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 3D 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 3D 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.