@article{fesmire_peal_ruff_moyer_mcparland_derks_o'neil_emke_johnson_ghosh_et al._2024, title={Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1232650}, abstractNote={Introduction Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses. Methods A custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 13 tumors were followed to act as untreated controls. Tumors were tracked over a 43–85 day period following a single INSPIRE treatment. Pulse widths of 500ns and 2000ns with voltages between 1000 V and 2000 V were investigated to determine the effect of these variables on treatment outcomes. Results Treatments administered at the lowest voltage (1000 V) reduced tumor volumes by 11 to 15%. Higher voltage (2000 V) treatments reduced tumor volumes by 84 to 88% and eliminated 33% and 80% of tumors when 500 ns and 2000 ns pulses were administered, respectively. Discussion Promising results were achieved without the use of chemotherapeutics, the use of general anesthesia, or the need for surgical resection in regions which are challenging to keep sterile. This novel therapeutic approach has the potential to expand the role of pulsed electric fields in veterinary patients, especially when general anesthesia is contraindicated, and warrants future studies to demonstrate the efficacy of INSPIRE as a solid tumor treatment.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Fesmire, Chris C. and Peal, Bridgette and Ruff, Jennifer and Moyer, Elizabeth and McParland, Thomas J. and Derks, Kobi and O'Neil, Erin and Emke, Carrie and Johnson, Brianna and Ghosh, Shatorupa and et al.}, year={2024}, month={Jan} }
 @article{petrella_levit_fesmire_tang_sano_2022, title={Polymer Nanoparticles Enhance Irreversible Electroporation In Vitro}, volume={69}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2022.3143084}, abstractNote={Expanding the volume of an irreversible electroporation treatment typically necessitates an increase in pulse voltage, number, duration, or repetition. This study investigates the addition of polyethylenimine nanoparticles (PEI-NP) to pulsed electric field treatments, determining their combined effect on ablation size and voltages. U118 cells in an in vitro 3D cell culture model were treated with one of three pulse parameters (with and without PEI-NPs) which are representative of irreversible electroporation (IRE), high frequency irreversible electroporation (H-FIRE), or nanosecond pulsed electric fields (nsPEF). The size of the ablations were compared and mapped onto an electric field model to describe the electric field required to induce cell death. Analysis was conducted to determine the role of PEI-NPs in altering media conductivity, the potential for PEI-NP degradation following pulsed electric field treatment, and PEI-NP uptake. Results show there was a statistically significant increase in ablation diameter for IRE and H-FIRE pulses with PEI-NPs. There was no increase in ablation size for nsPEF with PEI-NPs. This all occurs with no change in cell media conductivity, no observable degradation of PEI-NPs, and moderate particle uptake. These results demonstrate the synergy of a combined cationic polymer nanoparticle and pulsed electric field treatment for the ablation of cancer cells. These results set the foundation for polymer nanoparticles engineered specifically for irreversible electroporation.}, number={7}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Petrella, Ross A. and Levit, Shani L. and Fesmire, Christopher C. and Tang, Christina and Sano, Michael B.}, year={2022}, month={Jul}, pages={2353–2362} }
 @article{sano_fesmire_petrella_2021, title={Electro-Thermal Therapy Algorithms and Active Internal Electrode Cooling Reduce Thermal Injury in High Frequency Pulsed Electric Field Cancer Therapies}, volume={49}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-020-02524-x}, abstractNote={["Thermal tissue injury is an unintended consequence in current irreversible electroporation treatments due to the induction of Joule heating during the delivery of high voltage pulsed electric fields. In this study active temperature control measures including internal electrode cooling and dynamic energy delivery were investigated as a process for mitigating thermal injury during treatment. Ex vivo liver was used to examine the extent of thermal injury induced by 5000 V treatments with delivery rates up to five times faster than current clinical practice. Active internal cooling of the electrode resulted in a 36% decrease in peak temperature vs. non-cooled control treatments. A temperature based feedback algorithm (electro-thermal therapy) was demonstrated as capable of maintaining steady state tissue temperatures between 30 and 80 °C with and without internal electrode cooling. Thermal injury volumes of 2.6 cm", {:sup=>"3"}, " were observed for protocols with 60 °C temperature set points and electrode cooling. This volume reduced to 1.5 and 0.1 cm", {:sup=>"3"}, " for equivalent treatments with 50 °C and 40 °C set points. Finally, it was demonstrated that the addition of internal electrode cooling and active temperature control algorithms reduced ETT treatment times by 84% (from 343 to 54 s) vs. non-cooled temperature control strategies with equivalent thermal injury volumes."]}, number={1}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Sano, Michael B. and Fesmire, Christopher C. and Petrella, Ross A.}, year={2021}, month={Jan}, pages={191–202} }
 @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} }
 @article{fesmire_petrella_fogle_gerber_xing_sano_2020, title={Temperature Dependence of High Frequency Irreversible Electroporation Evaluated in a 3D Tumor Model}, volume={48}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-019-02423-w}, abstractNote={Electroporation is a bioelectric phenomenon used to deliver target molecules into cells in vitro and irreversible electroporation (IRE) is an emerging cancer therapy used to treat inoperable tumors in situ. These phenomena are generally considered to be non-thermal in nature. In this study, a 3D tumor model was used to investigate the correlation between temperature and the effectiveness of standard clinical IRE and high frequency (H-FIRE) protocols. It was found for human glioblastoma cells that in the range of 2 to 37 °C the H-FIRE lethal electric field threshold value, which describes the minimum electric field to cause cell death, is highly dependent on temperature. Increasing the initial temperature from 2 to 37 °C resulted in a significant decrease in lethal electric field threshold from 1168 to 507 V/cm and a 139% increase in ablation size for H-FIRE burst treatments. Standard clinical protocol IRE treatments resulted in a decrease in lethal threshold from 485 to 453 V/cm and a 7% increase in ablation size over the same temperature range. Similar results were found for pancreatic cancer cells which indicate that tissue temperature may be a significant factor affecting H-FIRE ablation size and treatment planning in vivo while lower temperatures may be useful in maintaining cell viability for transfection applications.}, number={8}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Fesmire, Christopher C. and Petrella, Ross A. and Fogle, Callie A. and Gerber, David A. and Xing, Lei and Sano, Michael B.}, year={2020}, month={Aug}, pages={2233–2246} }