在這篇文章中我們架構了穩態光子遷移系統的光學方法去量測淺層生物組織的生理參數，利用波長500到1350奈米的漫反射光譜及光的傳播理論模型精確算出組織的吸收係數與散射係數。同時將此吸收係數進一步做分析，求得生物組織的色團濃度，例如：帶氧血紅素、不帶氧血紅素、黑色素、水份、脂肪甚至是膠原蛋白的濃度。一般漫反射系統使用的演算法為擴散方程式，但此演算法有其一定的使用限制，當吸收與散射係數比例達到某種狀況下，則擴散方程式將會有失精準。於是本研究利用圖形處理器的多核心架構，進行被稱之為光子傳播理論之黃金標準的蒙地卡羅法平行運算，用以縮短蒙地卡羅法的運算時間。利用此法可以快於傳統方法約數百倍的時間，順利建構蒙地卡羅資料庫；此資料庫再來配合類神經網路模型準確地模擬光在生醫組織中傳播的各種情形與可能性，並且不會有擴散方程式會遭遇到的光學參數之限制。本研究中調配了模擬皮膚吸收散射的均質液態假體進行漫反射光譜的量測，並使用新的演算法去求出液態假體的光學參數，以實驗證明此演算法可以精準的算出假體的吸收散射。本研究也同時量測不同部位活體皮膚的吸收散射係數，並對不同量測部位進行組織色團濃度的分析，研究中同時比較了只對短波段(650到1000奈米)分析與加入長波段(1000到1350奈米)作分析的色團濃度結果，結果發現加入長波段的分析，可以得到較理想的色團濃度結果。

Typical diffuse reflectance systems can work with photon diffusion models to accurately determine the absorption coefficient (μ_a) and reduced scattering coefficient (μ_s') of tissues in the wavelength range from 650 to 1000 nm, where tissues have high-albedo so that the diffusion approximation is satisfied. In this thesis, we used a steady state diffuse reflectance system and a novel algorithm to determine the physiological parameters of superficial biological tissues at wavelengths ranging from 500 to 1350 nm. We combined the Monte Carlo method (which is accepted as the gold standard approach for photon migration modeling) with Compute Unified Device Architecture, in which a parallel computing platform and programming model were implemented by the graphics processing units to establish the reflectance database with high speed. We further utilize the database to establish a connection between the optical properties and diffuse reflectance spectra with Artificial Neural Network. With this novel model, we can accurately and immediately simulate every conditions of photon migrating in the tissue without any limitation. In this study, we employ this new algorithm to reveal the optical properties of different liquid phantoms and the performance of this model will be surveyed. We also measured different positions of human skin and recovered the absorption and reduces scattering spectra. The derived absorption spectra can be fit linearly with the known chromophore absorption spectra to obtain the concentration of chromophores including oxygenated hemoglobin, deoxygenated hemoglobin, water, melanin, and collagen. We found that the chromophore fitting performance by taking longer wavelength (1000 to 1350 nm) into account is more reasonable than that obtained by analyzing the short wavelength spectra (500 to 1000 nm) only.

[1] S. H. Tseng et al., “Noninvasive evaluation of collagen and hemoglobin contents and scattering property of in vivo keloid scars and normal skin using diffuse reflectance spectroscopy: pilot study,’’ J. Biomed. Opt. 17(7), 077005 (2012).
