Burst and continuous high frequency irreversible electroporation protocols evaluated in a 3D tumor model

Area of Science:

• Biomedical Engineering
• Oncology
• Electroporation

Background:

• High frequency irreversible electroporation (H-FIRE) is an emerging cancer therapy using alternating polarity pulses to destroy cancer cells.
• H-FIRE typically employs short, rapidly repeated pulses to create energy bursts for targeted cell membrane destruction.

Purpose of the Study:

• To investigate H-FIRE parameters using a 3D in vitro tumor model to identify optimal energy timing protocols.
• To determine the lethal electric field thresholds for different H-FIRE configurations and compare them to monopolar IRE.

Main Methods:

• Utilized a 3D in vitro tumor model to test various H-FIRE pulse timing protocols.
• Compared monopolar irreversible electroporation (IRE) with different H-FIRE configurations, including varying burst frequencies and pulse cycle types.
• Employed finite element simulations to predict ablation volumes based on different pulse voltages and electrode configurations.

Main Results:

• Monopolar IRE had a lethal threshold of 423 V/cm.
• Baseline H-FIRE showed a higher lethal threshold (818 V/cm), but increasing burst numbers reduced this to 535 V/cm.
• A diffuse H-FIRE protocol with continuous 4 µs pulse cycles at 100 Hz achieved the lowest lethal threshold (476 V/cm).
• Simulations predicted significant ablation volumes, with H-FIRE potentially creating larger volumes (up to 15.7 cm³ with 10 kV pulses) compared to standard IRE.

Conclusions:

• Pulse timing, electrode geometry, and delivery protocols are crucial for maximizing H-FIRE efficacy.
• Diffuse H-FIRE protocols demonstrate potential for creating larger, clinically relevant ablation volumes in cancer treatment.
• Optimized H-FIRE parameters can lower the lethal electric field threshold, enhancing its therapeutic potential.