Sequential finite element model of tissue electropermeabilization

Permeabilization, when observed on a tissue level, is a dynamic process resulting from changes in membrane permeability when exposing biological cells to external electric field (E). In this paper we present a sequential finite element model of E distribution in tissue which considers local changes in tissue conductivity due to permeabilization. These changes affect the pattern of the field distribution during the high voltage pulse application. The presented model consists of a sequence of static models (steps), which describe E distribution at discrete time intervals during tissue permeabilization and in this way present the dynamics of electropermeabilization. The tissue conductivity for each static model in a sequence is determined based on E distribution from the previous step by considering a sigmoid dependency between specific conductivity and E intensity. Such a dependency was determined by parameter estimation on a set of current measurements, obtained by in vivo experiments. Another set of measurements was used for model validation. All experiments were performed on rabbit liver tissue with inserted needle electrodes. Model validation was carried out in four different ways: 1) by comparing reversibly permeabilized tissue computed by the model and the reversibly permeabilized area of tissue as obtained in the experiments; 2) by comparing the area of irreversibly permeabilized tissue computed by the model and the area where tissue necrosis was observed in experiments; 3) through the comparison of total current at the end of pulse and computed current in the last step of sequential electropermeabilization model; 4) by comparing total current during the first pulse and current computed in consecutive steps of a modeling sequence. The presented permeabilization model presents the first approach of describing the course of permeabilization on tissue level. Despite some approximations (ohmic tissue behavior) the model can predict the permeabilized volume of tissue, when exposed to electrical treatment. Therefore, the most important contribution and novelty of the model is its potentiality to be used as a tool for determining parameters for effective tissue permeabilization.     

Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization

In electrochemotherapy (ECT) electropermeabilization, parameters (pulse amplitude, electrode setup) need to be customized in order to expose the whole tumor to electric field intensities above permeabilizing threshold to achieve effective ECT. In this paper, we present a model-based optimization approach toward determination of optimal electropermeabilization parameters for effective ECT. The optimization is carried out by minimizing the difference between the permeabilization threshold and electric field intensities computed by finite element model in selected points of tumor. We examined the feasibility of model-based optimization of electropermeabilization parameters on a model geometry generated from computer tomography images, representing brain tissue with tumor. Continuous parameter subject to optimization was pulse amplitude. The distance between electrode pairs was optimized as a discrete parameter. Optimization also considered the pulse generator constraints on voltage and current. During optimization the two constraints were reached preventing the exposure of the entire volume of the tumor to electric field intensities above permeabilizing threshold. However, despite the fact that with the particular needle array holder and pulse generator the entire volume of the tumor was not permeabilized, the maximal extent of permeabilization for the particular case (electrodes, tissue) was determined with the proposed approach. Model-based optimization approach could also be used for electro-gene transfer, where electric field intensities should be distributed between permeabilizing threshold and irreversible threshold-the latter causing tissue necrosis. This can be obtained by adding constraints on maximum electric field intensity in optimization procedure.     

Influence of head tissue conductivity in forward and inverse magnetoencephalographic simulations using realistic head models

The influence of head tissue conductivity on magnetoencephalography (MEG) was investigated by comparing the normal component of the magnetic field calculated at 61 detectors and the localization accuracy of realistic head finite element method (FEM) models using dipolar sources and containing altered scalp, skull, cerebrospinal fluid, gray, and white matter conductivities to the results obtained using a FEM realistic head model with the same dipolar sources but containing published baseline conductivity values. In the models containing altered conductivity values, the tissue conductivity values were varied, one at a time, between 10% and 200% of their baseline values, and then varied simultaneously. Although changes in conductivity values for a single tissue layer often altered the calculated magnetic field and source localization accuracy only slightly, varying multiple conductivity layers simultaneously caused significant discrepancies in calculated results. The conductivity of scalp, and to a lesser extent that of white and gray matter, appears especially influential in determining the magnetic field. Comparing the results obtained from models containing the baseline conductivity values to the results obtained using other published conductivity values suggests that inaccuracies can occur depending upon which tissue conductivity values are employed. We show the importance of accurate head tissue conductivities for MEG source localization in human brain, especially for deep dipole sources or when an accuracy greater than 1.4 cm is needed.     

In vivo results of a new focal tissue ablation technique: irreversible electroporation

This paper reports results of in vivo experiments that confirm the feasibility of a new minimally invasive method for tissue ablation, irreversible electroporation (IRE). Electroporation is the generation of a destabilizing electric potential across biological membranes that causes the formation of nanoscale defects in the lipid bilayer. In IRE, these defects are permanent and lead to cell death. This paper builds on our earlier theoretical work and demonstrates that IRE can become an effective method for nonthermal tissue ablation requiring no drugs. To test the capability of IRE pulses to ablate tissue in a controlled fashion, we subjected the livers of male Sprague-Dawley rats to a single 20-ms-long square pulse of 1000 V/cm, which calculations had predicted would cause nonthermal IRE. Three hours after the pulse, treated areas in perfusion-fixed livers exhibited microvascular occlusion, endothelial cell necrosis, and diapedeses, resulting in ischemic damage to parenchyma and massive pooling of erythrocytes in sinusoids. However, large blood vessel architecture was preserved. Hepatocytes displayed blurred cell borders, pale eosinophilic cytoplasm, variable pyknosis and vacuolar degeneration. Mathematical analysis indicates that this damage was primarily nonthermal in nature and that sharp borders between affected and unaffected regions corresponded to electric fields of 300-500 V/cm.     

Experimental characterization and numerical modeling of tissue electrical conductivity during pulsed electric fields for irreversible electroporation treatment planning

Irreversible electroporation is a new technique to kill cells in targeted tissue, such as tumors, through a nonthermal mechanism using electric pulses to irrecoverably disrupt the cell membrane. Treatment effects relate to the tissue electric field distribution, which can be predicted with numerical modeling for therapy planning. Pulse effects will change the cell and tissue properties through thermal and electroporation (EP)-based processes. This investigation characterizes these changes by measuring the electrical conductivity and temperature of ex vivo renal porcine tissue within a single pulse and for a 200 pulse protocol. These changes are incorporated into an equivalent circuit model for cells and tissue with a variable EP-based resistance, providing a potential method to estimate conductivity as a function of electric field and pulse length for other tissues. Finally, a numerical model using a human kidney volumetric mesh evaluated how treatment predictions vary when EP- and temperature-based electrical conductivity changes are incorporated. We conclude that significant changes in predicted outcomes will occur when the experimental results are applied to the numerical model, where the direction and degree of change varies with the electric field considered.     

Induced electric currents in models of man and rodents from 60 Hzmagnetic fields

Induced electric currents in models of man, rat and mouse from 60 Hz magnetic fields are computed using the impedance method. The models all have realistic shapes, and in the case of rodents, a homogeneous average tissue conductivity is assumed. The model of man is analyzed for two cases, a homogeneous average tissue conductivity and a heterogeneous model, both consisting of 1.3 cm cubical tissue cells whose conductivities are representative of the tissue within the cube. The results for various models and species, as well as different orientations of the magnetic field, are compared. The data presented are useful as the first step in dosimetry for 60 Hz magnetic fields, and for interspecies scaling of biological interactions related to the tissue induced electric currents     

Temperature distributions in the human leg for VLF-VHF exposures atthe ANSI-recommended safety levels

Using a block model of 1532 cubical cells, temperature distributions are calculated for the lowest 21 cm of the human leg for electric fields recommended in the ANSI RF safety guideline. The thermal model uses inhomogeneous volume-averaged tissue properties: blood-flow rate, metabolism, thermal conductivity, specific heat, etc. The SARs are obtained using the impedance method. A modified finite-difference technique is used to solve the 3-D heat-conduction equation for the thermal model. Numerical results are obtained for RF currents at 3 and 40 MHz projected for the E fields recommended by the ANSI Standard (614 and 61.4 V/m, respectively) and also for power densities one-tenth of that level. Temperatures as high as 41.6°C are obtained for some internal cells for the higher E fields while relatively moderate temperatures on the order of 37°C are obtained for the lower E fields. Some of the calculated results for the surface temperature have been compared and found to be in good agreement with the experimental data for initial rates of heating     

High-field transport in NiO and Ni1−xLixO thin films

Repetitive switching from the high- to the low-resistance state in thin films of NiO and Ni_1?xLi_xO with Ni electrodes is investigated in the doping range from 0 to 0·4 at % Li. As the voltage is increased, four different I–V characteristics are obtained in succession: (1) an initial high-resistance state, which exhibits at first zero and then quadratic dependence of conductivity on the applied electric field; (2) a second lower-resistance state with linear and then cubic I–V characteristics followed by an avalanche-like behavior displaying a pronounced current-controlled negative resistance; (3) a third low-resistance state; and (4) a final metallic state, corresponding to irreversible dielectric breakdown. The transitions between the first and third or second and third states are reversible and show cyclic switching behavior, exhibiting a voltage-dependent delay time. Transport and dielectric data as a function of Li content, voltage, frequency, and temperature are used to propose a model for the switching mechanism.     

The effect of electromotive-force generation on electrical properties of thin samarium sulfide films

Electrical properties of thin SmS polycrystalline films with various values of the lattice constant at T = 300–580 K are studied. Specific features of the temperature dependences of electrical conductivity at T > 450 K are revealed. The effect of generation of the electromotive force with magnitude as large as 1.3 V at T = 440–470 K is observed when the films were subjected to the pressure of a spherical indenter. It is shown that it is possible to transform SmS films into a high-resistivity state (with the difference in the resistivity by three orders of magnitude) by applying an electric field with the strength higher than 100 V/cm. All the results obtained are accounted for using a model of the phenomenon of the electromotive-force generation in SmS under uniform heating of the sample and can also be attributed to the variable valence of samarium ions with respect to the lattice defects.     

渍制钪酸盐钡钨阴极脉冲性能的研究

本文对渍制钪酸盐钡钨阴极的脉冲性能作了下述几方面的研究。(1)脉冲发射水平和逸出功分布;(2)脉冲运用下的电子初速分布;(3)脉冲工作比效应;(4)强场下的非常肖特基效应。 本阴极在Tk=850℃下能提供的脉冲发射电流密度大于20A/cm2;平均逸出功=1.7eV;发射的不均匀性与国外报道的M型阴极的相近;在脉冲运用下,电子速度的分散值低于氧化物阴极的。本阴极在场强高于1104V/cm时,出现非常肖特基效应,本文用S值来表征。本阴极的S值明显高于渍制铝酸盐钡钨阴极和L阴极的。造成非常肖特基效应的主要原因是表面逸出功不均匀。在脉冲工作比f=510-3410-2范围内,支取8.8A/cm2时,本阴极有良好的平坦f特性,所以适用于长脉冲、大功率毫米波器件。 最后结合国内外对这种阴极的表面分析结果,对本文的实验结果进行了讨论,这些讨论有助于阐明本阴极的发射机制。     

Experimental analysis of an MPD closed-cycle generator with quasi-equilibrium plasma

The first series of MPD experiments performed with the closed-cycle facility of the Comitato Nazionale per l'Energia Nucleare (CNEN) are described. The entire facility, a blowdown loop capable of producing a high-purity noble gas, alkali-seeded plasma of 2 MW thermal power, has been thoroughly tested and has performed satisfactorily. The performance of a small-scale MPD generator with quasi-equilibrium plasma is shown to be influenced by ceramic leakage and plasma insulation from ground. Operating at Hall parameters up to three, the open-circuit Faraday field (29 V/cm) remains over 80 percent of its ideal value and the Hall field (28 V/cm) over 50 percent of its theoretical value, it which electrode voltage drop and segmentation effects are taken into account. The deviations of measured values from theoretical ones for both electric fields and conductivity are explained, at least qualitatively, by a simplified analytical model of wall and ground-loop leakages.     

