螢光斷層造影技術與仿體驗證研究

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：61

、訪客IP：3.145.173.107

姓名

蘇初日(Chu-Jih Sue) 查詢紙本館藏

畢業系所

生物醫學工程研究所

論文名稱

螢光斷層造影技術與仿體驗證研究

相關論文

★ TFT-LCD前框卡勾設計之衝擊模擬分析與驗證研究	★ TFT-LCD 導光板衝擊模擬分析及驗證研究
★ 數位機上盒掉落模擬分析及驗證研究	★ 旋轉機械狀態監測-以傳動系統測試平台為例
★ 發射室空腔模態分析在噪音控制之應用暨結構聲輻射效能探討	★ 時頻分析於機械動態訊號之應用
★ VKF階次追蹤之探討與應用	★ 火箭發射多通道主動噪音控制暨三種線上鑑別方式
★ TFT-LCD衝擊模擬分析及驗證研究	★ TFT-LCD掉落模擬分析及驗證研究
★ TFT-LCD螢幕掉落破壞分析驗證與包裝系統設計	★ 主動式火箭發射噪音控制使用可變因子演算法
★ 醫學/動態訊號處理於ECG之應用	★ 光碟機之動態研究與適應性尋軌誤差改善
★ 具新型菲涅爾透鏡之超音波微噴墨器分析與設計	★ 醫用近紅外光光電量測系統之設計與驗証

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

螢光擴散光學斷層造影 (fluorescence diffusion optical tomography, FDOT)是新穎的醫學造影技術，透過偵測體內標靶藥物釋放之螢光訊息，並重建螢光產率 (fluorescent yield)在組織內的分佈，呈現出有助於腫瘤檢測、標靶藥物開發與治療效果評估的功能性影像。FDOT造影機制可分為兩個步驟，第一步為得知激發光與螢光在組織中傳遞情形，是藉由頻域式 (frequency domain)擴散光學斷層造影 (diffusion optical tomography, DOT)獲得組織光學係數分佈 ; 第二步為得知標靶螢光藥物在組織中螢光產出情形，是藉由連續波 (continuous wave)螢光分子斷層造影 (fluorescence molecular tomography, FMT)獲得組織螢光產率分佈。從上述兩步驟，可說明FDOT造影為DOT與FMT技術整合，即是將擴散光學方程式(diffusion equation)理論帶入螢光分子造影中，藉由分析組織光學結構，使螢光訊息特徵之解讀更為準確。
本論文著重於FDOT之量測系統開發、量測程序制定、及仿乳假體驗證等。量測系統包含可幅值調變 (amplitude modulation)之雙雷射模組 (780、830 nm)、雙偵測模組 (光電倍增管、光譜儀)、解調變 (demodulation)模組等。量測程序是根據螢光特徵擷取及數據校正需求。總共進行7圈環形掃描，前4圈為DOT掃描而後3圈為FMT掃描。仿乳假體驗證因使用兩種螢光劑 (ICG、HICPDNEs)，故先量測其最強螢光功率之濃度及螢光波段範圍。假體驗證則設計不同螢光置入物深度、置入物與背景螢光吸收係數對比度、及背景假體均勻性作為探討之變因。
研究結果顯示，當螢光置入物在均勻介質之背景，FDOT的影像特徵與DOT相比並無優勢，而深層之特徵形狀又優於淺層，位置準確性低於淺層。當螢光置入物在非均勻之背景，FDOT的螢光置入物之影像特徵準確性高於DOT及FMT，因FDOT具有腫瘤專一性顯影和組織光學特性分析之能力。置入物與背景之螢光吸收係數對比度越大，螢光置入物之特徵越顯著，而當對比度小於1會出現誤判影像特徵。

摘要(英)

