INTRODUCTION: The "Experimental Data and Geometric Analysis Repository", or EDGAR is an Internet-based archive of curated data that are freely distributed to the international research community for the application and validation of electrocardiographic imaging (ECGI) techniques. The EDGAR project is a collaborative effort by the Consortium for ECG Imaging (CEI, ecg-imaging.org), and focused on two specific aims. One aim is to host an online repository that provides access to a wide spectrum of data, and the second aim is to provide a standard information format for the exchange of these diverse datasets. METHODS: The EDGAR system is composed of two interrelated components: 1) a metadata model, which includes a set of descriptive parameters and information, time signals from both the cardiac source and body-surface, and extensive geometric information, including images, geometric models, and measure locations used during the data acquisition/generation; and 2) a web interface. This web interface provides efficient, search, browsing, and retrieval of data from the repository. RESULTS: An aggregation of experimental, clinical and simulation data from various centers is being made available through the EDGAR project including experimental data from animal studies provided by the University of Utah (USA), clinical data from multiple human subjects provided by the Charles University Hospital (Czech Republic), and computer simulation data provided by the Karlsruhe Institute of Technology (Germany). CONCLUSIONS: It is our hope that EDGAR will serve as a communal forum for sharing and distribution of cardiac electrophysiology data and geometric models for use in ECGI research.
Background: Intracardiac electrograms are an indispensable part during diagnosis of supraventriculararrhythmias, but atrial activity (AA) can be obscured by ventricular far-fields (VFF). Concepts based onstatistical independence like principal component analysis (PCA) cannot be applied for VFF removalduring atrial tachycardia with stable conduction.Methods: A database of realistic electrograms containing AAand VFF was generated. Both PCA and thenew technique periodic component analysis (πCA) were implemented, benchmarked, and applied toclinical data.Results: The concept of πCA was successfully verified to retain compromised AA morphology,showing high correlation (cc = 0.98 ± 0.01) for stable atrial cycle length (ACL). Performance ofPCA failed during temporal coupling (cc = 0.03 ± 0.08) but improved for increasing conductionvariability (cc = 0.77 ± 0.14). Stability of ACL was identified as a critical parameter for πCAapplication. Analysis of clinical data confirmed these findings.Conclusion: πCA is introduced as a powerful new technique for artifact removal in periodic signals.Its concept and performance were benchmarked against PCA using simulated data and demonstratedon measured electrograms.
PURPOSE: To evaluate two commonly used respiratory motion correction techniques for coronary magnetic resonance angiography (MRA) regarding their dependency on motion estimation accuracy and final image quality and to compare both methods to the respiratory gating approach used in clinical practice. MATERIALS AND METHODS: Ten healthy volunteers were scanned using a non-Cartesian radial phase encoding acquisition. Respiratory motion was corrected for coronary MRA according to two motion correction techniques, image-based (IMC) and reconstruction-based (RMC) respiratory motion correction. Both motion correction approaches were compared quantitatively and qualitatively against a reference standard navigator-based respiratory gating (RG) approach. Quantitative comparisons were performed regarding visible vessel length, vessel sharpness, and total acquisition time. Two experts carried out a visual scoring of image quality. Additionally, numerical simulations were performed to evaluate the effect of motion estimation inaccuracy on RMC and IMC. RESULTS: RMC led to significantly better image quality than IMC (P's paired Student's t-test were smaller than 0.001 for vessel sharpness and visual scoring). RMC did not show a statistically significant difference compared to reference standard RG (vessel length [99% confidence interval]: 86.913 [83.097-95.015], P = 0.107; vessel sharpness: 0.640 [0.605-0.802], P = 0.012; visual scoring: 2.583 [2.410-3.424], P = 0.018) in terms of vessel visualization and image quality while reducing scan times by 56%. Simulations showed higher dependencies for RMC than for IMC on motion estimation inaccuracies. CONCLUSION: RMC provides a similar image quality as the clinically used RG approach but almost halves the scan time and is independent of subjects' breathing patterns. Clinical validation of RMC is now desirable. J. Magn. Reson. Imaging 2015.
