臺灣博碩士論文加值系統

擴散反射光譜學（Diffuse Reflectance spectroscopy, DRS）被廣泛的應用在測量人體組織內的光學參數（即散射和吸收係數），和生理學上的特性或稱生理參數。測量的方法就是，在組織的表面放上一個光源，在固定的光源距離點上，偵測光從光源進入待測物表面後，經過多重散射最後反射到組織表面的反射光的光譜。另外，加上使用物理模型（diffusion equation）分析，即可推算出組織中的光電及生理參數，譬如：含氧和缺氧的血紅素濃度。經由這些光學或生理參數，可幫助判斷出組織的功能性差異，達到非侵入式測量。擴散反射光譜學有三種方法可以測量光子的群體移動： 時域（time domain）、頻域（freqency domain）、和穩定狀態或稱為連續波（continuous wave）。連續波的技術在儀器上相對地低廉，在資料採集時較為快速。在實驗文獻中，目前已證實這種方法最好以多個光源至探測點之距離及多個波長可以達到絕對值測量。但目前發表的光源與測量探測的距離約小於1.0cm，其測量的組織深度則會在小於0.3~0.5cm之間（探測深度大約是介於光源和測量探測器的長度距離的1/ 2或 1/3之間）。時域和頻域的技術有它的優勢在，當只有一個或少數幾個光源至探測點的距離測量時，可測量到更深層的組織訊號（約大於1.0cm）。
我們開發了一個連續波系統來測量或模擬組織溶液深層的光學及生理參數，尤其是偵測深層組織。我們測試只使用二個不同光源和偵測點的距離來做探測，以此測量組織光學和生理的特性。我們測試了漫反射光譜儀器在組織的模擬和正確地計算出不同的散射係數和吸收係數。除此之外，還測量人體上手臂的光學及生理參數，我們發現水的含量在大距離（大於1cm）的測量中影響散射及血液濃度的測量，但對血氧含量影響不大。

Diffuse reflectance spectroscopy (DRS) has been widely used to characterize tissue optical and physiological properties in brain function, breast cancer, exercise medicine, and photodynamic therapy. There are three approaches: time domain, frequency domain, and steady-state. Steady-state approach has the advantage of relatively inexpensive in instrumentation and fast in data acquisition. It has recently been proved theoretically that the separation of reduced scattering and absorption coefficients is possible using multiple wavelengths. The validation of absolute chromophore concentrations has been reported using a broad range of wavelengths and multiple source-detector separations at “shorter” distances (�T 1 cm). In order to investigate deeper in tissue, larger separation is necessary. In this study, we aim to develop a steady-state DRS system with two source-detector separations at a range of 1.5-3.5 cm. We tested the instrument using various optical tissue phantoms and 3 different white light sources at a wavelength range of 600 and 900 nm to reconstruct the reduced scattering coefficients and chromophore concentrations including water content, blue ink concentration, fat content, blood oxygen saturation and total hemoglobin concentration.In addition,we performanced DRS measurement on human forearms.In this thesis,We demonstrate and discuss the performance of reconstructed results.

第一章 緒論 6
1. 漫反射光譜學（Diffusion reflectance spectroscopy） 6
2. 光譜和生理參數的關係 7
3. 光學特性的模擬 8
4. 初步的人體實驗 9
第二章 理論基礎 10
1 擴散方程式 10
2. 擴散方程式中的光學和生理參數 11
第三章 實驗儀器簡介 13
1. 單光儀（Monochromator） 13
2. CCD攝影機（CCD camera） 14
3. 積分球（Integrating sphere） 14
4. 光纖（Fiber） 14
5. 光源 15
Olympus 15
Schott 15
Ocean 15
6. 分光光度計（Spectrophotometer） 15
分光光度計簡介 15
分光光度計的設計 16
7. 細胞耗氧量分析儀（Partial pressure oxygen） 16
第四章 實驗材料 17
1. 列表 17
2. 實驗樣品準備 17
Blue ink 17
Fat 17
Blood phantom 18
PBS 18
酵母 18
第五章 實驗操作 19
1. 實驗設計 19
2. 實驗操作步驟 19
3. Blue ink吸收光譜的測量 21
4. PO2 vs StO2的測量 21
5. WinSpec32 software using method 22
5.1 資料夾設定 22
5.1 校正光柵 22
5.2 ROI 設定 22
5.3 校正輸入光纖 23
5.4 Main 23
第六章 實驗結果 24
1 Blue ink phantom 24
2 Fat 29
3 Blood phantom 32
4 Arm 34
第七章 討論 38
Blue ink phantom 38
Fat 38
Blood phantom 38
Forearms 39
Future work 39
第八章 參考文獻 40
第九章 圖表目錄 44

