Abstract:

The Purkinje system is part of the fast-conducting ventricular excitation system. The anatomy of the Purkinje system varies from person to person and imposes a unique excitation pattern on the ventricular myocardium, which defines the morphology of the QRS complex of the ECG to a large degree. While it cannot be imaged in-vivo, it plays an important role for personalizing computer simulations of cardiac electrophysiology. Here, we present a new method to automatically model and customize the Purkinje system based on the measured electrocardiogram (ECG) of a patient. A graphbased algorithm was developed to generate Purkinje systems based on the parameters fibre density, minimal distance from the atrium, conduction velocity, and position and timing of excitation sources mimicking the bundle branches. Based on the resulting stimulation profile, the activation times of the ventricles were calculated using the fast marching approach. Predescribed action potentials and a finite element lead field matrix were employed to obtain surface ECG signals. The root mean square error (RMSE) between the simulated and measured QRS complexes of the ECGs was used as cost function to perform optimization of the Purkinje parameters. One complete evaluation from Purkinje tree generation to the simulated ECG could be computed in about 10 seconds on a standard desktop computer. The measured ECG of the patient used to build the anatomical model was matched via parallel simplex optimization with a remaining RMSE of 4.05 mV in about 16 hours. The approach presented here allows to tailor the structure of the Purkinje system through the measured ECG in a patient-specific way. The computationally efficient implementation facilitates global optimization.

Abstract:

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.

Abstract:

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.

Abstract:

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.

Abstract:

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.

Abstract:

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 [1]. Diese Initiative wurde inhaltlich wesentlich vom Direktor des National Institute of Health, dem Genetiker Francis Collins, vorangetrieben [2]. 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 [3].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. [4].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 [5]. 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.

Abstract:

A miniaturized ceramic atmospheric plasma source for the utilization in life sciences has been developed. It is manufactured in LTCC-technology (low temperature cofired ceramic). The plasma generation is based on buried electrodes which lead to a Dielectric Barrier Discharge (DBD). The employed technology allows small feature sizes (electrode width 150 μm, barrier thickness 40μm etc.) as well as precision in the μm range, resulting in a very low power consumption of the system (approx. 5 W). Thus, the maximum temperature at the point of use can be kept below 40 °C. The flexibility of the manufacturing process (layer lamination, screen printing, patterning with picosecond laser etc.) offers additional features like robust fluidic structures (channels, chambers, gas distribution etc.) as well as the direct implementation of electronic components. The technology concept as well as the design of the ceramic parts and the handhold matched to the multi-well plate format is demonstrated. The plasma of the system can be tuned depending on the assembly of the system and the electric excitation. To prove the biocompatibility and the experimental compatibility with cell cultures (low temperature at the point of use), a method for temperature measurements on the bottom of a multi-well plate was developed. First results of the impact of the plasma source on cell cultures are presented. The effects occurring in the plasma, as well as their effects on the cell cultures (ozone formation, ultraviolet radiation etc.) are separately considered. Furthermore, the cell tolerability of the treatment with the micro-plasma source is investigated with L929 fibroblast cells.

Abstract:

Generating meshes of complex structures in the human body like the heart organ is a prerequisite for computational simulations of of organ function. The quality of the conclusions derived from these simulations greatly depends on the quality and accuracy of the mesh they are based on. Volumetric computation domain can be represented by an equally-spaced voxel grid, or – in case of more sophisticated partial differential equation discretization methods (finite elements, finite volumes) – first, second or even higher order tetrahedral meshes. Here, we present a workflow that is capable of creating high quality meshes for such simulations. The workflow contains segmentation, surface mesh generation, volume mesh generation, and patient-specific parameter fitting to produce the desired results. While segmentation itself is a more or less unique mapping from a grayscale DICOM data set to a labeled, three-dimensional voxel mesh, different approaches exist for their transformation to a surface mesh. Our process involves a two-level approach for obtaining triangular or mixed rectangular surface meshes of desired quality and resolution. Both are crucial for the next step: obtaining a volumetric tetrahedral grid with the desired degrees of freedom. In the last step, a derivative-free parameter estimation approach is used to calibrate the dynamic behavior and tailor the model patient-specifically. All software used in the workflow is published under open source licenses and freely available. Its capability is demonstrated by means of an elastomechanical simulation of a human heart and yields measurable validation quantities in physiological ranges. We want to stress that the presented approach is generic and can easily be used for the model generation of other organs like liver, lungs or the aortic arch as well. The resulting meshes can be used for various types of simulations (electrical excitation propagation, blood flow) and use cases (clinical diagnostics, therapy planning etc.).

Abstract:

Nowadays, the surgical microscope is the goldstandard for microsurgical procedures. Additional functionalities such as surgical navigation, data injection or imageoverlay are providing additional valuable information to the surgeon. For substituting the conventional optical system by a fully-digital multi-camera setup the three dimensional (3D) reconstruction of the scenery in the field of view is required. However, for in camera-based systems, an exact alignment of the cameras is a challenging task. Therefore, a final adjustment through a digital image rotation becomes necessary. Even though the digital rotation is a commonly used procedure, it leads to unavoidable errors because of the discretized grid of the image. Previous research reported in literature has demonstrated that the method of digitally rotating the images combined with the Fourier interpolation delivers the results of best quality. Nevertheless, the performance evaluation of this algorithm was carried out rotating an image in multiple threestep rotations to a total of 90 or 180 degrees and comparing it to the original image rotated in one step. This is a valid approach because a rotation of 90 or 180 degrees does not produce rotation artifacts. In this research project, we verify the performance of the three-step rotation algorithm using recorded images for which the test pattern was rotated as ground truth. A series of photographs with a rotation angle of 3 to 45 degrees was created. The advantage of this setup is that the result of the digital rotation can be directly compared to the recorded image. In addition, with the knowledge obtained about the interpolation error, we can improve pixel matching in the further triangulation used for 3D reconstruction. By doing so, the estimation of the interpolation error helps to reduce the triangulation error.

Abstract:

Today, patients suffering from atrial arrhythmias like atrial flutter (AFlut) or atrial fibrillation (AFib) are examined in the EP-lab (electrophysiology lab) in order to understand and treat the disease. Multichannel catheters are advanced into the atria in order to measureelectric signals at manyintracardiacpositions simultaneously. Complementary to clinical learning,comprehension of the disease and therapeutic strategies can be improved with computer modeling of the heart. This way, hypotheses about initiation and perpetuation of the arrhythmia can be tested and ablation strategies can be assessed in-silico. Modeling and biosignal analysis can benefit from mutual fertilization. On the one hand, modeling can be improved and personalization can be achieved via high density mapping of the atria. On the other hand, new algorithms for the interpretation of multichannel electrograms can be developed and evaluated with synthetic signals from computer models of the atria. This article illustrates the synergetic potential by examples and highlights challenges to be addressed in the future.

Abstract:

Cardiac arrhythmias are a widely spread disease in industrialized countries. A common clinical treatment for this disease is radiofrequency ablation (RFA), in which high frequency alternating current creates a lesion on the myocardium. However, the formation of the lesion is not entirely understood. To obtain more information about ablation lesions (ALs) and their electrophysiological properties, we established an in-vitro setup to record electrical activity of rat myocardium. Electrical activity is measured by a circular shaped multielectrode array. This work was focused to gain more information by developing algorithms to process the measured electrical signals to collect different features, which may allow us to characterize an AL. First, pacing artefacts were detected and blanked. Subsequently, data were filtered. Afterwards, activations in atrial signals were detected using a non-linear energy operator (NLEO) and templates of these activations were generated. Finally, we determined different features on each activation in order to evaluate changes of unipolar as well as bipolar electrograms and considered these features before and after ablation. In conclusion, the majority of the signal features delivered significant differences between normal tissue and lesion. Among others, a reduction in peak to peak amplitude and a diminished spectral power in the band 0 to 100 Hz may be useful indicators for AL. These criteria should be verified in future studies with the aim of estimating indirectly the formation of a lesion.

Abstract:

We examined if ECG-based features are discrimi-native towards drowsiness. Twenty-five volunteers (1932 years) completed 7×40 minutes of monotonous overnight driving simulation, designed to induce drowsiness. ECG (512 s-1) was recorded continuously; subjective ratings of drowsiness on the Karolinska sleepiness scale (KSS) were polled every five minutes. ECG recordings were divided into 5-min segments, each associated with the mean of one self- and two observer-KSS ratings. Those mean KSS values were binarized to obtain two classes not drowsy and drowsy. The Q-, R- and T-waves in the recordings were detected; R-peak positions were manually reviewed; the Q- and T-detection method was tested against the manual annotations of Physio-nets QT database. Power spectral densities of RR intervals (RR-PSD) and quantiles of the empirical distribution of heart-rate corrected QTc intervals were estimated. Support-vector machines and random-holdout cross-validation were used for the estimation of the classification error. Using either RR-PSD or QTc features yielded mean test errors of 79.3 ± 0.3 % and 82.7 ± 0.5 %, respectively. Merging RR and QTc features improved the accuracy to 88.3 ± 0.2 %. QTc intervals of the class drowsy were generally prolonged com-pared to not drowsy. Our findings indicate that the inclusion of QT intervals contribute to the discrimination of driver sleepiness.

