Reliable Method for Fabricating Tissue‐Mimicking Materials With Designated Relative Permittivity and Conductivity at 128 MHz

Artificial materials that can simultaneously mimic the relative permittivity and conductivity of various human tissues are usually used in medical applications. However, the method of precisely designing these materials with designated values of both relative permittivity and conductivity at 3 T MRI resonance frequency is lacking. In this study, a reliable method is established to determine the compositions of artificial dielectric materials with designated relative permittivity and conductivity at 128 MHz. Sixty dielectric materials were produced using oil, sodium chloride, gelatin, and deionized water as the main raw materials. The dielectric properties of these dielectric materials were measured using the open‐ended coaxial line method at 128 MHz. Nonlinear least‐squares Marquardt–Levenberg algorithm was used to obtain the formula, establishing the relationship between the compositions of the dielectric materials and their dielectric properties at 128 MHz. The dielectric properties of the blood, gall bladder, muscle, skin, lung, and bone at 128 MHz were selected to verify the reliability of the obtained formula. For the obtained formula, the coefficient of determination and the expanded uncertainties with a coverage factor of k = 2 were 0.991% and 4.9% for relative permittivity and 0.992% and 6.4% for conductivity. For the obtained artificial materials measured using the open‐ended coaxial line method, the maximal difference of relative permittivity and conductivity were 1.0 and 0.02 S/m, respectively, with respect to the designated values. In conclusion, the compositions of tissue‐mimicking material can be quickly determined after the establishment of the formulas with the expanded uncertainties of less than 10%. Bioelectromagnetics. 2021;42:86–94. © 2020 Bioelectromagnetics Society.     

Complex Permittivity Differences Between Normal and Pathological Tissues: Mechanisms and Medical Significance

The complex permittivity dispersions of normal and pathological biological tissues are surveyed from audio to microwave frequencies. The mechanisms responsible for producing changes to biodlelectric properties are examined, and qualitative and quantitative predictions are made about these changes following the transformation of normal to malignant tissue. For the transformation of rat liver to hepatoma tissue, we predict a peak increase of 73% at 2 MHz for the permittivity, with elevations in conductivity relatively constant at 40-46% between 3 MHz-lGHz. Several features of the predictions are in accord with experimental measurements previously published. Transformed biodielectrlc properties are of potential significance for tissue characterization, medical imaging, diagnosis and therapy.     

Study on fish embryo responses to the treatment of cryoprotective chemicals using impedance spectroscopy

Investigations using electrical impedance spectroscopy to measure the responses of fish embryos to the cryoprotective chemicals, methanol and dimethyl sulphoxide (DMSO), were carried out. Zebrafish (Danio rerio) embryos were used as a model to study the newly proposed technique. The normalised permittivity and conductivity changes of the embryos were measured continuously over a 20-min period in a customised embryo-holding chamber. The normalised permittivity and conductivity spectra were obtained during embryo exposure to different concentrations of methanol (1.0, 2.0 and 3.0 M) and DMSO (0.5, 1.0 and 2.0 M) solutions. The results showed significant permittivity and conductivity changes after embryo exposure to methanol and DMSO at the optimum embryo loading level (six embryos). Embryos in different concentrations of methanol and DMSO also resulted in quantitative responses shown in the normalised permittivity and conductivity spectra. The results demonstrated that fish embryo membrane permeability to cryoprotective chemicals could be monitored in real-time. The measurement of permittivity at a lower frequency range (10–10³ Hz) and conductivity at a higher frequency range (10⁴–10⁶ Hz) during fish embryo exposure to cryoprotective chemicals using impedance spectroscopy can be used as a new tool for the fast screening of most effective cryoprotective chemicals. The results from the present study also demonstrated the possibility of quantifying the level of cryoprotective chemicals penetrating the fish embryos.     

Effect of DMSO on the dielectric properties of canine kidney tissue

The dielectric permittivity and conductivity of canine kidney tissue samples were measured at R_f frequencies between ?20 °C and +20 °C. Some of the kidneys had been perfused with DMSO (10%) in canine plasma, others with physiological saline alone. The DMSO greatly increases the conductivity of frozen tissue above that of tissue not treated with this cryoprotectant. Apparently, the chief reason for nonuniform heating of a partially frozen organ in a microwave field is the great change in tissue conductivity as it thaws. We suggest that the effect on the conductivity of tissue should be considered in the choice of a cryoprotectant for tissues which are to be thawed by microwave or radiofrequency irradiation.     

