An <i>in vivo</i> study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

Zhang, Bing; Liu, Fanning; Fang, Zheng; Ding, Lujia; Möser, Michael; Zhang, Wenjun

doi:10.1080/02656736.2021.1912417

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…Reduced muscle contractions have been achieved in multiple in vivo studies with application of biphasic pulses with pulse widths from 1 to 10 μs (of each phase) but only with equal interphase and interpulse delays with a duration of 1 to 5 μs 42 , 46 , 48 , 49 , 52 , 74 . Modifications of the interphase and interpulse delays have not been investigated as a method to reduce excitation within the H-FIRE protocols until recently when a theoretical argument for the extended interpulse delay while minimizing the interphase delay was presented 72 .…”

Section: Discussionmentioning

confidence: 99%

Muscle contractions and pain sensation accompanying high-frequency electroporation pulses

Cvetkoska

Maček-Lebar

Trdina

et al. 2022

Sci Rep

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To minimize neuromuscular electrical stimulation during electroporation-based treatments, the replacement of long monophasic pulses with bursts of biphasic high-frequency pulses in the range of microseconds was suggested in order to reduce muscle contraction and pain sensation due to pulse application. This treatment modality appeared under the term high-frequency electroporation (HF-EP), which can be potentially used for some clinical applications of electroporation such as electrochemotherapy, gene electrotransfer, and tissue ablation. In cardiac tissue ablation, which utilizes irreversible electroporation, the treatment is being established as Pulsed Field Ablation. While the reduction of muscle contractions was confirmed in multiple in vivo studies, the reduction of pain sensation in humans was not confirmed yet, nor was the relationship between muscle contraction and pain sensation investigated. This is the first study in humans examining pain sensation using biphasic high-frequency electroporation pulses. Twenty-five healthy individuals were subjected to electrical stimulation of the tibialis anterior muscle with biphasic high-frequency pulses in the range of few microseconds and both, symmetric and asymmetric interphase and interpulse delays. Our results confirm that biphasic high-frequency pulses with a pulse width of 1 or 2 µs reduce muscle contraction and pain sensation as opposed to currently used longer monophasic pulses. In addition, interphase and interpulse delays play a significant role in reducing the muscle contraction and/or pain sensation. The study shows that the range of the optimal pulse parameters may be increased depending on the prerequisites of the therapy. However, further evaluation of the biphasic pulse protocols presented herein is necessary to confirm the efficiency of the newly proposed HF-EP.

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Section: Discussionmentioning

confidence: 99%

Muscle contractions and pain sensation accompanying high-frequency electroporation pulses

Cvetkoska

Maček-Lebar

Trdina

et al. 2022

Sci Rep

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“…After PFA, the saline solution was expulsed from the abdominal cavity immediately using a suction pump. All rabbits recovered under veterinary supervision and continued to be housed for at least 3 days to obtain a visible ablation zone 14 . Ceftriaxone sodium with 20−80 mg/kg was intramuscularly injected daily to prevent infections for 3 days after treatments.…”

Section: Methodsmentioning

confidence: 99%

“…All rabbits recovered under veterinary supervision and continued to be housed for at least 3 days to obtain a visible ablation zone. 14 Ceftriaxone sodium with 20−80 mg/kg was intramuscularly injected daily to prevent infections for 3 days after treatments. All rabbits survived healthily until the scheduled euthanasia.…”

Section: Pfa Setup and Treatment Protocolmentioning

confidence: 99%

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A novel polarity configuration for enhancing ablation depth of pulsed field ablation: Design, modeling, and in vivo validation

