人體中含有許多潛藏的資訊，我們可以擷取並分析、進而解讀這些資訊來瞭解生理現象或疾病。例如在生物醫學中，藉由處理以及分析生物醫學影像來進行疾病的預防、檢測以及監控。本論文藉由光學虛擬活體組織切片影像了解位於人類皮膚中的膠原蛋白纖維的結構以及特徵，並定量分析皮膚中的膠原蛋白纖維的特徵，進而應用膠原蛋白纖維的特徵來探討跟人類醫學疾病的關聯性。因此本論文提出一個電腦輔助之膠原纖維特徵萃取以及量化膠原蛋白纖維特徵的演算法。由實驗結果以及與相關文獻之比較，本論文所提出之演算法不僅在生物醫學影像分析之領域具有極高的發展潛力，也於很多應用當中具備極大之醫學價值。

Human contains many hidden information and we can acquire, analyze hidden information and farther interpret hidden information to understand physiological phenomena or disease. In biomedical research, acquiring and analyzing biomedical images can efficaciously prevent and detect disease. In this thesis, we analyze and gain understanding the structure and features of collagen fibers in human skin by optical in vivo virtual biopsy images. For the application of biomedical images to investigate the relationship between features of collagen fibers and human medicine, a computer aided algorithm for quantifying features of collagen fiber is developed. The proposed algorithm has significant potential for biomedical image analysis and medical contributions. According to the results of this experiment we can come to the conclusion that our calculations are accurate.

[1] C.K. Sun, “Higher harmonic generation microscopy,” Advances in Biochemical Engineering/Biotechnology, vol. 95, pp. 17 - 56, 2005.
[2] S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE Journal of Selected Topics in Quantum Electronics, vol. 16, no. 3, pp. 478 - 492, 2010.
[3] S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, “Selective imaging in second-harmonic-generation microscopy with anisotropic radiation.” Journal of biomedical optics, vol.14, 2009.
[4] Falzon, G., S. Pearson, and R. Murison. "Analysis of collagen fibre shape changes in breast cancer." Physics in medicine and biology, vol53, no.23, pp. 6641, 2008.
[5] R. LaComb, O. Nadiarnykh, and P. J. Campagnola “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: Experiment and Simulation,” Biophysical Journal, vol. 94, pp.4504-4514, 2008.
[6] G. Falzon, S. Pearson1 and R. Murison “Analysis of collagen fiber shape changes in breast Cancer,” Physics in Medicine and Biology, vol.53, pp.6641-6652, 2008
[7] M.W. Conklin, J.C. Eickhoff, K.M. Riching, C.A. Pehlke, K.W. Eliceiri, P.P. Provenzano, A. Friedl, P.J. Keely, “Aligned collagen is a prognostic signature for survival in human breast carcinoma,” The American Journal of Pathology, vol. 178, no. 3, pp. 1221-1234, 2011.
[8] M. Sezgin and B. Sankur, “Survey over image thresholding techniques and quantitative performance evaluation,” Journal of electronic imaging, vol. 13, pp.146 – 165, 2004.
[9] N. Otsu, "A threshold selection method from gray-level histograms." IEEE transaction on systems, man, and cybernetics, vol.9 no.1, 1979.
[10] M. Sezgin, “Survey over image thresholding techniques and quantitative performance evaluation” Journal of Electronic imaging, vol.13, no.2, pp.146-168, 2004.
[11] J. Zhang and J. Hu,’’ Image segmentation based on 2D Otsu method with histogram analysis,” International Conference on Computer Science and Software Engineering, CSSE, vol. 6, pp. 105–108, 2008.
[12] R.C. Gonzalez and R.E. Woods, Digital Image Processing: Prentice-Hall, Englewood Cliffs, NJ, 2002.
[13] N. Bassiou and C. Kotropoulos "Color image histogram equalization by absolute discounting back-off," Computer Vision and Image Understanding, vol. 107, no.1, pp.108 -122, 2007.
[14] E. Zhu , J. Yin , G. Zhang and C. Hu, “A Gabor filter based fingerprint enhancement scheme using average frequency,” International Journal of Pattern Recognition and Artificial Intelligence, vol. 20, no. 3, pp.417-429, 2006.
[15] D. Dunn and W. E. Higgins “Optimal Gabor Filters for Texture Segmentation,” IEEE Transactions on Image Processing, vol. 4, no. 7, 1995.
[16] C. Gottschlich, “Curved Gabor Filters for Fingerprint Image Enhancement,” IEEE Transactions on Image Processing, vol. 21, no. 4, pp. 2220-2227, 2012
[17] B.S. Manjunath and W.Y. Ma. "Texture features for browsing and retrieval of image data." Pattern Analysis and Machine Intelligence, IEEE Transactions, vol.18, no.8, pp. 837-842, 1996.
[18] S. Yamamoto, Y. Nakajima, S. Tamura “Extraction of Fluorescent Dot Traces from a Scanning Laser Ophthalmoscope Image Sequence by Spatio-Temporal Image Analysis: Gabor Filter and Radon Transform Filtering,” IEEE Transactions on Biomedical Engineering, vol. 46, no. 11, 1999.
[19] D. Gabor. “Theory of communications,” Journal of International Electrical Engineers, vol. 93, part III, No. 26, pp. 427 - 457, 1946.
[20] J. G. Daugman, “Uncertainty relation for resolution in space, spatial frequency, and orientation optimized by two-dimensional visual cortical filters,” Optical Society of America, Journal, A: Optics and Image Science, vol. 2, pp. 1160 - 1169, 1985.
[21] A. Witkin, “Scale-space filtering: A new approach to multi-scale description”. In Acoustics, Speech, and Signal Processing, IEEE International Conference on ICASSP'84, vol. 9, pp. 150-153, 1984.
[22] T. Lindeberg, “Feature detection with automatic scale selection,” International journal of computer vision, vol. 30, no. 2, pp. 79 - 116, 1998.
[23] T. Lindeberg “Edge detection and ridge detection with automatic scale selection. ” International Journal of Computer Vision vol.30, no.2, pp.117-156, 1998
[24] K. Pearson, “Contributions to the mathematical theory of evolution. II. Skew variation in homogeneous material. ” Philosophical Transactions of the Royal Society of London. A, 186, 343-414., 1895
[25] S. Wu, H. Li, H. Yang, X. Zhang, Z. Li and S. Xu, "Quantitative analysis on collagen morphology in aging skin based on multiphoton microscopy." Journal of Biomedical Optics vol.16, no.4, 2011.
[26] A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W. L. Chen, Y. F. Chen, M.Y. Jeong, C. S. Kim, S. J. Chen and C. Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy”. Journal of biomedical optics, vol.18, no.3, 2013.
[27] P. Soille, Morphological Image Analysis: Principles and Applications: Springer-Verlag, 2003.
[28] W. Hu, H. Li, C. Wang, S. Gou, & L. Fu "Characterization of collagen fibers by means of texture analysis of second harmonic generation images using orientation-dependent gray level co-occurrence matrix method." Journal of Biomedical Optics vol.17, no.2, pp.71-79, 2012