This is a brief introduction to the emerging field of irreversible electroporation in medicine. Certain electrical fields when applied across a cell can have as a sole effect the permeabilization of the cell membrane, presumable through the formation of nanoscale defects in the cell membrane. Sometimes this process leads to cell death, primarily when the electrical fields cause permanent permeabilization of the membrane and the consequent loss of cell homeostasis, in a process known as irreversible electroporation. This is an unusual mode of cell death that is not understood yet. While the phenomenon of irreversible electroporation may have been known for centuries it has become only recently rigorously considered in medicine for various applications of tissue ablation. A brief historical perspective of irreversible electroporation is presented and recent studies in the field are discussed. This is an brief introduction to the emerging field of irreversible electroporation in medicine. Certain electrical fields when applied across a cell can have as a sole effect the permeabilization of the cell membrane, presumable through the formation of nanoscale defects in the cell membrane. Sometimes this process leads to cell death, primarily when the electrical fields cause permanent permeabilization of the membrane and the consequent loss of cell homeostasis, in a process known as irreversible electroporation. This is an unusual mode of cell death that is not fully understood yet. While the phenomenon of irreversible electroporation may have been known for centuries it has become only recently rigorously considered in medicine for various applications of tissue ablation. A brief historical perspective of irreversible electroporation is presentedfollowed by general reviews on the theory and experiment fundamentals and by reports on the most recent theoretical, experimental and clinical studies.

1;Title Page;2 2;Preface;7 3;Contents;12 4;Historical Review of Irreversible Electroporation in Medicine;14 4.1;Introduction;14 4.2;The 18^{th} and 19^{th} Centuries;15 4.3;First Half of the 20^{th} Century;16 4.4;1950 to 1970;18 4.5;1970 to 1990;20 4.6;1990 to 2000;23 4.7;2000 to 2008;25 4.8;References;28 5;Tissue Electroporation as a Bioelectric Phenomenon: Basic Concepts;35 5.1;Introduction;35 5.2;Overview of Basic Electricity Concepts;37 5.3;Cells and Tissues in Electrical Terms;43 5.4;Electroporation Threshold;47 5.5;Time Course of Currents and Electric Fields during Electroporation Pulses;54 5.6;Conductivity Changes Induced by Electroporation;61 5.7;Effect of Electroporation on Other Bioelectric Phenomena;65 5.8;References;67 6;Experimental Studies on Irreversible Electroporation of Cells;74 6.1;Introduction;74 6.2;Pore Formation;75 6.3;Resealing Process;80 6.4;Factors That Affect the Uptake, Efficiency and Viability of the Cells;82 6.5;Changes in the Cell Caused by Electroporation;87 6.6;Irreversible Electroporation Studies in Mammalian Cells;89 6.7;Discussion;90 6.8;References;90 7;Mechanism of Irreversible Electroporation in Cells: Insight from the Models;95 7.1;Introduction;95 7.2;Background: IRE in Planar Membranes;96 7.2.1;$Experimental Observations$;96 7.2.2;$Theory of Electroporation in Planar Membranes: Pore Energy$;97 7.2.3;$Mechanism of Membrane Rupture$;99 7.2.4;$Revised Effect of the Transmembrane Potential on Pore Energy$;100 7.2.5;$Dynamics of Membrane Rupture$;101 7.3;IRE in Cells under Voltage-Clamp Conditions;102 7.4;IRE in Cells in External Electric Field;103 7.4.1;$Transmembrane Potential and Pore Creation$;103 7.4.2;$Cell Deformation by the Field$;107 7.4.3;$Effect of Pores on Membrane Tension$;109 7.4.4;$Postshock Pore Shrinkage and Coarsening$;112 7.4.5;$Membrane Tension-Induced Leakage through Pores$;115 7.4.6;$Change in Ionic Concentrations and Colloidal-Osmotic Swelling$;117 7.4.7;$Other Processes Affecting Irreversibility of Electroporation$;119 7.5;Possible Mechanisms of Cell Death during IRE;122 7.6;Parameters of the Model;125 7.7;References;126 8;Thermal Aspects of Irreversible Electroporation;133 8.1;Introduction;133 8.2;Effects of Electroporation Fields;134 8.2.1;$Transmembrane Potential$;134 8.2.2;$Electric Field Threshold$;136 8.2.3;$Properties Change during Electroporation$;136 8.2.4;$Joule Heating$;138 8.2.5;$Thermal Regimes$;139 8.3;Determining the Temperature Distribution;139 8.3.1;$Derivation of Heat Diffusion Equation from 1^{st} Principles$;139 8.3.2;$Bioheat Equation$;141 8.3.3;$Bioheat Equation Transformation$;141 8.3.4;$Non-dimensionalized Form of the Bioheat Equation$;142 8.4;Modeling for Treatment Planning;143 8.4.1;$Models$;143 8.4.2;$Accuracy of 2D versus 3D$;144 8.4.3;$Boundary Conditions$;144 8.4.4;$Cell Constants$;146 8.4.5;$Heat Dissipation$;148 8.4.6;$Geometrical Considerations$;150 8.5;Special Considerations When Modeling Tissues;153 8.5.1;$Tissue Heterogeneity$;153 8.5.2;$Temperature Dependent Properties$;156 8.6;Assessing Thermal Effects;157 8.6.1;$Damage Equation$;157 8.6.2;$Analytical Model$;158 8.6.3;$Analytical Results$;159 8.6.4;$Equivalent Thermal Dose Equation$;160 8.7;Conclusion;161 8.8;References;161 9;Experimental Studies on Non-thermal Irreversible Electroporation in Tissue;165 9.1;Introduction;165 9.2;NTIRE of the Liver;165 9.3;NTIRE of the Prostate;177 9.4;NTIRE of the Heart and the Cardiovascular System;179 9.5;NTIRE in the Treatment of Tumors;185 9.6;Summary of Experimental Studies;189 9.7;References;190 10;Finite Element Modeling of in Vivo Electroporation;192 10.1;Introduction;192 10.2;Which Modeling Method to Use?;193 10.3;Finite Element Method;194 10.4;Geometrical Considerations;194 10.5;Physical Considerations;197 10.6;Biological Tissues;200 10.7;Model Verification and Validation;206 10.8;Summary;207 10.9;References;208 11;Optimization and Numerical Modeling in Irreversible Electroporation Treatment Planning;212 11.1;Introduction;212 11.2;A Brief