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ABSTRACT: Multi-scale cardiac modeling has made great advances over the last decade. Highly detailed atrial models were created and used for the investigation of initiation and perpetuation of atrial fibrillation. The next challenge is the use of personalized atrial models in clinical practice. In this study a framework of simple and robust tools is presented, which enables the generation and validation of patient-specific anatomical and electrophysiological atrial models. Introduction of rule-based atrial fiber orientation produced a realistic excitation sequence and a better correlation to the measured ECGs. Personalization of the global conduction velocity lead to a precise match of the measured P-wave duration. The use of a virtual cohort of nine patient and volunteer models averaged out possible model-specific errors. Intra-atrial excitation conduction was personalized manually from left atrial local activation time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps in ablation lesions. A fast marching level set approach to compute atrial depolarization was extended to incorporate anisotropy and conduction velocity heterogeneities and reproduced the monodomain solution. The presented chain of tools is an important step towards the use of atrial models for the patient-specific AF diagnosis and ablation therapy planing.
IEEE transactions on medical imaging. 05/2012;
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ABSTRACT: 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.
IEEE Transactions on Biomedical Engineering 03/2012; · 2.28 Impact Factor
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ABSTRACT: The impact of transmural infarctions of the left ventricle on the cardiac mechanical dynamics is evaluated for all 17 AHA
segments in a computer model. The simulation framework consists of two parts: an electrophysiological model and an elastomechanical
model of the ventricles. The electrophysiological model is used to simulate the electrophysiological processes on cellular
level, excitation propagation and the tension development. It is linked to the elastomechanical model, which is based on nonlinear
finite element analysis for continuum mechanics. Altogether, 18 simulations of the contraction of the ventricles were performed,
17 with an infarction in the respective AHA segment and one simulation for the control case. For each simulation, the mechanical
dynamics as well as the wall thickening of the infarct region were analyzed and compared to the corresponding region of the
control case. The simulation revealed details of the impact of the myocardial infarction on wall thickening as well as on
the velocity of the infarct region for most of the AHA segments.
KeywordsMyocardial Infarction–Heart Modeling–Finite Element Analysis
05/2011: pages 241-249;
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ABSTRACT: Atrial fibre architecture has complex patterns of bundles and layers and is known to impact on atrial electrophysiology, especially in fast-conducting bundles like Crista Terminalis, Bachmann?s bundle and pectinate muscles. Based on a priori knowledge of atrial fibre structure, we incorporated rule-based fibre orientation in seven volumetric models of human atria using a semi-automatic approach. We were able to introduce multiple layers of myofibres and regional heterogeneities of ion channels in the models. We evaluated the influence of complete atrial fibre architecture on multiple modelling scales. First, we simulated atrial excitation in the isotropic and anisotropic models using the model of Courtemanche et al. in combination with the monodomain approach. Second, we computed body surface potentials from the simulated transmembrane voltages and compared these to measured ECGs from the respective patients. Temporal behaviour of the atrial excitation sequences was significantly altered in the anisotropic models compared to the sequences in the isotropic models. Complete atrial activation was achieved approximately 20% faster in the anisotropic models mostly due to fast conducting myofibre bundles. Electrophysiological heterogeneities influenced right atrial transmembrane voltage distribution over time due to a less negative action potential plateau in Crista Terminalis cells. P-wave duration was significantly shorted by the introduction of atrial anisotropy and the error to measured P-wave duration was reduced. Furthermore, a pattern change in body surface potential distribution over time was observed. The anisotropic patterns showed a better match to the measurements. Thus, the modelling error by using generalised fibre architecture for patient-specific models was smaller than by using isotropic models. The results highlight the necessity to incorporate atrial anisotropy in personalised models to produce more realistic simulations. The semi-automatic approach allows the use of these models for future clinical applications.
Cardiac Physiome Conference 2011; 01/2011
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ABSTRACT: Patients suffering from the congenital Long-QT syndrome have been reported to react highly sensitive to the presence of β-adrenergic agents that are produced by the sympathetic nervous system. In this work we used an anisotropic and electrophysiologically heterogeneous insilico model to reproduce wedge experiments in which the Long-QT syndrome was induced pharmacologically. The integration of an intracellular signaling cascade allowed the prediction of the effects of adrenergic agents on the different subtypes of the Long-QT syndrome. For LQT1 the in-silico model predicted a QT prolongation in the transmural pseudo ECG without an increase in transmural dispersion of repolarization. For LQT2 and LQT3 the QT prolongation was accompanied by an increased transmural dispersion of repolarization. β-adrenergic tonus shortened the QT interval and increased transmural dispersion of repolarization. These findings were consistent with the experimental reports.
