title: Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies.
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.
authors.affiliation: Stanford University Medical Center, Department of Radiation Oncology, Division of Radiation Physics, Stanford, CA, USA.|UNC / NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sano
authors.affiliation: Stanford University Medical Center, Department of Urology, Stanford, CA, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Fan
authors.affiliation: Stanford University Medical Center, Department of Radiation Oncology, Division of Radiation Physics, Stanford, CA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
mesh_terms: D045744:Cell Line, Tumor; D018274:Electroporation / Q000379:methods; D006801:Humans; D011846:Radio Waves; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured