Startseite 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

  • Stefan Pollnow EMAIL logo , Lisa-Mareike Busch , Eike Moritz Wülfers , Robert Arnold und Olaf Dössel
Veröffentlicht/Copyright: 30. September 2016
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Current Directions in Biomedical Engineering
Aus der Zeitschrift Current Directions in Biomedical Engineering Band 2 Heft 1

Abstract

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.

Keywords: ablation lesion; extracellular potentials; in-vitro experiments; radiofrequency ablation

1 Introduction

Atrial fibrillation is one of the most frequent cardiac arrhthymias in the western world and radiofrequency ablation is a standard clinical procedure for treating this arrhythmia. According to Shurrab et al., the reccurence rate of an arrhythmia is around 35–40 [1]. In order to increase the success rate, a specific knowledge about the transmurality as well as the geometry of an ablation lesion is necessary. To date, several control methods exist to evaluate lesion formation, such as late gadolinium magnetic resonance imaging [2] or ultrasound [3]. Unfortunately, none of these methods offer robust criteria to assess ablation lesions. In-vitro experiments allow a unique chance to investigate cardiac electrophysiology of vital myocardium under controlled conditions. Thiagalingam et al. used a force-sensing catheter to evaluate the 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 lesions in a porcine model and demonstrated a high relation between changes of intracardiac EGMs and lesion transmurality [5]. However, the observational design of this study was limited. Therefore, further studies are required to determine the changes of EGMs due to lesion development under defined conditions. We established an in-vitro setup to measure the electrophysiological characteristics of rat myocardium by using simultaneously fluorescence-optical mapping and electrical techniques. In this study, we present the integration of a semi-automatic RFA procedure into the in-vitro setup. Therefore, it will be feasible to create ablation lesions and to determine the electrical activity of cardiac tissue immediately under defined conditions.

2 Methods

2.1 System overview

All animal experiments were approved by the local committee for animal welfare (35-9185.81/G-61/12). For defined measurment conditions, the rat myocardium is positioned in a tissue bath with heated Krebs-Henseleit solution, which allows the nutrition and oxygenation of the preparation for several hours. Fluorescence-optical mapping is performed from the bottom side of the tissue bath by using a voltage-sensitive dye (di-4-ANEPPS). A self-developed multielectrode array is used to measure the extracellular potentials of rat myocardium surrounding the acute ablation lesion. The electrical recordings are digitized with a data acquisition system from National Instruments and are analyzed by a custom written software in MATLAB 8.1 (The MathWorks Inc., Natick, MA, USA). For the in-vitro RFA procedure, we are using the electrosurgical unit MD1 (Micromed, Wurmlingen, Germany) with low power settings as well as manual control by a foot switch. The ablation electrode (diameter of 0.3 mm) is placed perpendicular onto the surface of the myocardium to create punctiform ablation lesions. We developed a controllable protection circuit board (CPCB) to ensure that no residual currents from the ablation electrode will damage the sensitive measurement equipment during the ablation. Moreover, the electrosurgical unit as well as the CPCB are controlled by a real-time system. This monitors the reproducible RFA procedure, which consists of three different sequences. In a first step, the measurement electrodes have to be disconnected safely from the amplifier system. Secondly, the electrosurgical unit is switched on by the real-time system to create lesions with fixed times and power settings. In a last step, the measurement electrodes are reconnected with the amplifier system to measure the electrical activity after the RFA procedure without a large time delay. Figure 1 shows the relationship between each component and their functional relation, which are explained in detail in the following sections.

Figure 1: Overview of the components and their functional relationship for the in-vitro RFA procedure.
Figure 1:

Overview of the components and their functional relationship for the in-vitro RFA procedure.

