Showing papers on "Irreversible electroporation published in 2009"

In vivo electrical conductivity measurements during and after tumor electroporation: conductivity changes reflect the treatment outcome.

Abstract: Electroporation is the phenomenon in which cell membrane permeability is increased by exposing the cell to short high-electric-field pulses. Reversible electroporation treatments are used in vivo for gene therapy and drug therapy while irreversible electroporation is used for tissue ablation. Tissue conductivity changes induced by electroporation could provide real-time feedback of the treatment outcome. Here we describe the results from a study in which fibrosarcomas (n = 39) inoculated in mice were treated according to different electroporation protocols, some of them known to cause irreversible damage. Conductivity was measured before, within the pulses, in between the pulses and for up to 30 min after treatment. Conductivity increased pulse after pulse. Depending on the applied electroporation protocol, the conductivity increase after treatment ranged from 10% to 180%. The most significant conclusion from this study is the fact that post-treatment conductivity seems to be correlated with treatment outcome in terms of reversibility.

Balloon catheter method for reducing restenosis via irreversible electroporation

Abstract: Restenosis or neointimal formation may occur following angioplasty or other trauma to an artery such as by-pass surgery. This presents a major clinical problem which narrows the artery. The invention provides a balloon catheter with a particular electrode configuration. Also provided is a method whereby vascular cells in the area of the artery subjected to the trauma are subjected to irreversible electroporation which is a non-thermal, non-pharmaceutical method of applying electrical pulses to the cells so that substantially all of the cells in the area are ablated while leaving the structure of the vessel in place and substantially unharmed due to the non-thermal nature of the procedure.

Non thermal irreversible electroporation: Novel technology for vascular smooth muscle cells ablation

Abstract: Background Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.

The feasibility of irreversible electroporation for the treatment of breast cancer and other heterogeneous systems.

Abstract: Developments in breast cancer therapies show potential for replacing simple and radical mastectomies with less invasive techniques. Localized thermal techniques encounter difficulties, preventing their widespread acceptance as replacements for surgical resection. Irreversible electroporation (IRE) is a non-thermal, minimally invasive focal ablation technique capable of killing tissue using electric pulses to create irrecoverable nano-scale pores in the cell membrane. Its unique mechanism of cell death exhibits benefits over thermal techniques including rapid lesion creation and resolution, preservation of the extracellular matrix and major vasculature, and reduced scarring. This study investigates applying IRE to treat primary breast tumors located within a fatty extracellular matrix despite IREs dependence on the heterogeneous properties of tissue. In vitro experiments were performed on MDA-MB-231 human mammary carcinoma cells to determine a baseline electric field threshold (1000 V/cm) to cause IRE for a given set of pulse parameters. The threshold was incorporated into a three-dimensional numerical model of a heterogeneous system to simulate IRE treatments. Treatment-relevant protocols were found to be capable of treating targeted tissue over a large range of heterogeneous properties without inducing significant thermal damage, making IRE a potential modality for successfully treating breast cancer. Information from this study may be used for the investigation of other heterogeneous tissue applications for IRE.

Electrical field and temperature model of nonthermal irreversible electroporation in heterogeneous tissues.

Abstract: Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive surgical technique that is part of the emerging field of molecular surgery, which holds the potential to treat diseases with unprecedented accuracy. NTIRE utilizes electrical pulses delivered to a targeted area, producing irreversible damage to the cell membrane. Because NTIRE does not cause thermal damage, the integrity of all other molecules, collagen, and elastin in the targeted area is preserved. Previous theoretical studies have only examined NTIRE in homogeneous tissues; however, biological structures are complex collections of diverse tissues. In order to develop electroporation as a precise treatment in clinical applications, realistic models are necessary. Therefore, the purpose of this study was to refine electroporation as a treatment by examining the effect of NTIRE in heterogeneous tissues of the prostate and breast. This study uses a two-dimensional finite element solution of the Laplace and bioheat equations to examine the effects of heterogeneities on electric field and temperature distribution. Three different heterogeneous structures were taken into account: nerves, blood vessels, and ducts. The results of this study demonstrate that heterogeneities significantly impact both the temperature and electrical field distribution in surrounding tissues, indicating that heterogeneities should not be neglected. The results were promising. While the surrounding tissue experienced a high electrical field, the axon of the nerve, the interior of the blood vessel, and the ducts experienced no electrical field. This indicates that blood vessels, nerves, and lactiferous ducts adjacent to a tumor treated with electroporation will survive, while the cancerous lesion is ablated. This study clearly demonstrates the importance of considering heterogeneity in NTIRE applications.

Electroporation in Biological Cell and Tissue: An Overview

Abstract: In this chapter, basics and mechanisms of electroporation are presented. Most important electric pulse parameters for electroporation efficiency for different applications that involve introduction of small molecules and macromolecules into the cell or cell membrane electrofusion are described. In all these applications, cell viability has to be preserved. However, in some biotechnological applications, such as liquid food sterilization or water treatment, electroporation is used as a method for efficient cell killing. For all the applications mentioned above, besides electric pulse parameters, other factors, such as electroporation medium composition and osmotic pressure, play significant roles in electroporation effectiveness. For controlled use of the method in all applications, the basic mechanisms of electroporation need to be known. The phenomenon was studied from the single-cell level and dense cell suspension that represents a simplified homogenous tissue model, to complex biological tissues. In the latter, different cell types and electric conductivity that change during the course of electric pulse application can significantly affect the effectiveness of the treatment. For such a complex situation, the design and use of suitable electrodes and theoretical modeling of electric field distribution within the tissue are essential. Electroporation as a universal method applicable to different cell types is used for different purposes. In medicine it is used for electrochemotherapy and genetherapy. In biotechnology it is used for water and liquid food sterilization and for transfection of bacteria, yeast, plant protoplast, and intact plant tissue. Understanding the phenomenon of electroporation, its mechanisms and optimization of all the parameters that affect electroporation is a prerequisite for successful treatment. In addition to the parameters mentioned above, different biological characteristics of treated cell affect the outcome of the treatment. Electroporation, gene electrotransfer and electrofusion are affected by cell membrane fluidity, cytoskeleton, and the presence of the cell wall in bacteria yeast and plant cells. Thus, electroporation parameters need to be specifically optimized for different cell types.

Irreversible electroporation using nanoparticles

Abstract: The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors. In embodiments, the methods comprise the use of high aspect ratio nanoparticles with or without modified surface chemistry.

Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

Abstract: Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism to inducing _apoptosis, we use a multicellular system model (spatial scale 100 microm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.

In vivo imaging of irreversible electroporation by means of electrical impedance tomography

Abstract: Electroporation, the increased permeability of cell membranes due to a large transmembrane voltage, is an important clinical tool. Both reversible and irreversible in vivo electroporation are used for clinical applications such as gene therapy and solid malignant tumor ablation, respectively. The primary advantage of in vivo electroporation is the ability to treat tissue in a local and minimally invasive fashion. The drawback is the current lack of control over the process. This paper is the first report of a new method for real-time three-dimensional imaging of an in vivo electroporation process. Using two needle electrodes for irreversible electroporation and a set of electrodes for reconstructing electrical impedance tomography (EIT) images of the treated tissue, we were able to demonstrate electroporation imaging in rodent livers. Histology analysis shows good correlation between the extent of tissue damage caused by irreversible electroporation and the EIT images. This new method may lead the way to real-time control over genetic treatment of diseases in tissue and tissue ablation.

Electric Field Redistribution due to Conductivity Changes during Tissue Electroporation: Experiments with a Simple Vegetal Model

Abstract: Electroporation, or electropermeabilization, is the phenomenon in which cell membrane permeability to ions and macromolecules is increased by exposing the cell to short high electric field pulses. In living tissues, such permeabilization boost can be used in order to enhance the penetration of drugs (electrochemotherapy) or DNA plasmids (electrogenetherapy) or to destroy undesirable cells (irreversible electroporation). During the application of the high voltage pulses required for in vivo electroporation treatments, the conductivity of the involved tissues increases due to the electroporation phenomenon. This alteration results in a redistribution of the electric field magnitude that should be taken into account at treatment planning in order to foresee the areas that will be treated by electroporation. In the last five years some authors have indeed started to include such conductivity alteration in their simulation models. However, little experimental evidence has been provided to support the fact that conductivity changes really have a significant role on the electric field distribution. By reporting experiments on potato tuber, here we show that conductivity increase due to electroporation has indeed a significant physiological effect on the result of the application of the pulses. For instance, we noticed that by taking into account such conductivity alteration during simulations the error in electroporated area estimation went down from 30 % to 3 % in a case in which electroporation was performed with two parallel needles. Furthermore we also show that the field redistribution process occurs in two stages: an immediate and fast (< 5 μs) redistribution after the pulse onset, probably only held up by the cell membrane charging process, and a slower, and less significant, redistribution afterwards probably related to slow, and moderate, changes in tissue conductivity during the pulse.

