Search

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.

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.

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.

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.

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.

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.

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].

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.

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.