Dielectric properties of human brain tissue measured less than 10 h postmortem at frequencies from 800 to 2450 MHz

The dielectric properties of gray matter in the frequency range of 800-2450 MHz were measured on 20 human brains immediately after excision, less than 10 h after death. The brains were obtained during autopsy of 10 male and 10 female humans who died at ages between 47.5 and 87.5 years [70.4 +/- 9.8 years, mean +/- standard deviation (SD)]. The tissue temperature at the measurement sites ranged between 18 and 25 degrees C (21.35 +/- 1.6 degrees C, mean +/- SD). On each brain, four specific locations on the temporal lobe were measured on the right and left sides, i.e., 160 different measurements of the dielectric properties were performed. The dielectric probe was placed on the intact arachnoid on a gyrus in the selected area. The measurements yielded a mean value (+/-SD) of gray matter equivalent conductivity of 1.13 +/- 0.12 and 2.09 +/- 0.16 S/m at 800 and 2450 MHz, respectively. The mean value of measured relative permittivity was 58.2 +/- 3.3 and 54.7 +/- 3.3 at 800 and 2450 MHz, respectively. Taking into account a positive temperature coefficient of equivalent conductivity, these measurements indicate that the equivalent conductivity of human gray matter at body temperature is somewhat higher than today's generally accepted value, which is based on measurements on animal tissue and excised samples of human tissue measured more than 24 h postmortem.     

INHIBITION OF EHRLICH TUMOR GROWTH IN MICE BY ELECTRIC INTERFERENCE THERAPY (IN VIVO STUDIES)

A study of solid tumor growth retardation by employing extremely low frequency (ELF) electric fields has been carried out. ELF electric fields were generated in tumor tissue in mice by the interference of two high frequency sinusoidal waves with the beat frequency centered at the tumor core. The results indicated a pronounced decrease in tumor growth rate in animals exposed to a 5-Hz interferential frequency for 1 hr daily. The 1 hr/day treatment produced a greater retardation effect than the 1 hr/week treatment. This indicates that treatment duration at the applied field frequency appears to play an important role in tumor growth delay. The dielectric properties of the tumor cells showed higher permittivity and conductivity values than homologous normal tissue. The permittivity of tumor cells treated daily with 5 Hz reaches nearly the same value as control tissue. Moreover, histological studies show that tumor tissues treated daily with the same frequency undergo partial regression and shrinkage of the aggregates of neoplastic cells leaving very little of them. We conclude that this new interferential technique is promising for tumor treatment in which a resonating electric field affects cell-to-cell communication.     

Dielectric Properties of Normal and Metastatic Lymph Nodes Ex Vivo From Lung Cancer Surgeries

The dielectric properties of normal and tumor human tissues have been widely reported in recent years. However, the dielectric properties of intrathoracic lymph nodes (LNs) have not been reported. In this communication, we measured the dielectric properties (i.e., permittivity and conductivity) of ex vivo intrathoracic LNs obtained from lung cancer surgeries. Results show that the permittivity and conductivity of metastatic LNs are higher than those of normal LNs over the frequency range of 1 MHz–4 GHz. Statistically significant differences are observed at single specific frequencies (64, 128, 298, 433, and 915 MHz and 2.45 GHz). Our study provides the basic data to support future-related research and fills the research gap on the dielectric properties of LNs in the lungs. Bioelectromagnetics. 2020;41:148–155. © 2020 Bioelectromagnetics Society.     

Microwave dielectric relaxation in muscle. A second look.

The dielectric permittivity and conductivity of muscle fibers from the giant barnacle, Balanus nubilus, have been measured at 1, 25, and 37 degrees C, between 10 MHz and 17 GHz. The dominant microwave dielectric relaxation process in these fibers is due to dipolar relaxation of the tissue water, which shows a characteristic relaxation frequency equal to that of pure water, ranging from 9 GHz (1 degree C) to 25 GHz (37 degree C). The total permittivity decrease, epsilon 0 -- epsilon infinity, due to this process accounts for approximately 95% of the water content of the tissue; thus, the major fraction of tissue water is dielectrically identical to the pure fluid on a picosecond time scale. A second dielectric process contributes significantly to the tissue dielectric properties between 0.1 and 1--5 GHz, and arises in part form Maxwell-Wagner effects due to the electrolyte content of the tissue, and in part from dielectric relaxation of the tissue proteins themselves.     

