Comparative Study of the Biological Responses to Conventional Pulse and High-Frequency Monopolar Pulse Bursts

Abstract

Given its nonthermal property and other advantages, irreversible electroporation (IRE) has quickly translated into clinical applications. An increasing number of clinical cases using IRE have also revealed crucial issues. The uneven distribution of the electric field caused by the heterogeneity of biological tissues has not been completely and effectively addressed to date. The use of high-frequency monopolar pulse bursts (HFMPBs) is expected to solve this problem. The high-frequency content of the HFMPB is used to ensure the uniform distribution of the electric field in the tissue. A temperature increase similar to that of the conventional pulse method does not cause thermal damage and results in a killing effect similar to that of the conventional technique. Meanwhile, the subpulse has a pulse duration of 1-100 μs, which remains unexplored and may induce new cell responses. This paper analyzes the HFMPB based on the frequency domain and infers that the cell death pathways under this pulse induce necrosis and other processes, such as apoptosis. The phosphatidylserine externalization rate had a peak value at a different inner frequency of HFMPB when the electric field was 1 kV/cm for melanoma cells. This new type of pulse is expected to solve the problem of the uneven distribution of the electric field without altering the cell killing effect. If this effect is also verified in tissue ablation, these new types of pulses will promote the clinical application of IRE.