Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation.
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ABSTRACT:
SUBMITTER: Chen X
PROVIDER: S-EPMC4637899 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:PurposeTo evaluate risk factors associated with alterations in venous structures adjacent to an ablation zone after percutaneous irreversible electroporation (IRE) of hepatic malignancies at subacute follow-up (1 to 3 days after IRE) and to describe evolution of these alterations at mid-term follow-up.Materials and methods43 patients (men/women, 32/11; mean age, 60.3 years) were identified in whom venous structures were located within a perimeter of 1.0 cm of the ablation zone at subacute follow-up after IRE of 84 hepatic lesions (primary/secondary hepatic tumors, 31/53). These vessels were retrospectively evaluated by means of pre-interventional and post-interventional contrast-enhanced magnetic resonance imaging or computed tomography or both. Any vascular changes in flow, patency, and diameter were documented. Correlations between vascular change (yes/no) and characteristics of patients, lesions, and ablation procedures were assessed by generalized linear models.Results191 venous structures were located within a perimeter of 1.0 cm of the ablation zone: 55 (29%) were encased by the ablation zone, 78 (41%) abutted the ablation zone, and 58 (30%) were located between 0.1 and 1.0 cm from the border of the ablation zone. At subacute follow-up, vascular changes were found in 19 of the 191 vessels (9.9%), with partial portal vein thrombosis in 2, complete portal vein thrombosis in 3, and lumen narrowing in 14 of 19. At follow-up of patients with subacute vessel alterations (mean, 5.7 months; range, 0 to 14 months) thrombosis had resolved in 2 of 5 cases; vessel narrowing had completely resolved in 8 of 14 cases, and partly resolved in 1 of 14 cases. The encasement of a vessel by ablation zone (OR = 6.36, p<0.001), ablation zone being adjacent to a portal vein (OR = 8.94, p<0.001), and the usage of more than 3 IRE probes (OR = 3.60, p = 0.035) were independently associated with post-IRE vessel alterations.ConclusionVenous structures located in close proximity to an IRE ablation zone remain largely unaffected by this procedure, and thrombosis is rare.
| S-EPMC4535980 | biostudies-literature
Project description:BackgroundHigh-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo.MethodsTen Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.ResultsHigher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P < 0.001) and heat shock protein 70 (HSP70) (0.03 ± 0.01 vs. 0.46 ± 0.09 vs. and 0.42 ± 0.07, F = 64.490, P < 0.001) were significantly different between the untreated, IRE and H-FIRE zones, but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone (both P > 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.ConclusionsH-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.
| S-EPMC8439989 | biostudies-literature
Project description:BackgroundThe effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy?ResultsThe electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw.ConclusionsThe observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.
| S-EPMC7667796 | biostudies-literature
Project description:PurposeAblation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow up after renal IRE in humans. Objectives are to assess computed tomography (CT) and magnetic resonance imaging (MRI) on the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE.MethodsProspective phase 2 study of IRE in nine patients with ten SRMs. MRI imaging was performed pre-IRE, 1 week, 3 months, 6 months and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and relation between the needle configuration volume (NCV; planned AZV) and CT- and MRI volumes were evaluated.ResultsEight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a non-diagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (respectively, 16.8 cm3 and 6.2 cm3) compared to the NCV (4.8 cm3). On MRI, median AZV increased 1-week post-IRE until 3 months post-IRE (respectively, 14.5 cm3 and 4.6 cm3) compared to the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planning and the post-treatment volumes. Inter-observer agreement between observers was excellent (CT 95% CI 0.82-0.95, MRI 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumour. Subtraction images confirmed non-enhancement on MRI in unclear enhancement cases (3/9). Directly after IRE, gas bubbles, perinephric stranding and edema were observed in all cases.ConclusionThe AZV increases immediately on CT until 3 months after IRE. On MRI, the AZV increases at 1 week until 3 months post-IRE. At 6 months the AZV starts decreasing until 12 months post-IRE on both CT and MRI. Enhancement was absent post-IRE, except for one residual tumour. Gas bubbles, perinephric stranding and edema are normal findings directly post-IRE.
| S-EPMC8480958 | biostudies-literature
Project description:During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture.
| S-EPMC4727979 | biostudies-literature
Project description:BackgroundIrreversible electroporation (IRE) ablation is a new technique that is used to eliminate malignant tumors through nonthermal approaches.ObjectiveThe purpose of this review was to evaluate the efficiency of IRE for hepatic malignant tumors.MethodsA systematic search was performed from PubMed, Embase, Web of science, Scopus and other potential literatures from references in relevant articles July 26th, 2016. Overall estimates of pooled standard mean difference (SMD) with 95% confidence interval (CI) were calculated for the changes of the pre- and post-IRE longest diameter, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and serum total bilirubin levels. Sensitivity analysis and publication bias and were performed after the pooled analysis, and the quality of the included literatures was appraised using Newcastle-Ottawa Scale (NOS).ResultsWe finally included 300 patients (mean age: 51 to 66.6 years; male: 182; female: 118) from 9 studies of hepatic malignant tumors. The meta-analysis showed that comparing with the initial values, the longest diameter of the tumors was significantly decreased at the last follow-up months after IRE. Furthermore, the ALP, AST and total bilirubin levels were increased at 1 day after IRE while returned to baseline at the last follow-up month. No risk of publication bias was found, and all literatures were assessed good quality according to NOS.ConclusionsThe pooled data indicated that IRE could be a minimal invasive and effective approach for patients who had preoperative poor liver function or those whose masses were in refractory locations where surgical resection was unsuitable.
