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The Development of the Methodology of Monitoring Experimental Tumors Using Multimodal Optical Coherence Tomography: the Choice of an Optimal Tumor Model

The Development of the Methodology of Monitoring Experimental Tumors Using Multimodal Optical Coherence Tomography: the Choice of an Optimal Tumor Model

Sirotkina М.А., Buyanova N.L., Kalganova Т.I., Karabut М.М., Elagin V.V., Kuznetsov S.S., Snopova L.B., Gelikonov G.V., Zaitsev V.Yu., Matveev L.А., Zagaynova E.V., Vitkin A., Gladkova N.D.
Keywords: experimental tumor model; colon adenocarcinoma Colo-26; optical coherence tomography; ОCТ; cross-polarized OCT; microangiopathic OCT.
СТМ, 2015, volume 7, issue 2, pages 6-15.

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The objective of the research was to study the features of transplantation, growth and visualization of experimental tumors of animals, using multi-functional optical coherence tomography (OCT) to develop the methodology of evaluation of individual tumor response to anti-cancer therapy.

Materials and Methods. The research was carried out using an experimental high-speed spectral-domain multimodal OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences (Russia). The technical characteristics of the system are the following: speed of information acquisition, 20,000 А-scans per second; 1.3 μm wavelength; frame size, approximately 4×2 mm; lateral resolution, 25 μm; and depth resolution, 10 μm. We evaluated cross-polarized (CP) and microangiopathic (МА) OCT images.

We performed an OCT study of the experimental tumor model of colon adenocarcinoma of mice Colo-26 on BALB/с mice (transplanted by suspension of tumor cells culture) inoculated subcutaneously into the thigh, intradermally into auricle, and in a dorsal skin-fold window chamber. In the case of a deep subcutaneous location of a nodule, skin flap over the tumor was surgically opened. CP OCT images were compared with histological preparations (stained using hematoxylin and eosine).

Results. It was established that a Colo-26 tumor growing subcutaneously is not suitable with OCT monitoring investigations. Applying of tumor model with opened skin flap made it possible considerably to increase the visualization depth; however, it is not feasible to use this method for everyday OCT monitoring. The tumor grown within a dorsal window chamber is optimal for the visualization of blood vessels by means the OCT. Nevertheless, the inflammation and edema sometimes observed at the tumor site impeded the МА OCT study. Superficial tumors on the auricle are available for OCT investigation throughout their entire depth if the size of nodule does not exceed 1.5 mm. The tumor model on the auricle is convenient for physiological studies of the state of the vessels during the tumor growth.

Conclusions. The optimal tumor model for dynamic multimodal OCT observation is a tumor on the auricle. Unlike a tumor located on the thigh it is characterized by a subcutaneous location of the nodule yet one which still remains accessible for visualization. The tumor evolving in the ear can be studied using dynamics which would be impossible for the tumor with opened skin flap. Tumors in the dorsal skin window can also be used for research, but the monitoring of their growth is limited to those that are no larger than 5–7 mm, as the nodule goes beyond the window due to the decreased elasticity of the skin, typical of these mice.

