Abstract:

AIMS: 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 remodelled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyse the effects of the drugs in a computational model of atrial electrophysiology. METHODS AND RESULTS: The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodelled 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 analysed 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. CONCLUSION: 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.

Abstract:

Signals obtained from biological systems exhibit pronounced complexity. The patterns of change contain valu- able information about the dynamics of underlying control mechanism of the complex biological systems. Human gait is a complex process with multiple inputs and numerous outputs. Various complexity analysis tools have been proposed to extract information from human gait time series. In this study, we used recently developed threshold based symbolic entropy to compare the spontaneous output of the human locomotors system during constrained and metronomically paced walking protocols. For that purpose, stride interval time series of healthy subjects who walked for 1 h at normal, slow and fast rates under different conditions was transformed into symbol sequences. Normalized corrected Shannon entropy (NCSE) was computed from the symbol sequences of the stride inter- val time series. The findings indicated that the unprompted output of human locomotors system is more complex during unconstrained normal walking as compared with slow, fast or metronomically paced walking

Abstract:

During the contraction of the ventricles, the ventricles interact with the atria as well as with the pericardium and the surrounding tissue in which the heart is embedded. The atria are stretched, and the atrioventricular plane moves toward the apex. The atrioventricular plane displacement (AVPD) is considered to be a major contributor to the ventricular function, and a reduced AVPD is strongly related to heart failure. At the same time, the epicardium slides almost frictionlessly on the pericardium with permanent contact. Although the interaction between the ventricles, the atria and the pericardium plays an important role for the deformation of the heart, this aspect is usually not considered in computational models. In this work, we present an electromechanical model of the heart, which takes into account the interaction between ventricles, pericardium and atria and allows to reproduce the AVPD. To solve the contact problem of epicardium and pericardium, a contact handling algorithm based on penalty formulation was developed, which ensures frictionless and permanent contact. Two simulations of the ventricular contraction were conducted, one with contact handling of pericardium and heart and one without. In the simulation with contact handling, the atria were stretched during the contraction of the ventricles, while, due to the permanent contact with the pericardium, their volume increased. In contrast to that, in the simulations without pericardium, the atria were also stretched, but the change in the atrial volume was much smaller. Furthermore, the pericardium reduced the radial contraction of the ventricles and at the same time increased the AVPD.

Abstract:

Tracking the location of medical devices in interventional X-ray data solves different problems. For example the motion information of the devices is used to determine cardiac or respiratory motion during X-ray guided procedures or device features are used as landmarks to register images. In this publication an approach using a 3D deformable catheter model is presented and used to track a coronary sinus (CS) catheter in 3D plus time through a complete rotational angiography sequence. The benefits of using voxel based models with attenuation information for 2D/3D registration are investigated in comparison to binary catheter models. The 2D/3D registration of the model allows to extract a 3D catheter shape from every individual 2D projection. The tracking accuracy is evaluated on simulated and clinical rotational angiography data of the contrast enhanced left atrium. The quantitative evaluation of the experiments delivers an average registration accuracy for all catheter electrodes of 0.23 mm in 2D and 0.95 mm in 3D when using an attenuation model of the catheter. The overall tracking accuracy is lower when using binary catheter models.

Abstract:

Cardiac ablation procedures during electrophysiology interventions are performed under x-ray guidance with a C-arm imaging system. Some procedures require catheter navigation in complex anatomies like the left atrium. Navigation aids like 3D road maps and external tracking systems may be used to facilitate catheter navigation. As an alternative to external tracking a fully automatic method is presented here that enables the calculation of the 3D location of the ablation catheter from individual 2D x-ray projections. The method registers a high resolution, deformable 3D attenuation model of the catheter to a 2D x-ray projection. The 3D localization is based on the divergent beam projection of the catheter. On an individual projection, the catheter tip is detected in 2D by image filtering and a template matching method. The deformable 3D catheter model is adapted using the projection geometry provided by the C-arm system and 2D similarity measures for an accurate 2D/3D registration. Prior to the tracking and registration procedure, the deformable 3D attenuation model is automatically extracted from a separate 3D cone beam CT reconstruction of the device. The method can hence be applied to various cardiac ablation catheters. In a simulation study of a virtual ablation procedure with realistic background, noise, scatter and motion blur an average 3D registration accuracy of 3.8 mm is reached for the catheter tip. In this study four different types of ablation catheters were used. Experiments using measured C-arm fluoroscopy projections of a catheter in a RSD phantom deliver an average 3D accuracy of 4.5 mm.