Peripheral nerve stimulation by gradient switching fields in magnetic resonance imaging

A heterogeneous model of the human body and the scalar potential finite difference method are used to compute electric fields induced in tissue by magnetic field exposures. Two types of coils are considered that simulate exposure to gradient switching fields during magnetic resonance imaging (MRI). These coils producing coronal (y axis) and axial (z axis) magnetic fields have previously been used in experiments with humans.The computed fields can, therefore, be directly compared to human response data. The computed electric fields in subcutaneous fat and skin corresponding to peripheral nerve stimulation (PNS) thresholds in humans in simulated MRI experiments range from 3.8 to 5.8 V/m for the fields exceeded in 0.5% of tissue volume (skin and fat of the torso). The threshold depends on coil type and position along the body, and on the anatomy and resolution of the human body model. The computed values are in agreement with previously established thresholds for neural stimulation.     

Characterization of Scattering Parameters Near a Flat Phantom for Wireless Body Area Networks

In this paper, the scattering parameters of two dipoles placed closely to a flat, homogeneous, biological tissue are characterized in the 2.4-GHz band. The impact of the presence of a flat phantom and of the height of a dipole above the phantom on the reflection coefficient is analyzed through measurements and simulations. The effect of the type of tissue on the reflection coefficient is also investigated by performing simulations for a range of relative permittivity and conductivity combinations spanning the whole range of human tissues at 2.4 GHz. A semiempirical path loss model, validated by measurements and simulations, is presented for wireless communication, for antenna heights from 2 mm up to 5 cm and antenna separations from 10 to 50 cm. Also, the influence of the relative permittivity and conductivity on the path loss is modeled, leading to a range of possible values and lower and upper boundaries for the path loss as a function of the antenna height. The combination of the range with the boundaries results in a best-case and worst-case path loss model for wireless body area networks. The models are validated with measurements on the torso of a human.     

iRGD-Liposomes Enhance Tumor Delivery and Therapeutic Efficacy of Antisense Oligonucleotide Drugs against Primary Prostate Cancer and Bone Metastasis

Nucleotide-based drugs, such as antisense oligonucleotides (ASOs), have unique advantages in treating human diseases as they provide virtually unlimited ability to target any gene. However, their clinical translation faces many challenges, one of which is poor delivery to the target tissue in vivo. This problem is particularly evident in solid tumors. Here, liposomes are functionalized with a tumor-homing and -penetrating peptide, iRGD, as a carrier of an ASO against androgen receptor (AR) for prostate cancer treatment. The iRGD-liposomes exhibit a high loading efficiency of AR-ASO, and an efficient knockdown of AR gene products is achieved in vitro, including AR splice variants. In vivo, iRGD-liposomes significantly increase AR-ASO accumulation in the tumor tissue and decrease AR expression relative to free ASOs in prostate tumors established as subcutaneous xenografts. Similar results are obtained with intra-tibial xenografts modeling metastasis to bones, the predominant site of metastasis for prostate cancer. In treatment studies, iRGD-liposomes markedly improve the AR-ASO efficacy in suppressing the growth of both subcutaneous xenografts and intra-tibial xenografts. The inhibitory effect on tumor growth is also significantly prolonged by the delivery of the AR-ASO in the iRGD-liposomes. Meanwhile, iRGD-liposomes does not increase ASO accumulation or toxicity in healthy organs. Overall, a delivery system that can significantly increase ASO accumulation and efficacy in solid tumors is provided here. These benefits are achieved without significant side effects, providing a way to increase the antitumor efficacy of ASOs.     

聚乙二醇丁二酸酯对铝电解电容器工作电解液性能的影响

以聚乙二醇(400)和丁二酸酐为原料,合成了聚乙二醇丁二酸酯(PEGS).考察了所制PEGS的添加量和pH值对工作电解液的闪火电压.电导率以及铝电解电容器性能的影响.结果表明:PEGS可以提高工作电解液的闪火电压,并有效抑制电导率的降低:当添加PEGS的质量分数为3%时,工作电解液的闪火电压最大可升高45V,电导率只降...     

