Irreversible electroporation (IRE) is a new tissue ablation technique in which micro to millisecond electrical pulses are delivered to undesirable tissue to produce cell necrosis through irreversible cell membrane permeabilization. IRE affects only the cell membrane and no other structure in the tissue. The goal of the study is to test our IRE tissue ablation methodology in the pig liver, provide first experience results on long term histopathology of IRE ablated tissue, and discuss the clinical implications of the findings. The study consists of: a) designing an IRE ablation protocol through a mathematical analysis of the electrical field during electroporation; b) using ultrasound to position the electroporation electrodes in the predetermined locations and subsequently to monitor the process; c) applying the predetermined electrotroporation pulses; d) performing histolopathology on the treated samples for up to two weeks after the procedure; and e) correlating the mathematical analysis, ultrasound data, and histology. We observed that electroporation affects tissue in a way that can be imaged in real time with ultrasound, which should facilitate real time control of electroporation during clinical applications. We observed cell ablation to the margin of the treated lesion with several cells thickness resolution. There appears to be complete ablation to the margin of blood vessels without compromising the functionality of the blood vessels, which suggests that IRE is a promising method for treatment of tumors near blood vessels (a significant challenge with current ablation methods). Consistent with the mechanism of action of IRE on the cell membrane only, we show that the structure of bile ducts, blood vessels, and connective tissues remains intact with IRE. We report extremely rapid resolution of lesions, within two weeks, which is consistent with retention of vasculature. We also document tentative evidence for an immunological response to the ablated tissue. Last, we show that mathematical predictions with the Laplace equation can be used in treatment planning.The IRE tissue ablation technique, as characterized in this report, may become an important new tool in the surgeon armamentarium.

Percutaneous prostate cryo-ablation has become an accepted treatment for primary prostate cancer. Thermal tissue ablation based on cold, however, does have some distinct limitations. These include, variable damage at the cryo lesions margin, injury to adjacent structures such as rectum, urethra and NVB (neurovascular bundle), and long procedure time due to the need for multiple freeze thaw cycles, that have limited the acceptance of this modality. Irreversible electroporation IRE, is a new non-thermal ablation modality that uses short pulses of DC electric current to create irreversible pore in the cell membrane, thus, causing cell death. This method theoretically should have significant advantages in ablating prostate tissue. Six males dogs had their prostates treated using IRE. Pulses were applied using a DC generator that delivered pulses in the microsecond range of duration, with a variable pulse interval and voltage range. IRE probes were placed percutaneously or trans-rectally using trans-rectal ultrasound guidance. In one of the dogs, the lesions were made purposely to include the rectum, urethra, and neurovascular bundle (NVB). Subjects were followed for 1 to 14 days before sacrifice. IRE lesions in the prostate had unique characteristics compared to thermal lesions. The margins of the IRE lesions was very distinct with a narrow zone of transition from normal to complete necrosis, there was complete destruction within the IRE lesion, and rapid resolution of the lesions with marked shrinkage within two weeks. Structures such as urethra, vessels, nerves, and rectum were unaffected by the IRE application. IRE lesions have characteristics that are distinctly different than thermal lesions. The differences could be very advantageous in a clinical setting, improving the results and acceptance of prostate ablation.

Irreversible electroporation represents a new nonthermal ablation modality. This study has produced values for prostate cancer treatment with irreversible electroporation.

We propose a new modality to perform atrial ablations, which holds the potential of providing very swift, precise, and complete transmurality with no local heating effects.

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.