Catheter ablation is a curative therapeutic approach for atrial fibrillation (AF). Ablation of rotational sources based on basket catheter measurements has been proposed as a promising approach in patients with persistent AF to complement pulmonary vein isolation. However, clinically reported success rates are equivocal calling for a mechanistic investigation under controlled conditions. We present a computational framework to benchmark ablation strategies considering the whole cycle from excitation propagation to electrogram acquisition and processing to virtual therapy. Fibrillation was induced in a patient-specific 3D volumetric model of the left atrium, which was homogeneously remodelled to sustain reentry. The resulting extracellular potential field was sampled using models of grid catheters as well as realistically deformed basket catheters considering the specific atrial anatomy. Virtual electrograms were processed to compute phase singularity density maps to target rotor tips with up to three circular ablations. Stable rotors were successfully induced in different regions of the homogeneously remodelled atrium showing that rotors are not constrained to unique anatomical structures or locations. Phase singularity density maps correctly identified and located the rotors (deviation < 10 mm) based on catheter recordings only for sufficient resolution (inter-electrode distance = 3 mm) and proximity to the wall (< 10 mm). Targeting rotor sites with ablation did not stop reentries in the homogeneously remodelled atria independent from lesion size (1-7 mm radius), from linearly connecting lesions with anatomical obstacles, and from the number of rotors targeted sequentially (up to 3). Our results show that phase maps derived from intracardiac electrograms can be a powerful tool to map atrial activation patterns, yet they can also be misleading due to inaccurate localization of rotor tips depending on electrode resolution and distance to the wall. This should be considered to avoid ablating regions that are in fact free of rotor sources of AF. In our experience, ablation of rotor sites was not successful to stop fibrillation. Our comprehensive simulation framework provides the means to holistically benchmark ablation strategies in silico under consideration of all steps invol
Aims Chronic left atrial enlargement (LAE) increases the risk of atrial fibrillation. Electrocardiogram (ECG) criteria might provide a means to diagnose LAE and identify patients at risk; however, current criteria perform poorly. We seek to characterize the potentially differential effects of atrial dilation vs. hypertrophy on the ECG P-wave. Methods and results We predict effects on the P-wave of (i) left atrial dilation (LAD), i.e. an increase of LA cavity volume without an increase in myocardial volume, (ii) left atrial concentric hypertrophy (LACH), i.e. a thickened myocardial wall, and (iii) a combination of the two. We performed a computational study in a cohort of 72 anatomical variants, derived from four human atrial anatomies. To model LAD, pressure was applied to the LA endocardium increasing cavity volume by up to 100%. For LACH, the LA wall was thickened by up to 3.3 mm. P-waves were derived by simulating atrial excitation propagation and computing the body surface ECG. The sensitivity regarding changes beyond purely anatomical effects was analysed by altering conduction velocity by 25% in 96 additional model variants. Left atrial dilation prolonged P-wave duration (PWd) in two of four subjects; in one subject a shortening, and in the other a variable change were seen. Left atrial concentric hypertrophy, in contrast, consistently increased P-wave terminal force in lead V1 (PTF-V1) in all subjects through an enlarged amplitude while PWd was unaffected. Combined hypertrophy and dilation generally enhanced the effect of hypertrophy on PTF-V1. Conclusion Isolated LAD has moderate effects on the currently used P-wave criteria, explaining the limited utility of PWd and PTF-V1 in detecting LAE in clinical practice. In contrast, PTF-V1 may be a more sensitive indicator of LA myocardial hypertrophy.
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.
AIMS: To test the ability of four circulating biomarkers of fibrosis, and of low left atrial voltage, to predict recurrence of atrial fibrillation after catheter ablation. BACKGROUND: Circulating biomarkers potentially may be used to improve patient selection for atrial fibrillation ablation. Low voltage areas in the left atrium predict arrhythmia recurrence when mapped in sinus rhythm. This study tested type III procollagen N terminal peptide (PIIINP), galectin-3 (gal-3), fibroblast growth factor 23 (FGF-23), and type I collagen C terminal telopeptide (ICTP), and whether low voltage areas in the left atrium predicted atrial fibrillation recurrence, irrespective of the rhythm during mapping. METHODS: 92 atrial fibrillation ablation patients were studied. Biomarker levels in peripheral and intra-cardiac blood were measured with enzyme-linked immunosorbent assay. Low voltage (<0.5mV) was expressed as a proportion of the mapped left atrial surface area. Follow-up was one year. The primary endpoint was recurrence of arrhythmia. The secondary endpoint was a composite of recurrence despite two procedures, or after one procedure if no second procedure was undertaken. RESULTS: The biomarkers were not predictive of either endpoint. After multivariate Cox regression analysis, high proportion of low voltage area in the left atrium was found to predict the primary endpoint in sinus rhythm mapping (hazard ratio 4.323, 95% confidence interval 1.337-13.982, p = 0.014) and atrial fibrillation mapping (hazard ratio 5.195, 95% confidence interval 1.032-26.141, p = 0.046). This effect was also apparent for the secondary endpoint. CONCLUSION: The studied biomarkers do not predict arrhythmia recurrence after catheter ablation. Left atrial voltage is an independent predictor of recurrence, whether the left atrium is mapped in atrial fibrillation or sinus rhythm.
PURPOSE: There is controversy about relevant EEG signal changes indicating adequate or inadequate anaesthesia. Differences of drug-induced and nociceptive mediated signal changes have not been studied in detail. The present study investigates whether signal changes during decreases of depth of anaesthesia due to surgical stimulation depend on different isoflurane concentrations during sufentanil anaesthesia. METHODS: Following IRB approval and written informed consent 28 patients (ASA: I; age 43 +/- 11 y) scheduled for elective abdominal surgery were included in the study. Anaesthesia: propofol (2.0 mg/kg) and sufentanil (1.0 micrograms/kg). Following endotracheal intubation (vecuronium 0.1 mg/kg) patients were normoventilated (P(ET)CO2: 36-38 mmHg). Randomly assigned to steady-state anaesthesia (group 1: P(ET)Isoflurane 0.2%, (14n); group 2: P(ET)Isoflurane 0.6%, (14n) during the start of surgery. Monitoring: heart rate (HF), mean arterial blood pressure (MAP), P(ET)CO2, arterial oxygen saturation and rectal temperature. EEG (16 channels referenced to Cz; CATEEM, Medisyst, Linden) recorded 5 min before until 10 min after the start of surgery. EEG-analysis (FFT: 4s, 256/s, 0.45-35.0 Hz): topographical distribution of power spectral densities (delta, theta, alpha 1, and alpha 2). Artifact control: ECG and EOG. RESULTS: Surgical stimulation resulted in increases of MAP in both groups (p < 0.05 vs BL), whereas HR was only slightly affected in group 2 when compared with BL. Other variables except of EEG data did not change over time. In group 1 (0.2% isoflurane) surgical stimulation resulted in decreases of delta over the whole cortex (F2, C3, P3, O1) and in marked increases of alpha predominantly at central leads (C3)(p < 0.05 vs BL). In group 2 (0.6% isoflurane) nociceptive stimulation was associated with decreases of faster waves (alpha: F3)(p < 0.05 vs BL) and increases in delta at fronto-central areas (F3, C3)(p < 0.05 vs BL). CONCLUSIONS: EEG recordings are useful in assessing pharmacodynamic drug effects. In contrast, intraoperative EEG recordings have a low correlation to clinical signs of changes in the anaesthetic state. Previous studies demonstrate paradoxical EEG-arousal reactions during isoflurane anaesthesia. The present data suggest that classical or even paradoxical EEG arousal due to nociceptive stimulation may depend on the isoflurane concentration. It seems reasonable that the ascending reticular formation is functionally blocked by isoflurane in a dose-dependent manner.
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.
The principle of interferometry has been applied to thin polymer films as they swell by sorption of gases or as they interact with biochemical material. Modern diode array technology allows the monitoring of changes in optical path-length at a fractional nanometre scale. Observation of the interference spectra makes discrimination between thickness and Fresnel refractive index effects possible. Thus, very sensitive sensors can be developed for measuring concentrations of gaseous and liquid organic solvents as well as specific antigen-antibody interactions.
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.
Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusion-induced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample.
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.
Models of cardiac tissue electrophysiology are an important component of the Cardiac Physiome Project, which is an international effort to build biophysically based multi-scale mathematical models of the heart. Models of tissue electrophysiology can provide a bridge between electrophysiological cell models at smaller scales, and tissue mechanics, metabolism and blood flow at larger scales. This paper is a critical review of cardiac tissue electrophysiology models, focussing on the micro-structure of cardiac tissue, generic behaviours of action potential propagation, different models of cardiac tissue electrophysiology, the choice of parameter values and tissue geometry, emergent properties in tissue models, numerical techniques and computational issues. We propose a tentative list of information that could be included in published descriptions of tissue electrophysiology models, and used to support interpretation and evaluation of simulation results. We conclude with a discussion of challenges and open questions.
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.
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
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.
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.
U. Eck, and G. Vossius. [A method for analysis of muscle activity during electric stimulation]. In Biomedizinische Technik. Biomedical Engineering, vol. 47 Suppl 1 Pt 2, pp. 517-520, 2002
The measurement of the surface-EMG during electrical stimulation requires the suppression of the stimulus pulse close to the source. This is necessary because of the discharge currents spreading within the human body caused by the stimulation pulse and the drift effects at the electrodes distorting the EMG-signal. A measurement-system will be presented, which splits the EMG in a detection and a processing path. A special converter keeps the base line at zero level. The detection path sets the gain of the recording amplifier and identifies the stimulation pulse to control its suppression. The processing of the EMG is conducted in the main path way. By these means the EMG including M-wave is undistorted and unbiased presented. The results will be discussed taking the physiology relevance into account.
U. Eck, G. Vossius, and R. Rupp. [The contribution of EMG for monitoring controlled electrostimulation in paralysis. 2.) Applications of EMG]. In Biomedizinische Technik. Biomedical Engineering, vol. 43 Suppl, pp. 118-120, 1998
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.
In the last few years, radioactive stents has been proved to inhibit neointima formation. This paper describes the actual status of producing such radioactive stents. After a short discussion of the different radioisotopes suitable for radioactive stents, potential production methods are discussed. The ion beam implantation of P-32 applied at the Karlsruhe Research Centre shall be described in more detail.
Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by -6, -18, and -11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker.
In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field.
A prerequisite for the further improvement in the quality of warming therapy is an accurate knowledge of the interactions between the microclimate in warming therapy devices and the thermal balance of the infant. For generating this knowledge, thermal manikins can be helpful. Suitable models capable of also simulating evaporative heat loss in preterm infants have, however, not been available to date. A thermal manikin representing an infant weighing 530 g and capable of simulating convective, radiative and also evaporative heat loss has now been developed. It comprises an outer shell made of porous, anatomically shaped clay, and is divided into six compartments each of which can be heated individually. Water-filled Gore-Tex bags located immediately beneath the shell are provided to simulate evaporation. In a clinical study, temperature profiles of 8 very small preterm infants were measured thermographically. Measurements in the manikin showed that highly comparable temperature profiles with only minor differences could be obtained. Total heat and water losses by the manikin were in good agreement with clinical values. Using the model described here it is possible to simulate the heat exchange of premature infants under extreme and accurately reproducible environmental conditions. This manikin may thus serve as a tool for comparative studies, for the development of warming therapy equipment, or for training purposes.
R. T. Frankenberger, O. Bussmann, W. Nahm, E. Konecny, and L. Gortner. Messung seitlicher Haupttemperaturprofile von Frühgeborenen in Inkubatoren mittels Thermograhpie - Measuring lateral skin temperature profile of premature infants in incubators with thermography. In Biomedizinische Technik. Biomedical Engineering, vol. 43(6) , pp. 174-178, 1998
Thermography enables the measurement of patients skin temperature profiles without stress caused by direct contact of probes to the skin. In previous incubator studies, frontal recordings were made through a hole in the top wall of the incubator hood. Using this method it is not possible to record the lateral temperature gradient from the back to the abdomen of the infant (in supine position), which is due to very limited heat loss near the incubator mattress. In this study temperature recordings were made from a lateral position. For this purpose a new front door of the incubator (Draeger 8000) was designed, which replaced the standard front door during measurements. In a clinical study thermography was compared to temperature measurements by standard thermistors. The mean difference between thermography and thermistors was 0.16 degree C. These results verify the use of thermography for measuring skin temperature of preterm infants in incubators.
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.
G. Gauglitz, A. Brecht, G. Kraus, and W. Nahm. Chemical and biochemical sensors based on interferometry at thin (multi-) layers. In Sensors and Actuators B: Chemical, vol. 11(1) , pp. 21-27, 1993
Spectral interferometry is presented as a tool to monitor the swelling of polymers caused by organic gases or hydrocarbons in waste water as well as the adsorption and interaction of antigens and antibodies in immunoreactions. Modern diode-array technology allows the consequent observation of changes in optical pathlength on a fractional nanometer scale with subsecond repetition times. The theory of multiple-reflection principles in white-light interferometry determines the possibilities and limitations of this method. The optical set-up and some applications in gas sensing and label-free immunosensing are discussed with respect to the sensitivity, selectivity and limits of detection at present.
G. Gauglitz, and W. Nahm. Observation of spectral interferences for the determination of volume and surface effects of thin films. In Fresenius Journal of Analytical Chemistry, vol. 341(3-4) , pp. 279 283, 1991
The application of a rapid scanning diode array spectrometer allows the time-resolved observation of the interferences caused by multiple reflections at the interfaces of thin films. This spectral interferometry enables the observation of changes in optical pathlengths and allows to separate volume-effects like polymer swelling from surface-effects like adsorption or deposition. Polymer/solvent interactions will give an example for an application of this method.
G. Gauglitz, and W. Nahm. Rapid optical sensors for the detection of organic solvent vapors. In Proc ACHEMA, pp. 3-4, 1991
BACKGROUND: The absorption of irrigation fluid during transurethral resection of the prostate (TURP) is determined primarily by hydrostatic pressure in the bladder and prostatic venous pressure. In comparison to spontaneously breathing patients, patients undergoing mechanical ventilation with positive pressure have a raised central venous pressure and a reduced venous return, both of which can influence intravascular absorption. The purpose of the prospective study was to compare the effects of general (GA) and spinal anaesthetic (SA) techniques on the perioperative absorption of irrigating fluid in patients undergoing TURP. METHODS: Forty patients undergoing TURP were randomised and assigned either to group GA or SA. Irrigating fluid absorption was traced by adding 1.5% (w/v) ethanol to the irrigating fluid. Perioperative blood ethanol concentration (BEC), haemoglobin concentration, haematocrit, serum sodium concentration and central venous pressure (CVP) were measured at 10-min intervals during TURP and at 30-min intervals while patients were recovering. Absorption routes were indexed by the BEC and changes in serum sodium concentrations. Where the BEC was greater than 0.05 mg.mL-1, absorption of irrigating fluid was assumed. For assessing the volume of irrigating fluid absorbed, the maximum BEC, the absorption rate, the area under the BEC curve (AUC), and the volumes calculated according to the Hahn nomogram (Volin) for each patient were taken into consideration. RESULTS: There were 15 cases of irrigating fluid absorption in patients receiving GA (75%), and 11 in those receiving SA (55%). CVP was significantly lower in spontaneously breathing patients with SA as compared to those with GA (P < 0.05). In patients with irrigating fluid absorption the maximum BEC (P < 0.02), as well as the rate of irrigant fluid absorption (P < 0.01), were significantly higher amongst patients receiving SA. In this group, the calculated area under the curve and the absorbed fluid volumes determined with the nomogram were significantly increased (P < 0.05). CONCLUSION: The absorption of irrigation fluid during the TURP is significantly more marked amongst spontaneously breathing patients with regional anaesthesia in comparison to patients undergoing general anaesthesia with positive pressure ventilation. The markedly lower central venous pressure before the start of irrigation should be considered as a possible cause of this effect.
H. Gehring, W. Nahm, J. Baerwald, E. Konecny, and P. Schmucker. Atem-Alkoholmeßgeräte mit elektrochemischem Sensor - Meßgenauigkeit bei Beatmung am Lungenmodell - Breath alcohol analyzers with electrochemical sensory--accuracy of measurements in lung model ventilation. In Biomedizinische Technik. Biomedical Engineering, vol. 41(3) , pp. 54-9, 1996
Absorption of irrigating fluid by blood vessels during endoscopic urological surgery may result in cardiac insufficiency, impairment of electrolyte metabolism and neurological disorders. For detection and quantification of the volume absorbed, ethanol is added to the irrigating fluid. The resulting blood alcohol concentration can be obtained by measuring the alcohol concentration in the expired air. For artificially ventilated patients receiving a general anesthetic, electrochemical sensors that remain uneffected by volatile anaesthetics are used. In the present study, the measuring accuracy of three different alcohol analyzers using electrochemical sensors was tested against an infrared reference sensor during simulated ventilation in a lung model, and the optimal trigger time point for sampling determined. All three devices tested show the same degree of accuracy as the reference. For manual endexpiratory triggering devices with short sampling times are best suitable. Portable devices powered by rechargeable batteries and usable with both spontaneously breathing and ventilated patients are recommended for clinical application.
One way of determining pulmonary CO2 elimination during anaesthesia is the breath-by-breath method. With this technique, CO2 analysis is carried out using either the mainstream method (MSM), that is, directly in the expired air flow, or in samples of expired air. A disadvantage of MSM is the lack of sensor signal correction for changes in the composition of the gas mixture and barometric pressure. Sidestream Systems (SSM) measure respiratory gas flow and gas con- centration with adequate accuracy, and also correct the measured values for gas composition and ambient parameters. Disadvantages of breath-by-breath analysis are the SSM-system-rela- ted delay and distortion of the CO2 curves. In the present study, a computer-assisted comparati- ve analysis of CO, elimination measurement by the sidestream and mainstream methods was carried out using ctiff erent mixtures of gases in a lung model. Under the selected conditions simulated in the lung model, evaluation of CO2 elimination using SSM and MSM is possible with an error of between 0 and 10 % versus reference Systems.Measu- ring accuracy of the MSM System in particular is found to depend directly on the composition of the gas mixture. Using the method described here, the measuring error of an SSM System in terms of delay and response time can be compensated with adequate accuracy.
The present paper examined the question as to the extent to which the taking of gas samples for the purpose of measuring the breath alcohol concentration (BAC) in the expired air of patients on artificial respiration is influenced by temperature and humidity. For this purpose a lung model standardized at different alcohol concentrations was used, in which the temperature (T: 25, 30 and 35 degrees C) and the relative humidity (RH: 50, 75 and 95%) were varied.
UNLABELLED: When looking for the possible cause of distortions in values measured for the determination of breath ethanol concentration (BEC) in artificially respirated patients, consideration must be given to the humidity and temperature of the gas examined. In the present study, the effects of humidified and warmed and of dry and cold air on the accuracy of a newly developed BEC measuring device, as compared to a reference model and to a conventional system, were examined in a lung model. METHODS: A temperature-regulated pediatric incubator was used containing a 10 I gas reservoir and a breath humidifier with temperature regulated water bath. This setup provided constant temperature and humidity in the gas examined during measurement period. In the 'expiration' the air was directed from the breath humidifier through a measuring unit via a 'mouthpiece' into the reference system (Alcotest 7110, Dräger Inc., Lübeck) and then out. The measuring unit consisted of sensors for the temperature and relative humidity, and of a connector for the three sample extraction systems (PES). PES I was the conventional system with a 100-cm gas-sample pipe (Alcomed 3010), PES II the newly developed system (AlcoMed 3011, both from Envitec, Wismar) with a 10-cm gas-sample pipe, and PES III with a 20-cm heated gas-sample pipe. During 'inspiration' 2 l of air was fed into the system to rinse the measuring unit and to fill the reservoir. 61 measurements were performed with dry and cold air, and 71 with humidified and warmed air, in the course of which the ethanol concentration was increased from 0 to 1.5/1000. Data were evaluated using regression analysis and the Bland & Altman method. RESULTS AND CONCLUSIONS: The constancy of the values set for temperature, relative humidity and absolute humidity in the lung model was given for all measurements. In the dry and cold air, the results from all three test systems coincided almost perfectly with the reference values. The measured BEC in the humidified and warmed air using sample-extraction systems II and III corresponded to a high degree with the reference, while in the case of PES I, only a moderate linear correlation was achieved. The temperature and humidity of the expired gas during artificial respiration influence the gas samples extracted for the purposes of BEC measurement. Newly developed sample-extraction systems II and III coincide with the reference system, even under respiration-simulated gas conditions.
