Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis

2010 ◽  
Vol 132 (3) ◽  
Author(s):  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Finite Element ◽  
Electric Field ◽  
Electric Fields ◽  
Joule Heating ◽  
Arterial Wall ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Phospholipid Bilayer ◽  
Tissue Ablation ◽  
Nonthermal Irreversible Electroporation

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.

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.

The Effect of Small Intestine Heterogeneity on Irreversible Electroporation Treatment Planning

2014 ◽  
Vol 136 (9) ◽  
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.

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 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 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 Comparative Modeling of Transcranial Magnetic and Electric Stimulation in Mouse, Monkey, and Human

2018 ◽  
Author(s):  
Ivan Alekseichuk ◽  
Kathleen Mantell ◽  
Sina Shirinpour ◽  
Alexander Opitz
Keyword(s):  
Finite Element ◽  
Field Strength ◽  
Electric Field ◽  
Electric Field Strength ◽  
Electric Fields ◽  
Mouse Brain ◽  
Electric Stimulation ◽  
Human Model ◽  
Brain Anatomy ◽  
List Type

ABSTRACTTranscranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin monkey, and human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans.HIGHLIGHTSTranslational research in brain stimulation should account for large differences in induced electric fields in different organismsWe simulate TMS and TES electric fields using anatomically realistic finite element models in three species: mouse, monkey, and humanTMS with a 70 mm figure-8 coil creates an approximately 2-times weaker electric field in a mouse brain than in monkey and human brains, where electric field strength is comparableTwo-electrode TES creates an approximately 100-times stronger electric field in a mouse brain and 3.5-times stronger electric field in a monkey brain than in a human brain

Phase Change Electrodes for Reducing Joule Heating During Irreversible Electroporation

2012 ◽  
Author(s):  
Christopher B. Arena ◽  
Roop L. Mahajan ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Electric Fields ◽  
Electric Field Distribution ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Thermal Processes ◽  
Ablation Volume ◽  
Extracellular Matrix Components ◽  
Membrane Defects ◽  
Viable Treatment

Irreversible electroporation (IRE) is a non-thermal tissue ablation modality that is gaining momentum as a viable treatment option for tumors and other non-cancerous pathologies [1]. The protocol consists of delivering a series of short (∼ 100 μs) and intense (∼ 1000 V/cm) pulsed electric fields through electrodes inserted directly into or around a targeted tissue. The pulses induce a rapid buildup of charge across the plasma membrane of cells comprising the tissue that results in the creation of permanent membrane defects, ultimately leading to cell death. Because the extent of cell death relies predominately on the extent of charge buildup and not thermal processes, extracellular matrix components are spared, including major nerve and blood vessel architecture. Additionally, the ablation volume is predictable based on the electric field distribution and visible in real-time via MRI, CT, and ultrasound.

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