超声激发高强度聚焦超声所致沸腾气泡散射声信号的研究

发布时间：2018-06-20 07:32

本文选题：高强度聚焦超声 + 空化　；参考：《重庆医科大学》2015年硕士论文

【摘要】：研究背景高强度聚焦超声(High Intensity Focused Ultrasound)已被广泛用于子宫肌瘤、肝癌、乳腺癌、胰腺癌、前列腺癌以及肾脏肿瘤等良/恶性实体肿瘤的无创治疗。其治疗原理是采用一定聚焦方式将体外低能量超声聚焦到体内形成一个能量高度集中的区域,通过热、空化等机制使该区域内组织产生不可逆凝固性坏死,而对焦域外组织不产生影响。当HIFU作用于组织时会在其焦点区域产生空化和(或)沸腾气泡,气泡的产生会影响声波的非线性传播,进而影响温度场。因此：空化/沸腾气泡的检测和控制成为研究的重点和难点。本文第一部分结合现有研究报道的空化和沸腾气泡的检测手段,控制HIFU作用于新鲜离体牛肝组织,分别获得不同的辐照参数实现三种辐照方式：1)单纯热损伤；2)单纯空化损伤；3)空化和沸腾同时发生。在此基础上,论文第二部分分别探究气泡对B超的散射1—3MHz宽带声信号(以下简称“1—3MHz宽带声散射信号”)与多普勒快速闪烁伪影(Twinkling Artifact, TA)实现HIFU所致空化/沸腾气泡检测。目的通过控制HIFU辐照参数获得单纯热损伤、单纯空化损伤、空化和沸腾同时发生的三种辐照方式,在此基础上探索使用1—3 MHz宽带声散射信号和多普勒快速闪烁伪影分别实现HIFU所致沸腾气泡、空化和沸腾气泡的检测,为检测、研究和认识HIFU声场中空化/沸腾气泡提供一种新的手段。方法1.单纯热损伤、单纯空化损伤、空化和沸腾同时发生辐照方式的实现采用0.94MHz的HIFU辐照新鲜离体牛肝组织,辐照过程中同步使用PCD、热电偶与B超分别检测5—10MHz宽带噪声、温升以及强回声,通过调节HIFU辐照参数(声强、脉冲重复频率、占空比和时间),分别实现单纯热损伤、单纯空化损伤、空化和沸腾同时发生的辐照方式。2.B超激发HIFU所致沸腾气泡1—3 MHz宽带声散射信号的研究使用HIFU参数：1)单纯热损伤：焦点ISAL 530 W/cm2,连续波,辐照时间80s；2)单纯空化损伤：焦点ISAL 4820 W/cm2,脉冲波(PRF和占空比分别为4 Hz和2%),辐照时间30 s；3)空化和沸腾同时发生：焦点ISAL 2890 W/cm2,脉冲波(PRF和占空比分别为4 Hz和50%),辐照时间20 s。分别使用上述三种辐照参数的HIFU作用于新鲜离体牛肝组织,过程中同步使用中心频率3.5 MHz的B超检测强回声,热电偶测量焦域处温升,通过与B超探头垂直放置的宽带换能器(中心频率5 MHz)检测气泡对B超声束的散射并量化为1—3 MHz宽带声散射信号的检测。按下述要求分析相应的数据：(1)通过分析单纯热损伤时辐照过程中及结束后的散射信号与温度、强回声、超谐波(4、5、6次谐波)之间的时序关系,确定1—3 MHz宽带声散射信号与沸腾气泡产生起始时间的时序关系及其活动规律；(2)对比单纯空化、空化和沸腾同时发生两组的声散射结果,区分空化与沸腾对1—3 MHz宽带声散射信号的贡献；(3)对比沸腾发生时B超工作与不工作下1—3 MHz宽带声信号的检测结果,确定1—3MHz宽带声信号的来源；(4)各辐照方式下分别检测来至焦点区域的脉冲回波信号,进一步确证使用1—3 MHz宽带声散射信号检测]HIFU所致沸腾气泡的可行性。3.多普勒激发HIFU所致空化/沸腾气泡快速闪烁伪影活动规律的研究分别使用所获得参数的HIFU作用于新鲜离体牛肝组织,采用彩色多普勒模式的B超同步检测辐照过程中以及辐照结束后的快速闪烁伪影与强回声,分别分析各辐照下的伪影及强回声变化,确定快速闪烁伪影随空化/沸腾气泡的活动规律。结果1.采用连续波、ISAL530 W/cm2、辐照时间80s,ISAL4820 W/cm2.脉冲波(PRF和占空比分别为4 Hz、2%)、辐照时间30s,ISAL 2890 W/cm2脉冲波(PRF和占空比分别为4 Hz、50%)、辐照时间20s分别辐照离体牛肝组织可实现单纯热损伤、单纯空化损伤、空化和沸腾同时发生的辐照方式。2.采用单纯热损伤的辐照参数,辐照过程中温升达到沸腾空化阈值后,1—3 MHz宽带声散射信号与高次谐波成分同时出现阶跃性升高；辐照结束后随着温度的下降,强回声面积减小,声散射信号幅度逐渐降低并以T=0.05 s周期性变化,最终强回声面积减小至辐照前水平的同时声散射信号幅度降低到背景噪声水平。3.对比单纯空化、空化和沸腾同时发生两组的B超声散射结果发现,“on”阶段两组由于空化作用皆处于较高水平；未受HIFU作用的“off”阶段以及辐照结束后,单纯空化损伤组未检测到1—3 MHz宽带声散射信号,而空化与沸腾同时发生组则可检测到且以T-0.05 s周期性变化。4.对比B超工作与不工作下的声散射结果发现,当沸腾气泡存在时只有在B超工作下才可检测到1—3 MHz宽带声信号。5.脉冲回波的检测结果可见,只有在沸腾发生组辐照结束即刻才可见来至焦点区域的脉冲回波信号,与B超工作下的声散射结果一致。6. HIFU辐照过程中沸腾发生时,“off”阶段可见TA的存在,随着辐照时间的延长TA的面积呈增大的趋势直至辐照结束；辐照结束后,TA的存在时间远小于强回声的存在时间；TA存在的整个过程中其面积始终大于强回声并覆盖强回声区域。7.当只产生空化气泡而未发生沸腾时,辐照过程中明显检测到TA的存在但未见回声增强,辐照结束后TA立即消失。结论1.采用连续波、ISAL530 W/cm2、辐照时间80s,ISAL4820 W/cm2、脉冲波(PRF和占空比分别为4 Hz、2%)、辐照时间30s,ISAL 2890 W/cm2脉冲波(PRF和占空比分别为4 HZ、50%)、辐照时间20s分别辐照离体牛肝组织可实现单纯热损伤、单纯空化损伤、空化和沸腾同时发生的辐照方式。2.分别在单纯热损伤、单纯空化损伤、空化和沸腾同时发生的辐照下结合1—3 MHz宽带声散射信号进行采集,结果发现：1)辐照过程中若只发生沸腾空化,1—3 MHz宽带声散射信号可以准确地检测出HIFU所致沸腾气泡产生的起始时刻；2)对比单纯空化、空化和沸腾同时发生两组的声散射结果可以排除空化对1—3 MHz宽带声散射信号的贡献；3)沸腾发生时对比B超工作与不工作下的检测结果说明1—3 MHz宽带声信息的来源为焦点区域沸腾气泡对声波的散射作用；4)脉冲回波的检测结果与B超声散射结果一致,进一步验证了借助B超声散射信息实现HIFU所致沸腾气泡检测的有效性。综上说明,当辐照过程中发生沸腾时,辐照结束后沸腾气泡的活动规律可以结合强回声与1—3 MHz宽带声散射信号的检测进行表征,特别是用于单纯热损伤辐照时还能准确地检测出HIFU所致沸腾气泡产生的起始时刻。3.辐照过程中可通过TA检测沸腾气泡的发生,辐照结束后也能反映其溶解过程；当使用脉冲进行辐照时,“off”阶段TA对空化泡具有很强的分辨能力可用于HIFU辐照过程中空化气泡的检测。表明TA可用于HIFU所致空化/沸腾气泡的检测并具有很好的灵敏性。