2.2 Controllable protection circuit board

The self-developed CPCB represents a main component of the in-vitro RFA procedure and has to fulfill the following requirements: high electrical isolation, fast switching rates, and small (negligible) influence on signal quality. Therefore, we used the electromechanical relay IM26GR (Axicom, Germany) to ensure the galvanic separation of each measurement channel (surge capability up to 2500 Vrms between open contacts). The switching operation of the relays is controlled by an external TTL signal with switching times less than 5 ms. In order to minimize electrical interference during the sensitive measurement phase, the relays are only active in the second sequence of the RFA procedure. Moreover, the control board (CB) monitors the switching state of each relay by using a monitoring voltage. After the successful switching of all relays (monitoring voltage grounded) the RFA procedure will be continued. The electrical components are powered by an external battery to reduce powerline noise.

2.3 Control board

The main component of the CB is the microcontroller ATxmega128A1U (Atmel Corporation, San Jose, CA, USA), which controls the different sequences during the RFA procedure and monitors the state of the CPCB as well as of the electrosurgical unit. We configured the controller with a self-developed C-program to ensure real-time behavior and to process user input. Before the RFA procedure, the microcontroller is programmed by a custom written software in MATLAB 8.1. Hereby, the user will specify the switching times of the relays and the ablation time. Furthermore, we used two controllable relays KT12-1A-40L (Meder, Germany) to connect the electrosurgical unit and the ablation electrode during the ablation process. This will reduce additional interfering signals on the ablation electrode during the measurement phase. After the successful configuration of the microcontroller and the manual start of the RFA procedure, the CB switches the relays on the CPCB. Afterwards, the relays on the CB are switched on and the electrosurgical unit is activated for a defined ablation time. In the last phase, the electrosurgical unit is switched off, the relays of the CB as well as the CPCB are reset and the electrical measurement is started.

2.4 Signal acquisition

For data acquisition, we used two portable 4-channel precision measurement systems, which were developed at the Institute of Biophysics of the Medical University of Graz. The acquired signals are amplified by a factor of 100 and filtered with an active 4th-order Bessel antialiasing filter (cutoff frequency: 20 kHz). The signals are simultaneously digitized with 100 ksps and 16-bit resolution (NI9215, National Instruments Germany GmbH, Munich, Germany).

2.5 Test phase

The above-mentioned components had to be integrated into the experimental setup. In this test phase, the complete RFA procedure and the interaction between the different components were examined carefully. For this purpose, conductive saline solution was used instead of living rat myocardium. We placed the multielectrode array, the ablation electrode, and a stimulus electrode in the tissue bath, which was filled with saline solution. A rectangular shaped current pulse with a duration of 1 ms was generated by a constant current stimulus isolator A365 (World Precision Instruments, Sarasota, FL, USA) to simulate the electrical activity of myocardium. The output power of the electrosurgical unit was set to 2 W. Noise power Pnoise of the acquired signal was determined as

(1)Pnoise=fsN⋅∑n=1N(u⁢(n)−μu⁢(n))2,

where n 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 Results

A complete RFA procedure with the different switching states of the relays on the CPCB, the ablation process and the electrical measurements are shown in Figure 2. The switching of the relays caused some ripple and two clear peaks in the measured signals. The stimuli started around 2 s after the ablation. Figure 3 shows the second sequence of the RFA procedure before the ablation. After the successful switching of the relays (active high), the switching signal of the electrosurgical unit was set (active low). The CB detected the switching of the relays via the monitoring voltage (not shown in Figure 3) and high-frequency current was supplied to the ablation electrode after a short time delay (around 5 ms). Interfering signals were acquired during the ablation, although the electrodes were separated from the amplifier system. After the ablation, the switching signal of each relay was reset (see Figure 4). The delay of the electrosurgical unit was around 3 ms. Figure 5 presents the recorded stimulus signal after the ablation. According to equation (1), the noise power was calculated to 0.0391 V2, which amounted in a signal-to-noise ratio (SNR) of 65.47 (18.16 dB).

Figure 2: Electrical recording, switching signal for the relays (Relay 1–6) on the CPCB (active low), and switching signal for the electrosurgical unit (active high) during the complete RFA procedure.
Figure 2:

Electrical recording, switching signal for the relays (Relay 1–6) on the CPCB (active low), and switching signal for the electrosurgical unit (active high) during the complete RFA procedure.

Figure 3: Switching signals for the relays (Relay 1–6) on the CPCB (active low) and for the electrosurgical unit (active high) at the beginning of the ablation. Insets present the time delays after the switching of the relays (around 1 ms; left) and the electrosurgical unit (around 5 ms; right).
Figure 3:

Switching signals for the relays (Relay 1–6) on the CPCB (active low) and for the electrosurgical unit (active high) at the beginning of the ablation. Insets present the time delays after the switching of the relays (around 1 ms; left) and the electrosurgical unit (around 5 ms; right).

Figure 4: Switching signals for the (Relay 1–6) on the CPCB (active low), and switching signal for the electrosurgical unit (active high) at the end of the ablation. The time delay of the electrosurgical unit was around 3 ms.
Figure 4:

Switching signals for the (Relay 1–6) on the CPCB (active low), and switching signal for the electrosurgical unit (active high) at the end of the ablation. The time delay of the electrosurgical unit was around 3 ms.

Figure 5: Measured stimulus signal of the stimulus generator. Inset illustrates the signal noise used for noise calculations.
Figure 5:

Measured stimulus signal of the stimulus generator. Inset illustrates the signal noise used for noise calculations.

4 Discussion

We developed a semi-automatic RFA procedure to create ablation lesions on living myocardium. For this purpose, a configurable real-time system controls and monitors independently the RFA procedure. In the test phase, the individual sequences of the RFA procedure were validated successfully. The sequential switching and the switching times of the relays as well as of the electrosurgical unit were verified. The CPCB, which was based on electromechanical relays, securely protected the sensitive amplifier system. A maximum ablation power of 8 W verified the dielectric strength of the CPCB. Additionally, we included a safety delay (waiting time) of 15 ms after the ablation to ensure the guaranteed switching of the electromechanical relays. Short-term ripples as well as sharp peaks occurred in the acquired signal due to switching processes of the relays. However, these irregularities are within the configurable waiting times and will not influence the subsequent electrical measurements. The determined SNR demonstrated that the CPCB did not strongly increase interfering signals. The irrectangular shape of the measured stimulus signal was probably caused by capacitive effects of the Ag/AgCl electrodes. The delay between the activation of the MD1 by the CB and the effective start of the ablation could be induced by an internal response time of the electrosurgical unit. A similar time delay was seen when this device was switched off. Therefore, it has to be regarded for further measurements that the relays of the CPCB should not switch during this time period. The safety requirements of the whole setup were also tested. Therefore, we investigated the failure behavior of the real-time system, which was less than 1 ms, as well as the clear separation between the ablation electrode and the electrosurgical unit during the active state of the relays. In conclusion, the presented in-vitro RFA procedure allows the creation of acute ablation lesions with varying geometry and transmurality under reproducible conditions. Furthermore, it is feasible to determine electrophysiological changes of myocardium surrounding the ablation lesion after approximately 20 ms.

Acknowledgement

The authors would like to thank Kurt Feichtinger and Manfred Schroll for their support.

Author’s Statement

Research funding: Stefan Pollnow is supported by a scholarship of the Karlsruhe School of Optics and Photonics (KSOP). Conflict of interest: Authors state no conflict of interest. Material and Methods: Informed consent: Informed consent is not applicable. Ethical approval: The conducted research 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 on atrial fibrillation ablation: a meta-analysis. J Am Heart Assoc. 2015;4:1–9.10.1161/JAHA.115.002476Suche in Google Scholar PubMed PubMed Central

[2] Vergara GR, Vijayakumar S, Kholmovski EG, Blauer JJ, Guttman MA, Gloschat C, et al. Real-time magnetic resonance imaging–guided radiofrequency atrial ablation and visualization of lesion formation at 3 Tesla. Heart Rhythm. 2011;8:295–303.10.1016/j.hrthm.2010.10.032Suche in Google Scholar PubMed PubMed Central

[3] Fahey BJ, Nightingale KR, McAleavey SA, Palmeri ML, Wolf PD, Trahey GE. Acoustic radiation force impulse imaging of myocardial radiofrequency ablation: Initial in vivo results. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52:631–41.10.1109/TUFFC.2005.1428046Suche in Google Scholar PubMed

