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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 n in vivo.n Methods::Ten Bama miniature swine were 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 and H-FIRE. Temperatures of the electrodes were measured 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 n t test or Mann-Whitney n U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch’s ANOVA test followed by Holm-Sidak’s multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis n H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and n post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.n Results::Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 n vs. 0.08 ± 0.05, n t= 2.408, n 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 n P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 ( n P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cmn 2vs. 3.20 ± 0.77 cmn 2, n t = 3.241, n P = 0.009) and 4 days (2.22 ± 0.83 cmn 2vs. 1.30 ± 0.50 cmn 2, n t = 2.343, n P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 n vs. 0.73 ± 0.06 n vs. 0.68 ± 0.07, n F = 241.300, n P 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 ( n P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cmn 2vs. 3.20 ± 0.77 cmn 2, n t = 3.241, n P = 0.009) and 4 days (2.22 ± 0.83 cmn 2vs. 1.30 ± 0.50 cmn 2, n t = 2.343, n P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 n vs. 0.73 ± 0.06 n vs. 0.68 ± 0.07, n F = 241.300, n P < 0.001) and heat shock protein 70 (HSP70) (0.03 ± 0.01 n vs. 0.46 ± 0.09 n vs. and 0.42 ± 0.07, n F= 64.490, n P 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C n vs. 16.20 ± 7.45°C, n t = 0.682, n P = 0.504). The Ktrans value (n r = 0.940, n P = 0.017) and the Kep value (n r = 0.895, n P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.n Conclusions::H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.