Electrocardiographic imaging (ECGI) has recently gained attention as a viable diagnostic tool for reconstructing cardiac electrical activity in normal hearts as well as in cardiac arrhythmias. However, progress has been limited by the lack of both standards and unbiased comparisons of approaches and techniques across the community, as well as the consequent difficulty of effective collaboration across research groups.. To address these limitations, we created the Consortium for Electrocardiographic Imaging (CEI), with the objective of facilitating collaboration across the research community in ECGI and creating standards for comparisons and reproducibility. Here we introduce CEI and describe its two main efforts, the creation of EDGAR, a public data repository, and the organization of three collaborative workgroups that address key components and applications in ECGI. Both EDGAR and the workgroups will facilitate the sharing of ideas, data and methods across the ECGI community and thus address the current lack of reproducibility, broad collaboration, and unbiased comparisons.
Cardiologists measure electric signals inside the human heart aiming at a better diagnosis and optimized therapy of atrial arrhythmias like atrial flutter and atrial fibrillation. The catheters that are used for this purpose are improving: now they are able to pick up the electric signals at up to 64 positions inside the heart simultaneously. The patterns of electric depolarization are sometimes very simple, comparable to plane waves. But in case of patients with severe atrial arrhythmias they can be quite complex: U-turns around a line of block, ectopic centres, break throughs, reentry circuits, rotors, fractionated signals and chaotic patterns are often observed. Methods of biosignal analysis can support the cardiologists in classifying the signals and extract information of high diagnostic relevance. Computer models of the electrophysiology of the human heart can serve to design better algorithms for data analysis and to test algorithms, because the ground truth is known.
G. Lenis, N. Pilia, T. Oesterlein, A. Luik, C. Schmitt, and O. Dössel. P wave detection and delineation in the ECG based on the phase free stationary wavelet transform and using intracardiac atrial electrograms as reference. In Biomedizinische Technik. Biomedical Engineering, vol. 61(1) , pp. 37-56, 2016
Robust and exact automatic P wave detection and delineation in the electrocardiogram (ECG) is still an interesting but challenging research topic. The early prognosis of cardiac afflictions such as atrial fibrillation and the response of a patient to a given treatment is believed to improve if the P wave is carefully analyzed during sinus rhythm. Manual annotation of the signals is a tedious and subjective task. Its correctness depends on the experience of the annotator, quality of the signal, and ECG lead. In this work, we present a wavelet-based algorithm to detect and delineate P waves in individual ECG leads. We evaluated a large group of commonly used wavelets and frequency bands (wavelet levels) and introduced a special phase free wavelet transformation. The local extrema of the transformed signals are directly related to the delineating points of the P wave. First, the algorithm was studied using synthetic signals. Then, the optimal parameter configuration was found using intracardiac electrograms and surface ECGs measured simultaneously. The reverse biorthogonal wavelet 3.3 was found to be optimal for this application. In the end, the method was validated using the QT database from PhysioNet. We showed that the algorithm works more accurately and more robustly than other methods presented in literature. The validation study delivered an average delineation error of the P wave onset of -0.32+/-12.41 ms when compared to manual annotations. In conclusion, the algorithm is suitable for handling varying P wave shapes and low signal-to-noise ratios.
AIMS: P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. METHODS AND RESULTS: Atrial excitation was triggered from seven different EAS in a cohort of eight anatomically personalized computational models. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed and separated by left and right atrial contributions. Mid-septal EAS yielded the highest PTF-V1. More anterior/superior and more inferior EAS yielded lower absolute PTF-V1 values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via Bachmann's Bundle (BB) for anterior/superior EAS and shifted towards posterior IACs for more inferior EAS. Non-conducting posterior IACs increased PTF-V1 by up to 150% compared to intact posterior IACs for inferior EAS. LA contribution to the P-wave integral was 24% on average. CONCLUSION: The electrical contributor's site of earliest activation and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites independent from LA size. This should be considered for interpretation of electrocardiographical signs of LA abnormality and LA enlargement.
Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way toward tailored therapies in the last years. To fully leverage in silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurately and reliably. In this work, two classes of optimization approaches are evaluated: gradient-based trust-region-reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that neither of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration.
BACKGROUND AND OBJECTIVE: Progress in biomedical engineering has improved the hardware available for diagnosis and treatment of cardiac arrhythmias. But although huge amounts of intracardiac electrograms (EGMs) can be acquired during electrophysiological examinations, there is still a lack of software aiding diagnosis. The development of novel algorithms for the automated analysis of EGMs has proven difficult, due to the highly interdisciplinary nature of this task and hampered data access in clinical systems. Thus we developed a software platform, which allows rapid implementation of new algorithms, verification of their functionality and suitable visualization for discussion in the clinical environment. METHODS: A software for visualization was developed in Qt5 and C++ utilizing the class library of VTK. The algorithms for signal analysis were implemented in MATLAB. Clinical data for analysis was exported from electroanatomical mapping systems. RESULTS: The visualization software KaPAVIE (Karlsruhe Platform for Analysis and Visualization of Intracardiac Electrograms) was implemented and tested on several clinical datasets. Both common and novel algorithms were implemented which address important clinical questions in diagnosis of different arrhythmias. It proved useful in discussions with clinicians due to its interactive and user-friendly design. Time after export from the clinical mapping system to visualization is below 5min. CONCLUSION: KaPAVIE(2) is a powerful platform for the development of novel algorithms in the clinical environment. Simultaneous and interactive visualization of measured EGM data and the results of analysis will aid diagnosis and help understanding the underlying mechanisms of complex arrhythmias like atrial fibrillation.
Whole-chamber mapping using a 64-pole basket catheter (BC) has become a featured approach for the analysis of excitation patterns during atrial fibrillation. A flexible catheter design avoids perforation but may lead to spline bunching and influence coverage. We aim to quantify the catheter deformation and endocardial coverage in clinical situations and study the effect of catheter size and electrode arrangement using an in silico basket model. Atrial coverage and spline separation were evaluated quantitatively in an ensemble of clinical measurements. A computational model of the BC was implemented including an algorithm to adapt its shape to the atrial anatomy. Two clinically relevant mapping positions in each atrium were assessed in both clinical and simulated data. The simulation environment allowed varying both BC size and electrode arrangement. Results showed that interspline distances of more than 20 mm are common, leading to a coverage of less than 50% of the left atrial (LA) surface. In an ideal in silico scenario with variable catheter designs, a maximum coverage of 65% could be reached. As spline bunching and insufficient coverage can hardly be avoided, this has to be taken into account for interpretation of excitation patterns and development of new panoramic mapping techniques.
D. Potyagaylo, O. Dossel, and P. van Dam. Influence of Modeling Errors on the Initial Estimate for Nonlinear Myocardial Activation Times Imaging Calculated With Fastest Route Algorithm. In IEEE Transactions on Biomedical Engineering, vol. 63(12) , pp. 2576-2584, 2016
Noninvasive reconstruction of cardiac electrical activity has a great potential to support clinical decision making, planning and treatment. Recently, significant progress has been made in the estimation of the cardiac activation from body surface potential maps (BSPMs) using boundary element method (BEM) with the equivalent double layer (EDL) as source model. In this formulation, noninvasive assessment of activation times results in a nonlinear optimization problem with an initial estimate calculated with the fastest route algorithm (FRA). Each FRAsimulated activation sequence is converted into the ECG. The best initialization is determined by the sequence providing the highest correlation between predicted and measured potentials.We quantitatively assess the effects of the forward modeling errors on the FRA-based initialization. We present three simulation setups to investigate the effects of volume conductor model simplifications, neglecting the cardiac anisotropy and geometrical errors on the localization of ectopic beats starting on the ventricular surface. For the analysis, 12-lead ECG and 99 electrodes BSPM system were used. The areas in the heart exposing the largest localization errors were volume conductor model and electrode configuration specific with an average error <10 mm. The results show the robustness of the FRA-based initialization with respect to the considered modeling errors.
ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.
T. Seidel, J.-C. Edelmann, and F. B. Sachse. Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions. In Annals of Biomedical Engineering, vol. 44(5) , pp. 1436-1448, 2016
Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 microm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale.
O. Dössel. Bildgebende Verfahren in der Medizin: Von der Technik zur medizinischen Anwendung. Springer-Verlag Berlin Heidelberg, 2016.
Dieses erfolgreiche Standardwerk beschreibt sämtliche bildgebenden Verfahren von der Röntgentechnik über den Ultraschall bis zu den Methoden der Tomographie. Es werden sowohl die technischen Grundlagen als auch die medizinischen Anwendungen erläutert.Das Lehrbuch zeichnet sich aus durch eine verständliche Darstellung, zahlreiche Illustrationen der grundlegenden Prinzipien sowie durch Bilder von den verschiedenen Modalitäten und von den Geräten.Die 2. Auflage wurde aktualisiert und enthält neue Trends und Entwicklungen, insbesondere beim Röntgen und Ultraschall. Kapitel über Magnetic Particle Imaging (MPI) wurden hinzugefügt.
P-wave assessment is frequently used in clinical practice to recognize atrial abnormalities. However, the use of P-wave criteria to diagnose specific atrial abnormalities such as left atrial enlargement has shown to be of limited use since these abnormalities can be difficult to distinguish using P-wave criteria to date. Hence, a mechanistic understanding how specific atrial abnormalities affect the P-wave is desirable. In this study, we investigated the effect of left atrial hypertrophy on P-wave morphology using an in silico approach. In a cohort of four realistic patient models, we homogeneously increased left atrial wall thickness in up to seven degrees of left atrial hypertrophy. Excitation conduction was simulated using a monodomain finite element approach. Then, the resulting transmembrane voltage distribution was used to calculate the corresponding extracellular potential distribution on the torso by solving the forward problem of electrocardiography. In our simulation setup, left atrial wall thickening strongly correlated with an increased absolute value of the P-wave terminal force (PTF) in Wilson lead V1 due to an increased negative amplitude while P-wave duration was unaffected. Remarkably, an increased PTF-V1 has often been associated with left atrial enlargement which is defined as a rather increased left atrial volume than a solely thickened left atrium. Hence, the observed contribution of left atrial wall thickness changes to PTF-V1 might explain the poor empirical correlation of left atrial enlargement with PTF-V1.
Computer simulations and imaging of human physiology and anatomy are effectively used for diagnostics and medical treatments and are thus a focus of scientific research. Suitable representation of data is a critical aspect to achieve best results. Therefore, we developed an interactive visualization scheme especially for the representation of cardiac arrhythmias based on a conventional mobile device and virtual reality (VR) goggles (Google Cardboard and Samsung Gear VR) in combination with a game engine. The aim of this paper is to raise awareness for this new technique, evaluate its potential and pro- pose a general workflow for such a visualization environment. The use of a conventional mobile device in combination with VR goggles creates a portable and low-cost system, equipped with enough processing power and pixel density for many types of applications. The user can interact with the data through head movement or a secondary controller. As current game engines support a wide range of additional input methods and controllers, the interaction method can be customized to fit the target audience. To evaluate this method, we conducted a survey with eight typical phenomena from the field of cardiac arrhythmias. The participants were asked to rate different performance aspects on a scale from one (very bad) to five (very good). All participants (N=27) rated the performance as fluent (median=5). Furthermore, most participants (70%) ranked the overall impression as very good (median=5). On the long run, the system can be used for education and presentations as well as improved planning and guidance of medical procedures.
Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intrac- ardiac electrograms (IEGMs) provide real-time informa- tion regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and inter- pretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenom- ena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was com- pared to an existing one and to clinical measurements of ve patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogo- nal catheter orientation, the presence of a second necrotic core in the near- eld of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.
The novel high-density mapping system RhythmiaTM Medical (Boston Scientific, Marlborough, USA) allows a fast and automatic acquisition of intracardiac electrograms (EGMs). For recording the ORION mini-basket catheter is used. Due to the small electrode surface, the spatial averaging is smaller than with other commonly used mapping catheters. This results in a higher quality of unipolar signals. However, these are still corrupted by noise such as high frequency interference. Within this project, methods were developed and benchmarked that can be applied to detect and remove these undesired components. An algorithm was implemented to detect and eliminate artificial peaks in the spectrum of the EGM. The filtered signals showed improved quality in time domain. The performance of the spectral peak detection resulted in a median sensitivity of 92.1% and in a median positive predictive value of 91.9%.
W. Kaltenbacher, M. Rottmann, and O. Dössel. An algorithm to automatically determine the cycle length coverage to identify rotational activity during atrial fibrillation a simulation study. In Current Directions in Biomedical Engineering, vol. 2(1) , pp. 167-170, 2016
Atrial fibrillation is the most common cardiac arrhythmia. Many physicians believe in the hypothesis that persistent atrial fibrillation is maintained by centers of rotatory activity. These so called rotors are sometimes found by physicians during catheter ablation or electrophysiological studies but there are also physicians who claim that they did not find any rotors at all. One reason might be that today rotors are mainly identified by visual inspection of the data. Thus we are aiming at an algorithm for rotor detection. We first developed an algorithm based on the local activation times of the intracardiac electrograms recorded by a multielectrode catheter that can automatically determine the cycle length coverage. This was done to get an objective view on possible rotors and therefore help to quantify whether a rotor was found or not. The algorithm was developed and evaluated in two different simulation setups, where it could reliably determine cycle length coverage. But we found out that effects like wave collision and slow conduction have strong influence on cycle length coverage. This prevents cycle length coverage from being suited as the only parameter to quantify whether a rotor is present or not. On the other hand we could confirm that rotors imply a cycle length coverage of >70% if the multielectrode catheter is centered in an area of <5 mm away from the rotor tip. Therefore cycle length coverage can at least be used in some situations to exclude the presence of possible rotors.
G. Lenis, A. Kramlich, T. Oesterlein, A. Luik, C. Schmitt, and O. Dössel. Development and Benchmarking of Activity Detection Algorithms for Intracardiac Electrograms Measured During Atrial Flutter. In Workshop Biosignal 2016. Innovation bei der Erfassung und Analyse bioelektrischer und bimagnetischer Signale, pp. 5-8, 2016
The post extrasystolic T wave change (PEST) is an electrocardiographic phenomenon in which the morphology of the normal T wave is altered for a short time after a ventricular ectopic beat (VEB). It has been observed in patients with other cardiac pathologies but it has not been proposed as a risk index for cardiac death. Since PEST seems to be potentiated in patients with depression of myocardial contractility, we hypothesize that PEST could be used to predict pump failure death (PFD) in patients with chronic heart failure (CHF). For the purpose of quantifying PEST, the parameters morphological change onset (MCO) and morphological change slope (MCS) were introduced. The MUSIC study was used to test the hypothesis. The patients in the study were separated according to its cause of death and comparisons of each cause against the others (including survivors) were carried out. In addition, the parameters MCO and MCS were divided into subgroups us- ing optimal values obtained from the corresponding ROC curves with the aim of analyzing predictability with respect to PFD. The results showed that no significant differences could be established and the proposed parameters do not seem to be related to any kind of cardiac death.