Irreversible electroporation to create tissue scaffolds

Abstract: The present invention provides engineered tissue scaffolds, engineered tissues, and methods of using them. The scaffolds and tissues are derived from natural tissues and are created using non-thermal irreversible electroporation (IRE). Use of IRE allows for ablation of cells of the tissue to be treated, but allows vascular and neural structures to remain essentially unharmed. Use of IRE thus permits preparation of thick tissue scaffolds and tissues due to the presence of vasculature within the scaffolds. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

Pilot study of irreversible electroporation for intracranial surgery

Abstract: Irreversible electroporation (IRE) is a new minimally invasive technique to treat cancer using intense but short electric pulses. This technique is unique because of its non-thermal mechanism of tissue ablation. Furthermore it can be predicted with numerical models and can be confirmed with ultrasound and MRI. We present some preliminary results on the safety of using irreversible electroporation for canine brain surgery. We also present the electric field (460 V/cm – 560 V/cm) necessary for focal ablation of canine brain tissue and provide some guidelines for treatment planning and execution. This preliminary study is the first step towards using irreversible electroporation as a brain cancer treatment.

A Preliminary Study to Delineate Irreversible Electroporation From Thermal Damage Using the Arrhenius Equation

Abstract: Intense but short electrical fields can increase the permeability of the cell membrane in a process referred to as electroporation. Reversible electroporation has become an important tool in biotechnology and medicine. The various applications of reversible electroporation require cells to survive the procedure, and therefore the occurrence of irreversible electroporation (IRE), following which cells die, is obviously undesirable. However, for the past few years, IRE has begun to emerge as an important minimally invasive nonthermal ablation technique in its own right as a method to treat tumors and arrhythmogenic regions in the heart. IRE had been studied primarily to define the upper limit of electrical parameters that induce reversible electroporation. Thus, the delineation of IRE from thermal damage due to Joule heating has not been thoroughly investigated. The goal of this study was to express the upper bound of IRE (onset of thermal damage) theoretically as a function of physical properties and electrical pulse parameters. Electrical pulses were applied to THP-1 human monocyte cells, and the percentage of irreversibly electroporated (dead) cells in the sample was quantified. We also determined the upper bound of IRE (onset of thermal damage) through a theoretical calculation that takes into account the physical properties of the sample and the electric pulse characteristics. Our experimental results were achieved below the theoretical curve for the onset of thermal damage. These results confirm that the region to induce IRE without thermal damage is substantial. We believe that our new theoretical analysis will allow researchers to optimize IRE parameters without inducing deleterious thermal effects.

Method for Treatment of Complications Associated with Arteriovenous Grafts and Fistulas Using Electroporation

Abstract: Electroporation devices and methods for use in the treatment of complications, such as thrombosis, stenotic segments, or infections, associated with an arteriovenous graft or fistula are provided. The devices include at least two electrodes. The electrodes are adapted to be positioned near the target zone of complication for applying electrical pulses and thereby causing electroporation. In a preferred embodiment, the electroporation pulses are sufficient to subject substantially all cells within the target zone to irreversible electroporation without creating a thermally damaging effect.

Irreversible electroporation to treat aberrant cell masses

Abstract: The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors.

Irreversible electroporation device and method for attenuating neointimal

Abstract: Restenosis or neointimal formation may occur following angioplasty or other trauma to an artery such as by-pass surgery. This presents a major clinical problem which narrows the artery. The invention provides a device and a method whereby vascular cells in the area of the artery subjected to the trauma are subjected to irreversible electroporation which is a non-thermal, non-pharmaceutical method of applying electrical pulses to the cells so that substantially all of the cells in the area are ablated while leaving the structure of the vessel in place and substantially unharmed due to the non-thermal nature of the procedure.

Fundamental Study on the Effects of Irreversible Electroporation Pulses on Blood Vessels with Application to Medical Treatment