Abstract:

Cardiac C-arm CT imaging delivers a tomographic region-of-interest reconstruction of the patient's heart during image guided catheter interventions. Due to the limited size of the flat detector a volume image is reconstructed, which is truncated in the cone-beam (along the patient axis) and the fan-beam (in the transaxial plane) direction. To practically address this local tomography problem correction methods, like projection extension, are available for first pass image reconstruction. For second pass correction methods, like metal artefact reduction, alternative correction schemes are required when the field of view is limited to a region-of-interest of the patient. In classical CT imaging metal artefacts are corrected by metal identification in a first volume reconstruction and generation of a corrected projection data set followed by a second reconstruction. This approach fails when the metal structures are located outside the reconstruction field of view. When a C-arm CT is performed during a cardiac intervention pacing leads and other cables are frequently positioned on the patients skin, which results in propagating streak artefacts in the reconstruction volume. A first pass approach to reduce this type of artefact is introduced and evaluated here. It makes use of the fact that the projected position of objects outside the reconstruction volume changes with the projection perspective. It is shown that projection based identification, tracking and removal of high contrast structures like cables, only detected in a subset of the projections, delivers a more consistent reconstruction volume with reduced artefact level. The method is quantitatively evaluated based on 50 simulations using cardiac CT data sets with variable cable positioning. These data sets are forward projected using a C-arm CT system geometry and generate artefacts comparable to those observed in clinical cardiac C-arm CT acquisitions. A C-arm CT simulation of every cardiac CT data set without cables served as a ground truth. The 3D root mean square deviation between the simulated data set with and without cables could be reduced for 96% of the simulated cases by an average of 37% (min -9%, max 73%) when using the first pass correction method. In addition, image quality improvement is demonstrated for clinical whole heart C-arm CT data sets when the cable removal algorithm was applied.

Abstract:

Radiofrequency ablation (RFA) therapy is the gold standard in interventional treatment of many cardiac arrhythmias. A major obstacle are non transmural lesions, leading to recurrence of arrhythmias. Recent clinical studies have suggested intracardiac electrogram (EGM) criteria as a promising marker to evaluate lesion development. Seeking for a deeper understanding of underlying mechanisms, we established a simulation approach for acute RFA lesions. Ablation lesions were modeled by a passive necrotic core surrounded by a borderzone with properties of heated myocardium. Herein, conduction velocity and electrophysiological properties were altered. We simulated EGMs during RFA to study the relation between lesion formation and EGM changes using the bidomain model. Simulations were performed on a three dimensional setup including a geometrically detailed representation of the catheter with highly conductive electrodes. For validation, EGMs recorded during RFA procedures in five patients were analyzed and compared to simulation results. Clinical data showed major changes in the distal unipolar EGM. During RFA, the negative peak amplitude decreased up to 104% and maximum negative deflection was up to 88% smaller at the end of the ablation sequence. These changes mainly occurred in the first 10 s after ablation onset. Simulated unipolar EGM reproduced the clinical changes, reaching up to 83% negative peak amplitude reduction and 80% decrease in maximum negative deflection for transmural lesions. In future work, the established model may enable the development of further EGM criteria for transmural lesions even for complex geometries in order to support clinical therapy.

Abstract:

Chronic atrial fibrillation (AF) is a complex disease with underlying changes in electrophysiology, calcium signaling and the structure of atrial myocytes. How these individual remodeling targets and their emergent interactions contribute to cell physiology in chronic AF is not well understood. To approach this problem, we performed in silico experiments in a computational model of the human atrial myocyte. The remodeled function of cellular components was based on a broad literature review of in vitro findings in chronic AF, and these were integrated into the model to define a cohort of virtual cells. Simulation results indicate that while the altered function of calcium and potassium ion channels alone causes a pronounced decrease in action potential duration, remodeling of intracellular calcium handling also has a substantial impact on the chronic AF phenotype. We additionally found that the reduction in amplitude of the calcium transient in chronic AF as compared to normal sinus rhythm is primarily due to the remodeling of calcium channel function, calcium handling and cellular geometry. Finally, we found that decreased electrical resistance of the membrane together with remodeled calcium handling synergistically decreased cellular excitability and the subsequent inducibility of repolarization abnormalities in the human atrial myocyte in chronic AF. We conclude that the presented results highlight the complexity of both intrinsic cellular interactions and emergent properties of human atrial myocytes in chronic AF. Therefore, reversing remodeling for a single remodeled component does little to restore the normal sinus rhythm phenotype. These findings may have important implications for developing novel therapeutic approaches for chronic AF.

Abstract:

Left atrial fibrosis is thought to contribute to the manifestation of atrial fibrillation (AF). Late Gadolinium enhancement (LGE) MRI has the potential to image regions of low perfusion, which can be related to fibrosis. We show that a simulation with a patient-specific model including left atrial regional fibrosis derived from LGE-MRI reproduces local activation in the left atrium more precisely than the regular simulation without fibrosis. AF simulations showed a spontaneous termination of the arrhythmia in the absence of fibrosis and a stable rotor center in the presence of fibrosis. The methodology may provide a tool for a deeper understanding of the mechanisms maintaining AF and eventually also for the planning of substrate-guided ablation procedures in the future.