Microsleep events (MSE) are short intrusions of sleep under the demand of sustained attention. They can impose a major threat to safety while driving a car and are considered one of the most significant causes of traffic accidents. Drivers fatigue and MSE account for up to 20% of all car crashes in Europe and at least 100,000 accidents in the US every year. Unfortunately, there is not a standardized test developed to quantify the degree of vigilance of a driver. To account for this problem, different approaches based on biosignal analysis have been studied in the past. In this paper, we investigate an electrocardiographic-based detection of MSE using morphological and rhythmical features. 14 records from a car driving simulation study with a high incidence of MSE were analyzed and the behavior of the ECG features before and after an MSE in relation to reference baseline values (without drowsiness) were investigated. The results show that MSE cannot be detected (or predicted) using only the ECG. However, in the presence of MSE, the rhythmical and morphological features were observed to be significantly different than the ones calculated for the reference signal without sleepiness. In particular, when MSE were present, the heart rate diminished while the heart rate variability increased. Time distances between P wave and R peak, and R peak and T wave and their dispersion increased also. This demonstrates a noticeable change of the autonomous regulation of the heart. In future, the ECG parameter could be used as a surrogate measure of fatigue.
P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could ex- plain both the higher risk for AF and higher P-wave ter- minal force (PTF) in ECG lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypoth- esize that LA hypertrophy, i.e. a thickening of the myocar- dial wall, also contributes to increased PTF-V1 and is part of the reason for the rather low specificity of increased PTF-V1 regarding LA enlargement. To show this, atrial excitation propagation was simulated in a cohort of four anatomically individualized models in- cluding rule-based myocyte orientation and spatial elec- trophysiological heterogeneity using the monodomain ap- proach. The LA wall was thickened symmetrically in steps of 0.66 mm by up to 3.96 mm. Interatrial conduction was possible via discrete connections at the coronary sinus, Bachmann’s bundle and posteriorly. Body surface ECGs were computed using realistic, heterogeneous torso mod- els. During the early P-wave stemming from sources in the RA, no changes were observed. Once the LA got activated, the voltage in V1 tended to lower values for higher degrees of hypertrophy. Thus, the amplitude of the late positive P- wave decreased while the amplitude of the subsequent neg- ative terminal phase increased. PTF-V1 and LA wall thick- ening showed a correlation of 0.95. The P-wave duration was almost unaffected by LA wall thickening (∆ ≤2 ms). Our results show that PTF-V1 is a sensitive marker for LA wall thickening and elucidate why it is superior to P-wave area. The interplay of LA hypertrophy and dilation might cause the poor empirical correlation of LA size and PTF- V1.
P-wave morphology correlates with the risk for AF. Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. Atrial excitation was triggered from seven different EAS on the epicardial surface around the sinus node region in eight anatomically personalized computational models including rule-based myocyte orientation and spatial electrophysiological heterogeneity. EAS1 was located midway between the tip of the right atrial appendage (RAA) and its junction with the superior vena cava (SVC), EAS2 at the superior part of the anterior wall, and EAS3 at the junction of the RAA and the SVC. EAS4 to EAS7 were uniformly distributed along the crista terminalis between EAS3 and orifice of the inferior vena cava (EAS7). IACs connected the atria at Bachmann’s bundle, coronary sinus and posteriorly. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed using realistic, heterogeneous torso models. Mid-septal EAS yielded the highest PTF-V1 measured as the product of the duration and the maximal amplitude of the negative phase of the P-wave in V1. More anterior/superior and more inferior EAS yielded lower absolute values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via BB for EAS1-3 and shifted towards posterior IACs for EAS 4-7. Non-conducting posterior IACs increased PTF-V1 by up to 150%. The electrical contributors EAS and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites. This should be considered when assessing LA anatomy based on the ECG.
Aim: P-wave morphology correlates with the risk for AF. Left atrial enlargement could explain both the higher risk for AF and higher P-wave terminal force in lead V1 (PTF-V1). However, PTF-V1 has been shown to correlate poorly with left atrial size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IACs), which both show tremendous variability. Methods: Atrial excitation was triggered from seven different EASs (Fig 1A,B) in eight anatomically personalized computational models including rule-based fiber orientation and spatial electrophysiological heterogeneity. IACs connected the atria at Bachmann’s bundle, coronary sinus, and posteriorly. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed using realistic, heterogeneous torso models of the same subjects. Results: Mid-septal EASs yielded the highest PTF-V1 measured as the product of the duration and the maximal amplitude of the negative phase of the P-wave in V1. More anterior/superior and more inferior EASs yielded lower absolute values deviating by a factor of up to 2.0 for adjacent EAS (Fig 1C). Earliest right-to-left activation was conducted via BB for EAS1-EAS3 and shifted towards posterior IACs for EAS4-EAS7. Non- conducting posterior IACs increased PTF-V1 by up to 150% (Fig 1D). Conclusions: Location of EAS in the right atrium and its proximity to functioning IACs affect PTF-V1 independently of the left atrial size and further support the caution that needs to be exercised when interpreting electrocardiographically signs of left atrial abnormality, which include PTF-V1.
Catheter ablation has become a very efficient strategy to terminate sustained cardiac arrhythmias like atrial flutter (AFlut). Identification of the optimal ablation spot, however, often proves difficult when scar from previous ablations is present. Although the application of electro-anatomical mapping systems allows to record thousands of intracardiac electrograms (EGMs) from each atrium, state-of-the-art techniques provide limited options for automatic signal processing. Goal of the presented research was the development of an algorithm to detect EGMs that present double potentials (DPs), as these often indicate functional or anatomical lines of block for cardiac excitation. Using an annotated database, we developed several features based on the morphological descriptors of DPs. These were used to train a binary decision tree which was able to detect DPs with a correct rate of over 90%.
Radiofrequency ablation (RFA) is a standard clinical procedure for treating many cardiac arrhythmias. In order to increase the success rate of this treatment, the evaluation of lesion development with the help of intracardiac electrogram (EGM) criteria has to be improved further. We are investigating in-vitro the electrophysiological characteristics of cardiac tissue by using fluorescence-optical and electrical techniques. In this project, it is intended to create ablation lesions under defined conditions in rat atria or ventricle and to determine the electrical activity in the myocardium surrounding these lesions less than 1 s after the ablation. Therefore, we developed a semi-automatic RFA procedure, which was integrated into an existing experimental setup. Firstly, a controllable protection circuit board was designed to galvanically isolate the sensitive amplifiers for measuring extracellular potentials during the ablation. Secondly, a real-time system was implemented to control and to autonomously monitor the RFA procedure. We verified each component as well as the different sequences of the RFA procedure. In conclusion, the expanded setup will be used in future in-vitro experiments to determine new EGM criteria to assess lesion formation during the RFA procedure.