Abstract: Background : Irreversible electroporation (IRE) is a biophysical phenomenon in which a series of electric field pulses selectively damages only the lipid bilayer of the cell membrane. This work is a fundamental study on the effect of IRE on blood vessels, evaluating the feasibility and efficiency of endovascular IRE to destroy vascular smooth muscle cells (VSMC) in the arterial wall. Methods & Results : Time dependent finite-element simulations of the electric field and bio-heat transfer equations were used to analyze the electric field and the temporal behavior of the temperature due to electroporation pulses. The Henriques and Moritz thermal damage integral was used to demonstrate that an endovascular electrode geometry exists with which IRE pulses can be applied across the arterial wall with no thermal damage. In-vitro experiments with VSMC compared different electroporation protocols in order to find the electric field threshold for efficient IRE. In-vivo experiments with rodents demonstrated for the first time that IRE can ablate the VSMC population of the arterial wall, and that the ablation persists at 28 days. By comparing eight different electroporation protocols it was demonstrated that best ablation efficiency can be achieved with 90 square direct current pulses of 100µs at a frequency of 4 Hz delivering electric field of 1,750 V/cm across the vessel wall. In addition, a separate experiment demonstrated that IRE attenuated neointimal formation in rodent carotid arteries evaluated 28 days following angioplasty damage. In-vivo experiments with New-Zealand white rabbits evaluated the use of endovascular IRE. Using custom made endovascular devices with four longitudinal electrodes on top of an inflatable balloon, IRE was successfully applied to the vessel walls of eight iliac arteries. Independent pathology analysis confirmed the efficient ablation of the VSMC population evaluated at 7 and 35. In-vivo experiment with the same animal model using angioplasty damaged iliac arteries, showed that endovascular IRE attenuated neointimal formation and luminal loss 35 days following angioplasty. Conclusions : Non-thermal IRE is an efficient cell ablation method that can be used in an endovascular minimally-invasive approach. It holds the potential to treat multiple clinical problems, in particular the problem of coronary restenosis and cardiac arrhythmias.

Method for visually monitoring an irreversible electroporation treatment, and magnetic resonance imaging apparatus with integrated electroporation treatment device

Abstract: In a method for implementing an irreversible electroporation treatment with an electroporation device having at least two treatment electrodes, magnetic resonance exposures are acquired for visual monitoring of the treatment, and magnetic resonance-compatible electrodes are used as treatment electrodes. A magnetic resonance imaging apparatus has an electroporation device integrated therein, so as to be operable by co-use of at least some of the same components that arte used for image data acquisition.

Method for treatment planning of tissue ablation by irreversible electroporation

Abstract: Irreversible electroporation has in recent years emerged as a promising new tissue ablation method. Successful tissue ablation by irreversible electroporation requires that the entire target tissue volume is subjected to a sufficiently high electric field, while the electric field in the surrounding healthy tissue is as low as possible to prevent damage. Both can be achieved by appropriate positioning of the electrodes and appropriate choice of electric parameters. We used a 3D finite element numerical models and a genetic optimization algorithm to determine the optimum electrode positioning and optimum amplitude of electric pulses for ablation of a realistic subcutaneous tumor model that was acquired from medical images. The calculated optimum treatment parameters predicted adequate electric field distribution in the whole tumor volume and minimal damage to the adjacent organ at risk. Our treatment planning method could be a useful tool in the clinical electroporation-based tissue ablation, e.g. treatment of cancer.

The Role of Electroporation

Abstract: A therapeutic application of electrical current to cardiac tissue for reviving the normal function (defibrillation, pacing) or for ablating pathological conduction pathways inevitably has to take into account the phenomenon of electroporation, the electric-field-induced rupture of sarcolemma that is usually evidenced by a drastic unselective increase in cell membrane permeability to small ions and large molecules. This chapter describes some aspects of this phenomenon in relation to cardiac therapy and research. Particularly, it provides evidences that (1) electroporation of the heart tissue can occur during clinically relevant intensities of the external electrical field and (2) electroporation can affect the outcome of defibrillation therapy, being both pro- and antiarrhythmic.

Pilot study on the enhancement of irreversible electroporation (IRE) with carbon nanotubes (CNT)

Abstract: Non-thermal irreversible electroporation (IRE) is a new, minimally invasive technique that has shown great promise for the ablation of tumors [1]. The procedure involves placing electrodes into or around a targeted tissue and delivering a series of low energy (intense but short) electric pulses for approximately one minute. These pulses induce irreversible structural changes in the cell membranes of the targeted tissue that lead to cell death. Because IRE affects only a single molecular component of the treated area, the cell membrane, it is the first true molecular surgery. IRE has the ability to create complete and predictable cell ablation with a sharp transition between normal and necrotic tissue.Copyright © 2009 by ASME

Irreversible electroporation device for use in attenuating neointimal

Abstract: Restenosis or neointimal formation may occur following angioplasty or other trauma to an artery such as by-pass surgery. This presents a major clinical problem which narrows the artery. The invention provides a device and a method whereby vascular cells in the area of the artery subjected to the trauma are subjected to irreversible electroporation which is a non-thermal, non-pharmaceutical method of applying electrical pulses to the cells so that substantially all of the cells in the area are ablated while leaving the structure of the vessel in place and substantially unharmed due to the non-thermal nature of the procedure.