Abstract:

The message of this article is that patient safety must be an essential part of thinking and planning in research for medical technology. Which aspects must be considered already in an early phase of any project are presented. The most important standards are listed briefly. Then the topics technical safety and electromagnetic compatibility (EMC), clinical evaluation, risk analysis, biological evaluation of materials, ergonomics, the special aspects of medical devices that include pharmacological components, and the requirements of software packages and implemented algorithms are discussed.Im vorliegenden Beitrag wird begründet, warum die Patientensicherheit vom ersten Tag an ein wesentlicher Bestandteil der Überlegungen und Planungen in der medizintechnischen Forschung sein muss. Es wird dargestellt, welche Aspekte insbesondere schon in den frühen Phasen eines Projektes berücksichtigt werden müssen. Die wichtigsten Normen werden nur kurz angesprochen. Dann werden die Themen technische Sicherheit und Elektromagnetische Verträglichkeit (EMV), klinische Prüfung, Risikoanalyse, biologische Bewertung von Materialien, Ergonomie, die Problematik von Medizintechnik mit pharmakologischen Komponenten und die Anforderungen an reine Softwarepakete für die Medizin und an implementierte Algorithmen genauer betrachtet.

Abstract:

Non-invasive localization of premature ventricular beat (PVB) foci is very important for medical treatment of numerous cardiac diseases. In this work a model-based method of reconstruction of ectopic center locations is investigated.Within the scope of this method patient's multichannel ECG is used as a reference for optimization of an electrophysiological cardiac model. This model is based on the cellular automaton principle and utilizes anatomical data of the patient. Optimized are coordinates of the ectopic focus as well as excitation conduction velocity of ventricular myocardium. Initial values for these parameters are obtained by solving the linearized problem of electrocardiography in terms of activation times. Optimization is performed by minimization of discrepancy between the simulated and reference ECGs.The aim of the current work is to estimate the quality of ectopic focus localization delivered by this method. Four sample ectopic beats have been simulated, with their foci located in different regions of the left ventricle. 1% Gaussian noise has been introduced into the resulting ECGs. In this way the "measured" ECG signals for this investigation have been obtained. Afterwards the origin of each ectopic beat has been reconstructed using the model-based approach. The method has demonstrated reliable localization of PVB foci, reconstruction errors have not exceeded 6.1 mm.

Abstract:

The distributions of transmembrane voltage (TMV) within the cardiac tissue are linearly connected with the patient's body surface potential maps (BSPMs) at every time instant. The matrix describing the relation between the respective distributions is referred to as the transfer matrix. This matrix can be employed to carry out forward calculations in order to find the BSPM for any given distribution of TMV inside the heart. Its inverse can be used to reconstruct the cardiac activity non-invasively, which can be an important diagnostic tool in the clinical practice.The computation of this matrix using the finite element method can be quite time-consuming. In this work, a method is proposed allowing to speed up this process by computing an approximate transfer matrix instead of the precise one. The method is tested on three realistic anatomical models of real-world patients. It is shown that the computation time can be reduced by 50% without loss of accuracy.

Abstract:

Over the last years, nonfluoroscopic in vivo cardiac mapping and navigation systems have been developed and successfully applied in clinical electrophysiology. Clearly, a trend can be observed to introduce more sensors into the measurement system so that physiological information can be gathered simultaneously and more efficiently and the duration of procedure can be shortened significantly. However, it would not be realistic to equip each catheter electrode with a localizer, e.g., by embedding a miniature magnetic location sensor. Therefore, in this paper, an alternate approach has been worked out to efficiently localize multiple catheter electrodes by considering the impedance between electrodes in the heart and electrode patches on the body surface. In application of the new technique, no additional expensive and sophisticated hardware is required other than the currently existing cardiac navigation system. A tank model and a computerized realistic human model are employed to support the development of the positioning system. In the simulation study, the new approach achieves an average localization error of less than 1 mm, which proves the feasibility of the impedance-based catheter positioning system. Consequently, the new positioning system can provide an inexpensive and accurate solution to improve the efficiency and efficacy of catheter ablation.

