Search

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 3 were observed for protocols with 60 °C temperature set points and electrode cooling. This volume reduced to 1.5 and 0.1 cm 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.

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., Competing Interests: Declaration of competing interest MBS, CCF, RAP, and LX have issued or pending patents related to IRE and H-FIRE technologies. MBS recieves royalties from AngioDynamics Inc. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols., Materials and Methods: Treatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01-0.08 seconds and energy delivery rates 25-300 μs/s were investigated. Organs were preserved at 4°C for 10-15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones., Results: A+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9-2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50-300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4-4.9 cm with energy delivery times of 7-80 minutes., Conclusions: H-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)