Catheter ablation has emerged as an effective treatment strategy for atrial fibrillation (AF) in recent years. During AF, complex fractionated atrial electrograms (CFAE) can be recorded and are known to be a potential target for ablation. Automatic algorithms have been developed to simplify CFAE detection, but they are often based on a single descriptor or a set of descriptors in combination with sharp decision classifiers. However, these methods do not reflect the progressive transition between CFAE classes. The aim of this study was to develop an automatic classification algorithm, which combines the information of a complete set of descriptors and allows for progressive and transparent decisions. We designed a method to automatically analyze CFAE based on a set of descriptors representing various aspects, such as shape, amplitude and temporal characteristics. A fuzzy decision tree (FDT) was trained and evaluated on 429 predefined electrograms. CFAE were classified into four subgroups with a correct rate of 81+/-3%. Electrograms with continuous activity were detected with a correct rate of 100%. In addition, a percentage of certainty is given for each electrogram to enable a comprehensive and transparent decision. The proposed FDT is able to classify CFAE with respect to their progressive transition and may allow objective and reproducible CFAE interpretation for clinical use.
By means of computer modeling general comprehension of electrophysiology (EP) of human atria can be improved and simulated patterns of ectopic foci, reentry and rotors can be created. On the other hand atrial electrograms are measured in the EP lab of many hospitals every day. In this contribution simulated and measured clinical signals are compared critically aiming at better understanding of atrial fibrillation and validation of computer modeling.
S. Bauer, T. Oesterlein, J. Schmid, and O. Dössel. Interactive visualization of cardiac anatomy and atrial excitation for medical diagnosis and research. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 400-404, 2015
State of the art biomedical engineering allows for acquiring enormous amounts of intracardiac data to aid diagnosis and treatment of cardiac arrhythmias. Modern catheters, which are used to acquire electrical information from within the heart, are capable of recording up to 64 channels simultaneously. The software available for data analysis, however, does not provide adequate performance to neither analyze nor visualize the acquired information in an appropriate manner. We present a software package that fascilitates interdisciplinary collaborations between engineers and physicians to adress open questions about pathophysiological mechanisms using data from everyday electrophysiogical studies. Therefore, a package has been compiled that enables algorithm development using MATLAB and subsequent visualization using the VTK C++ class libraries. The resulting application KaPAVIE, which is presented in this paper, is designed to meet the requirements from the clinical side and has been successfully applied in the clinical environment.
Cardiac electrical imaging, that is, reconstructing car- diac electrical activity from body surface measurements, is a technology with great potential. However, ill-posedness of this problem hinders its routine usage in clinical envi- ronment and continues to motivate the search for improve- ments on current methods. Messnarz et al. introduced an algorithm that constraints the reconstructed transmem- brane potential (TMP) to be non-decreasing over time dur- ing QRS-complex. This physiologically meaningful con- straint reduces the solution space of the problem and reg- ularizes the solution. However, this approach is compu- tationally extensive and can become prohibitive as spatial and temporal resolution of the problem increase. Here we compare three distinct options to reduce the computational load: downsampling the measurements in time, downsam- pling the measurements after filtering with an algorithm based on principal component analysis and non-linearly interpolating the potentials with a spline-based method. The data used were simulated TMPs that were forward propagated to the body surface in a densely sampled ge- ometry. The resulting body surface potential simulations were corrupted with noise and the inverse computed using a much coarser mesh to take geometry errors into account. The results indicate that reducing the dimension of the sig- nal in time does not reduce the quality of the solutions obtained, while the computational requirements decrease considerably, especially for the spline method.
M. Kircher, G. Lenis, and O. Dössel. Separating the effect of respiration from the Heart Rate Variability for cases of constant harmonic breathing. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 46-49, 2015
Heart Rate Variability studies are a known measure for the autonomous control of the heart rate. In special situations, its interpretation can be ambiguous, since the respiration has a major influence on the heart rate variability. For this reason it has often been proposed to measure Heart Rate Variability, while the subjects are breathing at a constant respiration rate. That way the spectral influence of the respiration is known. In this work we propose to remove this constant respiratory influence from the heart rate and the Heart Rate Variability parameters to gain respiration free autonomous controlled heart rate signal. The spectral respiratory component in the heart rate signal is detected and characterized. Subsequently the respiratory effect on Heart Rate Variability is removed using spectral filtering approaches, such as the Notch filter or the Raised Cosine filter. As a result new decoupled Heart Variability parameters are gained, which could lead to new additional interpretations of the autonomous control of the heart rate.
