scholarly journals Development of a thermal model for irreversible electroporation: an approach to estimate and optimize the IRE protocols

2021 ◽  
Author(s):  
Girindra Wardhana ◽  
João Pedro Almeida ◽  
Momen Abayazid ◽  
Jurgen J. Fütterer
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Bovine Liver ◽  
Input Voltage ◽  
Pulse Parameter ◽  
Active Electrode ◽  
Treatment Protocols ◽  
Temperature Changes ◽  
Electric Pulses ◽  
Ablation Area

Abstract Purpose Irreversible electroporation (IRE) is an emerging technique that has drawn attention in the field of cancer treatment. IRE uses non-thermal electric pulses to induce death of cancerous cells. However, recent studies have shown that the application of this technique may result in heating of the tissue. There is still room for improving its efficiency and defining better treatment protocols. This study investigates the optimal IRE protocols that avoiding the thermal damage during the IRE treatment. Methods Electrode and pulse parameter are investigated. Finite element models are created to evaluate the ablation area and the temperature changes in the tissue. The model is validated experimentally in bovine liver tissue, while the parameters were optimized using response surface method (RSM). Results From analysis of variance, the parameter of electrode distance and input voltage has significant effect to the temperature rise in the IRE treatment of bovine liver (P = 0.020 and P = 0.003 respectively). Meanwhile, only the input voltage significantly affects the ablation area (P < 0.001). The optimal result from RSM showed that for maximum ablation area 250.82mm2 with no thermal damage, the IRE protocol consisted of an active electrode length of 10 mm, a distance between electrodes of 10 mm, and the delivery of 50 pulses of 41.21 µs and 3000 V. Conclusions The approach presented in this study allows the optimization of the IRE protocols. An optimal IRE protocol that maximizes the ablation area was successfully calculated which can be applied with no risk of thermal damage to the tissue.

scholarly journals A Study on Nonthermal Irreversible Electroporation of the Thyroid

2019 ◽  
Vol 18 ◽  
pp. 153303381987630
Author(s):  
Yanpeng Lv ◽  
Yanfang Zhang ◽  
Jianwei Huang ◽  
Yunlong Wang ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Pulse Sequences ◽  
Cell Swelling ◽  
Tissue Type ◽  
Heterogeneous Structure ◽  
Treatment Protocols ◽  
Thyroid Ablation ◽  
Nonthermal Irreversible Electroporation

Background: Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation. Methods: Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results. Results: Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage. Conclusion: Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.

A Method to Delineate Irreversible Electroporation From Thermal Damage Validated Ex Vivo With Real-Time Temperature

2011 ◽  
Author(s):  
Paulo A. Garcia ◽  
John H. Rossmeisl ◽  
Thomas L. Ellis ◽  
Rafael V. Davalos
Keyword(s):  
Transmembrane Potential ◽  
Thermal Damage ◽  
Ex Vivo ◽  
Irreversible Electroporation ◽  
High Grade Glioma ◽  
Low Energy ◽  
Tissue Ablation ◽  
High Grade ◽  
Electric Pulses ◽  
Increase Membrane Permeability

Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death [1]. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with pulse delivery of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells [1]. Depending on the magnitude of the induced TMP, the electric pulses can have no effect, transiently increase membrane permeability, or cause cell death [1]. Our group has confirmed the safety of the procedure in brain with three experimental dogs [2]. We also treated a canine patient with IRE and radiation therapy for a non-resectable, high-grade glioma, resulting in complete remission of the tumor at four months [3].

scholarly journals Mathematical Modeling of Irreversible Electroporation for Treatment Planning

2007 ◽  
Vol 6 (4) ◽  
pp. 275-286 ◽  
Author(s):  
Jon F. Edd ◽  
Rafael V. Davalos
Keyword(s):  
Cancer Therapy ◽  
Treatment Planning ◽  
Lipid Bilayers ◽  
Irreversible Electroporation ◽  
Biological Tissues ◽  
Electrode Spacing ◽  
Treatment Protocols ◽  
Electric Pulses ◽  
Pulse Parameters ◽  
Wide Range