Abstract:

Atrial arrhythmias such as atrial flutter and atrial fibrillation are a burden for patients and a major challenge for modern healthcare systems. Identification of patients at risk to develop atrial arrhythmias at an early stage carries the potential to reduce the incidence by implementing appropriate strategies to mitigate the risks. Diagnostic methods based on the ECG are ideal risk markers due to their noninvasiveness and omnipresence. The left atrium (LA) plays a major role in the intiation and perpetuation of atrial reentry arrhythmias. However, the LA is not well represented in the P-wave derived through standard ECG leads. Here, we optimize ECG lead positions to maximize LA information content. Towards this end, we used a cohort of eight personalized computational models providing the unique opportunity to separate LA and right atrial (RA) contributions to the P-wave, which is not feasible in vivo. The location of maximum P-wave signal energy was located on the center of the chest for all subjects with marked overlap between regions of maximum LA and RA P-wave amplitude. The regions of highest ratio between LA and RA signal energy differed between patients. However, a region with LA signal energy being higher than that of the RA and providing a sufficiently large absolute P-wave amplitude was identified at the center of the back consistently across five models of the cohort. Optimized linear combinations of standard 12-lead signals yielded comparably good results. Our newly proposed electrode positions on the back as well as selected linear combinations of standard 12-lead signals improve the LA information content considerably. By using these, more relevant diagnostic information regarding the anatomical and electrophysiological properties of the LA can be derived in future.

Abstract:

Chronic kidney disease (CKD) affects more than 30 million patients in the European Union. CKD causes alterations in the extracellular plasma electrolyte concentrations, which affect cardiac electrophysiology. A total of 25% of all deaths of CKD patients are due to sudden cardiac death (SCD). Until recently, ventricular fibrillation was assumed to be the main reason. In a 2015 study, Wong et al. observed bradycardia and asystole as the predominant mechanisms of SCD in patients with CKD. This shows that the influence of electrolyte changes on the underlying mechanisms of pacemaking in the sinoatrial node (SAN) needs to be better understood. In this work, we have updated the computational model of the human SAN given by Fabbri et al. and investigated the CKD-induced change of [Ca2+]o (0.6-3mM), [K+]o (3-9mM) and [Na+]o (120-150mM) on pacemaking. [Ca2+]o had the most dominant effects on SAN function. Low [Ca2+]o caused severe bradycardia in the model (down to 17 bpm) for 0.6 mM. A critical concentration range of calcium in the subspace [Ca2+]sub was identified as the possible underlying mechanism for pacemaking. For increasing [Ca2+]o, the heart rate (HR) increased, resulting in 142 bpm for the highest calcium concentration. The effect of [K+]o variation was similar to the one for [Ca2+]o, but caused less pronounced change. The resultant changes due to variation of [Na+]o were relatively small. In this work, several potential mechanisms for SCD in CKD patients could be identified. The low HR for low [Ca2+]o is seen as a possible link to the observed bradycardia in CKD patients. The findings in this work could lead to a better surveillance of [Ca2+]o in hemodialysis patients, and therefore to a decrease in the SCD rate.

Abstract:

Future fully digital surgical visualization systems enable a wide range of new options. Caused by optomechanical limitations a main disadvantage of todays surgical microscopes is their incapability of providing arbitrary perspectives to more than two observers. In a fully digital microscopic system, multiple arbitrary views can be generated from a 3D reconstruction. Modern surgical microscopes allow replacing the eyepieces by cameras in order to record stereoscopic videos. A reconstruction from these videos can only contain the amount of detail the recording camera system gathers from the scene. Therefore, covered surfaces can result in a faulty reconstruction for deviating stereoscopic perspectives. By adding cameras recording the object from different angles, additional information of the scene is acquired, allowing to improve the reconstruction. Our approach is to use a fixed four-camera setup as a front-end system to capture enhanced 3D topography of a pseudo-surgical scene. This experimental setup would provide images for the reconstruction algorithms and generation of multiple observing stereo perspectives. The concept of the designed setup is based on the common main objective (CMO) principle of current surgical microscopes. These systems are well established and optically mature. Furthermore, the CMO principle allows a more compact design and a lowered effort in calibration than cameras with separate optics. Behind the CMO four pupils separate the four channels which are recorded by one camera each. The designed system captures an area of approximately 28mm × 28mm with four cameras. Thus, allowing to process images of 6 different stereo perspectives. In order to verify the setup, it is modelled in silico. It can be used in further studies to test algorithms for 3D reconstruction from up to four perspectives and provide information about the impact of additionally recorded perspectives on the enhancement of a reconstruction.

Abstract:

In neurovascular surgery the intraoperative fluorescence angiography has been proven to be a reliable contact-free optical imaging technique to visualize vascular blood-flow. This angiography is obtained by injecting a fluorescence dye e.g. indocyanine green and using an infrared camera system to visualize the fluorescence inside the vessel. Obviously this requires a medical approved dye and an additional camera setup and therefore generating risks and costs. Hence, the aim of our research is to develop a comparable technique for assessing the vascular function. This approach would not require dye nor an additional infrared camera setup. It is achieved by first preprocessing the video data of a camera that records only the visible spectrum and then filter it spatially as well as temporally. The prepared data is again processed to extract information about the vascular function and visualize it. This method would provide an option to compute and visualize the vascular function using the data recorded in the visible spectrum by the surgical microscopes. Given this contact-free optical imaging system, physiological information can be easily provided to the surgeon without an additional setup. In the case of comparable results with the state-of-the-art, this technique provides a straightforward optical intraoperative angiography. Further no drug approval is needed since no dye is injected.

Abstract:

Lung ventilation and perfusion analyses using chest imaging methods require a correct segmentation of the lung to offer anatomical landmarks for the physiological data. An automatic segmentation approach simplifies and accelerates the analysis. However, the segmentation of the lungs has shown to be difficult if collapsed areas are present that tend to share similar gray values with surrounding non-pulmonary tissue. Our goal was to develop an automatic segmentation algorithm that is able to approximate dorsal lung boundaries even if alveolar collapse is present in the dependent lung areas adjacent to the pleura. Computed tomography data acquired in five supine pigs with injured lungs were used for this purpose. First, healthy lung tissue was segmented using a standard 3D region growing algorithm. Further, the bones in the chest wall surrounding the lungs were segmented to find the contact points of ribs and pleura. Artificial boundaries of the dorsal lung were set by spline interpolation through these contact points. Segmentation masks of the entire lung including the collapsed regions were created by combining the splines with the segmentation masks of the healthy lung tissue through multiple morphological operations. The automatically segmented images were then evaluated by comparing them to manual segmentations and determining the Dice similarity coefficients (DSC) as a similarity measure. The developed method was able to accurately segment the lungs including the collapsed regions (DSCs over 0.96).

Abstract:

Cardiac excitation during atrial fibrillation (AFib) is changing dynamically, compromising the ability to identify underlying mechanisms by intracardiac catheter mapping. Statistical analysis of dominant excitation patterns may help to identify and subsequently eliminate the drivers of this tachycardia. As the morphology of local bipolar intracardiac electrograms (EGMs) depends on the orientation of the propagating excitation wave, its evaluation for a fixed multichannel catheter position can provide information about the stability of the depolarization pattern. Up to date, analysis of morphology is most often done by computing a similarity index or the recurrence rate of individual EGMs, reflecting how often similar excitations appear. We sougth to extend this approach to a classification based analysis technique. In each multichannel EGM, local activation waves (LAWs) were automatically detected by assessing instantaneous signal energy. A greedy algorithm was implemented to cluster LAWs based on their similiarity. New clusteres were formed when similarity fell below a predefined threshold. The concept was tested using simulated EGM data (quadratic patch of cardiac tissue, bidomain simulation, both planar and focal excitations, various catheter types). Results demonstrated that the algorithm correctly identified and classified the simulated excitation patterns. Subsequent quantitative analysis allowed to both discard singular classes of excitation and identify dominant excitations. The presented method forms the basis for statistical assessment of prevailing depolarization patterns, and for computation of additional features like conduction velocity, presence of focal sources, or dissociation when applied on multichannel data.