G. Lenis, F. Conz, and O. Dössel. Combining different ECG derived respiration tracking methods to create an optimal reconstruction of the breathing pattern. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 54-57, 2015
ECG derived respiration (EDR) is a technique applied to estimate the respiration signal using only the electrocardiogram (ECG). Different approaches have been proposed in the past on how respiration could be gained from the ECG. However, in many applications only one of them is used while the others are not considered at all. In this paper, we propose a new algorithm for the optimal linear combination of different EDR methods in order to create a more accurate estimation. Using two well known databases, it was statistically shown that an optimally chosen fixed set of coefficients for the linear combination delivers a better estimation than each of the methods used solely.
G. Lenis, T. Oesterlein, and O. Dössel. Orthogonal component analysis to remove ventricular far field in non periodic sustained atrial flutter. In Computing in Cardiology, vol. 42, pp. 669-672, 2015
Automatic signal processing of intracardiac electrograms plays a decisive role in the diagnosis and treatment of supraventricular arrhythmias. During sustained atrial flutter, a repetitive signal is measured in the atrium. However, the ventricular far field may overlap with the atrial activity and compromises the automatic signal processing tools during the intervention. Recently, a new method based on periodic component analysis was proposed as an artifact removal technique. The method works satisfactorily with highly periodic atrial activities but fails to reconstruct not regularly repeating signals .In order to account for that case, we developed a new method based on orthogonal component analysis to reconstruct the corrupted atrial electrocardiograms obscured by ventricular far field. We tested the method on synthetic signals and proved it to be successful. The reconstructed signals were of higher quality and the computation time was drastically shorter than the already existing periodic component analysis. We conclude that the new method can be used in realistic scenarios in the future.
ECG markers derived from the P-wave are used frequently to assess atrial function and anatomy, e.g. left atrial enlargement. While having the advantage of being routinely acquired, the processes under- lying the genesis of the P-wave are not understood in their entirety. Particularly the distinct contributions of the two atria have not been analyzed mechanistically. We used an in silico approach to simulate P-waves originating from the left atrium (LA) and the right atrium (RA) separately in two realistic models. LA contribution to the P-wave integral was limited to 30% or less. Around 20 % could be attributed to the first third of the P-wave which reflected almost only RA depolarization. Both atria contributed to the second and last third with RA contribution being about twice as large as LA contribution. Our results foster the comprehension of the difficulties related to ECG-based LA assessment.
The clinical efficacy in preventing the recurrence of atrial fibrillation (AF) is higher for amiodarone than for dronedarone. Moreover, pharmacotherapy with these drugs is less successful in patients with remodeled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyzed the effects of these two drugs in a computational model of atrial electrophysiology. The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodeled tissue and hERG mutations N588K and L532P. The pharmacodynamics of amiodarone and dronedarone were investigated with respect to their dose and heart rate dependence by evaluating 10 descriptors of action potential morphology and conduction properties. An arrhythmia score was computed based on a subset of these biomarkers and analyzed regarding circadian variation of drug concentration and heart rate. Action potential alternans at high frequencies was observed over the whole dronedarone concentration range at high frequencies, while amiodarone caused alternans only in a narrow range. The total score of dronedarone reached critical values in most of the investigated dynamic scenarios, while amiodarone caused only minor score oscillations. Compared with the other substrates, cAF showed significantly different characteristics resulting in a lower amiodarone but higher dronedarone concentration yielding the lowest score. Significant differences exist in the frequency and concentration-dependent effects between amiodarone and dronedarone and between different atrial substrates. Our results provide possible explanations for the superior efficacy of amiodarone and may aid in the design of substrate-specific pharmacotherapy for AF.
A. Loewe, Y. Xu, E. P. Scholz, O. Dössel, and G. Seemann. Understanding the cellular mode of action of vernakalant using a computational model: answers and new questions. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 418-422, 2015
Vernakalant is a new antiarrhythmic agent for the treatment of atrial fibrillation. While it has proven to be effective in a large share of patients in clinical studies, its underlying mode of action is not fully understood. In this work, we aim to link experimental data from the subcellular, tissue, and system level using an in-silico approach. A Hills equation-based drug model was extended to cover the frequency dependence of sodium channel block. Two model variants were investigated: M1 based on subcellular data and M2 based on tissue level data. 6 action potential (AP) markers were evaluated regarding their dose, frequency and substrate dependence. M1 comprising potassium, sodium, and calcium channel block reproduced the reported prolongation of the refractory period. M2 not including the effects on potassium channels reproduced reported AP morphology changes on the other hand. The experimentally observed increase of ERP accompanied by a shortening of APD90 was not reproduced. Thus, explanations for the drug-induced changes are provided while none of the models can explain the effects in their entirety. These results foster the understanding of vernakalants cellular mode of action and point out relevant gaps in our current knowledge to be addressed in future in-silico and experimental research on this aspiring antiarrhythmic agent.
