Feasibility of Employing Model-Based Optimization of Pulse Amplitude and Electrode Distance for Effective Tumor Electropermeabilization

Abstract

Abstract-In electrochemotherapy (ECT) electropermeabilization, parameters (pulse amplitude, electrode setup) need to be customized in order to expose the whole tumor to electric field intensities above permeabilizing threshold to achieve effective ECT. In this paper, we present a model-based optimization approach toward determination of optimal electropermeabilization parameters for effective ECT. The optimization is carried out by minimizing the difference between the permeabilization threshold and electric field intensities computed by finite element model in selected points of tumor. We examined the feasibility of model-based optimization of electropermeabilization parameters on a model geometry generated from computer tomography images, representing brain tissue with tumor. Continuous parameter subject to optimization was pulse amplitude. The distance between electrode pairs was optimized as a discrete parameter. Optimization also considered the pulse generator constraints on voltage and current. During optimization the two constraints were reached preventing the exposure of the entire volume of the tumor to electric field intensities above permeabilizing threshold. However, despite the fact that with the particular needle array holder and pulse generator the entire volume of the tumor was not permeabilized, the maximal extent of permeabilization for the particular case (electrodes, tissue) was determined with the proposed approach.Model-based optimization approach could also be used for electro-gene transfer, where electric field intensities should be distributed between permeabilizing threshold and irreversible threshold-the latter causing tissue necrosis. This can be obtained by adding constraints on maximum electric field intensity in optimization procedure.

Optimization of electrode position and electric pulse amplitude in electrochemotherapy

“…14,15,19,[24][25][26] We examined the adequacy for ECT of needle electrode array geometries by calculating the values of total electric current through the model (must be as low as possible to avoid nerve stimulation 27 and not exceed the capacities of the electric pulse generator 28 ) and volumes of reversibly and irreversibly electroporated tumor tissue and healthy tissue. Three-needle electrode pairs were best for the spherical and the realistic tumor geometry; they required the lowest total electric current and caused only a small volume of healthy tissue to be irreversibly electroporated (healthy tissue damage) (Figure 4).…”

“…14 Our present study took optimization one step further by optimizing for four different electrode geometries and for two additional parameters, i.e. distance between electrodes in a row and depth of electrode insertion, which lead to perhaps the most important practical result.…”

“…Since the electric field is one of the most important factors in ECT efficiency, modeling the electric field distribution is not only necessary for understanding the treatment, but is also a crucial step towards treatment planning. [12][13][14] This study presents the first use of an ECT optimization algorithm on several different tumor geometries.…”

Numerical modeling in electroporation-based biomedical applications

“…As a complementary work to in vivo experimenting, we can use analytical and numerical models to represent, as realistically as possible, real biological phenomena of, in our case, electroporation. [14][15][16][17][18] In this way we can better understand some of the processes involved and analyze and explain some experimental results. We can evaluate different electrical parameters in advance, such as pulse amplitude, duration, number of pulses.…”

Biomedical effects induced by the monocycle pulse

“…So, it is very critical to study the window effect of PEF on biological cells in order to precisely determine the PEF parameters and get effective therapeutic effects. The mechanism and threshold conditions of IEM have been extensively researched in the past few years (Lsambent, 1998;Chalise et al, 2006;Hu et al, 2009;Gurtovenko and Vattulainen, 2009;Pucihar et al, 2009;Sel et al, 2009;Hu et al, 2005;Joshi et al, 2002;Daniels and Rubinsky, 2009). Among the models and methods, an equivalent circuit method based on the multilayer dielectric model is popular to analyze the transmenbrane potential, the electric intensity threshold and the window effect.…”