Lasers in Medical Science

, Volume 27, Issue 4, pp 795–804 | Cite as

Quantitative analysis of optical coherence tomography and histopathology images of normal and dysplastic oral mucosal tissues

  • Oluyori Kutulola Adegun
  • Pete H. Tomlins
  • Eleni Hagi-Pavli
  • Gordon Mckenzie
  • Kim Piper
  • Dan L. Bader
  • Farida Fortune
Original Article

Abstract

Selecting the most representative site for biopsy is crucial in establishing a definitive diagnosis of oral epithelial dysplasia. The current process involves clinical examination that can be subjective and prone to sampling errors. The aim of this study was therefore to investigate the use of optical coherence tomography (OCT) for differentiation of normal and dysplastic oral epithelial samples, with a view to developing an objective and reproducible approach for biopsy site selection. Biopsy samples from patients with fibro-epithelial polyps (n = 13), mild dysplasia (n = 2), and moderate/severe dysplasia (n = 4) were scanned at 5-μm intervals using an OCT microscope and subsequently processed and stained with hematoxylin and eosin (H&E). Epithelial differentiation was measured from the rate of change (gradient) of the backscattered light intensity in the OCT signal as a function of depth. This parameter is directly related to the density of optical scattering from the cell nuclei. OCT images of normal oral epithelium showed a clear delineation of the mucosal layers observed in the matching histology. However, OCT images of oral dysplasia did not clearly identify the individual mucosal layers because of the increased density of abnormal cell nuclei, which impeded light penetration. Quantitative analysis on 2D-OCT and histology images differentiated dysplasia from normal control samples. Similar analysis on 3D-OCT datasets resulted in the reclassification of biopsy samples into the normal/mild and moderate/severe groups. Quantitative differentiation of normal and dysplastic lesions using OCT offers a non-invasive objective approach for localizing the most representative site to biopsy, particularly in oral lesions with similar clinical features.

Keywords

Imaging OCT Biopsy site Diagnosis Dysplasia 

Notes

Acknowledgements

The authors gratefully acknowledge the financial support of the Institute of Dentistry, Barts & the London, School of Medicine and Dentistry.