Abstract:

An improvement of biventricular pacing (BVP) could be possible by detecting the patient specific optimal pacemaker parameters. Body surface potential map (BSPM) is used to obtain the electrophysiology and pathology of an individual patient non-invasively. The clinical measurements of BSPM are used to parameterize the computer model of the heart to represent the individual pathology. The computer model of the heart is used to simulate the dyssynchrony of the ventricles and myocardial infarction (MI). Cardiac electrophysiology is simulated with ten Tusscher cell model, while excitation propagation is intended with adaptive cellular automaton at physiological and pathological conduction stages. The optimal electrode configurations are identified by minimizing the QRS duration error of healthy and pathology case with/without pacing between pre and post-implantation. Afterwards, the simulated ECGs for optimal pacing are compared to the post implantation clinically measured ECGs. The optimal electrode positions found by simulation are comparable to the ones meausured in hospital. The QRS duration reduction error between measured and simulated 12 ECG signals are similar with a constant offset of 15 ms. The personalized model present in this research is an effective tool for therapy planning of BVP in patients with congestive heart failure.

Abstract:

BACKGROUND: The efficacy of cardiac resynchronization therapy through biventricular pacing (BVP) has been demonstrated by numerous studies in patients suffering from congestive heart failure. In order to achieve a guideline for optimal treatment with BVP devices, an automated non-invasive strategy based on a computer model of the heart is presented. MATERIALS AND METHODS: The presented research investigates an off-line optimization algorithm regarding electrode positioning and timing delays. The efficacy of the algorithm is demonstrated in four patients suffering from left bundle branch block (LBBB) and myocardial infarction (MI). The computer model of the heart was used to simulate the LBBB in addition to several MI allocations according to the different left ventricular subdivisions introduced by the American Heart Association. Furthermore, simulations with reduced interventricular conduction velocity were performed in order to model interventricular excitation conduction delay. More than 800,000 simulations were carried out by adjusting a variety of 121 pairs of atrioventricular and interventricular delays and 36 different electrode positioning set-ups. Additionally, three different conduction velocities were examined. The optimization measures included the minimum root mean square error (E(RMS)) between physiological, pathological and therapeutic excitation, and also the difference of QRS-complex duration. Both of these measures were computed automatically. RESULTS: Depending on the patient's pathology and conduction velocity, a reduction of E(RMS) between physiological and therapeutic excitation could be reached. For each patient and pathology, an optimal pacing electrode pair was determined. The results demonstrated the importance of an individual adjustment of BVP parameters to the patient's anatomy and pathology. CONCLUSION: This work proposes a novel non-invasive optimization algorithm to find the best electrode positioning sites and timing delays for BVP in patients with LBBB and MI. This algorithm can be used to plan an optimal therapy for an individual patient.

Abstract:

The motion of the heart is a major challenge for cardiac imaging using CT. A novel approach to decrease motion blur and to improve the signal to noise ratio is motion compensated reconstruction which takes motion vector fields into account in order to correct motion. The presented work deals with the determination of local motion vector fields from high contrast objects and their utilization within motion compensated filtered back projection reconstruction. Image registration is applied during the quiescent cardiac phases. Temporal interpolation in parameter space is used in order to estimate motion during strong motion phases. The resulting motion vector fields are during image reconstruction. The method is assessed using a software phantom and several clinical cases for calcium scoring. As a criterion for reconstruction quality, calcium volume scores were derived from both, gated cardiac reconstruction and motion compensated reconstruction throughout the cardiac phases using low pitch helical cone beam CT acquisitions. The presented technique is a robust method to determine and utilize local motion vector fields. Motion compensated reconstruction using the derived motion vector fields leads to superior image quality compared to gated reconstruction. As a result, the gating window can be enlarged significantly, resulting in increased SNR, while reliable Hounsfield units are achieved due to the reduced level of motion artefacts. The enlargement of the gating window can be translated into reduced dose requirements.

Abstract:

A ray-based approach that models the geometric mapping properties of a flat optical detector based on a microlens array is presented. The investigated optical detector substitutes a single-aperture lens optic for planar and tomographic data acquisition in space-constrained small-animal imaging applications. The formalism implements forward mapping of a three-dimensional object volume onto a two-dimensional sensor surface as well as the backprojection (inverse mapping) of acquired sensor data sets. The object focus distance is the sole free parameter for the inverse mapping. By variation of the object focus distance, arbitrary object surface areas within the computed object images can be focused. The inverse mapping algorithm was applied to an experimentally acquired sensor data set from a three-dimensional phantom. The results are compared with focal point image formation.

