scholarly journals Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by “electric field sinks”

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Alexander Golberg ◽  
Bote G. Bruinsma ◽  
Basak E. Uygun ◽  
Martin L. Yarmush
Keyword(s):  
Electric Field ◽  
Cell Survival ◽  
Irreversible Electroporation ◽  
Tissue Heterogeneity

Effect of Three-Dimensional Electric Field and Heat Conduction to Electrodes on the Temperature Rise During Irreversible Electroporation

2011 ◽  
Author(s):  
Seiji Nomura ◽  
Kosaku Kurata ◽  
Hiroshi Takamatsu
Keyword(s):  
Heat Conduction ◽  
Electric Field ◽  
Temperature Rise ◽  
Heat Conduction Equation ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Three Dimensional ◽  
End Effects ◽  
Abnormal Cells ◽  
Novel Method

The irreversible electroporation (IRE) is a novel method to ablate abnormal cells by applying a high voltage between two electrodes that are stuck into abnormal tissues. One of the advantages of the IRE is that the extracellular matrix (ECM) may be kept intact, which is favorable for healing. For a successful IRE, it is therefore important to avoid thermal damage of ECM resulted from the Joule heating within the tissue. A three-dimensional (3-D) analysis was conducted in this study to predict temperature rise during the IRE. The equation of electric field and the heat conduction equation were solved numerically by a finite element method. It was clarified that the highest temperature rise occurred at the base of electrodes adjacent to the insulated surface. The result was significantly different from a two-dimensional (2-D) analysis due to end effects, suggesting that the 3-D analysis is required to determine the optimal condition.

scholarly journals Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1132 ◽  
Author(s):  
Philip M. Graybill ◽  
Rafael V. Davalos
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Pulsed Electric Field ◽  
Current Understanding ◽  
Vascular Effects ◽  
Cell Substrate ◽  
Membrane Effects ◽  
Cytoskeletal Disruption

Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.

scholarly journals Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE)

2015 ◽  
Vol 49 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Bor Kos ◽  
Peter Voigt ◽  
Damijan Miklavcic ◽  
Michael Moche
Keyword(s):  
Electric Field ◽  
Blood Vessels ◽  
Treatment Planning ◽  
Hepatic Vein ◽  
Thermal Ablation ◽  
Pulse Generator ◽  
Liver Tumors ◽  
Irreversible Electroporation ◽  
Distance Ratio ◽  
Contrast Enhanced Ct

AbstractBackground.Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.Materials and methods.The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy.Results.Output of the numerical treatment planning method shows that a 19.9 cm3irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months.Conclusions.Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

An Autonomous Cell Type Selective Irreversible Electroporation Microsystem Using Insulator Based Dielectrophoresis (IDEP)

2008 ◽  
Author(s):  
Hadi Shafiee ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Electric Field ◽  
Cancer Cells ◽  
Irreversible Electroporation ◽  
Cell Type ◽  
Electrode Arrays ◽  
Normal Cells ◽  
Dc Offset ◽  
Ac Field

Irreversible electroporation (IRE) is a method to kill cells by exposing the cell to intense electric field pulses[1]. It is postulated that the lipid bilayer rearranges to create permanent defects in the cell membrane which eventually leads to cell death via necrosis[1]. We postulate that the recurrence of cancer for patients treated for the disease would be minimized if their blood was monitored using a microdevice which would destroy existing or new exfoliated cancer cells. Dielectrophoresis (DEP) is the motion of polarizable particles that are suspended in an electrolyte when subjected to a spatially nonuniform electric field [2]. Insulator-based DEP uses insulating structures rather than electrode arrays to produce the nonuniform fields needed to drive DEP. We hypothesize that iDEP can enable the selective IRE of a particular cell type within a microfluidic platform. This manuscript demonstrates through modeling the feasibility of coupling iDEP with IRE using an AC field with a DC offset. Such a platform could be used to selectively destroy isolate cancer cells while not affecting normal cells.

scholarly journals The Effect of Conductivity Changes on Temperature Rise During Irreversible Electroporation

2020 ◽  
Author(s):  
Amir Khorasani
Keyword(s):  
Electrical Conductivity ◽  
Cell Death ◽  
Electric Field ◽  
Electric Field Intensity ◽  
Thermal Damage ◽  
Pulse Sequence ◽  
Irreversible Electroporation ◽  
Tissue Temperature ◽  
Comsol Multiphysics ◽  
Simulation Results

Purpose: Irreversible electroporation is a physical process which is used for killing the cancer cells. The process that leads to cell death in this method is a unique process. Thermal damage does not exist in this process. However, the temperature of the tissue also increases during the electroporation. In this study, we aim to investigate the effect of conductivity changes on tissue temperature increase during the irreversible electroporation process. Materials and Methods: To perform simulations and solve equations, COMSOL MultiPhysics has been used. Standard electroporation pulse sequence (8 pulses with different electric field intensities) was used as a pulse sequence in the simulation. Results: During the electroporation process, the electrical conductivity and the temperature of the tissue were increased. Changes in the tissue temperature in the simulation with variable electrical conductivity are more than in the simulation with constant electrical conductivity during the electroporation process. This difference for pulses with more vigorous electric field intensity and points closer to the electrodes has been achieved more. Conclusion: To more accurately estimate and calculate the temperature and thermal damage inside the tissue during the irreversible electroporation process, it is suggested to consider the effect of conductivity changes during this process.

scholarly journals Conductivity change with needle electrode during high frequency irreversible electroporation: a finite element study

