Optimization of a single insertion electrode array for the creation of clinically relevant ablations using high-frequency irreversible electroporation

Sano, Michael B.; DeWitt, Matthew R.; Teeter, Stephanie D.; Li, Xing

doi:10.1016/j.compbiomed.2018.02.009

Cited by 24 publications

(12 citation statements)

References 43 publications

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“…associated with thermal injury. This could be especially useful for evaluating treatments using elevated voltages (3000-10,000 V), 47 alternative pulse timing strategies, 39 applicator arrays, 60 or in novel delivery approaches. 61 In addition, the model has been tuned to exhibit the physical properties of liver tissue.…”

Section: Figmentioning

confidence: 99%

Thermochromic Tissue Phantoms for Evaluating Temperature Distribution in Simulated Clinical Applications of Pulsed Electric Field Therapies

Sano

DeWitt

2020

Bioelectricity

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Background: Irreversible electroporation (IRE) induces cell death through nonthermal mechanisms, however, in extreme cases, the treatments can induce deleterious thermal transients. This study utilizes a thermochromic tissue phantom to enable visualization of regions exposed to temperatures above 60°C. Materials and Methods: Poly(vinyl alcohol) hydrogels supplemented with thermochromic ink were characterized and processed to match the electrical properties of liver tissue. Three thousand volt high-frequency IRE protocols were administered with delivery rates of 100 and 200 ls/s. The effect of supplemental internal applicator cooling was then characterized. Results: Baseline treatments resulted thermal areas of 0.73 cm 2 , which decreased to 0.05 cm 2 with electrode cooling. Increased delivery rates (200 ls/s) resulted in thermal areas of 1.5 and 0.6 cm 2 without and with cooling, respectively. Conclusions: Thermochromic tissue phantoms enable rapid characterization of thermal effects associated with pulsed electric field treatments. Active cooling of applicators can significantly reduce the quantity of tissue exposed to deleterious temperatures.

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Section: Figmentioning

confidence: 99%

Thermochromic Tissue Phantoms for Evaluating Temperature Distribution in Simulated Clinical Applications of Pulsed Electric Field Therapies

Sano

DeWitt

2020

Bioelectricity

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“…The size and shape of hypothetical clinical ablations were determined using a finite element model of a treatment using a single electrode applicator and a distal grounding pad (Sano et al 2016(Sano et al , 2018 which incorporated the lethal thresholds determined in vitro. The steady state electric field distribution within a simulated abdomen (figures 2(e) and (f)) was calculated using the 2D axisymmetric Electric Currents module in COMSOL Multiphysics, solving equations ( 1)-(3).…”

Section: Mathematical Modeling Of Clinical H -Fire Ablationsmentioning

confidence: 99%

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

et al. 2018

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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 0.01 s per treatment. A 3D in vitro tumor model was used to investigate H-FIRE parameters in search of optimal energy timing protocols. Monopolar IRE treatments (100 × 100 µs positive polarity pulses) resulted in a lethal electric field threshold of 423 V cm. Baseline H-FIRE treatments (100 × 100 µs bursts of 2 µs pulses) resulted in a lethal threshold of 818 V cm. Increasing the number of H-FIRE bursts from 100× to 1000× reduced the lethal threshold to 535 V cm. An alternative diffuse H-FIRE protocol, which delivers 4 µs pulse cycles (one positive and one negative 2 µs pulse) continuously at 100 Hz, resulted in the lowest H-FIRE lethal threshold of 476 V cm. Finite element simulations using 5 kV pulses predict an IRE ablation volume of 3.9 cm (1.7 cm diameter) and a maximum H-FIRE ablation volume of 5.3 cm (2.4 cm diameter) when a clinical electrode and grounding pad configuration is used. Ablations as large as 15.7 cm (3.3 cm diameter) are predicted for H-FIRE treatments with 10 kV pulses. These results combine to demonstrate the importance of electrode geometry, pulse timing, and clinical delivery protocols for the creation of large clinically meaningful ablations.

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“…H-FIRE replaces the 100-ls pulses in IRE with the bursts of bipolar pulses with much smaller pulse widths (0.25-50 ls). To simplify the discussion of the H-FIRE pulse waveforms in this paper, we have adopted the notion P-D-N mentioned in Sano et al [3], where P, D, and N are the positive pulse width, pulse delay, and negative pulse width, respectively, and they are all measured in microseconds.…”

Section: Introductionmentioning

confidence: 99%

“…They demonstrated that the H-FIRE pulse waveforms at 4000 V/cm did not cause muscle contractions in a rat model, nor did they cause a significant temperature increase. Since then, much work has been done to further explore the use of H-FIRE with various pulse waveforms by computational [3,5], in vitro [6][7][8], ex vivo [9][10][11], and in vivo [12][13][14][15] studies. Sano et al [6] looked at the use of H-FIRE pulse waveforms with a sub-microsecond pulse width (i.e., 0.25-2-0.25 and 0.5-2-0.5) in a pancreatic tumor cell in vitro cell suspension model and showed this modality was effective at causing cell death.…”

Section: Introductionmentioning

confidence: 99%

An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

Zhang

Liu

Fang

et al. 2021

International Journal of Hyperthermia

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Purpose: To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models in vivo for a custom-made high-frequency irreversible electroporation (H-FIRE) generator. Materials and Methods: A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols (n ¼ 3 for each protocol) and an IRE protocol (n ¼ 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively. Results: All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 ls, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 ls, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 ls, 2000 V, and 180 bursts). Conclusion: Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.

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Optimization of a single insertion electrode array for the creation of clinically relevant ablations using high-frequency irreversible electroporation

Cited by 24 publications

References 43 publications

Thermochromic Tissue Phantoms for Evaluating Temperature Distribution in Simulated Clinical Applications of Pulsed Electric Field Therapies

Thermochromic Tissue Phantoms for Evaluating Temperature Distribution in Simulated Clinical Applications of Pulsed Electric Field Therapies

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

An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

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