在本篇論文中我們架構了穩態頻域光子遷移系統的光學方法去量測生物組織的生理參數，它是使用波長從600到1100奈米的近紅外光並利用光傳播理論模型去精確地得知組織的吸收係數和散射係數，同時利用此吸收係數和散射係數可以用來計算生物組織的色團濃度，例如：帶氧血紅素、不帶氧血紅素、水、脂質…等。在論文中我們使用穩態頻域光子遷移系統並搭配擴散探頭去量化活體皮膚的光學性質，首先我們測試了頻域光子遷移系統的振幅和相位的穩定性，這可以使我們了解系統的性能以及限制，其次我們利用量測四種不同吸收的樣品來探討系統收到訊號的線性程度，再來我們使用頻域光子遷移系統量測六種不同吸收和不同散射的液態假體，最後我們結合穩態系統和頻域光子遷移系統，使用穩態頻域光子遷移系統去測量液體假體，並量化液態假體的色團濃度，除此之外我們還使用穩態頻域光子遷移系統對活體的外側前臂做量測，並和穩態系統的結果做比較，再加以量化的生理濃度，最後我們的研究結果驗證了穩態頻域光子遷移系統是一個能用來定量組織組成的快速非侵入式光學方法。

In this thesis, we demonstrate the use of optical method, steady state frequency domain photon migration system (SSFDPM), to determine physiological parameters of biological tissues. It uses near-infrared light (from 600 to 1100 nm) coupled with mathematical photon transport models to accurately determine optical absorption (µa) and reduced scattering (µs′) properties of tissues. Absorption coefficient (µa) and reduced scattering coefficient (µs′) can be used to determine the chromophore concentrations, such as oxygenated hemoglobin, deoxygenated hemoglobin, water, and lipid, of biological tissues. Here, we employed the diffusing probe with the SSFDPM technique to quantify the optical properties of in-vivo skin. First, we characterize the stability of the amplitude and phase of the frequency domain photon migration system (FDPM) so that we can understand the limitations of our system. Second, we prepare four samples of different absorption to study the system linearity. Third, we use FDPM system to measure six liquid phantoms of various absorption and scattering properties. Finally, we combine the steady state (SS) and FDPM which is called SSFDPM to measure the liquid phantom, and quantify the chromophore concentrations of liquid phantoms. In addition, we carry out SSFDPM measurements on the in-vivo dorsal forearm and show the quantitative physiological concentration and compare with SS measurements. Our study reveals that the SSFDPM system provides a fast and noninvasive way for tissue composition quantification.

[1] Bureau of Health Promotion, Department of Health, R.O.C. (Taiwan), from: http://www.bhp.doh.gov.tw/BHPnet/Portal/Default.aspx
[2] G. T. Herman, "Fundamentals of Computerized Tomography: Image Reconstruction from Projections," Springer (2009).
[3] E. J. Hall, and D. J. Brenner, "Cancer risks from diagnostic radiology," The British Journal of Radiology 81, 362-378 (2008).
[4] D. J. Brenner, "Should we be concerned about the rapid increase in CT usage?," Reviews on Environmental Health 25, 63-68 (2010).
[5] M. D. Santis, E. Cesari, E. Nobili, G. Straface, A. F. Cavaliere, and A. Caruso, "Radiation effects on development," Birth Defects Res C Embryo Today 81, 177-182 (2007).
[6] X. Qian, and L. Wei, "The VDS based compressed sensing for abdomen MRI," Advances in Computational Mathematics and its Applications 1, 12-16 (2012).
[7] 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," Applied Optics 36, 10-20 (1997).
[8] A. J. Berger, V. Venugopalan, A. J. Durkin, T. Pham, and B. J. Tromberg, "Chemometric analysis of frequency-domain photon migration data: quantitative measurements of optical properties and chromophore concentrations in multicomponent turbid media," Applied Optics 39, 1659-1667 (2000).
[9] B. J. Tromberg, R. C. Haskell, S. J. Madsen, and L. O. Svaasand, "Characterization of tissue optical properties using photon density wave: modulation-frequency and boundary considerations," Comments on Molecular and Cellular Biophysics 8, 359-386 (1995).
[10] C. E. Elwell, M. Cope, A. D. Edwards, J. S. Wyatt, D. T. Delpy, and E. O. Reynolds, "Quantification of adult cerebral hemodynamics by near-infrared spectroscopy," Journal of Applied Physiology 77, 2753-2760 (1994).
[11] J. B. Fishkin, P. T. C. So, A. E. Cerussi, S. Fantini, M. A. Franceschini, and E. Gratton, "Frequency-domain method for measuring spectral properties in multiple-scattering media: methemoglobin absorption spectrum in a tissuelike phantom," Applied Optics 34, 1143-1155 (1995).
[12] J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, "Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Applied Optics 37, 3586-3593 (1998).
[13] A. H. Hielscher, J. R. Mourant, and I. J. Bigio, "Influence of particle size and concentration on the diffuse backscattering of polarized light from tissue phantoms and biological cell suspensions," Applied Optics 36, 125-135 (1997).
[14] F. Bevilacqua, P. Marquet, O. Coquoz, and C. Depeursinge, "Role of tissue structure in photon migration through breast tissues," Applied Optics 36, 44-51 (1997).
[15] I. S. Saidi, S. L. Jacques, and F. K. Tittel, "Mie and Rayleigh modeling of visible-light scattering in neonatal skin," Applied Optics 34, 7410-7418 (1995).
[16] C.-H. Chung, "Analysis of breast cancer detection using near-infrared," Department of Electrical Engineering, Nation Cheng Kung University (2011).
