The Experts below are selected from a list of 24873 Experts worldwide ranked by ideXlab platform
Boris Rubinsky - One of the best experts on this subject based on the ideXlab platform.
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Toward a clinical real time Tissue Ablation technology: combining electroporation and electrolysis (E2).
PeerJ, 2020Co-Authors: Enric Guenther, Paul Mikus, Michael K. Stehling, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Matteo Macchioro, Irinel Popescu, Boris RubinskyAbstract:Author(s): Guenther, Enric; Klein, Nina; Mikus, Paul; Botea, Florin; Pautov, Mihail; Lugnani, Franco; Macchioro, Matteo; Popescu, Irinel; Stehling, Michael; Rubinsky, Boris | Abstract: Background: Percutaneous image-guided Tissue Ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation-E2-affords Tissue Ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods: A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as Tissue behavior to enable real time Tissue Ablation of clinically relevant volumes. Results: Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of Tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the Ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: 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.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract: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.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible electroporation is a new Tissue Ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive Tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize Tissue Ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that Tissue Ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and Tissue Ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target Tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in Tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation Ablation protocols.
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Tissue Ablation by a Synergistic Combination of Electroporation and Electrolysis Delivered by a Single Pulse.
Annals of Biomedical Engineering, 2016Co-Authors: Mary Phillips, Narayan Raju, Hanush Krishnan, Boris RubinskyAbstract:A synergistic combination of electroporation and electrolysis (SEE) has been found with distinct advantages over Tissue Ablation by electrolysis or electroporation alone. Minimally invasive Tissue Ablation by electrolysis uses a low magnitude direct electric current to produce a lesion due to the creation of chemical products that result in cell death. Electroporation creates permeabilizations in the cell membrane which may lead to loss of cell homeostasis and cell death. When these two modes of Tissue Ablation are combined, a more effective method of cell death is achieved, likely due to the ability of electrolytic products to access the cell interior through the permeabilized cell membrane. Here, a new method of achieving SEE Tissue Ablation is obtained through the application of a single exponential decay pulse. This parametric study explores the mechanisms of damage as a function of the initial electric field and amount of delivered charge. It is seen that treatment parameters can dictate the mode of Tissue Ablation, either by SEE or by irreversible electroporation alone.
G S Gazelle - One of the best experts on this subject based on the ideXlab platform.
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saline enhanced radio frequency Tissue Ablation in the treatment of liver metastases
Radiology, 1997Co-Authors: Tito Livraghi, S N Goldberg, F Monti, A Bizzini, S Lazzaroni, Franca Meloni, S Pellicano, Luigi Solbiati, G S GazelleAbstract:PURPOSE: To assess the effect of intraparenchymal saline injection on the results of radio-frequency (RF) Tissue Ablation. MATERIALS AND METHODS: Ex vivo and in vivo animal RF Ablation was performed with and without intraparenchymal saline injection. Initially, saline was injected as a bolus (1-20 mL) before RF application. For subsequent in vivo studies, saline was injected as a bolus before RF application or continuously (1 mL/min) during RF application. Finally, 14 patients with liver metastases and one patient with primary cholangiocarcinoma were treated with the continuous infusion technique. A single RF electrode (tip exposure, 1-3 cm) was used with various Ablation parameters. RESULTS: With pretreatment bolus injection of saline, lesions measured 1.4 cm +/- 0.1, 1.6 cm +/- 0.2, and 1.2 cm +/- 0.1 in ex vivo liver, in vivo animal muscle, and in vivo animal liver, respectively. Without saline enhancement, lesion sizes were 1.0 +/- 0.2, 1.2 +/- 0.2, and 0.8 +/- 0.1 cm, respectively. With continuous sa...
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Saline-enhanced radio-frequency Tissue Ablation in the treatment of liver metastases.
Radiology, 1997Co-Authors: Tito Livraghi, S N Goldberg, F Monti, A Bizzini, S Lazzaroni, Franca Meloni, S Pellicano, Luigi Solbiati, G S GazelleAbstract:PURPOSE: To assess the effect of intraparenchymal saline injection on the results of radio-frequency (RF) Tissue Ablation. MATERIALS AND METHODS: Ex vivo and in vivo animal RF Ablation was performed with and without intraparenchymal saline injection. Initially, saline was injected as a bolus (1-20 mL) before RF application. For subsequent in vivo studies, saline was injected as a bolus before RF application or continuously (1 mL/min) during RF application. Finally, 14 patients with liver metastases and one patient with primary cholangiocarcinoma were treated with the continuous infusion technique. A single RF electrode (tip exposure, 1-3 cm) was used with various Ablation parameters. RESULTS: With pretreatment bolus injection of saline, lesions measured 1.4 cm +/- 0.1, 1.6 cm +/- 0.2, and 1.2 cm +/- 0.1 in ex vivo liver, in vivo animal muscle, and in vivo animal liver, respectively. Without saline enhancement, lesion sizes were 1.0 +/- 0.2, 1.2 +/- 0.2, and 0.8 +/- 0.1 cm, respectively. With continuous sa...
Nina Klein - One of the best experts on this subject based on the ideXlab platform.
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Toward a clinical real time Tissue Ablation technology: combining electroporation and electrolysis (E2).
