多光譜影像系統於生物醫學之應用

Biomedical applications of a hyperspectral imaging system based on Fourier transform spectroscopy

曾德玉(Te-Yu Tseng)

指導教授 ： 宋孔彬

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/博士(2011年)

https://doi.org/10.6342/NTU.2011.10435

摘要

本論文的內容主要建構一套可應用於生物醫學上的多光譜影像系統，並針對不同的生醫應用需求，延伸發展出分析多光譜資訊的工具。由於應用於生物醫學的檢測系統通常需要具備快速以及穩定的特性，為此本研究選用傅氏光譜儀作為多光譜系統的基礎架構，不僅可以高速擷取多光譜影像，並且無須太多複雜的光學架構。在此多光譜系統下，本研究也進行此系統的效能分析，並建立光譜的修正方法。
首先，本研究使用多光譜影像系統應用於量測金屬奈米粒子的散射光譜，這是因為金屬奈米粒子具有穩定與高散射強度的特性，讓金屬奈米粒子漸漸取代螢光分子作為光學檢測中的標記物的研究蓬勃地發展。由於要區別不同的金屬奈米粒子的種類，需要利用光譜儀觀察其獨特的散射光譜，若是將多種金屬奈米粒子同時應用在大面積的生醫感測晶片上，則散射光譜的擷取時間將非常驚人，因此需要高速的光譜擷取系統來搭配金屬奈米粒子的生醫應用發展。本研究成功地利用實驗室內所架設的影像式多光譜系統用於量測金屬奈米粒子的散射光譜，而且進一步使用光譜分析的工具來進行不同金屬奈米粒子的濃度定量，表現出未來可以應用於微陣列晶片的潛力。另外，本研究也利用此系統觀察到金屬奈米粒子的局部表面電漿的效應，未來亦可以用於生物環境的偵測。
另一生醫的應用部分，則是利用此系統量測組織漫散射光譜。在組織病變的進程時，組織漫散射光譜能夠反應出組織結構以及組織中生化成分的改變，因此可以利用量測到的組織漫散射光譜來能夠幫助診斷組織的病變。為了未來能與臨床應用結合，本研究將影像式光纖束用來收集組織的漫反射光譜，量測具有空間解析的組織漫反射光譜，並使用實驗室所建立的蒙地卡羅模擬工具得到組織中的光學參數，用以評斷組織中細胞型態或是生化成分的改變，希望未來能夠應用在臨床方面輔助診斷或是幫助治療。

關鍵字

多光譜影像系統 ； 傅氏轉換 ； 奈米粒子 ； 空間解析漫散射光譜

並列摘要

This dissertation describes the construction of a hyperspectral imaging system (HSIS) based on Fourier transform spectroscopy (FTS) and the combinations of the HSIS with spectral analysis methods for biomedical applications. The FTS-based HSIS owns high-speed acquisition of hyperspectral imaging and simply optical design, which are critical features for biomedical applications. System performances and spectral calibration methods of the FTS-based HSIS were well tested.
In the first biomedical application, we used the HSIS to measure scattering spectra from immobilized plasmonic nanoparticles. The current setup had acquisition time of 5 seconds and spectral resolution of 21.4 nm at 532.1 nm. We demonstrated the applicability of the HSIS in conjunction with spectral data analysis to quantify multiple types of plasmonic nanoparticles (PNPs) and detect small changes in localized surface plasmon resonance wavelengths of PNPs due to changes in the environmental refractive index.
In the second application, we also applied hyperspectral imaging to measure spatially-resolved diffuse reflectance spectra (DRS) in the visible range and an iterative inversion method based on forward Monte Carlo (MC) modeling to quantify optical properties of two-layered tissue models. We validated the inversion method using spectra experimentally measured from liquid tissue mimicking phantoms with known optical properties. Results of fitting simulated data showed that simultaneously considering the spatial and spectral information in the inversion process improves the accuracies of estimating the optical properties and the top layer thickness in comparison to methods fitting reflectance spectra measured with a single source-detector separation or fitting spatially-resolved reflectance at a single wavelength. Further development of the method could improve noninvasive assessment of physiological status and pathological conditions of stratified squamous epithelium and superficial stroma.

並列關鍵字

Hyperspectral imaging system ； Fourier transform ； plasmonic nanoparticle ； spatially-resolved diffuse reflectance spectroscopy

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