高強度聚焦超聲波(High-intensity Focused Ultrasound, HIFU) 治療和傳統開刀手術相比，有非侵入性、無輻射和流血量少的優勢，目前已知的應用有乳房、肝臟和前列腺等的腫瘤治療。其作用的機制主要是以機械效應和熱效應在生物體內產生高溫，使得細胞產生不可逆的凝固性壞死。燒灼時因為路徑點的初始溫度皆不同，因此如果以相同的燒灼時間，則會產生剛開始的路徑點燒灼時間不足，而其餘的路徑點因為熱擴散的影響燒灼時間過長，傷害到周圍的正常組織。
本研究的目的是建立達治療溫度為基礎的HIFU燒灼路徑規劃系統，透過超聲波影像建構腫瘤的三維模型並取得其空間座標，結合機械手臂的運動控制，讓機械手臂自動移動HIFU換能器，將HIFU聚焦點定位在腫瘤上進行熱治療。考量腫瘤形狀和熱在生物體內擴散的情形，規劃路徑點的間距和路徑行進的方式，以術前模擬推斷燒灼成效和縮短燒灼時間。
實驗部分以仿人體衰減係數的蛋白仿體和豬肉組織為假體，先測量燒灼點在介質中可能產生的位置偏移，其平均定位誤差為1.22 ± 0.42mm。再將熱電偶以線性和八相鄰的排列方式量測燒灼點周遭的溫升情形，以此作為路徑規劃時熱擴散的依據。最後，依照路徑形式和計算出來的單點停留時間，以機械手臂移動HIFU換能器對假體進行燒灼，以假體中產生變異的區域和模擬的燒灼區域做對照。實驗結果顯示螺旋向外路徑所需的燒灼時間最短，且其熱擴散影響也較容易控制，而S形路徑則在邊界的路徑點上容易產生不可預期的燒灼結果，但兩種路徑都大致能完全覆蓋預定的區域，此結果表示溫度估測的方法可以用來預測燒灼時間。

Compared with traditional tumor treatments, there are lots of advantages of using HIFU (High-intensity focused ultrasound) as a treatment method, such as noninvasiveness, radiation-free, woundless and faster recovery. HIFU has been successfully applied in treatment of solid tumors such as breast, liver, uterine fibroids, kidney, prostate, and brain.
In this study, we have developed a HIFU therapy system which is based on the achievement of temperature needed. With the assistance of B-mode ultrasonography, optic tracking, and robot navigation, we can build three dimension model of the tumor, access its spatial coordinate and position the focal point of HIFU on the tumor for further thermal treatment. Moreover, by considering of the thermal diffusion in the organism, both spiral and s-shape pathways can be planned prior to treatment to estimate the desired treatment time.
In-vitro protein phantom was used in the experiment to measure positioning accuracy of HIFU focal point. Temperature distribution surrounding the heating pattern during the heating of in-vitro protein phantoms and ex-vivo porcine tissues were measured via an eight-channel thermocouple system. Moreover, the treatment time for each targeted positions of the planned treated trajectory were automatically controlled to reach the targeted temperature and then moved to the next planning targeted position by the robot controller. Results showed that the averaged positioning error is 1.22 ±0.42mm. Compared the coagulation areas of the ablated phantom to different preplanned trajectories, the spiral trajectory can save the most of time and the thermal diffusion is evenly spread. However, s-shape heating trajectory required a longer treatment time and cause unpredictable result on the boundary. Yet, two heating trajectories both provide satisfactory treatment region coverage. In conclusion, this study provides insight and valuable knowledge when applying HIFU to treat large tumor volume in future clinical application.

[1] G.J. Lynn, R.L. Zwemer, A.J. Chick, and A.E. Miller, “A new method for the generation and use of focused ultrasound in experimental biology,” The Journal of General Physiology, vol. 26, pp. 179-193, 1946.
[2] W.J. Fry and F.J. Fry, “fundamental neurological research and human neurosurgery using intense ultrasound,” IRE Transactions on Medical Electronics, vol. ME-7(3), pp. 166-181, 1960.
[3] H. Pauly and H.P. Schwan, “Mechanism of absorption of ultrasound in liver tissue,” The Journal of the Acoustical Society of America, vol. 50, pp. 692-699, 1971.
[4] W.C. Dewey, D.E Thrall, and E.L. Gillette, “Hyperthermia and radiation – a selective thermal effect on chronically hypoxic tumor cells in vivo,” International Journal of Radiation Oncology Biology Physics, vol. 2(1-2), pp. 99-103, 1977.
[5] R. Maass-Moreno, C.A. Damianou, and N.T. Sanghvi, “Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part I. Analytical model,” The Journal of the Acoustical Society of America, vol. 100, pp. 2515-2521, 1996.
[6] R. Maass-Moreno, C.A. Damianou, and N.T. Sanghvi, “Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part II. In vitro study,” The Journal of the Acoustical Society of America, vol. 100, pp. 2522-2523, 1996.
