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We numerically propose a dual-band absorber in the infrared region based on periodic elliptical graphene-black phosphorus (BP) pairs. The proposed absorber exhibits near-unity anisotropic absorption for both resonances due to the combination of graphene and BP. Each of the resonances is independently tunable via adjusting the geometric parameters. Besides, doping levels of graphene and BP can also tune resonant properties effectively. By analyzing the electric field distributions, surface plasmon resonances are observed in the graphene-BP ellipses, contributing to the strong and anisotropic plasmonic response. Moreover, the robustness for incident angles and polarization sensitivity are also illustrated.

Purpose: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI)., Methods: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal images in both homogenous phantoms and heterogeneous tumours., Results: SAR simulations demonstrated excellent agreement with temperature rise distributions obtained with MR thermal imaging in homogeneous phantoms and clinical treatments of large soft-tissue sarcomas. The results demonstrate feasibility of preplanning appropriate relative phases of antennas for localising heat in tumour., Conclusions: Advances in the accuracy of computer simulation and non-invasive thermometry via MR thermal imaging have provided powerful new tools for optimisation of clinical hyperthermia treatments. Simulations agree well with MR thermal images in both homogeneous tissue models and patients with lower leg tumours. This work demonstrates that better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan.

In large multi-antenna systems, adaptive controllers can aid in steering the heat focus toward the tumor. However, the large number of sources can greatly increase the steering time. Additionally, controller performance can be degraded due to changes in tissue perfusion which vary non-linearly with temperature, as well as with time and spatial position. The current work investigates whether a reduced-order controller with the assumption of piecewise constant perfusion is robust to temperature-dependent perfusion and achieves steering in a shorter time than required by a full-order controller. The reduced-order controller assumes that the optimal heating setting lies in a subspace spanned by the best heating vectors (virtual sources) of an initial, approximate, patient model. An initial, approximate, reduced-order model is iteratively updated by the controller, using feedback thermal images, until convergence of the heat focus to the tumor. Numerical tests were conducted in a patient model with a right lower leg sarcoma, heated in a 10-antenna cylindrical mini-annual phased array applicator operating at 150 MHz. A half-Gaussian model was used to simulate temperature-dependent perfusion. Simulated magnetic resonance temperature images were used as feedback at each iteration step. Robustness was validated for the controller, starting from four approximate initial models: (1) a 'standard' constant perfusion lower leg model ('standard' implies a model that exactly models the patient with the exception that perfusion is considered constant, i.e., not temperature dependent), (2) a model with electrical and thermal tissue properties varied from 50% higher to 50% lower than the standard model, (3) a simplified constant perfusion pure-muscle lower leg model with +/-50% deviated properties and (4) a standard model with the tumor position in the leg shifted by 1.5 cm. Convergence to the desired focus of heating in the tumor was achieved for all four simulated models. The controller accomplished satisfactory therapeutic outcomes: approximately 80% of the tumor was heated to temperatures 43 degrees C and approximately 93% was maintained at temperatures <41 degrees C. Compared to the controller without model reduction, a approximately 9-25 fold reduction in convergence time was accomplished using approximately 2-3 orthonormal virtual sources. In the situations tested, the controller was robust to the presence of temperature-dependent perfusion. The results of this work can help to lay the foundation for real-time thermal control of multi-antenna hyperthermia systems in clinical situations where perfusion can change rapidly with temperature.

Purpose: Blood perfusion is a well-known factor that complicates accurate control of heating during hyperthermia treatments of cancer. Since blood perfusion varies as a function of time, temperature and location, determination of appropriate power deposition pattern from multiple antenna array Hyperthermia systems and heterogeneous tissues is a difficult control problem. Therefore, we investigate the applicability of a real-time eigenvalue model reduction (virtual source - VS) reduced-order controller for hyperthermic treatments of tissue with nonlinearly varying perfusion., Methods: We impose a piecewise linear approximation to a set of heat pulses, each consisting of a 1-min heat-up, followed by a 2-min cool-down. The controller is designed for feedback from magnetic resonance temperature images (MRTI) obtained after each iteration of heat pulses to adjust the projected optimal setting of antenna phase and magnitude for selective tumor heating. Simulated temperature patterns with additive Gaussian noise with a standard deviation of 1.0°C and zero mean were used as a surrogate for MRTI. Robustness tests were conducted numerically for a patient's right leg placed at the middle of a water bolus surrounded by a 10-antenna applicator driven at 150 MHz. Robustness tests included added discrepancies in perfusion, electrical and thermal properties, and patient model simplifications., Results: The controller improved selective tumor heating after an average of 4-9 iterative adjustments of power and phase, and fulfilled satisfactory therapeutic outcomes with approximately 75% of tumor volumes heated to temperatures >43°C while maintaining about 93% of healthy tissue volume < 41°C. Adequate sarcoma heating was realized by using only 2 to 3 VSs rather than a much larger number of control signals for all 10 antennas, which reduced the convergence time to only 4 to 9% of the original value., Conclusions: Using a piecewise linear approximation to a set of heat pulses in a VS reduced-order controller, the proposed algorithm greatly improves the efficiency of hyperthermic treatment of leg sarcomas while accommodating practical nonlinear variation of tissue properties such as perfusion.

Recent developments have reinvigorated clinical investigations of hyperthermia (HT) as a viable adjuvant treatment in the fight against cancer. Researchers are placing a greater emphasis on multi-modal approaches that include mild temperatures (40°C - 43°C) and standard therapies like radiation and chemotherapy than on achieving higher temperature treatments (43°C-45°C) which were pursued in the past. The emergence of robust computer simulation tools for accurate hyperthermia treatment planning has aided this resurgence by helping improve the quality of heating. This article outlines a recent collaborative study at Duke University to demonstrate the capabilities of a new suite of 3D electromagnetic and thermodynamic simulation tools for treatment planning of external hyperthermia treatments with a radio frequency (RF) phased array heat applicator. Following a brief introduction to the rationale for moderate temperature hyperthermia and current methodology for heating tissue at depth in the body, the article will present a new approach for improved heating based on treatment planning with electromagnetic simulation software tools. Procedures, benefits, and a comparison of simulated heating patterns with those measured in two clinical hyperthermia treatments of advanced fibrous histiocytoma (soft-tissue sarcoma) tumors will be presented.

The design and performance of annular antenna arrays with reflectors is presented. Arrays with three shapes of reflectors are analysed and simulated. These include the corner reflector, the circular reflector and the elliptical reflector. Power-density distributions within the annular arrays with and without reflectors are obtained by using the FDTD method. Also, the image theory method is used to verify the FDTD results in one case. By comparing the power-density distribution pattern of all four of the array designs (three with different reflectors, one without reflector), it is readily seen in each case that the array with reflectors yields better power-efficiency than the array without reflectors and the elliptical reflector yields the best performance. Comparisons of each array are made using 4, 6 and 8 antennae in the annular array. By using the optimized results of the elliptical reflector, the requirement for the input-power level to each antenna is greatly reduced.

Active microwave imaging (MWI) is emerging as a promising technique for the detection of biomedical anomalies such as breast cancer because of the high electrical contrasts between malignant tumors and normal tissue. Previously, we have developed fast two-dimensional forward and inverse scattering algorithms for MWI systems. In this paper, we report the full three-dimensional (3-D) forward scattering simulation in order to account for 3-D effects and to provide a fast solver in future 3-D nonlinear inverse scattering methods. The 3-D fast forward method is based on the stabilized biconjugate-gradient fast Fourier transform (BCGS-FFT) algorithm. The method has been validated for various MWI measurement scenarios. Using this fast simulation method, we demonstrate the importance of accounting for 3-D effects in MWI, and we compare numerical results with the measurements from an experimental prototype.

This paper explores the behaviour of the primary and secondary hot spots in homogeneous and two-dimensional inhomogeneous medium. Circular arrays are considered with a radius of up to five wavelengths. The number of sources and their positions in the array are varied, and the influence of these variations on the primary and secondary hot spots is observed. It is found that the primary hot spot reaches its final shape with the addition of a very small number of sources to the array. An increase in the number of sources results in a reduction of the normalized magnitude of the secondary hot spots, but the size of the normalized primary hot spot remains the same. An upper limit of sources in the array exists after which no further reduction of the secondary hot spots is observed. The finite-difference time-domain method (FDTD) is used to obtain the electric-field distribution in the inhomogeneous medium. A genetic algorithm is then applied to find the optimal positions of the antennae in the array.

The electrical conductivity and relative permittivity of malignant and normal human tissues were measured at frequencies from 50 to 900 MHz. The measurements were made between 23 and 25 degrees C using a network analyzer connected to a flat-ended coaxial probe that was pressed against the freshly excised tissue samples. The malignant tissues were of the following normal tissue origin: bladder, colon, kidney, liver, lung, lymph nodes, mammary gland, spleen, and testes. The normal tissues included: colon, kidney, liver, lung, mammary gland, and muscle. Normal tissue samples of bladder, lymph, spleen, and testes were not available. In general, at all frequencies tested, both conductivity and relative permittivity were greater in malignant tissue than in normal tissue of the same type. For tissues of the same type, the differences in electrical properties from normal to malignant were the least for kidney (about 6% and 4% average differences over the frequency range in permittivity and conductivity, respectively), and these differences were the greatest for mammary gland (about 233% and 577% average differences in permittivity and conductivity, respectively). To illustrate a potential use of these data in hyperthermia applications, frequency-selective heating of malignant tissue (modeled as a sphere) surrounded by host normal tissue is calculated from the measured electrical properties for certain tissues.

The magnitude of E-field patterns generated by an annular array prototype device has been calculated and measured. Two models were used to describe the radiating sources: a simple linear dipole and a stripline antenna model. The stripline model includes detailed geometry of the actual antennas used in the prototype and an estimate of the antenna current based on microstrip transmission line theory. This more detailed model yields better agreement with the measured field patterns, reducing the rms discrepancy by a factor of about 6 (from approximately 23 to 4%) in the central region of interest where the SEM is within 25% of the maximum. We conclude that accurate modeling of source current distributions is important for determining SEM distributions associated with such heating devices.

This paper develops and presents an application of Huygen's principle herein referred to as the equivalent uniformly illuminated aperture method (EUAM). This method is used to predict the E-field patterns of aperture antennas in both the near- and far-field regions. In applying this method the radiating aperture is mathematically replaced by an array of smaller, uniformly illuminated aperture sources. Thus the true aperture field is approximated in a step-wise manner by the individual sub-apertures that are uniformly illuminated by the field at the point on the aperture where the sub-aperture is located. This method is suitable for analysing any antenna if its aperture fields are known. Comparisons are made between this method, an equivalent dipole method, and experimental measurements. These calculations and measurements show that the EUAM is more accurate (especially in the near-field region), is much simpler to implement, and requires less execution time than the equivalent dipole method.

Temperature measurement using magnetic resonance imaging (MRI) of water self-diffusion is investigated. Diffusion images and derived temperatures are obtained in polyacrylamide gel phantom. The temperatures measured from MRI are compared with those from temperature probes to verify their accuracy. In general, the difference between temperatures determined from MRI diffusion images over 0.3 cm3 regions of interest and from temperature probes were 0.2 degrees C. It is concluded that current MRI technology allows noninvasive temperature tomography that is comparable with invasive thermometry with respect to temperature accuracy, has spatial and time resolutions that would be useful in hyperthermic oncology.

Intensive chemotherapy with autologous bone marrow transplantation is a promising approach for the treatment of breast cancer, provided that clonogenic tumor cells do not contaminate the patient's bone marrow. We have previously demonstrated that a combination of 4-hydroperoxycyclophosphamide (4-HC) and immunomagnetic purging (IMP) with monoclonal antibodies and microspheres could remove 4-5 logs of clonogenic breast cancer cells from a 10-fold excess of human bone marrow cells. In the present report we have evaluated an apparatus for separating tumor cells from a large volume of human marrow. This apparatus will permit preparation of large volumes of purged marrow for use in studies of intensive therapy with autologous marrow support. Bone marrow progenitor cell (CFU-GM) recovery following this IMP technique was 85% of the unpurged control, and suggests that marrow recovery following high dose systemic chemotherapy will not be adversely affected. A phase I study to evaluate marrow reconstitution following IMP is underway. Preliminary data suggest that this IMP method will not delay engraftment in breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support, but further study is required.

Measurements made on the interstitial microwave antennas used for hyperthermia cancer therapy indicate that the heating patterns vary with the insertion depths (defined as the distance from the antenna tip to air-tissue interface). The antennas are made of thin coaxial cables with a radiation gap or gaps on the outer conductor. The antennas are inserted into small polypropylene catheters implanted in the tumour volume. This type of antenna may be simulated as an asymmetric dipole with one arm being the tip section consisting of the expanded extension of the inner conductor, and the other arm being the section of the outer conductor from the gap to the insertion point (air-tissue interface). We use four of the antennas to form a 2 cm x 2 cm array. The antennas are positioned on the corners of a 2 cm square. Measurements on both single antennas and multi-antenna arrays show that the maximum heating is not stationary with position along the antenna when the depth of insertion is changed. This paper investigates the theoretical prediction of the changes in heating patterns of interstitial microwave antennas at different insertion depths. Each of the antennas in the array is simulated as an asymmetric dipole. The SAR (specific absorption rate) is computed by using the insulated dipole theory. The temperature distribution in absence of perfusion is obtained through a thermal simulation routine to convert the SAR pattern into the temperature pattern. Excellent qualitative agreement is found between the theoretical heating pattern and the measured pattern in a non-perfused phantom on a 2 cm x 2 antenna array. Since the insertion depths of the interstitial antennas are different from patient to patient, it is recommended that simulation of the heating be done before treatments, to confirm the delivery of power to the target region.

In this paper, we investigate an array of six interstitial microwave antennas used for hyperthermia cancer treatment. The purpose is to generate both uniform and controlled nonuniform heating patterns in biological tissue by phase modulating the signals applied to each antenna. The array consists of six antennas positioned on the corners of a hexagon. The distance between two diagonal antennas is 4 cm. The distributions of absorbed power per unit mass within the array are computed, and then converted into temperature distributions through a thermal conduction simulation. The SAR and temperature patterns are presented in both the lateral plane (perpendicular to the antennas) and the axial plane (parallel with the antennas). By proper phase modulation of microwave signals applied to each antenna, a uniform heating pattern can be produced within the entire array volume. Also, a peripheral heating pattern may be generated around the array; again, by using the proper phase modulation. The modulation schemes for generating both types of heating patterns are discussed.

We have investigated the effect of 5-hydroxytryptamine (5-HT) on SMT-2A mammary adenocarcinoma blood flow during localized microwave hyperthermia treatment. Tissue blood flow in isogeneic female W/Fu rats was estimated using 25-micron-diameter 113Sn-labeled microspheres. An intraarterial injection of 5-HT (1 mg/kg) into either conscious or anesthetized (Nembutal, 20 mg/kg) animals resulted in a 53% reduction in tumor blood flow, while that of the surrounding skeletal muscle remained unchanged. Because of the selective reduction in tumor perfusion, the blood flow of the normal and malignant tissue was equal after 5-HT injection. This blood flow equivalence remained unaltered after 45 min of heating at 42 degrees C. Consequently, the temperature in the tumor was not significantly different from that in the surrounding normal tissue. In contrast, when the tissues were heated at 42 degrees C without 5-HT, the tumor blood flow was significantly greater than that in the surrounding musculature, resulting in the tumor being 1 degree C lower than the muscle temperature. An intratumoral injection of 5-HT (0.25 mg) reduced the tumor blood flow by 92%, and the blood flow of the surrounding muscle was reduced by 57%. These tissue blood flows were not significantly altered by heating at 44 degrees C for 45 min, and the tumor temperature was 0.7 degrees C greater than that in the muscle. When heating at 44 degrees C was performed without 5-HT injection, the tissue temperatures were equal. Thus, both an intraarterial and an intratumoral injection of 5-HT prior to hyperthermia treatment significantly improved the temperature differential between the neoplastic and surrounding normal tissue. Of additional interest was the observation that an intratumoral injection of 0.15 M NaCl also resulted in a preferential increase in the tumor temperature.

