Experimental Characterization and Numerical Modeling of Tissue Electrical Conductivity during Pulsed Electric Fields for Irreversible Electroporation Treatment Planning

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.

Download Full-text

Optimization and Numerical Modeling in Irreversible Electroporation Treatment Planning

Irreversible Electroporation - Series in Biomedical Engineering ◽

10.1007/978-3-642-05420-4_8 ◽

2010 ◽

pp. 203-222 ◽

Cited By ~ 7

Author(s):

Anže Županič ◽

Damijan Miklavčič

Keyword(s):

Numerical Modeling ◽

Treatment Planning ◽

Irreversible Electroporation

Download Full-text

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.348 ◽

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.

Download Full-text

Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

Technology in Cancer Research & Treatment ◽

10.1177/153303460900800406 ◽

2009 ◽

Vol 8 (4) ◽

pp. 289-306 ◽

Cited By ~ 38

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.

Download Full-text

The Effect of Small Intestine Heterogeneity on Irreversible Electroporation Treatment Planning

Journal of Biomechanical Engineering ◽

10.1115/1.4027815 ◽

2014 ◽

Vol 136 (9) ◽

Cited By ~ 3

Author(s):

Mary Phillips

Keyword(s):

Finite Element ◽

Small Intestine ◽

Electric Field ◽

Treatment Planning ◽

Electric Fields ◽

Irreversible Electroporation ◽

Experimental Results ◽

Heterogeneous Structure ◽

Element Analysis

Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning.

Download Full-text

Microbial Decontamination by Pulsed Electric Fields (PEF) in Winemaking

10.5772/intechopen.101112 ◽

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.

Download Full-text

Irreversible Electroporation as an Alternative to Wound Debridement Surgery

Surgical Technology Online ◽

10.52198/21.sti.39.wh1452 ◽

2021 ◽

Vol 39 ◽

Author(s):

Bodhisatwa Das ◽

◽

Francois Berthiaume ◽

Keyword(s):

Electric Fields ◽

Chronic Wounds ◽

Wound Care ◽

Bacterial Load ◽

Healing Process ◽

Irreversible Electroporation ◽

Pulsed Electric Fields ◽

Wound Debridement ◽

Atrial Ablation ◽

Novel Approach

Debridement is a standard part of wound care that is used on both acute and chronic wounds. Current methods of wound debridement include: autolytic based on the natural immune response, surgical, enzymatic based on application of exogenous proteases, mechanical using water jets and ultrasound, and biological using live organisms such as maggots. The choice of individual methods involves a trade-off between speed of treatment, selectivity, and pain. Irreversible electroporation via the application of pulsed electric fields has been used as a novel approach for deep tissue ablation, sometimes in conjunction with chemotherapy, as in the case of tumors, and also in cases where high precision is needed in otherwise very fragile tissues, such as for treating diabetic neuropathy and in epicardial atrial ablation. This method could be readily extended to wound care as it is both rapid and relatively painless, and it is also effective at decreasing bacterial load and clearing biofilms. Furthermore, the process primarily targets cells leaving the extracellular matrix relatively intact, thus providing a suitable natural scaffold for host cellular invasion and regrowth. A unique aspect of the use of pulsed electric fields is that around the region where ablation is perfomed, electric fields of lower energy are dissipated into the healthy tissue. There is a range of electric fields that are known to stimulate cellular functions, in particular migration and proliferation, and that may contribute to the healing process after electroporation. While irreversible electroporation is a potentially useful alternative to other debridement methods, future clinical application awaits technological advances in electrode design that will enable precise delivery of the therapy in wounds of various sizes and depths.

Download Full-text