Irreversible Electroporation Application Research Articles

Irreversible Electroporation-Assisted Resection for Locally Advanced Pancreas Cancer.

A significant number of patients with advanced pancreatic cancer are unable to undergo resection due to vascular involvement. Irreversible electroporation (IRE) has shown promise in improving survival. This study sought to assess a novel IRE application whereby IRE was performed pre-resection to alter tissue plasticity and assist tumor removal from underlying vasculature when surgical excision was otherwise precluded. After multidisciplinary evaluation appropriate patients were consented for IRE therapy. All IRE cases were tracked prospectively using an institutional review board-approved database that was retrospectively queried for patients undergoing IRE-assisted resection (IRE-AR) for pancreatic adenocarcinoma located in the head/uncinate process. Patients who underwent other IRE therapy or had disease location elsewhere were excluded. 5 patients met the study inclusion criteria with a mean tumor size of 3.2cm (range 2.4-4.1cm). Using IRE-AR median recurrence free survival was 10.6months, with 21.6month overall survival. The average comprehensive complication index score was 23.23. One patient had grade 3 [or higher] complications and there were no 90day mortalities. Employing a high-starting voltage for ablation along resection margins allows for resection when margins are anticipated to be positive. Patients with locally advanced pancreatic adenocarcinoma who underwent IRE-AR had promising outcomes. This study reports IRE-AR as a novel approach for resecting locally advanced pancreatic adenocarcinoma. A prospective trial of IRE-AR for inoperable pancreatic adenocarcinoma will provide additional data for the long-term application of this approach.

Assessment of Hepatic Lesions After non-Thermal Tumor Ablation by Irreversible Electroporation in a Pig Model.

Irreversible electroporation (IRE) is a non-thermal and minimal invasive modality to ablate pathologic lesions such as hepatic tumors. Histological analysis of the initial lesions after IRE can help predict ablation efficacy. We aimed to investigate the histological characteristics of early hepatic lesions after IRE application using animal models. IRE (1500 V/cm, a pulse length of 100 μs, 60 or 90 pulses) was applied to the liver of miniature pigs. H&E and TUNEL staining were performed and analyzed. Ablated zones of pig liver were discolored and separated from the normal zone after IRE. Histologic characteristics of ablation zones included preserved hepatic lobular architecture with a unique hexagonal-like structure. Apoptotic cells were detected, and sinusoidal dilatation and blood congestion were observed, but hepatic arteries and bile ducts were intact around the ablation zones. The early lesions obtained by delivering monophasic square wave pulses through needle electrodes reflected typical histological changes induced by IRE. Therefore, it was found that the histological assessment of the early hepatic lesion after IRE can be utilized to predict the IRE ablation effect.

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.

Absence of (sub-)acute cerebral events or lesions after electroporation ablation in the left-sided canine heart

Irreversible electroporation (IRE) is a nonthermal ablation modality. A 200-J application can create deep myocardial lesions, but gas bubbles are created at the ablation electrode. Cerebral effects of these bubbles are unknown. The purpose of this study was to investigate gas microemboli-induced brain lesions after IRE and radiofrequency (RF) ablation to the left side of the canine heart, using magnetic resonance imaging (MRI) and histopathology. In 11 canines, baseline cerebral MRI scans were performed. In 9 animals, after retrograde femoral artery access, 12 ± 4 200-J IRE applications were administered in the ascending aorta. In 2 animals, 30 minutes of irrigated 30-W RF ablation using 10-30g of contact force was applied in the left ventricle. At days 1 and 5 after ablation, MRI was repeated. The brain tissue then was histopathologically examined. All ablations and follow-up were uneventful. Intracardiac echography confirmed gas bubble formation after each IRE application. Neurologic examination was normal. MRI scans were normal in all animals at day 1 and were normal in 10 of 11 animals at day 5. In 1 animal, a single <2-mm-diameter lesion in the right temporal region could not be excluded as a small infarct or early hemorrhagic site. Histopathologic analysis of the same region showed no pathologic changes. In all other animals, gross and microscopic pathology were normal. MRI images alone or in combination with histologic follow-up did not reveal treatment-related embolic events. Gross and microscopic pathology did not reveal evidence of treatment-related embolic events. IRE seems to be a safe ablation modality for the brain.

