Atypical atrial flutter (AFlut) is a reentrant arrhythmia which patients frequently develop after ablation for atrial fibrillation (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clinically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensitivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabiltiy on a clinical dataset. Finally, we tested how AFlut vulnerability of these substrates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut.
Conference Contributions (2)
A. Loewe, Y. Lutz, A. Fabbri, and S. Severi. Sinus Bradycardia Due to Electrolyte Changes as a Potential Pathomechanism of Sudden Cardiac Death in Hemodialysis Patients. In Biophysical Journal, vol. 116(3 suppl1) , pp. 231A, 2019
A. Wachter, A. Mohra, and W. Nahm. Development of a real-time virtual reality environment for visualization of fully digital microscope datasets. In Proceedings of SPIE, vol. 10868, pp. 108681F1-9, 2019
Current surgical microscope systems have excellent optical properties but still involve some limitations. A future fully digital surgical microscope may overcome some major limitations of typical optomechanical systems, like ergonomic restrictions or limited number of observers. Furthermore, it can leverage and provide the full potential of digital reality. To achieve this, the frontend, the reconstruction of the digital twin of the surgical scenery, as well as the backend, the 3-D visualization interface for the surgeon, need to work in real-time. To investigate the visualization chain, we developed a virtual reality environment allowing pretesting this new form of 3-D data presentation. In this study, we wanted to answer the following question: How must the visualization pipeline look like to achieve a real-time update of the 3-D digital reality scenery. With our current approach, we were able to obtain visualizations with a frame rate of 120 frames per second and a 3-D data update rate of approximately 90 datasets per second. In a further step, a first prototype of a real-time mixed-reality head mounted visualization system could be manufactured based on the knowledge gained during the virtual reality pretesting.
A computer system for determining Ventricular Far Field contribution in atrial electrograms of a patient. The system includes an interface module configured to receive a plurality of electrical signals generated by a plurality of sensors wherein the plurality of electrical signals relate to a plurality of locations in an atrium of the patient; a reference module configured to determine a reference signal reflecting electrical excitation of the patient's ventricles; and a data processing module. The data processing module is configured to select from the plurality of the received electrical signals such electrical signals which are recorded a number of conditions. The data processing module is further configured to determine a spatio-temporal distribution of the Ventricular Far Field inside the atrium by approximating the spatio-temporal distribution (VFFc) based on signal data of the selected signals by using an approximation model.
A catheter has a mapping assembly having a plurality of splines mounted at its distal portion. The splines each have a proximal end disposed at the distal portion of the catheter body and a distal end and configured as a Fibonacci spiral arm that diverges outwardly from the proximal end. The splines have a support arm with shape memory, a non-conductive covering in surrounding relation to the support arm, at least one location sensor mounted at or near the distal end, a plurality of electrodes mounted in surrounding relation to the non-conductive covering, and a plurality of electrode lead wires extending within the non-conductive covering. Each electrode lead wire is attached to a corresponding one of the electrodes.
S. Pollnow. Characterizing Cardiac Electrophysiology during Radiofrequency Ablation: An Integrative Ex vivo, In silico, and In vivo Approach. KIT Scientific Publishing / Karlsruhe Transactions on Biomedical Engineering. Dissertation. 2019
Catheter ablation is a major treatment for atrial tachycardias. Hereby, the precise monitoring of the lesion formation is an important success factor. This book presents computational, wet-lab, and clinical studies with the aim of evaluating the signal characteristics of the intracardiac electrograms (IEGMs) recorded around ablation lesions from different perspectives. The detailed analysis of the IEGMs can optimize the description of durable and complex lesions during the ablation procedure.
Student Theses (7)
A. Aracri. Simulation study: parameterization of a hemodynamics model and conception of a multidimensional sensitivity analysis. Institute for Anthropomatics and Robotics (KIT); Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2019
Strokes are the third leading cause of death in western countries, of which 87 % are ischemic. A common treatment is the recanalization of the occluded vessel and therapeutic hypothermia using body surface cooling. The latter is assumed to have a neuroprotective effect, lowering the metabolic rate of the undersupplied tissue and preventing inflammations. However, cooling of the entire body leads to side-effects such as cardiac arrhythmia and organ damage, especially of the lungs. Selective cooling of the carotid blood is a new promising treatment that has the potential to give more control over the cooling, decreasing the side-effects. A temporal and spatial knowledge of the cerebral blood flow and temperature is a necessity for regulating the rate of cooling. Central to the cerebral flow distribution is an arterial circular structure, the circle of Willis. Its redundant collaterals have a compensatory effect in case of ischemia. It varies strongly across patients and underlies anatomical variations, ultimately influencing the compensatory capabilities. In this work, a preexisting hemodynamic model based on the transmission-line approach was extended by a parameterization of patient-specific factors. A simulated study on the cerebral flow was performed, aiming to analyze the parameter sensitivity and interrelations. Stenoses in the M1 segment of the middle cerebral artery (MCA) and the internal carotid artery have been inspected and their respective compensatory mechanisms and influences on said mechanisms were analyzed. In case of a stenosed internal carotid artery (ICA), the mean terminal flow of the anterior cerebral artery (ACA) was reduced from 1.39ml/s to 1.01ml/s, the MCAs from 2.56ml/s to 1.9ml/s. A stenosed M1 segment caused the MCAs flow to be reduced from 2.56ml/s to 0.7ml/s while slightly increasing flow in every other cerebral artery. Anatomical variations, with one or multiple vessels of the circle of Willis (CoW) missing could cause further decrease of terminal vessel flow: up to 14.7 % for a stenosed ICA (missing A1 segment of the other side) and 2.4% for a stenosed MCA (missing P1 segment of the same side and posterior communicating artery (PCoA) of the other side) in regard to the reference mean flow. In case of a stenosed M1 segment, the MCA showed mean flows between 0.18ml/s and 1.34ml/s, depending on the degree of collateralization. This corresponds to a maximum compensation of 53 %. For a stenosed ICA, the collaterals had less effect: depending on the collateralization, the mean flows of the ACA / MCA varied between 0.99ml/s / 1.86ml/s and 1.04ml/s / 1.98ml/s. The model can be personalized according to the specific patient and, in combination with a temperature model, it can be used to monitor the hypothermia of patients suffering from ischemic strokes. The monitoring enables regulating the temperature to appropriate setpoints.
J. Brenneisen. Analyse und Vergleich verschiedener EIT Rekonstruktionsansätze anhand simulierter und gemessener Daten hinsichtlich herzsynchroner Pulsatilität. Institut für Biomedizinische Technik, Karlsruhe Institut für Technologie (KIT). Masterarbeit. 2019
Als Verfahren zum Monitoring der Lungenaktivität findet die elektrische Impedanztomographie (EIT) in den vergangenenen Jahren zunehmende Anwendung. Dabei wird vergleichsweise einfach, günstig und portabel mittels Elektrodengurt um die Brust des Patienten ein Messsignal aufgenommen. Daraus kann mit Hilfe mathematischer Rekonstruktionsalgorithmen ein Bild errechnet werden, welches die Ventilationsverhältnisse in der Lunge wiedergibt. Um aus den gemessenen Daten zusätzlich das Ventilations-Perfusions-Verhältnis (VPR) anzugeben, welches als Maß für den Gasaustausch in der Lunge von hohem klinischen Interesse ist, ist zusätzlich die Auswertung der Perfusion nötig. Die Perfusion wurde dabei mittels Blutvolumenänderung, die in einer herzsynchronen Pulsatilität im EIT-Signal resultiert, bestimmt. Ziel dieser Arbeit war