Atrial arrhythmias are frequently treated using catheter ablation during electrophysiological (EP) studies. However, success rates are only moderate and could be improved with the help of personalized simulation models of the atria. In this work, we present a workflow to generate and validate personalized EP simulation models based on routine clinical computed tomography (CT) scans and intracardiac electrograms. From four patient data sets, we created anatomical models from angiographic CT data with an automatic segmentation algorithm. From clinical intracardiac catheter recordings, individual conduction velocities were calculated. In these subject-specific EP models, we simulated different pacing maneuvers and measurements with circular mapping catheters that were applied in the respective patients. This way, normal sinus rhythm and pacing from a coronary sinus catheter were simulated. Wave directions and conduction velocities were quantitatively analyzed in both clinical measurements and simulated data and were compared. On average, the overall difference of wave directions was 15° (8%), and the difference of conduction velocities was 16 cm/s (17%). The method is based on routine clinical measurements and is thus easy to integrate into clinical practice. In the long run, such personalized simulations could therefore assist treatment planning and increase success rates for atrial arrhythmias.
Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusion-induced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample.
This review article gives a comprehensive survey of the progress made in computa- tional modeling of the human atria during the last 10 years. Modeling the anatomy has emerged from simple peanut-like structures to very detailed models including atrial wall and fiber di- rection. Electrophysiological models started with just two cellular models in 1998. Today, five models exist considering e.g. details of intracellular compartments and atrial heterogeneity. On the pathological side, modeling atrial remodeling and fibrotic tissue are other important aspects. The bridge to data that are measured in the catheter laboratory and on the body surface (ECG) is under construction. Every measurement can be used either for model personalization or for validation. Potential clinical applications are briefly outlined and future research perspectives are suggested.
Despite the commonly accepted notion that action potential duration (APD) is distributed heterogeneously throughout the ventricles and that the associated dispersion of repolarization is mainly responsible for the shape of the T-wave, its concordance and exact morphology are still not completely understood. This paper evaluated the T-waves for different previously measured heterogeneous ion channel distributions. To this end, cardiac activation and repolarization was simulated on a high resolution and anisotropic biventricular model of a volunteer. From the same volunteer, multichannel ECG data were obtained. Resulting transmembrane voltage distributions for the previously measured heterogeneous ion channel expressions were used to calculate the ECG and the simulated T-wave was compared to the measured ECG for quantitative evaluation. Both exclusively transmural (TM) and exclusively apico-basal (AB) setups produced concordant T-waves, whereas interventricular (IV) heterogeneities led to notched T-wave morphologies. The best match with the measured T-wave was achieved for a purely AB setup with shorter apical APD and a mix of AB and TM heterogeneity with M-cells in midmyocardial position and shorter apical APD. Finally, we probed two configurations in which the APD was negatively correlated with the activation time. In one case, this meant that the repolarization directly followed the sequence of activation. Still, the associated T-waves were concordant albeit of low amplitude.
T. Voigt, H. Homann, U. Katscher, and O. Doessel. Patient-individual local SAR determination: in vivo measurements and numerical validation. In Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 68(4) , pp. 1117-1126, 2012
Tissue heating during magnetic resonance measurements is a potential hazard at high-field MRI, and particularly, in the framework of parallel radiofrequency transmission. The heating is directly related to the radiofrequency energy absorbed during an magnetic resonance examination, that is, the specific absorption rate (SAR). SAR is a pivotal parameter in MRI safety regulations, requiring reliable estimation methods. Currently used methods are usually based on models which are neither patient-specific nor taken into account patient position and posture, which typically leads to the need for large safety margins. In this work, a novel approach is presented, which measures local SAR in a patient-specific manner. Using a specific formulation of Maxwell's equations, the local SAR is estimated via postprocessing of the complex transmit sensitivity of the radiofrequency antenna involved. The approximations involved in the proposed method are investigated. The presented approach yields a sufficiently accurate and patient-specific local SAR measurement of the brain within a scan time of less than 5 min.
Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting around 1% of the population. Several anti-arrhythmic drugs such as e.g. amiodarone or dronedarone influence cardiac electrophysiology reducing arrhythmias. However, the electrophysiological mechanisms underlying the initiation and persistence of AF are not completely understood yet.Methods: A mathematical model of atrial electrophysiology was modified to simulate the effects of chronic AF (cAF). Furthermore, ion channel conductivities were reduced according to the inhibition caused by two different concentrations of amiodarone and dronedarone. The resulting drug effects were investigated in healthy and cAF single-cells as well as in tissue. In a 1D tissue strand, restitution curves of the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) were computed. Furthermore, persistence of rotors in a 2D tissue patch was analyzed. For this purpose, four rotors were initiated in the cAF patch and then the drug effects were incorporated.Results: Dronedarone and amiodarone prolonged the atrial action potential duration of cAF cells, whereas high concentration of amiodarone slightly shortened it in healthy cells. Furthermore, both drugs increased the ERP and slowed the CV. Dronedarone shows the longer ERP and also a higher CV. As a result, the WL was prolonged by dronedarone and shortened by high concentration of amiodarone. Low concentration of amiodarone did not change the WL. In the 2D tissue patch, dronedarone altered significantly the trajectory of rotors, but did not terminate them.Conclusion: Computer simulations of the effects of antiarrhythmic drugs on cardiac electrophysiology are a helpful tool to better understand the mechanisms responsible for persistence and termination of AF. However, ion current measurement data available in literature show great variability of values depending on the species or temperature. Therefore, integration of drug effects into models of cardiac electrophysiology still needs to be improved.
Aims Amiodarone and cisapride are both known to prolong the QT interval, yet the two drugs have different effects on arrhythmia. Cisapride can cause torsades de pointes while amiodarone is found to be anti-arrhythmic. A computational model was used to investigate the action of these two drugs.Methods and results In a biophysically detailed model, the ion current conductivities affected by both drugs were reduced in order to simulate the pharmacological effects in healthy and ischaemic cells. Furthermore, restitution curves of the action potential duration (APD), effective refractory period, conduction velocity, wavelength, and the vulnerable window were determined in a one-dimensional (1D) tissue strand. Moreover, cardiac excitation propagation was computed in a 3D model of healthy ventricles. The corresponding body surface potentials were calculated and standard 12-lead electrocardiograms were derived. Both cisapride and amiodarone caused a prolongation of the QT interval and the refractory period. However, cisapride did not significantly alter the conduction-related properties, such as e.g. the wavelength or vulnerable window, whereas amiodarone had a larger impact on them. It slightly flattened the APD restitution slope and furthermore reduced the conduction velocity and wavelength.Conclusion Both drugs show similar prolongation of the QT interval, although they present different electrophysiological properties in the single-cell as well as in tissue simulations of cardiac excitation propagation. These computer simulations help to better understand the underlying mechanisms responsible for the initiation or termination of arrhythmias caused by amiodarone and cisapride.
Book Chapters (3)
O. Dössel. Patientenmodelle. In Innovationsreport 2012 - Personalisierte Medizintechnik, Deutsche Gesellschaft für Biomedizinische Technik (DGBMT), pp. 14-19, 2012
A. Kramlich, J. Bohnert, and O. Dössel. Transmembrane voltages caused by magnetic fields - numerical study of schematic cell models. In Magnetic Particle Imaging: A Novel Spio Nanoparticle Imaging Technique, T. Buzug, J. Borgert (eds), Springer-Verlag Berlin Heidelberg, pp. 337-342, 2012
Due to forthcoming use of MPI on humans there is an urgent need for a thorough research on possible adverse effects of this technique on patients health. However, the health impact of exposure to time-varying magnetic fields in a frequency range between 10 kHz and 100 MHz, such as the MPI drive field, are still poorly investigated.The current paper intends to give an overview on an in-silico approach to investigation of stimulating effects that could be caused by the MPI drive field. For this purpose, cell models of myocardiocyte, myocyte and neurocyte, as well as a suitable setup for the simulation of the exposure to time-varying magnetic fields have been developed. The evaluation of performed simulations was carried out on the basis of transmembrane voltage elevation and induced current densities.
