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Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 20, Iss. 3 — Jan. 30, 2012
  • pp: 2220–2239

Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast

Vivek J. Srinivasan, Harsha Radhakrishnan, James Y. Jiang, Scott Barry, and Alex E. Cable  »View Author Affiliations


Optics Express, Vol. 20, Issue 3, pp. 2220-2239 (2012)
http://dx.doi.org/10.1364/OE.20.002220


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Abstract

In vivo optical microscopic imaging techniques have recently emerged as important tools for the study of neurobiological development and pathophysiology. In particular, two-photon microscopy has proved to be a robust and highly flexible method for in vivo imaging in highly scattering tissue. However, two-photon imaging typically requires extrinsic dyes or contrast agents, and imaging depths are limited to a few hundred microns. Here we demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of neuronal cell bodies and cortical myelination up to depths of ~1.3 mm in the rat neocortex. Imaging does not require the administration of exogenous dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, using OCM we demonstrate in vivo, quantitative measurements of optical properties (index of refraction and attenuation coefficient) in the cortex, and correlate these properties with laminar cellular architecture determined from the images. Lastly, we show that OCM enables direct visualization of cellular changes during cell depolarization and may therefore provide novel optical markers of cell viability.

© 2012 OSA

OCIS Codes
(110.4500) Imaging systems : Optical coherence tomography
(170.0180) Medical optics and biotechnology : Microscopy
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.5380) Medical optics and biotechnology : Physiology
(170.6900) Medical optics and biotechnology : Three-dimensional microscopy

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: November 21, 2011
Revised Manuscript: January 5, 2012
Manuscript Accepted: January 5, 2012
Published: January 17, 2012

Virtual Issues
Vol. 7, Iss. 3 Virtual Journal for Biomedical Optics

Citation
Vivek J. Srinivasan, Harsha Radhakrishnan, James Y. Jiang, Scott Barry, and Alex E. Cable, "Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast," Opt. Express 20, 2220-2239 (2012)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-20-3-2220


