Computer-assisted assessment of colonic polyp histopathology using probe-based confocal laser endomicroscopy

  • Pushpak Taunk
  • Christopher D. Atkinson
  • David Lichtenstein
  • Eladio Rodriguez-Diaz
  • Satish K. SinghEmail author
Original Article



Probe-based confocal laser endomicroscopy (pCLE) is a promising modality for classifying polyp histology in vivo, but decision making in real-time is hampered by high-magnification targeting and by the learning curve for image interpretation. The aim of this study is to test the feasibility of a system combining the use of a low-magnification, wider field-of-view pCLE probe and a computer-assisted diagnosis (CAD) algorithm that automatically classifies colonic polyps.


This feasibility study utilized images of polyps from 26 patients who underwent colonoscopy with pCLE. The pCLE images were reviewed offline by two expert and five junior endoscopists blinded to index histopathology. A subset of images was used to train classification software based on the consensus of two GI histopathologists. Images were processed to extract image features as inputs to a linear support vector machine classifier. We compared the CAD algorithm’s prediction accuracy against the classification accuracy of the endoscopists.


We utilized 96 neoplastic and 93 non-neoplastic confocal images from 27 neoplastic and 20 non-neoplastic polyps. The CAD algorithm had sensitivity of 95%, specificity of 94%, and accuracy of 94%. The expert endoscopists had sensitivities of 98% and 95%, specificities of 98% and 96%, and accuracies of 98% and 96%, while the junior endoscopists had, on average, a sensitivity of 60%, specificity of 85%, and accuracy of 73%.


The CAD algorithm showed comparable performance to offline review by expert endoscopists and improved performance when compared to junior endoscopists and may be useful for assisting clinical decision making in real time.


Confocal laser endomicroscopy Colorectal cancer Polyp histology Machine learning 


Funding information

This work was supported by CSR&D and BLR&D Merit Review Awards I01CX001146 and I01BX004455 from the United States Department of Veterans Affairs. This material is the result of work supported with resources and the use of facilities at the VA Boston Healthcare System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Compliance with ethical standards

Disclosure of financial arrangements

The authors do not have any relevant disclosures to report.


