Irreversible Electroporation Pulses Research Articles

Influence of Joule heating during single-cell electroporation simulation under IRE and H-FIRE pulses

Conventional irreversible electroporation (IRE) and high-frequency irreversible electroporation (H-FIRE) pulses have been widely employed in many biomedical and food applications. To investigate the effect of Joule heating generated by pulsed electric fields on cell electroporation, single-cell electroporation models without (EP only) and with the consideration of Joule heating (EP+T) were subjected to the equivalent energy IRE and H-FIRE pulses. The simulation results showed that with the consideration of Joule heating, the transmembrane voltage of the anodic point (TMPA) reached the electroporation threshold (∼1 V) faster, and a significant increase in the plasma membrane conductivity (σA) and pore number (kp) was found. We further evaluated the effect of the pulse burst repetition frequency (PBRF) of H-FIRE pulses on cell electroporation based on the EP+T model, and discovered kp increased with frequency when PBRF lower than 2 kHz, whereas it decreased with frequency for PBRF higher than 2 kHz. The accumulation of the ratio of the perforation area to the cell membrane area (sum of Ap/A) during the 400th pulse was also reversed when PBRF was 2 kHz. Our results indicated that Joule heating generated by repetitive pulse delivery would facilitate electroporation, and the effect of PBRF on cell electroporation was non-monotonic.

Irreversible Electroporation Balloon Therapy for Palliative Treatment of Obstructive Urethral Transitional Cell Carcinoma in Dogs.

Progression of transitional cell carcinoma (TCC) in dogs often leads to urinary obstruction. This observational pilot study aimed to evaluate the safety and efficacy of irreversible electroporation (IRE) balloon therapy for the palliative treatment of TCC with partial urethral obstruction. Three client-owned dogs diagnosed with TCC causing partial urethral obstruction were enrolled. After ultrasonographic and cystoscopic examination, IRE pulse protocols were delivered through a balloon catheter device inflated within the urethral lumen. After the procedure, the patients were kept overnight for monitoring and a recheck was planned 28 days later. No complication was observed during the procedure and postprocedural monitoring. After 28 days, one dog had a complete normalization of the urine stream, one dog had stable stranguria, and one dog was presented with a urethral obstruction secondary to progression of the TCC. On recheck ultrasound, one dog had a 38% diminution of the urethral mass diameter whereas the other two dogs had a mass stable in size. IRE balloon therapy seems to be a feasible and apparently safe minimally invasive novel therapy for the palliative treatment of TCC causing urethral obstruction. Further studies are needed to better characterize the safety, efficacy, and outcome of this therapy.

Polymer Nanoparticles Enhance Irreversible Electroporation In Vitro

Expanding the volume of an irreversible electroporation treatment typically necessitates an increase in pulse voltage, number, duration, or repetition. This study investigates the addition of polyethylenimine nanoparticles (PEI-NP) to pulsed electric field treatments, determining their combined effect on ablation size and voltages. U118 cells in an in vitro 3D cell culture model were treated with one of three pulse parameters (with and without PEI-NPs) which are representative of irreversible electroporation (IRE), high frequency irreversible electroporation (H-FIRE), or nanosecond pulsed electric fields (nsPEF). The size of the ablations were compared and mapped onto an electric field model to describe the electric field required to induce cell death. Analysis was conducted to determine the role of PEI-NPs in altering media conductivity, the potential for PEI-NP degradation following pulsed electric field treatment, and PEI-NP uptake. Results show there was a statistically significant increase in ablation diameter for IRE and H-FIRE pulses with PEI-NPs. There was no increase in ablation size for nsPEF with PEI-NPs. This all occurs with no change in cell media conductivity, no observable degradation of PEI-NPs, and moderate particle uptake. These results demonstrate the synergy of a combined cationic polymer nanoparticle and pulsed electric field treatment for the ablation of cancer cells. These results set the foundation for polymer nanoparticles engineered specifically for irreversible electroporation.

Feasibility of Linear Irreversible Electroporation Ablation in the Coronary Sinus.

Previous studies demonstrated that the coronary sinus (CS) is an important target for ablation in persistent atrial fibrillation. However, radiofrequency ablation in the CS is associated with coronary vessel damage and tamponade. Animal data suggest irreversible electroporation (IRE) ablation can be a safe ablation modality in vicinity of coronary arteries. We investigated the feasibility of IRE in the CS in a porcine model. Ablation and pacing was performed in the CS in six pigs (weight 60-75 kg) using a modified 9-French steerable linear hexapolar Tip-Versatile Ablation Catheter. Pacing maneuvers were performed from distal to proximal segments of the CS to assess atrial capture thresholds before and after IRE application. IRE ablations were performed with 100 J IRE pulses. After 3-week survival animals were euthanized and histological sections from the CS were analyzed. A total of 27 IRE applications in six animals were performed. Mean peak voltage was 1509 ± 36 V, with a mean peak current of 22.9 ± 1.0 A. No complications occurred during procedure and 3-week survival. At 30 min post ablation 100% isolation was achieved in all animals. At 3 weeks follow-up pacing thresholds were significant higher as compared to baseline. Histological analysis showed transmural ablation lesions in muscular sleeves surrounding the CS. IRE ablation of the musculature along the CS using a multi-electrode catheter is feasible in a porcine model.

Sensing of Yeast Inactivation by Electroporation

Irreversible electroporation is a treatment to control microorganisms in food without harming food palatable aspects. The treatment by electroporation is dependent on the electric field amplitude, pulse durations and pulse repetitions. This study was carried out as a further investigation on the effects of irreversible electroporation pulse amplitude on S. cerevisiae and methods to verify the occurrence of irreversible electroporation, such as cell viability hemocytometer, macroscopic impedance measurements, scanning electron microscopy and numerical simulations. Active yeasts in wine represent a small portion of the volume (<; 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> cell/mL), which challenges macroscopic impedance analysis. Irreversible electroporation proved to reach active yeast limits established by standards within 500 kV/m. We detected a 15% increase in the in pulse current measurements for a 100-fold yeast viability decrease to 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> cells/ml. Scanning electron microscopic images show details of yeast surface damage which may be PEF-triggered. Electric fields above 1 MV/m on the cell wall and release of intracellular substance caused by membrane permeability increase may directly contribute to yeast inactivation. Electroporation combined with instantaneous current-voltage measurements may be an adequate procedure for reducing yeast numbers in the industry.

Maxwell's equations explain why irreversible electroporation will not heat up a metal stent

Irreversible Electroporation (IRE) is a promising clinical ablation therapy for the treatment of cancer, but issues with the generation of heat must be solved before safe and effective clinical results can be obtained. In the present study, we show that a metal stent will not be noticeably heated up by IRE pulses under typical clinical conditions. Derivation of this non-intuitive result required the application of Maxwell's equations to the tissue-stent configuration. Subsequently, straightforward and arguably accurate simplifications of the electric field generated by two needles in tissue surrounding a metal stent have enabled the modeling of the heat generation and the transport of heat in IRE procedures. Close to a stent that is positioned in between two needles, temperatures in a typical run of 100 s, 1 Hz pulses, may remain notably lower than without the stent. This is the explanation of the experimentally observed low temperature rim of viable tissue around the stent, whereas all tissue was non-viable without stent, found in tissue model experiments.

Efficacy of multi-electrode linear irreversible electroporation.

We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model. The study was performed in six pigs (weight 60-75kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications. Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.

250Efficacy of multi-electrode linear irreversible electroporation

Abstract Background We investigated the efficacy of linear irreversible electroporation (IRE) ablation in a porcine model. Methods The study was performed in 6 pigs (weight 60-75kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear 7 polar 7F electrode catheter with 2.5mm electrodes and 2.5mm inter-electrode spacing was placed in good epicardial contact. A single IRE application was delivered using 50 Joules (J) at 1 site and 100 J at 2 other sites, in random sequence, using a standard monophasic defibrillator connected to all 7 electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. 82 histological sections from all 18 electroporation lesions were analyzed. Results A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 J and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50J and 100J lesions were 3.2 mm (interquartile range [IQR], 3.1 – 3.6) and 5.5 mm (IQR, 4.6 – 6.6) (P &amp;lt; 0.001), respectively. Median lesion width of the 50J and 100J lesions were 3.9 mm (IQR, 3.7 – 4.8) and 5.4 mm (IQR, 5.0 - 6.3), respectively(P &amp;lt; 0.001). Longitudinal sections showed continuous lesions for 100J lesions. Conclusion Epicardial linear application of IRE pulses is effective in creating continuous deep lesions. Ablation characteristics and lesion size Peak voltageV Peak currentA Peak resistanceΩ SlicesN Depthmm Widthmm 50 J 1079.2 ± 81.1 14.5 ± 2.3 71.8 ± 15.6 26 3.2 (3.1 - 3.6) 3.9 (3.7 - 4.8) 100J 1609.5 ± 56.8 20.2 ± 1.7 80.0 ± 9.5 56 5.5 (4.6 - 6.6) 5.4 (5.0 - 6.3) P-value† &amp;lt;0.001 &amp;lt;0.001 Data is displayed as mean ± SD or median (interquartile range) where appropriate.†assessed by general linear mixed models Abstract Figure. Transversal histological sections