Time domain dielectric spectroscopy study of human cells. II. Normal and malignant white blood cells.

The dielectric properties of human lymphocyte suspensions were studied by time domain dielectric spectroscopy (TDDS). Nine populations of malignant and normal lymphocytes were investigated. Analysis of the dielectric parameters of cell structural parts were performed in the framework of Maxwell-Wagner mixture formula and the double-shell model of cell. The specific capacitance of the cell membranes was estimated by the Hanai-Asami-Koisumi formula. It was shown that the dielectric permittivity, capacitance and conductivity values of cell membranes are higher for normal lymphocytes than for the malignant ones. The difference of the same parameters for normal B- and T-cells is also discussed.     

红光促进难治性创面愈合的研究

目的:探讨红光照射对难治性创面的创缘组织中血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达及治疗难治性创面的临床效果。方法:收集2008年6月-2010年12月因难治性创面入住笔者单位治疗的40例患者,按治疗方法分为红光照射治疗组20例和常规治疗组20例。常规治疗组患者创面以0.5%碘伏与水胶体敷料换药。治疗组在常规治疗的基础上加用红光照射。于治疗后第7天、14天、21天切取创缘组织,研究红光照射对创缘组织中VEGF的影响,并比较两组患者的创面愈合率和愈合时间。结果:临床实验中,治疗组创缘组织中的VEGF含量明显高于对照组(P<0.01);治疗组创面愈合率明显高于对照组(P<0.01);治疗组的愈合时间低于对照组(P<0.05)。结论:红光照射能显著提高创缘组织中VEGF含量,减少创面愈合时间,促进愈合。     

Dielectric properties of porcine brain tissue in the transition from life to death at frequencies from 800 to 1900 MHz

Ten experiments on pigs were performed to investigate possible postmortem changes of the dielectric properties of brain gray matter in the frequency range of 800-1900 MHz. After keeping the animals in stable anaesthesia for at least 45 min, they were euthanatised by an intravenous injection of hypertonic potassium chloride (KCl), causing cardiac arrest within 3 min. Measurements of the dielectric properties were performed repeatedly from at least 45 min prior to death to 18 h after euthanasia. The anaesthesia regimen was chosen to minimize influence on brain tissue characteristics such as brain water content, intracranial blood volume, and cerebral blood flow. The data showed a decline of mean gray matter equivalent conductivity of about 15% at 900 MHz and about 11% at 1800 MHz within the first hour after death. The decline in permittivity was less pronounced (about 3-4%) and almost frequency independent. The results indicate that in vitro measurements of dielectric properties of brain tissue underestimate equivalent conductivity as well as permittivity of living tissue. These changes may affect the generally accepted data of dielectric properties of brain tissue widely used in RF dosimetry.     

红光促进难治性创面愈合的研究

目的：探讨红光照射对难治性创面的创缘组织中血管内皮细胞生长因子（vascular endothelial growth factor,VEGF）的表达及治疗难治性创面的临床效果。方法：收集2008年6月-2010年12月因难治性创面入住笔者单位治疗的40例患者,按治疗方法分为红光照射治疗组20例和常规治疗组20例。常规治疗组患者创面以0.5%碘伏与水胶体敷料换药。治疗组在常规治疗的基础上加用红光照射。于治疗后第7天、14天、21天切取创缘组织,研究红光照射对创缘组织中VEGF的影响,并比较两组患者的创面愈合率和愈合时间。结果：临床实验中,治疗组创缘组织中的VEGF含量明显高于对照组（P〈0.01）;治疗组创面愈合率明显高于对照组（P〈0.01）;治疗组的愈合时间低于对照组（P〈0.05）。结论：红光照射能显著提高创缘组织中VEGF含量,减少创面愈合时间,促进愈合。     

Complex Dielectric Properties of Sulfate-Reducing Bacteria Suspensions

Sulfate-reducing bacteria (SRB) can potentially enhance the remediation of heavy metals in the subsurface. Previous geophysical research has demonstrated the sensitivity of electrical measurements to SRB-mediated mineral transformation in porous media. However, the inherent dielectric properties of SRB and their direct contribution to the electrical properties of porous media are poorly understood. We studied the complex dielectric properties of SRB (Desulfovibrio vulgaris) suspensions at different concentrations and at different growth stages using a two-electrode dielectric spectroscopy measurement over the frequency range of 20 Hz to 1 MHz. Our results show higher dielectric responses (relative dielectric permittivity, real and imaginary conductivity) occurred with higher bacteria concentration at frequencies <10 kHz. Additionally, permittivity and conductivity both decreased as cells aged from mid-log phase to late stationary phase. Our results suggest that dielectric spectroscopy measurements can be used to noninvasively monitor biomass and various growth stages of SRB. Our work advances the interpretation of electrical signals associated with SRB observed in the subsurface.     