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Epstein JB, Sciubba J, Silverman S Jr, Sroussi HY (2007) Utility of toluidine blue in oral premalignant lesions and squamous cell carcinoma: continuing research and implications for clinical practice. Head Neck 29(10):948–958PubMedCrossRefGoogle Scholar
  2. 2.
    Epstein JB, Silverman S Jr, Epstein JD, Lonky SA, Bride MA (2008) Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue. Oral Oncol 44(6):538–544PubMedCrossRefGoogle Scholar
  3. 3.
    Balas C, Papoutsoglou G, Potirakis A (2008) In vivo molecular imaging of cervical neoplasia using acetic acid as biomarker. Ieee Journal of Selected Topics in Quantum Electronics 14(1):29–42CrossRefGoogle Scholar
  4. 4.
    Zagaynova EV, Streltsova OS, Gladkova ND, Snopova LB, Gelikonov GV, Feldchtein FI et al (2002) In vivo optical coherence tomography feasibility for bladder disease. J Urol 167(3):1492–1496PubMedCrossRefGoogle Scholar
  5. 5.
    Gambichler T, Hyun J, Moussa G, Tomi NS, Boms S, Altmeyer P et al (2007) Optical coherence tomography of cutaneous lupus erythematosus correlates with histopathology. Lupus 16(1):35–38PubMedCrossRefGoogle Scholar
  6. 6.
    Abbey LM, Kaugars GE, Gunsolley JC, Burns JC, Page DG, Svirsky JA et al (1995) Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80(2):188–191PubMedCrossRefGoogle Scholar
  7. 7.
    Fischer DJ, Epstein JB, Morton TH, Schwartz SM (2004) Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med 33(2):65–70PubMedCrossRefGoogle Scholar
  8. 8.
    Keenan SJ, Diamond J, McCluggage WG, Bharucha H, Thompson D, Bartels PH et al (2000) An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN). J Pathol 192(3):351–362PubMedCrossRefGoogle Scholar
  9. 9.
    Guillaud M, Cox D, Adler-Storthz K, Malpica A, Staerkel G, Matisic J et al (2004) Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus. Cytometry A 60(1):81–89PubMedCrossRefGoogle Scholar
  10. 10.
    Bouquot JE, Speight PM, Farthing PM. Epithelial dysplasia of the oral mucosa-diagnostic problems and prognostic features J Cdip. 2006: 11–21.Google Scholar
  11. 11.
    Bohringer HJ, Boller D, Leppert J, Knopp U, Lankenau E, Reusche E et al (2006) Time-domain and spectral-domain optical coherence tomography in the analysis of brain tumor tissue. Lasers Surg Med 38(6):588–597PubMedCrossRefGoogle Scholar
  12. 12.
    Schmitt JM (1999) Optical coherence tomography (OCT): a review. Ieee Journal of Selected Topics in Quantum Electronics 5(4):1205–1215CrossRefGoogle Scholar
  13. 13.
    Fercher AF, Drexler W, Hitzenberger CK, Lasser T (2003) Optical coherence tomography - principles and applications. Rep Prog Phys 66(2):239–303CrossRefGoogle Scholar
  14. 14.
    Tomlins PH, Wang RK (2005) Theory, developments and applications of optical coherence tomography. J Phys D Appl Phys 38(15):2519–2535CrossRefGoogle Scholar
  15. 15.
    Zysk AM, Nguyen FT, Oldenburg AL, Marks DL, Boppart SA (2007) Optical coherence tomography: a review of clinical development from bench to bedside. J Biomed Opt 12(5):051403PubMedCrossRefGoogle Scholar
  16. 16.
    Kramoreva LI, Rozhko YI (2010) Optical coherence tomography (Review). J Appl Spectrosc 77(4):449–467CrossRefGoogle Scholar
  17. 17.
    Hearnden V (2011) Developing tissue engineered models of oral mucosa and oral cancer to study novel therapeutic and diagnostic techniques. [Electronic thesis]. University of Sheffield, SheffieldGoogle Scholar
  18. 18.
    Wilder-Smith P, Hammer-Wilson MJ, Zhang J, Wang Q, Osann K, Chen Z et al (2007) In vivo imaging of oral mucositis in an animal model using optical coherence tomography and optical Doppler tomography. Clin Cancer Res 13(8):2449–2454PubMedCrossRefGoogle Scholar
  19. 19.
    Ozawa N, Sumi Y, Chong C, Kurabayashi T (2009) Evaluation of oral vascular anomalies using optical coherence tomography. Br J Oral Maxillofac Surg 47(8):622-626Google Scholar
  20. 20.
    Ozawa N, Sumi Y, Shimozato K, Chong C, Kurabayashi T (2009) In vivo imaging of human labial glands using advanced optical coherence tomography. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108(3):425–429PubMedCrossRefGoogle Scholar
  21. 21.
    Ridgway JM, Armstrong WB, Guo S, Mahmood U, Su J, Jackson RP et al (2006) In vivo optical coherence tomography of the human oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg 132(10):1074–1081PubMedCrossRefGoogle Scholar
  22. 22.
    Pommerencke T, Steinberg T, Dickhaus H, Tomakidi P, Grabe N (2008) Nuclear staining and relative distance for quantifying epidermal differentiation in biomarker expression profiling. BMC Bioinformatics 9:473PubMedCrossRefGoogle Scholar
  23. 23.
    Broekaert D, Van Oostveldt P, Coucke P, De Bersaques J, Gillis E, Reyniers P (1986) Nuclear differentiation and ultimate fate during epidermal keratinization. Two-wavelength and cytofluorometric DNA investigations completed by computerized scanning image analysis. Arch Dermatol Res 279(2):100–111PubMedCrossRefGoogle Scholar
  24. 24.
    Drezek R, Guillaud M, Collier T, Boiko I, Malpica A, Macaulay C et al (2003) Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture. J Biomed Opt 8(1):7–16PubMedCrossRefGoogle Scholar
  25. 25.
    Peter H. Tomlins, Robert A. Ferguson, Christian Hart and Peter Woolliams. Point-Spread Function Phantoms for Optical Coherence Tomography. NPL Reports National Physical Laboratory; August 2009. Report No.: 1754–2944.Google Scholar
  26. 26.
    Levitz D, Thrane L, Frosz M, Andersen P, Andersen C, Andersson-Engels S et al (2004) Determination of optical scattering properties of highly-scattering media in optical coherence tomography images. Opt Express 12(2):249–259PubMedCrossRefGoogle Scholar
  27. 27.
    Bohringer HJ, Lankenau E, Stellmacher F, Reusche E, Huttmann G, Giese A (2009) Imaging of human brain tumor tissue by near-infrared laser coherence tomography. Acta Neurochir 151(5):507–517CrossRefGoogle Scholar
  28. 28.
    Welzel J, Reinhardt C, Lankenau E, Winter C, Wolff HH (2004) Changes in function and morphology of normal human skin: evaluation using optical coherence tomography. Br J Dermatol 150(2):220–225PubMedCrossRefGoogle Scholar
  29. 29.
    van der Meer FJ, Faber DJ, Perree J, Pasterkamp G, Baraznji Sassoon D, van Leeuwen TG (2005) Quantitative optical coherence tomography of arterial wall components. Lasers Med Sci 20(1):45–51PubMedCrossRefGoogle Scholar
  30. 30.
    Tsai MT, Lee HC, Lee CK, Yu CH, Chen HM, Chiang CP et al (2008) Effective indicators for diagnosis of oral cancer using optical coherence tomography. Opt Express 16(20):15847–15862PubMedCrossRefGoogle Scholar
  31. 31.
    Tsai MT, Lee CK, Lee HC, Chen HM, Chiang CP, Wang YM et al (2009) Differentiating oral lesions in different carcinogenesis stages with optical coherence tomography. J Biomed Opt 14(4):044028PubMedCrossRefGoogle Scholar
  32. 32.
    Woolliams PD, Tomlins PH (2011) The modulation transfer function of an optical coherence tomography imaging system in turbid media. Phys Med Biol 56(9):2855–2871PubMedCrossRefGoogle Scholar
  33. 33.
    Tomlins PH, Adegun O, Hagi-Pavli E, Piper K, Bader D, Fortune F (2010) Scattering attenuation microscopy of oral epithelial dysplasia. J Biomed Opt 15(6):066003PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd 2011

Authors and Affiliations

  • Oluyori Kutulola Adegun
    • 1
  • Pete H. Tomlins
    • 1
  • Eleni Hagi-Pavli
    • 1
  • Gordon Mckenzie
    • 2
  • Kim Piper
    • 1
  • Dan L. Bader
    • 3
  • Farida Fortune
    • 1
  1. 1.Barts & The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of DentistryQueen Mary University of LondonLondonUK
  2. 2.Michelson Diagnostics LtdOrpingtonUK
  3. 3.School of Engineering and Materials ScienceQueen Mary University of LondonLondonUK

Personalised recommendations