Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Confocal laser endomicroscopy and endocytoscopy

Alexander Meining, MD
Section Editor
John R Saltzman, MD, FACP, FACG, FASGE, AGAF
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF


Confocal laser endomicroscopy and endocytoscopy are emerging endoscopic technologies that permit high-resolution assessment of gastrointestinal mucosal histology at a cellular and sub-cellular level. Endomicroscopy and endocytoscopy dramatically expand the imaging capabilities of flexible endoscopy by their ability to obtain "optical biopsies" of nearly any accessible endoluminal surface.

The examinations are carried out in vivo with real-time image display. The techniques have primarily been applied to the differentiation of colon polyps and for the detection of dysplasia and neoplasia in conditions such as Barrett's esophagus and ulcerative colitis. Since the first visible neoplastic changes in epithelial cancers occur at a cellular level, these imaging techniques may allow for earlier diagnosis and treatment. In addition, confocal laser endomicroscopy and endocytoscopy may allow for targeted biopsies of abnormal mucosa, thereby decreasing the number of biopsies required to diagnose dysplasia or neoplasia while increasing diagnostic yield.

This topic will review confocal laser endomicroscopy and endocytoscopy, including the technical aspects of the procedures, their indications, and efficacies. Chromoendoscopy, magnification endoscopy, optical coherence tomography, narrow band imaging, and autofluorescence endoscopy are discussed elsewhere. (See "Chromoendoscopy" and "Magnification endoscopy" and "Optical coherence tomography in the gastrointestinal tract" and "Barrett's esophagus: Evaluation with narrow band imaging" and "Barrett's esophagus: Evaluation with autofluorescence endoscopy".)


Confocal laser endomicroscopy — Confocal laser endomicroscopy (CLE) is based upon the principle of illuminating a tissue with a low-power laser and then detecting fluorescent light reflected from the tissue [1]. The laser is focused at a specific depth and only light reflected back from that plane is refocused and able to pass through the pinhole confocal aperture. As a result, scattered light from above and below the plane of interest is not detected, increasing spacial resolution. The area being examined is scanned in the horizontal and vertical planes and an image is reconstructed. In this manner, microscopic imaging of biological tissue in vivo is possible due to the high lateral resolution of confocal imaging.

