近年來超音波技術已經被廣泛應用在臨床醫學的診斷與治療中，並有研究發現若搭配傳統對比劑微氣泡能有助於診斷上判斷與治療效率，例如超音波對比影像、腫瘤治療、血栓治療及標靶性的藥物控制遞送。由於微氣泡於體內循環時的存在時間過短，大大限制此技術推展至臨床應用的可能性。而相變液滴為一種新式的超音波對比劑，能夠在體內環境穩定存在時間較久，因此逐漸取代過去使用的微氣泡。當相變液滴受到超音波脈衝作用而被激發汽化，從原本的液態形式快速轉變為氣態，此過程稱為聲學激發相變液滴汽化。而聲學激發相變液滴汽化對於臨床上診斷與治療有關，若了解汽化過程的物理機制，並且可以同時偵測ADV事件的發生，則會對於正在使用ADV應用或研究的人有很大幫助。
因此，本研究的目的是藉由在光聲學共焦系統下觀察相變液滴於組織模擬仿體內汽化，使用被動式穴蝕效應偵測與主動式穴蝕效應偵測其單顆相變液滴汽化過程伴隨的特徵訊號，並透過聲學訊號分析與光學影像拍攝釐清其汽過程化的機制；最後討論實際將相變液滴應用時汽化的情形，藉由群體相變液滴汽化產生的特徵訊號，評估在未來進行ADV特徵造影的可行性。
實驗中主要分為單顆與群體相變液滴汽化兩大主軸。在單顆相變液滴汽化於聲學共焦系統以5 MHz聚焦式超音波搭配相變液滴作用於仿體觀察聲學激發相變液滴，並使用2.25 MHz探頭進行被動式穴蝕效應偵測其產生的特徵訊號，另外在主動式穴蝕效應偵測中，使用25 MHz高頻探頭發射載波訊號觀察相變液滴汽化過程體積型態變化，討論特徵訊號產生的原因。此外，本研究也對於不同的相變液滴粒徑大小，使用不同的定量方式討論粒徑對特徵訊號之影響。最後於群體相變液滴汽化產生的特徵訊號發展成M-mode造影。
結果方面，我們發現當相變液滴汽化伴隨的特徵訊號可分為兩個部分，其中一個是來自氣核膨脹過程中劇烈脹縮產生的突波訊號，其轉為頻域觀察為一寬頻訊號，並發現寬頻訊號的強度與粒徑無關。另一個訊號來自汽化後形成ADV氣泡的脹縮運動，當氣泡從脹至最大並壓縮至最小時候產生一低頻訊號，並發現低頻訊號的強度與隨著粒徑增大而縮小。由於寬頻訊號的產生來自氣核劇烈脹縮，其在單為時間內體積變化幅度要比氣泡脹縮大。因此，寬頻訊號的強度較低頻訊號要大。另外，在群體相變液滴汽化中，由於氣核在同一時間汽化產生突波訊號，並也可從M-mode造影時的氣核膨脹訊號比氣泡振動訊號強，因此未來若使用氣核膨脹產生的寬頻訊號將會比氣泡振動訊號要更適合偵測ADV事件的發生。

