S. E. Geneser, R. M. Kirby, D. Xiu, and F. B. Sachse. Stochastic Markovian modeling of electrophysiology of ion channels: reconstruction of standard deviations in macroscopic currents. In J Theor Biol, vol. 245(4) , pp. 627-637, 2007
Markovian models of ion channels have proven useful in the reconstruction of experimental data and prediction of cellular electrophysiology. We present the stochastic Galerkin method as an alternative to Monte Carlo and other stochastic methods for assessing the impact of uncertain rate coefficients on the predictions of Markovian ion channel models. We extend and study two different ion channel models: a simple model with only a single open and a closed state and a detailed model of the cardiac rapidly activating delayed rectifier potassium current. We demonstrate the efficacy of stochastic Galerkin methods for computing solutions to systems with random model parameters. Our studies illustrate the characteristic changes in distributions of state transitions and electrical currents through ion channels due to random rate coefficients. Furthermore, the studies indicate the applicability of the stochastic Galerkin technique for uncertainty and sensitivity analysis of bio-mathematical models.
A. Khawaja, and O. Dössel. Predicting the QRS complex and detecting small changes using principal component analysis. In Biomed Tech (Berl), vol. 52(1) , pp. 11-17, 2007
In this paper, a new method for QRS complex analysis and estimation based on principal component analysis (PCA) and polynomial fitting techniques is presented. Multi-channel ECG signals were recorded and QRS complexes were obtained from every channel and aligned perfectly in matrices. For every channel, the covariance matrix was calculated from the QRS complex data matrix of many heartbeats. Then the corresponding eigenvectors and eigenvalues were calculated and reconstruction parameter vectors were computed by expansion of every beat in terms of the principal eigenvectors. These parameter vectors show short-term fluctuations that have to be discriminated from abrupt changes or long-term trends that might indicate diseases. For this purpose, first-order poly-fit methods were applied to the elements of the reconstruction parameter vectors. In healthy volunteers, subsequent QRS complexes were estimated by calculating the corresponding reconstruction parameter vectors derived from these functions. The similarity, absolute error and RMS error between the original and predicted QRS complexes were measured. Based on this work, thresholds can be defined for changes in the parameter vectors that indicate diseases.
R. Miri, M. Reumann, D. Farina, B. Osswald, and O. Dössel. Computer assisted optimization of biventricular pacing assuming ventricular heterogeneity. In 11th Mediterranean Conference on Medical and Biomedical Engineering and Computingand Computing, vol. 16(15) , pp. 541-544, 2007
Reduced cardiac output, dysfunction of the conduction system, atrio-ventricular block, bundle branch blocks and remodeling of the chambers are results of congestive heart failure (CHF). Biventricular pacing as Cardiac Resynchronization Therapy (CRT) is a recognized therapy for the treatment of heart failure. The present paper investigates an automated non-invasive strategy to optimize CRT with respect to electrode positioning and timing delays based on a complex threedimensional computer model of the human heart. The anatomical model chosen for this study was the segmented data set of the Visible Man and a set of patient data with dilated ventricles and left bundle branch block. The excitation propagation and intra-ventricular conduction were simulated with Ten Tusscher electrophysiological cell model and adaptive cellular automaton. The pathologies simulated were a total atrioventricular (AV) block and a left bundle branch block (LBBB) in conjunction with reduced interventricular conduction velocities. The simulated activation times of different myocytes in the healthy and diseased heart model are compared in terms of root mean square error. The outcomes of the investigation show that the positioning of the electrodes, with respect to proper timing delay influences the efficiency of the resynchronization therapy. The proposed method may assist the surgeon in therapy planning.
Activation of human ether-a-go-go-related gene 1 (hERG1) K+ channels mediates cardiac action potential repolarization. Drugs that activate hERG1 channels represent a mechanism-based approach for the treatment of long QT syndrome, a disorder of cardiac repolarization associated with ventricular arrhythmia and sudden death. Here, we characterize the mechanisms of action and the molecular determinants for binding of RPR260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR), a recently discovered hERG1 channel activator. Channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured by using the two-microelectrode voltage-clamp technique. RPR induced a concentration-dependent slowing in the rate of channel deactivation and enhanced current magnitude by shifting the voltage dependence of inactivation to more positive potentials. This mechanism was confirmed by demonstrating that RPR slowed the rate of deactivation, but did not increase current magnitude of inactivation-deficient mutant channels. The effects of RPR on hERG1 kinetics and magnitude could be simulated by reducing three rate constants in a Markov model of channel gating. Point mutations of specific residues located in the S4S5 linker or cytoplasmic ends of the S5 and S6 domains greatly attenuated or ablated the effects of 3 μM RPR on deactivation (five residues), inactivation (one residue), or both gating mechanisms (four residues). These findings define a putative binding site for RPR and confirm the importance of an interaction between the S4S5 linker and the S6 domain in electromechanical coupling of voltage-gated K+ channels.