Since CLE relies upon tissue fluorescence, intravenous and/or topically applied contrast agents are required. Intravenous fluorescein is used to highlight the vasculature, lamina propria, and intracellular spaces of this tissue being examined. However, it does not stain cell nuclei. Nuclear staining can be achieved using topical contrast agents such as acriflavine and cresyl violet, but there is concern over mutagenic potential with the topical agents. (See 'Adverse events' below.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Mar 9, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. ASGE Technology Committee. Confocal laser endomicroscopy. Gastrointest Endosc 2014; 80:928.
  2. Meining A, Frimberger E, Becker V, et al. Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy. Clin Gastroenterol Hepatol 2008; 6:1057.
  3. Chen Y, Shah R, Douglas K, et al. Miami Classification (MC) of Probe-Based Confocal Laser Endomicroscopy (pCLE) Findings in the Pancreaticobiliary (PB) System for Evaluation of Indeterminate Strictures: Interim Results From an International Multicenter Registry (Abstract). Gastrointestinal Endosc 2010; 71:AB134.
  4. Wallace MB, Fockens P. Probe-based confocal laser endomicroscopy. Gastroenterology 2009; 136:1509.
  5. Inoue H, Kazawa T, Sato Y, et al. In vivo observation of living cancer cells in the esophagus, stomach, and colon using catheter-type contact endoscope, "Endo-Cytoscopy system". Gastrointest Endosc Clin N Am 2004; 14:589.
  6. Eberl T, Jechart G, Probst A, et al. Can an endocytoscope system (ECS) predict histology in neoplastic lesions? Endoscopy 2007; 39:497.
  7. Inoue H, Yokoyama A, Kudo SE. [Ultrahigh magnifying endoscopy: development of CM double staining for endocytoscopy and its safety]. Nihon Rinsho 2010; 68:1247.
  8. Sasajima K, Kudo SE, Inoue H, et al. Real-time in vivo virtual histology of colorectal lesions when using the endocytoscopy system. Gastrointest Endosc 2006; 63:1010.
  9. Inoue H, Sasajima K, Kaga M, et al. Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial. Endoscopy 2006; 38:891.
  10. Becker V, von Delius S, Bajbouj M, et al. Intravenous application of fluorescein for confocal laser scanning microscopy: evaluation of contrast dynamics and image quality with increasing injection-to-imaging time. Gastrointest Endosc 2008; 68:319.
  11. Kiesslich R, Burg J, Vieth M, et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 2004; 127:706.
  12. Polglase AL, McLaren WJ, Skinner SA, et al. A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest Endosc 2005; 62:686.
  13. Becker V, Wallace MB, Fockens P, et al. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc 2010; 71:1260.
  14. Konda VJ, Meining A, Jamil LH, et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy 2013; 45:1006.
  15. Thiberville L, Salaün M, Lachkar S, et al. Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy. Eur Respir J 2009; 33:974.
  16. Ohigashi T, Kozakai N, Mizuno R, et al. Endocytoscopy: novel endoscopic imaging technology for in-situ observation of bladder cancer cells. J Endourol 2006; 20:698.
  17. Sonn GA, Jones SN, Tarin TV, et al. Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy. J Urol 2009; 182:1299.
  18. Kiesslich R, Goetz M, Burg J, et al. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology 2005; 128:2119.
  19. Matysiak-Budnik T, Coron E, Mosnier JF, et al. In vivo real-time imaging of human duodenal mucosal structures in celiac disease using endocytoscopy. Endoscopy 2010; 42:191.
  20. Günther U, Daum S, Heller F, et al. Diagnostic value of confocal endomicroscopy in celiac disease. Endoscopy 2010; 42:197.
  21. Leong RW, Nguyen NQ, Meredith CG, et al. In vivo confocal endomicroscopy in the diagnosis and evaluation of celiac disease. Gastroenterology 2008; 135:1870.
  22. Pohl H, Rösch T, Tanczos BT, et al. Endocytoscopy for the detection of microstructural features in adult patients with celiac sprue: a prospective, blinded endocytoscopy-conventional histology correlation study. Gastrointest Endosc 2009; 70:933.
  23. Kiesslich R, Goetz M, Neurath MF. Confocal laser endomicroscopy for gastrointestinal diseases. Gastrointest Endosc Clin N Am 2008; 18:451.
  24. Trovato C, Sonzogni A, Ravizza D, et al. Celiac disease: in vivo diagnosis by confocal endomicroscopy. Gastrointest Endosc 2007; 65:1096.
  25. Zambelli A, Villanacci V, Buscarini E, et al. Confocal laser endomicroscopy in celiac disease: description of findings in two cases. Endoscopy 2007; 39:1018.
  26. Pohl H, Tanczos BT, Rudolph B, et al. Probe-based confocal laser microscopy identifies criteria predictive of active celiac sprue. Dig Dis Sci 2012; 57:451.
  27. Meining A, Schwendy S, Becker V, et al. In vivo histopathology of lymphocytic colitis. Gastrointest Endosc 2007; 66:398.
  28. Kiesslich R, Hoffman A, Goetz M, et al. In vivo diagnosis of collagenous colitis by confocal endomicroscopy. Gut 2006; 55:591.
  29. Meining A, Saur D, Bajbouj M, et al. In vivo histopathology for detection of gastrointestinal neoplasia with a portable, confocal miniprobe: an examiner blinded analysis. Clin Gastroenterol Hepatol 2007; 5:1261.
  30. Pohl H, Rösch T, Vieth M, et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett's oesophagus. Gut 2008; 57:1648.
  31. Wallace MB, Sharma P, Lightdale C, et al. Preliminary accuracy and interobserver agreement for the detection of intraepithelial neoplasia in Barrett's esophagus with probe-based confocal laser endomicroscopy. Gastrointest Endosc 2010; 72:19.