Abstract:

Cardiac tissue exhibits spatially heterogeneous electrophysiological properties. In cardiac diseases, these properties also change in time. This study introduces a framework to investigate their role in cardiac ischemia using mathematical modeling and computational simulations at cellular and tissue level. Ischemia was incorporated by reproducing effects of hyperkalemia, acidosis, and hypoxia with a human electrophysiological model. In tissue, spatial heterogeneous ischemia was described by central ischemic (CIZ) and border zone. Anisotropic conduction was simulated with a bidomain approach in an anatomical ventricle model including realistic fiber orientation and transmural, apico-basal, and interventricular electrophysiological heterogeneities. A model of electrical conductivity in a human torso served for ECG calculations. Ischemia increased resting but reduced peak voltage, action potential duration, and upstroke velocity. These effects were strongest in subepicardial cells. In tissue, conduction velocity decreased towards CIZ but effective refractory period increased. At 10 min of ischemia 19% of subepi- and 100% of subendocardial CIZ cells activated with a delay of 34.6+/-7.8 ms and 55.9+/-18.8 ms, respectively, compared to normal. Significant ST elevation and premature T wave end appeared only with the subepicardial CIZ. The model reproduced effects of ischemia at cellular and tissue level. The results suggest that the presented in silico approach can complement experimental studies, e.g., in understanding the role of ischemia or the onset of arrhythmia.

Abstract:

Atrial fibrillation is the most common cardiac arrhythmia and often leads to severe complications such as stroke and other embolic incidents. Areas of complex fractionated atrial activity are in the focus of electrophysiologists and have been used as a target for catheter ablation therapy. The underlying mechanisms of complex fractionated atrial electrograms (CFAEs) are not entirely understood. CFAEs may contain concurrent rhythmic episodes of signals with differing characteristic frequencies (CFs). We propose a new algorithm to detect multiple periodicities in atrial signals.First, we preprocess the signal by applying Teager's non-linear energy operator. Next, the first three characteristic frequencies are detected in the frequency spectrum. Information contained in the harmonics is used to recursively detect the exact frequency. Frequency information is then transformed into the time domain, where repeated occurance of signal activity according to the respective cycle length is found. Further, the detection rate and the mean distance to gravity are calculated as key figures to determine more characteristics of the periodicity.The algorithm performs well in detecting the rhythmic components of atrial signals. It has been tested using real patient data acquired during electrophysiological studies in sinus rhythm, atrial flutter and several forms of atrial fibrillation, as well as with simulated data produced by a cellular automaton at our research group.Its application may provide new insights into atrial signals especially CFAEs and the interpretation of characteristic and dominant frequencies. It can be the foundation of displaying rhythmicity and CF information onto the 3D representation of the patient's atrium and give the physician an impression of the organization and regularity of cardiac electrograms.

Abstract:

QT interval correction on measured ECGs is an important issue for pharmaceutical research on the way to new drugs. Pharmaceutical industries have to thoroughly investigate potential effects of their drugs on QT intervals since QT pro- longation is considered as a marker of the proarrhythmia risk. As QT interval depends on RR interval there is an obvious in- terest in modeling the QT-RR relationship. Static formulas to correct QT for RR are well known, but a dynamic dependency is also observed. Two models of dynamic QT-RR relationships are introduced to eliminate the heart rate dependent part out of the QT interval. These models are based on heart cell measure- ments and simulations and are validated by Holter ECG data.

Abstract:

Atrial fibrillation is the most common cardiac arrhythmia in humans. The precise cellular mechanisms underlying atrial fibrillation are still poorly understood. Recent studies have identified several genetic defects as predisposing factors for this pathology. One of the identified genetic defects is the mutation N588K, which affects the cardiac IKr channel. Genetic variants in this channel have been identified to modify ventricular repolarization. The aim of this work is to investigate the effect of this mutation on atrial repolarization and the predisposition to atrial fibrillation.Measured data obtained with whole cell voltage clamp technique of wild-type and mutated hERG channel were implemented in the Courtemanche et al. ionic model. For this purpose, channel kinetics and density of the model were adjusted using parameter fitting to the measured data. By this way, the effects of the mutation in the hERG channel could be analyzed in the whole cell and in tissue, as well. The channel mutation N588K showed a gain of function effect, causing a rapid repolarization and consequently, a shortening of the action potential duration. Computer simulations of a schematic anatomical model of the right atrium were then carried out to investigate the excitation propagation and the repolarization.The action potential duration of the mutant cell was reduced to 116 ms and the effective refractory period to 220 ms. Both factors are linked to a shortening of the wavelength, indicating that the mutation N588K predisposes the initiation and perpetuation of atrial fibrillation.

