O. Doessel. Longitudinal and transverse gauge factors of polycrystalline strain. In Sensors and Actuators, vol. 6(3) , pp. 169-179, 1984
The gauge factor of strain gauges is calculated considering the longitudinal and transverse strain sensitivity of the resistivity. The general result is applied to free wire strain gauges, adhered foil strain gauges and thin film strain gauges. The relation between the gauge factor and the piezoresistive constant..
In time resolved luminescence spectra, taken within the temperature range of 1180 K, the two lowest excited states of rare gas crystals are observed. One of them, the long lived 3 state is identified as the initial state for transient absorption. The transient absorption spectra (1180 K) indicate strong similarities between self-trapped excitons in the crystals and free excimers, but only in the energy region up to 1.5 eV above the lowest excited state 3. Higher energy levels and the continuum states of the self-trapped exciton are strongly influenced by solid state effects. The Journal of Chemical Physics is copyrighted by The American Institute of Physics
O. Dössel. Biomechanic models and image guided interventions. In Biomedizinische Technik. Biomedical Engineering, vol. 60(6) , pp. 519-520, 2015
O. Dössel. Modelling and simulation in medicine the virtual patient. In Information Technology, vol. 52(5) , pp. 239-241, 2010
O. Dössel. Patient safety in medical technology research. Patientensicherheit in der medizintechnischen Forschung. In Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, vol. 52(6) , pp. 579-583, 2009
The message of this article is that patient safety must be an essential part of thinking and planning in research for medical technology. Which aspects must be considered already in an early phase of any project are presented. The most important standards are listed briefly. Then the topics technical safety and electromagnetic compatibility (EMC), clinical evaluation, risk analysis, biological evaluation of materials, ergonomics, the special aspects of medical devices that include pharmacological components, and the requirements of software packages and implemented algorithms are discussed.Im vorliegenden Beitrag wird begründet, warum die Patientensicherheit vom ersten Tag an ein wesentlicher Bestandteil der Überlegungen und Planungen in der medizintechnischen Forschung sein muss. Es wird dargestellt, welche Aspekte insbesondere schon in den frühen Phasen eines Projektes berücksichtigt werden müssen. Die wichtigsten Normen werden nur kurz angesprochen. Dann werden die Themen technische Sicherheit und Elektromagnetische Verträglichkeit (EMV), klinische Prüfung, Risikoanalyse, biologische Bewertung von Materialien, Ergonomie, die Problematik von Medizintechnik mit pharmakologischen Komponenten und die Anforderungen an reine Softwarepakete für die Medizin und an implementierte Algorithmen genauer betrachtet.
O. Dössel. Inverse problem of electro- and magnetocardiography: Review and recent progress. In Int. J. Bioelectromagnetism, vol. 2(2) , 2000
More than 20 years of research in imaging of bioelectric sources in the human heart have passed and a lot of effort has been devoted to the topic. In spite of that the method is not established in clinical practice but still just an interesting research topic of enthusiastic scientist. A review together with a comprehensive literature survey is given in this article. Recent developments and new trends are outlined.
O. Dössel, and J. Bohnert. Safety considerations for magnetic fields of 10 mT to 100 mT amplitude in the frequency range of 10 kHz to 100 kHz for magnetic particle imaging. In Biomedizinische Technik. Biomedical Engineering, vol. 58(6) , pp. 611-621, 2013
Abstract Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI.
O. Dössel, B. David, M. Fuchs, J. Krüger, W. H. Kullmann, and K. M. Ludeke. A modular approach to multichannel magnetometry. In Clinical Physics and Physiological Measurement : an Official Journal of the Hospital Physicists' Association, Deutsche Gesellschaft fur Medizinische Physik and the European Federation of Organisations for Medical Physics, vol. 12 Suppl B, pp. 75-79, 1991
A 19-channel SQUID system for biomagnetic measurements has been developed. This system differs from standard instruments in its modular approach. Various gradiometers can be coupled to the SQUIDs, the cryogenic system allows the exchange of single channels and the electronics is based on a cassette system. Problems with thermal insulation, vibrations of the gradiometers and tilted gradiometer geometries are discussed and solutions are presented.
A modular multichannel SQUID-system, in which every single channel can be optimized or replaced individually, is presented. The DC-SQUIDs based on the materials NbN/MgO are prepared by thin film technology and show noise values below 10μΦ0/√Hz. A simplified way of coupling the modulation and feedback current directly to the coupling coil is realized The complete SQUID module including the superconducting shield was miniaturized down to a diameter of 5mm. The gradiometers are wire wound and an as made balancing better than 10−3 is achieved. The cryogenic system was optimized with respect to low vibrations and low helium boil off rate. Simple conductive paint with precisely adjusted surface resistivity is used for RF-shielding. The complete SQUID-electronic of one channel has been realized on one single board and uses a new bias modulation scheme to completely suppress intrinsic 1/f noise. The noise level of the complete system is below 10fT/√Hz. Biomagnetic measurements of the human heart and brain are presented. Single current dipole reconstructions and current density imaging techniques can be used to find the underlying sources. Using a special coil positioning system an overlay of the functional current images with morphological MR-images can be carried out.
Current sources in the human body can be localized by measuring the biomagnetic fields with multichannel SQUID systems. Important system aspects are the noise level, the ambient field suppression, the dynamic range, the reliability, the number of channels, and the arrangement of gradiometers. From the users point of view the most important quality factor is the accuracy with which a current dipole can be localized. A test procedure is proposed to determine the localization power of the system. A 31-channel-SQUID system is presented together with the results of the test. The crucial parts of the system determining the accuracy are pointed out.
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.
Cardiac arrhythmia is currently investigated from two different points of view. One considers ECG bio-signal analysis and investigates heart rate variability, baroreflex control, heart rate turbulence, alternans phenomena, etc. The other involves building computer models of the heart based on ion channels, bio-domain models and forward calculations to finally reach ECG and body surface potential maps. Both approaches aim to support the cardiologist in better understanding of arrhythmia, improving diagnosis and reliable risk stratification, and optimizing therapy. This article summarizes recent results and aims to trigger new research to bridge the different views.
O. Dössel, F. B. Sachse, G. Seemann, and C. D. Werner. Computermodelle der elektrophysiologischen Eigenschaften des Herzens - Computer models of the electrophysiological properties of the heart. In Biomedizinische Technik, vol. 47(9-10) , pp. 250-257, 2002
Computer models of the heart can improve the understanding of the electrophysiological processes in healthy and diseased heart. They become more and more important for detailled diagnosis of arrhythmias and for optimization of therapy. Models of myocardium cells known today are described - they are based on the properties of all relevant ion channels in the cell membrane. Then it is demonstrated, how many cells can be joined to form a cell patch and how finally the complete heart can be modelled. A simpler approach is using a so called cellular automaton that allows for a significant reduction of calculation time while sacrifying some accordance to reality. Adaptive cellular automatons allow for a fast simulation with acceptable accuracy. Using them some results were gained for the simulation of typical arrhythmias, in the field of validation using an animal model and for therapy planning with RF-ablation.
O. Dössel, and G. Seemann. Modeling cardiac electric fields. In Int. J. Bioelectromagnetism, vol. 5(1) , pp. 9-13, 2003
Computer models of the electrophysiological processes in the human heart become increasingly precise and detailed. The dream of supporting diagnosis of arrhythmias and planning of therapeutic interventions comes into reach. Recent progress in the field of cellular models (including e.g. pathological cases), in the field of coupled cell patches (including e.g. heterogeneity) and in the field of validation (including e.g. intracardial multi-channel recordings) are reported.
Cardiologists measure electric signals inside the human heart aiming at a better diagnosis and optimized therapy of atrial arrhythmias like atrial flutter and atrial fibrillation. The catheters that are used for this purpose are improving: now they are able to pick up the electric signals at up to 64 positions inside the heart simultaneously. The patterns of electric depolarization are sometimes very simple, comparable to plane waves. But in case of patients with severe atrial arrhythmias they can be quite complex: U-turns around a line of block, ectopic centres, break throughs, reentry circuits, rotors, fractionated signals and chaotic patterns are often observed. Methods of biosignal analysis can support the cardiologists in classifying the signals and extract information of high diagnostic relevance. Computer models of the electrophysiology of the human heart can serve to design better algorithms for data analysis and to test algorithms, because the ground truth is known.
INTRODUCTION: The "Experimental Data and Geometric Analysis Repository", or EDGAR is an Internet-based archive of curated data that are freely distributed to the international research community for the application and validation of electrocardiographic imaging (ECGI) techniques. The EDGAR project is a collaborative effort by the Consortium for ECG Imaging (CEI, ecg-imaging.org), and focused on two specific aims. One aim is to host an online repository that provides access to a wide spectrum of data, and the second aim is to provide a standard information format for the exchange of these diverse datasets. METHODS: The EDGAR system is composed of two interrelated components: 1) a metadata model, which includes a set of descriptive parameters and information, time signals from both the cardiac source and body-surface, and extensive geometric information, including images, geometric models, and measure locations used during the data acquisition/generation; and 2) a web interface. This web interface provides efficient, search, browsing, and retrieval of data from the repository. RESULTS: An aggregation of experimental, clinical and simulation data from various centers is being made available through the EDGAR project including experimental data from animal studies provided by the University of Utah (USA), clinical data from multiple human subjects provided by the Charles University Hospital (Czech Republic), and computer simulation data provided by the Karlsruhe Institute of Technology (Germany). CONCLUSIONS: It is our hope that EDGAR will serve as a communal forum for sharing and distribution of cardiac electrophysiology data and geometric models for use in ECGI research.
Mapping of electrical endocardial activity is an important task for cardiac diagnosis and surgical treatment planning. Different kinds of catheters measure this activity with a limited number of electrodes. In recent years an increasing number of mapping systems is used in clinical routine. Various systems have been introduced and discussed in literature. This work deals with the localization of catheter electrodes in the heart with advanced techniques of digital image processing. The catheters - developed by various enterprises - differ in shape, handling and amount of electrodes. They are specified and presented in detail. Digital image analysis techniques like filters, Fourier and Hough transformation build the background and basics for this work. The main part describes the methods for the detection of the electrodes and the catheter strings. With these methods, it is possible to setup computer models for each catheter. The computer models can be used e. g. in numerical field calculation together with medical tomographic datasets.
At the current state of technology, multichannel simultaneous recording of combined electric potentials and magnetic fields should constitute the most powerful tool for separation and localization of focal brain activity. We performed an explorative study of multichannel simultaneous electric SEPs and magnetically recorded SEFs. MEG only sees tangentially oriented sources, while EEG signals include the entire activity of the brain. These characteristics were found to be very useful in separating multiple sources with overlap of activity in time. The electrically recorded SEPs were adequately modelled by three equivalent dipoles located: (1) in the region of the brainstem, modelling the P14 peak at the scalp, (2) a tangentially oriented dipole, modelling the N20-P20 and N30-P30 peaks, and part of the P45, and (3) a radially oriented dipole, modelling the P22 peak and part of the P45, both located in the region of the somatosensory cortex. Magnetically recorded SEFs were adequately modelled by a single equivalent dipole, modelling the N20-P20 and N30-P30 peaks, located close to the posterior bank of the central sulcus, in area 3b (mean deviation: 3 mm). The tangential sources in the electrical data were located 6 mm on average from the area 3b. MEG and EEG was able to locate the sources of finger stimulated SEFs in accordance with the somatotopic arrangement along the central fissure. A combined analysis demonstrated that MEG can provide constraints to the orientation and location of sources and helps to stabilize the inverse solution in a multiple-source model of the EEG.
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.
The paper is addressed to detect the parameters of a sphere-center coordinates and radius based on a stack of CT slices. It is proposing a new hierarchical Hough transform approach. In the first step, all slices are taken into consideration sequentially and a 2D accumulator array is used to obtain the coordinates (x"0,y"0), the projecting value of the sphere center into every X-Y-plane. In this step, also a new type of 2D Hough transform for circle or circular detection is proposed based on an effective point filtering. In the second step, the radii of the circles in the different slices are obtained using 1D accumulator arrays. In the last step, the coordinate z"0 and the radius R of the sphere are acquired using a 2D planar Hough transform based on the correlation between the radii of circles, the coordinates z of the slice and the sphere radius. The hierarchical Hough transform is applied to analyze the structure of femoral head of human hip joints. Compared to the established Hough transform techniques for 3D object detection, the hierarchical Hough transform reduces storage space and calculation time significantly and it has a good robustness to noise in the images.
Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and noninvasively reconstructed in a digitized model of the patient’s three-dimensional heart, which has led to clinical interest in ECGI’s ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI’s ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose ‘best’ practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique towards a useful role in clinical practice.
Electrocardiographic imaging (ECGI) has recently gained attention as a viable diagnostic tool for reconstructing cardiac electrical activity in normal hearts as well as in cardiac arrhythmias. However, progress has been limited by the lack of both standards and unbiased comparisons of approaches and techniques across the community, as well as the consequent difficulty of effective collaboration across research groups.. To address these limitations, we created the Consortium for Electrocardiographic Imaging (CEI), with the objective of facilitating collaboration across the research community in ECGI and creating standards for comparisons and reproducibility. Here we introduce CEI and describe its two main efforts, the creation of EDGAR, a public data repository, and the organization of three collaborative workgroups that address key components and applications in ECGI. Both EDGAR and the workgroups will facilitate the sharing of ideas, data and methods across the ECGI community and thus address the current lack of reproducibility, broad collaboration, and unbiased comparisons.
A multi-layer technology, based on YBaCuO as the superconducting material and SrTiO3 as the insulating material, is described. Patterning is performed by photolithography and Ar-ion-beam etching under fiat incidence. Using a resist bake-out prior to the etching, step angles in the patterned lower film of less than 20 degrees are obtained. Superconducting 10-turn thin-film coils have been fabricated with transition temperatures of up to 83 K and critical current densities at 77 K of 2*105 A cm-2. Furthermore we have fabricated a thin-film flux transformer and combined it in flip-chip configuration with a low-noise YBCO step-edge DC SQUID. We measured a magnetic field resolution of the complete magnetometer of 200 fT Hz-1/2 at 1 Hz, dominated by the SQUID noise itself.
B. David, O. Dössel, and W. Kullmann. Gehirn-Funktionsdiagnostik mit SQUID-Matrizen / Functional brain diagnosis by SQUID. In Philips - Unsere Forschung in Deutschland, vol. 4, pp. 63-65, 1988
Ziel dieses neuen medizinischen Diagnoseverfahren ist es, mit sog. supraleitenden Quanten-Intererenz-Detektoren (SQUIDs), die durch neuronale Ströme im Gehirn hervorgerufen magnetischen Felder außerhalb des menschlichen Kopfes zu messen, um so ein Bild von der Funktion des Gehirns zu erstellen.
NbN/MgO/NbN Josephson tunnel junctions have been prepared using various barrier preparation conditions. The energy of the sputtered MgO particles arriving at the substrate was found to be the most important parameter. Tunnel junctions (10*10 mu m2) with Vm values of up to 23 mV have been fabricated. The optimized NbN/MgO/NbN junction process is extended to a reliable whole-wafer process for DC SQUID fabrication.
We have designed and fabricated three types of high- SQUID (superconducting quantum interference device) magnetometers based on step-edge Josephson junctions using three different concepts of coupling magnetic flux into the SQUID: (i) a single pickup loop galvanically coupled to the SQUID, (ii) a flux transformer inductively coupled to the SQUID and (iii) a multiloop pickup loop used directly as the SQUID inductance. On a substrate we achieved an effective flux capture area of and for the inductively coupled and multiloop devices, respectively. Due to the low white noise levels of for the inductively coupled magnetometer and for the multiloop device high quality magnetocardiograms were recorded inside a magnetically shielded room without signal averaging.
Three magnetometers based on dc superconducting quantum interference devices (SQUIDs) fabricated from YBa2Cu3O7 x have been operated in a magnetically shielded room using a flux-locked loop involving additional positive feedback with bias current reversal. Two of these devices, integrated multiloop dc SQUIDs with outer diameters of 7 mm, achieved white noise levels of 10 fT/√Hz for bicrystal junctions and 30 fT/√Hz for step‐edge junctions. The third magnetometer involved a flux transformer with a 10×10 mm2 pickup coil connected to a 16-turn input coil which was inductively coupled to a bicrystal SQUID. This device achieved a white noise of 16.2 fT/√Hz. High quality magnetocardiograms were obtained without signal averaging.
D. Farina, and O. Dössel. Non-invasive model-based localization of ventricular ectopic centers from multichannel ECG. In International Journal of Applied Electromagnetics and Mechanics, vol. 30(3-4) , pp. 289-297, 2009
Non-invasive localization of premature ventricular beat (PVB) foci is very important for medical treatment of numerous cardiac diseases. In this work a model-based method of reconstruction of ectopic center locations is investigated.Within the scope of this method patient's multichannel ECG is used as a reference for optimization of an electrophysiological cardiac model. This model is based on the cellular automaton principle and utilizes anatomical data of the patient. Optimized are coordinates of the ectopic focus as well as excitation conduction velocity of ventricular myocardium. Initial values for these parameters are obtained by solving the linearized problem of electrocardiography in terms of activation times. Optimization is performed by minimization of discrepancy between the simulated and reference ECGs.The aim of the current work is to estimate the quality of ectopic focus localization delivered by this method. Four sample ectopic beats have been simulated, with their foci located in different regions of the left ventricle. 1% Gaussian noise has been introduced into the resulting ECGs. In this way the "measured" ECG signals for this investigation have been obtained. Afterwards the origin of each ectopic beat has been reconstructed using the model-based approach. The method has demonstrated reliable localization of PVB foci, reconstruction errors have not exceeded 6.1 mm.
D. Farina, Y. Jiang, and O. Dössel. Acceleration of FEM-based transfer matrix computation for forward and inverse problems of electrocardiography. In Med Biol Eng Comput, vol. 47(12) , pp. 1229-1236, 2009
The distributions of transmembrane voltage (TMV) within the cardiac tissue are linearly connected with the patient's body surface potential maps (BSPMs) at every time instant. The matrix describing the relation between the respective distributions is referred to as the transfer matrix. This matrix can be employed to carry out forward calculations in order to find the BSPM for any given distribution of TMV inside the heart. Its inverse can be used to reconstruct the cardiac activity non-invasively, which can be an important diagnostic tool in the clinical practice.The computation of this matrix using the finite element method can be quite time-consuming. In this work, a method is proposed allowing to speed up this process by computing an approximate transfer matrix instead of the precise one. The method is tested on three realistic anatomical models of real-world patients. It is shown that the computation time can be reduced by 50% without loss of accuracy.
In this work an optimization-based method of modeling the cardiac activity is presented. The method employs a personalized anatomical 3D model of the patients thorax provided by the segmentation of MRI data as well as an electrophysiological model of the heart.Cellular automaton is used to model the propagation of depolarization and repolarization fronts through the myocardium. The form of action potential (AP) curves was previously derived from the coupled myocardium cell models developed by Noble, Priebe-Beuckelmann and ten Tusscher. The results provided by these three cell models are compared.A series of body surface potential maps (BSPMs) is calculated, the signals on the nodes representing the electrodes are recorded, providing thus a simulated multichannel ECG. A root-mean-square of the difference between simulated and measured ECGs is taken as a criterion for optimization of heart model parameters.The method provides a time-dependent distribution of transmembrane voltages within the heart muscle of a patient.
T. Fritz, C. Wieners, G. Seemann, H. Steen, and O. Dössel. Simulation of the contraction of the ventricles in a human heart model including atria and pericardium : Finite element analysis of a frictionless contact problem. In Biomechanics and Modeling in Mechanobiology, vol. 13(3) , pp. 627-641, 2014
During the contraction of the ventricles, the ventricles interact with the atria as well as with the pericardium and the surrounding tissue in which the heart is embedded. The atria are stretched, and the atrioventricular plane moves toward the apex. The atrioventricular plane displacement (AVPD) is considered to be a major contributor to the ventricular function, and a reduced AVPD is strongly related to heart failure. At the same time, the epicardium slides almost frictionlessly on the pericardium with permanent contact. Although the interaction between the ventricles, the atria and the pericardium plays an important role for the deformation of the heart, this aspect is usually not considered in computational models. In this work, we present an electromechanical model of the heart, which takes into account the interaction between ventricles, pericardium and atria and allows to reproduce the AVPD. To solve the contact problem of epicardium and pericardium, a contact handling algorithm based on penalty formulation was developed, which ensures frictionless and permanent contact. Two simulations of the ventricular contraction were conducted, one with contact handling of pericardium and heart and one without. In the simulation with contact handling, the atria were stretched during the contraction of the ventricles, while, due to the permanent contact with the pericardium, their volume increased. In contrast to that, in the simulations without pericardium, the atria were also stretched, but the change in the atrial volume was much smaller. Furthermore, the pericardium reduced the radial contraction of the ventricles and at the same time increased the AVPD.
M. Fuchs, W. H. Kullmann, and O. Dössel. Functional imaging of neuronal brain activities. Overlay of distributed neuromagnetic current density images and morphological MR images. In European Radiology, vol. 3(1) , pp. 41-43, 1993
Neuromagnetic imaging is a relatively new diagnostic tool for examination of electrical activities in the nervous system. It is based on the non-invasive detection of extremely weak magnetic fields around the human body with superconducting quantum interference device (SQUID) detectors. Often the equivalent current dipole model is used to describe the centre of the electrical activity. New current density reconstruction methods enable the imaging of the spatial extent and structure of neuronal activities. For practical use in medical diagnosis a combination of the abstract neuromagnetic images with MR or CT images is required in order to match the functional activity with anatomy and morphology. The neuromagnetic images can be overlaid onto three-dimensional morphological images with spatially arbitrarily selectable slices. The matching of both imaging modalities is discussed. On the basis of the detection of auditory evoked magnetic fields, neuromagnetic images are reconstructed with linear estimation theory algorithms. The MR images are used as a priori information of the volume conductor geometry and allow an attachment of functional and morphological properties.
M. A. Golombeck, O. Dössel, and J. Raiser. Improvement of patient return electrodes in electrosurgery by experimental investigations and numerical field calculations. In Med Biol Eng Comput, vol. 41(5) , pp. 519-528, 2003
Numerical field calculations and experimental investigations were performed to examine the heating of the surface of human skin during the application of a new electrode design for the patient return electrode. The new electrode is characterised by an equipotential ring around the central electrode pads. A multi-layer thigh model was used, to which the patient return electrode and the active electrode were connected. The simulation geometry and the dielectric tissue parameters were set according to the frequency of the current. The temperature rise at the skin surface due to the flow of current was evaluated using a two-step numerical solving procedure. The results were compared with experimental thermographical measurements that yielded a mean value of maximum temperature increase of 3.4 degrees C and a maximum of 4.5 degrees C in one test case. The calculated heating patterns agreed closely with the experimental results. However, the calculated mean value in ten different numerical models of the maximum temperature increase of 12.5 K (using a thermodynamic solver) exceeded the experimental value owing to neglect of heat transport by blood flow and also because of the injection of a higher test current, as in the clinical tests. The implementation of a simple worst-case formula that could significantly simplify the numerical process led to a substantial overestimation of the mean value of the maximum skin temperature of 22.4 K and showed only restricted applicability. The application of numerical methods confirmed the experimental assertions and led to a general understanding of the observed heating effects and hotspots. Furthermore, it was possible to demonstrate the beneficial effects of the new electrode design with an equipotential ring. These include a balanced heating pattern and the absence of hotspots.
I. M. Graf, G. Seemann, D. L. Weiss, and O. Dössel. Influence of electrophysiological heterogeneity on electrical stimulation in healthy and failing human hearts. In Medical & Biological Engineering & Computing, vol. 43(6) , pp. 783-792, 2005
The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+-Ca2+ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.
D. Grundler, B. David, and O. Doessel. Experimental investigation of the kinetic inductance in YBa2Cu3O7 square washer superconducting quantum interference devices. In Journal of Applied Physics, vol. 77(10) , pp. 5273-5277, 1995
We have fabricated Y1Ba2Cu3O7-x step-edge junction dc superconducting quantum interference devices (SQUIDs) and characterized their noise performance. The current-voltage characteristics of our SQUIDs are of resistively shunted junction type with critical current densities jc of about 104 A/cm2 and maximum flux to voltage transfer functions...
D. Grundler, J. P. Krumme, B. David, and O. Dössel. YBa2Cu3O7 ramp-type junctions and superconducting quantum interference devices with an ultrathin barrier of NdGaO3. In Applied Physics Letters, vol. 65(14) , pp. 1841-1843, 1994
We have fabricated ramp-type Josephson junctions and SQUIDs (superconducting quantum interference devices) using an ultrathin barrier layer of NdGaO3 as weak contact between the YBa2Cu3O7 electrodes. The junctions operate up to 82 K, exhibiting current-voltage characteristics of the resistively-hunted-unction type. A normal-state resistance of up to....
We have fabricated YBa2Cu3O7 ramp-type junctions incorporating a barrier layer of NdGaO3 with a nominal thickness of 2 nm. The junctions exhibit pronounced Josephson effects and operate up to 82 K. The characteristics are well described within the resistively shunted junction model. We observe large hysteresis parameters βc even at elevated temperatures. The output voltage of a high-Tc dc SQUID is found to benefit from the intrinsic junction capacitance.
C. Haase, D. Schäfer, O. Dössel, and M. Grass. Model based 3D CS-catheter tracking from 2D X-ray projections: binary versus attenuation models. In Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society, vol. 38(3) , pp. 224-231, 2014
Tracking the location of medical devices in interventional X-ray data solves different problems. For example the motion information of the devices is used to determine cardiac or respiratory motion during X-ray guided procedures or device features are used as landmarks to register images. In this publication an approach using a 3D deformable catheter model is presented and used to track a coronary sinus (CS) catheter in 3D plus time through a complete rotational angiography sequence. The benefits of using voxel based models with attenuation information for 2D/3D registration are investigated in comparison to binary catheter models. The 2D/3D registration of the model allows to extract a 3D catheter shape from every individual 2D projection. The tracking accuracy is evaluated on simulated and clinical rotational angiography data of the contrast enhanced left atrium. The quantitative evaluation of the experiments delivers an average registration accuracy for all catheter electrodes of 0.23 mm in 2D and 0.95 mm in 3D when using an attenuation model of the catheter. The overall tracking accuracy is lower when using binary catheter models.
Cardiac ablation procedures during electrophysiology interventions are performed under x-ray guidance with a C-arm imaging system. Some procedures require catheter navigation in complex anatomies like the left atrium. Navigation aids like 3D road maps and external tracking systems may be used to facilitate catheter navigation. As an alternative to external tracking a fully automatic method is presented here that enables the calculation of the 3D location of the ablation catheter from individual 2D x-ray projections. The method registers a high resolution, deformable 3D attenuation model of the catheter to a 2D x-ray projection. The 3D localization is based on the divergent beam projection of the catheter. On an individual projection, the catheter tip is detected in 2D by image filtering and a template matching method. The deformable 3D catheter model is adapted using the projection geometry provided by the C-arm system and 2D similarity measures for an accurate 2D/3D registration. Prior to the tracking and registration procedure, the deformable 3D attenuation model is automatically extracted from a separate 3D cone beam CT reconstruction of the device. The method can hence be applied to various cardiac ablation catheters. In a simulation study of a virtual ablation procedure with realistic background, noise, scatter and motion blur an average 3D registration accuracy of 3.8 mm is reached for the catheter tip. In this study four different types of ablation catheters were used. Experiments using measured C-arm fluoroscopy projections of a catheter in a RSD phantom deliver an average 3D accuracy of 4.5 mm.
Cardiac C-arm CT imaging delivers a tomographic region-of-interest reconstruction of the patient's heart during image guided catheter interventions. Due to the limited size of the flat detector a volume image is reconstructed, which is truncated in the cone-beam (along the patient axis) and the fan-beam (in the transaxial plane) direction. To practically address this local tomography problem correction methods, like projection extension, are available for first pass image reconstruction. For second pass correction methods, like metal artefact reduction, alternative correction schemes are required when the field of view is limited to a region-of-interest of the patient. In classical CT imaging metal artefacts are corrected by metal identification in a first volume reconstruction and generation of a corrected projection data set followed by a second reconstruction. This approach fails when the metal structures are located outside the reconstruction field of view. When a C-arm CT is performed during a cardiac intervention pacing leads and other cables are frequently positioned on the patients skin, which results in propagating streak artefacts in the reconstruction volume. A first pass approach to reduce this type of artefact is introduced and evaluated here. It makes use of the fact that the projected position of objects outside the reconstruction volume changes with the projection perspective. It is shown that projection based identification, tracking and removal of high contrast structures like cables, only detected in a subset of the projections, delivers a more consistent reconstruction volume with reduced artefact level. The method is quantitatively evaluated based on 50 simulations using cardiac CT data sets with variable cable positioning. These data sets are forward projected using a C-arm CT system geometry and generate artefacts comparable to those observed in clinical cardiac C-arm CT acquisitions. A C-arm CT simulation of every cardiac CT data set without cables served as a ground truth. The 3D root mean square deviation between the simulated data set with and without cables could be reduced for 96% of the simulated cases by an average of 37% (min -9%, max 73%) when using the first pass correction method. In addition, image quality improvement is demonstrated for clinical whole heart C-arm CT data sets when the cable removal algorithm was applied.
Purpose: Three-dimensional (3-D) reconstruction of the coronary arteries during a cardiac catheter-based intervention can be performed from a C-arm based rotational x-ray angiography sequence. It can support the diagnosis of coronary artery disease, treatment planning, and intervention guidance. 3-D reconstruction also enables quantitative vessel analysis, including vessel dynamics from a time-series of reconstructions.Methods: The strong angular undersampling and motion effects present in gated cardiac reconstruction necessitate the development of special reconstruction methods. This contribution presents a fully automatic method for creating high-quality coronary artery reconstructions. It employs a sparseness-prior based iterative reconstruction technique in combination with projection-based motion compensation.Results: The method is tested on a dynamic software phantom, assessing reconstruction accuracy with respect to vessel radii and attenuation coefficients. Reconstructions from clinical cases are presented, displaying high contrast, sharpness, and level of detail.Conclusions: The presented method enables high-quality 3-D coronary artery imaging on an interventional C-arm system.
E. Hansis, D. Schäfer, O. Dössel, and M. Grass. Evaluation of iterative sparse object reconstruction from few projections for 3-D rotational coronary angiography. In IEEE Transactions on Medical Imaging, vol. 27(11) , pp. 1548-1555, 2008
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.
E. Hansis, D. Schäfer, O. Dössel, and M. Grass. Automatic optimum phase point selection based on centerline consistency for 3D rotational coronary angiography. In International Journal of Computer Assisted Radiology and Surgery, vol. 3(3-4) , pp. 355-361, 2008
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.
E. Hansis, D. Schäfer, O. Dössel, and M. Grass. Projection-based motion compensation for gated coronary artery reconstruction from rotational x-ray angiograms. In Physics in Medicine and Biology, vol. 53(14) , pp. 3807-3820, 2008
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.
The specific absorption rate (SAR) is a limiting constraint in sequence design for high-field MRI. SAR estimation is typically performed by numerical simulations using generic human body models. This entails an intrinsic uncertainty in present SAR prediction. This study first investigates the required detail of human body models in terms of spatial resolution and the number of soft tissue classes required, based on finite-differences time-domain simulations of a 3 T body coil. The numerical results indicate that a resolution of 5 mm is sufficient for local SAR estimation. Moreover, a differentiation between fatty tissues, water-rich tissues, and the lungs was found to be essential to represent eddy current paths inside the human body. This study then proposes a novel approach for generating individualized body models from whole-body water-fat-separated MR data and applies it to volunteers. The SAR hotspots consistently occurred in the arms due to proximity to the body coil as well as in narrow regions of the muscles. An initial in vivo validation of the simulated fields in comparison with measured B(1) -field maps showed good qualitative and quantitative agreement. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc.
OBJECT: Parallel transmission facilitates a relatively direct control of the RF transmit field. This is usually applied to improve the RF field homogeneity but might also allow a reduction of the specific absorption rate (SAR) to increase freedom in sequence design for high-field MRI. However, predicting the local SAR is challenging as it depends not only on the multi-channel drive but also on the individual patient. MATERIALS AND METHODS: The potential of RF shimming for SAR management is investigated for a 3 T body coil with eight independent transmit elements, based on Finite-Difference Time-Domain (FDTD) simulations. To address the patient-dependency of the SAR, nine human body models were generated from volunteer MR data and used in the simulations. A novel approach to RF shimming that enforces local SAR constraints is proposed. RESULTS: RF shimming substantially reduced the local SAR, consistently for all volunteers. Using SAR constraints, a further SAR reduction could be achieved with only minor compromises in RF performance. CONCLUSION: Parallel transmission can become an important tool to control and manage the local SAR in the human body. The practical use of local SAR constraints is feasible with consistent results for a variety of body models.
The specific absorption rate (SAR) is an important safety criterion, limiting many MR protocols with respect to the achievable contrast and scan duration. Parallel transmission enables control of the radiofrequency field in space and time and hence allows for SAR management. However, a trade-off exists between radiofrequency pulse performance and SAR reduction. To overcome this problem, in this work, parallel transmit radiofrequency pulses are adapted to the position in sampling k-space. In the central k-space, highly homogeneous but SAR-intensive radiofrequency shim settings are used to achieve optimal performance and contrast. In the outer k-space, the homogeneity requirement is relaxed to reduce the average SAR of the scan. The approach was experimentally verified on phantoms and volunteers using field echo and spin echo sequences. A reduction of the SAR by 25-50% was achieved without compromising image quality.
In this study the performance of a planar array for magnetic induction tomography (MIT) was investigated and the results of measurements to determine the precision and sensitivity of the sensor were undertaken. A planar-array MIT system utilizing flux-linkage minimization for the primary field has been constructed and evaluated. The system comprises 4 printed excitation coils of 4 turns which were shielded, 8 surface-mount inductors of inductance 10 microH as sensor, mounted such that in principle no primary-field flux threads them, and a calibration coil to produce a strong primary field. The excitation current was multiplexed via relays to drive the excitation and reference coils. The noise values were similar in real and imaginary components in the lower frequencies and the factor to which the primary field could be reduced was greatest in the nearest coil. Methods for determining the true real and imaginary components and for flux-linkage minimization for the primary field for variations in channel sensitivities are described and the results of measurements of the system's noise and drift are given. A SNR of 47 dB was observed at 4 MHz when a 0.3 Sm-1 saline filled tank of dimensions 20 cmx20 cmx10 cm was placed centrally over the array. Finally, images were reconstructed from measurements of saline samples in a free space background, with the samples moved past the array in 21 1 cm steps to emulate mechanical scanning of the array. The image reconstruction characteristics of the planar array in conjunction with the reconstruction technique employed are discussed.
A. M. Janssen, D. Potyagaylo, O. Dössel, and T. F. Oostendorp. Assessment of the equivalent dipole layer source model in the reconstruction of cardiac activation times on the basis of BSPMs produced by an anisotropic model of the heart. In Medical & Biological Engineering & Computing, 2017
Promising results have been reported in noninvasive estimation of cardiac activation times (AT) using the equivalent dipole layer (EDL) source model in combination with the boundary element method (BEM). However, the assumption of equal anisotropy ratios in the heart that underlies the EDL model does not reflect reality. In the present study, we quantify the errors of the nonlinear AT imaging based on the EDL approximation. Nine different excitation patterns (sinus rhythm and eight ectopic beats) were simulated with the monodomain model. Based on the bidomain theory, the body surface potential maps (BSPMs) were calculated for a realistic finite element volume conductor with an anisotropic heart model. For the forward calculations, three cases of bidomain conductivity tensors in the heart were considered: isotropic, equal, and unequal anisotropy ratios in the intra- and extracellular spaces. In all inverse reconstructions, the EDL model with BEM was employed: AT were estimated by solving the nonlinear optimization problem with the initial guess provided by the fastest route algorithm. Expectedly, the case of unequal anisotropy ratios resulted in larger localization errors for almost all considered activation patterns. For the sinus rhythm, all sites of early activation were correctly estimated with an optimal regularization parameter being used. For the ectopic beats, all but one foci were correctly classified to have either endo- or epicardial origin with an average localization error of 20.4 mm for unequal anisotropy ratio. The obtained results confirm validation studies and suggest that cardiac anisotropy might be neglected in clinical applications of the considered EDL-based inverse procedure.
Y. Jiang, D. Farina, M. Bar-Tal, and O. Dössel. An impedance based catheter positioning system for cardiac mapping and navigation. In IEEE Transactions on Biomedical Engineering, vol. 56(8) , pp. 1963-1970, 2009
Over the last years, nonfluoroscopic in vivo cardiac mapping and navigation systems have been developed and successfully applied in clinical electrophysiology. Clearly, a trend can be observed to introduce more sensors into the measurement system so that physiological information can be gathered simultaneously and more efficiently and the duration of procedure can be shortened significantly. However, it would not be realistic to equip each catheter electrode with a localizer, e.g., by embedding a miniature magnetic location sensor. Therefore, in this paper, an alternate approach has been worked out to efficiently localize multiple catheter electrodes by considering the impedance between electrodes in the heart and electrode patches on the body surface. In application of the new technique, no additional expensive and sophisticated hardware is required other than the currently existing cardiac navigation system. A tank model and a computerized realistic human model are employed to support the development of the positioning system. In the simulation study, the new approach achieves an average localization error of less than 1 mm, which proves the feasibility of the impedance-based catheter positioning system. Consequently, the new positioning system can provide an inexpensive and accurate solution to improve the efficiency and efficacy of catheter ablation.
Y. Jiang, C. Qian, R. Hanna, D. Farina, and O. Dössel. Optimization of the electrode positions of multichannel ECG for the reconstruction of ischemic areas by solving the inverse electrocardiographic problem. In International Journal of Bioelectromagnetism (Cover Article), vol. 11(1) , pp. 27-37, 2009
A. Jung, N. Kayhan, G. Reinerth, O. Dössel, and C. F. Vahl. Mechanisch induzierte Dissoziation von Kalzium vom kontraktilen Apparat elektrisch stimulierter, intakter, menschlicher, atrialer Trabekel. In Zeitschrift für Herz-, Thorax- und Gefäßchirurgie, vol. 18(5) , pp. 246-253, 2004
Die kurzzeitige Kalzium-Akkumulation im myokardialen Gewebe bei isotoner Kontraktion ist von klinischer Bedeutung, da die Kalziumüberladung des Zytosols ursächlich an der Entstehung von Rhythmusstörungen beteiligt ist. Unklar ist derzeit, woher das überschüssige Kalzium stammt, ob aus intrazellulären Speichern, modifizierten Membranströmen oder von Seiten des kontraktilen Apparates. Ziel dieser Arbeit ist es zu klären, 1) an welcher Stelle in der Zelle das Kalzium freigesetzt wird und 2) ob das Ausmaß der Aktin-Myosin- Überlappung oder die Anzahl angelagerter Querbrücken die Pufferkapazität des kontraktilen Apparates für Kalzium mitbestimmen.Methoden Muskeltrabekel von 18 Patienten, die sich einer Herzoperation unterzogen, wurden untersucht. Während isometrischer Kontraktion der Präparate setzte kurzzeitige, sinusoidale Längenvibration (Frequenz: 125 Hz, Amplitude: 14% ML) ein. Besonderes Augenmerk lag hierbei auf der Reaktion des Kalzium-Signals (Indikator: Fura-2/AM). In einer zweiten Messreihe wurde dieser Versuch nach Zugabe von 10 mM BDM wiederholt, das bekannt ist für seine Kraftminderung durch Senkung der Kalzium-Sensitivität des Troponin C. Im dritten Versuchsblock wurde permanente Vibration angewandt.Ergebnisse 1) Induzierte Vibration reduzierte die aktive Kraft auf das Niveau der Ruhekraft. Zeitgleich kam es zu einer messbaren Zunahme des Kalziums im Zytosol. 2) Bei subtotaler Inhibition der elektromechanischen Kopplung durch BDM erreichte die aktive Kraft 10,4% der Kontrolle bei nahezu unverändertem Kalziumsignal (Kalzium-Zeit-Integral unter BDM: 91,9±3,2% der Kontrolle). Vibration führte unter diesen Bedingungen zu einer Kraftinhibition, ohne dass eine zusätzliche Kalzium-Freisetzung erreicht wurde. 3) Permanente Vibration reduzierte die Kraftamplitude des supramaximal aktivierten Präparates auf 28% (1,3±0,4 mN). Gleichzeitig stieg das Kalzium-Zeit-Integral auf 114,5±4,7%.Schlussfolgerung Die Befunde sprechen dafür, dass die Reduktion der Anzahl angelagerter Querbrücken beim Verkürzungsvorgang zu einer Verminderung der Empfindlichkeit des kontraktilen Apparates für Kalzium führt. Die verminderte Pufferkapazität des kontraktilen Apparates für Kalzium wird messbar durch eine Zunahme der Kalziumkonzentration im Zytosol, wenn bereits angelagerte Querbrücken durch Vibration mechanisch gelöst werden oder wenn die Anlagerung von Querbrücken durch permanente Vibration verhindert wird. Dieser Befund erklärt die klinische Beobachtung, dass die akute Nachlastsenkung häufig mit dem Auftreten von Rhythmusstörungen verbunden ist.
The electric conductivity can potentially be used as an additional diagnostic parameter, e.g., in tumour diagnosis. Moreover, the electric conductivity, in connection with the electric field, can be used to estimate the local SAR distribution during MR measurements. In this study, a new approach, called electric properties tomography (EPT) is presented. It derives the patient's electric conductivity, along with the corresponding electric fields, from the spatial sensitivity distributions of the applied RF coils, which are measured via MRI. Corresponding numerical simulations and initial experiments on a standard clinical MRI system underline the principal feasibility of EPT to determine the electric conductivity and the local SAR. In contrast to previous methods to measure the patient's electric properties, EPT does not apply externally mounted electrodes, currents, or RF probes, thus enhancing the practicability of the approach. Furthermore, in contrast to previous methods, EPT circumvents the solution of an inverse problem, which might lead to significantly higher spatial image resolution.
The imaging performance of metal plate/phosphor screens which are used for the creation of portal images in radiotherapy is investigated by using Monte Carlo simulations. To this end the modulation transfer function, the noise power spectrum and the detective quantum efficiency [DQE(f)] are calculated for different metals and phosphors and different thicknesses of metal and phosphor for a range of spatial resolutions. The interaction of x-rays with the metal plate/phosphor screen is modeled with the EGS4 electron gamma shower code. Optical transport in the phosphor is modeled by simulating scattering and reabsorption events of individual optical photons. It is shown that metals with a high atomic number perform better than lighter metals in maximizing the DQE(f). It is furthermore shown that the DQE(f) for the metal plate/phosphor screen alone is nearly x-ray quantum absorption limited up to spatial frequencies of 0.4 cycles/mm. In addition, it is argued that the secondary quantum sink of optical photons imposed by the optical chain (mirror, lenses and video camera) leads to a significant degradation of the signal-to-noise ratio at spatial frequencies which are most important for successful registration of portal images. Therefore, the conclusion is that a replacement of the optical chain by a flat array of photodiodes placed directly under the phosphor will lead to a substantial improvement in image quality of portal images.
Ventricular wall deformation is widely assumed to have an impact on the morphology of the T-wave that can be measured on the body surface. This study aims at quantifying these effects based on an in silico approach. To this end, we used a hybrid, static-dynamic approach: action potential propagation and repolarization were simulated on an electrophysiologically detailed but static 3-D heart model while the forward calculation accounted for ventricular deformation and the associated movement of the electrical sources (thus, it was dynamic). The displacement vectors that describe the ventricular motion were extracted from cinematographic and tagged MRI data using an elastic registration procedure. To probe to what extent the T-wave changes depend on the synchrony/asynchrony of mechanical relaxation and electrical repolarization, we created three electrophysiological configurations, each with a unique QT time: a setup with physiological QT time, a setup with pathologically short QT time (SQT), and pathologically long QT time (LQT), respectively. For all three electrophysiological configurations, a reduction of the T-wave amplitude was observed when the dynamic model was used for the forward calculations. The largest amplitude changes and the lowest correlation coefficients between the static and dynamic model were observed for the SQT setup, followed by the physiological QT and LQT setups.
This paper examined the effects that different tissue conductivities had on forward-calculated ECGs. To this end, we ranked the influence of tissues by performing repetitive forward calculations while varying the respective tissue conductivity. The torso model included all major anatomical structures like blood, lungs, fat, anisotropic skeletal muscle, intestine, liver, kidneys, bone, cartilage, and spleen. Cardiac electrical sources were derived from realistic atrial and ventricular simulations. The conductivity rankings were based on one of two methods: First, we considered fixed percental conductivity changes to probe the sensitivity of the ECG regarding conductivity alterations. Second, we set conductivities to the reported minimum and maximum values to evaluate the effects of the existing conductivity uncertainties. The amplitudes of both atrial and ventricular ECGs were most sensitive for blood, skeletal muscle conductivity and anisotropy as well as for heart, fat, and lungs. If signal morphology was considered, fat was more important whereas skeletal muscle was less important. When comparing atria and ventricles, the lungs had a larger effect on the atria yet the heart conductivity had a stronger impact on the ventricles. The effects of conductivity uncertainties were significant. Future studies dealing with electrocardiographic simulations should consider these effects.
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.
Radiofrequency ablation (RFA) therapy is the gold standard in interventional treatment of many cardiac arrhythmias. A major obstacle are non transmural lesions, leading to recurrence of arrhythmias. Recent clinical studies have suggested intracardiac electrogram (EGM) criteria as a promising marker to evaluate lesion development. Seeking for a deeper understanding of underlying mechanisms, we established a simulation approach for acute RFA lesions. Ablation lesions were modeled by a passive necrotic core surrounded by a borderzone with properties of heated myocardium. Herein, conduction velocity and electrophysiological properties were altered. We simulated EGMs during RFA to study the relation between lesion formation and EGM changes using the bidomain model. Simulations were performed on a three dimensional setup including a geometrically detailed representation of the catheter with highly conductive electrodes. For validation, EGMs recorded during RFA procedures in five patients were analyzed and compared to simulation results. Clinical data showed major changes in the distal unipolar EGM. During RFA, the negative peak amplitude decreased up to 104% and maximum negative deflection was up to 88% smaller at the end of the ablation sequence. These changes mainly occurred in the first 10 s after ablation onset. Simulated unipolar EGM reproduced the clinical changes, reaching up to 83% negative peak amplitude reduction and 80% decrease in maximum negative deflection for transmural lesions. In future work, the established model may enable the development of further EGM criteria for transmural lesions even for complex geometries in order to support clinical therapy.
A continuum light emission extending from the infrared to the ultraviolet has been observed in highly excited Xe and Kr crystals. The light is emitted by an electron plasma with an electron density of about 10 to the 18th per cu cm. The kinetic energies of the electrons correspond to an electron temperature of about 2000 K for a lattice temperature of 15 K (Kr) and 60 K (Xe). This electron plasma represents a case of an extreme thermal nonequilibrium between electrons and the lattice consisting of neutrals and ions.
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.
F. Kreuder, B. Schreiber, C. Kausch, and O. Dössel. A structure-based method for on-line matching of portal images for an optimal patient set-up in radiotherapy. In Philips Journal of Research, vol. 51(2) , pp. 317-337, 1998
In radiotherapy, portal images are used to ensure a correct patient position during every radiation session. A reliable on-line verification is of clinical interest to interrupt the radiation in time in case the patient is not at the right position. A great problem for successful image registration is the poor image quality of portal images. They are corrupted by noise and of very low contrast. A method directly based on the grey levels is not sufficient. Therefore a structure-based method was developed which is almost insensitive to distrubances (air bubbles, noise, slowly varying grey levels). In most cases the selection of a region of interest (ROI) can be omitted. Besides the automatical segmentation of the radiation field, only the structures relevant for matching the anatomy are enhanced by using a bandpass filter. It is possible to detect the maximum correlation between different image modalities reliably (simulator image, digitally reconstructed radiograph, portal image). By using Fast Fourier Transformation (FFT), the calculation time is smaller than five seconds, which enables a clinical on-line verification. We have matched 1139 pairs of images of different modalities and various regions of the body (pelvis, nasopharyngeal space, head, lung). The success rate is greater than 95%.
S. Krey, B. David, R. Eckart, and O. Dössel. Low noise operation of integrated YBa2Cu3O7 magnetometers in static magnetic fields. In Applied Physics Letters, vol. 72(24) , pp. 3205-3207, 1998
The noise of two integrated YBa2Cu3O7-SrTiO3-YBa2Cu3O7 multilayer magnetometers in static magnetic fields up to 110 µT is investigated: An inductively coupled magnetometer with integrated flux transformer and a multiloop magnetometer. In both samples, only a moderate increase of the low frequency flux noise is found in high fields, due to the high epitaxial quality of the involved multilayer films. So for moderately shielded or unshielded applications in the earth's magnetic field, high-quality integrated YBa2Cu3O7 magnetometers can be operated with low excess noise.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.
