臺灣博碩士論文加值系統

空穴效應在已被證明在治療超音波應用中發揮關鍵的作用。HIFU治療中的空穴效應提升聲能的吸收，有效地增加組織中聚焦區域的加熱效應，而其中空穴效應中的慣性空穴導致氣泡趨於不穩定，造成治療中潛在不期望的聚焦損傷。為了確保安全，我們努力構建一個即時檢測和低成本的被動式空穴效應檢測水聽器（Passive Cavitation Detector；PCD），用於監測與控制HIFU在治療過程中的空穴活動。本研究的目標是開發高靈敏度和寬頻帶的PCD，換能器主要包含三個部分：壓電層、匹配層和背對層。PZT-5A為壓電層；匹配層由填充環氧樹脂的陽極氧化鋁模板組成，AAO-epoxy複合匹配層的聲阻抗為9.5 MRayls，使得壓電層能與水中或組織的聲阻能匹配，提升聲能轉換的效率。此外，選擇鈦棒（Titanium）的作為背對層材料並黏合至壓電層上，Titanium此材料具有很高的聲阻抗係數，可以吸收壓電陶瓷片背向發射的聲波，減少背向雜波影響。利用PiezoCAD模擬，得知此設計能有效的提升PCD之接收頻寬與靈敏度。本研究所開發出來的1 MHz PCD能有效接收2 MHz聚焦式換能器所誘發空穴效應之訊號，可以判斷在不同電壓輸出時，是否有空穴效應之現象產生。




關鍵字：高能聚焦超音波、空穴效應、被動式空穴效應檢測水聽器、陽極氧化鋁、PZT-5A

Acoustic cavitation has been shown to play key role in therapeutic ultrasound applications. Cavitation activity in High-Intensity Focus Ultrasound (HIFU) treatment significantly enhances the absorption of the acoustic energy, effectively accelerates heating the focal region in the tissue. And the bubbles activity of inertial cavitation tends to grow unstable, it may cause potentially undesirable focal damage. To ensure the safety, we endeavor to construct a real-time and low-cost Passive Cavitation Detection (PCD) for monitoring and controlling cavitation activity during HIFU treatmants. The goal of this study is to develop a PCD with high sensitivity and wide bandwidth. The transducer contains three parts, which are piezoelectric ceramic, matching layer, and a backing layer. Piezoelectric layer is PZT-5A. The matching layer is composed of anodic aluminum oxide (AAO) template filled with Epotek 301 epoxy, so that the piezoelectric with matching layer can match the acoustic resistance of water or tissue and improve the efficiency of sound energy conversion. In addition, Titanium is selected as a backing layer material and bonded to the piezoelectric layer. Titanium has a high acoustic impedance coefficient. It can absorb the sound waves radiated from the piezoelectric ceramic and reduce the influences of backing noise. Using the PiezoCAD simulation, it is known that this design can effectively improve the receiving bandwidth and sensitivity of PCD. The 1 MHz PCD developed by this research institute can effectively receive the cavitation effect signal induced by the 2 MHz HIFU transducer. It can determine whether there is a cavitation effect at different voltage outputs.
Keyword: HIFU, Cavitation, Passive Cavitation Detection, Anodic Aluminum Oxide, PZT-5A

目錄
摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VII
表目錄 X
第 一 章 緒論 1
1.1 研究背景 1
1.2 空穴效應 2
1.3 空穴效應與氣泡的關係 6
1.4 空穴效應的應用 7
1.5 Passive Cavitation Detector 9
研究目的 10
第 二 章 理論基礎 11
2.1 超音波概述 11
2.2 壓電效應 14
2.3 壓電材料簡介 16
2.3.1 壓電材料特性參數 17
2.3.2 PZT與PVDF之比較 19
2.4 超音波換能器結構 20
2.4.1 匹配層 21
2.4.2 背對層 23
第 三 章 材料與方法 24
3.1 PCD設計 24
3.1.1 超音波換能器模擬 24
3.1.2 壓電片選擇 25
3.1.3 匹配層設計 26
3.1.4 背對層設計 27
3.2 製作流程 28
3.2.1 匹配層 (Matching layer) 28
3.2.2 背對層 (Backing layer) 30
3.2.3 封裝 31
3.3 阻抗匹配電路 33
3.4 特性化測試 34
3.4.1 阻抗分析 34
3.4.2 聲速測量 35
3.4.3 脈衝回波測試（Pulse-echo measurement） 36
3.4.4 PCD之靈敏度 37
3.5 產生空穴效應的超音波參數設計 39
3.6 實驗系統架構 40
第 四 章 實驗結果 43
4.1 匹配層與背對層之模擬 43
4.1.1 匹配層模擬 43
4.2 換能器原型 47
4.3 脈衝回波測試 48
4.3.1 PiezoCAD模擬結果 48
4.3.2 實驗測試結果 50
4.4 水聽器之靈敏度量測結果 52
4.5 空穴效應特性分析 53
4.5.1 PCD頻譜分析方法評估空穴效應 53
4.5.2 1mm Hydrophone 頻譜分析方法評估空穴效應 56
第 五 章 結論與探討 57
5.1 結論 57
5.2 討論 57
5.2.1 匹配層 57
5.2.2 背對層 58
5.2.3 壓電層 58
5.2.4 PCD與 Hydrophone空穴效應頻譜分析 59
5.3 未來展望 59
第 六 章 參考文獻 60

[1] K. S. Suslick, "Ultrasound: its chemical, physical, and biological effects," 1988.
[2] D. L. Miller, N. B. Smith, M. R. Bailey, G. J. Czarnota, K. Hynynen, I. R. S.Makin, "Overview of therapeutic ultrasound applications and safety considerations," Journal of Ultrasound in Medicine, vol. 31, no. 4, pp. 623-634, 2012.
[3] J. Hoła and K. Schabowicz, "State-of-the-art non-destructive methods for diagnostic testing of building structures–anticipated development trends," Archives of civil and mechanical engineering, vol. 10, no. 3, pp. 5-18, 2010.
[4] P. L. Carson, P. R. Fischella, and T. V. Oughton, "Ultrasonic power and intensities produced by diagnostic ultrasound equipment," Ultrasound in medicine & biology, vol. 3, no. 4, pp. 341-350, 1978.
[5] M. S. Canney, M. R. Bailey, L. A. Crum, V. A. Khokhlova, and O. A. Sapozhnikov, "Acoustic characterization of high intensity focused ultrasound fields: A combined measurement and modeling approach," The Journal of the Acoustical Society of America, vol. 124, no. 4, pp. 2406-2420, 2008.
[6] Y. Zhou, L. Zhai, R. Simmons, and P. Zhong, "Measurement of high intensity focused ultrasound fields by a fiber optic probe hydrophone," The Journal of the Acoustical Society of America, vol. 120, no. 2, pp. 676-685, 2006.
[7] J. J. Martinez, R. J. Myers, T. J. Carlson, Z. D. Deng, J. S. Rohrer, K. A. Caviggia, C. M. Woodley, M. A. Weiland, "Design and implementation of an underwater sound recording device," Sensors, vol. 11, no. 9, pp. 8519-8535, 2011.
[8] D. M. Hallow, A. D. Mahajan, T. E. McCutchen, and M. R. Prausnitz, "Measurement and correlation of acoustic cavitation with cellular bioeffects," Ultrasound in medicine & biology, vol. 32, no. 7, pp. 1111-1122, 2006.
[9] T. Leighton, The acoustic bubble. Academic press, 2012.
[10] B. Verhaagen and D. F. Rivas, "Measuring cavitation and its cleaning effect," Ultrasonics sonochemistry, vol. 29, pp. 619-628, 2016.
[11] W. Lauterborn, T. Kurz, R. Geisler, D. Schanz, and O. Lindau, "Acoustic cavitation, bubble dynamics and sonoluminescence," Ultrasonics sonochemistry, vol. 14, no. 4, pp. 484-491, 2007.
[12] Z. Izadifar, P. Babyn, and D. Chapman, "Ultrasound Cavitation/Microbubble Detection and Medical Applications," Journal of Medical and Biological Engineering, pp. 1-18, 2018.
[13] P. N. Burns and S. R. Wilson, "Microbubble contrast for radiological imaging: 1. Principles," Ultrasound quarterly, vol. 22, no. 1, pp. 5-13, 2006.
[14] I. Lentacker, I. De Cock, R. Deckers, S. De Smedt, and C. Moonen, "Understanding ultrasound induced sonoporation: definitions and underlying mechanisms," Advanced drug delivery reviews, vol. 72, pp. 49-64, 2014.
[15] K. E. Morgan, J. S. Allen, P. A. Dayton, J. E. Chomas, A. Klibaov, and K. W. Ferrara, "Experimental and theoretical evaluation of microbubble behavior: Effect of transmitted phase and bubble size," IEEE transactions on ultrasonics, ferroelectrics, and frequency control, vol. 47, no. 6, pp. 1494-1509, 2000.
[16] P.-C. Chu, W.-Y. Chai, C.-H. Tsai, S.-T. Kang, C.-K. Yeh, and H.-L. Liu, "Focused ultrasound-induced blood-brain barrier opening: association with mechanical index and cavitation index analyzed by dynamic contrast-enhanced magnetic-resonance imaging," Scientific reports, vol. 6, p. 33264, 2016.
[17] W. Lauterborn and R. Mettin, "Acoustic cavitation: bubble dynamics in high-power ultrasonic fields," in Power Ultrasonics: Elsevier, pp. 37-78, 2015.
[18] Y. Zhou, K. Yang, J. Cui, J. Ye, and C. Deng, "Controlled permeation of cell membrane by single bubble acoustic cavitation," Journal of controlled release, vol. 157, no. 1, pp. 103-111, 2012.
[19] W. G. Pitt, G. A. Husseini, and B. J. Staples, "Ultrasonic drug delivery–a general review," Expert opinion on drug delivery, vol. 1, no. 1, pp. 37-56, 2004.
[20] D. Omata, Y. Negishi, R. Suzuki, Y. Oda, Y. Endo-Takahashi, and K. Maruyama, "Nonviral gene delivery systems by the combination of bubble liposomes and ultrasound," in Advances in genetics, vol. 89: Elsevier, 2015, pp. 25-48.
[21] A. F. Prokop, A. Soltani, and R. A. Roy, "Cavitational mechanisms in ultrasound-accelerated fibrinolysis," Ultrasound in medicine & biology, vol. 33, no. 6, pp. 924-933, 2007.
[22] E. A. Neppiras, "Acoustic cavitation," Physics reports, vol. 61, no. 3, pp. 159-251, 1980.
[23] D. Dowsett, Radiological sciences dictionary: keywords, names and definitions. CRC Press, 2009.
[24] M. N. Patil and A. B. Pandit, "Cavitation–a novel technique for making stable nano-suspensions," Ultrasonics Sonochemistry, vol. 14, no. 5, pp. 519-530, 2007.
[25] J. Klima, A. Frias-Ferrer, J. González-García, J. Ludvik, V. Saez, and J. Iniesta, "Optimisation of 20 kHz sonoreactor geometry on the basis of numerical simulation of local ultrasonic intensity and qualitative comparison with experimental results," Ultrasonics sonochemistry, vol. 14, no. 1, pp. 19-28, 2007.
[26] J. Yasuda, S. Yoshizawa, and S.-i. Umemura, "Efficient generation of cavitation bubbles and reactive oxygen species using triggered high-intensity focused ultrasound sequence for sonodynamic treatment," Japanese Journal of Applied Physics, vol. 55, no. 7S1, p. 07KF24, 2016.
[27] S. Haqshenas and N. Saffari, "Multi-resolution analysis of passive cavitation detector signals," in Journal of Physics: Conference Series, vol. 581, no. 1, p. 012004: IOP Publishing, 2015.
[28] P. R. Gogate and A. M. Kabadi, "A review of applications of cavitation in biochemical engineering/biotechnology," Biochemical Engineering Journal, vol. 44, no. 1, pp. 60-72, 2009.
[29] S. Wang, B. Huang, Y. Wang, and L. Liao, "Comparison of enhancement of pentachlorophenol sonolysis at 20 kHz by dual-frequency sonication," Ultrasonics sonochemistry, vol. 13, no. 6, pp. 506-510, 2006.
[30] C.-T. Lu, Y.-Z. Zhao, H. L. Wong, J. Cai, L. Peng, and X.-Q. Tian, "Current approaches to enhance CNS delivery of drugs across the brain barriers," International journal of nanomedicine, vol. 9, p. 2241, 2014.
[31] K. Johansen, J. H. Song, and P. Prentice, "Performance characterisation of a passive cavitation detector optimised for subharmonic periodic shock waves from acoustic cavitation in MHz and sub-MHz ultrasound," Ultrasonics sonochemistry, vol. 43, pp. 146-155, 2018.
[32] Y.-F. Zhou, "High intensity focused ultrasound in clinical tumor ablation," World journal of clinical oncology, vol. 2, no. 1, p. 8, 2011.
[33] C.-H. Fan, C.-Y. Ting, Y.-C. Chang, K.-C. Wei, H.-L. Liu, and C.-K. Yeh, "Drug-loaded bubbles with matched focused ultrasound excitation for concurrent blood–brain barrier opening and brain-tumor drug delivery," Acta biomaterialia, vol. 15, pp. 89-101, 2015.
[34] L. Hegedüs, "Thyroid ultrasound," Endocrinology and metabolism clinics of North America, vol. 30, no. 2, pp. 339-360, 2001.
[35] K. K. Shung, "Diagnostic ultrasound: Past, present, and future," J Med Biol Eng, vol. 31, no. 6, pp. 371-4, 2011.
[36] R. K. Pooh and A. Kurjak, "3D/4D sonography moved prenatal diagnosis of fetal anomalies from the second to the first trimester of pregnancy," ed: Taylor & Francis, 2012.
[37] N. Datta, A. Bose, H. Kapoor, and S. Gupta, "Head and neck cancers: results of thermoradiotherapy versus radiotherapy," International Journal of Hyperthermia, vol. 6, no. 3, pp. 479-486, 1990.
[38] J. Overgaard et al., "Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology," International Journal of Hyperthermia, vol. 25, no. 5, pp. 323-334, 2009.
[39] M. Ahmed and S. N. Goldberg, "Thermal ablation therapy for hepatocellular carcinoma," Journal of vascular and interventional radiology, vol. 13, no. 9, pp. S231-S243, 2002.
[40] 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, no. 4, pp. 291-302, 2008.
[41] J. Vappou, C. Maleke, and E. E. Konofagou, "Quantitative viscoelastic parameters measured by harmonic motion imaging," Physics in Medicine & Biology, vol. 54, no. 11, p. 3579, 2009.
[42] S. Ibsen, C. E. Schutt, and S. Esener, "Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment," Drug design, development and therapy, vol. 7, p. 375, 2013.
[43] A. Qabur and K. Alshammari, "A Systematic Review of Energy Harvesting from Roadways by using Piezoelectric Materials Technology," Innov Ener Res, vol. 7, no. 191, pp. 2576-1463.1000191, 2018.
[44] G. Gautschi, "Piezoelectric sensors," in Piezoelectric Sensorics: Springer, pp. 73-91, 2002.
[45] K. Uchino, "High electromechanical coupling piezoelectrics: relaxor and normal ferroelectric solid solutions," Solid State Ionics, vol. 108, no. 1-4, pp. 43-52, 1998.
[46] Measurement specialties Piezo Film Sensors Technical Manual, 1998.
[47] H. Kitsunai, T. Suzuki, M. Ishikawa, N. Kawashima, E. Ohdaira, M. Kurosawa, S. Takeuchi, "Development of miniature hydrophone with PZT film deposited by hydrothermal method," in Ultrasonics Symposium, 2004 IEEE, 2004, vol. 3, pp. 2201-2205: IEEE.
[48] F. Bauer, "PVDF shock sensors: Applications to polar materials and high explosives," IEEE transactions on ultrasonics, ferroelectrics, and frequency control, vol. 47, no. 6, pp. 1448-1454, 2000.
[49] V. M. do Nascimento, V. L. d. S. N. Button, J. M. Maia, E. T. Costa, and E. J. V. Oliveira, "Influence of backing and matching layers in ultrasound transducer performance," in Medical Imaging 2003: Ultrasonic Imaging and Signal Processing, vol. 5035, pp. 86-97: International Society for Optics and Photonics. , 2003
[50] T. Yang, X. Wang, W. Liu, Y. Shi, and F. Yang, "Double-layer anti-reflection coating containing a nanoporous anodic aluminum oxide layer for GaAs solar cells," Optics express, vol. 21, no. 15, pp. 18207-18215, 2013.
[51] H. Fang, Y. Chen, C. Wong, W. Qiu, H. Chan, J. Dai, Q. Li, Q. Yan, "Anodic aluminum oxide–epoxy composite acoustic matching layers for ultrasonic transducer application," Ultrasonics, vol. 70, pp. 29-33, 2016.
[52] H. M. Levy and Shimshon, "Basic RF Technic and Laboratory Manual," 2002.
[53] J. Li, W. Ren, G. Fan, and C. Wang, "Design and Fabrication of Piezoelectric Micromachined Ultrasound Transducer (pMUT) with Partially-Etched ZnO Film," Sensors, vol. 17, no. 6, p. 1381, 2017.