[Abstract]:Background high intensity focused ultrasound (High Intensity Focused Ultrasound) has been widely used in the noninvasive treatment of benign / malignant solid tumors such as uterine myoma, liver cancer, breast cancer, pancreatic cancer, prostate cancer, and renal tumor. The principle of the treatment is to focus on the body with a certain focus on the body to form a high energy in the body. The region in the degree of concentration produces irreversible coagulant necrosis in the region by heat and cavitation, but it does not affect the outside of the focal region. When HIFU acts on the tissue, it produces cavitation and (or) bubbling bubbles in its focal region. The production of bubbles will affect the nonlinear propagation of sound waves and affect the temperature field. The detection and control of boiling bubbles have become the focus and difficulty of the study. In the first part, the first part of this paper is combined with the existing detection methods of cavitation and boiling bubbles to control the effect of HIFU on fresh isolated bovine liver tissues, and the different irradiation parameters are obtained to achieve three irradiation methods: 1) simple heat damage; 2) pure cavitation damage; 3) cavitation. On this basis, the second part of the paper explores the scattering of bubble to B ultrasonic 1 - 3MHz wideband sound signal (hereinafter referred to as "1 - 3MHz wideband acoustic scattering signal") and Doppler fast glint artifact (Twinkling Artifact, TA) to realize HIFU induced cavitation / boiling gas bubble detection. The purpose is to control the parameters of HIFU irradiation. Three kinds of radiation modes, such as simple heat damage, pure cavitation damage, cavitation and boiling, are used to explore the use of 1 to 3 MHz wideband acoustic scattering signals and Doppler fast scintillation artifacts to detect HIFU induced boiling bubbles, cavitation and boiling bubbles, and to investigate and understand cavitation / boiling bubble extraction in HIFU sound field. For a new method. Method 1. pure heat damage, pure cavitation damage, cavitation and boiling simultaneously irradiated 0.94MHz HIFU irradiated fresh isolated bovine liver tissues. PCD was used synchronously during irradiation, and 5 to 10MHz broadband noise, temperature rise and strong echo were detected by thermocouples and B ultrasonic, and HIFU irradiation parameters were adjusted by adjusting the parameters of radiation (sound). Strong, pulse repetition frequency, duty cycle and time), the study of simple heat damage, pure cavitation damage, cavitation and boiling mode.2. B ultrasonic induced HIFU induced boiling bubbles 1 - 3 MHz wideband acoustic scattering signals using HIFU parameters: 1) simple heat damage: focus ISAL 530 W/cm2, continuous wave, irradiation time 80s; 2) single Pure cavitation damage: focal ISAL 4820 W/cm2, pulse wave (PRF and duty ratio 4 Hz and 2%, respectively), irradiation time 30 s; 3) cavitation and boiling simultaneously: focal ISAL 2890 W/cm2, pulse wave (PRF and duty ratio 4 Hz and 50% respectively), and irradiation time 20 s. Using Three irradiated parameters in fresh isolated bovine liver tissues, respectively. During the process, the strong echo is detected synchronously with a B-mode ultrasonic of 3.5 MHz at the center frequency. The thermocouple measure the temperature rise at the focal region. The scattering of the bubbles to the B-ultrasonic