PeerJ, 2020Co-Authors: Enric Guenther, Paul Mikus, Michael K. Stehling, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Matteo Macchioro, Irinel Popescu, Boris RubinskyAbstract:Author(s): Guenther, Enric; Klein, Nina; Mikus, Paul; Botea, Florin; Pautov, Mihail; Lugnani, Franco; Macchioro, Matteo; Popescu, Irinel; Stehling, Michael; Rubinsky, Boris | Abstract: Background: Percutaneous image-guided Tissue Ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation-E2-affords Tissue Ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods: A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as Tissue behavior to enable real time Tissue Ablation of clinically relevant volumes. Results: Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of Tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the Ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: 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.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract: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.
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Synergistic combination of electrolysis and electroporation for Tissue Ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based Tissue Ablation technologies. This paper reports results from the first large animal study of a new non-thermal Tissue Ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed Ablation.
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Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform
Journal of Translational Medicine and Research, 2016Co-Authors: Boris Rubinsky, Paul Mikus, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Enric Gunther, Vlad Herlea, Catalin Pecheanu, Michael K. StehlingAbstract:A new minimally invasive Tissue Ablation technique, that combines the biophysical processes of electroporation and electrolysis, is introduced. The technology employs electrode needles inserted in the target Tissue to deliver an Electrolytic Electroporation Waveform (EEW) in the form of an exponential decay voltage, several tens of microsecond long. A case study in a large animal model demonstrates that clinically significant size lesions can be achieved with a single, milliseconds long EEW. Ablation with EEW has major advantages over the comparable Tissue Ablation techniques of electrolysis, reversible electroporation and irreversible electroporation. EEW is orders of magnitude faster than conventional electrolytic Ablation. EEW does not require the use of muscle relaxant as irreversible electroporation and EEW does not require injection of drugs as reversible electroporation. This new technology is simple to use and may become an important addition to the minimally invasive surgery armamentarium.
Michael K. Stehling - One of the best experts on this subject based on the ideXlab platform.
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Toward a clinical real time Tissue Ablation technology: combining electroporation and electrolysis (E2).
PeerJ, 2020Co-Authors: Enric Guenther, Paul Mikus, Michael K. Stehling, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Matteo Macchioro, Irinel Popescu, Boris RubinskyAbstract:Author(s): Guenther, Enric; Klein, Nina; Mikus, Paul; Botea, Florin; Pautov, Mihail; Lugnani, Franco; Macchioro, Matteo; Popescu, Irinel; Stehling, Michael; Rubinsky, Boris | Abstract: Background: Percutaneous image-guided Tissue Ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation-E2-affords Tissue Ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods: A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as Tissue behavior to enable real time Tissue Ablation of clinically relevant volumes. Results: Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of Tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the Ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: 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.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract: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.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible electroporation is a new Tissue Ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive Tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize Tissue Ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that Tissue Ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and Tissue Ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target Tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in Tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation Ablation protocols.
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Synergistic combination of electrolysis and electroporation for Tissue Ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based Tissue Ablation technologies. This paper reports results from the first large animal study of a new non-thermal Tissue Ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed Ablation.
Paul Mikus - One of the best experts on this subject based on the ideXlab platform.
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Toward a clinical real time Tissue Ablation technology: combining electroporation and electrolysis (E2).
PeerJ, 2020Co-Authors: Enric Guenther, Paul Mikus, Michael K. Stehling, Nina Klein, Florin Botea, Mihail Pautov, Franco Lugnani, Matteo Macchioro, Irinel Popescu, Boris RubinskyAbstract:Author(s): Guenther, Enric; Klein, Nina; Mikus, Paul; Botea, Florin; Pautov, Mihail; Lugnani, Franco; Macchioro, Matteo; Popescu, Irinel; Stehling, Michael; Rubinsky, Boris | Abstract: Background: Percutaneous image-guided Tissue Ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation-E2-affords Tissue Ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods: A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as Tissue behavior to enable real time Tissue Ablation of clinically relevant volumes. Results: Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of Tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the Ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
PeerJ, 2017Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract:Author(s): Klein, Nina; Guenther, Enric; Mikus, Paul; Stehling, Michael; Rubinsky, Boris | Abstract: 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.
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Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for Tissue Ablation
2016Co-Authors: Nina Klein, Paul Mikus, Enric Guenther, Michael K. Stehling, Boris RubinskyAbstract: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.
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Electrolytic Effects During Tissue Ablation by Electroporation
Technology in Cancer Research & Treatment, 2016Co-Authors: Liel Rubinsky, Enric Guenther, Paul Mikus, Michael K. Stehling, Boris RubinskyAbstract:Nonthermal irreversible electroporation is a new Tissue Ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive Tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize Tissue Ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that Tissue Ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and Tissue Ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target Tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in Tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation Ablation protocols.
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Synergistic combination of electrolysis and electroporation for Tissue Ablation
PLOS ONE, 2016Co-Authors: Michael K. Stehling, Liel Rubinsky, Enric Guenther, Paul Mikus, Nina Klein, Boris RubinskyAbstract:Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based Tissue Ablation technologies. This paper reports results from the first large animal study of a new non-thermal Tissue Ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed Ablation.