OBJECTIVE:The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes.METHODS:Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293.RESULTS:TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) by 31+/-3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil.CONCLUSIONS:Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.
BackgroundMultiple wavelets and rotors are accused of maintaining atrial fibrillation (AF). However, snake-like excitation patterns have recently been observed in AF. So far, computer models have investigated AF in a simplified anatomical model. In this work, pulmonary vein firing is simulated to investigate the initiation and maintenance of AF in a realistic anatomical model.Methods and ResultsThirty-five ectopic foci situated around all pulmonary veins were simulated by a unidirectional conduction block. The excitation propagation was simulated by an adaptive cellular automaton on a realistic 3-dimensional atrial anatomy. Atrial fibrillation was initiated in 65.7% of the simulations. Stable excitation patterns were broken up in anatomically heterogeneous regions, creating a streak-like excitation pattern similar to snakes. Multiple wavelets and rotors could be observed in anatomically smooth areas at the atria's roofs.ConclusionsThe influence of macroscopic anatomical structures on the course of AF seems to play an important role in the excitation propagation in AF. The computer simulations indicate that multiple mechanisms contribute to the maintenance of AF.
An optimal electrode position, atrio-ventricular (AV) and interventricular (VV) delay in cardiac resynchronization therapy (CRT) improves its success. An optimization strategy does not yet exist. A computer model of the Visible Man and a patient heart was used to simulate an atrio-ventricular and a left bundle branch block with 0%, 20% and 40% reduction in interventricular conduction velocity, respectively. The minimum error between physiological excitation and pathology/therapy was automatically computed for 12 different electrode positions. AV and VV delay timing was adjusted accordingly. The results show the importance of individually adjusting the electrode position as well as the timing delays to the patient's anatomy and pathology, which is in accordance with current clinical studies. The presented methods and strategy offer the opportunity to carry out non-invasive, automatic optimization of CRT preoperatively. The model is subject to validation in future clinical studies.
M. Reumann, B. Osswald, and O. Doessel. Noninvasive, automatic optimization strategy in cardiac resynchronization therapy. In Anadolu Kardiyoloji Dergisi : AKD = the Anatolian Journal of Cardiology, vol. 7 Suppl 1, pp. 209-212, 2007
OBJECTIVE: Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. METHODS: Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. RESULTS: Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. CONCLUSION: The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.
The anticholinergic antiparkinson drug orphenadrine is an antagonist at central and peripheral muscarinic receptors. Orphenadrine intake has recently been linked to QT prolongation and Torsade-de-Pointes tachycardia. So far, inhibitory effects on I Kr or cloned HERG channels have not been examined. HERG channels were heterologously expressed in a HEK 293 cell line and in Xenopus oocytes and HERG current was measured using the whole cell patch clamp and the double electrode voltage clamp technique. Orphenadrine inhibits cloned HERG channels in a concentration dependent manner, yielding an IC50 of 0.85 μM in HEK cells. Onset of block is fast and reversible upon washout. Orphenadrine does not alter the half-maximal activation voltage of HERG channels. There is no shift of the half-maximal steady-state-inactivation voltage. Time constants of direct channel inactivation are not altered significantly and there is no use-dependence of block. HERG blockade is attenuated significantly in mutant channels lacking either of the aromatic pore residues Y652 and F656. In conclusion, we show that the anticholinergic agent orphenadrine is an antagonist at HERG channels. These results provide a novel molecular basis for the reported proarrhythmic side effects of orphenadrine
Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (Kir)2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V Kir2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V Kir2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.
Experimental investigations of the nonlinear properties of superconducting niobium coplanar waveguide resonators are reported. The nonlinearity due to a current dependent kinetic inductance of the center conductor is strong enough to realize bifurcation of the nonlinear oscillator. When driven with two frequencies near the threshold for bifurcation, parametric amplification with a gain of +22.4 dB is observed.