Apparatus for the electrical characterisation of conductive fluids

Non-invasive and fully automated conductimetric measurements of electrolyte and bacterial samples were achieved in a closed volume test cell, comprising a magnetic field coil and detector. By monitoring field induced currents in sample electrolytes the magnitude of the sample current was shown to vary as the inverse of the sample impedance. The impedance characteristic was shown to be that of an LCR resonant circuit. This characteristic is primarily a function of the applied frequency and the solution/cell properties being dependent on the solution conductivity and dielectric permittivity at any given concentration. Small changes in sample dielectric permittivity in the presence of a large background conductivity are shown to be significant.The apparatus described can provide fixed or swept frequency conductivity measurements in the range 1 kHz to 2.25 MHz with a lower conductivity sensitivity of 0.9 × 10⁻³ Scm⁻¹. Bulk impedimetric characteristics of cell suspensions are derived by a two stage measurement.     

Alteration of the passive electrical properties of lymphocyte membranes induced by GM1 and GM3 glycolipids.

The electrical conductivity of normal human lymphocyte suspensions has been measured in the frequency range from 10 kHz to 100 MHz, where a well-pronounced conductivity dispersion occurs, caused by the surface polarization at the interface between the cell membrane and the extracellular solution. We have investigated the alteration of the passive electrical properties of the cytoplasmatic cell membrane induced by two different gangliosides (GM1 and GM3) inserted, at various concentrations, into the outer leaflet of membrane double layer. The alterations observed in the dielectric parameters (the membrane conductivity and the membrane permittivity) derived on the basis of a 'double-shell' model, result in an overall increase of the ion permeation across the membrane and an enhanced polarizability of its hydrophilic region for both gangliosides investigated. The relevance of these alterations is discussed.     

Appearance of tenascin in healing skin of the mouse: possible involvement in seaming of wounded tissues

Distribution of the extracellular matrix glycoprotein tenascin during wound healing in mouse skin was studied immunohistochemically. Within 24 hours after wounding, and preceding the formation of granulation tissue, tenascin appeared in the basement membranes beneath epidermis and hair follicles adjacent to the wound edges and in the wounded edges of cutaneous muscle layer. Granulation tissue began to form in the wound space at about 1-2 days and was immediately covered by epidermis. Tenascin first appeared in the periphery of the granulation tissue beneath healing epidermis and around the wounded edges of cutaneous muscle layer. Then the tenascin-positive area extended into the inner region of granulation tissue. At about 5-7 days, all of the granulation tissue was intensely stained with anti-tenascin serum. Tenascin immunoreactivity decreased as granulation tissue was replaced with reconstructed dermal tissue at 7-14 days. In most cases, tenascin staining persisted longest in the dermis beneath the healing epidermis and at the juncture of healing edges of cutaneous muscle layer. It disappeared at about 10-14 days after wounding. These findings suggest that tenascin may play an important role in the seaming of wounded tissues.     

Differences in membrane electrical properties between C3H 10T1/2 mouse embryo fibroblasts and their ionizing radiation and chemically transformed counterparts

Membrane electrical properties of mouse embryo fibroblasts and their ionizing radiation and chemically transformed counterparts were investigated using dielectric relaxation measurements in the radio frequency range. This determination is possible because, in the radio frequency range, suspensions of cells in an electrolyte buffer show a conductivity dispersion due to interfacial polarization. An analysis of the experimental data based on a single-shell model showed that conductivity and permittivity of the membranes of both radiation and chemically transformed fibroblasts were lower than in normal cells. In addition, the conductivity of the cytoplasm was higher in both transformed cell types than in the normal mouse fibroblasts. We discuss the significance of these findings in view of the possible structural and functional modifications brought about by the process of neoplastic transformation.     

