Multiphoton Tomography and Cross-Polarization Optical Coherence Tomography for Diagnosing Brain Gliomas: Pilot Study

Progress in the surgery of infiltratively growing gliomas is closely related to intraoperative diagnostics. Currently the most promising methods of optical imaging in the field of intraoperative identification of glioma boundaries and of grade of tumor are those providing high spatial resolution, such as optical coherence tomography (OCT) and multiphoton tomography (MPT). Nevertheless, for routine clinical use, evidence-based criteria are required. In this work the results of parallel ex vivo analysis of specimens of different grades of gliomas and of peritumoral areas obtained through the use of MPT and cross-polarization OCT (CP OCT) are compared with simultaneous histological descriptions and are presented in order to reveal the usefulness of each method in neurooncology.

1. Kohler B.A., Ward E., McCarthy B.J., Schymura M.J., Ries L.A., Eheman C., Jemal A., Anderson R.N., Ajani U.A., Edwards B.K. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 2011; 103(9): 714–736, https://doi.org/10.1093/jnci/djr077.
2. Ostrom Q.T., Gittleman H., Farah P., Ondracek A., Chen Y., Wolinsky Y., Stroup N.E., Kruchko C., Barnholtz-Sloan J.S. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 2013; 15(Suppl 2): ii1–ii56, https:/ /doi.org/10.1093/neuonc/not151.
3. Louis D.N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Cavenee W.K., Ohgaki H., Wiestler O.D., Kleihues P., Ellison D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131(6): 803–820, https://doi.org/10.1007/s00401-016-1545-1.
4. Almeida J.P., Chaichana K.L., Rincon-Torroella J., Quinones-Hinojosa A. The value of extent of resection of glioblastomas: clinical evidence and current approach. Curr Neurol Neurosci Rep 2014; 15(2): 517, https://doi.org/10.1007/s11910-014-0517-x.
5. Sanai N., Berger M.S. Glioma extent of resection and its impact on patient outcome. Neurosurgery 2008; 62(4): 753–766, https://doi.org/10.1227/01.neu.0000318159.21731.cf.
6. Sanai N., Polley M.Y., McDermott M.W., Parsa A.T., Berger M.S. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 2011; 115(1): 3–8, https://doi.org/10.3171/2011.2.jns10998.
7. Anokhina Yu.E., Gaidar B.V., Martynov B.V., Svistov D.V., Papayan G.V., Grigorievsky D.I. Prognostic significance of surgery volume under fluorescent intraoperative diagnostic applications in patients with malignant brain gliomas. Vestnik rossiyskoy voenno-meditsinskoy akademii 2014; 1(45): 19–24.
8. Stummer W., Reulen H.J., Meinel T., Pichlmeier U., Schumacher W., Tonn J.C., Rohde V., Oppel F., Turowski B., Woiciechowsky C., Franz K., Pietsch T.; ALA-Glioma Study Group. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008; 62(3): 564–576, https://doi.org/10.1227/01.neu.0000317304.31579.17.
9. McGirt M.J., Chaichana K.L., Gathinji M., Attenello F.J., Than K., Olivi A., Weingart J.D., Brem H., Quinoñes-Hinojosa A.R. Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 2009; 110(1): 156–162, https://doi.org/10.3171/2008.4.17536.
10. McGirt M.J., Chaichana K.L., Attenello F.J., Weingart J.D., Than K., Burger P.C., Olivi A., Brem H., Quinoñes-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery 2008; 63(4): 700–707, https://doi.org/10.1227/01.neu.0000325729.41085.73.
11. Sanai N., Berger M.S. Extent of resection influences outcomes for patients with gliomas. Rev Neurol (Paris) 2011; 167(10): 648–654, https://doi.org/10.1016/j.neurol.2011.
    07.004.
12. Lacroix M., Abi-Said D., Fourney D.R., Gokaslan Z.L., Shi W., DeMonte F., Lang F.F., McCutcheon I.E., Hassenbusch S.J., Holland E., Hess K., Michael C., Miller D., Sawaya R. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001; 95(2): 190–198, https://doi.org/10.3171/jns.2001.95.2.0190.
13. Colditz M.J., Jeffree R.L. Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection. Part 1: Clinical, radiological and pathological studies. J Clin Neurosci 2012; 19(11): 1471–1474, https://doi.org/10.1016/j.jocn.2012.03.009.
14. Stummer W., Pichlmeier U., Meinel T., Wiestler O.D., Zanella F., Reulen H.J.; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006; 7(5): 392–401, https://doi.org/10.1016/s1470-2045(06)70665-9.