Pyramidal GaAs structures on top of GaAs/AlAs distributed Bragg reflectors are investigated as candidates for true three-dimensional cavities with potentially low mode volume and high quality-factor. Different types of single and coupled resonators with base lengths of a few microns are realized using a combination of molecular-beam epitaxy, electron-beam lithography, and wet chemical etching. Embedded InGaAs quantum dots are utilized as light sources to verify the resonator modes. Furthermore, a spatially localized emission through the pyramid facets indicates the future possibility of coupling cavity modes to optical fibers. This could be interesting within the context of single photon emitters.
D. L. Weiss, D. U. J. Keller, G. Seemann, and O. Dössel. The influence of fibre orientation, extracted from different segments of the human left ventricle, on the activation and repolarization sequence: a simulation study. In Europace, vol. 9(suppl 6) , pp. vi96-vi104, 2007
Aims This computational study examined the influence of fibre orientation on the electrical processes in the heart. In contrast to similar previous studies, human diffusion tensor magnetic resonance imaging measurements were used.Methods The fibre orientation was extracted from distinctive regions of the left ventricle. It was incorporated in a single tissue segment having a fixed geometry. The electrophysiological model applied in the computational units considered transmural heterogeneities. Excitation was computed by means of the monodomain model; the accompanying pseudo-electrocardiograms (ECGs) were calculated.Results The distribution of fibre orientation extracted from the same transversal section showed only small variations. The fibre information extracted from the equal circumferential but different longitudinal positions showed larger differences, mainly in the imbrication angle. Differences of the endocardial myocyte orientation mainly affected the beginning of the activation sequence. The transmural propagation was faster in areas with larger imbrication angles leading to a narrower QRS complex in pseudo-ECGs.Conclusion The model can be expanded to simulate electrophysiology and contraction in the whole heart geometry. Embedded in a torso model, the impact of fibre orientation on body surface ECGs and their relation to local pseudo-ECGs can be identified.
In dynamic magnetic resonance imaging (MRI) studies, the motion kinetics or the contrast variability are often hard to predict, hampering an appropriate choice of the image update rate or the temporal resolution. A constant azimuthal profile spacing (111.246 degrees), based on the Golden Ratio, is investigated as optimal for image reconstruction from an arbitrary number of profiles in radial MRI. The profile order is evaluated and compared with a uniform profile distribution in terms of signal-to-noise ratio (SNR) and artifact level. The favorable characteristics of such a profile order are exemplified in two applications on healthy volunteers. First, an advanced sliding window reconstruction scheme is applied to dynamic cardiac imaging, with a reconstruction window that can be flexibly adjusted according to the extent of cardiac motion that is acceptable. Second, a contrast-enhancing k-space filter is presented that permits reconstructing an arbitrary number of images at arbitrary time points from one raw data set. The filter was utilized to depict the T1-relaxation in the brain after a single inversion prepulse. While a uniform profile distribution with a constant angle increment is optimal for a fixed and predetermined number of profiles, a profile distribution based on the Golden Ratio proved to be an appropriate solution for an arbitrary number of profiles.
. Functional Imaging and Modeling of the Heart. Springer, 2007.
This book constitutes the refereed proceedings of the 4th International Conference on Functional Imaging and Modeling of the Heart, FIMH 2007, held in Salt Lake City, UT, USA in June 2007.The 48 revised full papers presented were carefully reviewed and selected from numerous submissions. The contributions describe both experimental and computational studies and cover topics such as imaging and image analysis, cardiac electrophysiology, electro- and magnetocardiography, cardiac mechanics and clinical application, imaging and anatomical modeling.
O. Dössel. Lecture notes - electromagnetics and numerical calculation of fields. Institut für Biomedizinische Technik, Universität Karlsruhe (TH), 2007.
