Abstract:

Ablation strategies to prevent episodes of paroxysmal atrial fibrillation (AF) have been subject to many clinical studies. The issues mainly concern pattern and transmurality of the lesions. This paper investigates ten different ablation strategies on a multilayered 3-D anatomical model of the atria with respect to 23 different setups of AF initiation in a biophysical computer model. There were 495 simulations carried out showing that circumferential lesions around the pulmonary veins (PVs) yield the highest success rate if at least two additional linear lesions are carried out. The findings compare with clinical studies as well as with other computer simulations. The anatomy and the setup of ectopic beats play an important role in the initiation and maintenance of AF as well as the resulting therapy. The computer model presented in this paper is a suitable tool to investigate different ablation strategies. By including individual patient anatomy and electrophysiological measurement, the model could be parameterized to yield an effective tool for future investigation of tailored ablation strategies and their effects on atrial fibrillation.

Abstract:

A 3-D reconstruction of the coronary arteries offers great advantages in the diagnosis and treatment of cardiovascular disease, compared to 2-D X-ray angiograms. Besides improved roadmapping, quantitative vessel analysis is possible. Due to the heart's motion, rotational coronary angiography typically provides only 5-10 projections for the reconstruction of each cardiac phase, which leads to a strongly undersampled reconstruction problem. Such an ill-posed problem can be approached with regularized iterative methods. The coronary arteries cover only a small fraction of the reconstruction volume. Therefore, the minimization of the mbiL(1) norm of the reconstructed image, favoring spatially sparse images, is a suitable regularization. Additional problems are overlaid background structures and projection truncation, which can be alleviated by background reduction using a morphological top-hat filter. This paper quantitatively evaluates image reconstruction based on these ideas on software phantom data, in terms of reconstructed absorption coefficients and vessel radii. Results for different algorithms and different input data sets are compared. First results for electrocardiogram-gated reconstruction from clinical catheter-based rotational X-ray coronary angiography are presented. Excellent 3-D image quality can be achieved.

Abstract:

The quality of three-dimensional (3D) reconstructions of the coronary arteries from rotational coronary angiography depends on the selected phase point. Inconsistencies in the projection data, due to heart motion, degrade the image quality. Here, a method for the automatic selection of the optimum phase points for reconstruction is presented.The method aims at determining heart phases with minimum inconsistency of the motion state in the selected projection data. This is achieved by calculating an error measure which describes the inconsistency of the vessel centerline geometry in three dimensions for all cardiac phases. The phases with minimum inconsistency are then selected as optimum reconstruction phases. The method's feasibility was tested on 22 clinical cases. One late-diastolic and one end-systolic optimum phase were determined automatically for each case. For comparison, three observers visually determined the optimum phases.Overall, 82% of the 44 automatically determined phases delivered optimum image quality, only 5% showed considerably lower quality than the visually determined optimum phase. For all 22 cases at least one of the two automatically determined phases yielded optimum quality.In a first test the method proved to robustly determine optimum reconstruction phase points.

Abstract:

Three-dimensional reconstruction of coronary arteries can be performed during x-ray-guided interventions by gated reconstruction from a rotational coronary angiography sequence. Due to imperfect gating and cardiac or breathing motion, the heart's motion state might not be the same in all projections used for the reconstruction of one cardiac phase. The motion state inconsistency causes motion artefacts and degrades the reconstruction quality. These effects can be reduced by a projection-based 2D motion compensation method. Using maximum-intensity forward projections of an initial uncompensated reconstruction as reference, the projection data are transformed elastically to improve the consistency with respect to the heart's motion state. A fast iterative closest-point algorithm working on vessel centrelines is employed for estimating the optimum transformation. Motion compensation is carried out prior to and independently from a final reconstruction. The motion compensation improves the accuracy of reconstructed vessel radii and the image contrast in a software phantom study. Reconstructions of human clinical cases are presented, in which the motion compensation substantially reduces motion blur and improves contrast and visibility of the coronary arteries.

Abstract:

Die großen Trends der Medizintechnik Biomolekularisierung, Miniaturisierung, Computerisierung werden beschrieben und die gesellschaftlichen Rahmenbedingungen, unter denen in Zukunft Innovationen der Medizintechnik entstehen, werden analysiert. Einige Fokusthemen der Medizintechnik werden etwas detaillierter betrachtet: Was sind die interessanten Forschungsvorhaben von heute, die möglicherweise morgen Wirklichkeit werden?

