Abstract
Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50–100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a well-defined volume. Challenges with IRE include complex treatment planning and the induction of intense muscle contractions. High frequency IRE (H-FIRE) uses bursts of ultrashort (0.25–5 μs) alternating polarity pulses to produce more predictable ablations and alleviate muscle contractions associated with IRE. However, H-FIRE generally ablates smaller volumes of tissue than IRE. This study shows that asymmetric H-FIRE waveforms can be used to create ablation volumes equivalent to standard IRE treatments. Lethal thresholds (LT) of 505 V/cm and 1316 V/cm were found for brain cancer cells when 100 μs IRE and 2 μs symmetric H-FIRE waveforms were used. In contrast, LT as low as 536 V/cm were found for 2 μs asymmetric H-FIRE waveforms. Reversible electroporation thresholds were 54% lower than LTs for symmetric waveforms and 33% lower for asymmetric waveforms indicating that waveform symmetry can be used to tune the relative sizes of reversible and irreversible ablation zones. Numerical simulations predicted that asymmetric H-FIRE waveforms are capable of producing ablation volumes which were 5.8–6.3x larger than symmetric H-FIRE waveforms indicating that in vivo investigation of asymmetric waveforms is warranted.
Highlights
Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50–100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a welldefined volume
Ivey et al found a lethal threshold of 492 ± 41 V/cm for U87 cells treated with an identical IRE protocol when cells were cultured in 3D gels made with a 2% collagen mixture[26] rather than the Matrigel material used in this study
These results indicated that culture conditions had a relatively small impact on lethal thresholds in comparison to other experimental parameters. 2D culture protocols were substantially less complex and less expensive than those required for producing and maintaining 3D cultures
Summary
Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50–100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a welldefined volume. Irreversible electroporation (IRE) is an emerging cancer therapy which uses high intensity electrical pulses to focally ablate solid tumors[1]. A series of approximately 100 electrical pulses, 1000 to 3000 V in amplitude and 50 to 100 μs in duration, are delivered These electrical pulses locally increase cell transmembrane potentials above a critical lethal threshold to create permanent nanoscale defects, which result in rapid cell death. Patients must receive significant doses of chemical paralytics and pulse delivery is synchronized with the heart-beat to ensure pulses are delivered during the absolute refractory period[19] This is challenging since it significantly changes the clinical workflow in comparison to other focal therapies and can increase the overall treatment time. H-FIRE replaces the long duration monopolar IRE pulses (Fig. 1a) with a burst of alternating polarity pulses www.nature.com/scientificreports/
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