Abstract:

Anatomical voxel models are used for example for dosimetric assessment and numerical field calculations. For best matching between models and patients properties an accurate model should be created by Magnetic Resonance Imaging or Computer Tomography images for every patient. Due to complexity, time and costs this is not always possible. In contrast 3D laser scanning is a fast and easy method to gain information about a patients body surface. In this work generic organ models are developed to fit into the laser scan envelope of any patient. One model set was processed as to fit to the volume reference values of the International Commission on Radiological Protections of six different ages. To accomplish a more realistic shape, orthogonal scaling factors are used to simulate growth in three different directions.

Abstract:

The tomographic reconstruction of the beating heart requires dedicated methods. One possibility is gated reconstruction, where only data corresponding to a certain motion state are incorporated. Another one is motioncompensated reconstruction with a pre-computed motion vector field, which requires a preceding estimation of the motion. Here, results of a new approach are presented: simultaneous reconstruction of a three-dimensional object and its motion over time, yielding a fully four-dimensional representation. The object motion is modeled by a time-dependent elastic transformation. The reconstruction is carried out with an iterative gradient-descent algorithm which simultaneously optimizes the three-dimensional image and the motion parameters. The method was tested on a simulated rotational X-ray acquisition of a dynamic coronary artery phantom, acquired on a C-arm system with a slowly rotating C-arm. Accurate reconstruction of both absorption coefficient and motion could be achieved. First results from experiments on clinical rotational X-ray coronary angiography data are shown. The resulting reconstructions enable the analysis of both static properties, such as vessel geometry and cross-sectional areas, and dynamic properties, like magnitude, speed, and synchrony of motion during the cardiac cycle.

Abstract:

A modified mass-spring system for simulating the passive and active elastomechanical properties of the myocardial tissue was presented in a previous publication. The previously presented results are combined with the method also published earlier to use continuum mechanics calculate passive forces in a mass-spring system directly starting from the energy density function of the stress-strain relation. An efficient method for volume preservation is presented and the implementation of an implicit time integration method for solving the systems equations of motion is described. The computational complexity of the system is analyzed and shown to be of O(n). At the end several simulations are conducted to demonstrate the method.

Abstract:

A volumetric mass-spring system for simulating the passive and active elastomechanical properties of the myocardial tissue is presented. A 3D computer model containing information about the fiber, sheet, and sheet-normal directions and about the modeled objects physiological properties, is used to initialize the systems structure.Using an electrophysiology model and a force development model, contracting forces are introduced to the systems elements at each time step of the simulation loop.Using the methods of continuum mechanics, suitable springs functions were derived analytically from the energy density function of describing the hyperelastic properties of heart. That eliminated the need of springs parametrization. An efficient method for volume preservation is used to ensure the conservation of the model's volume under deformation.Implicit time integration is implemented to solve the equations of motion, that improves the stability of the simulation and allows larger simulation time steps. An iterative solver that take advantage of the sparsity of the system's matrices is used and the systems complexity is shown to be of O(n) where n is the the count of the models elements.

Abstract:

The forward problem of electrocardiography aims at obtaining a better understanding of cardiac electrophysiological activities, by means of computer modeling and simulation. Whereas, the inverse electrocardiographic problem provides a direct insight of electrical sources into the heart without interventional procedures. Nowadays, the forward and inverse problems are mostly solved in static models, which do not take into account heart motion and respiration. Besides heart motion, neglecting respiration may also lead to remarkable uncertainties in both forward and inverse solutions. In the present work a dynamic lung model is developed. With this model the effect of respiration on the forward and inverse solutions is studied.

