@article{petrella_fesmire_kaufman_topasna_sano_2020, title={Algorithmically Controlled Electroporation: A Technique for Closed Loop Temperature Regulated Pulsed Electric Field Cancer Ablation}, volume={67}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2019.2956537}, abstractNote={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 μs 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 °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 °C hyperthermic conditions which were not feasible without active feedback. Baseline closed-loop treatments at 20 °C resulted in ablations measuring 9.9 ± 0.3 mm in diameter while 37 °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.}, number={8}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Petrella, Ross Aaron and Fesmire, Christopher C. and Kaufman, Jacob D. and Topasna, Nomi and Sano, Michael B.}, year={2020}, pages={2176–2186} }
 @article{sano_petrella_kaufman_fesmire_xing_gerber_fogle_2020, title={Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms}, volume={121}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2020.103807}, abstractNote={Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Sano, Michael B. and Petrella, Ross A. and Kaufman, Jacob D. and Fesmire, Christopher C. and Xing, Lei and Gerber, David and Fogle, Callie A.}, year={2020}, month={Jun} }