Abstract:

This paper is about the construction of an ultra- wideband microwave (UWB) simulation environment and about the construction of a model of the human head in- cluding regions of stroke. It calculates the propagation of microwaves within a wide frequency range through biolog- ical tissues. The simulations will be used to guide the de- velopment of a new system for early detection of stroke with UWB. The simulation has to be as close as possible to the real physiological properties of human tissues including the dispersive effects.

Abstract:

Intracardiac electrograms are essential for the diagnosis and treatment of various cardiac arrhythmias. To gain reliable information about structural alterations of underlying tissue, it is necessary to interpret these electrograms correctly. Therefore it has to be understood how other parameters influence the signal. Realistic 3D geometries were created and simulated using the bidomain model. Based on these simulations, the influences of catheter orientation, tissue thickness and conduction velocity on the amplitudes of intracardiac electrograms were evaluated.

Abstract:

ECG imaging is a non-invasive technique of characterizing the electrical activity and the corresponding excitation conduction of the heart using body surface ECG. The method may provide great opportunities in the planning of cardiac interventions and in the diagnosis of cardiac diseases. This work introduces an algorithm for the imaging of transmembrane voltages that is based on a Kalman filter with an augmented measurement model. In the latter, a regularization term is integrated as additional measurement. The filter is trained using a-priori-knowledge from a simulation model. Two effects are investigated: the influence of the training data on the reconstruction quality and the representation of a-priori knowledge in the trained covariance matrices. The proposed algorithm shows a promising quality of reconstruction and may be used in the future to introduce generic physiological knowledge in solutions of cardiac source imaging.

Abstract:

With ECG imaging it is possible to reconstruct cardiac electrical activity noninvasively from measurements of the electrocardiogram (ECG). To facilitate the recon- struction, an MRI- or CT- based model of the body is re- quired, which is represented as a volume conductor. A mathematically ill-posed problem is solved to reconstruct the cardiac sources from potentials collected on the body surface. To obtain a body surface potential map (BSPM) electrodes are ideally placed allover the entire thorax. In practical applications, however, the number of electrodes is limited and the placing is subject to constraints. We in- vestigate the effect of different electrode setups on the ill- posedness of the inverse problem. In particular, electrode setups are chosen to comply with constraints for female pa- tients in the catheter lab.

Abstract:

Heterogeeities of the ventricular electrophysiol- ogy play a major role in the generation of the T-wave mor- phology and amplitude. The exact way of the distribution of electrophysiological differences is not known. In this work, a numerical approach is presented in which the excitation propagation of different heterogeneity distributions of IKs are simulated and the multi-channel ECG is calculated. The ECG data are evaluated against measured ECGs. The most realistic configuration is a combination of transmural and apico-basal heterogeneity with 35% of Endo, 30% of M and 35% of Epi cells and an apico-basal gradient with a factor of 2. This specific setup has a correlation of around 90% and a root mean square error of around 0.0795.