Cross-Polarization Optical Coherence Tomography in Comparative in vivo and ex vivo Studies of the Optical Properties of Normal and Tumorous Brain Tissues

The aim of the study was to provide visual and quantitative evaluation of tumorous and normal brain tissue images obtained by cross-polarization optical coherence tomography (CP OCT) in a comparative in vivo and ex vivo study.

Materials and Methods. The CP OCT as a non-damaging noninvasive optical method for tissue structure imaging was used in the study. It enables obtaining volumetric images of 2.4×2.4×1.25 mm³ in size in real time within a short time of 26 s. The objects were tumorous and normal brain tissues of 12 experimental animals (Wistar rats): 4 — intact, 4 — with induced malignant glioma 101.8 and 4 — with induced malignant glioma C6.

The cortex and white matter in intact rats and the central part of the tumor (from the cortical surface) in rats with tumor models were imaged by CP OCT first in vivo, and then the same regions were scanned ex vivo. To evaluate quantitatively the CP OCT data, the calculation of the attenuation coefficients for each type of tissue was done.

Results. Qualitative image analysis of normal brain tissues and gliomas showed that the ex vivo CP OCT images have the intensity and the attenuation rate (in both the initial and orthogonal polarizations) greater than those obtained in vivo. Quantitative analysis of the CP OCT images revealed significant differences (p<0.02) between the attenuation coefficients (for both tumors and the white matter) found in vivo (5.5 [4.8; 5.8] mm^–1 for glioma 101.8; 3.2 [2.4; 4.3] mm^–1 for glioma C6; and 7.5 [7.0; 8.0] mm^–1 for the normal white matter) as compared with those found ex vivo (7.0 [5.9; 8.1] mm^–1 for glioma 101.8; 6.8 [6.2; 7.9] mm^–1 for glioma C6; and 9.0 [8.4; 9.5] mm^–1 for the normal white matter). For the cerebral cortex, no significant difference was found in this case (5.8 [4.9; 6.6] mm^–1 versus 6.3 [5.5; 7.1] mm^–1, p=0.34). A comparison of the attenuation coefficients between the cortex and the white matter, as well as the white matter and malignant tissues, showed significant differences both in vivo and ex vivo. Cortex has got unique characteristics on in vivo CP OCT images that disappear on ex vivo CP OCT images.

Conclusion. The present comparative analysis of the optical properties of white matter and tumorous tissues of the brain allow us to conclude that the CP OCT images obtained ex vivo show a full qualitative similarity with the in vivo CP OCT images. The quantitative evaluation of the CP OCT signals revealed a significant difference in the attenuation coefficient (p<0.005) between the tumorous tissue and the white matter both in ex vivo and in vivo study. When the optical coefficients of tissues are evaluated in vivo, it is necessary to introduce corrections based on the known differences between the ex vivo and in vivo attenuation coefficients.