The goal of this research was to classify cardiac excitation patterns during atrial fibrillation (AFib). For this purpose, virtual models of intracardiac mapping catheters were moved across in-silico cardiac tissue to extract local activation times (LATs) of each catheter electrode from simulated cardiac action potential (AP) signals. The resulting LAT patterns consisting of the LATs of all electrodes resemble patterns measured in clinical cases. The LATs represent the input information for features that were used to separate four different excitation patterns during AFib. Those four excitation patterns were plane wave, ectopic focus (spherical wave), rotor (spiral wave) and block. A feature selection algorithm was used to investigate the features concerning their power to classify the different simulated excitation patterns. The scores of the selected features were used to train and optimize a support vector machine (SVM). The optimized and cross-validated SVM was then used to classify the simulated cardiac excitation patterns. The achieved overall classification accuracy of this SVM model was 98.4 %.
This work investigates the impact of time constant offset in the body surface potential map (BSPM) on the recon- struction quality in electrocardiographic imaging (ECGI). For this purpose, a study comparing four different approaches for the reconstruction of the transmembrane voltage distribution (TMV) was carried out. From this four methods two of them were newly designed to estimate and remove the offset from the BSPM. The first approach uses a new formulation of the Tikhonov-Greensite method as augmented regularization to estimate and remove the time constant offset during the reconstruction. The second algorithm is related to classical signal processing. It applies a mode filter to remove the time constant offset in the BSPM and afterwards reconstructs the ventricular ectopic beat (VEB) using the Tikhonov-Greensite regularization. It can be shown that the time constant offset has a significant influence on the reconstruction quality and should be removed. The preferred method to remove time constant offset is the mode filter.
The arrhythmogenic mechanisms of atrial fibrillation (AF) are still not well understood. Increased atrial fibrosis is a structural hallmark in patients with persistent AF. We assessed the electrogram signature rotational activity and their spatial relationship to low voltage areas in patients with persistent AF. Computer simulations implicating 3- dimensional atrial tissue with different amount of atrial fibrosis were used to assess development and stability of rotational activities during AF. Rotor anchoring occurred at the borderzone between fibrosis and healthy atrial tissue with 12 consecutive rotations prior to rotor extinction. Rotational activity in fibrotic tissue resulted in fractionated signals and were overlapped with large negative electrograms in unipolar recording mode from neighboring healthy tissue impressing as a focal source. Necessary conditions for development and stability of rotational activities around fibrosis were on the one hand a minimum size of atrial fibrosis area equal or larger than 10mm x 10mm and on the other hand the degree of atrial fibrosis of 40%. Clinical data showed that AF termination sites were located within low voltage areas (displaying <0,5mV in AF on the multielectrode mapping catheter) in 80% and at their borderzones in 20% of cases.
Aiming for patient specific treatment of atrial fibrillation, cardiologists in the EP-lab (ElectroPhysiology-lab) intend to identify the pattern of depolarization waves in the atria by measuring endocardial electrograms with multichannel catheters. Hereby the pattern of plane waves, ectopic foci, lines of block, or rotors are of special interest. Data acquisition is performed with various multichannel catheters, and all four patterns leave different fingerprints in the electrograms. In this work we extract features from the activation sequence in the electrograms that can support the cardiologist to identify the underlying depolarization pattern. To this end computer simulations of fundamental depolarization scenarios were carried out and the corresponding activation patterns were analyzed.
M. Rottmann, J. Zürn, U. Arslan, K. Klingel, and O. Dössel. Effects of fibrosis on the extracellular potential based on 3D reconstructions from histological sections of heart tissue. In Current Directions in Biomedical Engineering, vol. 2(1) , pp. 675-678, 2016
Atrial fibrillation is the most common arrhythmia. However, the mechanisms of AF are not completely understood. It is known that fractionated signals are measured in AF but the etiology of fractionated signals is still not clear. The central question is to evaluate the effects of segmented fibrotic areas in histological tissue sections on the extracellular potential in a simulation study. We calculated the transmembrane voltages and extracellular potentials from the excitation wave front around a 3D fibrotic area from mouse hearts that were reconstructed from histological tissue sections. Extracellular potentials resulted in fragmented signals and differed strongly by stimulations from different directions. The transmural angle of the excitation waves had a significantly influence on the signal morphologies. We suggest for future clinical systems to implement the possibility for substrate mapping by stimulations from different directions in sinus rhythm.
Atrial arrhythmia is the most common cardiac arrhythmia. Parameters such as conduction velocity (CV), CV restitution etc. are under analysis in order to understand the cardiac arrhythmias. A number of methods have been proposed for CV calculation in simulation as well as clinical environments. Regional CV gives the information about the magnitude and direction of the propagating depolarization wavefronts on the atrium with homogeneous and heterogeneous tissue. The CV in different regions can provide important quantitative electrophysiological information about the underlying tissue. In this work the regional CV has been calculated using simulated local activation times (LAT) on clinical atrial geometries. Regions with homogeneous and heterogeneous propagation were manually selected for LAT simulation and later the regional CV has been calculated. The calculated CV for both the homogeneous and heterogeneous cases for all the clinical cases have been visualized on the atrial geometries. The visualization of the CV on the atrium represents insight into the regional behavior of the atrial substrate. The benefit of the region-specific study in clinical context is that it could enable the localization of critical sites in the patient specific atrial anatomies. Thus, this could aid physicians in cardiac therapies.
B. Verma, T. G. Oesterlein, A. Luik, C. Schmitt, and O. Dössel. Combined analysis of unipolar and bipolar electrograms for local activation time annotation near the stimulus site of paced rhythms.. In Dreilandertagung Swiss, Austrian, and German society of Biomedical Engineering, 2016
B. Verma, T. Oesterlein, A. Luik, C. Schmitt, and O. Dössel. Combined analysis of unipolar and bipolar electrograms for local activation time annotation near the stimulus site of paced rhythms. In Current Directions in Biomedical Engineering, vol. 2, 2016
E. M. Wülfers, O. Dössel, and G. Seemann. Regularity of node distribution impacts conduction velocities in finite element simulations of the heart. In Computing in Cardiology, vol. 43, pp. 177-180, 2016
The monodomain model and finite element method are often used together to compute electrical excitation conduction in cardiac tissue. It is known that the choice of using mass lumping as well as the used ionic current integration method affect the resulting conduction velocities (CVs), especially at coarse resolutions. We describe how the regularity of node arrangement in tetrahedral grids also affects simulated CVs in a similar magnitude. We compare activation times (ATs) over a distance of 21.4 mm at different resolutions to a high resolution reference solution from a previously published benchmark. We show that triangulated grids are able to be within 10% of the reference solution up to a grid resolution of 0.6 mm, while results from regular grids already diverge by more than that at 0.4 mm. At 0.7 mm, a regular grid yields an AT of 80.01 ms, where a triangulated grid with less nodes results in 47.52 ms (reference solution 42.82 ms). We investigate how gradual perturbation of nodes from a regular grid effects AT, finding that CV monotonically increases with degree of node perturbation.
One promising application of electrocardiographic (ECG) imaging is noninvasive reconstruction of atrial activities. However, despite numerous clinical studies, which are mostly concerned with complex irregular excitation patterns, there are relatively few in silico investigations on the imaging of ectopic activation. In the present work, we explore the localization accuracy of ECG imaging regarding atrial focal sites. For the forward calculations, we used four realistic geometrical models with complex anatomical structure and a rule-based fiber orientation embedded into the atrial model. Excitation propagation was simulated with the monodomain model. For each geometrical model, 20 activation sequences originating from the posterior wall of the left atrium were simulated. Based on the bidomain theory, the body surface potential maps resulting from these focal events were computed. For the inverse reconstructions, we employed a full-search procedure based on the fastest route algorithm assuming uniform excitation propagation. Localization errors were revealed to be dependent on the model-specific atrial geometry. We also performed similarity analysis for the first halves of the P wave duration, which improved the results in three models.
An imaging apparatus and method are provided. The probe for an imaging apparatus includes a manually manipulable proximal portion; a straight distal portion with a distal tip for locating at a site to define an observational field; and a curved portion between the proximal portion and the distal portion. The imaging method includes the steps of locating a distal tip of an imaging probe at a site to define an observational field; irradiating the observational field from the distal tip; and collecting a return signal at the distal tip; wherein the probe comprises a manually manipulable proximal portion. The apparatus and method provided herein are useful for various applications including but not limited to endomicroscopy and other microsurgical procedures performed under optical stereoscopic magnified visualization, such as neurosurgery, ENT/facial surgery and spinal surgery.
This disclosure generally relates to medical systems and methods. In one aspect of the invention, a method includes determining a fluorescent light intensity at one or more points on each of multiple recorded images, and producing an image based on the determined fluorescent light intensity at the one or more points.
A. Loewe. Modeling human atrial patho-electrophysiology from ion channels to ECG : substrates, pharmacology, vulnerability, and P-waves. KIT Scientific Publishing. Dissertation. 2016
Half of the patients suffering from atrial fibrillation (AF) cannot be treated adequately, today. This thesis presents multi-scale computational methods to advance our understanding of patho-mechanisms, to improve the diagnosis of patients harboring an arrhythmogenic substrate, and to tailor therapy. The modeling pipeline ranges from ion channels on the subcellular level up to the ECG on the body surface. The tailored therapeutic approaches carry the potential to reduce the burden of AF.
T. Oesterlein. Multichannel Analysis of Intracardiac Electrograms. Supporting Diagnosis and Treatment of Cardiac Arrhythmias. Dissertation. 2016
Cardiologists diagnose and treat atrial tachycardias using electroanatomical mapping systems. These can be combined with multipolar catheters to record intracardiac electrograms. Within this thesis, various signal processing techniques were implemented and benchmarked to analyze electrograms. They support the physician in diagnosis and treatment of atrial flutter and atrial fibrillation. The developed methods were assessed using simulated data and demonstrated on clinical cases.
D. Potyagaylo. Non-Invasive Electrocardiographic Imaging of Ventricular Activities: Data-Driven and Model-Based Approaches. Dissertation. 2016
J. Schmid. Microwave Imaging for Stroke Diagnostics. Dissertation. 2016
Microwave imaging can offer a non-harmful and mobile way of imaging strokes. In this work three imaging algorithms are introduced and the tests whether they are able to image cerebral bleeding are published. Additionally, it contains the development of a phantom with permittivities comparable to a human head.
Student Theses (22)
R. Andlauer. Investigation of the effect of left atrial anatomy alterations on p-wave morphology in a computational model. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
P-wave assessment can offer a simple and inexpensive means to diagnose left atrial enlargement, which is a predictor for atrial fibrillation. However, the underlying influence of left atrial enlargement on the P-wave is not fully understood. Furthermore, P-wave markers to assess left atrial enlargement show poor sensitivity or specificity - potentially due to other left atrial abnormalities similarly affecting P-wave morphology as left atrial enlargement. In an in silico approach, the left atrium was dilated by mechanical inflation. In another approach, the left atrial myocardium was homogeneously thickened in four patient models. To generate torso meshes containing the modified atria, an existing method to mesh tetrahedral torsos was applied for left atrial wall thickening. For left atrial dilation, a new method was developed to generate tetrahedral torso meshes from organ surfaces. Afterwards, the P-waves were simulated for the two different left atrial anatomical alterations. Left atrial wall thickening resulted in an increased P-terminal force in V1 and an increased P-wave area. For left atrial dilation, the resulting P-waves were not realistic, as the underlying electrophysiological simulation method was not es- tablished yet. Furthermore, left atrial dilation was only applied to a single model. Thus, the results were unreliable. Considering this, the results suggest a prolonged P-wave duration, P-wave notching and an increased P-wave amplitude in aV L to be correlated with left atrial dilation.
U. Arslan. Auswirkungen von Fibrose auf kreisenden Erregungen und Erregungen unterschiedlicher Richtungen im Vorhof. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Bachelorarbeit. 2016
A. Baumeister. Konzeption und Analyse eines erweiterbaren, skalierbaren und modularen Frameworks für die Mikrowellen-Bildgebung. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Bachelorarbeit. 2016
In addition to already established imaging techniques like magnet resonance imaging (MRI) or computed tomography (CT), microwave imaging systems have been developed recently and their usage for biomedical applications e.g. stroke detection is researched. Microwave imaging is a promising technique which is expected to lead to a portable and cost effective detection system.For image reconstruction in this area there exists a wide range of approaches and algorithms from radar approaches like beamforming algorithms to tomographic approaches which are based on optimisation problems.An important part of this development is the adaption and optimisation of algorithms used for microwave imaging.In this thesis, a software architecture of an object-oriented framework, which can be used for development of different algorithms, was developed.In addition to the algorithm development, the main purpose of the framework is to provide the opportunity to compare different algorithms of microwave imaging techniques based on equal input data or image size. For an easy extensibility of the framework a modular concept was developed which also respects the requirements of parallel computing of algorithms on a computation cluster.To proof the useability of the software architecture for microwave imaging in the context of stroke detection, different signal processing techniques are integrated into the framework.The basic image reconstruction algorithm used is a beamforming algorithm based on the delay-and-sum principle.This algorithm uses ultra-wideband signals calculated through a finite-difference time domain simulation of a three dimensional head phantom model. Both the reconstruction results and the perfomance of the software architecture was analysed with respect to the scalability of the developed concept.
A. Hahn. Optimization of the measurement setup and the first-guess-model of a microwave tomography system for imaging experimental measurement data. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Diplomarbeit. 2016
Stroke and Traumatic Brain Injury is one of the main causes of death in modern society. Regarding hemorrhagic stroke and other intracranial bleeding, fast and mobile imaging technology is in focus of development to support reliable information on the patients disease. Microwave tomography is a promising technology for future use in intracranial diagnostics. Beside the abdication of X-rays, this development should be mobile and pro- vide real-time measurement supporting the right decision for the correct care.The measurement of complex permittivity values is the recommended information for final image results. Beside the measurement setup, development of image reconstruction algorithms and optimization of nonlinear solvers are in focus of current research. In this project, Gauss-Newton-Optimization is used for approximation. MEEP is used for the forward calculation of the propagating field. Regarding an existing framework, PETSc is implemented for the most important software features like, preconditioning and Gauss- Newton implementation with line search algorithm as well as regularization.Hardware optimization is done by a change of the measurement setup, like antenna po- sitions, number of antennas, amplifiers and the first-guess model. An outlook for further improvements is given.
S. Huck. Implementation and Evaluation of Signal Preprocessing Techniques for Novel Intracardiac High-Density Mapping. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
The novel high-density mapping system RhythmiaTM Medical from Boston Scientific allows a fast and automatic acquisition of endocardial signals. For recording the ORION mini-basket catheter is used which consists of 64 electrodes. Due to the small electrode surface of 0.4mm2, the spatial averaging is smaller than in other commonly used mapping catheters. This results in a higher quality of unipolar signals. Furthermore, the big number of electrodes and the small inter-electrode spacing lead to a high resolution of local activation time maps.An export of the raw data, which were recorded during mapping, was possible. In this thesis, preprocessing techniques for the unipolar signals were implemented and evaluated. Furthermore, local activation time maps were generated. Two preprocessing techniques were implemented with the requirement to identify and eliminate artificial peaks in a spectrum. The peak detection algorithm automatically identified artificial peaks by analysis of their heights in a spectrum. The fundamental frequency calculation was based on the automatic peak detection, but additionally considered if peaks were harmonics of a fundamental frequency. For suppression a Gaussian Notch filter was used. The performance of each identification technique was evaluated using respectively a data set containing manual annotations of 28 spectra. The peak detection resulted in a median sensitivity of 92.1% and in a median positive predictive value of 91.9%. The performance of the fundamental frequency calculation method yielded a median sensitivity and positive predictive value of 100%. Furthermore, the quality of the unipolar electrograms were compared with electrograms derived from the EnSite Velocity mapping system, recorded using the Constellation big-basket catheter. Therefore, the signal-to-noise ratio was calculated. Electrograms which were recorded using the ORION catheter demonstrated a higher signal quality. Three local activation time maps were generated. These maps contained 1403 - 1756 collected measuring points. The visual inspection confirmed a qualitative agreement. The comparison in phase space showed good quantitative agreement with resulting root-mean-square errors of 12.0 - 19.6 ms.
N. Khaled. Development of a novel multielectrode array using microsystem technology for measurements of extracellular potentials in rat myocardium. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
Cardiac arrhythmias are an increasing health care issue, especially in developed countries. Currently, the most prevalent treatment is radio frequency ablation. With however, the most common significantly detrimental arrhythmia, atrial fibrillation, having a recurrence rate of about 20 % at the 18-month mark, a deeper understanding of ablation lesion physiology is necessary to improve the radio frequency ablation procedure.An in vitro set-up is used to investigate electrophysiological behaviour before and directly after the creation of an ablation lesion on vital rat myocardium. A sensor is required to acquire electrical signals needed to characterise the tissue. A multielectrode design with eight measuring sites serves as a basis for the sensor. This multielectrode array has to integrate into the existing in vitro set-up and avoid adversely affecting the cardiac tissue sample.A morphological analysis is used to create multiple concepts by breaking down the design task into constituent subfunctions. These concepts are assessed, reworked, and then turned into a final design for construction. Using a casting process in specialised moulds, a flexible, durable, and biocompatible multielectrode array is manufactured from polydimethylsiloxane and silver. Roadblocks encountered in insulating individual silver wires, to prevent electrical shorts, are circumvented by improving the manufacturing process. Finished multielectrode array prototypes undergo various electrical tests, including a vital tissue test, to investigate their function.With a satisfactory design accuracy, the prototypes manage to perform electrophysiological signal acquisition as intended. Further research using the multielectrode array in the in vitro set-up, aims to further understanding in the underlying mechanisms of cardiac tissue ablation.
L. Kienle. Local activation time based methods for parameter estimation of different excitations in atrial fibrillation. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
A. Kramlich. Development and Benchmarking of Algorithms for the Characterization of Intracardiac Electrograms Measured during Atrial Flutter. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
Automatic signal processing of intracardiac electrograms (EGM) is an important step towards improvement of the diagnostic process and the treatment of atrial flutter. This thesis is concerned with two parts of the signal processing workflow: detection of activity within the recorded EGMs and classification of the EGMs (detection of EGMs with double potentials).For the purposes of the first objective a series of well-established activity detection algorithms as well as new algorithms developed as part of this work were implemented and tested. The five chosen algorithms were based on the NLEO, Hilbert transform, wavelet transform, matched filter and the so called voltage-based approach. The performance of each algorithm was evaluated using a database consisting of approximately 3,000 manually annotated EGMs. Some of the parameters of each algorithm with the strongest influence on the outcome were optimized with regard to the performance of the algorithm on the database. Finally, a comprehensive comparison of the performance results of the algorithms was conducted. With appropriate optimization of the parameters all of the five algorithms evaluated in this thesis performed with correct rates in the range of 91.093.3 %. Further improvements leading to correct rates up to 9495 % were discussed. For the accomplishment of the second objective a classifier for distinguishing between regular EGMs and EGMs with double potentials was developed. For this purpose a set of descriptors was introduced. As before the EGM database was used for the training and the cross-validation of the classifier. The descriptors proposed for the classification showed to be sufficient for an accurate detection of double potentials. The classifiers itself, however, relied on the results of activity detection, which is why the performance of the classifier depended on the accuracy of the underlying activity detection algorithm. The highest obtained correct rate for the classification was 90.9 %.
Y. Lutz. Influence of electrolyte change on sinus node function. A new player regarding sudden cardiac death in patients with chronic kidney disease?. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
Chronic kidney disease (CKD) affects more than 30 million patients in the European Union . 25 % of all deaths in this population are due to sudden cardiac death (SCD) [1 5]. Until recently, ventricular fibrillation was assumed to be the main reason. In a 2015 study, Wong et al. showed that bradycardia and asystole are the predominant mecha- nisms of SCD in patients with CKD . This shows that the underlying mechanisms in the pacemaking of the sinoatrial node (SAN) need to be further analyzed. In this work, a computational model of the human SAN by Fabbri et al.  is used to investigate the CKD-induced electrolyte changes on SAN cell electrophysiology. The original model does not show a stable output for low [Ca2+]o. Furthermore, the model lacks a variable formu- lation of [Na+]i. Since low [Ca2+]o occur in heamodialysis patients and variable [Na+]i is required if the electrolyte concentrations change, a model adaption was performed. A simplex-downhill algorithm and the evaluation of several AP markers was used to adapt the dynamics of the L-type calcium current ICaL.The achieved action potential (AP) shape for the model optimization yielded good accor- dance with the AP shape of the original model. Additionally, the adapted model resulted in physiological excitation of APs down to 0.6mM of [Ca2+]o. The unoptimized model exhibited a critical concentration of ≈1.18 mM. A critical concentration range of calcium in the subspace [Ca2+]sub was identified as possible underlying mechanisms for pacemak- ing. Besides the model adaptation, the main part of this work was the evaluation of the impact of electrolyte changes on the model. Therefore, a wide range of maximal and minimal extracellular electrolyte concentrations in HD patients were determined. [Ca2+]o had the most dominant effects in the original and adapted model. Low [Ca2+]o led to a significant increase in cycle length (CL). The longest achieved CL in the original Fabbri et al. model was 2918 ms, which correlated with a +358 % increase compared to reference CL of 814ms. The related low heart rate of 21bpm can be seen as a possible link to the observed bradycardia in HD patients. For increasing calcium concentration the CL declined, resulting in 383 ms for the highest calcium concentration in the original model. The process of extracellular potassium variation was similar to the one for calcium but resulted in less pronounced maximum and minimum values. The resultant changes in the variation of [Na+]o were relatively small. Variable [Na+]i showed compensating effects compared to the original model.In summary, the adaptations in the Fabbri et al. model led to a more stable output for low [Ca2+]o and to the more realistic assumption of variable [Na+]i. In this work, it showed that the variation of [Ca2+]o had dominating effect on the model electrophysiology. In this context, a critical range of [Ca2+]sub was identified as possible mechanism that af- fects pacemaking. The L-type calcium current ICaL was identified as the main pacemaker current, while the influence of the funny current If or the Na+-Ca2+ exchanger INaCa were relatively small in the critical calcium concentration range.
