Seng Khoon Teh

Diagnostic potential of near-infrared Raman spectroscopy in the stomach: differentiating dysplasia from normal tissue

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 dysplasia from normal gastric mucosa tissue. A rapid-acquisition dispersive-type NIR Raman system was utilised for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 76 gastric tissue samples obtained from 44 patients who underwent endoscopy investigation or gastrectomy operation were used in this study. The histopathological examinations showed that 55 tissue specimens were normal and 21 were dysplasia. Both the empirical approach and multivariate statistical techniques, including principal components analysis (PCA), and linear discriminant analysis (LDA), together with the leave-one-sample-out cross-validation method, were employed to develop effective diagnostic algorithms for classification of Raman spectra between normal and dysplastic gastric tissues. High-quality Raman spectra in the range of 800–1800 cm−1 can be acquired from gastric tissue within 5 s. There are specific spectral differences in Raman spectra between normal and dysplasia tissue, particularly in the spectral ranges of 1200–1500 cm−1 and 1600–1800 cm−1, which contained signals related to amide III and amide I of proteins, CH3CH2 twisting of proteins/nucleic acids, and the C=C stretching mode of phospholipids, respectively. The empirical diagnostic algorithm based on the ratio of the Raman peak intensity at 875 cm−1 to the peak intensity at 1450 cm−1 gave the diagnostic sensitivity of 85.7% and specificity of 80.0%, whereas the diagnostic algorithms based on PCA-LDA yielded the diagnostic sensitivity of 95.2% and specificity 90.9% for separating dysplasia from normal gastric tissue. Receiver operating characteristic (ROC) curves further confirmed that the most effective diagnostic algorithm can be derived from the PCA-LDA technique. Therefore, NIR Raman spectroscopy in conjunction with multivariate statistical technique has potential for rapid diagnosis of dysplasia in the stomach based on the optical evaluation of spectral features of biomolecules.

Integrated Raman spectroscopy and trimodal wide-field imaging techniques for real-time in vivo tissue Raman measurements at endoscopy

We report an integrated Raman spectroscopy and trimodal (white-light reflectance, autofluorescence, and narrow-band) imaging techniques for real-time in vivo tissue Raman measurements at endoscopy. A special 1.8 mm endoscopic Raman probe with filtering modules is developed, permitting effective elimination of interference of fluorescence background and silica Raman in fibers while maximizing tissue Raman collections. We demonstrate that high-quality in vivo Raman spectra of upper gastrointestinal tract can be acquired within 1 s or subseconds under the guidance of wide-field endoscopic imaging modalities, greatly facilitating the adoption of Raman spectroscopy into clinical research and practice during routine endoscopic inspections.

Diagnosis of gastric cancer using near-infrared Raman spectroscopy and classification and regression tree techniques.

The purpose of this study is to apply near-infrared (NIR) Raman spectroscopy and classification and regression tree (CART) techniques for identifying molecular changes of tissue associated with cancer transformation. A rapid-acquisition NIR Raman system is utilized for tissue Raman spectroscopic measurements at 785-nm excitation. 73 gastric tissue samples (55 normal, 18 cancer) from 53 patients are measured. The CART technique is introduced to develop effective diagnostic algorithms for classification of Raman spectra of different gastric tissues. 80% of the Raman dataset are randomly selected for spectral learning, while 20% of the dataset are reserved for validation. High-quality Raman spectra in the range of 800 to 1800 cm(-1) are acquired from gastric tissue within 5 s. The diagnostic sensitivity and specificity of the learning dataset are 90.2 and 95.7%; and the predictive sensitivity and specificity of the independent validation dataset are 88.9 and 92.9%, respectively, for separating cancer from normal. The tissue Raman peaks at 875 and 1745 cm(-1) are found to be two of the most significant features to discriminate gastric cancer from normal tissue. NIR Raman spectroscopy in conjunction with the CART technique has the potential to provide an effective and accurate diagnostic means for cancer detection in the gastric system.

Near-infrared Raman spectroscopy for early diagnosis and typing of adenocarcinoma in the stomach

The aim of this study was to evaluate the feasibility of using near‐infrared (NIR) Raman spectroscopy for early diagnosis and typing of intestinal and diffuse adenocarcinoma of the stomach.

In vivo detection of epithelial neoplasia in the stomach using image-guided Raman endoscopy

This study explores the utility of a novel image-guided Raman endoscopy technique for in vivo distinction of gastric cancer from normal tissue during clinical gastroscopy. The rapid-acquisition fiber-optic Raman endoscopy system developed was employed for in vivo gastric tissue Raman measurements at 785 nm laser excitation. A total of 1063 in vivo Raman spectra were acquired from 238 tissue sites of 67 gastric patients who underwent endoscopic ultrasound staging procedure, in which 934 Raman spectra were from 121 normal tissue sites whereas 129 Raman spectra were from 117 neoplastic gastric tissue sites. Gastric Raman spectra were fitted and reconstructed by using a linear combination of the eight basis reference spectra from the biochemicals (i.e., actin, albumin, collagen, DNA, histones, pepsinogen, phospholipids and triolein) in gastric tissue and also compared with the in vivo gastric Raman spectra measured. The resulting fit coefficients were further utilized through recursive partitioning techniques to develop diagnostic algorithms for gastric cancer diagnosis. High-quality in vivo Raman spectra in the range of 800-1800 cm(-1) can be acquired from gastric mucosa within 0.5s. The fit coefficients from albumin, nucleic acid, phospholipids and histones were found to be the most significant features for construction of the diagnostic model, giving rise to an overall accuracy of 93.7% (i.e., sensitivity of 94.0% (110/117) and specificity of 93.4% (113/121)) for in vivo discrimination of cancerous tissue from normal gastric tissue after the leave-one tissue site-out, cross-validation technique. This work demonstrates for the first time that image-guided Raman endoscopy technique has promising potential for the non-invasive, in vivo diagnosis and detection of gastric cancer at the molecular level.

