Simulation of the influence of voltage level and pulse spacing on the efficiency, aggressiveness and uniformity of the electroporation process in tissues using meshless techniques

• Published in: International journal for numerical methods in biomedical engineering 2020-03, Vol.36 (3), p.e3304-n/a
• Main Authors: Vélez Salazar, Fabián M., Patiño Arcila, Iván D., Ruiz Villa, Carlos A.
• Format: Article
• Language: English
• Subjects: Algorithms; Cell membranes; Computer Simulation; Concentration gradient; Domains; Efficiency; Electric potential; Electric pulses; Electroporation; Electroporation - methods; electroporation aggressiveness; electroporation efficiency; electroporation uniformity; extra‐intracellular drug transport; Finite volume method; Internalization; Intracellular; Mass transport; Membrane permeability; Meshless methods; meshless techniques; Oscillations; Singular value decomposition; Tissues; Voltage
• ISSN: 2040-7939; 2040-7947
• DOI: 10.1002/cnm.3304

Electroporation is a widely used method consisting of application of high‐voltage, short‐duration electric pulses to increase cell membrane permeability, allowing cellular internalization of medications. In this work, the influence of two primary parameters, voltage level (V) and pulse spacing (N), on electroporation efficiency, uniformity and aggressiveness, as quantified by the total mass transport to viable cells, intracellular concentration gradients and an aggressiveness factor introduced here, is studied by means of numerical simulations of drug transport in electroporated tissues. The global method of approximate particular solutions (Global MAPS) is used to solve the governing equations, together with domain scaling, singular value decomposition and smoothing algorithms, to address the ill‐conditioning of the final system and suppress small scale oscillations. The accuracy of Global MAPS is evaluated by comparing the initial extracellular concentration, Ce, and final intracellular concentration, Ci, with previous finite volume method results, obtaining similar behavior of Ce and Ci along the tissue domain, with some differences for Ci in high‐gradient zones. According to the Global MAPS results, the influence of V and N on Ci is only significant over a certain range, within which the largest drug transport to viable cells occurs. In general, both electroporation efficiency and aggressiveness change in nonuniform manner with V and decrease with N, whereas the electroporation uniformity decreases as V increases and N decreases. The contour plots obtained here can be considered useful tools to compare electroporation‐based treatments in terms of their efficiency, aggressiveness and uniformity, assisting in the selection of a suitable treatment plan for cancer. Implementation of Global MAPS to simulate drug transport in electroporated tissues, avoiding the use of domain mesh and demanding a smaller number of spatial points compared to meshed techniques. Prediction of the extracellular and intracellular concentrations of drug in tissues considering three stages: prepulse diffusion, pulse and postinitial pulse diffusion. Parametric study of the influence of the voltage level and pulse spacing on electroporation efficiency, uniformity and aggressiveness, obtaining useful contour plots to compare electroporation‐based treatments among them and select the optimum ones.