Electric Field Distribution In Tissue Research Articles

Musa acuminata as electroporation model

Electrochemotherapy (ECT) and Irreversible electroporation (IRE) are cancer treatments based on electric field distribution in tissues. Solanum tuberosum (potato tissue) phantom is known to mimic changes in the electrical conductivity that occur in animal tissues during electroporation (EP). Electric field distribution is assessed through enzymatic staining. However, the 24-h wait for this assessment could slow agile response scenarios. We developed and validated the Musa acuminata (cavendish banana) conductivity model, which quickly evaluates EP by tissue staining. We investigated the frequency response of the tissue using impedance spectroscopy analysis, conductivity changes, and enzymatic staining. We optimized three usual EP models: adapted Gompertz, smoothed Heaviside, and the sigmoid or logistic function. We found dielectric parameters in banana tissue similar to those in potato (electrical conductivity of 0.035 S/m and relative permittivity of 4.1×104). The coefficients of determination R2 were 99.94% (Gompertz), 99.85% (Heaviside), and 99.58% (sigmoid). The sigmoid and Heaviside functions described the calibration and validation electric currents with 95% confidence. We observed the electroporated areas in bananas 3h30m after EP. Staining was significant after 450 V/cm. The conductivity model of Musa acuminata suits treatment planning, hardware development, and training scenarios. Banana phantom supports the 3Rs practice and is a reliable alternative for potato in EP studies.

Ex Vivo and In Silico Feasibility Study of Monitoring Electric Field Distribution in Tissue during Electroporation Based Treatments

Magnetic resonance electrical impedance tomography (MREIT) was recently proposed for determining electric field distribution during electroporation in which cell membrane permeability is temporary increased by application of an external high electric field. The method was already successfully applied for reconstruction of electric field distribution in agar phantoms. Before the next step towards in vivo experiments is taken, monitoring of electric field distribution during electroporation of ex vivo tissue ex vivo and feasibility for its use in electroporation based treatments needed to be evaluated. Sequences of high voltage pulses were applied to chicken liver tissue in order to expose it to electric field which was measured by means of MREIT. MREIT was also evaluated for its use in electroporation based treatments by calculating electric field distribution for two regions, the tumor and the tumor-liver region, in a numerical model based on data obtained from clinical study on electrochemotherapy treatment of deep-seated tumors. Electric field distribution inside tissue was successfully measured ex vivo using MREIT and significant changes of tissue electrical conductivity were observed in the region of the highest electric field. A good agreement was obtained between the electric field distribution obtained by MREIT and the actual electric field distribution in evaluated regions of a numerical model, suggesting that implementation of MREIT could thus enable efficient detection of areas with insufficient electric field coverage during electroporation based treatments, thus assuring the effectiveness of the treatment.

Nucleic Acids Electrotransfer-Based Gene Therapy (Electrogenetherapy): Past, Current, and Future

About 25 years after the publication of the first report on gene transfer in vitro in cultured cells by the means of electric pulses delivery, reversible cell electroporation for gene transfer and gene therapy (DNA electrotransfer) is at a cross in its development. Present knowledge on the effects of cell exposure to appropriate electric field pulses, particularly at the level of the cell membrane, is reported here. The importance of the models of electric field distribution in tissues and of the correct choice of electrodes and applied voltages is highlighted. The mechanisms involved in DNA electrotransfer, which include cell electropermeabilization and DNA electrophoresis, are also surveyed. This knowledge has allowed developing new nucleic acids electrotransfer conditions using combinations of permeabilizing pulses of high voltage and short duration, and of electrophoretic pulses of low voltage and long duration, which are very efficient and safer. Feasibility of electric pulses delivery for gene transfer in humans is discussed taking into account that electric pulses delivery is already regularly used for localized drug delivery in the treatment of cutaneous and subcutaneous solid tumors by electrochemotherapy. Because recent technological developments made DNA electrotransfer more and more efficient and safer, this non-viral gene therapy approach is now ready to reach the clinical stage. A good understanding of DNA electrotransfer principles and the respect of safe procedures will be key elements for a successful future transfer DNA electrotransfer into the clinics.

A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy

Permeabilising electric pulses can be advantageously used for DNA electrotransfer in vivo for gene therapy, as well as for drug delivery. In both cases, it is essential to know the electric field distribution in the tissues: the targeted tissue must be submitted to electric field intensities above the reversible permeabilisation threshold (to actually permeabilise it) and below the irreversible permeabilisation threshold (to avoid toxic effects of the electric pulses). A three-dimensional finite element model was built. Needle electrodes of different diameters were modelled by applying appropriate boundary conditions in corresponding grid points of the model. The observations resulting from the numerical calculations, like the electric field distribution dependence on the diameter of the electrodes, were confirmed in appropriate experiments in rabbit liver tissue. The agreement between numerical predictions and experimental observations validated our model. Then it was possible to make the first precise determination of the magnitude of the electric field intensity for reversible (362±21 V/cm, mean±S.D.) and for irreversible (637±43 V/cm) permeabilisation thresholds of rabbit liver tissue in vivo. Therefore the maximum of induced transmembrane potential difference in a single cell of the rabbit liver tissue can be estimated to be 394±75 and 694±136 mV, respectively, for reversible and irreversible electroporation threshold. These results carry important practical implications.