Abstract

Electroporation (EP), the increase of cell membrane permeability due to the application of electric pulses, is a universal phenomenon with a broad range of applications. In medicine, some of the foremost EP-based tumor treatments are electrochemotherapy (ECT), irreversible electroporation, and gene electrotransfer (GET). The electroporation phenomenon is explained as the formation of cell membrane pores when a transmembrane cell voltage reaches a threshold value. Predicting the outcome of an EP-based tumor treatment consists of finding the electric field distribution with an electric threshold value covering the tumor (electroporated tissue). Threshold and electroporated tissue are also a function of the number of pulses, constituting a complex phenomenon requiring mathematical modeling. We present OpenEP, an open-source specific purpose simulator for EP-based tumor treatments, modeling among other variables, threshold, and electroporated tissue variations in time. Distributed under a free/libre user license, OpenEP allows the customization of tissue type; electrode geometry and material; pulse type, intensity, length, and frequency. OpenEP facilitates the prediction of an optimal EP-based protocol, such as ECT or GET, defined as the critical pulse dosage yielding maximum electroporated tissue with minimal damage. OpenEP displays a highly efficient shared memory implementation by taking advantage of parallel resources; this permits a rapid prediction of optimal EP-based treatment efficiency by pulse number tuning.

Highlights

  • Electroporation (EP), the increase of cell membrane permeability due to the application of electric pulses, is a universal phenomenon with a broad range of applications

  • The electroporation phenomenon is explained as the formation of aqueous pores in the cell membrane when a transmembrane voltage induced by a given pulsing protocol reaches a threshold value

  • OpenEP simulator usage is illustrated with five typical EP treatments from the literature (GET, ECT, HFire and Irreversible Electroporation (IRE)), followed by an OpenEP simulator performance analysis

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Summary

Introduction

Electroporation (EP), the increase of cell membrane permeability due to the application of electric pulses, is a universal phenomenon with a broad range of applications. With the aim of understanding and optimizing EP-based treatments in terms of electrical variables, several parameters must be considered: pulse duration, frequency, number of pulses, applied voltage, number of electrodes, and their placement, among others In this context, mathematical and computational modeling became a powerful tool for studying and predicting the outcome of EP-based protocols. The electroporation phenomenon is explained as the formation of aqueous pores in the cell membrane when a transmembrane voltage induced by a given pulsing protocol reaches a threshold value. This is known as the standard EP model or phenomenological model. Another version of this model consists of measuring experimentally the electroporated area and choosing the threshold as the electric field isoline that matches the electroporated area

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