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

Arnold, Robert

Busch, Lisa-Mareike

Dössel, Olaf

Pollnow, Stefan

Wülfers, Eike Moritz

English

KITopen

Current Directions in Biomedical Engineering 2016; 2(1): 77–81Open AccessStefan Pollnow*, Lisa-Mareike Busch, Eike Moritz Wülfers, Robert Arnold and Olaf DösselIntegration of a semi-automatic in-vitro RFAprocedure into an experimental setupDOI 10.1515/cdbme-2016-0020Abstract: Radiofrequency ablation (RFA) is a standardclinical procedure for treating many cardiac arrhythmias.In order to increase the success rate of this treatment, theevaluation of lesiondevelopmentwith thehelp of intracar-diac electrogram (EGM) criteria has to be improved further.We are investigating in-vitro the electrophysiological char-acteristics of cardiac tissue by using fluorescence-opticaland electrical techniques. In this project, it is intendedto create ablation lesions under defined conditions in ratatria or ventricle and to determine the electrical activityin the myocardium surrounding these lesions less than1 s after the ablation. Therefore, we developed a semi-automatic RFA procedure, which was integrated into anexisting experimental setup. Firstly, a controllable protec-tion circuit board was designed to galvanically isolate thesensitive amplifiers for measuring extracellular potentialsduring the ablation. Secondly, a real-time system was im-plemented to control and to autonomously monitor theRFA procedure. We verified each component as well as thedifferent sequences of the RFA procedure. In conclusion,the expanded setup will be used in future in-vitro exper-iments to determine new EGM criteria to assess lesionformation during the RFA procedure.Keywords: ablation lesion; extracellular potentials;in-vitro experiments; radiofrequency ablation.*Corresponding author: Stefan Pollnow, Institute of BiomedicalEngineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12,76128 Karlsruhe, Germany, E-mail: publications@ibt.kit.eduLisa-Mareike Busch and Olaf Dössel: Institute of BiomedicalEngineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12,76128 Karlsruhe, GermanyEike Moritz Wülfers: Institute of Biomedical Engineering, KarlsruheInstitute of Technology (KIT), Kaiserstr. 12, 76128 Karlsruhe,Germany; and Institute for Experimental Cardiovascular Medicine,University Heart Centre Freiburg/Bad Krozingen, Medical Center -University of Freiburg, Elsässer Straße 2q, 79110 Freiburg, Germany;and Faculty of Medicine, University of Freiburg, Fahnenbergplatz,79085 Freiburg, Germany, E-mail: eike.moritz.wuelfers@uniklinik-freiburg.deRobert Arnold: Institute of Biophysics, Medical Univer-sity of Graz, Harrachgasse 21/IV, 8010 Graz, Austria,E-mail: robert.arnold@medunigraz.at1 IntroductionAtrial fibrillation is one of the most frequent cardiac ar-rhthymias in the western world and radiofrequency ab-lation is a standard clinical procedure for treating thisarrhythmia. According to Shurrab et al., the reccurencerate of an arrhythmia is around 35–40 [1]. In order toincrease the success rate, a specific knowledge about thetransmurality as well as the geometry of an ablation le-sion is necessary. To date, several control methods ex-ist to evaluate lesion formation, such as late gadoliniummagnetic resonance imaging [2] or ultrasound [3]. Un-fortunately, none of these methods offer robust criteriato assess ablation lesions. In-vitro experiments allow aunique chance to investigate cardiac electrophysiologyof vital myocardium under controlled conditions. Thia-galingam et al. used a force-sensing catheter to evaluatethe importance of catheter contact force in a porcine ex-vivo model [4]. Moreover, Otomo et al. investigated the(EGM)-based criteria to assess single point ablation le-sions in a porcinemodel and demonstrated a high relationbetween changes of intracardiac EGMs and lesion trans-murality [5]. However, the observational design of thisstudy was limited. Therefore, further studies are requiredto determine the changes of EGMs due to lesion develop-ment under defined conditions. We established an in-vitrosetup to measure the electrophysiological characteristicsof rat myocardium by using simultaneously fluorescence-optical mapping and electrical techniques. In this study,we present the integration of a semi-automatic RFA proce-dure into the in-vitro setup. Therefore, it will be feasibleto create ablation lesions and to determine the electri-cal activity of cardiac tissue immediately under definedconditions.2 Methods2.1 System overviewAll animal experiments were approved by the local com-mittee for animal welfare (35-9185.81/G-61/12). For defined© 2016 Stefan Pollnow et al., licensee De Gruyter.This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License.78 | S. Pollnow et al.: In-vitro RFA proceduremeasurment conditions, the rat myocardium is positionedin a tissue bath with heated Krebs-Henseleit solution,which allows the nutrition and oxygenation of the prepa-ration for several hours. Fluorescence-optical mapping isperformed from the bottom side of the tissue bath by usinga voltage-sensitive dye (di-4-ANEPPS). A self-developedmultielectrode array is used to measure the extracellularpotentials of rat myocardium surrounding the acute ab-lation lesion. The electrical recordings are digitized witha data acquisition system from National Instruments andare analyzed by a custom written software in MATLAB 8.1(The MathWorks Inc., Natick, MA, USA). For the in-vitroRFA procedure, we are using the electrosurgical unit MD1(Micromed, Wurmlingen, Germany) with low power set-tings as well as manual control by a foot switch. Theablation electrode (diameter of 0.3mm) is placed perpen-dicular onto the surface of themyocardium to create punc-tiform ablation lesions. We developed a controllable pro-tection circuit board (CPCB) to ensure that no residual cur-rents from the ablation electrodewill damage the sensitivemeasurement equipment during the ablation. Moreover,the electrosurgical unit as well as the CPCB are controlledby a real-time system. This monitors the reproducible RFAprocedure, which consists of three different sequences. Ina first step, the measurement electrodes have to be dis-connected safely from the amplifier system. Secondly, theelectrosurgical unit is switched on by the real-time systemto create lesions with fixed times and power settings. Ina last step, the measurement electrodes are reconnectedwith the amplifier system tomeasure the electrical activityafter the RFAprocedurewithout a large time delay. Figure 1shows the relationship between each component and theirfunctional relation, which are explained in detail in thefollowing sections.2.2 Controllable protection circuit boardThe self-developed CPCB represents a main component ofthe in-vitro RFA procedure and has to fulfill the follow-ing requirements: high electrical isolation, fast switchingrates, and small (negligible) influence on signal quality.Therefore, we used the electromechanical relay IM26GR(Axicom, Germany) to ensure the galvanic separationof each measurement channel (surge capability up to2500Vrms between open contacts). The switching opera-tion of the relays is controlled by an external TTL signalwith switching times less than 5ms. In order to minimizeelectrical interference during the sensitive measurementphase, the relays are only active in the second sequenceof the RFA procedure. Moreover, the control board (CB)Protectioncircuit boardAmplifiersystemSignalsControl relaysRFAgeneratorMultielectrodearrayControl boardConfiguration andcontrolPCFeedbackControlablationSignalsSignalsMyocardiumAblation MeasurementFigure 1: Overview of the components and their functionalrelationship for the in-vitro RFA procedure.monitors the switching state of each relay by using a mon-itoring voltage. After the successful switching of all relays(monitoring voltage grounded) the RFA procedure will becontinued. The electrical components are powered by anexternal battery to reduce powerline noise.2.3 Control boardThe main component of the CB is the microcontrollerATxmega128A1U (Atmel Corporation, San Jose, CA, USA),which controls the different sequences during the RFAprocedure and monitors the state of the CPCB as well asof the electrosurgical unit. We configured the controllerwith a self-developed C-program to ensure real-time be-havior and to process user input. Before the RFA pro-cedure, the microcontroller is programmed by a customwritten software in MATLAB 8.1. Hereby, the user willspecify the switching times of the relays and the ablationtime. Furthermore, we used two controllable relays KT12-1A-40L (Meder, Germany) to connect the electrosurgicalunit and the ablation electrode during the ablation