Abstract:

In case of chest pain, immediate diagnosis of myocardial ischemia is required to respond with an appropriate treatment. The diagnostic capability of the electrocardiogram (ECG), however, is strongly limited for ischemic events that do not lead to ST elevation. This computational study investigates the potential of different electrode setups in detecting early ischemia at 10 minutes after onset: standard 3-channel and 12-lead ECG as well as body surface potential maps (BSPMs). Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard 12-lead ECG. To this end, a simulation study was performed for 765 different locations and sizes of ischemia in the left ventricle. Improvements by adding a single, subject specifically optimized electrode were similar to those of the BSPM: 211% increased detection rate depending on the desired specificity. Adding right-sided Wilson leads had negligible effect. Absence of ST deviation could not be related to specific locations of the ischemic region or its transmurality. As alternative to the ST time integral as a feature of ST deviation, the K point deviation was introduced: the baseline deviation at the minimum of the ST-segment envelope signal, which increased 12-lead detection rate by 7% for a reasonable threshold.

Abstract:

AIMS: Human ether-a-go-go-related gene (hERG) missense mutations N588K and L532P are both associated with atrial fibrillation (AF). However, the underlying gain-of-function mechanism is different. The aim of this computational study is to assess and understand the arrhythmogenic mechanisms of these genetic disorders on the cellular and tissue level as a basis for the improvement of therapeutic strategies. METHODS AND RESULTS: The IKr formulation of an established model of human atrial myocytes was adapted by using the measurement data of wild-type and mutant hERG channels. Restitution curves of the action potential duration and its slope, effective refractory period (ERP), conduction velocity, reentry wavelength (WL), and the vulnerable window (VW) were determined in a one-dimensional (1D) tissue strand. Moreover, spiral wave inducibility and rotor lifetime in a 2D tissue patch were evaluated. The two mutations caused an increase in IKr regarding both peak amplitude and current integral, whereas the duration during which IKr is active was decreased. The WL was reduced due to a shorter ERP. Spiral waves could be initiated by using mutation models as opposed to the control case. The frequency dependency of the VW was reversed. CONCLUSION: Both mutations showed an increased arrhythmogenicity due to decreased refractory time in combination with a more linear repolarization phase. The effects were more pronounced for mutation L532P than for N588K. Furthermore, spiral waves presented higher stability and a more regular pattern for L532P. These in silico investigations unveiling differences of mutations affecting the same ion channel may help to advance genotype-guided AF prevention and therapy strategies.

Abstract:

BACKGROUND: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air-liquid interface. RESULTS: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air-liquid interphase (ALI) by using the ALI deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stober method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the ALI were less sensitive to silica NPs as evidenced by reduced cytotoxicity and inflammatory responses. CONCLUSION: Amorphous silica NPs induced qualitatively similar cellular responses under submerged conditions and at the ALI. However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the ALI are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method.

Abstract:

The goal of ECG-imaging (ECGI) is to reconstruct heart electrical activity from body surface potential maps. The problem is ill-posed, which means that it is extremely sensitive to measurement and modeling errors. The most commonly used method to tackle this obstacle is Tikhonov regularization, which consists in converting the original problem into a well-posed one by adding a penalty term. The method, despite all its practical advantages, has however a serious drawback: The obtained solution is often over-smoothed, which can hinder precise clinical diagnosis and treatment planning. In this paper, we apply a binary optimization approach to the transmembrane voltage (TMV)-based problem. For this, we assume the TMV to take two possible values according to a heart abnormality under consideration. In this work, we investigate the localization of simulated ischemic areas and ectopic foci and one clinical infarction case. This affects only the choice of the binary values, while the core of the algorithms remains the same, making the approximation easily adjustable to the application needs. Two methods, a hybrid metaheuristic approach and the difference of convex functions (DC), algorithm were tested. For this purpose, we performed realistic heart simulations for a complex thorax model and applied the proposed techniques to the obtained ECG signals. Both methods enabled localization of the areas of interest, hence showing their potential for application in ECGI. For the metaheuristic algorithm, it was necessary to subdivide the heart into regions in order to obtain a stable solution unsusceptible to the errors, while the analytical DC scheme can be efficiently applied for higher dimensional problems. With the DC method, we also successfully reconstructed the activation pattern and origin of a simulated extrasystole. In addition, the DC algorithm enables iterative adjustment of binary values ensuring robust performance.

Abstract:

Electrocardiographic imaging (ECG imaging) is a method to depict electrophysiological processes in the heart. It is an emerging technology with the potential of making the therapy of cardiac arrhythmia less invasive, less expensive, and more precise. A major challenge for integrating the method into clinical workflow is the seamless and correct identification and localization of electrodes on the thorax and their assignment to recorded channels. This work proposes a camera-based system, which can localize all electrode positions at once and to an accuracy of approximately 1+/-1 mm. A system for automatic identification of individual electrodes is implemented that overcomes the need of manual annotation. For this purpose, a system of markers is suggested, which facilitates a precise localization to subpixel accuracy and robust identification using an error-correcting code. The accuracy of the presented system in identifying and localizing electrodes is validated in a phantom study. Its overall capability is demonstrated in a clinical scenario.

Abstract:

There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.

