Histological and Mathematical Analysis of the Irreversibly Electroporated Liver Tissue.

Irreversible electroporation has clinically been used to treat various types of cancer. A plan on how to apply irreversible electroporation before practicing is very important to increase the ablation area and reduce the side effects. Several electrical models have been developed to predict the ablation area with applied electric energy. In this experiment, the static relationship between applied electric energy and ablated area was mathematically and experimentally investigated at 10 hours after applying irreversible electroporation. We performed the irreversible electroporation on the liver tissue of Sprague Dawley rats (male, 8 weeks, weighing 250-350 g). The ablated area was measured based on histological analysis and compared with the mathematical calculation from the electric energy, assuming that the tissue is homogeneous. The ablated area increased with the increase in applied electric energy. The numerically calculated contour lines of electric energy density overlapped well with the apoptotic area induced by the irreversible electroporation. The overlapped area clearly showed that the destructive threshold of apoptosis between electrodes is electric energy density level of 5.9 × 105 J/m3. The results of the present study suggested that the clinical results of the irreversible electroporation on a liver tissue could be predicted through mathematical calculation.

Changes of apoptosis in tumor tissues with time after irreversible electroporation.

Irreversible electroporation is a novel method of ablating living tissues through its non-thermal effects, unlike radiofrequency ablation which has a severe problem of heat sink. It is due to high-energy direct current which leads to permanent disruption of lipid bilayer integrity in terms of exchanges between intra- and extracellular components via nano-sized pores. That finally causes irreversible damage to cellular homeostasis. Irreversibly damaged cells may undergo apoptosis followed by necrosis with time after electroporation. This damage can make it possible to monitor the ablated area with time post-IRE through MR imaging and an ultrasound system. Most previous studies have investigated the immediate response of undesired tissue to IRE. In our study, we showed changes of tumor tissues with time post-IRE by histological analysis and MR imaging. Tissues under IRE ablation showed a peak apoptotic rate at 24 h after IRE ablation with viable tissues at the peripheral rim of treated tissues in histological analysis. This phenomenon was also observed with no enhancement on contrast-enhanced MR images due to devascularization of IRE ablated zones.