G. Seemann, M. W. Krueger, and M. Wilhelms. Elektrophysiologische Modellierung und Virtualisierung für die Kardiologie - Methoden und potenzielle Anwendungen. In Der virtuelle Patient, W. Niederlag, H. Lemke, H. Lehrach (eds), Health Academy, pp. 98-116, 2012
Simulationen des elektrophysiologischen Verhaltens des Herzens fördern das Verständnis über die Mechanismen innerhalb des Herz-Kreislauf-Systems. Darüber hinaus werden diese mathematischen Modelle die Diagnose und Therapie von Patienten, die unter Herzerkrankungen leiden, unterstützen. In dieser Arbeit wird die Vorgehensweise für die Modellierung der elektrischen Funktion des Herzens beschrieben. Hierfür werden die Modellierung der Geometrie, der kardialen Elektrophysiologie, der elektrischen Erregungsausbreitung und der EKG-Berechnung kurz erläutert. Die seit Kurzem mehr und mehr untersuchten Fälle Ischämie und personalisierte Vorhofmodellierung werden beispielhaft beschrieben und zeigen, wie die Modellierung des Herzens dazu benutzt werden kann, um Kardiologen bei der Beantwortung von offenen Fragen zu unterstützen.
M. W. Keller, G. Seemann, and O. Dössel. Simulating extracellular microelectrode recordings on cardiac tissue preparations in a bidomain model. In Biomedizinische Technik / Biomedical Engineering, vol. 57(s1) , pp. 814, 2012
M. W. Krueger. Towards Personalized Clinical in-silico Modeling of Atrial Anatomy and Electrophysiology. In cDEMRIS 2012, 2012
Biophysical models of the human atria have proven to aid the understanding of disease mechanisms and therapeutic measures in basic research. Atrial modeling is currently in a transition from the sole use in basic research to future clinical applications.In order to use biophysical models in a clinical environment, the anatomical and electrophysiological models need to be personalized to the specific patient. The methods for this require to be largely automatic and should also allow for the evaluation of the simulation outcome. A-priori knowledge of the human anatomy and electrophysiology needs to be merged with MRI, ECG and intracardiac electrogram data to achieve such model personalization. Additionally, information from DE-MRI can be transferred into complex atrial models to evaluate ablation therapy outcome for the specific patient.In the future, complex models will continue to allow for a further understanding of pathological mechanisms, but they will also enable the development of simplified models which can be introduced into the clinic. Interactive virtual atria will in such manner pave the way for model-based personalized radio-frequency ablation planning.
M. W. Krueger, G. Seemann, and O. Dössel. Towards personalized biophysical models of atrial anatomy and electrophysiology in clinical environments. In Biomedizinische Technik / Biomedical Engineering, vol. 57(s1) , 2012
Model-based segmentation approaches have been proven to produce very accurate segmentation results while simultaneously providing an anatomic labeling for the segmented structures. However, variations of the anatomy, as they are often encountered e.g. on the drainage pattern of the pulmonary veins to the left atrium, cannot be represented by a single model. Automatic model selection extends the model-based segmentation approach to handling significant variational anatomies without user interaction. Using models for the three most common anatomical variations of the left atrium, we propose a method that uses an estimation of the local fit of different models to select the best fitting model automatically. Our approach employs the support vector machine for the automatic model selection. The method was evaluated on 42 very accurate segmentations of MRI scans using three different models. The correct model was chosen in 88.1 % of the cases. In a second experiment, reflecting average segmentation results, the model corresponding to the clinical classification was automatically found in 78.0 % of the cases.
G. Lenis, T. Baas, and O. Dössel. Rhythmical and morphological features of the ECG following a premature ventricular contraction. In 46. Jahrestagung der DGBMT im VDE. Proceedings BMT 2012(s1) , 2012
The analysis of the heart rate turbulence (HRT) can be used to evaluate the risk of sudden cardiac death. For that purpose ectopic beats have to be classified. A method for automatic ectopic beat detection and classification based on a Support-Vector-Machine (SVM) was developed before. In this work an analysis similar to the HRT was carried out on the morphological features of the QRS complex and the T wave of the ECG following a ventricular premature contractions (VPC). A study of 56 subjects, suffering from a various number of ventricular premature contractions was conducted.