Abstract:

Umfassende Darstellung der Bandbreite bildgebender Modalitäten in der Medizin (z. B. Projektionsröntgen, Computertomographie und Magnetresonanztomographie)Detaillierte Information zu jedem Verfahren über das physikalische Grundprinzip, die gerätetechnische Umsetzung, die Qualitätsparameter und die medizinischen Applikationen.Für Studierende technischer Diplom-, Bachelor- und Masterstudiengänge an Universitäten und Fachhochschulen auf dem Gebiet der Biomedizinischen Technik aber auch für Studierende der Medizin sowie für Praktiker in der medizintechnischen Industrie und im medizinischen Bereich

Abstract:

The guide Heart rate signals provide valuable information for assessing the state of autonomic nervous system that control functioning of heart. Heart rate variability analysis is an important non-invasive tool that has been widely used for assessing autonomic control of heart using linear and non-linear techniques since last three decades. Different methods used to detect these beats include ECG, blood pressure etc. but ECG has great importance because it gives a complete and clear waveform. Heart rate variability analysis is a tool that assesses the autonomic nervous system. It is based on the measurement of changing heart rate signals. In past two decades a large number of research efforts were made and a number of techniques were proposed for heart rate variability. In this study, the techniques used for HRV analysis includes linear (time and frequency domain) and non-linear techniques. We have used different classifiers and their methods to check heart rate variations in healthy cases and diseased cases. Methods showing highest accuracy include Naïve Bayes method of Bayes classifier; sequential minimal optimization (SMO) of functions classifier, lazy locally weighted learning (LWL) method, AdaBoost and logical model tree. Among all these methods LMT (logical model tree) is considered as best method with the accuracy level of 92.5%. In this study 10 folds cross-validation was used as test option. Cross-validation is a technique to assess the accuracy of results where the goal is predicted. In 10 folds cross-validation 10 times repetition occurs and the result is obtained by taking mean accuracy.

Abstract:

Orientations of myocytes impact electric excitation propagation and mechanical contraction in the human heart. Measured fiber angles in experiments are obtained from different species (e. g. rat, canine, dog, human heart) and vary by various reasons. It is unclear to what ex- tent non-exact fiber angles impact the quality of computa- tional simulations. In this paper, mechanical simulations with different ventricular angles were performed and com- pared. The simulations covered the complete heart with both ventricles, both atria and the pericardium and were performed using finite element method. Helix angles were varied between 20\0 and 70\0 on endocardium and \070\0 and \020\0 on epicardium. Results showed that fiber ori- entations had only a minor contribution to the difference between endsystolic and enddiastolic pressure of < 8.3 %. The influence on stroke volume as well as AVPD is sig- nificant (changes by 34 % for SV and 241 % for APVD) , but it could not be observed that a higher AVPD yields a higher stroke volume. Concludingly, fiber orientations are important for reliable computational simulations of human hearts and should be incorporated with great care.

Abstract:

For the purpose of accurate preclinical drug screening and particularly to evaluate the risk of undesired cardiac arrhyth- mias or drug induced toxicity, human embryonic stem cell derived cardiomyocytes clusters can be used. A novelty micrcocavity array screening platform has been developed to facilitate recordings of extracellular field potentials and de- tect QT prolongation and cardiotoxic effects. The measured signal is similar to a human ECG with a missing P wave. In order to automate the drug screening process and delineate the filed potential recordings a signal-analyzing algorithm has been developed.

Abstract:

The risk stratification of sudden cardiac death after my- ocardial infarction plays an important role in cardiology. It influences the treatment of a patient and the use of im- plantable devices. However, the majority of well known methods for stratifying risk still fail to predict sudden car- diac death with high accuracy. The heart rate turbulence delivers good results that could be complemented by study- ing ECG morphology. For this purpose, the post extrasys- tolic T wave change was studied in this work. 10 patients with structural healthy ventricles were paced in the right ventricular apex and the subsequent response of the heart was measured in the ECG. Complementary, computer sim- ulations of the human transmembrane voltages and poste- rior ECG reconstruction were also carried out. Morpho- logical changes in the post extrasystolic T wave and its restitution to the original shape were measurable in every patient of this study. The patients presented diminished or alternating postectopic T waves and prolongation of T wave duration. However, the simulation does not present significant T wave changes. Furthermore, the new mor- phological parameters do not seem to correlate with the standard HRT parameters.

Abstract:

Pharmacological therapy of atrial fibrillation (AF) is still a major clinical challenge. Particularly AF of early onset has a significant familiar component and was asso- ciated with various gene mutations. In this study, we de- signed and optimized antiarrhythmic agents for atrial sub- strates affected by human ether-a`-go-go-related gene mu- tations L532P and N588K. A virtual multichannel blocker was designed aiming at a restoration of the wild-type (WT) action potential (AP) on the single cell and tissue level. Furthermore, the amiodarone and dronedarone concen- trations yielding the smallest difference between WT and mutated APs were identified. The WT AP at a basic cy- cle length (BCL) of 1000 ms could be restored by signifi- cant block of IK r and IK ur (\039%) and less pronounced block of IKs, ICa,L, Ib,Na, and Ib,Ca (&#63743;17%) for both mutations. Effective dronedarone concentrations of 88 nM for L532P and 40 nM for N588K yielded matches almost as good while amiodarone could not sufficiently restore the WT AP. APD90 restitution was effectively restored by the tuned N588K agent whereas differences of up to 34 ms were observed for low BCLs using the tuned L532P agent. Our results provide insight into the pharmacodynamic re- sponse of mutated myocytes and may aid in the optimiza- tion of patient group-specific therapeutic approaches.