es, den Einfluss zu untersuchen, den verschiedene Rekonstruktionsalgorithmen und dieWahl derer Parameter - hinsichtlich dieser herzsynchronen Pulsatilität - auf das resultierende Bild haben. Dazu wurde in einem ersten Schritt ein Simulationsmodell implementiert, die Pulsatilität mittels einer kugelförmigen Impedanzänderung approximiert und anschließend eine Simulation durchgeführt. Um die erzielten Ergebnisse adäquat vergleichen zu können, wurden neben mehreren Simulationsszenarien auch die Auswertungskriterien, anhand derer die Rekonstruktionsergebnisse quantifiziert werden können, entwickelt. Dabei wurde zuerst der statische Fall eingehender betrachtet, mit dem die wichtige Wahl des korrekten Hyperparameters durchgeführt wird. Davon ausgehend wurden die Rekonstruktionseinflüsse im dynamischen Fall untersucht. Sowohl die Variation der Gefäßgröße als auch die Änderung der Leitfähigkeiten eines stark durchbluteten Gebietes, sowie die Einflüsse von anderen Gewebeschichten wurden dazu beleuchtet. Auch das Einbringen von Vorwissen, das genutzt werden kann, um das schlecht gestellte Rekonstruktionsproblem zu verbessern, wurde untersucht. In einem letzten Schritt wurden die untersuchten Rekonstruktionsalgorithmen auf real gemessene Daten angewendet, um den Einsatz in der Praxis zu testen. Zusammenfassend lässt sich festhalten, dass eine Rekonstruktion der herzsynchronen Pulsatilität aus simulierten Daten gut möglich war. Das Vorhandensein einer Impedanzänderung wurde eindeutig erkannt. Auch die Variation verschiedener Einflussfaktoren konnte quantitativ erfasst werden. Die Einflüsse verschiedener Rekonstruktionsalgorithmen waren dabei erkennbar. Abschließend lieferte die Anwendung auf gemessene Daten ein plausibles Rekonstruktionsergebnis. Die rekonstruierte Lungenlage stimmte gut mit dem MRT-Bild überein.
R. Hattiangdi. 3D sensitivity analysis of human EIT measurements based on EIT forward simulation in the context of pulmonary perfusion monitoring. Hochschule Karlsruhe - Technik und Wirtschaft; Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2019
Electrical Impedance Tomography (EIT) is a radiation-free functional imaging modality used in biomedical applications, primarily, to obtain real-time images of the lungs. Since its invention, there has been an increasing scientific and clinical interest in this technology driven by the clinical need for monitoring and assessing the regional lung function at the bedside. One of the existing drawbacks of this measurement technique is, that it generates two-dimensional images from data which is influenced by three-dimensional parameters. One such parameter is pulmonary perfusion. This thesis aims to analyze the sensitivity of the measurements to a change in the conductivity due to perfusion at certain locations within the body. The aim is to estimate the contribution of varying conductivity on the readings and consequentially, generate a three-dimensional sensitivity profile which could help in better interpretation and understanding of the EIT. This profile can be used as a guideline by technicians, while developing new reconstruction algorithms, to correctly estimate the context of the measured signals. In order to achieve this, forward simulations were carried out on an FEM model of the human thorax. The model was generated by segmentation of MRI images. It was infused with spheres with higher conductivities at distinct locations in the lungs to simulate pulmonary perfusion. The results generated by the simulated measurements were calculated and compared to quantify the change in the output with respect to change in the position of the sphere relative to the belt. The main results that were sought out were: the sensitivity of the EIT measurements to perfusion and how the reconstructed images projected the effects of pulmonary perfusion in 3D, on the 2D reconstruction plane. The results obtained were in accordance with the hypotheses. The sensitivity analysis showed a varying profile which showed that the sensitivity reduced as the perfusion occurred higher up in the lung. The expected effects were also visible in the reconstructed images, which showed the position error as well as amplitude response to the perfusion changes.
