Projects / Programmes
Electroporation-based treatments with new high-frequency electroporation pulses
| Code |
Science |
Field |
Subfield |
| 2.06.00 |
Engineering sciences and technologies |
Systems and cybernetics |
|
| Code |
Science |
Field |
| T115 |
Technological sciences |
Medical technology |
| Code |
Science |
Field |
| 2.06 |
Engineering and Technology |
Medical engineering
|
Electroporation, electroporator, high-frequency bipolar electric pulses, magnetic resonance imaging, numerical modelling
Researchers (14)
Organisations (2)
Abstract
More than 10 000 patients have been treated with electroporation-based treatments in more than 150 hospitals in Europe after the development of the first clinical device in 2006, comparable values are also for USA. Moreover, there are currently ongoing tens of clinical trials worldwide evaluating electroporation-based treatments.
In electroporation-based treatments, the electroporation pulses have fundamental frequency of 5 kHz or lower. The tissues in the body have at these frequencies a large impedance range. The electric field distribution in the body is thus very inhomogeneous during the delivery of classical electroporation pulses. Because of the inhomogeneous electric field distribution inside the body, the effects of electroporation-based treatments are also inhomogeneous in the body and thus less effective. Electroporation-based treatments thus require extensive numerical optimizations to cover the entire treatment area with sufficient electric field. At higher pulse frequencies tissues in the body have a smaller impedance range, and recent studies suggest that with shorter high-frequency bipolar electroporation pulses, electroporation of the tissues in the body could be more homogeneous, and that high-frequency electroporation pulses can achieve effective treatment without muscle contraction.
Our group regularly follows the development of commercial and laboratory prototype electroporation devices and we conclude that the first problem arises as there are no suitable electroporation devices for thoroughly analysing the effects of high-frequency electroporation pulses. The second problem arises as some groups independently to high-frequency treatments researchers concluded that high-frequency bipolar electroporation pulses can cause cancellation effect. Therefore we will develop a new prototype electroporation device that will generate high-frequency monopolar, bipolar and asymmetric bipolar electroporation pulses from 100 ns to 1 ms pulse duration, pulse amplitude up to 4 kV, and pulse repetition rate up to 5 MHz. For the first time, we will analyse thoroughly the high-frequency electroporation pulses in vitro as well as in vivo. Current electroporation models for electric field distribution in tissue are stationary and the changing of tissue impedance with the frequency of the pulses is not included. We will develop a new model in frequency domain and include the frequency characteristics of the tissue, and thus more precisely determine the electric field distribution of the high-frequency electroporation pulses in the tissue. Previous studies suggest a presence of cancellation effect in the field of high-frequency electroporation pulses. We will analyse thoroughly the range of electroporation pulse parameters and determine the equivalent parameters of high-frequency electroporation pulses regarding currently used classical electroporation pulses. We will systematically analyse the findings that the high-frequency electroporation pulses distribute in the tissue more homogeneously than classical electroporation pulses by indirect observation of electric field distribution using magnetic resonance imaging, and the findings that at the equivalent high-frequency electroporation pulses do not cause muscle contractions and pain by quantitative evaluation of muscle contractions and unpleasant sensations.
The expected results would significantly influence the development of current electroporation-based treatments because they would improve coverage of the entire treatment area with sufficient electric field. This would most likely increase the efficiency of the treatments, reduce the scattering of the results and simplify the treatment planning. The expected results would also reduce the muscle contraction and excitation of nerves and thus reduce the unpleasant sensations, movement of tissue and electrodes during the treatment, and improve the safety of treatments close to nerves.
Significance for science
More than 10 000 patients have been treated with electroporation-based treatments in more than 150 hospitals in Europe after the development of the first clinical device in 2006, comparable values are also for USA. Moreover, there are currently tens of clinical trials worldwide evaluating electroporation-based treatments ongoing. The expected results would significantly influence the development of current electroporation-based treatments because they would improve the coverage of the entire treatment area with sufficient electric field while minimizing the damage to the surrounding tissue. This will most likely increase the efficiency of the treatments, reduce the scattering of the results and simplify the treatment planning. The expected results would also reduce the muscle contractions and excitation of nerves and thus reduce the unpleasant sensations, movement of tissue and electrodes during the treatment, and improve the safety of treatments close to nerves. The new method for generating high-frequency electroporation pulses will enable the development of not yet developed clinical high-frequency electroporation devices. The new frequency-domain electroporation model will enable numerical treatment planning of pre-clinical and clinical studies. As high-frequency electroporation pulses are a relatively unexplored space of parameters, expected results will contribute to the fundamental understanding of the cell membrane and tissue permeabilization. It is also expected that these findings will influence the development of related technologies such as cryopreservation of tissues and food processing. With more homogeneous electric field distribution of the electroporation pulses in the tissue non-toxic cryoprotectants which normally do not cross the cell membrane could be used for cryopreservation of human tissues, plant germplasm, and food.
Significance for the country
More than 10 000 patients have been treated with electroporation-based treatments in more than 150 hospitals in Europe after the development of the first clinical device in 2006, comparable values are also for USA. Moreover, there are currently tens of clinical trials worldwide evaluating electroporation-based treatments ongoing. The expected results would significantly influence the development of current electroporation-based treatments because they would improve the coverage of the entire treatment area with sufficient electric field while minimizing the damage to the surrounding tissue. This will most likely increase the efficiency of the treatments, reduce the scattering of the results and simplify the treatment planning. The expected results would also reduce the muscle contractions and excitation of nerves and thus reduce the unpleasant sensations, movement of tissue and electrodes during the treatment, and improve the safety of treatments close to nerves. The new method for generating high-frequency electroporation pulses will enable the development of not yet developed clinical high-frequency electroporation devices. The new frequency-domain electroporation model will enable numerical treatment planning of pre-clinical and clinical studies. As high-frequency electroporation pulses are a relatively unexplored space of parameters, expected results will contribute to the fundamental understanding of the cell membrane and tissue permeabilization. It is also expected that these findings will influence the development of related technologies such as cryopreservation of tissues and food processing. With more homogeneous electric field distribution of the electroporation pulses in the tissue non-toxic cryoprotectants which normally do not cross the cell membrane could be used for cryopreservation of human tissues, plant germplasm, and food.
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