Der Effekt von Temperatur und Luftfeuchtigkeit auf die Gasprobenentnahme zur Messung der Atem-Alkoholkonzentration (AAK) wurde zwischen 0 und 1,5‰ in einem Lungenmodell bei Messungen sowohl in trockener und kühler als auch in feuchter und angewärmter Luft untersucht. Methodik: Neben dem herkömmlichen Probenentnahmesystem (PES) mit einem 100 cm langen Schlauch (Alcomed 3010®, PES I) wurde ein weiterentwickeltes Gerät mit verbessertem Gasprobentransport (AlcoMed 3011®, beide Fa. Envitec, Wismar) und 10 cm kurzem (PES II) sowie 20 cm kurzem und auf 36°C beheiztem Gasprobenschlauch (PES III) gegenüber einem Referenzsystem mit Infrarot-Sensor (Alcotest 7110®, Fa. Dräger, Lübeck) eingesetzt. Ergebnisse: In der trockenen und kühlen Luft entsprachen die Meßergebnisse aller 3 Testsysteme fast idealerweise den Referenzwerten. Bei den Messungen in feuchter und angewärmter Luft bestand diese Übereinstimmung für das PES II und III, während das PES I keinen linearen Zusammenhang mit den Referenzwerten zeigte. Schlußfolgerung: Die Temperatur und die Luftfeuchtigkeit hat einen erheblichen Einfluß auf die AAK-Messung bei beatmeten Patienten und ist bei der Probenentnahme zu berücksichtigen.
H. Gehring, W. Nahm, K. F. Klotz, A. Knipper, K. Zimmermann, J. Baerwald, and P. Schmucker. Messung der Atem-Alkoholkonzentration mit einem neuen elektronischen Sensor. Modelluntersuchung zur Querempfindlichkeit gegenüber volatile Anästhetika und klinische Anwendung - Measurement of expired alcohol concentrations with a new electrochemical sensor. A model investigation to determine interference with volatile anesthetics and clinical application. In Der Anaesthesist, vol. 45(2) , pp. 154-62, 1996
UNLABELLED: Absorption of irrigating fluid in transurethral prostatic resection (TURP) and percutaneous nephrolitholapaxy (PNL) into veins or delayed absorption due to fluid extravasation may result in a TURP syndrome. The measurement of end-tidal breath alcohol concentration (et AC) as a monitor of absorption of irrigating fluid labelled with 2% ethanol is limited by the disturbance of infrared sensors by volatile anaesthetics and nitrous oxide (N2O) (Fig. 2). An electrochemical sensor is acceptable for this method. The aim of the present study was the evaluation of breath alcohol measurements using an electrochemical sensor device (Alcomed 3010, Envitec). The stability of the sensor in the presence of volatile anaesthetics was examined using a lung model. In a clinical investigation, the device was then applied to spontaneously breathing or mechanically ventilated patients inhaling volatile anaesthetics during endoscopic urological surgery. METHOD: A two-chamber lung model filled with water for performing noninvasive measurements at the mouth of a patient has already been introduced by Brunner et al. (Fig. 1). With the addition of different amounts of ethanol to the temperature-controlled water, a constant ethanol concentration is achievable in the air above the water that is dependent on adjustments of the ventilator. Increasing concentrations of volatile anaesthetics (isoflurane, enflurane, halothane, and sevoflurane) were added to the fresh gas flow (2 l O2/3 l N2O) and etACs were measured using the manually triggered self-absorbent electrochemical sensor. First, regression equations were established between breath alcohol concentrations and increased volatile anaesthetic concentrations. Regression equations were then established between end-tidal anaesthetic gas concentrations and vaporizer adjustments in order to rule out an influence of ethanol on the anaesthetic gas monitor Ultima V (Datex). In the clinical investigation, 53 intubated and ventilated patients (33 undergoing PNL, 20 undergoing TURP) and 48 patients breathing spontaneously (32 with inhalation anaesthesia, 16 with spinal anaesthesia) were investigated. The etAC was measured with the Alcomed 3010 and compared with gas-chromatographically registered blood alcohol concentrations (BAC). The study had previously been approved by the Ethical Committee of the Medical University of Luebeck. Patients with liver disease and a history of toxic abuse were excluded. Only one value per patient (maximum BAC) was included in the statistics in order to avoid a cluster effect. RESULTS: The lung model experiments demonstrated that the measurement of etAC with an electrochemical sensor is free of interference by volatile anaesthetics (Table 1). The slope of the regression between the measured alcohol concentration and increased concentrations of anaesthetics did not differ significantly from baseline values. The measurement of end-tidal anaesthetic concentrations was not significantly different from vaporizer adjustments in the presence of increased alcohol concentrations (Table 2). During the clinical investigation, a regression between etAC and BAC was determined for both groups. For the group of patients breathing spontaneously, the correlation coefficient was 0.961 and the regression equation revealed etAC = 0.5677*BAC-0.1303 (Fig. 5). However, in the group of ventilated patients a biphasic course was shown that was dependent on BAC (Fig. 6). At BAC < 0.4%, a similar correlation (r = 0.856) to the spontaneously breathing group could be seen (regression equation: etAC = 0.617*BAC-0.020). Above 0.4% BAC there was no acceptable correlation (r = 0.444, regression equation: etAC = 0.202*BAC+0.104). CONCLUSIONS: The tested electrochemical sensor does not interfere with volatile anaesthetics and N2O as demonstrated by a lung model. There is a good correlation between etAC and BAC measurements in patients breathing spontaneously with special regard to the slope of the regression (s = 0.57).
H. Gehring, W. Nahm, K. F. Klotz, O. Zais, R. Schreiber, and P. Schüren. Plasmavolumenbestimmung mit dem Farbstoff ICG bei Änderung des intravasalen Volumens - Plasma volume determination with ICG dye in changes of intravascular volume. In Infusionstherapie und Transfusionsmedizin, vol. 23, pp. 86-91, 1996
Ziel: Die Messung des aktuellen intravasalen Volumens mit Hilfe der Indikator-Verdünnungsmethode ist sowohl von klini-schem als auch von wissenschaftlichem Interesse. Bei der Ver-wendung des rasch eliminierten Farbstoffes Indocyanin-Grün (ICG) sind wiederholte Messungen und damit Verlaufskontrollen möglich. In der vorliegenden Studie sollten folgende Fragen geprüft werden: 1. Stimmen die von uns mit der ICG-Methode bei gesunden Probanden bestimmten Werte mit den in der Literatur angegebenen Kontrollwerten überein, und ist somit die Grundlage für die Durchführung weiterer klinischer Studien gegeben, und 2. Stimmen die Differenzen der vor und nach Eigenblutentnahme bzw. Retransfusion bestimmten Werte für das Plasmavolumen mit den tatsächlich entnommenen bzw. retransfundierten Volumina überein? Design: Prospektive Studie (an je 20 gesunden weiblichen bzw. männlichen Probanden). Rahmen: Forschungslabor einer anästhesiologischen Universitätsklinik. Teilnehmer: Je 20 gesunde weibliche bzw. männliche Probanden. Interventionen: Plasmavolumenbestimmung mit ICG vor und nach Entnahme von 10% des ge-schätzten Blutvolumens und nach Retransfusion. Ergebnisse: In der Gruppe der Frauen betrug das Plasmavolumen pro Körperoberfläche (PV/KO) 1639 ± 198 und bei den Männern 1687 ± 224 ml/m2 (Mittelwert ± SD). Durch die Eigenblutspende wurde den Frauen 188 ± 23 und den Männern 149 ± 26 ml/m2 PV entzogen. Die PV-Messung mit ICG ergab für diesen Ent-zug einen Wert von 198 ± 174 bzw. 171 ± 158 ml/m2 und für die Retransfusion 190 ± 169 bzw. 142 ± 154 ml/m2. Schluβfolgerungen: Die Kontrollwerte liegen in dem in der Literatur be-schriebenen Normbereich. Die gemessenen Differenzen der Plasmavolumina vor und nach Eigenblutspende bzw. nach Retransfusion stimmen mit den tatsächlich entnommenen Plasmavolumina im Mittel gut überein. Bei der klinischen Beurteilung im Einzelfall ist die methodisch bedingte hohe Standardabweichung zu berücksichtigen.
BACKGROUND: The most common complication during percutaneous nephrolithotripsy (PNL) is the destruction of organ structures with extravasation of the irrigation fluid into the retroperitoneal space. Consequently, there is an increased risk of a urosepsis and a complicated therapeutic course. In this study we aimed to show that extravascular absorption could be differentiated from intravascular absorption due to their unique absorption characteristics, and that these characteristics enable a prediction of possible post-operative complications. METHODS: In a prospective study of 31 patients with PNL, ethanol was added to the irrigating fluid and blood ethanol concentration (BEC) was measured by gas chromatography during the endoscopic procedure and in the recovery room. Following the guidelines of Hahn, patients were divided into two groups: group EVA, in whom extravasation had occurred with subsequent absorption; group IVA, those with intravascular absorption. Patients' post-operative progress along with diagnoses of renal perforations or bleeding, or signs of infection or sepsis, were comprehensively listed. RESULTS: EVA was diagnosed in 19 cases, and IVA in 12 cases. Maximum BEC levels were achieved after 20 min (median) in the IVA group, and 75 min in the EVA group (P < 0.05). Apart from their significantly higher demand for opioids (P < 0.05), EVA patients had been hospitalised for a substantially and significantly longer period of time (P < 0.01). Although without statistical significance, there was a higher rate of peri-operatively confirmed complications and prolonged intensive therapeutic treatment in the extravasation group. CONCLUSION: Retroperitoneal extravasation can be identified by using ethanol monitoring during and after PNL. Afflicted patients require considerably longer hospitalisation, probably because of the additional injury to surrounding organ structures.
S. E. Geneser, R. M. Kirby, D. Xiu, and F. B. Sachse. Stochastic Markovian modeling of electrophysiology of ion channels: reconstruction of standard deviations in macroscopic currents. In J Theor Biol, vol. 245(4) , pp. 627-637, 2007
Markovian models of ion channels have proven useful in the reconstruction of experimental data and prediction of cellular electrophysiology. We present the stochastic Galerkin method as an alternative to Monte Carlo and other stochastic methods for assessing the impact of uncertain rate coefficients on the predictions of Markovian ion channel models. We extend and study two different ion channel models: a simple model with only a single open and a closed state and a detailed model of the cardiac rapidly activating delayed rectifier potassium current. We demonstrate the efficacy of stochastic Galerkin methods for computing solutions to systems with random model parameters. Our studies illustrate the characteristic changes in distributions of state transitions and electrical currents through ion channels due to random rate coefficients. Furthermore, the studies indicate the applicability of the stochastic Galerkin technique for uncertainty and sensitivity analysis of bio-mathematical models.
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.