G. Lenis, T. Baas, and O. Dössel. Artefaktdetektion im Elektrokardiogramm, um eine robustere Extrasystolenerkennung und Klassifizierung zu ermöglichen. In Biosignalverarbeitung und Magnetische Methoden in der Medizin. Proceedings BBS 2012, 2012
Die Analyse der Herz Raten Turbulenz (HRT) dient der Vorhersage eines ploetzlichen Herztodes. Hierzu muessen die ektopen Schlaege im EKG ausgewertet werden. Zur automatischen Detektion und Klassifikation ektoper Schlaege wurde 2010 eine Methode entwickelt, welche auf Basis einer Support-Vector-Machine (SVM) die Schlaege klassifiziert. Artefakte im EKG-Signal fuehren nicht selten zur Fehlklassifizierung, da sie nicht vollstaendig von ektopen Schlaegen unterschieden werden koennen. Um die Genauigkeit die HRT Analyse zu verbessern, wurde ein Algorithmus zur automatischen Unterscheidung von Artefakten und ektopen Schlaegen entwickelt.
Whole organ scale patient specific biophysical simulations contribute to the understanding, diagnosis and treatment of complex diseases such as cardiac arrhythmia. However, many individual steps are required to bridge the gap from an anatomical scan to a personal- ized biophysical model. In biophysical modeling, differential equations are solved on spatial domains represented by volumetric meshes of high resolution and in model-based segmentation, surface or volume meshes represent the patients geometry. We simplify the personalization pro- cess by representing the simulation mesh and additional relevant struc- tures relative to the segmentation mesh. Using a surface correspondence preserving model-based segmentation algorithm, we facilitate the inte- gration of anatomical information into biophysical models avoiding a complex processing pipeline. In a simulation study, we observe surface correspondence of up to 1.6mm accuracy for the four heart chambers. We compare isotropic and anisotropic atrial excitation propagation in a personalized simulation.
D. Potyagaylo, W. H. W. Schulze, and O. Dössel. Solving the transmembrane potential based inverse problem of ECG under physiological constraints on the solution range. In Biomedizinische Technik / Biomedical Engineering, vol. 57(s1) , pp. 170, 2012
In this paper we propose an iteratively regularized Gauss-Newton method to solve the inverse ECG problem and efficiently choose the parameter of regularization. The classical stopping criterium for this regularization technique Morozov discrepancy principle, cannot be used in our application because the noise level estimate and problem model error are typically not available. We formulate the stopping rule based on the statistical formulation of the parameter and the physiological nature of the sought solution. With Laplace operator as a regularization matrix, the regularization parameter can be seen as an indirect measure of deviation in the solution: smaller parameters lead to a broader solution range. From our knowledge about electrophysiology of the heart we can assume values of −85 mV and +25 mV as a lower and an upper estimates for transmembrane potentials. Under this assumption we stop Gaus-Newton iteration as soon as the difference between solution smallest and largest values achieves 110 mV. Three simulation protocols confirm our ansatz: the proposed method was compared with the commonly used in the feld L-curve based Tikhonov method, showing superior performance during an initial phase of an ectopic heart activation sequence.
Cardiac electrophysiology procedures are routinely used to treat patients with rhythm disorders. The success rates of ablation procedures and cardiac resynchronization therapy are still sub-optimal. Recent advances in medical imaging, image processing and cardiac biophysical modeling have the potential to improve patient outcome. This manuscript provides an overview of how these advances have been translated into the clinical environment.
W. H. W. Schulze, D. Potyagaylo, and O. Dössel. Activation time imaging in the presence of myocardial ischemia: Choice of initial estimates for iterative solvers. In Computing in Cardiology, 2011, vol. 39, pp. 961-964, 2012
In this work, a simulation study is performed that demonstrates how activation times of cardiac action potentials can be reconstructed from body surface potential maps (BSPMs). An extrasystole is simulated in the ventricles, which are affected by myocardial ischemia or necrosis, and the related BSPM is calculated. Initial estimates are required for iterative algorithms that solve the related non-linear reconstruction problem. As a good initial estimate is essential for a proper reconstruction, the robustness of two methods is tested against the influence of pathological conditions: the critical times method and a linear timeintegral based method. While the first method extrapolates activation times into inactive tissue in this study, the latter carves out ischemic or necrotic tissue as homogeneous regions. In an outlook, a concept for the combination of both methods is proposed.
