scholarly journals EXTH-14. PULSED ELECTRIC FIELDS FOR THE TREATMENT OF BRAIN TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi85-vi85
Author(s):  
Shirley Sharabi ◽  
David Last ◽  
Dianne Daniels ◽  
Itzik Cooper ◽  
Yael Bresler ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Point Source ◽  
Electric Fields ◽  
Growth Rates ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Residual Tumor ◽  
Minimal Invasive ◽  
Control Group ◽  
Reversible Electroporation

Abstract When high pulsed electric fields (PEFs) are applied to the brain electroporation occurs. Depending on the electric fields strength, irreversible electroporation, inducing necrotic cell death or reversible electroporation, inducing BBB disruption may occur. We have developed a unique minimally-invasive setup for treating brain tumors employing a single insulated intracranial electrode with an exposed tip placed within the tumor and an external surface electrode. This unique setup, termed point-source electroporation, provides intratumoral irreversible-electroporation (inducing necrosis) with surrounding reversible BBB disruption, enabling efficient delivery of systemically administered drugs into the infiltrating zone. Treatment duration is 1–2 min. An efficacy study conducted with 120 glioma-bearing rats resulted in suppressed tumor growth rates in the electroporation+Cisplatin group (1.1±0.1) relative to growth rates in the control group (5.2±1.0), p< 0.047, and in the Cisplatin-only group p< 0.012 (3.92±1.0) (Welch’s F(2,12.73)=10.84; p< 0.002; ω2=0.28). Kaplan-Meir analysis revealed that electroporation+Cisplatin prolonged survival significantly (χ2=7.54; p< 0.006). Immunofluorescence analysis revealed significant infiltration of peripheral macrophages and CD8+ cells in the residual tumor. A finite elements simulation demonstrated the feasibility for obtaining clinically-relevant treatment volumes (~6cm diameter) using a single 3mm (diameter) intracranial catheter. Additionally, we discovered that low PEFs, an order of magnitude lower than electroporation threshold, can also transiently disrupt the BBB by a different mechanism, enabling penetration of both small (Gd/NaF) and large (Evans blue bound to serum albumin) molecules and immune cells, non-invasively. The extent of BBB disruption, measured in mice using delayed-contrast MRI, was found to be linearly dependent both on the electric field strength (r2=0.9,p< 0.03) and on the number of applied pulses (r2=0.94,p< 0.003). These results demonstrate the feasibly of applying combined systemic chemotherapy with point-source electroporation, a minimal-invasive/rapid treatment of PEFs, for obtaining significant antineoplastic effects. Furthermore, low PEFs may be applied non-invasively, rapidly and repeatedly for obtaining reversible BBB disruption.

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 Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for tissue ablation

2016 ◽  
Author(s):  
Nina Klein ◽  
Enric Guenther ◽  
Paul Mikus ◽  
Michael K Stehling ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Exponential Decay ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Electrical Currents ◽  
New Device ◽  
Reversible Electroporation ◽  
Electrolytic Ablation ◽  
Synergistic Combination ◽  
Single Exponential

Background: Electrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2). Method: A new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW), was applied to the pig liver and the effect of various parameters on the extent of tissue ablation was examined with histology. Results: Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue Discussion: The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.

scholarly journals Effect of Pulsed Electric Fields on the Growth and Acidification Kinetics of Lactobacillus delbrueckii Subsp. bulgaricus

Foods ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1146
Author(s):  
Kaidi Peng ◽  
Mohamed Koubaa ◽  
Olivier Bals ◽  
Eugène Vorobiev
Keyword(s):  
Electric Fields ◽  
Growth Rates ◽  
Specific Growth ◽  
Pulsed Electric Fields ◽  
Lactobacillus Delbrueckii ◽  
Accelerated Growth ◽  
Specific Growth Rates ◽  
The Impact ◽  
Kinetics Of ◽  
Lactobacillus Delbrueckii Subsp