R. Menges. Quantifying PEST in Holter ECGs and evaluating its usage to stratify risk of cardiac death. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). . 2016
K. Naib. Development of a novel multielectrode array using microsystem technology for measurements of extracellular potentials in rat myocardium. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
Cardiac arrhythmias are an increasing health care issue, especially in developed countries. Currently, the most prevalent treatment is radio frequency ablation. With however, the most common significantly detrimental arrhythmia, atrial fibrillation, having a recurrence rate of about 20 % at the 18-month mark, a deeper understanding of ablation lesion physiology is necessary to improve the radio frequency ablation procedure.An in vitro set-up is used to investigate electrophysiological behaviour before and directly after the creation of an ablation lesion on vital rat myocardium. A sensor is required to acquire electrical signals needed to compute intracardiac electrograms. A multielectrode design with eight measuring sites serves as a basis for the sensor. This multielectrode array has to integrate into the existing in vitro set-up and avoid adversely affecting the cardiac tissue sample.A morphological analysis is used to create multiple concepts by breaking down the design task into constituent subfunctions. These concepts are assessed, reworked, and then turned into a final design for construction. Using a casting process in specialised moulds, a flexible, durable, and biocompatible multielectrode array is manufactured from polydimethylsiloxane and silver. Roadblocks encountered in insulating individual silver wires, to prevent electrical shorts, are circumvented by improving the manufacturing process. Finished multielectrode array prototypes undergo various electrical tests, including a vital tissue test, to investigate their function.With a satisfactory design accuracy, the prototypes manage to perform electrophysiological signal acquisition as intended. Further research using the multielectrode array in the in vitro set-up, aims to further understanding in the underlying mechanisms of cardiac tissue ablation.
H. Nguyen Cong. Estimation of local cardiac conduction velocity based on intra-cardiac recordings. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, afflicting around 1-2% of the population. Although more than half of the AF-attacks are not even noticed by the patients, it is associated with a 5-fold increased risk of stroke and can be life threatening in combination with ischemic strokes. Furthermore the risk of death due to AF-related strokes is doubled . One of the causes for atrial fibrillation or cardiac arrhythmia in general can be re-entry. This phenomenon occurs in diseased or damaged tissue, when excitation conduction is delayed. In this case excitation does not follow its designated path anymore whereby muscle contraction gets out of sync, which consequent- ly leads to a decrease in blood delivery rate. Effective treatment e.g. by radiofrequency ablation needs proper information about the location of those areas. Conduction velocity (CV) provides an important quantity in identifying potential reetrant circuits and thus the position of the diseased tissue zones .In this thesis a novel point-based approach for conduction velocity estimation was tested. Therefore several simulation experiments, varying surface-to-volume ratio and intracel- lular conductivity were made using a tetrahedron model of an atrial tissue strip. The impact of different conduction velocities on the extracellular potential was investigated by analyzing specific characteristics of the voltage curves like amplitude, signalwidth or slope within the recorded unipolar electrograms. Furthermore analytic functions for each marker were approximated and tested upon reliability towards noise and electrode di- stance from the tissue surface. While both amplitude and signalwidth generated almost no estimation error facing white gaussian noise above 125 dB signal-to-noise-ratio (SNR), only signalwidth could withstand the effect of rising electrode distance with tolerable va- lues below 25% error for all distances. The major deviation was recorded within the first 2 mm of electrode distance, hence for further tests with clinical data the boundaries should definitely set below 2 mm and above 125 dB SNR, while using signalwidth-estimation. Successful tests with clinical data are yet to make.
A. Noshadi. 3D reconstruction of ablation lesions in rat myocardium and semi-automatic segmentation of pathologic swine lungs. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
This thesis discusses methods developed for two separate medical image processing problems.Many cardiac arrhythmias, such as atrial fibrillation (AF), are currently treated with radiofrequency ablation (RFA). However, this therapy method has high recurrence rates. The success of the ablation depends on the formation of reliably transmural lesions. In order to improve the success rate of the RFA procedure, the electrophysiological changes in cardiac tissue are investigated which occur with lesion formation. Electrical and fluorescence-optical measurements are made on myocardial tissue from rats. In this thesis, magnetic resonance imaging (MRI) data sets of rat ventricles containing acute ablation lesions were used to reconstruct the three-dimensional (3D) shape of the lesions and to determine their transmurality. The lesion areas in the MRI slices were manually segmented after preprocessing was performed to increase lesion visibility. The 3D geometry of the lesions was then modeled by creating alpha shapes which comprised the segmented regions of the image slices. The analysis of slice segmentation and lesion volume results showed that the low image quality led to high variations in segmentation and lesion volumes. The implemented methods can be applied on new data sets with higher quality to obtain better results.For the analysis of the perfusion in injured swine lungs using electrical impedance tomography (EIT), the study animals were captured in a computed tomography (CT) scanner simultaneously with the EIT measurements to obtain reference data for the validation of the results. The goal of this thesis was to implement an algorithm for the segmentation of the lungs including lesions from the CT images. A semi-automatic segmentation method was developed which was able to detect lung boundaries even if lesions were present in the dorsal regions of the lungs touching the pleura. For this purpose, a region growing algorithm was combined with a spline interpolation approximating the pleura through points detected on the rib surfaces. The developed method delivered accurate segmentation results for the lung regions which where captured with the EIT measurements. The attained segmentation masks had Dice similarity coefficients over 0.96 in reference to manual segmentations performed by physicians.
A. Pala. Mechanische Modellierung von deformierten Multielektrodenkathetern. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Bachelorarbeit. 2016
M. Pfeiffer. Investigation of the contrast source inversion method for microwave brain tomoghraphy. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
In this work, the Contrast Source Inversion algorithm is investigated, with the goal of re-constructing two-dimensional slice images of the complex permittivity of the human brain for stroke diagnosis. The algorithm is explained in detail. Enhancements of the method, such as a multiplicative total variation constraint and frequency hopping are discussed. Multiple numerical models of varying levels of abstraction and their reconstructions are presented. The work is concluded by a discussion of the strengths and shortcomings of the algorithm within the context of stroke diagnosis.