Abstract:

Es wird eine Methode beschrieben, wie medizinische Bilder des Herzens modellbasiert mit EKG-Daten verknüpft werden können, um damit zu einer spezifischen Diagnostik und zu einer besseren Therapieplanung in der Kardiologie zu gelangen. Zunächst wird aus MRT- oder CT-Bildern des Patienten die Geometrie seines Herzens ermittelt. Elektrokardiographische Messungen an der Körperoberfläche (EKG oder Body Surface Potential Mapping) und aus dem Inneren des Herzens (intracardial mapping) werden aufgenommen und die Orte der Messung in den Bilddatensatz eingetragen (registration). Ein elektrophysiologisches Computermodell vom Herzen des Patienten wird mit Hilfe der elektrophysiologischen Messdaten iterativ angepasst. Schließlich entsteht im Computer ein virtuelles Herz des Patienten, welches sowohl die Geometrie als auch die Elektrophysiologie wiedergibt. Ein Modell der Vorhöfe hat beispielsweise das Potenzial, die Ursachen von Vorhofflimmern zu erkennen und die Radiofrequenz-Ablationsstrategie zu optimieren. Ein Modell der Ventrikel des Herzens kann helfen, genetisch bedingte Rhythmusstörungen besser zu verstehen oder auch die Parameter bei der kardialen Resynchronisationstherapie zu optimieren. Die Modellierung des Herzens mit einem Infarktgebiet könnte die elektrophysiologischen Auswirkungen des Infarktes beschreiben und die Risikostratifizierung für gefährliche ventrikuläre Arrhythmien unterstützen oder die Erfolgsrate bei ventrikulären Ablationen erhöhen.

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.

Abstract:

Multi-scale, multi-physical heart models have not yet been able to include a high degree of accuracy and resolution with respect to model detail and spatial resolution due to computational limitations of current systems. We propose a framework to compute large scale cardiac models. Decomposition of anatomical data in segments to be distributed on a parallel computer is carried out by optimal recursive bisection (ORB). The algorithm takes into account a computational load parameter which has to be adjusted according to the cell models used. The diffusion term is realized by the monodomain equations. The anatomical data-set was given by both ventricles of the Visible Female data-set in a 0.2 mm resolution. Heterogeneous anisotropy was included in the computation. Model weights as input for the decomposition and load balancing were set to (a) 1 for tissue and 0 for non-tissue elements; (b) 10 for tissue and 1 for non-tissue elements. Scaling results for 512, 1024, 2048, 4096 and 8192 computational nodes were obtained for 10 ms simulation time. The simulations were carried out on an IBM Blue Gene/L parallel computer. A 1 s simulation was then carried out on 2048 nodes for the optimal model load. Load balances did not differ significantly across computational nodes even if the number of data elements distributed to each node differed greatly. Since the ORB algorithm did not take into account computational load due to communication cycles, the speedup is close to optimal for the computation time but not optimal overall due to the communication overhead. However, the simulation times were reduced form 87 minutes on 512 to 11 minutes on 8192 nodes. This work demonstrates that it is possible to run simulations of the presented detailed cardiac model within hours for the simulation of a heart beat.

Abstract:

The classic tool of assessing learning progress are written tests and assignments. In large groups of students the workload often does not allow in depth evaluation during the course. Thus our aim was to modify the course to include active learning methods and student centered teaching. We changed the course structure only slightly and established new assessment methods like minute papers, short tests, mini-projects and a group project at the end of the semester. The focus was to monitor the learning progress during the course so that problematic issues could be addressed immediately. The year before the changes 26.76 % of the class failed the course with a grade average of 3.66 (Pass grade is 4.0/30 % of achievable marks). After introducing student centered teaching, only 14 % of students failed the course and the average grade was 3.01. Grades were also distributed more evenly with more students achieving better results. We have shown that even in large groups of students with > 100 participants student centered and active learning is possible. Although it requires a great work overhead on the behalf of the teaching staff, the quality of teaching and the motivation of the students is increased leading to a better learning environment.

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). Models of ion channels can be described by Hogdkin-Huxley equations or by Markovian models. They consider rate constants that are complex functions depending on the transmembrane voltage. Each transition has two rate constants described by several parameters. These parameters need to be varied in order to minimize the difference between measured and simulated ion channel kinetics. Since this minimization procedure is multidimensional and the function can have several local minima, conventional optimization strategies like Powells algorithm and conjugate gradient do not ensure to find the global minimum. To overcome this, a PSO was implemented that inserts several dependent particles randomly into the search space. It is based on the social behavior of swarms. As the particles are independent during each iteration the procedure can be calculated in parallel. The measurement data used for this work were current traces of a voltage-clamp protocol of reggae mutant hERG channels. The same protocol as for the measurement was assigned to the model of Lu et al. describing hERG function with a Markovian model. The value to be minimized was the sum of mean square errors between measured and simulated currents at certain time instances. Both Powell and PSO were started several times with random starting values. In 94% of the cases PSO found the minimum compared to 16% for Powell. On the other hand PSO needed approximately 100 times more function evaluations. The parallelization decreased the overall time needed by the PSO to about the same amount Powell needed. Therefore, the parallel PSO is a fast and reliable approach for adapting ion channel models to measured data.

