Endoscopic confocal laser-microscopy for the intraoperative nerve recognition: is it feasible?

David Benjamin Ellebrecht; Sönke von Weihe

doi:10.1515/bmt-2021-0171

Article

Endoscopic confocal laser-microscopy for the intraoperative nerve recognition: is it feasible?

David Benjamin Ellebrecht and Sönke von Weihe

Published/Copyright: December 17, 2021

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From the journal Biomedical Engineering / Biomedizinische Technik Volume 67 Issue 1

Abstract

Surgeons lose most of their tactile tissue information during minimal invasive surgery and need an additional tool of intraoperative tissue recognition. Confocal laser microscopy (CLM) is a well-established method of tissue investigation. The objective of this study was to analyze the feasibility and diagnostic accuracy of CLM nervous tissue recognition. Images taken with an endoscopic CLM system of sympathetic ganglions, nerve fibers and pleural tissue were characterized in terms of specific signal-patterns ex-vivo. No fluorescent dye was used. Diagnostic accuracy of tissue classification was evaluated by newly trained observers (sensitivity, specificity, PPV, NPV and interobserver variability). Although CLM images showed low CLM image contrast, assessment of nerve tissue was feasible without any fluorescent dye. Sensitivity and specificity ranged between 0.73 and 0.9 and 0.55–1.0, respectively. PPVs were 0.71–1.0 and the NPV range was between 0.58 and 0.86. The overall interobserver variability was 0.36. The eCLM enables to evaluate nervous tissue and to distinguish between nerve fibers, ganglions and pleural tissue based on backscattered light. However, the low image contrast and the heterogeneity in correct tissue diagnosis and a fair interobserver variability indicate the limit of CLM imaging without any fluorescent dye.

Keywords: confocallaser microscopy; diagnostic accuracy; medical engineering; minimal invasive surgery; nervous tissue; sympathetic trunk

Corresponding author: David Benjamin Ellebrecht, Department of Thoracic Surgery, LungClinic Großhansdorf, Wöhrendamm 80, 22927 Großhansdorf, Germany, E-mail: d.ellebrecht@lungenclinic.de

Research funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Informed consent: Not applicable.
Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board or equivalent committee (ethics committee of the University of Luebeck; Reg.-No.: 20-427).

References

1. Dip, F, Aleman, R, Socolovsky, M, Villalba, N, Falco, J, Menzo, EL, et al.. Nerve spectroscopy: understanding peripheral nerve autofluorescence through photodynamics. Surg Endosc 2021;35:7104–11. 10.1007/s00464-020-08227-7.10.1007/s00464-020-08227-7Search in Google Scholar PubMed

2. Balog, J, Sasi-Szabo, L, Kinross, J, Lewis, MR, Muirhead, LJ, Veselkov, K, et al.. Intraoperative tissue identification using rapid evaporative ionization mass spectrometry. Sci Transl Med 2013;5:194ra93.10.1126/scitranslmed.3005623Search in Google Scholar PubMed

3. Crawshaw, B, Delaney, CP. Gastrointestinal surgery: real-time tissue identification during surgery. Nat Rev Gastroenterol Hepatol 2013;10:624–5.10.1038/nrgastro.2013.176Search in Google Scholar PubMed

4. Minsky, M, inventor. Microscopy apparatus patent US3013467A; 1957.Search in Google Scholar

5. Ellebrecht, DB, Latus, S, Schlaefer, A, Keck, T, Gessert, N. Towards an optical biopsy during visceral surgical interventions. Visceral Med 2020;36:70–9. 10.1159/000505938.10.1159/000505938Search in Google Scholar PubMed PubMed Central

6. Kiesslich, R, Burg, J, Vieth, M, Gnaendiger, J, Enders, M, Delaney, P, et al.. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 2004;127:706–13.10.1053/j.gastro.2004.06.050Search in Google Scholar PubMed