  1. 1.
    Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37:4–66CrossRefGoogle Scholar
  2. 2.
    Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319(9):525–532PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, Ackroyd F, Shike M, Kurtz RC, Hornsby-Lewis L, Gerdes H, Stewart ET (1993) Prevention of colorectal cancer by colonoscopic polypectomy. The national polyp study workgroup. N Engl J Med 329(27):1977–1981PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Butterly LF, Chase MP, Pohl H, Fiarman GS (2006) Prevalence of clinically important histology in small adenomas. Clin Gastroenterol Hepatol 4(3):343–348PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Gupta N, Bansal A, Rao D, Early DS, Jonnalagadda S, Wani SB, Edmundowicz SA, Sharma P, Rastogi A (2012) Prevalence of advanced histological features in diminutive and small colon polyps. Gastrointest Endosc 75(5):1022–1030PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Huang CS, O'brien MJ, Yang S, Farraye FA (2004) Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway. Am J Gastroenterol 99(11):2242–2255PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Lieberman D, Moravec M, Holub J, Michaels L, Eisen G (2008) Polyp size and advanced histology in patients undergoing colonoscopy screening: implications for CT colonography. Gastroenterology 135(4):1100–1105PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Levin B, Lieberman DA, McFarland B et al (2008) Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the american cancer society, the US multi-society task force on colorectal cancer, and the american college of radiology. CA Cancer J Clin 58(3):130–160PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Winawer SJ, Zauber AG, Fletcher RH, Stillman JS, O'Brien MJ, Levin B, Smith RA, Lieberman DA, Burt RW, Levin TR, Bond JH, Brooks D, Byers T, Hyman N, Kirk L, Thorson A, Simmang C, Johnson D, Rex DK, US Multi-Society Task Force on Colorectal Cancer, American Cancer Society (2006) Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US multi-society task force on colorectal cancer and the american cancer society. Gastroenterology 130(6):1872–1885PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Ignjatovic A, East JE, Suzuki N, Vance M, Guenther T, Saunders BP (2009) Optical diagnosis of small colorectal polyps at routine colonoscopy (detect inspect characterise resect and DISCARD; DISCARD trial): a prospective cohort study. Lancet Oncol 10(12):1171–1178PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Rex DK, Kahi C, O'Brien M, Levin TR, Pohl H, Rastogi A, Burgart L, Imperiale T, Ladabaum U, Cohen J, Lieberman DA (2011) 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(3):419–422PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Dhar A, Johnson KS, Novelli MR, Bown SG, Bigio IJ, Lovat LB, Bloom SL (2006) Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique. Gastrointest Endosc 63(2):257–261PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Rodriguez-Diaz E, Castanon DA, Singh SK, Bigio IJ (2011) Spectral classifier design with ensemble classifiers and misclassification-rejection: application to elastic-scattering spectroscopy for detection of colonic neoplasia. J Biomed Opt 16(6):67009CrossRefGoogle Scholar
  14. 14.
    Rodriguez-Diaz E, Huang Q, Cerda SR, O'Brien MJ, Bigio IJ, Singh SK (2015) Endoscopic histological assessment of colonic polyps using elastic scattering spectroscopy. Gastrointest Endosc 81(3):539–547PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Rastogi A, Keighley J, Singh V, Callahan P, Bansal A, Wani S, Sharma P (2009) High accuracy of narrow band imaging without magnification for the real-time characterization of polyp histology and its comparison with high-definition white light colonoscopy: a prospective study. Am J Gastroenterol 104(10):2422–2430PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Sikka S, Ringold DA, Jonnalagadda S, Banerjee B (2008) Comparison of white light and narrow band high definition images in predicting colon polyp histology, using standard colonoscopes without optical magnification. Endoscopy 40(10):818–822PubMedCrossRefGoogle Scholar
  17. 17.
    Gupta N, Bansal A, Rao D, Early DS, Jonnalagadda S, Edmundowicz SA, Sharma P, Rastogi A (2012) Accuracy of in vivo optical diagnosis of colon polyp histology by narrow-band imaging in predicting colonoscopy surveillance intervals. Gastrointest Endosc 75(3):494–502PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Ladabaum U, Fioritto A, Mitani A, Desai M, Kim JP, Rex DK, Imperiale T, Gunaratnam N (2013) Real-time optical biopsy of colon polyps with narrow band imaging in community practice does not yet meet key thresholds for clinical decisions. Gastroenterology 144(1):81–91PubMedCrossRefGoogle Scholar
  19. 19.
    Rastogi A, Rao DS, Gupta N, Grisolano SW, Buckles DC, Sidorenko E, Bonino J, Matsuda T, Dekker E, Kaltenbach T, Singh R, Wani S, Sharma P, Olyaee MS, Bansal A, East JE (2014) Impact of a computer-based teaching module on characterization of diminutive colon polyps by using narrow-band imaging by non-experts in academic and community practice: a video-based study. Gastrointest Endosc 79(3):390–398PubMedCrossRefGoogle Scholar
  20. 20.
    Rex DK (2009) Narrow-band imaging without optical magnification for histologic analysis of colorectal polyps. Gastroenterology 136(4):1174–1181PubMedCrossRefGoogle Scholar
  21. 21.
    Singh R, Bhat YM, Thurairajah PH, Shetti MP, Jayanna M, Nind G, Tam W, Walmsey R, Bourke M, Moss A, Chen R, Bampton P, Roberts-Thomson I, Schoeman M, Tucker G (2013) Is narrow band imaging superior to high-definition white light endoscopy in the assessment of diminutive colorectal polyps? J Gastroenterol Hepatol 28(3):472–478PubMedCrossRefGoogle Scholar
  22. 22.
    Pohl J, Nguyen-Tat M, Pech O, May A, Rabenstein T, Ell C (2008) Computed virtual chromoendoscopy for classification of small colorectal lesions: a prospective comparative study. Am J Gastroenterol 103(3):562–569PubMedCrossRefGoogle Scholar
  23. 23.
