Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses

Yao, Chenguo; Lv, Yanpeng; Dong, Shoulong; Zhao, Yajun; Li, Hongmei

doi:10.1371/journal.pone.0173181

Cited by 19 publications

(14 citation statements)

References 51 publications

(44 reference statements)

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“…The general idea was to develop a more accurate mathematical model with which the IRE process can be simulated. This idea is viable, as supported by the literature, e.g., the study to make an optimal pre-clinic IRE treatment planning with a mathematical model [ 8 , 9 ], optimal design of IRE electrodes [ 10 , 11 ], and understanding of the synergistic effectiveness of IRE combined with other treatments [ 3 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro

et al. 2018

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PurposeThe aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro.MethodsHeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette. Trypan blue staining technique was used to evaluate cell death after 4 hours of incubation following IRE treatment. Peleg-Fermi model was used in the study to build the statistical relationship using the cell viability data obtained from the in vitro experiments. A finite element model of IRE for the electric field distribution was also built. Comparison of ablation zones between the statistical model and electric threshold model (drawn from the finite element model) was used to show the accuracy of the proposed statistical model in the description of the ablation zone and its applicability in different pulse-setting parameters.ResultsThe statistical models describing the relationships between HeLa cell death and pulse length and the number of pulses, respectively, were built. The values of the curve fitting parameters were obtained using the Peleg-Fermi model for the treatment of cervical cancer with IRE. The difference in the ablation zone between the statistical model and the electric threshold model was also illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in IRE.ConclusionsThis study concluded that: (1) the proposed statistical model accurately described the ablation zone of IRE with cervical cancer cells, and was more accurate compared with the electric field model; (2) the proposed statistical model was able to estimate the value of electric field threshold for the computer simulation of IRE in the treatment of cervical cancer; and (3) the proposed statistical model was able to express the change in ablation zone with the change in pulse-setting parameters.

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Section: Introductionmentioning

confidence: 99%

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro

et al. 2018

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“…However, it is interesting to note that the current in the experiments with one pulse train was significantly smaller than that in the experiments with multiple pulse trains (P < 0.001). However, the ablation volumes generated by pulse trains with higher current (experiments 2-10 and [12][13][14][15][16][17][18][19][20] were found to be similar with that generated by pulse trains with lower current (experiments 1 and 11) (P ¼ 0.136). The reasons behind these phenomena are worth studying further, as it would be useful for avoiding the crash of a pulse generator when higher pulse strengths are applied for larger ablation volumes.…”

Section: Resultsmentioning

confidence: 66%

“…It is noted that many previous studies showed that potatoes are a highly relevant and well-accepted model in the in vitro study of IRE due to its similar manner in responding to the electroporation as mammalian cells [15][16][17][18]. Therefore, the use of the potato model for the in vitro study is widely accepted, such as the design of new IRE electrode [15,17] and the improved pulse delivery method [19,20]. A custom-made electric pulse generator and a monopolar IRE electrode were used to perform the experiments (Fig.…”

Section: Methodsmentioning

confidence: 99%

An In Vitro Experimental Study of the Pulse Delivery Method in Irreversible Electroporation

Zhang

Möser

Zhang

et al. 2017

Journal of Engineering and Science in Medical Diagnostics and Therapy

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The purpose of this study was to investigate the feasibility of generating larger ablation volumes using the pulse delivery method in irreversible electroporation (IRE) using a potato model. Ten types of pulse timing schemes and two pulse repetition rates (1 pulse per 200 ms and 1 pulse per 550 ms) were proposed in the study. Twenty in vitro experiments with five samples each were performed to check the effects on the ablation volumes for the ten pulse timing schemes and two pulse repetition rates. At the two pulse repetition rates (1 pulse per 200 ms and 1 pulse per 550 ms), the largest ablation volumes achieved were 1634.1 mm3± 122.6 and 1828.4 mm3±160.9, respectively. Compared with the baseline approach (no pulse delays), the ablation volume was increased approximately by 62.8% and 22.6% at the repetition rates of 1 pulse per 200 ms and 1 pulse per 550 ms, respectively, using the pulse timing approach (with pulse delays). With the pulse timing approach, the ablation volumes generated at the lower pulse repetition rate were significantly larger than those generated at the higher pulse repetition rate (P < 0.001). For the experiments with one pulse train (baseline approach), the current was 5.2 A±0.4. For the experiments with two pulse trains, the currents were 6.4 A±0.9 and 6.8 A±0.9, respectively (P = 0.191). For the experiments with three pulse trains, the currents were 6.6 A±0.6, 6.9 A±0.6, and 6.5 A±0.6, respectively (P = 0.216). For the experiments with five pulse trains, the currents were 6.6 A±0.9, 6.9 A±0.9, 6.5 A±1.0, 6.5 A±1.0, and 5.7 A±1.2, respectively (P = 0.09). This study concluded that: (1) compared with the baseline approach used clinically, the pulse timing approach is able to increase the volume of ablation; but, the pulse timing scheme with the best performance might be various with the tissue type; (2) the pulse timing approach is still effective in achieving larger ablation volumes when the pulse repetition rate changes; but, the best pulse timing scheme might be different with the pulse repletion rate; (3) the current in the base line approach was significantly smaller than that in the pulse timing approach.

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“…SHV pulses created a large electroporated area that was more susceptible to subsequent LLV pulses, therefore significantly enhancing the ablation area. This modality of pulsed electric fields was reported in a previous study to enlarge the ablation area of potato tissue in vitro 42 . However, enhancement of the cell cytotoxic effect by combining SHV pulses with LLV pulses has not yet been explored.…”

Section: Introductionmentioning

confidence: 72%

Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

Yao

Zhao

et al. 2017

Sci Rep

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Irreversible electroporation (IRE) uses ~100 μs pulsed electric fields to disrupt cell membranes for solid tumor ablation. Although IRE has achieved exciting preliminary clinical results, implementing IRE could be challenging because of volumetric limitations at the ablation region. Combining short high-voltage (SHV: 1600V, 2 μs, 1 Hz, 20 pulses) pulses with long low-voltage (LLV: 240–480 V, 100 μs, 1 Hz, 60–80 pulses) pulses induces a synergistic effect that enhances IRE efficacy. Here, cell cytotoxicity and tissue ablation were investigated. The results show that combining SHV pulses with LLV pulses induced SKOV3 cell death more effectively, and compared to either SHV pulses or LLV pulses applied alone, the combination significantly enhanced the ablation region. Particularly, prolonging the lag time (100 s) between SHV and LLV pulses further reduced cell viability and enhanced the ablation area. However, the sequence of SHV and LLV pulses was important, and the LLV + SHV combination was not as effective as the SHV + LLV combination. We offer a hypothesis to explain the synergistic effect behind enhanced cell cytotoxicity and enlarged ablation area. This work shows that combining SHV pulses with LLV pulses could be used as a focal therapy and merits investigation in larger pre-clinical models and microscopic mechanisms.

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Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses

Cited by 19 publications

References 51 publications

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro

An In Vitro Experimental Study of the Pulse Delivery Method in Irreversible Electroporation

Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

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