本文選題：高強度聚焦超聲 + 空化��； 參考：《重慶醫(yī)科大學》2015年碩士論文

【摘要】：研究背景高強度聚焦超聲(High Intensity Focused Ultrasound)已被廣泛用于子宮肌瘤、肝癌、乳腺癌、胰腺癌、前列腺癌以及腎臟腫瘤等良/惡性實體腫瘤的無創(chuàng)治療。其治療原理是采用一定聚焦方式將體外低能量超聲聚焦到體內(nèi)形成一個能量高度集中的區(qū)域,通過熱、空化等機制使該區(qū)域內(nèi)組織產(chǎn)生不可逆凝固性壞死,而對焦域外組織不產(chǎn)生影響。當HIFU作用于組織時會在其焦點區(qū)域產(chǎn)生空化和(或)沸騰氣泡,氣泡的產(chǎn)生會影響聲波的非線性傳播,進而影響溫度場。因此：空化/沸騰氣泡的檢測和控制成為研究的重點和難點。本文第一部分結合現(xiàn)有研究報道的空化和沸騰氣泡的檢測手段,控制HIFU作用于新鮮離體牛肝組織,分別獲得不同的輻照參數(shù)實現(xiàn)三種輻照方式：1)單純熱損傷；2)單純空化損傷；3)空化和沸騰同時發(fā)生。在此基礎上,論文第二部分分別探究氣泡對B超的散射1—3MHz寬帶聲信號(以下簡稱“1—3MHz寬帶聲散射信號”)與多普勒快速閃爍偽影(Twinkling Artifact, TA)實現(xiàn)HIFU所致空化/沸騰氣泡檢測。目的通過控制HIFU輻照參數(shù)獲得單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生的三種輻照方式,在此基礎上探索使用1—3 MHz寬帶聲散射信號和多普勒快速閃爍偽影分別實現(xiàn)HIFU所致沸騰氣泡、空化和沸騰氣泡的檢測,為檢測、研究和認識HIFU聲場中空化/沸騰氣泡提供一種新的手段。方法1.單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生輻照方式的實現(xiàn)采用0.94MHz的HIFU輻照新鮮離體牛肝組織,輻照過程中同步使用PCD、熱電偶與B超分別檢測5—10MHz寬帶噪聲、溫升以及強回聲,通過調(diào)節(jié)HIFU輻照參數(shù)(聲強、脈沖重復頻率、占空比和時間),分別實現(xiàn)單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生的輻照方式。2.B超激發(fā)HIFU所致沸騰氣泡1—3 MHz寬帶聲散射信號的研究使用HIFU參數(shù)：1)單純熱損傷：焦點ISAL 530 W/cm2,連續(xù)波,輻照時間80s；2)單純空化損傷：焦點ISAL 4820 W/cm2,脈沖波(PRF和占空比分別為4 Hz和2%),輻照時間30 s；3)空化和沸騰同時發(fā)生：焦點ISAL 2890 W/cm2,脈沖波(PRF和占空比分別為4 Hz和50%),輻照時間20 s。分別使用上述三種輻照參數(shù)的HIFU作用于新鮮離體牛肝組織,過程中同步使用中心頻率3.5 MHz的B超檢測強回聲,熱電偶測量焦域處溫升,通過與B超探頭垂直放置的寬帶換能器(中心頻率5 MHz)檢測氣泡對B超聲束的散射并量化為1—3 MHz寬帶聲散射信號的檢測。按下述要求分析相應的數(shù)據(jù)：(1)通過分析單純熱損傷時輻照過程中及結束后的散射信號與溫度、強回聲、超諧波(4、5、6次諧波)之間的時序關系,確定1—3 MHz寬帶聲散射信號與沸騰氣泡產(chǎn)生起始時間的時序關系及其活動規(guī)律；(2)對比單純空化、空化和沸騰同時發(fā)生兩組的聲散射結果,區(qū)分空化與沸騰對1—3 MHz寬帶聲散射信號的貢獻；(3)對比沸騰發(fā)生時B超工作與不工作下1—3 MHz寬帶聲信號的檢測結果,確定1—3MHz寬帶聲信號的來源；(4)各輻照方式下分別檢測來至焦點區(qū)域的脈沖回波信號,進一步確證使用1—3 MHz寬帶聲散射信號檢測]HIFU所致沸騰氣泡的可行性。3.多普勒激發(fā)HIFU所致空化/沸騰氣泡快速閃爍偽影活動規(guī)律的研究分別使用所獲得參數(shù)的HIFU作用于新鮮離體牛肝組織,采用彩色多普勒模式的B超同步檢測輻照過程中以及輻照結束后的快速閃爍偽影與強回聲,分別分析各輻照下的偽影及強回聲變化,確定快速閃爍偽影隨空化/沸騰氣泡的活動規(guī)律。