Abstract:

The sinus node (SN) is the primary pacemaker of the heart. It is a heterogeneous structure in the right atrium composed of two types of cells with different electrophysiological properties. One type is distributed more densely in the periphery the other in the center. Different gap junction types and densities exist leading to a heterogeneity in conduction. It is supposed that this complex interplay of heterogeneities is the basic mechanism that the small SN is able to electrically drive the surrounding atrial muscle. If this interplay is disturbed, the function of the SN can be effected massively. In this simulation study we want to demonstrate the effects of the L532P mutation in hERG called reggae on SN electrophysiology.Mutant hERG channels were expressed in xenopus oocytes and the channel properties were measured with voltage-clamp technique. The data showed mainly a shift of the steady-state inactivation to more positive potentials. This leads to an increase of the ionic current during the depolarized phase. The data was integrated in the heterogeneous rabbit SN model of Zhang et al. by adapting the parameters of the IKr channel with aid of optimization methods using the same stimulation protocol as in the measurements.The most sensitive parameter was the shift voltage of the steady-state inactivation from -19.2 mV in the physiological case to 10.1 mV in the mutant model. When inserting this mutant IKr in the central SN model the ability of the central cells to depolarize spontaneously was eliminated. Peripheral cell still beat but are affected by the mutation. The slope of the pre-potential and the upstroke velocity were not changed. The maximum diastolic potential was increased by 2 mV and the maximum systolic potential decreased by 1.5 mV. The diastolic interval was shortened slightly by 3 ms. The main effect was a reduction of the action potential duration from 108 ms to 84 ms leading to a frequency increase from 6.37 Hz to 7.62 Hz.These effects lead to a changing SN function. The increase of the shift voltage is in good agreement with the measured changes. Especially the loss of auto-rhythmicity in the central zone is expected to change the overall SN activity. Although peripheral SN cells beat faster we expect a bradycardial function of the complete SN because of electrotonic interactions with the silent central SN cells and the low resting membrane voltage of surrounding atrial muscle cells. In a further study this suggestion has to be investigated in an anisotropic and heterogeneous 3D model.

Abstract:

The modelling of the relationship between QT and RR intervals is an important issue for pharmaceuticalresearch on the way to new drugs. Pharmaceutical industries have to thoroughly investigate potential effects of their medicines on QT intervals since QT prolongation is considered as a marker of the proarrhythmia risk. As QT intervals depend on RR intervals there is an obvious interest in modelling the QT-RR relationship. Static formulas to correct QT for RR are well known, but a dynamic dependencyis mainly observed.Two models of dynamic QT-RR relationships are introduced to eliminate the heart rate dependent part out of the QT interval. These models are based on heart cell measurements and simulations and are validated by Holter ECG data.

Abstract:

Numerous studies about the effects in human body of high frequency magnetic fields on the one hand and extremely low frequency fields on the other hand have been carried out. This is not the case for the mid frequency range around 100 kHz. When applying external magnetic fields to the human body in this frequency range both electric stimulation and thermal heating effects have to be considered. Magnetic Particle Imaging (MPI), a new imaging technique, and Hyperthermia, a tumor treatment therapy, both apply magnetic fields in a frequency range around 100 kHz. In MPI thermal heating of the body has to be prevented, whereas in Hyperthermia a temperature increase of about 4 K in the target region is desirable. Induced currents may lead to muscle stimulation which is not acceptable above a certain threshold. This paper presents the results of induced current densities and SAR in a numeric field calculation simulation. For the model of the human body the torso of the Visible Man Dataset has been employed, along with the dielectric properties of biological tissues investigated by Gabriel & Gabriel. The model has been exposed to a sinusoidal magnetic field with an amplitude of 10 mT. The results of the induced current densities and SAR values have been compared with the currently valid official guidelines for limiting exposure to time-varying electric, magnetic and electromagnetic fields by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). It turns out that limits of induced current densities are reached by applying a magnetic flux density of 10 mT and the SAR limit even is exceeded.

