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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林文澧 | |
dc.contributor.author | Hsin-Yu Wu | en |
dc.contributor.author | 吳欣瑜 | zh_TW |
dc.date.accessioned | 2021-06-15T04:46:25Z | - |
dc.date.available | 2012-08-12 | |
dc.date.copyright | 2010-08-12 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-05 | |
dc.identifier.citation | [1] N. Sheikov, N. McDannold, F. Jolesz, Y. Z. Zhang, K. Tam, and K. Hynynen. Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier. Ultrasound Med Biol 2006; 32: 1399-409.
[2] S.B. Raymond, J. Skoch, K. Hynynen, and B. J. Bacskai. Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo. J Cereb Blood Flow Metab 2007; 27: 393-403. [3] M. Fechheimer, J.F. Boylan, S. Parker, J.E. Sisken , G.L. Patel, S.G. Zimmer. Transfection of mammalian-cells with plasmid DNA by scrape loading and sonication loading. Proc Natl Sci USA 1987; 84(32): 8463-8467. [4] K. Tachibana, T. Uchida, K. Ogawa, N. Yamashita, K. Tamura. Induction of cell-membrane porosity by ultrasound. Lancet 1999; 353(9162):1409. [5] C.X. Deng, F. Sieling, H. Pan, J. Cui. Ultrasound-induced cell membrane porosity. Ultrasound Med Biol 2004; 30(4): 519-526. [6] H.R. Guzman, A.J. MaNamara, D.X. Nguyen. Bioeffects caused by changes in acoustic cavitation bubble density and cell concentration: a unified explanation based on cell-to-bubble ratio and blast radius. Ultrasound Med Biol 2003; 29(8):1211-1222. [7] K. Hynynen, N. McDannold, N. Vykhodtseva, and F.A. Jolesz. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology, 2001; 220: 640-6. [8] K. Hynynen, N. McDannold, N. Vykhodtseva, and F. A. Jolesz. Non-invasive opening of BBB by focused ultrasound. Acta Neurochir Suppl; 86. [9] N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen. Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 2004; 30: 979-89. [10] K. Hynynen, N. McDannold, N. A. Sheikov, F. A. Jolesz, and N. Vykhodtseva,. Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 2005; 24: 12-20. [11] N. McDannold, N. Vykhodtseva, S. Raymond, F. A. Jolesz, and K. Hynynen,. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. Ultrasound Med Biol 2005; 31: 1527-37. [12] K. Hynynen, N. McDannold, N. Vykhodtseva, S. Raymond, R. Weissleder, F.A. Jolesz, and N. Sheikov. Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug Delivery. J Neurosurg 2006; 105: 445-54. [13] M. Kinoshita, N. McDannold, F.A. Jolesz, and K. Hynynen. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption. Proc Natl Acad Sci U S A 2006; 103: 11719-23. [14] M. Kinoshita, N. McDannold, F.A. Jolesz, and K. Hynynen. Targeted delivery of antibodies through the blood-brain barrier by MRI-guided focused ultrasound. Biochem Biophys Res Commun 2006; 340: 1085-90. [15] N. McDannold, N. Vykhodtseva, and K. Hynynen. Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity. Phys Med Biol 2006; 51: 793-807. [16] K. Hynynen. Focused ultrasound for blood-brain disruption and delivery of therapeutic molecules into the brain. Expert Opin Drug Deliv 2007; 4: 27-35. [17] N. McDannold, N. Vykhodtseva, and K. Hynynen. Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: a feasibility study. Ultrasound Med Biol 2007; 33; 584-90. [18] L.H. Treat, N. McDannold, N. Vykhodtseva, Y. Zhang, K. Tam, and K. Hynynen. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer 2007; 121: 901-7. [19] N. McDannold, N. Vykhodtseva, and K. Hynynen. Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol 2008; 34: 930-7. [20] N. McDannold, N. Vykhodtseva, and K. Hynynen. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol 2008; 34: 834-40. [21] N. Sheikov, N. McDannold, S. Sharma, and K. Hynynen. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol, 2008; 34: 1093-104. [22] S.B. Raymond, L.H. Treat, J.D. Dewey, N.J. McDannold, K. Hynynen, B.J. Bacskai. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer’s disease mouse models. PLoS ONE 2008; 3(5): e2175. [23] L.J. Jeanneret. The targeted delivery of cancer drugs across the blood–brain barrier: chemical modifications of drugs or drug-nanoparticles? Drug Discovery Today 2008;13.1 [24] R.G. Thorne and C. Nicholson. In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. PNAS 2006; 103(14): 5567–5572. [25] M.R. Dreher , W. Liu , C.R. Michelich , M.W. Dewhirst , F. Yuan , A. Chilkoti. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. Journal of the National Cancer Institute 2006; 98: 5. [26] S. Wang, B. Baseri, J.J. Chio, Y.S. Tung, B. Morrison, and E.E. Konofagou. Delivery of fluorescent dextrans through the ultrasound-induced blood-brain barrier opening in mice. IEEE IUSP 2008. [27] J.J. Chio, S. Wang, Y.S. Tung, B. Morrison, and E.E. Konofagou. Molecules of varipus pharmacologically-relevant sizes can cross the ultrasound-indiced blood-brain barrier opening in vivo. Ultrasound Med Biol 2009; 1-10. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45803 | - |