[4] Thiagalingam A, Da Zavilla A, Foley L, Guerrero JL, Lambert H, Leo G, et al. Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter. J Cardiovasc Electrophysiol. 2010;21:806–11.10.1111/j.1540-8167.2009.01693.xSuche in Google Scholar PubMed

[5] Otomo K, Uno K, Fujiwara H, Isobe M, Iesaka Y. Local unipolar and bipolar electrogram criteria for evaluating the transmurality of atrial ablation lesions at different catheter orientations relative to the endocardial surface. Heart Rhythm. 2010;7:1291–300.10.1016/j.hrthm.2010.06.014Suche in Google Scholar PubMed

Published Online: 2016-9-30
Published in Print: 2016-9-1

©2016 Stefan Pollnow et al., licensee De Gruyter.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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https://doi.org/10.1515/cdbme-2016-0020
Schlagwörter für diesen Artikel
ablation lesion; extracellular potentials; in-vitro experiments; radiofrequency ablation
Creative Commons
BY-NC-ND 4.0

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  67. Cryopreservation of cells using defined serum-free cryoprotective agents
  68. New bioreactor vessel for tissue engineering of human nasal septal chondrocytes
  69. Determination of the membrane hydraulic permeability of MSCs
  70. Climate retainment in carbon dioxide incubators
  71. Multiple factors influencing OR ventilation system effectiveness
  72. Evaluation of an app-based stress protocol
  73. Medication process in Styrian hospitals
  74. Control tower to surgical theater
  75. Development of a skull phantom for the assessment of implant X-ray visibility
  76. Surgical navigation with QR codes
  77. Investigation of the pressure gradient of embolic protection devices
  78. Computer assistance in femoral derotation osteotomy: a bottom-up approach
  79. Automatic depth scanning system for 3D infrared thermography
  80. A service for monitoring the quality of intraoperative cone beam CT images
  81. Resectoscope with an easy to use twist mechanism for improved handling
  82. In vitro simulation of distribution processes following intramuscular injection
  83. Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs
  84. A flexible standalone system with integrated sensor feedback for multi-pad electrode FES of the hand
  85. Smart control for functional electrical stimulation with optimal pulse intensity
  86. Tactile display on the remaining hand for unilateral hand amputees
  87. Effects of sustained electrical stimulation on spasticity assessed by the pendulum test
  88. An improved tracking framework for ultrasound probe localization in image-guided radiosurgery
  89. Improvement of a subviral particle tracker by the use of a LAP-Kalman-algorithm
  90. Learning discriminative classification models for grading anal intraepithelial neoplasia
  91. Regularization of EIT reconstruction based on multi-scales wavelet transforms
  92. Assessing MRI susceptibility artefact through an indicator of image distortion
  93. EyeGuidance – a computer controlled system to guide eye movements
  94. A framework for feedback-based segmentation of 3D image stacks
  95. Doppler optical coherence tomography as a promising tool for detecting fluid in the human middle ear
  96. 3D Local in vivo Environment (LivE) imaging for single cell protein analysis of bone tissue
  97. Inside-Out access strategy using new trans-vascular catheter approach
  98. US/MRI fusion with new optical tracking and marker approach for interventional procedures inside the MRI suite
  99. Impact of different registration methods in MEG source analysis
  100. 3D segmentation of thyroid ultrasound images using active contours
  101. Designing a compact MRI motion phantom
  102. Cerebral cortex classification by conditional random fields applied to intraoperative thermal imaging
  103. Classification of indirect immunofluorescence images using thresholded local binary count features
  104. Analysis of muscle fatigue conditions using time-frequency images and GLCM features
  105. Numerical evaluation of image parameters of ETR-1
  106. Fabrication of a compliant phantom of the human aortic arch for use in Particle Image Velocimetry (PIV) experimentation
  107. Effect of the number of electrodes on the reconstructed lung shape in electrical impedance tomography
  108. Hardware dependencies of GPU-accelerated beamformer performances for microwave breast cancer detection
  109. Computer assisted assessment of progressing osteoradionecrosis of the jaw for clinical diagnosis and treatment