Computational modeling is an important tool to advance our knowledge on cardiac diseases and their underlying mechanisms. Computational models of conduction in cardiac tissues require identification of parameters. Our knowledge on these parameters is limited, especially for diseased tissues. Here, we assessed and quantified parameters for computational modeling of conduction in cardiac tissues. We used a rabbit model of myocardial infarction (MI) and an imaging-based approach to derive the parameters. Left ventricular tissue samples were obtained from fixed control hearts (animals: 5) and infarcted hearts (animals: 6) within 200 μm (region 1), 250-750 μm (region 2) and 1,000-1,250 μm (region 3) of the MI border. We assessed extracellular space, fibroblasts, smooth muscle cells, nuclei and gap junctions by a multi-label staining protocol. With confocal microscopy we acquired three-dimensional (3D) image stacks with a voxel size of 200 × 200 × 200 nm. Image segmentation yielded 3D reconstructions of tissue microstructure, which were used to numerically derive extracellular conductivity tensors. Volume fractions of myocyte, extracellular, interlaminar cleft, vessel and fibroblast domains in control were (in %) 65.03 ± 3.60, 24.68 ± 3.05, 3.95 ± 4.84, 7.71 ± 2.15, and 2.48 ± 1.11, respectively. Volume fractions in regions 1 and 2 were different for myocyte, myofibroblast, vessel, and extracellular domains. Fibrosis, defined as increase in fibrotic tissue constituents, was (in %) 21.21 ± 1.73, 16.90 ± 9.86, and 3.58 ± 8.64 in MI regions 1, 2, and 3, respectively. For control tissues, image-based computation of longitudinal, transverse and normal extracellular conductivity yielded (in S/m) 0.36 ± 0.11, 0.17 ± 0.07, and 0.1 ± 0.06, respectively. Conductivities were markedly increased in regions 1 (+75, +171, and +100%), 2 (+53, +165, and +80%), and 3 (+42, +141, and +60%). Volume fractions of the extracellular space including interlaminar clefts strongly correlated with conductivities in control and MI hearts. Our study provides novel quantitative data for computational modeling of conduction in normal and MI hearts. Notably, our study introduces comprehensive statistical information on tissue composition and extracellular conductivities on a microscopic scale in the MI border zone. We suggest that the presented data fill a significant gap in modeling parameters and extend our foundation for computational modeling of cardiac conduction.
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.
U. Guttenberg, H. J. Holländer, and G. Vossius. [Various kinds of stimulation systems for organization and use of functional electrostimulation in paraplegic patients]. In Biomedizinische Technik. Biomedical Engineering, vol. 35 Suppl 3, pp. 120-121, 1990
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.
A. Hansjürgens, and K. Meyer-Waarden. Feldverteilung ausgewählter Parameter interferiender mittelfrequener Ströme in inhomogenen biologischen Medien. In Biomedizinische Technik - Ergänzungsband, vol. 25, pp. 298-300, 1980
BACKGROUND: Genetic predisposition is believed to be responsible for most clinically significant arrhythmias; however, suitable genetic animal models to study disease mechanisms and evaluate new treatment strategies are largely lacking. METHODS AND RESULTS: In search of suitable arrhythmia models, we isolated the zebrafish mutation reggae (reg), which displays clinical features of the malignant human short-QT syndrome such as accelerated cardiac repolarization accompanied by cardiac fibrillation. By positional cloning, we identified the reg mutation that resides within the voltage sensor of the zebrafish ether-à-go-go-related gene (zERG) potassium channel. The mutation causes premature zERG channel activation and defective inactivation, which results in shortened action potential duration and accelerated cardiac repolarization. Genetic and pharmacological inhibition of zERG rescues recessive reg mutant embryos, which confirms the gain-of-function effect of the reg mutation on zERG channel function in vivo. Accordingly, QT intervals in ECGs from heterozygous and homozygous reg mutant adult zebrafish are considerably shorter than in wild-type zebrafish. CONCLUSIONS: With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish reg represents the first animal model for human short-QT syndrome.
T. Helgason, P. Lukas, and G. Vossius. [Use of evolution strategy as a control algorithm in functional electrostimulation]. In Biomedizinische Technik. Biomedical Engineering, vol. 34 Suppl, pp. 159-160, 1989
Oligomers with a dimethylsiloxane backbone coated as thin films on different substrate surfaces were thermally as well as photochemically cross-linked. The structure and the degree of cross-linking were examined spectroscopically. Diffusion of different gases in the thin polymer films was measured by time resolved infrared ATR-spectroscopy. The process of diffusion is almost immediately followed by a swelling of the polymer proportional to gas concentration. Therefore diffusion may also be measured by spectral interferometry, giving a very sensitive device for optical sensing of hydrocarbons. Furthermore, diffusion in polymers may be measured very accurately by spatially resolved UV/Vis-spectroscopy. Diffusion coefficients may also be determined indirectly from the equilibrium of monomers and excimers indicated by the fluorescence intensities. This method allows the in situ observation of the cross-linking process.
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.
OBJECTIVE: To develop and test a method for standardized calibration of pulse oximeters. METHODS: A novel pulse oximeter calibration technique capable of simulating the behavior of real patients is discussed. It is based on an artificial finger with a variable spectral-resolved light attenuator in conjunction with an extensive clinical database of time-resolved optical transmission spectra of patients fingers in the wavelength range 600-1000 nm. The arterial oxygen saturation of the patients at the time of recording was derived by analyzing a corresponding blood sample with a CO-oximeter. These spectra are used to compute the modulation of the light attenuator which is attached to the artificial finger. This calibration method was tested by arbitrarily playing back recorded spectra to pulse oximeters and comparing their display to the value they displayed when the spectra were recorded. RESULTS: We were able to demonstrate that the calibrator could generate physiological signals which are accepted by a pulse oximeter. We also present some experience of playing back recorded patient spectra. The mean difference between the original reading of the pulse oximeters and the display when attached to the calibrator is 1.2 saturation points (displayed oxygen saturation SpO2) with a standard deviation of 1.9 saturation points. CONCLUSIONS: The tests have shown the capabilities of a spectral light modulator for use as a possible calibration standard for pulse oximeters. If some improvements of the current prototype can be achieved we conclude from the experience with the device that this novel concept for the calibration of pulse oximeters is feasible and that it could become an important tool for assessing the performance of pulse oximeters.
E. Hughes, B. Taccardi, and F. B. Sachse. A heuristic streamline placement technique for visualization of electrical current flow. In J Flow Visualization and Image Processing, vol. 13(1) , pp. 53-66, 2006
Streamline techniques are frequently applied for scientific visualization of two- and three-dimensional electric fields. Streamline distributions are expected to reflect important features of the underlying fields such as the locations of sources and sinks as well as variations of the field density. Streamline techniques fulfilling these demands in arbitrary fields are currently not developed.In this work, we present a heuristic technique, which aims at creating a linear relationship between a streamline distribution and the density of an underlying electric current field. The technique is based on a sequential optimization algorithm for placement of seed points of streamlines. In each step, a set of random trial seed points is created. Each point of the trial set is temporarily added to the set of best seed points. Streamlines are generated from the enhanced set and the fit of their distribution and the field density is determined. The best point is selected and added to the set of best seed points. The iteration ends after generation of a pre-given number of best seed points. Several examples illustrate results of this technique applied to electric current fields of small complexity and in more extensive cardiothoracic electric fields. Additionally, we characterized, with statistical studies, the influence of parameters of the algorithm on the relationship between streamline distribution and field density.
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, vol. 56(6) , pp. 1013-1025, 2018
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.
The interaction of spiral waves of excitation with atrial anatomy remains unclear. This simulation study isolates the role of atrial anatomical structures on spiral wave spontaneous drift in the human atrium. We implemented realistic and idealised 3D human atria models to investigate the functional impact of anatomical structures on the long-term ( approximately 40 s) behaviour of spiral waves. The drift of a spiral wave was quantified by tracing its tip trajectory, which was correlated to atrial anatomical features. The interaction of spiral waves with the following idealised geometries was investigated: (a) a wedge-like structure with a continuously varying atrial wall thickness; (b) a ridge-like structure with a sudden change in atrial wall thickness; (c) multiple bridge-like structures consisting of a bridge connected to the atrial wall. Spiral waves drifted from thicker to thinner regions and along ridge-like structures. Breakthrough patterns caused by pectinate muscles (PM) bridges were also observed, albeit infrequently. Apparent anchoring close to PM-atrial wall junctions was observed. These observations were similar in both the realistic and the idealised models. We conclude that spatially altering atrial wall thickness is a significant cause of drift of spiral waves. PM bridges cause breakthrough patterns and induce transient anchoring of spiral waves.
Atrial fibrillation (AF) is a common cardiac disease of genuine clinical concern with high rates of morbidity, leading to major personal and National Health Service costs. Computer modelling of AF using biophysically detailed cellular models with realistic 3D anatomical geometry allows investigation of the underlying ionic mechanisms in far more detail than with experimental physiology. We have developed a 3D virtual human atrium that combines detailed cellular electrophysiology including ion channel kinetics and homeostasis of ionic concentrations with anatomical details. The segmented anatomical structure and the multi- variable nature of the system make the 3D simulations of AF computationally large and intensive.
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.
UNLABELLED: The electroencephalogram (EEG) and middle latency auditory evoked responses (MLAER) have been proposed for assessment of the depth of anesthesia. However, a reliable monitor of the adequacy of anesthesia has not yet been defined. In a multicenter study, we tested whether changes in the EEG and MLAER after a tetanic stimulus applied to the wrist could be used to predict subsequent movement in response to skin incision in patients anesthetized with 1 minimum alveolar anesthetic concentration (MAC) isoflurane in N2O. We also investigated whether the absolute values of any of these variables before skin incision was able to predict subsequent movement. After the induction of anesthesia with propofol and facilitation of tracheal intubation with succinylcholine, 82 patients received 1 MAC isoflurane (0.6%) in N2O 50% without an opioid or muscle relaxant. Spontaneous EEG and MLAER to auditory click-stimulation were recorded from a single frontoparietal electrode pair. MLAER were severely depressed at 1 MAC isoflurane. At least 20 min before skin incision, a 5-s tetanic stimulus was applied at the wrist, and the changes in EEG and MLAER were recorded. EEG and MLAER values were evaluated before and after skin incision for patients who did not move in response to tetanic stimulation. Twenty patients (24%) moved after tetanic stimulation. The changes in the EEG or MLAER variables were unable to predict which patients would move in response to skin incision. Preincision values were not different between patients who did and did not move in response to skin incision for any of the variables. MLAER amplitude increased after skin incision. We conclude that it is unlikely that linear EEG measures or MLAER variables can be of practical use in titrating isoflurane anesthesia to prevent movement in response to noxious stimulation. IMPLICATIONS: Reliable estimation of anesthetic adequacy remains a challenge. Changes in spontaneous or auditory evoked brain activity after a brief electrical stimulus at the wrist could not be used to predict whether anesthetized patients would subsequently move at the time of surgical incision.