[7] A.V. Zaitsev, N.T. Sanghvi, S. Ikenberry, J.F. Worzalla, R.M. Schultz, and T.D. Self, “High intensity focused ultrasound(HIFU) treatment of human pancreatic cancer,” IEEE Ultrasound Symposium, San Antonio ,TX, pp. 1295-1298, 1996.
[8] M.M. Paul, D.C. Mark, and R.H. Gail, “The intensity dependence of lesion position shift during focused ultrasound surgery,” Ultrasound in Med. & Biol., vol. 26, no. 3, pp. 441-450, 2000.
[9] H. Tang, C.C. Wang, D. Blankschtein, and R. Langer, “An investigation of the role of cavitation in low-frequency ultrasound –mediated transdermal drug transport,” Pharm Res, vol. 19(8), pp. 1160-1169, 2002.
[10] W.S. Chen, C. Lafon, T.J. Matula, and S. Vaczy, “Mechanisms of lesion formation in high intensity focused ultrasound therapy,” Ultrasonics Symposium, vol. 2, pp. 1443-1446, 2002.
[11] K. Takegami, Y. Kaneko, T. Watanabe, T. Maruyama, Y. Matsumoto, and H. Nagawa , “Polyacrylamide gel containing egg white as new model for irradiation experiments using focused ultrasound,” Ultrasound in Medicine and Biology, vol. 30, pp. 1419-1422, 2004.
[12] U. Techavipoo, Q. Chen, and T. Varghese, “Ultrasonic noninvasive temperature estimation using echoshift gradient maps: simulation results,” Ultrason Imaging, vol. 27, pp. 166-180, 2005.
[13] Y.S. Tung, H.L. Liu, C.C. Wu, K.C. J u, W.S. Chen, and W.L. Lin, “Contrast-agent-enhanced ultrasound thermal ablation,” Ultrasound in Medicine and Biology, vol. 32, pp. 1103-1110, 2006.
[14] Y. Zhou, S.G. Kargl, K. Kim, and J.H. Hwang, “Comparison of pathway in high intensity focused ultrasound lesion production,” The Journal of the Acoustical Society of America, vol. 122(5), pp. 3007, 2007.
[15] C.C. Wu, C.N. Chen, M.C. Ho, W.S. Chen, and P.H. Lee, “Using the acoustic interference pattern to locate the focus of a high-intensity focused ultrasound (HIFU) transducer,” Ultrasound in Med. & Biol., vol. 34, pp. 137-146, 2008.
[16] X.Q. Jian, L.S. Wu, Z.H. Li, and J.G. Yin, “Temperature field FDTD simulation of HIFU in human body tissues,” The 2nd International Conference on Bioinformatics and Biomedical Engineering (ICBBE), Shanghai, pp. 759-762, 2008.
[17] Y.S. Kim, H. Rhim, M.J. Choi, H.K. Lim, and D. Choi, “High-intensity focused ultrasound therapy: An overview for radiologists,” Korean Journal of Radiology, vol. 9(4), pp. 291-302, 2008.
[18] K.H. Lin, S.Y. Young, M.C. Hsu, H. Chan, Y.Y. Chen, and W.L. Lin, “Focused ultrasound thermal therapy system with ultrasound image guidance and temperature measurement feedback,” 30th Annual International IEEE EMBS Conference, Vancouver ,BC, pp. 2522-2525, 2008.
[19] M.S. Canney, M.R. Bailey, and L.A. Crum, “Acoustic characterization of high intensity focused ultrasound fields: A combined measurement and modeling approach,” The Journal of the Acoustical Society of America, vol. 124(4), pp. 2406-2420, 2008.
[20] 王修含，「以光聲效應為主之雷射光熱治療定量式熱影像」， 碩士論文，台灣大學 生醫電子與資訊學研究所，2009。
[21] C.H. Farny, R.G. Holt, and R.A. Roy, "The correlation between bubble-enhanced HIFU heating and cavitation power," IEEE Transactions on Biomedical Engineering, vol. 57(1), pp. 175-184, 2010.
[22] J. Seo, N. Koizumi, K. Yoshinaka, N. Sugita, A. Nomiya, Y. Homma, Y. Matsumoto, and M. Mitsuishi, “Three-dimensional computer-controlled acoustic pressure scanning and quantification of focused ultrasound,” IEEE Transaction on Ultrasonics, Ferroelectrics and Frequency Control, vol. 57, pp. 883-891, 2010.
[23] D. Li, G. Shen, H. Luo, J. Bai, and Y. Chen, “A study of heating duration and scanning path in focused ultrasound surgery,” Journal of Medical Systems, vol. 35(5), pp. 779-786, 2011.
[24] Y. Zhou, “Generation of uniform lesions in high intensity focused ultrasound ablation,” Ultrasonics. Vol. 53(2), pp. 495-505, 2013.
[25] 安治宇，「應用於肝腫瘤治療之超音波影像輔助機械手臂HIFU燒灼系統」，博士資格考，中央大學 機械工程研究，2013。
[26] 許家豪，「應用於HIFU熱治療之超音波影像輔助機械手臂定位系統」， 碩士論文，中央大學 生物醫學工程研究所，2014。