高能聚焦超音波之燒灼技術改良：即時超音波焦點定位法、蛋白質變異監測、避免表淺組織燒傷，與利用超音波顯影劑增大燒灼焦斑

Abstract

高能聚焦超音波系統因非侵入式治療優點已廣泛利用腫瘤的治療上。非侵入治療方式對於病人的優點為不需要開刀，減少對健康組織的傷害。不過這樣的優點的挑戰在於如何監測整個燒灼治療過程。目前主要的監測方式為診斷式超音波及磁振掃描影像兩種方式。因為超音波為機械波的一種，因此在不介質中傳遞時會產生折射現象，所以實際的聚焦位置會與幾何的聚焦位置有所偏差，因此本論文希望利用新的方法輔助目前利用馬達精密定位幾何焦點的方式，利用診斷式超音波的缺點為高能聚焦超音波會對診斷式超音波影像產生干擾，因此必須將觀察的時間與治療的時間相互錯開，否則無法達到即時觀察的目標。不過本研究發現焦點位置的干擾信號最為強烈，因此可以利用這干擾訊號達到定位的效能。 另一個監測治療用超音波的方式為磁振掃描影像，目前主要的觀察為磁振掃描影像中分析燒灼區域溫度場。本論文利用另一磁振掃描影像序列，可用於反映蛋白質變異程度，進行燒灼區域的蛋白質變異程度的分析，並與溫度場分析及超音波影響觀察的燒灼區域比較分析結果。 高能聚焦超音波系統對於燒灼的其中一項缺點為會造成皮膚的燒傷，尤其是當燒灼目標接近皮膚時更容易造成。因此為了避免皮膚燒傷對病人產生不必要的疼痛，所以本論文利用人工腹水的方式避免皮膚燒傷，於動物實驗上得到良好的驗證。 高能聚焦超音波系統的另一項缺點為單一聚焦燒灼區域太小，因此欲完成腫瘤治療往往需要花費數小時，所以最近的研究皆利用微小氣泡即超音波顯影劑增加單一燒灼體積，一般而言超音波顯影劑可以增加治療區域體積為3至4倍。本論文探討不同濃度的超音波顯影劑對於燒灼焦斑體積的影響效果。此方向研究在仿體上的效果已於先前研究發現當超音波顯影劑濃度太高時，焦班會產生於仿體表面而不是在焦點位置，本論文針對動物實驗中，不同濃度超音波顯影劑對燒灼效果的影響。 關鍵詞：超音波顯影劑、高能聚焦超音波、磁造影引導、組織傷害、熱治療。

One of the main problems encountered when using conventional B-mode ultrasound (US) for targeting and monitoring purposes during ablation therapies employing high-intensity focused US (HIFU) is the appearance of strong interference in the obtained diagnostic US images. In this study, instead of avoiding the interference noise, we demonstrate how we used it to locate the focus of the HIFU transducer in both in-vitro tissue-mimicking phantoms and an ex-vivo tissue block. We found that when the B-mode image plane coincided with the HIFU focal plane, the interference noise was maximally converged and enhanced compared with the off-focus situations. Stronger interference noise was recorded when the angle between the US image plane and the HIFU axis was less than or equal to 90. By intentionally creating a target (group of bubbles) at the 3.5-MHz HIFU focus (7.1 mm in length and 0.7 mm in diameter), the position of the maximal noise convergence coincided well with the target. The differenced between the predicted focus and the actual one (bubbles) on x and z axes (axes perpendicular to the HIFU central axis, Fig. 1) were both about 0.9 mm. For y axis (HIFU central axis), the precision was within 1.0 mm. For tissue block ablation, the interference noise concentrated at the position of maximal heating of the HIFU-induced lesions. The proposed method can also be used to predict the position of the HIFU focus by using a low intensity output scheme before permanent changes in the target tissue were made. The utilization of magnetic resonance imaging (MRI) for HIFU not only real-time monitoring of HIFU ablation but also allows the evaluation of HIFU-induced lesions after treatment. Our study proposed an interleaved dual gradient-echo technique to simultaneously estimate temperature changes and magnetization transfer (MT) contrast, reflecting respectively heating conditions and degree of tissue damage during HIFU treatment. If the target hepatocellular carcinoma (HCC) is close to the surface of the liver, HIFU may overheat intervening tissue such as the diaphragm, abdominal wall, and skin. To avoid this complication, we propose inducing artificial ascites in the abdominal cavity so as to separate the liver from the peritoneum, and to serve as a heat sink to cool overlying structures and thereby avoid inducing permanent damage. Target tissue that was 10 mm below the liver surface was ablated in 12 New Zealand White rabbits: 6 in the experimental group and 6 in the control group. Artificial ascites was established in the experimental group by injecting normal saline into the abdominal cavity until the pressure reached 150 mmH2O. Artificial ascites not only reduced the probability and extent of thermal damage to intervening structures (P<0.05), but also had no adverse affect on the efficacy of HIFU ablation (P>0.05). One of the major disadvantages of HIFU ablation was the small lesion size and thus the long treatment duration. In this study, the effect of using ultrasound contrast agent (UCA) to enlarge the lesion size was studied both in vitro and in vivo. The mechanisms of lesion formation in the presence of UCA microbubbles were studied in vitro and in vivo.