BACKGROUND: Middle latency auditory evoked responses (MLAER) as a measure of depth of sedation are critically dependent on data quality and the analysis technique used. Manual peak labeling is subject to observer bias. This study investigated whether a user-independent index based on wavelet transform can be derived to discriminate between awake and unresponsive states during propofol sedation. METHODS: After obtaining ethics committee approval and written informed consent, 13 volunteers and 40 patients were studied. In all subjects, propofol was titrated to loss of response to verbal command. The volunteers were allowed to recover, then propofol was titrated again to the same end point, and subjects were finally allowed to recover. From three MLAER waveforms at each stage, latencies and amplitudes of peaks Pa and Nb were measured manually. In addition, wavelet transform for analysis of MLAER was applied. Wavelet transform gives both frequency and time information by calculation of coefficients related to different frequency contents of the signal. Three coefficients of the so-called wavelet detail level 4 were transformed into a single index (Db3d4) using logistic regression analysis, which was also used for calculation of indices for Pa, Nb, and Pa/Nb latencies. Prediction probabilities for discrimination between awake and unresponsive states were calculated for all MLAER indices. RESULTS: During propofol infusion, subjects were unresponsive, and MLAER components were significantly depressed when compared with the awake states (P < 0.001). The wavelet index Db3d4 was positive for awake and negative for unresponsive subjects with a prediction probability of 0.92. CONCLUSION: These data show that automated wavelet analysis may be used to differentiate between awake and unresponsive states. The threshold value for the wavelet index allows easy recognition of awake versus unresponsive subjects. In addition, it is independent of subjective peak identification and offers the advantage of easy implementation into monitoring devices.
Chronic atrial fibrillation (AF) is a complex disease with underlying changes in electrophysiology, calcium signaling and the structure of atrial myocytes. How these individual remodeling targets and their emergent interactions contribute to cell physiology in chronic AF is not well understood. To approach this problem, we performed in silico experiments in a computational model of the human atrial myocyte. The remodeled function of cellular components was based on a broad literature review of in vitro findings in chronic AF, and these were integrated into the model to define a cohort of virtual cells. Simulation results indicate that while the altered function of calcium and potassium ion channels alone causes a pronounced decrease in action potential duration, remodeling of intracellular calcium handling also has a substantial impact on the chronic AF phenotype. We additionally found that the reduction in amplitude of the calcium transient in chronic AF as compared to normal sinus rhythm is primarily due to the remodeling of calcium channel function, calcium handling and cellular geometry. Finally, we found that decreased electrical resistance of the membrane together with remodeled calcium handling synergistically decreased cellular excitability and the subsequent inducibility of repolarization abnormalities in the human atrial myocyte in chronic AF. We conclude that the presented results highlight the complexity of both intrinsic cellular interactions and emergent properties of human atrial myocytes in chronic AF. Therefore, reversing remodeling for a single remodeled component does little to restore the normal sinus rhythm phenotype. These findings may have important implications for developing novel therapeutic approaches for chronic AF.
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....
Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.
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.
Atrial fibrillation (AF) is the most common arrhythmia of the heart in industrialized countries. Its generation and the transitory behavior of paroxysmal AF are still not well understood. In this work we examine the interaction of two activation sources via an isthmus as possible cause for the initiation of fibrillation episodes. For this study, the electrophysiological model of Bueno-Orovio, Cherry and Fenton is adapted to atrial electrophysiology, both for physiological and electrophysiologically remodeled conditions due to AF. We show that the interaction of the pacemakers, combined with the geometrical constraints of the isthmus, can produce fibrillatory-type irregularities, which we quantify by the loss of spatial phase coherence in the transmembrane voltage. Transitions to irregular behavior occur when the frequencies of the pacemakers exceed certain thresholds, suggesting that AF episodes are initiated by frequency changes of the activating sources (sinus node, ectopic focus).
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
AIMS: P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. METHODS AND RESULTS: Atrial excitation was triggered from seven different EAS in a cohort of eight anatomically personalized computational models. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed and separated by left and right atrial contributions. Mid-septal EAS yielded the highest PTF-V1. More anterior/superior and more inferior EAS yielded lower absolute PTF-V1 values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via Bachmann's Bundle (BB) for anterior/superior EAS and shifted towards posterior IACs for more inferior EAS. Non-conducting posterior IACs increased PTF-V1 by up to 150% compared to intact posterior IACs for inferior EAS. LA contribution to the P-wave integral was 24% on average. CONCLUSION: The electrical contributor's site of earliest activation and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites independent from LA size. This should be considered for interpretation of electrocardiographical signs of LA abnormality and LA enlargement.
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.
Atypical atrial flutter (AFlut) is a reentrant arrhythmia which patients frequently develop after ablation for atrial fibrillation (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clinically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensitivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabiltiy on a clinical dataset. Finally, we tested how AFlut vulnerability of these substrates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut.
BACKGROUND: Complementary to clinical and experimental studies, computational cardiac modeling serves to obtain a comprehensive understanding of the cardiovascular system in order to analyze dysfunction, evaluate existing, and develop novel treatment strategies. OBJECTIVES: We describe the basics of multiscale computational modeling of cardiac electrophysiology from the molecular ion channel to the whole body scale. By modeling cardiac ischemia, we illustrate how in silico experiments can contribute to our understanding of how the pathophysiological mechanisms translate into changes observed in diagnostic tools such as the electrocardiogram (ECG). MATERIALS AND METHODS: Quantitative in silico modeling spans a wide range of scales from ion channel biophysics to ECG signals. For each of the scales, a set of mathematical equations describes electrophysiology in relation to the other scales. Integration of ischemia-induced changes is performed on the ion channel, single-cell, and tissue level. This approach allows us to study how effects simulated at molecular scales translate to changes in the ECG. RESULTS: Ischemia induces action potential shortening and conduction slowing. Hence, ischemic myocardium has distinct and significant effects on propagation and repolarization of excitation, depending on the intramural extent of the ischemic region. For transmural and subendocardial ischemic regions, ST segment elevation and depression, respectively, were observed, whereas intermediate ischemic regions were found to be electrically silent (NSTEMI). CONCLUSIONS: In silico modeling contributes quantitative and mechanistic insight into fundamental ischemia-related arrhythmogenic mechanisms. In addition, computational modeling can help to translate experimental findings at the (sub-)cellular level to the organ and body context (e. g., ECG), thereby providing a thorough understanding of this routinely used diagnostic tool that may translate into optimized applications.
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.
Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain-velocity relationships and reviewed related experimental and computational studies. We presented results from our experimental studies on rabbit papillary muscle, which supported a biphasic relationship of strain and velocity under uni-axial straining conditions. In the low strain range, the strain-velocity relationship was positive. Conduction velocity peaked with 0.59 m/s at 100% strain corresponding to maximal force development. In the high strain range, the relationship was negative. Conduction was reversibly blocked at 118+/-1.8% strain. Reversible block occurred also in the presence of streptomycin. Furthermore, our studies revealed a moderate hysteresis of conduction velocity, which was reduced by streptomycin. We reconstructed several features of the strain-velocity relationship in a computational study with a myocyte strand. The modeling included strain-modulation of intracellular conductivity and stretch-activated cation non-selective ion channels. The computational study supported our hypotheses, that the positive strain-velocity relationship at low strain is caused by strain-modulation of intracellular conductivity and the negative relationship at high strain results from activity of stretch-activated channels. Conduction block was not reconstructed in our computational studies. We concluded this work by sketching a hypothesis for strain-modulation of conduction and conduction block in papillary muscle. We suggest that this hypothesis can also explain uni-axially measured strain-conduction velocity relationships in other types of cardiac tissue, but apparently necessitates adjustments to reconstruct pressure or volume related changes of velocity in atria and ventricles
K. Meyer-Waarden, and U. Faust. Untersuchungen der elektrischen Quellenstruktur des Warmblüterherzens und deren Beziehung zum Thorax - Ekg. In Arch. Kreislaufforschg., vol. 67, pp. 233-265, 1972
Als Folge der Erregung der einzelnen Herzmuskelzellen bildet sich im Körper ein elektrisches Potential- und Strömungsfeld aus, das auf der Körperoberfläche als Elektrokardiogramm gemessen werden kann. Der räumlich-zeitliche Verlauf der Erregung im Herzmuskel wird auf der Körperoberfläche abgebildet. Die Abbildungsfunktion zu finden, ist Gegenstand vieler Untersuchungen in der Vergangenheit gewesen. Aus theoretischen Erwägungen, die von Helmholtz (7) abgeleitet wurden, geht hervor, daß keine Eindeutigkeit zwischen der Potentialverteilung in einem quellfreien Medium und einer Quellanordnung im lnnern derselben besteht, mit anderen Worten, die Potentialverteilung auf der Körperoberfläche kann durch eine unendliche Vielzahl verschiedener Quellanordnungen im Thorax erzeugt werden. Aus diesem Grund könnte man annehmen, daß eine Ekg-Diagnostik völlig unmöglich sei. Nur durch zusätzliche Annahmen, über die zeitlich-räumliche Verteilung der Quellen im Herzmuskel wird die Vieldeutigkeit eingeschränkt. Eine Eindeutigkeit läßt sich jedoch nicht herstellen; deshalb muß eine Diagnose sich weitgehend auf den Vergleich von zeitlichen Spannungsänderungen, die unter vorgegebenen Meßbedingungen gewonnen werden, beschränken. DieVieldeutigkeit weiterhin einzuschränken, ist Ziel der Untersuchungen.
K. Meyer-Waarden, and H. U. May. Transkutane elektrische Nervenstimulation mit nieder- und mittelfrequenten Strömen - ein Vergleich. In Schmerz, vol. 1, pp. 23-29, 1982
Die Arbeit gibt eine systematische Übersicht über die elektrophysikalischen und physiologischen Grundlagen der Wirkungen von Strömen unterschiedlicher Frequenz, ausgehend vom Gleichstrom über den niederfrequenten und mittelfreguenten Strom bis zum Hochfrequenzstrom.
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.
The cardiac muscarinic receptor (M2R) regulates heart rate, in part, by modulating the acetylcholine (ACh) activated K+ current IK,ACh through dissociation of G-proteins, that in turn activate KACh channels. Recently, M2Rs were noted to exhibit intrinsic voltage sensitivity, i.e. their affinity for ligands varies in a voltage dependent manner. The voltage sensitivity of M2R implies that the affinity for ACh (and thus the ACh effect) varies throughout the time course of a cardiac electrical cycle. The aim of this study was to investigate the contribution of M2R voltage sensitivity to the rate and shape of the human sinus node action potentials in physiological and pathophysiological conditions. We developed a Markovian model of the IK,ACh modulation by voltage and integrated it into a computational model of human sinus node. We performed simulations with the integrated model varying ACh concentration and voltage sensitivity. Low ACh exerted a larger effect on IK,ACh at hyperpolarized versus depolarized membrane voltages. This led to a slowing of the pacemaker rate due to an attenuated slope of phase 4 depolarization with only marginal effect on action potential duration and amplitude. We also simulated the theoretical effects of genetic variants that alter the voltage sensitivity of M2R. Modest negative shifts in voltage sensitivity, predicted to increase the affinity of the receptor for ACh, slowed the rate of phase 4 depolarization and slowed heart rate, while modest positive shifts increased heart rate. These simulations support our hypothesis that altered M2R voltage sensitivity contributes to disease and provide a novel mechanistic foundation to study clinical disorders such as atrial fibrillation and inappropriate sinus tachycardia.