Fluorescence diffusion optical tomography (FDOT) is a novel medical imaging technique. FDOT can present functional images that contribute to tumor detection, target drug development and therapeutic evaluation. FDOT can be divided into two steps. The first step is to obtain the distribution of optical coefficient that the excitation light and the fluorescence transmit in the tissue by diffusion optical tomography (DOT) in frequency domain; the second step is to know the distribution of fluorescent yield by fluorescence molecular tomography (FMT) in continuous wave.
This thesis focuses on the development of measurement system and program and the verification of breast phantom. The measurement system consists of dual laser modules (780, 830 nm )、dual detection modules (photomultiplier, spectrometers) and demodulation modules. The total of measurement program are 7 ring scans. Because the breast phantom verification use of two kinds of fluorescent agent (ICG, HICPDNEs), so we measure the concentration of the strongest fluorescence power and the fluorescence wavelength band. Phantom was designed of different depths of fluorescence inclusion, contrast of inclusion-background fluorescent absorption coefficient and background homogeneity.
The results show that when the fluorescent inclusion is in an uniform background, FDOT is worse than DOT, while the shape of the deep is superior to the shallow, and the position accuracy is lower than the shallow. When fluorescent inclusion is in an inhomogeneous background, FDOT is superior to DOT and FMT because FDOT has specificity for tumor and optical analysis of tissue. The greater the contrast of the fluorescence absorption coefficient between the inclusion and the background, the features of the fluorescent inclusion are more obvious, and when the contrast is less than 1, the wrong features were appeared.

關鍵字(中)

★ 螢光分子影像
★ 擴散光學
★ 斷層造影
★ 組織光學量測
★ 光學係數重建

關鍵字(英)

★ fluorescent molecular imaging
★ diffusion optics
★ tomography
★ tissue optical measurement
★ optical coefficient reconstruction

論文目次

第一章緒論.................1
1-1 研究動機..................1
1-2 研究背景..................2
1-3 文獻回顧..................4
1-3-1 螢光分子影像發展.........4
1-3-2 螢光擴散光學檢測技術.....4
1-4 研究範疇..................8
第二章理論基礎.............10
2-1 乳房組織光學..............10
2-1-1 組織光學...............10
2-1-2 乳房光學特性............12
2-2 標靶螢光顯影劑.........12
2-2-1 靛氫綠光學特性..........12
2-2-2 顯影劑組成與應用.........14
2-3 組織擴散光學量測........15
2-3-1 光學量測技術.............15
2-3-2 光學掃描模式.............17
2-4 螢光影像重建方法........18
2-4-1 螢光擴散光學方程式........18
2-4-2 影像重建原理與流程........21
第三章量測系統與元件.........24
3-1 量測方法與流程..........24
3-1-1 螢光擴散光學量測方法.......24
3-1-2 量測流程與數據校正.........26
3-2 量測系統架構............29
3-3 光電元件特性................34
第四章實驗設計與造影系統驗證..41
4-1 具螢光劑成份之仿乳假體製作...41
4-1-1 螢光劑材料特性............41
4-1-2 仿乳假體材料特性..........44
4-2 假體量測與影像重建..........45
4-2-1 假體參數設計..............45
4-2-2 假體量測數據與影像重建.....48
第五章結論與未來展望.............75

