高频不可逆电穿孔与不可逆电穿孔消融治疗小型猪肝脏的比较：DCE-MRI 随访与病理观察。

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

机构信息

Medical School of Chinese People's Liberation Army, Beijing 100853, China.

Department of Radiology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin 300162, China.

出版信息

Chin Med J (Engl). 2021 Jun 24;134(17):2081-2090. doi: 10.1097/CM9.0000000000001663.

DOI:10.1097/CM9.0000000000001663

PMID:34172620

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8439989/

Abstract

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 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 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 by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures 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 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, 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°C vs. 16.20 ± 7.45°C, 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.

摘要

背景

高频不可逆电穿孔（H-FIRE）是一种新型的下一代纳米刀技术，具有缓解不可逆电穿孔（IRE）引起的肌肉收缩的优势。然而，具有不同消融参数的 IRE 和 H-FIRE 之间的区别尚不清楚。本研究旨在比较两种治疗方法的体内疗效。

方法

将 10 头巴马小型猪分为两组：5 头在 1 天组，5 头在 7 天组。通过体积转移常数（Krans）、摄取常数（Kep）和动态对比增强磁共振成像（DCE-MRI）的血管外细胞外体积分数（Ve）值、消融区大小和组织学分析比较 IRE 和 H-FIRE 消融的效果。每只动物均接受 IRE 和 H-FIRE 治疗。在消融过程中测量电极温度。在 7 天组中，在消融后 1、4 和 7 天获得 DCE-MRI 图像。两组所有动物均在消融后 1 天或 7 天安乐死，随后收集 IRE 和 H-FIRE 处理的肝组织进行组织学检查。Student's t 检验或Mann-Whitney U 检验用于比较任意两组。单因素方差分析（ANOVA）检验和 Welch's ANOVA 检验后进行 Holm-Sidak 多重比较检验、重复测量的单因素方差分析后进行 Bonferroni 检验或 Kruskal-Wallis H 检验后进行 Dunn's 多重比较检验，用于多组比较和事后分析。Pearson 相关系数检验用于分析两个变量之间的关系。

结果

在第 4 天，IRE 区的 Ve 高于 H-FIRE 区（0.14±0.02 vs. 0.08±0.05，t=2.408，P=0.043），但在所有时间点，Ktrans 和 Kep 均无明显差异（均 P＞0.05）。对于 IRE 区，第 7 天的最大 Ktrans 明显高于第 1 天（P=0.033）。H-FIRE 消融区的大小明显大于 IRE 区 1 天（4.74±0.88 cm2 vs. 3.20±0.77 cm2，t=3.241，P=0.009）和 4 天（2.22±0.83 cm2 vs. 1.30±0.50 cm2，t=2.343，P=0.041）。凋亡指数（0.05±0.02 vs. 0.73±0.06 vs. 0.68±0.07，F=241.300，P＜0.001）和热休克蛋白 70（HSP70）（0.03±0.01 vs. 0.46±0.09 vs. 和 0.42±0.07，F=64.490，P＜0.001）在未处理区、IRE 区和 H-FIRE 区之间差异显著，但 IRE 区和 H-FIRE 区之间的凋亡指数或 HSP70 无显著差异（均 P＞0.05）。两个区域的电极温度变化无显著差异（18.00±3.77°C vs. 16.20±7.45°C，t=0.682，P=0.504）。H-FIRE 区的 Ktrans 值（r=0.940，P=0.017）和 Kep 值（r=0.895，P=0.040）与消融区的肝细胞数量呈正相关。