Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Microscopic imaging in endoscopy: endomicroscopy and endocytoscopy

Nature Reviews Gastroenterology & Hepatology volume 11, pages 11–18 (2014)Cite this article

Subjects

Key Points

  • Confocal laser endomicroscopy (CLE) and endocytoscopy are two technically different methods to obtain high-resolution microscopic images during ongoing endoscopy

  • Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract and the hepatobiliary-pancreatic system during endoscopy

  • In expert hands, on-site microscopy can be used to minimize sampling error and to guide endoscopic therapy

  • CLE has enabled new insights into pathophysiology by its ability to provide tissue microscopy in its native environment

Abstract

Performing real-time microscopy has been a vision of endoscopists since the very early phases of gastrointestinal endoscopy. Confocal endomicroscopy, an adaption of confocal laser scanning microscopy, and endocytoscopy, an adaption of white-light microscopy, have been introduced into the endoscopic armamentarium in the past decade. Both techniques yield on-site histological information. Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract, and also the hepatobiliary-pancreatic system, during endoscopy. Such microscopic information has been successfully used in expert hands to minimize sampling error by 'smart', microscopically targeted biopsies and to guide endoscopic interventions. However, endomicroscopy is also unique in its ability to dynamically visualize cellular processes in their native environment free of artefacts. This ability enables fundamental insights into mechanisms of human diseases in clinical and translational science.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Endomicroscopy of the colon with eCLE.
Figure 2: Endomicroscopy of the colon with pCLE.
Figure 3: Endomicroscopy of Barrett oesophagus.
Figure 4: Endomicroscopy of the stomach.
Figure 5: Magnification endoscopy and endocytoscopy of the colon.

Similar content being viewed by others

References

  1. Kudo, S. et al. Diagnosis of colorectal tumorous lesions by magnifying endoscopy. Gastrointest. Endosc. 44, 8–14 (1996).

    Article  CAS  Google Scholar 

  2. Brown, S. R., Baraza, W. & Hurlstone, P. Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database of Systematic Reviews. Issue 1. Art. No.: CD006439 http://dx.doi.org/10.1002/14651858.CD006439.pub2.

  3. Murthy, S., Goetz, M., Hoffman, A. & Kiesslich, R. Novel colonoscopic imaging. Clin. Gastroenterol. Hepatol. 10, 984–987 (2012).

    Article  Google Scholar 

  4. Hoffman, A. et al. High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial. Endoscopy 42, 827–833 (2010).

    Article  CAS  Google Scholar 

  5. Goetz, M. Molecular imaging in GI endoscopy. Gastrointest. Endosc. 76, 1207–1209 (2012).

    Article  Google Scholar 

  6. Mahmood, U. Optical molecular imaging approaches in colorectal cancer. Gastroenterology 138, 419–422 (2010).

    Article  CAS  Google Scholar 

  7. Wallace, M. B. & Fockens, P. Probe-based confocal laser endomicroscopy. Gastroenterology 136, 1509–1513 (2009).

    Article  Google Scholar 

  8. Kiesslich, R., Goetz, M., Vieth, M., Galle, P. R. & Neurath, M. F. Technology insight: confocal laser endoscopy for in vivo diagnosis of colorectal cancer. Nat. Clin. Pract. Oncol. 4, 480–490 (2007).

    Article  Google Scholar 

  9. De Palma, G. D. & Wallace, M. B., Giovannini, M. Confocal laser endomicroscopy. Gastroenterol. Res. Pract. 2012, 216209 (2012).

    Article  Google Scholar 

  10. Goetz, M., Watson, A. & Kiesslich, R. Confocal laser endomicroscopy in gastrointestinal diseases. J. Biophotonics 4, 498–508 (2011).

    Article  Google Scholar 

  11. Neumann, H. et al. Review article: in vivo imaging by endocytoscopy. Aliment. Pharmacol. Ther. 33, 1183–1193 (2011).

    Article  CAS  Google Scholar 

  12. Buchner, A. M. et al. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138, 834–842 (2010).

    Article  Google Scholar 

  13. Kudo, S. E. et al. Diagnosis of colorectal lesions with a novel endocytoscopic classification—a pilot study. Endoscopy 43, 869–875 (2011).

    Article  Google Scholar 

  14. Kodashima, S. et al. Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy. Endoscopy 38, 1115–1121 (2006).

    Article  CAS  Google Scholar 

  15. Wallace, M. B. et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment. Pharmacol. Ther. 31, 548–552 (2010).

    Article  CAS  Google Scholar 

  16. Kiesslich, R. et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127, 706–713 (2004).

    Article  Google Scholar 

  17. Polglase, A. L. et al. A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest. Endosc. 62, 686–695 (2005).

    Article  Google Scholar 

  18. Goetz, M. et al. Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet. Gastrointest. Endosc. 70, 959–968 (2009).

    Article  Google Scholar 

  19. Kiesslich, R. et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127, 706–713 (2004).

    Article  Google Scholar 

  20. Goetz, M. et al. Near-infrared confocal imaging during mini-laparoscopy: a novel rigid endomicroscope with increased imaging plane depth. J. Hepatol. 53, 84–90 (2010).