Abstract:

Atrial fibrillation (AF) is a common arrhythmia with progressive nature. This progression is partly caused by AF itself by modifying amongst others the electrophysiological properties of the myocytes. These changes are referred to as electrical remodeling and were integrated in a computational model of human atrial myocytes in this work.In particular, the maximum conductivities of Ito, IK1, IKs, IKur, ICa,L, INa,Ca, and the Ca2+ leak current from the sarcoplasmic reticulum, as well as the cell capacitance were altered. In an additional setup, the influence of potential gap junction remodeling was investigated.Wavelength was reduced from 225 mm to 110 mm, respectively 92 mm when considering gap junction remodeling at a basic cycle length of 400 ms. Action potential morphology was changed from spike-and-dome to a more triangular repolarization phase. However, our results show that including IKur remodeling prevents the plateau phase from disappearing completely.

Abstract:

Catheter ablation of atrial fibrillation (AF) is still challenging and the sustaining mechanisms are discussed controversially. Basket mapping has emerged to a promising technique to detect temporary events like focal impulses fast changing fibrillation waves or meandering rotors.The aim of this study was to evaluate the atrial coverage of the basket catheter with respect to the distance of the electrodes to the endocardial surface and inter spline separation.

Abstract:

Atrial fibrillation (AF) is still a major health problem in the western society. Especially for familial AF, the pharmacological therapy is still not sufficiently successful. In this work, channel blocker properties were in-silico adapted to optimize drug therapy for patients suffering from familial AF. The Courtemanche-Ramirez-Nattel (CRN) cell model was the basis for the simulations. Adaptations in the model due to familial AF were implemented using an existing description of the L532P mutation. A fitting algorithm was designed which adapted all conductivities of the ion channels described in the CRN model to restore the healthy action potential (AP). To find the minimal deviation of the healthy AP and the AP of the L532P mutation, the trust-region-reflective algorithm was used. The best matched APs were achieved by a significant blockade of the IKr and the IKur current. 1D tissue strand simulations were performed using different basic cycle lengths (BCL) to evaluate the results of the optimization. It was shown that for the found adaptation of the conductivities, the AP duration, and the progressions of the conduction velocity, effective refractory period, and wavelength (WL) could be restored. The WL was increased by 53.37% compared to the mutation and had a value of 233.48 mm (BCL = 1 s).

Abstract:

Ectopic beats are a common cause for cardiac arrhythmia. The methods presented in this paper deal with the evaluation of the features that are used by an existing classifier to distinguish between normal, supraventricular ectopic and ventricular ectopic beats. In order to classify the beats, a support vector machine (SVM) is used. Since noisy features can confuse the classifier and downgrade its performance, high quality features should be chosen. In the end, the performance should be improved by using only the selected features after the evaluation process. For this purpose, a receiver operating character- istic (ROC) analysis was conducted first. Secondly, the Gini diversity index (GDI) was calculated for every feature which is often used as split criterion in decision trees. As a third evaluation tool, the information gain ratio (IGR) was applied to estimate the quality of the features. To conclude the evaluation part, a fourth analysis was implemented. The ROC was applied again to the beats that are falsely classified in a first run-through. This was a first step into a deeper investigation of the dependency among features. As result of the evaluation process, a feature ranking was built and 36 of the 55 features were chosen to build the new SVM. A training and testing process was conducted using beats of the MIT-BIH-Arrhythmia- Database. A correct rate of 98.574%, a sensitivity of 98.592% and a positive predictive value of 99.062% were achieved.

Abstract:

Fibrosis is strongly linked with the mechanisms of atrial fibrillation (AF), the most common arrhythmia. Direct electrotonic coupling between atrial myocytes and fibroblast has been suggested to contribute to these mechanisms. We use a 3D biophysical model of the atria to study the effects of fibrosis on atrial electrophysiology. Realistic tissue geometry, regional heterogeneity and myofiber anisotropy are integrated in the model. The model also accounts for the effects AF induced ionic remodeling, which has been shown to promote AF. The model simulations demonstrated that fibrosis significantly reduced both the atrial conduction velocity and action potential duration. Both these factors contributed to a large (45%) reduction of the atrial activation wavelength. This is comparable with the wavelength reduction (65%) due to ionic remodeling. As a result, the sustenance of re- entrant waves in the 3D atria was substantially increased with both fibrosis and remodeling. Hence, the elecrotonic changes induced by fibrosis can be comparable to those due to ionic remodeling, and both factors can provide substrate for re-entry in the 3D atria model.

Abstract:

Post-ablation atrial flutter(AF) is a frequently occurring arrhythmia after treatment for persistent atrial fibrillation. However, mapping the flutter circuit using intracardiac electrograms is often challenging due to low signal voltage and scar areas caused by prior substrate modification. In addition, signals are frequently compromised by ventricular far field (VFF) artifacts, which obscure atrial activity (AA). This work introduces a new approach for VFF removal, which is based on the Periodic Component Analysis (&#1113099;CA). It utilizes the stable temporal relationship between AA and VFF, which poses a problem for other techniques like Principal Component Analysis (PCA) when both components superpose. A benchmark using simulated electrograms demonstrated significantly better correlation for this case when comparing pure AA to the reconstructed data using &#1113099;CA instead of PCA (0.98 vs. 0.90, p<0.001). Its benefit for diagnosis is demonstrated on clinical data.

Abstract:

Electrocardiographic imaging (ECGI) is a non-invasive diagnostical tool solving the inverse problem of ECG, which means the reconstruction of electrical potentials in the heart from the ECG data. The ill-posednees of this problem makes necessary addition of a-priori information. A typical approach is the Tikhonov regularization looking for the best balance between minimizing the data misfit and the regularization term which characterizes desired properties of the solution. However, the quality of an obtained solution, and as a result its clinical relevance, could be significantly improved by application of methods for non-smooth regularization. In this work we introduced a possible dictionary definition for the electrical sources in the heart: we subdivided the heart into 100 pieces and considered them to constitute the columns of our dictionary. We also provided a short discussion on differences between synthesis and analysis models, tested the analysis algorithm with a penalty matrix which is not related to the defined dictionary (discrete gradient operator for all heart points) and compared the performance of these three algorithms for two simulated ventricular ectopic foci. The analysis method with the gradient operator showed a slightly superior performance although all methods correctly identified the regions of interest.

Abstract:

The problem of non-invasively finding cardiac electri- cal sources from body surface potential maps (BSPM) is ill-posed. A standard Tikhonov regularization approach to the problem produces a solution biased toward the elec- trodes and thus to the left ventricular epicardium, which limits its potential to reconstruct endocardial sources. In this work we consider a transmembrane voltages based in- verse problem of ECG for the identification of extrasys- tole origins from simulated BSPM. With use of a pair of heart wall epicardial/endocardial extrasystoles and a pair of septal ectopic foci we demonstrate the performance of the inverse procedures while firstly solving the problem for all nodes, then for epicardium and endocardium sep- arately. Based on the observations and the logic behind the gradient of sources we define simple rules on how to classify an extrasystole under consideration according to these 3 reconstructions. Furthermore, when the amount of noise is known, we propose a new method with two regu- larization parameters which assign different weightings to endocardial and epicardial components of the solution.

Abstract:

Solving the inverse problem of electrocardiography could help to diagnose and to plan the treatment of heart diseases. The conductivity distribution within the body is important to solve the inverse problem. In this work the influence of neglecting an organ as an inhomogeneity on the forward and inverse problem was investigated. For different simplified body models optimal conductivities were determined by minimizing the error between the BSPMs produced by this model and reference BSPMs calculated with a complex model containing eight segmented organs. The BSPMs from simulated catheter stimulations were used for the optimization. With the obtained optimal conductivities lead-field matrices were calculated and compared to the lead-field matrix of the complex model. Besides the heart, the lungs and the intracardial blood, we found that the liver also plays an important role to describe the relationship between the activation in the heart and the body surface potential map correctly.

Abstract:

There is still a need for research to understand the co- herences of the origin of arrhythmias such like rotors and possible ablation strategies. The aim of this work was the analysis of typical signal characteristics near a rotor cen- ter. Rotors were simulated on 2D patch geometry (100 mm x 100 mm) with spatial resolution of 0.1mm. Based on extracellular potentials, different features were evalu- ated: Local activation time, peak to peak amplitude, steep- est negative slope and approximate entropy were com- pared regarding their ability to indicate the rotor tip lo- cation. Furthermore, typical signal patterns of different mapping catheters centered at the rotor tip position were analyzed. The determined maximum distances between the focal point of phase singularities and determined centers by the peak to peak amplitudes were maximal 1.7 mm.

Abstract:

Direction of propagation (DOP) and conduction velocity (CV) of excitation waves are essential parameters to identify targets for catheter ablation of cardiac arrhythmias. Most approaches to determine the DOP and CV rely on manual anno- tation. Many, time-consuming measurements with mapping catheters are required. Aim of this work was to quantitatively extract the DOP and the CV of wavefronts from intracardiac electrograms with a single shot measurement. We used a simulation database of planar waves computed with a cellular automaton with different CVs between 500 mm/s and 1100 mm/s. By comparing the correct values of CV and DOP with the computed values from the developed algorithm the median CV- error was between 7 mm/s and 50 mm/s and the median DOP- error variated between 1\0 and 4\0.