Abstract:

A common treatment of focal ventricular tachycardia is the catheter ablation of triggering sites. They have to be found manually by the physician during an intervention in a catheter lab. Thus, a method for determining the position of the focus automatically is desired. The inverse problem of electrocardiography addresses this problem by reconstructing the source of the ectopic beats using the surface ECG. This problem is ill-posed and therefore needs specific methods for solving it. We propose a machine learning approach for localisation of the ectopic foci in the heart to assist cardiologists with their therapy planning.We simulated 600 120-lead ECGs with different known excitation origins in the heart using a cellular automaton followed by a forward calculation. Features from the ECGs were used as input for a support vector regression (SVR). We assumed a functional relation between features from the ECG and the excitation origin. To benchmark SVR, we also used the well-known Tikhonov 0th order regularisation to reconstruct the transmembrane potentials in the heart and detect the location of the ectopic foci. Parameters for SVR and regularisation were chosen using a grid search minimising the error between estimated and true excitation origin. Compared to the Tikhonov regularisation method, SVR achieved a smaller deviation between estimated and real excitation origin evaluated with 6-fold cross validation. Future work could investigate on the behaviour on data from simulations with other torso and electrophysiological models, the influence of other methods for feature extraction and finally the evaluation with clinical data.

Abstract:

Hyperthermia during radiofrequency ablation causes reversible and irreversible changes of the electrophysiological properties of cardiac tissue. However, the mechanisms are incompletely understood. We studied changes of conduction velocity (CV) in rat myocardium under hyperthermic conditions from macroscopic to microscopic scale by using simultaneous optical mapping and a miniaturized electrode array. Atrial preparations from five rats were superfused at tissue bath temperatures between 36.7°C and 43.8°C. Optical mapping data showed an elevated median CV by 21% when increasing the temperature from 36.7°C to 42.0°C. CV did not increase above 42.0°C. Electrical measurements revealed a similar temperature dependence of CV between 36.7°C and 42.0°C, i.e. an increase of median CV by 26%. The consolidation of optical and electrical data in this study allowed investigation of excitation during global hyperthermia. Macroscopic optical mapping and microscopic electrical measurements demonstrated that hyperthermia strongly influenced electrical propagation at a microscopic scale.

Abstract:

Radiofrequency ablation is the gold standard for treating cardiac arrhythmias. However, the success rate of this procedure depends on numerous parameters. Wet lab experiments provide the opportunity to investigate cardiac electrophysiology under reproducible conditions. To evaluate the electrophysiological changes of ablated myocardium in these studies it is necessary to consider the three-dimensional (3D) geometry of the lesions. For this purpose, we investigated the usage of different magnetic resonance imaging (MRI) sequences as well as an image processing procedure to analyze in-vitro preparations. To differentiate signal intensities between nonablated and ablated tissue we evaluated FISP (fast imaging with steady-state precession; delivering dominantly T1-weighted images) and RARE (rapid acquisition with relaxation enhancement; delivering dominantly T2-weighted images). After image processing, the ablated tissue was segmented in each image slice forming a 3D volume. The geometry of the lesion was modeled by the boundary of this volume. It was generally feasible to distinguish between healthy myocardium and ablated tissue as well as to determine lesion transmurality. The analysis of the reconstructed lesion geometries from FISP and RARE MRI showed a high agreement, however T2-weighted sequences showed larger lesion volumes as well as higher variations in segmentation compared to T1- mapping. FISP with higher quality may be used to reconstruct the 3D geometry of the ablation lesions.

Abstract:

Modelling the interaction of the heart and the vascular system allows to study the pumping efficiency of the heart in a controlled environment under various cardiac and vascular conditions such as arrhythmias, dyssynchronies, regions of stiffened myocardium, valvular stenoses or decreased vascular compliances. To pose realistic hemodynamic boundary conditions to a four-chambered elastomechanical heart model, we developed a lumped element model of the closed loop human vascular system. Systemic and pulmonary circulations were each represented by a three-element Windkessel model emptying into a venous compliance. Both circulations were coupled by connecting the venous compliances to the corresponding atrium via venous resistances. Cardiac valves were represented by ideal diodes and resistances. Strong coupling between the heart and the vascular system model was accomplished by estimating the cardiac pressures that lead to continuous flows across the model interfaces. Active regulatory mechanisms were not considered. Pressures, flows and volumes throughout the circulatory system were simulated until a steady state was reached and the effects of model parameters on these hemodynamic parameters were evaluated in a sensitivity analysis. Increasing the systemic peripheral resistance by 50% caused an 8% decrease in stroke volume (SV) and a 33% increase in mean arterial pressure. Increased venous resistance descreased the E/A wave ratio of the atrioventricular flow and led to a reduced SV by impeding passive cardiac filling. Increasing the arterial compliance decreased mean cardiac pressures, while only slightly reducing the SV. Larger arterial resistances mainly caused higher peak systolic pressures. Furthermore, we show that embedding the heart model into surrounding elastic tissue by forcing permanent contact at the pericardial surface leads to more realistic time courses of atrial volumes and atrial pressure-volume curves composed of an A and a V loop as found in measurements. In conclusion, this work enables simulations of diseases that involve significant cardiovascular interaction.

Abstract:

Intracardiac electrogram recordings during atrial fibrillation (AFib) are characterized by irregular rhythms and complex morphologies. Hence, analysis in the time domain is a difficult task. The so called dominant frequency DF is a spectrum based approach that aims at finding the most relevant frequency in a signal providing information about the rate and dynamics of AFib. However, in recent years various studies reported controversial results regarding the clinical relevance of the DF. In this work, a definition of the DF at a fundamental scale is proposed as the rate at which action potentials are triggered in atrial cells. The most common method to estimate the DF in literature, labeled as DFSpec, is examined in comparison to the proposed definition. A signal processing study using synthetic signals verified that the DFSpec is stable for all changes in morphology of atrial activations. However, it is also demonstrated that the DFSpec becomes unstable for variations above 20% in the cycle length of a signal. Spectrum based DF estimation should be interpreted in a critical manner and is not advisable for study endpoints or clinical markers.

Abstract:

Recent studies about the development of endocardial radiofrequency (RF) ablation lesions (ALs) tried to identify reliable electrogram (EGM) markers for assessment of lesion transmurality. Additional clinically relevant information for physicians can be provided by examining endocardial EGM parameters like signal morphology, amplitude or time points in the signal. We investigated EGM features of the pulmonary vein ostia before and after RF ablation for three point-shaped lesions. Using high-density (HD) mapping, local activation time (LAT) and voltage maps were created, which provided information about the RF ALs regarding the lesion size and showed activation time delay as well as low-voltage areas with bipolar peak-to-peak voltages smaller than 2mV. The time delay of the depolarization front comparing the activation times anterior and posterior to the RF AL was up to 51.5 ms. In a circular area with 5mm radius around an RF AL the mean peak-to-peak voltage decreased by 62-94% to about 0.12-0.44mV and the mean maximal absolute EGM derivative was reduced by 65-96 %. Comparing the results of this study with EGMs of similar clinical settings confirmed our expectations regarding the low-voltage areas caused by the ablation procedure. An improved understanding of the electrophysiological changes is of fundamental importance to provide more information for enhanced RF ablation assessment.

Abstract:

Optical methods of imaging biological tissues are non-contact and low-risk techniques, which are of great advantage over conventional medical imaging modalities such as X-ray computed tomography (CT) and ultrasound imaging. On the microscopic level, scattering property of biological tissues is associated with tissue inhomogeneity. By detecting the backscattered light signal, structures of different reflectance can be distinguished. Coherent-gating gets rid of unwanted light resulting in further improvements of signal-to-noise ratio (SNR) and image contrast. Recent years optical imaging methods based on coherent-gating, optical coherence tomography (OCT) in particular, have been applied to medical diagnosis for its ability to localize pathological changes in tissues. Even cellular-resolution images have been demonstrated, where enlarged nuclei of neoplastic cells are visualized. However, a realistic modeling of microscopic image resolution and contrast using such methods are rarely reported. In this work, simulation of en face images from low-coherence interferometry (LCI) and spectral domain OCT (SD-OCT) is performed by our self-developed Matlab tool-kit. The image resolution and contrast are then examined with different system configurations, i.e. objectives with different numerical apertures (NAs), low-coherent light source of various central wavelength, bandwidth and optical power. Unlike the standard applications in ophthalmology, the tissue model in our tool-kit is designed to be less transparent than the eye. Thus the microscopic image contrast of such methods on turbid tissues is studied. This tool-kit can be further used to evaluate the performance of LCI or OCT systems for en face imaging, as well as to improve system design.

Abstract:

Acquiring adequate mapping data in patients with atrial fibrillation is still one of the main obstacles in the treatment of this atrial arrhythmia. Due to the lack of catheters with both a panoramic field of view and sufficient electrode density for simultaneous mapping, electrophysiologists are forced to fall back on sequential mapping techniques. But, because activation patterns change rapidly during atrial fibrillation, they cannot be mapped sequentially. We propose that mapping tissue properties which are time independent, in contrast, allows a sequential approach. Here, we use the shortest measured electrogram cycle length to estimate the effective refractory period of the underlying tissue in a simulation study. Atrial fibrillation was simulated in a spherical model of the left atrium comprised of regions with varied refractory period. We found that the minimal measured electrogram cycle length correlates with the effective refractory period of the underlying tissue if the regions with distinct refractory properties are large enough and if the absolute difference in effective refractory periods is sufficient. This approach is capable of identifying regions of lowered effective refractory period without the need for cardioversion. Those regions are likely to harbor drivers of atrial fibrillation, which emphasizes the necessity of their localization.

Abstract:

Atrial arrhythmias like atrial fibrillation and atrial flutter are a major health challenge in developed countries. Radiofrequency ablation performed via intracardiac catheters is a curative therapy for these reentrant arrhythmias. However, the optimal location of ablation lesions is not straightforward to determine, particularly for complex activation patterns. Thus, a clinical need for tools to intuitively visualize complex activation patterns and to provide a platform to evaluate different ablation strategies in dry runs is apparent. Here, we present a virtual reality system that allows to interactively simulate atrial excitation propagation and place ablation lesions. Our software builds on the IMHOTEP framework for the Unity3D engine and implements a multithreaded model-view-controller design pattern. Excitation propagation is computed using a fast marching approach considering refractoriness. Interactive rewind and playback is supported through a combination of the flyweight pattern for simulation data with complete snapshots for key frames. The system was evaluated in a user study using the HTC ViveTM headset including two controllers. For high fidelity virtual reality interaction, a minimum frame rate of 60 per second is required. In a biatrial anatomical model comprising 36,059 nodes (Figure 1), even complex activation patterns with multiple wavefronts could be simulated and rendered down to 2x slow motion (1 sec activation sequence displayed during 2 sec wall time) on a desktop machine. Results of the user study suggest added value regarding the comprehension of arrhythmias and ablation options and very good intuitiveness of the user interface requiring almost no teach-in. The virtual reality tool is ready to be used for educational purposes and prepared to import personalized models supporting diagnosis and therapy planning for atrial arrhythmias in the future.

Abstract:

The heart rate variability (HRV) is a measure which is commonly used to assess sympathetic and parasympathetic auto-nomic function. It is well known, that respiration can have a strong influence on HRV. Especially, a phenomenon called Respiratory Sinus Arrythmia (RSA) modulates the RR intervals and is a major contributor to the HRV. The interpreta-tion of common HRV parameters can be ambiguous due to different respiration rates and patterns. To assess this ambi-guity, the coupling of RSA on HRV was quantified and the HRV parameters were compared during different respirato-ry states.A pilot study with five healthy subjects was performed. A three lead ECG was acquired and the respiration was estimat-ed by measuring the aeration of the lungs using the PulmoVista 500 by Dräger. This device uses Electrical Impedance Tomography (EIT) to monitor impedance changes due to the changing amount of air within the lungs during respira-tion. The subjects were asked to breath at controlled respiration rates of 8, 15 and 24 breaths per minute as well as spon-taneously for 1 min each. In addition, to analyze HRV during apnoic phases without any respiration, the subjects were asked to hold their breath for 40s at end-inspiration and end-expiration. After preprocessing of the ECG and the respiration signal, the coupling between the measured respiration and the RR intervals was quantified using the Granger causality. If significant coupling was present, the HRV was separated from its respiratory influence using an ARMAX model. The measured respiration hereby formed the exogeneous input to the filter. Finally, common HRV parameters were calculated for the original and the decoupled RR intervals.We showed, that coupling strength depends on respiratory rates, which might complicate HRV interpretation. Moreo-ver, the coupling is decreased during spontaneous breathing in comparison to controlled respiration. Additionally we found, that HRV parameters during apnoic phases differ from decoupled HRV parameters during spontaneous or con-trolled respiration.

Abstract:

Electrocardiographic imaging (ECGI) could help in diagnosis and treatment of atrial fibrillation (AF), the most common life-threatening arrhythmia. Based on a previous work by Figuera et al. on the reconstruction of epicardial potentials (EP) during AF, we explore the performance of a Tikhonov regularization with two spatial constraints for transmembrane voltage (TMV) based ECGI. We develop a new method to impose epi-endocardial similarity and show its benefit for ECGI of atrial activity. Apart from TMVs, local activation times and dominant frequency are evaluated as target parameters. In the AF models studied, joint reconstruction of epi- and endocardial TMVs showed performance comparable to the previously reported EPs imaging.

Abstract:

Atrial fibrillation and atrial flutter are the most common atrial arrhythmias placing a heavy burden on patients and posing a challenge on healthcare systems. If patients at risk to develop atrial arrhythmias can be identified at an early stage, the arrhythmia incidence can be lowered by implementing appropriate strategies to mitigate the risks. Diagnostic methods based on the ECG are ideal risk markers due to their noninvasiveness and omnipresence. The left atrium (LA) plays a major role in the initiation and perpetuation of atrial reentry arrhythmias. However, the LA is not well represented in the P-wave derived through standard ECG leads. Here, we optimize ECG leads to maximize LA information content. Towards this end, we used a cohort of eight personalized computational models providing the unique opportunity to separate LA and right atrial (RA) contributions to the P-wave, which is not feasible in vivo. The location of maximum P-wave signal energy was located on the center of the chest for all subjects with marked overlap between regions of maximum LA and RA P-wave amplitude. The regions of highest ratio between LA and RA signal energy differed between patients. However, a region with LA signal energy being higher than that of the RA and providing a sufficiently large absolute P-wave signal energy was identified at the lower left quadrant of the back consistently across most subjects of the cohort. Optimized linear combinations of standard 12-lead signals (considering the eight independent leads) yielded comparably good results amplifying LA information by more than one order of magnitude. Our newly proposed electrode positions on the back as well as selected combinations of standard ECG signals improve the LA information content considerably. By using these, more relevant diagnostic information regarding anatomical and electrophysiological properties of the LA can be derived in future.

Abstract:

Chronic kidney disease appears worldwide. In the United States, the number of patients suffering from kid- ney failure doubled from 1998 to 2010. A common treat- ment for these patients is haemodialysis. However, the frequency of deaths caused by cardiovascular diseases is up to 10% to 30% higher in patients undergoing dialysis than in the general population. To analyse the underly- ing effects and for a possible risk prediction, a continuous monitoring of the ionic concentrations that are influenced by dialysis is desired. In this work, a method for the re- construction of the ionic concentrations of calcium and potassium from the ECG is proposed. In a first step, 91 monodomain simulations with the ten Tusscher ventricular cell model were performed for different extracellular ionic concentrations. From there, a standard 12-lead ECG was extracted. Calcium and potassium changes yielded ECGs clearly differing in amplitude and morphology. In a second step, the simulated ECG signals were used for reconstruc- ting the ionic concentrations directly from the ECG. Fea- tures were extracted from the signals designed to describe changes caused by varied ionic concentrations. The in- verse problem, i.e. coming back from the ECG features to the ionic concentrations was solved by regression with an artificial neural network. Results for potassium estimation yield an error of 0.00±0.28 mmol/l (mean±standard de- viation) calculated with 7-fold cross validation. The esti- mation error for calcium was 0.00±0.08 mmol/l. Although these results underline the suitability of the method, the used ECGs differed from the observed in a clinical envi- ronment. However, simulations allow an evaluation un- der controlled conditions of a particular effect that was intended to be investigated. As the application to clinical data is yet missing, this study can be seen as a proof of concept showing that an artificial neural network is capa- ble of exactly estimating potassium and calcium concen- trations from ECG features. 1. Introduction Haemodialysis therapy is a common treatment method for patients suffering from chronic kidney disease (CKD) in the terminal stage. The amount of people in the United States suffering from kidney failure increased from 320,000 in 1998 to 650,000 in 2010. The frequency of deaths caused by cardiovascular events within the dialysis patient group is up to 10% to 30% higher than in gene- ral population [1]. Patients suffering from end-stage CKD experience high variations of blood electrolyte concentra- tions. These can directly influence the functioning of the heart. Thus, research on cardiovascular links could im- prove therapy and risk stratification. One tool which is capable of capturing the electrophysiological properties of the heart in a non-invasive way is the electrocardiogram (ECG). It is known, that electrolyte concentrations of po- tassium (K+) and calcium (Ca2+) affect the ECG [2]. Un- til now, a determination of the concentrations is connec- ted to a blood test. Hence, continuous monitoring of the ionic concentration is impracticable. However, the ECG as a continuous, non-invasive monitoring tool could shed a light on the relation between heart diseases and changes in the ionic concentration particularly after leaving the strictly supervised clinical area where dialysis takes place, i.e allowing a monitoring at home. Articles have been pub- lished showing that the reconstruction of extracellular K+ concentration can be done using just one feature from the ECG with a quadratic regression [3]. In this study, we tried to estimate both K+ and Ca2+ concentrations from the ECG. Therefore, we examined simulated ECGs at dif- ferent concentration levels and designed features descri- bing the observed changes in the ECG. A subset of these was used in connection with a machine learning method to reconstruct the concentrations. 2. Methods 2.1. Simulations A total number of 91 computer simulations of the car- diac electrophysiology were performed at whole heart