L. Meyer-Hilberg. Modeling of the Flow Behavior of a Bolus in a Flow Phantom for Intraoperative ICG Fluorescence Angiography. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2019
This topic was embedded in the project of measuring blood flow intraoperativly with an optical system (surgical microscope). Measuring blood flow is important to assess the tissues perfusion. In case of hypoperfusion, the function of the tissue cannot be maintained and irreversible damages are possible. To visualize the flow dynamics in the blood, the fluores- cence dye Indocyanine Green (ICG) is injected intravenously and the dyes’ fluorescence is captured with a NIR camera. The performance of methods which assess the blood flow dynamics cannot be determined on living subjects. To facilitate the performance testing, a blood flow phantom was set up within the scope of this thesis. The main goals of this thesis were the design and the installation of the injection mimicking setup and its validation. Since no detailed flow profile of the fluids’ dynamic was available, an in-silico simulation of the flow phantom was implemented via COMSOL Multiphysics. In comparison to previous theses, the focus was on the diffusion and and convection processes of the fluorescence dye for different dimensioning of the ICG dyed bolus. The spatio-temporal morphology of the fluorescence signal depends with some constraint on the volume flow of the liquid media. For the design of the flow phantom, blood analogs were researched to obtain the flow behavior of whole blood, to support the fluorescence of ICG and to avoid impairment of the optical detection. With an ICG concentration of 0.005 g , l the optical detection of the ICG bolus was successful. The in-silico simulation of the flow dynamics and the distribution of the ICG dye showed similar results: the first but not the second boundary of the ICG bolus was detectable for a chosen dimensioning of the ICG dyed bolus. The technical model developed within the scope of this thesis shows promising results for further research. The propagation of the excitation and the fluorescence light can be calculated based on the calculated ICG distribution within the given geometry. With the optical part of the modeling, the distribution of ICG will be better understood and the development of methods which assess the blood flow will be supported.
O. Pauer. Modeling of the human cerebral circulation adaption of a hemodynamics model based on avolio for temperature calculation. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2019
Stroke is the third-most widespread cause of death in western countries. 87 % of them are ischemic strokes. The current standard therapy often involves the placement of a catheter into the affected artery. Simultaneously, hypothermia of the whole body is exercised, which slows down the metabolism of the entire human body. A new promising therapy is currently developed. It involves a cooling catheter that is placed into the common carotid artery. The catheter cools the blood flow into the affected area. However, during the therapy it is not possible to measure the cerebral temperatures without further harm for the patient. The temperatures therefore need to be simulated in a computational model, which includes most of the human arterial system. The currently used hemodynamic model included detailed arterial structures of the arms and the torso, which captured ~35 % percent of the model. However, these parts were not relevant for the temperature simulation in the cerebral region. The hypothesis was, that the arterial structures of the arms and the torso can be modeled in a more efficient way without losing cerebral influence during a stenosis. Therefore, an alternative for the modeling of these parts was desired. The chosen replacement for the arterial structures was the three element Windkessel (WK) model. The modeling of the WK was done using equation based modeling. The differential equations of the WK were implemented consistent with the current model using C code in s-function blocks of Simulink. The WK were then connected to the model at the corresponding segments. The replacements reduced the model by 304 parameters, which equals around a third of the former model. The adaption influenced the flow curves and the average flow into the replaced structures and in the cerebral region. The change in average flow rates was smaller than 5 %. After the adaption, the elements of the WK were optimized using a trust region reflective optimization, which was conducted in Matlab (lsqnonlin). The optimization improved the curve forms of the flows into the replaced arterial structure. Additionally, a sensitivity analysis of the WK parameters was executed. The results showed, that the resistors inside the Windkessel model had the highest influence. However, this influence was very small. In the end, the influence of a stenosis on the adapted model was executed and evaluated. The influence of a stenosis on the average flow into the replaced arterial structures did not change. In conclusion, the replacement had a neglectable influence on the hemodynamic model. The optimization improved the outcome of the flow curves and the sensitivity analysis showed, that the parameters do not significantly change the characteristics of the model. In the future, the outcome of the adaption can be further evaluated and the optimization could be further extended.
