A Preliminary Study to Delineate Irreversible Electroporation From Thermal Damage Using the Arrhenius Equation

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Hadi Shafiee ◽  
Paulo A. Garcia ◽  
Rafael V. Davalos
Keyword(s):  
Physical Properties ◽  
Upper Bound ◽  
Thermal Damage ◽  
Electric Pulse ◽  
Irreversible Electroporation ◽  
Human Monocyte ◽  
Electrical Fields ◽  
Reversible Electroporation ◽  
Electrical Pulses ◽  
Pulse Characteristics

Intense but short electrical fields can increase the permeability of the cell membrane in a process referred to as electroporation. Reversible electroporation has become an important tool in biotechnology and medicine. The various applications of reversible electroporation require cells to survive the procedure, and therefore the occurrence of irreversible electroporation (IRE), following which cells die, is obviously undesirable. However, for the past few years, IRE has begun to emerge as an important minimally invasive nonthermal ablation technique in its own right as a method to treat tumors and arrhythmogenic regions in the heart. IRE had been studied primarily to define the upper limit of electrical parameters that induce reversible electroporation. Thus, the delineation of IRE from thermal damage due to Joule heating has not been thoroughly investigated. The goal of this study was to express the upper bound of IRE (onset of thermal damage) theoretically as a function of physical properties and electrical pulse parameters. Electrical pulses were applied to THP-1 human monocyte cells, and the percentage of irreversibly electroporated (dead) cells in the sample was quantified. We also determined the upper bound of IRE (onset of thermal damage) through a theoretical calculation that takes into account the physical properties of the sample and the electric pulse characteristics. Our experimental results were achieved below the theoretical curve for the onset of thermal damage. These results confirm that the region to induce IRE without thermal damage is substantial. We believe that our new theoretical analysis will allow researchers to optimize IRE parameters without inducing deleterious thermal effects.

Irreversible Electroporation (IRE) to Treat Brain Tumors

2008 ◽  
Author(s):  
Paulo A. Garcia ◽  
John Robertson ◽  
John Rossmeisl ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Brain Tumors ◽  
High Voltage ◽  
Electric Pulse ◽  
Irreversible Electroporation ◽  
Transient Effect ◽  
Electric Pulses ◽  
Thermal Cell ◽  
Reversible Electroporation

Electroporation is the phenomenon in which permeability of the cell membrane to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high voltage electric pulses [1]. The application of the electric pulse can have no effect, can have a transient effect known as reversible electroporation, or can cause permanent permeation known as irreversible electroporation (IRE) which leads to non-thermal cell death by necrosis [1, 2].

scholarly journals Chemical Enhancement of Irreversible Electroporation: A Review and Future Suggestions

2019 ◽  
Vol 18 ◽  
pp. 153303381987412 ◽  
Author(s):  
Ying Chen ◽  
Michael A. J. Moser ◽  
Yigang Luo ◽  
Wenjun Zhang ◽  
Bing Zhang
Keyword(s):  
Tumor Cell ◽  
Irreversible Electroporation ◽  
Structural Defects ◽  
Chemical Enhancement ◽  
Large Size ◽  
Risk Of Injury ◽  
Reversible Electroporation ◽  
Thermal Therapies ◽  
Electrical Pulses ◽  
Preclinical And Clinical Studies

Irreversible electroporation has raised great interest in the past decade as a means of destroying cancers in a way that does not involve heat. Irreversible electroporation is a novel ablation technology that uses short high-voltage electrical pulses to enhance the permeability of tumor cell membranes and generate irreversible nano-sized structural defects or pores, thus leading to cell death. Irreversible electroporation has many advantages over thermal therapies due to its nonthermal mechanism: (1) reduced risk of injury to surrounding organs and (2) no “heat-sink” effect due to nearby blood vessels. However, so far, it has been difficult for irreversible electroporation to completely ablate large tumors (eg, >3 cm in diameter). In order to overcome this problem, many preclinical and clinical studies have been performed to improve the efficacy of IRE in the treatment of large size of tumors through a chemical perspective. Due to the distribution of electric field, irreversible electroporation region, reversible electroporation region, and intact region can be found in the treatment of irreversible electroporation. Thus, 2 types of chemical enhancements of irreversible electroporation were discussed in the article, such as the reversible electroporation region enhanced and the irreversible electroporation region enhanced. Specifically, the state-of-the-art results regarding the following approaches that have the potential to be used in the enhancement of irreversible electroporation were systematically reviewed in the article, including (1) combination with cytotoxic drugs, (2) calcium electroporation, (3) modification of cell membrane, and (4) modification of the tumor cell microenvironment. In the end, we concluded with 4 issues that should be addressed in the future for improving irreversible electroporation further in a chemical way.