Effect of interphase and interpulse delay in high-frequency irreversible electroporation pulses on cell survival, membrane permeabilization and electrode material release

To achieve high efficiency of electroporation and to minimize unwanted side effects, the electric field parameters must be optimized. Recently, it was suggested that biphasic high-frequency irreversible electroporation (H-FIRE) pulses reduce muscle contractions. However, it was also shown for sub-microsecond biphasic pulses that the opposite polarity phase of the pulse cancels the effect of the first phase if the interphase delay is short enough. We investigated the effect of interphase and interpulse delay (ranging from 0.5 to 10,000 µs) of 1 µs biphasic H-FIRE pulses on cell membrane permeabilization, on survival of four mammalian cell lines and determined metal release from aluminum, platinum and stainless steel electrodes. Biphasic H-FIRE pulses were compared to 8 × 100 µs monophasic pulses. We show that a longer interphase and interpulse delay results in lower cell survival, while the effects on cell membrane permeabilization are ambiguous. The cancellation effect was observed only for the survival of one cell line. Application of biphasic H-FIRE pulses results in lower metal release from electrodes but the interphase and interpulse delay does not have a large effect. The electrode material, however, importantly influences metal release – the lowest release was measured from platinum and the highest from aluminum electrodes.

A 2-D Cell Layer Study on Synergistic Combinations of High-Voltage and Low-Voltage Irreversible Electroporation Pulses.

The goal of this study is to further investigate the effect of this combination on a 2-D cell layer tumor model. 2-D layers of tumor cells are exposed to various SHV and LLV combinations, and the results of propidium iodide (PI) and fluorescein diacetate staining are examined to correlate treatment protocols with the ensuing irreversible and reversible electroporation areas. The combination of SHV+LLV pulses produces a larger area of electroporation and ablation than LLV+SHV pulses, LLV pulses alone, and SHV pulses alone. Judiciously combining SHV and LLV pulses can produce a synergistic effect that enlarges the electroporation-induced ablation area. A hypothetical explanation for this effect is that it involves a combination of pore expansion and electrolysis induced by LLV pulses in the area that had been reversibly permeabilized by the SHV pulses. This paper is valuable for the design of improved IRE protocols and provides a hypothesis for the mechanisms involved.

A Conceivable Mechanism Responsible for the Synergy of High and Low Voltage Irreversible Electroporation Pulses.

Irreversible electroporation (IRE), is a new non-thermal tissue ablation technology in which brief high electric field pulses are delivered across the target tissue to induce cell death by irreversible permeabilization of the cell membrane. A deficiency of conventional IRE is that the ablation zone is relatively small, bounded by the irreversible electroporation isoelectric field margin. In the previous studies we have introduced a new treatment protocol that combines few short high voltage (SHV) pulses with long low-voltage (LLV) pulses. In the previous studies, we also have shown that the addition of few SHV pulses increases by almost a factor of two the area ablated by a protocol that employs only the LLV pulses. This study employs potato and gel phantom to generate a plausible explanation for the mechanism. The study provides circumstantial evidence that the mechanism involved is the production of electrolytic compounds by the LLV pulse sequence, which causes tissue ablation beyond the margin of the irreversible electroporation isoelectric field generated by the SHV pulses, presumable to the reversible electroporation isoelectric field margin generated by the SHV pulses.