關鍵詞：相變液滴、聲學激發相變液滴汽化、被動式穴蝕效應偵測、主動式穴蝕效應偵測

Ultrasou¬nd has been used in a variety of clinical settings and therapy, which can improve efficiency of therapy by microbubbles (MBs), including contrast imaging, gas embolotherapy, cancer detection and drug delivery. However, the short lifetime of MBs in the circulation limits the clinical applications. Comparing to MBs, phase-change droplets (PCDs) are much stable in the circulation. PCDs will triggered vaporize into bubbles under ultrasound sonication, and this transient process is called acoustic droplet vaporization (ADV). ADV are related to the clinical diagnosis and therapy, if understanding of the physical mechanisms of ADV process, and can be monitored in real-time of ADV will be a great help for applications.
The aim of this study is to find out the mechanism during ADV by investigating the acoustic signatures of phase-change droplets and figured out their correlations with the physical behaviors observed with high-speed optical imaging. In the acoustic detection, we use pass cavitation detection (PCD) and active cavitation detection (ACD) to clarify the mechanism during ADV.
The research are divided into single and group droplet vaporization.5 MHz HIFU were transmitted to induce ADV of single droplet in a 200-μm agar tube at the mutual focus. A 2.25-MHz or 25-MHz US transducer was confocally-arranged with the mutual focus for simultaneous PCD and ACD. PCD was conducted to passively acquire the acoustic signatures emitted during ADV, whilst ACD was conducted to interrogate the morphological evolution of bubbles using a low-pressure US pulse. Finally, we use the characteristic signatures to develop M-mode imaging.
In the results, a broadband shock wave was observed in the beginning of PCD signal. Since internal gas nucleation is the necessary process of ADV, the first half signal may indicate the occurrence of an ADV event, and the second half signal may further reveal the degrees of expansion and oscillation of the bubble. These acoustic signatures provide opportunities for monitoring ADV dynamics with acoustic detection.



Keywords: phase-change droplets (PCDs)、acoustic droplet vaporization (ADV)、pass cavitation detection (PCD) 、active cavitation detection (ACD)

目錄
第一章 緒論 1
1.1 超音波對比劑 1
1.1.1 傳統超音波對比劑-微氣泡 1
1.1.2 新式超音波對比劑-相變液滴 4
1.2 相變液滴之應用 6
1.2.1 相變液滴應用於診斷上 6
1.2.2 相變液滴應用於治療上 7
1.3 聲學激發相變液滴物理機制探討 10
1.3.1 光學影像攝影 11
1.3.2 聲學訊號分析 12
1.4 研究動機與目的 16
1.4.1 光聲學共焦於相變液滴物理機制探討 16
1.5 論文架構 18
第二章 實驗材料與方法 19
2.1 概論 19
2.2 相變液滴製備與物理性測 19
2.2.1 相變液滴製備 19
2.2.2 相變液滴物理性觀測 21
2.2.2.1 光學定性觀察 21
2.2.2.2 濃度與粒徑分布量測 21
2.3 仿體製備 22
2.4 被動式與主動式穴蝕效應偵測原理探討 23
2.5 單顆相變液滴汽化觀測 25
2.5.1 被動式穴蝕效應偵測 26
2.5.1.1 系統架構 26
2.5.1.2 實驗步驟 28
2.5.1.3 訊號分析處理 29
2.5.2 主動式穴蝕效應偵測 31
2.5.2.1 系統架構 32
2.5.2.2 實驗步驟 33
2.5.2.3 訊號分析處理 34
2.6 群體相變液滴汽化觀測 35
2.6.1 被動式穴蝕效應偵測 35
2.6.1.1 系統架構 36
2.6.1.2 實驗步驟 36
2.6.1.3 訊號分析處理 37
2.6.1.4 影像分析處理 37
第三章 結果與討論 39
3.1 相變液滴定性量測 39
3.1.1 相變液滴定性觀測 39
3.1.2 相變液滴粒徑分布 39
3.2 單顆相變液滴汽化 41
3.2.1 光聲學共焦觀測結果 41
3.2.2 被動式穴蝕效應偵測 45
3.2.2.1 特徵訊號出現時間點 45
3.2.2.2 不同粒徑對特徵訊號影響 51
3.2.3 主動式穴蝕效應偵測 56
3.2.3.1 不同粒徑對ADV氣泡影響 56
3.3 群體相變液滴汽化 62
3.3.1 被動式穴蝕效應偵測 62
3.3.1.1 群體汽化對特徵訊號影響 62
3.3.2 ADV對比影像 64
第四章 結果與未來工作 66
4.1 結論 66
4.1 未來工作 68
參考文獻 70

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