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Diagnostic of Lung Cancer: Confocal Bronchoscopy

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Interventions in Pulmonary Medicine

Abstract

With the recent development of confocal endomicroscopy, bronchoscopy has now entered the era of in vivo microscopic imaging. Confocal fluorescence endomicroscopy is based on the principle of confocal microscopy, where the microscope objective has been replaced by fiber-optic probes. Two endomicroscope systems could theoretically be used for human explorations, differing by the position of the scanning system into the device. Due to the respiratory tract size, the only system currently available, called “probe-based confocal laser endomicroscopy” (or pCLE), uses the principle of proximal scanning. This system produces images through a 1 mm flexible miniprobe that can enter the 2 mm working channel of the bronchoscope. pCLE has a lateral resolution of 3 μm and produces real-time imaging at nine frames per second. pCLE has the capability to image, at a microscopic scale, the fluorescence of the bronchial epithelial and subepithelial layers, as well as the more distal parts of the lungs, from the terminal bronchioles down to the alveolar ducts and sacs. Confocal endomicroscopy can be coupled with nuclear fluorescent dyes and has the potential to image targeted fluorescent molecular probes. Potential applications of FCFM include “optical biopsy” of early bronchial cancers, bronchial wall remodeling evaluation, diffuse peripheral lung disease exploration, as well as in vivo diagnosis of peripheral lung nodules.

This review details the capabilities and possible limitations of confocal microendoscopy for proximal and distal lung exploration with special focus on lung cancer imaging in vivo.

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References

  1. St Croix CM, Leelavanichkul K, Watkins SC. Intravital fluorescence microscopy in pulmonary research. Adv Drug Deliv Rev. 2006;58(7):834–40.

    Article  CAS  PubMed  Google Scholar 

  2. MacAulay C, Lane P, Richards-Kortum R. In vivo pathology: microendoscopy as a new endoscopic imaging modality. Gastrointest Endosc Clin N Am. 2004;14(3):595–620. xi

    Article  PubMed  Google Scholar 

  3. Boyette LB, Reardon MA, Mirelman AJ, Kirkley TD, Lysiak JJ, Tuttle JB, Steers WD. Fiberoptic imaging of cavernous nerves in vivo. J Urol. 2007;178(6):2694–700.

    Article  PubMed  Google Scholar 

  4. Le Goualher G, Perchant A, Genet M, Cave C, Viellerobe B, Berier F, Abrat B, Ayache N. Towards optical biopsies with an integrated fibered confocal fluorescence microscope. In: Barillot C, Haynor DR, Hellier P, editors. Medical image computing and computer-assisted intervention. Berlin: Springer; 2004. p. 761–8.

    Google Scholar 

  5. Vincent P, Maskos U, Charvet I, Bourgeais L, Stoppini L, Leresche N, Changeux JP, Lambert R, Meda P, Paupardin-Tritsch D. Live imaging of neural structure and function by fibred fluorescence microscopy. EMBO Rep. 2006;7(11):1154–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hoffman A, Goetz M, Vieth M, Galle PR, Neurath MF, Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy. 2006;38(12):1275–83.

    Article  CAS  PubMed  Google Scholar 

  7. Thiberville L, Moreno-Swirc S, Vercauteren T, Peltier E, Cave C, Bourg HG. In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy. Am J Respir Crit Care Med. 2007;175:22–31.

    Article  PubMed  Google Scholar 

  8. Thiberville L, Salaun M, Lachkar S, Dominique S, Moreno-Swirc S, Vever-Bizet C, Bourg-Heckly G. Human in-vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy. Eur Respir J. 2009;33(5):974–85.

    Article  CAS  PubMed  Google Scholar 

  9. Kiesslich R, Goetz M, Neurath MF. Virtual histology. Best Pract Res Clin Gastroenterol. 2008;22(5):883–97.

    Article  PubMed  Google Scholar 

  10. Guillaud M, Richards-Kortum R, Follen M. Paradigm shift: a new breed of pathologist. Gynecol Oncol. 2007;107(1 Suppl 1):S46–9.

    Article  PubMed  Google Scholar 

  11. Musani A, Sims MW, Sareli C, Russell W, McLaren W, Delaney P, Litzky L, Panettieri RA. A pilot study of the feasibility of confocal endomicroscopy for examination of the human airway. J Bronchol Interv Pulmonol. 2010;17(2):126–30.

    Article  Google Scholar 

  12. Meining A, Schwendy S, Becker V, Schmid RM, Prinz C. In vivo histopathology of lymphocytic colitis. Gastrointest Endosc. 2007;66(2):398–9. discussion 400

    Article  PubMed  Google Scholar 

  13. Peng Q, Brown SB, Moan J, Nesland JM, Wainwright M, Griffiths J, Dixon B, Cruse-Sawyer J, Vernon D. Biodistribution of a methylene blue derivative in tumor and normal tissues of rats. J Photochem Photobiol B. 1993;20(1):63–71.

    Article  CAS  PubMed  Google Scholar 

  14. Thiberville L, Salaün M, Lachkar S, Moreno-Swirc S, Bourg-Heckly G. In-vivo confocal endomicroscopy of peripheral lung nodules using 488nm/660 nm induced fluorescence and topical methylene blue (abstract). In: Proceedings of European Respiratory Society Meeting. Berlin: European Respiratory Society; 2008. p. 263s.

    Google Scholar 

  15. Thiberville L, Salaün M, Moreno-Swirc S, Bourg Heckly G. In vivo endoscopic microimaging of the bronchial epithelial layer using 660 nm fibered confocal fluorescence microscopy and topical methylene blue. In: European Respiratory Society Meeting. Stockolm: Eur Resp J; 2007. p. 712S.

    Google Scholar 

  16. Gabrecht T, Andrejevic-Blant S, Wagnieres G. Blue-violet excited autofluorescence spectroscopy and imaging of normal and cancerous human bronchial tissue after formalin fixation. Photochem Photobiol. 2007;83(2):450–8.

    Article  CAS  PubMed  Google Scholar 

  17. Richards-Kortum R, Sevick-Murac E. Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem. 1996;47:555–606.

    Article  CAS  PubMed  Google Scholar 

  18. Bourg Heckly G, Thiberville L, Vever-Bizet C, Vielerobe B. In vivo endoscopic autofluorescence microspectro-imaging of bronchi and alveoli. Proc SPIE. 2008;6851.

    Google Scholar 

  19. Qu J, MacAulay C, Lam S, Palcic B. Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling and in vivo measurements. Opt Eng. 1995;34:3334–43.

    Article  CAS  Google Scholar 

  20. Jean F, Bourg-Heckly G, Viellerobe B. Fibered confocal spectroscopy and multicolor imaging system for in vivo fluorescence analysis. Opt Express. 2007;15(7):4008–17.

    Article  PubMed  Google Scholar 

  21. Skala MC, Squirrell JM, Vrotsos KM, Eickhoff JC, Gendron-Fitzpatrick A, Eliceiri KW, Ramanujam N. Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues. Cancer Res. 2005;65(4):1180–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Peyrot DA, Lefort C, Steffenhagen M, Mansuryan T, Ducourthial G, Abi-Haidar D, Sandeau N, Vever-Bizet C, Kruglik SG, Thiberville L, Louradour F, Bourg-Heckly G. Development of a nonlinear fiber-optic spectrometer for human lung tissue exploration. Biomed Opt Express. 2012;3(5):840–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pavlova I, Hume KR, Yazinski SA, Flanders J, Southard TL, Weiss RS, Webb WW. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung. J Biomed Opt. 2012;17(3):036014.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Weibel ER, Sapoval B, Filoche M. Design of peripheral airways for efficient gas exchange. Respir Physiol Neurobiol. 2005;148(1–2):3–21.

    Article  PubMed  Google Scholar 

  25. Weibel ER, Hsia CC, Ochs M. How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol. 2007;102(1):459–67.

    Article  PubMed  Google Scholar 

  26. Yick CY, von der Thusen JH, Bel EH, Sterk PJ, Kunst PW. In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function. Respir Res. 2011;12(1):85.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kiesslich R, Burg J, Vieth M, Gnaendiger J, Enders M, Delaney P, Polglase A, McLaren W, Janell D, Thomas S, Nafe B, Galle PR, Neurath MF. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology. 2004;127(3):706–13.

    Article  PubMed  Google Scholar 

  28. Becker V, von Delius S, Bajbouj M, Karagianni A, Schmid RM, Meining A. 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(2):319–23.

    Article  PubMed  Google Scholar 

  29. Lane P, Lam S, McWilliams A, leRiche J, Anderson M, MacAulay C. Confocal fluorescence microendoscopy of bronchial epithelium. J Biomed Opt. 2009;14(2):024008.