Nonthermal Irreversible Electroporation for Tissue Decellularization

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Electrical Parameters ◽  
Irreversible Damage ◽  
Tissue Scaffold ◽  
Electrical Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Tissue Scaffolding ◽  
Living Tissues

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

Cancer Cells Ablation with Irreversible Electroporation

2005 ◽  
Vol 4 (6) ◽  
pp. 699-705 ◽  
Author(s):  
Liron Miller ◽  
Jonathan Leor ◽  
Boris Rubinsky
Keyword(s):  
Cancer Cell ◽  
Irreversible Electroporation ◽  
Single Pulse ◽  
Cell Ablation ◽  
Reversible Electroporation ◽  
Electrical Pulses ◽  
Hepatocarcinoma Cells ◽  
Multiple Pulses ◽  
A New Technique

In this study we perform in vitro irreversible electroporation (IRE) experiments with human hepatocarcinoma cells (HepG2) to investigate IRE as a new technique for undesirable tissue ablation. Irreversible electroporation (IRE) is the irreversible permeabilization of the cell membrane through the application of microsecond through millisecond electrical pulses. Until now IRE was studied only as an undesirable condition during the use of reversible electroporation in gene therapy and electrochemotherapy. There was a possibility that the IRE ablation domain is mostly superimposed on the electrical pulses induced Joule heating thermal ablation domain. This study demonstrates that there is a real and substantial domain of electrical parameters for IRE ablation of cancer that is distinct from the thermal domain and which results in complete cancer cell ablation. Experiments show that the application of 1500 V/cm in three sets of ten pulses of 300 microseconds each can produce complete cancer cell ablation. We also find that the use of multiple pulses appears to be more effective for cancer cell ablation than the application of the same energy in one single pulse.

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 Study and modulation of cardiac electroporation with a novel model utilizing human induced pluripotent stem cells

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Maizels ◽  
E Heller ◽  
M Landesberg ◽  
I Huber ◽  
G Arbel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Medical Center ◽  
Irreversible Electroporation ◽  
Public Institution ◽  
Cardiovascular Research ◽  
Protocol Optimization ◽  
Reversible Electroporation ◽  
Induced Pluripotent

Abstract Background Cardiac electroporation is a promising novel non-thermal ablation method, gaining significant interest with recent first-in-man data suggesting effective cardiac lesion generation with no collateral damage. Nevertheless, significant knowledge gaps exist regarding its electrophysiological consequences in cardiomyocytes, including; cell specificity, protocol optimization, irreversibility threshold, recovery time-constants, and the mechanistic nature of its cytolytic and anti-arrhythmic properties. Purpose Establishing an innovative in-vitro model for the study of cardiac electroporation-ablation, utilizing human induced pluripotent stem cells (hiPSCs). Methods and results Healthy-control hiPSC-derived cardiomyocytes were enzymatically dissociated and seeded as circular cell sheets (hiPSC-CCSs). Electroporation-ablation experiments were performed using a custom designed high-frequency electroporation (HF-EP) generator. Two needle-shaped electrodes were used for HF-EP delivery (Figure 1). Subsequently, detailed voltage- and Ca2+-mapping studies of the hiPSC-CCSs were conducted (Figure 2). HF-EP application resulted in the generation of electrically isolated lesions within the hiPSC-CCSs (Figure 3). Further characterization of the temporal changes and electrophysiological properties following electroporation revealed that; (1) lesions persisted over prolonged periods of time (days), indicating irreversible electroporation, (2) a temporal decrease in lesion dimensions was noted, consistent with a significant reversible electroporation component (Figures 3–5), (3) most tissue recovery had occurred within the first 15 minutes following electroporation, with little recovery beyond that time-frame, (4) increasing pulse-number augmented lesion area as well as the proportion of irreversible damage, and (5) electroporation sensitization was achieved by increasing extracellular Ca2+, indicating its crucial role in electroporation cytolysis, potentially via direct cellular toxicity and apoptosis facilitation (Figures 5–6). Finally, evaluating for HF-EP anti-arrhythmic properties, we targeted multiple rotors or focal triggered-activity generated in the hiPSC-CCSs. HF-EP application generated sustained line-blocks, isolating arrhythmogenic substrates within the hiPSC-CCSs while blocking the propagation of arrhythmic wavefronts (Figure 7). Conclusion Our results demonstrate the ability to study cardiac electroporation utilizing hiPSC-derived cardiomyocytes, provide novel insights into its temporal and electrophysiological characteristics, facilitate electroporation protocol optimization, screen for potential electroporation sensitizers, and to study its mechanistic nature and anti-arrhythmic properties. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Division of Cardiology, and Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center - Tel Hashomer, Ramat-Gan, Israel Figures 1–4 Figures 5–7

