Rapid Fiber-optic Raman Spectroscopy for Real-Time In Vivo Detection of Gastric Intestinal Metaplasia during Clinical Gastroscopy

Abstract

We report a unique simultaneous fingerprint (FP) and highwavenumber (HW) Raman spectroscopy technique coupled with a beveled fiber-optic Raman probe for improving in vivo detection of gastric intestinal metaplasia (IM)-precancerous lesions in realtime during clinical gastroscopy. A total of 4,520 high-quality in vivo FP/HW gastric Raman spectra (normal ¼ 4,178; IM ¼ 342) were acquired from 157 gastric patients undergoing endoscopic examination. Multivariate diagnostic algorithms based on principal components analysis and linear discriminant analysis together with the leave-one tissue site-out, cross-validation on in vivo tissue Raman spectra yield the diagnostic sensitivities of 89.3%, 89.3%, and 75.0%; specificities of 92.2%, 84.4%, and 82.0%; positive predictive values of 52.1%, 35.2%, and 28.4%; and negative predictive values of 98.9%, 98.8%, and 97.2%, respectively, by using the integrated FP/HW, FP, and HW Raman techniques for identifying IM from normal gastric tissue. Further, ROC curves generated show that the integrated FP/HW Raman technique gives the integration area under the ROC curve of 0.92 for IM classification, which is superior to either FP (0.89) or HW Raman (0.86) technique alone. This work demonstrates for the first time that the simultaneous FP/HW fiber-optic Raman spectroscopy has great potential to enhance early diagnosis of gastric precancer in vivo during routine endoscopic examination. Cancer Prev Res; 9(6); 476-83. Ó2016 AACR.

Biomedical optical spectroscopy for the early diagnosis of gastrointestinal neoplasms

“…The receiver operating characteristic (ROC) curve analysis showed that FP/ HW Raman technology gave an area under the ROC curve (AUROC) of 0.92 (FP: 0.89, HW: 0.86) for gastric intestinal metaplasia classification. 57 …”

Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique

“…The enhanced clustering accuracy using hybrid RS‐OCT technique can be explained by its capability to simultaneously uncover both the rich biochemical and biomolecular information (ie, proteins, lipids, DNA and water content, etc.) with FP/HW RS and complementary tissue morphology information (eg, attenuation coefficients) represented by the OCT imaging . Most noticeably from the above analysis (Tables ), the alveolar process is classified with a significant higher sensitivity than other anatomical locations, signifying that the alveolar process has a unique morphology (Figures and ) and molecular profile (Figures and ) compared to the lateral tongue and floor of the mouth.…”

“…Prominent FP Raman peaks were identified in the oral cavity as follows: 853 cm −1 ( v (C─C) proteins), 1004 cm −1 ( ν s (C─C) ring breathing of phenylalanine), 960 cm −1 ( ν s (P─O) of hydroxyapatite), 1078 cm −1 ( ν (C─C) of lipids), 1265 cm −1 (amide III v (C─N) and δ(N─H) of proteins), 1302 cm −1 (CH 2 twisting and wagging of lipids), 1445 cm −1 ( δ (CH 2 ) deformation of proteins and lipids) and 1655 cm −1 (amide I v (C═O) of proteins) in the FP range . In the HW range, intense Raman peaks are also observed: that is, 2850 and 2885 cm −1 (symmetric and asymmetric CH 2 stretching of lipids), 2940 cm −1 (CH 3 stretching of proteins) and the broad Raman band of water (OH stretching vibrations peaking at ~3250 and ~3400 cm −1 ) that are related to the local conformation and interactions of OH‐bonds in the intracellular and extracellular space of oral tissue . The difference Raman spectra (ie, lateral tongue − floor of mouth, alveolar process − floor of mouth, and alveolar process − lateral tongue) ± 1SD (shaded area) are shown in Figure B.…”

“…Remarkably, the significantly reduced water contribution to the Raman spectrum was found in the lateral tongue and the floor of the mouth (Figure B). This is possibly due to the increased lipids of the lateral tongue and the mouth floor, reducing their water permeability and the correspondingly reduced water content reflected by the reduced Raman peaks at 3250 and 3400 cm −1 assigned to the OH stretching vibrations .…”

“…The Raman path is launched from the fiber‐optic Raman probe, focused by the converging lens, and deflected by 90 ° using the LPDM, and then focused onto the tissue surface through the glass window . In vivo oral Raman spectra were acquired within 0.5 s by using the RS‐OCT technique coupled with a simultaneous fingerprint (FP: 800‐1800 cm −1 ) and high wavenumber (HW: 2800‐3600 cm −1 ) RS system . The FP/HW RS system comprises a 785 nm diode laser (maximum output: 300 mW, B&W TEK Inc.), a high‐throughput reflective imaging spectrograph (Acton LS‐785 f/2, Newark, DE; Princeton Instruments Inc., Trenton, NJ) equipped with a customized 830 g/mm gold‐coated grating that has a ~85% diffraction efficiency in the NIR range of 800‐1200 nm.…”