| S-EPMC5351595 | biostudies-literature
Project description:Introduction: Pulsed electric field (PEF) cardiac ablation has been recently proposed as a technique to treat drug resistant atrial fibrillation by inducing cell death through irreversible electroporation (IRE). Improper PEF dosing can result in thermal damage or reversible electroporation. The lack of comprehensive and systematic studies to select PEF parameters for safe and effective IRE cardiac treatments hinders device development and regulatory decision-making. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been proposed as an alternative to animal models in the evaluation of cardiac electrophysiology safety. Methods: We developed a novel high-throughput in vitro assay to quantify the electric field threshold (EFT) for electroporation (acute effect) and cell death (long-term effect) in hiPSC-CMs. Monolayers of hiPSC-CMs were cultured in high-throughput format and exposed to clinically relevant biphasic PEF treatments. Electroporation and cell death areas were identified using fluorescent probes and confocal microscopy; electroporation and cell death EFTs were quantified by comparison of fluorescent images with electric field numerical simulations. Results: Study results confirmed that PEF induces electroporation and cell death in hiPSC-CMs, dependent on the number of pulses and the amplitude, duration, and repetition frequency. In addition, PEF-induced temperature increase, absorbed dose, and total treatment time for each PEF parameter combination are reported. Discussion: Upon verification of the translatability of the in vitro results presented here to in vivo models, this novel hiPSC-CM-based assay could be used as an alternative to animal or human studies and can assist in early nonclinical device development, as well as inform regulatory decision-making for cardiac ablation medical devices.
| S-EPMC9869257 | biostudies-literature
Project description:Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for "electric field sinks" in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures.
| S-EPMC4329566 | biostudies-other
Project description:Skin scar formation is a complex process that results in the formation of dense extracellular matrix (ECM) without normal skin appendages such as hair and glands. The absence of a scarless healing model in adult mammals prevents the development of successful therapies. We show that irreversible electroporation of skin drives its regeneration with all accessory organs in normal adult rats. Pulsed electric fields at 500 V, with 70 μs pulse duration and 1000 pulses delivered at 3 Hz, applied through two electrodes separated by 2 mm lead to massive cell death. However, the ECM architecture of the skin was preserved. Six months after the ablation, the epidermis, sebaceous glands, panniculus carnosus, hair follicles, microvasculature and arrector pili muscle were altogether re-formed in the entire ablated area. These results suggest a key role of the ECM architecture in the differentiation, migration and signalling of cells during scarless wound healing. Copyright © 2016 John Wiley & Sons, Ltd.
| S-EPMC5555830 | biostudies-literature
Project description:Background and aimIrreversible electroporation (IRE) was confirmed to control several solid tumors effectively in vivo. Our preclinical study aimed to assess the feasibility and safety of IRE in the breast of rabbit.MethodsThirty New Zealand white rabbits were randomly divided into 3 groups of 10 rabbits (control group, IRE group A, and B). Two mono-electrode needles were inserted into the breast tissue by percutaneous puncture. Electrocardiogram and vital signs were monitored before, during, and after ablation. Histopathology, immunohistochemistry, and transmission electron microscopy were examined at 0 hours, 12 hours, 24 hours, 4 days, 7 days, 14 days, and 28 days after ablation.ResultsAll the rabbits survived the procedure with no significant adverse effects. Intra-operative ventricular arrhythmias occurred in 1 rabbit from IRE group B and was immediately relieved after ablation. Reversible subcutaneous hemorrhage was observed in 8 rabbits from IRE group A and 7 rabbits from IRE group B. No skin was burnt, however, pectoralis major muscle injuries were found in all rabbits. Histopathological and ultrastructural examination revealed the coexistence of cell necrosis and apoptosis. HE, TUNEL, and Masson staining revealed breast tissue injury and the recovery of damage by fibrous tissue and granulation tissue. Notably, the structures of mammary gland lobules and interstitial components of the breasts were well preserved.ConclusionsOur study suggests that IRE destroys breast cancer while effectively preserving the skin, the structure of mammary gland lobules, and interstitial components. IRE may be a promising technique to locally control breast cancer and to maintain the esthetic of the breast.
| S-EPMC5521795 | biostudies-literature