The Enhancement of Tumor Ablation Effect by The Combination of High-Frequency and Low-Voltage Bipolar Electroporation Pulses

The H-FIRE (high-frequency irreversible electroporation) protocol employs high-frequency bipolar pulses (HFBPs) with a width of ∼1 μs for tumor ablation with slight muscle contraction. However, H-FIRE pulses need a higher electric field to generate a sufficient ablation effect, which may cause undesirable thermal damage. Objective: Recently, combining short high-voltage IRE monopolar pulses with long low-voltage IRE monopolar pulses was shown to enlarge the ablation region. This finding indicates that combining HFBPs with low-voltage bipolar pulses (LVBPs), which are called composited bipolar pulses (CBPs), may enhance the ablation effect. Methods: This study designed a pulse generator by modifying a full-bridge inverter. The cell suspension and 3-D tumor mimic experiments (U251 cells) were performed to examine the enhancement of the ablation effect. Results: The generator outputs HFBPs with 0-±2.5 kV and LVBPs with 0-±0.3 kV in one period. The pulse parameters are adjustable by programming on a human-computer interface. The cell suspension experiments showed that CBPs could enhance cytotoxicity, as compared to HFBPs with no cell-killing effect. Even at lower electric energy, the cell viability by CBPs was significantly lower than that of the HFBPs protocol. The ablation experiments on the 3-D tumor mimic showed that the CBPs could create a larger connected ablation area. In contrast, the HFBPs protocol with a similar dose generated a nonconnected ablation area. Conclusion: Results indicate that the CBPs protocol can enhance the ablation effect of HFBPs protocol. Significance: This proposed generator that uses the CBPs principle may be a useful tool for tumor ablation.