Wang Jianfeng, Lin Kan, Zheng Wei, Ho Khek Yu, Teh Ming, Yeoh Khay Guan, Huang Zhiwei
Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119260.
Faraday Discuss. 2016 Jun 23;187:377-92. doi: 10.1039/c5fd00151j.
This study aims to assess the clinical utility of a rapid fiber-optic Raman spectroscopy technique developed for enhancing in vivo diagnosis of gastric precancer during endoscopic examination. We have developed a real-time fiber-optic Raman spectroscopy system capable of simultaneously acquiring both fingerprint (FP) (i.e., 800-1800 cm(-1)) and high-wavenumber (HW) (i.e., 2800-3600 cm(-1)) Raman spectra from gastric tissue in vivo at endoscopy. A total of 5792 high-quality in vivo FP/HW Raman spectra (normal (n = 5160); dysplasia (n = 155), and adenocarcinoma (n = 477)) were acquired in real-time from 441 tissue sites (normal (n = 396); dysplasia (n = 11), and adenocarcinoma (n = 34)) of 191 gastric patients (normal (n = 172); dysplasia (n = 6), and adenocarcinoma (n = 13)) undergoing routine endoscopic examinations. Partial least squares discriminant analysis (PLS-DA) together with leave-one-patient-out cross validation (LOPCV) were implemented to develop robust spectral diagnostic models. The FP/HW Raman spectra differ significantly between normal, dysplasia and adenocarcinoma of the stomach, which can be attributed to changes in proteins, lipids, nucleic acids, and the bound water content. PLS-DA and LOPCV show that the fiber-optic FP/HW Raman spectroscopy provides diagnostic sensitivities of 96.0%, 81.8% and 88.2%, and specificities of 86.7%, 95.3% and 95.6%, respectively, for the classification of normal, dysplastic and cancerous gastric tissue, superior to either the FP or HW Raman techniques alone. Further dichotomous PLS-DA analysis yields a sensitivity of 90.9% (10/11) and specificity of 95.9% (380/396) for the detection of gastric dysplasia using FP/HW Raman spectroscopy, substantiating its clinical advantages over white light reflectance endoscopy (sensitivity: 90.9% (10/11), and specificity: 51.0% (202/396)). This work demonstrates that the fiber-optic FP/HW Raman spectroscopy technique has great promise for enhancing in vivo diagnosis of gastric precancer during routine endoscopic examination.
本研究旨在评估一种快速光纤拉曼光谱技术的临床实用性，该技术是为增强内镜检查期间胃癌前病变的体内诊断而开发的。我们开发了一种实时光纤拉曼光谱系统，能够在内镜检查时从胃组织中同时获取指纹（FP）（即800 - 1800 cm⁻¹）和高波数（HW）（即2800 - 3600 cm⁻¹）拉曼光谱。从191例接受常规内镜检查的胃疾病患者（正常（n = 172）；发育异常（n = 6）；腺癌（n = 13））的441个组织部位（正常（n = 396）；发育异常（n = 11）；腺癌（n = 34））实时获取了总共5792条高质量的体内FP/HW拉曼光谱。采用偏最小二乘判别分析（PLS - DA）结合留一患者交叉验证（LOPCV）来建立稳健的光谱诊断模型。胃的正常组织、发育异常组织和腺癌组织的FP/HW拉曼光谱存在显著差异，这可归因于蛋白质、脂质、核酸和结合水含量的变化。PLS - DA和LOPCV表明，光纤FP/HW拉曼光谱对正常、发育异常和癌性胃组织分类的诊断敏感性分别为96.0%、81.8%和88.2%，特异性分别为86.7%、95.3%和95.6%，优于单独的FP或HW拉曼技术。进一步的二分PLS - DA分析显示，使用FP/HW拉曼光谱检测胃发育异常的敏感性为90.9%（10/11），特异性为95.9%（380/396），证实了其相对于白光反射内镜检查的临床优势（敏感性：90.9%（10/11），特异性：51.0%（202/396））。这项工作表明，光纤FP/HW拉曼光谱技术在增强常规内镜检查期间胃癌前病变的体内诊断方面具有巨大潜力。
