Irreversible Electroporation Ablation: Is All the Damage Nonthermal?

Abstract

To determine whether high-dose irreversible electroporation (IRE) ablation induces thermal effects in normal liver tissue. Animal care and use committee approval was obtained prior to the experiments. IRE ablation (n = 78) was performed by a single four-person team in vivo in 22 porcine livers by applying electric current to two 1.3-cm-diameter circular flat-plate electrodes spaced 1 cm apart. Cardiac-gated IRE pulses (n = 40-360) were systematically applied at varying voltages (1500-2900 V). End temperatures at the ablation zone center were measured and were correlated with ablation time, energy parameters, and resultant treatment effect as determined at gross pathologic and histopathologic examination. Temperatures were then monitored at the center and periphery of four ablations created by using a four-electrode IRE array (3000 V, 90 pulses per electrode pair). Data were analyzed by using multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis, as appropriate. Temperature rose above the 34°C baseline after IRE in all flat-plate experiments and correlated linearly (R(2) = 0.39) with IRE "energy dose" (product of voltage and number of pulses) and more tightly in univariate analysis with both voltage and number of pulses. Thus, mean temperatures as high as 86°C ± 3 (standard deviation) were seen for 2500 V and 270 pulses. Ablations of 90 pulses or more at 2500 V produced temperatures of 50°C or greater and classic gross and histopathologic findings of thermal coagulation (pyknotic nuclei and streaming cytoplasm). For lower IRE doses (ie, 2100 V, 90 pulses), temperatures remained below 45°C, and only IRE-associated pathologic findings (ie, swollen sinusoids, dehydrated cells, and hemorrhagic infiltrate) were seen. For the four-electrode arrays, temperatures measured 54.2°C ± 6.1 at the electrode surfaces and 38.6°C ± 3.2 at the ablation zone margin. In some conditions of high intensity, IRE can produce sufficient heating to induce "white zone" thermal coagulation. While this can be useful in some settings to increase tumor destruction, further characterization of the thermal profile created with clinical electrodes and energy parameters is therefore needed to better understand the best ways to avoid unintended damage when ablating near thermally sensitive critical structures.