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Abstract
We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 µs at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%), in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.
Highlights
Invasive tissue ablation has become of central importance in the modern surgery armamentarium
The initial parameters tested were derived from electrical parameters of reversible electroporation and employed an electric field of 2000 V/cm and 800 ms total duration of the electric pulses (EP)
In the following set of tests the EP were delivered in two perpendicular directions for a more complete coverage of the tumor
Summary
Invasive tissue ablation has become of central importance in the modern surgery armamentarium. As an alternative to surgical resection, a number of minimally invasive methods have been developed to destroy specific areas of undesirable tissues. Most of these techniques are thermal using cold, e.g. cryosurgery [1,2,3] or heat, e.g. radiofrequency [4,5]. Irreversible electroporation, the ability of certain electrical pulses to permanently permeabilize the cell membrane, has been known for over three decades. For most of this period irreversible electroporation (IRE) was used primarily for ablation of microorganisms and cells in vitro and studied only as an upper limit of electrical parameters for reversible tissue electroporation applications. Our group has pursued the understanding of the electrical fields and processes that produce IRE with single cell micro-electroporation technology [10,11]
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