Algorithmically Controlled Electroporation: A Technique for Closed Loop Temperature Regulated Pulsed Electric Field Cancer Ablation

摘要

Objective: To evaluate the effect of a closed-loop temperature based feedback algorithm on ablative outcomes for pulsed electric field treatments. Methods: A 3D tumor model of glioblastoma was used to assess the impact of 2 mu s duration bipolar waveforms on viability following exposure to open and closed-loop protocols. Closed-loop treatments evaluated transient temperature increases of 5, 10, 15, or 22 degrees C above baseline. Results: The temperature controlled ablation diameters were conditionally different than the open-loop treatments and closed-loop treatments generally produced smaller ablations. Closed-loop control enabled the investigation of treatments with steady state 42 degrees C hyperthermic conditions which were not feasible without active feedback. Baseline closed-loop treatments at 20 degrees C resulted in ablations measuring 9.9 +/- 0.3 mm in diameter while 37 degrees C treatments were 20% larger (p < 0.0001) measuring 11.8 +/- 0.3 mm indicating that this protocol induces a thermally mediated biological response. Conclusion: A closed-loop control algorithm which modulated the delay between successive pulse waveforms to achieve stable target temperatures was demonstrated. Algorithmic control enabled the evaluation of specific treatment parameters at physiological temperatures not possible with open-loop systems due to excessive Joule heating. Significance: Irreversible electroporation is generally considered to be a non-thermal ablation modality and temperature monitoring is not part of the standard clinical practice. The results of this study indicate ablative outcomes due to exposure to pulses on the order of one microsecond may be thermally mediated and dependent on local tissue temperatures. The results of this study set the foundation for experiments in vivo utilizing temperature control algorithms.