    Article  Google Scholar 

  21. Dunbar, K. B., Montgomery, E. A. & Canto, M. I. The learning curve of in vivo confocal laser endomicroscopy for prediction of Barrett's esophagus [abstract]. Gastroenterology 134 (Suppl. 1), A62–A63 (2008).

    Google Scholar 

  22. Kiesslich, R. et al. Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology 132, 874–882 (2007).

    Article  Google Scholar 

  23. Sanduleanu, S. et al. A. In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. Clin. Gastroenterol. Hepatol. 8, 371–378 (2010).

    Article  Google Scholar 

  24. Kuiper, T. et al. New classification for probe-based confocal laser endomicroscopy in the colon. Endoscopy 43, 1076–1081 (2011).

    Article  CAS  Google Scholar 

  25. Kiesslich, R. et al. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin. Gastroenterol. Hepatol. 4, 979–987 (2006).

    Article  Google Scholar 

  26. Dunbar, K. B., Okolo, P. 3rd, Montgomery, E. & Canto, M. I. Confocal laser endomicroscopy in Barrett's esophagus and endoscopically inapparent Barrett's neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest. Endosc. 70, 645–654 (2009).

    Article  Google Scholar 

  27. Pohl, H. et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett's oesophagus. Gut 57, 1648–1653 (2008).

    Article  CAS  Google Scholar 

  28. Bajbouj, M. et al. Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus. Endoscopy 42, 435–440 (2010).

    Article  CAS  Google Scholar 

  29. Wang, P. et al. Classification of histological severity of Helicobacter pylori-associated gastritis by confocal laser endomicroscopy. World J. Gastroenterol. 16, 5203–5210 (2010).

    Article  Google Scholar 

  30. Kiesslich, R. et al. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology 128, 2119–2123 (2005).

    Article  Google Scholar 

  31. Guo, Y. T. et al. Diagnosis of gastric intestinal metaplasia with confocal laser endomicroscopy in vivo: a prospective study. Endoscopy 40, 547–553 (2008).

    Article  Google Scholar 

  32. Li, W. B. et al. Characterization and identification of gastric hyperplastic polyps and adenomas by confocal laser endomicroscopy. Surg. Endosc. 24, 517–524 (2010).

    Article  Google Scholar 

  33. Li, W. B. et al. Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions. Gut 60, 299–306 (2011).

    Article  Google Scholar 

  34. Ji, R., Zuo, X. L., Li, C. Q., Zhou, C. J. & Li, Y. Q. Confocal endomicroscopy for in vivo prediction of completeness after endoscopic mucosal resection. Surg. Endosc. 25, 1933–1938 (2011).

    Article  Google Scholar 

  35. Jeon, S. R. et al. Optical biopsies by confocal endomicroscopy prevent additive endoscopic biopsies before endoscopic submucosal dissection in gastric epithelial neoplasias: a prospective, comparative study. Gastrointest. Endosc. 74, 772–780 (2011).

    Article  Google Scholar 

  36. Buchner, A. M. et al. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138, 834–842 (2010).

    Article  Google Scholar 

  37. Shahid, M. W. et al. Diagnostic accuracy of probe-based confocal laser endomicroscopy in detecting residual colorectal neoplasia after EMR: a prospective study. Gastrointest. Endosc. 75, 525–533 (2012).

    Article  Google Scholar 

  38. Kuiper, T., van den Broek, F. J., van Eeden, S., Fockens, P. & Dekker, E. Feasibility and accuracy of confocal endomicroscopy in comparison with narrow-band imaging and chromoendoscopy for the differentiation of colorectal lesions. Am. J. Gastroenterol. 107, 543–550 (2012).

    Article  CAS  Google Scholar 

  39. Meining, A. et al. Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy. Clin. Gastroenterol. Hepatol. 6, 1057–1060 (2008).

    Article  Google Scholar 

  40. Loeser, C. S., Robert, M. E., Mennone, A., Nathanson, M. H. & Jamidar, P. Confocal endomicroscopic examination of malignant biliary strictures and histologic correlation with lymphatics. J. Clin. Gastroenterol. 45, 246–252 (2011).

    Article  Google Scholar 

  41. Talreja, J. P. et al. Interpretation of probe-based confocal laser endomicroscopy of indeterminate biliary strictures: is there any interobserver agreement? Dig. Dis. Sci. 57, 3299–3302 (2012).

    Article  Google Scholar 

  42. Meining, A. et al. Classification of probe-based confocal laser endomicroscopy findings in pancreaticobiliary strictures. Endoscopy 44, 251–257 (2012).

    Article  CAS  Google Scholar 

  43. Konda, V. J. et al. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest. Endosc. 74, 1049–1060 (2011).

    Article  Google Scholar 

  44. Inoue, H. et al. Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial. Endoscopy 38, 891–895 (2006).

    Article  CAS  Google Scholar 

  45. Kumagai, Y. et al. Endocytoscopic observation for esophageal squamous cell carcinoma: can biopsy histology be omitted? Dis. Esophagus 22, 505–512 (2009).