The specific absorption rate (SAR) in a biological sample irradiated by electromagnetic fields between the metal plates of a transmission line can be altered significantly by the spacing of the metal plates and the distance between neighboring samples. The SAR in spherical biological samples is calculated for a number of neighboring sample arrangements and metal-plate spacings by using the method of images and induced dipole coupling. For a decrease in metal-plate spacing, the derived equations predict an increase in SAR within a sample and a decrease in SAR with a decrease in neighboring-sample spacing. The calculations are compared with measurements made with the aid of an array of 1-in radius metal hemispheres on the lower plate of two parallel plates (thus forming an image system). The hemisphere on which measurements are taken is insulated from the metal plate and is connected via a coaxial center conductor to an HP 3582A spectrum analyzer that measures the voltage and hence the electric field intensity at the hemisphere. Measurements made at a frequency where wavelength is large compared with sample size (48 Hz) are in good agreement with calculations.

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposure cell is a section of X-band waveguide that was modified by the addition of a center conductor to form a small TEM cell within the waveguide structure. The ELF signal is applied to the center conductor of the TEM cell. The applied ELF electric field generates an electrostrictive force on the surface of the brain tissue. This force causes the tissue to vibrate at a frequency equal to twice the frequency of the applied sinusoidal signal. An X-band signal is fed through the waveguide, scattered by the vibrating sample, and detected by a phase-sensitive receiver. Using a time-averaging spectrum analyzer, a vibration sensitivity of approximately 0.2 nmp-p can be achieved. The amplitude of the brain tissue vibrational response is constant for vibrational frequencies below 50 Hz; between 50 and 200 Hz resonant phenomena were observed; and above 200 Hz the amplitude fall-off is rapid.

In previous experiments changes were found in calcium-ion efflux from chick-brain tissue that had been exposed in vitro to 147-MHz radiation across a specific range of power densities when the field was amplitude modulated at 16 Hz. In the present study, 50-MHz radiation, similarly modulated as a sinusoid, was found to produce changes in calcium-ion efflux from chick brains exposed in vitro in a Crawford cell. Exposure conditions were optimized to broaden any power-density window and to enhance the opportunity to detect changes in the calcium-ion efflux. The results of a power-density series demonstrated two effective ranges: One spanning a range from 1.44 to 1.67 mW/cm2, and the other including 3.64 mW/cm2, which were bracketed by no-effect results at 0.72, 2.17, and 4.32 mW/cm2. peaks of positive findings are associated with near-identical rates of energy absorption: 1.4 microW/g at 147 MHz, and 1.3 microW/g at 50 MHz, which indicates that the enhanced-efflux phenomenon is more dependent on the intensity of fields in the brain than on the power density of incident radiation. In addition, the phenomenon appears to occur at multiples of some, as yet unknown, rate of radiofrequency (RF) energy absorption. Because of the extremely small increments of temperature associated with positive findings (less than 4 X 10(-4) degrees C), and the existence of more than one productive absorption rate, a solely thermal explanation appears extremely unlikely.

Rat brain was exposed to 591-MHz, continuous-wave (CW) microwaves at 13.8 or 5.0 mW/cm2 to determine the effect on nicotinamide adenine dinucleotide, reduced (NADH), adenosine triphosphate (ATP) and creatine phosphate (CP) levels. On initiation of the in vivo microwave exposures, fluorimetrically determined NADH rapidly increased to a maximum of 4.0%-12.5% above pre-exposure control levels at one-half minute, than decreased slowly to 2% above control at three minutes, finally increasing slowly to 5% above control level at five minutes. ATP and CP assays were performed on sham- and microwave-exposed brain at each exposure time. At 13.8 mW/cm2, brain CP level was decreased an average of 39.4%, 41.1%, 18.2%, 13.1%, and 36.4% of control at exposure points one-half, one, two three, and five minutes, respectively, and brain ATP concentration was decreased an average of 25.2%, 15.2%, 17.8%, 7.4%, and 11.2% of control at the corresponding exposure periods. ATP and CP levels of rat brain exposed to 591-MHz cw microwaves at 5mW/cm2 for one-half and one minute were decreased significantly below control levels at these exposure times, but were not significantly different from the 13.8 mW/cm2 exposures. For all exposures, rectal temperature remained constant. Heat loss through the skull aperture caused brain temperature to decrease during the five-minute exposures. This decrease was the same in magnitude for experimental and control subjects. Changes in NADH, ATP, and CP levels during microwave exposure cannot be attributed to general tissue hyperthermia. The data support the hypothesis that microwave exposure inhibits mitochondrial electron transport chain function, which results in decreased ATP and CP levels in brain.