Left atrial fibrosis is thought to contribute to the manifestation of atrial fibrillation (AF). Late Gadolinium enhancement (LGE) MRI has the potential to image regions of low perfusion, which can be related to fibrosis. We show that a simulation with a patient-specific model including left atrial regional fibrosis derived from LGE-MRI reproduces local activation in the left atrium more precisely than the regular simulation without fibrosis. AF simulations showed a spontaneous termination of the arrhythmia in the absence of fibrosis and a stable rotor center in the presence of fibrosis. The methodology may provide a tool for a deeper understanding of the mechanisms maintaining AF and eventually also for the planning of substrate-guided ablation procedures in the future.
Computational atrial models aid the understanding of pathological mechanisms and therapeutic measures in basic research. The use of biophysical models in a clinical environment requires methods to personalize the anatomy and electrophysiology (EP). Strategies for the automation of model generation and for evaluation are needed. In this manuscript, the current efforts of clinical atrial modeling in the euHeart project are summarized within the context of recent publications in this field. Model-based segmentation methods allow for the automatic generation of ready-to-simulate patient-specific anatomical models. EP models can be adapted to patient groups based on a-priori knowledge, and to the individual without significant further data acquisition. ECG and intracardiac data build the basis for excitation personalization. Information from late enhancement (LE) MRI can be used to evaluate the success of radio-frequency ablation (RFA) procedures and interactive virtual atria pave the way for RFA planning. Atrial modeling is currently in a transition from the sole use in basic research to future clinical applications. The proposed methods build the framework for model-based diagnosis and therapy evaluation and planning. Complex models allow to understand biophysical mechanisms and enable the development of simplified models for clinical applications.
Multiscale 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 electrocardiograms. 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.
BACKGROUND: The prevalence of atrial fibrillation is increased in patients with end-stage renal disease. Previous studies suggested that extracellular electrolyte alterations caused by hemodialysis (HD) therapy could be proarrhythmic. METHODS: Multiscale models were used for a consequent analysis of the effects of extracellular ion concentration changes on atrial electrophysiology. Simulations were based on measured electrolyte concentrations from patients with end-stage renal disease. RESULTS: Simulated conduction velocity and effective refractory period are decreased at the end of an HD session, with potassium having the strongest influence. P-wave is prolonged in patients undergoing HD therapy in the simulation as in measurements. CONCLUSIONS: Electrolyte concentration alterations impact atrial electrophysiology from the action potential level to the P-wave and can be proarrhythmic, especially because of induced hypokalemia. Analysis of blood electrolytes enables patient-specific electrophysiology modeling. We are providing a tool to investigate atrial arrhythmias associated with HD therapy, which, in the future, can be used to prevent such complications.
A fully oxygen-compatible ion-beam sputter deposition process (IBS) has been implemented for investigation of four film/substrate couples: (103)/(110)YBCO on (110)SrTiO3 (STO) and on (100)NdGaO3 (NGO), and (100)/(010)YBCO on (110)NGO and on (100)STO. For comparison, some (103)/(110)YBCO films have also been prepared by off-axis rf-magnetron sputtering. Below about 600 °C semiconducting, sub-nm flat, and perfectly single-crystalline YBCO films crystallize on these substrates with a crystallographic unit cell of about 1/3 of the Cu-O subcell of YBCO and perfect registration with the Ti4+-O and Ga3+-O sublattice of STO and NGO, respectively. At higher temperature superconducting YBCO films grow coherently epitaxially in the first....
Objectives: This study hypothesized that P-wave morphology and timing under left atrial appendage (LAA) pacing change characteristically immediately upon anterior mitral line (AML) block. Background: Perimitral flutter commonly occurs following ablation of atrial fibrillation and can be cured by an AML. However, confirmation of bidirectional block can be challenging, especially in severely fibrotic atria. Methods: The study analyzed 129 consecutive patients (66 ± 8 years, 64% men) who developed perimitral flutter after atrial fibrillation ablation. We designed electrocardiography criteria in a retrospective cohort (n = 76) and analyzed them in a validation cohort (n = 53). Results: Bidirectional AML block was achieved in 110 (85%) patients. For ablation performed during LAA pacing without flutter (n = 52), we found a characteristic immediate V1 jump (increase in LAA stimulus to P-wave peak interval in lead V1) as a real-time marker of AML block (V1 jump ≥30 ms: sensitivity 95%, specificity 100%, positive predictive value 100%, negative predictive value 88%). As V1 jump is not applicable when block coincides with termination of flutter, absolute V1 delay was used as a criterion applicable in all cases (n = 129) with a delay of 203 ms indicating successful block (sensitivity 92%, specificity 84%, positive predictive value 90%, negative predictive value 87%). Furthermore, an initial negative P-wave portion in the inferior leads was observed, which was attenuated in case of additional cavotricuspid isthmus ablation. Computational P-wave simulations provide mechanistic confirmation of these findings for diverse ablation scenarios (pulmonary vein isolation ± AML ± roof line ± cavotricuspid isthmus ablation). Conclusions: V1 jump and V1 delay are novel real-time electrocardiography criteria allowing fast and straightforward assessment of AML block during ablation for perimitral flutter.
G. Lenis, T. Baas, and O. Dössel. Ectopic beats and their influence on the morphology of subsequent waves in the electrocardiogram. In Biomedical Engineering / Biomedizinische Technik, vol. 58(2) , pp. 109-119, 2013
Ventricular ectopic beats (VEBs) trigger a characteristic response of the heart called heart rate turbulence (HRT). The HRT can be used to predict sudden cardiac death in patients with a history of myocardial infarction. In this work, we present a reliable algorithm to detect and classify ectopic beats. Every electrocardiogram (ECG) is processed with innovative filtering techniques, artifact detection methods, and a robust multichannel analysis to produce accurate annotation results. For the classification task, a support vec- tor machine was used. Furthermore, a new approach to the analysis of HRT is proposed. The HRT is interpreted as the response of a second-order system to an external perturbation. The system theoretical parameters were estimated. The influence of VEB on the morphology of subsequent T waves was also analyzed. A strong influence was detected in the study with 14 patients experiencing frequent VEB. The evolution of the morphology of the T wave with every new beat was studied, and it could be concluded that an exponential shape underlies this dynamic process and was called morphological heart rate turbulence (MHRT). Parameters were defined to quantify the MHRT. The analysis of the MHRT could help to understand the influence of an ectopic beat on the repolarization processes of the heart and more accurately stratify the risk of sudden cardiac death.
This study examines the effect of mental workload on the electrocardiogram (ECG) of participants driving the Lane Change Task (LCT). Different levels of mental workload were induced by a secondary task (n-back task) with three levels of difficulty. Subjective data showed a significant increase of the experienced workload over all three levels. An exploratory approach was chosen to extract a large number of rhythmical and morphological features from the ECG signal thereby identifying those which differentiated best between the levels of mental workload. No single rhythmical or morphological feature was able to differentiate between all three levels. A group of parameters were extracted which were at least able to discriminate between two levels. For future research, a combination of features is recommended to achieve best diagnosticity for different levels of mental workload.
Heart rate variability (HRV) plays an important role in medicine and psychology because it is used to quantify imbalances of the autonomic nervous system (ANS). An important manifestations of the ANS on HRV is also directly related to respiration and it is called respiratory sinus arrhythmia (RSA). This is a controlled phenomenon that leads to a synchronized coupling between respiration and instantaneous heart rate. Thus, the portion of HRV that is not related to respiration, and could potentially contain undiscovered diagnostic value, is overlapped and remains hidden in a standard HRV analysis. In such cases, a decoupling procedure would deliver a discriminated HRV analysis and possible new insights about the regulation of the cardiovascular system. In this work, we propose an algorithm based on Granger's causality to measure coupling between respiration and HRV. In the case of significant coupling, we estimate and cancel the respiration driven HRV component using a linear filtering approach. We tested the method using synthetic signals and prove it to deliver a reliable coupling measurement in 96.3% of the cases and reconstruct respiration free signals with a median correlation coefficient of 0.992. Afterwards, we applied our method to signals recorded during paced respiration and during natural breathing. We demonstrated that coupling is dependent on respiratory frequency and that it maximizes at 0.3 Hz. Furthermore, the HRV parameters measured during paced respiration tend to level among subjects after decoupling. The intersubject variability of HRV parameter is also decreased after the separation process. During natural breathing, coupling is notoriously lower to non-existing and decoupling has little impact on HRV. We conclude that the method proposed here can be used to investigate the diagnostic value of respiration independent HRV parameters.
G. Lenis, N. Pilia, A. Loewe, W. H. W. Schulze, and O. Dössel. Comparison of Baseline Wander Removal Techniques considering the Preservation of ST Changes in the Ischemic ECG: A Simulation Study. In Computational and Mathematical Methods in Medicine, vol. 2017(Article ID 9295029) , pp. 13, 2017
The most important ECG marker for the diagnosis of ischemia or infarction is a change in the ST segment. Baseline wander is a typical artifact that corrupts the recorded ECG and can hinder the correct diagnosis of such diseases. For the purpose of finding the best suited filter for the removal of baseline wander, the ground truth about the ST change prior to the corrupting artifact and the subsequent filtering process is needed. In order to create the desired reference, we used a large simulation study that allowed us to represent the ischemic heart at a multiscale level from the cardiac myocyte to the surface ECG. We also created a realistic model of baseline wander to evaluate five filtering techniques commonly used in literature. In the simulation study, we included a total of 5.5 million signals coming from 765 electrophysiological setups. We found that the best performing method was the wavelet-based baseline cancellation. However, for medical applications, the Butterworth high-pass filter is the better choice because it is computationally cheap and almost as accurate. Even though all methods modify the ST segment up to some extent, they were all proved to be better than leaving baseline wander unfiltered.
G. Lenis, N. Pilia, T. Oesterlein, A. Luik, C. Schmitt, and O. Dössel. P wave detection and delineation in the ECG based on the phase free stationary wavelet transform and using intracardiac atrial electrograms as reference. In Biomedizinische Technik. Biomedical Engineering, vol. 61(1) , pp. 37-56, 2016
Robust and exact automatic P wave detection and delineation in the electrocardiogram (ECG) is still an interesting but challenging research topic. The early prognosis of cardiac afflictions such as atrial fibrillation and the response of a patient to a given treatment is believed to improve if the P wave is carefully analyzed during sinus rhythm. Manual annotation of the signals is a tedious and subjective task. Its correctness depends on the experience of the annotator, quality of the signal, and ECG lead. In this work, we present a wavelet-based algorithm to detect and delineate P waves in individual ECG leads. We evaluated a large group of commonly used wavelets and frequency bands (wavelet levels) and introduced a special phase free wavelet transformation. The local extrema of the transformed signals are directly related to the delineating points of the P wave. First, the algorithm was studied using synthetic signals. Then, the optimal parameter configuration was found using intracardiac electrograms and surface ECGs measured simultaneously. The reverse biorthogonal wavelet 3.3 was found to be optimal for this application. In the end, the method was validated using the QT database from PhysioNet. We showed that the algorithm works more accurately and more robustly than other methods presented in literature. The validation study delivered an average delineation error of the P wave onset of -0.32+/-12.41 ms when compared to manual annotations. In conclusion, the algorithm is suitable for handling varying P wave shapes and low signal-to-noise ratios.
A. Loewe, and O. Dössel. Commentary: Virtual In-Silico Modeling Guided Catheter Ablation Predicts Effective Linear Ablation Lesion Set for Longstanding Persistent Atrial Fibrillation: Multicenter Prospective Randomized Study. In Frontiers in Physiology, vol. 8, pp. 1113, 2017
In case of chest pain, immediate diagnosis of myocardial ischemia is required to respond with an appropriate treatment. The diagnostic capability of the electrocardiogram (ECG), however, is strongly limited for ischemic events that do not lead to ST elevation. This computational study investigates the potential of different electrode setups in detecting early ischemia at 10 minutes after onset: standard 3-channel and 12-lead ECG as well as body surface potential maps (BSPMs). Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard 12-lead ECG. To this end, a simulation study was performed for 765 different locations and sizes of ischemia in the left ventricle. Improvements by adding a single, subject specifically optimized electrode were similar to those of the BSPM: 211% increased detection rate depending on the desired specificity. Adding right-sided Wilson leads had negligible effect. Absence of ST deviation could not be related to specific locations of the ischemic region or its transmurality. As alternative to the ST time integral as a feature of ST deviation, the K point deviation was introduced: the baseline deviation at the minimum of the ST-segment envelope signal, which increased 12-lead detection rate by 7% for a reasonable threshold.
AIMS: Human ether-a-go-go-related gene (hERG) missense mutations N588K and L532P are both associated with atrial fibrillation (AF). However, the underlying gain-of-function mechanism is different. The aim of this computational study is to assess and understand the arrhythmogenic mechanisms of these genetic disorders on the cellular and tissue level as a basis for the improvement of therapeutic strategies. METHODS AND RESULTS: The IKr formulation of an established model of human atrial myocytes was adapted by using the measurement data of wild-type and mutant hERG channels. Restitution curves of the action potential duration and its slope, effective refractory period (ERP), conduction velocity, reentry wavelength (WL), and the vulnerable window (VW) were determined in a one-dimensional (1D) tissue strand. Moreover, spiral wave inducibility and rotor lifetime in a 2D tissue patch were evaluated. The two mutations caused an increase in IKr regarding both peak amplitude and current integral, whereas the duration during which IKr is active was decreased. The WL was reduced due to a shorter ERP. Spiral waves could be initiated by using mutation models as opposed to the control case. The frequency dependency of the VW was reversed. CONCLUSION: Both mutations showed an increased arrhythmogenicity due to decreased refractory time in combination with a more linear repolarization phase. The effects were more pronounced for mutation L532P than for N588K. Furthermore, spiral waves presented higher stability and a more regular pattern for L532P. These in silico investigations unveiling differences of mutations affecting the same ion channel may help to advance genotype-guided AF prevention and therapy strategies.
Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way toward tailored therapies in the last years. To fully leverage in silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurately and reliably. In this work, two classes of optimization approaches are evaluated: gradient-based trust-region-reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that neither of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration.
A. Loewe, Y. Lutz, M. Wilhelms, D. Sinnecker, P. Barthel, E. P. Scholz, O. Dössel, G. Schmidt, and G. Seemann. In-silico assessment of the dynamic effects of amiodarone and dronedarone on human atrial patho-electrophysiology.. In Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, vol. 16(S4) , pp. iv30-iv38, 2014
AIMS: The clinical efficacy in preventing the recurrence of atrial fibrillation (AF) is higher for amiodarone than for dronedarone. Moreover, pharmacotherapy with these drugs is less successful in patients with remodelled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyse the effects of the drugs in a computational model of atrial electrophysiology. METHODS AND RESULTS: The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodelled tissue and hERG mutations N588K and L532P. The pharmacodynamics of amiodarone and dronedarone were investigated with respect to their dose and heart rate dependence by evaluating 10 descriptors of action potential morphology and conduction properties. An arrhythmia score was computed based on a subset of these biomarkers and analysed regarding circadian variation of drug concentration and heart rate. Action potential alternans at high frequencies was observed over the whole dronedarone concentration range at high frequencies, while amiodarone caused alternans only in a narrow range. The total score of dronedarone reached critical values in most of the investigated dynamic scenarios, while amiodarone caused only minor score oscillations. Compared with the other substrates, cAF showed significantly different characteristics resulting in a lower amiodarone but higher dronedarone concentration yielding the lowest score. CONCLUSION: Significant differences exist in the frequency and concentration-dependent effects between amiodarone and dronedarone and between different atrial substrates. Our results provide possible explanations for the superior efficacy of amiodarone and may aid in the design of substrate-specific pharmacotherapy for AF.
The implementation and first in vivo results of a novel coronary magnetic resonance angiography (MRA) protocol allowing simultaneous acquisition of multiple geometrically independent 3D imaging stacks are presented. Each imaging stack is acquired in a separate cardiac phase using an individual magnetization preparation and navigator-based gating and prospective motion correction. Each stack covers one of the main coronary vessels. Thus, an improvement of scan efficiency was achieved, which was used in this study to reduce total scan time at standard image quality. Experiments performed in healthy volunteers and in patients using a two-stack approach yielded a total scan time reduction of 50% with an image quality equivalent to standard single-stack coronary MRA.
D. Manke, K. Nehrke, P. Bornert, P. Rosch, and O. Dössel. Respiratory motion in coronary magnetic resonance angiography: a comparison of different motion models. In Journal of Magnetic Resonance Imaging : JMRI, vol. 15(6) , pp. 661-671, 2002
PURPOSE: To assess respiratory motion models for coronary magnetic resonance angiography (CMRA). In this study various motion models that describe the respiration-induced 3D displacements and deformations of the main coronary arteries were compared.MATERIALS AND METHODS: Multiple high-resolution 3D coronary MR images were acquired in healthy volunteers using navigator-based respiratory gating, each depicting the coronary vessels at different respiratory motion states. In the images representing the different inspiratory states the displacements and deformations of the main coronary vessels with respect to the end-expiratory state were determined, by means of elastic registration. Several correction models (superior-inferior (SI) translation, 3D translation, and 3D affine transformation) were tested and compared with respect to their ability to map a selected inspiratory to the end-expiratory motion state.RESULTS: 3D translation was found to be superior over SI translation, which is commonly used for prospective motion correction in CMRA. The 3D affine transformation was found to be the best correction model considered in this study. Furthermore, a large intersubject variability of the model parameters was observed.CONCLUSION: The results of this study indicate that a patient-adapted 3D correction model (3D translation or better 3D affine) will considerably improve prospective motion correction in CMRA.
Motion is one major problem of magnetic resonance imaging (MRI) of the coronary vessels. Despite of cardiac motion of the beating heart itself respiratory motion has to be considered (see MR movie of respiratory motion of the heart). Respiratory motion is commonly suppressed by gating techniques, which reduce scan efficiency. In principle modern MR scanners are able to correct those motion patterns prospectively, which can be described by a 3D affine transformation. A prospective motion correction approach could be used to increase the respiratory gating window and in consequence to reduce scan time. However, in order to achieve a sufficient correction the motion must be described quantitatively. In this initial study the respiratory motion of the heart (coronary vessels) was analysed and a new motion model described by an affine transformation was compared to two rigid motion models. The affine transformation model achieved a better fit (mean error < 1 mm for coronary vessels) than a rigid motion model describing translation in all directions (mean error < 2 mm) and a rigid motion model covering only superior-inferior motion (mean error <6 mm).
D. Manke, P. Rösch, K. Nehrke, P. Börnert, and O. Dössel. Model evaluation and calibration for prospective respiratory motion correction in coronary MR angiography based on 3-D image registration. In IEEE Transactions on Medical Imaging, vol. 21(9) , pp. 1132-1141, 2002
Image processing was used as a fundamental tool to derive motion information from magnetic resonance (MR) images, which was fed back into prospective respiratory motion correction during subsequent data acquisition to improve image quality in coronary MR angiography (CMRA) scans. This reduces motion artifacts in the images and, in addition, enables the usage of a broader gating window than commonly used today to increase the scan efficiency. The aim of the study reported in this paper was to find a suitable motion model to be used for respiratory motion correction in cardiac imaging and to develop a calibration procedure to adapt the motion model to the individual patient. At first, the performance of three motion models [one-dimensional translation in feet-head (FH) direction, three-dimensional (3-D) translation, and 3-D affine transformation] was tested in a small volunteer study. An elastic image registration algorithm was applied to 3-D MR images of the coronary vessels obtained at different respiratory levels. A strong intersubject variability was observed. The 3-D translation and affine transformation model were found to be superior over the conventional FH translation model used today. Furthermore, a new approach is presented, which utilizes a fast model-based image registration to extract motion information from time series of low-resolution 3-D MR images, which reflects the respiratory motion of the heart. The registration is based on a selectable global 3-D motion model (translation, rigid, or affine transformation). All 3-D MR images were registered with respect to end expiration. The resulting time series of model parameters were analyzed in combination with additionally acquired motion information from a diaphragmatic MR pencil-beam navigator to calibrate the respiratory motion model. To demonstrate the potential of a calibrated motion model for prospective motion correction in coronary imaging, the approach was tested in CMRA examinations in five volunteers.
R. Miri, and O. Dössel. Computerized optimization of biventricular pacing using body surface potential map. In Conf Proc IEEE Eng Med Biol Soc, vol. 2009, pp. 2815-2818, 2009
An improvement of biventricular pacing (BVP) could be possible by detecting the patient specific optimal pacemaker parameters. Body surface potential map (BSPM) is used to obtain the electrophysiology and pathology of an individual patient non-invasively. The clinical measurements of BSPM are used to parameterize the computer model of the heart to represent the individual pathology. The computer model of the heart is used to simulate the dyssynchrony of the ventricles and myocardial infarction (MI). Cardiac electrophysiology is simulated with ten Tusscher cell model, while excitation propagation is intended with adaptive cellular automaton at physiological and pathological conduction stages. The optimal electrode configurations are identified by minimizing the QRS duration error of healthy and pathology case with/without pacing between pre and post-implantation. Afterwards, the simulated ECGs for optimal pacing are compared to the post implantation clinically measured ECGs. The optimal electrode positions found by simulation are comparable to the ones meausured in hospital. The QRS duration reduction error between measured and simulated 12 ECG signals are similar with a constant offset of 15 ms. The personalized model present in this research is an effective tool for therapy planning of BVP in patients with congestive heart failure.
R. Miri, I. M. Graf, J. V. Bayarri, and O. Dössel. Applicability of body surface potential map in computerized optimization of biventricular pacing. In Annals of Biomedical Engineering, vol. 38(3) , pp. 865-875, 2010
Biventricular pacing (BVP) could be improved by identifying the patient-specific optimal electrode positions. Body surface potential map (BSPM) is a non-invasive technique for obtaining the electrophysiology and pathology of a patient. The study proposes the use of BSPM as input for an automated non-invasive strategy based on a personalized computer model of the heart, to identify the patient pathology and specific optimal treatment with BVP devices. The anatomy of a patient suffering from left bundle branch block and myocardial infarction is extracted from a series of MR data sets. The clinical measurements of BSPM are used to parameterize the computer model of the heart to represent the individual pathology. Cardiac electrophysiology is simulated with ten Tusscher cell model and excitation propagation is calculated with adaptive cellular automaton, at physiological and pathological conduction levels. The optimal electrode configurations are identified by evaluating the QRS error between healthy and pathology case with/without pacing. Afterwards, the simulated ECGs for optimal pacing are compared to the post-implantation clinically measured ECGs. Both simulation and clinical optimization methods identified the right ventricular (RV) apex and the LV posterolateral regions as being the optimal electrode configuration for the patient. The QRS duration is reduced both in measured and simulated ECG after implantation with 20 and 14%, respectively. The optimized electrode positions found by simulation are comparable to the ones used in hospital. The similarity in QRS duration reduction between measured and simulated ECG signals indicates the success of the method. The computer model presented in this work is a suitable tool to investigate individual pathologies. The personalized model could assist therapy planning of BVP in patients with congestive heart failure. The proposed method could be used as prototype for further clinically oriented investigations of computerized optimization of biventricular pacing.
R. Miri, M. Reumann, D. Farina, and O. Dössel. Concurrent optimization of timing delays and electrode positioning in biventricular pacing based on a computer heart model assuming 17 left ventricular segments. In Biomedizinische Technik. Biomedical Engineering, vol. 54(2) , pp. 55-65, 2009
BACKGROUND: The efficacy of cardiac resynchronization therapy through biventricular pacing (BVP) has been demonstrated by numerous studies in patients suffering from congestive heart failure. In order to achieve a guideline for optimal treatment with BVP devices, an automated non-invasive strategy based on a computer model of the heart is presented. MATERIALS AND METHODS: The presented research investigates an off-line optimization algorithm regarding electrode positioning and timing delays. The efficacy of the algorithm is demonstrated in four patients suffering from left bundle branch block (LBBB) and myocardial infarction (MI). The computer model of the heart was used to simulate the LBBB in addition to several MI allocations according to the different left ventricular subdivisions introduced by the American Heart Association. Furthermore, simulations with reduced interventricular conduction velocity were performed in order to model interventricular excitation conduction delay. More than 800,000 simulations were carried out by adjusting a variety of 121 pairs of atrioventricular and interventricular delays and 36 different electrode positioning set-ups. Additionally, three different conduction velocities were examined. The optimization measures included the minimum root mean square error (E(RMS)) between physiological, pathological and therapeutic excitation, and also the difference of QRS-complex duration. Both of these measures were computed automatically. RESULTS: Depending on the patient's pathology and conduction velocity, a reduction of E(RMS) between physiological and therapeutic excitation could be reached. For each patient and pathology, an optimal pacing electrode pair was determined. The results demonstrated the importance of an individual adjustment of BVP parameters to the patient's anatomy and pathology. CONCLUSION: This work proposes a novel non-invasive optimization algorithm to find the best electrode positioning sites and timing delays for BVP in patients with LBBB and MI. This algorithm can be used to plan an optimal therapy for an individual patient.