聚合条件对PEDT导电性及相对分子质量的影响

采用化学原位氧化聚合法制备了导电聚合物3,4-聚乙烯二氧噻吩(PEDT)薄膜。系统研究了不同工艺条件对聚合物电导率的影响。发现单体与氧化剂体积比为1∶4、溶剂含量90%(体积分数)、加入聚合改良剂0.5%(体积分数)、反应温度–5℃时可以获得较高电导率(>20S/cm)薄膜。首次结合元素分析法,研究了工艺条件对聚合物相对分子质量的影响,结果表明,聚合温度25℃,ψ(单体:氧化剂:聚合改良剂)=1∶4∶2的条件下,所合成的PEDT可获得最大平均相对分子质量(1068)和聚合度(7.6),并对相应的机理进行了探讨。     

The Frenkel–Poole Effect in the Ionization of an Acceptor Impurity of Boron in Diamond in a Strong Electric Field

Journal of Communications Technology and Electronics - The conductivity of epitaxial diamond films lightly doped with boron has been studied at strong electric fields up to ~5 × 105 V/ cm. It...     

Electric field stimulation of cardiac myocytes during postnatal development

Studies on cardiac cell response to electric field stimulation are important for understanding basic phenomena underlying cardiac defibrillation. In this work, we used a model of a prolate spheroidal cell in a uniform external field (Klee and Plonsey, 1976) to predict the threshold electric field (ET) for stimulation of isolated ventricular myocytes of rats at different ages. The model assumes that ET is primarily determined by cell shape and dimensions, which markedly change during postnatal development. Neonatal cells showed very high ET, which progressively decreased with maturation (experimental mean values were 29, 21, 13, and 5.9 and 6.3 V/cm for 3-6, 13-16, 20-21, 28-35, and 120-180 day-old rats, respectively, P < 0.001; theoretical values were 24, 18, 11, 9, and 6 V/cm, respectively). Estimated maximum membrane depolarization at threshold (deltaVT approximately equals 35 mV, under our experimental conditions) was reasonably constant during development, except for cells from 1-mo-old animals, in which deltaVT was lower than at other ages. We conclude that the model reasonably correlates ET with cell geometry and size in most cases. Our results might be relevant for the development of efficient procedures for defibrillation of pediatric patients.     

An analytical model for surface EMG generation in volume conductors with smooth conductivity variations

A nonspace invariant model of volume conductor for surface electromyography (EMG) signal generation is analytically investigated. The volume conductor comprises planar layers representing the muscle and subcutaneous tissues. The muscle tissue is homogeneous and anisotropic while the subcutaneous layer is inhomogeneous and isotropic. The inhomogeneity is modeled as a smooth variation in conductivity along the muscle fiber direction. This may reflect a practical situation of tissues with different conductivity properties in different locations or of transitions between tissues with different properties. The problem is studied with the regular perturbation theory, through a series expansion of the electric potential. This leads to a set of Poisson's problems, for which the source term in an equation and the boundary conditions are determined by the solution of the previous equations. This set of problems can be solved iteratively. The solution is obtained in the two-dimensional Fourier domain, with spatial angular frequencies corresponding to the longitudinal and perpendicular direction with respect to the muscle fibers, in planes parallel to the detection surface. The series expansion is truncated for the practical implementation. Representative simulations are presented. The proposed model constitutes a new approach for surface EMG signal simulation with applications related to the validation of methods for information extraction from this signal.     

Magnetically induced currents in the canine heart: a finite elementstudy

A moderately detailed three-dimensional (3-D) finite element model of the conductive anatomy of a canine thorax was used to determine the fields and currents induced by a time-varying magnetic field that has been shown to cause irregular heart beats in canines. The 3-D finite element model of the canine thorax was constructed from CT scans and includes seven isotropic tissue conductivities and the anisotropic conductivity of skeletal muscle. The authors use this model to estimate the stimulation threshold associated with stimulation of the heart by the time-varying magnetic field of a figure-eight coil. Variants of the thoracic model were also constructed to examine the sensitivity of model results to variations in model size, shape, and conductive inhomogeneity and anisotropy. The authors' results show that myocardial fields were only mildly sensitive to thoracic size. However, model shape and conductive inhomogeneity and anisotropy substantially influenced the magnitude and distribution of myocardial fields and currents. The authors' results suggest that an induced peak field magnitude of ≈1 V/cm is required to stimulate the heart with the magnetic excitation simulated in this study