S. Pollnow, G. Schwaderlapp, A. Loewe, and O. Dössel. Monitoring the dynamics of acute radiofrequency ablation lesion formation in thin-walled atria – a simultaneous optical and electrical mapping study. In Biomedical Engineering / Biomedizinische Technik, vol. 65(3) , pp. 327-341, 2020
Background Radiofrequency ablation (RFA) is a common approach to treat cardiac arrhythmias. During this intervention, numerous strategies are applied to indirectly estimate lesion formation. However, the assessment of the spatial extent of these acute injuries needs to be improved in order to create well-defined and durable ablation lesions. Methods We investigated the electrophysiological characteristics of rat atrial myocardium during an ex vivo RFA procedure with fluorescence-optical and electrical mapping. By analyzing optical data, the temporal growth of punctiform ablation lesions was reconstructed after stepwise RFA sequences. Unipolar electrograms (EGMs) were simultaneously recorded by a multielectrode array (MEA) before and after each RFA sequence. Based on the optical results, we searched for electrical features to delineate these lesions from healthy myocardium. Results Several unipolar EGM parameters were monotonically decreasing when distances between the electrode and lesion boundary were smaller than 2 mm. The negative component of the unipolar EGM [negative peak amplitude (Aneg)] vanished for distances lesser than 0.4 mm to the lesion boundary. Median peak-to-peak amplitude (Vpp) was decreased by 75% compared to baseline. Conclusion Aneg and Vpp are excellent parameters to discriminate the growing lesion area from healthy myocardium. The experimental setup opens new opportunities to investigate EGM characteristics of more complex ablation lesions.
Optical mapping is widely used as a tool to investigate cardiac electrophysiology in ex vivo preparations. Digital filtering of fluorescence-optical data is an important requirement for robust subsequent data analysis and still a challenge when processing data acquired from thin mammalian myocardium. Therefore, we propose and investigate the use of an adaptive spatio-temporal Gaussian filter for processing optical mapping signals from these kinds of tissue usually having low signal-to-noise ratio (SNR). We demonstrate how filtering parameters can be chosen automatically without additional user input. For systematic comparison of this filter with standard filtering methods from the literature, we generated synthetic signals representing optical recordings from atrial myocardium of a rat heart with varying SNR. Furthermore, all filter methods were applied to experimental data from an ex vivo setup. Our developed filter outperformed the other filter methods regarding local activation time detection at SNRs smaller than 3 dB which are typical noise ratios expected in these signals. At higher SNRs, the proposed filter performed slightly worse than the methods from literature. In conclusion, the proposed adaptive spatio-temporal Gaussian filter is an appropriate tool for investigating fluorescence-optical data with low SNR. The spatio-temporal filter parameters were automatically adapted in contrast to the other investigated filters.
Radiofrequency ablation has become a first-line approach for curative therapy of many cardiac arrhythmias. Various existing catheter designs provide high spatial resolution to identify the best spot for performing ablation and to assess lesion formation. However, creation of transmural and nonconducting ablation lesions requires usage of catheters with larger electrodes and improved thermal conductivity, leading to reduced spatial sensitivity. As trade-off, an ablation catheter with integrated mini electrodes was introduced. The additional diagnostic benefit of this catheter is still not clear. In order to solve this issue, we implemented a computational setup with different ablation scenarios. Our in silico results show that peak-to-peak amplitudes of unipolar electrograms from mini electrodes are more suitable to differentiate ablated and nonablated tissue compared to electrograms from the distal ablation electrode. However, in orthogonal mapping position, no significant difference was observed between distal electrode and mini electrodes electrograms in the ablation scenarios. In conclusion, catheters with mini electrodes bring about additional benefit to distinguish ablated tissue from nonablated tissue in parallel position with high spatial resolution. It is feasible to detect conduction gaps in linear lesions with this catheter by evaluating electrogram data from mini electrodes.
Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty. In comparison, unipolar electrograms are not sensitive to wavefront direction, but measurements are susceptible to distal activity. This study proposes a method for local CV calculation from optical mapping measurements, termed the circle method (CM). The local CV is obtained as a weighted sum of CV values calculated along different chords spanning a circle of predefined radius centered at a CV measurement location. As a distinct maximum in LAT differences is along the chord normal to the propagating wavefront, the method is adaptive to the propagating wavefront direction changes, suitable for electrical conductivity characterization of heterogeneous myocardium. In numerical simulations, CM was validated characterizing modeled ablated areas as zones of distinct CV slowing. Experimentally, CM was used to characterize lesions created by radiofrequency ablation (RFA) on isolated hearts of rats, guinea pig, and explanted human hearts. To infer the depth of RFA-created lesions, excitation light bands of different penetration depths were used, and a beat-to-beat CV difference analysis was performed to identify CV alternans. Despite being limited to laboratory research, studies based on CM with optical mapping may lead to new translational insights into better-guided ablation therapies.
