High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

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.Irreversible electroporation (IRE) has recently emerged as a non-thermal treatment modality to destroy tumors [1-3] and other non-cancerous pathologies [4-6]. The protocol involves delivering a series of short and intense electric pulses through electrodes inserted directly into, or placed around, the target tissue. The pulses are designed to generate an electric field between the electrodes capable of inducing a rapid buildup of charge across the plasma membrane of cells, commonly referred to as a transmembrane potential