Ex vivo Visualization of Human Gliomas with Cross-Polarization Optical Coherence Tomography: Pilot Study

Optical coherence tomography (OCT) is a promising method of optical diagnostics in neurosurgery. This paper presents the initial results of using cross-polarization OCT (CP OCT) for the visualization of glioma tissue. CP OCT can detect the scattering and polarization properties of tissues and thereby provide more information about their structure than traditional OCT.

The aim of the study was to evaluate the capabilities of CP OCT as an imaging tool for the visualization of glial tumors with different degrees of malignancy.

Materials and Methods. The study was performed on material obtained from the intraoperative biopsies (ex vivo specimens) of 18 patients with gliomas ranging from Grade I to Grade IV. Seventy nine samples of tumor and non-tumor tissue were studied using the CP OCT device developed the Institute of Applied Physics of the Russian Academy of Sciences (Nizhny Novgorod, Russia). 361 CP OCT images were acquired and analyzed. They were compared with histological data seen in sections coincident with the planes of the OCT scans.

Results. The correspondence between the CP OCT images of human brain tissue and glial tumors and their morphological features was determined. A comparative evaluation of the characteristics of the CP OCT signals of glial tumors Grade I–IV and non-cancerous brain tissue was carried out.

Conclusion. The morphological features of white matter and glial tumors can be differentiated based on the intensity, homogeneity and attenuation of the CP OCT signals. The use of high-speed spectral CP OCT device appears to have great potential in the neurosurgery practice.

1. Huang D., Swanson E.A., Lin C.P., Schuman J.S., Stinson W.G., Chang W., Hee M.R., Flotte T., Gregory K., Puliafito C.A., Fujimoto J.G. Optical coherence tomography. Science 1991; 254(5035): 1178–1181, https://doi.org/10.1126/science.1957169.
2. Fercher A.F., Hitzenberger C.K., Kamp G., El-Zaiat S.Y. Measurement of intraocular distances by backscattering spectral interferometry. Optics Communications 1995; 117(1–2): 43–48, https://doi.org/10.1016/0030-4018(95)00119-s.
3. Su M.I., Chen C.Y., Yeh H.I., Wang K.T. Concise review of optical coherence tomography in clinical practice. Acta Cardiol Sin 2016; 32(4): 381–386.
4. Osiac E., Bălşeanu T.A., Cătălin B., Mogoantă L., Gheonea C., Dinescu S.N., Albu C.V., Cotoi B.V., Tica O.S., Sfredel V. Optical coherence tomography as a promising imaging tool for brain investigations. Rom J Morphol Embryol 2014; 55(2 Suppl): 507–512.
5. Murthy R.K., Haji S., Sambhav K., Grover S., Chalam K.V. Clinical applications of spectral domain optical coherence tomography in retinal diseases. Biomed J 2016; 39(2): 107–120, https://doi.org/10.1016/j.bj.2016.04.003.
6. Zhang Y., Chen Y., Yu Y., Xue X., Tuchin V.V., Zhu D. Visible and near-infrared spectroscopy for distinguishing malignant tumor tissue from benign tumor and normal breast tissues in vitro. J Biomed Opt 2013; 18(7): 077003, https://doi.org/10.1117/1.jbo.18.7.077003.
7. 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.
8. 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.
9. 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. Science Translational Medicine 2015; 7: 292ra100, https://doi.org/10.1126/scitranslmed.3010611.
10. Sanai N., Berger M.S. Glioma extent of resection and its impact on patient outcome. Neurosurgery 2008; 62(4): 753–764, https://doi.org/10.1227/01.neu.0000318159.21731.cf.
11. 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.
12. 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.
13. Bizheva K., Unterhuber A., Hermann B., Povazay B., Sattmann H., Fercher A.F., Drexler W., Preusser M., Budka H., Stingl A., Le T. Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography. J Biomed Opt 2005; 10(1): 11006, https://doi.org/10.111 7/1.1851513.
14. Kantelhardt S.R., Finke M., Schweikard A., Giese A. Evaluation of a completely robotized neurosurgical operating microscope. Neurosurgery 2013; 72: A19–A26, https://doi.org/10.1227/NEU.0b013e31827235f8.
15. 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.
16. Lankenau E., Klinger D., Winter C., Malik A., Müller H.H., Oelckers S., Pau H.-W., Just T., Hüttmann G. Combining optical coherence tomography (OCT) with an operating microscope. In: Advances in medical engineering. Vol 114. Springer Berlin Heidelberg; 2007; p. 343–348, https://doi.org/10.1007/978-3-540-68764-1_57.
17. Nakaji H., Kouyama N., Muragaki Y., Kawakami Y., Iseki H. Localization of nerve fiber bundles by polarization-sensitive optical coherence tomography. J Neurosci Methods 2008; 174(1): 82–90, https://doi.org/10.1016/j.jneumeth.2008.07.004.
18. de Boer J.F., Srinivas S.M., Park B.H., Pham T.H., Zhongping C., Milner T.E., Nelson J.S. Polarization effects in optical coherence tomography of various biological tissues. IEEE J Sel Top Quantum Electron 1999; 5(4): 1200–1204, https://doi.org/10.1109/2944.796347.
19. Kuranov R., Sapozhnikova V., Turchin I., Zagainova E., Gelikonov V., Kamensky V., Snopova L., Prodanetz N. Complementary use of cross-polarization and standard OCT for differential diagnosis of pathological tissues. Opt Express 2002; 10(15): 707–713, https://doi.org/10.1364/oe.10.000707.
20. Chen W., Wang D., Du X., He Y., Chen S., Shao Q., Ma C., Huang B., Chen A., Zhao P., Qu X., Li X. Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes. Med Oncol 2015; 32(3): 43, https://doi.org/10.1007/s12032-015-0487-0.
21. Wang H., Akkin T., Magnain C., Wang R., Dubb J., Kostis W.J., Yaseen M.A., Cramer A., Sakadžić S., Boas D. Polarization sensitive optical coherence microscopy for brain imaging. Opt Lett 2016; 41(10): 2213–2216, https://doi.org/10.1364/ol.41.002213.
22. Gladkova N., Kiseleva E., Robakidze N., Balalaeva I., Karabut M., Gubarkova E., Feldchtein F. Evaluation of oral mucosa collagen condition with cross-polarization optical coherence tomography. J Biophotonics 2013; 6(4): 321–329, https://doi.org/10.1002/jbio.201200059.
23. Gladkova N., Kiseleva E., Streltsova O., Prodanets N., Snopova L., Karabut M., Gubarkova E., Zagaynova E. Combined use of fluorescence cystoscopy and cross-polarization OCT for diagnosis of bladder cancer and correlation with immunohistochemical markers. J Biophotonics 2013; 6(9): 687–698. https://doi.org/10.1002/jbio.201200105.
24. Gubarkova E.V., Dudenkova V.V., Feldchtein F.I., Timofeeva L.B., Kiseleva E.B., Kuznetsov S.S., Shakhov B.E., Moiseev A.A., Gelikonov V.M., Gelikonov G.V., Vitkin A., Gladkova N.D. Multi-modal optical imaging characterization of atherosclerotic plaques. J Biophotonics 2015, https://doi.org/10.1002/jbio.201500223.
25. Gelikonov V.M., Gelikonov G.V., Shilyagin P.A. Linear-wavenumber spectrometer for high-speed spectral-domain optical coherence tomography. Optics and Spectroscopy 2009; 106(3): 459–465, https://doi.org/10.1134/s0030400x09030242.
26. Moiseev A.A., Gelikonov G.V., Terpelov D.A., Shilyagin P.A., Gelikonov V.M. Noniterative method of reconstruction optical coherence tomography images with improved lateral resolution in semitransparent media. Laser Physics Letters 2013; 10(12): 125601, https://doi.org/10.1088/1612-2011/10/12/125601.
27. 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.
28. Tuchin V.V. Lazery i volokonnaya optika v biomeditsinskikh issledovaniyakh [Lasers and fiber optics in biomedical research]. Moscow: FIZMALIT; 2010; 488 p.
29. Angiogenesis. In: Brain tumor pathology: current diagnostic hotspots and pitfalls. Springer Netherlands; 2006; p. 189–198, https://doi.org/10.1007/1-4020-3998-0_15.
30. Bevilacqua F., Piguet D., Marquet P., Gross J.D., Tromberg B.J., Depeursinge C. In vivo local determination of tissue optical properties: applications to human brain. Appl Opt 1999; 38(22): 4939–4950, https://doi.org/10.1364/ao.38.004939.
31. Amberger V.R., Hensel T., Ogata N., Schwab M.E. Spreading and migration of human glioma and rat C6 cells on central nervous system myelin in vitro is correlated with tumor malignancy and involves a metalloproteolytic activity. Cancer Res 1998; 58(1): 149–158.
32. Alaminos M., Dávalos V., Ropero S., Setién F., Paz M.F., Herranz M., Fraga M.F., Mora J., Cheung N.K., Gerald W.L., Esteller M. EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma. Cancer Res 2005; 65(7): 2565–2571, https://doi.org/10.1158/0008-5472.can-04-4283.
33. Brat D.J., Perry A.Astrocytic and oligodendroglial tumor. In: Practical surgical neuropathology. New York: Churchill Livingstone; 2010; p. 63–102, https://doi.org/10.1016/b978-0-443-06982-6.00005-5.
34. 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.
35. Miller C.R., Perry A. Glioblastoma. Arch Pathol Lab Med 2007; 131(3): 397–406.

Yashin K.S., Gubarkova E.V., Kiseleva E.B., Kuznetsov S.S., Karabut M.M., Timofeeva L.B., Snopova L.B., Moiseev A.A., Medyanik I.А., Kravets L.Ya., Gladkova N.D. Ex vivo Visualization of Human Gliomas with Cross-Polarization Optical Coherence Tomography: Pilot Study. Sovremennye tehnologii v medicine 2016; 8(4): 14, https://doi.org/10.17691/stm2016.8.4.02