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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李百祺 | |
| dc.contributor.author | Szu-Chia Chen | en |
| dc.contributor.author | 陳思嘉 | zh_TW |
| dc.date.accessioned | 2021-06-15T02:51:13Z | - |
| dc.date.available | 2012-08-11 | |
| dc.date.copyright | 2009-08-11 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-05 | |
| dc.identifier.citation | [1] Furie, B. and B.C. Furie, Mechanisms of thrombus formation. N Engl J Med, 2008. 359(9): p. 938-49.
[2] 何敏夫, 血液學. 2005, 台北: 合記. 第三版, p. 555-6. [3]http://diaglab.vet.cornell.edu/clinpath/modules/,Cornell University. [4] Hacke, W., et al., Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA, 1995. 274(13): p. 1017-25. [5] Hacke, W., et al., Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet, 1998. 352(9136): p. 1245-51. [6] Datta, N.R., et al., Head and Neck Cancers - Results of Thermoradiotherapy Versus Radiotherapy. International Journal of Hyperthermia, 1990. 6(3): p. 479-86. [7] Overgaard, J., 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, 1996. 12(1): p. 3-20. [8] Datta, N.R., et al., Head and neck cancers: results of thermoradiotherapy versus radiotherapy. International Journal of Hyperthermia, 1990. 6(3): p. 479-86. [9] Kim, Y.S., et al., High-intensity focused ultrasound therapy: An overview for radiologists. Korean Journal of Radiology, 2008. 9(4): p. 291-302. [10] Goldberg, B.B., J.B. Liu, and F. Forsberg, Ultrasound contrast agents: a review. Ultrasound Med Biol, 1994. 20(4): p. 319-33. [11] Ruan, J.L., Preparation and Applications of Targeted Ultrasounic Contrast Agents. 2008, National Taiwan University. [12] Ellegala, D.B., et al., Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation, 2003. 108(3): p. 336-41. [13] Lanza, G.M. and S.A. Wickline, Targeted ultrasonic contrast agents for molecular imaging and therapy. Curr Probl Cardiol, 2003. 28(12): p. 625-53. [14] Lindner, J.R., Molecular imaging with contrast ultrasound and targeted microbubbles. J Nucl Cardiol, 2004. 11(2): p. 215-21. [15] Martin, M.J., et al., Enhanced detection of thromboemboli with the use of targeted microbubbles. Stroke, 2007. 38(10): p. 2726-32. [16] Schumann, P.A., et al., Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi. Invest Radiol, 2002. 37(11): p. 587-93. [17] Lauterborn, W., et al., Acoustic cavitation, bubble dynamics and sonoluminescence. Ultrason Sonochem, 2007. 14(4): p. 484-91. [18] Morgan, K.E., et al., Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size. IEEE Trans Ultrason Ferroelectr Freq Control, 2000. 47(6): p. 1494-509. [19] Prokop, A.F., A. Soltani, and R.A. Roy, Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol, 2007. 33(6): p. 924-33. [20] http://www.sonochemistry.info/,Sonochemistry centre of Coventry University. [21] Burns, P.N. and S.R. Wilson, Microbubble contrast for radiological imaging: 1. Principles. Ultrasound Q, 2006. 22(1): p. 5-13. [22] Neppiras E.A., Acoustic cavitation. Physics Reports. 1980. 61(3): p. 159-251. [23] Chen, W.S., et al., The effect of surface agitation on ultrasound-mediated gene transfer in vitro. J Acoust Soc Am, 2004. 116(4 Pt 1): p. 2440-50. [24] Francis, C.W., et al., Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol, 1995. 21(3): p. 419-24. [25] Everbach, E.C. and C.W. Francis, Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz. Ultrasound Med Biol, 2000. 26(7): p. 1153-60. [26] Hajri, Z., et al., An investigation of the physical forces leading to thrombosis disruption by cavitation. J Thromb Thrombolysis, 2005. 