包覆空氣微脂體於高頻超音波影像與聲學非線性性質研究與應用

Echogenic Liposomes in High-Frequency Ultrasound Imaging and Nonlinear Properties Investigations

盧聖介(Sheng-Chieh Lu)

指導教授 ： 葉秩光

國立清華大學/原子科學院/生醫工程與環境科學系/碩士(2008年)

摘要

自Bangham博士發現微脂體以來，微脂體被發展成藥物輸送載子與超音波對比劑。由於微脂體的粒徑可以控制在1 μm以下，因此能應用在高頻超音波上。高頻超音波不但能提升影像的解析度與偵測靈敏度，並且還能降低機械參數減少組織傷害。本研究利用自組的高頻超音波系統以偵測這些小粒子並成像。然後將測試微脂體的非線性性質，包含共振頻率、高階諧振散射與破裂。
我們提出一系列實驗模型做測試。這些實驗包含利用25 MHz高頻超音波系統成像，本研究測試影響微脂體高頻影像品質的因素，包含回溶緩衝液溫度、回溶稀釋比例與震盪混合時間。結果顯示用4-7℃緩衝液以1比3的比例稀釋微脂體，震盪混合在30秒以內的條件下有持續10分鐘以上的生命週期。再來，我們以general Herring equation預測微脂體共振頻率範圍，預測結果顯示微脂體共振頻率在約8 MHz到14 MHz之間並以實驗量測微脂體衰減係數得在8 MHz到10 MHz之間的能量吸收有相對高值。我們選用的頻率為10 MHz用來測試微脂體的高階諧波訊號並將其與馬達系統結合應用成二階諧波成像，結果發現微脂體在10 MHz聲波刺激下以二倍頻(20 MHz)成像的CTR值約為12至15 dBs，並且會有超諧波訊號的產生。最後是利用超頻超音波影像系統觀察微脂體在1.5 MHz聲波發射下的破裂行為，發現微脂體在0.15 MPa聲壓下的高頻影像已出現下降趨勢，並在0.50 MPa聲壓下會在很短的時間(10秒內)降至背景值。
以上的研究都是在生物體外下進行，在這些研究之後，我們應用這些結果至兩個生物模型上。一是利用10 MHz頻率刺激帶DNA微脂體進行3T3-L1的基因傳遞實驗，另一個為以1.5 MHz HIFU刺激(10 W)微脂體在老鼠腦內進行血腦障壁開啟的實驗。並發現微脂體在10 MHz聲波刺激下能提昇基因傳遞率由約5 %至約16 %，並且可以維持高細胞存活率。而血腦障壁的確可以HIFU結合微脂體產生穴蝕效應而開啟。

關鍵字

微脂體 ； 超音波

並列摘要

無資料

並列關鍵字

Liposomes ； Ultrasound

參考文獻

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