Image-Guided Raman Endoscopic Probe for In Vivo Early Detection of High Grade Dysplasia

Abstract

Objective: Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically detecting the biomolecular changes associated with diseased transformation. We have designed a rapid-acquisition dispersive-type near infrared (NIR) Raman system equipped with a specially designed Raman endoscopic probe which can be passed through the instrument channel of conventional endoscopes to acquire tissue Raman spectroscopic measurements at 785 nm laser excitation during endoscopy. The purpose of this study was to investigate the feasibility of applying this prototype for distinguishing high grade dysplasia from normal gastric mucosa tissues in vivo at endoscopy. Materials and Methods: A total of 24 in vivo tissue Raman spectra were acquired from different sites of the gastric antrum, in which 17 were from 4 patients who underwent endoscopic inspection for gastric cancer surveillance and 7 were from 1 patient who underwent endoscopic submucosal dissection (ESD). Histopathogical examinations of biopsy specimens obtained from the scanned sites of the 4 surveillance patients showed normal findings, while the dissected specimen from the ESD confirmed high grade dysplasia. Results: High-quality Raman spectra in the range of 800-1800 cm-1 were collected from in vivo gastric tissues 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 normal and dysplasia, particularly in the spectral ranges of 850-900 cm-, 1000-1090 cm-, 1200-1305 cm- and 1600-1800 cm-, which contain signals related to hydroxyproline for collagen, phenylalanine, amide III, amide I and C=C stretching of lipids. The ratio of Raman intensities at 1450 to 1655 cm- provided a diagnostic sensitivity of 100%, specificity of 82.4% for identifying dysplasia from normal gastric tissues. The intensity ratio-based diagnostic algorithm achieved an integration area under the receiver operating characteristics curve of 0.9, confirming the diagnostic potential of near-infrared Raman spectroscopy for in vivo gastric dysplasia detection. Conclusion: This is the first in vivo Raman endoscopic spectroscopy in conjunction with white-light reflectance imaging to be used for distinguishing dysplasia from normal gastric mucosal tissues in real-time. This study suggests that near-infrared Raman technique may be a clinically useful endoscopic tool for in vivo detection and diagnosis of precancerous lesions in human stomach.