The heart rate is mediated by the G protein-coupled muscarinic receptor (M2R) activating the acetylcholine (ACh)-dependent K+ current (IKACh). Here, a novel model for IKACh gating is presented based on recent findings that M2R agonist binding is voltage-sensitive. Furthermore, ACh and pilocarpine (Pilo) manifest opposite voltage-dependent IKACh modulation. In a previous work, a 4-state Markov model of M2R reconstructing the voltage-dependent change in agonist affinity was proposed. In this work, a 2-state Markov model of IKACh gating purely dependent on the Gβγ concentration is proposed. IKACh is modeled based on the description of Zhang et al. Measurement data are used to parametrize the combined M2R and IKACh model for both ACh and Pilo. The channel model has a linear Gβγ dependent forward and a constant backward rate. For ACh and Pilo, optimal values of model parameters are found reconstructing the measured opposite voltage-dependent change in agonist affinity. The combined model is able to reconstruct the measured data regarding the agonist and voltage-dependent properties of the M2R-IKACh channel complex. In future studies, this channel will be integrated in a sinus node model to investigate the effect of the channel properties on heart rate
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is mainly sustained by reentrant circuits and rapid ectopic activity. In the present study, we performed computer simulations using a 3D human atrial model including fibre orientation, electrophysiological heterogeneities and tissue anisotropy. Membrane kinetics were described as in the human atrial action potential model by Maleckar et al., including AF-induced ionic remodeling. The impact of ionic changes on reentrant activity was investigated by characterizing arrhythmia stability, rotor dynamics and dominant frequency (DF). Our simulations show that reentrant circuits tend to organize around the pulmonary veins and the right atrial appendage. Simulated IK1 and INa blocks lead to slower DF in the whole atria, expanded wave meandering and reduction of secondary wavelets. INaK block slightly reduces DF and does not notably change the propagation pattern. Regularity and coupling indices of electrograms are usually higher in the right atrium than in the left atrium, entailing a higher likelihood of arrhythmia generation in the latter, as occurs in AF patients.
Generally, models of cardiac electrophysiology describe physiologic conditions in detail. However, other conditions, such as drug interactions or mutations of ion channels are of interest for research. Therefore, the simulated ion currents have to be fitted to measured voltage or patch clamp data. In this work, three different methods for the model parametrization were compared: one based on Powells algorithm implemented in a modular C++ framework and two optimization techniques realized in Matlab. The latter two approaches differed in solving the ordinary differential equations describing the channel gating. They can either be approximated numerically or solved analytically, since the transmembrane voltage is a piecewise constant function during the applied clamp protocol. All three methods were compared regarding computing time and quality of the fit using least squares. The modular C++ framework was slower than the numerical Matlab method, which took longer than the analytical one. The quality of the fit was similar for almost all analyzed methods. Therefore, the analytical method grants a fast and reliable solution for the calibration of ion current models for applications with constant membrane voltage, as e.g. in case of voltage or patch clamp data.
Various types of heart disease are associated with structural remodeling of cardiac cells. In this work, we present a software framework for automated analyses of structures and protein distributions involved in excitation-contraction coupling in cardiac muscle cells (myocytes). The software framework was designed for processing sets of three-dimensional image stacks, which were created by fluorescent labeling and scanning confocal microscopy of ventricular myocytes from a rabbit infarction model. Design of the software framework reflected the large data volume of image stacks and their large number by selection of efficient and automated methods of digital image processing. Specifically, we selected methods with small user interaction and automated parameter identification by analysis of image stacks. We applied the software framework to exemplary data yielding quantitative information on the arrangement of cell membrane (sarcolemma), the density of ryanodine receptor clusters and their distance to the sarcolemma. We suggest that the presented software framework can be used to automatically quantify various aspects of cellular remodeling, which will provide insights in basic mechanisms of heart diseases and their modeling using computational approaches. Further applications of the developed approaches include clinical cardiological diagnosis and therapy planning.
Anatomically realistic computational models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. In recent years, novel techniques have been developed to construct structurally-detailed, image-based models of 3D atrial anatomy. However, computational models still do not contain full descriptions of the atrial intramural myofiber architecture throughout the entire atria. To address this, a semi-automatic rule-based method was developed for generating multi-layer myofiber orientations in the human atria. The rules for fiber generation are based on the careful anatomic studies of Ho, Anderson and co-workers using dissection, macrophotography and visual tracing of fiber tracts. Separately, a series of high color contrast images were obtained from sheep atria with a novel confocal surface microscopy method. Myofiber orientations in the normal sheep atria were estimated by eigen-analyis of the 3D image structure tensor. These data have been incorporated into an anatomical model that provides the quantitative representation of myofiber architecture in the atrial chambers. In this study, we attempted to compare the two myofiber generation approaches. We observed similar myo-bundle structure in the human and sheep atria, for example in Bachmann's bundle, atrial septum, pectinate muscles, superior vena cava and septo-pulmonary bundle. Our computational simulations also confirmed that the preferential propagation pathways of the activation sequence in both atrial models is qualitatively similar, largely due to the domination of the major muscle bundles.
T. Baas. ECG based analysis of the ventricular repolarisation in the human heart. KIT Scientific Publishing. Dissertation. 2012
ECG recordings provide diagnostic relevant information on the de- and repolarisation sequences of the heart. A modification of the repolarisation sequence is assumed to cause Torsades de Pointes. Especially drug induced effects on the repolarisation processes are in focus, since some non-cardiac drugs have been associated with sudden cardiac death in the 1990s. The analysis of the ventricular repolarisation using a set of parameters depicting the morphology of the T-wave is introduced in this work. Therefore, new methods of fully automatic patient-specific QRS detection, beat classification and precise T-wave delineation are presented. Using these methods, medical studies are investigated regarding the modification of the T-wave by different compounds. Also the impact of the heart rate on the morphology of the T-wave is part of this research.The reliable identification of ventricular ectopic beats allows an analysis of the influence of these beats on subsequent heart beats. It turned out that the morphology of subsequent heart beats can significantly be changed. This might give new information on the proarrythmical risk of ventricular ectopic beats.
J. Bohnert. Effects of time-varying magnetic fields in the frequency range 1 kHz to 100 kHz upon the human body. KIT Scientific Publishing. Dissertation. 2012
In this work, the physiological effects of time-varying magnetic fields up to 100 kHz have been investigated, namely magnetic stimulation and body warming. Simulation studies were based on numerical calculations on sophisticated cell and body models. In addition, magnetic stimulation thresholds have been determined experimentally. The project was carried out within the scope of the development of Magnetic Particle Imaging, a new imaging technology for medical diagnostics.
H. Homann. SAR Prediction and SAR Management for Parallel Transmit MRI. KIT Scientific Publishing. Dissertation. 2012
Parallel transmission enables control of the RF field in high-field Magnetic Resonance Imaging (MRI). However, the approach has also caused concerns about the specific absorption rate (SAR) in the patient body. The present work provides new concepts for SAR prediction. A novel approach for generating human body models is proposed, based on a water-fat separated MRI pre-scan. Furthermore, this work explores various approaches for SAR reduction.
O. Jarrousse. Modified mass-spring system for physically based deformation modeling. KIT Scientific Publishing. Dissertation. 2012
Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented.
C. Schilling. Analysis of atrial electrogram. KIT Scientific Publishing. Dissertation. 2012
This work provides methods to measure and analyze features of atrial electrograms - especially complex fractionated atrial electrograms (CFAEs) - mathematically. Automated classification of CFAEs into clinical meaningful classes is applied and the newly gained electrogram information is visualized on patient specific 3D models of the atria. Clinical applications of the presented methods showed that quantitative measures of CFAEs reveal beneficial information about the underlying arrhythmia.