2019 ◽  
Vol 25 (4) ◽  
pp. 237-242
Author(s):  
Amir Khorasani ◽  
Seyed Mohammad Firoozabadi ◽  
Zeinab Shankayi
Keyword(s):  
Electrical Conductivity ◽  
Electric Field ◽  
Field Intensity ◽  
High Frequency ◽  
Pulse Width ◽  
Electric Field Intensity ◽  
Electric Field Distribution ◽  
Irreversible Electroporation ◽  
Tissue Conductivity ◽  
Conductivity Change

Abstract Irreversible electroporation (IRE) is a process in which the cell membrane is damaged and leads to cell death. IRE has been used as a minimally invasive ablation tool. This process is affected by some factors. The most important factor is the electric field distribution inside the tissue. The electric field distribution depends on the electric pulse parameters and tissue properties, such as the electrical conductivity of tissue. The present study focuses on evaluating the tissue conductivity change due to high-frequency and low-voltage (HFLV) as well as low-frequency and high-voltage (LFHV) pulses during irreversible electroporation. We were used finite element analysis software, COMSOL Multiphysics 5.0, to calculate the conductivity change of the liver tissue. The HFLV pulses in this study involved 4000 bipolar and monopolar pulses with a frequency of 5 kHz, pulse width of 100 µs, and electric field intensity from 100 to 300 V/cm. On the other hand, the LFHV pulses, which we were used, included 8 bipolar and monopolar pulses with a frequency of 1 Hz, the pulse width of 2 ms and electric field intensity of 2500 V/cm. The results demonstrate that the conductivity change for LFHV pulses due to the greater electric field intensity was higher than for HFLV pulses. The most significant conclusion is the HFLV pulses can change tissue conductivity only in the vicinity of the tip of electrodes. While LFHV pulses change the electrical conductivity significantly in the tissue of between electrodes.

scholarly journals A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

2016 ◽  
Vol 50 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Shirley Sharabi ◽  
Bor Kos ◽  
David Last ◽  
David Guez ◽  
Dianne Daniels ◽  
...  
Keyword(s):  
Cell Death ◽  
Electric Field ◽  
Statistical Model ◽  
Blood Brain Barrier ◽  
Linear Regression Analysis ◽  
Irreversible Electroporation ◽  
Brain Barrier ◽  
Individual Treatment ◽  
Fermi Model ◽  
Blood Brain

BackgroundElectroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning.Material and methodsCell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments.ResultsLinear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r2= 0.79; p < 0.008, r2= 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes.ConclusionsThe statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.

scholarly journals Establishing Irreversible Electroporation Electric Field Potential Threshold in A Suspension In Vitro Model for Cardiac and Neuronal Cells

2021 ◽  
Vol 10 (22) ◽  
pp. 5443
Author(s):  
Sahar Avazzadeh ◽  
Barry O’Brien ◽  
Ken Coffey ◽  
Martin O’Halloran ◽  
David Keane ◽  
...  
Keyword(s):  
Cell Death ◽  
Electric Field ◽  
Cell Viability ◽  
Cardiac Fibroblasts ◽  
Irreversible Electroporation ◽  
Field Potential ◽  
Optimal Threshold ◽  
Delayed Cell Death ◽  
Significant Difference

Aims: Irreversible electroporation is an ablation technique being adapted for the treatment of atrial fibrillation. Currently, there are many differences reported in the in vitro and pre-clinical literature for the effective voltage threshold for ablation. The aim of this study is a direct comparison of different cell types within the cardiovascular system and identification of optimal voltage thresholds for selective cell ablation. Methods: Monophasic voltage pulses were delivered in a cuvette suspension model. Cell viability and live–dead measurements of three different neuronal lines, cardiomyocytes, and cardiac fibroblasts were assessed under different voltage conditions. The immediate effects of voltage and the evolution of cell death was measured at three different time points post ablation. Results: All neuronal and atrial cardiomyocyte lines showed cell viability of less than 20% at an electric field of 1000 V/cm when at least 30 pulses were applied with no significant difference amongst them. In contrast, cardiac fibroblasts showed an optimal threshold at 1250 V/cm with a minimum of 50 pulses. Cell death overtime showed an immediate or delayed cell death with a proportion of cell membranes re-sealing after three hours but no significant difference was observed between treatments after 24 h. Conclusions: The present data suggest that understanding the optimal threshold of irreversible electroporation is vital for achieving a safe ablation modality without any side-effect in nearby cells. Moreover, the evolution of cell death post electroporation is key to obtaining a full understanding of the effects of IRE and selection of an optimal ablation threshold.

scholarly journals Macroscopic Modeling of In Vivo Drug Transport in Electroporated Tissue

2016 ◽  
Vol 138 (3) ◽  
Author(s):  
Bradley Boyd ◽  
Sid Becker
Keyword(s):  
Electric Field ◽  
Mass Transport ◽  
Drug Transport ◽  
Irreversible Electroporation ◽  
Drug Uptake ◽  
Macroscopic Model ◽  
Uniform Electric Field ◽  
Macroscopic Modeling ◽  
Reversible Electroporation

This study develops a macroscopic model of mass transport in electroporated biological tissue in order to predict the cellular drug uptake. The change in the macroscopic mass transport coefficient is related to the increase in electrical conductivity resulting from the applied electric field. Additionally, the model considers the influences of both irreversible electroporation (IRE) and the transient resealing of the cell membrane associated with reversible electroporation. Two case studies are conducted to illustrate the applicability of this model by comparing transport associated with two electrode arrangements: side-by-side arrangement and the clamp arrangement. The results show increased drug transmission to viable cells is possible using the clamp arrangement due to the more uniform electric field.

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