Abstract
BackgroundFor electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. In response to conventional, unipolar pulses, the electrical impedance of a tissue varies as a function of the local electric field, leading to a redistribution of the field. These dynamic impedance changes, which depend on the tissue type and the applied electric field, need to be quantified a priori, making mathematical modeling complicated. Here, it is shown that the impedance changes during high-frequency, bipolar electroporation therapy are reduced, and the electric field distribution can be approximated using the analytical solution to Laplace's equation that is valid for a homogeneous medium of constant conductivity.MethodsTwo methods were used to examine the agreement between the analytical solution to Laplace's equation and the electric fields generated by 100 µs unipolar pulses and bursts of 1 µs bipolar pulses. First, pulses were applied to potato tuber tissue while an infrared camera was used to monitor the temperature distribution in real-time as a corollary to the electric field distribution. The analytical solution was overlaid on the thermal images for a qualitative assessment of the electric fields. Second, potato ablations were performed and the lesion size was measured along the x- and y-axes. These values were compared to the analytical solution to quantify its ability to predict treatment outcomes. To analyze the dynamic impedance changes due to electroporation at different frequencies, electrical impedance measurements (1 Hz to 1 MHz) were made before and after the treatment of potato tissue.ResultsFor high-frequency bipolar burst treatment, the thermal images closely mirrored the constant electric field contours. The potato tissue lesions differed from the analytical solution by 39.7 ± 1.3 % (x-axis) and 6.87 ± 6.26 % (y-axis) for conventional unipolar pulses, and 15.46 ± 1.37 % (x-axis) and 3.63 ± 5.9 % (y-axis) for high- frequency bipolar pulses.ConclusionsThe electric field distributions due to high-frequency, bipolar electroporation pulses can be closely approximated with the homogeneous analytical solution. This paves way for modeling fields without prior characterization of non-linear tissue properties, and thereby simplifying electroporation procedures.
Highlights
For electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume
Thermal imaging allows for indirect visualization of electric field evolution Images obtained from the thermal camera provide a qualitative assessment of the electric field distribution in potato tissue
When using highfrequency bipolar bursts, the temperature distributions were more closely emulated by the electric field distributions (Figure 3A) than the unipolar pulses (Figure 3B)
Summary
For electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. Electroporation is a phenomenon in which transient nanoscale defects referred to as ‘pores’, form in the cell membrane in response to an externally applied electric field. This increases cell permeability to molecules that before could not pass through the membrane and decreases membrane resistance [1,2]. Electroporation is characterized as reversible when the pores reseal, the membrane recovers after treatment, and the cell survives [3] This effect is commonly used for introducing chemotherapeutic drugs into tumor cells during electrochemotherapy [4] or for transfer of DNA molecules inside cells during electrogenetherapy [5]. IRE has shown great promise in the non-thermal ablation of tumors while obviating the need for adjuvant drugs [7,8]
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