Abstract:

Muscle anisotropy is important for the realistic solution of the forward problem of electrocardiography. Whenever computer models of patient-specific anatomies are created usually no information about the muscle fiber arrangement in the heart or skeletal muscle is available. As in-vivo imaging techniques that can determine fiber orientation like Diffusion Tensor MRI are time-consuming and susceptible to motion artifacts, cardiac fiber orientation is frequently described using simplified rules. However, for the skeletal muscle there are only few suggestions for a rule-based implementation of fiber orientation into patient-specific models. In this work we evaluated a rule-based approach from the literature together with two new methods by comparing the corresponding forward calculated body surface potential maps (BSPMs) with the BSPM resulting from a reference skeletal muscle fiber distribution extracted from the thin-section photos of the Visible Man dataset (Journal of Computing and Information Technology vol.6, pp. 95-101 1998). The skeletal muscle anisotropy ratio was set to 3:1. The following fiber orientation setups were evaluated: A) the torso is divided into twelve sectors (cross-section perspective) and fiber direction was assumed to be perpendicular to the bisector as proposed by Klepfer et al. (IEEE Trans. Biomed. Eng. vol. 44, no. 8, pp. 706-719 1997); B) A 3D Sobel filter was used on the torso geometry filled with a gradient from inside to outside which generated a vector that was normal to the thoracic surface in every voxel. Fiber orientation was assumed to be perpendicular to the plane formed by these normal vectors and the direction from head to feet (longitudinal torso orientation); C) Same procedure as in B) but additionally, the back muscles which are known to have a longitudinal orientation were integrated accordingly. Potentials were extracted at 64 electrode positions from the BSPMs. The RMS was calculated at these electrode positions between the reference fiber distribution and the respective rule-based approaches. The RMS was comparable between A) and B) (8.8e-5 vs. 8.9e-5) leading to the conclusion that the twelve discrete sectors introduced no significant error. A) and B) performed also well compared to a modified version of the reference dataset where the longitudinal component of the fiber vectors was set to zero (8.3e-5). Including the longitudinal components of the back muscles as done in C) enhances the RMS to 5.5e-5. If the skeletal muscle anisotropy was neglected and only cardiac fiber orientation was taken into account, the RMS improved (!) further to only 4.0e-5. Thus it can be concluded that neglecting the longitudinal component (A) and B)) or accounting for it with a highly simplified approach (C)) is not sufficient. In cases where no detailed information about the skeletal muscle fiber arrangement is available, it is better to entirely neglect its anisotropic influence.

Abstract:

The Purkinje network plays a major role for realistically simulating the activation sequence of the ventricles. In this work, we describe a method to create an endocardial stimulation profile that describes the location and time instant of ventricular stimulation, thus mimicking the His-Purkinje conduction system. By adapting model parameters stimulation profiles can be generated for different ventricular anatomies with minimal manual interaction. The stimulation profile parameters are evaluated by analyzing the excitation propagation in a three-dimensional, heterogeneous and anisotropic model of the human ventricles which are embedded in an anatomically detailed torso geometry. The calculated QRS complexes are in good agreement with the corresponding clinical recordings on the same proband.

Abstract:

The human atria contain fine structures, which can hardly be distinguished with common medical imaging techniques. However, some of these structures play an important role in the electrophysiologic depolarisation sequence of the atria. We present a semi-automatic algorithm to segment the sinus node, Bachmann’s Bundle and the Terminal Crest in given anatomical shape models of the atria. The algorithm bases on anatomical knowledge of the atria and only requires the user to provide few distinct landmarks in the atria as input. Incorporation of these structures into patient individual atrial geometries augments the electrophysiological correctness of the models.

Abstract:

Electrode positions and timing delays influence the efficacy of biventricular pacing (BVP). Accordingly, the study focus is on BVP optimization, using a detailed three-dimensional electrophysiological model of the human heart, adapted to patient specific anatomy and pathophysiology. The research is effectuated on ten heart models with left bundle branch block and myocardial infarction derived from magnetic resonance and computer tomography data. Cardiac electrical activity is simulated with ten Tusscher cell model and adaptive cellular automaton, at physiological and pathological conduction levels. The optimization methods are based on a comparison between the electrical response of the healthy and diseased heart models, measured in terms of root mean square error (ERMS) of the excitation front and QRS duration error (EQRS). Intra- and inter-method associations of the pacing electrodes and timing delays variables were analyzed with statistical methods, i.e. t-test for dependent data, one-way ANOVA for electrode pairs and Pearson model for equivalent parameters from the two optimization methods. The results indicate that lateral left ventricle and upper or middle septal area are frequently (60% of cases) the optimal position of the left and right electrode, respectively. Statistical analysis proves that the two optimization methods are in good agreement. In conclusion, a non-invasive pre-operative BVP optimization strategy based on computer simulations can be used to identify the most beneficial patient specific electrode configuration and timing delays.

