Digestive Diseases and Sciences

, Volume 47, Issue 11, pp 2424–2433 | Cite as

In Vivo Detection of Morphological and Microvascular Changes of the Colon in Association with Colitis Using Fiberoptic Confocal Imaging (FOCI)

  • Wendy J. McLaren
  • Peter Anikijenko
  • Steven G. Thomas
  • Peter M. Delaney
  • Roger G. King


Using a well-established rodent model of inflammatory bowel disease (IBD), the present study examined changes in the microvasculature of the colonic mucosa in association with ulcerative colitis (UC). The results were compared to microscopic alterations in tissue morphology to establish a temporal relationship between microcirculatory dysfunction and IBD pathology. Mild colitis was induced in rats by the oral consumption of 5% dextran sulfate sodium (DSS) in drinking water. Control animals were provided with water ad libitum. After 3, 5, and 7 days of oral ingestion of DSS, anesthetized rats were laparotomized. The mucosal surface of the distal colon was then examined using fiber optic confocal imaging (FOCI; excitation 488 nm argon ion laser, detection above 515 nm). Changes in the mucosal architecture were examined following the topical application of the fluorescent dye, tetracycline hydrochloride. Tetracycline hydrochloride, an antibiotic used widely in clinical medicine, enabled imaging of the crypts at the surface of the mucosa. Spatial changes in the microvascular structure were assessed following the intravenous administration of fluorescein isothiocyanate dextran (FITC-dextran). Confocal images were correlated with clinical parameters, including weight loss, occult blood, and stool consistency. Attenuation of the colonic epithelium was detected on day 3 colitis. Morphological changes including crypt loss, crypt distortion, and inflammatory cell infiltrate were detected on day 5 and day 7 colitis. Dual channel imaging showed the mucosal capillary network outlining the stromal confines of the mucus-secreting glands in control tissue. Experimental colitis resulted in diffuse hypervascularity and tortuosity of the capillary vessels. Evidence of increased vessel leakiness (leakage of FITC-dextran from the lumen) was first detected on day 5 colitis. Complete disruption of the normal honeycomb pattern of the vessels and capillary dilation was evident after 7 days of DSS ingestion. These findings suggest that the pathogenesis of ulcerative colitis is associated with changes in the vascular architecture as demonstrated in vivo using confocal microscopy.

fiber optic confocal imaging colitis crypt microvasculature dextran sulfate sodium 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Deckelbaum LI, Lam JK, Cabin HS, Clubb KS, Long MB: Discrimination of normal and atherosclerotic aorta by laserinduced fluorescence. Lasers Surg Med 7(4):330–335, 1987Google Scholar
  2. 2.
    Wang TD, Crawford JM, Feld MS, Wang Y, Itzkan I, Van Dam J: In vivo identification of colonic dysplasia using fluorescence endoscopic imaging. Gastrointest Endosc 49:447–455, 1999Google Scholar
  3. 3.
    Fiarman GS, Nathanson MH, West AB, Deckelbaum LI, Kelly L, Kapadia CR: Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy. Dig Dis Sci 40(6):1261–1268, 1995Google Scholar
  4. 4.
    Davies RJH: Ultraviolet radiation damage in DNA. Biochem Soc Trans 23:407–418, 1995Google Scholar
  5. 5.
    McLaren WJ, Anikijenko P, Barkla DH, Delaney PM, King RG: In vivo detection of experimental ulcerative colitis in rats using fibre-optic confocal imaging (FOCI). Dig Dis Sci 46(10):2263–2276, 2001Google Scholar
  6. 6.
    Araki K, Furuya Y, Kobayashi M, Matsuura K, Ogata T, Isozaki H: Comparison of mucosal microvasculature between the proximal and distal human colon. J Electron Microsc 45:202–206, 1996Google Scholar
  7. 7.
    Papworth GD, Delaney PM, Bussau LJ, Vo LT, King RG: In vivo fibre optic confocal imaging of microvasculature and nerves in the rat vas deferens and colon. J Anat 192(4):489–495, 1998Google Scholar
  8. 8.
    Murthy SNS, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ: Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci 38(9):1722–1734, 1993Google Scholar
  9. 9.
    Browning J, Gannon B: Mucosal microvascular organisation of the rat colon. Acta Anat 126:73–77, 1986Google Scholar
  10. 10.
    Skinner SA, O'Brien PE: The microvascular structure of the normal colon in rats and humans. J Surg Res 61:482–490, 1996Google Scholar
  11. 11.
    Cooper HS, Murthy SNS, Shah RS, Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69(2):238–249, 1993Google Scholar
  12. 12.
    Foitzik T, Kruschewski M, Kroesen A, Buhr HJ: Does microcirculation play a role in the pathogenesis of inflammatory bowel diseases? Int J Color Dis 14:29–34, 1999Google Scholar
  13. 13.
    Donnellan WL: Early histological changes in ulcerative colitis. A light and electron microscopy study. Gastroenterology 50(4):519–540, 1968Google Scholar
  14. 14.
    Busch C, Gawad KA, Prenzel KL, Knoefel WT, Izbicki JR, Broelsch CE: Angioarchitecture of the terminal vascular system in inflammatory bowel disease–a comparative corrosionanatomic study. Scanning 18:385–389, 1996Google Scholar
  15. 15.
    Leung FW, Koo A: Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. Dig Dis Sci 36(6):727–732, 1991Google Scholar
  16. 16.
    Edwards FC, Truelove SC: The course and prognosis of ulcerative colitis, part III–complications. Gut 5:1–15, 1964Google Scholar
  17. 17.
    Wakefield AJ, Sankey EA, Dhillon AP, Sawyerr AM, More L, Sim R, Pittilo RM, Rowles PM, Hudson M, Lewis AA: Granulomatous vasculitis in Crohn's disease. Gastroenterology 100(5 Pt 1):1279–1287, 1991Google Scholar
  18. 18.
    Franzeck UK, Munch R, Wachter M, Vesti B, Ammann R, Bollinger A: Dynamic fluorescence video endoscopy for intravital evaluation of gastrointestinal mucosal blood flow. Gastrointest Endosc 39(6):806–809, 1993Google Scholar
  19. 19.
    Maunoury V, Mordon S, Klein O, Colombel JF: Fluorescence endoscopic imaging study of anastomotic recurrence of Crohn's disease. Gastrointest Endosc 43(6):603–604, 1996Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Wendy J. McLaren
    • 1
  • Peter Anikijenko
    • 2
  • Steven G. Thomas
    • 2
  • Peter M. Delaney
    • 2
  • Roger G. King
    • 1
  1. 1.Department of PharmacologyMonash UniversityClaytonAustralia
  2. 2.Optiscan Imaging LtdNotting HillAustralia

Personalised recommendations