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References

  1. B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
  2. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
  3. W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron18(3), 351–357 (1997).
  4. E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun.188(1-4), 25–29 (2001).
  5. P. Theer, M. T. Hasan, and W. Denk, “Two-photon imaging to a depth of 1000 μm in living brains by use of a Ti:Al2O3 regenerative amplifier,” Opt. Lett.28(12), 1022–1024 (2003).
  6. D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express17(16), 13354–13364 (2009).
  7. M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods111(1), 29–37 (2001).
  8. J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett.19(8), 590–592 (1994).
  9. A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
  10. J. Binding, J. Ben Arous, J. F. Léger, S. Gigan, C. Boccara, and L. Bourdieu, “Brain refractive index measured in vivo with high-NA defocus-corrected full-field OCT and consequences for two-photon microscopy,” Opt. Express19(6), 4833–4847 (2011).
  11. M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
  12. V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Quantitative cerebral blood flow with optical coherence tomography,” Opt. Express18(3), 2477–2494 (2010).
  13. G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, and J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett.20(21), 2258 (1995).
  14. K. F. Palmer and D. Williams, “Optical-properties of water in near-infrared,” J. Opt. Soc. Am.64(8), 1107–1110 (1974).
  15. D. J. Faber, F. J. van der Meer, M. C. G. Aalders, and T. van Leeuwen, “Quantitative measurement of attenuation coefficients of weakly scattering media using optical coherence tomography,” Opt. Express12(19), 4353–4365 (2004).
  16. R. Samatham, S. L. Jacques, and P. Campagnola, “Optical properties of mutant versus wild-type mouse skin measured by reflectance-mode confocal scanning laser microscopy (rCSLM),” J. Biomed. Opt.13(4), 041309 (2008).
  17. V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett.35(1), 43–45 (2010).
  18. W. Drexler, U. Morgner, F. X. Kärtner, C. Pitris, S. A. Boppart, X. D. Li, E. P. Ippen, and J. G. Fujimoto, “In vivo ultrahigh-resolution optical coherence tomography,” Opt. Lett.24(17), 1221–1223 (1999).
  19. T. Goto, R. Hatanaka, T. Ogawa, A. Sumiyoshi, J. Riera, and R. Kawashima, “An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats,” J. Neurophysiol.104(6), 3388–3412 (2010).
  20. P. Rubio-Garrido, F. Pérez-de-Manzo, C. Porrero, M. J. Galazo, and F. Clascá, “Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent,” Cereb. Cortex19(10), 2380–2395 (2009).
  21. L. E. Enright, S. Zhang, and T. H. Murphy, “Fine mapping of the spatial relationship between acute ischemia and dendritic structure indicates selective vulnerability of layer V neuron dendritic tufts within single neurons in vivo,” J. Cereb. Blood Flow Metab.27(6), 1185–1200 (2007).
  22. T. Takano, G. F. Tian, W. Peng, N. Lou, D. Lovatt, A. J. Hansen, K. A. Kasischke, and M. Nedergaard, “Cortical spreading depression causes and coincides with tissue hypoxia,” Nat. Neurosci.10(6), 754–762 (2007).
  23. T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009).
  24. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express15(7), 4083–4097 (2007).
  25. B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
  26. K. A. Kasischke, E. M. Lambert, B. Panepento, A. Sun, H. A. Gelbard, R. W. Burgess, T. H. Foster, and M. Nedergaard, “Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions,” J. Cereb. Blood Flow Metab.31(1), 68–81 (2011).
  27. R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A.88(21), 9382–9386 (1991).
  28. L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett.80(3), 627–630 (1998).
  29. W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods4(9), 717–719 (2007).
  30. W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res.27(1), 45–88 (2008).
  31. N. R. Kreisman and J. C. LaManna, “Rapid and slow swelling during hypoxia in the CA1 region of rat hippocampal slices,” J. Neurophysiol.82(1), 320–329 (1999).
  32. P. G. Aitken, D. Fayuk, G. G. Somjen, and D. A. Turner, “Use of intrinsic optical signals to monitor physiological changes in brain tissue slices,” Methods18(2), 91–103 (1999).
  33. M. Müller and G. G. Somjen, “Intrinsic optical signals in rat hippocampal slices during hypoxia-induced spreading depression-like depolarization,” J. Neurophysiol.82(4), 1818–1831 (1999).
  34. L. Tao, D. Masri, S. Hrabetová, and C. Nicholson, “Light scattering in rat neocortical slices differs during spreading depression and ischemia,” Brain Res.952(2), 290–300 (2002).
  35. T. M. Polischuk, C. R. Jarvis, and R. D. Andrew, “Intrinsic optical signaling denoting neuronal damage in response to acute excitotoxic insult by domoic acid in the hippocampal slice,” Neurobiol. Dis.4(6), 423–437 (1998).
  36. R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods18(2), 185–196, 179 (1999).
  37. M. E. Moseley, Y. Cohen, J. Kucharczyk, J. Mintorovitch, H. S. Asgari, M. F. Wendland, J. Tsuruda, and D. Norman, “Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system,” Radiology176(2), 439–445 (1990).
  38. M. E. Moseley, Y. Cohen, J. Mintorovitch, L. Chileuitt, H. Shimizu, J. Kucharczyk, M. F. Wendland, and P. R. Weinstein, “Early detection of regional cerebral-ischemia in cats - comparison of diffusion-weighted and T2-weighted MRI and spectroscopy,” Magn. Reson. Med.14(2), 330–346 (1990).
  39. M. Hoehn-Berlage, D. G. Norris, K. Kohno, G. Mies, D. Leibfritz, and K. A. Hossmann, “Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances,” J. Cereb. Blood Flow Metab.15(6), 1002–1011 (1995).
  40. H. Wang, A. J. Black, J. F. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, and T. Akkin, “Reconstructing micrometer-scale fiber pathways in the brain: multi-contrast optical coherence tomography based tractography,” Neuroimage58(4), 984–992 (2011).
  41. P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J.66(1), 259–267 (1994).
  42. D. S. Tuch, “Q-ball imaging,” Magn. Reson. Med.52(6), 1358–1372 (2004).
  43. V. J. Wedeen, P. Hagmann, W. Y. I. Tseng, T. G. Reese, and R. M. Weisskoff, “Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging,” Magn. Reson. Med.54(6), 1377–1386 (2005).

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