15. Zehri A.H., Ramey W., Georges J.F., Mooney M.A., Martirosyan N.L., Preul M.C., Nakaji P. Neurosurgical confocal endomicroscopy: a review of contrast agents, confocal systems, and future imaging modalities. Surg Neurol Int 2014; 5: 60, https://doi.org/10.4103/2152-7806.131638.
16. Kantelhardt S.R., Kalasauskas D., König K., Kim E., Weinigel M., Uchugonova A., Giese A. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue. J Neurooncol 2016; 127(3): 473–482, https://doi.org/10.1007/s11060-016-2062-8.
17. Böhringer H.J., Boller D., Leppert J., Knopp U., Lankenau E., Reusche E., Hüttmann G., Giese A. Time-domain and spectral-domain optical coherence tomography in the analysis of brain tumor tissue. Lasers Surg Med 2006; 38(6): 588–597, https://doi.org/10.1002/lsm.20353.
18. Assayag O., Grieve K., Devaux B., Harms F., Pallud J., Chretien F., Boccara C., Varlet P. Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography. Neuroimage Clin 2013; 2: 549–557, https://doi.org/10.1016/j.nicl.2013.04.005.
19. Kantelhardt S.R., Leppert J., Krajewski J., Petkus N., Reusche E., Tronnier V.M., Hüttmann G., Giese A. Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo. Neuro Oncol 2007; 9(2): 103–112, https://doi.org/10.1215/15228517-2006-034.
20. Kantelhardt S.R., Leppert J., Kantelhardt J.W., Reusche E., Hüttmann G., Giese A. Multi-photon excitation fluorescence microscopy of brain-tumour tissue and analysis of cell density. Acta Neurochir (Wien) 2009; 151(3): 253–262, https://doi.org/10.1007/s00701-009-0188-6.
21. Grutzendler J., Yang G., Pan F., Parkhurst C.N., Gan W.-B. Transcranial two-photon imaging of the living mouse brain. Cold Spring Harb Protoc 2011; 2011(9): pdb.prot065474, https://doi.org/10.1101/pdb.prot065474.
22. Fumagalli S., Coles J.A., Ejlerskov P., Ortolano F., Bushell T.J., Brewer J.M., De Simoni M.G., Dever G., Garside P., Maffia P., Carswell H.V. In vivo real-time multiphoton imaging of T lymphocytes in the mouse brain after experimental stroke. Stroke 2011; 42(5): 1429–1436, https://doi.org/10.1161/strokeaha.110.603704.
23. Kobat D., Horton N.G., Xu C. In vivo two-photon microscopy to 1.6-mm depth in mouse cortex. J Biomed Opt 2011; 16(10): 106014, https://doi.org/10.1117/1.3646209.
24. Wang K., Horton N.G., Xu C. Going deep: brain imaging with multi-photon microscopy. Optics and Photonics News 2013; 24(11): 32–39, https://doi.org/10.1364/opn.24.11.000032.
25. Kantelhardt S.R., Finke M., Schweikard A., Giese A. Evaluation of a completely robotized neurosurgical operating microscope. Neurosurgery 2013; 72(Suppl 1): A19–A26, https://doi.org/10.1227/NEU.0b013e31827235f8.
26. Finke M., Kantelhardt S., Schlaefer A., Bruder R., Lankenau E., Giese A., Schweikard A. Automatic scanning of large tissue areas in neurosurgery using optical coherence tomography. Int J Med Robot 2012; 8(3): 327–336, https://doi.org/10.1002/rcs.1425.
27. Lankenau E., Klinger D., Winter C., Malik A., Müller H., Oelckers S., Pau H.-W., Just T., Hüttmann G. Combining optical coherence tomography (OCT) with an operating microscope. In: Advances in medical engineering. Springer Berlin Heidelberg; 2007; p. 343–348, https://doi.org/10.1007/978-3-540-68764-1_57.
28. Böhringer H.J., Lankenau E., Stellmacher F., Reusche E., Hüttmann G., Giese A. Imaging of human brain tumor tissue by near-infrared laser coherence tomography. Acta Neurochir (Wien) 2009; 151(5): 507–517, https://doi.org/10.1007/s00701-009-0248-y.
29. de Boer J.F., Milner T.E. Review of polarization sensitive optical coherence tomography and Stokes vector determination. J Biomed Opt 2002; 7(3): 359–371, https://doi.org/10.1117/1.1483879.
30. Kiseleva E., Kirillin M., Feldchtein F., Vitkin A., Sergeeva E., Zagaynova E., Streltzova O., Shakhov B., Gubarkova E., Gladkova N. Differential diagnosis of human bladder mucosa pathologies in vivo with cross-polarization optical coherence tomography. Biomed Opt Express 2015; 6(4): 1464–1476, https://doi.org/10.1364/BOE.6.001464.