Abstract:

Atrial fibrillation (AFib) is the most common cardiac arrhythmia. Areas in atrial tissue with complex fractionated atrial electrograms (CFAEs) are among others responsible for the maintenance of AFib. Those areas are ideal target sites for ablation to eliminate AFib and restore sinus rhythm. As CFAEs are associated with high fibrillatory frequency, automated identification of CFAEs with spectral analysis helps developing objective strategies for AFib ablation. While the application of current techniques is restricted, this paper introduces a new approach to determine characteristic frequencies during AFib. By using Teagers energy operator we calculate the signal envelope and study its spectrum after Fast Fourier Transformation. Harmonic analysis of distinctive peaks in the power spectrum is carried out to assess characteristic frequencies of a CFAE. While the currently available methods only find one dominant frequency in the spectrum of the signal, our method is capable to find multiple characteristic frequencies, if present. Since it is believed that during AFib the atrium is activated by one or multiple wavelets, our method opens new opportunities for investigation of multiple wavelets propagation.

Abstract:

Areas in atrium tissue with complex fractionated atrial electrograms (CFAEs) are among others responsible for the maintenance of atrial fibrillation (AFib). Those areas are ideal target sites for ablation to eliminate AFib and restore normal rhythm. An automated identification of CFAEs with signal processing algorithms is essential to develop an objective strategy for AFib ablation. This paper introduces a new approach to locate signal complexes corresponding to electrophysiological activity. The idea behind this algorithm is based on the idea of Pan-Tompkins QRS-detection algorithm. However in this approach, the extracted signal feature is the signal energy and therefore the algorithm takes into account not only information of the frequency but also of the amplitude. With adaptive thresholding the algorithm is capable to manage changes in the signal dynamics. The results were validated by experts and the algorithm shows a robust performance.

Abstract:

High performance computing is required to make feasible simulations of whole organ models of the heart with biophysically detailed cellular models in a clinical setting. Increasing model detail by simulating electrophysiology and mechanical models increases computation demands. We present scaling results of an electro mechanical cardiac model of two ventricles and compare them to our previously published results using an electrophysiological model only. The anatomical data-set was given by both ventricles of the Visible Female data-set in a 0.2 mm resolution. Fiber orientation was included. Data decomposition for the distribution onto the distributed memory system was carried out by orthogonal recursive bisection. Load weight ratios for non tissue vs. tissue elements used in the data decomposition were 1:1, 1:2, 1:5, 1:10, 1:25, 1:38.85, 1:50 and 1:100. The ten Tusscher et al. (2004) electrophysiological cell model was used and the Rice et al. (1999) model for the computation of the calcium transient dependent force. Scaling results for 512, 1024, 2048, 4096, 8192 and 16,384 processors were obtained for 1 ms simulation time. The simulations were carried out on an IBM Blue Gene/L supercomputer. The results show linear scaling from 512 to 16,384 processors with speedup factors between 1.82 and 2.14 between partitions. The most optimal load ratio was 1:25 for on all partitions. However, a shift towards load ratios with higher weight for the tissue elements can be recognized as can be expected when adding computational complexity to the model while keeping the same communication setup. This work demonstrates that it is potentially possible to run simulations of 0.5 s using the presented electro-mechanical cardiac model within 1.5 hours.

Abstract:

Orthogonal recursive bisection (ORB) algorithm can be used as data decomposition strategy to distribute a large data set of a cardiac model to a distributed memory supercomputer. It has been shown previously that good scaling results can be achieved using the ORB algorithm for data decomposition. However, the ORB algorithm depends on the distribution of computational load of each element in the data set. In this work we investigated the dependence of data decomposition and load balancing on different rotations of the anatomical data set to achieve optimization in load balancing. The anatomical data set was given by both ventricles of the Visible Female data set in a 0.2 mm resolution. Fiber orientation was included. The data set was rotated by 90 degrees around x, y and z axis, respectively. By either translating or by simply taking the magnitude of the resulting negative coordinates we were able to create 14 data sets of the same anatomy with different orientation and position in the overall volume. Computation load ratios for non tissue vs. tissue elements used in the data decomposition were 1:1, 1:2, 1:5, 1:10, 1:25, 1:38.85, 1:50 and 1:100 to investigate the effect of different load ratios on the data decomposition. The ten Tusscher et al. (2004) electrophysiological cell model was used in monodomain simulations of 1 ms simulation time to compare performance using the different data sets and orientations. The simulations were carried out for load ratio 1:10, 1:25 and 1:38.85 on a 512 processor partition of the IBM Blue Gene/L supercomputer. The results show that the data decomposition does depend on the orientation and position of the anatomy in the global volume. The difference in total run time between the data sets is 10 s for a simulation time of 1 ms. This yields a difference of about 28 h for a simulation of 10 s simulation time. However, given larger processor partitions, the difference in run time decreases and becomes less significant. Depending on the processor partition size, future work will have to consider the orientation of the anatomy in the global volume for longer simulation runs.