Abstract:

The sinoatrial node (SAN) is the natural pacemaker of our heart. How this small tissue is able to drive a remarkably larger number of intrinsically quiescent atrial cells is still debated; a computational investigation of the underlying mechanisms can help to better understand the SAN’s ability to pace-and-drive the surrounding atrium. Aim of this work is to elucidate how the human SAN action potential can successfully be captured by and propagate into the surrounding atrial tissue. The Fabbri et al. and the Courtemanche et al. models were used to describe the human SAN and atrial cells, respectively. The behaviour of two coupled regions was investigated varying the interregional conductivity (σ) and relative size. Simulations showed that it requires at least an isopotential SAN region 2.85 times wider than the atrial one. A 1D strand of homogeneously coupled SAN and atrial elements was used to identify an interval for σ showing pace-and-drive behaviour (100 SAN vs 100 atrial elements) and to investigate the source-sink interplay (10, 50 or 100 SAN elements vs 100 atrial elements). The 1D strand showed pace-and-drive behaviour for 𝜎 = 0.08 − 36 S/m; a stronger source, with a higher number of SAN elements, led to a wider 𝜎 range that allowed pace-and-drive behaviour, whereas a stronger sink did not affect the behaviour of the tissue. This preliminary work shows the ability of a small human SAN region to pace-and-drive the surrounding atrial tissue. Further investigations are needed to explore different conductivity configurations, including spatial gradients.

Abstract:

Atrial fibrillation (AF) is the most common type of arrhythmia encountered in clinical practice but its maintaining mechanisms remain elusive. Over the last years, various theories have been proposed to target AF mechanisms. Recently, there has been an increasing interest in understanding how spiral waves and rotors sustain AF and how they might be therapeutic targets for catheter-based ablation. Phase mapping has recently been used as a robust method to characterize the spatiotemporal variability of electrical activities. In this study, we propose an independent approach for basket catheter electrogram (EGM) processing to detect rotors in AF. An improved version of the sinusoidal recomposition method for the local activation timings (LATs) has been developed and 3D phase maps have been reconstructed. An algorithm able to detect stable and meandering rotors on the left atrium (LA) surface was then developed. This workflow has been validated on synthetic EGMs and in silico showing excellent results. On in vivo data, we found 4.0±3.4 and 4.6±5.0 localized and meandering rotors with a persistence in time: 303.2 ±58.2ms and 302.3±52.0ms respectively.

Abstract:

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.

Abstract:

Atrial fibrillation is a common cardiac arrhythmia. The disturbance of the normal repolarization process due to heterogeneous myocyte-fibroblast coupling might play a role for this disease. We investigate this interaction in the heterogeneous atrium using a computational approach. Human atrial myocyte computational models represent- ing 10 different regions of the atrium were each coupled to a human atrial fibroblast model and the impact of the myocyte-fibroblast coupling on action potential measures was investigated. Myocytes from the pulmonary vein are affected most by the coupling to fibroblasts. Action potential amplitude is reduced from 105 mV to 94 mV and the upstroke velocity changes from 192 V/s to 152 V/s, potentially reducing the conduction velocity. In general, the action potential dura- tion of myocytes with short action potentials is prolonged and that of those with long is shortened. The large effect on pulmonary vein action potentials is mainly due to reduced IK1 in these cells compared to other regions of the atrium. The strong effects of fibroblast cou- pling to pulmonary vein myocytes are likely to be an addi- tional reason for the crucial role of the pulmonary veins in atrial fibrillation.

Abstract:

Electrical impedance tomography (EIT) can trace ventilation and perfusion related changes in electrical properties of lung tissue. So far, the ability of EIT to assess lung perfusion has been examined experimentally by electron-beam and single-photon-emission computerized tomography (CT) in healthy or globally injured lungs [1,2].

Abstract:

The invention relates to a system for visualizing characteristic tissue with a colorant in a surgical region. The system contains a detection unit which detects light from at least one object point in the surgical region. The system has a computer unit which is connected to the detection unit and drives a visualization unit which displays an image of an area in the surgical region. The computer unit determines the color coordinate in a color space with respect to the light from a point from the object point in the surgical region. Depending on the position of the color coordinate determined with respect to the object point, the computer unit calculates a color coordinate information ("0", "1") for controlling the visualization unit by comparing information concerning the determined color coordinate of the object point with information concerning a characteristic reference color coordinate.

Abstract:

The electrocardiogram (ECG) captures the electrical activity of the heart that is projected onto the surface of the body. This signal can be recorded in a simple and cost effective manner making it available for a wide variety of mobile and stationary applications. Thus, over the last 100 years, the ECG has become the gold standard for the diagnosis of many cardiac afflictions. This is still relevant nowadays because cardiovascular diseases are a major topic of concern for our society accounting for almost 30 % of all causes of death worldwide. In particular, the ischemic heart disease is the single most common cause of death. Other cardiac arrhythmias, such as atrial fibrillation and atrial flutter, affect approximately 2 to 3 % of the population in the European Union leading to estimated costs of about 26 billion euros per year. In all these cases, the ECG is the mandatory first step leading to a reliable diagnosis and successful treatment.In this thesis, we have developed a series of signal processing algorithms capable of automatically extracting rhythmical and morphological properties from the ECG with the aim of supporting the decision making in the diagnostic process. In our first research project, we investigated a phenomenon called postextrasystolic T wave change (PEST) and postulated that the biomarkers obtained from the ECG during PEST could be used to predict pump failure progression death (PFD). The second project dealt with the creation of an algorithm to accurately detect and delineate the P wave in the ECG using as ground truth the electrograms recorded inside the atria. Our third investigation aimed at a deeper understanding of a physiological phenomenon called respiratory sinus arrhythmia (RSA). Here, we developed an algorithm that separates the heart rate variability (HRV) into a respiration driven component and a respiration independent part. The respiration free HRV could deliver new insights about the regulation of the cardiovascular system. In the fourth and final study, we investigated the impact of mental workload on the ECG while driving a car and discovered a variety of features that can help to detect a dangerous state of mind and protect the driver from a car crash.We conclude that well designed signal processing methods for the ECG have the potential of reducing the burden for the cardiac patient and the amount of accidents on the road

Abstract:

Kardiale Arrhythmien sind Störungen des Herzrhythmus, welche von unregelmäßigem Herzschlag kommen. Vorhofflimmern ist die am weitesten verbreitete Herzrhythmusstörung und ist mit zunehmendem Alter weiter verbreitet. Thromboembolische Ereignisse und Störungen der Hämodynamik können als Begleiterscheinungen von Vorhofflimmern (AFib) auftreten und eine signifikant gesteigerte Morbidität und Mortalität zur Folge haben. Die Be- handlung von AFib erfolgt mit Medikamenten und zudem mit Hilfe der Katheterablation. Im Zuge der Ablation versuchen Ärzte die Bereiche arrhythmogenen Substrats zu lokalisieren. Danach werden kleine Ablationsnarben im Herzgewebe erzeugt, welche die Ausbreitung abnormaler elektrischer Erregungen im Herzen unterdrücken sollen. Die Erfolgsraten dieser Prozedur erreichen bis zu 70% nach zwei oder drei Ablationen. Im Zuge diese Arbeiten wurden die Regionen arrhythmogenen Substrats lokalisiert, und die Details der Erregungsausbreitung über dieses Substrat wurden bestimmt. Im Verlauf dieser Arbeit wurden klinische Daten, experimentelle Daten und Simulationen für die Analyse genutzt. Simulationen wurden genutzt um die lokale Aktivierungszeit (LAT) auf klinischen Anatomien zu bestimmen. Experimentelle Daten wurden mit Hilfe eines Elektrodenpatches von einem Hund herzen erfasst. Klinische Daten wurden mit Hilfe eines elektroanatomischen Mappingsystems im Rahmen klinischer Routineuntersuchungen aufgezeichnet. Die aufgezeichneten Daten wurden einer Vorverarbeitung unterzogen um messtechnische und geometrische Artefakte wie das ventrikuläre Fernfeld (VFF) oder hoch- und niederfrequentes Rauschen zu unterdrücken. Eine Vielzahl von Merkmalen wurden aus den vorbearbeiteten Daten gewonnen. Dies waren die Bestimmung des Stimulationsprokotolls, die Abschätzung der Dauer der fraktionierten Aktivität, die Korrelation der Morphologie, Spitzen-zu-Spitzen Amplitude, Bestimmung der QRS Komplexe, lokale Aktivierungszeit, die Bestimmung einer stabilen Katheterposition und die Markierung der Region des arrhythmogenen Substrats. Die Methode zur Bestimmung von Richtung und Geschwindigkeit der Erregungsausbreitung wurde bestimmt. Ein grafisches Nutzerinterface (GUI) wurde entwickelt zur Bestimmung der Ausbreitungsgeschwindigkeit und darauf basierender regionaler Analyse. Simulierte Daten wurden genutzt um die Leistungsfähigkeit der entwickelten Algorithmen zu beurteilen. Zur Simulation der LAT auf klinischen Anatomien wurde die fast marching Methode (FaMaS) genutzt. In diesen Simulationen war die goldene Wahrheit für eine Beurteilung der Parameterabschätzung bekannt. Ein umsichtiger und erfolgreicher Versuch wurde unternommen, um Muster und Geschwindig- keit der Erregungsausbreitung auf dem Vorhof zu bestimmen. Dies wurde auf Basis der LAT Zeit und stabiler Katheterpositionen durchgeführt. Interessante Regionen wurden zudem als wahrscheinliche Regionen eines arrhythmogenen Substrats im linken Vorhof markiert. Dies wurde auf Grundlage mehr als eines Merkmals und visueller Beurteilung deren Verteilung im Vorhof durchgeführt. Für die stimulierten Daten wurde die Aktivität der S1 und S2 Erregung verglichen um Änderungen in der Erregungsausbreitung abzuschätzen. Die Auswertung der experimentellen Daten wurde in Kooperation mit internationalen Partnern aus den USA durchgeführt. Für verschiedene Szenarien wurden dabei Richtung und Muster der Erregungsausbreitung abgeschätzt. Die zeitliche und räumliche Informationen der vorgeschlagenen Method war dabei genau kontrolliert. Mit den Auswertemethoden aus dieser Arbeit können die wahrscheinliche Region des arrhythmogenen Substrats und der Verlauf der Erregungsausbreitung auf dem Vorhof für Vorhofflimmern und Vorhofflattern bestimmt werden. Diese können dem behandelnden Arzt bei der Planung der Ablationstherapie und erfolgreicher Durchführung helfen.

Abstract:

Atrial arrhythmias like atrial fibrillation (AFib) or atrial flutter (AFlut) are a major challenge for modern healthcare systems in terms of prevalence and high costs. AFib itself is the most common arrhythmia among humans that correlates with cardiac diseases like heart failure, sudden cardiac death, or stroke. Chronic AFib is associated with a fivefold increase of stroke occurence [1] and affects already more than 2.2 percent of the population, with an estimated increase of patients within the next years [2].The early detection of patients at risk becomes more and more important for the punctual treatment to reduce the incidence. The human body surface electrocardiogram (ECG) is a proved method for the early detection due to its routinely non-invasive use in a large number of examinations.In this work, three distinct topics were treated in order to improve the diagnostic potential of the ECG regarding the atria. First, simulated atrial body surface potential maps (BSPMs) of different anatomical models were analyzed to find an optimal lead configuration for maximal left atrial information. The resulting lead configurations were also investigated for robustness in clinical practice. Second, a low voltage area LVA was induced into the left atrium (LA) for the investigation of changes in Pwave morphology. Therefore, a modeling approach based on clinical examinations was used for the creation of the LVA. Lastly, the behavior of heterogeneous electrophysiological tissue properties was assessed under pacing from the sinoatrial node (SN) and the left atrial appendage (LAA) [3]. Here, the key components were the determination of the activation sequence and the investigation of the repolarization in different atrial regions.Lead positions maximizing the left atrial information differed between the models, neverthe- less an area slightly down left to the center of the back was found that was suitable for the usage in clinical practice. The created LVA model combined with the insertion of the LVA to the LA anterior heart wall resulted in insignificant small impacts on the body surface ECG. The investigation of the heterogeneous model pointed out that the last activated atrial areas occurred in the right atrium (RA) independent from the pacing position. Moreover it was shown that the repolarization sequence was prolonged in the case of pacing from the LAA. The results improved the understanding of the atrial electrophysiology and offer new insights into the examination and interpretation of the atrial P and TAwave of the ECG.

Abstract:

Cardiac arrhythmia like atrial flutter is a threat to the human health. Often the cause of theillness cannot be determined precisely. The treatment is difficult and often combined withintervention like radio frequency catheter ablation where diseased tissue on the atrium iselectrically isolated by a lesion induced by the heated tip of the ablation catheter. An electrophysiological examination precedes with the help of different kinds of mapping catheters.Electrodes at the end of those mapping catheters are capable to detect cardiac excitations andsave the temporal and spatial information in local activation time maps which serve as theinput for the methods used in this thesis. Especially slow conducting areas are consideredarrhythmic and may cause the looping excitation to persist and can therefore be the source ofthe arrhythmia. The conduction velocity describes the direction and the magnitude of thepropagation of the wave fronts of the electrical excitation leading to the muscle contractionof the human heart. In that matter the determination of the conduction velocity (CV) plays afundamental role in the process of placing lesions in arrhythmogenic tissue thus being ableto save healthy areas in the process. Additionally, the success rate of the procedure may beimproved by helping the treating physician to locate all possible areas for the cause of thearrhythmia which otherwise might be missed. This thesis will explain and evaluate two majorapproaches for the estimation of the conduction velocity for both simulated and clinicaldata sets. With the help of trigonometric functions like the law of cosine the triangulationapproach is capable to estimate the CV between three points. The polynomial fit makes useof the least squares approach and selects viable points for the estimation of the CV in a smallarea around a point of interest. Under the influence of noise added to simulated data bothalgorithms are statistically compared in consideration of the robustness and the accuracy ofthe results. Two clinical data sets will be analysed and the results are interpreted towards thequestion if they are applicable in medical environment. In simulated data under the influenceof noise up to a certain level the triangulation approach yields conduction velocity maps(CV maps) which show local heterogeneities but is not capable to determine the exact CVeven in noise free data. The results of the polynomial fit are very close to the ground truthvalue for the CV in simulated data but suffer heavily under the influence of noise. In clinicaldata both algorithms are capable to locate slow conducting tissue and display the excitationdirection of the propagation. The polynomial fit approach gives the propagation directioneven in very noisy data whereas the triangulation loses this capability when the noise levelsurpasses a certain value. The triangulation seems to yield results with higher resolution andborders of possibly arrhythmogenic tissue patches can be determined more precisely.

Abstract:

A prevalent artifact in intra-atrial electrograms is the ventricular far field. Thats why most commonly, bipolar signals are used in clinical practice, even though the morphology and amplitude of the original unipolar electrograms is distorted in bipolar signals.In this thesis, methods are introduced that allow for a third class of signals: unipolar signals that exclusively exhibit signal components arising from local sources. Or put another way, a novel reference potential is computed that comprises of all the activity far from the current catheter position.There are two classes of methods. Map-based methods need a 4D map of the ventricular far field, recorded in advance, preferably in sinus rhythm. Simultaneous methods, on the other hand, are able to work entirely with the signals currently measured by the catheters electrodes.Map-based methods were quantitatively benchmarked with simulated data of two simulations, and they were also applied to clinical data. The simultaneous methods were applied to clinical data, and a first attempt has been made to develop a benchmark, using clinical data in sinus rhythm.The results confirmed that the ventricular far field can be successfully estimated by spatio- temporal modeling, and subsequently be removed from atrial electrograms.

