Targeting rotor sites with ablation did not stop reentries in the homogeneously remodelled atria independent from lesion size 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. This study hypothesized that P-wave morphology and timing under left atrial appendage LAA pacing change characteristically immediately upon anterior mitral line AML block.
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. Furthermore, an initial negative P-wave portion in the inferior leads was observed, which was attenuated in case of additional cavotricuspid isthmus ablation.
V1 jump and V1 delay are novel real-time electrocardiography criteria allowing fast and straightforward assessment of AML block during ablation for perimitral flutter. 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.
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.
A speed of 0. For clinical cases, the CV magnitude range of 0. The P2P amplitude of 0.
Synonyms and antonyms of Solution in the German dictionary of synonyms
The correlation of 0. In this paper, a method is presented and validated which calculates the CV for the deformed catheter and changing wall contact. 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.
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 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. 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. 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. 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. 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. In den Lebenswissenschaften ist die Individualisierte Medizin aktuell ein zentrales Thema, vielleicht ein Hype.
Individualisierte Medizin, das ist eine gute Botschaft, betont sie doch die Wertigkeit des einzelnen Patienten. Die Behandlung dieser Gebiete bedarf einer separaten nachfolgenden Betrachtung. 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. Wichtige Grenzen der wissenschaftlichen Politik- bzw. Das setzt eine Selbstbegrenzung voraus. Das bedarf immer einer gegenseitigen kritischen Begleitung. Die Wissenschaft dient dem Erkenntnisgewinn.
Wenn dieses angenommen, akzeptiert werden kann, dann sind die Technikwissenschaften Wissenschaften, dann betreiben Radiologie und Nuklearmedizin Wissenschaft science. Wissenschaft wird von Menschen betrieben und getragen. Bildgebung in Klinik und Forschung: Beitrag zur Individualisierten Medizin?
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. 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. 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. 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 In conclusion, the algorithm is suitable for handling varying P wave shapes and low signal-to-noise ratios.
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: Using synthetic input data and different ion current formulations from the Courtemanche et al. 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. 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.
Clinical data for analysis was exported from electroanatomical mapping systems. 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. 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 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.
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. 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.
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. This web interface provides efficient, search, browsing, and retrieval of data from the repository. 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.
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. Analysis of clinical data confirmed these findings. Its concept and performance were benchmarked against PCA using simulated data and demonstratedon measured electrograms.
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. 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. 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.
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 predefined electrograms. In addition, a percentage of certainty is given for each electrogram to enable a comprehensive and transparent decision. 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.
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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. 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. 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. 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 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. 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.
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. 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. 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. In addition, image quality improvement is demonstrated for clinical whole heart C-arm CT data sets when the cable removal algorithm was applied. 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.
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. These changes mainly occurred in the first 10 s after ablation onset. 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.
Left atrial fibrosis is thought to contribute to the manifestation of atrial fibrillation AF. 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. 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: Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard lead ECG.
To this end, a simulation study was performed for 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: 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: 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. 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. Spiral waves could be initiated by using mutation models as opposed to the control case. The frequency dependency of the VW was reversed. 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 LP than for NK. Furthermore, spiral waves presented higher stability and a more regular pattern for LP. These in silico investigations unveiling differences of mutations affecting the same ion channel may help to advance genotype-guided AF prevention and therapy strategies. 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. 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 A 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. 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.
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.
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.
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. 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. 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. 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. 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. 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. 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.
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. 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.
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. 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.
SOLUTION - Definition and synonyms of Solution in the German dictionary
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. 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. 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. 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. Several anti-arrhythmic drugs such as e. However, the electrophysiological mechanisms underlying the initiation and persistence of AF are not completely understood yet. 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. 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. Dronedarone and amiodarone prolonged the atrial action potential duration of cAF cells, whereas high concentration of amiodarone slightly shortened it in healthy cells.
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.
Meaning of "Solution" in the German dictionary
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.
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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 lead electrocardiograms were derived. Both cisapride and amiodarone caused a prolongation of the QT interval and the refractory period. Examples of use in the German literature, quotes and news about Solution. Mit der Version 7. Wie in Kapitel 3. Solution of a question 69 J. Solution of a question 70 Whitworth. Solution of a question 70 A. Solution of a question.
Solution of a question 70 M. Ingrid Reisch, Kirsten Dierolf, Der Sicherheitsexperte und international SAP Solution Manager 7. Mit der neuen Version 7. Neuer Name, gleicher Abzock-Trick: