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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63423
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dc.contributor.advisor劉子銘(Tzu-Ming Liu)
dc.contributor.authorTsung-Yuan Hsiehen
dc.contributor.author謝宗原zh_TW
dc.date.accessioned2021-06-16T16:40:47Z-
dc.date.available2015-10-12
dc.date.copyright2012-10-12
dc.date.issued2012
dc.date.submitted2012-09-07
dc.identifier.citation1] Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter, “ Molecular Biology of the Cell, 4th edition.” Garland Science; 2002.
[2] Sobin, L. and Wittekind, C. “ Breast Tumours. ” TNM Online, 2003
[3] Douglas Hanahan and Robert A. Weinberg “Hallmarks of Cancer: The Next Generation. ” Cell 2011;144 ,646-674
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[5] Ala-Aho R, Johansson N, Baker AH, et al. “Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells. ” Int J Cancer 2002; 97: 283-916.
[6] Tester AM, Waltham M, Oh SJ, et al. “Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice. ” Cancer Res 2004; 64: 652-8
[7] Rob Cairns, Ioanna Papandreou and Nicholas Denko, “Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment.” Mol Cancer Res 2006;4:61-70.
[8] Tord Hompland, Arne Erikson, Mikael Lindgren, Tore Lindmo and Catharina de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter.” Journal of Biomedical Optics 2008, 13(5), 054050
[9] Mary K. Chelberg, Effie C. Tsilibary, Alan R. Hauser, et al, “Type IV Collagen-mediated Melanoma Cell Adhesion and Migration: Involvement of Multiple, Distinct Domains of the Collagen Molecule. ” Cancer Res 1989;49:4796-4802.
[10] Mikala Egeblad, Morten G Rasch and Valerie M Weaver, “Dynamic interplay between the collagen scaffold and tumor evolution.” Current Opinion in Cell Biology 2010, 22:697–706
[11] D. Taskiran, E. Taskiran, H. Yercan, and F. Z. Kutay, “Quantification of total collagen in rabbit tendon by the Sirius red method,” Tr. J.Medical Sciences1999 ,29:7–9 .
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[13] E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher,and R. K. Jain, “Dynamic imaging of collagen and its modulation intumors in vivo using second-harmonic generation,” Nat. Med. 2003,9:796–800 .
[14] Ming-Rung Tsai, Yu-Wei Chiu, Men Tzung Lo and Chi-Kuang Sun, “Second-harmonic generation imaging of collagen fibers in myocardium for atrial fibrillation diagnosis.” Journal of Biomedical Optics 2010,15(2): 026002
[15] Vladimir Bobek, Katarina Kolostova, Daniela Pinterova, Grzegorz Kacprzak, Jaroslaw Adamiak, Jerzy Kolodziej, Michael Boubelik, Martina Kubecova and Robert M. Hoffman,“A Clinically Relevant, Syngeneic Model of Spontaneous, Highly Metastatic B16 Mouse Melanoma.” Anticancer research 2010,30: 4799-4804
[14] Ming-Rung Tsai, Yu-Wei Chiu, Men Tzung Lo and Chi-Kuang Sun, “Second-harmonic generation imaging of collagen fibers in myocardium for atrial fibrillation diagnosis.” Journal of Biomedical Optics 2010,15(2): 026002
[16] V. Hovhannisyan,W.Lo,C.Hu,S.-J.Chen,and C.Y.Dong,“Dynamics of femtosecond laser photo-modification of collagen fibers,”Optics Express,vol.16,no.11,pp.7958-7968,May 2008.
[17] R.Boyd,Nolinear Optics. Academic Press,third ed.,2003
[18] Ho-Che Kuo, “Monitoring Thermally Induced Alteration of Collagen by SHG”,National Sun Yat-Sen University 2005
[19] Robert.W.Boyd “Nonlinear Optics.3rd Ed” Amsterdam:Academic Press 2007
[20] Chi-Kuang Sun “Higher harmonic generation microscopy” Adv Biochem Engin/Biotechnol;95:17-56 2005
[21] Han-Wen Liu “Investigation of vascular permeability and diffusion coefficient and accumulation changes in time and space of nano-drug carriers in mouse tissues with multiphoton microscopy”National Taiwan University,2011
[22] M.Born and E.Wolf,Principles of Optics(Pergamon Press,Oxfoed,1980).
[23] S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, 'In vivo developmental biology study using noninvasive multi-harmonic generation microscopy,' Optics Express 11 (23), pp. 3093-3099 2003
[24] Vladimir Bobek“A Clinically Relevant, Syngeneic Model of Spontaneous Highly Metastatic B16 Mouse Melanoma”Anticance research 30:4799-4804 2010.
[25] Christopher Bayan ,Jonathan M.Levitt, Eric Miller,David Kaplan,and Irene Georgakoudi“Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels”Journal of appliedPhysics 105,102042 2009.
[26] R.M. Haralick, “Statistical and structural approaches to texture,” Proc. IEEE, Vol. 67, pp.784-804 1979.
[27] Jon R. Berry, John Goutsias “A Comparative Study of Matrix Measures for Maximum Likelihood Texture Classification”, IEEE Transaction on
Systems, Man, and Cybernetics, VOLUME 21, NO. 1, JAN, 1991
[28]Chia-Wei Li,“The Application of Texture Analysis on Defect Detection”National Taiwan university of science and technology,2006.
[29] Szu-Yu Chen, “In vivo optical virtual biopsy of human skin by using harmonic generation microscopy”National Taiwan University,2009
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63423-
dc.description.abstract惡性腫瘤一直為十大死因榜首,許多研究也環繞在探討其生長機制以及如何治癒,早期檢測和早期治療,術後所復發的機率能有效地降低。目前所研究的方向不單只針對腫瘤細胞,而是包含其所生長的微腫瘤環境。此環境能使腫瘤細胞壯大,且大為增加轉移及侵犯周邊組織的機會。微腫瘤環境中的膠原蛋白纖維,在正常組織下扮演調節細胞間溝通的角色,也被發現與腫瘤遷移有所關聯,因此也能成為判斷腫瘤轉移的指標之一。
為了能夠早期觀察微腫瘤環境,我們採用了非線性光學顯微術。其特點是非侵入性,且能夠即時在活體上進行觀測,且對生物體的傷害也較小。此平台上的二倍頻訊號也能觀察具有非中心對稱的膠原蛋白纖維,我們透過小鼠耳部腫瘤模型,觀察不同時期的微腫瘤環境,並擷取膠原蛋白纖維的二倍頻影像。透過影像分析找尋不同階段膠原蛋白纖維的變化,並將影像進行量化。我們採用灰階共生矩陣、方向指數等方式來進行判斷。在本論文的研究中發現,在正常的膠原蛋白纖維呈現均勻捲曲的情況,而隨著腫瘤的生長,膠原蛋白纖維愈來愈空洞且直線化。
zh_TW
dc.description.provenanceMade available in DSpace on 2021-06-16T16:40:47Z (GMT). No. of bitstreams: 1
ntu-101-R99548013-1.pdf: 3711371 bytes, checksum: 69d4d022abc7a0069aaf592996ce2f35 (MD5)
Previous issue date: 2012
en
dc.description.tableofcontents中文摘要………………………………………………………………………………3
英文摘要………………………………………………………………………………4
第一章 緒論…………………………………………………………………………..7
1-1 腫瘤…………………………………………………………………7
1-2 腫瘤治療方式與腫瘤微環境………………………………………8
1-3 腫瘤轉移……………………………………………………………9
1-4 研究動機…………………………………………………………..11
第二章 光學倍頻顯微術理論………………………………………………………13
2-1 非線性光學及倍頻………………………………………………...13
2-2 雙光子螢光………………………………………………………...18
2-3共軛焦螢光顯微術…………………………………………………23
2-4傅立葉轉換…………………………………………………………25
第三章 實驗架構與材料方法………………………………………………………28
3-1光學系統……………………………………………………………28
3-2細胞培養……………………………………………………………29
3-3 動物飼養及觀察…………………………………………………...30
3-4取像參數……………………………………………………………32
3-5分析方法……………………………………………………………32

第四章 實驗結果……………………………………………………………………40
4-1 腫瘤組織微環境變化觀測………………………………………...40
4-1-1 正常小鼠組織非線性線性多光子顯微影像……………...40
4-1-2黑色素瘤細胞株影像………………………………………42
4-2 黑色素瘤動物模型………………………………………………...44
4-3二倍頻顯微術於正常小鼠不同區域………………………………46
4-4二倍頻顯微術於黑色素瘤…………………………………………49
4-4-1黑色素瘤不同時期的灰階共生矩陣………………………50
4-4-2黑色素瘤不同時期的方向指數及二次矩…………………55
4-4-3 黑色素瘤不同時期的膠原蛋白結構……………………...56
4-5 黑色素瘤同一區域的變化………………………………………...57
4-5-1黑色素瘤同一區域的灰階共生矩陣………………………58
4-5-2黑色素瘤同一區域的方向指數及二次矩…………………59
4-5-3 黑色素瘤同一區域的膠原蛋白結構……………………...60
4-6 不同深度之膠原蛋白變化
4-6-1正常小鼠膠原蛋白深度之變化……………………...........61
4-6-2腫瘤小鼠之膠原蛋白深度變化……………………...........67
4-6-3 對照組之膠原蛋白深度變化……………………..............71
第五章 結論與未來展望……………………………………………………………74
參考文獻……………………………………………………………………………...76
dc.language.isozh-TW
dc.subject灰階共生矩陣zh_TW
dc.subject微腫瘤環境zh_TW
dc.subject膠原蛋白纖維zh_TW
dc.subject非線性光學顯微術zh_TW
dc.subjecttumor microenvironmenten
dc.subjectcollagen fiberen
dc.subjectnonlinear optical microscopyen
dc.subjectgray level co-occurrence matrixen
dc.title以二倍頻顯微術影像量化小鼠內腫瘤之膠原蛋白不同階段改變zh_TW
dc.titleIn vivo quantify the mouse intra tumors collagen at different stage of change with Second harmonic generation microscopy images.en
dc.typeThesis
dc.date.schoolyear100-2
dc.description.degree碩士
dc.contributor.oralexamcommittee孫啟光(Chi-Kuang Sun),朱家瑜(Chia-Yu Chu),林文澧(Win-Li Lin),李佳翰(Chia-Han Li)
dc.subject.keyword微腫瘤環境,膠原蛋白纖維,非線性光學顯微術,灰階共生矩陣,zh_TW
dc.subject.keywordtumor microenvironment,collagen fiber,nonlinear optical microscopy,gray level co-occurrence matrix,en
dc.relation.page78
dc.rights.note有償授權
dc.date.accepted2012-09-10
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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