[17] 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," Applied Optics 35, 2304-2314 (1996).
[18] R. Bays, G. Wagnières, D. Robert, D. Braichotte, J.-F. Savary, P. Monnier, and H. v. d. Bergh, "Clinical determination of tissue optical properties by endoscopic spatially resolved reflectometry," Applied Optics 35, 1756-1766 (1996).
[19] R. A. Weersink, J. E. Hayward, K. R. Diamond, and M. S. Patterson, "Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy," Photochemistry and Photobiology 66, 326-335 (1997).
[20] F. Bevilacqua, D. Piguet, P. Marquet, J. D. Gross, B. J. Tromberg, and C. Depeursinge, "In vivo local determination of tissue optical properties: applications to human brain," Applied Optics 38, 4939-4950 (1999).
[21] E. L. Hull, M. G. Nichols, and T. H. Foster, "Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes," Physics in Medicine and Biology 43, 3381-3404 (1998).
[22] S. J. Matcher, M. Cope, and D. T. Delpy, "In vivo measurements of the wavelength dependence of tissue-scattering coefficients between 760 and 900 nm measured with time-resolved spectroscopy," Applied Optics 36, 386-396 (1997).
[23] T. J. Farrell, M. S. Patterson, and B. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo," Medical Physics 19, 879-888 (1992).
[24] 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," Applied Physics Letters 74, 874-876 (1999).
[25] B. J. Tromberg, L. O. Svaasand, T.-T. Tsay, and R. C. Haskell, "Properties of photon density waves in multiple-scattering media," Applied Optics 32, 607-616 (1993).
[26] E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, "Fluorescence lifetime spectroscopic imaging with measurements of photon migration," Annals of the New York Academy of Sciences 838, 46-57 (1998).
[27] B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, "Phase measurement of light absorption and scatter in human tissue," Review of Scientific Instruments 69, 3457-3481 (1998).
[28] M. Gerken, and G. W. Faris, "Frequency-domain immersion technique for accurate optical property measurements of turbid media," Optics Letters 24, 1726-1728 (1999).
[29] S. Fantini, M.-A. Franceschini, J. S. Maier, S. A. Walker, B. B. Barbieri, and E. Gratton, "Frequency-domain multichannel optical detector for noninvasive tissue spectroscopy and oximetry," Optical Engineering 34, 32-42 (1995).
[30] T. H. Pham, O. Coquoz, J. B. Fishkin, E. Anderson, and B. J. Tromberg, "Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy," Review of Scientific Instruments 71, 2500-2513 (2000).
[31] G. Zonios, and A. Dimou, "Modeling diffuse reflectance from semi-infinite turbid media: application to the study of skin optical properties," Optics Express 14, 8661-8674 (2006).
[32] Q. Liu, and N. Ramanujam, "Scaling method for fast Monte Carlo simulation of diffuse reflectance spectra from multilayered turbid media," Journal of the Optical Society of America A 24, 1011-1025 (2007).
[33] S.-H. Tseng, C. Hayakawa, B. J. Tromberg, J. Spanier, and A. J. Durkin, "Quantitative spectroscopy of superficial turbid media," Optical Letter 30, 3165-3167 (2005).
[34] S.-H. Tseng, C. K. Hayakawa, J. Spanier, and A. J. Durkin, "Determination of optical properties of superficial volumes of layered tissue phantoms," I IEEE Transactions on Biomedical Engineering 55, 335-339 (2008).
[35] S.-H. Tseng, A. Grant, and A. J. Durkin, "In vivo determination of skin near-infrared optical properties using diffuse optical spectroscopy," Journal of Biomedical Optics 13, 014016 (2008).
[36] A. M. Grant, K. Sry, R. Saager, F. Ayers, T. J. Pfefer, K. M. Kelly, S.-H. Tseng, and A. J. Durkin, "Diffuse optical spectroscopy of melanoma-simulating silicone phantoms," Biomedical Applications of Light Scattering III 7187, 718702 (2009).
[37] S.-H. Tseng, P. Bargo, A. Durkin, and N. Kollias, "Chromophore concentrations, absorption andscattering properties of human skin in-vivo," Optics Express 17, 14599-14617 (2009).
[38] S.-H. Tseng, C.-K. Hsu, J. Yu-Yun Lee, S.-Y. Tzeng, W.-R. Chen, and Y.-K. Liaw, "Noninvasive evaluation of collagen and hemoglobin contents and scattering property of in vivo keloid scars and normal skin using diffuse reflectance spectroscopy: pilot study," Journal of Biomedical Optics 17, 077005 (2012).
[39] L. V. Wang, and H.-I. Wu, "Biomedical Optics: Principles and Imaging, " John Wiley & Sons, Inc. (2007).
[40] 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," Journal of the Optical Society of America A 11, 2727-2741 (1994).
[41] A. Kienle, M. S. Patterson, N. Dögnitz, R. Bays, G. Wagnieres, and H. v. d. Bergh, "Noninvasive determination of the optical properties of two-layered turbid media," Applied Optics 37, 779-791 (1998).
[42] H. J. v. Staveren, C. J. M. Moes, J. v. Marie, S. A. Prahl, and M. J. C. v. Gemert, "Light scattering in Intralipid-10% in the wavelength range of 400-1100 nm," Applied Optics 30, 4507-4514 (1991).
[43] Hamamatsu Photonics (Japan), from: http://jp.hamamatsu.com/en/index.html
[44] A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, "In vivo optical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy," Physics in Medicine and Biology 46, 2227-2237 (2001).
[45] R. M. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. Sterenborg, "The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy," Physics in Medicine and Biology 44, 967-981 (1999).