Ultrasonic Therapy Using Cavitation: Induction and Detection

以超音波破壞微氣泡之穴蝕效應近年來在診斷及治療上皆有許多重要的應用。由於超音波的深度聚焦特性，使非侵入式之治療方法具有相當的可行性。在超音波所有非加熱性的效應中，穴蝕效應在治療方面，具有相當高之潛力。 穴蝕效應對人體組織或細胞造成損傷，主要的成因為微氣泡之破裂。造成穴蝕效應之微氣泡稱為穴蝕核。欲探討穴蝕效應治療法，本研究分為誘發及偵測兩方面來討論。就誘發條件上來說，由於人體中之穴蝕核濃度過低且分布不均，造成誘發穴蝕效應的條件難以控制及預測。解決的方法之一為注射超音波對比劑至人體中。超音波對比劑可以提供大量之穴蝕核，且其對聲波有強散射回音的特性，可利用做為偵測之工作。本研究所採用之穴蝕核以Levovist®及微脂體微氣泡為主。另外，我們選擇中心頻率為1 MHz之探頭做為誘發穴蝕效應之用，探頭最大的負壓值為1.6 MPa。本研究並提出兩類波形以有效誘發穴蝕效應，分別為串接法及重疊法。而偵測穴蝕效應方面，本研究利用穴蝕產生之寬頻訊號，輔以商用超音波儀B-mode影像之亮度變化，以量化穴蝕效應的程度。此外，為避免諧波訊號對偵測的干擾，選用中心頻率為10 MHz之探頭以偵測穴蝕效應。 本研究已建立一套實驗系統，探討有效誘發超音波穴蝕效應的條件，並能準確偵測穴蝕效應之程度。我們亦建立穴蝕實驗有關之模擬，模擬之模型工具為Rayleigh-Plesset方程式及Runge-Kutta法，以觀察氣泡在液體中，受聲波驅動時氣泡的半徑變化，進一步將模擬與前述之穴蝕效應實驗做結合。研究結果發現串接共振及非共振頻率訊號以及重疊共振頻率及次諧波頻之訊號，較傳統之單頻訊號有較佳之效果。研究之長期目標為配合微脂體之靶向功能及藥物輸送功能，開發創新之惡性腫瘤治療技術，藉以提升超音波惡性腫瘤治療之效能。Cavitation based ultrasound therapy has received considerable research attention. Due to ultrasound’s focusing capability at depth, noninvasive cancer treatment may be possible. Acoustically driven cavitation can cause tissue necrosis as a result of microbubble destruction. These microbubbles are also known as cavitation nuclei. In this study, we concentrate on the following two topics related to acoustic cavitation: induction and detection. For induction, acoustic cavitation is difficult to control and predict without injection of microbubbles, because concentration of the inherent cavitation nuclei is low and the distribution is not uniform. Ultrasound contrast agent can provide a sufficient concentration of cavitation nuclei and the strong backscattering property can also be used for detection. In this study, liposomal microbubbles and Levovist® were used as the cavitation nuclei. The center frequency was 1 MHz and the maximum rarefactional pressure was 1.6 MPa. Two methods for efficient induction of cavitation were proposed: the cascade method and the superposition method. The cascade method cascades a signal at the bubbles resonance frequency with a signal at a lower frequency for destruction. The superimposition method adds a signal at its resonance frequency with a signal at the subharmonic frequency. For detection, the wide-band signal induced by cavitation was measured and used to detect cavitation. The signal was also correlated with the video intensity in B-mode. A 10 MHz transducer was used to avoid the interference from the harmonics. An experimental system was built. Simulation tools for cavitation were also developed based Rayleigh-Plesset equations and the Runge-Kutta method were adopted to calculate radius of the microbubbles. Both simulations and experimental results show that cavitation can be more efficiently induced using both the proposed methods. The long-term objective of this research is to develop innovative therapeutic technologies for efficient cancer treatment in combination with liposomal capabilities of targeting and drug delivery.目錄 第一章 緒論 1 1.1 前言 1 1.2 超音波治療上應用之演進 3 1.3 穴蝕效應 5 1.4穴蝕效應之超音波治療 7 1.5 研究動機與目標 8 1.6 論文架構 10 第二章 模擬方法與結果 11 2.1 Rayleigh-Plesset方程式 11 2.2 微氣泡半徑對聲壓之響應 16 2.3 發射波形設計 19 2.4 模擬結果 20 2.4.1 串接法 20 2.4.2 重疊法 22 第三章 實驗方法與結果 25 3.1 誘發方法 25 3.1.1 對比劑 25 3.2 偵測方法 28 3.2.1 影像亮度法 28 3.2.2 ICD法 29 3.3 實驗系統架構 31 3.3.1 實驗用仿體 31 3.3.2 實驗系統架構 31 3.4 實驗設計及結果 34 3.4.1 聲壓vs. 穴蝕效應 34 3.4.2 週期數vs. 穴蝕效應 35 3.4.3 串接法 36 3.4.4 重疊法 37 第四章 分析與討論 41 4.1 影像亮度法與ICD法之結果分析與討論 41 4.2 串接法 44 4.2.1 串接法模擬之討論 44 4.3 重疊法 49 4.4 微氣泡殼層參數 51 第五章 結論及未來工作 54 參考文獻 57 附錄 微脂體的製作方法 6