Irreversible Electroporation (IRE) is a new drug-free method to ablate undesirable tissue of particular use in cancer therapy. IRE achieves cell death within the targeted tissue through a series of electric pulses that elevate the transmembrane potentials to an extent that permanently damages the lipid bilayers throughout the treated region. Although the IRE procedure is easy to perform, treatment planning is complicated by the fact that the electric field distribution within the tissue, the greatest single factor controlling the extents of IRE, depends non-trivially on the electrode configuration, pulse parameters and any tissue heterogeneities. To address this difficulty, we instruct on how to properly model IRE and discuss the benefit of modeling in designing treatment protocols. The necessary theoretical basis is introduced and discussed through the detailed analysis of two classic dual-electrode configurations from electrochemotherapy: coaxial disk electrodes and parallel needle electrodes. Dimensionless figures for these cases are also provided that allow cell constants, treated areas, and the details of heating to be determined for a wide range of conditions, for uniform tissues, simply by plugging in the appropriate physical property values and pulse parameters such as electrode spacing, size, and pulse amplitude. Complexities, such as heterogeneous tissues and changes in conductivity due to electroporation, are also discussed. The synthesis of these details can be used directly by surgeons in treatment planning. Irreversible electroporation is a promising new technique to treat cancer in a targeted manner without the use of drugs; however, it does require a detailed understanding of how electric currents flow within biological tissues. By providing the understanding and tools necessary to design an IRE protocol, this study seeks to facilitate the translation of this new and exciting cancer therapy into clinical practice.

scholarly journals Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Tomaz Jarm ◽  
Tadej Krmac ◽  
Ratko Magjarevic ◽  
Bor Kos ◽  
Helena Cindric ◽  
...  
Keyword(s):  
Pulse Generator ◽  
Irreversible Electroporation ◽  
Residual Effects ◽  
Ventricular Pacing ◽  
Experimental Conditions ◽  
Active Electrode ◽  
Cardiac Pacemakers ◽  
Electric Pulses ◽  
Treatment Zone ◽  
Tissue Heating

Abstract Background The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy? Results The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw. Conclusions The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.

Hyperspectral image-based analysis of thermal damage for ex-vivo bovine liver utilizing radiofrequency ablation

2021 ◽  
pp. 101564
Author(s):  
Mohamed Hisham Aref ◽  
Ibrahim H. Aboughaleb ◽  
Abou-Bakr M. Youssef ◽  
Yasser H. El-Sharkawy
Keyword(s):  
Radiofrequency Ablation ◽  
Thermal Damage ◽  
Hyperspectral Image ◽  
Ex Vivo ◽  
Bovine Liver

Effect of Three-Dimensional Electric Field and Heat Conduction to Electrodes on the Temperature Rise During Irreversible Electroporation

2011 ◽  
Author(s):  
Seiji Nomura ◽  
Kosaku Kurata ◽  
Hiroshi Takamatsu
Keyword(s):  
Heat Conduction ◽  
Electric Field ◽  
Temperature Rise ◽  
Heat Conduction Equation ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Three Dimensional ◽  
End Effects ◽  
Abnormal Cells ◽  
Novel Method

The irreversible electroporation (IRE) is a novel method to ablate abnormal cells by applying a high voltage between two electrodes that are stuck into abnormal tissues. One of the advantages of the IRE is that the extracellular matrix (ECM) may be kept intact, which is favorable for healing. For a successful IRE, it is therefore important to avoid thermal damage of ECM resulted from the Joule heating within the tissue. A three-dimensional (3-D) analysis was conducted in this study to predict temperature rise during the IRE. The equation of electric field and the heat conduction equation were solved numerically by a finite element method. It was clarified that the highest temperature rise occurred at the base of electrodes adjacent to the insulated surface. The result was significantly different from a two-dimensional (2-D) analysis due to end effects, suggesting that the 3-D analysis is required to determine the optimal condition.

Adapting the Cassini Curve to Approximate In Vivo Irreversible Electroporation Ablations in Porcine Liver

2013 ◽  
Author(s):  
Paulo A. Garcia ◽  
Christopher B. Arena ◽  
Robert E. Neal ◽  
S. Nahum Goldberg ◽  
Eliel Ben-David ◽  
...  
Keyword(s):  
Cell Death ◽  
Transmembrane Potential ◽  
Tumor Tissue ◽  
Irreversible Electroporation ◽  
Low Energy ◽  
Porcine Liver ◽  
Electric Pulses ◽  
Focal Ablation ◽  
Increase Membrane Permeability

Irreversible electroporation (IRE) is a new minimally invasive non-thermal focal ablation technique that has been used for the treatment of spontaneous tumors in canine and human patients [1, 2]. The procedure typically involves placing two electrodes into or around a tumor and delivering a series of low energy electric pulses to kill tumor tissue with sub-millimeter resolution. The pulses generate an electric field that alters the resting transmembrane potential (TMP) of the cells. Depending on the magnitude of the induced TMP, the electric pulses can have no effect, reversibly increase membrane permeability, or cause cell death in the case of IRE.