T. Oesterlein, G. Lenis, A. Luik, C. Schmitt, and O. Dössel. Optimized Approach for the Detection of Active Segments in Intracardiac Electrograms Measured during Atrial Flutter. In 42nd International Congress on Electrocardiology Conference Book of Abstracts, 2015
S. Pollnow, and O. Dössel. In-vitro studies for investigating the electrophysiology of cardiac tissue with acute ablation lesions. In Atrial Signals 2015, 2015
S. Pollnow, G. Seemann, and O. Dössel. Simultaneous optical and electrical characterization of cardiac tissue with acutely created lesions. In CRC Conference: Cardiac Arrhythmia Mechanisms, 2015
Over the last decades, the information content derived from cardiac electric and magnetic field measurements has been debated. Our co-workers Wilhelms et al. inves- tigated electrically silent acute ischemia in human ven- tricles caused by occlusion of a coronary artery. In the present work, we extend the previous study by calculating associated magnetic fields produced by early stage acute ischemia with varying transmural extent. Multiscale com- putational simulations were performed for calculations of body surface potential maps (BSPM) and magnetocardio- grams (MCG) on a magnetometer sensor matrix situated above the anterior chest wall. Depending on the ischemia size, the ST-segments of the simulated electrocardiograms (ECG) experienced depression for subendocardial cases and elevation for transmural ischemia. One intermedi- ate extent resulted in a zero ST-segment which makes it diagnostically indistinguishable from the healthy case. Magnetic field calculations for this electrically silent is- chemia also revealed no difference compared to the control case. Otherwise, both ECG and MCG signals during ST- segments showed either depression or elevation from zero line. In this simulation study, MCG did not deliver addi- tional information to uncover electrically silent ischemia. For a general conclusion, further in-silico investigations with different ischemia shapes, sizes and positions should be performed and clinical studies with recordings of both ECG and MCG signals have to be conducted.
ECG imaging as noninvasive method is aiming to reconstruct the distribution of the transmembrane voltage amplitudes (TMVs) from the body surface potential map (BSPM). Due to the ill-posedness, standard approaches like the Tikhonov regularization method cause blurring and artefacts in the solution. To suppress blurring and artefacts, this work investigated a model based approach, the unscented Kalman filter (UKF). The intention of this paper is to show the potential of an UKF approach by using an idealized parametrization.
M. Rottmann, G. Seemann, and O. Dössel. Analysis of characteristic signal morphologies of double potentials near block lines in an atrial simulation model. In Biomedical Technology/ Biomedical Engineering, 2015
Atrial fibrillation is a common irregular heart rhythm. Until today there is still a need for research to quantify typical signal characteristics of rotors, which can induce atrial fibrillation. In this work, signal characteristics of a stable and a more unstable rotor in a realistic heart model including fiber orientation were analyzed with the following methods: peak-to-peak amplitude, Hilbert phase, approximate entropy and RS-difference. In this simulation model the stable rotor rotated with a cycle length of 145 ms and stayed in an area of 1.5 mm x 3 mm. Another more unstable rotor with a cycle length of 190 ms moved in an area of 10 mm × 4 mm. In a distance of 2 mm to the rotor tip, the peak-to-peak amplitude decreased significantly, whereas the RS-difference and the approximate entropy were maximal. The rotor center trajectories were detected by phase singularity points determined by the Hilbert transform. We showed that more unstable rotors resulted in more amplitude changes over time and also the cycle length differed more. Furthermore, we presented typical activation time patterns of the Lasso catheter centered at the rotor tip and in different distances to the rotor tip. We suggest that cardiologists use a combination of the described methods to determine a rotor tip position in a more robust manner.
This handout describes the simulation dataset KIT-20-PVC_Simulation-1906-10-30, which was contributed by the Karlsruhe Institute of Technology (KIT) to the Experimental Data and Geometric Analysis Repository (EDGAR) database.