Experimental model of occluded biliary metal stent recanalization using irreversible electroporation via a tubular catheter

Purpose To demonstrate the feasibility of irreversible electroporation (IRE) for treating biliary metal stent occlusion in an experimental liver model. Methods and materials IRE was performed using an expandable tubular IRE-catheter placed in nitinol stents in the porcine liver. A 3-electrode IRE-catheter was connected to an IRE-generator and one hundred 100μs pulses of constant voltage (300, 650, 1000, and 1300 V) were applied. Stent occlusion was simulated by insertion of liver tissue both ex vivo (n = 94) and in vivo in 3 pigs (n = 14). Three scenarios of the relationship between the stent, electrodes, and inserted tissue (double contact, single contact, and stent mesh contact) were studied. Electric current was measured and resistance and power calculated. Pigs were sacrificed 72 h post-procedure. Harvested samples (14 experimental, 13 controls) underwent histopathological analysis. Results IRE application was feasible at 300 and 650 V for the single and double contact setup in both ex vivo and in vivo studies. Significant differences in calculated resistance between double contact and single contact settings were observed (ex-vivo p ˂ 0.0001, in-vivo p = 0.02; Mann–Whitney). A mild temperature increase of the surrounding liver parenchyma was noted with increasing voltage (0.9–5.9 °C for 300–1000 V). The extent of necrotic changes in experimental samples in vivo correlated with the measured electric current (r 2 = 0.39, p = 0.01). No complications were observed during or after the in-vivo procedure. Conclusion Endoluminal IRE using an expandable tubular catheter in simulated metal stent occlusion is feasible. The relationship of active catheter electrodes to stent ingrowth tissue can be estimated based on resistance values.

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.

In vivo analysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation.

Aims Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation.Methods and resultsIn six 60–75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 μL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 μL of gas, for 30 and 60 s ablation time, respectively.Conclusion Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations.

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

Cancer Treatments of the Irreversible Electroporation

Irreversible electroporation (IRE) is a kind of non-thermal tumor treatment strategy. Based on this, Nanoknife emerged, which is approved by FDA in 2011. From then on, clinical application of nanosecond electrical pulsed have showed an explosive growth. At the cell level, the biophysical mechanism of nonthermal irreversible electroporation of electrical pulsed was studied. At the animal level, it has studied the safety of irreversible electroporation and preclinical animal experiments, also the clinical application of irreversible electroporation. We reviewed Animal studies of IRE and Clinical application of IRE. Also traditional medical imaging methods such as CT, magnetic resonance imaging (MRI) and ultra-sound imaging can be used in the IRE therapy. The evidences can prove the beneficial effects and safety of IRE in tumor treatment and verify the potential of IRE in clinical treatment to some extent. However, larger clinical trials are still needed to confirm these conclusions. Hopefully, as we go deeper into IRE, we get a more thorough understanding of it and the application will appear in various fields.

The Safety of Irreversible Electroporation on Nerves Adjacent to Treated Tumors.