Abstract:

Three-dimensional (3-D) reconstruction of the coronary arteries from a rotational X-ray angiography sequence can support diagnosis of coronary artery disease, treatment planning, and intervention guidance during catheter interventions. 3-D reconstruction enables quantitative vessel analysis, including vessel dynamics from a time-series of reconstructions. This contribution presents a method for reconstructing coronary arteries with high contrast and high level of detail. It employs an iterative reconstruction algorithm in combination with projection-based motion compensation. An efficient implementation using a graphics processing unit delivers reconstruction times close to clinically acceptable values. Reconstructions from clinical human cases, acquired on an interventional C-arm system, are presented. Excellent image quality is achieved.

Abstract:

Image registration is used to reduce movement artifacts caused by contracting heart muscle in transmembrane voltage measurements using fluorescence microscopy. The applied registration methods include Thin-Plate Splines (TPS) and Gaussian Elastic Body Splines (GEBS). Landmarks are established automatically using regional cross-correlation. Then these landmarks are filtered for meaningful correspondences by requiring a minimum correlation coefficient and clustering adjacent and identical displacements. Registration of an image sequence showing a contracting muscle is realized by spatially aligning the images at maximum contraction and at rest. For the other images the movement of the muscle is interpolated using an analytical description of the contraction of heart muscle.TPS cause amplification of displacements at the image border, while GEBS restrict landmarks influence to a local region. Over a set of 81 images GEBS are shown to register images better and more robust than TPS, which in some cases cannot reduce movements. Validation through visualization of transmembrane voltages on contracting muscle reveals that GEBS registration removes movement artifacts better than TPS. Image regions with prominent structures are successfully tackled by GEBS registration.

Abstract:

Ventricular premature beats (VPB) occur when a cardiac depolarization is initiated from a focus in the ventricle instead of the sinoatrial node. Because the ventricular electrical excitation is not started from the intraventriclular conduction system, the excitation propagation in the ventricles behaves in an abnormal manner. This results in an extra asynchronous contraction of the ventricles. In addition VPBs can trigger life-threatening heart arrhythmias. Applying catheter ablation can cure VPB. Therefore it is of importance to localize the origin of VPB using a non-invasive approach before interventional treatment. In this work the inverse problem of electrocardiography is deployed to reconstruct electrical sources in the ventricles, from which the origin of VPB can be identified. By using a spatiotemporal maximum a posteriori (MAP) based regularization the quality of reconstructions is improved. In this work forward calculations with various VPBs are employed to construct a statistical a priori information.

Abstract:

Solving the forward problem of electrocardiography provides a better understanding of electrical activities in the heart. The inverse problem of electrocardiography enables a direct view of cardiac sources without catheter interventions. Today the forward and inverse computation is most often performed in a static model, which doesn't take into account the heart motion and may result in considerable errors in both forward and inverse solutions. In this work a dynamic heart model is developed. With this model the effect of the heart motion on the forward and inverse solutions is investigated.

Abstract:

Computer simulations can significantly improve comprehension of cardiac electrophysiology. A mathematical model for the simulation of complex cardiac electrophysiology is the bidomain model. A new tool, acCELLerate, was developed using the PETSc library [1] for a parallel time and memory efficient implementation of the bidomain equations enabling the computation of large scale cardiac simulations. It offers an extensible modular structure. The optimization of the cost-intensive solution of the elliptical part of the bidomain equation was achieved by analyzing several iterative Krylov subspace methods and preconditioners provided by PETSc. Best performance results were achieved by using a combination of minimal residual method (MinRes), conjugate residual method (CR) or conjugate grandient method (CG) as solver with adjusted successive over-relaxation preconditioning (SOR). A validation proved the authenticity of the new tool.

Abstract:

Many studies conducted on patients suffering from congestive heart failure have shown the efficacy of cardiac resynchronization therapy (CRT). The presented research investigates an off-line optimization algorithm based on different electrode positioning and timing delays. A computer model of the heart was used to simulate left bundle branch block (LBBB), myocardial infarction (MI) and reduction of intraventricular conduction velocity in order to customize the patient symptom. The optimization method evaluates the error between the healthy heart and pathology with/without pacing in terms of activation time and QRS length. Additionally, a torso model of the patient is extracted to compute the body surface potential map (BSPM) and to simulate the ECG with Wilson leads to validate the results obtained by the electrophysiological heart model optimization.