Diagnosis of atrial flutter caused by ablation of atrial fibrillation is complex due to ablation scars. This paper presents an approach to replicate the clinically measured flutter circuit in a dynamic computer model. In a first step, important anatomical features of the flutter circuit are extracted manually based on the clinical measurement. With the help of this information, the electrical excitation propagation is simulated on the atrial geometry using the fast marching method. The simulated flutter circuit is used to estimate the global and local conduction velocity by approximating it iteratively. The parameterized flutter simulation is supposed to support the physician during diagnosis and treatment of atrial flutter.
L. A. Unger, M. Rottmann, G. Seemann, and O. Dössel. Detecting phase singularities and rotor center trajectories based on the Hilbert transform of intraatrial electrograms in an atrial voxel model. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 38-41, 2015
This work aimed at the detection of rotor centers within the atrial cavity during atrial fibrillation on the basis of phase singularities. A voxel based method was established which employs the Hilbert transform and the phase of unipolar electrograms. The method provides a 3D overview of phase singularities at the endocardial surface and within the blood volume. Mapping those phase singularities from the inside of the atria at the endocardium yielded rotor center trajectories.We discuss the results for an unstable and a more stable rotor. The side length of the areas covered by the trajectories varied from 1.5mm to 10 mm. These results are important for cardiologists who target rotors with RF ablation in order to cure atrial fibrillation.
The success rate of the cardiac ablation procedure to cure atrial fibrillation is moderate and depends on the experience and expertise of the physicians. It could be increased by precisely locating arrhythmogenic substrates. The aim of this work is to present a simple and feasible method to analyze intraatrial electrograms to identify the arrhythmogenic substrate on the atrium, under sinus rhythm and pacing sequences. The change in the depolarization wavefront propagation, resulting from consecutive triggering at a point in the coronary sinus (CS), can be an indication of the arrhythmogenic substrate. The region specific study enables the localization of critical sites in the patient specific atrial anatomy. This could aid the physicians in ascertaining the efficacy of cardiac therapies. In this work the point- to-point analysis of the intraatrial electrograms was carried out.
Catheter ablation is the most widely used minimum invasive technique to cure atrial arrhythmias. However, the success rate of the treatment is still moderate and depends on the experience and expertise of the physicians. The aim of this work is to present a simple and feasible method to identify the arrhythmogenic areas on the atrium based on the duration of atrial activities in the intraatrial electrograms. Depolarization waves are created by giving pacing impulses from coronary sinus (CS). The duration of the activity triggered from sinus node (SN) and pacing sequences are analysed by calculating the duration of the activity to mark regions with long atrial activitywaves. The intraatrial electrograms have been analysed on the basis of temporal and spatial information. The region specific study may favour the localization of the critical sites in the patient specific atrial anatomy and aid the physician in ascertaining the efficacy of the cardiac therapies. The identification of suitable markers for critical patterns of the depolarization waves may be crucial to guide an effective ablation treatment. In this work a novel study for point-to-point analysis of the intraatrial electrograms was carried out.
The fiber orientation in the atria has a significant contribution to the electrophysiologic behavior of the heart and to the genesis of arrhythmia. Atrial fiber orientation has a direct effect on excitation propagation, activation patterns and the P-wave. We present a rule-based algorithm that works robustly on different volumetric meshes composed of either isotropic hexahedra or arbitrary tetrahedra as well as on 3-dimensional triangular surface meshes in patient-specific geometric models. This method fosters the understanding of general pro-arrhythmic mechanisms and enhances patient-specific modeling approaches.
Using OpenCL, we developed a cross-platform software to compute electrical excitation conduction in cardiac tissue. OpenCL allowed the software to run parallelized and on different computing devices (e.g., CPUs and GPUs).We used the macroscopic mono-domain model for excitation conduction and an atrial myocyte model by Courtemanche et al. for ionic currents. On a CPU with 12 HyperThreading-enabled Intel Xeon 2.7 GHz cores, we achieved a speed-up of simulations by a factor of 1.6 against existing software that uses OpenMPI. On two high-end AMD FirePro D700 GPUs the OpenCL software ran 2.4 times faster than the OpenMPI implementation. The more nodes the discretized simulation domain contained, the higher speed-ups were achieved.