Abstract:

Cardiac arrhythmias are a widely spread disease in industrialized countries. A common clinical treatment for this disease is radio frequency ablation (RFA), in which high frequency alternating current creates a lesion on the myocardium. However, the formation of the lesion is not entirely understood and non-transmural or incomplete lesions lead to high recurrence rates. To obtain more information about ablation lesions (ALs) and their electrophysiological properties, we established an in-vitro setup to record electrical activity of rat myocardium under well-defined conditions. Electrical activity is measured by a circular shaped multielec- trode array.This work was focused to obtain more information by developing an algorithm to process the measured electrical signals to collect different features, which may allow us to characterize an AL. The algorithm was separated in different parts and designed to process unipolar and bipolar data simultaneously. First, pacing artifacts were detected and blanked. Subsequently, the recorded data were processed by a filtering algorithm created to match the power density spectrum of the recorded signal. Afterwards, activations in atrial signals were detected using the nonlinear energy operator (NLEO) or the negative slope (NS) method and templates of these activations were generated. Finally, we determined different features on each activation in order to evaluate changes of unipolar as well as bipolar electrograms and considered these features before and after ablation. For further investigation local activation time (LAT) maps as well as conduction velocity (CV) were determined. In conclusion, some of the signal features delivered significant differences between healthy tissue and lesion. Among others, a reduction in peak to peak amplitude (P2P) and a shift of the bandwidth towards lower frequencies may be useful indicators for AL. Also, a reduction of the maximum of the NS was a significant indicator for an AL. These criteria should be verified in future studies with the aim of estimating indirectly the formation of a lesion. The results of this work could help to improve the success rates currently achieved by RFA.

Abstract:

Atrial fibrillation, atrial flutter and ventricular tachycardia are widespread diseases, especially in advanced age. According to the Federal Statistical Office, more than 19265 people died from atrial fibrillation and atrial flutter in 2015 [1]. In these diseases, unexpected electrical signals occur in the heart. Firstly, these diseases are treated with medication, but if that does not help, so-called catheter ablation treatments are used. For this, an ablation catheter is inserted into the heart and then scars the corresponding area which send the undesirable signals. However, in order to determine exactly where this ablation is to take place, so-called mapping catheters are used. Mapping catheter measure the heart activities. The amplitudes of the measured signals are an important factor for the treating cardiologist to recognize the undesirable heart activities. In setting the ablation scars, the cardiologists often rely on their vast experience. In addition, the success rate of this treatment is 60-80% in the first trial, which increases to 90% after a second intervention [2]. In order to examine more closely, how reliable the used markers are: The intracardiac signals are measured in this work using computer modelling, with modifications of certain parameters. This is intended to better interpret the measured signals in future...

Abstract:

Approximately 13% of the worldwide population suffers from chronic kidney disease (CKD). Patients suffering from CKD often undergo dialysis therapies to compensate the changes of the ionic concentrations. Moreover, cardiovascular disease (CVD) is the main cause of death in CKD patients. In this study, the connection between the variation of the electrolyte concentrations and the electrophysiology of the heart will be studied, in order to justify the relation between both diseases. The results are based on a computational model, as it is a helpful, cheap and an ethically accepted tool for studying cardiac electrophysiology. The ventricular cell model presented by Himeno et al. was used for analyzing a variation of extracellular sodium, potassium and calcium within different ranges as done in a previous work. Simulations were carried out on cellular level and on tissue level for a ventricular simulation. On cellular level calcium and potassium changes showed variations in the form of the action potentials, and of parameters like the action potential duration or the resting membrane voltage. Changes in the action potential due to a variation of extracellular sodium were not as prominent as for calcium and potassium. In order to simulate the depolarization dispersion of the cells within the ventricles, an apicobasal and a transmural formulation of the Himeno et al. model were proposed. Results from simulations with these formulations accorded with results obtained from in vivo experiments. As a next step, ventricular simulations were carried out and forward calculated for the extraction of the electrocardiogram (ECG). First, the Himeno et al. model was evaluated for tissue simulations, by analyzing the wave propagation. As the model was considered capable for tissue modelling in the tissue study, ventricular simulations with extracellular ionic variation were performed. To evaluate the realism of the resulting ECGs, features were calculated and compared as done in a previous work. A dependence of the evaluated features on the extracellular ionic concentration was found. The results were in accordance with the literature for those features that have already been investigated. In this study the relation between electrolyte concentrations and the electrophysiology of the heart was proved by analyzing the morphology of the action potential and the ECG. These results could be helpful for further studies investigating the reconstruction of the ionic concentrations based on signal processing of the ECG.

Abstract:

Electrical Impedance Tomography (EIT) is a relatively new imaging and monitoring method to monitor pulmonary health at the bedside.The EIT has been successfully applied for monitoring of the ventilation and is thought to have clinical potential, since this method is non-invasive, inexpensive, long-term able and allows live monitoring at the patients bed.The analysis of pulmonary perfusion by means of EIT is still matter of research, which is the missing information beside the ventilation to analyse pulmonary gas exchange efficiency. During the research for this thesis, the influence of the pulmonary artery pressure (PAP) on the EIT signal is observed in order to investigate the perfusion information in EIT measurements. The analyses have been carried out on six pigs of an experimental study during respiratory hold phases.In the first part of the thesis a method was established automatically detecting these respiratory hold sequences, the PEEP, which influences the blood pressure and flow, and un-physiological segments of the pulmonary artery pressure (PAP) measured during the study. The latter was performed in order to gain a reliable PAP signal, which served as hemodynamic comparison parameter. During the second part of this work the EIT segments at the time of respiratory hold phases were analysed. At first, the components were segmented into intervals of one heartbeat (from R-peak of the electrocardiogram to the succeeding R-peak) via detecting the R-peaks of the regarding electrocardiogram (ECG) signal. The approach of examining whether the EIT can be used for quantifying blood flow, was adopted from the paper Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia by Martin Proença et al, which based on a human study. It implied the calculation of the time between the respective R-peak and the start of the next EIT slope, which was called pulse arrival time (PTT). This parameter was assumed to represent the time between the ejection of blood out of the ventricle and the arrival at the respective point in the lung. The PTT was approximated to anti-correlate to the PAP and so give EIT-based information about the hemodynamic in the lung. In order to approve this thesis, two approaches to gain EIT timing information, namely the template and correlation approach, were implemented and applied in this work. All in all, the high correlation between the PAP and the time shift of the cardiac pulsatility component in EIT signals of the paper could not be found in this thesis. In which way the methods were implemented and possible reasons for the different results compared to the Proença paper are introduced and discussed.

Abstract:

Current surgical microscopic systems are limited in providing a stereoscopic view to multiple users. When trying to provide higher degree of freedom in the perspective of additional observers, the optomechanical effort increases rapidly. This is limiting current systems to two or three observers. An approach to offer free choice of view is to digitalize the microscopic system and generate multiple arbitrary views from a 3D reconstruction. Modern commercial surgical microscopes allow for recording stereoscopic videos. However, filming is only possible through the two channels used for the eyes. A reconstruction can only contain the amount of detail the recording camera system gathers from the scene. For deviating stereoscopic perspectives, the reconstruction can become defective through masking and occlusion. By adding cameras recording the object from different angles, additional informa- tion of the scene is acquired, allowing to improve the reconstruction. Current research at IBT tries to optimize the effort in hardware and software to give a sufficient reconstruction of a surgical scene to allow a change of view. Yet multicamera systems for application in microsurgery are not commercially available. Therefore, a four-camera setup was designed, allowing verification of the reconstruction from multiple observing perspectives. Its concept is based on current surgical microscopes as these systems are well established and optically mature. As in a surgical microscope we used a setup with common main objective (CMO). Behind the CMO four pupils separate the channels which are filmed by one camera each. The designed system is able to image an area of approximately 28 mm × 28 mm with four cameras. Thus, allowing to process stereo images of 6 different stereo bases. The setup can be used in further studies to test algorithms for 3D reconstruction from up to four cameras and angles. In order to verify the setup, it was modelled in Zemax OpticStudio. To improve the feasibility of the setup, simulations of tolerance affected parts were conducted. This way relations of performance and tolerances can be denoted, and alternative setups with reduced susceptibility are suggested.