pro-cess. This will reduce additional interfering signals on theablation electrode during the measurement phase. Afterthe successful configuration of themicrocontroller and themanual start of the RFA procedure, the CB switches therelays on the CPCB. Afterwards, the relays on the CB areswitched on and the electrosurgical unit is activated for adefinedablation time. In the last phase, the electrosurgicalS. Pollnow et al.: In-vitro RFA procedure | 79unit is switched off, the relays of the CB aswell as the CPCBare reset and the electrical measurement is started.2.4 Signal acquisitionFor data acquisition, we used two portable 4-channel pre-cision measurement systems, which were developed atthe Institute of Biophysics of the Medical University ofGraz. The acquired signals are amplified by a factor of 100and filtered with an active 4th-order Bessel antialiasingfilter (cutoff frequency: 20 kHz). The signals are simultane-ously digitizedwith 100 ksps and 16-bit resolution (NI9215,National InstrumentsGermanyGmbH,Munich,Germany).2.5 Test phaseThe above-mentioned components had to be integratedinto the experimental setup. In this test phase, the com-plete RFA procedure and the interaction between the dif-ferent components were examined carefully. For this pur-pose, conductive saline solutionwas used instead of livingrat myocardium. We placed the multielectrode array, theablation electrode, and a stimulus electrode in the tissuebath, which was filled with saline solution. A rectangularshaped current pulse with a duration of 1ms was gener-ated by a constant current stimulus isolator A365 (WorldPrecision Instruments, Sarasota, FL, USA) to simulate theelectrical activity of myocardium. The output power of theelectrosurgical unit was set to 2W. Noise power Pnoise ofthe acquired signal was determined asPnoise =fsN ·N∑︁n=1(u(n) − µu(n))2, (1)wheren are the samples of the considered interval of noise,fs is the sample rate (100 kHz), u(n) is the signal, and µu(n)is the mean value of the signal u(n).3 ResultsA complete RFA procedure with the different switchingstates of the relays on the CPCB, the ablation process andthe electrical measurements are shown in Figure 2. Theswitching of the relays caused some ripple and two clearpeaks in the measured signals. The stimuli started around2 s after the ablation. Figure 3 shows the second sequenceof the RFA procedure before the ablation. After the suc-cessful switching of the relays (active high), the switchingsignal of the electrosurgical unit was set (active low). TheCB detected the switching of the relays via the monitoring0 5 10 15 20 25–6–4–2024681012Switching signalRelay 1–6Measurement channelSwitching signalHF on/offAmplitude (V)Time (s)Figure 2: Electrical recording, switching signal for the relays(Relay 1–6) on the CPCB (active low), and switching signal forthe electrosurgical unit (active high) during the complete RFAprocedure.2.6 2.8 3 3.2 3.4 3.6 3.8–6–4–2024681012Switching signalRelay 1–6Measurement channelSwitching signalHF on/offAmplitude (V)Time (s)10 ms100 mV100 mV5 msFigure 3: Switching signals for the relays (Relay 1–6) on the CPCB(active low) and for the electrosurgical unit (active high) at thebeginning of the ablation. Insets present the time delays after theswitching of the relays (around 1ms; left) and the electrosurgicalunit (around 5ms; right).voltage (not shown in Figure 3) and high-frequency cur-rent was supplied to the ablation electrode after a shorttimedelay (around5ms). Interfering signalswere acquiredduring the ablation, although the electrodes were sepa-rated from the amplifier system. After the ablation, theswitching signal of each relay was reset (see Figure 4). Thedelay of the electrosurgical unit was around 3ms. Figure 5presents the recorded stimulus signal after the ablation.According to equation (1), the noise power was calculated80 | S. Pollnow et al.: In-vitro RFA procedure8.665 8.67 8.675 8.68 8.685 8.69 8.695 8.7–8–6–4–20246Switching signalRelay 1–6Measurement channelSwitching signalHF on/offAmplitude (V)Time (s)Figure 4: Switching signals for the (Relay 1–6) on the CPCB (activelow), and switching signal for the electrosurgical unit (active high)at the end of the ablation. The time delay of the electrosurgical unitwas around 3ms.12.3 12.32 12.34 12.36 12.38 12.4–2–1.8–1.6–1.4–1.2–1–0.8–0.6–0.4–0.20Amplitude (V)Time (s)2 