  110. Evaluation of reconstruction parameters of electrical impedance tomography on aorta detection during saline bolus injection
  111. Evaluation of open-source software for the lung segmentation
  112. Automatic determination of lung features of CF patients in CT scans
  113. Image analysis of self-organized multicellular patterns
  114. Effect of key parameters on synthesis of superparamagnetic nanoparticles (SPIONs)
  115. Radiopacity assessment of neurovascular implants
  116. Development of a desiccant based dielectric for monitoring humidity conditions in miniaturized hermetic implantable packages
  117. Development of an artifact-free aneurysm clip
  118. Enhancing the regeneration of bone defects by alkalizing the peri-implant zone – an in vitro approach
  119. Rapid prototyping of replica knee implants for in vitro testing
  120. Protecting ultra- and hyperhydrophilic implant surfaces in dry state from loss of wettability
  121. Advanced wettability analysis of implant surfaces
  122. Patient-specific hip prostheses designed by surgeons
  123. Plasma treatment on novel carbon fiber reinforced PEEK cages to enhance bioactivity
  124. Wear of a total intervertebral disc prosthesis
  125. Digital health and digital biomarkers – enabling value chains on health data
  126. Usability in the lifecycle of medical software development
  127. Influence of different test gases in a non-destructive 100% quality control system for medical devices
  128. Device development guided by user satisfaction survey on auricular vagus nerve stimulation
  129. Empirical assessment of the time course of innovation in biomedical engineering: first results of a comparative approach
  130. Effect of left atrial hypertrophy on P-wave morphology in a computational model
  131. Simulation of intracardiac electrograms around acute ablation lesions
  132. Parametrization of activation based cardiac electrophysiology models using bidomain model simulations
  133. Assessment of nasal resistance using computational fluid dynamics
  134. Resistance in a non-linear autoregressive model of pulmonary mechanics
  135. Inspiratory and expiratory elastance in a non-linear autoregressive model of pulmonary mechanics
  136. Determination of regional lung function in cystic fibrosis using electrical impedance tomography
  137. Development of parietal bone surrogates for parietal graft lift training
  138. Numerical simulation of mechanically stimulated bone remodelling
  139. Conversion of engineering stresses to Cauchy stresses in tensile and compression tests of thermoplastic polymers
  140. Numerical examinations of simplified spondylodesis models concerning energy absorption in magnetic resonance imaging
  141. Principle study on the signal connection at transabdominal fetal pulse oximetry
  142. Influence of Siluron® insertion on model drug distribution in the simulated vitreous body
  143. Evaluating different approaches to identify a three parameter gas exchange model
  144. Effects of fibrosis on the extracellular potential based on 3D reconstructions from histological sections of heart tissue
  145. From imaging to hemodynamics – how reconstruction kernels influence the blood flow predictions in intracranial aneurysms
  146. Flow optimised design of a novel point-of-care diagnostic device for the detection of disease specific biomarkers
  147. Improved FPGA controlled artificial vascular system for plethysmographic measurements
  148. Minimally spaced electrode positions for multi-functional chest sensors: ECG and respiratory signal estimation
  149. Automated detection of alveolar arches for nasoalveolar molding in cleft lip and palate treatment
  150. Control scheme selection in human-machine- interfaces by analysis of activity signals
  151. Event-based sampling for reducing communication load in realtime human motion analysis by wireless inertial sensor networks
  152. Automatic pairing of inertial sensors to lower limb segments – a plug-and-play approach
  153. Contactless respiratory monitoring system for magnetic resonance imaging applications using a laser range sensor
  154. Interactive monitoring system for visual respiratory biofeedback
  155. Development of a low-cost senor based aid for visually impaired people
  156. Patient assistive system for the shoulder joint
  157. A passive beating heart setup for interventional cardiology training
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Heruntergeladen am 3.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cdbme-2016-0020/html?lang=de
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