The effect of temperature and thermal dose (equivalent minutes at 43 degrees C) on ultrasonic attenuation in fresh dog muscle, liver, and kidney in vitro, was studied over a temperature range from room temperature to 70 degrees C. The effect of temperature on ultrasonic absorption in muscle was also studied. The attenuation experiments were performed at 4.32 MHz, and the absorption experiments at 4 MHz. Attenuation and absorption increased at temperatures higher than 50 degrees C, and eventually reached a maximum at 65 degrees C. The rate of change of tissue attenuation as a function of temperature was between 0.239 and 0.291 Np m-1 MHz-1 degree C-1 over the temperature range 50-65 degrees C. A change in attenuation and absorption was observed at thermal doses of 100-1000 min, where a doubling of these loss coefficients was observed over that measured at 37 degrees C, presumably the result of changes in tissue composition. The maximum attenuation or absorption was reached at thermal dosages on the order of 10(7) min. It was found that the rate at which the thermal dose was applied (i.e., thermal dose per min) plays a very important role in the total attenuation absorption. Lower thermal dose rates resulted in larger attenuation coefficients. Estimation of temperature-dependent absorption using a bioheat equation based thermal model predicted the experimental temperature within 2 degrees C.
Time shifts in echo signals returning from a heated volume of tissue correlate well with the temperature changes. In this study the relationship between these time shifts (or delays) and the tissue temperature was investigated in excised muscle tissue (turkey breast) as a possible dosimetric method. Heat was induced by the repeated activation of a sharply focused high-intensity ultrasound beam. Pulse echoes were sent and received with a confocal diagnostic transducer during the brief periods when the high-intensity ultrasonic beam was inactive. The change in transit time between echoes collected at different temperatures was estimated using cross-correlation techniques. With spatial-peak temporal-peak intensities (ISPTP) of less than 950W/cm2, the delay versus temperature relationship was fit to a linear equation with highly reproducible coefficients. The results confirmed that for spatial-peak temperature increases of approximately 10 degrees C, temperature-dependent changes in velocity were the single most important factor determining the observed delay, and a linear approximation could produce accurate temperature estimations. Nonlinear phenomena that occurred during the high-intensity irradiation had no significant effect on the measured delay. At ISPTP of 1115-2698 W/cm2, the delay-temperature relationship showed a similar monotonically decreasing pattern, but as the temperature peaked its slope gradually increased. This may reflect the curvilinear nature of the velocity-temperature relationship, but it may also be related to irreversible tissue modifications and to the use of the spatial-peak temperature to experimentally characterize the temperature changes. Overall, the results were consistent with theoretical predictions and encourage further experimental work to validate other aspects of the technique.
High-intensity focused ultrasound (HIFU) was used to treat Morris rat hepatoma 3924A implanted in the liver. Treatment was administered with a lens-focused 4-MHz transducer that created a focused beam of 550 W/cm2 at peak intensity. One hundred twelve rats with liver tumors were divided into two groups of 56 each. Group 1 received HIFU therapy while group 2 (the control group) did not. All rats were killed immediately or 1, 3, 7, 14, 21, or 28 days after treatment. Eight rats in each group were killed at each interval for pathologic and biochemical studies. Significant inhibition of the tumor growth was seen in the HIFU-treated group, with tumor growth inhibition rates of 65.4% to 93.1% from the third to the 28th day after treatment. Ultrasound-treated tumors showed direct thermal cytotoxic necrosis and fibrosis. An additional 56 ACl rats with liver tumors were divided into four groups of 14 each. Group 1 received doxorubicin hydrochloride intraperitoneally and HIFU therapy; group 2, HIFU therapy; group 3, doxorubicin hydrochloride; and group 4 (the control group), neither HIFU nor doxorubicin hydrochloride. Significantly improved survival rates were noted in HIFU-treated animals (groups 1 and 2) compared with those of groups 3 and 4. These data suggest that HIFU may be a useful method for local treatment of hepatic tumors.
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