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Biomedical subjects

C A Cain

Publications and source records attributed to C A Cain.

14 recordsLinked to original sources

Direct computation of ultrasound phased-array driving signals from a specified temperature distribution for hyperthermia.

This paper presents a new method which obtains ultrasound hyperthermia applicator phased-array element driving signals from a desired temperature distribution. The approach combines a technique which computes array element driving signals from focal point locations and intensities with a new technique which calculates focal point locations and power deposition values from temperature requirements. Temperature specifications appear here as upper and lower bounds within the tumor volume, and a focal point placement algorithm chooses focal patterns capable of achieving the temperature range objective. The linear algebraic structure of the method allows rapid calculation of both the phased-array driving signals and an approximate temperature field response. Computer simulations verify the method with a spherical section array (SSA) for a variety of temperature specifications and blood perfusion values. This scheme, which applies to any phased-array geometry, completes an essential step in both treatment planning and feedback for hyperthermia with ultrasound phased-array applicators.

Acoustics

A spherical-section ultrasound phased array applicator for deep localized hyperthermia.

Computer simulation shows that a new ultrasound phased-array with nonplanar geometry has considerable potential as an applicator for deep localized hyperthermia. The array provides precise control over the heating pattern in three dimensions. The array elements form a rectangular lattice on a section of a sphere. Therefore, the array has a natural focus at its geometric center when all its elements are driven in phase. When compared to a planar array with similar dimensions, the spherical-section array provides higher focal intensity gain which is useful for deep penetration and heat localization. Furthermore, the relative grating-lobe level (with respect to the focus) is lower for scanned foci synthesized with this array (compared to a planar array with equal center-to-center spacing and number of elements). This could be the key to the realization of phased-array applicator systems with a realistic number of elements. The spherical-section array is simulated as a spot-scanning applicator and, using the pseudo-inverse pattern synthesis method, to directly synthesize heating patterns overlaying the tumor geometry. A combination of the above two methods can be used to achieve the desired heating pattern in the rapidly varying tumor environment.

Computer Simulation

Time-temperature analysis of cell killing of BHK cells heated at temperatures in the range of 43.5 degrees C to 57.0 degrees C.

Baby hamster kidney (BHK) cells were heated at temperatures in the range of 43.5 degrees C to 57.0 degrees C to determine the time-temperature relationship of cell killing. The cells were grown on 0.025 mm thick pieces of mylar to minimize warm-up times. After heating, the cells were plated for the colony formation assay. The endpoints of 1%, 10%, or 90% isosurvival, or the D0 values of the survival curves were used to construct plots of the logarithm of the reciprocol of the exposure time versus the reciprocol of the absolute temperature. The data for each endpoint resulted in a straight line plot, indicating that the time-temperature relationship for cell killing remained constant from 43.5 degrees C to 57.0 degrees C; namely, a 1.8-fold increase in exposure time was required for a 1 degree C decrease in temperature in order to obtain isosurvival. Heated BHK cells were also examined using electron microscopy. The threshold level of altered morphology was the dissociation of polyribosomal structure and the formation of electron-dense granules within the mitochondria. The time-temperature relationship for the induction of this altered morphology was identical to that for the 90% isosurvival endpoint. Hence, the appearance of altered morphology appears to be related to cell killing.

Animals

Ultrasonic reflection mode imaging of the nonlinear parameter B/A. II: Signal processing.

The nonlinear acoustic interaction between a reflected single-frequency sinusoid and a broadband pump waveform propagating in the opposite direction produces phase changes in the probe proportional to the nonlinear parameter B/A in the spatial region of interaction. The instantaneous phase change along the received probe can be expressed as the convolution of the pump waveform with the spatial distribution of B/A along the propagation path over which the pump and reflected probe interact. In theory, the phase modulated sinusoidal probe can be processed (phase detection and deconvolution) to produce an "A-mode" representation of B/A. If the pump is an intense unipolar impulse and the probe a swept-frequency sinusoid, then the pump interacts with the probe at each point along the propagation path at a unique frequency. Thus the phase modulation that carries information about the spatial distribution of B/A can be extracted from the phase spectrum by a simple Fourier transformation analogous to the space to frequency mapping so basic to magnetic resonance imaging. If the impulsive pump is replaced by another swept-frequency sinusoid, then the phase change in the probe due to B/A at a particular point along the propagation path will be spread out for the duration of the pump along the probe. Passage of the received signal through an appropriate matched filter restores spatial coherence to the phase information in the probe so that it can be processed as if the pump were a broadbanded impulse. This approach suggests a means of approaching the design of effective pump waveforms that can resolve a wide range of spatial frequencies in (B/A)(x).

Algorithms

Absence of heart-rate effects in isolated frog heart irradiated with pulse modulated microwave energy.