Abstract:

The output data generated in whole heart simula- tions are usually single or multiple parameters at each point in the simulation space. Visualizing data sets of gigabyte size puts great stress on the hardware and can be slow and tedious. Creating animated movies to analyze the excitation propaga- tion can take hours on standard systems. We present two par- allel visualization techniques to improve rendering of large datasets from cardiac simulations.The Scalable Parallel Visualization Networking (SPVN) toolkit provides the ability to assist in optimizing the utility and functionality of the aggregate resources in visualization clusters. Run time visualization offers the opportunity to visu- alize the results of cardiac simulations on the fly on High Per- formance Computers. Parallel visualization techniques enable fast manipulation of high resolution whole heart data sets and simulation results. The SPVN system has the potential to be linked with the simulation environment similar to the run time visualization described.Future efforts will focus on creating a simulation and visu- alization environment with appropriate characteristics for clinical setting. Specifically, speed, intuitive control and the ability to render diverse signals will likely be critical to drive adoption in the clinical setting.

Abstract:

Atrial Fibrillation (AFib) is the most common cardiac arrhythmia. Despite the considerable clinical experience and accumulated evidence from experimental data, the exact mechanism of AFib and their elimination by catheter ablation techniques is still unknown. The aim of this work is to investigate measured intracardiac ECGs with methods of signal processing and multivariate statistical techniques to get a better understanding of atrial excitation during atrial fibrillation. Therefor intracardiac ECGs measured in the coronary sinus during sinus rhythm, atrial flutter and atrial fibrillation were processed and compared. After fragmentation into patterns, the data is analysed by Principal Component Analysis (PCA). Using this new representation of the original data a clustering process is performed and the time-distance between the found clusters is calculated. The main goal of this study is to give quantitative data on spread of depolarization during AFib. The developed algorithms can also be used to analyse complex fractionated atrial electrograms (CFAEs) in further studies.

Abstract:

The curative therapy of atrial fibrillation (AF) is still challenging. Although the electrophysiologists know many strategies to cure AF, the underlying mechanisms are still mostly unknown. Also the optimal ablation strategy for paroxysmal and long-lasting persistent AF is not known. Complex fractionated atrial electrograms (CFAEs) are becoming more and more important in the ablation strategies, especially for long-lasting persistant AF. Automated detection and signal analysis of CFAEs is essential in supporting the physicians during the ablation procedure. The robust algorithm to locate CFAEs presented in the contribution by Nguyen, Schilling and Dössel delivers a good bases for postprocessing and signal analysis of CFAEs. It is employing a non-linear energy operator combined with thresholding. In this paper this new algorithm is tested on clinical data and compared to clinically accepted algorithms.

Abstract:

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the western world. Genetic variants in the cardiac I Kr channel have been identified to influence ventricular repolarization. The aim of this work is to investigate the effect of the mutation N588K on atrial repolarization and the predisposition to AF. Experimental data of N588K mutated hERG channel were incorporated in an atrial ionic model using parameter fitting. The effects of the mutation were analyzed in cell and tissue. N588K showed a gain of function effect, causing a rapid repolarization and a shortening of the action potential duration. Computer simulations of a schematic right atrial geometry were used to investigate the excitation conduction properties. The effective refractory period of mutant cells were reduced from 317 to 233 ms at 1 Hz. The conduction velocity is not significantly influenced by the mutation. Nevertheless, the wavelength of mutant cells is for all frequencies smaller, indicating that the mutation N588K predisposes the initiation and perpetuation of AF.