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.
Background: Intracardiac electrograms are an indispensable part during diagnosis of supraventriculararrhythmias, but atrial activity (AA) can be obscured by ventricular far-fields (VFF). Concepts based onstatistical independence like principal component analysis (PCA) cannot be applied for VFF removalduring atrial tachycardia with stable conduction.Methods: A database of realistic electrograms containing AAand VFF was generated. Both PCA and thenew technique periodic component analysis (πCA) were implemented, benchmarked, and applied toclinical data.Results: The concept of πCA was successfully verified to retain compromised AA morphology,showing high correlation (cc = 0.98 ± 0.01) for stable atrial cycle length (ACL). Performance ofPCA failed during temporal coupling (cc = 0.03 ± 0.08) but improved for increasing conductionvariability (cc = 0.77 ± 0.14). Stability of ACL was identified as a critical parameter for πCAapplication. Analysis of clinical data confirmed these findings.Conclusion: πCA is introduced as a powerful new technique for artifact removal in periodic signals.Its concept and performance were benchmarked against PCA using simulated data and demonstratedon measured electrograms.
BACKGROUND AND OBJECTIVE: Progress in biomedical engineering has improved the hardware available for diagnosis and treatment of cardiac arrhythmias. But although huge amounts of intracardiac electrograms (EGMs) can be acquired during electrophysiological examinations, there is still a lack of software aiding diagnosis. The development of novel algorithms for the automated analysis of EGMs has proven difficult, due to the highly interdisciplinary nature of this task and hampered data access in clinical systems. Thus we developed a software platform, which allows rapid implementation of new algorithms, verification of their functionality and suitable visualization for discussion in the clinical environment. METHODS: A software for visualization was developed in Qt5 and C++ utilizing the class library of VTK. The algorithms for signal analysis were implemented in MATLAB. Clinical data for analysis was exported from electroanatomical mapping systems. RESULTS: The visualization software KaPAVIE (Karlsruhe Platform for Analysis and Visualization of Intracardiac Electrograms) was implemented and tested on several clinical datasets. Both common and novel algorithms were implemented which address important clinical questions in diagnosis of different arrhythmias. It proved useful in discussions with clinicians due to its interactive and user-friendly design. Time after export from the clinical mapping system to visualization is below 5min. CONCLUSION: KaPAVIE(2) is a powerful platform for the development of novel algorithms in the clinical environment. Simultaneous and interactive visualization of measured EGM data and the results of analysis will aid diagnosis and help understanding the underlying mechanisms of complex arrhythmias like atrial fibrillation.
Whole-chamber mapping using a 64-pole basket catheter (BC) has become a featured approach for the analysis of excitation patterns during atrial fibrillation. A flexible catheter design avoids perforation but may lead to spline bunching and influence coverage. We aim to quantify the catheter deformation and endocardial coverage in clinical situations and study the effect of catheter size and electrode arrangement using an in silico basket model. Atrial coverage and spline separation were evaluated quantitatively in an ensemble of clinical measurements. A computational model of the BC was implemented including an algorithm to adapt its shape to the atrial anatomy. Two clinically relevant mapping positions in each atrium were assessed in both clinical and simulated data. The simulation environment allowed varying both BC size and electrode arrangement. Results showed that interspline distances of more than 20 mm are common, leading to a coverage of less than 50% of the left atrial (LA) surface. In an ideal in silico scenario with variable catheter designs, a maximum coverage of 65% could be reached. As spline bunching and insufficient coverage can hardly be avoided, this has to be taken into account for interpretation of excitation patterns and development of new panoramic mapping techniques.
OBJECTIVE: Atrial tachycardia (AT) still pose a major challenge in catheter ablation. Although state-of-the-art electroanatomical mapping systems allow to acquire several thousand intracardiac electrograms (EGMs), algorithms for diagnostic analysis are mainly limited to the amplitude of the signal (voltage map) and the local activation time~(LAT map). We applied spatio-temporal analysis of EGM activity to generate maps indicating reentries and diastolic potentials, thus identifying and localizing the driving mechanism of AT. METHODS: First, the time course of active surface area (ASA) is determined during one basic cycle length (BCL). The global cycle length coverage (gCLC) reflects the relative duration within one BCL for which activity was present in each individual atrium. A local cycle length coverage (lCLC) is computed for circular sub-areas with 20mm diameter. The simultaneous active surface area sASA is determined to indicate the spatial extent of depolarizing tissue. RESULTS: Combined analysis of these spatial scales allowed to correctly identify and localize the driving mechanism: gCLC values of 100% were indicative for atria harbouring a reentrant driver. lCLC could detect micro reentries within an area of 1.651.28cm in simulated data and differentiate them against focal sources. Mid-diastolic potentials, being potential targets for catheter ablation, were identified as the areas showing confined activity based on sASA values. CONCLUSION: The concept of spatio-temporal activity analysis proved successful and correctly indicated the tachycardia mechanism in 20 simulated AT scenarios and three clinical data sets. SIGNIFICANCE: Automatic interpretation of intracardiac mapping data could help to improve the treatment strategy in complex cases of AT.
BACKGROUND: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air-liquid interface. RESULTS: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air-liquid interphase (ALI) by using the ALI deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stober method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the ALI were less sensitive to silica NPs as evidenced by reduced cytotoxicity and inflammatory responses. CONCLUSION: Amorphous silica NPs induced qualitatively similar cellular responses under submerged conditions and at the ALI. However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the ALI are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method.
PURPOSE: To evaluate two commonly used respiratory motion correction techniques for coronary magnetic resonance angiography (MRA) regarding their dependency on motion estimation accuracy and final image quality and to compare both methods to the respiratory gating approach used in clinical practice. MATERIALS AND METHODS: Ten healthy volunteers were scanned using a non-Cartesian radial phase encoding acquisition. Respiratory motion was corrected for coronary MRA according to two motion correction techniques, image-based (IMC) and reconstruction-based (RMC) respiratory motion correction. Both motion correction approaches were compared quantitatively and qualitatively against a reference standard navigator-based respiratory gating (RG) approach. Quantitative comparisons were performed regarding visible vessel length, vessel sharpness, and total acquisition time. Two experts carried out a visual scoring of image quality. Additionally, numerical simulations were performed to evaluate the effect of motion estimation inaccuracy on RMC and IMC. RESULTS: RMC led to significantly better image quality than IMC (P's paired Student's t-test were smaller than 0.001 for vessel sharpness and visual scoring). RMC did not show a statistically significant difference compared to reference standard RG (vessel length [99% confidence interval]: 86.913 [83.097-95.015], P = 0.107; vessel sharpness: 0.640 [0.605-0.802], P = 0.012; visual scoring: 2.583 [2.410-3.424], P = 0.018) in terms of vessel visualization and image quality while reducing scan times by 56%. Simulations showed higher dependencies for RMC than for IMC on motion estimation inaccuracies. CONCLUSION: RMC provides a similar image quality as the clinically used RG approach but almost halves the scan time and is independent of subjects' breathing patterns. Clinical validation of RMC is now desirable. J. Magn. Reson. Imaging 2015.
Optical mapping is widely used as a tool to investigate cardiac electrophysiology in ex vivo preparations. Digital filtering of fluorescence-optical data is an important requirement for robust subsequent data analysis and still a challenge when processing data acquired from thin mammalian myocardium. Therefore, we propose and investigate the use of an adaptive spatio-temporal Gaussian filter for processing optical mapping signals from these kinds of tissue usually having low signal-to-noise ratio (SNR). We demonstrate how filtering parameters can be chosen automatically without additional user input. For systematic comparison of this filter with standard filtering methods from the literature, we generated synthetic signals representing optical recordings from atrial myocardium of a rat heart with varying SNR. Furthermore, all filter methods were applied to experimental data from an ex vivo setup. Our developed filter outperformed the other filter methods regarding local activation time detection at SNRs smaller than 3 dB which are typical noise ratios expected in these signals. At higher SNRs, the proposed filter performed slightly worse than the methods from literature. In conclusion, the proposed adaptive spatio-temporal Gaussian filter is an appropriate tool for investigating fluorescence-optical data with low SNR. The spatio-temporal filter parameters were automatically adapted in contrast to the other investigated filters.
Radiofrequency ablation has become a first-line approach for curative therapy of many cardiac arrhythmias. Various existing catheter designs provide high spatial resolution to identify the best spot for performing ablation and to assess lesion formation. However, creation of transmural and nonconducting ablation lesions requires usage of catheters with larger electrodes and improved thermal conductivity, leading to reduced spatial sensitivity. As trade-off, an ablation catheter with integrated mini electrodes was introduced. The additional diagnostic benefit of this catheter is still not clear. In order to solve this issue, we implemented a computational setup with different ablation scenarios. Our in silico results show that peak-to-peak amplitudes of unipolar electrograms from mini electrodes are more suitable to differentiate ablated and nonablated tissue compared to electrograms from the distal ablation electrode. However, in orthogonal mapping position, no significant difference was observed between distal electrode and mini electrodes electrograms in the ablation scenarios. In conclusion, catheters with mini electrodes bring about additional benefit to distinguish ablated tissue from nonablated tissue in parallel position with high spatial resolution. It is feasible to detect conduction gaps in linear lesions with this catheter by evaluating electrogram data from mini electrodes.
L. M. Popp, G. Seemann, and O. Dössel. A simulation study of the reaction of human heart to biphasic electrical shocks. In BMC Cardiovascular Disorders, vol. 4, pp. 9, 2004
BACKGROUND: This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. METHODS: The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. RESULTS: The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. CONCLUSIONS: The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses.
The goal of ECG-imaging (ECGI) is to reconstruct heart electrical activity from body surface potential maps. The problem is ill-posed, which means that it is extremely sensitive to measurement and modeling errors. The most commonly used method to tackle this obstacle is Tikhonov regularization, which consists in converting the original problem into a well-posed one by adding a penalty term. The method, despite all its practical advantages, has however a serious drawback: The obtained solution is often over-smoothed, which can hinder precise clinical diagnosis and treatment planning. In this paper, we apply a binary optimization approach to the transmembrane voltage (TMV)-based problem. For this, we assume the TMV to take two possible values according to a heart abnormality under consideration. In this work, we investigate the localization of simulated ischemic areas and ectopic foci and one clinical infarction case. This affects only the choice of the binary values, while the core of the algorithms remains the same, making the approximation easily adjustable to the application needs. Two methods, a hybrid metaheuristic approach and the difference of convex functions (DC), algorithm were tested. For this purpose, we performed realistic heart simulations for a complex thorax model and applied the proposed techniques to the obtained ECG signals. Both methods enabled localization of the areas of interest, hence showing their potential for application in ECGI. For the metaheuristic algorithm, it was necessary to subdivide the heart into regions in order to obtain a stable solution unsusceptible to the errors, while the analytical DC scheme can be efficiently applied for higher dimensional problems. With the DC method, we also successfully reconstructed the activation pattern and origin of a simulated extrasystole. In addition, the DC algorithm enables iterative adjustment of binary values ensuring robust performance.
G. Reinerth, G. Seemann, O. Dössel, C. F. Vahl, and S. Hagl. Elektrophysiologische Modellierung des Herzens zur Planung von herzchirurgischen und kardiologischen Eingriffen. In Herzschrittmachertherapie und Elektrophysiologie, vol. 14(1) , pp. 742-746, 2003
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.
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.
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.
OBJECT: Most functional magnetic resonance imaging (fMRI) experiments use gradient-echo echo planar imaging (GE EPI) to detect the blood oxygenation level-dependent (BOLD) effect. This technique may fail in the presence of anatomy-related susceptibility-induced field gradients in the human head. In this work, we present a novel 3D compensation method in combination with a template-based correction that can be optimized over particular regions of interest to recover susceptibility-induced signal loss without acquisition time penalty. MATERIALS AND METHODS: Based on an evaluation of B(0) field maps of eight subjects, slice-dependent gradient compensation moments are derived for maximal BOLD sensitivity in two compromised regions: the orbitofrontal cortex and the amygdala areas. A modified EPI sequence uses these additional gradient moments in all three imaging directions. The method is compared to non-compensated, template-based and subject-specific correction gradients and also in a breath-holding experiment. RESULTS: The slice-dependent gradient compensation method significantly improves signal intensity/BOLD sensitivity by about 35/43% in the orbitofrontal cortex and by 17/30% in the amygdala areas compared to a conventional acquisition. Template-based correction and subject-specific correction perform equally well. The BOLD sensitivity in the breath hold experiment is effectively increased in compensated regions. CONCLUSION: The new method addresses the problem of susceptibility-induced signal loss, without compromising temporal resolution. It can be used for event-related functional experiments without requiring additional subject-specific calibration or calculation time.
A model of the electromechanical behavior of a myocardial region is presented. The model combines an electrophysiological, a force development and an excitation propagation model. All of these models incorporate the effects of deformation of the myocardium. An extension of the traditional bidomain model for excitation propagation is proposed. The extension describes the stretch dependency of the conductivity tensor of the intra- and extracellular space and is constructed outgoing from physically motivated assumptions, which simplify the behavior of the conductivity tensor. The extension makes usage of the deformation gradient tensor, which is a foundation in the theory of continuums mechanics. The performed simulations illustrate some effects of myocardial electromechanical behavior.
Knowledge of the distribution of electrical fields in the human body is of importance for scientists, engineers and physicians. This paper shows one way to achieve this knowledge by numerical calculation based on macroscopic models of the human body. An anatomical model is created by preprocessing, segmentation and classification of the digital images within the Visible Man data set. Conductivity models are derived, which describe the distribution of electrical conductivity in the human body. A conductivity model is applied to solve an exemplary forward problem in electrophysiology, which consist of the calculation of the electrical field distribution arising from cardiac sources. The cardiac sources are obtained by a model of the excitation process within the heart. The calculation of electrical fields is carried out numerically by employing the finite difference method.
Catheter ablation has emerged as an effective treatment strategy for atrial fibrillation (AF) in recent years. During AF, complex fractionated atrial electrograms (CFAE) can be recorded and are known to be a potential target for ablation. Automatic algorithms have been developed to simplify CFAE detection, but they are often based on a single descriptor or a set of descriptors in combination with sharp decision classifiers. However, these methods do not reflect the progressive transition between CFAE classes. The aim of this study was to develop an automatic classification algorithm, which combines the information of a complete set of descriptors and allows for progressive and transparent decisions. We designed a method to automatically analyze CFAE based on a set of descriptors representing various aspects, such as shape, amplitude and temporal characteristics. A fuzzy decision tree (FDT) was trained and evaluated on 429 predefined electrograms. CFAE were classified into four subgroups with a correct rate of 81+/-3%. Electrograms with continuous activity were detected with a correct rate of 100%. In addition, a percentage of certainty is given for each electrogram to enable a comprehensive and transparent decision. The proposed FDT is able to classify CFAE with respect to their progressive transition and may allow objective and reproducible CFAE interpretation for clinical use.
The motion of the heart is a major challenge for cardiac imaging using CT. A novel approach to decrease motion blur and to improve the signal to noise ratio is motion compensated reconstruction which takes motion vector fields into account in order to correct motion. The presented work deals with the determination of local motion vector fields from high contrast objects and their utilization within motion compensated filtered back projection reconstruction. Image registration is applied during the quiescent cardiac phases. Temporal interpolation in parameter space is used in order to estimate motion during strong motion phases. The resulting motion vector fields are during image reconstruction. The method is assessed using a software phantom and several clinical cases for calcium scoring. As a criterion for reconstruction quality, calcium volume scores were derived from both, gated cardiac reconstruction and motion compensated reconstruction throughout the cardiac phases using low pitch helical cone beam CT acquisitions. The presented technique is a robust method to determine and utilize local motion vector fields. Motion compensated reconstruction using the derived motion vector fields leads to superior image quality compared to gated reconstruction. As a result, the gating window can be enlarged significantly, resulting in increased SNR, while reliable Hounsfield units are achieved due to the reduced level of motion artefacts. The enlargement of the gating window can be translated into reduced dose requirements.
In den Lebenswissenschaften ist die Individualisierte Medizin aktuell ein zentrales Thema, vielleicht ein Hype. Das bestätigen auch synonyme, erweiternde und klärende Begriffe wie Personalisierte Medizin, Customized Medicine, Stratifizierende Medizin oder Präzisionsmedizin. In einer State of the Union Address an die Bevölkerung der Vereinigten Staaten von Amerika hat Präsident Barack Obama 2015 die Bedeutung der Präzisionsmedizin hervorgehoben . Diese Initiative wurde inhaltlich wesentlich vom Direktor des National Institute of Health, dem Genetiker Francis Collins, vorangetrieben . Individualisierte Medizin, das ist eine gute Botschaft, betont sie doch die Wertigkeit des einzelnen Patienten. Für klinisch tätige Ärzte ist das bereits eine Selbstverständlichkeit. Die Bedeutung eines Wortes, und das sei mit einem Lächeln hinzugefügt, zeigt sich nach Wittgenstein im Gebrauch der Sprache .Die Nationale Akademie der Wissenschaften Leopoldina, die acatech Deutsche Akademie der Technikwissenschaften und die Union der Deutschen Akademien der Wissenschaften haben im Dezember 2014 eine Stellungnahme über Voraussetzungen und Konsequenzen der Individualisierten Medizin publiziert. Darin wird der Fokus, wie im Vorwort ausgeführt, auf molekulare, genetische und pharmakologische Aspekte der Onkologie gelegt, einen Bereich, in dem die Individualisierung am weitesten fortgeschritten ist. Diese Beschränkung bedeutet, dass andere eng assoziierte Themen, wie die Patienten- und Versorgungsperspektiven, der Bereich der Medizintechnik oder neue Erkrankungen, beispielsweise in der Psychiatrie, in dieser Studie nicht beleuchtet werden. Die Behandlung dieser Gebiete bedarf einer separaten nachfolgenden Betrachtung. .Vor einer Betrachtung wesentlicher Beiträge allein der Bildgebung in der Individualisierten Medizin seien wenige vorausschickende Bemerkungen zu zwei Grenz-Fragen der Wissenschaft gemacht. Was steht für und gegen Stellungnahmen der genannten Akademien? Erfüllt die Beschäftigung mit der Bildgebung Kriterien der Wissenschaft?Eine der Aufgaben der Akademien ist es, Ordnung in die vorhandenen Aussagen und auch damit vorhandene Daten zu bringen, die in unterschiedlichen Disziplinen hervorgebracht werden, um daraus ein Gesamtbild zu formen. Weiterhin sollen Empfehlungen gegeben werden, wie die Entwicklungen günstig zu beeinflussen sind . Wichtige Grenzen der wissenschaftlichen Politik- bzw. Gesellschaftsberatung bilden etwa Katastrophenwarnungen und Heilsverheißungen, andererseits nicht-altruistische, sondern dem Eigeninteresse dienende, wie auch politisierende Verlautbarungen. Das setzt eine Selbstbegrenzung voraus.Wünschenswert ist bei wissenschaftlichem Handeln der Respekt von und vor Grenzen, ist die Distanz zur Macht. Diese Macht kann der Politik, der Ökonomie und auch den Medien zugeschrieben werden; fatal sind Nähe oder gar Einfluss von Ideologien. Dabei wird nicht nur ein behutsamer Umgang mit Empfehlungen angesprochen; im wissenschaftlichen Handeln sind gerade beim Gegenstand der Bildgebung Berührungen mit der und sogar Überlappungen mit Interessen der Industrie möglich, teilweise gewünscht und fruchtbar. Letztlich ist es ja immer die Industrialisierung, die medizinischen Fortschritt, sei er pharmakologisch oder technologisch abbildbar, breiten Bevölkerungsgruppen und entlegenen Standorten zugänglich macht. Das bedarf immer einer gegenseitigen kritischen Begleitung.Die Wissenschaft dient dem Erkenntnisgewinn. Dazu gehört eine methodische Suche nach Wahrheit, die alle Befähigten überprüfen und nachvollziehen können. Wenn dieses angenommen, akzeptiert werden kann, dann sind die Technikwissenschaften Wissenschaften, dann betreiben Radiologie und Nuklearmedizin Wissenschaft (science). Dann bedarf es nicht der Aufzählung von Nobelpreisen oder ähnlichen Anerkennungen in der Scientific Community. Dann bedarf es nicht der Aufzählung fachlicher Beispiele; die Methoden und die Technologien fallen nicht vom Himmel. Wissenschaft wird von Menschen betrieben und getragen. An Pioniere der Bildgebung, an Personen, wie Wilhelm Conrad Röntgen, Marie Curie, Godfrey Hounsfield, Peter Mansfield, Paul Lauterbur oder Stephan Hell sei erinnert.* Dieses Editorial wird zeitgleich in Nuklearmedizin publiziert. Schober O, Dössel O, Ermert H et al. Bildgebung in Klinik und Forschung: Beitrag zur Individualisierten Medizin? Nuklearmedizin 2017; 56: 157-161; https://doi.org/10.3413/2017-05-0002.
Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.
S. Schuler, A. Wachter, and O. Dössel. Electrocardiographic Imaging Using a Spatio-Temporal Basis of Body Surface Potentials—Application to Atrial Ectopic Activity. In Frontiers in Physiology, vol. 9:1126, 2018
Electrocardiographic imaging (ECGI) strongly relies on a priori assumptions and additional information to overcome ill-posedness. The major challenge of obtaining good reconstructions consists in finding ways to add information that effectively restricts the solution space without violating properties of the sought solution. In this work, we attempt to address this problem by constructing a spatio-temporal basis of body surface potentials (BSP) from simulations of many focal excitations. Measured BSPs are projected onto this basis and reconstructions are expressed as linear combinations of corresponding transmembrane voltage (TMV) basis vectors. The novel method was applied to simulations of 100 atrial ectopic foci with three different conduction velocities. Three signal-to-noise ratios (SNR) and bases of six different temporal lengths were considered. Reconstruction quality was evaluated using the spatial correlation coefficient of TMVs as well as estimated local activation times (LAT). The focus localization error was assessed by computing the geodesic distance between true and reconstructed foci. Compared with an optimally parameterized Tikhonov-Greensite method, the BSP basis reconstruction increased the mean TMV correlation by up to 22, 24, and 32% for an SNR of 40, 20, and 0 dB, respectively. Mean LAT correlation could be improved by up to 5, 7, and 19% for the three SNRs. For 0 dB, the average localization error could be halved from 15.8 to 7.9 mm. For the largest basis length, the localization error was always below 34 mm. In conclusion, the new method improved reconstructions of atrial ectopic activity especially for low SNRs. Localization of ectopic foci turned out to be more robust and more accurate. Preliminary experiments indicate that the basis generalizes to some extent from the training data and may even be applied for reconstruction of non-ectopic activity.
ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.
Electrocardiographic imaging (ECG imaging) is a method to depict electrophysiological processes in the heart. It is an emerging technology with the potential of making the therapy of cardiac arrhythmia less invasive, less expensive, and more precise. A major challenge for integrating the method into clinical workflow is the seamless and correct identification and localization of electrodes on the thorax and their assignment to recorded channels. This work proposes a camera-based system, which can localize all electrode positions at once and to an accuracy of approximately 1+/-1 mm. A system for automatic identification of individual electrodes is implemented that overcomes the need of manual annotation. For this purpose, a system of markers is suggested, which facilitates a precise localization to subpixel accuracy and robust identification using an error-correcting code. The accuracy of the presented system in identifying and localizing electrodes is validated in a phantom study. Its overall capability is demonstrated in a clinical scenario.