結果1.采用連續(xù)波、ISAL530 W/cm2、輻照時間80s,ISAL4820 W/cm2.脈沖波(PRF和占空比分別為4 Hz、2%)、輻照時間30s,ISAL 2890 W/cm2脈沖波(PRF和占空比分別為4 Hz、50%)、輻照時間20s分別輻照離體牛肝組織可實現(xiàn)單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生的輻照方式。2.采用單純熱損傷的輻照參數(shù),輻照過程中溫升達到沸騰空化閾值后,1—3 MHz寬帶聲散射信號與高次諧波成分同時出現(xiàn)階躍性升高；輻照結束后隨著溫度的下降,強回聲面積減小,聲散射信號幅度逐漸降低并以T=0.05 s周期性變化,最終強回聲面積減小至輻照前水平的同時聲散射信號幅度降低到背景噪聲水平。3.對比單純空化、空化和沸騰同時發(fā)生兩組的B超聲散射結果發(fā)現(xiàn),“on”階段兩組由于空化作用皆處于較高水平；未受HIFU作用的“off”階段以及輻照結束后,單純空化損傷組未檢測到1—3 MHz寬帶聲散射信號,而空化與沸騰同時發(fā)生組則可檢測到且以T-0.05 s周期性變化。4.對比B超工作與不工作下的聲散射結果發(fā)現(xiàn),當沸騰氣泡存在時只有在B超工作下才可檢測到1—3 MHz寬帶聲信號。5.脈沖回波的檢測結果可見,只有在沸騰發(fā)生組輻照結束即刻才可見來至焦點區(qū)域的脈沖回波信號,與B超工作下的聲散射結果一致。6. HIFU輻照過程中沸騰發(fā)生時,“off”階段可見TA的存在,隨著輻照時間的延長TA的面積呈增大的趨勢直至輻照結束；輻照結束后,TA的存在時間遠小于強回聲的存在時間；TA存在的整個過程中其面積始終大于強回聲并覆蓋強回聲區(qū)域。7.當只產(chǎn)生空化氣泡而未發(fā)生沸騰時,輻照過程中明顯檢測到TA的存在但未見回聲增強,輻照結束后TA立即消失。結論1.采用連續(xù)波、ISAL530 W/cm2、輻照時間80s,ISAL4820 W/cm2、脈沖波(PRF和占空比分別為4 Hz、2%)、輻照時間30s,ISAL 2890 W/cm2脈沖波(PRF和占空比分別為4 HZ、50%)、輻照時間20s分別輻照離體牛肝組織可實現(xiàn)單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生的輻照方式。2.分別在單純熱損傷、單純空化損傷、空化和沸騰同時發(fā)生的輻照下結合1—3 MHz寬帶聲散射信號進行采集,結果發(fā)現(xiàn)：1)輻照過程中若只發(fā)生沸騰空化,1—3 MHz寬帶聲散射信號可以準確地檢測出HIFU所致沸騰氣泡產(chǎn)生的起始時刻；2)對比單純空化、空化和沸騰同時發(fā)生兩組的聲散射結果可以排除空化對1—3 MHz寬帶聲散射信號的貢獻；3)沸騰發(fā)生時對比B超工作與不工作下的檢測結果說明1—3 MHz寬帶聲信息的來源為焦點區(qū)域沸騰氣泡對聲波的散射作用；4)脈沖回波的檢測結果與B超聲散射結果一致,進一步驗證了借助B超聲散射信息實現(xiàn)HIFU所致沸騰氣泡檢測的有效性。綜上說明,當輻照過程中發(fā)生沸騰時,輻照結束后沸騰氣泡的活動規(guī)律可以結合強回聲與1—3 MHz寬帶聲散射信號的檢測進行表征,特別是用于單純熱損傷輻照時還能準確地檢測出HIFU所致沸騰氣泡產(chǎn)生的起始時刻。3.輻照過程中可通過TA檢測沸騰氣泡的發(fā)生,輻照結束后也能反映其溶解過程；當使用脈沖進行輻照時,“off”階段TA對空化泡具有很強的分辨能力可用于HIFU輻照過程中空化氣泡的檢測。表明TA可用于HIFU所致空化/沸騰氣泡的檢測并具有很好的靈敏性。
[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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R454.3

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