  32. Bajbouj M, Vieth M, Rösch T, et al. Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus. Endoscopy 2010; 42:435.
  33. Kiesslich R, Gossner L, Goetz M, et al. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol 2006; 4:979.
  34. Badreddine R, Wang K, Ganapathy A, et al. Confocal laser microscopy (CLM) guided endoscopic mucosal resection in Barrett's esophagus with high grade dysplasia. Gastrointest Endosc 2008; 67:AB179.
  35. Sharma P, Meining AR, Coron E, et al. Real-time increased detection of neoplastic tissue in Barrett's esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial. Gastrointest Endosc 2011; 74:465.
  36. Jayasekera C, Taylor AC, Desmond PV, et al. Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett's esophagus neoplasia. Endoscopy 2012; 44:1089.
  37. Canto MI, Anandasabapathy S, Brugge W, et al. In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc 2014; 79:211.
  38. Wallace MB, Crook JE, Saunders M, et al. Multicenter, randomized, controlled trial of confocal laser endomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barrett's esophagus. Gastrointest Endosc 2012; 76:539.
  39. Kitabatake S, Niwa Y, Miyahara R, et al. Confocal endomicroscopy for the diagnosis of gastric cancer in vivo. Endoscopy 2006; 38:1110.
  40. Kakeji Y, Yamaguchi S, Yoshida D, et al. Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study. Endoscopy 2006; 38:886.
  41. Zhang JN, Li YQ, Zhao YA, et al. Classification of gastric pit patterns by confocal endomicroscopy. Gastrointest Endosc 2008; 67:843.
  42. Bok GH, Jeon SR, Cho JY, et al. The accuracy of probe-based confocal endomicroscopy versus conventional endoscopic biopsies for the diagnosis of superficial gastric neoplasia (with videos). Gastrointest Endosc 2013; 77:899.
  43. Li WB, Zuo XL, Li CQ, et al. Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions. Gut 2011; 60:299.
  44. Jeon SR, Cho WY, Jin SY, 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 2011; 74:772.
  45. Buchner AM, Shahid MW, Heckman MG, et al. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 2010; 138:834.
  46. Buchner AM, Ghabril MS, Krishna M. High-resolution confocal endomicroscopy probe system for in vivo diagnosis of colorectal neoplasia. Gastroenterol 2008; 135:AB295.
  47. Hurlstone DP, Baraza W, Brown S, et al. In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia. Br J Surg 2008; 95:636.
  48. Kuiper T, van den Broek FJ, van Eeden S, et al. New classification for probe-based confocal laser endomicroscopy in the colon. Endoscopy 2011; 43:1076.
  49. Li CQ, Xie XJ, Yu T, et al. Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy. Am J Gastroenterol 2010; 105:1391.
  50. Kiesslich R, Goetz M, Lammersdorf K, et al. Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology 2007; 132:874.
  51. Hurlstone DP, Thomson M, Brown S, et al. Confocal endomicroscopy in ulcerative colitis: differentiating dysplasia-associated lesional mass and adenoma-like mass. Clin Gastroenterol Hepatol 2007; 5:1235.
  52. Meining A, Chen YK, Pleskow D, et al. Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience. Gastrointest Endosc 2011; 74:961.
  53. Slivka A, Gan I, Jamidar P, et al. Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study. Gastrointest Endosc 2015; 81:282.
  54. Napoléon B, Lemaistre AI, Pujol B, et al. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy 2015; 47:26.
  55. Konda VJ, Koons A, Siddiqui UD, et al. Optical biopsy approaches in Barrett's esophagus with next-generation optical coherence tomography. Gastrointest Endosc 2014; 80:516.
  56. Dunbar KB, Kiesslich R, Deiner K, et al. Confocal Laser Endomicroscopy Image Interpretation: Interobserver Agreement Among Gastroenterologists and Pathologists. Gastrointest Endosc 2007; 65:AB348.
  57. Kuiper T, Kiesslich R, Ponsioen C, et al. The learning curve, accuracy, and interobserver agreement of endoscope-based confocal laser endomicroscopy for the differentiation of colorectal lesions. Gastrointest Endosc 2012; 75:1211.
  58. Dunbar KB, Montgomer EA, Canto MI. The Learning Curve of In Vivo Confocal Laser Endomicroscopy for Prediction. Gastroenterol 2008; 134:A62.
  59. Kiesslich R, Anagnostopoulos G, Axon A, et al. Interobserver Variation and Standardized Training for Confocal Laser Endomicroscopy Image Interpretation in the Upper and Lower GI Tract. Gastrointest Endosc 2007; 65:AB354.
  60. Kimura S, Inoue H, Sato Y, et al. Ex vivo visualization of Helicobacter pylori using an endocytoscopic probe. Biomed Res 2006; 27:255.
  61. Yan BM, Van Dam J. In vivo real-time endocytoscopic visualization of blood flow in rectal microvasculature. Endoscopy 2008; 40:534.
  62. Pohl H, Koch M, Khalifa A, et al. Evaluation of endocytoscopy in the surveillance of patients with Barrett's esophagus. Endoscopy 2007; 39:492.
  63. Kaise M, Ohkura Y, Iizuka T, et al. Endocytoscopy is a promising modality with high diagnostic accuracy for gastric cancer. Endoscopy 2015; 47:19.
  64. Mori Y, Kudo S, Ikehara N, et al. Comprehensive diagnostic ability of endocytoscopy compared with biopsy for colorectal neoplasms: a prospective randomized noninferiority trial. Endoscopy 2013; 45:98.
  65. Wallace MB, Meining A, Canto MI, et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 2010; 31:548.
  66. Olliver JR, Wild CP, Sahay P, et al. Chromoendoscopy with methylene blue and associated DNA damage in Barrett's oesophagus. Lancet 2003; 362:373.
  67. Burleson GR, Caulfield MJ, Pollard M. Ozonation of mutagenic and carcinogenic polyaromatic amines and polyaromatic hydrocarbons in water. Cancer Res 1979; 39:2149.