1. H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein,S. M. Hahn, and A. G. Yodh, "Broadband reflectance measurements of light penetration, blood oxygenation,hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy," J Biomed Opt 10, 14004 (2005)
2. H. W. Wang, J. C. Finlay, K. Lee, T. C. Zhu, M. E. Putt, E. Glatstein, C. J. Koch, S. M. Evans, S. M. Hahn,T. M. Busch, and A. G. Yodh, "Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis," J Biomed Opt
12, 034023 (2007).
3. B. W. Pogue and M. S. Patterson, “Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory,” Phys. Med. Biol. 39, 1157–1180 ~1994.
4. S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A.Walker, B. Barbieri, and E. Gratton, “Frequency-domain multichannel optical detector for noninvasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 ~1995.
5. J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, and B. J.Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Opt. 36, 10–20 ~1997.
6. T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, “Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy,” Rev. Sci. Instrum.71, 2500–2513 ~2000.
7. M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 28, 2331–2336~1989.
8. A. Kienle and M. S. Patterson, “Improved solutions of the steady-state and the time-resolved diffusion equations for reflectance from a semi-infinite medium,” J. Opt. Soc. Am. 14, 246–254 ~1997.
9. R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini,“Noninvasive absorption and scattering spectroscopy of bulk diffusive media: an application to the optical characterization of human breast,” Appl. Phys. Lett. 74, 874–876~1999.
10. L. Reynolds, C. Johnson, and A. Ishimaru, “Diffuse reflectance from a finite blood medium: applications to the modeling of fiber optic catheters,” Appl. Opt. 15, 2059–2067 ~1976.
11. T. J. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 ~1992.
12. A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,”Appl. Opt. 35, 2304–2314 ~1996.
13. R. Bays, G. Wagnie`res, D. Robert, D. Braichotte, J.-F. Savary, P. Monnier, and H. van den Bergh, “Clinical determination of tissue optical properties by endoscopic spatially resolved reflectometry,” Appl. Opt. 35, 1756–1766 ~1996.
14. R. A. Weersink, J. Hayward, K. Diamond, and M. Patterson,“Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 ~1997.
15. F. Bevilacqua, D. Piguet, P. Marquet, J. Gross, B. Tromberg, and C. Depeursinge, “In vivo local determination of tissue optical properties: applications to human brain,” Appl. Opt.38, 4939–4950 ~1999.
16. E. L. Hull, M. G. Nichols, and T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-stimulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 ~1998.
17. R. M. P. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. C. M. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44, 967–981 ~1999.
18. R. A. Weersink, J. Hayward, K. Diamond, and M. Patterson,“Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 ~1997.
19. F. Bevilacqua, D. Piguet, P. Marquet, J. Gross, B. Tromberg,and C. Depeursinge, “In vivo local determination of tissue optical properties: applications to human brain,” Appl. Opt.38, 4939–4950 ~1999.
20. S. Merritt,G. Gulsen, G. Chiou, Y. Chu,C. Deng, A. E. Cerussi, A. J. Durkin, B. J. Tromberg, O. Nalcioglu, “Comparison of Water and Lipid Content Measurements Using Diffuse Optical Spectroscopy and MRI in Emulsion Phantoms”.
21. E. L. Hull, M. G. Nichols, and T. H. Foster, "Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes," Phys Med Biol 43, 3381-3404 (1998).
22. T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847-2861(2002).

23. S. Srinivasan, B. W. Pogue, S. D. Jiang, H. Dehghani, C. Kogel, S. Soho, J. J. Gibson, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, ‘‘Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography,’’ Proc. Natl. Acad. Sci. U.S.A. 100(21), 12349–12354 (2003).
24. M. Solonenko, R. Cheung, T. M. Busch, A. Kachur, G. M. Griffin, T. Vulcan, T. C. Zhu, H. W. Wang, S. M. Hahn, and A. G. Yodh, ‘‘Invivo reflectance measurement of optical properties, blood oxygenation and motexafin lutetium uptake in canine large bowels, kidneys, and prostates,’’ Phys. Med. Biol. 47(6), 857–873 (2002)
25. R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams, and B. J. Tromberg, ‘‘Boundary conditions for the diffusion equation in radiative transfer,’’ J. Opt. Soc. Am. A 11(10), 2727–2741(1994).
26. A. Corlu, T. Durduran, R. Choe, M. Schweiger, E. M. C. Hillman, S. R. Arrige, and A. G. Yodh, ‘‘Uniqueness and wavelength optimization in continuous-wave multispectral diffuse optical tomography,’’ Opt. Lett. 28(23), 2339–2341 (2003).
27. H. J. van Staveren, C. J. M. Moes, J. van Marie, S. A. Prahl, and M. J. C. van Gemert, ‘‘Light scattering in Intralipid-10% in the wavelength range of 400–1100 nm,’’ Appl. Opt. 30(31), 4507–4514(1991).
28. J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio,‘‘Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,’’ Appl. Opt. 36(4), 949–957 (1997).
29. S. A. Prahl, ‘‘Optical properties spectra,’’ see http://omic.ogi.edu/spectra/index.html ~2001!.
30. Hamaoka et al.J.B.O. Vol.5 No.1 (2000) (TRS)
31. E. Gratton et al. Phil. Trans. R. Soc. Lond. B (1997) (FD-Msep)
32. S. J. Matcher et al Appl. Optics. (1997) Vol. 36 No.1 (TRS)
33. Paola Taroni et al. Photochem. Photobiol. Sci. Vol.2 124-129 (2003)
34. Ye Yang et al Opt. Exp Vol. 15 No.27 . (2007) (CW)
35. Takashi et al Clinical Science Vol 101 p. 715 (2001) (Spatially resolved oximeter)
36. Toi Van Vo et al, IEEE Tans on Biomed Eng, Vol. 54, No.3 (2007)(FD Heterdyne System)
37. Huijuan Zhao et al Appl. Optics. (2005) Vol. 44 No.10 (TR DOT)
38. Xiaoman’s measurements (Muscle in the leg)