J. A. McDougall

Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat

In the presence of iron, dihydroartemisinin forms free radicals and causes cell death. Since most cancer cells have high rates of iron intake, dihydroartemisinin would have selective cytotoxic effect on cancer cells. The present experiment was designed to study the effect of dihydroartemisinin and ferrous sulfate on the growth of implanted fibrosarcoma in the rat. We found that the growth rate of the tumor was significantly retarded by daily oral administration of ferrous sulfate followed by dihydroartemisinin. No significant tumor growth retardation effect was observed in rats treated with either dihydroartemisinin or ferrous sulfate alone. The drug treatment did not significantly affect body weight compared with untreated tumor-implanted animals and no apparent toxic effect was observed after drug treatment. An artemisinin analog-ferrous salt combination may provide a novel approach for cancer therapy.

RF heating of implanted spinal fusion stimulator during magnetic resonance imaging

Radio frequency (RF) heating of an implanted spinal fusion stimulator (SpF) during magnetic resonance imaging (MRI) was studied on a full-size human phantom. Heating during MRI scans (GE Signa 4X, 1.5 T) was measured with RF-transparent fiberoptic sensors. With the implant correctly connected, the maximum temperature rises were less than 2/spl deg/C during the 26 min that the scans were at maximum RF power. At the tip of a broken stimulator lead (connecting the SpF generator and its electrodes), the maximum temperature rise was 11-14/spl deg/C. Regular 4-min scans of the spinal cord produced similar temperature rises at the broken tip. After the generator and the leads were removed, heating at the electrode connector tip was less than 1.5/spl deg/C. The control temperature rises at the same locations, without the stimulator, were less than 0.5/spl deg/C. This study shows that spinal fusion stimulator heating is within the Food and Drug Administration safety guideline of 2/spl deg/C. However, if a lead wire is broken, it is unsafe during MRI scans. Radiological examinations will be necessary to ensure the integrity of the implant.

A quarter century of in vitro research: a new look at exposure methods.

The specific absorption rate (SAR) distributions in radio frequency–exposed solutions containing suspended or plated cells in vessels used for in vitro research were calculated by the finite-difference-time-domain method, graphed in color, and statistically analyzed in terms of uniformity for application to research on safety of wireless devices. The uniformity of SAR was quantified by visual inspection of colored plots, histograms, means, standard deviations, and maximums for the cell suspensions exposed in test tubes, Petri dishes, and rectangular flasks. Exposure sources included plane waves, transverse electromagnetic (TEM) cells, and striplines used at frequencies of 837, 2450, or 3,000 MHz. The results demonstrated that the most nonuniform SARs for plated or suspended cells in solution occurred for exposures of test tubes and rectangular flasks with plane waves, polarized for maximal absorption. The most uniform SARs for a layer of cells occurred for exposure of Petri dishes oriented for weakest coupling to the fields in a TEM cell. Additional improvement in uniformity was found to be possible by restricting the edge of the layer of cells from being too near the edges of the dish. It was not possible to achieve satisfactory uniformity in the SAR in cell suspensions exposed in standard vessels to any of the sources. The best but not satisfactory SAR uniformity was observed for cells suspended in the lowest 1-ml volume of the liquid contained in a test tube exposed at the bottom in a TEM cell. Experimental measurements of average SAR by temperature change for this case varied from 18% higher to 26% lower than finite difference time domain–derived values. The most uniform SAR distribution for cell suspensions in nonstandard containers was found for a rectangular slab configuration exposed in a stripline with the plates separated from the media by a thin layer of insulation. It is possible to experimentally implement this model by placing a fluid-filled thin-wall rectangular container tightly between the plates of a stripline. Bioelectromagnetics 20:21–39, 1999.

Electrochemical treatment of mouse and rat fibrosarcomas with direct current

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten rats in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study, i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice. and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.

Development of a rat head exposure system for simulating human exposure to RF fields from handheld wireless telephones.

The aim of this project was to develop an animal exposure system for the biological effect studies of radio frequency fields from handheld wireless telephones, with energy deposition in animal brains comparable to those in humans. The finite-difference time-domain (FDTD) method was initially used to compute specific absorption rate (SAR) in an ellipsoidal rat model exposed with various size loop antennas at different distances from the model. A 3 x 1 cm rectangular loop produced acceptable SAR patterns. A numerical rat model based on CT images was developed by curve-fitting Hounsfield Units of CT image pixels to tissue dielectric properties and densities. To design a loop for operating at high power levels, energy coupling and impedance matching were optimized using capacitively coupled feed lines embedded in a Teflon rod. Sprague Dawley rats were exposed with the 3 x 1 cm loop antennas, tuned to 837 or 1957 MHz for thermographically determined SAR distributions. Point SARs in brains of restrained rats were also determined thermometrically using fiberoptic probes. Calculated and measured SAR patterns and results from the various exposure configurations are in general agreement. The FDTD computed average brain SAR and ratio of head to whole body absorption were 23.8 W/kg/W and 62% at 837 MHz, and 22.6 W/kg/W and 89% at 1957 MHz. The average brain to whole body SAR ratio was 20 to 1 for both frequencies. At 837 MHz, the maximum measured SAR in the restrained rat brains was 51 W/kg/W in the cerebellum and 40 W/kg/W at the top of the cerebrum. An exposure system operating at 837 MHz is ready for in vivo biological effect studies of radio frequency fields from portable cellular telephones. Two-tenths of a watt input power to the loop antenna will produce 10 W/kg maximum SAR, and an estimated 4.8 W/kg average brain SAR in a 300 g medium size rat.