Ultrasound Hyperthermia: Dose Estimation and Device Design

2012 ◽  
Author(s):  
Danica Gordon ◽  
Chandrasekhar Thamire
Keyword(s):  
Cancer Treatment ◽  
Treatment Modality ◽  
Thermal Damage ◽  
Operating Parameter ◽  
Cell Types ◽  
Temperature History ◽  
Device Design ◽  
High Frequency Ultrasound ◽  
Treatment Protocols ◽  
Thermal Coagulation

As a cancer treatment modality, thermal ablation offers the advantages of being less invasive and posing fewer post-procedural complications compared to traditional cancer therapies. It involves destroying cancerous cells by subjecting them to the appropriate amount of heat dose. In the present study, high frequency ultrasound (US) ablation is theoretically examined for effectiveness as a treatment modality for intraluminal and extracorporeal cancer treatment. Objectives of this study are to 1) develop thermal-damage correlations for a variety of cancer cells and 2) design US treatment devices, based on thermal damage correlations developed, and treatment planning protocols. To achieve these goals, thermal damage information for different cell types is first determined from earlier studies or pilot experiments. Required US doses for specific tissues are determined next through numerical experiments. Device design and estimation of thermal coagulation contours is then performed by comparing temperature-history data against the thermal-damage data for a range of device parameters. Treatment protocols are finally developed based on the analysis of the results for a range of applicable device parameters. Results are presented in terms of correlations for the volume and location of ablated tissue corresponding to a range of operating parameter values.

Ultrasound Hyperthermia: Dose Estimation and Device Design for Intraluminal and External Delivery

2012 ◽  
Author(s):  
Danica Gordon ◽  
Chandrasekhar Thamire
Keyword(s):  
Thermal Damage ◽  
Treatment Time ◽  
The Body ◽  
Thermal Therapy ◽  
Surrounding Tissue ◽  
Temperature History ◽  
Published Data ◽  
Device Design ◽  
Treatment Protocols ◽  
Thermal Coagulation

Thermal ablation in the context of this study refers to destroying cancer cells by heating them to supraphysiological temperatures for appropriate times. Once the tumor cells and a small layer of surrounding tissue cells are killed, they are absorbed by the body over time. Compared to open surgery, radiation, and chemotherapy, thermal therapy can be less expensive and pose less risk of harmful post-procedural complications, while possessing the potential to be effective [1]. Currently microwave and radiofrequency ablation are in use for local hyperthermia; however, they lack the ability to focus heat into the target zones effectively or treat larger tumors without affecting the surrounding healthy tissue. In the current study, high frequency ultrasound (US) ablation is examined as a treatment modality because of its ability to focus and control heat effectively. Objectives of this study are to 1) develop thermal-damage correlations for US thermal therapy and 2) design delivery devices and associated treatment planning protocols. To achieve these goals, thermal damage information is first evaluated for a variety of cells and tissues from published data or pilot experiments. Required US dose levels are determined next through numerical experiments, followed by device design and estimation of thermal coagulation contours by comparing the temperature-history data against the thermal-damage data. Based on the analysis of the results for a range of parameters, namely, the applicator power, geometry, frequency, coolant parameters, treatment time, and tissue perfusion, treatment protocols are developed. Intraluminal, external, and interstitial modes of delivery are considered for focal sites in a variety of target areas. In the following sections, methods followed and sample results obtained are presented.

In Vivo Validation of Irreversible Electroporation Electric Field Threshold for Prostate Tissue

2013 ◽  
Author(s):  
Robert E. Neal ◽  
Helen Kavnoudias ◽  
Franklin Rosenfeldt ◽  
Ruchong Ou ◽  
James Marron ◽  
...  
Keyword(s):  
Thermal Ablation ◽  
Conventional Treatment ◽  
Irreversible Electroporation ◽  
Blood Perfusion ◽  
Complete Regression ◽  
Safety Study ◽  
Electric Pulses ◽  
Transmembrane Potentials ◽  
Focal Ablation

Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses needle electrodes to deliver a series of brief (100μs duration) electric pulses into the targeted region. These alter cellular transmembrane potentials, destabilizing the membranes in a manner that kills the cells while sparing major vasculature and other sensitive structures. IRE can therefore be used in regions ineligible for surgical resection or thermal ablation. Treatments result in rapid lesion creation and resolution [1], are unaffected by the blood perfusion “heat sink”, can be planned with numerical modeling [2], and its effects can be readily monitored with various imaging modalities [3]. Therapeutic ire has proven effective in the treatment of experimental [4] and clinical tumors. A human safety study attained complete regression in 46 of 69 tumors ineligible or unresponsive to conventional treatment [5], and veterinary case studies convey its utility in large difficult tumors [6, 7].

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