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研究生: 黃翊倫
Huang, Yi-Luan
論文名稱: 相變液滴於流場環境中汽化對氣體栓塞治療之研究
Characterization of Acoustic Droplet Vaporization under Flow Conditions for Gas Embolotherapy
指導教授: 葉秩光
Yeh, Chih-Kuang
口試委員: 劉浩澧
Liu, Hao-Li
廖愛禾
Liao, Ai-Ho
陳文翔
Chen, Wen-Shiang
學位類別: 碩士
Master
系所名稱: 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年: 2013
畢業學年度: 101
語文別: 中文
論文頁數: 87
中文關鍵詞: 聲學激發相變液滴汽化流動條件氣體擴散全氟戊烷相變液滴氣體栓塞治療
外文關鍵詞: Acoustic droplet vaporization, flow condition, gas diffusion, perfluoropentane droplet, gas embolotherapy
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  • 高能聚焦式超音波已經被證實可以汽化包覆全氟碳化物的相變液滴產生氣泡,此過程稱為聲學激發相變液滴汽化。相變液滴汽化後產生的氣泡,可應用在氣體栓塞治療術上。但相變液滴的汽化是快速且劇烈的,汽化後氣泡表面的介面活性分子會降低,進而影響氣泡穩定度。因此汽化後氣泡的生長將可能會受到不同汽化參數與血流環境等條件影響。
    本研究欲觀察相變液滴汽化後之生長情形,為貼近活體狀況,在此探討流動狀態下(流速介在21.4–44.1 mm/s)氣泡平均粒徑隨時間的變化。接著改變流場速度、相變液滴的濃度與流體黏滯度;更進一步的改變聲學參數如聲壓、脈衝長度、脈衝重複頻率。實驗架構則是使用光聲共焦系統,此系統整合高能聚焦式超音波探頭的汽化系統、高頻超音波影像系統與光學的高速相機。將相變液滴以固定流速下流經管徑為200 μm纖維透析管,並使用中心頻率為2 MHz的高能聚焦式超音波探頭給予汽化,而此系統所能觀測氣泡生長最長的時間可達1.2秒。清楚了解超音波參數與生成氣泡之間的關係後,進一步將相變液滴注射入小黑鼠體內,藉由體外最佳化參數汽化,並透過窗型觀測腔觀察相變液滴於體內汽化的情形。
    經超音波汽化後的氣泡會逐漸變大,並且氣泡的平均粒徑約在0.5–1秒內達到穩定的大小,其平均粒徑約是剛形成氣泡的兩倍(約初始相變液滴平均粒徑的十倍)。氣泡變大的原因是因溶液中所含之氣體擴散進氣泡內,導致氣泡粒徑逐漸變大,當氣體內外壓力平衡時便會達到穩定的平均粒徑,而此粒徑約是剛形成氣泡時的兩倍大小。氣泡的生長趨勢不受流速影響;但氣泡的平均粒徑卻與相變液滴的濃度、緩衝液的黏滯度有關,上述兩者條件與觀測系統所使用的纖維管與外界循環水槽彼此交換氣體的速率有關。調控聲學參數的部分,當汽化聲壓高於汽化的聲壓閾值時,對於氣泡的生長沒有影響。而增加超音波的脈衝長度與脈衝重複頻率將會使生成的氣泡穩定性下降,導致數量大幅減少,而氣泡平均粒徑會提升。此外,若增加脈衝重複頻率將比增加脈衝長度提供更強的氣泡擊破能力。體外實驗已掌握最佳汽化的聲學參數,將此參數應用到活體上,可觀察到汽化後的氣泡確實可以降低血流流速或是造成血管栓塞。
    本研究可藉由調控超音波聲學參數改變生成氣泡的粒徑與數量,因此針對不同的臨床應用調整最佳化的汽化參數將是可行的。未來可將腫瘤細胞種在窗型觀測腔內,再將相變液滴於腫瘤附近的區域汽化,造成血管栓塞,進一步的監控此方式是否能有效的抑制腫瘤組織的生長。


