Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver:follow-up of DCE-MRI and pathological observations

Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.