Near-infrared Raman spectroscopy for optical diagnosis in the stomach: identification of Helicobacter-pylori infection and intestinal metaplasia

Raman spectroscopy is a unique vibrational spectroscopic technique which can be used to probe biochemicals and biomolecular structures and conformations of tissues. The main objective of this study is to evaluate the feasibility of applying near‐infrared (NIR) Raman spectroscopy for identification of nonneoplastic lesions (Helicobacter‐pylori (Hp) infection, and intestinal metaplasia (IM)) highly associated with stomach cancer. A rapid‐acquisition NIR Raman spectroscopic system was used for tissue Raman measurements at 785 nm excitation, and a total of 88 gastric tissue samples (57 normal; 11 Hp‐infection; 20 IM) from 56 patients were measured. The principal components analysis (PCA) and linear discriminant analysis (LDA) techniques were implemented to develop effective diagnostic algorithms for classification of Raman spectra of different gastric tissue types. High‐quality Raman spectra in the range of 800‐1800 cm−1 were acquired from gastric tissue within 5 seconds. Significant spectral differences in Raman spectra were observed among normal, Hp‐infection and IM gastric tissue, particularly in the spectral ranges of 848–917, 960–1015, 1088–1133, 1206–1213, 1277–1313, 1395–1445, 1517–1549, 1607–1690, and 1714–1767 cm−1 which contained signals related to proteins, lipids and porphyrin. PCA‐LDA algorithms developed together with leave one patient out, cross validation technique yield diagnostic sensitivities of 91.7%, 80.0%, and 80.0%, and specificities of 80.0%, 100%, and 92.7%, respectively, for classification of normal, Hp‐infection and IM gastric tissues. This work demonstrates the utility of NIR Raman spectroscopy for early diagnosis of Hp‐infection and IM lesions in the gastric at the molecular level.

Image-guided near-infrared Raman spectroscopy for in vivo detection of gastric dysplasia

The purpose of this study was to investigate the feasibility of applying a rapid near-infrared (NIR) Raman endoscopy system coupled with narrow band imaging technique for distinguishing dysplasia from normal gastric mucosa tissue during clinical gastroscopy.

Abstract 1165: Image-guided Raman endoscopy for in vivo clinical detection of cancer in the stomach

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Objective: Raman spectroscopy is a unique optical vibrational spectroscopic technique that is capable of noninvasively probing biomolecular changes associated with cancerous transformation. The aim of this study was to investigate the feasibility of a novel imaged-guided Raman endoscopy system developed for distinguishing cancer lesions from the non-cancerous tissues in the human stomach in vivo. Materials and Methods: A fiber-optic Raman endoscopy system was utilized for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 20 in vivo gastric Raman measurement sites were used in this study, in which 15 sites were from 10 patients who underwent gastroscopic inspection, and 5 were from the suspicious lesion sites of 5 patients who underwent endoscopic ultrasound procedure. The histopathogical examinations on the biopsied tissues from the Raman measurement sites showed that 15 were non-cancerous and 5 were cancers. Multivariate statistical algorithms including principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to determine the diagnostic sensitivity and specificity. Results: High-quality in vivo gastric Raman spectra in the range of 800-1800 cm−1 can be collected in less than 1 second, together with the simultaneous utilization of white-light reflectance imaging modality for guiding the Raman endoscopic probe to the suspicious tissue sites. Raman spectral shapes were significantly different between non-cancerous and cancers, particularly in the spectral ranges of 850-900 cm−1, 1000-1090 cm−1, 1200-1305 cm−1 and 1600-1800 cm−1 which contain signals related to hydroxyproline for collagen, phenylalanine, amide III, amide I and C=C stretching of lipids. The Raman technique together with PCA-LDA-based analytic algorithm yielded diagnostic sensitivity of 96.1% and specificity of 100% for detection of cancer from the non-cancerous gastric tissues in vivo. Conclusion: This study illustrates for the first time that the image-guided Raman endoscopy technique has promising clinical potential for rapid in vivo diagnosis of cancer tissues in the stomach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1165.

Raman spectroscopy for optical diagnosis of laryngeal cancer

In this report, the diagnostic ability of near-infrared (NIR) Raman spectroscopy for identifying the malignant tumors from normal tissues in the larynx was studied. A rapid NIR Raman system was utilized. Multivariate statistical techniques were employed to develop effective diagnostic algorithms. Raman spectra in the range of 800-1,800 cm-1 differed significantly between normal and malignant tumor tissues. The diagnostic algorithms can yielded a diagnostic sensitivity of 92.9% and specificity 83.3% for separating malignant tumors from normal laryngeal tissues. NIR Raman spectroscopy with multivariate statistical techniques has a potential for the non-invasive detection of malignant tumors in the larynx.