Changes in heating patterns of interstitial microwave antenna arrays at different insertion depths

The changes in heating patterns of interstitial microwave antennas at different insertion depths were investigated in a static phantom at 915 MHz. Antennas for the Clini-Therm Mark VI system were inserted 5-15 cm into muscle-equivalent material, through nylon catheters. The phantom was heated with arrays of antennas at 2 cm spacings for 60 s at 15 W per antenna. Midplane and transverse heating patterns were determined thermographically with the antennas inserted parallel or perpendicular to the split of the phantom. Hot spots, independent of heating near the junction plane, were observed in the midplane of the 2 x 2 and 2 x 4 arrays at 2.8 cm from the insertion end. The magnitudes of these hot spots were reduced by 40-45 per cent as insertion depth was increased from 7 to 10.5 cm. With insertion depths of more than 11.5 cm the hot spots gradually diminished and heating occurred mostly near the junction plane. The observed heating patterns were caused by changes in impedance of the antenna arrays at different insertion depths. The impedance mismatch had resulted in different wave propagation within the tissue material which produced different radiation patterns. During treatments, because heating varies with insertion depth, great care must be exercised in monitoring temperatures.

Changes in heating patterns due to perturbations by thermometer probes at 915 and 434 MHz

The changes in heating patterns due to perturbations by thermometer probes in microwave fields were investigated in static phantoms at 915 and 434 MHz. Thermograms taken parallel to the plane of E and H fields, at depths of up to 2 cm, indicated heating changes of +25 to -45 per cent at 915 MHz and +/- 15 per cent at 434 MHz. The amount of perturbation is dependent on the length, size and location of the probes in the RF fields and their orientations to the electric field. If proper probe placement techniques are not observed when metallic probes are involved, hot and cool spots can be generated and shifted to sites that are not measured. Therefore misleading temperatures can result when changes in heating patterns are not detected. Perturbation also varies with applicator designs and phantom geometry. If thermistors and thermocouples are used, the effects of perturbation should be investigated with individual applicators under applicable clinical conditions.

Perturbations due to the use of catheters with non-perturbing thermometry probes

Perturbations due to the use of catheters with non-perturbing thermometry probes were investigated in static phantom at 915 MHz. Fibre optic probes for the Luxtron and Clini-Therm thermometry systems, and Vitek probes for the BSD hyperthermia systems, were inserted in closed-end catheters at depths up to 2 cm in the phantom and exposed parallel to the E-field. The probes alone produced 0-12 per cent changes in heating and catheters alone were 0-20 per cent. When the probes were inserted in catheters, perturbations were 0-12 per cent at the surface and 1 cm depth, and 5-15 per cent at 2 cm depth. Even with non-perturbing probes it is important to place catheters perpendicular to the E-field during microwave hyperthermia.

Evaluation of captive bolus applicators

Three square (L, M, MS) and one rectangular (HN) applicators with captive boluses were provided by the Clini-Therm Corporation for evaluation. Surface cooling is achieved by attaching a mineral oil captive bolus to the built in water-circulating tubes at the aperture of the applicators. These applicators were tested on a phantom with a 2-cm fat slab over 10-cm-thick muscle. Surface and sagittal heating patterns were obtained using a thermograph. All captive-bolus applicators have heating patterns similar to that of the regular Clini-Therm applicators. Due to hot spots at the edges of the applicators where the E fields terminate, these modified applicators should not be placed in direct contact with patients when boluses are not used. Tests with Clini-Therm regular water bolus instead of the captive oil bolus indicated that the orientation of water flow should be parallel to the E field to minimize perturbation of the heating patterns. Thermal conduction studies showed that the captive bolus reacts too slowly for skin temperature control. The modified captive bolus applicators did not improve the performance of the system.

FDTD simulations of Clini-Therm applicators on inhomogeneous planar tissue models

A finite-difference time-domain (FDTD) algorithm was used to compute SAR distributions in planar fat-muscle phantom exposed to the Clini-Therm microwave applicators. The models consisted of a 30 X 30 X 7.5 cm phantom and a 15 X 15 cm, 10 X 10 cm or 7.5 X 7.5 cm aperture dielectric slab loaded applicator. The phantom was either filled with muscle material or with 1.0 cm fat on 6.5 cm muscle. A mineral oil bolus was placed on the fat-muscle model with its integrated water channels parallel to the electric or magnetic field. The FDTD resolution was 3 mm and the applicators were excited with a Gaussian pulse. The computations required 6000-8000 time steps to reach steady state, with 45-48 Mwords on a Cray Y-MP C-90 in 1000-1200 CPU seconds. The electric field components at 915 MHz were obtained by summing the Fourier coefficients at each grid point during each time step and SAR was determined. The results were qualitatively compared to existing and published thermographic heating patterns with good agreement. The computed electric field distributions had provided a three dimensional view into the problem space to investigate and understand wave propagation phenomena in complex inhomogeneous configurations that were not feasible with experimental models.