To evaluate the safety of irreversible electroporation (IRE) on the sciatic nerve after IRE ablation of adjacent tumor. In this study, VX2 tumors were implanted adjacent to the sciatic nerves in 26 New Zealand white rabbits. The rabbits were divided into 3 groups 10 days after implantation, with 2 treatment groups of 10 rabbits each and a control group of 6 rabbits. In 1 of the treatment groups (IRE-S group), the rabbits underwent ablation with a single IRE application, and in the other group (IRE-D group) the rabbits underwent 2 IRE applications. IRE ablation was performed under ultrasonographic guidance. The 26 rabbits were euthanized as follows: half of the animals in each group on the seventh day and the rest on the 28th day after IRE ablation. The sciatic nerves were removed for histopathologic evaluation immediately after euthanasia. Sections from selected specimens were stained with hematoxylin and eosin and Masson's trichrome method for collagen; immunohistochemistry was performed for S100 and neurofilaments (markers for Schwann cells and axons, respectively). Clinical, radiologic, laboratory, and pathologic findings were analyzed. The nerves from the IRE-S and IRE-D groups showed preserved endoneurial architecture and the presence of numerous small-caliber axons along with Schwann cell hyperplasia, consistent with axonal regeneration. The tumor lesions were completely necrosed. A fibrous scar was observed in the adjacent muscle tissue, confirming ablation at the site. Nerve damaged also showed in the control group for tumor advanced and no signs of repair; the tumor showed rapid progression. The nerves adjacent to the tumor may undergo severe damage after IRE ablation, but their function and structure can return to normal in a short time. IRE ablation may be a feasible treatment option for tumors situated adjacent to nerves.

Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant

Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.

Irreversible Electroporation in Interventional Oncology: Where We Stand and Where We Go.

Irreversible electroporation (IRE) is the latest in the series of image-guided locoregional tumor ablation therapies. IRE is performed in a nearly non-thermal fashion that circumvents the "heat sink effect" and allows for IRE application in proximity to critical structures such as bile ducts or neurovascular bundles, where other techniques are unsuitable. IRE appears generally feasible and initial reported results for tumor ablation in the liver, pancreas and prostate are promising. Additionally, IRE demonstrates a favorable safety profile. However, site-specific complications include bile leaking or vein thrombosis and may be more severe after pancreatic IRE compared to liver or prostate ablation. There is limited clinical evidence in support of the use of IRE in the kidney. In contrast, pulmonary IRE has so far failed to demonstrate efficacy due to practicability limitations. Hence, this review will provide a state-of-the-art update on available clinical evidence of IRE regarding feasibility, safety and oncologic efficacy. The future role of IRE in the minimally invasive treatment of solid tumors will be discussed. • Preclinical findings of IRE have been successfully translated into clinical settings.• Non-thermal ablation is able to prevent the "heat sink effect" and collateral damage.• IRE should primarily be applied to tumors adjacent to sensitive structures (e. g. bile ducts).IRE efficacy appears promising in the liver, pancreas and prostate with tolerable morbidity.• In contrast, there are no evidential benefits of IRE in the lung parenchyma. Citation Format: • Savic LJ, Chapiro J, Hamm B et al. Irreversible Electroporation in Interventional Oncology: Where We Stand and Where We Go. Fortschr Röntgenstr 2016; 188: 735 - 745.

Irreversible Electroporation Ablation: Creation of Large-Volume Ablation Zones in in Vivo Porcine Liver with Four-Electrode Arrays