31. Yashin К.S., Karabut M.M., Fedoseeva V.V., Khalansky A.S., Matveev L.A., Elagin V.V., Kuznetsov S.S., Kiseleva E.B., Kravets L.Y., Medyanik I.А., Gladkova N.D. Multimodal optical coherence tomography in visualization of brain tissue structure at glioblastoma (experimental study). Sovremennye tehnologii v medicine 2016; 8(1): 73–81, https://doi.org/10.17691/stm2016.8.1.10.
32. Khalansky A.S., Kondakova L.I. Transplanted rat glioma 101.8. I. Biological characteristics. Klinicheskaya i eksperimental’naya morfologiya 2013; 4(8): 63–68.
33. Senft C., Bink A., Franz K., Vatter H., Gasser T., Seifert V. IIntraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011; 12(11): 997–1003, https://doi.org/10.1016/s1470-2045(11)70196-6.
34. Valdés P.A., Kim A., Leblond F., Conde O.M., Harris B.T., Paulsen K.D., Wilson B.C., Roberts D.W. Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery. J Biomed Opt 2011; 16(11): 116007, https://doi.org/10.1117/1.3646916.
35. Sanai N., Snyder L.A., Honea N.J., Coons S.W., Eschbacher J.M., Smith K.A., Spetzler R.F. Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas. J Neurosurg 2011; 115(4): 740–748, https://doi.org/10.3171/2011.6.jns11252.
36. Yashin К.S., Gubarkova E.V., Kiseleva E.B., Kuznetsov S.S., Karabut M.M., Medyanik I.А., Kravets L.Y., Gladkova N.D. Ex vivo imaging of human gliomas by cross-polarization optical coherence tomography: pilot study. Sovremennye tehnologii v medicine 2016; 8(4): 14–22, https://doi.org/10.17691/stm2016.8.4.02.
37. Shubina O.S, Teltsov L.P., Komusova O.I. Cytological and morphometric features perednetemennoy neurons of the cerebral cortex of white rats. Sovremennye problemy nauki i obrazovaniya 2015; 2(1). URL: http://www.science-education.ru/en/article/view?id=19078.
38. Kantelhardt S.R., Leppert J., Kantelhardt J.W., Reusche E., Hüttmann G., Giese A. Multi-photon excitation fluorescence microscopy of brain-tumour tissue and analysis of cell density. Acta Neurochir (Wien) 2009; 151(3): 253–262, https://doi.org/10.1007/s00701-009-0188-6.
39. Rodriguez C.L., Szu J.I., Eberle M.M., Wang Y., Hsu M.S., Binder D.K., Park B.H. Decreased light attenuation in cerebral cortex during cerebral edema detected using optical coherence tomography. Neurophotonics 2014; 1(2): 025004, https://doi.org/10.1117/1.NPh.1.2.025004.
40. Eschbacher J., Martirosyan N.L., Nakaji P., Sanai N., Preul M.C., Smith K.A., Coons S.W., Spetzler R.F. In vivo intraoperative confocal microscopy for real-time histopathological imaging of brain tumors. J Neurosurg 2012; 116(4): 854–860, https://doi.org/10.3171/2011.12.jns11696.
41. Schlosser H.G., Suess O., Vajkoczy P., van Landeghem F.K., Zeitz M., Bojarski C. Confocal neurolasermicroscopy in human brain — perspectives for neurosurgery on a cellular level (including additional comments to this article). Cent Eur Neurosurg 2010; 71(1): 13–19, https://doi.org/10.1055/s-0029-1237735.
42. Kantelhardt S.R., Leppert J., Krajewski J., Petkus N., Reusche E., Tronnier V.M., Huttmann G., Giese A. Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo. Neuro Oncol 2007; 9(2): 103–112, https://doi.org/10.1215/15228517-2006-034.
43. Kut C., Chaichana K.L., Xi J., Raza S.M., Ye X., McVeigh E.R., Rodriguez F.J., Quiñones-Hinojosa A., Li X. Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography. Sci Transl Med 2015; 7(292): 292ra100, https://doi.org/10.1126/scitranslmed.3010611.

Dudenkova V.V., Yashin K.S., Kiseleva E.B., Kuznetsov S.S., Timofeeva L.B., Khalansky A.S., Elagin V.V., Gubarkova E.V., Karabut M.M., Pavlova N.P., Medyanik I.A., Kravets L.Ya., Gladkova N.D. Multiphoton Tomography and Cross-Polarization Optical Coherence Tomography for Diagnosing Brain Gliomas: Pilot Study. Sovremennye tehnologii v medicine 2016; 8(4): 64, https://doi.org/10.17691/stm2016.8.4.09