Depth Filtration Assisted by Electrical Fields

1993 ◽  
Vol 27 (10) ◽  
pp. 95-99 ◽  
Author(s):  
G. S. Solt
Keyword(s):  
Electrical Properties ◽  
Physical Properties ◽  
Filtration Efficiency ◽  
Particle Removal ◽  
Electrical Field ◽  
Electrical Fields ◽  
Main Drawback ◽  
Depth Filtration ◽  
Conductivity Water ◽  
The Relationship

Depth filtration of liquids is a well established process. Its main drawback is that it does not effectively remove particles smaller than about 2-3 µm diameter, because they do not normally approach near enough to the surface of the medium to become attached to it. A static electrical field overcomes this by promoting electrophoretic movement of the particles. The work has studied particle removal from low conductivity water through fibrous depth filters and has covered a variety of fibres with different physical properties. The results yield a fibre efficiency series, which suggest the relationship between filtration efficiency and the electrical properties of the fibre.

scholarly journals A Study on Nonthermal Irreversible Electroporation of the Thyroid

2019 ◽  
Vol 18 ◽  
pp. 153303381987630
Author(s):  
Yanpeng Lv ◽  
Yanfang Zhang ◽  
Jianwei Huang ◽  
Yunlong Wang ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Pulse Sequences ◽  
Cell Swelling ◽  
Tissue Type ◽  
Heterogeneous Structure ◽  
Treatment Protocols ◽  
Thyroid Ablation ◽  
Nonthermal Irreversible Electroporation

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.

Design of an Irreversible Electroporation System for Clinical Use

2007 ◽  
Vol 6 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Claudio Bertacchini ◽  
Pier Mauro Margotti ◽  
Enrico Bergamini ◽  
Andrea Lodi ◽  
Mattia Ronchetti ◽  
...  
Keyword(s):  
High Voltage ◽  
Traditional Approach ◽  
Irreversible Electroporation ◽  
Target Volume ◽  
High Energy ◽  
Target Tissue ◽  
Clinical Use ◽  
Safety Issues ◽  
Electrical Pulses ◽  
Effective Delivery

Irreversible electroporation is an ablation modality in which microseconds, high-voltage electrical pulses are applied to induce cell necrosis in a target tissue. To perform irreversible electroporation it is necessary to use a medical device specifically designed for this use. The design of an irreversible electroporation system is a complex task in which the effective delivery of high energy pulses and the safety of the patient and operator are equally important. Pulses of up to 3000 V of amplitude and 50 A of current need to be generated to irreversibly electroporate a target volume of approximately 50 to 70 cm3 with as many as six separate electrodes; therefore, a traditional approach based on high voltage amplifiers becomes hard to implement. In this paper, we present the process that led to the first irreversible electroporator capable of such performances approved for clinical use. The main design choices and its architecture are outlined. Safety issues are also explained along with the solutions adopted.

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