Experimental and Analytical Studies on Contact Irreversible Electroporation for Superficial Tumor Treatment

Abstract

Irreversible electroporation (IRE) is attracting much attention as a less-invasive therapy to ablate abnormal tissues. With a pair of electrodes inserted into the tissue, the IRE perforates the targeted cells non-thermally by a train of intensive electric pulses that exceeds a certain threshold. Since only the cells are necrotized percutaneously, the extracellular matrix is kept intact in the IRE, which is favorable for prompt tissue regeneration. In this study, we demonstrated that the IRE is also applicable to treat superficial targets such as melanoma, nevus, and tumors on gastrointestinal surface. A pair of 1-mm dia. stainless steel rods fixed 5 mm apart in an acrylic plate was contacted on an agarose gel containing fibroblasts. A sequence of 15 to 90 pulses of 1 kV was then applied to the gel via electrodes. All pulses were 10 µs in length and oscillated at 100 ms intervals. The boundary between dead and alive cell regions was determined at the surface and vertical cross section by using fluorescent staining. The necrotic cell area was also predicted by a numerical solution to the equation of electric field. Those determined with an assumption that the potential difference of 1 V between the cell membrane induces irreversible cell breakdown agreed well with the necrotic cell area and maximal depth in the experiment at low pulse number. However, the experiment showed the increase in the necrotic area with increasing the pulse repetition. Since application of multiple pulses perforates the highly resistive cell membrane, our study indicated the importance of taking into account the change in the electrical properties due to cell destruction.

Mathematical modeling of the thermal effects of irreversible electroporation for in vitro, in vivo, and clinical use: a systematic review

“…In addition, more details about the applied model parameters were included in Supplementary Appendix 6. In the included studies, the subjects were modeled in one-dimensional [25,30,50,64], two-dimensional [3,24,26- [3,24,27], IRENA [79,81], Marc/Mentat (MSC Software Corp., Santa Ana, CA) [47,75], and QuickField (Terra Analysis, Denmark) [54]. Generally, numerical calculations were performed on three-dimensional subjects using the software package COMSOL Multiphysics, which uses Finite Element Method.…”

“…] is the gradient and U [V] is the scalar electric potential [3,24,26,27,29,31,33,34,[36][37][38][39][40][41][42][43][44][45][46][47][48][50][51][52][53][54][55][56][57][58][59]62,63,65,66,[68][69][70]75,[78][79][80]. Here, the vector quantities are expressed in bold and italic, while the scalar quantities have remained unchanged.…”

“…The electric-field and temperature distributions of IRE have been calculated for multiple tissue types. For example, IRE has been applied to artery [33,34,36,41], brain [31,40,57,66,69,73], breast [28,29,35], cervix [78], eye [44], in vitro cell suspension [30,43,47,60,61,75], kidney [45,63,65], liver [3,24,[37][38][39]46,48,53,54,62,71,72,74,76,77,79,80], pancreas [52,70], prostate [28,32,49,50,56,64,67,…”

Comprehensive review on thermal aspects of nonthermal irreversible electroporation

“…The thermal damage index described in Section 3.1 is then calculated from the temperature history to which the tissue is exposed. Several numerical simulations have been carried out at a single point in the tissue (one‐dimensional [1D]) 5,41,137,138 or using 2D 1,2,46,47,52,79,139–156 and 3D models 12–14,24,30,38,128,139,157–179 . Most studies did not include vascular structures, such as blood vessels, in their models.…”

Determination of the critical electric field strength for therapeutic irreversible electroporation by using a three-dimensional cell culture model

“…A major factor affecting IRE outcome is a distribution of the electric field because cells are damaged by a potential difference across the cell membrane. Therefore, previous studies focused on the experimentally determined ablated area as connected to the electric field estimated from a numerical analysis (Arena et al, 2012;Kurata et al, 2013). However, Determination of the critical electric field strength for therapeutic irreversible electroporation by using a threedimensional cell culture model pulse length, repetition, and interval are also important factors that determine the ablated area (Al-Sakere et al, 2007;Jiang et al, 2015a;Jiang et al, 2015b;Maor et al, 2009) because the overall energy input and the time needed for repairing partially damaged cell membrane may influence the results of IRE.…”