    Article  PubMed  Google Scholar 

  30. Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR, Neurath MF. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology. 2003;124(4):880–8.

    Article  PubMed  Google Scholar 

  31. Taghavi SA, Membari ME, Dehghani SM, Eshraghian A, Hamidpour L, Khademalhoseini F. Comparison of chromoendoscopy and conventional endoscopy in the detection of premalignant gastric lesions. Can J Gastroenterol. 2009;23(2):105–8.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Marion JF, Waye JD, Present DH, Israel Y, Bodian C, Harpaz N, Chapman M, Itzkowitz S, Steinlauf AF, Abreu MT, Ullman TA, Aisenberg J, Mayer L. Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial. Am J Gastroenterol. 2008;103(9):2342–9.

    Article  PubMed  Google Scholar 

  33. Inoue H, Kazawa T, Sato Y, Satodate H, Sasajima K, Kudo SE, Shiokawa A. 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(3):589–94. x–xi

    Article  PubMed  Google Scholar 

  34. Shibuya K, Yasufuku K, Chiyo M, Nakajima T, Fujiwara T, Nagato K, Suzuki H, Iyoda A, et al. Endo-cytoscopy system is a novel endoscopic technology to visualize microscopic imaging of the tracheobronchial tree (abstract). In: European Respiratory Meeting. Berlin: Eur Resp J; 2008. p. 263s.

    Google Scholar 

  35. Thiberville L, Salaün M, Lachkar S, Dominique S, Moreno-Swirc S, Vever-Bizet C, Bourg HG. In-vivo confocal fluorescence endomicroscopy of lung cancer. J Thorac Oncol. 2009;4(9):S49–51.

    Google Scholar 

  36. Salaun M, Roussel F, Hauss PA, Lachkar S, Thiberville L. In vivo imaging of pulmonary alveolar proteinosis using confocal endomicroscopy. Eur Respir J. 2010;36(2):451–3.

    Article  CAS  PubMed  Google Scholar 

  37. Thiberville L, Salaün M, Hauss PA, Lachkar S, Dominique S. In vivo microimaging of the alveolar capillary network during alveoscopy (abstract). In: European Respiratory Society Meeting. Vienna; 2009.

    Google Scholar 

  38. Arenberg DA, Gildea T, Wilson D. Proposed classification of probe-based confocal laser endomicroscopy (PCLE) findings for evaluation of indeterminate peripheral lung nodules. Am J Respir Crit Care Med. 2011;183:A6097.

    Google Scholar 

  39. Hsu ER, Gillenwater AM, Hasan MQ, Williams MD, El-Naggar AK, Richards-Kortum RR. Real-time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular-specific contrast agent. Int J Cancer. 2006;118(12):3062–71.

    Article  CAS  PubMed  Google Scholar 

  40. Hsiung PL, Hardy J, Friedland S, Soetikno R, Du CB, Wu AP, Sahbaie P, Crawford JM, Lowe AW, Contag CH, Wang TD. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat Med. 2008;14(4):454–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Morisse H, Heyman L, Salaun M, Favennec L, Picquenot JM, Bohn P, Thiberville L. In vivo and in situ imaging of experimental invasive pulmonary aspergillosis using fibered confocal fluorescence microscopy. Med Mycol. 2012;50(4):386–95.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinique Pneumologique, Hôpital Charles Nicolle, Rouen University Hospital, 1 rue de Germont, Rouen, 76000, France

    Luc Thiberville MD

  2. Department of Pulmonary Medicine, Rouen University Hospital, Rouen, France

    Luc Thiberville MD & Mathieu Salaun MD

Authors
  1. Luc Thiberville MD
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  2. Mathieu Salaun MD
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Correspondence to Luc Thiberville MD .

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Editors and Affiliations

  1. Clínica Corachan and Bellvitge, University Hospital, Barcelona, Spain

    Jose Pablo Díaz-Jimenez

  2. Pulmonary Department, Clinica y Maternidad Colon, Pulmonary Research Department, IIC Mar del Plata, Buenos Aires, Argentina

    Alicia N. Rodriguez

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Thiberville, L., Salaun, M. (2018). Diagnostic of Lung Cancer: Confocal Bronchoscopy. In: Díaz-Jimenez, J., Rodriguez, A. (eds) Interventions in Pulmonary Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-58036-4_15

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  • DOI: https://doi.org/10.1007/978-3-319-58036-4_15

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