Biosynthesis of wound ethylene in morning-glory flower tissue

Production of wound ethylene was investigated in rib segments excised from flower buds of morning-glory (Ipomoea tricolor). Segments of the ribs were cut from buds 2 days before flower opening, floated overnight on 5 mm KCl solution, and transferred to agar the following morning. These immature segments evolved only a small quantity of ethylene during incubation on agar, with most of the production occurring in the morning. When such segments were wounded mechanically early in the afternoon, the rate of ethylene production rose more than 10-fold within 1 hour and returned to a low rate after about 3 hours.Production of ethylene by both untreated and wounded rib segments was inhibited more than 95% by overnight pretreatment with the ethoxy analog of rhizobitoxine (3 x 10(-5) and 10(-4)m). After overnight exposure of segments to 9 muml-methionine-U-(14)C, the specific radioactivity of the ethylene evolved by untreated and wounded tissue was determined and compared to the specific radioactivities of carbon atoms 3 plus 4 of methionine and S-methylmethionine (SMM) extracted from the segments. The specific radioactivity of methionine was about one-half that of SMM; neither value was significantly affected by wounding. The specific radioactivity of ethylene evolved by untreated tissue was close to that of SMM. In wounded tissue the specific radioactivity of the ethylene evolved was lower, but still above that of methionine. These results are consistent with the interpretations that wound ethylene is synthesized from carbon atoms 3 plus 4 of either SMM or methionine. On the basis of earlier experiments with senescing rib segments, it is suggested that methionine serves as the precursor of the wound ethylene.     

Dielectric behavior of the frog lens in the 100 Hz to 500 MHz range. Simulation with an allocated ellipsoidal-shells model.

In an attempt to correlate the passive electrical properties of the lens tissue with its structure, we measured ac admittances for isolated frog lenses, lens nuclei, and homogenate of cortical fiber cells, over the frequency range 10(2)-5.10(8) Hz. The whole lenses molded into discoid shape show a characteristic "two-step" dielectric dispersion with a huge permittivity increment of the order of 10(5) at 1 kHz. Of the two subdispersions disclosed, dispersion 1 has a permittivity increment (delta epsilon) of 2.10(5) with a characteristic frequency (fc) of 2 kHz, and dispersion 2 has a delta epsilon of 400 with an fc of 2 MHz. In terms of loss tangent, these dispersions are more clearly located as two separate peaks. Data are analyzed using an allocated ellipsoidal-shells model which has been developed by taking into account fiber orientation inside the lens tissue. Dispersion 1 is assigned to the equatorial cortex, where fiber cells run parallel to the applied electric field, and dispersion 2 to the nucleus with a complex fiber arrangement and also to the polar cortex, in which the fiber alignment is predominantly perpendicular. In addition, the model analysis reveals that, in the frog lens, the nucleus occupies approximately 30% in volume and that relative permittivity and conductivity for the cell interior are, respectively, 45 and 3 mS/cm for the cortical cells, and 28 and 0.3 mS/cm for the nuclear cells.     

Radiofrequency interaction with conductive colloids: Permittivity and electrical conductivity of single‐wall carbon nanotubes in saline

Conductive nanoparticles may enhance tissue heating during radiofrequency (RF) irradiation. Specific absorption rate (SAR) is known to rise with the electrical conductivity of tissue. However, no studies to date have measured the relationship between complex permittivity and nanoparticle concentration in tissue‐like samples. The complex permittivities of colloids containing single‐wall carbon nanotubes (SWCNTs) in normal (0.9%) saline were measured from 20 MHz to 1 GHz. Carbon concentrations ranged from 0 to 93 mM (0.06% volume), based on SWCNT weight per volume. Measurements were made with 0.02% Pluronic F108 surfactant added to the colloids to prevent SWCNT flocculation. The data were fit to the Cole–Cole relaxation model with an added constant phase angle element to correct for electrode polarization effects at low RF frequencies. Electrode polarization effects increased with carbon concentration. The real parts of the permittivities of the colloids increased with carbon concentration. The static conductivity rose linearly with carbon concentration, doubling from 0 to 93 mM. The SAR of the colloids is expected to increase with RF frequency, based on the properties of the imaginary part of the permittivity. Bioelectromagnetics 31:582–588, 2010. © 2010 Wiley‐Liss, Inc.