Translated Abstract
Since the end of the twentieth century, focused ultrasound has made great development in clinical field, among which high intensity focused ultrasound (HIFU) has been more and more applied. Cavitation, for a long time, has been avoided as much as possible in conventional HIFU because of its waste and sheltering to acoustic energy. However, researches of last decade verified that cavitation bubbles could sigficantly enhance HIFU therapy, and even a large number of trials employed man-made ultrassound contrast agents (UCAs) to achieve higher efficiency. Nevertheless, intravenous injection has been considered as the most risky method. HIFU is also considered to be an effective cavitation source, which is the starting point of this dissertation. With the help of optical and acoustical methods, both cavitation intensity and type of HIFU were detected and evaluated, based on which an optimum range of parameter for generating cavitation was discovered. Therefore, a cavitation bubble enhanced thermal ablation self-induced by pulsed HIFU (pHIFU) was investigated. In order to verify the effectiveness and feasibility of this therapy protocol, this dissertation studies cavitation in water, (BSA) phantoms, tissues ex vivo and living animals. Specific works are listed below:
(1) HIFU cavitation field was more exactly characterized through sonoluminescence or sonochemiluminescnece (SL/SCL). SL/SCL is the most direct indicator of inertial cavitation, which can intuitively present the distribution and activity of cavitation bubbles. In this dissertation, an acoustic radiation force counterbalanced system was set up to make SCL images more valuable. A standing-wave field was constructed to restrict the displacement of bubbles, making them oscillate and collapse near the inceptive positions (ranging 1/4 wavelength). The results showed that the standing-wave field was effective when the acoustic power (APW) was relatively low; When the APW was higher than a certain value, ‘oversaturated’ would appeare at the focal region, while bubble clusters only existed at pre- and post-focal region; We investagated the cavitation when the APW was quite low, and found that bubbles could arrange at the focal region uniformly. This phenomenon provides possibility to inhibit ‘oversaturated’ through reducing unwanted energy aggregation, among which is to use pulse mode.
(2) SL inside a polyacrylamide phantom treated by pHIFU was observed, and the pulse parameters were systematically investigated. Comparing with researches in water, SL inside a phantom was more valuable. First of all, numerical calculations and preliminary experiments were performed to investigate the proper APW; Then the APW was fixed at 19.5W. And by adjusting pulse duration (PD) and pulse repetation frequency (PRF) step by step, the influences of parameters on cavitation were systematrically investagated. The results showed that, when the APW was 19.5W, pHIFU was much easier than continuous HIFU (cHIFU) to generate cavitation at the focal region. When PD was increased from 1 to 23 cycles, SL intensity presented the trend of first increasing and then decreasing, and 6 cycles was the maximum value; The same changes happened to PRFs, and 10kHz was the maximum value; CHIFU, as the control group, could not even generate cavitation or SL inside the phantom.
(3) Based on the discovered parameters, thermal ablation inside a bovine serum albumin (BSA) phantom induced by pHIFU was investigated. CHIFU was also performed as a control group. The effectiveness of pHIFU induced thermal ablation was initially verified. With the help of high speed photography, the temporal evolution of thermal coagulation was recorded; Also, the temperature-time curve (T-T curve) was also recorded by a thermal couple. The results showed that the self-induced cavitation bubbles could act as a stimulator to enhance the nonlinearity and absorptive of local tissue; Then functioned along with the following pulses, these bubbles could violently oscillate within tiny regions to generate more heat deposit; Different from cavitation itself, heat deposit requires certain time span, therefore the PD should be increased to 10~12 cycles.
(4) According to the results in phantom, the PD and PRF were set to 12 cycles and 10kHz, respectively. Investigations on tissues ex vivo and living animals were performed. For tissues ex vivo, swine liver and thigh muscle were treated for 20 seconds, and then cut through the axis. The sections of the lesion were compared with control group. It showed that pHIFU had higher efficiency of thermal ablation than cHIFU; H&E results proofed that the lesions were composed of thermal and mechanical damages, which verified that cavitation bubbles generated inside the tissue and promoted the development of thermal coagulation. On the other hand, a living animal trial platform was set up, and a B-mode diagnostic device was employed to navigate the therapy and to evaluate the lesion. The imagse showed that lesions inside the liver had strong echos which were white contrast in the images. These investigations verified the effectiveness and feasibility of this treatment protocol in living animals.
In conclusion, this work offers theoretical and experimental basis for cavitation bubble enhanced thermal ablation self-induced by ten-microsecond pHIFU.
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