In vivo results of a new focal tissue ablation technique:: Irreversible electroporation

In vivo results of a new focal tissue ablation technique:: Irreversible electroporation
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DOI:
10.1109/tbme.2006.873745
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发表时间:
2006-07-01
影响因子:
4.6
通讯作者:
Rubinsky, Boris
Rubinsky, Boris
中科院分区:
工程技术2区
文献类型:
--
作者:
Edd, Jon F.;Horowitz, Liana;Rubinsky, Boris

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本文报告了体内实验的结果,证实了一种新的微创组织消融方法,不可逆电穿孔(IRE)的可行性。电穿孔是在生物膜上产生不稳定的电势,导致脂质双层中形成纳米级缺陷。在IRE中,这些缺陷是永久性的,并导致细胞死亡。本文建立在我们早期的理论工作,并表明,IRE可以成为一种有效的方法,非热组织消融,不需要药物。为了测试IRE脉冲以受控方式消融组织的能力,我们将雄性Sprague-Dawley大鼠的肝脏置于1000 V/cm的单个20 ms长的方波脉冲下,计算预测该方波脉冲将导致非热IRE。脉冲后3小时,灌注固定肝脏中的治疗区域表现出微血管闭塞、内皮细胞坏死和渗出,导致实质缺血性损伤和血窦中红细胞大量汇集。然而,大血管结构被保留。肝细胞边界模糊,胞浆淡嗜酸性,核固缩,空泡变性。数学分析表明,这种损伤主要是非热性质的,受影响和未受影响区域之间的尖锐边界对应于300-500 V/cm的电场。
This paper reports results of in vivo experiments that confirm the feasibility of a new minimally invasive method for tissue ablation, irreversible electroporation (IRE). Electroporation is the generation of a destabilizing electric potential across biological membranes that causes the formation of nanoscale defects in the lipid bilayer. In IRE, these defects are permanent and lead to cell death. This paper builds on our earlier theoretical work and demonstrates that IRE can become an effective method for nonthermal tissue ablation requiring no drugs. To test the capability of IRE pulses to ablate tissue in a controlled fashion, we subjected the livers of male Sprague-Dawley rats to a single 20-ms-long square pulse of 1000 V/cm, which calculations had predicted would cause nonthermal IRE. Three hours after the pulse, treated areas in perfusion-fixed livers exhibited microvascular occlusion, endothelial cell necrosis, and diapedeses, resulting in ischemic damage to parenchyma and massive pooling of erythrocytes in sinusoids. However, large blood vessel architecture was preserved. Hepatocytes displayed blurred cell borders, pale eosinophilic cytoplasm, variable pyknosis and vacuolar degeneration. Mathematical analysis indicates that this damage was primarily nonthermal in nature and that sharp borders between affected and unaffected regions corresponded to electric fields of 300-500 V/cm.