Investigating the mechanisms underlying the genesis and conduction of electrical excitation in the atria at physiological and pathological states is of great importance. To provide knowledge concerning the mechanisms of excitation, we constructed a biophysical detailed and anatomically accurate computer model of human atria that incorporates both structural and electrophysiological heterogeneities. The three-dimensional geometry was extracted from the visible female dataset. The sinoatrial node (SAN) and atrium, including crista terminalis (CT), pectinate muscles (PM), appendages (APG) and Bachmann's bundle (BB) were segmented in this work. Fibre orientation in CT, PM and BB was set to local longitudinal direction. Descriptions for all used cell types were based on modifications of the Courtemanche et al. model of a human atrial cell. Maximum conductances of Ito, IKr and ICa,L were modified for PM, CT, APG and atrioventricular ring to reproduce measured action potentials (AP). Pacemaker activity in the human SAN was reproduced by removing IK1, but including If, ICa,T, and gradients of channel conductances as described in previous studies for heterogeneous rabbit SAN. Anisotropic conduction was computed with a monodomain model using the finite element method. The transversal to longitudinal ratio of conductivity for PM, CT and BB was 1:9. Atrial working myocardium (AWM) was set to be isotropic. Simulation of atrial electrophysiology showed initiation of APs in the SAN centre. The excitation spread afterwards to the periphery near to the region of the CT and preferentially towards the atrioventricular region. The excitation extends over the right atrium along PM. Both CT and PM activated the right AWM. Earliest activation of the left atrium was through BB and excitation spread over to the APG. The conduction velocities were 0.6ms-1 for AWM, 1.2ms-1 for CT, 1.6ms-1 for PM and 1.1ms-1 for BB at a rate of 63bpm. The simulations revealed that bundles form dominant pathways for atrial conduction. The preferential conduction towards CT and along PM is comparable with clinical mapping. Repolarization is more homogeneous than excitation due to the heterogeneous distribution of electrophysiological properties and hence the action potential duration.
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.
In this work, a new framework is presented that is suitable to solve the cardiac bidomain equation efficiently using the scientific computing library PETSc. Furthermore, the framework is able to modularly combine different ionic channels and is flexible enough to include arbitrary heterogeneities in ionic or coupling channel density. The ability of this framework is demonstrated in an example simulation in which the three-dimensional electrophysiological heterogeneity was adjusted in order to get a positive T-wave in the body electrocardiogram (ECG).
C. Stehning, P. Bornert, K. Nehrke, and O. Dössel. Free breathing 3D balanced FFE coronary magnetic resonance angiography with prolonged cardiac acquisition windows and intra-RR motion correction. In Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 53(3) , pp. 719-723, 2005
A shortcoming of today's coronary magnetic resonance angiography (MRA) is its low total scan efficiency (<5%), as only small well-defined fractions of the respiratory (50%) and cardiac (10%) cycle are used for data acquisition. These precautions are necessary to prevent blurring and artifacts related to respiratory and cardiac motion. Hence, scan times range from 4 to 9 min, which may not be tolerated by patients. To overcome this drawback, an ECG-triggered, navigator-gated free breathing radial 3D balanced FFE sequence with intra-RR motion correction is investigated in this study. Scan efficiency is increased by using a long cardiac acquisition window during the RR interval. This allows the acquisition of a number of independent k-space segments during each cardiac cycle. The intersegment motion is corrected using a self-guided epicardial fat tracking procedure in a postprocessing step. Finally, combining the motion-corrected segments forms a high-resolution image. Experiments on healthy volunteers are presented to show the basic feasibility of this approach.
A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is the time-consuming examination necessitated by extensive scout scanning and precise slice planning. To improve ease of use and cover larger parts of the anatomy, it appears desirable to image the entire heart with high spatial resolution instead. For this purpose, an isotropic 3D-radial acquisition was employed in this study. This method allows undersampling of k-space in all three spatial dimensions, and its insensitivity to motion enables extended acquisitions per cardiac cycle. We present initial phantom and in vivo results obtained in volunteers that demonstrate large volume coverage with high isotropic spatial resolution. We were able to visualize all major parts of the coronary arteries retrospectively from the volume data set without compromising the image quality. The scan time ranged from 10 to 14 min during free breathing at a heart rate of 60 bpm, which is comparable to that of a thin-slab protocol comprising multiple scans for each coronary artery.
This paper describes the measurement of a data set used to create a three-dimensional (3-D) parametric model of atrial anatomy. A short introduction to porcine and human atrial anatomy is given and important anatomical differences are noted. The data acquisition techniques are described. A pig heart was arrested in diastole and perfusion fixed in-situ at physiological pressures with the chest open but the pericardium intact, then excised, cast and mounted. A six-degree-of-freedom measurement arm was used to measure three-dimensional epicardial surface geometry and fiber angles. An epicardial surface model was created using a computer aided design (CAD ) software program for reverse engineering. The model was used to direct the dissection of the heart into small tissue blocks from which endocardial fiber angles and wall thicknesses were measured. Tissue blocks were then cryo-sectioned for histology and the identification of conducting system structures. Figures and images illustrate the resulting surface model, the acquired fiber angles and wall thickness. This preliminary work provides a foundation for building a three-dimensional anatomically detailed model suitable as a mesh for computational analysis of atrial mechanics and electrophysiology.
A ray-based approach that models the geometric mapping properties of a flat optical detector based on a microlens array is presented. The investigated optical detector substitutes a single-aperture lens optic for planar and tomographic data acquisition in space-constrained small-animal imaging applications. The formalism implements forward mapping of a three-dimensional object volume onto a two-dimensional sensor surface as well as the backprojection (inverse mapping) of acquired sensor data sets. The object focus distance is the sole free parameter for the inverse mapping. By variation of the object focus distance, arbitrary object surface areas within the computed object images can be focused. The inverse mapping algorithm was applied to an experimentally acquired sensor data set from a three-dimensional phantom. The results are compared with focal point image formation.
Background: During atrial fibrillation, heterogeneities and anisotropies result in a chaotic propagation of the depolarization wavefront. The electrophysiological parameter called conduction velocity (CV) influences the propagation pattern over the atrium. We present a method that determines the regional CV for deformed catheter shapes, which result due to the catheter movement and changing wall contact.Methods: The algorithm selects stable catheter positions, finds the local activation times (LAT), considers the wall contact and calculates all CV estimates within the area covered by the catheter. The method is evaluated with simulated data and then applied to four clinical data sets. Both sinus rhythm activity as well as depolarization wavefronts initiated by stimulation are analyzed. The regional CV is compared with the fractionation duration (FD) and peak-to-peak (P2P) voltages. A speed of 0.5 m/s was defined to create the simulated LAT.Results: After analyzing the simulated LAT with clinical catheter spatial coordinates, the median CV of 0.5 m/s with an interquartile range of 0.22 and exact CV direction vectors were obtained. For clinical cases, the CV magnitude range of 0.08 m/s to 1.0 m/s was obtained. The P2P amplitude of 0.7 mV to 3.7 mV and the mean FD from 40.79ms to 48.66ms was obtained. The correlation of 0.86 was observed between CV and P2P amplitude, and 0.62 between CV and FD.Conclusion: In this paper, a method is presented and validated which calculates the CV for the deformed catheter and changing wall contact. In an exemplary clinical data set correlation between regional CV with FD and the P2P voltage was observed.
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.
T. Voigt, U. Katscher, and O. Doessel. Quantitative conductivity and permittivity imaging of the human brain using electric properties tomography. In Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 66(2) , pp. 456-466, 2011
The electric properties of human tissue can potentially be used as an additional diagnostic parameter, e.g., in tumor diagnosis. In the framework of radiofrequency safety, the electric conductivity of tissue is needed to correctly estimate the local specific absorption rate distribution during MR measurements. In this study, a recently developed approach, called electric properties tomography (EPT) is adapted for and applied to in vivo imaging. It derives the patient's electric conductivity and permittivity from the spatial sensitivity distributions of the applied radiofrequency coils. In contrast to other methods to measure the patient's electric properties, EPT does not apply externally mounted electrodes, currents, or radiofrequency probes, which enhances the practicability of the approach. This work shows that conductivity distributions can be reconstructed from phase images and permittivity distributions can be reconstructed from magnitude images of the radiofrequency transmit field. Corresponding numerical simulations using finite-difference time-domain methods support the feasibility of this phase-based conductivity imaging and magnitude-based permittivity imaging. Using this approximation, three-dimensional in vivo conductivity and permittivity maps of the human brain are obtained in 5 and 13 min, respectively, which can be considered a step toward clinical feasibility for EPT. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc.
T. Voigt, K. Nehrke, O. Doessel, and U. Katscher. T(1) corrected B(1) mapping using multi-TR gradient echo sequences. In Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 2010
This work presents a new approach toward a fast, simultaneous amplitude of radiofrequency field (B(1)) and T(1) mapping technique. The new method is based on the "actual flip angle imaging" (AFI) sequence. However, the single pulse repetition time (TR) pair used in the standard AFI sequence is replaced by multiple pulse repetition time sets. The resulting method was called "multiple TR B(1)/T(1) mapping" (MTM). In this study, MTM was investigated and compared to standard AFI in simulations and experiments. Feasibility and reliability of MTM were proven in phantom and in vivo experiments. Error propagation theory was applied to identify optimal sequence parameters and to facilitate a systematic noise comparison to standard AFI. In terms of accuracy and signal-to-noise ratio, the presented method outperforms standard AFI B(1) mapping over a wide range of T(1). Finally, the capability of MTM to determine T(1) was analyzed qualitatively and quantitatively, yielding good agreement with reference measurements. Magn Reson Med, 2010. (c) 2010 Wiley-Liss, Inc.
In magnetic induction tomography reducing the influence of the primary excitation field on the sensors can provide a significant improvement in SNR and/or allow the operating frequency to be reduced. For the purposes of imaging, it would be valuable if all, or a useful subset, of the detection coils could be rendered insensitive to the primary field for any excitation coil activated. Suitable schemes which have been previously suggested include the use of axial gradiometers and coil-orientation methods (Bx sensors). This paper examines the relative performance of each method through computer simulation of the sensitivity profiles produced by a single sensor, and comparison of reconstructed images produced by sensor arrays. A finite-difference model was used to determine the sensitivity profiles obtained with each type of sensor arrangement. The modelled volume was a cuboid of dimensions 50 cmx50 cmx12 cm with a uniform conductivity of 1 S m-1. The excitation coils were of 5 cm diameter and the detection coils of 5 mm diameter. The Bx sensors provided greater sensitivity than the axial gradiometers at all depths, other than on the surface layer of the volume. Images produced using a single-planar array were found to contain distortion which was reduced by the addition of a second array.
In this paper, we present an efficient method to estimate changes in forward-calculated body surface potential maps (BSPMs) caused by variations in tissue conductivities. For blood, skeletal muscle, lungs, and fat, the influence of conductivity variations was analyzed using the principal component analysis (PCA). For each single tissue, we obtained the first PCA eigenvector from seven sample simulations with conductivities between ±75% of the default value. We showed that this eigenvector was sufficient to estimate the signal over the whole conductivity range of ±75%. By aligning the origins of the different PCA coordinate systems and superimposing the single tissue effects, it was possible to estimate the BSPM for combined conductivity variations in all four tissues. Furthermore, the method can be used to easily calculate confidence intervals for the signal, i.e., the minimal and maximal possible amplitudes for given conductivity uncertainties. In addition to that, it was possible to determine the most probable conductivity values for a given BSPM signal. This was achieved by probing hundreds of different conductivity combinations with a numerical optimization scheme. In conclusion, our method allows to efficiently predict forward-calculated BSPMs over a wide range of conductivity values from few sample simulations.
Conduction velocity (CV) and CV restitution are important substrate parameters for understanding atrial arrhythmias. The aim of this work is to (i) present a simple but feasible method to measure CV restitution in-vivo using standard circular catheters, and (ii) validate its feasibility with data measured during incremental pacing. From five patients undergoing catheter ablation, we analyzed 8 datasets from sinus rhythm and incremental pacing sequences. Every wavefront was measured with a circular catheter and the electrograms were analyzed with a cosine-fit method that calculated the local CV. For each pacing cycle length, the mean local CV was determined. Furthermore, changes in global CV were estimated from the time delay between pacing stimulus and wavefront arrival. Comparing local and global CV between pacing at 500 and 300 ms, we found significant changes in 7 of 8 pacing sequences. On average, local CV decreased by 2015% and global CV by 1713%. The method allows for in-vivo measurements of absolute CV and CV restitution during standard clinical procedures. Such data may provide valuable insights into mechanisms of atrial arrhythmias. This is important both for improving cardiac models and also for clinical applications, such as characterizing arrhythmogenic substrates during sinus rhythm.
Atrial arrhythmias, such as atrial flutter or fibrillation, are frequent indications for catheter ablation. Recorded intracardiac electrograms (EGMs) are, however, mostly evaluated subjectively by the physicians. In this paper, we present a method to quantitatively extract the wave direction and the local conduction velocity from one single beat in a circular mapping catheter signal. We simulated typical clinical EGMs to validate the method. We then showed that even with noise, the average directional error was below 10(°) and the average velocity error was below 5.4 cm/s. In a realistic atrial simulation, the method could clearly distinguish between stimuli from different pulmonary veins. We further analyzed eight clinical data segments from three patients in normal sinus rhythm and with stimulation. We obtained stable wave directions for each segment and conduction velocities between 70 and 115 cm/s. We conclude that the method allows for easy quantitative analysis of single macroscopic wavefronts in intracardiac EGMs, such as during atrial flutter or in typical clinical stimulation procedures after termination of atrial fibrillation. With corresponding simulated data, it can provide an interface to personalize electrophysiological (EP) models. Furthermore, it could be integrated into EP navigation systems to provide quantitative data of high diagnostic value to the physician
Cardiac tissue exhibits spatially heterogeneous electrophysiological properties. In cardiac diseases, these properties also change in time. This study introduces a framework to investigate their role in cardiac ischemia using mathematical modeling and computational simulations at cellular and tissue level. Ischemia was incorporated by reproducing effects of hyperkalemia, acidosis, and hypoxia with a human electrophysiological model. In tissue, spatial heterogeneous ischemia was described by central ischemic (CIZ) and border zone. Anisotropic conduction was simulated with a bidomain approach in an anatomical ventricle model including realistic fiber orientation and transmural, apico-basal, and interventricular electrophysiological heterogeneities. A model of electrical conductivity in a human torso served for ECG calculations. Ischemia increased resting but reduced peak voltage, action potential duration, and upstroke velocity. These effects were strongest in subepicardial cells. In tissue, conduction velocity decreased towards CIZ but effective refractory period increased. At 10 min of ischemia 19% of subepi- and 100% of subendocardial CIZ cells activated with a delay of 34.6+/-7.8 ms and 55.9+/-18.8 ms, respectively, compared to normal. Significant ST elevation and premature T wave end appeared only with the subepicardial CIZ. The model reproduced effects of ischemia at cellular and tissue level. The results suggest that the presented in silico approach can complement experimental studies, e.g., in understanding the role of ischemia or the onset of arrhythmia.
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.
This work deals with the simulation of the electrical cardiac excitation propagation based on anatomical models of the human heart and body. The generation of anatomical models applying different techniques of digital image processing to medical image data is described as well as the generation of electrophysiological models based on these anatomical models. Different spatial and temporal physical field distributions, e.g. the transmembrane potential, the current sources and the extracellular potentials, are calculated and visualized in sinus rhythm case as well as in pathological cases.
M. Wilhelms, O. Dössel, and G. Seemann. In silico investigation of electrically silent acute cardiac ischemia in the human ventricles. In IEEE Transactions on Biomedical Engineering, vol. 58(10) , pp. 2961-2964, 2011
Acute cardiac ischemia, which is caused by the occlusion of a coronary artery, often leads to lethal ventricular arrhythmias or heart failure. The early diagnosis of this pathology is based on changes of the electrocardiogram (ECG), i.e. mainly shifts of the ST segment. However, the underlying mechanisms responsible for these shifts are not completely understood. Furthermore, clinical observations indicate that some acute ischemia cases can hardly be detected using standard 12-lead ECG only. Therefore, multi-scale computer simulations of cardiac ischemia using realistic models of human ventricles were carried out in this work. For this purpose, the transmembrane voltage distributions in the heart and the corresponding body surface potentials were computed with varying transmural extent of the ischemic region at different ischemia stages. Some of the simulated ischemia cases were electrically silent, i.e. they could hardly be identified in the 12-lead ECG.
Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation. In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential alternans. To assess the models ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate action potential and restitution properties, as well as the initiation of reentrant circuits.
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.
OBJECT: Multiple contrasts are often helpful for a comprehensive diagnosis. In 3D abdominal MRI, breath-hold techniques are preferred for single contrast acquisitions to avoid respiratory artifacts. In this paper, highly accelerated parallel MRI is used to acquire large 3D abdominal volumes with two different contrasts within a single breath-hold. MATERIAL AND METHODS: In vivo studies have been performed on six healthy volunteers, combining T (1)- and T (2)-weighted, gradient- or spin-echo based scans, as well as water/fat resolved imaging in a single breath-hold. These 3D scans were acquired with an acceleration factor of six, using a prototype 32-element receive array. RESULTS: The presented approach was tested successfully on all volunteers. The whole liver area was covered by a FOV of 350 x 250 x 200 mm(3) for all scans with reasonable spatial resolution. Arbitrary scan protocols generating different contrasts have been shown to be combinable in this single breath-hold approach. Good spatial correspondence with negligible spatial offset was achieved for all different scan combinations acquired in overall breath-hold times between 15 and 25 s. CONCLUSION: Enabled by highly parallel imaging technology, this study demonstrates the technical feasibility and the promising image quality of single breath-hold dual contrast MRI.
R. Winkelmann, P. Bornert, and O. Dössel. Ghost artifact removal using a parallel imaging approach. In Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 54(4) , pp. 1002-1009, 2005
Parallel imaging techniques, which use several receive coils simultaneously, have been shown to enable a significant scan time reduction by subsampling k-space. Nevertheless, the data acquired with multiple coils in parallel exhibit some redundancy if the number of receive coils exceeds the subsampling factor. This redundancy leads to an overdetermination of the reconstruction problem, which is generally used to optimize the signal-to-noise ratio (SNR). However, it can yield further information about the quality of the reconstructed image, and can thus be used to identify and correct image artifacts. While some known approaches try to solve this problem in k-space, this study addresses it in the spatial domain and uses a modified SENSE reconstruction to reduce or completely remove ghost-type artifacts arising from processes such as motion or flow during data acquisition. Phantom and in vivo studies show significant improvements in image quality after correction, and serve as a basis for the discussion of the performance and limitations of this new approach.
Parallel imaging techniques, which in principle represent procedures of unfolding a reduced dataset, are well known and well established in MR imaging. This paper presents a further application of one particular reconstruction method, the SENSE algorithm, considered from a different point of view to remove potential foldover in conventional images acquired with multiple receive coils. Based on the coil sensitivity information, a body coverage map in the excited plane is calculated. This is used together with the measured raw data in a SENSE-type reconstruction to optimize the signal-to-noise ratio (SNR) as well as to remove foldover reliably by unfolding the image to a larger field of view. The reconstruction is performed automatically, without any user interaction, and does not affect data acquisition. Based on phantom and in vivo studies, which retain high image quality after the removal, the potential and limits of this approach are discussed, also taking into account future scanner hardware that will support a large number of parallel receiver channels.
The steady-state free precessing (SSFP) sequences, widely used in MRI today, acquire data only during a short fraction of the repetition time (TR). Thus, they exhibit a poor scan efficiency. In this paper, a novel approach to extending the acquisition window for a given TR without considerably modifying the basic sequence is explored for radial SSFP sequences. The additional data are primarily employed to increase the signal-to-noise ratio, rather than to improve the temporal resolution of the imaging. The approach is analyzed regarding its effect on the image SNR (signal to noise ratio) and the reconstruction algorithm. Results are presented for phantom experiments and cardiac functions studies. The gain in SNR is most notable in rapid imaging, since SNR enhancement for a constant repetition time may be used to compensate for the increase in noise resulting from angular undersampling.
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.
PURPOSE: To demonstrate a rapid MR technique that combines imaging and R2* mapping based on a single radial multi-gradient-echo (rMGE) data set. The technique provides a fast method for online monitoring of the administration of (super-)paramagnetic contrast agents as well as image-guided drug delivery. MATERIALS AND METHODS: Data are acquired using an rMGE sequence, resulting in interleaved undersampled radial k-spaces representing different echo times (TEs). These data sets are reconstructed separately, yielding a series of images with different TEs used for pixelwise R2* mapping. A fast numerical algorithm implemented on a real-time reconstruction platform provides online estimation of the relaxation rate R2*. Simultaneously the images are summed for the computation of a high-resolution image. RESULTS: Convenient high-resolution R2* maps of phantoms and the liver of a healthy volunteer were obtained. In addition to stable intrinsic baseline maps, the proposed technique provides particularly accurate results for the high relaxation rates observed during the presence of (super-)paramagnetic contrast agents. Assuming that the change in R2* is proportional to the concentration of the agent, the technique offers a rough estimate for dynamic dosage. CONCLUSION: The simultaneous online display of morphological and parametric information permits convenient, quantitative surveillance of contrast-agent administration.
H. A. Wischmann, M. Fuchs, and O. Dössel. Effect of the signal-to-noise ratio on the quality of linear estimation reconstuctions of distributed current sources. In Brain Topography, vol. 5(2) , pp. 189-194, 1992
Currently, linear estimation reconstruction is the only feasible method for extracting information about spatially distributed current sources from measurements of neural magnetic fields. We present the results of a systematic study of the effect of the signal-to-noise ratio on the imaging quality of one such algorithm in over-as well as undetermined circumstances. In particular, we will discuss the necessary trade-off between the contradictory goals of a minimum norm of the reconstructed current density distribution and of a minimal deviation of the reconstructed fields from the measured fields. As an example, we show the reconstruction of a simple arrangement of two nearly parallel dipoles in two different depths inside a spherical volume conductor, discussing the differences between the computer simulation without noise and simulation with a realistic noise level.
O. Dössel. Bildgebende Verfahren in der Medizin: Von der Technik zur medizinischen Anwendung. Springer-Verlag Berlin Heidelberg, 2016.
Dieses erfolgreiche Standardwerk beschreibt sämtliche bildgebenden Verfahren von der Röntgentechnik über den Ultraschall bis zu den Methoden der Tomographie. Es werden sowohl die technischen Grundlagen als auch die medizinischen Anwendungen erläutert.Das Lehrbuch zeichnet sich aus durch eine verständliche Darstellung, zahlreiche Illustrationen der grundlegenden Prinzipien sowie durch Bilder von den verschiedenen Modalitäten und von den Geräten.Die 2. Auflage wurde aktualisiert und enthält neue Trends und Entwicklungen, insbesondere beim Röntgen und Ultraschall. Kapitel über Magnetic Particle Imaging (MPI) wurden hinzugefügt.
O. Dössel. Lecture notes - electromagnetics and numerical calculation of fields. Institut für Biomedizinische Technik, Universität Karlsruhe (TH), 2007.
O. Dössel. Vorlesungsskript 05 - Lineare Elektrische Netze. Institut für Biomedizinische Technik, Universität Karlsruhe (TH), 2005.
O. Dössel. Bildgebende Verfahren in der Medizin: von der Technik zur medizinischen Anwendung. Springer, Berlin, Heidelberg, New York. 2000.
Umfassende Darstellung der Bandbreite bildgebender Modalitäten in der Medizin (z. B. Projektionsröntgen, Computertomographie und Magnetresonanztomographie)Detaillierte Information zu jedem Verfahren über das physikalische Grundprinzip, die gerätetechnische Umsetzung, die Qualitätsparameter und die medizinischen Applikationen.Für Studierende technischer Diplom-, Bachelor- und Masterstudiengänge an Universitäten und Fachhochschulen auf dem Gebiet der Biomedizinischen Technik aber auch für Studierende der Medizin sowie für Praktiker in der medizintechnischen Industrie und im medizinischen Bereich
O. Dössel. Vertrauen in die Technikwissenschaften, Vertrauen in die Medizintechnik?!. In Debatte - Vertrauen in die/in der Wissenschaft?, Berlin-Brandenburgische Akademie der Wissenschaften, pp. 75-81, 2013
VERTRAUEN IN DIE / IN DER WISSENSCHAFT?Streitgespräche in den Wissenschaftlichen Sitzungen der Versammlung der Akademiemitglieder am 30. November 2012 und am 14. Juni 2013
O. Dössel. Patientenmodelle. In Innovationsreport 2012 - Personalisierte Medizintechnik, Deutsche Gesellschaft für Biomedizinische Technik (DGBMT), pp. 14-19, 2012
O. Dössel. homo technicus - passt sich die Technik an den Menschen an oder der Mensch an die Technik?. In Evolution. Theorie, Formen und Konsequenzen eines Paradigmas in Natur, Technik und Kultur, V. Gerhardt, K. Lucas, S. Stock (eds), Berlin-Brandenburgischen Akadamie der Wissenschaften. Akademie Verlag, pp. 141-149, 2011
O. Dössel. Ablation von Vorhofarrhythmien. In Computerassistierte Chirurgie, P. Schlag, S. Eulenstein, T. Lange, M. Kleemann (eds), Elsevier, Urban & Fischer, München, pp. 469-477, 2010
O. Dössel. Medizintechnik 2025 - Trends und Visionen. In Gesundheitswesen 2025: Implikationen, Konzepte, Visionen, W. Niederlag, H. Lemke, E. Nagel, O. Dössel (eds), Dresden Health Academy, pp. 115-126, 2008
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?