7. Kiesslich, R, Goetz, M, Burg, J, Stolte, M, Siegel, E, Maeurer, MJ, et al.. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology 2005;128:2119–23.10.1053/j.gastro.2004.12.035Search in Google Scholar PubMed

8. Kiesslich, R, Goetz, M, Vieth, M, Galle, PR, Neurath, MF. Confocal laser endomicroscopy. Gastrointest Endoscopy Clin N Am 2005;15:715–31.10.1016/j.giec.2005.08.010Search in Google Scholar PubMed

9. Hoffman, A, Goetz, M, Vieth, M, Galle, PR, Neurath, MF, Kiesslich, R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy 2006;38:1275–83.10.1055/s-2006-944813Search in Google Scholar PubMed

10. Kiesslich, R, Goetz, M, Angus, EM, Hu, Q, Guan, Y, Potten, C, et al.. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 2007;133:1769–78.10.1053/j.gastro.2007.09.011Search in Google Scholar PubMed

11. Kiesslich, R, Goetz, M, Vieth, M, Galle, PR, Neurath, MF. Technology insight: confocal laser endoscopy for in vivo diagnosis of colorectal cancer. Nat Clin Pract Oncol 2007;4:480–90.10.1038/ncponc0881Search in Google Scholar PubMed

12. De Palma, GD. Confocal laser endomicroscopy in the “in vivo” histological diagnosis of the gastrointestinal tract. World J Gastroenterol 2009;15:5770–5.10.3748/wjg.15.5770Search in Google Scholar PubMed PubMed Central

13. Goetz, M, Watson, A, Kiesslich, R. Confocal laser endomicroscopy in gastrointestinal diseases. J Biophot 2011;4:498–508.10.1002/jbio.201100022Search in Google Scholar PubMed

14. Fugazza, A, Gaiani, F, Carra, MC, Brunetti, F, Levy, M, Sobhani, I, et al.. Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases: a systematic review and meta-analysis. BioMed Res Int 2016;2016:4638683.10.1155/2016/4638683Search in Google Scholar PubMed PubMed Central

15. Chen, SP, Liao, JC. Confocal laser endomicroscopy of bladder and upper tract urothelial carcinoma: a new era of optical diagnosis? Curr Urol Rep 2014;15:437.10.1007/s11934-014-0437-ySearch in Google Scholar PubMed PubMed Central

16. Streba, CT, Giltan, AM, Gheonea, IA, Demetrian, A, Soimu, AV, Saftoiu, A, et al.. Utility of confocal laser endomicroscopy in pulmonology and lung cancer. Rom J Morphol Embryol 2016;57:1221–7.Search in Google Scholar

17. De Palma, GD, Luglio, G, Esposito, D. Confocal laser endomicroscopy in breast surgery. Breast Cancer Res Treat 2015;154:439.10.1007/s10549-015-3619-5Search in Google Scholar PubMed

18. Breuskin, D, Divincenzo, J, Kim, YJ, Urbschat, S, Oertel, J. Confocal laser endomicroscopy in neurosurgery: a new technique with much potential. Minim Invasive Surg 2013;2013:851819.10.1155/2013/851819Search in Google Scholar PubMed PubMed Central

19. Foersch, S, Heimann, A, Ayyad, A, Spoden, GA, Florin, L, Mpoukouvalas, K, et al.. Confocal laser endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo. PLoS One 2012;7:e41760.10.1371/journal.pone.0041760Search in Google Scholar PubMed PubMed Central

20. Goetz, M, Kiesslich, R, Dienes, HP, Drebber, U, Murr, E, Hoffman, A, et al.. In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time. Endoscopy 2008;40:554–62.10.1055/s-2008-1077296Search in Google Scholar PubMed

21. Fuks, D, Pierangelo, A, Validire, P, Lefevre, M, Benali, A, Trebuchet, G, et al.. Intraoperative confocal laser endomicroscopy for real-time in vivo tissue characterization during surgical procedures. Surg Endosc 2019;33:1544–52.10.1007/s00464-018-6442-3Search in Google Scholar PubMed

22. Ellebrecht, DB, Gebhard, MP, Horn, M, Keck, T, Kleemann, M. Laparoscopic confocal laser microscopy without fluorescent injection: a pilot ex vivo study in colon cancer. Surg Innovat 2016;23:341–6.10.1177/1553350616637690Search in Google Scholar PubMed

23. Ellebrecht, DB, Kuempers, C, Horn, M, Keck, T, Kleemann, M. Confocal laser microscopy as novel approach for real-time and in-vivo tissue examination during minimal-invasive surgery in colon cancer. Surg Endosc 2019;33:1811–7.10.1007/s00464-018-6457-9Search in Google Scholar PubMed

24. Ellebrecht, DB, Kuempers, C, Perner, S, Kugler, C, Kleemann, M. Confocal Laser Microscopy without fluorescent dye in minimal-invasive thoracic surgery: an ex-vivo pilot study in lung cancer. Biomed Tech Biomed Eng 2020.10.1515/bmt-2020-0162Search in Google Scholar PubMed

25. Gessert, N, Bengs, M, Wittig, L, Dromann, D, Keck, T, Schlaefer, A, et al.. Deep transfer learning methods for colon cancer classification in confocal laser microscopy images. Int J Comput Assist Radiol Surg 2019;14:1837–45.10.1007/s11548-019-02004-1Search in Google Scholar PubMed

26. R-Core-Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018. Available from: https://www.R-project.org.Search in Google Scholar

27. Ellebrecht, DB, Heßler, N, Schlaefer, A, Gessert, N. Confocal laser microscopy for in vivo intraoperative application: diagnostic accuracy of investigator and machine learning strategies. Visceral Med 2021;37:533–41. 10.1159/000517146.10.1159/000517146Search in Google Scholar PubMed PubMed Central

28. Ellebrecht, DB, Kuempers, C, Perner, S, Kugler, C, Kleemann, M. Confocal laser microscopy without fluorescent dye in minimal-invasive thoracic surgery: an ex-vivo pilot study in lung cancer. Biomed Tech Biomed Eng 2021;66:285–92.10.1515/bmt-2020-0162Search in Google Scholar

29. Cardinali, DP. The Enlarged Autonomic Nervous System. Autonomic Nervous System – basic and clinical aspects. Switzerland: Springer International Publishing; 2017.10.1007/978-3-319-57571-1Search in Google Scholar

30. He, K, Zhou, J, Yang, F, Chi, C, Li, H, Mao, Y, et al.. Near-infrared intraoperative imaging of thoracic sympathetic nerves: from preclinical study to clinical trial. Theranostics 2018;8:304–13.10.7150/thno.22369Search in Google Scholar PubMed PubMed Central

31. Stelzle, F, Rohde, M, Riemann, M, Oetter, N, Adler, W, Tangermann-Gerk, K, et al.. Autofluorescence spectroscopy for nerve-sparing laser surgery of the head and neck-the influence of laser-tissue interaction. Laser Med Sci 2017;32:1289–300.10.1007/s10103-017-2240-8Search in Google Scholar PubMed

32. Crowe, CS, Liao, JC, Curtin, CM. Optical biopsy of peripheral nerve using confocal laser endomicroscopy: a new tool for nerve surgeons?. Arch Plast Surg 2015;42:626–9.10.5999/aps.2015.42.5.626Search in Google Scholar PubMed PubMed Central

33. Hoffman, A, Rey, JW, Mueller, L, Hansen, T, Goetz, M, Tresch, A, et al.. Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract. Dig Liver Dis 2014;46:140–5.10.1016/j.dld.2013.09.004Search in Google Scholar PubMed

Received: 2021-05-30

Accepted: 2021-11-26

Published Online: 2021-12-17

Published in Print: 2022-02-23

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Articles in the same Issue

https://doi.org/10.1515/bmt-2021-0171

Keywords for this article

confocallaser microscopy; diagnostic accuracy; medical engineering; minimal invasive surgery; nervous tissue; sympathetic trunk