Fertilized eggs of Gallus domesticus were exposed continuously during their 21-day incubation period to either 50- or 60-Hz sinusoidal electric fields at an average intensity of 10 Vrms/m. The exposure apparatus was housed in an environmental room maintained at 37 degrees C and 55-60% relative humidity (RH). Within 1.5 days after hatching, the chickens were removed from the apparatus and tested. The test consisted of examining the effect of 50- or 60-Hz electromagnetic fields at 15.9 Vrms/m and 73 nTrms (in a local geomagnetic field of 38 microT, 85 degrees N) on efflux of calcium ions from the chicken brain. For eggs exposed to 60-Hz electric fields during incubation, the chicken brains demonstrated a significant response to 50-Hz fields but not to 60-Hz fields, in agreement with the results from commercially incubated eggs [Blackman et al., 1985a]. In contrast, the brains from chicks exposed during incubation to 50-Hz fields were not affected by either 50- or 60-Hz fields. These results demonstrate that exposure of a developing organism to ambient power-line-frequency electric fields at levels typically found inside buildings can alter the response of brain tissue to field-induced calcium-ion efflux. The physiological significance of this finding has yet to be established.

A comparison of the effects of continuous-wave, sinusoidal-amplitude-modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague-Dawley rats (175-225 g). Brain NADH fluorescence, adenosine triphosphate (ATP) concentration, and creatine phosphate (CP) concentration were determined as a function of modulation frequency. Brain temperatures of animals were maintained between -0.1 and -0.4 degrees C from the preexposure temperature when subjected to as much as 20 mW/cm2 (average power) CW, pulsed, or sinusoidal-amplitude modulated 591-MHz radiation for 5 min. Sinusoidal-amplitude-modulated exposures at 16-24 Hz showed a trend toward preferential modulation frequency response in inducing an increase in brain NADH fluorescence. The pulse-modulated and sinusoidal-amplitude-modulated (16 Hz) microwaves were not significantly different from CW exposures in inducing increased brain NADH fluorescence and decreased ATP and CP concentrations. When the pulse-modulation frequency was decreased from 500 to 250 pulses per second the average incident power density threshold for inducing an increase in brain NADH fluorescence increased by a factor of 4--ie, from about 0.45 to about 1.85 mW/cm2. Since brain temperature did not increase, the microwave-induced increase in brain NADH and decrease in ATP and CP concentrations was not due to hyperthermia. This suggests a direct interaction mechanism and is consistent with the hypothesis of microwave inhibition of mitochondrial electron transport chain function of ATP production.

We have previously reported that in vitro exposure of chick forebrain tissue to 50-MHz radiofrequency (RF) electromagnetic radiation, amplitude modulated (AM) at 16 Hz, would enhance the efflux of calcium ions within only two power-density ranges: one from 1.44 to 1.67 mW/cm2, and the other including 3.64 mW/cm2. No effect on efflux occurred at 0.37, 0.72, 2.17, and 4.32 mW/cm2. We confirmed and extended these results by testing at another set of power densities, which included the range of the previous study. Forebrain tissue from 1-7-day-old chickens was labeled in vitro with radioactive calcium ions (30 min, at 37 degrees C), rinsed, placed in a physiological salt solution, and then exposed for 20 min to 50-MHz radiation, AM at 16 Hz, in a transverse electric and magnetic field (TEM) cell maintained at 37 degrees C. The solution was then assayed for radioactive calcium activity. A power-density series was tested. An enhanced efflux of calcium ions was found at 1.75, 3.85, 5.57, 6.82, 7.65, 7.77, and 8.82 mW/cm2; no change was observed at 0.75, 2.30, 4.50, 5.85, 7.08, 8.19, 8.66, 10.6, and 14.7 mW/cm2. Power density is converted to specific absorption rate (SAR) by 0.36 mW/kg per mW/cm2. Even the highest SAR tested (0.005 W/kg) is much too low to result in generalized heating of the sample and thus to be the underlying cause of the enhanced response. A hypothetical mechanism is proposed involving dynamic systems that may account for the power-density dependency as well as for part of the frequency dependency observed with both modulated RF radiation and extremely-low-frequency (ELF) fields.

Autoradiographic maps of brain activity in rats exposed to pulsed or continuous-wave (CW) microwave radiation were made using [14C]2-deoxy-D-glucose ([14C]2-DG). Special emphasis was given to measurements of activity in the auditory system because previous work had shown that pulsed microwave radiation can elicit auditory responses in man and other animals. In particular, one middle ear was ablated in nine rats to attenuate the transmission of air-borne sound to one cochlea. The resulting imbalance in auditory input for four animals not exposed to microwave radiation was reflected as a bilateral asymmetry of [14C]2-DG uptake at the inferior colliculus and medial geniculate body. In contrast, a symmetrical pattern of uptake at these structures in an animal exposed to pulsed microwave radiation showed that this stimulus bypasses the middle ear in eliciting auditory responses. This result established the utility of the [14C]2-DG method for demonstrating a known effect of microwave radiation on brain activity. The results also revealed responses at auditory nuclei in 4 animals exposed to CW microwave radiation. These responses, which have not been observed with other methods, were evident at the power densities of 2.5 and 10 mW/sq. cm. To exclude the possibility that CW microwave radiation produced this result by direct action on brain tissue, additional data were obtained from two rats with one cochlea destroyed. In both animals, the uptake of [14C]2-DG at the inferior colliculus and medial geniculate body was virtually identical to the uptake in animals not exposed to microwave radiation, i.e. greatest on the side of the brain contralateral to the intact cochlea. This finding, coupled with the finding of a bilateral symmetry of [14C]2-DG uptake in the auditory pathways of animals with one middle ear ablated, confirmed the hypothesis that auditory responses to CW microwave radiation originate within the cochlea. Effects on brain activity outside of the auditory system were not found in qualitative analyses of autoradiographs for the conditions of exposure to CW microwave radiation noted above or for exposure to pulsed microwave radiation at the average power density of 2.5 mW/sq. cm.

This paper presents calculations for the electric field and absorbed power density distribution in chick brain tissue inside a test tube, using an off-center spherical model. It is shown that the off-center spherical model overcomes many of the limitations of the concentric spherical model, and permits a more realistic modeling of the brain tissue as it sits in the bottom of the test tube surrounded by buffer solution. The effect of the unequal amount of buffer solution above the upper and below the lower surfaces of the brain is analyzed. The field distribution is obtained in terms of a rapidly converging series of zonal harmonics. A method that permits the expansion of spherical harmonics about an off-center origin in terms of spherical harmonics at the origin is developed to calculate in closed form the electric field distribution. Numerical results are presented for the absorbed power density distribution at a carrier frequency of 147 MHz. It is shown that the absorbed power density increases toward the bottom of the brain surface. Scaling relations are developed by keeping the electric field intensity in the brain tissue the same at two different frequencies. Scaling relations inside, as well as outside, the brain surface are given. The scaling relation distribution is calculated as a function of position, and compared to the scaling relations obtained in the concentric spherical model. It is shown that the off-center spherical model yields scaling ratios in the brain tissue that lie between the extreme values predicted by the concentric and isolated spherical models.

The present experiments were designed to investigate the effects of microwave hyperthermia on the microcirculation of normal and malignant tissues in female Wistar/Furth rats. During the localized heating of anesthetized rats, the hind leg musculature surrounding the SMT-2A mammary adenocarcinoma was heated at either 39 degrees, 42 degrees, or 44 degrees. Neither the body temperature, cardiac output, heart rate, nor systemic arterial pressure were significantly altered by heating at these temperatures for up to 60 min. Our results demonstrate that the changes in vascular resistance which occur during hyperthermic treatment are dependent upon both the temperature and the tissue heated. When the tumor (1.2 g)-bearing hind leg was heated to 39 degrees, the tissue vascular resistance and blood flow were unaltered even after 45 min of heating. Heating at 42 degrees and 44 degrees caused an initial vasoconstriction in the tumor, which was subsequently followed by marked vasodilation. This transient initial decrease in blood flow was not, however, observed in the skeletal muscle at either temperature. With prolonged heating at 42 degrees and 44 degrees, the muscle blood flow increased by a factor of 1.6 and 3.2, respectively. In contrast, malignant tissue blood flow increased by a factor of 1.3, and this maximum increase was observed only when the tumor was heated at 44 degrees for more than 45 min. Nevertheless, even with this proportionally greater increase in the blood flow of the surrounding normal tissue, it was never more than that of the tumor. As a consequence, the tumor temperature during hyperthermic treatment was always either less than or equal to that in the surrounding normal musculature.

We have studied the effects of low-power-density microwave (MW) radiation (continuous and pulsed wave with average power density of 10 milliwatts/sq cm and range of 5 to 50 milliwatts/sq cm; frequency, 1.0 GHz) on the uptake and action of methotrexate (MTX), the inhibition of DNA synthesis in L1210 murine leukemia cells in vitro, and the MTX treatment of mice bearing this leukemia. Using short-term tissue culture techniques, MTX concentrations of 0.2 microM, and MW exposure times of 20 min, we have found that continuous-wave low-power-density MW irradiation enhances the uptake of [3H]MTX as compared to nonirradiated controls. The enhancement is observed in only a small range of power densities (5 to 25 milliwatts/sq cm) and is in an inverted-U-shaped relationship. MW irradiation alone has an inhibitory effect on the [3H]deoxyuridine incorporation into DNA. Compared to cell suspensions treated with MTX alone, groups treated with MW irradiation followed by MTX exhibit an augmentation of inhibition of DNA synthesis as measured by [3H]deoxyuridine incorporation. Combined treatment of L1210-bearing mice with MW irradiation and MTX in vivo prolonged the duration of survival over that of animals treated with MTX alone, indicating a greater killing of leukemia cells. These results suggest that the therapeutic index of MTX may be improved by the use of MW irradiation at low power densities.

Transverse electric and magnetic field (TEM) cells are often designed to subject samples to electromagnetic radiation of intrinsic impedance (E/H) that is the same as in free space, 377 omega. Earlier work has shown this value to be correct for the RF region above about 2 kHz. In this study, measurements of magnetic fields in the extremely low frequency regions and at DC indicate the E/H ratio to be around 300 omega for frequencies less than 2 kHz in cells of a particular design. This lower value indicates that care should be taken in estimating AC magnetic field intensities from electric field measurements in TEM cells at frequencies below 2 kHz.

Two independent laboratories have demonstrated that electromagnetic radiation at specific frequencies can cause a change in the efflux of calcium ions from brain tissue in vitro. In a local geomagnetic field (LGF) at a density of 38 microTesla (microT), 15- and 45-Hz electromagnetic signals (40 Vp-p/m in air) have been shown to induce a change in the efflux of calcium ions from the exposed tissues, whereas 1- and 30-Hz signals do not. We now show that the effective 15-Hz signal can be rendered ineffective when the LGF is reduced to 19 microT with Helmholtz coils. In addition, the ineffective 30-Hz signal becomes effective when the LGF is changed to +/- 25.3 microT or to +/- 76 microT. These results demonstrate that the net intensity of the LGF is an important variable. The results appear to describe a resonance-like relationship in which the frequency of the electromagnetic field that can induce a change in efflux is proportional to a product of LGF density and an index, 2n + 1, where n = 0,1. These phenomenological findings may provide a basis for evaluating the apparent lack of reproducibility of biological effects caused by low-intensity extremely-low-frequency (ELF) electromagnetic signals. In future investigations of this phenomenon, the LGF vector should be explicitly described. If the underlying mechanism involves a general property of tissue, then research conducted in the ambient electromagnetic environment (50/60 Hz) may be subjected to unnoticed and uncontrolled influences, depending on the density of the LGF.

Hyperthermia is attractive as a potential adjunctive modality in the treatment of cancer, especially those cancers that are more resistant to conventional modalities. In the present study, we characterized the response of two pancreatic cancer cell lines to hyperthermia alone. In so doing, we utilized and characterized a novel exposure system that heats by 915-MHz continuous wave microwave (MW) radiation, with microprocessor control of the power input via temperature monitoring of the sample and simultaneous visualization and recording of temperature parameters. Samples, consisting of cells in 25-cm2 culture flasks with 10 ml of medium, were exposed to MWs in a stripline for 1 h at MW-induced temperatures of 37, 41.5, 42.5, 43.5, or 44.5 degrees C. The specific absorption rate was 132 W/kg for all temperatures. In addition, 37 degrees C waterbath controls were concurrently run. The colony formation assay was used to assess cytotoxicity. No significant difference was found between 37 degrees C waterbath and 37 degrees C MW controls. Significant differences in the thermosensitivity of the two cell lines were found, with the most drug-sensitive cell line showing the greatest thermosensitivity. However, hyperthermia alone was not very effective as a single cytotoxic modality in either cell line. The MW-hyperthermia-induction system provided precise, automated temperature control (+/- 0.2 degrees C), and ease of utilization and data management.

This paper compares two methods for determining the radio frequency absorbed power in tissue: from the measured electrical properties of the tissue, and from the induced temperature rise per unit time. In previous research, we measured the ratio frequency electrical properties of muscle, mammary gland, and malignant mammary tissue (SMT-2A mammary adenocarcinoma) in female W/Fu isogeneic rats. From those measurements we calculated for each tissue the power absorption versus frequency, and formed the ratio of malignant-to-normal power absorption. This ratio exhibited a peak within the 150 to 400 MHz range, indicating a selective absorption of power in this type of malignant tissue over that of the normal host tissue. In the present study, by an entirely different method, we have directly tested the results of our earlier research. We filled a 20-cm-long section of rigid coaxial line (ordinarily air filled) with either normal (beef muscle or fat) or malignant (SMT-2A) tissue, and measured the temperature increase versus time at the irradiated tissue surface for the same absorbed power in each tissue type. We made the measurements from 50 to 915 MHz, and found that the initial temperature increase per second per watt absorbed (dT/dt/Pa) was greater in malignant tissue than in muscle or fat at each frequency tested, with the greatest differences occurring below 450 MHz. Power absorption based on the measured values of dT/dt/Pa was again greatest for the malignant tissue (SMT-2A mammary adenocarcinoma) within the 150 to 400 MHz range.

The effects of hyperthermia, alone and in conjunction with microwave exposure, on brain energetics were studied in anesthetized male Sprague-Dawley rats. The effect of temperature on adenosine triphosphate concentration [ATP] and creatine phosphate concentration [CP] was determined in the brains of rats that were maintained at 35.6, 37.0, 39.0, and 41.0 degrees C. At 37, 39, and 41 degrees C brain [ATP] and [CP] were down 6.0, 10.8, and 29.2%, and 19.6, 28.7, and 44%, respectively, from the 35.6 degrees C control concentrations. Exposure of the brain to 591-MHz radiation at 13.8 mW/cm2 for 0.5, 1.0, 3.0, and 5.0 min caused further decreases (below those observed for 30 degrees C hyperthermia only) of 16.0, 29.8, 22.5, and 12.3% in brain [ATP], and of 15.6, 25.1, 21.4, and 25.9% in brain [CP] after 0.5, 1.0, 3.0, and 5.0 min, respectively. Recording of brain reduced nicotinamide adenine dinucleotide (NADH) fluorescence before, during, and after microwave exposure showed an increase in NADH fluorescence during microwave exposure that returned to preexposure levels within 1 min postexposure. Continuous recording of brain temperatures during microwave exposures showed that brain temperature varied between -0.1 and +0.05 degrees C. Since the microwave exposures did not induce tissue hyperthermia, it is concluded that direct microwave interaction at the subcellular level is responsible for the observed decrease in [ATP] and [CP].

