Summary form only given. A new topologically-correct hybrid transformer model is developed for low- and mid-frequency transient simulations. Power transformers have a conceptually simple design, but behaviors can be very complex. Selection of the most suitable representation for a given behavior depends on the type of transformer to be simulated, the frequency range, and other factors such as the internal design of the transformer and available parameters or design data. Here, a modular model suitable for frequencies up to 3-5 kHz is developed, utilizing a duality-based lumped-parameter saturable core, matrix descriptions of leakage and capacitive effects, and frequency-dependent coil resistance. Implementation and testing of this model was done for 15-kVA 208D-120Y 3-legged and 150 kVA 12, 470Y-208Y 5-legged transformers. The basis and development of the model is presented, along with a discussion of necessary parameters and the approaches for obtaining them.

Hybrid Transformer Model for Transient Simulation: Part I - Development and Parameters

High-frequency irreversible electroporation (H-FIRE) has emerged as an alternative to conventional irreversible electroporation (IRE) to overcome the issues associated with neuromuscular electrical stimulation that appear in IRE treatments. In H-FIRE, the monopolar pulses typically used in IRE are replaced with bursts of short bipolar pulses. Currently, very little is known regarding how the use of a different waveform affects the cell death dynamics and mechanisms. In this study, human pancreatic adenocarcinoma cells were treated with a typical IRE protocol and various H-FIRE schemes with the same energized time. Cell viability, membrane integrity and Caspase 3/7 activity were assessed at different times after the treatment. In both treatments, we identified two different death dynamics (immediate and delayed) and we quantified the electric field ranges that lead to each of them. While in the typical IRE protocol, the electric field range leading to a delayed cell death is very narrow, this range is wider in H-FIRE and can be increased by reducing the pulse length. Membrane integrity in cells suffering a delayed cell death shows a similar time evolution in all treatments, however, Caspase 3/7 expression was only observed in cells treated with H-FIRE.

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Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

Irreversible Electroporation of the Pancreas: Definitive Local Therapy without Systemic Effects

For irreversible-electroporation (IRE)-based therapies, the underlying electric field distribution in the target tissue is influenced by the electroporation-induced conductivity changes and is important for predicting the treatment zone. Objective: In this study, we characterized the liver tissue conductivity changes during high-frequency irreversible electroporation (H-FIRE) treatments of widths 5 and 10 μs and proposed a method for predicting the ablation zones. Methods: To achieve this, we created a finite-element model of the tissue treated with H-FIRE and IRE pulses based on experiments conducted in an in-vivo rabbit liver study. We performed a parametric sweep on a Heaviside function that captured the tissue conductivity versus electric field behavior to yield a model current close to the experimental current during the first burst/pulse. A temperature module was added to account for the current increase in subsequent bursts/pulses. The evolution of the electric field at the end of the treatment was overlaid on the experimental ablation zones determined from hematoxylin and eosin staining to find the field thresholds of ablation. Results: Dynamic conductivity curves that provided a statistically significant relation between the model and experimental results were determined for H-FIRE. In addition, the field thresholds of ablation were obtained for the tested H-FIRE parameters. Conclusion: The proposed numerical model can simulate the electroporation process during H-FIRE. Significance: The treatment planning method developed in this study can be translated to H-FIRE treatments of different widths and for different tissue types.

Characterization of Conductivity Changes During High-Frequency Irreversible Electroporation for Treatment Planning