Abstract:

Atrial fibrillation is the most frequent cardiac arrhythmia and often shows a progressive development. An important source of supraventricular extrasystoles triggering paroxysmal atrial fibrillation are the pulmonary veins. Electrograms recorded using an intracardiac catheter can help to improve the classification and quantification of the different atrial excitations. This study presents a framework to recognize and quantify different atrial excitation patterns and to merge them into groups using a clustering method on the basis of the local activation time. The resulting templates can be annotated by physicians and used as a training data set for a classifier to allocate following data. On the basis of the classification result statistics about the origin and occurrence rate of the different excitation patterns could be provided.

Abstract:

Electrocardiographic imaging (ECGI) facilitates the non-invasive reconstruction of electrical activity in the entire heart at once. ECGI requires both recordings of multi-channel ECG signals as well as an MRI-based model of the thorax. The model is used to solve the underlying Poissons problem, which relates the gradient of transmembrane voltages in the heart to the ECG and is a spatial differential equation. In ECGI, this relationship has to be established before starting inverse calculations, i.e. the forward problem has to be solved. It solution depends strongly on the spatial discretization of the model, as its resolution affects the representation of the source gradients. To study the convergence of resolution-related effects in the forward problem, we use a simplified thorax model which allows for very high resolutions. An ECG is produced for the excitation origin of a premature ventricular contraction in the apex. The study reveals that the greatest resolution-related effects vanish below a resolution of 5 mm of the cardiac tissue. At below 1 mm, resolution effects stabilize and only marginal effects from the spatial structure of the mesh persist down to a resolution of 0.25 mm.

Abstract:

(Poster)

Abstract:

Verfahren zur quantitativen Darstellung des Blutflusses in einer Gewebe- oder Adernregion basierend auf einem Signal eines in das Blut injizierten Kontrastmittels, wobei – zu aufeinander folgenden Zeitpunkten mehrere Einzelbilder (4) des von der Gewebe- oder Adernregion abgegebenen Signals aufgenommen und gespeichert werden, – für Bildpunkte von Einzelbildern (4) jeweils anhand des Signals eine für den Blutfluss charakteristische Größe und pro Bildpunkt eine weitere, für die Position der Adern charakteristische Größe aus dem Signal bestimmt wird, – diese Größen jeweils für die Bildpunkte bildpunktweise überlagert dargestellt (14) werden, – auf die Einzelbilder (4) vor der Bestimmung der Zeitpunkte eine Bewegungskompensation (7) angewandt wird, – zur Bewegungskompensation (7) über ein Kantendetektionsverfahren Kantenbilder von Einzelbildern (4) erzeugt werden, – Kantenbilder miteinander korreliert werden, um einen Verschiebungsvektor zu bestimmen und – die Korrelation des Kantenbildes eines Einzelbildes (4) jeweils mit einem Referenzbild erfolgt, welches weiterentwickelt wird, indem die Kantenbilder zweier miteinander korrelierter und verschobener Einzelbilder (4) im Referenzbild ergänzt werden.

Abstract:

Verfahren zum Ableiten medizinischer Größen aus einer Bildfolge medizinischer Bilddaten welche mit einer Kamera (4) aufgenommen werden, wobei Einzelbilder (11) der Bildfolge gespeichert werden und aus mehreren Einzelbildern (11) jeweils mindestens eine medizinische Größe abgeleitet und dargestellt wird, wobei bei der Aufnahme der Bildfolge Metadaten (17) aufgezeichnet werden, welche Aufschluss über die Aufnahmebedingungen geben und den Einzelbildern (11) zugeordnet werden und solche Daten als Metadaten (17) aufgezeichnet werden, welche sich auf die Helligkeit der Bilddaten auswirken, dadurch gekennzeichnet, dass als Metadaten (17) für die Helligkeitskorrektur (13) eingestellte Verstärkungsfaktoren einer die Bildfolge aufnehmenden Kamera (4) und Zeitpunkte, an denen sie geändert wurden, aufgezeichnet werden und als medizinische Größe ein Blutfluss in einem Gewebe- oder Aderngebiet aus der Bildfolge abgeleitet wird und die Kamera (4) durch unterschiedliche Verstärkungsfaktoren an eine unterschiedlich starke Fluoreszenz eines aufzunehmenden Gewebe- oder Aderngebiets angepasst wird, in welches zur Bestimmung des Blutflusses ein Fluoreszenzfarbstoff appliziert wird.

Abstract:

A magnetic resonance imaging system (300) acquires magnetic resonance data (358) from a subject (318) that may include an electrically conductive object (e.g. an implant or a medical device). The magnetic resonance imaging system includes a radio-frequency transmitter (314) for generating a radio-frequency transmit field for acquiring the magnetic resonance data using a radio-frequency antenna (310). The radio-frequency transmitter has multiple transmit channels. The radio-frequency antenna comprises multiple antenna elements (312) each adapted to connect to an antenna element. The amplitude and phase values of the RF transmit field of each of the transmit channels can be selected such that the magnetic field generated by the RF antenna is minimized at the location of the electrically conductive object, thereby reducing RF heating of the object.

