| BackgroundHigh intensity focused ultrasound was widely used in the noninvasive therapy of benign or malignant solid tumors such as Uterine fibroid, liver tumor, breast tumor, pancreatic cancer, prostate cancer, renal tumor and so on. The principle of this treatment is to focus low-energy ultrasound in vitro to form a highly focused energy area in vivo with some methods through mechanism such as heat and cavitation, result in irreversible coagulation necrosis of tissue produced in the focal region, but do not have effect on the tissues outside the focal. Cavitation and (or) boiling bubbles would produce in its focus area when HIFU was used to exposure the tissues, which turn to affect the propagation of sound, and then had influence on the temperature field. Therefore, the detection and control of cavitation/boiling bubbles became an important and difficult research. The first part of the paper would achieve the exposure regimes of 1) purely thermal damage,2) purely cavitation damage and 3) cavitation plus boiling occur with the help of existing bubble detection methods reported in the literature, on this basis, the second part explored the use of 1-3 MHz broadband acoustic signal from B-mode ultrasound scattered by bubble (Hereinafter referred to as "1-3 MHz broadband acoustic scattering signal") and Doppler Twinkling artifact to detect HIFU-induced cavitation and boiling bubble respectively.PurposeTo achieve the exposure regimes of purely thermal damage, purely cavitation damage and cavitation plus boiling occur by controlling parameters of HIFU. On this basis, we explore the use of 1-3 MHz broadband acoustic scattering signal and Doppler Twinkling artifact to detect HIFU-induced boiling bubble, HIFU-induced cavitation and boiling bubble, respectively, providing a new means for the detection, research and awareness of cavitation/boiling bubbles in HIFU field.Methods1. The achievement of regimes with only thermal damage, only cavitation damage and cavitation plus boiling occur respectivelyHIFU of 0.94MHz was used to exposure fresh bovine tissue in vitro.5-10MHz broadband noise, temperature and hyperecho were detected with PCD, thermocouple and B-mode ultrasound synchronously, respectively. To achieve the regimes with purely thermal damage, purely cavitation damage and cavitation plus boiling occur, respectively, by adjusting the HIFU exposure parameters (sound intensity, pulse repetition frequency, duty cycle and time).2. The study of B-mode ultrasound-stimulated 1-3 MHz broadband noise signal scatted by B-mode ultrasound from HIFU-induced boiling bubbleHIFU parameters of 1) purely thermal damage:ISSAL of 530 W/cm2, continuous wave, exposure time for 80s; 2) purely cavitation damage:ISAL of 4816.7 W/cm2, pulse wave (PRF is 4Hz and duty cycle is 2%), exposure time for 30s; 3) cavitation plus boiling occur:ISAL of 2890W/cm2, pulse wave (PRF is 4Hz and duty cycle is 50%), exposure time for 20s. HIFU of parameters above were used to expose fresh bovine liver tissue in vitro. Hyperecho was detected with B-mode ultrasound, temperature of focal region was measured by thermocouple, scattering signal of B-mode ultrasound was obtained by broadband transducer (center frequency 5 MHz) placed vertically with B-mode ultrasound and quantized as 1-3 MHz broadband acoustic scattering signal synchronously. The data was analyzed corresponding to the following requirement:(1) The relationship between 1-3 MHz broadband acoustic scattering signal, hyperecho and ultra-harmonics (4,5,6 harmonic) during and after HIFU was analyzed, to make sense the detection of boiling bubble with 1-3 MHz broadband acoustic scattering signal as well as its activity patterns.(2) Distinguishing the contribution of cavitation from boiling to 1-3 MHz broadband acoustic scattering signal by comparing 1-3 MHz broadband acoustic scattering signal during only cavitation and cavitation plus boiling occur.(3) By Comparing 1-3 MHz broadband acoustic signal with and without B-mode ultrasound when boiling occurred, and determine the source of 1-3 MHz broadband acoustic signal.