1. Potapov A.A., Goryaynov S.A., Okhlopkov V.A., Pitskhelauri D.I., Kobyakov G.L., Zhukov V.Y., Gol’bin D.A., Svistov D.V., Martynov B.V., Krivoshapkin A.L., Gaytan A.S., Anokhina Y.E., Varyukhina M.D., Gol’dberg M.F., Kondrashov A.V., Chumakova A.P. Clinical guidelines for the use of intraoperative fluorescence diagnosis in brain tumor surgery. Zh Vopr Neirokhir Im N N Burdenko 2015; 79(5): 91–101, https://doi.org/10.17116/neiro201579591-101.
2. Selbekk T., Jakola A.S., Solheim O., Johansen T.F., Lindseth F., Reinertsen I., Unsgard G. Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochir (Wien) 2013; 155(6): 973–980, https://doi.org/10.1007/s00701-013-1647-7.
3. Semin P.A., Krivoshapkin A.L., Melidi E.G., Kanygin V.V. Frameless neuronavigation and its application in the course of surgery of cerebral mass lesions. Neyrokhirurgiya 2004; 2: 20–24.
4. Fahlbusch R., Samii A. Editorial: Intraoperative MRI. Neurosurg Focus 2016; 40(3): E3, https://doi.org/10.3171/2015.12.focus15631.
5. 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.
6. Díez Valle R., Tejada Solis S., Idoate Gastearena M.A., García de Eulate R., Domínguez Echávarri P., Aristu Mendiroz J. Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience. J Neurooncol 2011; 102(1): 105–113, https://doi.org/10.1007/s11060-010-0296-4.
7. 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.
8. Stummer W., Pichlmeier U., Meinel T., Wiestler O.D., Zanella F., Reulen H.J. 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.
9. Vasefi F., MacKinnon N., Farkas D.L., Kateb B. Review of the potential of optical technologies for cancer diagnosis in neurosurgery: a step toward intraoperative neurophotonics. Neurophotonics 2016; 4(1): 011010, https://doi.org/10.1117/1.nph.4.1.011010.
10. Yashin K.S., Kravets L.Y., Gladkova N.D., Gelikonov G.V., Medyanik I.A., Karabut M.M., Kiseleva E.B., Shilyagin P.A. Optical coherence tomography in neurosurgery. Zh Vopr Neirokhir Im N N Burdenko 2017; 81(3): 107–115, https://doi.org/10.17116/neiro2017813107-115.
11. 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.
12. 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.
13. Herrero-Garibi J., Cruz-Gonzalez I., Parejo-Diaz P., Jang I.K. Optical coherence tomography: its value in intravascular diagnosis today. Rev Esp Cardiol 2010; 63(8): 951–962, https://doi.org/10.1016/s1885-5857(10)70189-4.
14. Mathews M.S., Su J., Heidari E., Levy E.I., Linskey M.E., Chen Z. Neuroendovascular optical coherence tomography imaging and histological analysis. Neurosurgery 2011; 69(2): 430–439, https://doi.org/10.1227/neu.0b013e318212bcb4.
15. Lankenau E.M., Krug M., Oelckers S., Schrage N., Just T., Hüttmann G. iOCT with surgical microscopes: a new imaging during microsurgery. Advanced Optical Technologies 2013; 2(3), https://doi.org/10.1515/aot-2013-0011.
16. Zagaynova E., Gladkova N., Shakhova N., Gelikonov G., Gelikonov V. Endoscopic OCT with forward-looking probe: clinical studies in urology and gastroenterology. J Biophotonics 2008; 1(2): 114–128, https://doi.org/10.1002/jbio.200710017.
17. Sun C., Lee K.K., Vuong B., Cusimano M.D., Brukson A., Mauro A., Munce N., Courtney B.K., Standish B.A., Yang V.X. Intraoperative handheld optical coherence tomography forward-viewing probe: physical performance and preliminary animal imaging. Biomed Opt Express 2012; 3(6): 1404–1412, https://doi.org/10.1364/boe.3.001404.
18. Kut C., Chaichana K.L., Xi J., Raza S.M., Ye X., McVeigh E.R., Rodriguez F.J., Quinones-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.
19. 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.
20. 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/10.1117/1.1851513.
21. Boppart S.A., Brezinski M.E., Pitris C., Fujimoto J.G. Optical coherence tomography for neurosurgical imaging of human intracortical melanoma. Neurosurgery 1998; 43(4): 834–841, https://doi.org/10.1097/00006123-199810000-00068.
22. Yuan W., Kut C., Liang W., Li X. Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection. Sci Rep 2017; 7: 44909, https://doi.org/10.1038/srep44909.
23. Gubarkova E.V., Kirillin M.Y., Dudenkova V.V., Timashev P.S., Kotova S.L., Kiseleva E.B., Timofeeva L.B., Belkova G.V., Solovieva A.B., Moiseev A.A., Gelikonov G.V., Fiks I.I., Feldchtein F.I., Gladkova N.D. Quantitative evaluation of atherosclerotic plaques using cross-polarization optical coherence tomography, nonlinear, and atomic force microscopy. J Biomed Opt 2016; 21(12): 126010, https://doi.org/10.1117/1.jbo.21.12.126010.
24. 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.
25. 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.
26. Yashin К.S., Gubarkova E., Kiseleva E., 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(3): 14–22, https://doi.org/10.17691/stm2016.8.4.02.
27. Khalansky A.S., Kondakova L.I., Gelperina S.Е. Transplanted rat glioma 101.8. II. The application in experimental neurooncology and therapy. Klinicheskaya i eksperimental’naya morfologiya 2014; 1(9): 50–59.
28. Gelikonov V.M., Gelikonov G.V. New approach to cross-polarized optical coherence tomography based on orthogonal arbitrarily polarized modes. Laser Physics Letters 2006; 3(9): 445–451, https://doi.org/10.1002/lapl.200610030.
29. Matveev L.A., Zaitsev V.Y., Gelikonov G.V., Matveyev A.L., Moiseev A.A., Ksenofontov S.Y., Gelikonov V.M., Sirotkina M.A., Gladkova N.D., Demidov V., Vitkin A. Hybrid M-mode-like OCT imaging of three-dimensional microvasculature in vivo using reference-free processing of complex valued B-scans. Opt Lett 2015; 40(7): 1472–1475, https://doi.org/10.1364/ol.40.001472.
30. 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.

Kiseleva E.B., Yashin K.S., Moiseev A.A., Sirotkina M.A., Timofeeva L.B., Fedoseeva V.V., Alekseeva A.I., Medyanik I.A., Karyakin N.N., Kravets L.Ya., Gladkova N.D. Cross-Polarization Optical Coherence Tomography in Comparative in vivo and ex vivo Studies of the Optical Properties of Normal and Tumorous Brain Tissues. Sovremennye tehnologii v medicine 2017; 9(4): 177, https://doi.org/10.17691/stm2017.9.4.22