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
O. Dössel. Mathematische Modelle vom Herzen. In Debatte - Mathematisierung der Natur, Berlin-Brandenburgische Akademie der Wissenschaften, pp. 83-85, 2006
Mathematisierung der NaturStreitgespräche in den Wissenschaftlichen Sitzungen der Versammlung der Berlin-Brandenburgischen Akademie der Wissenschaftenam 10. Dezember 2004 und 27. Mai 2005
O. Dössel. Röntgentechnik. In Bildgebende Verfahren in der Medizin, Springer, pp. 1-69, 2000
O. Dössel. Biologische Wirkung ionisierender Strahlen und Dosimetrie. In Bildgebende Verfahren in der Medizin, pp. 146-154, 2000
O. Dössel. Neue Werkzeuge in der Medizin - Medizintechnik und Biomedizin. In Die Technische Universität an der Schwelle zum 21. Jahrhundert : Festschrift zum 175jährigen Bestehen der Universität Karlsruhe (TH), H. Kunle, S. Fuchs (eds), Berlin ; Heidelberg [u.a.] : Springer, pp. 285-304, 2000
O. Dössel, and T. M. Buzug. Bildgebung. In Biomedizinische Technik - Faszination, Einführung, Überblick, U. Morgenstern, M. Kraft (eds), Berlin [u.a.] : De Gruyter, pp. 271-326, 2014
O. Dössel, B. David, and M. Fuchs. A multichannel SQUID system for current density imaging. In Biomagnetism: clinical aspects, Proceedings of the 8. International Conference on Biomagnetism, Münster, 19-24 August 1991, M. Hoke, S. Erne, Y. Okada (eds), Excerpta Medica, Amsterdam, pp. 837-841, 1992
O. Dössel, B. David, M. Fuchs, J. Krüger, and H. A. Wischmann. Simple test procedures for multichannel squid systems. In Biomagnetism: fundamental research and clinical applications; proceedings of the 9th International Conference on Biomagnetism (BIOMAG '93 Vienna), C. Baumgartner, L. Deecke (eds), Amsterdam, Elsevier/IOS Press, pp. 515-520, 1995
Papers from the 4th International Conference on Superconducting and Quantum Effect Devices and their Applications held in Berlin, Germany, June 18-21, 1991.Detailliertere InformationenSuperconducting devices and their applications: proceedings of the 4th international conference SQUID '91 (session on superconducting devices), Berlin, Fed. Rep. of Germany, June 18-21, 1991Von Hans Koch, H. LübbigMitwirkende Personen Hans KochEdition: illustratedVeröffentlicht von Springer-Verlag, 1992Original von University of MichiganDigitalisiert am 10. Dez. 2007ISBN 0387553967, 9780387553962603 Seiten
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.
O. Dössel, M. W. Krueger, and G. Seemann. Personalized Electrophysiological Modeling of the Human Atrium. In Cardiac Mapping, M. Shenesa, G. Hindricks, M. Borggrefe, G. Breithardt, M. E. Josephson (eds), Wiley-Blackwell, pp. 150-158, 2013
Numerical and patient-specific models of the human atrial anatomy and electrophysiology have a high potential to enhance our knowledge regarding pathological conditions and to increase the outcome of diagnosis and therapy. This chapter briefly describes the current state of the art in modeling of generalized human atria. Furthermore, the chapter demonstrates ways to personalize human atrial anatomy and electrophysiology based on a variety of measurement data from, e.g. late enhancement magnetic resonance imaging (MRI), patch clamp technique, intracardiac electrograms and body surface potential maps. Wherever patient data cannot be collected, patient-group specific behavior can be integrated. Some examples of the personalization process are described and the validation process is discussed together with future options for personalization, validation and application.
O. Dössel, and G. Seemann. Computer model of the electrical excitation of the heart. In Modelling and Control in Biomedical Systems. A Proceedings Volume from the 5th IFAC Symposium Hilton on the Park, Melbourne, Australia, 21-23 August, D. D. Feng, E. R. Carson (eds), Oxford: Pergamon, pp. 179-184, 2003
I. H. d. Boer, W. Maurer, F. R. Schneider, and O. Dössel. Matching von dreidimensionalen Elektrodenpositionen ausgehend von biplanaren Röntgenbildverstärkern und CCD-Farbkameras. In Bildverarbeitung für die Medizin 1999, H. Evers, G. Glombitza, T. Lehmann, H. Meinzer (eds), Springer, Berlin Heidelberg New York, pp. 70-74, 1999
P. Deuflhard, O. Dössel, and A. K. Louis. More mathematics into medicine!!. In Production Factor Mathematics, K. L. Martin Grötschel (eds), Berlin, Heidelberg : Springer-Verlag Berlin Heidelberg, pp. 357-377, 2010
This article presents three success stories that show how the coaction of mathematics and medicine has pushed a development towards patient specific models on the basis of modern medical imaging and virtual labs, which, in the near future, will play an increasingly important role. Thereby the interests of medicine and mathematics seem to be consonant: either discipline wants the results fast and reliably. As for the medical side, this means that the necessary computations must run in shortest possible times on a local PC in the clinics and that their results must be accurate and resilient enough so that they can serve as a basis for medical decisions. As for the mathematical side, this means that highest level requirements for the efficiency of the applied algorithms and the numerical and visualization software have to be met. Yet there is still a long way to go, until anatomically correct and medically useful individual functional models for the essential body parts and for the most frequent.
M. Fuchs, and O. Dössel. Online head position determination for MEG-measurements. In Biomagnetism: Clinical aspects, M. Hoke, S. Erne, Y. Okada, G. Romani (eds), Excerpta Medica, Amsterdam, pp. 869-873, 1992
M. Fuchs, M. Wagner, H. A. Wischmann, and O. Dössel. Cortical current imaging by morphologically constrained reconstructions. In Biomagnetism: fundamental research and clinical applications; proceedings of the 9th International Conference on Biomagnetism (BIOMAG '93 Vienna), C. Baumgartner, L. Deecke (eds), Amsterdam, Elsevier/IOS Press, pp. 320-325, 1995
M. Fuchs, M. Wagner, H. A. Wischmann, and O. Dössel. Possibilities of functional brain imaging using a combination of MEG and MRT. In Oscillatory Event-Related Brain Dynamics (Nato Science Series: A:), C. Pantev, T. Elbert, B. Lütkenhöner (eds), New York: Plenum Press, pp. 435-457, 1994
D. Grundler, B. David, and O. Dössel. Low-frequency noise in YBa2Cu3O7 dc SQUIDS and magnetometers. In Applied Superconductivity 1995: Proceedings of Eucas, the Second European Conference on Applied Superconductivity, D. DewHughes (eds), Institute of Physics conference series, Edinburgh, Scotland, 3-6 July, pp. 1625-1628, 1995
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.
R. Laudahn, T. I. M., W. H. Kullmann, M. Fuchs, O. Dössel, and B. Bromm. Early somatosensory evoked magnetic fields studied with a multichannel first order gradiometer system. In Biomagnetism: clinical aspects, Proceedings of the 8. International Conference on Biomagnetism, Münster, 19-24 August 1991, M. Hoke, S. Erne, Y. Okada, G. Romani (eds), Excerpta Medica, Amsterdam, pp. 259-262, 1992
M. Wagner, M. Fuchs, H. A. Wischmann, K. Ottenberg, and O. Dössel. Cortex segmentation from 3D MR images for MEG reconstructions. In Biomagnetism: fundamental research and clinical applications; proceedings of the 9th International Conference on Biomagnetism (BIOMAG '93 Vienna), C. Baumgartner, L. Deecke (eds), Amsterdam, Elsevier/IOS Press, pp. 433-438, 1995
H. A. Wischmann, M. Fuchs, M. Wagner, and O. Dössel. Current density imaging: a time series reconstruction implementing a "best fixed distributions" constraint. In Biomagnetism: fundamental research and clinical applications; proceedings of the 9th International Conference on Biomagnetism (BIOMAG '93 Vienna), C. Baumgartner, L. Deecke (eds), Amsterdam, Elsevier/IOS Press, pp. 427-432, 1995
Conference Contributions (539)
O. Doessel, and W. Germer. Sensoren für Spannung, Kraft und Verformung. In DPG-Verhandlungen, vol. 6, pp. 1417-1424, 1984
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.
O. Doessel, C. Werner, and F. Sachse. Modelling of normal and arrhythmogenic electrical excitation of the human heart. In World Congress on Medical Physics, vol. 27, pp. 205, 2000
O. Dössel. Biomedical Engineering as a Major within Electrical Engineering and Information Technology - Pros and Cons. In Proc. IFMBE, vol. 25(Pt 12) , pp. 344, 2009
O. Dössel. Funktionelle Computermodelle des Patienten für Diagnose und Therapie. In VDE-Kongress 2006 - Innovations for Europe - Fachtagungsberichte der ITG/BMBF - GMM - ETG - GMA - DGBMT, pp. 443-447, 2006
Nachdem in der Vergangenheit statische Computermodelle von der Anatomie des Patienten entwickelt wurden, stehen heute funktionelle Modelle im Vordergrund der Forschung, in denen beispielsweise Bewegungsabläufe oder physiologische Prozesse im Körper modelliert werden. Zielsetzung ist das bessere Verständnis der funktionellen Prozesse (Grundlagenforschung), die vertiefende Diagnose (Etiologie, Erkennen der Ursachen einer Erkrankung) und die systematische Optimierung der Therapie. Daneben können auch Lern-Werkzeuge für Ärzte daraus abgeleitet werden (Learning and Training). Um zu diesen Zielen zu gelangen, müssen funktionelle Vorgänge im Körper quantitativ verstanden und modelliert werden (Mathematical Physiology, Computational Biology). Erst die mathematische Beschreibung erlaubt die sichere Vorhersage. Vor Erreichen dieses Zieles ist viel Grundlagenforschung nötig, da viele funktionelle Abläufe im Körper noch nicht quantitativ bekannt sind. Oft bedeutet dies, dass Erkrankungen bis zur zellulären Ursache und bis zu den komplexen biologischen Regelkreisen mathematisch beschrieben werden müssen
O. Dössel. Principles of sensor error correction. In CompEuro '89., 'VLSI and Computer Peripherals. VLSI and Microelectronic Applications in Intelligent Peripherals and their Interconnection Networks', Proceedings, 1989
The different principles of sensor error correction are classified with respect to intrinsic or extrinsic compensation techniques, analog or digital techniques, and integrated or discrete techniques, and typical examples are given. Advantages and disadvantages of the different methods are analyzed, and future trends are outlined. One logical continuation of these trends is the application-specific IC for sensor signal amplification and error correction. On the other hand, inexpensive multipurpose ICs (e.g. an A/D converter and a microprocessor together with a small primary electronics to adapt the IC to the individual sensor type) should also find applications
O. Dössel, W. Bauer, D. Farina, C. Kaltwasser, and O. Skipa. Imaging of bioelectric sources in the heart using a cellular automaton model. In Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, vol. 2, pp. 1067-1070, 2005
The approach to solve the inverse problem of electrocardiography presented here is using a computer model of the individual heart of a patient. It is based on a 3D-MRI dataset. Electrophysiologically important tissue classes are incorporated using rules. Source distributions inside the heart are simulated using a cellular automaton. Finite Element Method is used to calculate the corresponding body surface potential map. Characteristic parameters like duration and amplitude of transmembrane potential or velocity of propagation are optimized for selected tissue classes or regions in the heart so that simulated data fit to the measured data. This way the source distribution and its time course of an individual patient can be reconstructed.
A modular multichannel superconducting quantum interference device (SQUID) system, in which every channel can be optimized or replaced individually, was further improved. The number of channels was increased to 31. The noise level is better than 10 fT/√Hz. A novel way of RF shielding using conductive paint avoids degradation of the SQUID characteristics due to RF interference without introducing significant extra noise, so that the system works without any Faraday cage. A simplified way of coupling the modulation and feedback signal directly to the SQUID was developed and tested successfully. The SQUID module with superconducting connections to the gradiometer and its superconducting shield was miniaturized to an outer diameter of 5 mm, so that it can be placed near the gradiometer without introducing significant unbalance. Tests have demonstrated that the accuracy of the system with respect to the localization of a single current dipole is better than 2 mm
A modular low-noise seven-channel SQUID-magnetometer for biomagnetic measurements was developed. The DC-SQUIDs are prepared by thin film technology based on the materials NbN-MgO-NbN, and show a flux noise below 10 μΦ0/√Hz. The signal is picked up with first-order wire-wound gradiometers of 2-cm diameter and coupled to the SQUIDs by integrated coupling coils. Individual channels can be replaced from the system, and various gradiometers can be used giving a flexible modular system. The electronics are based on the flux-locked-loop method extended by a bias modulation technique to reduce 1/f noise. The overall system noise is below 20 fT/√Hz. Biomagnetic measurements on auditory evoked fields have been carried out
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.
O. Dössel, Y. Jiang, and W. H. W. Schulze. Localization of the origin of premature beats using an integral method. In International Journal of Bioelectromagnetism, vol. 13(4) , pp. 178-183, 2011
A method to reconstruct integrals of transmembrane voltages in the heart from measured integrals of Body Surface Potential Maps (BSPM) is proposed. It is applied to localize the origin of premature beats in the heart (extrasystoles). In contrast to other proposals no specific assumption about the slope of the transmembrane voltage during depolarization is made, in particular it must not be a step function. This way the non-linear problem of localizing ectopic foci based on activation times is translated into a linear inverse problem. A Maximum-A-Posteriori (MAP) estimator is applied to solve the ill-posed linear inverse problem. Successful localization of ventricular extrasystoles is demonstrated using computer simulations. Even endocardial, midmyocardial and epicardial foci can be separated.
The objective of personalised modelling of the atria is to improve comprehension of the etiology of atrial arrhythmias, to enable specific diagnosis and to optimise therapy. We start with CT or MR datasets and use adapted segmentation procedures to build a patient-specific 3D-model of the atria. Then we include fibre direction based on the rules of atrial anatomy. Work in progress is also considering late enhancement MRI in order to add areas of fibrotic tissue. Next we can use BSPM data of the P-wave and solve the inverse problem of ECG to get a hypothesis about the spread of depolarisation. Finally we use intracardiac catheter signals (e.g. using a circular catheter) to measure direction and conduction velocity of depolarisation waves (sinus rhythm, atrial flutter, or following stimulation). All this is integrated into a personalised model of the atria of an individual patient. Our next goal will be to properly add ablation lines into the model.The research leading to these results has partly received funding from the European Communitys Seventh Framework Programme (FP7/2007-2013) under grant agreement n 224495 (euHeart project).
A framework for step-by-step personalization of a computational model of human atria is presented. Beginning with anatomical modeling based on CT or MRI data, next fiber structure is superimposed using a rule-based method. If available, late-enhancement-MRI images can be considered in order to mark fibrotic tissue. A first estimate of individual electrophysiology is gained from BSPM data solving the inverse problem of ECG. A final adjustment of electrophysiology is realized using intracardiac measurements. The framework is applied using several patient data. First clinical application will be computer assisted planning of RF-ablation for treatment of atrial flutter and atrial fibrillation.
Today, patients suffering from atrial arrhythmias like atrial flutter (AFlut) or atrial fibrillation (AFib) are examined in the EP-lab (electrophysiology lab) in order to understand and treat the disease. Multichannel catheters are advanced into the atria in order to measureelectric signals at manyintracardiacpositions simultaneously. Complementary to clinical learning,comprehension of the disease and therapeutic strategies can be improved with computer modeling of the heart. This way, hypotheses about initiation and perpetuation of the arrhythmia can be tested and ablation strategies can be assessed in-silico. Modeling and biosignal analysis can benefit from mutual fertilization. On the one hand, modeling can be improved and personalization can be achieved via high density mapping of the atria. On the other hand, new algorithms for the interpretation of multichannel electrograms can be developed and evaluated with synthetic signals from computer models of the atria. This article illustrates the synergetic potential by examples and highlights challenges to be addressed in the future.
O. Dössel, and A. Loewe. Computer Modelling pharmakologischer Effekte. In Frühjahrstagung der Deutschen Gesellschaft für Kardiologie, 2017
By means of computer modeling general comprehension of electrophysiology (EP) of human atria can be improved and simulated patterns of ectopic foci, reentry and rotors can be created. On the other hand atrial electrograms are measured in the EP lab of many hospitals every day. In this contribution simulated and measured clinical signals are compared critically aiming at better understanding of atrial fibrillation and validation of computer modeling.
O. Dössel, and F. R. Schneider. Opportunities and limitation of non-invasive bioelectric imaging of the heart. In Proc. EMBEC 99, pp. 1188-1189, 1999
The spatial resolution of Bioelectric Imaging of the Heart was investigated. Based on the measurement of a multichannel Electrocardiogram (ECG) or Magnetocardiogram (MCG) images of epicardial potential distributions can be reconstructed. The imaging properties of this method have been investigated using Computer simulations. The spatial resolution depends strongly on the number and arrangement of electrodes and magnetometers, on the noise level of the sensors and on the individual morphology of the patient. Artefacts show up if errors in the torso model (geometry and/or impedance values) occur.
O. Dössel, F. R. Schneider, and M. Müller. Optimization of electrode positions for multichannel electrocardiography with respect to electrical imaging of the heart. In Engineering in Medicine and Biology Society, 1998. Proceedings of the 20th Annual International Conference of the IEEE, vol. 1, pp. 71-74, 1998
A procedure to find the optimal electrode positions for multichannel electrocardiography is presented. The criterion is the ability to reconstruct images of the electrical activity of the heart. Singular value decomposition of the lead field matrix is the chosen approach. The finite element method is used for numerical field calculation to determine the lead field matrix. Estimates on the expected measurement error play an important role in the optimization procedure. The optimal arrangement of electrodes is compared with other electrode positions reported in the literature using different optimization criteria. Body surface potential maps (BSPM) are measured on a healthy volunteer using the optimized electrode arrangement and preliminary epicardial potential patterns are reconstructed
Atrial fibrillation (AF) ablation guided by basket catheter mapping has shown to be beneficial. Yet, the initial excitement is mitigated by a growing skepticism due to the difficulty in verifying the protocol in multicenter studies. Overall, the underlying assumptions of rotor ablation require further verification. The aim of this study was therefore to test such hypotheses by using computational modeling. The 3D left atrial geometry of an AF patient was segmented from a pre-operative MR scan. Atrial activation was simulated on the 3D anatomy using the monodomain approach and a variant of the Courtemanche action potential model. Ablated tissue was assigned zero conductivity. Reentry was successfully initialized by applying a single suitably delayed extra stimulus. Unipolar electrograms were computed at the simulated electrode positions. The final dataset was generated by varying location of reentry and catheter position within the LA. The effect of inter-electrode distance and distance to the atrial wall was studied in relation to the ability to recover rotor trajectory, as computed by a novel algorithm described here. The effect of rotor ablation was also assessed.
P-wave assessment is frequently used in clinical practice to recognize atrial abnormalities. However, the use of P-wave criteria to diagnose specific atrial abnormalities such as left atrial enlargement has shown to be of limited use since these abnormalities can be difficult to distinguish using P-wave criteria to date. Hence, a mechanistic understanding how specific atrial abnormalities affect the P-wave is desirable. In this study, we investigated the effect of left atrial hypertrophy on P-wave morphology using an in silico approach. In a cohort of four realistic patient models, we homogeneously increased left atrial wall thickness in up to seven degrees of left atrial hypertrophy. Excitation conduction was simulated using a monodomain finite element approach. Then, the resulting transmembrane voltage distribution was used to calculate the corresponding extracellular potential distribution on the torso by solving the forward problem of electrocardiography. In our simulation setup, left atrial wall thickening strongly correlated with an increased absolute value of the P-wave terminal force (PTF) in Wilson lead V1 due to an increased negative amplitude while P-wave duration was unaffected. Remarkably, an increased PTF-V1 has often been associated with left atrial enlargement which is defined as a rather increased left atrial volume than a solely thickened left atrium. Hence, the observed contribution of left atrial wall thickness changes to PTF-V1 might explain the poor empirical correlation of left atrial enlargement with PTF-V1.
Atrial fibrillation is the most common cardiac arrhythmia and often leads to severe complications such as stroke and other embolic incidents. Areas of complex fractionated atrial activity are in the focus of electrophysiologists and have been used as a target for catheter ablation therapy. The underlying mechanisms of complex fractionated atrial electrograms (CFAEs) are not entirely understood. CFAEs may contain concurrent rhythmic episodes of signals with differing characteristic frequencies (CFs). We propose a new algorithm to detect multiple periodicities in atrial signals.First, we preprocess the signal by applying Teager's non-linear energy operator. Next, the first three characteristic frequencies are detected in the frequency spectrum. Information contained in the harmonics is used to recursively detect the exact frequency. Frequency information is then transformed into the time domain, where repeated occurance of signal activity according to the respective cycle length is found. Further, the detection rate and the mean distance to gravity are calculated as key figures to determine more characteristics of the periodicity.The algorithm performs well in detecting the rhythmic components of atrial signals. It has been tested using real patient data acquired during electrophysiological studies in sinus rhythm, atrial flutter and several forms of atrial fibrillation, as well as with simulated data produced by a cellular automaton at our research group.Its application may provide new insights into atrial signals especially CFAEs and the interpretation of characteristic and dominant frequencies. It can be the foundation of displaying rhythmicity and CF information onto the 3D representation of the patient's atrium and give the physician an impression of the organization and regularity of cardiac electrograms.
QT interval correction on measured ECGs is an important issue for pharmaceutical research on the way to new drugs. Pharmaceutical industries have to thoroughly investigate potential effects of their drugs on QT intervals since QT pro- longation is considered as a marker of the proarrhythmia risk. As QT interval depends on RR interval there is an obvious in- terest in modeling the QT-RR relationship. Static formulas to correct QT for RR are well known, but a dynamic dependency is also 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 measure- ments and simulations and are validated by Holter ECG data.
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.
There is a large interest in analysing the QT-interval, as a prolonged QT-interval can cause the development of ventricular tachyarrhythmias such as Torsade de Pointes. One major part of QT-analysis is T-end detection. Three automatic T-end delineation methods based on wavelet fil- terbanks (WAM), correlation (CORM) and Principal Com- ponent Analysis PCA (PCAM) have been developed and applied to Physionet QT database. All algorithms tested on Physionet QT database showed good results, while PCAM produced better results than WAM and CORM achieved best results. Standard de- viation in sampling points (fs=250Hz) have been 33.3 (WAM), 8.0 (PTDM) and 7.8 (CORM). It could be shown that WAM is prone to interference while CORM is the most stable method even under bad conditions. Further- more it was possible to detect significant QT-prolongation caused by Moxifloxacin in Thorough QT Study # 2 us- ing CORM. QT-prolongation is significantly correlated to blood plasma concentration of Moxifloxacin.
Prolongation of the ECG QT-interval is a risk factor as it can cause the development of ventricular tachyarrhythmias such as Torsade de Points and ventricular fibrillation often leading to sudden cardiac death. Thus there is a large interest in analysing the QT-interval in the ECG. One major part of ECG QT-analysis is T-end detection. A method for automatic T-end detection is presented and validated by the Physionet QT-database. The delineation algorithm presented here is based on a correlation method. Results have been compared to hand marked T-waves in the Physionet QT-database. The algorithm produced significantly better results than using the standard wavelet method.