Isolated frog hearts were irradiated with pulse modulated microwave energy synchronized with the ECG. No statistically significant or otherwise observable differences were found between the heart rate of irradiated groups and the nonirradiated control group. Experiments were performed to explore the possible effects of currents induced between the recording electrodes. Increases in heart rate occurred when applied current pulses between 20 and 30 mA were synchronized with the ECG during an interval from 200 msec to 300 msec after the peak of the P wave.

Animals

Analysis of temperature responses to diffused ultrasound focal fields produced by a sector-vortex phased array.

The sector-vortex applicator, a disc-shaped ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. Temperature distribution patterns resulting from these acoustic fields have been simulated by solving a steady-state bioheat equation numerically for a wide range of blood perfusion rates. These results suggest that the sector-vortex array will be particularly suitable for heating non-superficial small tumours. The temperature distribution pattern changes due to variations in blood perfusion are interpreted based on spatial frequency domain Fourier analysis of temperature responses to different power deposition patterns. The system behaves like a low-pass spatial frequency filter.

Biophysical Phenomena

The concentric-ring array for ultrasound hyperthermia: combined mechanical and electrical scanning.

While two-dimensional phased arrays can be electronically focused and steered in three dimensions without physically moving the applicator, they generally require a relatively large number of small transducer elements and, consequently, complex drive electronics. A configuration that does not require a large number of elements is that of a concentric-ring array. The field conjugation method can be used to produce a focal spot (or multiple spots) along the array axis. The resulting focal regions are very small and need to be steered transversely to heat tumours of typical size. However, steering the focused beam away from the array axis results in annular heating patterns which are often associated with undesired secondary foci (hot spots). In this paper, a method based on combining electrical and mechanical scanning using a concentric-ring applicator is presented. Advantages of the new method over the mechanically scanned fixed-focus transducers, currently in use, are pointed out. Computer simulations are conducted to investigate the possibility of heating different size tumours by appropriately combining the two scanning techniques. The bioheat transfer equation is solved numerically and temperature distributions associated with relevant heating patterns are presented and discussed. The simulations demonstrate the possibility of the combined technique to produce useful heating patterns which cannot be produced by either technique separately.

Biomechanical Phenomena

Optimization of the intensity gain of multiple-focus phased-array heating patterns.

A new technique for enhancing the intensity gain at the focal points in multiple-focus patterns is introduced. The new technique is shown to be effective in reducing the interference typically associated with multiple-focus patterns. This reduction in interference patterns allows multiple-focus scanning to generate highly localized heating. Simulation results indicate that multiple-focus scanning not only provides an alternative to single-focus scanning, but also achieves better localization in the heating pattern. The maximization of intensity gain of multiple-focus heating patterns significantly reduces the pre-focal-depth high-temperature regions that can be caused by single-focus scanning. This is shown by computer simulation of a two-dimensional cylindrical-section array (CSA2D) as a heating applicator. Two series of simulations are presented in which different scan trajectories were used to therapeutically heat a small deep-seated target volume. In every case the heating pattern was generated using single-focus scanning and multiple-focus scanning (with and without intensity gain maximization). Multiple-focus scanning with gain maximization offers the best localization of heating to the target volume of the three methods.

Biophysical Phenomena

Insonation of fixed porcine kidney by a prototype sector-vortex-phased array applicator.

The sector-vortex applicator, an ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. A perfused tissue phantom, consisting of an alcohol-fixed porcine kidney with thermocouples placed in the cortex, is insonated by a prototype sector-vortex applicator with 16 sectors and two tracks at an ultrasound frequency of 750 kHz. Steady-state temperature distributions are measured for a wide range of perfusion rates. Results demonstrate that the radius of the heated region can be controlled effectively by choosing the focal mode of the applicator as it is predicted by theoretical analysis.

Animals

Radiant heat-induced hyperthermia in mice: in vivo effects on the immune system.

Whole-body hyperthermia (WBH) in mice was induced by 2-4-h exposure to radiant heat resulting in core body temperatures of 38.5-40.4 degrees C, and correlated directly with the magnitude and duration of heat treatment. Two-hour heat treatments in this temperature range did not consistently affect generation of antibody-forming cells in vivo, while 4-h treatments at temperatures greater than or equal to 40 degrees C significantly suppressed the antibody-forming cell response. The capacity of lymphocytes from similarly heated mice to generate antibody-forming cells in vitro was not affected, suggesting that the observed in vivo suppression may be mediated by circulating factors rather than by some heat-induced alteration in the cells themselves. In vivo treatment did not alter T-cell responsiveness to the mitogen Con-A or delayed-type hypersensitivity responses to sheep red blood cells. Quantitative and flow cytometric assessment of splenic and thymic lymphocyte numbers showed that WBH did not alter absolute numbers of lymphocytes but did temporarily change the proportions of lymphocyte subsets. An immediate increase in splenic L3T4+ cells was observed, followed within 18 h by an overall decrease in Lyt 2+ and Thy 1.2+ T-cells. In the thymus the percentages of mature T cells increased. In general, only minimal effects of heat on the immune responses of normal mice could be demonstrated.

Animals