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.

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.

Irreversible Electroporation Using the Vasculature of an Organ as Fluid Electrodes

2012 ◽  
Author(s):  
Michael B. Sano ◽  
Christopher B. Arena ◽  
Paulo A. Garcia ◽  
Rafael V. Davalos
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Electric Fields ◽  
Bile Ducts ◽  
Electric Field Intensity ◽  
Irreversible Electroporation ◽  
Intensity Threshold ◽  
Nerve Conduits ◽  
Biophysical Process ◽  
And Function

Electroporation is a non-linear biophysical process in which the application of pulsed electric fields leads to an increase in permeability of cells, presumably through the creation of nanoscale pores in the lipid bilayer [1]. At low pulsing energy, this permeability is reversible and cellular health and function is maintained. Once a critical electric field intensity threshold is surpassed the cell membrane is unable to recover and cell death is induced in a precise and controllable manner with sub-millimeter resolution [2]. This process is referred to as irreversible electroporation (IRE). IRE does not rely on thermal mechanisms and preserves the structure of the underlying extracellular matrix (ECM) as well as nerve conduits and bile ducts [3].

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 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.

Irreversible Electroporation in Medicine

2007 ◽  
Vol 6 (4) ◽  
pp. 255-259 ◽  
Author(s):  
Boris Rubinsky
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Historical Perspective ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Cell Homeostasis ◽  
Electrical Fields ◽  
A Cell

This is a brief introduction to the emerging field of irreversible electroporation in medicine. Certain electrical fields when applied across a cell can have as a sole effect the permeabilization of the cell membrane, presumable through the formation of nanoscale defects in the cell membrane. Sometimes this process leads to cell death, primarily when the electrical fields cause permanent permeabilization of the membrane and the consequent loss of cell homeostasis, in a process known as irreversible electroporation. This is an unusual mode of cell death that is not understood yet. While the phenomenon of irreversible electroporation may have been known for centuries it has become only recently rigorously considered in medicine for various applications of tissue ablation. A brief historical perspective of irreversible electroporation is presented and recent studies in the field are discussed.

scholarly journals Evaluation of electroporated area using 2,3,5-triphenyltetrazolium chloride in a potato model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung Jeong ◽  
Hongbae Kim ◽  
Junhyung Park ◽  
Ki Woo Kim ◽  
Sung Bo Sim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Target Tissue ◽  
Triphenyltetrazolium Chloride ◽  
Tissue Model ◽  
Electric Pulses ◽  
Reversible Electroporation ◽  
Over Time

AbstractIrreversible electroporation (IRE) is a tissue ablation method, uses short high electric pulses and results in cell death in target tissue by irreversibly permeabilizing the cell membrane. Potato is commonly used as a tissue model for electroporation experiments. The blackened area that forms 12 h after electric pulsing is regarded as an IRE-ablated area caused by melanin accumulation. Here, the 2,3,5-triphenyltetrazolium chloride (TTC) was used as a dye to assess the IRE-ablated area 3 h after potato model ablation. Comparison between the blackened area and TTC-unstained white area in various voltage conditions showed that TTC staining well delineated the IRE-ablated area. Moreover, whether the ablated area was consistent over time and at different staining times was investigated. In addition, the presumed reversible electroporation (RE) area was formed surrounding the IRE-ablated area. Overall, TTC staining can provide a more rapid and accurate electroporated area evaluation.

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

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3190 ◽  
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.

An Experimental and Numerical Investigation of Phase Change Electrodes for Therapeutic Irreversible Electroporation

2013 ◽  
Vol 135 (11) ◽  
Author(s):  
Christopher B. Arena ◽  
Roop L. Mahajan ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Phase Change ◽  
Electric Fields ◽  
Heat Dissipation ◽  
Transfer Problem ◽  
New Technology ◽  
Irreversible Electroporation ◽  
Surrounding Tissue ◽  
High Dose ◽  
Target Tissue ◽  
Ablation Volume

Irreversible electroporation (IRE) is a new technology for ablating aberrant tissue that utilizes pulsed electric fields (PEFs) to kill cells by destabilizing their plasma membrane. When treatments are planned correctly, the pulse parameters and location of the electrodes for delivering the pulses are selected to permit destruction of the target tissue without causing thermal damage to the surrounding structures. This allows for the treatment of surgically inoperable masses that are located near major blood vessels and nerves. In select cases of high-dose IRE, where a large ablation volume is desired without increasing the number of electrode insertions, it can become challenging to design a pulse protocol that is inherently nonthermal. To solve this problem we have developed a new electrosurgical device that requires no external equipment or protocol modifications. The design incorporates a phase change material (PCM) into the electrode core that melts during treatment and absorbs heat out of the surrounding tissue. Here, this idea is reduced to practice by testing hollow electrodes filled with gallium on tissue phantoms and monitoring temperature in real time. Additionally, the experimental data generated are used to validate a numerical model of the heat transfer problem, which is then applied to investigate the cooling performance of other classes of PCMs. The results indicate that metallic PCMs, such as gallium, are better suited than organics or salt hydrates for thermal management, because their comparatively higher thermal conductivity aids in heat dissipation. However, the melting point of the metallic PCM must be properly adjusted to ensure that the phase transition is not completed before the end of treatment. When translated clinically, phase change electrodes have the potential to continue to allow IRE to be performed safely near critical structures, even in high-dose cases.

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 High Frequency Electroporation for Cancer Therapy

2011 ◽  
Author(s):  
Christopher B. Arena ◽  
Michael B. Sano ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
High Frequency ◽  
Thermal Injury ◽  
Transmembrane Potential ◽  
Irreversible Electroporation ◽  
Chemotherapeutic Drugs ◽  
Reversible Electroporation ◽  
Biophysical Mechanism ◽  
Membrane Defects

Electroporation is a non-linear biophysical mechanism in which the application of an external pulsed electric field leads to an increase in the permeability of cellular membranes. The extent of electroporation is attributed to the induced buildup of charge across the membrane, and consequently, transmembrane potential (TMP). Increasing the TMP has been described to produce various permeabilizing effects, wherein the formation of hydrophilic, aqueous pores becomes energetically favorable [1]. If the pulse parameters are tuned such that the membrane defects are only temporary, and the cell remains viable, the process is termed reversible electroporation. As a cancer therapy, reversible electroporation has been employed to increase the cellular uptake of chemotherapeutic drugs. Irreversible electroporation (IRE) results when membrane defects are permanent, leading to cell death. Recently, IRE has been recognized as an independent means to destroy tumors without the use of adjuvant drugs and prior to the onset of thermal injury [2].

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