Abstract:

A computer-implemented method for calculating a multi-dimensional wavelet transform in an image processing system comprising a plurality of computation units includes receiving multi-dimensional image data. An overlap value corresponding to a number of non-zero filter coefficients associated with the multi-dimensional wavelet transform is identified. Then the multi-dimensional image data is divided into a plurality of multi-dimensional arrays, wherein the multi-dimensional arrays overlap in each dimension by a number of pixels equal to the overlap value. A multi-dimensional wavelet transform is calculated for each multi-dimensional array, in parallel, across the plurality of computation units

Abstract:

A computer-implemented method for reconstruction of a magnetic resonance image includes acquiring a first incomplete k-space data set comprising a plurality of first k-space lines spaced according to an acceleration factor and one or more calibration lines. A parallel imaging reconstruction technique is applied to the first incomplete k-space data to determine a plurality of second k-space lines not included in the first incomplete k-space data set, thereby yielding a second incomplete k-space data set. Then, the parallel imaging reconstruction technique is applied to the second incomplete k-space data to determine a plurality of third k-space lines not included in the second incomplete k-space data, thereby yielding a complete k-space data set.

Abstract:

This work presents methods to advance electrophysiological simulations of intracardiac electrograms (IEGM). An experimental setup is introduced, which combines electrical measurements of extracellular potentials with a method for optical acquisition of the transmembrane voltage in-vitro. Thereby, intracardiac electrograms can be recorded under defined conditions. Using experimental and clinical signals, detailed simulations of IEGMs are parametrized, which can support clinical diagnosis.

Abstract:

In this work, a mathematical model of an elastically deformable basket catheter has been derived and implemented. It can be put into a patient-specic atrium dened by a triangular mesh. A graphical user interface has been developed that allows catheter positioning with immediate visual feedback. Catheter positions can be generated, saved and opened, and a quick view on the unipolar and full or pairwise bipolar electrogram is possible if the simulated extracellular potentials are available for that geometry.The catheter model has been parameterized to reject the geometry of a Constellation and FIRMap catheter, respectively. A representative set of clinically relevant catheter positions in a patient-specic left and right atrial geometry has been generated in close collaboration with an experienced cardiologist. Combined visualizations of the atrial geometry, the electrogram of selected electrodes and the transmembrane voltage distribution have been produced. It was noted that the electrode spacing must be smaller than half the wave length to be able to identify individual linear wavefronts and calculate the wave propagation velocity and direction. Statistics of atrial coverages, spline-spline distances and electrode-endocard distances have been created and compared between the Constellation and FIRMap basket catheter. The FIRMap catheter yields a better atrial coverage, but the Constellation catheter electrodes generally come to lie closer to the myocardium and therefore provide electrograms with a better signal-to-noise ratio. In addition, due tothe smaller distance between the Constellation electrodes, the activations can be localized more precisely in space and time.Furthermore, a new storage format for simulation data has been introduced. It allows to read signals at given locations in fractions of a second. Before, this process took about one hour.In future, catheter statistics like the atrial coverage and the spline-spline distance can be compared to catheter positions mapped in the clinic. But most notably, signal processing has to be done with the xtracted electrograms. It has to be evaluated whether interesting events like ectopic foci, rotors and flutter circuits can really be detected and localized with basket catheters, or if sequential high density mapping will remain the only approach providing sucient coverage and resolution.

Abstract:

In the course of this work, two clinical cases of AFlut were examined with the goal of simulating the clinical flutter circuit in a computer model in order to support the physician during diagnosis and therapy of AFlut. Initially, anatomical features of the flutter circuit such as scars, were detected manually. With the help of the manual detection, the electrodes were classified and their signals analyzed. The analysis results did not show correlations between the morphology of the intracardiac EGM and the anatomical feature of the location of the corresponding electrode. Thus, the analysis results did not allow an automated detection of anatomical characteristics of the flutter circuit. The manual detection was used to parametrize the flutter circuit. Subsequently, the latter was simulated using the FaMa algorithm. The implemented methods enabled the FaMaS to deal with anatomical conditions of the clinical geometry, and thus to simulate clinical flutter circuits. In a further step, the FaMaS was used to estimate the global CV which provided good results. For the simulation of clinical cases of AFlut, it was necessary to estimate the local CV, for example to consider slow conduction areas. For simulated test cases, the estimation of the local CV led to good results. The local estimation for clinical cases of AFlut required several constraints. The clinical LAT maps which provided a basis for the approximation of the local CV, were interpolated and manually modified in the range of clinically realistic values. Besides, the range of the permissible CV was limited. By estimating the local CV, the propagation on the atrial surface can be approximated. The clinical measurement was not patterned exactly as the resulting LATs showed. To conclude, the FaMa algorithm was extended by implementations which enabled the fast simulation of clinical cases of AFlut, at which anatomical features of the flutter circuit were detected manually. The average CV can be approximated by the implemented global estimation method. With the help of the local estimation, the excitation propagation can be described, but the LAT results deviated too much from the clinical measurement. Due to manual editing, the procedure is not yet usable for automatic processing of clinical cases of AFlut. All in all, this work provided the interface between the clinical measurement and the simulation of AFlut in a fast computer model. The simulated flutter circuit was parametrized, and described the clinical measurement qualitatively.