To prospectively determine optimal parameters with which to achieve defined large target zones of coagulation by using irreversible electroporation (IRE) with four-electrode arrays and the time needed to achieve this treatment effect in an in vivo animal model. This study was approved by the animal care and use committee. Ultrasonography (US)-guided IRE ablation (n = 90) was performed in vivo in 69 pig livers with an array of four electrodes (18 gauge) and an electroporation generator. Cardiac-gated 100-µsec IRE pulses were applied sequentially between the six sets of electrode pairs at 2250-3000 V. Multiple algorithms of energy deposition and electrode configuration were studied, including interelectrode spacing (1.5-2.5 cm), number of IRE pulses applied consecutively to each electrode pair (10, 20, 50, and 100), and number of times per cycle each electrode pair was activated (one to 10). Resultant zones of treatment were measured with US 1.5-3 hours after IRE and confirmed at gross and histopathologic examination. Data and ablation times were compared to determine the optimal algorithms with which to achieve 4-7-cm areas of treatment effect in the shortest time possible. In addition, the IRE current applied was correlated with ablation size. Data were analyzed by using analysis of variance with multiple comparisons, t tests, or nonparametric statistics. For 2.5-cm spacing, ablation diameter was increased by increasing either the overall time of energy application or the number of cycles of 20 pulses (P < .01 for both). IRE application of less than four cycles (or continuous IRE application of 100 pulses) did not result in contiguous ablation. However, sequentially increasing the number of cycles of IRE from four to 10 increased both the electrical current applied (from 14.4 A ± 0.4 to 17.6 A ± 0.7, P = .0004) and ablation diameter (from 5.6 cm ± 0.3 to 6.6 cm ± 0.3, P = .001). Although division of application into cycles did not alter coagulation at 2.0- and 1.5-cm spacing, application of energy to diagonal electrode pairs increased coagulation. Thus, one 100-pulse cycle (11.0 minutes ± 1.4) produced 4.8 cm ± 0.3 of ablation for 2.0-cm spacing with diagonal pairs but only 4.1 cm ± 0.3 of ablation without diagonal pairs (7.5 minutes ± 1.0, P < .03 for both). With four-electrode arrays, IRE can create large contiguous zones of treatment effect in clinically acceptable ablation times; parameters can be tailored to achieve a wide range of ablation sizes. Cyclical deposition of IRE application is beneficial, particularly for larger interprobe spacing, most likely owing to alterations of electrical conductivity that occur after successive applications of IRE energy.

Irreversible Electroporation Ablation: Creation of Large-Volume Ablation Zones in in Vivo Porcine Liver with Four-Electrode Arrays

Purpose To prospectively determine optimal parameters with which to achieve defined large target zones of coagulation by using irreversible electroporation (IRE) with four-electrode arrays and the time needed to achieve this treatment effect in an in vivo animal model. Materials and Methods This study was approved by the animal care and use committee. Ultrasonography (US)–guided IRE ablation (n = 90) was performed in vivo in 69 pig livers with an array of four electrodes (18 gauge) and an electroporation generator. Cardiac-gated 100-µsec IRE pulses were applied sequentially between the six sets of electrode pairs at 2250–3000 V. Multiple algorithms of energy deposition and electrode configuration were studied, including interelectrode spacing (1.5–2.5 cm), number of IRE pulses applied consecutively to each electrode pair (10, 20, 50, and 100), and number of times per cycle each electrode pair was activated (one to 10). Resultant zones of treatment were measured with US 1.5–3 hours after IRE and confirmed at gross and histopathologic examination. Data and ablation times were compared to determine the optimal algorithms with which to achieve 4–7-cm areas of treatment effect in the shortest time possible. In addition, the IRE current applied was correlated with ablation size. Data were analyzed by using analysis of variance with multiple comparisons, t tests, or nonparametric statistics. Results For 2.5-cm spacing, ablation diameter was increased by increasing either the overall time of energy application or the number of cycles of 20 pulses (P < .01 for both). IRE application of less than four cycles (or continuous IRE application of 100 pulses) did not result in contiguous ablation. However, sequentially increasing the number of cycles of IRE from four to 10 increased both the electrical current applied (from 14.4 A ± 0.4 to 17.6 A ± 0.7, P = .0004) and ablation diameter (from 5.6 cm ± 0.3 to 6.6 cm ± 0.3, P = .001). Although division of application into cycles did not alter coagulation at 2.0- and 1.5-cm spacing, application of energy to diagonal electrode pairs increased coagulation. Thus, one 100-pulse cycle (11.0 minutes ± 1.4) produced 4.8 cm ± 0.3 of ablation for 2.0-cm spacing with diagonal pairs but only 4.1 cm ± 0.3 of ablation without diagonal pairs (7.5 minutes ± 1.0, P < .03 for both). Conclusion With four-electrode arrays, IRE can create large contiguous zones of treatment effect in clinically acceptable ablation times; parameters can be tailored to achieve a wide range of ablation sizes. Cyclical deposition of IRE application is beneficial, particularly for larger interprobe spacing, most likely owing to alterations of electrical conductivity that occur after successive applications of IRE energy. © RSNA, 2013 Online supplemental material is available for this article.