Abstract:

The treatment of ventricular arrhythmia often requires detailed information about the location of ectopic beats. A noninvasive procedure is adopted to achieve this purpose. The aim of this work is the reconstruction of ectopic foci by using the critical point theory introduced by Greensite and Huiskamp [1]. The reliability and adaptability of the obtained simulation results are evaluated with regard to the reconstruction error.The reconstruction of bioelectrical sources from measured body surface potentials is an ill-posed problem and requires regularization. The advantage of the presented method is to deal with a well-posed formulation of the problem. Locations of ectopic beats can be detected by the critical point theorem. Four simulated ectopic centers have been localized to evaluate the method. The influence of Gaussian noise is considered.The reconstruction depends on the effective rank of a singular value decomposition (SVD) of the multi-channel ECG matrix. Regarding lower ranks, many critical points presenting ectopic foci can be observed. For higher ranks, the detection leads more and more to a stable estimation of ectopic locations. The detected critical points are shown to be reliable approximations of the simulated ectopic foci.

Abstract:

Increasing biophysical detail in multi physical, multiscale cardiac model will demand higher levels of parallelism in multi-core approaches to obtain fast simulation times. As an example of such a highly parallel multi-core approaches, we develop a completely distributed bidomain cardiac model implemented on the IBM Blue Gene/L architecture. A tissue block of size 50 times 50 times 100 cubic elements based on ten Tusscher et al. (2004) cell model is distributed on 512 computational nodes. The extracellular potential is calculated by the Gauss-Seidel (GS) iterative method that typically requires high levels of inter-processor communication. Specifically, the GS method requires knowledge of all cellular potentials at each of it iterative step. In the absence of shared memory, the values are communicated with substantial overhead. We attempted to reduce communication overhead by computing the extracellular potential only every 5th time step for the integration of the cell models. We also investigated the effects of reducing inter-processor communication to every 5th, 10th, 50th iteration or no communication within the GS iteration. While technically incorrect, these approximation had little impact on numerical convergence or accuracy for the simulations tested. The results suggest some heuristic approaches may further reduce the inter-processor communication to improve the execution time of large-scale simulations.

Abstract:

The number of implanted cardiac pacemakers and defibrillators is constantly increasing. At the same time, more and more of those patients use wireless mobile communication devices.Aim of this work was the development of a pacemaker-electrode model and its “implantation” into a detailed anatomical correct voxel model. Additionally generic body models were examined. It consists of several layers with varying thickness and conductivity/permittivity values corresponding to different tissue types. This approach was chosen to avoid numerical errors at tilted boundaries. The excitation sources were modeled as generic dipoles and as plane waves operating at the frequency range normally used by cellular phones and wireless networks (900 to 2450 MHz). The dipoles were designed to provide maximum radiation efficiency at the frequencies of interest. Finally numerical calculation of induced fields by external signal sources were conducted. The results were then evaluated regarding the compliance to the guidelines of ICNIRP and a draft by DIN/VDE.For the Visible Man model, the computed specific absorption rate (SAR) values were well below the thresholds both for single and multi-antenna setups and for all frequencies of interest if the power did not exceed the regulatory specifications. The same results were obtained for the electrical field values determined at commonly used implantation sites for pacemakers. For some tissue configurations in the generic model, higher SAR values than allowed by regulations could be observed.

Abstract:

The development of new devices used for defibrillation and cardioversion is often supported by numerical simulations of the induced electric potentials and current distributions. The commonly used tools incorporate isotropic models of the tissue properties present in the human torso. A comparative study was conducted to characterize the influence of anisotropic compared to isotropic tissue modeling. Defibrillation shocks with amplitudes of 1000 V and 2000 V were simulated and a set of varying conductivity values and anisotropy ratios was examined. The inclusion of tissue anisotropy produced significantly smaller values for current density compared to isotropic calculations especially in the myocardial tissue.

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.

Abstract:

The sinus node (SN), which is the primary pacemaker of the heart, is a heterogeneous structure, i.e. there is a difference between center and periphery regarding morphology, electrophysiology and electrical coupling. The behavior of the whole SN in detail is difficult to investigate experimentally. Therefore, realistic computer models are helpful to understand the electrophysiological mechanisms quantitatively. In this work, different models of the SN including heterogeneity are benchmarked.Several approaches considering SN heterogeneity exist. One possible description of the electrical conduction is the mosaic model, in which the density of two discrete cell types, central and peripheral cells, is varied from the center to the periphery of the SN. The gradient model is another approach for this task. As the name implies, there is a gradual transition in cell morphology and electrophysiology between the center and periphery.The behavior of single nodal cells were described best by the rabbit SN model of Zhang et al. [1], offering explicit formulations for central and peripheral cells. A one-dimensional model of the SN and surrounding atrial tissue and a two-dimensional slice of the SN and adjoining crista terminalis (CT) were applied. Both approaches describing electrical conduction were compared using these different geometric models, in order to find the most exact model in relation to measured data describing activation patterns and action potential durations.