Book Chapters (1)
O. Dössel. Kausalität bei der Entstehung, der Diagnose und der Therapie von Krankheiten - aus dem Blickwinkel des Ingenieurs. In Kausalität in der Technik, . Lucas Klaus (eds), Berlin-Brandenburgische Akad. der Wiss., pp. 69-80, 2007
Vorträge im Rahmen der wissenschaftlichen Sitzungen der Technikwissenschaftlichen Klasse am 24. Februar, 5. Mai und 18. Oktober 2006
A computer model of the human heart is presented, that starts with the electrophysiology of single myocardial cells including all relevant ion channels, spans the de- and repolarization of the heart including the generation of the Electrocardiogram (ECG) and ends with the contraction of the heart that can be measured using 4D Magnetic Resonance Imaging (MRI). The model can be used to better understand physiology and pathophysiology of the heart, to improve diagnostics of infarction and arrhythmia and to enable quantitative therapy planning. It can also be used as a regularization tool to gain better solutions of the ill-posed inverse problem of ECG. Movies of the evolution of electrophysiology of the heart can be reconstructed from Body Surface Potential Maps (BSPM) and MRI, leading to a new non-invasive medical imaging technique.
D. Farina, and O. Dössel. Model-based approach to the localization of infarction. In Proc. Computers in Cardiology, vol. 34, pp. 173-176, 2007
A model-based approach to noninvasively determine the location and size of the infarction scar is proposed, that in addition helps to estimate the risk of arrhythmias. The approach is based on the optimization of an electrophysiological heart model with an introduced infarction scar to fit the multichannel ECG measured on the surface of the patient's thorax. This model delivers the distributions of transmembrane voltages (TMV) within the ventricles during a single heart cycle. The forward problem of electrocardiography is solved in order to obtain the simulated ECG of the patient. This ECG is compared with the measured one, the difference is used as the criterion for optimization of model parameters, which include the site and size of infarction scar.
Based on the Weiner-Hermite polynomial chaos expansion, the stochastic Galerkin method efficiently computes nu- merical solutions for stochastic systems. Unlike such tech- niques as sensitivity analysis, perturbation methods, and second moment-analysis, this method is applicable to a large number of systems while requiring less computational effort than sampling based stochastic methods like Monte Carlo. We utilize the stochastic Galerkin method to assess the impact of stochastic rate coefficients on the predictions of Markovian cardiac ion channel models
E. Hansis, D. Schäfer, M. Grass, and O. Dössel. An iterative method for the reconstruction of the coronary arteries from rotational x-ray angiography. In Proc. SPIE, Medical Imaging 2007: Physics of Medical Imaging, vol. 6510, pp. 651026, 2007
Three-dimensional (3D) reconstruction of the coronary arteries offers great advantages in the diagnosis and treatment of cardiovascular diseases, compared to two-dimensional X-ray angiograms. Besides improved roadmapping, quantitative analysis of vessel lesions is possible. To perform 3D reconstruction, rotational projection data of the selectively contrast agent enhanced coronary arteries are acquired with simultaneous ECG recording. For the reconstruction of one cardiac phase, the corresponding projections are selected from the rotational sequence by nearest-neighbor ECG gating. This typically provides only 5-10 projections per cardiac phase. The severe angular undersampling leads to an ill-posed reconstruction problem. In this contribution, an iterative reconstruction method is presented which employs regularizations especially suited for the given reconstruction problem. The coronary arteries cover only a small fraction of the reconstruction volume. Therefore, we formulate the reconstruction problem as a minimization of the L1-norm of the reconstructed image, which results in a spatially sparse object. Two additional regularization terms are introduced: a 3D vesselness prior, which is reconstructed from vesselness-filtered projection data, and a Gibbs smoothing prior. The regularizations favor the reconstruction of the desired object, while taking care not to over-constrain the reconstruction by too detailed a-priori assumptions. Simulated projection data of a coronary artery software phantom are used to evaluate the performance of the method. Human data of clinical cases are presented to show the method's potential for clinical application.