Fang

Yan

et al. 2023

Medical Physics

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BackgroundPulsed field ablation (PFA) has been increasingly used to cut off the delivery of abnormal electrical signals in the treatment of cardiac arrhythmias. A successful cut off requires forming a layer of transmural damage on the heart wall, and this layer depends on the depth of ablation by PFA.PurposeThis study aims to propose a novel polarity configuration of PFA to increase the ablation depth in the treatment of cardiac arrhythmias.MethodA novel polarity configuration was designed for a multi‐electrode system, where the number of electrodes is greater than two. The polarity configuration in such multi‐electrode system is called the paired‐electrode interlaced configuration (PIC). The existing configuration called the single‐electrode interlaced configuration (SIC) was used to compare with the PIC. To both the SIC and PIC, a full‐SIC or a full‐PIC is called when all electrodes (anode, cathode) in a catheter is used otherwise partial‐SIC or partial‐PIC is called. By the comparison between the full‐SIC and full‐PIC, the benefit of the PIC was exhibited as opposed to the SIC, but an extra ablation step was added in the PIC in order to form a continuous ablation zone. The other comparative study was taken between a partial‐PIC and a partial‐SIC with the same number of ablation step. In this study, a rabbit model was built by infusing 0.4% saline solution (at 37°C) into the rabbit's abdominal cavity which surrounds the liver. This model was considered as a biometric environment of the heart, namely cardiac‐mimetic model (CMM).ResultThe experimental results have shown that the full‐PIC is superior to the full‐SIC in the ablation depth, specifically in both the maximum (4.14 ± 0.55 mm vs. 3.35 ± 0.26 mm, p < 0.01) and the minimum (3.18 ± 0.29 mm vs. 2.76 ± 0.28 mm, p < 0.05), and in the ablation width, specifically only in the maximum (8.27 ± 0.76 mm vs. 7.09 ± 0.51 mm, p = 0.019) under an identical ablation time (i.e., 5 s). It is noted that the minimum ablation width did not show a significant difference between the full‐PIC and full‐SIC (specifically, 5.61 ± 0.86 mm vs. 4.67 ± 0.73 mm, p = 0.069). Considering the lethal electric field threshold (LEFT) to be 600 V/cm for liver tissues, the maximum and minimum ablation depth generated by the full‐PIC was found larger than that by the full‐SIC (3.90 vs. 3.52 mm, and 3.03 vs. 2.48 mm, respectively) in the simulation. Meanwhile, similar experiment results by comparing the partial‐PIC and partial‐SIC have been obtained, which shows a significant increase in both the maximum ablation depth (4.81 ± 0.87 mm vs. 3.30 ± 0.73 mm, p < 0.001) and the maximum ablation width (8.19 ± 0.85 mm vs. 6.47 ± 1.13 mm, p = 0.001).Conclusions(1) The electric field in the PIC is concentrated around the pair of electrodes, and the pattern of the field is a significant factor in the energy delivery along the direction of the depth. (2) The increase of the ablation depth can significantly expand the range of the tissue on the heart, where the PFA can apply, and can therefore readily form a layer of transmural damage on the heart wall at positions at which the wall is thicker.

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“…Parameter-wise, long micro-millisecond-range electric field pulses such as the European Standard Operating Procedures for Electrochemotherapy (ESOPE) have been used for decades [9,10,20]. It is a safe and effective procedure; however, microsecond protocols can be associated with undesirable side-effects such as muscle contractions in vivo or electrochemical reactions negatively affecting plasmid DNA [20,21]. For that reason, studies of the application of shorter, nanosecond pulsed electric fields (nsPEFs) on different biological systems are needed.…”

Section: Introductionmentioning

confidence: 99%

Transfection by Electroporation of Cancer and Primary Cells Using Nanosecond and Microsecond Electric Fields

et al. 2022

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Gene transfer into primary immune cells as well as into cell lines is essential for scientific and therapeutical applications. One of the methods used for gene transfer is electroporation (EP). EP is a method where a pulsed electric field (PEF) causes a highly transient permeability of the targeted cell membrane. In this work, we present the electrotransfection of CHO-K1, 4T1 cell lines, and primary murine DCs with detectable protein-encoding plasmids in the sub-microsecond range. Microsecond (µs)- and nanosecond (ns)-range pulsed electric field transfection protocols were used. The efficiency of electrotransfection was evaluated using green fluorescent protein (GFP)-encoding plasmids (4.7 kbp; p-EGFP-N1) and plasmids expressing a firefly luciferase and red fluorescent protein (tdTomato) (8.5 kbp; pcDNA3.1(+)/Luc2 = tdT)). It was shown that the used nsPEFs protocol (7 kV/cm × 300 ns × 100, 1 MHz) ensured a better transfection efficiency than µsPEFs (1.2 kV/cm × 100 µs × 8, 1 Hz). Plasmid size and concentration had a strong impact on the cell transfection efficiency too. We also showed that there were no significant differences in transfection efficiency between immature and mature DCs. Finally, the nsPEF protocols were successfully applied for the stable transfection of the CHO-K1 cell line with the linearized pcDNA3.1(+)/Luc2 = tdT plasmid. The results of the study are applicable in gene therapy and DNA vaccination studies for the derivation of optimal electrotransfection conditions.

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An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

Cited by 8 publications

References 32 publications

Muscle contractions and pain sensation accompanying high-frequency electroporation pulses

Muscle contractions and pain sensation accompanying high-frequency electroporation pulses

A novel polarity configuration for enhancing ablation depth of pulsed field ablation: Design, modeling, and in vivo validation

Transfection by Electroporation of Cancer and Primary Cells Using Nanosecond and Microsecond Electric Fields

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