Conference Contributions (14)
S. Pollnow, R. Arnold, M. Werber, O. Dössel, and G. Seemann. Hyperthermia dependence of cardiac conduction velocity in rat myocardium: Optical mapping and cardiac near field measurements. In 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 3688-3691, 2017
Hyperthermia during radiofrequency ablation causes reversible and irreversible changes of the electrophysiological properties of cardiac tissue. However, the mechanisms are incompletely understood. We studied changes of conduction velocity (CV) in rat myocardium under hyperthermic conditions from macroscopic to microscopic scale by using simultaneous optical mapping and a miniaturized electrode array. Atrial preparations from five rats were superfused at tissue bath temperatures between 36.7°C and 43.8°C. Optical mapping data showed an elevated median CV by 21% when increasing the temperature from 36.7°C to 42.0°C. CV did not increase above 42.0°C. Electrical measurements revealed a similar temperature dependence of CV between 36.7°C and 42.0°C, i.e. an increase of median CV by 26%. The consolidation of optical and electrical data in this study allowed investigation of excitation during global hyperthermia. Macroscopic optical mapping and microscopic electrical measurements demonstrated that hyperthermia strongly influenced electrical propagation at a microscopic scale.
Radiofrequency ablation is the gold standard for treating cardiac arrhythmias. However, the success rate of this procedure depends on numerous parameters. Wet lab experiments provide the opportunity to investigate cardiac electrophysiology under reproducible conditions. To evaluate the electrophysiological changes of ablated myocardium in these studies it is necessary to consider the three-dimensional (3D) geometry of the lesions. For this purpose, we investigated the usage of different magnetic resonance imaging (MRI) sequences as well as an image processing procedure to analyze in-vitro preparations. To differentiate signal intensities between nonablated and ablated tissue we evaluated FISP (fast imaging with steady-state precession; delivering dominantly T1-weighted images) and RARE (rapid acquisition with relaxation enhancement; delivering dominantly T2-weighted images). After image processing, the ablated tissue was segmented in each image slice forming a 3D volume. The geometry of the lesion was modeled by the boundary of this volume. It was generally feasible to distinguish between healthy myocardium and ablated tissue as well as to determine lesion transmurality. The analysis of the reconstructed lesion geometries from FISP and RARE MRI showed a high agreement, however T2-weighted sequences showed larger lesion volumes as well as higher variations in segmentation compared to T1- mapping. FISP with higher quality may be used to reconstruct the 3D geometry of the ablation lesions.
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.
Atrial fibrillation (AF) is the most common cardiac ar- rhythmia seen in clinical practice and its treatment by an- tiarrhythmic drugs is still non-effective. Radiofrequency catheter ablation (RFA) has been widely accepted as a strategy to prevent AF by creating myocardial lesions to block the AF electrical wavefront propagation and elimi- nate arrhythmogenic tissue. In this study, we analyzed the electrophysiological impact of different RFA time duration strategies through a controlled animal protocol. Electrical activity of the isolated right atrium of rats, under different RFA time strategies on the epicardium, was acquired dur- ing 4 s on the endocardium by electrical Mapping (EM) and simultaneously on the endocardium by Optical Map- ping (OM), respectively. Analyses were concentrated on both time and frequency domain, through analysis of sig- nal’s morphology, local activation time, conduction veloc- ity, dominant frequency (DF), and organization index (OI). The morphology of the optical and electrical signals was altered as the ablation time increased, making it difficult to identify activation times. Moreover, DF and OI decreased with increasing ablation time implied in fragmented elec- trograms. Through the characterization of traditional met- rics applied to the electrical and optical data, it was pos- sible to identify important changes, in time and frequency, inside the ablated regions.
Cardiac arrhythmias such as atrial fibrillation occur frequently in industrialized countries. Radiofrequency ablation (RFA) is a standard treatment if drug therapy fails. This minimally invasive surgery aims at stabilizing the heart rhythm on a permanent basis. However, the procedure commonly needs to be repeated because of the high recurrence rate of arrhythmias. Non-transmural lesions as well as gaps within linear lesions are among the main problems during the RFA. The assessment of lesion formation is not adequate in state of the art procedures. Therefore, the aim of this study is to investigate the short-term reversibility of lesions using human electrograms recorded by a high-density mapping system during an electrophysiological study (EPS). A predefined measurement protocol was executed during the EPS in order to create three ablation points in the left atrium. Subsequently, after preprocessing the recorded signals, electrogram (EGM) paths were formed along the endocardial surface of the atrium. By analyzing changes of peak to peak amplitudes of unipolar EGMs before and after ablation, it was possible to distinguish lesion area and healthy myocardium. The peak to peak amplitudes of the EGMs decreased by 40-61% after 30 seconds of ablation. Furthermore, we analyzed the morphological changes of EGMs surrounding the lesion. High-density mapping data showed that not only the tissue, which had direct contact with the catheter tip during the RFA, but also the surrounding tissue was affected. This was demonstrated by low peak to peak amplitudes in large areas with a width of 14 mm around the center of the ablation lesion. After right pulmonary vein isolation, high-density mapping was repeated on the previous lesions. The outer region of RFA-treated tissue appears to recover as opposed to the central core of the ablation point. This observation suggests that the meaningfulness of an immediate remap after ablation during an EPS may lead the physician to false conclusions.