M. Ifland, D. L. Weiss, and O. Doessel. Modeling of ischemia in electrophysiological models of human ventricular myocytes. In 41. Jahrestagung der DGBMT im VDE. Proceedings BMT 2007, vol. 52, 2007
Y. Jiang, D. Farina, and O. Dössel. An improved spatio-temporal maximum a posteriori approach to solve the inverse problem of electrocardiography. In 41. Jahrestagung der DGBMT im VDE. Proceedings BMT 2007, vol. 52, 2007
Y. Jiang, D. Farina, and O. Dössel. Reconstruction of myocardial infarction using the improved spatio-temporal MAP-based regularization. In Proc. the 6th International Symposium on Noninvasive Functional Source Imaging of the Brain and Heart and the International Conference on Functional Biomedical Imaging, 2007
The congenital long-QT syndrome is commonly associated with a high risk for polymorphic ventricular tachy-cardia and sudden cardiac death. This is probably due to an intensification of the intrinsic heterogeneities present in ventricular myocardium. Increasing the electrophysiological heterogeneities amplifies the dispersion of repolarization which directly affects the morphology of the T wave in the ECG. The aim of this work is to investigate the effects of LQT2, a specific subtype of the long-QT syndrome (LQTS), on the Body Surface Potential Maps (BSPM) and the ECG. In this context a three-dimensional, heterogeneous model of the human ventricles is used to simulate both physiological and pathological excitation propagation. The results are used as input for the forward calculation of the BSPM and ECG. Characteristic QT prolongation is simulated correctly. The main goal of this study is to prepare and evaluate a simulation environment that can be used prospectivley to find features in the ECG or the BSPM that are characteristic for the LQTS. Such features might be used to facilitate the identification of LQTS patients.
D. U. J. Keller, D. L. Weiss, O. Dössel, and G. Seemann. Transferring ventricular myocyte orientation to individual patient data based on diffusion tensor MRI measurements. In Tagungsband 6. Jahrestagung der Deutschen Gesellschaft für Computer- und Roboterassistierte Chirurgie e. V., pp. 255-258, 2007
Atrial fibrillation (AF) induced electrical remodelling of ionic channels shortens action potential duration and reduces atrial excitability. Experimental data of AF-induced electrical remodelling (AFER) from two previous studies on human atrial myocytes were incorporated into a human atrial cell computer model to simulate their effects on atrial electrical behaviour. The dynamical behaviors of excitation scroll waves in an anatomical 3D homogenous model of human atria were studied for control and AF conditions. Under control condition, scroll waves meandered in large area and became persistent when entrapped by anatomical obstacles. In this case, a mother rotor dominated atrial excitation. Action potentials from several sites behaved as if the atrium were paced rapidly. Under AF conditions, AFER increased the stability of re-entrant scroll waves by reducing meander. Scroll wave break up leads to wavelets underpinning sustained chronic AF. Our simulation results support the hypothesis that AF-induced electrical remodelling perpetuates and sustains AF.
M. W. Krueger, D. L. Weiss, and O. Doessel. Intraventricular outweighs transmural dispersion of repolarization after epicardial pacing in a virtual human left ventricle. In 41. Jahrestagung der DGBMT im VDE. Proceedings BMT 2007, vol. 52, 2007
M. W. Krueger, D. L. Weiss, G. Seemann, and O. Dössel. Die Begrenztheit theoretischer Modelle der menschlichen Biologie und ihr großer Nutzen für das Verständnis des Körpers. In Challenges and Limitations of Models in Science and Theology, 2007
R. Miri, M. Reumann, D. Farina, B. Osswald, and O. Dössel. Optimizing A-V and V-V delay in cardiac resynchronization therapy in simulations including ventricle heterogeneity. In 5th IASTED International Conference on Biomedical Engineering BioMED 2007, 2007
Congestive heart failure (CHF) is affecting more than 15 million people in the western population with an increasing number. Biventricular pacing as Cardiac Resynchronization Therapy (CRT) is a recognized therapy for the treatment of heart failure. The present paper investigates the optimal pacing sites and stimuli delays for stimulation, based on a complex three-dimensional computer model of the human heart. The anatomical features were derived from the Visible Man data set. The excitation propagation and intraventricular conduction were simulated with Ten Tusscher electrophysiological cell model and an adaptive cellular automaton. Biventricular pacing in AV block III and LBBB with different interventricular conduction delays were investigated. The simulated activation times of different myocytes in the healthy and diseased heart model are compared in terms of root mean square error (ERMS). The outcomes of the investigation underline that the positioning of the electrodes considering a proper atrioventricular and intraventricular delay influences the efficiency of the resynchronization therapy. The results of this optimization strategy may assist the surgeon in therapy planning.