Computing in Cardiology, 2010; 10/2010
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ABSTRACT: Patients suffering from the congenital Long-QT syndrome have been reported to react highly sensitive to the presence of beta-adrenergic agents that are produced by the sympathetic nervous system. In this work we used an anisotropic and electrophysiologically heterogeneous in- silico model to reproduce wedge experiments in which the Long-QT syndrome was induced pharmacologically. The integration of an intracellular signaling cascade allowed the prediction of the effects of adrenergic agents on the different subtypes of the Long-QT syndrome. For LQT1 the in-silico model predicted a QT prolongation in the transmural pseudo ECG without an increase in transmural dispersion of repolarization. For LQT2 and LQT3 the QT prolongation was accompanied by an increased transmural dispersion of repolarization. beta-adrenergic tonus shortened the QT interval and increased transmural dispersion of repolarization. These findings were consistent with the experimental reports.
Proceedings Computing in Cardiology; 01/2010
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ABSTRACT: The shape of a simulated excitation wavefront depends on the underlying spatial resolution. The aim of this work is twofold: On the one hand we investigated the dependency of the wavefront on spatial resolution by simulating the excitation spread in three virtual patches of ventricular tissue that have different resolutions. On the other hand we simulate a realistic excitation sequence in an anisotropic and electrophysiologically heterogeneous biventricular model. Our patch experiments with different spatial resolutions demonstrated that resolutions below 0.2 mm led to a deformation of the excitation wavefront to non-elliptical shapes. The biventricular model with 0.2 mm grid size shows realistic excitation spread and conduction velocities. Similar biventricular models in conjunction with a computational representation of the thorax will be used in future to predict the effects of changes on the ion-channel level on the ECG.
Proceedings BMT 2010, 44. DGBMT Jahrestagung, 3-Länder-Tagung D-A-CH, Rostock; 01/2010
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ABSTRACT: Simulations of the electrophysiological behavior of the heart improve the comprehension of the mechanisms of the cardiovascular system. Furthermore, the mathematical modeling will support diagnosis and therapy of patients suffering from heart diseases. In this paper, the chain of modeling of the electrical function in the heart is described. The components are explained briefly, namely modeling of cardiac geometry, reconstructing the cardiac electrophysiology and excitation propagation. Additionally, the mathematical methods allowing to implement and solve these models are outlined. The three recently more investigated cases atrial fibrillation, ischemia and long-QT syndrome are described and show how cardiac modeling can support cardiologists in answering their open questions.
Information Technology. 01/2010; 52(5):242-249.
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ABSTRACT: Motivation: Anatomical models of the heart can be used to conduct multi-physics simulations. These simulations can aid basic and clinical research and are being translated into clinical practice nowadays.Problem statement: The human myocardium has very complex fiber structure, which has a strong impact on cardiac physiology. To understand and evaluate 3D fiber orientation in volumetric cardiac models, it is often necessary to project these onto printed pictures.Approach: Images of myocardial fibers using color-coded cylinders, color-coded streamlines and anaglyph methods are compared. Results: Streamlines provide a good distinction of myocardial bundles. Cylinders show the most accurate results. Color-coded representations reveal abrupt changes in fiber direction. Anaglyph visualizations give an illusion of depth in 2D prints and can display overlaying bundles. Conclusions: Streamlines are superior in imaging global fiber orientation, whereas cylinders give better results for local structures. Color-coding increases information where fiber structure is very complex, e.g. in the atria. Anaglyph images cause a loss in color information but help the viewer to understand the 3D object. Overall, it is necessary to choose the appropriate method of picturing fibers for specific tasks.
KIT PhD Symposium 2010; 01/2010
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ABSTRACT: Current models of the human atria represent geometries of single individuals or base on statistical data. We present a work-flow for the creation of patient-specific atrial models. Furthermore we show a framework to compare simulated P- waves and body surface potential maps (BSPMs) of individual patients with measurements. Models of the atrial and thorax anatomy were segmented from MRI data. Volumetric atrial models were semi-automatically enhanced with electrophys- iologically (EP) relevant structures. Simulations were performed on an anisotropic voxel-based mesh and were forward calculated to obtain simulated BSPMs. BSPMs were acquired using a 64 electrode ECG system. Comparison of simulated and measured P-waves in Einthoven leads showed a general agreement of both, although no personalization of the atrial electrophysiology model was performed. P-wave duration was longer in the simulations, highlighting the need for elec- trophysiological model personalization. Simulated and measured BSPMs revealed similar patterns. The presented method enables realistic simulations of atrial activation on patient-specific volumetric atrial models with EP relevant myocardial structures resulting in computed ECGs (P-wave) and BSPMs with show physiological morphologies
Biomedizinische Technik / Biomedical Engineering; 01/2010 · 0.53 Impact Factor
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ABSTRACT: The sympathetic nervous system influences important cardiac parameters like heart rate, action potential duration (APD) and
myocyte contractility. To model its effects on ventricular electrophysiology we integrated an existing description of beta
adrenergic signaling pathways into a recent version of the ten Tusscher model of human cardiac electrophysiology. We considered
three main target proteins that were phosphorylated by protein kinase A: the slow delayed potassium channel IKs, the L-type calcium channel ICaL and phospholamban (PLB). Besides shortened APDs we observed a leftward shifted currentvoltage relationship of IKs and an increased channel conductivity. The L-type calcium channel open probability as well as its availability were elevated
by the adrenergic stimulation. Due to a reduction of the inhibiting function of PLB on the calcium ATPase, the calcium uptake
Iup into the sarcoplasmic reticulum was increased. Including intracellular signaling pathways into models of cellular electrophysiology
will open new possibilities for the in silico evaluation of physiological and pathological processes. Future work will therefore
focus on investigating the influence of adrenergic effects on the tissue and ECG level.