The aim of this work was to investigate the effect of pulsed electric fields (PEF) on the growth and acidification kinetics of Lactobacillus delbrueckii subsp. bulgaricus CFL1 during fermentation. The PEF treatments were applied during the fermentation process using a recirculation pump and a PEF treatment chamber coupled with a PEF generator. The medium flow rate through the chamber was first optimized to obtain the same growth and acidification kinetics than the control fermentation without medium recirculation. Different PEF intensities (60–428 V cm−1) were then applied to the culture medium to study the impact of PEF on the cells’ behavior. The growth and acidification kinetics were recorded during the fermentation and the specific growth rates µ, pH, and acidification rate (dpH/dt) were assessed. The results obtained showed a biphasic growth by applying high PEF intensities (beyond 285 V cm−1) with the presence of two maximal specific growth rates and a decrease in the acidification activities. It was demonstrated that the cells were stressed during the PEF treatment, but presented an accelerated growth after stopping it, leading thereby to similar absorbance and pH at the end of the fermentation. These results show the great potential of PEF technology to be applied to generate low acidified products by performing PEF-assisted fermentations.

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 Modeling of Inactivation of Biofilm Composing Bacteria with Low Intensity Electric Field: Prediction of Lowest Intensity and Mechanism

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Mokhamad Tirono ◽  
Suhariningsih
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Staphylococcus Epidermidis ◽  
Treatment Time ◽  
Irreversible Electroporation ◽  
Pockels Effect ◽  
Low Intensity ◽  
Reversible Electroporation ◽  
Effect Of Treatment ◽  
Number Of Bacteria

Sterilization using high-intensity electric fields is detrimental to health if safety is inadequate, so it is necessary to study the possibility of sterilization using low-intensity electric fields. This study aims to determine the lowest electric field intensity and treatment time to deactivate the bacteria that make up the biofilms and explain the mechanism of inactivation. The study samples were biofilms from the bacteria Pseudomonas aeruginosa and Staphylococcus epidermidis grown on the catheter. The modeling formula was developed from the Pockels effect and the Weibull distribution with the treatment using a square pulse-shaped electric field with a pulse width of 50 μs and an intensity of 2.0-4.0 kV/ cm. The results showed that the threshold for irreversible electroporation of both samples occurred in the treatment using an electric field with an intensity of 3.5 kV/cm and 3.75 kV/ cm, respectively, where the size and type of Gram of bacteria influenced. Moreover, the time of the treatment had an effect when irreversible electroporation occurred. However, when there was reversible electroporation, the effect of treatment time on the reduction in the number of bacteria was not significant. Also, changes in conductivity affected the reduction in the number of bacteria when reversible electroporation occurred.

Electroporation-based Therapy for Brain Tumors: A Review

2021 ◽  
Author(s):  
Zheng Fang ◽  
Lingchao Chen ◽  
Michael Moser ◽  
W.J. (Chris) Zhang ◽  
Zhiyong Qin ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Review Paper ◽  
Cell Model ◽  
Irreversible Electroporation ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Blood Brain ◽  
Reversible Electroporation

Abstract Electroporation-based therapy (EBT), as a high-voltage-pulse technology has been prevalent with favorable clinical outcomes in the treatment of various solid tumors. The aim of this review paper is to promote the clinical translation of EBT for brain tumors. First, we briefly introduced the mechanism of pore formation in a cell membrane activated by external electric fields using a single cell model. Then, we summarized and discussed the current in vitro and in vivo preclinical studies, in terms of (1) the safety and effectiveness of EBT for brain tumors in animal models, and (2) the blood-brain barrier (BBB) disruption induced by EBT. Two therapeutic effects could be achieved in EBT for brain tumors simultaneously, i.e., the tumor ablation induced by irreversible electroporation (IRE) and transient blood-brain barrier (BBB) disruption induced by reversible electroporation (RE). The BBB disruption could potentially improve the uptake of anti-tumor drugs thereby enhancing brain tumor treatment. The challenges that hinder the application of EBT in the treatment of human brain tumors are discussed in the review paper as well.