R. Miri, M. Reumann, D. U. J. Keller, D. Farina, and O. Dössel. A non-invasive computer based optimization strategy of biventricular pacing. In Tagungsband 6. Jahrestagung der Deutschen Gesellschaft für Computer- und Roboterassistierte Chirurgie e. V., pp. 133-136, 2007
R. Miri, M. Reumann, D. Keller, D. Farina, and O. Dössel. Computer based optimization of biventricular pacing according to the left ventricular 17 myocardial segments. In Proceedings of the 29th Annual International Conference of the IEEE EMBS, pp. 1418-1421, 2007
Drug-induced long QT syndrome is a disorder characterized by impaired repolarization of the ventricular action potential which can lead to arrhythmia and sudden death. The most common form involves block of hERG1a channels which encode Ikr current in myocytes. Compounds which activate hERG1a channels could then provide an effective treatment for this disorder. We have studied a recently identified hERG1a activator, PD-118057, using the two microelectrode voltage clamp technique to analyze its affect on hERG1a current expressed in Xenopus oocytes. At 10 microM, PD118057 enhanced wild-type hERG1a current by slowing the rate of inactivation and shifting the voltage dependence to more positive potentials. Consistent with an inactivation perturbing mechanism, PD118057 failed to enhance the current magnitude of an inactivation removed hERG1a mutant channel, G628C/S631C. Unlike other hERG1a activators such as RPR260243, PD118057 did not alter the rate of hERG1a deactivation, suggesting a distinct binding site on the channel protein. Wild-type dEAG1 does not exhibit C-type inactivation and, as expected was unaffected by 10 microM PD118057. A single mutation in the S6 domain (Ala478Gly) of dEAG1 introduced a fast inactivation mechanism with similar time constants as for hERG1a channels. Ala478Gly dEAG current magnitude was enhanced by PD118057 in a concentration dependent manner through removal of the fast inactivation process. In contrast, other S6 mutations that introduce a marginally slower inactivation mechanism did not exhibit sensitivity to PD118057.
Heart Failure is the most common cardiac disease worldwide; supraventricular arrhythmia the most common cardiac arrhythmia. The understanding of these diseases advances treatment options. Ablation therapy is a well accepted non-pharmacological option in the treatment of atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing devices has been shown successful in patients with severe heart failure. However, an optimization or even individual therapy planning is not standard or not even carried out today. These non-pharmacological treatments can be investigated and optimized with the help of computer models of the heart. Different ablation strategies are applied to terminate the arrhythmia in the virtual environment and a comparison of strategies can be carried out. With respect to cardiac resynchronization therapy, the computer model allows for automatic and non-invasive optimization of electrode positions and timing delays. With clinical validation, the presented computer models and methods have the potential to contribute to individualized therapy planning.
We introduce a framework to characterize and visualize the transverse tubular system of cardiac myocytes imaged with confocal microscopy. We imaged rabbit ventricular cells and cell segments with fluorescein linked to dextran. The image datasets were deconvolved with the Richardson-Lucy algorithm using the point spread function extracted from images of fluorescent beads. The transverse tubular system (t-system) was segmented with the methods of digital image processing. We reconstructed single transverse tubules and quantitatively described these in terms of length, cross-sectional area, ellipticity and orientation. These results should yield geometric markers for studies of protein distribution and provide insights into the function of the t-system.
D. L. Weiss, G. Seemann, and O. Doessel. A framework for incorporation of arbitrary 3D electrophysiological heterogeneities in simulations of the human heart. In 41. Jahrestagung der DGBMT im VDE. Proceedings BMT 2007, vol. 52, 2007
D. L. Weiss, G. Seemann, and O. Dössel. The end of T wave need not coincide with final repolarization in tissue: a simulation study. In Heart Rhythm, vol. 4(5s) , pp. 159, 2007
Heterogeneity of ion channel properties within human ventricular tissue determines the sequence of repolarization under healthy conditions. In this computational study, the impact of different extend of electrophysiological heterogeneity in both human ventricles on the ECG was investigated by a forward calculation of the cardiac electrical signals on the body surface. The gradients ranged from solely transmural, interventricular and apico-basal up to full combination of these variations. As long interventricular heterogeneities were neglected, the transmural gradient generated a positive T wave that was increased when apico-basal variations were considered. Inclusion of interventricular changes necessitated the incorporation of both transmural and apico-basal heterogeneities to reproduce the positive T wave.