W. Nahm, and G. Gauglitz. Dünne Polymerfilme als Sensoren für Kohlenwasserstoffe.. In GIT Fachz Lab, vol. 7, pp. 889-893, 1990
W. Nahm, and H. Gehring. Non-invasive in vivo measurement of blood spectrum by time-resolved near-infrared spectroscopy. In Sensors and Actuators B: Chemical, vol. 29(1) , pp. 174-179, 1995
Investigation of rapid near-infrared (NIR) spectroscopy in combination with the fibre optics for biomedical sensing is presented. Modern diode-array technology enables sensitive measurement of changes in tissue absorbance caused by blood pulsation. In order to describe the dynamics of this system a multi-layer model based on pulse wave theory is used. The evaluation of the pulsatile part of tissue absorbance at different wavelengths allows the construction of both pulsatile and static tissue spectra. The absorption monitoring of an injected bolus of indocyanine green is presented of non-invasive measurement of an arterial blood spectrum.
Considering the fundamental difficulties to define the term 'depth of anaesthesia', a more feasible concept for assessment of 'adequacy of anaesthesia' will be explained. The basic requirements for a monitoring index are definite response, gradual scaling and independence from the anaesthetic technique used. Additionally the index should be predictive for appearance of clinical signs of an inadequate anaesthesia. Different signal-processing methods will be discussed to extract the relevant information from both the spontaneous and the evoked brain electrical activity. In this context well established methods like spectral analysis are investigated in combination with new and more sophisticated methods like bispectral analysis or wavelet decomposition. Since no single-parameter index has been defined for monitoring depth of anaesthesia, a set of EEG parameters may be more useful to take into account intra- and interindividual variability. In parallel to the description of the monitor concept, the investigation of neural nets and fuzzy techniques, in addition to or in substitution of conventional statistical methods, will be introduced. Examples are given for data quality assessment, parameter extraction and re-classification.
Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.
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.
Activation of human ether-a-go-go-related gene 1 (hERG1) K+ channels mediates cardiac action potential repolarization. Drugs that activate hERG1 channels represent a mechanism-based approach for the treatment of long QT syndrome, a disorder of cardiac repolarization associated with ventricular arrhythmia and sudden death. Here, we characterize the mechanisms of action and the molecular determinants for binding of RPR260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR), a recently discovered hERG1 channel activator. Channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured by using the two-microelectrode voltage-clamp technique. RPR induced a concentration-dependent slowing in the rate of channel deactivation and enhanced current magnitude by shifting the voltage dependence of inactivation to more positive potentials. This mechanism was confirmed by demonstrating that RPR slowed the rate of deactivation, but did not increase current magnitude of inactivation-deficient mutant channels. The effects of RPR on hERG1 kinetics and magnitude could be simulated by reducing three rate constants in a Markov model of channel gating. Point mutations of specific residues located in the S4S5 linker or cytoplasmic ends of the S5 and S6 domains greatly attenuated or ablated the effects of 3 μM RPR on deactivation (five residues), inactivation (one residue), or both gating mechanisms (four residues). These findings define a putative binding site for RPR and confirm the importance of an interaction between the S4S5 linker and the S6 domain in electromechanical coupling of voltage-gated K+ channels.
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.
D. Potyagaylo, O. Dossel, and P. van Dam. Influence of Modeling Errors on the Initial Estimate for Nonlinear Myocardial Activation Times Imaging Calculated With Fastest Route Algorithm. In IEEE Transactions on Biomedical Engineering, vol. 63(12) , pp. 2576-2584, 2016
Noninvasive reconstruction of cardiac electrical activity has a great potential to support clinical decision making, planning and treatment. Recently, significant progress has been made in the estimation of the cardiac activation from body surface potential maps (BSPMs) using boundary element method (BEM) with the equivalent double layer (EDL) as source model. In this formulation, noninvasive assessment of activation times results in a nonlinear optimization problem with an initial estimate calculated with the fastest route algorithm (FRA). Each FRAsimulated activation sequence is converted into the ECG. The best initialization is determined by the sequence providing the highest correlation between predicted and measured potentials.We quantitatively assess the effects of the forward modeling errors on the FRA-based initialization. We present three simulation setups to investigate the effects of volume conductor model simplifications, neglecting the cardiac anisotropy and geometrical errors on the localization of ectopic beats starting on the ventricular surface. For the analysis, 12-lead ECG and 99 electrodes BSPM system were used. The areas in the heart exposing the largest localization errors were volume conductor model and electrode configuration specific with an average error <10 mm. The results show the robustness of the FRA-based initialization with respect to the considered modeling errors.
OBJECTIVE:The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes.METHODS:Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293.RESULTS:TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) by 31+/-3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil.CONCLUSIONS:Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.
The waveguide invariant in shallow water environments has been widely studied in the context of passive sonar. The invariant provides a relationship between the frequency content of a moving broadband source and the distance to the receiver, and this relationship is not strongly affected by small perturbations in environment parameters such as sound speed or bottom features. Recent experiments in shallow water suggest that a similar range-frequency structure manifested as striations in the spectrogram exists for active sonar, and this property has the potential to enhance the performance of target tracking algorithms. Nevertheless, field experiments with active sonar have not been conclusive on how the invariant is affected by the scattering kernel of the target and the sonar configuration (monostatic vs bistatic). The experimental work presented in this paper addresses those issues by showing the active invariance for known scatterers under controlled conditions of bathymetry, sound speed profile and high SNR. Quantification of the results is achieved by introducing an automatic image processing approach inspired on the Hough transform for extraction of the invariant from spectrograms. Normal mode simulations are shown to be in agreement with the experimental results.
BACKGROUND: Considering the rates of sudden cardiac death (SCD) and pump failure death (PFD) in chronic heart failure (CHF) patients and the cost-effectiveness of their preventing treatments, identification of CHF patients at risk is an important challenge. In this work, we studied the prognostic performance of the combination of an index potentially related to dispersion of repolarization restitution (Deltaalpha), an index quantifying T-wave alternans (IAA) and the slope of heart rate turbulence (TS) for classification of SCD and PFD. METHODS: Holter ECG recordings of 597 CHF patients with sinus rhythm enrolled in the MUSIC study were analyzed and Deltaalpha, IAA and TS were obtained. A strategy was implemented using support vector machines (SVM) to classify patients in three groups: SCD victims, PFD victims and other patients (the latter including survivors and victims of non-cardiac causes). Cross-validation was used to evaluate the performance of the implemented classifier. RESULTS: Deltaalpha and IAA, dichotomized at 0.035 (dimensionless) and 3.73 muV, respectively, were the ECG markers most strongly associated with SCD, while TS, dichotomized at 2.5 ms/RR, was the index most strongly related to PFD. When separating SCD victims from the rest of patients, the individual marker with best performance was Deltaalpha>/=0.035, which, for a fixed specificity (Sp) of 90%, showed a sensitivity (Se) value of 10%, while the combination of Deltaalpha and IAA increased Se to 18%. For separation of PFD victims from the rest of patients, the best individual marker was TS </= 2.5 ms/RR, which, for Sp=90%, showed a Se of 26%, this value being lower than Se=34%, produced by the combination of Deltaalpha and TS. Furthermore, when performing SVM classification into the three reported groups, the optimal combination of risk markers led to a maximum Sp of 79% (Se=18%) for SCD and Sp of 81% (Se=14%) for PFD. CONCLUSIONS: The results shown in this work suggest that it is possible to efficiently discriminate SCD and PFD in a population of CHF patients using ECG-derived risk markers like Deltaalpha, TS and IAA.
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.
R. Rupp, G. Vossius, and H. J. Gerner. [Contribution of EMG to monitoring controlled electrostimulation in paralysis: 1) Realization of a modular EMG recording hardware]. In Biomedizinische Technik. Biomedical Engineering, vol. 43 Suppl, pp. 242-244, 1998
F. B. Sachse, K. Glänzel, and G. Seemann. Modeling of protein interactions involved in cardiac tension development. In Int. J. Bifurcation and Chaos, vol. 13(12) , pp. 3561-3578, 2003
Fibroblasts are abundant in cardiac tissue. Experimental studies suggested that fibroblasts are electrically coupled to myocytes and this coupling can impact cardiac electrophysiology. In this work, we present a novel approach for mathematical modeling of electrical conduction in cardiac tissue composed of myocytes, fibroblasts, and the extracellular space. The model is an extension of established cardiac bidomain models, which include a description of intra-myocyte and extracellular conductivities, currents and potentials in addition to transmembrane voltages of myocytes. Our extension added a description of fibroblasts, which are electrically coupled with each other and with myocytes. We applied the extended model in exemplary computational simulations of plane waves and conduction in a thin tissue slice assuming an isotropic conductivity of the intra-fibroblast domain. In simulations of plane waves, increased myocyte-fibroblast coupling and fibroblast-myocyte ratio reduced peak voltage and maximal upstroke velocity of myocytes as well as amplitudes and maximal downstroke velocity of extracellular potentials. Simulations with the thin tissue slice showed that inter-fibroblast coupling affected rather transversal than longitudinal conduction velocity. Our results suggest that fibroblast coupling becomes relevant for small intra-myocyte and/or large intra-fibroblast conductivity. In summary, the study demonstrated the feasibility of the extended bidomain model and supports the hypothesis that fibroblasts contribute to cardiac electrophysiology in various manners.
F. B. Sachse, G. Seemann, K. Chaisaowong, and D. Weiß. Quantitative reconstruction of cardiac electromechanics in human myocardium: Assembly of electrophysiological and tension generation models. In J. Cardiovasc. Electrophysiol., vol. 14(S10) , pp. S210-S218, 2003
Mathematical models of cardiac anatomy and physics provide information, which help to understand structure and behavior of the heart. Miscellaneous cardiac phenomena can only be adequately described by combination of models representing different aspects or levels of detail. Coupling of these models necessitates the definition of appropriate interfaces. Adequateness and efficiency of interfaces is crucial for efficient application of the combined models.In this work an integrated model is presented consisting of several models interconnected by interfaces. The integrated model allows the reconstruction of macroscopic electro-mechanical processes in the heart. The model comprises a three-dimensional are of left ventricular anatomy represented as truncated ellipsoid. The integrated model includes electrophysiological, tension development and elastomechanical models of myocardium at levels of single cell, proteins, and tissue patches, respectively.The model is exemplified by simulations of extracorporated left ventricle of small mammals. These simulations yield temporal distributions of electrophysiological parameters as well as descriptions of electrical propagation and mechanical deformation. The simulations show characteristic macroscopic ventricular function resulting from the interplay between cellular electrophysiology, electrical excitation propagation, tension development, and mechanical deformation.