20(1): p. 27-32. [27] Molina, C.A., et al., Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke, 2006. 37(2): p. 425-9. [28] Datta, S., et al., Correlation of cavitation with ultrasound enhancement of thrombolysis. Ultrasound Med Biol, 2006. 32(8): p. 1257-67. [29] Cintas, P., et al., Enhancement of enzymatic fibrinolysis with 2-MHz ultrasound and microbubbles. J Thromb Haemost, 2004. 2(7): p. 1163-6. [30] Suchkova, V., et al., Enhancement of fibrinolysis with 40-kHz ultrasound. Circulation, 1998. 98(10): p. 1030-5. [31] Birnbaum, Y., et al., Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles. Circulation, 1998. 97: p. 130-4. [32] Wu, Y., et al., Binding and lysing of blood clots using MRX-408. Invest Radiol, 1998. 33(12): p. 880-5. [33] Xie, F., et al., Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis. Ultrasound Med Biol, 2005. 31(7): p. 979-85. [34] Zhao, S., et al., Radiation-force assisted targeting facilitates ultrasonic molecular imaging. Mol Imaging, 2004. 3(3): p. 135-48. [35] Yeh, C.K., et al., Dual high-frequency difference excitation for contrast detection. IEEE Trans Ultrason Ferroelectr Freq Control, 2008. 55(10): p. 2164-76. [36] Cheng, Y.J., Preparation and Biomedical Applications of Ultrasonic Microbubbles. 2007, National Taiwan University. [37] Oberle, V., et al., Efficient transfer of chromosome-based DNA constructs into mammalian cells. Biochim Biophys Acta, 2004. 1676(3): p. 223-30. [38] Lai, C.Y., et al., Quantitative relations of acoustic inertial cavitation with sonoporation and cell viability. Ultrasound Med Biol, 2006. 32(12): p. 1931-41. [39] Datta, S., et al., Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent. Ultrasound Med Biol, 2008. 34(9): p. 1421-33. [40] Kruse, D.E., C.K. Yeh, and K.W. Ferrara, A new imaging strategy utilizing wideband transient response of ultrasound contrast agents, in IEEE International Ultrasonics Symposium, 2003. p. 424-8. [41] Cherin, E., et al., Microbubble contrast agent destruction using 20-25 MHz ultrasound, in IEEE International Ultrasonics Symposium, 2005. p. 751-4. [42] Yeh, C.K., S.Y. Su, and C.C. Shen, Microbubble destruction by dual-high-frequency ultrasound excitation. IEEE Trans Ultrason Ferroelectr Freq Control, 2009. 56(5): p. 1113-8. [43] Shi, W.T. and F. Forsberg, Ultrasonic characterization of the nonlinear properties of contrast microbubbles. Ultrasound Med Biol, 2000. 26(1): p. 93-104. [44] Tang, M.X. and R.J. Eckersley, Nonlinear propagation of ultrasound through microbubble contrast agents and implications for imaging. IEEE Trans Ultrason Ferroelectr Freq Control, 2006. 53(12): p. 2406-15. [45] Khokhlova, V.A., et al., Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom. J Acoust Soc Am, 2006. 119(3): p. 1834-48. [46] Chomas, J.E., et al., Mechanisms of contrast agent destruction. IEEE Trans Ultrason Ferroelectr Freq Control, 2001. 48(1): p. 232-48. [47] Klibanov, A.L., et al., Destruction of contrast agent microbubbles in the ultrasound field: the fate of the microbubble shell and the importance of the bubble gas content. Acad Radiol, 2002. 9 Suppl 1: p. S41-5. [48] Rychak, J.J., et al., Enhanced targeting of ultrasound contrast agents using acoustic radiation force. Ultrasound Med Biol, 2007. 33(7): p. 1132-9. [49] Dayton, P., et al., Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles. Ultrasound Med Biol, 1999. 25(8): p. 1195-201. [50] Dayton, P.A., J.S. Allen, and K.W. Ferrara, The magnitude of radiation force on ultrasound contrast agents. J Acoust Soc Am, 2002. 112(5 Pt 1): p. 2183-92. [51] Dayton, P.A., et al., A preliminary evaluation of the effects of primary and secondary radiation forces on acoustic contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control, 1997. p. 1264 -77. [52] Fowlkes, J.B., et al., The role of acoustic radiation force in contrast enhancement techniques using bubble-based ultrasound contrast agents. J Acoust Soc Am, 1993. 93: p. 2348. [53] Rychak, J.J., A.L. Klibanov, and J.A. Hossack, Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: In vitro verification. IEEE Trans Ultrason Ferroelectr Freq Control, 2005. 52(3): p. 421-33. [54] Rychak, J.J., et al., Acoustic radiation force enhances ultrasound contrast agent retention to P-selectin in vivo. in IEEE International Ultrasonics Symposium, 2005: p. 1703-7 [55] Lum, A.F., et al., Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles. J Control Release, 2006. 111(1-2): p. 128-34. [56] Shortencarier, M.J., et al., A method for radiation-force localized drug delivery using gas-filled lipospheres. IEEE Trans Ultrason Ferroelectr Freq Control, 2004. 51(7): p. 822-31. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44326 | - |
| dc.description.abstract | 缺血性中風、心肌梗塞與深層靜脈栓塞等常見疾病與血栓的形成息息相關，臨床上注射血栓溶解劑所伴隨的內出血等副作用，使得發展安全以及更有效率的血栓溶解治療方式成為目前重要的研究課題。直至今日，歷經約30年的研究，超音波應用於血栓溶解治療為目前極具潛力的治療模式。許多研究團隊利用低頻超音波 (20 kHz~2 MHz) 與超音波對比劑所誘發的穴蝕效應，幫助血栓溶解劑更深入血栓內部進而增加血栓溶解的治療成效。也有研究指出，即使無血栓溶解劑的存在，超音波與對比劑的作用機制亦可造成血栓的溶解破壞。也因此，本研究的主要目的為嘗試提升超音波應用於血栓溶解治療的效能以及安全性，分別從超音波的使用頻率與靶向性超音波對比劑兩方面著手：(1) 靶向性超音波對比劑：超音波對比劑的加入可以降低誘發穴蝕效應所需要的能量，此外隨著新興生物科技的發展，藉由超音波對比劑的表面修飾，可以達到專一性辨認血栓、增加血栓局部對比劑濃度的效果。在靶向誘發穴蝕效應的作用下，希望可藉此提升體外低頻超音波輔助血栓溶解治療的安全性以及效能。(2) 超音波的使用頻率：不同於先前的研究，本研究配合臨床上的需求，嘗試發展結合觀測血栓生成以及即時溶解治療的高頻超音波系統(> 20 MHz)，並使用雙頻激發方式企圖使高頻超音波成功誘發穴蝕效應，以期將具有高空間解析度的血管內超音波應用於臨床上的血栓溶解治療，達到診治合一的目的。本研究的實驗結果顯示：1. 實驗室自製靶向性超音波對比劑的確具有標靶能力，並且具有增強血塊局部區域穴蝕效應的潛能，在未來的臨床應用上，可望在避免血管損傷的安全操作下提升血栓溶解效能。2. 聲場強度大小是影響高頻超音波能否誘發穴蝕效應的主因。因此，高頻超音波系統礙於探頭孔徑大小的限制而無法提供足夠能量誘發穴蝕效應，將造成血管內超音波應用於血栓溶解作用上的困難，也因此未來仍會以體外低頻超音波做為血栓溶解治療的研究主軸。 | zh_TW |
| dc.description.abstract | Ischemic stroke, myocardial infarction and deep vein thrombosis are common diseases which are related to thrombosis. Systemic thrombolytic therapy is one of the most widely used treatments for recanalization of the occluded vessel. However, the administration of thrombolytic agents has a major disadvantage of inducing comprehensive hemorrhage and may cause death. Therefore, there is a clinical need for treatment methods to increase the effectiveness of complete reperfusion without increasing the probability of bleeding. Several studies have shown that low-frequency ultrasound (20 kHz~2 MHz) enhances enzymatic thrombolysis by increasing the transport of thrombolytic agents into clots through cavitation-related mechanisms. Besides, there were some studies shown a thrombolytic potential of ultrasound in combination with ultrasound contrast agent even without the presence of thrombolytic agents. Thus, the use of ultrasound to enhance and accelerate the thrombolysis of occluded vessels is an area of active investigation. The purpose of this study was to develop two approaches for improving the efficiency and safety of ultrasound-assisted thrombolysis which were base upon the therapeutic frequency we chosen and the use of targeted contrast agents：(1). Targeted ultrasound contrast agent：Ultrasound contrast agents, mainly microbubbles, are good nuclei for reducing the threshold for cavitation induction. By the virtue of the rapid discovery of novel biomarkers and affinity ligands, targeted ultrasound contrast agents are developed to recognize thrombi and thereby increasing the local concentration of microbubbles. One hypothesis of the present study was that a targeted ultrasound contrast agent can enhance both the thrombolytic efficacy and safety in transcutaneous (noninvasive) ultrasound for the same reason. (2). The ultrasound frequency： For clinical need, we were trying to develop a high-frequency ultrasound system with high-resolution for imaging and a possible combined diagnostic and therapeutic in vivo application using the same transducer. Thus, one component of this study is the investigation of the feasibility of sonothrombolysis by using intravascular ultrasound (IVUS, > 20 MHz). Here we used the dual high-frequency method to induce cavitation and estimate its intensity by measuring differential ICD, acoustic intensity of the low frequency component. According to the experimental results, we conclude that：1. Our thrombus-targeted ultrasound contrast agent was capable of targeting specific sites and has the potential for inducing localized cavitation thus avoiding the possible endothelial damage in the clinical application. 2. The magnitude of acoustic intensity plays a major rule in the cavitation induction using high-frequency ultrasound. Besides, due to the limitation of high-frequency ultrasound aperture size, sonothrombolysis using intravascular ultrasound may not be feasible. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T02:51:13Z (GMT). No. of bitstreams: 1 ntu-98-R96945014-1.pdf: 6977650 bytes, checksum: 69b0701d32b52564ef75af8517bf5f9b (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 口試委員會審定書...........................................................................................................i
中文摘要..........................................................................................................................ii 英文摘要.........................................................................................................................iv 第1章 緒論 1 1.1 血栓症 1 1.2 血栓溶解劑 2 1.3 醫用超音波 4 1.4 超音波對比劑 6 1.5 穴蝕效應 9 1.6 超音波在血栓溶解治療的應用 12 1.7 研究動機與目標 17 1.8 論文架構 19 第2章 低頻超音波輔助血栓溶解實驗 20 2.1 實驗材料與方法 20 2.1.1 超音波對比劑 20 2.1.2 血塊製備 21 2.1.3 實驗系統架構 21 2.1.4 血栓溶解作用成效評估 22 2.2 實驗結果討論 24 第3章 靶向性對比劑輔助低頻超音波血栓溶解實驗 30 3.1 實驗材料與方法 30 3.1.1 靶向性超音波對比劑 30 3.1.2 血塊製備 32 3.1.3 靜態與流動實驗系統架構 32 3.1.4 血栓溶解作用成效評估 34 3.2 結果與討論 35 第4章 高頻超音波誘發穴蝕效應實驗 41 4.1 實驗材料與方法 41 4.1.1 超音波對比劑 41 4.1.2 穴蝕效應之偵測 41 4.1.2.1 B-mode 影像亮度觀察法 41 4.1.2.2 定量穴蝕效應—Inertial Cavitation Dose 41 4.2 血管內超音波誘發穴蝕效應 43 4.2.1 實驗系統架構 43 4.2.2 初步實驗結果與討論 44 4.3 雙頻激發方法誘發穴蝕效應 45 4.3.1 實驗架構驗證 46 4.3.2 高頻探頭誘發穴蝕效應 48 4.4 實驗結果討論 51 第5章 結論與未來工作 54 第6章 參考文獻 61 | |
| dc.language.iso | zh-TW | |
| dc.title | 靶向超音波於血栓溶解之研究 | zh_TW |
| dc.title | A Study on Targeted-Ultrasound Assisted Thrombolysis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王水深,葉秩光,王士豪,沈哲州 | |
| dc.subject.keyword | 血栓溶解劑,超音波對比劑,穴蝕效應,雙頻激發,血管內超音波,靶向性超音波對比劑, | zh_TW |
| dc.subject.keyword | Thrombolytic agent,Ultrasound contrast agent,Cavitation,Dual high-frequency method,Intravascular ultrasound,Thrombus-targeted ultrasound contrast agent., | en |
| dc.relation.page | 64 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-08-05 | |
| dc.contributor.author-college | 電機資訊學院 | zh_TW |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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