Rapid impedance spectroscopy for monitoring tissue impedance, temperature, and treatment outcome during electroporation-based therapies.

OBJECTIVE Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue; this results in changes in electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time (~10s); this timeframe is much larger than pulse periods used with EBTs (~1s). In this study, we utilize rapid EIS techniques to develop a methodology for characterizing electroporation (EP) and thermal effects associated with high-frequency irreversible EP (H-FIRE) in real-time by monitoring inter-burst impedance changes. METHODS A charge-balanced, bipolar rectangular chirp signal is proposed for rapid EIS. Validation of rapid EIS measurements against a commercial potentiostat was conducted in potato tissue using flat-plate electrodes and thereafter for the measurement of impedance changes throughout IRE treatment. Flat-plate electrodes were then utilized to uniformly heat potato tissue; throughout high-voltage H-FIRE treatment, low-voltage inter-burst impedance measurements were used to continually monitor impedance change and to identify a frequency at which thermal effects are delineated from EP effects. RESULTS Inter-burst impedance measurements (1.8 kHz 4.93 MHz) were accomplished at 216 discrete frequencies. Impedance measurements at frequencies above ~1 MHz served to delineate thermal and EP effects in measured impedance. CONCLUSION We demonstrate rapid-capture (<<1s) EIS which enables monitoring of inter-burst impedance in real-time. For the first time, we show impedance analysis at high frequencies can delineate thermal effects from EP effects in measured impedance. SIGNIFICANCE The proposed waveform demonstrates the potential to perform inter-burst EIS using PEFs compatible with existing pulse generator topologies.