12/2009: pages 1033-1036;
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ABSTRACT: The Purkinje network plays a major role for realistically simulating the activation sequence of the ventricles. In this work,
we describe a method to create an endocardial stimulation profile that describes the location and time instant of ventricular
stimulation, thus mimicking the His-Purkinje conduction system. By adapting model parameters stimulation profiles can be generated
for different ventricular anatomies with minimal manual interaction. The stimulation profile parameters are evaluated by analyzing
the excitation propagation in a three-dimensional, heterogeneous and anisotropic model of the human ventricles which are embedded
in an anatomically detailed torso geometry. The calculated QRS complexes are in good agreement with the corresponding clinical
recordings on the same proband.
12/2009: pages 145-148;
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ABSTRACT: Skeletal muscle fiber orientation is important for the realistic calculation of body surface ECGs. However if computer models of patient-specific anatomies are created, usually no information about the muscle fiber arrangement is available. In this work we evaluated a published rule based approach to describe skeletal muscle fiber orientation together with two new methods. The quality of the respective fiber orientation approximation was assessed by comparing the forward calculated body surface potential maps (BSPMs) with the BSPM that was derived from a gold standard. Although all three methods showed comparable results the complete omission of skeletal muscle fiber orientation enhanced the BSPM even further. Thus it can be concluded that the characterization of skeletal muscle fiber orientation using a simplified approach is not feasible. In cases where no detailed information about the skeletal muscle fiber arrangement is available, it is better to entirely neglect its anisotropic influence.
Computers in Cardiology, 2009; 10/2009
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ABSTRACT: Cisapride is a drug to help gastric problems. It is limited because of reports of the side-effect long QT syndrome which predisposes to arrhythmias. In this computatinal study, the effects of Cisapride on human ventricular myocytes are investigated in-silico. From literature reported effects of the drug on ion channel level are included into a virtual human ventricular cell. Cisapride has the most dominating effect on the rapid delayed rectifier current IKr. A shift in the activation and inactivation and mainly a reduction of conductivity is seen. This leads to the prolongation of the APD comparable to the long QT syndrome. In future studies, the stability of the heart under the influence of this drug will be evaluated
FMBE Proceedings World Congress on Medical Physics and Biomedical Engineering; 01/2009
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Chaste Userstextquoteright & Developerstextquoteright Workshop; 01/2009
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IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering; 01/2009
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ABSTRACT: Electrophysiological modeling of the heart enable quantitative description of electrical processes during normal and abnormal
excitation. Cell models describe e.g. the properties of the cell membrane and the gating process of ionic channels. New measurement
data is available for these channels for physiological and some pathological states. These data should be included in the
models to enhance their features. In this work we describe a framework adapting ion channel models to measurement data by
using a particle swarm optimization (PSO). As an example the data of whole-cell voltage-clamp measurements of the reggae mutation
in hERG was integrated into a Markovian chain model describing I
Kr.
12/2008: pages 2507-2510;
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ABSTRACT: Simulation of cardiac excitation is often a trade-off between accuracy and speed. A promising minimal, time-efficient cell model with four state variables has recently been presented together with parametrizations for ventricular cell behaviour. In this work, we adapt the model parameters to reproduce atrial excitation properties as given by the Courtemanche model. The action potential shape is considered as well as the restitution of action potential duration and conduction velocity. Simulation times in a single cell and a tissue patch are compared between the two models. We further present the simulation of a sinus beat on the atria in a realistic 3D geometry using the fitted minimal model in a monodomain simulation.
Computers in Cardiology, 2008; 10/2008
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ABSTRACT: After mathematical modeling of the healthy heart now modeling of diseases comes into the focus of research. Modeling of arrhythmias already shows a large degree of realism. This offers the chance of more detailed diagnosis and computer assisted therapy planning. Options for genetic diseases (channelopathies like Long-QT-syndrome), infarction and infarction-induced ventricular fibrillation, atrial fibrillation (AF) and cardiac resynchronization therapy are demonstrated.
IFMBE Proceedings; 01/2008
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ABSTRACT: 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.
Computers in Cardiology, 2007; 11/2007