Irreversible electroporation, as a nonthermal therapy of prostate cancer, has been used in clinic for several years The mechanism of irreversible electroporation ablation is thermal independent; thus, the main structures (eg, rectum, urethra, and neurovascular bundle) in prostate are spared during the treatment, which leads to the retention of prostate function However, various clinical trials have shown that muscle contractions occur during this therapy, which warrants deep muscle anesthesia Use of high-frequency bipolar pulses has been proposed to reduce muscle contractions during treatment, which has already triggered a multitude of studies at the cellular and animal scale In this study, we first investigated the efficacy and safety of high-frequency bipolar pulses in human prostate cancer ablation There are 40 male patients with prostate cancer aged between 51 and 85 years involved in this study All patients received 250 high-frequency bipolar pulse bursts with the repeat frequency of 1 Hz Each burst comprised 20 individual pulses of 5 microseconds, so one burst total energized time was 100 microseconds The number of the electrodes ranged 2 to 6, depending on tumor size A small amount of muscle relaxant was still needed, so there were no visible muscle contractions during the pulse delivery process Four weeks after treatment, it was found that the ablation margins were distinct in magnetic resonance imaging scans, and the prostate capsule and urethra were retained Eight patients underwent radical prostatectomy for pathological analysis after treatment, and the results of hematoxylin and eosin staining revealed that the urethra and major vasculature in prostate have been preserved By overlaying the electric field contour on the ablation zone, the electric field lethality threshold is determined to be 522 ± 74 V/cm This study is the first to validate the feasibility of tumor ablation by high-frequency bipolar pulses and provide valuable experience of irreversible electroporation in clinical applications

https://journals.sagepub.com/doi/pdf/10.1177/1533033818789692

First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer.

Objective: To minimize the effect of muscle contractions during irreversible electroporation (IRE), this paper attempts to research the ablation effect and muscle contractions by applying high-frequency IRE (H-FIRE) ablation to liver tissue in vivo . Methods: An insulated needle electrode was produced by painting an insulating coating on the outer surface of the needle electrode tip. A series of experiments were conducted using insulated needle electrodes and traditional needle electrodes to apply H-FIRE pulses and traditional monopolar IRE pulses to rabbit liver tissues. The finite element model of the rabbit liver tissue was established to determine the lethal thresholds of H-FIRE in liver tissues. Muscle contractions were measured by an accelerometer. Results: With increased constitutive pulse width and pulse voltage, the ablation area and muscle contraction strength are also increased, which can be used to optimize the ablation parameters of H-FIRE. Under the same pulse parameters, the ablation areas are similar for the two types of electrodes, and the ablation region has a clear boundary. H-FIRE and insulated needle electrodes can mitigate the extent of muscle contractions. The lethal thresholds of H-FIRE in rabbit liver tissues were determined. Conclusion: This paper describes the relationships between the ablation area, muscle contractions, and pulse parameters; the designed insulated needle electrodes can be used in IRE for reducing muscle contraction. Significance: The study provides guidance for treatment planning and reducing muscle contractions in the clinical application of H-FIRE.

Bipolar Microsecond Pulses and Insulated Needle Electrodes for Reducing Muscle Contractions During Irreversible Electroporation

High-frequency bipolar high-voltage pulsed electric field can be used in tumor ablation to uniform the electric field distribution in the ablated region and inhibit muscle contraction effectively. Developing a high-frequency bipolar pulsed power generator (HBPPG) with wide range of specifications, such as voltage magnitude, waveform, repetition rate, and pulsewidth, is of great significance for promoting the clinical application of irreversible electroporation. Hence, in this article, a novel modular high-voltage HBPPG circuit topology is proposed for such application. Each module consists of an H-bridge and an isolated inductor. Theoretical analysis, simulation, and experimental results show that this generator perfectly combines the advantages of solid-state Marx and bridge circuit, with high stability and redundancy. The pulse frequency, pulse duration, and waveform can be flexibly adjusted by a controller software algorithm according to load parameters. The viability of the proposed HBPPG is demonstrated by PSpice simulation and equal-scale prototype. The key parameters of the developed HBPPG are as follows: voltage amplitude up to ±10 kV with 500 ns–5 μ s pulsewidths, 500 kHz within the burst, and 10 kHz within the continuation limited by the input high-voltage dc power supply. All the pulse parameters can be programmed arbitrarily.

