Download full-text


Available from: Matej Rebersek, Sep 03, 2014
23 Reads
  • Source
    • "6(b)]. It was shown, that out of several theoretical equations proposed for the description of such a relationship, the best fit to the experimental data was given by (1)–(4) [25]. In Fig. 6(c), the dependences of the amplitude of a squarewave electric pulse required to electroporate 50% of cells, E 0.5 , on the pulse duration are presented for human erythrocytes [18], [26], CHO [26], and mouse hepatoma MH-22A cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Here, theoretical relationships between the parameters of the electric pulse, which is necessary to porate the cell by electric pulse of various shapes, have been obtained. The theoretical curves were compared with the experimental relationships. Experiments were carried out with human erythrocytes and mouse hepatoma MH-22A cells. The fraction of electroporated MH-22A cells was determined from the extent of the release of intracellular potassium ions and erythrocytes – from the extent of their hemolysis after long (20–24 h) incubation in 0.63% NaCl solution at 4 oC. The dependence of the fraction of electroporated cells on the amplitude of the electric field pulse was determined for pulses with the duration from 95 ns to 2 ms. The shapes of theoretical dependencies are in agreement with experimental ones. The cell poration time depended on the intensity of the pulse: the shorter the pulse duration, the higher the electric field strength has to be. This dependence is much more pronounced for pulses shorter than 1 μs. For example, if the pulse amplitude required to electroporate 50% of human erythrocytes increased from 1.0 to 1.76 kV/cm, when the duration of a square-wave pulse was reduced from 2 ms to 20 μs, it increased from 3 to 12 kV/cm, when the pulse duration was reduced from 950 to 95 ns. The relationships between the electric field strength required for electroporation and the frequency of the applied ac field were calculated for different pulse lengths. It has been obtained that although the electric field strength is constant for frequencies less than 10 kHz but its value depends on the pulse length decreasing with increasing pulse duration. At higher frequencies electric field strength is dependent on the frequency of the ac field.
    IEEE Transactions on Plasma Science 10/2013; 41(10):2913-2919. DOI:10.1109/TPS.2013.2276918 · 1.10 Impact Factor
  • Source
    • "electroporation pulses) [1-3]. The efficiency of electroporation strongly depends on pulse parameters such as pulse amplitude, pulse duration, number of pulses and repetition frequency [4]. In order to successfully electropermeabilize a cell membrane the induced transmembrane voltage needs to exceed a given value that depends on cell or tissue type (e.g. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Electroporation based therapies and treatments (e.g. electrochemotherapy, gene electrotransfer for gene therapy and DNA vaccination, tissue ablation with irreversible electroporation and transdermal drug delivery) require a precise prediction of the therapy or treatment outcome by a personalized treatment planning procedure. Numerical modeling of local electric field distribution within electroporated tissues has become an important tool in treatment planning procedure in both clinical and experimental settings. Recent studies have reported that the uncertainties in electrical properties (i.e. electric conductivity of the treated tissues and the rate of increase in electric conductivity due to electroporation) predefined in numerical models have large effect on electroporation based therapy and treatment effectiveness. The aim of our study was to investigate whether the increase in electric conductivity of tissues needs to be taken into account when modeling tissue response to the electroporation pulses and how it affects the local electric distribution within electroporated tissues. Methods: We built 3D numerical models for single tissue (one type of tissue, e.g. liver) and composite tissue (several types of tissues, e.g. subcutaneous tumor). Our computer simulations were performed by using three different modeling approaches that are based on finite element method: inverse analysis, nonlinear parametric and sequential analysis. We compared linear (i.e. tissue conductivity is constant) model and non-linear (i.e. tissue conductivity is electric field dependent) model. By calculating goodness of fit measure we compared the results of our numerical simulations to the results of in vivo measurements. Results: The results of our study show that the nonlinear models (i.e. tissue conductivity is electric field dependent: σ(E)) fit experimental data better than linear models (i.e. tissue conductivity is constant). This was found for both single tissue and composite tissue. Our results of electric field distribution modeling in linear model of composite tissue (i.e. in the subcutaneous tumor model that do not take into account the relationship σ(E)) showed that a very high electric field (above irreversible threshold value) was concentrated only in the stratum corneum while the target tumor tissue was not successfully treated. Furthermore, the calculated volume of the target tumor tissue exposed to the electric field above reversible threshold in the subcutaneous model was zero assuming constant conductivities of each tissue.Our results also show that the inverse analysis allows for identification of both baseline tissue conductivity (i.e. conductivity of non-electroporated tissue) and tissue conductivity vs. electric field (σ(E)) of electroporated tissue. Conclusion: Our results of modeling of electric field distribution in tissues during electroporation show that the changes in electrical conductivity due to electroporation need to be taken into account when an electroporation based treatment is planned or investigated. We concluded that the model of electric field distribution that takes into account the increase in electric conductivity due to electroporation yields more precise prediction of successfully electroporated target tissue volume. The findings of our study can significantly contribute to the current development of individualized patient-specific electroporation based treatment planning.
    BioMedical Engineering OnLine 02/2013; 12(1):16. DOI:10.1186/1475-925X-12-16 · 1.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Electrochemotherapy is a local treatment that utilizes electric pulses in order to achieve local increase in cytotoxicity of some anticancer drugs. The success of this treatment is highly dependent on parameters such as tissue electrical properties, applied voltages and spatial relations in placement of electrodes that are used to establish a cell-permeabilizing electric field in target tissue. Non-thermal irreversible electroporation techniques for ablation of tissue depend similarly on these parameters. In the treatment planning stage, if oversimplified approximations for evaluation of electric field are used, such as U/d (voltage-to-distance ratio), sufficient field strength may not be reached within the entire target (tumor) area, potentially resulting in treatment failure. Results In order to provide an aid in education of medical personnel performing electrochemotherapy and non-thermal irreversible electroporation for tissue ablation, assist in visualizing the electric field in needle electrode electroporation and the effects of changes in electrode placement, an application has been developed both as a desktop- and a web-based solution. It enables users to position up to twelve electrodes in a plane of adjustable dimensions representing a two-dimensional slice of tissue. By means of manipulation of electrode placement, i.e. repositioning, and the changes in electrical parameters, the users interact with the system and observe the resulting electrical field strength established by the inserted electrodes in real time. The field strength is calculated and visualized online and instantaneously reflects the desired changes, dramatically improving the user friendliness and educational value, especially compared to approaches utilizing general-purpose numerical modeling software, such as finite element modeling packages. Conclusion In this paper we outline the need and offer a solution in medical education in the field of electroporation-based treatments, e.g. primarily electrochemotherapy and non-thermal irreversible tissue ablation. We present the background, the means of implementation and the fully functional application, which is the first of its kind. While the initial feedback from students that have evaluated this application as part of an e-learning course is positive, a formal study is planned to thoroughly evaluate the current version and identify possible future improvements and modifications.
    BMC Medical Education 10/2012; 12(1):102. DOI:10.1186/1472-6920-12-102 · 1.22 Impact Factor
Show more