Today, patients suffering from atrial arrhythmias like atrial flutter (AFlut) or atrial fibrillation (AFib) are examined in the EP-lab (electrophysiology lab) in order to understand and treat the disease. Multichannel catheters are advanced into the atria in order to measureelectric signals at manyintracardiacpositions simultaneously. Complementary to clinical learning,comprehension of the disease and therapeutic strategies can be improved with computer modeling of the heart. This way, hypotheses about initiation and perpetuation of the arrhythmia can be tested and ablation strategies can be assessed in-silico. Modeling and biosignal analysis can benefit from mutual fertilization. On the one hand, modeling can be improved and personalization can be achieved via high density mapping of the atria. On the other hand, new algorithms for the interpretation of multichannel electrograms can be developed and evaluated with synthetic signals from computer models of the atria. This article illustrates the synergetic potential by examples and highlights challenges to be addressed in the future.
C. Gross, S. Pollnow, O. Dössel, and G. Lenis. Automatic feature extraction algorithms for the assessment of in-vitro electrical recordings of rat myocardium with ablation lesions. In Current Directions in Biomedical Engineering, vol. 3(2) , pp. 249-252, 2017
Cardiac arrhythmias are a widely spread disease in industrialized countries. A common clinical treatment for this disease is radiofrequency ablation (RFA), in which high frequency alternating current creates a lesion on the myocardium. However, the formation of the lesion is not entirely understood. To obtain more information about ablation lesions (ALs) and their electrophysiological properties, we established an in-vitro setup to record electrical activity of rat myocardium. Electrical activity is measured by a circular shaped multielectrode array. This work was focused to gain more information by developing algorithms to process the measured electrical signals to collect different features, which may allow us to characterize an AL. First, pacing artefacts were detected and blanked. Subsequently, data were filtered. Afterwards, activations in atrial signals were detected using a non-linear energy operator (NLEO) and templates of these activations were generated. Finally, we determined different features on each activation in order to evaluate changes of unipolar as well as bipolar electrograms and considered these features before and after ablation. In conclusion, the majority of the signal features delivered significant differences between normal tissue and lesion. Among others, a reduction in peak to peak amplitude and a diminished spectral power in the band 0 to 100 Hz may be useful indicators for AL. These criteria should be verified in future studies with the aim of estimating indirectly the formation of a lesion.
Lung ventilation and perfusion analyses using chest imaging methods require a correct segmentation of the lung to offer anatomical landmarks for the physiological data. An automatic segmentation approach simplifies and accelerates the analysis. However, the segmentation of the lungs has shown to be difficult if collapsed areas are present that tend to share similar gray values with surrounding non-pulmonary tissue. Our goal was to develop an automatic segmentation algorithm that is able to approximate dorsal lung boundaries even if alveolar collapse is present in the dependent lung areas adjacent to the pleura. Computed tomography data acquired in five supine pigs with injured lungs were used for this purpose. First, healthy lung tissue was segmented using a standard 3D region growing algorithm. Further, the bones in the chest wall surrounding the lungs were segmented to find the contact points of ribs and pleura. Artificial boundaries of the dorsal lung were set by spline interpolation through these contact points. Segmentation masks of the entire lung including the collapsed regions were created by combining the splines with the segmentation masks of the healthy lung tissue through multiple morphological operations. The automatically segmented images were then evaluated by comparing them to manual segmentations and determining the Dice similarity coefficients (DSC) as a similarity measure. The developed method was able to accurately segment the lungs including the collapsed regions (DSCs over 0.96).
Recent studies about the development of endocardial radiofrequency (RF) ablation lesions (ALs) tried to identify reliable electrogram (EGM) markers for assessment of lesion transmurality. Additional clinically relevant information for physicians can be provided by examining endocardial EGM parameters like signal morphology, amplitude or time points in the signal. We investigated EGM features of the pulmonary vein ostia before and after RF ablation for three point-shaped lesions. Using high-density (HD) mapping, local activation time (LAT) and voltage maps were created, which provided information about the RF ALs regarding the lesion size and showed activation time delay as well as low-voltage areas with bipolar peak-to-peak voltages smaller than 2mV. The time delay of the depolarization front comparing the activation times anterior and posterior to the RF AL was up to 51.5 ms. In a circular area with 5mm radius around an RF AL the mean peak-to-peak voltage decreased by 62-94% to about 0.12-0.44mV and the mean maximal absolute EGM derivative was reduced by 65-96 %. Comparing the results of this study with EGMs of similar clinical settings confirmed our expectations regarding the low-voltage areas caused by the ablation procedure. An improved understanding of the electrophysiological changes is of fundamental importance to provide more information for enhanced RF ablation assessment.
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.
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.