scholarly journals Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

2009 ◽  
Vol 8 (4) ◽  
pp. 289-306 ◽  
Author(s):  
Axel T. Esser ◽  
Kyle C. Smith ◽  
T. R. Gowrishankar ◽  
James C. Weaver
Keyword(s):  
Cell Death ◽  
Electric Field ◽  
Spatial Scale ◽  
Electric Fields ◽  
Solid Tumor ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Underlying Mechanism ◽  
Tumor Ablation ◽  
Nanosecond Pulsed Electric Fields

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.

scholarly journals Antitumor Effect and Immune Response of Nanosecond Pulsed Electric Fields in Pancreatic Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Jing Zhao ◽  
Shuochun Chen ◽  
Lu Zhu ◽  
Liang Zhang ◽  
Jingqi Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Electric Fields ◽  
Morphological Changes ◽  
Pulsed Electric Fields ◽  
Control Group ◽  
Pancreatic Cancer Cells ◽  
Nanosecond Pulsed Electric Fields

Nanosecond pulsed electric fields (nsPEFs) have emerged as a novel and effective strategy for the non-surgical and minimally invasive removal of tumors. However, the effects of nsPEFs treatment on the tumor immune microenvironment remain unknown. In this study, the changes in the morphology and function of pancreatic cancer cells after nsPEFs were assessed and the modifications in the immune profile in pancreatic cancer models were investigated. To this end, electrodes were inserted with different parameters applied to ablate the targeted tumor tissues. Tumor development was found to be inhibited, with decreased volumes post-nsPEFs treatment compared with control tumors (P &lt; 0.05). Hematoxylin and eosin staining showed morphological changes in pancreatic cancer cells, Ki-67 staining confirmed the effects of nsPEFs on tumor growth, and caspase-3 staining indicated that nsPEFs caused apoptosis in the early stages after treatment. Three days after nsPEFs, positron emission tomography demonstrated little residual metabolic activity compared with the control group. Gene expression profiling identified significant changes in immune-related pathways. After treatment with nsPEFs, CD8+ T lymphocytes increased. We showed that nsPEFs led to a significant decrease in immune suppressive cells, including myeloid derived suppressor cells, T regulatory cells, and tumor-associated macrophages. In addition, the levels of TNF-α and IL-1β increased (P &lt; 0.05), while the level of IL-6 was decreased (P &lt; 0.05). NsPEFs alleviated the immunosuppressive components in pancreatic cancer stroma, including hyaluronic acid and fibroblast activation protein-α. Our data demonstrate that tumor growth can be effectively inhibited by nsPEFs in vivo. NsPEFs significantly altered the infiltration of immune cells and triggered immune response.

scholarly journals Microbial Decontamination by Pulsed Electric Fields (PEF) in Winemaking

2021 ◽  
Author(s):  
Carlota Delso ◽  
Alejandro Berzosa ◽  
Jorge Sanz ◽  
Ignacio Álvarez ◽  
Javier Raso
Keyword(s):  
Cell Viability ◽  
Electric Fields ◽  
High Intensity ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Low Energy ◽  
Energy Requirements ◽  
Short Pulses ◽  
Thermal Technique ◽  
Very Short Pulses

Pulsed Electric Fields (PEF) is a non-thermal technique that causes electroporation of cell membranes by applying very short pulses (μs) of a high-intensity electric field (kV/cm). Irreversible electroporation leads to the formation of permanent conductive channels in the cytoplasmic membrane of cells, resulting in the loss of cell viability. This effect is achieved with low energy requirements and minimal deterioration of quality. This chapter reviews the studies hitherto conducted to evaluate the potential of PEF as a technology for microbial decontamination in the winemaking process for reducing or replacing the use of SO2, for guaranteeing reproducible fermentations or for wine stabilization.

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