Intestinal-type gastric carcinogenesis is a complex multi-step disease, and early precursors (e.g. intestinal metaplasia (IM), dysplasia) can be very challenging to identify using conventional white-light endoscopic imaging. This study aims to assess the capability of Raman spectroscopy for multi-class elucidation of intestinal-type gastric carcinogenesis sequence in vivo for improving precancer detection at endoscopy. We employ a novel image-guided Raman endoscopy technique developed for in vivo gastric tissue Raman measurement within 0.5 s during clinical endoscopic examination. We have acquired a total of 1277 in vivo Raman spectra from 83 gastric patients associated with intestinal-type carcinogenesis. In vivo Raman spectroscopy integrated with semi-quantitative spectral modelling (e.g. DNA, lipids, glycoprotein, proteins and blood) reveals the progressive changes of biochemical constituents in gastric tissue associated with preneoplastic and neoplastic transformation (i.e., IM, dysplasia and adenocarcinoma). Multi-class probabilistic partial least squares-discriminant analysis (PLS-DA) diagnostic algorithms based on in vivo Raman spectra are able to identify normal mucosa with sensitivity of 75.88% and specificity of 87.21%; IM with sensitivity of 46.67% and specificity of 87.55%; dysplasia with sensitivity of 83.33%; specificity of 95.80%, and adenocarcinoma with sensitivity of 84.91% and specificity 95.57%, respectively. This work demonstrates that Raman spectroscopy is a sensitive biomolecular probe for monitoring intestinal-type gastric carcinogenesis to realize early diagnosis and detection of precancer and early gastric cancer in vivo during clinical endoscopic examination.
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