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Raman spectroscopy is a unique optical vibrational spectroscopic technique which is capable of probing biochemical and biomolecular structures and conformations associated with disease transformation. Raman probe is a key component to facilitate the in vivo tissue diagnosis by using Raman spectroscopy. The diagnostic performance of the two different endoscope-based fiber-optic Raman probe designs (i.e., beveled and volume Raman probes) were evaluated for real-time, in vivo diagnosis of gastric dysplasia at endoscopy. The beveled Raman probe provides approximately 2-fold improvements in tissue Raman to autofluorescence intensity ratios as compared to the use of volume Raman probe. The diagnostic accuracy of gastric dysplasia using beveled Raman probe is 93.0% (sensitivity of 92.5%; specificity of 93.1%), which is superior to the diagnostic performance (accuracy of 88.4%; sensitivity of 85.8%; specificity of 88.6%) using the volume Raman probe. Biomolecular modeling is finally employed to extract the different Raman active components interrogated by the two types of endoscope-based Raman probes.

We report a novel simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic Raman spectroscopy developed for in vivo diagnosis of intestinal metaplasia (IM) in the stomach under wide-field endoscopic imaging. The FP/HW Raman endoscopy technique was performed to differentiate IM from normal tissues with sensitivity of 89% and specificity of 83%. This study shows the great potential of the FP/HW Raman endoscopic technique for early diagnosis of non-neoplastic gastric disease in vivo during routine endoscopic examination.

This work aims to apply a fiber-optic Raman spectroscopy technique for in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the fingerprint (FP) (i.e., 800–1800 cm -1 ) and high-wavenumber (HW) (i.e., 2800–3600 cm -1 ) Raman spectra for real-time assessment of colorectal carcinogenesis. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy has the potential for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.

Raman spectroscopy represents a unique optical vibrational technique based on the fundamental premise of inelastic light scattering. Raman spectroscopy enables histopathological assessment at the biomolecular level. We have developed a fiber-optic depth-resolved near-infrared (NIR) Raman endoscopy technique integrated with on-line diagnostic algorithms for in vivo real-time epithelial diagnostics under multimodal wide-field imaging (i.e., white light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 450 patients who previously underwent Raman endoscopy (n=1900 spectra) was used to render diagnostic models for identifying gastric precancer (i.e., dysplasia) based on probabilistic partial least squares (PLS) - discriminant analysis (DA). The on-line Raman endoscopy technique was tested prospectively on (n=5) patients for real-time in vivo gastric epithelium tissue diagnosis. The fiber-optic confocal Raman endoscopic technique developed could prospectively identify gastric dysplasia in real-time with a sensitivity: 81.3% (61/75) and specificity 88.3% (188/213) on spectrum basis. On lesion basis, all dysplastic lesions were identified. This study successfully demonstrates for the first time the prospective real-time in vivo diagnosis of gastric precancer using depth-resolved Raman endoscopy.

Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of depth-resolved near-infrared (NIR) Raman endoscopy integrated with on-line diagnostic algorithms, in vivo real-time epithelial diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 43 patients who previously underwent Raman endoscopy (n=146 spectra) was used to render a robust model based on partial least squares - discriminant analysis (PLS-DA) for diagnosis of dysplasia in Barrett’s esophagus. The Raman endoscopy technique was validated prospectively on 2 new esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal high-grade dysplasia in vivo with an accuracy of 85.9% (sensitivity: 91.3% (21/23): specificity 83.3% (40/48)) on spectrum basis. This study realizes for the first time depth-resolved Raman endoscopy for real-time in vivo diagnosis of dysplasia in Barrett’s epithelium at the biomolecular level.

A rapid image-guided Raman endoscopy system integrated with on-line diagnostic scheme is developed for in vivo Raman tissue diagnosis (optical biopsy) in the upper GI during clinical gastrointestinal endoscopy under multimodal wide-field imaging guidance. The real-time Raman endoscopy technique was tested prospectively on new gastric patients (n=4) and could identify dysplasia in vivo with sensitivity of 81.5% (22/27) and specificity of 87.9% (29/33). This study realizes for the first time the novel image-guided Raman endoscopy as a screening tool for real-time, online diagnosis of gastric cancer and precancer in vivo at endoscopy.

Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of near-infrared (NIR) Raman endoscopy integrated with diagnostic algorithms, in vivo real-time Raman diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 177 patients who previously underwent Raman endoscopy (n=2510 spectra) was used to render two robust models based on partial least squares - discriminant analysis (PLS-DA) for esophageal and gastric cancer diagnosis. The Raman endoscopy technique was validated prospectively on 4 new gastric and esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal cancer in vivo with a sensitivity of 88.9% (8/9) and specificity of 100.0% (11/11) and gastric cancers with a sensitivity of 77.8% (14/18) and specificity of 100.0% (13/13). This study realizes for the first time the image-guided Raman endoscopy for real-time in vivo diagnosis of malignancies in the esophagus and gastric at the biomolecular level.

A near-infrared Raman spectroscopy system integrated with multimodal endoscopic imaging has been developed for in vivo diagnosis and detection of gastric malignancies during clinical gastroscopic examinations. In this study, 1238 high-quality in vivo Raman spectra in the range 800–1800 cm -1 were acquired from gastric normal and malignant tissue within 0.5 second from 81 patients under the guidance of white-light (WL), narrow-band (NB) and autofluorescence (AF) imaging during clinical endoscopy. Significant differences in Raman spectral shapes and intensities between normal and malignant gastric mucosal tissue were observed, particularly in the spectral ranges 800–900, 1000–1100, 1250–1450 and 1600–1800 cm -1 , which primarily contain signals related to proteins, nucleic acids and lipids. Partial least squares discriminant analysis (PLS-DA) could identify in vivo Raman spectra of neoplasia with a sensitivity of 82.9% and specificity of 88.9% using leave-one-tissue site out cross validation. This study demonstrates that in vivo Raman spectroscopy in conjunction with multimodal endoscopic imaging modalities holds a great promise for improving the early diagnosis of gastric malignancies.

A near-infrared Raman spectroscopy system integrated with multimodal endoscopic imaging has been developed for the early noninvasive in vivo diagnosis and detection of gastric malignancies. High-quality in vivo Raman spectra in the range 800-1800 cm -1 can be acquired from gastric normal and premalignant (dysplastic) mucosal tissue within 1 second under the guidance of white-light and narrow-band gastroscopic imaging during clinical gastroscopy. Prominent differences in Raman spectral shapes and intensities are observed between normal and dysplastic gastric mucosal tissue, particularly in the spectral ranges 800-900, 1250-1450 and 1600-1800 cm -1 , which primarily contain signals related to proteins, nucleic acids and lipids. The empirical intensity ratio algorithm I 875 /I 1450 classifies in vivo Raman spectra of dysplasia with a sensitivity of 100% and specificity of 100%. Our initial investigations show that in vivo Raman spectroscopy in conjunction with multimodal endoscopic imaging modalities holds a great promise for improving the early diagnosis of gastric malignancies.

Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with diseased transformation. The purpose of this study was to explore near-infrared (NIR) Raman spectroscopy for identifying precancer (dysplasia) from normal gastric mucosa tissues. High-quality Raman spectra in the range of 800-1800 cm-1 can be acquired from gastric tissue within 5 seconds. Raman spectra showed significant differences between normal and dysplastic tissue, particularly in the spectral ranges of 850-900, 1,200-1,290 and 1,500-1,800 cm-1 which contained signals related to hydroxyproline, amide III and amide I of proteins, and C=C stretching of lipids, respectively. The ratio of Raman intensities at 875 to 1,450 cm-1 provided good differentiation between normal and dysplastic gastric tissue (unpaired Students' t -test, p