A Novel High-Frequency Bipolar Pulsed Power Generator for Biological Applications

Irreversible electroporation (IRE) uses ~100 μs pulsed electric fields to disrupt cell membranes for solid tumor ablation. Although IRE has achieved exciting preliminary clinical results, implementing IRE could be challenging because of volumetric limitations at the ablation region. Combining short high-voltage (SHV: 1600V, 2 μs, 1 Hz, 20 pulses) pulses with long low-voltage (LLV: 240–480 V, 100 μs, 1 Hz, 60–80 pulses) pulses induces a synergistic effect that enhances IRE efficacy. Here, cell cytotoxicity and tissue ablation were investigated. The results show that combining SHV pulses with LLV pulses induced SKOV3 cell death more effectively, and compared to either SHV pulses or LLV pulses applied alone, the combination significantly enhanced the ablation region. Particularly, prolonging the lag time (100 s) between SHV and LLV pulses further reduced cell viability and enhanced the ablation area. However, the sequence of SHV and LLV pulses was important, and the LLV + SHV combination was not as effective as the SHV + LLV combination. We offer a hypothesis to explain the synergistic effect behind enhanced cell cytotoxicity and enlarged ablation area. This work shows that combining SHV pulses with LLV pulses could be used as a focal therapy and merits investigation in larger pre-clinical models and microscopic mechanisms.

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Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

With the increasingly extensive and in-depth applications of all solid-state high-voltage nanosecond pulse generators in the defense and industrial fields, the development of traditional pulse generators faces many key issues, such as high-voltage drive isolation, compact design, and reduced weight. Hence, a novel circuit topology for a self-triggered high-frequency nanosecond pulse generator is proposed. Through high potential energy-gaining technology of the interstage capacitance, this generator does not need a complicated metal–oxide–semiconductor field-effect transistor isolation drive circuit, and there are also no switching dynamic and static voltage equalization problems. This kind of generator is very suitable for compact assembly with only a single external gate driver. High voltage output can be realized by quantizing multilevel module stacking according to actual needs. At the same time, the generator has a high repetition rate and long life. The characteristic parameters of the 20-stage superposition experimental prototype are as follows: an output voltage amplitude of 15.3 kV with a rising time of approximately 45 ns, a repetition rate of 10 kHz in the pulse train, and a pulsewidth of 200–1000 ns.

Self-Triggering High-Frequency Nanosecond Pulse Generator

In this work, we study the performance of sub-gradient method (SubGM) on a natural nonconvex and nonsmooth formulation of low-rank matrix recovery with $\ell_1$-loss, where the goal is to recover a low-rank matrix from a limited number of measurements, a subset of which may be grossly corrupted with noise. We study a scenario where the rank of the true solution is unknown and over-estimated instead. The over-estimation of the rank gives rise to an over-parameterized model in which there are more degrees of freedom than needed. Such over-parameterization may lead to overfitting, or adversely affect the performance of the algorithm. We prove that a simple SubGM with small initialization is agnostic to both over-parameterization and noise in the measurements. In particular, we show that small initialization nullifies the effect of over-parameterization on the performance of SubGM, leading to an exponential improvement in its convergence rate. Moreover, we provide the first unifying framework for analyzing the behavior of SubGM under both outlier and Gaussian noise models, showing that SubGM converges to the true solution, even under arbitrarily large and arbitrarily dense noise values, and--perhaps surprisingly--even if the globally optimal solutions do not correspond to the ground truth. At the core of our results is a robust variant of restricted isometry property, called Sign-RIP, which controls the deviation of the sub-differential of the $\ell_1$-loss from that of an ideal, expected loss. As a byproduct of our results, we consider a subclass of robust low-rank matrix recovery with Gaussian measurements, and show that the number of required samples to guarantee the global convergence of SubGM is independent of the over-parameterized rank.

Jianhao Ma

Papers

Bipolar Microsecond Pulses and Insulated Needle Electrodes for Reducing Muscle Contractions During Irreversible Electroporation

A Novel High-Frequency Bipolar Pulsed Power Generator for Biological Applications

Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

Self-Triggering High-Frequency Nanosecond Pulse Generator

Global Convergence of Sub-gradient Method for Robust Matrix Recovery: Small Initialization, Noisy Measurements, and Over-parameterization