修正式蒙地卡羅逆向擬合模型於活體漫反射光譜研究:人體皮膚組織

Abstract

漫反射光譜為非侵入式技術，目前主要開發用來偵測組織的組成及病變，因細胞的內部變化與組織結構的不同，很多時後可能無法直接從肉眼觀察出來，但其變化卻能反應於組織光學性質的改變。而本論文的量測目標為人體皮膚，希望能利用非侵入方式偵測出人體皮膚中各吸收物質的濃度，以輔助未來臨床上診斷的使用。 在萃取組織光學方法中，主要透過蒙地卡羅法建立組織模型模擬光子於組織中的散射與吸收，計算出不同組織光學係數下的漫反射光譜，並藉由模擬光譜與量測光譜的比對，逆向擬合定量出組織的光學參數。本論文致力於改善組織模型及逆向擬合流程，建立出更貼近真實活體組織的模型，以及能縮小模擬光譜與實際量測光譜間誤差的逆向擬合方法。 本論文亦設計了兩大實驗，欲藉由實驗結果佐證本論文方法之可行性及穩定性，分別為以非侵入式方法改變人體皮膚的黑色素含量以及血紅素及血氧濃度含量，其中黑色素變化實驗中，亦搭配比較倍頻顯微術量測的結果。 本論文的修正式逆向擬合模型與其他研究最大的不同在於，其中所使用的順向組織模型更貼近人體皮膚組織的真實情況，採用三層模型，且各層散射也使用不同參數，而逆向擬合之流程設計，也讓擬合結果在血紅素吸收有特殊波型之波段的誤差明顯降低，而整體擬合效果也有所提升。活體實驗的部分，黑色素實驗中漫反射光譜量測結果與倍頻顯微術之結果有相近的變化趨勢，且其結果顯示黑色素濃度因陽光曝曬而增加的反應可能會有時間上的延遲。而血紅素及血氧濃度調變的初步實驗結果，目前有量出些許變化，但不是很明顯。目前兩大實驗初步結果皆有一定趨勢，未來若能進行更多次重複性實驗，能更有力證明此逆向方法之穩定性。

Diffuse reflectance spectroscope (DRS) is a non-invasive method, used to detect the construction and pathological changes of tissues. In many times, the changes in the cells or the pathological changes of tissue cannot be detected by visual examination, however, those changes of tissue under surface correspond on the different optical properties. The target tissue of this research is human skin, we hope to extract the concentration of every absorbance in human skin through non-invasive diffuse reflectance spectroscope to help the clinical diagnosis in the future. In the methods of extracting optical properties of tissues, the interactions of photon in tissue can be simulated by Monte Carlo method. The different diffuse reflectance spectra can be calculated by assigning different optical parameters. To compare the simulated spectra and the target spectra, the optical properties of measurement tissue can be extracted by inverse Monte Carlo method. In this study, the tissue model and the inverse fitting model were improved, and the new tissue model is not only more similar to the human skin tissue, but also decrease the error between measurement spectra and fitted spectra. Two main experiments were done in this thesis to validate the feasibility and the stability of this improved inverse Monte Carlo fitting method. One experiment is about changing the melanin concentration of human skin by sunlight exposure, the other is about changing the blood concentration and oxygen saturation of skin tissue by arterial occlusion. In the melanin concentration experiment, the comparison between results of harmonic generation microscopy (HGM) and DRS were also proposed in this thesis. Different from previous studies, the tissue model used in this research is three-layered model, and the different scattering coefficients are considered, which makes the model more similar to the real skin tissue. In addition, the new inverse fitting process improve the fitting results of full spectrum, especially the spectrum in the wavelength where hemoglobin has characteristic absorption peaks. In the melanin experiments, the results of DRS and HGM show a similar trend, and the results also show that there might be some time delay of the increase of melanin concentration after sunlight exposure. Moreover, the results of hemoglobin experiments show that there are some changes of hemoglobin concentration and oxygen saturation after arterial occlusion, but not very obvious. In conclusion, the preliminary results showed some reasonable trends. In the future, some experiments strep can be improved and it still need more measurement data to verify the reliability and stability of this inverse fitting method.