B. Smardanski. Diagnosing hypo- and hyperkalemia and hypo- and hypercalcemia with the 12-lead ECG. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2019
Sudden, drastic changes in blood ion concentrations are common and clinically silent in patients with renal disease, from which around 42 million people in the US suffer. While otherwise healthy patients can tolerate mild hyperkalemia (i.e. high serum potassium), this condition can be life-threatening in patients suffering from cardiac disease. A non-invasive, robust, unobtrusive method for estimation of potassium and calcium concentrations in blood serum would be an important clinical advancement, providing basis for continuous monitoring an early warning for high-risk patients. During hemodialysis, patients underwent a high-resolution 12-lead electrocardiogram (ECG) recording and had 1-7 extracorporeal blood tests taken. Such data from 127 sessions of overall 42 patients was used as basis for this work. Signal processing methods were applied for signal-to-noise Ratio (SNR) improvement, followed by an averaging procedure condensing the continuous signal down to single beat ECG templates. Each template was then reduced to 14 features, whose correlations with the targets were positively assessed in previous works. Two novel features relating to the curvature of the T wave were also included. For the purpose of feature extraction a novel algorithm for finding onset and offset of the T wave was developed, which outperformed existing algorithms in a test scenario with artificially generated ECG signals. Initially, a global method for estimating potassium and calcium based on the features was developed. 112 different parametrizations of shallow neural network were tested, which all led to unsatisfactory estimation resolution.Features that exhibited the best linear dependencies with the targets out of the 14 initially chosen features were selected. Using these features and applying a 2-point calibration for each session, a simple linear model was set up, which delivered an estimation error of 0.09 mmol/l ± 0.54 mmol/l (mean ± standard deviation) for potassium and −0.01 mmol/l ± 0.12 mmol/l for calcium, after a 10-fold cross-validation. When the calibration procedure was done only with the information of the first session for each patient the estimation results were −0.2 mmol/l ± 0.68 mmol/l for potassium and −0.00 mmol/l ± 0.14 mmol/l for calcium. The methods for estimation of potassium and calcium blood ion concentration using clinical ECG data could not achieve the results of studies using simulated data. Nevertheless, the novel method presented in this work, featuring a patient-specific calibration, performs up to par with state of the art methods, exhibiting acceptable accuracy, making it clinically relevant for first-level remote monitoring of high-risk patients.
I. Tabet. Development and Quantitative Analysis of Automatic Electrical Impedance Tomography Signal Component Detection and Separation Algorithms. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2019
Pulmonary diseases are responsible for over 3 million deaths per year worldwide and more people are currently suffering from underdiagnosed pulmonary diseases. A proper diagnosis of pulmonary diseases requires an adequate respiratory monitoring. With the electrical impedance tomography (EIT) it is already possible to visualize the distribution of air inside the lungs and even the estimation of pulmonary perfusion by the use of the indicator dilution theory provides promising results. For perfusion estimation, a bolus of saline solution is injected to monitor the impedance changes caused by the higher conductivity of the injected indicator. However, this has only been shown for measurements in absence of respiration so far which requires a potentially strenuous ventilatory hold. This thesis deals with the detection of bolus signals during mechanical ventilation and their separation from respiration, which might further allow for a clinically more accepted method. The bolus detection was realized using a matched filter (MF) approach and evaluated on measured data with regard to sensitivity and specificity. Synthetic EIT signals were generated and used to analyze a separation based on frequency filtering. The separation quality was investigated using multiple error and similarity measures to compare original and separated signals. The automatic bolus detection algorithm provided satisfying results with a sensitivity over 96 % and specificity of 92 % for bolus injections with 5 % NaCl concentration. Further- more, the separation of those signals yielded correlation coefficients greater 0.94. However, morphological signal parameter differed between bolus signals before and after separation, which could lead to a misinterpretation of EIT indicator perfusion measurements.