Abstract:

The force generated by the human heart depends on various characteristics such as the length of the cardiomyocytes, the strain of the cardiomyocytes as well as the contraction velocity. Another aspect is the activation time of each cardiomyocyte. Physiologically the cardiomyocytes are activated through the Purkinje tree from the apex upwards to the base plane. The contraction will follow this activation pattern (inhomogeneous activation) which results in a different distribution of the contraction force than without respecting these local activation times (homogeneous activation).To simulate the inhomogeneous activation, I implemented the functionality to process local activation times for the cardiac simulation framework CardioMechanics, developed at the Institute of Biomechanical Engineering at the Karlsruhe Institute of Technology.To evaluate the effects of these activation times, Ive done multiple simulations with various settings. In this work, a three-dimensional heart mesh based on a real human heart is used. This mesh consists of 39067 nodes and 61272 cells. The passive stresses were calculated by using the Guccione model and the MooneyRivlin model. Two different models were used for the calculation of the active stress. These were the DoubleHill model and the Lumens model.The central clinical question whether the calculation with the local activation times is more precise than the calculation without the local activation times can be negated. The simulations did show changes to a smaller maximum pressure in the four chambers of the heart, but the differences were below 5%, so they could be neglected in favor of a 17.23% faster computation time (with the Lumens model).

Abstract:

A multimodal spectral domain optical coherence tomography (SD-OCT) and non-linear optical microscopy (NLOM) imaging platform is developed. The SD-OCT engine based on a broad bandwidth Ti:sapphire laser is designed and implemented into a customized NLOM system featuring simultaneous acquisition of second harmonic generation, two- photon excitation fluorescence and coherent anti-Stokes Raman scattering imaging. The control software for acquisition, signal processing and optimization of the OCT data including a graphical user interface is developed in Matlab, for easy integration into the software platform of the NLOM engine based on ScanImage. The SD-OCT system is optimized to achieve sub-3 µm axial resolution with a signal to noise ratio of ~95 dB. The performance of the multimodal platform is evaluated with in vivo zebrafish imaging.

Abstract:

In the recent past, various studies tried to assess and utilize high-density mapping in clinical practice. Studying the additional value of high-density mapping is of fundamental impor- tance regarding modern cardiac arrhythmia treatment. Enhancing the treatment of cardiac arrhythmias like atrial fibrillation or atrial flutter can be achieved by improving different parts in the treatment chain, like the mapping itself, the signal processing or the measurement method. Progress with regard to hardware and software development is part of the research in biomedical engineering with the goal to provide improved clinical tools for physicians and the overall clinical personnel. The goal of this thesis is the visualization of ablation lesions using the data of a modern high-density mapping system and the assessment of the later developed myocardial scar. Technically solving the task of lesion assessment can be done by identifying reliable markers in the intracardiac electrograms (EGMs) and comparing these markers with similar previous clinical or in-silico studies. Furthermore, the development of a mapping tool for research purposes is tested through the example of a so called path-driven EGM analysis. The investigated high-density mapping data of this research are data sets of a clinical setup where point-shaped radiofrequency (RF) ablation lesions were created on a line of an ipsilateral circumferential antral pulmonary vein isolation. Analyzing these data sets with the developed algorithms and methods leads to the conclusion that in low-voltage areas close to ablation lesions, high-density mapping ensures a higher availability of evaluable intracardiac EGMs. Additional data improves the basis of ablation lesion assessment and the possibility to search for EGM markers regarding lesion size or geometry. This is a main reason why further clinical or in-silico studies using high-density mapping data could play a crucial role in the search of reversible or irreversible electrophysiological effects of RF ablation. To ensure the correctness of the developed 3D maps I statistically compared uni- and bipolar parameters and analyzed the relation of the excitation propagation with the theoretically expected outcome. We further examined an activation time delay of the depolarization front (51.5 ms) by comparing the activation times measured in regions anterior and posterior to the RF ablation lesions. EGM markers like the decrease of the bipolar peak- to-peak voltage (62-94 %) and the decline of the mean maximal absolute EGM derivative (65-96 %) mostly matched with the results of previous studies.Even though there are still not enough EGM markers to provide convincing clinically relevant information, the potential of this branch of research for possible future projects on lesion formation, gap detection or even transmurality seems promising. Fast acquisition of high resolved electroanatomical data together with a combination of visual map investigation and EGM analysis is going to lead to improvements in future research and treatment.

Abstract:

Preoperative planning of complex and multifragmentary bone fractures is important in order to ensure a safe and successful surgery. For this purpose, a surgical planning tool was developed in a virtual reality environment in a previous work. However, this preop- erative planning tool requires a surface model of the segmented bone fragments. In order to ensure a fast and convenient preoperative planning, the segmentation workflow for the data generation should be embedded into the same virtual reality environment. Therefore, innovative segmentation tools in a virtual reality setting were developed in this work. This comprises an initial semi-automatic segmentation based on the Graph Cut method, an automatic generation of a 3D surface mesh representing the segmentation on the basis of the Marching Cubes algorithm including an anti-aliasing filtering as well as novel virtual reality tools for manual postprocessing the surface mesh.The implemented Graph Cut segmentation was performed in 3D and yielded promising results in terms of accuracy and performance with little user effort. Especially for larger data, the computation time was quite good and much better compared to previous work. Moreover, the Graph Cut segmentation can be updated by setting new seed points inter- actively which performed even faster than the initial segmentation.In order to compensate for inaccuracies of the initial semi-automatic segmentation, vir- tual reality tools were developed to manually post-process the surface mesh. These tools combine 2D imaging tools within the clinical scan and 3D mesh forming tools in an in- novative approach. For instance these tools can be used to separate connected segments, to indent and inflate the surface mesh or to add and remove single voxels in the clinical scan. Certain optimizations allowed a performant interaction of the tools as well as the automatic update of the 3D surface mesh and the displayed segmentation within the clin- ical scan. The tools obtained good results in terms of accuracy, handling and usability. However, the accuracy of the mesh forming tools was limited by the voxel resolution of the clinical data due to the fact that the mesh forming tools were performed in the voxel domain.In addition to a quantitative evaluation of the segmentation result in terms of accuracy, computation time and user effort, the developed segmentation tools were evaluated qual- itatively with respect to usability by means of a research study of 20 test persons.

Abstract:

Acquiring adequate mapping data in patients with atrial fibrillation (AFib) is one of the main obstacles in the treatment of this arrhythmia. Due to the lack of catheters with both a panoramic field of view and sufficient electrode density for simultaneous mapping, electrophysiologists are forced to fall back on sequential mapping techniques to identify activation patterns. However, this approach is insufficient for rapidly changing patterns as they typically occur during AFib. In contrast to activation time mapping, substrate mapping avoids this drawback by analyzing time independent tissue properties. While most of the existing methods for substrate mapping do not reflect actual tissue properties but certain electrogram features, the results suffer from dependencies on parameters of data analysis or are limited to harmonic signals. Here, we investigate the potential and limitations of measured electrogram cycle lengths to derive information about the effective refractory period of the underlying tissue during sequences of AFib. Following theoretical considerations, areas with decreased effective refractory period are likely to harbor AFib drivers.In a first step, different parametrizations of the Courtemanche-Ramirez-Nattel model with varying ERP served as substrates for bidomain simulations of AFib in a spherical model of the left atrium. Circular regions of deviating effective refractory period with radii between 9 mm and 19 mm were imposed. We found that the minimal measured electrogram cycle length correlates with the effective refractory period of the underlying tissue if the regions with distinct refractory properties are large enough and if the absolute difference in effective refractory periods is significant. Rhythms of high complexity which cause many other mapping approaches to come up against limiting factors favor the here introduced method as statistics profit from the variability in observed events.In a second step, the clinical feasibility of using measured cycle length statistics to conclude on the underlying ERP of the tissue was investigated. Lacking ground truth data providing reliable in vivo information on the ERP of the tissue, final validations of our hypotheses remain due. The 25 % quantile of cycle lengths was used rather than the minimum in favor of improved robustness in clinical application. The cycle length analysis in patient data yielded physiologically reasonable results with locally low gradients but globally differing statistics. Both the in silico and the clinical test of concept study suggested that applying statistical measures such as the 25 % quantile to measured electrogram cycle lengths is capable of revealing information on the effective refractory period of the underlying tissue. This, in turn, is of particular clinical interest, as regions of lowered effective refractory period are likely to harbor AFib drivers.

Abstract:

The Subject of this work is producing the phantoms used for investigation of contrast image in Confocal Laser Endomicroscopy (CLE). Created phantoms should simulate the simplified cellular structure of human tissue after injection with fluorescein sodium (FS). FS is diffused into the intracellular and extracellular fluids but not into cell nuclei. Phantom would have fluorescent matrix (simulating these fluids) and glass particles (simulating cell nuclei). Several experiments have been performed in order to research the best production method - including both process and used materials for matrix base of the samples - in order to continue further investigation. There were two production methods, based on different materials for matrix base - elastomer and acrylate. Chosen phantoms were optically characterized with help of spectrophotometer. All of the made phantoms and experimental samples were imaged by CLE. Investigation of contrast of these images has been performed. With the help of histograms that presented CLE images, the contrast has been tightly investigated.