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.
Computer aided simulations of the heart provide knowledge for cardiologic diagnosis and therapy. A model of the myocardium is presented which allows the reconstruction of electrical and mechanical processes with inclusion of feedback mechanisms. The model combines detailed models of cellular electrophysiology and force development with models of the electrical current flow and the mechanical behavior of the myocardium. Results of simulations show the connection between the electrical excitation process and the following mechanical deformation in a three dimensional, anisotropic area of the myocardium. Keywords: Mechano-Electrical Feedback, Electro-Mechanical Feedback, Cellular Models, Electrophysiology, Excitation-Propagation
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.
F. B. Sachse, M. Wolf, C. D. Werner, and K. Meyer-Waarden. Extension of anatomical models of the human body: three dimensional interpolation of muscle fiber orientation based on restrictions. In Journal of Computing and Information Technology, vol. 6(1) , pp. 95-101, 1998
This paper is the extension of a detailed anatomical model (Sachse et al., 1996a) (Sachse et al., 1996b) with the three-dimensional orientation of skeletal muscle fibres (Figure 1). The orientation is interpolated basing on two sets with restrictions of different types. The first set consists of points for which the orientation is known. The second set consists of points with an assigned normal of orientation. These sets are created by detection with manual or automatic methods using techniques of digital image processing. The interpolation works iteratively employing the averaging orientations in the 6-neighbourhood. The average of neighbouring orientations is calculated by determination of their principal axis.
With scanning confocal microscopy we obtained three-dimensional (3D) reconstructions of the transverse tubular system (t-system) of rabbit ventricular cells. We accomplished this by labeling the t-system with dextran linked to fluorescein or, alternatively, wheat-germ agglutinin conjugated to an Alexa fluor dye. Image processing and visualization techniques allowed us to reconstruct the t-system in three dimensions. In a myocyte lying flat on a coverslip, t-tubules typically progressed from its upper and lower surfaces. 3D reconstructions of the t-tubules also suggested that some of them progressed from the sides of the cell. The analysis of single t-tubules revealed novel morphological features. The average diameter of single t-tubules from six cells was estimated to 448172nm (mean SD, number of t-tubules 348, number of cross sections 5323). From reconstructions we were able to identify constrictions occurring every 1.871.09m along the principal axis of the tubule. The cross-sectional area of these constrictions was reduced to an average of 57.727.5% (number of constrictions 170) of the adjacent local maximal areas. Principal component analysis revealed flattening of t-tubular cross sections, confirming findings that we obtained from electron micrographs. Dextran- and wheat-germ agglutinin-associated signals were correlated in the t-system and are therefore equally good markers. The 3D structure of the t-system in rabbit ventricular myocytes seems to be less complex than that found in rat. Moreover, we found that t-tubules in rabbit have approximately twice the diameter of those in rat. We speculate that the constrictions (or regions between them) are sites of dyadic clefts and therefore can provide geometric markers for colocalizing dyadic proteins. In consideration of the resolution of the imaging system, we suggest that our methods permit us to obtain spatially resolved 3D reconstructions of the t-system in rabbit cells. We also propose that our methods allow us to characterize pathological defects of the t-system, e.g., its remodeling as a result of heart failure.
BACKGROUND AND PURPOSE: Atomoxetine is a selective noradrenaline reuptake inhibitor, recently approved for the treatment of attention-deficit/hyperactivity disorder. So far, atomoxetine has been shown to be well tolerated, and cardiovascular effects were found to be negligible. However, two independent cases of QT interval prolongation, associated with atomoxetine overdose, have been reported recently. We therefore analysed acute and subacute effects of atomoxetine on cloned human Ether-a-Go-Go-Related Gene (hERG) channels. EXPERIMENTAL APPROACH: hERG channels were heterologously expressed in Xenopus oocytes and in a human embryonic kidney cell line and hERG currents were measured using voltage clamp and patch clamp techniques. Action potential recordings were made in isolated guinea-pig cardiomyocytes. Gene expression and channel surface expression were analysed using quantitative reverse transcriptase polymerase chain reaction, Western blot and the patch clamp techniques. KEY RESULTS: In human embryonic kidney cells, atomoxetine inhibited hERG current with an IC(50) of 6.3 micromol.L(-1). Development of block and washout were fast. Channel activation and inactivation were not affected. Inhibition was state-dependent, suggesting an open channel block. No use-dependence was observed. Inhibitory effects of atomoxetine were attenuated in the pore mutants Y652A and F656A. In guinea-pig cardiomyocytes, atomoxetine lengthened action potential duration without inducing action potential triangulation. Overnight incubation with high atomoxetine concentrations resulted in a decrease of channel surface expression. CONCLUSIONS AND IMPLICATIONS: Whereas subacute effects of atomoxetine seem negligible under therapeutically relevant concentrations, hERG channel block should be considered in cases of atomoxetine overdose and when administering atomoxetine to patients at increased risk for the development of acquired long-QT syndrome.
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.
BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.
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.
The anticholinergic antiparkinson drug orphenadrine is an antagonist at central and peripheral muscarinic receptors. Orphenadrine intake has recently been linked to QT prolongation and Torsade-de-Pointes tachycardia. So far, inhibitory effects on I Kr or cloned HERG channels have not been examined. HERG channels were heterologously expressed in a HEK 293 cell line and in Xenopus oocytes and HERG current was measured using the whole cell patch clamp and the double electrode voltage clamp technique. Orphenadrine inhibits cloned HERG channels in a concentration dependent manner, yielding an IC50 of 0.85 μM in HEK cells. Onset of block is fast and reversible upon washout. Orphenadrine does not alter the half-maximal activation voltage of HERG channels. There is no shift of the half-maximal steady-state-inactivation voltage. Time constants of direct channel inactivation are not altered significantly and there is no use-dependence of block. HERG blockade is attenuated significantly in mutant channels lacking either of the aromatic pore residues Y652 and F656. In conclusion, we show that the anticholinergic agent orphenadrine is an antagonist at HERG channels. These results provide a novel molecular basis for the reported proarrhythmic side effects of orphenadrine
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.
Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization based on fluorescent labeling, three-dimensional scanning confocal microscopy, image processing and reconstruction of tissue micro-structure at sub-micrometer resolution. We applied this methodology to normal rabbit ventricular tissue and tissue from hearts with myocardial infarction. Our analysis revealed that the volume fraction of fibroblasts increased from 4.830.42% (meanstandard deviation) in normal tissue up to 6.510.38% in myocardium from infarcted hearts. The myocyte volume fraction decreased from 76.209.89% in normal to 73.488.02% adjacent to the infarct. Numerical field calculations on three-dimensional reconstructions of the extracellular space yielded an extracellular longitudinal conductivity of 0.2640.082 S/m with an anisotropy ratio of 2.0951.11 in normal tissue. Adjacent to the infarct, the longitudinal conductivity increased up to 0.4000.051 S/m, but the anisotropy ratio decreased to 1.2950.09. Our study indicates an increased density of gap junctions proximal to both fibroblasts and myocytes in infarcted versus normal tissue, supporting previous hypotheses of electrical coupling of fibroblasts and myocytes in infarcted hearts. We suggest that the presented methodology provides an important contribution to modeling normal and diseased tissue. Applications of the methodology include the clinical characterization of disease-associated remodeling. 1.
In open heart surgery the patient is connected to a heart-lung machine which pumps and oxygenizes the blood. The body core temperature is reduced by cooling the blood in a heat exchanger to reduce oxygen consumption of the tissues and so protect organs from hypoxia. Monitoring of vital parameters is crucial for safety of the patient. However, only little information is available from direct measurement. Models of haemodynamics and heat exchange in the human body are presented in this paper which provide the perfusionist with detailed data on blood flow and temperature in regions of the body which cannot be accessed by measurement devices. Simulation is performed on a real-time hardware platform which receives measured signals from the heart-lung machine via a serial interface.
Deep hypothermic circulatory arrest is necessary for some types of cardiac and aortic surgery. Perfusion of the brain can be maintained using a heart-lung machine and unilateral antegrade cerebral perfusion (ACP). Cooling rates during extracorporeal circulation depend on local perfusion. A core temperature of 24-25 degrees C is aimed at to extend ischemic tolerance of tissues. Information on cerebral perfusion and temperature is important for the safety of patients but hardly accessible to measurement. A combined simulation model of haemodynamics and temperature is presented in this paper. The haemodynamics model employs the transmission line approach and integrates the Circle of Willis. This allows for parametrization of individual aberrations. Simulation results of cerebral perfusion are shown for two configurations of the Circle of Willis. The temperature model provides spatial information on temperature fields. It considers heat transfer in the various tissues retrieving data of local tissue perfusion from the haemodynamics model. The combined model is evaluated by retrospective simulation of two aortic operations.
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).
Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (Kir)2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V Kir2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V Kir2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.
T. Seidel, J.-C. Edelmann, and F. B. Sachse. Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions. In Annals of Biomedical Engineering, vol. 44(5) , pp. 1436-1448, 2016
Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 microm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale.
The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling.
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.