The Accumulation and Effects of Liposomal Doxorubicin in Tissues Treated by Radiofrequency Ablation and Irreversible Electroporation in Liver: In Vivo Experimental Study on Porcine Models.

To compare the accumulation and effect of liposomal doxorubicin in liver tissue treated by radiofrequency ablation (RFA) and irreversible electroporation (IRE) in in vivo porcine models. Sixteen RFA and 16 IRE procedures were performed in healthy liver of two groups of three pigs. Multi-tined RFA parameters included: 100W, target temperature 105°C for 7min. 100 IRE pulses were delivered using two monopolar electrodes at 2250V, 1Hz, for 100 µsec. For each group, two pigs received 50mg liposomal doxorubicin (0.5mg/kg) as a drip infusion during ablation procedure, with one pig serving as control. Samples were harvested from the central and peripheral zones of the ablation at 24 and 72h. Immunohistochemical analysis to evaluate the degree of cellular stress, DNA damage, and degree of apoptosis was performed. These and the ablation sizes were compared. Doxorubicin concentrations were also analyzed using fluorescence photometry of homogenized tissue. RFA treatment zones created with concomitant administration of doxorubicin at 24h were significantly larger than controls (2.5 ± 0.3cm vs. 2.2 ± 0.2cm; p = 0.04). By contrast, IRE treatment zones were negatively influenced by chemotherapy (2.2 ± 0.4cm vs. 2.6 ± 0.4cm; p = 0.05). At 24h, doxorubicin concentrations in peripheral and central zones of RFA were significantly increased in comparison with untreated parenchyma (0.431 ± 0.078µg/g and 0.314 ± 0.055µg/g vs. 0.18 ± 0.012µg/g; p < 0.05). Doxorubicin concentrations in IRE zones were not significantly different from untreated liver (0.191 ± 0.049µg/g and 0.210 ± 0.049µg/g vs. 0.18 ± 0.012µg/g). Whereas there is an increased accumulation of periprocedural doxorubicin and an associated increase in ablation zone following RFA, a contrary effect is noted with IRE. These discrepant findings suggest that different mechanisms and synergies will need to be considered in order to select optimal adjuvants for different classes of ablation devices.

A Study on Nonthermal Irreversible Electroporation of the Thyroid.

Background:Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation.Methods:Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results.Results:Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage.Conclusion:Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.

Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy

Purpose: This study evaluates the effects of various pulsing paradigms, on the irreversible electroporation (IRE) lesion, induced electric current, and temperature changes using a perfused porcine liver model.Materials and methods: A 4-monopolar electrode array delivered IRE therapy varying the pulse length and inter-pulse delay to six porcine mechanically perfused livers. Pulse paradigms included six forms of cycled pulsing schemes and the conventional pulsing scheme. Finite element models provided further insight into the effects of cycled pulsing on the temperature and thermal injury distribution.Results: ‘Single pulse cycle with no interpulse delay’ deposited maximum average energy (2.34 ± 0.35 kJ) and produced the largest ratio of thermally damaged tissue area and IRE ablation area from all other pulse schemes (18.22% 8.11, p < .0001 all pairwise comparisons). These compared favorably to the conventional algorithm (2.09 ± 0.37 kJ, 3.49% 2.20, p < .0001, all comparisons). Though no statistical significance was found between groups, the ‘5 pulse cycle, 0 s delay’ pulse paradigm produced the largest average IRE ablation cross sectional area (11.81 ± 1.97 cm2), while conventional paradigm yielded an average of 8.90 ± 0.91 cm2. Finite element modeling indicated a ‘10 pulse cycle, 10 s delay’ generated the least thermal tissue damage and ‘1 pulse cycle, 0 s delay’ pulse cycle sequence the most (0.47 vs. 3.76 cm2), over a lengthier treatment time (16.5 vs. 6.67 minutes).Conclusions: Subdividing IRE pulses and adding delays throughout the treatment can reduce white tissue coagulation and electric current, while maintaining IRE treatment sizes.

Electrical Characterization of Human Biological Tissue for Irreversible Electroporation Treatments.

Irreversible electroporation (IRE) is a cancer therapy that uses short, high-voltage electrical pulses to treat tumors. Due to its predominantly non-thermal mechanism and ability to ablate unresectable tumors, IRE has gained popularity in clinical treatments of both liver and pancreatic cancers. Existing computational models use electrical properties of animal tissue that are quantified a priori to predict the area of treatment in three dimensions. However, the changes in the electrical properties of human tissue during IRE treatment are so far unexplored. This work aims to improve models by characterizing the dynamic electrical behavior of human liver and pancreatic tissue. Fresh patient samples of each tissue type, both normal and tumor, were collected and IRE pulses were applied between two parallel metal plates at various voltages. The electrical conductivity was determined from the resistance using simple relations applicable to cylindrical samples. The results indicate that the percent change in conductivity during IRE treatments varies significantly with increasing electric field magnitudes. This percent change versus applied electric field behavior can be fit to a sigmoidal curve, as proposed in prior studies. The generic conductivity data from human patients from this work can be input to computational software using patient-specific geometry, giving clinicians a more accurate and personalized prediction of a given IRE treatment.

Clinically applicable irreversible electroporation for eradication of micro-organisms.

Irreversible electroporation (IRE) is utilized in interventional radiology to treat cancer patients. In this study we evaluated invitro the antimicrobial effect of IRE. We demonstrated that using IRE with clinically established parameters has a marked effect on pathogenic micro-organisms and is synergistic to antimicrobials when both are combined. Our results point to the potential of IRE as a treatment modality for deep-seated infections.

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

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.

Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model

PurposeTo compare the intensity of muscle contractions in irreversible electroporation (IRE) treatments when traditional IRE and high-frequency IRE (H-FIRE) waveforms are used in combination with a single applicator and distal grounding pad (A+GP) configuration. Materials and MethodsAn ex vivo in situ porcine model was used to compare muscle contractions induced by traditional monopolar IRE waveforms vs high-frequency bipolar IRE waveforms. Pulses with voltages between 200 and 5,000 V were investigated, and muscle contractions were recorded by using accelerometers placed on or near the applicators. ResultsH-FIRE waveforms reduced the intensity of muscle contractions in comparison with traditional monopolar IRE pulses. A high-energy burst of 2-μs alternating-polarity pulses energized for 200 μs at 4,500 V produced less intense muscle contractions than traditional IRE pulses, which were 25–100 μs in duration at 3,000 V. ConclusionsH-FIRE appears to be an effective technique to mitigate the muscle contractions associated with traditional IRE pulses. This may enable the use of voltages greater than 3,000 V necessary for the creation of large ablations in vivo.

Parameters optimization of bipolar high frequency pulses on tissue ablation and inhibiting muscle contraction

Irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors, but it is challenged due to the unintended induction of muscle contractions, which must be avoided by neuromuscular blockade in clinic. In this study, high frequency irreversible electroporation (H-FIRE), which replaces the monopolar IRE pulses with a burst of bipolar pulses, was used for tissues ablation on rabbit liver through Plate Electrodes. The bursts with different individual pulse durations maintain a constant total energized time (100 μs), burst number (90), and inter-burst delay (1 s). An accelerometer was used to measure the muscle contraction intensity. After the experiments, the tissue sections were made for pathological analysis. The experimental results show that all the cells are intact in the treated tissues that were harvested immediately. The tissues, which were harvested three days after the experiments, have an obvious ablation area, and the necrosis degree is increased with the pulse voltage and individual pulse width of the bursts. The extent of muscle contractions caused by H-FIRE is less than IRE. In addition, the simulations of electric field distribution near the vessels in liver tissues show that with the increase of the frequency and decrease of the pulse duration of the bursts, the electric field distribution will be more uniform. Compared with the lethal thresholds, bursts with larger pulse width can ablate the liver tissues effectively. Integrating into account the ablation effect and muscle contraction, we consider that H-FIRE with the individual pulse durations for 5 μs, electric field intensity for 2000 V/cm, can replace the traditional IRE, which have a good ablation effects and less extent of muscle contractions for animals.

High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model.

High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood–brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm3. In one dog, nonuniform ablations were observed, with viable tumor cells remaining around foci of intratumoral mineralization. In conclusion, high-frequency irreversible electroporation pulses can be delivered to brain tumors, including areas adjacent to critical vasculature, and are capable of producing clinically relevant volumes of tumor ablation. Mineralization may complicate achievement of complete tumor ablation.