[2] Iris Riemann, Peter Fischer, Martin Kaatz, Tobias W. Fischer, Peter Elsner, Enrico Dimitrov, Annette Reif, Karsten Konig, “Optical tomography of pigmented human skin biopsies’’ Proc. SPIE. 5312, Lasers in Surgery (2004)
[3] A. N. Bashkatov1, E. A. Genina, V. I. Kochubey and V. V. Tuchin ‘’Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000nm’’ J. Phys. D: Appl. Phys. 38 (2005) 2543–2555
[4] Hans Roehrig ; Xiliang Gu ; Jiahua Fan, “Physical evaluation of color and monochrome medical displays using an imaging colorimeter’’ Proc. SPIE 8673, Medical Imaging (2013)
[5] Gerhard Grubauer, Peter M. Elias, and Kenneth R. Feingold, “Transepidermal water loss: the signal for recovery of barrier structure and function’’ Journal of Lipid Research, 30, 323-333(1989)
[6] Camilla A. Thorling ; Yuri Dancik ; Clinton W. Hupple ; Gregory Medley ; Xin Liu ; Andrei V. Zvyagin ; Tom A. Robertson ; Frank J. Burczynski ; Michael S. Roberts, “Multiphoton microscopy and fluorescence lifetime imaging provide a novel method in studying drug distribution and metabolism in the rat liver in vivo’’ J. Biomed. Opt. 16(8), 086013(2013)
[7] Ryosuke Tanaka, Shu-ichiro Fukushima, Kunihiko Sasaki, Yuji Tanaka, Hiroyuki Murota, Takeshi Matsumoto, Tsutomu Araki, Takeshi Yasui, “In vivo visualization of dermal collagen fiber in skin burn by collagen-sensitive second-harmonic-generation microscopy’’ Journal of Biomedical Optics 18(6), 061231 (2013)
[8] F. Bevilacqua et al., “In vivo local determination of tissue optical properties: applications to human brain,” Appl. Opt. 38(22), 4939–4950 (1999).
[9] A. Cerussi et al., “In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy,” J. Biomed. Opt. 11(4), 044005 (2006).
[10] S. H. Tseng, A. Grant, and A. J. Durkin, “In vivo determination of skin near-infrared optical properties using diffuse optical spectroscopy,” J. Biomed. Opt. 13(1), 014016 (2008).
[11] Bays R, Wagnières G, Robert D, Braichotte D, Savary JF, Monnier P, van den Bergh H, “Clinical determination of tissue optical properties by endoscopic spatially resolved reflectometry,’’ Appl. Opt. 35(10), 1756–1766 (1996).
[12] F. Bevilacqua and C. Depeursinge, “Monte Carlo study of diffuse reflectance at source-detector separations close to one transport mean free path,” J. Opt. Soc. Am. A 16(12), 2935–2945 (1999).
[13] A. D. Kim, C. Hayakawa, and V. Venugopalan, “Estimating optical properties in layered tissues by use of the Born approximation of the radiative transport equation,” Opt. Lett. 31(8), 1088–1090 (2006).
[14] S. H. Tseng et al., “Quantitative spectroscopy of superficial turbid media,” Opt. Lett. 30(23), 3165–3167 (2005).
[15] S. H. Tseng et al., “Investigation of a probe design for facilitating the uses of the standard photon diffusion equation at short source-detector separations: Monte Carlo simulations,” J. Biomed. Opt. 14(5), 054043 (2009).
[16] A. Ishimaru, Wave Propagation and Scattering in Random Media, Academic Press, Waltham, MA (1978).
[17] S. H. Tseng et al., “Chromophore concentrations, absorption and scattering properties of human skin in-vivo,” Opt. Express 17(17), 14599–14617 (2009).
[18] Farrell TJ, Patterson MS, Wilson B. “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,’’ Med Phys. 19(4), 879-88 (1992).
[19] L. Wang, and S. L. Jacques, Monte Carlo Modeling of Light Transport in Multi-Layered Tissues in Standard C (University of Texas M. D. Anderson Cancer Center, Houston, Tex, 1992-1993).
[20] David B. Kirk, “NVIDIA CUDA software and GPU parallel computing architecture,’’ NVIDIA Corporation (2006-2008).
[21] Johan A. K. Suykens, Joos. L. Vandewallee, and Bart L. R. Moor, “Artificial Neural Networks for Modelling and Control of Nonlinear Systems,’’ ISBN, 0-7923-9678-2 (1996).
[22] L. V. Wang, and H. I. Wu, Biomedical Optics:principles and imagine (John Wiley & Sons, Inc., New Jercy, 2007).
[23] 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, 2727-2741 (1994).
[24] 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,’’ Med Phys 19, 879-888 (1992).
[25] M. S. Patterson, S. J. Madsen, J. D. Moulton, and B. C. Wilson, “Diffusion equation representation of photon migration in tissue,’’ in Microwave Symposium Digest, 1991., IEEE MTT-S International, pp. 905-908 vol.902 (1991).
[26] A. Kienle, M. S. Patterson, N. Dögnitz, R. Bays, G. Wagnieres, and H. van den Bergh, “Noninvasive Determination of the Optical Properties of Two-Layered Turbid Media,’’ Appl. Opt. 37, 779-791 (1998).