T. Baas, K. Gräfe, A. Khawaja, and O. Dössel. Investigation of parameters highlighting drug induced small changes of the T-wave's morphology for drug safety studies. In Conf Proc IEEE Eng Med Biol Soc, pp. 3796-3799, 2011
In guideline E14, the American Food and Drug Administration (FDA) requests for clinical studies to investigate the prolongation of the heart rate corrected QT-interval (QTc) of the ECG. As drug induced QT-prolongation can be caused by changes in the repolarisation of the ventricles, it is so far a thorough ECG biomarker of risk for ventricular tachyarrhythmias and Torsade de Pointes (TdP). Ventricular repolarisation changes not only change QT but also influence the morphology of the T-wave. In a (400 mg single dose) Moxifloxacin positive control study both, QTc and several descriptors describing the T-wave morphology have been measured. Moxifloxacin is changing two shape dependent descriptors significantly (P<0.05) about 3 to 4 hours after a 400 mg oral single dose of Moxifloxacin.
T. Baas, H. Köhler, H. Malberg, and O. Dössel. Automatic blood pressure segmentation algorithm for analysing morphology changes. In Biomedizinische Technik / Biomedical Engineering (Proceedings BMT2010), vol. 55(1) , pp. 168-171, 2010
Simultaneous recording of ECG, Atrial Blood Pressure (ABP) and respiration is possible and sometimes done to investigate cardiovascular and respiration coupling. But analysis most often concentrates on Heart Rate Variability (HRV) and Blood Pressure Variability (BPV). Although analysis of HRV and BPV has lead to important clinical information in the past, an investigation of the morphology of the time course of ECG and ABP could reveal additional diagnostic information.To analyse the morphology of the Blood Bressure (PB) wave a detection of characteristic points, outliers and boundaries is necessary. A wavelet based algorithm for blood pressure segmentation with outlier detection is presented in this paper. It is tested on 108 records with durations of 30 minutes each.
Orientations of myocytes impact electric excitation propagation and mechanical contraction in the human heart. Measured fiber angles in experiments are obtained from different species (e. g. rat, canine, dog, human heart) and vary by various reasons. It is unclear to what ex- tent non-exact fiber angles impact the quality of computa- tional simulations. In this paper, mechanical simulations with different ventricular angles were performed and com- pared. The simulations covered the complete heart with both ventricles, both atria and the pericardium and were performed using finite element method. Helix angles were varied between 20\0 and 70\0 on endocardium and \070\0 and \020\0 on epicardium. Results showed that fiber ori- entations had only a minor contribution to the difference between endsystolic and enddiastolic pressure of < 8.3 %. The influence on stroke volume as well as AVPD is sig- nificant (changes by 34 % for SV and 241 % for APVD) , but it could not be observed that a higher AVPD yields a higher stroke volume. Concludingly, fiber orientations are important for reliable computational simulations of human hearts and should be incorporated with great care.
L. Baron, A. Loewe, and O. Dössel. From clinics to the virtual beating heart a general modeling workflow for patient-specific electromechanical heart simulations. In BMTMedPhys 2017, vol. 62(S1) , pp. S70, 2017
Generating meshes of complex structures in the human body like the heart organ is a prerequisite for computational simulations of of organ function. The quality of the conclusions derived from these simulations greatly depends on the quality and accuracy of the mesh they are based on. Volumetric computation domain can be represented by an equally-spaced voxel grid, or – in case of more sophisticated partial differential equation discretization methods (finite elements, finite volumes) – first, second or even higher order tetrahedral meshes. Here, we present a workflow that is capable of creating high quality meshes for such simulations. The workflow contains segmentation, surface mesh generation, volume mesh generation, and patient-specific parameter fitting to produce the desired results. While segmentation itself is a more or less unique mapping from a grayscale DICOM data set to a labeled, three-dimensional voxel mesh, different approaches exist for their transformation to a surface mesh. Our process involves a two-level approach for obtaining triangular or mixed rectangular surface meshes of desired quality and resolution. Both are crucial for the next step: obtaining a volumetric tetrahedral grid with the desired degrees of freedom. In the last step, a derivative-free parameter estimation approach is used to calibrate the dynamic behavior and tailor the model patient-specifically. All software used in the workflow is published under open source licenses and freely available. Its capability is demonstrated by means of an elastomechanical simulation of a human heart and yields measurable validation quantities in physiological ranges. We want to stress that the presented approach is generic and can easily be used for the model generation of other organs like liver, lungs or the aortic arch as well. The resulting meshes can be used for various types of simulations (electrical excitation propagation, blood flow) and use cases (clinical diagnostics, therapy planning etc.).
S. Bauer, T. Oesterlein, J. Schmid, and O. Dössel. Interactive visualization of cardiac anatomy and atrial excitation for medical diagnosis and research. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 400-404, 2015
State of the art biomedical engineering allows for acquiring enormous amounts of intracardiac data to aid diagnosis and treatment of cardiac arrhythmias. Modern catheters, which are used to acquire electrical information from within the heart, are capable of recording up to 64 channels simultaneously. The software available for data analysis, however, does not provide adequate performance to neither analyze nor visualize the acquired information in an appropriate manner. We present a software package that fascilitates interdisciplinary collaborations between engineers and physicians to adress open questions about pathophysiological mechanisms using data from everyday electrophysiogical studies. Therefore, a package has been compiled that enables algorithm development using MATLAB and subsequent visualization using the VTK C++ class libraries. The resulting application KaPAVIE, which is presented in this paper, is designed to meet the requirements from the clinical side and has been successfully applied in the clinical environment.
I. H. d. Boer, F. B. Sachse, and O. Dössel. Matching of intracardial and extracorporal electrode positions with segmented volume datasets of the human thorax. In Proc. CARS 1999, pp. 1006, 1999
I. H. d. Boer, F. B. Sachse, and O. Dössel. Entwicklung eines 4-Kamera-Systems zur Lokalisation einer Elektrodenanordnung auf dem Thorax. In Biomedizinische Technik, vol. 43-1, pp. 56-57, 1998
I. H. d. Boer, F. B. Sachse, and O. Dössel. 3D-Lokalisation von Elektroden bei der Multikanal-EKG-Ableitung mittels Analyse von Stereofarbaufnahmen. In Biomedizinische Technik, vol. 42(s2) , pp. 129-130, 1997
Die 3D-Lokalisation mit Hilfe von zwei CCD-Kameras ermöglicht die Elektrodenanordnung bei der Multikanal-EKG-Ableitung durch Zuordnung von Meßkanal zu Elektrodenort. Als Referenzobjekt dient ein Würfelmodell mit farbigen Eckkugeln zur Ermittlung der Weltkoordinaten im kartesischen Weltkoordinatensystem. Jede Farbaufnahme dieses Referenzobjekts wird in Grauwerte umgewandelt und mit einer vorgegebenen Maske korreliert. Zur 3D-Lokalisation erfolgen zwei Farbaufnahmen der farbig gekennzeichneten Elektrodenanordnung, die sich auf dem Oberkörper des Patienten befindet. Aufstellen und Lösen des Gleichungssystems wird für n Elektroden wiederholt und die Farbinformation danach genutzt, um jeder Elektrode eineutig einen Meßkanal zuzuordnen.
J. Bohnert, and O. Doessel. Simulations of temperature increase due to time varying magnetic fields up to 100 kHz. In 5th European IFMBE Conference, IFMBE Proceedings, vol. 37, pp. 303-306, 2011
Magnetic Particle Imaging (MPI) benefits from the non-linear magnetization curve of magnetic nano-particles. Magnetic fields applied in this new imaging modality are of fre- quencies in the kHz-range. Little research has been carried out upon absorbed power and temperature increase caused by time- varying fields in that frequency range. Presented here are tem- perature distributions in a human body model exposed to mag- netic fields of 10 kHz to 100 kHz. A numerical human model has been placed within field generating coils. The finite elements model for the field calculation and the Pennes Bio-heat equation for the temperature distribution with and without perfusion and heat transfer by convection have been used. The results indicate that the absorbed power does lead to local temperature increase but not up to a hazardous level, if certain thresholds for the mag- netic fields are considered.
J. Bohnert, and O. Dössel. Calculation and evaluation of current densities and thermal heating in the body during MPI. In Magnetic Nanoparticles: Particle Science, Imaging Technology, and Clinical Applications : Proceedings of the First International Workshop on Magnetic Particle Imaging, vol. Auflage: 1, pp. 162-168, 2010
In Magnetic Particle Imaging (MPI) the human body is exposed to magnetic fields of the lower kHz-range. The effects of those fields to biological tissue are yet to be determined. According to Faraday's Law, time-varying magnetic fields induce rotating electric fields. In body tissues, the induced electric field may cause an electric current, the formation of electric dipoles or the reorientation of present dipoles, depending on the strength of the magnetic field, the frequency and the properties of the body tissue, i.e. electrical conductivity and permittivity. Both electrical conductivity and permittivity vary with the frequency of the applied field. In case of a circular loop, the induced current density is proportional to the radius, the rate of change of the magnetic flux density and the conductivity of the tissue. Low frequency electric currents are able to stimulate skeletal muscles. Because of the capacitive characteristic of the cell membrane, the stimulating effect decreases with rising frequency. Furthermore, very short impulses (t ≪ 1 ms) cannot open the Na-ion channels involved in nerve stimulation as effectively as longer ones. At higher frequencies, energy absorption becomes an issue. Exposure to electro-magnetic fields can lead to local temperature increase. The amount of absorbed energy per tissue weight is expressed by the specific absorption rate (SAR). The aim of this work is to calculate and evaluate the effects of the magnetic fields applied in MPI and propose ways to minimize them. At the same time, the risk of painful muscle stimulation should be minimized, even if MPI satisfies the requirements related to patient safety. In order to fulfill this task, simulation studies as well as experiments are being carried out. The following sections give an overview about the projects that are running or will be started in the near future.
Since the idea of Magnetic Particle Imaging (MPI) has been initially published in 2005, a lot of effort has been invested to improve temporal and spatial resolution. Most recently, first in vivo 3D real-time MPI scans were presented revealing details of a beating mouse heart . In MPI, besides a strong time-constant field gradient, an alternating magnetic field of about 25 kHz frequency is applied to the patient. For the development of a new imaging technique, it is important to investigate the effects of the induced fields with respect to current densities and specific absorption rates (SAR) to ensure safe operation. This work presents simulations of the fields induced by a typical MPI laboratory setup and an MPI system scaled up to whole body dimensions.
Magnetic Particle Imaging (MPI) is a new tomographic imaging technique based on magnetization of ferromagnetic nano-particles. Magnetic fields of different strengths and frequencies generate and move a field free point (FFP) over the field of view, inducing a signal of the magnetic particles, if present. The magnetic fields induce current densities of high amplitude in the patients body and deposit an amount of power that might lead to painful warming in the patients periphery. Based on the specifications of the MPI system, an optimized coil configuration is suggested here, reducing high peak values of current densities and specific absorption rate (SAR), by running the field generating coils of different radius with optimized currents. The results presented here are based on numerical field calculations with a simple cylindrical model, used for the optimization procedure, and the Visible Man data-set, for evaluating the optimization results.
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.
J. Bohnert, M. Reumann, T. Faber, and O. Dössel. Investigation of curative ablation techniques for atrial fibrillation in a computer model. In Gemeinsame Jahrestagung der Deutschen, der Österreichischen und der Schweizerischen Gesellschaft für Biomedizinische Technik, 2006
Catheter ablation of complex atrial arrhythmias is a frequently applied procedure, but its success rates are only moderate and highly dependent on the experience of the physician. Personalized atrial simulation models could assist the physician in treatment planning and thus increase success rates. In this work we created a personalized anatomical model for a specific patient from CT image data. Left atrial conduction velocity and local wave directions were determined from intracardiac electrogram (EGM) recordings. We simulated normal sinus rhythm and the clinical pacing protocol using a Cellular Automaton. The incidence direction and conduction velocity were extracted from the simulated data and compared to the results of the clinical EGMs of the same patient. We then showed that the incidence angles differed by less than 15% and that the conduction velocity error was below 12 cm/s. This implies that the model has similar electric properties compared to the real atria. In conclusion, we have presented a workflow for model personalization and validation.
N. H. Busch, F. B. Sachse, C. D. Werner, and O. Dössel. Segmentation klinischer vierdimensionaler magnetresonanztomographischer Aufnahmen mittels Aktiver Kontur Modelle und haptischer Interaktion. In Biomedizinische Technik, vol. 43-1, pp. 526-529, 1998
P. Carrillo, G. Seemann, E. Scholz, D. L. Weiss, and O. Dössel. Impact of the hERG Channel Mutation N588K on the Electrical Properties of the Human Atrium. In 4th European Conference of the International Federation for Medical and Biological Engineering, IFMBE Proc., vol. 22(22) , pp. 2583-2586, 2009
Atrial fibrillation is the most common cardiac arrhythmia in humans. The precise cellular mechanisms underlying atrial fibrillation are still poorly understood. Recent studies have identified several genetic defects as predisposing factors for this pathology. One of the identified genetic defects is the mutation N588K, which affects the cardiac IKr channel. Genetic variants in this channel have been identified to modify ventricular repolarization. The aim of this work is to investigate the effect of this mutation on atrial repolarization and the predisposition to atrial fibrillation.Measured data obtained with whole cell voltage clamp technique of wild-type and mutated hERG channel were implemented in the Courtemanche et al. ionic model. For this purpose, channel kinetics and density of the model were adjusted using parameter fitting to the measured data. By this way, the effects of the mutation in the hERG channel could be analyzed in the whole cell and in tissue, as well. The channel mutation N588K showed a gain of function effect, causing a rapid repolarization and consequently, a shortening of the action potential duration. Computer simulations of a schematic anatomical model of the right atrium were then carried out to investigate the excitation propagation and the repolarization.The action potential duration of the mutant cell was reduced to 116 ms and the effective refractory period to 220 ms. Both factors are linked to a shortening of the wavelength, indicating that the mutation N588K predisposes the initiation and perpetuation of atrial fibrillation.
Cardiac electrical imaging, that is, reconstructing car- diac electrical activity from body surface measurements, is a technology with great potential. However, ill-posedness of this problem hinders its routine usage in clinical envi- ronment and continues to motivate the search for improve- ments on current methods. Messnarz et al. introduced an algorithm that constraints the reconstructed transmem- brane potential (TMP) to be non-decreasing over time dur- ing QRS-complex. This physiologically meaningful con- straint reduces the solution space of the problem and reg- ularizes the solution. However, this approach is compu- tationally extensive and can become prohibitive as spatial and temporal resolution of the problem increase. Here we compare three distinct options to reduce the computational load: downsampling the measurements in time, downsam- pling the measurements after filtering with an algorithm based on principal component analysis and non-linearly interpolating the potentials with a spline-based method. The data used were simulated TMPs that were forward propagated to the body surface in a densely sampled ge- ometry. The resulting body surface potential simulations were corrupted with noise and the inverse computed using a much coarser mesh to take geometry errors into account. The results indicate that reducing the dimension of the sig- nal in time does not reduce the quality of the solutions obtained, while the computational requirements decrease considerably, especially for the spline method.
A modular, 9-channel high-Tc SQUID system for magnetocardiography (MCG) was developed and tested in an unshielded environment. Galvanically-coupled magnetometers made from Y-Ba-Cu-O films, with intrinsic white noise levels as low as 70 fT/√Hz, are used as SQUID sensors. In an unshielded environment, a noise level of about 1 pT/√Hz for each channel was achieved using an active noise compensation system. A new digital planar gradiometer is proposed. First magnetocardiograms recorded in an unshielded environment are presented
B. David, O. Dössel, D. Grundler, and J. P. Krumme. SQUID-Module aus Hoch-Tc-Supraleitern für die Magnetometrie. In Supraleitung und Tieftemperaturtechnik, zum Statusseminar, Berichte zu F&E-Projekten aus dem Förderbereich Physikalische Technologie des Bundesministeriums für Forschung und Technologie, pp. 79-85, 1994
Ziel des Forschungsvorhabens ist die Herstellung von SQUID-Anordnungen aus Hochtemperatur-Supraleitern (HTSL), mit denen die Messung biomagnetischer Signale möglich ist. Dazu werden Magnetometer bestehend aus Flußantennen und dc-SQUID-Sensoren aufgebaut, und zu elektronischen Gradiometern zusammengefaßt. Rauscharme dc-SQUIDs, basierend auf einer zuverlässigen Josephsonkontakt-Technologie und eine HTSL-Mehrlagentechnologie sind dafür eine notwendige Voraussetzung. Neben den routinemäßig verwendeten YBa2Cu3O7 (YBCO)-Stufen-Kontakten wurden SIS-Rampen-Kontakte entwickelt, die NdGaO3 als Barrierenmaterial verwenden
D. Farina, and O. Dössel. Non-invasive model-based localization of ventricular ectopic centers from multichannel ECG. In Proceedings of the 10th Workshop on Optimization and Inverse Problems in Electromagnetism, 2008
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.
D. Farina, and O. Dössel. Influence of cardiac activity in midmyocardial cells on resulting ECG: Simulation study. In Biomedizinische Technik, 2006
T. V. Franz, and O. Dössel. A three dimensional model for the simulation of arrythmia mechanic. In Proc. EMBEC 99, pp. 1226-1227, 1999
This study deals with a mathematical model of the cellular action potential with its underlying ionic currents in human myocardium based on the Luo-Rudy phase II cell model. The activation process is calculated in a three dimensional patch taking into account the behaviour of each single cell membrane and an anisotropic pattern as it is known for the right ventricel. The propagation is simulated using the Finite Difference Method in Time.
Cardiac computer modeling can help to gain a deeper insight into the physiological processes of the heart. In this work we present a new electromechanical modeling framework which allows to simulate the contraction of the atria in a model of the whole heart with realistic bound- ary conditions. For the active tension development (TD) we used a model, which was originally developed to describe the TD of the ventricles. However, TD in the atria differs significantly from that of the ventricles. On that account, we adapted the TD model to the measurement data of the atria. The modeling framework allows to obtain a realistic motion of the atria during the contraction cycle.
T. Fritz, O. Jarrousse, and O. Dössel. Adapting a mass-spring system to energy density function describing myocardial mechanics. In Proceedings of the 4th European Congress for Medical and Biomedical Engineering 2008. 23-27 November 2008, Antwerp, Belgium, vol. 22, pp. 2003-2006, 2008
T. Fritz, O. Jarrousse, D. Keller, G. Seemann, and O. Dössel. In silico analysis of the impact of transmural myocardial infarction on cardiac mechanical dynamics for the 17 AHA segments. In Proceedings of the 6th International Conference on Functional Imaging and Modeling of the Heart, vol. LNCS, 6666, pp. 241-249, 2011
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
T. Fritz, O. Jarrousse, G. Seemann, and O. Dössel. Analyzing the transmural electromechanical heterogeneity of the left ventricle in a computer model. In Biomedizinische Technik / Biomedical Engineering (Proceedings BMT2010), vol. 55(Suppl 1) , 2010
There is a large number of published studies analyzing the inhomogeneously distributed electrophysiological properties of the ventricles in a computer model. However only few of them deal with the impact on the hearts mechanics. In 2003 Cordeiro and colleagues  analyzed the influence of the transmural left ventricular electrophysiological heterogeneity on the myocardial mechanics. Therefore, they examined the unloaded cell shortening of sub-epicardial cells, sub-endocardial cells, and cells from the middle of the wall, isolated from canine left ventricle.In this work a heterogenous electromechanical model was used to reconstruct these experiments of Cordeiro et al. in the computer. A simulation framework, which is consisting of an electrophysiological cell model, a tension development model and an elastomechanical model was used to simulate the cell shortening. Two experiments with different heterogeneities had been conducted. The first experiment examined, how the heterogeneity of the membrane channels influences the cell shortening. In the second experiment the additional impact of the heterogeneity of the intracellular calcium handling was analyzed. The results of the simulations were compared qualitatively to the findings of Cordeiro et al.
T. Fritz, G. Seemann, and O. Dössel. Analyzing transmural myocardial infarction of the left ventricle using computer modeling. In 4th Cardiac Physiome Workshop, vol. Poster, 2011
Elastomechanical modeling of the heart can help to gain a deeper insight into the mechanical dynamics of the heart. Furthermore it can help to enhance diagnostic strategies and to investigate new therapeutic approaches. Phase contrast magnetic resonance imaging allows to directly measure the velocity vector field of the myocardial motion over the cardiac cycle. Aim of this work was to analyze the impact of transmural myocardial infarction on the velocity vector field of the left ventricle in a numerical model of the heart. For this purpose a multi-scale electromechanical computer framework was used. It consisted of two parts: an electrophysiological model and an elastomechanical model. The electrophysiological model described the electrophysiological processes on cellular level, the excitation propagation as well as the tension development. It was was linked to an elastomechanical model which was based on nonlinear continuum mechanics using the finite element method. The computer framework was used to simulate the contraction of the heart with left ventricular transmural infarctions, differing in size, location and stiffness of the scar tissue. For each simulation, the velocity vector field of the infarct region was analyzed and compared to the corresponding region of the control case. The simulations revealed a direct impact of the myocardial infarction on the magnitude and orientation of the velocity vectors of the affected region.
M. Fuchs, H. A. Wischmann, and O. Dössel. Overlay of neuromagnetic current density images and morphological MR images. In Proc. SPIE, Visualization in Biomedical Computing, vol. Vol. 1808, pp. 676-684, 1992
Neuromagnetic imaging is a relatively new diagnostic tool for examination of electric activities in the nervous system. It is based on the noninvasive detection of extremely weak magnetic fields around the human body with superconducting quantum interference device (SQUID) detectors. `Equivalent current dipoles' and linear estimation reconstructions of current distributions both with spherical volume conductor models are used to localize the neural activity. For practical use in medical diagnosis a combination of the abstract neuromagnetic images with magnetic resonance (MR)- or computer tomography (CT)-images is required in order to match the functional activity with anatomy and morphology. The neuromagnetic images can be overlayed onto three-dimensional morphological images with spatially arbitrarily selectable slices. The matching of both imaging modalities is discussed. Based on the detection of auditory evoked magnetic fields, neuromagnetic images are reconstructed with linear estimation theory algorithms. The MR images are used as a-priori information of the volume conductor geometry and they allow an attachment of functional and morphological properties.
M. A. Golombeck, and O. Dössel. MR-tomography on patients with heart pacemakers-a numerical study. In Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, vol. 2, pp. 1076-1079, 2004
Patients having a heart pacemaker are not allowed to go to MR tomography (MRT). One of the most dangerous effects is the heating of the tissue around the electrode caused by the coupling to the RF field of the MR system. Experiments have been carried out using tanks filled with saline water and large heating has sometimes been observed. Other experiments e.g. with electrodes in the brain did not show any heating at all. In this work numerical studies have been carried out to understand the different results. In conclusion it is suggested that MRT could be possible if the "normal" geometry of the wires of a heart pacemaker is ensured and an open MR system is used.
M. A. Golombeck, and O. Dössel. Magnetic resonance imaging and implanted electrodes: Deduction of rules for reducing hazards for patients by the use of numerical methods. In Biomedizinische Technik, vol. 48-1, pp. 366-367, 2003
M. A. Golombeck, and O. Dössel. Simulation der Auswirkung medizinischer Therapie- und Diagnosemethoden auf den menschlichen Körper unter der besonderen Berücksichtigung von Implantaten. In Biomedizinische Technik, vol. 45-1, 2000
M. A. Golombeck, C. H. Riedel, and O. Dössel. Calculation of the Dielectric Properties of Biological Tissue using simple Models of Cell Patches. In Biomedizinische Technik, vol. 47-1, pp. 253-256, 2002
M. A. Golombeck, M. Tabbert, and O. Dössel. Numerische Berechnung elektromagnetischer Felder in einem Oberkörperphantom mit Elektroden bei der Magnetresonanztomographie. In Biomedizinische Technik, vol. 46-1, pp. 464-465, 2001
M. A. Golombeck, J. Thiele, and O. Dössel. Magnetic resonance imaging with implanted neurostimulators: numerical calculation of the induced heating. In Biomedizinische Technik, vol. 47-1, pp. 660-663, 2002
Magnetic resonance imaging (MRI) is still contraindicated in patients with implanted active medical devices, as the applied radiofrequency (RF) fields can lead to significant heating of the implants and the electrodes. A head model with an implanted deep brain stimulation electrode (DBS) was exposed to a continuous RF-field similar to the excitational field used in MRI at a frequency of 64 MHz. In this study a two-step procedure for the accurate estimation of electrode-heating during MRI is presented. First the energy loss was calculated in the frequency domain during an applied RF-pulse. Then a thermodynamic algorithm taking heat transfer mechanisms into account was used. The applied method showed to be numerically stable and gave more accurate results than first calculated using a simple worst-case approximation.
M. Graeser, J. Bohnert, and O. Doessel. Abschätzung der muskelstimulierenden Wirkung von Magnetwechselfeldern im kHz-Bereich. Estimating thresholds for stimulating muscles by alternating magnetic fields in the kHz-range. In Biomedizinische Technik / Biomedical Engineering (Proceedings BMT2010), vol. 55(s1) , 2010
Alternating magnetic fields induce AC currents in conductive materials. These currents can depolarize the cell-membrane, causing an action potential. In current literature stimulation thresholds for alternating magnetic fields were published up to a frequency of 1 kHz only. Beyond 1 kHz there are thresholds for electrode stimulation only. To convey these thresholds for magnetic fields the current densities caused by the alternating magnetic fields in an anatomical model were calculated. With these current densities the necessary flux densities were reevaluated. The intention of this paper was the development of a system for inductive stimulation of peripheral muscles to validate the simulation in the frequency range from 1 kHz to 50kHz.
I. M. Graf, G. Seemann, and O. Dössel. Theoretical research on the influence of defibrillator paddle position on the human ventricular myocardium. In Proc. CinC, vol. 31, pp. 97-101, 2004
M. Grafmüller, S. Seitz, and O. Dössel. Adaption of generic anatomic organ models on patient specific data sets. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25(4) , pp. 884-887, 2009
Anatomical voxel models are used for example for dosimetric assessment and numerical field calculations. For best matching between models and patients properties an accurate model should be created by Magnetic Resonance Imaging or Computer Tomography images for every patient. Due to complexity, time and costs this is not always possible. In contrast 3D laser scanning is a fast and easy method to gain information about a patients body surface. In this work generic organ models are developed to fit into the laser scan envelope of any patient. One model set was processed as to fit to the volume reference values of the International Commission on Radiological Protections of six different ages. To accomplish a more realistic shape, orthogonal scaling factors are used to simulate growth in three different directions.
Computer simulations and imaging of human physiology and anatomy are effectively used for diagnostics and medical treatments and are thus a focus of scientific research. Suitable representation of data is a critical aspect to achieve best results. Therefore, we developed an interactive visualization scheme especially for the representation of cardiac arrhythmias based on a conventional mobile device and virtual reality (VR) goggles (Google Cardboard and Samsung Gear VR) in combination with a game engine. The aim of this paper is to raise awareness for this new technique, evaluate its potential and pro- pose a general workflow for such a visualization environment. The use of a conventional mobile device in combination with VR goggles creates a portable and low-cost system, equipped with enough processing power and pixel density for many types of applications. The user can interact with the data through head movement or a secondary controller. As current game engines support a wide range of additional input methods and controllers, the interaction method can be customized to fit the target audience. To evaluate this method, we conducted a survey with eight typical phenomena from the field of cardiac arrhythmias. The participants were asked to rate different performance aspects on a scale from one (very bad) to five (very good). All participants (N=27) rated the performance as fluent (median=5). Furthermore, most participants (70%) ranked the overall impression as very good (median=5). On the long run, the system can be used for education and presentations as well as improved planning and guidance of medical procedures.
Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intrac- ardiac electrograms (IEGMs) provide real-time informa- tion regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and inter- pretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenom- ena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was com- pared to an existing one and to clinical measurements of ve patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogo- nal catheter orientation, the presence of a second necrotic core in the near- eld of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.
C. Gross, S. Pollnow, O. Dössel, and G. Lenis. Automatic feature extraction algorithms for the assessment of in-vitro electrical recordings of rat myocardium with ablation lesions. In Current Directions in Biomedical Engineering, vol. 3(2) , pp. 249-252, 2017
Cardiac arrhythmias are a widely spread disease in industrialized countries. A common clinical treatment for this disease is radiofrequency ablation (RFA), in which high frequency alternating current creates a lesion on the myocardium. However, the formation of the lesion is not entirely understood. To obtain more information about ablation lesions (ALs) and their electrophysiological properties, we established an in-vitro setup to record electrical activity of rat myocardium. Electrical activity is measured by a circular shaped multielectrode array. This work was focused to gain more information by developing algorithms to process the measured electrical signals to collect different features, which may allow us to characterize an AL. First, pacing artefacts were detected and blanked. Subsequently, data were filtered. Afterwards, activations in atrial signals were detected using a non-linear energy operator (NLEO) and templates of these activations were generated. Finally, we determined different features on each activation in order to evaluate changes of unipolar as well as bipolar electrograms and considered these features before and after ablation. In conclusion, the majority of the signal features delivered significant differences between normal tissue and lesion. Among others, a reduction in peak to peak amplitude and a diminished spectral power in the band 0 to 100 Hz may be useful indicators for AL. These criteria should be verified in future studies with the aim of estimating indirectly the formation of a lesion.
The delineation of anatomical structures in medical images can be achieved in an efficient and robust manner using statistical anatomical organ models, which has been demonstrated for an already considerable set of organs, including the heart. While it is possible to provide models with sufficient shape variability to cope, to a large extent, with inter-patient variability, as long as object topology is conserved, it is a fundamental problem to cope with topological organ variability. We address this by creating a set of model variants and selecting the most appropriate model variant for the patient at hand. We propose a hybrid method combining model-based image analysis with a guided region growing approach for automated anatomical variant selection and apply it to the left atrium in cardiac CT images. Concerning the human heart, the left atrium is the most variable sub-structure with a variable number of pulmonary veins draining into it. It is of large clinical interest in the context of atrial fibrillation and related interventions.
R. Hanna, Y. Jiang, D. Farina, and O. Dössel. Imaging of cardiac electrical sources using a novel spatio-temporal MAP-based regularization method. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/2, pp. 813-816, 2009
E. Hansis, O. Dössel, and M. Grass. Motion-compensated iterative sparse data reconstruction for interventional 3-D coronary artery imaging. In Nuclear Science Symposium Conference Record 2008, pp. 4280-4284, 2008
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.
E. Hansis, H. Schomberg, K. Erhard, O. Dössel, and M. Grass. Four-dimensional cardiac reconstruction from rotational x-ray sequences: first results for 4D coronary angiography. In Proc. SPIE, Medical Imaging 2009: Physics of Medical Imaging, vol. 7258, pp. 72580B1-11, 2009
The tomographic reconstruction of the beating heart requires dedicated methods. One possibility is gated reconstruction, where only data corresponding to a certain motion state are incorporated. Another one is motioncompensated reconstruction with a pre-computed motion vector field, which requires a preceding estimation of the motion. Here, results of a new approach are presented: simultaneous reconstruction of a three-dimensional object and its motion over time, yielding a fully four-dimensional representation. The object motion is modeled by a time-dependent elastic transformation. The reconstruction is carried out with an iterative gradient-descent algorithm which simultaneously optimizes the three-dimensional image and the motion parameters. The method was tested on a simulated rotational X-ray acquisition of a dynamic coronary artery phantom, acquired on a C-arm system with a slowly rotating C-arm. Accurate reconstruction of both absorption coefficient and motion could be achieved. First results from experiments on clinical rotational X-ray coronary angiography data are shown. The resulting reconstructions enable the analysis of both static properties, such as vessel geometry and cross-sectional areas, and dynamic properties, like magnitude, speed, and synchrony of motion during the cardiac cycle.
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. Hoefele, F. B. Sachse, C. D. Werner, and O. Dössel. Elastische Registrierung multimodaler dreidimensionaler medizinischer Datensätze am Beispiel des Visible Female Datensatzes. In Biomedizinische Technik, vol. 45-1, pp. 503-504, 2000
The novel high-density mapping system RhythmiaTM Medical (Boston Scientific, Marlborough, USA) allows a fast and automatic acquisition of intracardiac electrograms (EGMs). For recording the ORION mini-basket catheter is used. Due to the small electrode surface, the spatial averaging is smaller than with other commonly used mapping catheters. This results in a higher quality of unipolar signals. However, these are still corrupted by noise such as high frequency interference. Within this project, methods were developed and benchmarked that can be applied to detect and remove these undesired components. An algorithm was implemented to detect and eliminate artificial peaks in the spectrum of the EGM. The filtered signals showed improved quality in time domain. The performance of the spectral peak detection resulted in a median sensitivity of 92.1% and in a median positive predictive value of 91.9%.
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
M. Janich, G. Seemann, J. Thiele, and O. Dössel. Elastic registration of optical images showing heart muscle contraction. In 4th European Conference of the International Federation for Medical and Biological Engineering ECIFMBE 2008, vol. 22(7) , pp. 676-679, 2008
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.
O. Jarrousse, T. Fritz, and O. Dössel. Modeling breast tissue mechanics from Prone to supine positions with a modified mass-spring system. In Proceedings BMT 2010, 44. DGBMT Jahrestagung, 3-Länder-Tagung D-A-CH, Rostock, vol. 55(S1) , pp. 87-90, 2010
A volumetric mass-spring system, originally developed for myocardial mechanics modeling , is used to simulate the elasto-mechanical deformation of several breast datasets from prone to supine positions. Segmented MRI datasets of pa- tients in prone position, available from the online repository provided by Susan C. Hagness at the University of Wisconsin- Madison  were used in the biomechanical simulations. These models were considered to be consisting of two materi- als, fat and fibroconnective/glandular tissues. Each tissue is represented as a nearly incompressible Neo-Hookean elastic isotropic material. Each simulation was conducted in two steps: in the first step, the unloaded model is generated by apply- ing gravity forces to the original model pointing toward the body. The unloaded model is then used in the second step, by applying gravity forces. Eventually, the breast model in supine position is obtained.
O. Jarrousse, T. Fritz, and O. Dössel. Implicit time integration in a volumetric mass-spring system for modeling myocardial elastomechanics. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/4, pp. 876-879, 2009
A modified mass-spring system for simulating the passive and active elastomechanical properties of the myocardial tissue was presented in a previous publication. The previously presented results are combined with the method also published earlier to use continuum mechanics calculate passive forces in a mass-spring system directly starting from the energy density function of the stress-strain relation. An efficient method for volume preservation is presented and the implementation of an implicit time integration method for solving the systems equations of motion is described. The computational complexity of the system is analyzed and shown to be of O(n). At the end several simulations are conducted to demonstrate the method.
O. Jarrousse, T. Fritz, and O. Dössel. A volumetric mass-spring system for modeling myocardial elastomechanics. In The Cardiac Physiome: Multi-scale and Multi-physics Mathematical Modelling Applied to the Heart, 2009
A volumetric mass-spring system for simulating the passive and active elastomechanical properties of the myocardial tissue is presented. A 3D computer model containing information about the ﬁber, sheet, and sheet-normal directions and about the modeled objects physiological properties, is used to initialize the systems structure.Using an electrophysiology model and a force development model, contracting forces are introduced to the systems elements at each time step of the simulation loop.Using the methods of continuum mechanics, suitable springs functions were derived analytically from the energy density function of describing the hyperelastic properties of heart. That eliminated the need of springs parametrization. An efficient method for volume preservation is used to ensure the conservation of the model's volume under deformation.Implicit time integration is implemented to solve the equations of motion, that improves the stability of the simulation and allows larger simulation time steps. An iterative solver that take advantage of the sparsity of the system's matrices is used and the systems complexity is shown to be of O(n) where n is the the count of the models elements.
O. Jarrousse, T. Fritz, and O. Dössel. A modifed mass-spring system for myocardial mechanics modeling. In Proceedings of the 4th European Congress for Medical and Biomedical Engineering 2008. 23-27 November 2008, Antwerp, Belgium, vol. 22, pp. 1943-1946, 2008
Y. Jiang, D. Farina, and O. Dössel. The inverse problem of electrocardiography in realistic environment. In Conference on Applied Inverse Problems, 2009
Y. Jiang, D. Farina, and O. Dössel. Localization of the origin of ventricular premature beats by reconstruction of electrical sources using spatio-temporal MAP-based regularization. In Proc. 4th European Conference of the International Federation for Medical and Biological Engineering, vol. 22, pp. 2511-2514, 2008
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.
Y. Jiang, D. Farina, and O. Dössel. Effect of heart motion on the solutions of forward and inverse electrocardiographic problem - a simulation study. In Proc. Computers in Cardiology, pp. 365-368, 2008
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.
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
Y. Jiang, W. Hong, D. Farina, and O. Dössel. Solving the inverse problem of electrocardiography in a realistic environment using a spatio-temporal LSQR-Tikhonov hybrid regularization method. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/2, pp. 817-820, 2009
Y. Jiang, Y. Meng, D. Farina, and O. Dössel. Effect of respiration on the solutions of forward and inverse electrocardiographic problems - a simulation study. In Proc. Computers in Cardiology, pp. 17-20, 2009
The forward problem of electrocardiography aims at obtaining a better understanding of cardiac electrophysiological activities, by means of computer modeling and simulation. Whereas, the inverse electrocardiographic problem provides a direct insight of electrical sources into the heart without interventional procedures. Nowadays, the forward and inverse problems are mostly solved in static models, which do not take into account heart motion and respiration. Besides heart motion, neglecting respiration may also lead to remarkable uncertainties in both forward and inverse solutions. In the present work a dynamic lung model is developed. With this model the effect of respiration on the forward and inverse solutions is studied.
Y. Jiang, C. Qian, R. Hanna, D. Farina, and O. Dössel. Optimization of electrode positions of a wearable ECG monitoring system for efficient and effective detection of acute myocardial infarction. In Proc. Computers in Cardiology, 2009
Y. Jiang, C. Qian, R. Hanna, D. Farina, and O. Dössel. Optimization of the electrode positions of multichannel ECG for the reconstruction of ischemic areas by solving the inverse electrocardiographic problem. In Proc. the 7th International Symposium on Noninvasive Functional Source Imaging of the Brain and Heart and the International Conference on Functional Biomedical Imaging, 2009
A new method to predict changes in a lead-field matrix induced by conductivity variations of a single body tissue is proposed. The approach is based on the princi- ple component analysis (PCA) with three initial lead-field matrices transformed to vectors as input. For each tissue blood, lungs, muscles and fat a PCA was carried out. Further, for each tissue the default conductivity value and the conductivity varied by ±50 % were used to calculate the sample lead-field matrices. The results of the PCAs in- dicate that for every tissue the first principle component suffices to predict the conductivity-induced changes in the samples. With an interpolation of the scores we addition- ally show that the prediction is not bound to the sample ma- trices but moreover every matrix within each conductivity range is possibly estimated and conclusively predicted.
The Purkinje system is part of the fast-conducting ventricular excitation system. The anatomy of the Purkinje system varies from person to person and imposes a unique excitation pattern on the ventricular myocardium, which defines the morphology of the QRS complex of the ECG to a large degree. While it cannot be imaged in-vivo, it plays an important role for personalizing computer simulations of cardiac electrophysiology. Here, we present a new method to automatically model and customize the Purkinje system based on the measured electrocardiogram (ECG) of a patient. A graphbased algorithm was developed to generate Purkinje systems based on the parameters fibre density, minimal distance from the atrium, conduction velocity, and position and timing of excitation sources mimicking the bundle branches. Based on the resulting stimulation profile, the activation times of the ventricles were calculated using the fast marching approach. Predescribed action potentials and a finite element lead field matrix were employed to obtain surface ECG signals. The root mean square error (RMSE) between the simulated and measured QRS complexes of the ECGs was used as cost function to perform optimization of the Purkinje parameters. One complete evaluation from Purkinje tree generation to the simulated ECG could be computed in about 10 seconds on a standard desktop computer. The measured ECG of the patient used to build the anatomical model was matched via parallel simplex optimization with a remaining RMSE of 4.05 mV in about 16 hours. The approach presented here allows to tailor the structure of the Purkinje system through the measured ECG in a patient-specific way. The computationally efficient implementation facilitates global optimization.
R. Kalayciyan, D. U. J. Keller, G. Seemann, and O. Dössel. Creation of a realistic endocardial stimulation profile for the visible man dataset. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/4, pp. 934-937, 2009
W. Kaltenbacher, M. Rottmann, and O. Dössel. An algorithm to automatically determine the cycle length coverage to identify rotational activity during atrial fibrillation a simulation study. In Current Directions in Biomedical Engineering, vol. 2(1) , pp. 167-170, 2016
Atrial fibrillation is the most common cardiac arrhythmia. Many physicians believe in the hypothesis that persistent atrial fibrillation is maintained by centers of rotatory activity. These so called rotors are sometimes found by physicians during catheter ablation or electrophysiological studies but there are also physicians who claim that they did not find any rotors at all. One reason might be that today rotors are mainly identified by visual inspection of the data. Thus we are aiming at an algorithm for rotor detection. We first developed an algorithm based on the local activation times of the intracardiac electrograms recorded by a multielectrode catheter that can automatically determine the cycle length coverage. This was done to get an objective view on possible rotors and therefore help to quantify whether a rotor was found or not. The algorithm was developed and evaluated in two different simulation setups, where it could reliably determine cycle length coverage. But we found out that effects like wave collision and slow conduction have strong influence on cycle length coverage. This prevents cycle length coverage from being suited as the only parameter to quantify whether a rotor is present or not. On the other hand we could confirm that rotors imply a cycle length coverage of >70% if the multielectrode catheter is centered in an area of <5 mm away from the rotor tip. Therefore cycle length coverage can at least be used in some situations to exclude the presence of possible rotors.
After myocardial infarction, ischemic lesions within the myocardium can be the origin of malignant arrhythmias by the mechanism of re-entry. Surface-ECG and MR-imaging data can be used to detect and classify such re- gions in a non-invasive way. For this purpose a model of the electric conductivity of the tissues within the pa- tients chest and a model of cardiac sources must be constructed out of MR-imaging data. Employing finite- element algorithms the inverse problem of electrocardiology can then be solved, leading to the reconstructionof electrical sources within the myocardium during the process of depolarisation and repolarisation.
M. Karl, G. Seemann, F. Sachse, O. Dössel, and V. Heuveline. Time and memory efficient implementation of the cardiac bidomain equations. In 4th European Conference of the International Federation for Medical and Biological Engineering, IFMBE Proceedings, vol. 22, 2008
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  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.
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.
D. U. J. Keller, O. Dössel, and G. Seemann. Simulating cardiac excitation in a high resolution biventricular model. In Proceedings BMT 2010, 44. DGBMT Jahrestagung, 3-Länder-Tagung D-A-CH, Rostock, vol. 55(s1) , pp. 205-208, 2010
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.
D. U. J. Keller, O. Dössel, and G. Seemann. Evaluation of rule-based approaches for the incorporation of skeletal muscle fiber orientation in patient-specific anatomies. In Proceedings Computers in Cardiology, vol. 36, pp. 181-184, 2009
Muscle anisotropy is important for the realistic solution of the forward problem of electrocardiography. Whenever computer models of patient-specific anatomies are created usually no information about the muscle fiber arrangement in the heart or skeletal muscle is available. As in-vivo imaging techniques that can determine fiber orientation like Diffusion Tensor MRI are time-consuming and susceptible to motion artifacts, cardiac fiber orientation is frequently described using simplified rules. However, for the skeletal muscle there are only few suggestions for a rule-based implementation of fiber orientation into patient-specific models. In this work we evaluated a rule-based approach from the literature together with two new methods by comparing the corresponding forward calculated body surface potential maps (BSPMs) with the BSPM resulting from a reference skeletal muscle fiber distribution extracted from the thin-section photos of the Visible Man dataset (Journal of Computing and Information Technology vol.6, pp. 95-101 1998). The skeletal muscle anisotropy ratio was set to 3:1. The following fiber orientation setups were evaluated: A) the torso is divided into twelve sectors (cross-section perspective) and fiber direction was assumed to be perpendicular to the bisector as proposed by Klepfer et al. (IEEE Trans. Biomed. Eng. vol. 44, no. 8, pp. 706-719 1997); B) A 3D Sobel filter was used on the torso geometry filled with a gradient from inside to outside which generated a vector that was normal to the thoracic surface in every voxel. Fiber orientation was assumed to be perpendicular to the plane formed by these normal vectors and the direction from head to feet (longitudinal torso orientation); C) Same procedure as in B) but additionally, the back muscles which are known to have a longitudinal orientation were integrated accordingly. Potentials were extracted at 64 electrode positions from the BSPMs. The RMS was calculated at these electrode positions between the reference fiber distribution and the respective rule-based approaches. The RMS was comparable between A) and B) (8.8e-5 vs. 8.9e-5) leading to the conclusion that the twelve discrete sectors introduced no significant error. A) and B) performed also well compared to a modified version of the reference dataset where the longitudinal component of the fiber vectors was set to zero (8.3e-5). Including the longitudinal components of the back muscles as done in C) enhances the RMS to 5.5e-5. If the skeletal muscle anisotropy was neglected and only cardiac fiber orientation was taken into account, the RMS improved (!) further to only 4.0e-5. Thus it can be concluded that neglecting the longitudinal component (A) and B)) or accounting for it with a highly simplified approach (C)) is not sufficient. In cases where no detailed information about the skeletal muscle fiber arrangement is available, it is better to entirely neglect its anisotropic influence.
D. U. J. Keller, R. Kalayciyan, O. Dössel, and G. Seemann. Fast creation of endocardial stimulation profiles for the realistic simulation of body surface ECGs. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/4, pp. 145-148, 2009
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.
D. U. J. Keller, G. Seemann, D. L. Weiss, and O. Dössel. Detailed anatomical modeling of human ventricles based on diffusion tensor MRI. In Gemeinsame Jahrestagung der Deutschen, der Österreichischen und der Schweizerischen Gesellschaft für Biomedizinische Technik, vol. 50/1, 2006
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
M. W. Keller, and O. Dössel. Towards simultaneous optical and electrical characterization of the electrode tissue interface in catheter measurements of atrial electrophysiology. In Biomedizinische Technik / Biomedical Engineering (Proc. BMT 2011), vol. 56(s1) , 2011
Complex fractionated atrial electrograms (CFAE) are a target for catheter ablation as they coincide with areas of slow conduction. In this study we simulated different vol- ume fractions of diffuse and patchy fibrosis up to 50 %. Catheter signals for different electrode spacings were cal- culated and characteristic features were compared to a clinical database of CFAE-signals. A linear slowing of global conduction velocities was found independent of the type of fibrosis. For patchy fibrosis, electrograms displayed fractionation, which was not seen for diffuse fibrosis of the same degree. In comparison to clinical data, simulated electrograms showed up to 10 zero crossings per electro- gram, which was also seen for clinical EGMs with medium fractionation (class 2 of 3). For both, clinical (84 %) and simulated (88 %) signals, a significant difference in ampli- tude is present between fractionated and non-fractionated signals.
M. W. Keller, C. Schilling, A. Luik, C. Schmitt, and O. Dössel. Descriptors for a classification of complex fractionated atrial electrograms as a guidance for catheter ablation of atrial fibrillation. In Biomedizinische Technik / Biomedical Engineering, vol. 55(s1) , pp. 100-103, 2010
Atrial fibrillation (AFib) is a frequent and serious cardiac arrhythmia. A successful method to treat AFib is catheter ab- lation. Areas with complex fractionated atrial electrograms (CFAE) are ideal targets for catheter ablation. Concerning the ablation strategy and the search for CFAEs the physician is mainly dependent on his own judgment. For this reason ablation strategies are highly operator dependent. In this work a set of seven descriptors is presented which show promising results concerning a classification of measured atrial electrograms. The descriptors are evaluated on a database of 25 CFAE sig- nals. The results reveal a possible discrimination between CFAE classes which could be a valuable support for physicians curing AFib
Creating transmural ablation scars in a reliable way is a key issue in improvement of therapeutical pro- cedures for cardiac arrhythmias. About one third of the patients has to undergo several procedures till arrhythmic episodes are successfully treated. Morphological features of intracardiac electrograms might contribute to evaluate scar transmurality during the ablation procedure. We an- alyzed intracardiac signals before, during and after point- wise ablation in patients with atrial flutter. Unipolar elec- trograms of the distal electrode showed a relative decrease in amplitude of the second extremum of up to 99 % with a mean of 84±20.6 % after the endpoint of ablation.
Intracardiac electrograms are the key in under- standing, interpretation and treatment of cardiac arrhythmias. However, electrogram morphologies are strongly variable due to catheter position, orientation and contact. Simulations of intracardiac electrograms can improve comprehension and quantification of influencing parameters and therefore reduce misinterpretations. In this study simulated intracardiac electro- grams are analyzed regarding tilt angles of the catheter relative to the propagation direction, el