    Kim YS, Kim D, Chung SJ, Park MJ, Shin CS, Cho S–H, Kim JS, Song IS (2011) Differentiating small polyp histologies using real-time screening colonoscopy with Fuji intelligent color enhancement. Clin Gastroenterol Hepatol 9(9):744–749.e1PubMedCrossRefGoogle Scholar
  24. 24.
    Schachschal G, Mayr M, Treszl A, Balzer K, Wegscheider K, Aschenbeck J, Aminalai A, Drossel R, Schröder A, Scheel M, Bothe CH, Bruhn JP, Burmeister W, Stange G, Bähr C, Kießlich R, Rösch T (2014) Endoscopic versus histological characterisation of polyps during screening colonoscopy. Gut 63(3):458–465PubMedCrossRefGoogle Scholar
  25. 25.
    Lee CK, Lee S-H, Hwangbo Y (2011) Narrow-band imaging versus i-scan for the real-time histological prediction of diminutive colonic polyps: a prospective comparative study by using the simple unified endoscopic classification. Gastrointest Endosc 74(3):603–609PubMedCrossRefGoogle Scholar
  26. 26.
    Canto MI, Anandasabapathy S, Brugge W, Falk GW, Dunbar KB, Zhang Z, Woods K, Almario JA, Schell U, Goldblum J, Maitra A, Montgomery E, Kiesslich R, Confocal Endomicroscopy for Barrett's Esophagus or Confocal Endomicroscopy for Barrett's Esophagus (CEBE) Trial Group (2014) In vivo endomicroscopy improves detection of barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc 79(2):211–221PubMedCrossRefGoogle Scholar
  27. 27.
    Sharma P, Meining AR, Coron E, Lightdale CJ, Wolfsen HC, Bansal A, Bajbouj M, Galmiche JP, Abrams JA, Rastogi A, Gupta N, Michalek JE, Lauwers GY, Wallace MB (2011) 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 74(3):465–472PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Buda A, Hatem G, Neumann H, D' Incà R, Mescoli C, Piselli P, Jackson J, Bruno M, Sturniolo GC (2014) Confocal laser endomicroscopy for prediction of disease relapse in ulcerative colitis: a pilot study. J Crohns Colitis 8(4):304–311PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Kiesslich R, Duckworth CA, Moussata D, Gloeckner A, Lim LG, Goetz M, Pritchard DM, Galle PR, Neurath MF, Watson AJM (2012) Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 61(8):1146–1153PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Liu JJ, Wong K, Thiesen AL, Mah SJ, Dieleman LA, Claggett B, Saltzman JR, Fedorak RN (2011) Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest Endosc 73(6):1174–1180PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Liu JJ, Madsen KL, Boulanger P, Dieleman LA, Meddings J, Fedorak RN (2011) Mind the gaps: confocal endomicroscopy showed increased density of small bowel epithelial gaps in inflammatory bowel disease. J Clin Gastroenterol 45(3):240–245PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Moussata D, Goetz M, Gloeckner A, Kerner M, Campbell B, Hoffman A, Biesterfeld S, Flourie B, Saurin JC, Galle PR, Neurath MF, Watson AJM, Kiesslich R (2011) Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo. Gut 60(1):26–33PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, Neurath MF, Mudter J (2012) Assessment of crohn's disease activity by confocal laser endomicroscopy. Inflamm Bowel Dis 18(12):2261–2269PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Meining A, Chen YK, Pleskow D, Stevens P, Shah RJ, Chuttani R, Michalek J, Slivka A (2011) Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience. Gastrointest Endosc 74(5):961–968PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Buchner AM, Shahid MW, Heckman MG, Krishna M, Ghabril M, Hasan M, Crook JE, Gomez V, Raimondo M, Woodward T, Wolfsen HC, Wallace MB (2010) Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138(3):834–842PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Kuiper T, van den Broek FJC, van Eeden S, Fockens P, Dekker E (2012) Feasibility and accuracy of confocal endomicroscopy in comparison with narrow-band imaging and chromoendoscopy for the differentiation of colorectal lesions. Am J Gastroenterol 107(4):543–550PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Shahid MW, Buchner AM, Raimondo M, Woodward TA, Krishna M, Wallace MB (2012) Accuracy of real-time vs. blinded offline diagnosis of neoplastic colorectal polyps using probe-based confocal laser endomicroscopy: a pilot study. Endoscopy 44(4):343–348PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Shahid MW, Buchner AM, Heckman MG, Krishna M, Raimondo M, Woodward T, Wallace MB (2012) Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging for small colorectal polyps: a feasibility study. Am J Gastroenterol 107(2):231–239PubMedCrossRefGoogle Scholar
  39. 39.
    Ussui VM, Wallace MB (2012) Confocal endomicroscopy of colorectal polyps. Gastroenterol Res Pract 2012:545679PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Wallace M, Lauwers GY, Chen Y, Dekker E, Fockens P, Sharma P, Meining A (2011) Miami classification for probe-based confocal laser endomicroscopy. Endoscopy 43(10):882–891PubMedCrossRefGoogle Scholar
  41. 41.
    André B, Vercauteren T, Buchner AM, Wallace MB, Ayache N (2011) A smart atlas for endomicroscopy using automated video retrieval. Med Image Anal 15(4):460–476PubMedCrossRefGoogle Scholar
  42. 42.
    André B, Vercauteren T, Buchner AM, Krishna M, Ayache N, Wallace MB (2012) Software for automated classification of probe-based confocal laser endomicroscopy videos of colorectal polyps. World J Gastroenterol 18(39):5560–5569PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Duda RO, Hart PE, Stork DG (2001) Pattern classification. John Wiley & Sons, New YorkGoogle Scholar
  44. 44.
    Jain AK (1989) Fundamentals of digital image processing. 5, illustrated. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
  45. 45.
    Vapnik VN (1998) Statistical learning theory. John Wiley & Sons, New YorkGoogle Scholar

Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Division of Digestive Diseases and NutritionUniversity of South Florida Morsani College of MedicineTampaUSA
  2. 2.Department of Medicine, Section of GastroenterologyVA Boston Healthcare SystemBostonUSA
  3. 3.Boston Medical CenterBoston University School of MedicineBostonUSA
  4. 4.Research Service, VA Boston Healthcare SystemBostonUSA
  5. 5.Boston University School of Medicine & College of EngineeringBoston UniversityBostonUSA

Personalised recommendations