Modulating electrolytic tissue ablation with reversible electroporation pulses

Phillips, Mary; Raju, Narayan; Rubinsky, Liel; Rubinsky, Boris

doi:10.1142/s233954781550003x

Cited by 32 publications

(29 citation statements)

References 18 publications

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“…The study in this article and in Phillips et al 26,27 leads to new insight with regard to the design of optimal electroporationbased tissue ablation protocols. It is evident that electrolysis occurs in all electroporation protocols and must be considered.…”

Section: Discussionmentioning

confidence: 81%

“…Figure 5 is an attempt to summarize this understanding using a possible qualitative display of the different domains in which electrolysis and electroporation induce tissue ablation in a superposition effect, as a function of electric fields and delivery time. This figure is also relevant to the study in Phillips et al 26,27 and defines the domains in which the combination of electroporation products of electrolysis can be used for tissue ablation.…”

Section: Discussionmentioning

confidence: 96%

“…The center of the region braced by the electrodes is not contaminated by the electrolytic products. Figure 4 shows the extent of the pH front affected region during the tissue ablation study in the prostate shown in figure 1 of Phillips et al 27 We applied 1000 V across 2 stainless steel needles (NanoKnife, AngioDynamics, New York; gage 16) separated by 1.0 cm. Eight, 100-microsecond long pulses were applied at a frequency of 10 Hz.…”

Section: Methodsmentioning

confidence: 99%

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Electrolytic Effects During Tissue Ablation by Electroporation

Rubinsky

Guenther

Mikus

et al. 2016

Technol Cancer Res Treat

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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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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

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Electrolytic Effects During Tissue Ablation by Electroporation

Rubinsky

Guenther

Mikus

et al. 2016

Technol Cancer Res Treat

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“…Our hypothesis is that they are caused by electric breakdown across ionized electrolysis produced gases near the electrodes. The hypothesis is based on a number of recent studies, which demonstrate that electrolysis occurs near the electrodes during electroporation [16][17][18][19][20][21], especially in NTIRE where the current and the delivered charge are high and never accounted for [20]. To eliminate any harm to patients during this study we have developed a new experimental technique that combines clinical data with the use of a tissue phantom and measurements made with medical ultrasound, a microphone, MRI and optical recording.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Electrical breakdown in tissue electroporation

Guenther¹,

Klein²,

Mikus³

et al. 2015

Biochemical and Biophysical Research Communications

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Electroporation, the permeabilization of the cell membrane by brief, high electric fields, has become an important technology in medicine for diverse application ranging from gene transfection to tissue ablation. There is ample anecdotal evidence that the clinical application of electroporation is often associated with loud sounds and extremely high currents that exceed the devices design limit after which the devices cease to function. The goal of this paper is to elucidate and quantify the biophysical and biochemical basis for this phenomenon. Using an experimental design that includes clinical data, a tissue phantom, sound, optical, ultrasound and MRI measurements, we show that the phenomenon is caused by electrical breakdown across ionized electrolysis produced gases near the electrodes. The breakdown occurs primarily near the cathode. Electrical breakdown during electroporation is a biophysical phenomenon of substantial importance to the outcome of clinical applications. It was ignored, until now.

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“…Recently, we have developed a new minimally invasive tissue ablation technology that combines electrolysis with electroporation, delivered as an Electrolytic Electroporation Waveform (EEW) (9)(10)(11).…”

Section: Introduction Introductionmentioning

confidence: 99%

Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform

Rubinsky¹,

Günther²,

Botea³

et al. 2016

JTMR

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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.

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Modulating electrolytic tissue ablation with reversible electroporation pulses

Cited by 32 publications

References 18 publications

Electrolytic Effects During Tissue Ablation by Electroporation

Electrolytic Effects During Tissue Ablation by Electroporation

Electrical breakdown in tissue electroporation

Minimally Invasive, Non-Thermal Tissue Ablation with a Single Exponential Decay Electrolytic Electroporation Waveform

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