參考文獻

[1] 行政院衛生署國民健康局，癌症登記報告 (2017)。
https://www.hpa.gov.tw/home/index.aspx
[2] 郭文娟。非侵入式生醫斷層影像簡介。師範大學光電科技研究所，物理雙月刊8月 (2006)。
[3] Etta D. Pisano, C. Gatsonis, E. Hendrick, M. Yaffe, J. K. Baum, S. Acharyya, E. F. Conant,L. L. Fajardo, L. Bassett, C. D’Orsi, R. Jong and M. Rebner, “Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening,” New England Journal of Medicine, 355(17), 1840 - 1840 (2006).
[4] 黃獻樑、程紹儀。乳癌的篩檢。台灣家庭醫學醫學會。
https://www.tafm.org.tw/ehc-tafm/s/w/ebook/people_other/journalContent/358
[5] 偉成醫師，乳癌檢查與知識網。
http://www.mdesign.tw/display/breast/examination.php
[6] T.J. Brukilacchio, “A diffuse optical tomography system combined with X-ray mammography for improved breast cancer detection,”　Tufts University, Ph.D. Thesis (2003).
[7] F. Stuter, J. Ripoll and M. Rudin, “Fluorescence Molecular Tomography: Principles and
Potential for Pharmaceutical Research, ” Pharmaceutics, 3(2), 229 - 274 (2011).
[8] R. Karl, R. Malin, “2 Americans, 1 German win chemistry Nobel,” AP News (2014).
[9] 王宥翔。螢光擴散光學斷層與電腦斷層雙模系統之光學系統執行。國立陽明大學
生醫光電研究所碩士論文 (2012)。
[10] 簡佑軒。仿乳腫瘤特徵之近紅外光頻域式量測系統分析與驗證。國立中央大學機
械工程研究所碩士論文 (2013)。
[11] 林孟隆。開發超音波結構影像為基礎之小動物腫瘤螢光擴散光學斷層掃描術。國立陽明大學醫學工程研究所碩士論文 (2014)。
[12] Adam B. Milstein, Seungseok Oh, Kevin J. Webb, Charles A. Bouman, Quan Zhang,
David A. Boas, and R. P. Millane, “Fluorescence optical diffusion tomography,” Appl.
Opt. 42, 3081-3094 (2003).
[13] E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy and C. L. Hutchinson, “Fluorescence and Absorption Contrast Mechanisms for Biomedical Optical Imaging Using Frequency-Domain Techniques,” American Society for Photobiology. 66(1), 55 - 64 (1997).
[14] J. M. I. Maarek, D. P. Holschneider and J. Harimoto, “Fluorescence of indocyanine green in blood: intensity dependence on concentration and stabilization with sodium polyaspartate,” Photochemistry and Photobiology. 65, 157 - 164 (2001).
[15] J. Lee and E. M. Sevick-Muraca, “Three-dimensional fluorescence enhanced optical tomography using referenced frequencydomain photon migration measurements at emission and excitation wavelengths,” Optical Society of America. 19(4), 759 - 771 (2002).
[16] A. B. Milstein, J. J. Stott, S. Oh, D. A. Boas, R. P. Millane, C. A. Bouman and K. J. Webb, “Fluorescence optical diffusion tomography using multiple-frequency data,” Optical Society of America. 21(6), 1035 - 1049 (2004).
[17] A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas and B. J. Bacskai, “Time resolved fluorescence tomography of turbid media based on lifetime contrast,”. Optics Express. 14(25), 12255 - 12270 (2006).
[18] A. Koenig, L. Herve, A. D. Silva, J. M. Dinten, J. Boutet, M. Berger, V. Josserand, J. L. Coll, P. Peltie and P. Rizo, “fDOT for in vivo follow-up of tumor development in mice lungs,” SPIE-OSA. 6629(662915) (2007).
[19] L. Herve, A. Koenig, A. D. Silva, M. Berger, J. Boutet, J. M. Dinten, P. Peltie and P. Rizo, “Noncontact fluorescence diffuse optical tomography of heterogeneous media,” Applied Optics. 46(22) (2007).
[20] A. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Optics Express. 15(11), 6696 - 6716 (2007).
[21] Y. Tan and H. Jiang, “Diffuse optical tomography guided quantitative fluorescence molecular tomography,” Applied Optics. 47(12), 2011 - 2016 (2008).
[22] A.Koenig, L. Herve, J. Boutet, M. Berger, J. M. Dinten, A. D. Silva, P. Peltie and P. Rizo, “Fluorescence diffuse optical tomography for arbitrary shaped small animals,” 2015 IEEE 12th International Symposium on. 1457 - 1461 (2015).
[23] C. T. Xu, J. Axelsson and S. A. Engels, “Fluorescence diffuse optical tomography using upconverting nanoparticles,” Appl. Phys. Lett. 94, 251107 (2009).
[24] X. Zhang, C. T. Badea, G. A. Johnson J. Axelsson and S. A. Engels, “Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy,” Journal of Biomedical Optics. 14(6), 064010 (2009).
[25] X. Liu, X. Guo, F. Liu, Y. Zhang, H. Zhang, G. Hu and J. Bai, “Imaging of Indocyanine Green Perfusion in Mouse Liver With Fluorescence Diffuse Optical Tomography,” IEEE Transactions on Biomedical Engineering. 58(8), 2139 - 2143 (2011).
[26] 張靜婷。活體小動物螢光斷層影像系統雛型設計與實驗。國立陽明大學醫學工程研究所碩士論文 (2013)。
[27] L. Y. Chen, Min-Cheng Pan and Min-Chun Pan, “Fluorescence Diffuse Optical Imaging：Simulation,” Optic. National Central University, Taiwan (R.O.C.) (2016).
[28] G. M. Hale and M. R. Querry, “Optical constants of water in the 200 nm to 200 µm
wavelength region,” Appl. Opt. 12, 555 - 563 (1973).
[29] Paul Beard, “Biomedical Photoacoustic Imaging,” Interface Focus, 1, 602 - 631 (2011).
[30] L. V. Wang, H. I. Wu, Biomedical optics : principles and imaging, John Wiley & Sons, Inc., New Jersey (2007).
[31] V. V. Tuchin, Tissue optics : light scattering methods and instruments for medical diagnosis, 2nd edition, SPIE Press, Bellingham, Washington, USA (2007).
[32] B. J. Tromberg, A. E. Cerussi, D. Jakubowski, N. Shah, F. Bevilacqua, A. J. Berger, J. Butler and R. F. Holcombe, “Functional diffuse optical spectroscopy of human breast tissue,” The 14th Annual Meeting of the IEEE, 1, 259-260 (2001).
[33] S. Vikram, M. Jyothsna, P. Mazhuvanchary, K. Sanjay, “Noninvasive Optical Imaging and In Vivo Cell Tracking of Indocyanine Green Labeled Human Stem Cells Transplanted at Superficial or In-Depth Tissue of SCID Mice,” Stem Cells International. 606415 (2015).
[34] T. Handa, R. G. Katare, S. Sasaguri and T. Sato, “Preliminary experience for the evaluation of the intraoperative graft patency with real color charge-coupled device camera system: an advanced device for simultaneous capturing of color and near-infrared images during coronary artery bypass graft,” Interactive Cardio Vascular and Thoracic Surgery, 9(2), 150–154 (2009).
[35] D. Roblyer, R. Richards-Kortum, K. Sokolov, M. D. Williams, C. Kurachi and A. M. Gillenwater, “Multispectral optical imaging device for in vivo detection of oral neoplasia,” Journal of Biomedical Optics, 13(2), 024019 (2008).
[36] A. Hellebust, and R. Richards-Kortum, “Advances in molecular imaging: targeted optical contrast agents for cancer diagnostics,” Nanomedicine. 7(3), 429 – 445 (2012).
[37] J. R. Rajian, M. L. Fabiilli, J. B. Fowlkes, P. L. Carson and X. Wang, “Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion,” Optics Express, 19(15), 14335 - 14347 (2011).
[38] G. M. Turner, G. Zacharakis, A. Soubret, J. Ripoll and V. Ntziachristos, “Complete-angle projection diffuse optical tomography by use of early photons,” Opt. Lett. 30, 409 - 411 (2005).
[39] M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsh and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. 105, 19126 - 19131 (2008).
[40] M. S. Patterson and B. W. Pougue, “Mathematical model for time-resolved and frequency-
domain fluorescence spectroscopy in biological tissues,” Applied Optics. 33(10), 1963 - 1974 (1994).
[41] 嚴中成。三維近紅外光擴散光學斷層影像重建之數值計算研究。國立中央大學機械工程研究所碩士論文 (2016)。
[42] 羅沛恩。螢光擴散光學斷層模擬及演算法。國立陽明大學醫學工程研究所碩士論文 (2012)。
[43] 游釗銘。頻域式擴散光學造影之乳房掃描暨檢測系統研究。國立中央大學機械工程研究所博士論文 (2015)。
[44] 石珮君。多重光電倍增管校正模組設計製作及其於擴散光學斷層造影系統應用。國立中央大學機械工程研究所碩士論文 (2017)。
[45] “Flame Miniature Spectrometer User Manual,” Ocean Optics®, For Products: FLAME-
S, FLAME-T (2016).
[46] Semrock®光學濾片特性。
https://www.semrock.com/FilterDetails.aspx?id=FF01-736/128-25
[47] 光電倍增管構造示意圖。維基百科，自由的百科全書。
https://zh.wikipedia.org/wiki/%E5%85%89%E7%94%B5%E5%80%8D%E5%A2%9
E%E7%AE%A1
[48] “The WITS$ guide to selecting a photodetector,” HAMAMATSU®, Optical Sensor Hub
Articals (2016).
[49] R. Michels, F. Foschum and A. Kienle, “Optical properties of fat emulsions,” Optical Express, 16, 5907-5925 (2008).
[50] V. Ntziachristos, X. H. Ma, A. G. Yodh and B. Chance, “Multichannel photon counting
instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum., 70(193), 193–201 (1999).
[51] 邱建忠。近紅外光頻域式量測系統於固態乳房仿體之量測與分析研究。國立中央
大學生物醫學工程研究所碩士論文 (2011)。

指導教授

潘敏俊(Min-Chun Pan)

審核日期

2018-1-12

推文