Dynamic finite-element model for efficient modelling of electric currents in electroporated tissue

In silico experiments (numerical simulations) are a valuable tool for non-invasive research of the influences of tissue properties, electrode placement and electric pulse delivery scenarios in the process of electroporation. The work described in this article was aimed at introducing time dependent effects into a finite element model developed specifically for electroporation. Reference measurements were made ex vivo on beef liver samples and experimental data were used both as an initial condition for simulation (applied pulse voltage) and as a reference value for numerical model calibration (measured pulse current). The developed numerical model is able to predict the time evolution of an electric pulse current within a 5% error over a broad range of applied pulse voltages, pulse durations and pulse repetition frequencies. Given the good agreement of the current flowing between the electrodes, we are confident that the results of our numerical model can be used both for detailed in silico research of electroporation mechanisms (giving researchers insight into time domain effects) and better treatment planning algorithms, which predict the outcome of treatment based on both spatial and temporal distributions of applied electric pulses.

[1]  Damijan Miklavčič,et al.  Electroporation-based applications in biotechnology. , 2015, Trends in biotechnology.

[2]  T. L. Ellis,et al.  Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine Patient , 2011, Technology in cancer research & treatment.

[3]  Rafael V. Davalos,et al.  Experimental Characterization and Numerical Modeling of Tissue Electrical Conductivity during Pulsed Electric Fields for Irreversible Electroporation Treatment Planning , 2012, IEEE Transactions on Biomedical Engineering.

[4]  D. Miklavčič,et al.  Cell membrane electroporation- Part 1: The phenomenon , 2012, IEEE Electrical Insulation Magazine.

[5]  Damijan Miklavcic,et al.  Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy , 2010, Biomedical engineering online.

[6]  Damijan Miklavčič,et al.  In situ monitoring of electric field distribution in mouse tumor during electroporation. , 2015, Radiology.

[7]  Damijan Miklavcic,et al.  Modeling of electric field distribution in tissues during electroporation , 2013, Biomedical engineering online.

[8]  Jon F Edd,et al.  Mathematical Modeling of Irreversible Electroporation for Treatment Planning , 2007, Technology in cancer research & treatment.

[9]  Francis A. Duck,et al.  Thermal Properties of Tissue , 1990 .

[10]  D Miklavcic,et al.  Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. , 1995, Cancer research.

[11]  John C. Bischof,et al.  A Review of Basic to Clinical Studies of Irreversible Electroporation Therapy , 2015, IEEE Transactions on Biomedical Engineering.

[12]  Damijan Miklavcic,et al.  Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation , 2012, Physics in medicine and biology.

[13]  Boris Rubinsky,et al.  A statistical model for multidimensional irreversible electroporation cell death in tissue , 2010, Biomedical engineering online.

[14]  Hadi Shafiee,et al.  A preliminary study to delineate irreversible electroporation from thermal damage using the arrhenius equation. , 2009, Journal of biomechanical engineering.

[15]  Damijan Miklavcic,et al.  The influence of skeletal muscle anisotropy on electroporation: in vivo study and numerical modeling , 2010, Medical & Biological Engineering & Computing.

[16]  J. Yi,et al.  Changes of apoptosis in tumor tissues with time after irreversible electroporation. , 2013, Biochemical and biophysical research communications.

[17]  Karin Nielsen,et al.  Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. , 2014, Journal of vascular and interventional radiology : JVIR.

[18]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.

[19]  Francis A. Duck,et al.  Physical properties of tissue : a comprehensive reference book , 1990 .

[20]  Thomas L Ellis,et al.  A Parametric Study Delineating Irreversible Electroporation from Thermal Damage Based on a Minimally Invasive Intracranial Procedure , 2011, Biomedical engineering online.

[21]  Damijan Miklavčič,et al.  Electroporation-based technologies for medicine: principles, applications, and challenges. , 2014, Annual review of biomedical engineering.

[22]  Damijan Miklavčič,et al.  Electrochemotherapy: from the drawing board into medical practice , 2014, BioMedical Engineering OnLine.

[23]  L. Mir,et al.  Sequential Finite Element Model of Tissue Electropermeabilisation , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[24]  Boris Rubinsky,et al.  Electric Field Redistribution due to Conductivity Changes during Tissue Electroporation: Experiments with a Simple Vegetal Model , 2009 .

[25]  Damijan Miklavcic,et al.  A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue , 2014, PloS one.

[26]  B. Rubinsky,et al.  Tissue Ablation with Irreversible Electroporation , 2005, Annals of Biomedical Engineering.

[27]  D Miklavcic,et al.  A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. , 2000, Biochimica et biophysica acta.

[28]  Micaela Liberti,et al.  Modeling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case , 2015, Biomedical engineering online.

[29]  Christophe Geuzaine,et al.  Gmsh: A 3‐D finite element mesh generator with built‐in pre‐ and post‐processing facilities , 2009 .

[30]  Damijan Miklavcic,et al.  Robustness of Treatment Planning for Electrochemotherapy of Deep-Seated Tumors , 2010, The Journal of Membrane Biology.

[31]  L. Mir,et al.  Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. , 1991, European journal of cancer.

[32]  Tomaz Slivnik,et al.  Sequential finite element model of tissue electropermeabilization , 2005, IEEE Transactions on Biomedical Engineering.

[33]  Rafael V. Davalos,et al.  In Vivo Irreversible Electroporation Kidney Ablation: Experimentally Correlated Numerical Models , 2015, IEEE Transactions on Biomedical Engineering.

[34]  D. Miklavčič,et al.  Assessing how electroporation affects the effective conductivity tensor of biological tissues , 2012 .

[35]  Damijan Miklavčič,et al.  Electroporation in Food Processing and Biorefinery , 2014, The Journal of Membrane Biology.

[36]  Damijan Miklavcic,et al.  Ex Vivo and In Silico Feasibility Study of Monitoring Electric Field Distribution in Tissue during Electroporation Based Treatments , 2012, PloS one.

[37]  P Raskmark,et al.  In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. , 1999, Biochimica et biophysica acta.

[38]  L. Mir,et al.  Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. , 1988, Biochemical pharmacology.