title: Fiber-optic Raman spectroscopy for in vivo diagnosis of gastric dysplasia.
abstract: 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.
authors.affiliation: Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576. biehzw@nus.edu.sg.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576. biehzw@nus.edu.sg.
authors.forename: Kan
authors.initials: K
authors.lastname: Lin
authors.affiliation: Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576. biehzw@nus.edu.sg.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119260.
authors.forename: Khek Yu
authors.initials: KY
authors.lastname: Ho
authors.affiliation: Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119074.
authors.forename: Ming
authors.initials: M
authors.lastname: Teh
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119260.
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.affiliation: Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576. biehzw@nus.edu.sg.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging; D005336:Fiber Optic Technology / Q000379:methods*; D006801:Humans; D011230:Precancerous Conditions / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging*