UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States of America. Author to whom any correspondence should be addressed.
Phys Med Biol. 2018 Jul 6;63(13):135022. doi: 10.1088/1361-6560/aacb62.
High frequency irreversible electroporation (H-FIRE) is an emerging cancer therapy which uses bursts of alternating polarity pulses to target and destroy the membranes of cells within a predictable volume. Typically, 2 µs pulses are rapidly repeated 24-50 times to create a 48-100 µs long energy burst. Bursts are repeated 100× at 1 Hz, resulting in an integrated energized time of 0.01 s per treatment. A 3D in vitro tumor model was used to investigate H-FIRE parameters in search of optimal energy timing protocols. Monopolar IRE treatments (100 × 100 µs positive polarity pulses) resulted in a lethal electric field threshold of 423 V cm. Baseline H-FIRE treatments (100 × 100 µs bursts of 2 µs pulses) resulted in a lethal threshold of 818 V cm. Increasing the number of H-FIRE bursts from 100× to 1000× reduced the lethal threshold to 535 V cm. An alternative diffuse H-FIRE protocol, which delivers 4 µs pulse cycles (one positive and one negative 2 µs pulse) continuously at 100 Hz, resulted in the lowest H-FIRE lethal threshold of 476 V cm. Finite element simulations using 5 kV pulses predict an IRE ablation volume of 3.9 cm (1.7 cm diameter) and a maximum H-FIRE ablation volume of 5.3 cm (2.4 cm diameter) when a clinical electrode and grounding pad configuration is used. Ablations as large as 15.7 cm (3.3 cm diameter) are predicted for H-FIRE treatments with 10 kV pulses. These results combine to demonstrate the importance of electrode geometry, pulse timing, and clinical delivery protocols for the creation of large clinically meaningful ablations.
高频不可逆电穿孔（H-FIRE）是一种新兴的癌症治疗方法，它利用交替极性脉冲的爆发来靶向和破坏可预测体积内的细胞膜。通常，2 μs 的脉冲会快速重复 24-50 次，以产生 48-100 μs 长的能量爆发。爆发重复 100 次，频率为 1 Hz，每次治疗的集成通电时间为 0.01 s。使用 3D 体外肿瘤模型来研究 H-FIRE 参数，以寻找最佳的能量定时方案。单极 IRE 治疗（100×100 μs 正性极性脉冲）导致致死电场阈值为 423 V/cm。基线 H-FIRE 治疗（100×100 μs 的 2 μs 脉冲爆发）导致致死阈值为 818 V/cm。将 H-FIRE 爆发次数从 100 次增加到 1000 次，致死阈值降低到 535 V/cm。另一种弥散的 H-FIRE 方案，以 100 Hz 连续传递 4 μs 脉冲周期（一个正 2 μs 脉冲和一个负 2 μs 脉冲），导致最低的 H-FIRE 致死阈值为 476 V/cm。使用 5 kV 脉冲进行的有限元模拟预测，当使用临床电极和接地垫配置时，IRE 消融体积为 3.9 cm（1.7 cm 直径），最大 H-FIRE 消融体积为 5.3 cm（2.4 cm 直径）。当使用 10 kV 脉冲进行 H-FIRE 治疗时，预测消融体积可达 15.7 cm（3.3 cm 直径）。这些结果结合起来证明了电极几何形状、脉冲定时和临床传递方案对创建大的临床相关消融的重要性。
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