Treatment of Spontaneous Tumors With Algorithmically Controlled Electroporation.

Objective: To study the safety and efficacy of algorithmically controlled electroporation (ACE) against spontaneous equine melanoma.

Methods: A custom temperature sensing coaxial electrode was paired with a high voltage pulse generation system with integrated temperature feedback controls. Computational modeling and ex vivo studies were conducted to evaluate the system's ability to achieve and maintain target temperatures.

A novel in vitro model of clinical cryoablation to investigate the transition zone for focal tumor ablation.

Cryoablation (CA) of solid tumors is highly effective at reducing tumor burden and eliminating small, early stage tumors. However, complete ablation is difficult to achieve and cancer recurrence is a significant barrier to treatment of larger tumors compared to resection. In this study, we explored the relationship between temperature, ice growth, and cell death using a novel in vitro model of clinical CA with the Visual-ICE (Boston Scientific) system, a clinically approved and widely utilized device.

Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE): Assessment of Dose, Temperature, and Voltage on Experimental and Clinical Treatment Outcomes.

Objective: This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation.

Methods: INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.

Polymer Nanoparticles Enhance Irreversible Electroporation In Vitro.

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).

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

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.

Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms.

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.

Irreversible electroporation is a thermally mediated ablation modality for pulses on the order of one microsecond.

Irreversible electroporation (IRE) is generally considered to be a non-thermal ablation modality. This study was designed to examine the relative effect of temperature on IRE ablation sizes for equivalent dose treatments with constitutive pulses between 1 and 100 µs. 3D in-vitro brain tumor models maintained at 10 °C, 20 °C, 30 °C, or 37 °C were exposed to 500 V treatments using a temperature control algorithm to limit temperature increases to 5 °C.

Electro-Thermal Therapy Algorithms and Active Internal Electrode Cooling Reduce Thermal Injury in High Frequency Pulsed Electric Field Cancer Therapies.

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.

Temperature Dependence of High Frequency Irreversible Electroporation Evaluated in a 3D Tumor Model.

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.

Simplified Non-Thermal Tissue Ablation With a Single Insertion Device Enabled by Bipolar High-Frequency Pulses.

Objective: To demonstrate the feasibility of a single electrode and grounding pad approach for delivering high frequency irreversible electroporation treatments (H-FIRE) in in-vivo hepatic tissue.

Methods: Ablations were created in porcine liver under surgical anesthesia by adminstereing high frequency bursts of 0.5-5.

High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones-A Laboratory Investigation Using Mechanically Perfused Liver.

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.

Burst and continuous high frequency irreversible electroporation protocols evaluated in a 3D tumor model.

High frequency irreversible electroporation (H-FIRE) is an emerging cancer therapy which uses bursts of alternating polarity pulses to target and destroy the membranes of cells within a predictable volume. Typically, 2 µs pulses are rapidly repeated 24-50 times to create a 48-100 µs long energy burst. Bursts are repeated 100×  at 1 Hz, resulting in an integrated energized time of 0.