In vivo detection of experimental ulcerative colitis in rats using fiberoptic confocal imaging (FOCI)

Fiberoptic confocal imaging (FOCI) is a noninvasive microscopic technique t hat enables subsurface imaging of living tissue in vivo. The aim of the pre sent study was to assess the suitability of FOCI for the in vivo detection of early subsurface changes in the mucosal architecture of the colon in a r at model of ulcerative colitis. Mild colitis was induced in Sprague-Dawley rats (180-250 g) by the oral ingestion of 5% (w/v) dextran sulfate sodium ( DSS; Mr 40,000 Da) in drinking water. Control animals were provided with wa ter ad libitum. After three, five or seven days of oral consumption of DSS, the mucosal surface of the colon of anesthetised rats was surgically expos ed. Morphological changes in the mucosa were examined (Optiscan F900e perso nal confocal system with rigid endomicroscope attachment; excitation 488 nm argon ion laser, detection above 515 nm) following the topical application of a fluorescent dye (fluorescein, eosin, or acridine orange). Confocal im ages were correlated with conventional histology and clinical parameters in cluding occult blood and stool consistency. Histological evaluation of colo n sections demonstrated that DSS-induced colitis was characterized by focal loss of mucous crypts, loss of epithelial cells, and neutrophilic infiltra tion into the mucosa. The extent of mucosal damage was positively correlate d with the time of ingestion of DSS. Morphological changes associated with disease activity could be detected microscopically in vivo using FOCI but w ere not evident by visual inspection of the colon surface. Acridine orange enabled imaging of the colonic crypts at the surface of the mucosa. Morphol ogical changes associated with colitis, including inflammatory cell infiltr ate, crypt loss, and crypt distortion, could be detected using this fluorop hore. Application of fluorescein and eosin enabled subsurface imaging of th e lamina propria surrounding the crypts; however, no change in structure wa s detected in association with colitic disease activity. This study has sho wn that the topical application of acridine orange enables in vivo imaging of early colitis in a rat model. FOCI may be suitable for the diagnosis and monitoring of human inflammatory bowel disease.