    Article  CAS  Google Scholar 

  46. Sasajima, K. et al. Real-time in vivo virtual histology of colorectal lesions when using the endocytoscopy system. Gastrointest. Endosc. 63, 1010–1017 (2006).

    Article  Google Scholar 

  47. Kudo, S. E. et al. Diagnosis of colorectal lesions with a novel endocytoscopic classification—a pilot study. Endoscopy 43, 869–875 (2011).

    Article  Google Scholar 

  48. Mori, Y. et al. Comprehensive diagnostic ability of endocytoscopy compared with biopsy for colorectal neoplasms: a prospective randomized noninferiority trial. Endoscopy 45, 98–105 (2013).

    Article  CAS  Google Scholar 

  49. Goetz, M., Ansems, J. V., Galle, P. R., Schuchmann, M. & Kiesslich, R. In vivo real-time imaging of the liver with confocal endomicroscopy permits visualization of the temporospatial patterns of hepatocyte apoptosis. Am. J. Physiol. Gastrointest. Liver Physiol. 301, G764–G772 (2011).

    Article  CAS  Google Scholar 

  50. Bojarski, C. et al. In vivo diagnosis of acute intestinal graft-versus-host disease by confocal endomicroscopy. Endoscopy 41, 433–438 (2009).

    Article  CAS  Google Scholar 

  51. Watson, A. J. et al. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 129, 902–912 (2005).

    Article  Google Scholar 

  52. Kiesslich, R. et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 133, 1769–1778 (2007).

    Article  Google Scholar 

  53. Liu, J. J. et al. Mind the gaps: confocal endomicroscopy showed increased density of small bowel epithelial gaps in inflammatory bowel disease. J. Clin. Gastroenterol. 45, 240–245 (2011).

    Article  Google Scholar 

  54. Liu, J. J. et al. Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest. Endosc. 73, 1174–1180 (2011).

    Article  Google Scholar 

  55. Kiesslich, R. et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 61, 1146–1153 (2012).

    Article  CAS  Google Scholar 

  56. Moussata, D. et al. Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo. Gut 60, 26–33 (2011).

    Article  Google Scholar 

  57. Lim, L. G. et al. A. Confocal endomicroscopy in the evaluation of gastric and duodenal epithelial gaps in patients with Crohn's disease and ulcerative colitis [abstract]. Gut 59 (Suppl. 3) A261 (2010).

    Google Scholar 

  58. Turcotte, J. F. et al. Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointest. Endosc. 77, 624–630 (2013).

    Article  Google Scholar 

  59. Meining, A. & Wallace, M. B. Endoscopic imaging of angiogenesis in vivo. Gastroenterology 134, 915–918 (2008).

    Article  Google Scholar 

  60. Ji, R. et al. Mucosal barrier defects in gastric intestinal metaplasia: in vivo evaluation by confocal endomicroscopy. Gastrointest. Endosc. 75, 980–987 (2012).

    Article  Google Scholar 

  61. Lin, K. Y., Maricevich, M., Bardeesy, N., Weissleder, R. & Mahmood, U. In vivo quantitative microvasculature phenotype imaging of healthy and malignant tissues using a fiber-optic confocal laser microprobe. Transl. Oncol. 1, 84–94 (2008).

    Article  Google Scholar 

  62. Tous, R. et al. The anatomy of an optical biopsy semantic retrieval system. IEEE MultiMedia 19, 16–27 (2012).

    Article  Google Scholar 

  63. Rex, D. K. et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest. Endosc. 73, 419–422 (2011).

    Article  Google Scholar 

  64. Atrya, R. & Goetz, M. Molecular imaging in gastroenterology. Nat. Rev. Gastroenterol. Hepatol. http://dx.doi.org/10.1038/nrgastro.2013.123.

Download references

Author information

Authors and Affiliations

  1. Innere Medizin I, Universitätsklinikum Tübingen, Otfried-Müller-Straße 10, Tübingen, 72076, Germany

    Martin Goetz & Nisar P. Malek

  2. St. Marienkrankenhaus, Richard-Wagner-Straße 14, Frankfurt, 60318, Germany

    Ralf Kiesslich

Authors
  1. Martin Goetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nisar P. Malek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ralf Kiesslich
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M. Goetz contributed to all aspects of this manuscript. N. P. Malek made a substantial contribution to discussion of content and reviewed/editing the manuscript before submission. R. Kiesslich researched data for the article, made a substantial contribution to discussion of content, and reviewed/editing the manuscript before submission.

Corresponding author

Correspondence to Martin Goetz.

Ethics declarations

Competing interests

M. Goetz receives research support from Pentax and Optiscan. R. Kiesslich receives research support from Pentax. N. Malek declares no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goetz, M., Malek, N. & Kiesslich, R. Microscopic imaging in endoscopy: endomicroscopy and endocytoscopy. Nat Rev Gastroenterol Hepatol 11, 11–18 (2014). https://doi.org/10.1038/nrgastro.2013.134

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2013.134

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing