High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction.
High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction.
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DOI：
10.1186/1475-925x-10-102
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发表时间：
2011-11-21
影响因子：
3.9
通讯作者：
Davalos RV
中科院分区：
文献类型：
--
作者：
Arena CB;Sano MB;Rossmeisl JH Jr;Caldwell JL;Garcia PA;Rylander MN;Davalos RV
治疗性不可逆电穿孔（IRE）是一种新兴的肿瘤非热消融技术。该技术涉及传递一系列单极电脉冲，通过增加跨膜电位永久破坏癌细胞质膜的稳定性，从而导致组织病变的发展。临床上，IRE需要施用麻痹剂以防止治疗期间与电脉冲递送相关的肌肉收缩。这项研究表明，通过应用高频，双极爆发，肌肉收缩可以在IRE期间消除，而不影响细胞死亡的非热机制。结合分析，数值和实验技术进行了研究高频不可逆电穿孔（H-FIRE）。确定跨膜电位响应于任意电场的理论模型被用来确定用于体内治疗的最佳爆发频率和振幅。基于电场分布预测热损伤的有限元模型被用于设计用于体内实验的非热方案。将H-FIRE应用于大鼠的大脑，并通过放置在颈胸交界处的加速度计定量肌肉收缩。术后进行MRI和组织学评价以评估消融。在250 kHz或500 kHz的H-FIRE期间，没有观察到肌肉收缩的视觉或触觉证据，而所有IRE方案均导致颈胸交界处可检测到肌肉收缩。H-FIRE在脑组织中产生消融性损伤，这是非热IRE治疗的细胞形态学特征。具体而言，靶区域内的组织死亡完全一致，并且在病变和正常脑之间存在尖锐的过渡区。H-FIRE是一种可行的非热组织消融技术，可消除使用单极电脉冲进行的IRE治疗中观察到的肌肉收缩。因此，它有可能在临床上进行，而无需给予麻痹剂。
Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.