S. Wieland, N. Kikillus, T. Baas, M. Braecklein, and A. Bolz. Screening device for identification of patients with paroxysmal atrial fibrillation to prevent ischemic strokes. In Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, vol. 2007, pp. 3693-3696, 2007
The most frequently occurring cardiac arrhythmia in the adulthood is atrial fibrillation. In Germany, the number of sick people is estimated at 800,000. Patients who suffer from atrial fibrillation often do not sense any symptoms of the illness. Through the uncontrolled blood flow in the atrium, a blood clot, which can lead to the blood circulation for an embolism or for a stroke, can form itself. These persons must be recognized, because of their increased stroke risk in order to be able to attend it. In this work, the chest strap CorBelt, developed by the company Corscience GmbH&Co.KG, is equipped with an algorithm for the recognition of atrial fibrillation with the aid of heart rate variability.
M. Reumann. Computer assisted optimisation of non-pharmacological treatment of congestive heart failure and supraventricular arrhythmia. KIT Scientific Publishing. Dissertation. 2007
Heart Failure is the most common cardiac disease worldwide; supraventricular arrhythmia the most common cardiac arrhythmia. The understanding of these diseases advances treatment options. Ablation therapy and atrial antitachycardial pacing are non-pharmacological options in the treatment of atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing devices has been shown successful in patients with severe heart failure. However, an optimization or even individual therapy planning is not standard or not even carried out today.
Student Theses (6)
T. Baas. Konzeption, Entwicklung und Durchführung eines automatischen Performancetests für die Erkennung von Vorhofflimmern. Bachelorarbeit. 2007
Im Rahmen dieser Arbeit wurde ein Teststand zur Verifizierung eines am Institut für Biomedizinische Technik entwickelten und auf dem mobilen EKG-Gerät CorBELT implementierten Algorithmus zur Erkennung von Vorhofflimmern unter Verwendung der Herzratenvariabilität entwickelt und aufgebaut. Die Problematik bei der Entwicklung des Teststandes lag in der kontinuierlichen Ausgabe der digitalen Signale. Hierbei musste sichergestellt werden, dass die Spannungswerte mit genau der Frequenz ausgegeben werden, mit der die Daten vorher abgetastet wurden. Dies stellte sich unter Microsoft Windows als äußerst problematisch dar. Hier verhindert das Prozessmanagement eine kontinuierliche Ausgabe. Da Latenzzeiten bei der Ausgabe das EKG-Signal und damit die Analyse verfälschen, wurde die Ausgabeeinheit in ein externes Mikrocontrollerboard verlegt. Dieses besitzt ein eigenes Prozessmanagement, welches die Stabilität der Ausgabefrequenz sicherstellt. Im Anschluss wurde die Verifikation unter Verwendung zweier Datensätze aus der Physionetdatenbank durchgeführt. Die erhaltenen Ergebnisse wurden analysiert. Dabei wurde bestätigt, dass der Algorithmus den Vorgaben entsprechend auf dem Brustgurt CorBELT implementiert wurde und dass EKG-Signale von Patienten mit Vorhofflimmern von gesunden EKG-Signalen unterschieden werden. Die Sensitivität liegt bei 97,74 %, die Spezifität bei 92,59 %. Die Sensitivität bei EKG-Signalen von Patienten mit Erkrankung an Vorhofflimmern, in denen jedoch kein Vorhofflimmern auftritt, liegt bei 95,83 %. Der Algorithmus arbeitet auf dem Brustgurt CorBELT zur Zufriedenheit. Daher ist es im Anschluss an diese Arbeit möglich, mit dem Gerät klinische Studien durchzuführen.
M. Ifland. Modeling of ischemia in electrophysiological models of human ventricular myocytes. Universität Karlsruhe. Diplomarbeit. 2007
M. W. Krüger. Erhöhung der transmuralen Dispersion der Repolarisation durch epikardiale Stimulation eines virtuellen linken Ventrikels. Institut für Biomedizinische Technik, Universität Karlsruhe (TH). . 2007
S. Lurz. Entwicklung schneller Optimierungsstrategien für die kardiale Resynchronisationstherapie im Computermodell. Universität Karlsruhe (TH), Institut für Biomedizinische Technik. Bachelorarbeit. 2007
C. Schilling. Mikrocontroller-basiertes Zweikanal-Messmodul mit Sinusgenerator an SD/MMC oder UART. Institut für Biomedizinische Technik, Universität Karlsruhe (TH). . 2007
C. Schilling. Online-Extraktion von Primitivobjekten aus Laserradardaten. FOM, Forschungsgesellschaft für Angewandte Naturwissenschaften (FGAN); Institut für Nachrichtentechnik, Universität Karlsruhe (TH). Diplomarbeit. 2007