This report describes some experimental measurements of the internal field levels induced within isolated chick-forebrains irradiated at 50, 147, and 450 MHz, under essentially the same conditions as those used in the in vitro calcium-ion efflux experiments. Ratios of incident power at 50/147 MHz and 147/450 MHz that are needed to establish the same probe output are given and comparisons made with values predicted by different spherical models. Data predicted by the layered-sphere model were found to be in close agreement with measured values for the 50/147-MHz ratio. Agreement for the 147/450-MHz ratio was poorer.

We have previously shown that 16-Hz, sinusoidal electromagnetic fields can cause enhanced efflux of calcium ions from chick brain tissue, in vitro, in two intensity regions centered on 6 and 40 Vp-p/m. Alternatively, 1-Hz and 30-Hz fields at 40 Vp-p/m did not cause enhanced efflux. We now demonstrate that although there is no enhanced efflux associated with a 42-Hz field at 30, 40, 50, or 60 Vp-p/m, a 45-Hz field causes enhanced efflux in an intensity range around 40 Vp-p/m that is essentially identical to the response observed for 16-Hz fields. Fields at 50 Hz induce enhanced efflux in a narrower intensity region between 45 and 50 Vp-p/m, while radiofrequency carrier waves, amplitude modulated at 50 Hz, also display enhanced efflux over a narrow power density range. Electromagnetic fields at 60 Hz cause enhanced efflux only at 35 and 40 Vp-p/m, intensities slightly lower than those that are effective at 50 Hz. Finally, exposures over a series of frequencies at 42.5 Vp-p/m reveal two frequency regions that elicit enhanced efflux--one centered on 15 Hz, the other extending from 45 to 105 Hz.

One-GHz microwave (MW) irradiation at a power density of 5 mW/cm2 was combined with methotrexate (MTX) in an attempt to treat more effectively central nervous system (CNS) L1210 leukemia in DBA/2J mice. When mice with CNS leukemia were treated with the combination of MW and MTX, there was no improvement in survival compared with a group of animals treated with MTX alone; however, the group that received MTX before the MW exposure had a significantly reduced survival time compared with the group treated with MTX alone or with the group to which MTX was administered after MW.

Three key compounds in brain energy metabolism have been measured during and after exposure to continuous wave radiofrequency radiation at 200, 591, and 2,450 MHz. Frequency-dependent changes have been found for all three compounds. Changes in NADH fluorescence have been measured on the surface of a surgically uncovered rat brain during exposure. At 200 and 591 MHz, NADH fluorescence increased in a dose-dependent manner between approximately 1 and 10 mW/cm2, then became constant at higher exposures. There was no effect at 2,450 MHz. Levels of ATP and CP were measured in whole brain after exposure. The ATP levels were decreased at 200 and 591 MHz but not at 2,450 MHz. The CP levels decreased only at 591 MHz. The effect of duration of exposure (up to 5 min) was investigated for all compounds at 200 MHz and 2,450 MHz, and exposures to 20 minutes were examined at 591 MHz. Temperature in the rat brain was essentially constant for all exposures. A general mechanism for inhibition of the mitochondrial electron transport chain and the CP-kinase reaction pathway by radiofrequency radiation has been proposed.

To explain a carrier frequency dependence reported for radiofrequency (RF)-induced calcium-ion efflux from brain tissue, a chick-brain hemisphere bathed in buffer solution is modeled as a sphere within the uniform field of the incident electromagnetic wave. Calculations on a spherical model show that the average electric-field intensity within the sample remains the same at different carrier frequencies if the incident power density (Pi) is adjusted by an amount that compensates for the change in complex permittivity (epsilon *r) and the change of wavelength, as a function of carrier frequency. The resulting formula for transforming Pi is seen to follow the pattern of both positive and negative demonstrations of calcium-ion efflux that have been observed at carrier frequencies of 50, 147, and 450 MHz. Indeed, all results obtained at these three frequencies, when related by Pi's that produce the same average electric-field intensity within the sample, are seen to be in agreement; no prediction is contradicted by an experiment.

Presented here are the numerical relationships between incident power densities that produce the same average electric field intensity within a chick brain half immersed in buffered saline solution and exposed to a uniform electromagnetic field at carrier frequencies of 50, 147, and 450 MHz. Calculations are based on modeling the buffer solution as a spherical shell in air with an inner concentric sphere of brain tissue. The results support our earlier conclusion that calcium efflux results obtained at different carrier frequencies are in agreement when related by the electric field within the brain.

The question of how pulsed microwaves induce auditory effects in animals and man leads to an examination of the parameters which determine the frequencies of maximum reception by the skull, and the positions of maximum energy deposition within the brain. The interaction of microwaves with a nerve membrane model and with live nerve cells is also discussed, as well as planned experiments to determine the microwave properties of membranes.