Display options
Share it on

Cancers (Basel). 2021 Jun 29;13(13). doi: 10.3390/cancers13133234.

Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging.

Cancers

Gabriel Giardina, Alexander Micko, Daniela Bovenkamp, Arno Krause, Fabian Placzek, Laszlo Papp, Denis Krajnc, Clemens P Spielvogel, Michael Winklehner, Romana Höftberger, Greisa Vila, Marco Andreana, Rainer Leitgeb, Wolfgang Drexler, Stefan Wolfsberger, Angelika Unterhuber

Affiliations

  1. Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
  2. Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
  3. QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
  4. Christian Doppler Laboratory for Applied Metabolomics, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
  5. Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
  6. Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

PMID: 34209497 PMCID: PMC8267638 DOI: 10.3390/cancers13133234

Abstract

Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph. First-level binary classification for discrimination of pituitary gland and adenomas was performed by feature extraction via radiomic analysis on OCT and MPM images and achieved an accuracy of 88%. Second-level multi-class classification was performed based on molecular analysis of the specimen via LSRM to discriminate pituitary adenomas subtypes with accuracies of up to 99%. Chemical compounds such as lipids, proteins, collagen, DNA and carotenoids and their relation could be identified as relevant biomarkers, and their spatial distribution visualized to provide deeper insight into the chemical properties of pituitary adenomas. Thereby, the aim of the current work was to assess a unique label-free and non-invasive multimodal optical imaging platform for pituitary tissue imaging and to perform a multiparametric morpho-molecular metabolic analysis and classification.

Keywords: Raman spectroscopy; image analysis; multimodal imaging; multiphoton microscopy; optical coherence tomography; pituitary gland and adenomas; radiomics; second harmonic generation; two-photon excitation fluorescence

References

  1. J Biomed Opt. 2014;19(7):071412 - PubMed
  2. Nat Rev Endocrinol. 2011 May;7(5):257-66 - PubMed
  3. Int J Mol Sci. 2019 Jul 10;20(14): - PubMed
  4. Sci Rep. 2019 Feb 28;9(1):3007 - PubMed
  5. Surg Oncol. 2019 Dec;31:119-131 - PubMed
  6. J Photochem Photobiol B. 2009 Apr 2;95(1):46-57 - PubMed
  7. Lasers Med Sci. 2007 Nov;22(4):229-36 - PubMed
  8. Anal Chim Acta. 2011 Oct 17;704(1-2):47-56 - PubMed
  9. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19494-9 - PubMed
  10. Analyst. 2018 Apr 16;143(8):1735-1757 - PubMed
  11. Eur Radiol Exp. 2018 Nov 14;2(1):36 - PubMed
  12. Opt Lett. 2003 Jun 1;28(11):905-7 - PubMed
  13. Photodiagnosis Photodyn Ther. 2019 Sep;27:156-161 - PubMed
  14. Cancers (Basel). 2021 Mar 12;13(6): - PubMed
  15. Annu Rev Pathol. 2009;4:97-126 - PubMed
  16. Cancer. 2004 Aug 1;101(3):613-9 - PubMed
  17. Sci Adv. 2020 Jul 10;6(28):eaba6156 - PubMed
  18. Adv Drug Deliv Rev. 2016 Feb 1;97:4-27 - PubMed
  19. Eur J Endocrinol. 2014 Oct;171(4):519-26 - PubMed
  20. Biomed Eng Online. 2003 May 17;2:13 - PubMed
  21. J Neurosurg. 2008 Aug;109(2):306-12 - PubMed
  22. J Endocrinol Invest. 2019 Apr;42(4):443-451 - PubMed
  23. Pituitary. 2013 Dec;16(4):545-53 - PubMed
  24. Anal Chem. 2011 May 1;83(9):3224-31 - PubMed
  25. Molecules. 2019 Oct 04;24(19): - PubMed
  26. J Neurosurg. 2020 Apr 17;:1-8 - PubMed
  27. Appl Spectrosc. 2003 Nov;57(11):1363-7 - PubMed
  28. J Neurosurg. 2019 May 31;132(6):1739-1746 - PubMed
  29. Biopolymers. 1984 Feb;23(2):235-56 - PubMed
  30. Eur J Cancer. 2012 Mar;48(4):441-6 - PubMed
  31. J Neurosurg. 1986 Dec;65(6):733-44 - PubMed
  32. Biomed Opt Express. 2018 Feb 28;9(3):1375-1388 - PubMed
  33. Photochem Photobiol Sci. 2019 May 15;18(5):997-1008 - PubMed
  34. Photodiagnosis Photodyn Ther. 2020 Sep;31:101932 - PubMed
  35. Methods Mol Biol. 2010;594:155-62 - PubMed
  36. Biomed Opt Express. 2020 Nov 09;11(12):7003-7018 - PubMed
  37. Cancer Res. 2010 Jun 1;70(11):4759-66 - PubMed
  38. Best Pract Res Clin Endocrinol Metab. 2019 Apr;33(2):101278 - PubMed
  39. J Nucl Med. 2019 Jun;60(6):864-872 - PubMed
  40. Eur J Nucl Med Mol Imaging. 2021 Jun;48(6):1795-1805 - PubMed
  41. Biochem Biophys Res Commun. 2018 Oct 7;504(3):582-589 - PubMed
  42. Acta Neuropathol. 2017 Oct;134(4):521-535 - PubMed
  43. Biotech Histochem. 2005 Mar-Apr;80(2):73-8 - PubMed
  44. Anal Chem. 2003 Aug 15;75(16):4312-8 - PubMed
  45. Sci Rep. 2018 Jun 20;8(1):9417 - PubMed
  46. J Microsc. 2000 Nov;200(Pt 2):83-104 - PubMed
  47. J Neurooncol. 2014 May;117(3):379-94 - PubMed
  48. Pituitary. 2018 Aug;21(4):362-370 - PubMed

Publication Types

Grant support