beam is detected by the broadband transducer (center frequency 5 MHz) perpendicular to the B-ultrasonic probe and the detection of the 1 to 3 MHz wideband sound scattering signal. The corresponding data are analyzed by the following requirements: (1) pass by (1) The time series relation between the scattering signal of the radiation process and the end of the heat damage and the temperature, the strong echo and the super harmonic (4,5,6 subharmonic) is analyzed. The time series relation and the activity rule of the 1 - 3 MHz wideband sound scattering signal and the initiation time of the boiling bubble are determined. (2) the sound dispersion of two groups is occurring at the same time as simple cavitation, cavitation and boiling. The result is to distinguish the contribution of cavitation and boiling to 1 - 3 MHz wideband acoustic scattering signals; (3) the detection results of B-ultrasonic and 1 to 3 MHz wideband sound signals during the contrast boiling, and determine the source of the 1 - 3MHz wideband sound signal; (4) the pulse echo signals from the focal regions are detected in each irradiation mode, and further confirmed The feasibility of detection of boiling bubbles caused by]HIFU by 1 to 3 MHz wideband acoustic scattering signals.3. Doppler excitation HIFU induced cavitation / boiling bubble rapid glint artifact After the fast glint artifact and strong echo after the end, the artifact and the strong echo change under each irradiation are analyzed, and the motion of the fast glint artifact with the cavitation / boiling bubble is determined. Results 1. use continuous wave, ISAL530 W/cm2, irradiation time 80s, ISAL4820 W/cm2. pulse wave (PRF and duty ratio is 4 Hz, 2% respectively), irradiation time 30s, ISAL 2890 W /cm2 pulse wave (PRF and duty ratio are 4 Hz, 50% respectively). Irradiation time 20s irradiated isolated bovine liver tissues can achieve simple heat damage, pure cavitation damage, and the simultaneous irradiation mode of cavitation and boiling of.2. adopts the radiation parameters of simple heat damage. After the temperature rise reaches the threshold of boiling cavitation, 1 to 3 MHz broadband sound scattering signals At the same time, there is a step increase with the high order harmonic component, with the decrease of the temperature and the decrease of the strong echo area, the amplitude of the acoustic scattering signal decreases gradually and the T=0.05 s periodically changes, and the final intensity of the strong echo is reduced to the level before the irradiation, and the amplitude of the sound scattering signal is reduced to the background noise level.3. compared to the pure cavitation. Two groups of B ultrasonic scattering results of cavitation and boiling found that the two groups in the "on" stage were all at a high level due to cavitation; the 1 to 3 MHz wideband acoustic scattering signals were not detected in the simple cavitation damage group after the "off" stage and after the irradiation, while the simultaneous formation of cavitation and boiling could be detected and T -0.05 s periodic variation.4. contrasts the results of the sound scattering of B ultrasonic and non working. It is found that the detection results