[27] T. Sheng-Hao, C. K. Hayakawa, H. Spanier, and A. J. Durkin, “Determination of Optical Properties of Superficial Volumes of Layered Tissue Phantoms,’’ Biomedical Engineering, IEEE Transactions on 55, 335-339 (2008).
[28] L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,’’ Computer Methods and Programs in Biomedicine 47, 131-146 (1995).
[29] M. Testorf, U. Österberg, B. Pogue, and K. Paulsen, “Sampling of Time- and Frequency-Domain Signals in Monte Carlo Simulations of Photon Migration,’’ Appl. Opt. 38, 236-245 (1999).
[30] I. V. Yaroslavsky, A. N. Yaroslavsky, V. V. Tuchin, and H. J. Schwarzmaier, “Effect of the scattering delay on time-dependent photon migration in turbid media,’’ Appl Opt 36, 6529-6538 (1997).
[31] Zhiyi Yang, Yating Zhu, and Yong Pu, “Parallel Image Processing Based on CUDA,’’ IEEE Computer Science and Software Engineering, vol 3, 198-201 (2008).
[32] Erik Alerstam, William Chun Yip Lo, Tianyi David Han, Jonathan Rose, Stefan Andersson-Engels, and Lothar Lilge, “Next-generation acceleration and code optimization for light transport in turbid media using GPUs,’’ J. Biomed. Opt. 15, 035002 (2010).
[33] Noboru Murata, and Shuji Yoshizawa, “Network Information Criterion-Determining the Number of Hidden Units for an Artificial Neural Network Model,’’ IEEE Transactions on Neural Networks, Vol. 5, No. 6 (1994).
[34] R. Rojas, and Springer-Verlag, “Neural Networks’’, chapter 7 (1996).
[35] L. Kou and D. Labrie and P. Chylek, “Refractive indices of water and ice
in the 0.65-2.5nm spectral range’’ Appl. Opt, 32, 3531--3540, (1993)
[36] HG van Staveren, CJM Moes, J van Marle, SA Prahl, MJC van Gemert, “Light scattering in Intralipid-10% in the wavelength range of 400-1100 nanometers,’’ Appl. Opt, 30, 4507-4514 (1991).
[37] ST Flock, SL Jacques, BC. Wilson, WM Star, MJC van Gemert, “Optical Properties of Intralipid: A phantom medium for light propagation studies,’’ Lasers in Surgery and Medicine 12:510-519 (1992).
[38] John W. Pickering, Scott A. Prahl, Niek van Wieringen, Johan F. Beek, Henricus J. C. M. Sterenborg, and Martin J. C. van Gemert, “Double-integrating-sphere system for measuring the optical properties of tissue,’’ Appl. Opt, Vol. 32, Issue 4, 399-410 (1993).
[39] Scott Prahl, “Everything I think you should know about Inverse Adding-Doubling’’, chapter 4.2 (2011).
[40] Richard A. Schwarz, Wen Gao, Dania Daye, Michelle D. Williams, Rebecca Richards-Kortum, and Ann M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,’’ Appl. Opt, Vol. 47, Issue 6, 825-834 (2008).
[41] S. L. Jacques, “Melanosome absorption coefficient,” (1998), http://omlc.ogi.edu/spectra/melanin/mua.html.
[42] S. Prahl, “Hemoglobin absorption coefficient,” (1999), http://omlc.ogi.edu/spectra/hemoglobin/index.html.
[43] V. Podrazky and V. Sedmerova, “Densities of collagen dehydrated by some organic solvents,” Experientia, 22(12), 792 (1966).
[44] P. Taroni et al., “Diffuse optical spectroscopy of breast tissue extended to 1100 nm,” J. Biomed. Opt, 14(5), 054030 (2009).
[45] H. H. Mitchell, T. S. Hamilton, F. R. Steggerda and H. W. Bean, “The chemical composition of the adult human body and its bearing on the biochemistry of growth,’’ J. Biol. Chem. 1945, 158:625-637(1945).
[46] Cheng-Lun Tsai, Ji-Chung Chen, Wen-Jwu Wang, “Near-infrared Absorption Property of Biological Soft Tissue Constituents,’’ J. Med. Biol. Eng, 21(1): 7-14 2001.
[47] L. G. Weyer, “Near-infrared spectroscopy of organic substances”, Appl. Spectrosc. Rev. 21: 1-43, 1985.