mV2 msFigure 5:Measured stimulus signal of the stimulus generator. Insetillustrates the signal noise used for noise calculations.to 0.0391 V2, which amounted in a signal-to-noise ratio(SNR) of 65.47 (18.16 dB).4 DiscussionWe developed a semi-automatic RFA procedure to createablation lesions on living myocardium. For this purpose,a configurable real-time system controls and monitors in-dependently the RFA procedure. In the test phase, theindividual sequences of the RFA procedure were validatedsuccessfully. The sequential switching and the switchingtimes of the relays as well as of the electrosurgical unitwere verified. The CPCB, which was based on electrome-chanical relays, securely protected the sensitive amplifiersystem. A maximum ablation power of 8W verified thedielectric strength of the CPCB. Additionally, we includeda safety delay (waiting time) of 15ms after the ablation toensure the guaranteed switching of the electromechanicalrelays. Short-term ripples as well as sharp peaks occurredin the acquired signal due to switching processes of therelays. However, these irregularities are within the con-figurable waiting times and will not influence the sub-sequent electrical measurements. The determined SNRdemonstrated that the CPCB did not strongly increase in-terfering signals. The irrectangular shape of the measuredstimulus signal was probably caused by capacitive effectsof the Ag/AgCl electrodes. The delay between the activa-tion of the MD1 by the CB and the effective start of theablation could be induced by an internal response timeof the electrosurgical unit. A similar time delay was seenwhen this device was switched off. Therefore, it has tobe regarded for further measurements that the relays ofthe CPCB should not switch during this time period. Thesafety requirements of the whole setup were also tested.Therefore, we investigated the failure behavior of the real-time system, which was less than 1ms, as well as theclear separation between the ablation electrode and theelectrosurgical unit during the active state of the relays.In conclusion, the presented in-vitroRFA procedure allowsthe creation of acute ablation lesions with varying geome-try and transmurality under reproducible conditions. Fur-thermore, it is feasible to determine electrophysiologicalchanges of myocardium surrounding the ablation lesionafter approximately 20ms.Acknowledgment: The authors would like to thank KurtFeichtinger and Manfred Schroll for their support.Author’s StatementResearch funding: Stefan Pollnow is supported by a schol-arship of the Karlsruhe School of Optics and Photonics(KSOP). Conflict of interest: Authors state no conflict of in-terest. Material andMethods: Informed consent: Informedconsent is not applicable. Ethical approval: The conductedresearch is not related to either human or animals use.References[1] Shurrab M, Di Biase L, Briceno DF, Kaoutskaia A, Haj-Yahia S,Newman D, et al. Impact of contact force technology onS. Pollnow et al.: In-vitro RFA procedure | 81atrial fibrillation ablation: a meta-analysis. J Am Heart Assoc.2015;4:1–9.[2] Vergara GR, Vijayakumar S, Kholmovski EG, Blauer JJ, GuttmanMA, Gloschat C, et al. Real-time magnetic resonance imag-ing–guided radiofrequency atrial ablation and visualization oflesion formation at 3 Tesla. Heart Rhythm. 2011;8:295–303.[3] Fahey BJ, Nightingale KR, McAleavey SA, Palmeri ML, WolfPD, Trahey GE. Acoustic radiation force impulse imaging ofmyocardial radiofrequency ablation: Initial in vivo results. IEEETrans Ultrason Ferroelectr Freq Control. 2005;52:631–41.[4] Thiagalingam A, Da Zavilla A, Foley L, Guerrero JL, LambertH, Leo G, et al. Importance of catheter contact force duringirrigated radiofrequency ablation: evaluation in a porcineex vivo model using a force-sensing catheter. J CardiovascElectrophysiol. 2010;21:806–11.[5] Otomo K, Uno K, Fujiwara H, Isobe M, Iesaka Y. Localunipolar and bipolar electrogram criteria for evaluating thetransmurality of atrial ablation lesions at different catheterorientations relative to the endocardial surface. Heart Rhythm.2010;7:1291–300.

Integration of a semi-automatic in-vitro RFA procedure into an experimental setup

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Integration of a semi-automatic in-vitro RFA procedure into an experimental setup

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