of.5. pulse echo of 1 to 3 MHz wideband sound signals can be detected only under the B-mode ultrasonic wave when the boiling bubbles exist. Only the pulse echo signals coming to the focal region can be seen only when the irradiation group is exposed to the end of radiation, and B When the results of ultrasonic scattering under ultra work are consistent with the boiling of.6. HIFU, the existence of TA is seen in the "off" stage. With the prolongation of the irradiation time, the area of TA increases until the end of the irradiation. After the radiation, the existence time of TA is far less than the existence of the strong echo; the area of the existence of TA is always large in the whole process. When Yu Qiang echoes and covers the strong echo region.7., when only cavitation bubbles are produced and no boiling is produced, the presence of TA is obviously detected in the irradiation process, but the echo is not enhanced, and TA immediately disappeared after irradiation. Conclusion 1. use continuous wave, ISAL530 W/cm2, irradiation time 80s, ISAL4820 W/ cm2, pulse wave (PRF and occupying ratio are 4 Hz, 2%), irradiated. 30s, ISAL 2890 W/cm2 pulse wave (PRF and duty ratio are 4 HZ, 50%, respectively). Irradiation time 20s irradiated isolated bovine liver tissues can achieve simple heat damage, pure cavitation damage, cavitation and boiling simultaneous irradiation.2. respectively in the simple heat damage, pure cavitation damage, cavitation and boiling simultaneous irradiation of 1 to 3 MHz under the irradiation. The wide-band acoustic scattering signals are collected, and the results are as follows: 1) if only boiling cavitation occurs during the irradiation process, 1 to 3 MHz wideband acoustic scattering signals can accurately detect the starting time of HIFU induced boiling bubbles; 2) comparison of pure cavitation, two groups of cavitation and boiling at the same time can eliminate the cavitation to 1 to 3 MHz broadband The contribution of the acoustic scattering signal; 3) the results of the comparison between the B ultrasonic and the non work indicate that the source of the 1 to 3 MHz wideband sound information is the scattering of the boiling bubbles in the focus area, and 4) the detection results of the pulse echo are in agreement with the results of the B-ultrasonic scattering, and the HIFU is verified by the help of the B-ultrasonic scattering information. The effectiveness of boiling bubble detection shows that the movement of boiling bubbles after irradiation can be characterized by the detection of strong echo and 1 to 3 MHz wideband acoustic scattering signals, especially for the initiation of the initiation of boiling bubbles caused by HIFU. In the process of.3. irradiation, the occurrence of boiling bubbles can be detected by TA, and the dissolution process can be reflected after the irradiation. When the pulse is irradiated, the "off" stage TA has a strong resolution to the cavitation bubble in the process of HIFU irradiation. It shows that TA can be used to detect the cavitation / boiling bubble caused by HIFU. It has good sensitivity.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R454.3

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