    The vaporization of perfluorocarbon droplets into gaseous bubbles using high-intensity focus ultrasound (HIFU) was referred to as acoustic droplet vaporization (ADV). This technique provides large bubbles for the applications of gas embolotherapy. However, the rapid volume expansion during ADV reduces the density of surfactant molecules and decreases the stability of bubbles. The characteristics of bubble population might vary under different acoustic and hemodynamic conditions.
    This study investigated the effects of different experimental parameters on the temporal evolution of ADV bubbles with the flowing conditions of 21.4–44.1 mm/s. The effects of acoustic parameters included peak rarefaction pressure, pulse duration, and pulse repetition frequency (PRF) and other parameters such as droplet concentrations, flow velocities, fluid viscosities were also considered. The experiments were performed in an integrated acousto-optical system comprising an HIFU transmission system, a high-frequency ultrasound imaging system, and a high-speed optical microscope. A 2-MHz HIFU transducer was used to transmit acoustic pulses to vaporize the droplets in a 200-μm semipermeable tube. Simultaneous acoustic and optical observations of bubble population were performed to monitor bubble population at up to 1.2 s after the onset of ADV. The experiments were also performed in mice bearing dorsal skinfold window chambers for observing the ADV effects in vivo.
    The results show that the bubbles can grow to a stable equilibrium size which is almost 2-fold larger in diameter than first vaporization in 0.5–1 s. Although the growth trend did not depend on flow velocity, it was dependent on fluid viscosity and droplet concentration since they dominate the gas content of the host medium. The result was correlated with the rates of gas uptake in bubbles and gas exchange between the inside and outside of the wall in the semipermeable tube. Varying the acoustic pressure resulted in no remarkable effects on the temporal evolution of bubble population as long as the acoustic pressure exceeded the ADV threshold pressure. Increasing both the pulse duration and PRF markedly reduces the stability of bubbles by increasing the permeability of their shells to gas. Besides, lengthening the PRF provides superior performance in bubble disruption than increasing pulse duration for the same total pulse energy. The results of the intravital microscopy have shown the ability of the post-ADV growing bubbles to reduce the blood flow or cause the embolism.
    This study suggests that the characteristics of ADV bubble population may be regulated using different acoustic parameters. Determining optimal acoustic parameters to produce bubbles with sizes which are suitable for gas embolotherapy may be feasible. Future study is to investigate the effectiveness of the improved gas embolotherapy in the inhibition of tumor progression.

    第一章 緒論 1 1.1 肝癌 1 1.1.1 肝癌的形成 2 1.1.2 肝癌治療 3 1.1.3 新式超音波對比劑-相變液滴應用在氣栓治療上 5 1.2 超音波對物質作用之相互效應 6 1.2.1 機械效應 6 1.2.2 熱效應 7 1.2.3 穴蝕效應 7 1.3 新式超音波對比劑-相變液滴 9 1.3.1 相變液滴之物理特性 9 1.3.2 聲學激發相變液滴汽化 11 1.3.3 相變液滴汽化之物理機制 16 1.3.4 相轉變微氣泡之穩定性 17 1.4 相變液滴之應用 21 1.4.1 相變液滴應用於診斷上 21 1.4.2 相變液滴應用於治療上 23 1.5 研究目的與動機 24 第二章 實驗材料與方法 26 2.1 概論 26 2.2 相變液滴之製程與粒徑分布 26 2.2.1 相變液滴之製備 26 2.2.2 光學定性分析 29 2.2.3 粒徑分析 29 2.3 相變液滴於體外汽化架構 30 2.3.1 光聲共焦系統 30 2.3.2 探頭校正 34 2.3.3 針筒式注射幫浦之流速校正 37 2.3.4 緩衝液製備 37 2.4 聲學偵測相變液滴汽化後之特性 38 2.5 數據分析 39 2.5.1 相變液滴汽化之廢液分析 39 2.5.2 光學景深選擇 40 2.5.3 光學程式分析 42 2.5.4 聲學程式分析 44 2.5.5 數據統計 45 2.6 窗型觀測腔 45 第三章 實驗結果與討論 48 3.1 相變液滴性質與汽化效率 48 3.1.1 相變液滴粒徑分布 48 3.1.2 相變液滴汽化效率定量測試 50 3.2 ADV氣泡於流場中的行為 57 3.2.1 相變液滴濃度對ADV氣泡生長的影響 57 3.2.2 環境流速對ADV氣泡生長的影響 59 3.2.3 汽化聲壓與ADV氣泡的影響 61 3.2.4 改變相變液滴之脈衝長度 64 3.2.5 改變相變液滴之脈衝重複頻率 68 3.2.6 改變相變液滴所在環境之緩衝液 75 3.3 窗型觀測腔模型觀測ADV於活體汽化 76 第四章 結論與未來展望 79 4.1 結論 79 4.2 未來工作 80 參考資料 81

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