Student Theses (26)
S. Bauer. Estimating intracellular conductivity tensors from fluorescent labeling and three-dimensional scanning confocal microscopy data of rabbit tissue. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
In this work, an in-silico model of conduction, based on confocal microscopic data of rabbit ventricular tissue, was developed. Confocal microscopy combined with fluorescent tissue labeling are able to image the tissue geometry with high resolution. This information was used to gain further insights into the anisotropy of electrical conduction in the myocardium, which is highly dependent on the specific tissue geometry. The cell nucleus, gap junction connexin43, fibroblasts and collagen were labeled with fluorescent dyes of different spectra. In a previous work, these data were used to quantify the volume fractions of myocytes, fibroblasts and the extracellular space. Additionally, the extracellular conductivity tensor was estimated and the amount of coupling gap junctions in the vicinity of fibroblasts was quantified. In this work, the intracellular conductivity tensors was estimated from the confocal microscopic data. Therefore, the myocytes were segmented and the gap junction density in-between myocytes was extracted. With assuming conductivities for intracellular liquid and gap junction resistance, a numerical field calculation was performed for three principal directions in order to extract intracellular conductivity tensors.
L.-M. Busch. Modeling of the elastomechnical properties of radio-frequency ablation scars: influence of different lesion patterns on cardiac contraction. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
P. Caroli. Simulation der Kinetik von Silicia-Nanopartikeln unter Berücksichtigung der Größe, Ladung, Dosis, Agglomeration und Proteinkorona. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
H. Gao. Aufbau und Ansteuerung einer High-Power-LED-Lichtquelle, für die fluoreszenzoptische Messung der Transmembranspannung von Kardiomyozyten. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
H. Hettmann. Benchmarking electrophysiological models of human atrial myocytes. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
Investigating remedies for atrial fibrillation and the mechanisms underlying this tachycardia, the opportunities to operate directly on human atrial myocytes are limited since it is not easy to get experimental data of human atrial tissue in satisfactory quality. The results obtained with experiments on animals are also of limited validity and have to be adjusted because of the differences to human cell physiology. In silico studies, as a further possibility of scientific research, enable the computer based examination of physiological processes during atrial fibrillation as well as the supporting and inhibiting effects the respective drugs hypothetically have on them.In recent years, several mathematical cell models were published, which are a helpful device for the improved comprehension of atrial electrophysiology by computer simulations. Especially the atrial cell model developed by Courtemanche et al. was investigated in previous studies and reveals weaknesses is some aspects, as for instance the intracellular calcium handling.The aim of the current work is the comparison of the model of Courtemanche et al. with the four other mathematical cell models developed by Nygren et al., Maleckar et al., Koivumäki et al., and Bueno-Orovio et al. in order to determine the model, which is best suitable for simulations of healthy and also pathologically altered tissue. For this purpose, various simulations of single cells, as well as of one- and two-dimensional tissue patches are carried out using the five cell models. Aside from the examination of the physiological correctness and accordance to experimental data of human atrial myocytes, the results obtained by simulations are also compared among each other with regard to stability and velocity of the computation.
R. Jones. Towards a personalised volume conductor parameterisation in ECG imaging. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
N. Konrad. Methoden für die Integration von Ionenstrommessdaten in Modelle kardialer Elektrophysiologie. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
A. Kurz. In-silico assessment of the influence of the membrane voltage and agonist/antagonist binding dependent muscarinic M2 receptor on IKACh in the rabbit sinus node. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
S. Laubersheimer. Simulationsbasierte Kalibrierung eines Teilkörperzählers mit Reinstgermaniumdetektoren für den Nachweis inkorporierter Radionuklide. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
G. Lenis. Analysing rhythmical and morphological ECG properties to detect the influence of ectopic beats. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
V. Lupici-Baltzer. Automatic initiation and investigation of atrial fibrillation in electrically remodeled tissue. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
P. Mackens. 3D reconstruction of ECG electrode positions from multiple photographic images. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
R. Moss. Simulation of the chronotropic effect of voltage dependent M2 receptor agonist binding on the rabbit sinus node and atrium. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
The normal heart rate is mediated by the G-protein-coupled, acetylcholine (ACh)- activated inward rectifier K+ current (IK,ACh). A unique feature of IK,ACh is the so- called relaxation gating property that contributes to increased current at hyperpolarized membrane potentials. This Bachelor thesis is considering a novel explanation for IK,ACh relaxation based upon recent findings that G-protein-coupled receptors are intrinsically voltage sensitive and that the muscarinic agonists acetylcholine and pilocarpine manifest opposite voltage-dependent IK,ACh modulation. Based on experimental and computa- tional findings, [Moreno-Galindo et al., 2011] proposed that IK,ACh relaxation represents a voltage-dependent change in agonist affinity as a consequence of a voltage-dependent conformational change in the muscarinic receptor.