  1. Von Minckwitz G., Untch M., Blohmer J.-U., Costa S.D., Eidtmann H., Fasching P.A., Gerber B., Eiermann W., Hilfrich J., Huober J., Jackisch C., Kaufmann M., Konecny G.E., Denkert C., Nekljudova V., Mehta K., Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012; 30(15): 1796–1804,
  2. Vaupel P. Prognostic potential of the pre-therapeutic tumor oxygenation status. Adv Exp Med Biol 2009; 645: 241–246,
  3. Yoo S.Y., Kim J.-S., Sung K.W., Jeon T.Y., Choi J.Y., Moon S.H., Son M.H., Lee S.H., Yoo K.H., Koo H.H. The degree of tumor volume reduction during the early phase of induction chemotherapy is an independent prognostic factor in patients with high-risk neuroblastoma. Cancer 2013; 119(3): 656–664,
  4. Standish B.A., Lee K.K.C., Jin X., Mariampillai A., Munce N.R., Wood M.F.G., Wilson B.C., Vitkin I.A., Yang V.X.D. Interstitial Doppler optical coherence tomography as a local tumor necrosis predictor in photodynamic therapy of prostatic carcinoma: an in vivo study. Cancer Res 2008; 68(23): 9987–9995,
  5. Davoudi B., Morrison M., Bizheva K., Yang V.X.D., Dinniwell R., Levin W., Vitkin I.A. Optical coherence tomography platform for microvascular imaging and quantification: initial experience in late oral radiation toxicity patients. J Biomed Opt 2013; 18(7): 076008,
  6. Zaitsev V.Yu., Gelikonov V.M., Matveev L.A., Gelikonov G.V., Matveyev A.L., Shilyagin P.A., Vitkin I.A. Recent trends in multimodal optical coherence tomography. I. Polarization-sensitive OCT and conventional approaches to OCT elastography. Radiophysics and Quantum Electronics 2014; 57(1): 52–66,
  7. Zaitsev V.Yu., Vitkin I.A., Matveev L.A., Gelikonov V.M., Matveyev A.L., Gelikonov G.V. Recent trends in multimodal optical coherence tomography. II. The correlation-stability approach in OCT elastography and methods for visualization of microcirculation. Radiophysics and Quantum Electronics 2014; 57(3): 210–225,
  8. Daenen L.G.M., Roodhart J.M.L., van Amersfoort M., Dehnad M., Roessingh W., Ulfman L.H., Derksen P.W.B., Voest E.E. Chemotherapy enhances metastasis formation via VEGFR-1–expressing endothelial cells. Cancer Res 2011; 71(22): 6976–6985,
  9. Lee W.-C., Chang C.-H., Ho C.-L., Chen L.-C., Wu Y.-H., Chen J.-T., Wang Y.-L., Lee T.-W. Early detection of tumor response by FLT/MicroPET imaging in a C26 Murine colon carcinoma solid tumor animal model. J Biomed Biotechnol 2011,
  10. Park H., Na K. Conjugation of the photosensitizer Chlorin e6 to pluronic F127 for enhanced cellular internalization for photodynamic therapy. Biomaterials 2013; 34(28): 6992–7000,
  11. Gobin A.M., Lee M.H., Halas N.J., James W.D., Drezek R.A., West J.L. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. NanoLetters 2007; 7(7): 1929–1934,
  12. Song H.-W., Lee S.-W., Jung M.-H., Kim K.R., Yang S., Won Park J., Jeong M.-S., Jung M.Y., Kim S. Optical monitoring of tumors in BALB/c nude mice using optical coherence tomography. Journal of the Optical Society of Korea 2013; 17(1): 91–96,
  13. Skala M.C., Fontanella A., Hendargo H., Dewhirst M.W., Izatt J.A. Combined hyperspectral and spectral domain optical coherence tomography microscope for non-invasive hemodynamic imaging. Opt Lett 2009; 34(3): 289–291,
  14. Leitgeb R., Hitzenberger C., Fercher A. Performance of fourier domain vs. time domain optical coherence tomography. Opt Express 2003; 11(8): 889–894,
  15. 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,
  16. Gelikonov V.M., Gelikonov G.V., Kasatkina I.V., Terpelov D.A., Shilyagin P.A. Coherent noise compensation in spectral-domain optical coherence tomography. Optics and Spectroscopy 2009; 106(6): 895–900,
  17. Gelikonov V.M., Gelikonov G.V., Terpelov D.A., Shabanov D.V., Shilyagin P.A. Suppression of image autocorrelation artefacts in spectral domain optical coherence tomography and multiwave digital holography. Quantum Electronics 2012; 42(5): 390,
  18. Shilyagin P.A., Gelikonov G.V., Gelikonov V.M., Moiseev A.A., Terpelov D.A. Achromatic registration of quadrature components of the optical spectrum in spectral domain optical coherence tomography. Quantum Electronics 2014; 44(7): 664,
  19. Gelikonov V.M., Gelikonov G.V. New approach to cross-polarized optical coherence tomography based on orthogonal arbitrarily polarized modes. Laser Phys Lett 2006; 3(9): 445–451,
  20. Matveev L.A., Zaitsev V.Yu., Gelikonov G.V., Matveyev A.L., Moiseev A.A., Ksenofontov S.Yu., 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,
  21. Li C.-Y., Shan S., Huang Q., Braun R.D., Lanzen J., Hu K., Lin P., Dewhirst M.W. Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Nat Cancer Inst 2000; 92(2): 143–147,
  22. Prikaz Minzdravsotsrazvitiya RF ot 23.08.2010 №708n “Ob utverzhdenii Pravil laboratornoy praktiki” [Ministry of Health and Social Development of the Russian Federation Decree No.708n as of Aug 23, 2010 “On good laboratory practices of the Russian Federation”].
  23. Mezhdunarodnye rekomendatsii (eticheskiy kodeks) po provedeniyu mediko-biologicheskikh issledovaniy s ispol’zovaniem zhivotnykh [International guiding principles (ethical code) for biomedical research involving animals]. 1985.
  24. Kiseleva Е., 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;
  25. Kirillin M.Yu., Farhat G., Sergeeva E.A., Kolios M.C., Vitkin A. Speckle statistics in OCT images: Monte Carlo simulations and experimental studies. Opt Lett 2014; 39(12): 3472–3475,
  26. Mariampillai A., Standish B.A., Moriyama E.H., Khurana M., Munce N.R., Leung M.K.K., Jiang J., Cable A., Wilson B.C., Vitkin I.A., Yang V.X.D. Speckle variance detection of microvasculature using swept-source optical coherence tomography. Opt Lett 2008; 33(13): 1530–1532,
  27. Mariampillai A., Leung M.K.K., Jarvi M., Standish B.A., Lee K., Wilson B.C., Vitkin A., Yang V.X.D. Optimized speckle variance OCT imaging of microvasculature. Opt Lett 2010; 35(8): 1257–1259,
Sirotkina М.А., Buyanova N.L., Kalganova Т.I., Karabut М.М., Elagin V.V., Kuznetsov S.S., Snopova L.B., Gelikonov G.V., Zaitsev V.Yu., Matveev L.А., Zagaynova E.V., Vitkin A., Gladkova N.D. The Development of the Methodology of Monitoring Experimental Tumors Using Multimodal Optical Coherence Tomography: the Choice of an Optimal Tumor Model . Sovremennye tehnologii v medicine 2015; 7(2): 6–15,

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