Abstract No. 377 - CT findings after irreversible electroporation ablation in a porcine model: Radiologic-pathologic correlation

Purpose To characterize computed tomography (CT) findings after irreversible electroporation (IRE) in a porcine model Materials and Methods Twenty two CT-guided IRE lesions were created in livers of 12 pigs. Energy was delivered at 2250-3000 V (pulse length, 90-100 μsec; pulse repetition, 70-90) by using two 18-gauge electrodes with 2-2.5 cm active tip, 1.5-2.0 cm distance between electrodes and a Nanoknife generator (Angiodynamics, Fremont, CA). Triple-phase multi-detector CT imaging was performed prior to IRE application and immediately before euthanasia (2 hours after ablation). Multiple CT imaging features were studied, including: dimensions; coagulation zone attenuation; and presence, as well as characteristics of post ablation enhancement. Zones of ablation were evaluated at gross and histopathologic examination, correlated with CT findings, and subjected to statistical analysis. Results The mean ablation volume measured by CT imaging and gross pathology was 31.8 cm 3 [95% CI: (14.3, 49.4)] and 15.2 cm 3 [95% CI: (12.8,17.6)]. Using a mixed-effects regression model, the two volume means are significantly different (p=0.04) with the size of the ablation zone on the CT appearing larger than the gross size (p=0.0416). Two hours after IRE energy application, the ablation zone appeared as a well demarcated hypoattenuating area. Mean pre, arterial and portal HU for the zone of ablation was 79.6 [95% CI: (73.1, 87.2), 64.3 [95% CI: (57.3, 72.0)], and 73.9 [95% CI: (61.8, 86.1). An incomplete rim of enhancement was observed surrounding the zone of ablation in both the arterial and portal phase with a median thickness of 2.5 mm. Histologic examination revealed a clear demarcation between the ablated liver and adjacent unaffected parenchyma. Coagulation zone was characterized by hepatocellular dissociation often associated with hemorrhage and sinusoidal dilatation. Conclusion CT imaging in the acute period after IRE depicts the ablation zone as a hypoattenuating lesion with a surrounding rim of enhancement. However, it appears to overestimate the dimensions of the ablative injury.

Irreversible Electroporation in Eradication of Rabbit VX2 Liver Tumor

PurposeTo show the effectiveness and safety of irreversible electroporation (IRE) in treating large tumor models. Materials and MethodsVX2 liver tumor implantation was performed in 35 New Zealand White Rabbits. The rabbits were divided into three groups 1 week after implantation. The control group included 15 rabbits; the remaining 20 rabbits were divided into two IRE treatment groups. For the treatment groups, 10 rabbits underwent ablation with a single IRE application (IRE-S group), and 10 rabbits underwent ablation with multiple IRE applications (IRE-M group). Treatments and outcomes were analyzed using ultrasound, contrast-enhanced computed tomography (CT), and immunohistologic staining (hematoxylin and eosin [H&E], P-53, Ki-67, CD30, and vascular endothelial growth factor receptor [VEGFR] staining, and terminal deoxynucleotidyl-transferase–mediated 2'-deoxyuridine 5'-triphosphate [dUTP]–biotin nick-end labeling [TUNEL] assay). ResultsMultiple IRE ablations consistently produced complete cell death in all the animals in the IRE-M group (n = 10, IRE ablation time 2.45 minutes ± 0.3). The results were validated with ultrasound, CT, H&E, Ki-67, P53, and TUNEL assay. A high level of CD30-positive cells were identified in the IRE groups. A sharply demarcated ablation zone with no damage to surrounding vital structures was observed in all IRE-treated tissues. No complications during or after ablation were observed in any of the animals. ConclusionsThe effects of IRE were shown in a large tumor model with single and multiple IRE ablations (IRE-S and IRE-M treatment groups); complete ablation of the tumor was seen in the IRE-M group. These findings successfully show the beneficial effects and safety of IRE in the treatment of tumors and validate its potential as a clinically translatable treatment.