U. Stilla, B. Friedmann, and K. Meyer-Waarden. Berechnung elektrischer Felder in biologischen Geweben auf der Basis von klassifizierten NMR-Bilddaten. In Biomedizinische Technik, vol. 32, pp. 288-292, 1987
BACKGROUND: There are no published data showing the three-dimensional sequence of repolarization and the associated potential fields in the ventricles. Knowledge of the sequence of repolarization has medical relevance because high spatial dispersion of recovery times and action potential durations favors cardiac arrhythmias. In this study we describe measured and simulated 3-D excitation and recovery sequences and activation-recovery intervals (ARIs) (measured) or action potential durations (APDs) (simulated) in the ventricular walls.METHODS: We recorded from 600 to 1400 unipolar electrograms from canine ventricular walls during atrial and ventricular pacing at 350-450 ms cycle length. Measured excitation and recovery times and ARIs were displayed as 2-D maps in transmural planes or 3-D maps in the volume explored, using specially developed software. Excitation and recovery sequences and APD distributions were also simulated in parallelepipedal slabs using anisotropic monodomain or bidomain models based on the Lou-Rudy version 1 model with homogeneous membrane properties.RESULTS: Simulations showed that in the presence of homogeneous membrane properties, the sequence of repolarization was similar but not identical to the excitation sequence. In a transmural plane perpendicular to epicardial fiber direction, both activation and recovery pathways starting from an epicardial pacing site returned toward the epicardium at a few cm distance from the pacing site. However, APDs were not constant, but had a dispersion of approximately 14 ms in the simulated domain. The maximum APD value was near the pacing site and two minima appeared along a line perpendicular to fiber directions, passing through the pacing site. Electrical measurements in dog ventricles showed that, for short cycle lengths, both excitation and recovery pathways, starting from an epicardial pacing site, returned toward the epicardium. For slower pacing rates, pathways of recovery departed from the pathway of excitation. Highest ARI values were observed near the pacing site in part of the experiments. In addition, maps of activation-recovery intervals showed mid-myocardial clusters with activation-recovery intervals that were slightly longer than ARIs closer to the epi- or endocardium, suggesting the presence of M cells in those areas. Transmural dispersion of measured ARIs was on the order of 20-25 ms. Potential distributions during recovery were less affected by myocardial anisotropy than were excitation potentials
Experimental investigations of the nonlinear properties of superconducting niobium coplanar waveguide resonators are reported. The nonlinearity due to a current dependent kinetic inductance of the center conductor is strong enough to realize bifurcation of the nonlinear oscillator. When driven with two frequencies near the threshold for bifurcation, parametric amplification with a gain of +22.4 dB is observed.
There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.
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.
G. Vossius. [Possibilities of functional electrostimulation in clinical use]. In Biomedizinische Technik. Biomedical Engineering, vol. 35 Suppl 3, pp. 115-117, 1990
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.
Pyramidal GaAs structures on top of GaAs/AlAs distributed Bragg reflectors are investigated as candidates for true three-dimensional cavities with potentially low mode volume and high quality-factor. Different types of single and coupled resonators with base lengths of a few microns are realized using a combination of molecular-beam epitaxy, electron-beam lithography, and wet chemical etching. Embedded InGaAs quantum dots are utilized as light sources to verify the resonator modes. Furthermore, a spatially localized emission through the pyramid facets indicates the future possibility of coupling cavity modes to optical fibers. This could be interesting within the context of single photon emitters.
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
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.
D. L. Weiss, M. Ifland, F. B. Sachse, G. Seemann, and O. Dössel. Modeling of cardiac ischemia in human myocytes and tissue including spatiotemporal electrophysiological variations / Modellierung kardialer Ischämie in menschlichen Myozyten und Gewebe. In Biomedizinische Technik/Biomedical Engineering, vol. 54(3) , pp. 107-125, 2009
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.
Bioelectric source measurements are influenced by the measurement location as well as the conductive properties of the tissues. Volume conductor effects such as the poorly conducting bones or the moderately conducting skin are known to affect the measurement precision and accuracy of the surface electroencephalography (EEG) measurements. This paper investigates the influence of age via skull conductivity upon surface and subdermal bipolar EEG measurement sensitivity conducted on two realistic head models from the Visible Human Project. Subdermal electrodes (a.k.a. subcutaneous electrodes) are implanted on the skull beneath the skin, fat, and muscles. We studied the effect of age upon these two electrode types according to the scalp-to-skull conductivity ratios of 5, 8, 15, and 30 : 1. The effects on the measurement sensitivity were studied by means of the half-sensitivity volume (HSV) and the region of interest sensitivity ratio (ROISR). The results indicate that the subdermal implantation notably enhances the precision and accuracy of EEG measurements by a factor of eight compared to the scalp surface measurements. In summary, the evidence indicates that both surface and subdermal EEG measurements benefit better recordings in terms of precision and accuracy on younger patients.
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.
. Functional Imaging and Modeling of the Heart. Springer, 2007.
This book constitutes the refereed proceedings of the 4th International Conference on Functional Imaging and Modeling of the Heart, FIMH 2007, held in Salt Lake City, UT, USA in June 2007.The 48 revised full papers presented were carefully reviewed and selected from numerous submissions. The contributions describe both experimental and computational studies and cover topics such as imaging and image analysis, cardiac electrophysiology, electro- and magnetocardiography, cardiac mechanics and clinical application, imaging and anatomical modeling.
A. Bolz, and W. Urbaszek. Technik in der Kardiologie: Eine interdisziplinäre Darstellung. Berlin, Heidelberg: Springer, 2002.
Diagnose und Therapie von Herz-Kreislauf-Erkrankungen erfordern eine immer engere Zusammenarbeit von Ärzten, Naturwissenschaftlern und Ingenieuren. Das vorliegende Lehrbuch wagt daher den Versuch eines Brückenschlages zwischen den Disziplinen. Im ersten Drittel werden die medizinischen Grundlagen der wichtigsten Herz-Kreislauffunktion und -erkrankungen vermittelt. Auf dieser Basis wird der Aufbau und die Funktionsweise der bekannten Diagnose- und Therapieverfahren aus dem Bereich der Kardiologie erläutert. Dies umfasst sowohl den aktuellen Stand der Technik als auch die neuesten Trends.Das Buch richtet sich somit an Studierende, Lernende und Praktizierende in medizinischen, natur- und ingenieurwissenschaftlichen Berufen. Ziel des Buches ist es, ein gegenseitiges VerstAndnis zu wecken, um neue Techniken sinnvoll entwickeln und sicher anwenden zu können
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
A. Hahn. Realisierung eines mikrowellenbasierten Tomographie-Systems zur Schlaganfalldiagnose. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT), Karlsruhe. 2015.
Stroke is one of the main causes of death in western society. Regarding the two types, hemmorrhagic or ischemic stroke, fundamentally different treatment is necessary. In diagnosis of stroke, several imaging technologies like CT or MRT are already established but very expensive und not transportable. Microwave tomography is a promising technology to create a solution in order to improve diagnosis of hemorrhagic stroke. The developement of a measurement setup utilized for stroke detection is done using FDTD- Simulation to test the design and antennas. In this work, the approach was performed using a rectangular antenna-array with Vivaldi antennas for measurement. Therefor, a simple but realistic head-phantom with permittivity values comparable to human tissue was used. The simulation and measurement results are calculated by a software framework. It includes forward calculation using the MEEP-Framework and Gauss- Newton optimization for the update of values. The ill-posed inverse Problem is regularized by Tikhonov algorithm.
E. Konecny, and W. Nahm. Physikalische Messtechniken in der Medizin. Zentrum für Fernstudien & universitäre Weiterbildung, UNI Kaiserslautern, 1996.
M. Reumann, M. Mohr, O. Dössel, and A. Diez. Vorlesung, Übung und Tutorium im koordinierten Zusammenspiel. Ein Lehr-/Lernpaket schnüren - Grundlagenveranstaltung. Berendt, Brigitte, 2006.
F. B. Sachse. Computational cardiology : modelling of anatomy, electrophysiology, and mechanics. Springer, Heidelberg. 2004.
Book Chapters (38)
J. Abke, W. Nahm, and E. Konecny. Implementierung einer Bispektralanalyse in LabVIEW zur Beurteilung von Narkosetiefe über das EEG. In Virtuelle Instrumente in der Praxis - Meßtechnik, R. Jamal, H. Jaschinski (eds), VDE-Verlag, pp. 256-264, 1998
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
M. Daumer, W. Nahm, M. Scholz, and F. Danneger. Online Monitoring mit virtuellen Instrumenten. In Virtuelle Instrumente in der Praxis - Meßtechnik, R. Jamal, H. Jaschinski (eds), VDE-Verlag, pp. 265-270, 1998
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.
O. Doessel. Neue Materialien für Sensoren mit Dünnfilm-Dehnungsmeßstreifen. In Sensoren, Meßaufnehmer, expert verlag, pp. , 1987
O. Doessel. Neue Materialien für Sensoren mit Dünnfilm-Dehnungsmeßstreifen. In Sensoren/Meßaufnehmer, K. Bonfig (eds), Technische Akademie Esslingen, pp. 7-1, 1986
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
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
J. Petersen, G. Stockmanns, and W. Nahm. EEG Analysis for Assessment of Depth of Anaesthesia. In Fuzzy Systems in Medicine, P. Szczepaniak, P. Lisboa, J. Kacprzyk (eds), Physica-Verlag, Heidelberg, pp. , 2000
Up to now one unsolved challenge in anaesthesia is the assessment of depth of anaesthesia during surgery. No general purpose on-line monitoring system predicting depth or quality of anaesthesia exists. The analysis of spontaneous (EEG) and evoked electrical brain activities (AEP) leads to methods assessing depth of anaesthesia. A monitor concept was developed consisting of the three functional components EEG recorder, pre-processor and knowledge based discriminator including an inductive learning algorithm generating fuzzy decision trees. By their statistical evaluation feature vectors for training Kohonen networks are selected aplied for re-classification tests of clinical study data.
F. B. Sachse, G. Seemann, and R. Mayer. Modelling of Electro-Mechanics in the Heart: Mathematical and Numerical Aspects. In High Performance Scientific Computing, W. Juling (eds), Scientific Supercomputing Center Karlsruhe, pp. 36-37, 2003
F. B. Sachse, C. D. Werner, and G. Seemann. Simulation of Cardiac Electrophysiology and Electrocardiography. In Computer Simulation and Experimental Assessment of Cardiac Electrophysiology, N. Virag, O. Blanc, L. Kappenberger (eds), Futura Publishing, Armonk, New York, pp. 97-104, 2001
G. Seemann, M. W. Krueger, and M. Wilhelms. Elektrophysiologische Modellierung und Virtualisierung für die Kardiologie - Methoden und potenzielle Anwendungen. In Der virtuelle Patient, W. Niederlag, H. Lemke, H. Lehrach (eds), Health Academy, pp. 98-116, 2012
Simulationen des elektrophysiologischen Verhaltens des Herzens fördern das Verständnis über die Mechanismen innerhalb des Herz-Kreislauf-Systems. Darüber hinaus werden diese mathematischen Modelle die Diagnose und Therapie von Patienten, die unter Herzerkrankungen leiden, unterstützen. In dieser Arbeit wird die Vorgehensweise für die Modellierung der elektrischen Funktion des Herzens beschrieben. Hierfür werden die Modellierung der Geometrie, der kardialen Elektrophysiologie, der elektrischen Erregungsausbreitung und der EKG-Berechnung kurz erläutert. Die seit Kurzem mehr und mehr untersuchten Fälle Ischämie und personalisierte Vorhofmodellierung werden beispielhaft beschrieben und zeigen, wie die Modellierung des Herzens dazu benutzt werden kann, um Kardiologen bei der Beantwortung von offenen Fragen zu unterstützen.
M. 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
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 chang