(4) Detecting the pulse-echo signal of the focus area under each exposure, further confirmed the feasibility of using scattering signal to detect boiling bubble.3. The study of activity rhythm of Doppler-stimulated Twinkling artifact from HIFU-induced cavitation/boiling bubbleHIFU of parameters obtained above were used to expose fresh bovine liver tissue in vitro, respectively. B-mode ultrasound was adjusted to color Doppler to detect Twinkling artifact and hyperecho during and after HIFU synchronously. Making sure to use Twinkling artifact to detect HIFU-induced cavitation/boiling bubble by analyzing the variation of Twinkling artifact and hyperecho in different regimes.Results1. HIFU of parameters:ISAL of 530 W/cm2, continuous wave, exposure time for 80s; ISAL of 4816.7 W/cm2, pulse wave (PRF is 4Hz and duty cycle is 2%), exposure time for 30s; ISAL of 2890W/cm2, pulse wave (PRF is 4Hz and duty cycle is 50%), exposure time for 20s was used to expose fresh bovine liver tissue in vitro, respectively, which could achieve the exposure regimes of purely thermal damage, purely cavitation damage and cavitation plus boiling occurred.2. When purely thermal damage work, step-increase of both 1-3 MHz broadband acoustic scattering signal and higher harmonic components occurred after temperature rose to boiling cavitation threshold. The hyperechoic area decreased, the amplitude of 1-3 MHz broadband acoustic scattering signal decreased and changed cyclically with T= 0.05 s, with temperature decreased. Finally, hyperechoic area is reduced to the level before exposure, while 1-3 MHz broadband acoustic scattering signal decrease to the level of background noise.3. Compared scattering from B-mode ultrasound in only cavitation occurred with result in cavitation plus boiling occurred, and found that, the amplitude both of groups are at a high level due to cavitation in "on" phase; In "off" phase and after HIFU without HIFU, there wasn’t any 1-3 MHz broadband acoustic scattering signal being detected in the group of only cavitation, while 1-3 MHz broadband acoustic scattering signal in the group of cavitation plus boiling and changed cyclically with T= 0.05 s.4. Compared the result with and without B-mode ultrasound, and found that 1-3 MHz broadband acoustic signal was detected only with B-mode ultrasound.5. Pulse-echo test results showed that pulse-echo signal only occurred in the momentary end of the exposure, which consistent with scattering results of B-mode ultrasound.6. When boiling occurred during HIFU, TA was visible in the stage of "off", whose area showed an increasing trend until the end of irradiation with time. After irradiation, the time TA existed was much less than hyperecho, but the area of TA was larger than hyperecho and covered the hyperechoic area.7. When pure cavitation bubbles occurred without boiling during exposure, TA was detected significantly but no hyperecho, and disappeared immediately after the end of exposure.Conclusion1. HIFU of parameters:ISAL of 530 W/cm2, continuous wave, exposure time for 80s; ISAL of 4816.7 W/cm2, pulse wave (PRF is 4Hz and duty cycle is 2%), exposure time for 30s; ISAL of 2890W/cm, pulse wave (PRF is 4Hz and duty cycle is 50%), exposure time for 20s was used to expose fresh bovine liver tissue in vitro, respectively, which could achieve the exposure regimes of purely thermal damage, purely cavitation damage and cavitation plus boiling occurred.2. When combined with acquisition 1-3 MHz broadband acoustic scattering signal in the exposure regimes of purely thermal damage, purely cavitation damage and cavitation plus boiling occurred, and found that:1) The onset time of boiling bubble occurred could be detected accurately with scattering signal of B-mode ultrasound when only boiling occurred during exposure; 2) The contribution of cavitation to 1-3 MHz broadband acoustic scattering signal could be excluded by the result of only cavitation damage and cavitation plus boiling occurred; 3) Compared the results of modulation with and without B-mode ultrasound suggest that the source of 1-3 MHz broadband acoustic came from the scattering of boiling bubble of the focus area to sound waves; 4) Test results pulse-echo test consistent with scattering of B-mode ultrasound further demonstrated the effectiveness to achieve HIFU-induced boiling bubble by means of scattering signal of B mode ultrasound.In summary, If boiling cavitation occurred during exposure, the activity patterns of boiling bubble could be characterized combining hyperecho and 1-3 MHz broadband acoustic scattering signal. Particularly for purely thermal damage, the onset time of boiling bubble occurred could be detected accurately with scattering signal of B-mode ultrasound.3. TA could be used to detect the occurrence of boiling bubble during exposure and also reflect its dissolution; When pulse was used in exposure, TA has a strong ability to distinguish cavitation bubble and can be used to detect cavitation bubbles during HIFU. It indicated that HIFU-induced cavitation/boiling bubble could be detected by TA and had good sensitivity. |
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