Abstract:

Cisapride is a drug to help gastric problems. It is limited because of reports of the side-effect long QT syndrome which predisposes to arrhythmias. In this computatinal study, the effects of Cisapride on human ventricular myocytes are investigated in-silico. From literature reported effects of the drug on ion channel level are included into a virtual human ventricular cell. Cisapride has the most dominating effect on the rapid delayed rectifier current IKr. A shift in the activation and inactivation and mainly a reduction of conductivity is seen. This leads to the prolongation of the APD comparable to the long QT syndrome. In future studies, the stability of the heart under the influence of this drug will be evaluated

Abstract:

Magnetic Resonance Imaging (MRI) is a widely used means of imaging and becoming increasingly popular for cardiac applications as well. But for patients with im- planted pacemakers, the use of MRI is not allowed in Eu- rope and the United States due to potentially hazardous interactions of the RF pulses with the pacemaker-electrode system. Here heating at the tip of the electrode is regarded as the most important one.In this simulation study, the occurring current densities and E-fields should be determined by employing numerical field calculation. Computer models of metallic objects like straight wires, simplified pacemakers and a replication a commercial bipolar electrode were placed in a plexiglas box positioned inside a birdcage coil. The results con- firmed findings of previous in-vitro studies regarding the influence of size and position of the exposed objects and thereby proved the validity of the presented approach.

Abstract:

Patient-specific model adaptation and validation requires a comparison of simulations with measured patient data. For patients suffering from atrial fibrillation, such data is mainly available as intracardiac catheter signals. In this work, we demonstrate the simulation of clinically relevant catheter data as measured using circular mapping catheters (such as Lasso or Orbiter) and coronary sinus catheters using atrial simulations on a realistic geometry. Four circular catheters are modeled using a projection technique for two distinct types of application. We show that in sinus rhythm, the choice of a distinct electrophysiological model does not impair the signal quality. Finally, we compare simulated potentials to a real clinical measurement. In the future, with patient- specific models available, such comparisons can constitute an important interface for personalizing cardiac models.

Abstract:

Intracardiac catheter recordings are available in common clinical practice. They can therefore be employed to adapt and validate atrial computer models of individual patients. Hence, their information content needs to be analyzed quantitatively. During treatment of atrial arrhythmia such as atrial flutter or fibrillation, the location of ectopic foci in the pulmonary veins is of special interest. In this study, virtual catheter signals are extracted from an atrial simulation on a realistic geometry with normal sinus rhythm as well as ectopic stimuli in all four pulmonary veins. Using a simplified Pan-Tompkins algorithm, the activation times are determined. Based on the analysis of the activation sequence in a circular mapping catheter simulated on the posterior left atrial wall, all four ectopic foci can clearly be associated with the pulmonary vein they came from. For a catheter on the anterior wall, this is possible for three of the four ectopic beats. Despite the knowledge gathered for the personalization of patient models, such simulations may help cardiologists to better classify measured signals.

Abstract:

Patient-specific cardiac simulations are approaching clinical applications. They could for example improve the treatment of atrial fibrillation (AF). Currently, many patients suffering from AF are treated with minimally-invasive catheter ablation. Using this technique, trigger sources for AF (mainly the pulmonary veins), are electrically isolated from the rest of the atrium. However, a large set of different ablation strategies is currently used in clinical practice. Therefore, the choice of a certain ablation strategy as well as the probability for successful and sustained AF termination are strongly dependent on the experience of the cardiologist. Atrial simulations could assist the cardiologist in the choice of a suitable method for an individual patient. For this, the atrial models have to be adapted to the patient. Besides anatomical modeling, several challenges must be faced in this process. First, an appropriate model of cellular electrophysiology and excitation conduction must be chosen. The model must provide the necessary accuracy and at the same time be fast enough for clinical applications. As a trade-off between accuracy and speed, we propose a minimal model adapted to atrial electrophysiology. Second, a main problem is the adaptation of physiological parameters in the patient-specific model as well as its validation. Therefore, an interface between clinical data and the model is needed. Data collected in standard clinical workflow are mainly intracardiac catheter ECGs. We therefore present techniques to model such catheter measurements. Signals from both circular mapping catheters (such as Lasso or Orbiter) as well as Coronary Sinus catheters can be simulated and compared to clinical signals. These are important steps towards clinical applications of atrial models. The long-term goal then is to assist the cardiologist in the choice of the best treatment for an individual patient.