T. Oesterlein. Monocular steady-state visual evoked potential based brain-computer interfaces by utilizing frequency/phase relationships. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
A Brain-Computer Interface based on Steady-State Visual Evoked Potentials was set up. It used both frequency and phase coding. Stimulation was performed monocular to retain situational awareness. Different signal processing algorithms were compared to retrieve the user's intend, namely the DFT, LockIn Analyzer and Canonical Correlation Analysis. The comparison and performance analysis was done offline using data of 10 subjects. Afterwards, prove of concept was achieved using a 6 command BCI to control a model fork truck.
M. Pfeifer. Investigation of the heart rates influence to the QT-RR dynamics and the morphology of the T-wave in healthy subjects. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
Introduction: Ventricular repolarization (VR) analysis plays a crucial role in the in- vestigation of cardiac diseases and drug safety studies. Most of the methods have been primarily directed towards the duration of the ventricles de- and repolarization: the QT interval. In newer times, morphological repolarization properties, represented by the T wave, are focused more frequently. Within numerous factors affecting the VR, the heart rates (HRs) influence remains vague in nowadays literature. Hence, in this study the HRs influence to the VR is investigated.Methods: The study included data recorded by a surface electrocardiogram (ECG) from 10 male subjects during a cardiac stress test. Based on the QT-RR hysteresis loops, expo- nential and elliptical descriptors were extracted. In order to describe the QT-RR relation dynamically, a first order system identification was applied. Moreover, morphological T wave descriptors representing width, symmetrical properties and slimness were calculated.Results: The exponential and elliptical descriptors showed a qualitative dependence, which proved difficult to quantify. By low model residuals, the first order system approx- imation was an appropriate approach with increasing goodness for less dynamics. The T wave descriptors revealed a significant HR correlation in the upper HR range, whereas no deterministic influence was observed for HRs below 100bpm.Conclusions: Dynamic first order systems represent a more appropriate approach in or- der to describe the QT-RR relation compared to static methods. Since higher HRs are attained quite seldom during Holter ECGs, the morphology of the T wave can be assumed independently from the HR in the clinical context.
M. Remmler. Entwicklung einer Software zur Rekonstruktion der Aktivitätsverteilung in ausgedehnten Flächenkontaminationen aufgrund von Messungen mit einem portablen y-Scanner. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
J. Richter. Modeling the tension development and the active contraction of the human atria. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
D. Roth. Powerline Communications in Computertomographiesystemen. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
D.-T. Rudolph. Non-invasive imaging of cardiac conduction velocities. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
J. Schmid. Optimierte Parameteranpassung für Simulationen der menschlichen Vorhofelektrophysiologie. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
S. Schuler. Simulation von intrakardialen Elektrogrammen während der Katheterablation. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
B. C. Schwab. Towards a quantitative understanding of the electrophysiological role of cardiac fibroblasts. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2012
F. Schäuble. Extraktion und Analyse von Aktivierungszeiten aus fluoreszenzoptischen Messdaten. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
B. Verma. Analysis of clinical 3D activation time data for the personalization of human atrial models. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2012
The dissertation work has been performed on the Topic Analysis of 3D activation time data for personalization of human atrial models. In the initial phase, conduction velocity has been calculated for test environments in 2D and 3D planes, simulation data and then on clinical data. The simulation environments were created using fast marching level set method and cellular automaton, with different temporal resolutions. The output obtained from all the cases were then studied and comparision of con- duction velocity was made to check the accuracy of method adopted for conduction velocity calculation. The interpretation out of the results obtained during the study helps in obtaining the personalized human atrial model. This could help in patient specific study and therapy prediction, for example, individual model based ablation therapy and in future the arrhythmia study.
E. M. Wülfers. A confocal microscopy based approach to analyze microstructural remodeling of ventricular myocytes in diseased hearts. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
M. Zaimovic. In silico analysis of the velocity vector field of the human ventricles and comparison with PC-MRI data. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012