N. Pilia. Characterization and reconstruction of ionic concentrations in the human ventricles analyzing the action potential and the surface ECG. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
In the United States of America, 13.1% of the population suffer from chronic kidney dis- ease (CKD) . Patients suffering from end-stage CKD are often treated by haemodialysis where ionic concentrations of calcium, potassium and sodium get corrected. 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 . The electrocardiogram (ECG) as a continuous, non-invasive monitoring tool could permit new insights into pos- sible links between heart diseases and changed ionic concentrations. In this work, methods for reconstruction of the ionic concentrations from the ECG are evaluated. In a first step, monodomain simulations with the ten Tusscher ventricular cell model  were performed on single cell, strand and whole heart level for different extracellular concentrations. The latter simulations were forward calculated and a standard 12-lead ECG was extracted. Extracellular sodium was varied between 120mmol/l and 150mmol/l, extracellular cal- cium between 0.6mmol/l and 3mmol/l, and extracellular potassium between 3mmol/l and 9 mmol/l as done in . These ranges are comparable to clinically observed ionic con- centrations. Sodium concentration changes showed minimal variations on all three simula- tion levels and were excluded from further investigations. Calcium and potassium changes yielded action potentials and ECGs clearly differing in amplitudes and morphologies. In a second step, 91 simulated ECG signals at different potassium and calcium concentrations - each including one beat - were used for reconstructing the ionic concentrations directly from the ECG. Features were extracted from the signals designed to describe changes caused by varied ionic concentrations. The inverse problem, i.e. coming back from the ECG features to the ionic concentrations was solved by regression. Two methods from literature  , linear regression, linear regression with regularisation (both with a linear and third order polynomial model), random forest regression and regression by artificial neural networks were implemented. Best results for potassium estimation were achieved by neural network regression yielding an estimation error of 0.007 mmol/l±0.2402 mmol/l (mean±standard deviation). Calcium estimation was best performed by third order poly- nomial regression achieving an estimation error of -0.0010 mmol/l±0.0511 mmol/l. Errors were calculated by 13-fold cross validation. Further investigations on the behaviour of the methods could be performed using simulated signals, which are generated with other models, and real measurements. Nevertheless, these first results seem to be very promis- ing: an adequate estimation of potassium and calcium concentrations could be shown to be possible.
F. Plappert. Determining the degree of dissociation in electrical conduction using intracardiac high-density mapping data. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
F. Rafdionza. Analysis of the RS-Difference in Various Excitations of Human Atria. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2016
This thesis focuses on the analysis of the parameter RS difference in intracardiac signals with various type of excitations propagations. Particularly, the excitation propagation of planar waves and ectopic focus are to be analyzed, as well as influence of catheter with various lengths and circular excitations in a three-dimensional heart model. Furthermore, the variations of RS difference in terms of those parameters are to be discussed in this thesis. This project is written in order to discuss how far does RS-difference parameter contribute to detailed diagnosis of atrial fibrillation (AF), and which factors could affect such parameter.
C. Ritter. ECG offset pattern removal and support vector regression for the ECG inverse problem. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
ECG imaging as a noninvasive technology has the aim to reconstruct the transmembrane potential distribution in the human ventricles based on the known body surface potential map. For patients suffering from ventricular ectopic beats (VEB), ECG imaging has also the task to localize the VEB origin.Besides the ill-posedness of ECG imaging, during the measurement in the catheter lab noise and signal artifacts can be occur. A very often signal corruption is time constant offset. It has a negative significant influence on the reconstruction and localization quality. In this work, we studied three different offset patterns, with two different quality criteria on two different time points. It can be shown that offset substracting methods arising either from the field of optimization or the field of signal processing can significantly improve the reconstruction and localization quality.In order to reduce the computational effort for ECG imaging, a machine learning algorithm was used to calculate directly the origin coordinates. This proof of concept will show that ECG imaging can be seen as a regression task and therefore solved with a support vector regression algorithm.
S. Schuler. Developing and coupling a lumped parameter model of the closed loop human vascular system to a model of cardiac mechanics. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
F. Schäuble. Auswertung uni - und bipolarer Elektrogramme bei intrakardialen Messungen mittels MiFiTM Ablationskatheter. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Masterarbeit. 2016
Atrial flutter is ranked among the most common cardiac diseases in western civilizations. Although not directly lethal, the evoked functional deficit of the atria increases the risks for both strokes and atrial stenosis . Beside drug therapy, catheter ablation is the golden standard to silence unphysiological patterns of electrical activation . Boston Scientific is one supplier for keyhole surgical equipment to perform such interventions. Recently, the company has released the novel IntellaTip MiFiTM XP Temperature Ab- lation Catheter as part of its innovation program for the RhythmiaTM System. Thereby, the 7 - electrode MiFiTM catheter is advertised to resolve electrophysiological and structural details in high definition due to 3 de - novo microelectrodes integrated in the ablation electrode. Although medical reports are available, a scientific evaluation of its technical capabilities has not been published to date which motivates this thesis. This work intro- duces developed semi-automatic signal preprocessing algorithms to enhance the signal quality of both uni - and bipolar intracardiac electrograms. As signal filtering for these signals is not standardized, a comprehensive filter study was performed from which a set of Butterworth - filters was identified to be the most e↵ective. For subsequent data processing the 12 - channel electrocardiogram signals were considered as well as data from both the 10-electrode coronary sinus and the 64-electrode OrionTM basket catheters. Likewise, structural data was incorporated obtained via impedance and magnetic localization strategies [5, 6]. Signal processing and evaluation used Mathworks Matlab R2016a (Version 9.0) software. Outcomes comprise the development of a program that allows characterization of electrical behavior of intact and ablated regions with respect to signal morphology, amplitude and propagation velocity. Thereby, MiFiTMs distance and orientation against the wall is taken into account. As far as the microelectrodes are concerned, they proofed to record electrical signals with fine spatial sensitivity. This was evaluated based on several well-commented scenarios within the clinical datasets. In conclusion, this work can be regarded as the first step towards an algorithm enabling a semi - automatic evaluation of artificial lesions post ablation therapies. Likewise, it defines a solid base for future work in this regard.
E. M. Wülfers. A comparison of mathematical models and numerical schemes for simulating body surface potential maps on realistic geometries. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2016
Computational cardiac electrophysiology is an important tool in researching cardiovas- cular diseases and their treatments. This thesis describes mathematical models and nu- merical methods to compute electrophysiological activity in computational models of the heart and human body. The models presented comprise the mono- and bidomain models for electrically active tissue, as well as mathematical models of single cardiac cells.The mono- and bidomain models pose partial differential equations (PDEs). The finite dif- ferences method (FDM) and the more flexible finite element method (FEM) are presented as appropriate solution techniques. Both methods transform the PDEs into problems of linear algebra, namely sparse matrix-vector equations, which can be solved using itera- tive algorithms. Single cell models are posed in form of ordinary differential equations for which appropriate solution methods are described as well.The numerical methods and their various parameters are tested thoroughly in an estab- lished benchmark setup of the monodomain model. Results show that the newly imple- mented FEM produces more accurate results especially on coarse geometries. In fact, spa- tial resolution becomes almost irrelevant (within the tested range of 0.1 mm to 0.5 mm) when using the variant with a consistent mass matrix and a sufficiently irregular spatial sampling.Subsequently, similar tests are performed using the bidomain model, both on isolated tis- sue models, and on such that are surrounded with a passive conductive medium. Lastly, the methods are applied to a realistic geometry. A setup from a previously published sim- ulation study based on monodomain FDM simulations is redone using bidomain FEM simulations, greatly reducing the size of the simulation geometry from 181 million to less than half a million nodes. Resulting simulated body surface potential maps (BSPMs) and electrocardiograms (ECGs) do not completely match the previously simulated, but are promising first steps. Work remains to be done on proper adaption of bidomain con- ductivities to the monodomain setup or measured data. The results obtained using FEM are especially promising with regard to a possible coupling of electrophysiological simu- lations with mechanical simulations, where the simulation geometry is deformed during simulation.