Modulating the Cell Death Immune Response for Electroporation Treatments.

Irreversible electroporation (IRE) is a minimally invasive ablation technique that compromises integrity of the cell membrane through the application of short duration, high voltage electric pulses to induce cell death. Adverse effects of IRE such as muscle contractions are reduced with higher frequency biphasic pulsing, commonly known as high-frequency irreversible electroporation (H-FIRE). IRE and H-FIRE treatments have shown to increase immune activation through the induction of both immediate and delayed cell death, indicated by the release of damage-associated molecular pathways, antigens, and proteins.

Tumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood-brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.

Toward Large Ablations With Single-Needle High-Frequency Irreversible Electroporation in Vivo.

Irreversible electroporation (IRE) is a minimally thermal tissue ablation modality used to treat solid tumors adjacent to critical structures. Widespread clinical adoption of IRE has been limited due to complicated anesthetic management requirements and technical demands associated with placing multiple needle electrodes in anatomically challenging environments. High-frequency irreversible electroporation (H-FIRE) delivered using a novel single-insertion bipolar probe system could potentially overcome these limitations, but ablation volumes have remained small using this approach.

Credibility assessment of in silico clinical trials for medical devices.

In silico clinical trials (ISCTs) are an emerging method in modeling and simulation where medical interventions are evaluated using computational models of patients. ISCTs have the potential to provide cost-effective, time-efficient, and ethically favorable alternatives for evaluating the safety and effectiveness of medical devices. However, ensuring the credibility of ISCT results is a significant challenge.

Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model.

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death.

Harnessing the Electrochemical Effects of Electroporation-Based Therapies to Enhance Anti-tumor Immune Responses.

This study introduces a new method of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue.

Spatiotemporal estimations of temperature rise during electroporation treatments using a deep neural network.

The nonthermal mechanism for irreversible electroporation has been paramount for treating tumors and cardiac tissue in anatomically sensitive areas, where there is concern about damage to nearby bowels, ducts, blood vessels, or nerves. However, Joule heating still occurs as a secondary effect of applying current through a resistive tissue and must be minimized to maintain the benefits of electroporation at high voltages. Numerous thermal mitigation protocols have been proposed to minimize temperature rise, but intraoperative temperature monitoring is still needed.

A sharp interface Lagrangian-Eulerian method for flexible-body fluid-structure interaction.

This paper introduces a sharp-interface approach to simulating fluid-structure interaction (FSI) involving flexible bodies described by general nonlinear material models and across a broad range of mass density ratios. This new flexible-body immersed Lagrangian-Eulerian (ILE) scheme extends our prior work on integrating partitioned and immersed approaches to rigid-body FSI. Our numerical approach incorporates the geometrical and domain solution flexibility of the immersed boundary (IB) method with an accuracy comparable to body-fitted approaches that sharply resolve flows and stresses up to the fluid-structure interface.

PIRET-A Platform for Treatment Planning in Electroporation-Based Therapies.

Unlabelled: Tissue electroporation is the basis of several therapies. Electroporation is performed by briefly exposing tissues to high electric fields. It is generally accepted that electroporation is effective where an electric field magnitude threshold is overreached.

Real-Time Temperature Rise Estimation during Irreversible Electroporation Treatment through State-Space Modeling.

To evaluate the feasibility of real-time temperature monitoring during an electroporation-based therapy procedure, a data-driven state-space model was developed. Agar phantoms mimicking low conductivity (LC) and high conductivity (HC) tissues were tested under the influences of high (HV) and low (LV) applied voltages. Real-time changes in impedance, measured by Fourier Analysis SpecTroscopy (FAST) along with the known tissue conductivity and applied voltages, were used to train the model.

Extended interpulse delays improve therapeutic efficacy of microsecond-duration pulsed electric fields.

Irreversible electroporation (IRE), or pulsed field ablation, employs microsecond-duration pulsed electric fields to generate targeted cellular damage without injury to the underlying tissue architecture. Biphasic, burst-type waveforms (termed high-frequency IRE, or H-FIRE) have garnered attention for their ability to elicit clinically relevant ablation volumes while reducing several undesirable side effects (muscle contractions/electrochemical effects) seen with monophasic pulses. Pulse width is generally the main (or only) parameter considered during burst construction, with little attention given to the delays within the burst.

A Comparative Modeling Study of Thermal Mitigation Strategies in Irreversible Electroporation Treatments.

Irreversible electroporation (IRE), also referred to as nonthermal pulsed field ablation (PFA), is an attractive focal ablation modality for solid tumors and cardiac tissue due to its ability to destroy aberrant cells with limited disruption of the underlying tissue architecture. Despite its nonthermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested as a potential means to limit thermal damage.

An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields.

The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing.

Properties of tissue within prostate tumors and treatment planning implications for ablation therapies.

Irreversible electroporation (IRE) is a promising alternative therapy for the local treatment of prostate tumors. The procedure involves the direct insertion of needle electrodes into the target zone, and subsequent delivery of short but high-voltage pulses. Successful outcomes rely on adequate exposure of the tumor to a threshold electrical field.

High-frequency irreversible electroporation brain tumor ablation: exploring the dynamics of cell death and recovery.

Improved therapeutics for malignant brain tumors are urgently needed. High-frequency irreversible electroporation (H-FIRE) is a minimally invasive, nonthermal tissue ablation technique, which utilizes high-frequency, bipolar electric pulses to precisely kill tumor cells. The mechanisms of H-FIRE-induced tumor cell death and potential for cellular recovery are incompletely characterized.

A Theoretical Argument for Extended Interpulse Delays in Therapeutic High-Frequency Irreversible Electroporation Treatments.

Unlabelled: High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay (d)-negative phase-interpulse delay (d) pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively.

Objective: We sought to determine whether modifications to the delays within H-FIRE bursts could yield a more desirable clinical outcome in terms of ablation volume versus extent of tissue excitation.

Full-field microscale strain measurements of a nitinol medical device using digital image correlation.

Computational modeling and simulation are commonly used during the development of cardiovascular implants to predict peak strains and strain amplitudes and to estimate the associated durability and fatigue life of these devices. However, simulation validation has historically relied on comparison with surrogate quantities like force and displacement due to barriers to direct strain measurement-most notably, the small spatial scale of these devices. We demonstrate the use of microscale two-dimensional digital image correlation (2D-DIC) to directly characterize full-field surface strains on a nitinol medical device coupon under emulated physiological and hyperphysiological loading.

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

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.

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology.

Irreversible electroporation (IRE) has established a clinical niche as an alternative to thermal ablation for the eradication of unresectable tumors, particularly those near critical vascular structures. IRE has been used in over 50 independent clinical trials and has shown clinical success when used as a standalone treatment and as a single component within combinatorial treatment paradigms. Recently, many studies evaluating IRE in larger patient cohorts and alongside other novel therapies have been reported.