dc.description.abstract | 在腦部疾病治療中,血腦屏障是欲傳遞藥物的主要限制,而聚焦式超音波可以非侵入性並且選擇性的使血腦屏障暫時通透,使得原本無法通過的大分子進入腦中。但若傳遞效率太低仍不足以治療腦部疾病。本研究探討以1 MHz的聚焦式超音波搭配超音波顯影劑將血腦屏障開啟後,在相同位置再施予一次聚焦式超音波不再注射超音波顯影劑來強化藥物輸送的效果。同時也比較不同大小的粒子在相同超音波參數下開啟血腦屏障傳遞的情形,以及多施打一次超音波對不同大小粒子所造成的影響。
本實驗使用300- 400克大鼠,僅剃除頭頂毛髮後進行超音波治療。超音波參數為1 Hz重複頻率、10 ms脈衝長度、震盪時間60秒,以水診器量測經頭殼衰減後之聲壓為0.54 MPa。將血腦屏障暫時開啟後,注射欲傳遞到腦中的粒子(本實驗使用70 nm氧化鐵、3 kDa和70 kDa dextran),待超音波顯影劑衰減後在相同位置施打第二次超音波。實驗完成後以感應耦合電漿質譜儀和微盤分光光譜儀定量腦中粒子含量。 由感應耦合電漿質譜儀定量出強化組和非強化組的腦中的鐵離子含量有統計學上顯著差異,氧化鐵同時也是磁振造影T2*WI顯影劑,可以在即時影像上監控氧化鐵進入腦中含量。微盤分光光譜儀結果指出,在血腦屏障開啟情況下,3 kDa dextran進入腦中的量較70 kDa dextran多,但多給予一次超音波震盪,70 kDa dextran進入腦中的量大幅提升,和原本相比具有統計學上顯著差異;而3 kDa dextran的強化組與非強化組則差異不大。此結果可顯示,經由上述治療策略來強化粒子在腦組織輸送,在較大的粒子上其強化效果較顯著。 | zh_TW |
dc.description.abstract | The blood-brain barrier (BBB) is the major limiting factor to delivering therapeutic agents to the brain for disease treatment. Focused ultrasound (FUS) was shown to be able to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened BBB. In this study, we investigated the delivery enhancement of nanoparticles and macromolecules into brain tissue using additional sonication after the BBB was temporarily opened by FUS with microbubbles. We examined the BBB opening induced by FUS and microbubbles dependence on the agent’s molecular weight with MR image and inductively coupled plasma mass spectrometry (ICP-MS).
After the injection of microbubbles, one MHz FUS immediately sonicated at the target location of the brains of 300-400g Wistar rats through skulls to noninvasively open the BBB. After the complete decay of microbubbles, an additional sonication was applied without further microbubble injection to enhance the delivery of iron oxide (70 nm) or dextran (3 kDa or 70 kDa) particles into the sonicated brain tissues. The amount of particles in the brain tissue was measured using ICP-MS and microplate reader. ICP-MS results showed that FUS with a low dosage of microbubbles could only result in a small amount of iron oxide nanoparticles delivered into the brain tissues (extracellular space~50nm). However, an additional FUS sonication could enhance nanoparticles delivered into brain tissues up to 20-fold. The result of microplate reader showed that 3 kDa and 70 kDa dextrans were both diffusively distributed throughout the targeted brain region, while 70 kDa dextran appeared more punctuative. The amount of 70 kDa dextran significantly increased with an additional sonication, but not for 3 kDa dextran. This sonication strategy can effectively enhance the delivery of nanoparticles and macromolecules into the sonicated brain tissues, and it is more effectively to larger macromolecules and to nanoparticle with low dose of microbubble injection. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T04:46:25Z (GMT). No. of bitstreams: 1 ntu-99-R97548010-1.pdf: 1140723 bytes, checksum: b7a7e4d99699b15fe803ac6e41aaf920 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 誌謝 i
摘要 ii Abstract iii 目錄 v 表目錄 vii 圖目錄 viii 第一章 序論 1 1-1 血腦屏障 1 1-2 聚焦式超音波 1 1-2-1 超音波之物理效應 1 1-2-2 超音波開啟血腦屏障 2 1-2-3 超音波進行藥物傳遞in vitro 2 1-2-4 超音波進行藥物傳遞in vivo 3 1-3 研究動機 4 第二章 材料與方法 8 2-1 超音波裝置 8 2-2 動物手術 8 2-3 施打超音波 9 2-4 Evans Blue評估血腦屏障開啟 10 2-5 氧化鐵的定性、定量 11 2-5-1 磁振造影 11 2-5-2 感應耦合電漿質譜儀 11 2-6 Dextran的定量和定性 12 2-6-1微盤分光光譜儀 12 2-6-2螢光顯微鏡 12 2-7 資料分析 12 第三章 實驗結果 21 3-1 Evans Blue評估血腦屏障開啟 21 3-2 氧化鐵定性和定量 22 3-2-1 磁振造影 22 3-2-2 感應耦合電漿質譜儀 23 3-3 Dextran的定量和定性 23 3-3-1 微盤分光光譜儀 23 3-3-2 螢光顯微鏡 24 第四章 討論 34 4-1 血腦屏障開啟 34 4-2磁振造影 36 4-3感應耦合電漿質譜儀 36 4-4微盤分光光譜儀 37 4-5螢光顯微鏡 38 第五章 結論 39 第六章 未來規劃 40 參考文獻 41 附錄 46 | |
dc.language.iso | zh-TW | |
dc.title | 超音波結合微氣泡強化奈米顆粒與大分子在腦組織之累積與磁振造影之監控 | zh_TW |
dc.title | Enhancement of Nanoparticle and Macromolecule Delivery into Brain Tissue with Ultrasound and Microbubbles and Monitoring with MR Image | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林峰輝,謝銘鈞,張富雄 | |
dc.subject.keyword | 聚焦式超音波,超音波顯影劑,血腦屏障,藥物輸送,奈米粒子, | zh_TW |
dc.subject.keyword | focused ultrasound,microbubbles,blood-brain barrier,drug delivery,nanoparticles, | en |
dc.relation.page | 46 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-05 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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