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

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  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,” Science 248(4951), 73–76 (1990).
  3. W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(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. Express 17(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. Methods 111(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. Methods 1(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. Express 19(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. Express 12(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. Express 18(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. Express 12(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. Cortex 19(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. Express 15(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. Methods 4(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,” Methods 18(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,” Methods 18(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,” Radiology 176(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,” Neuroimage 58(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).

2011

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. Express 19(6), 4833–4847 (2011).

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).

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,” Neuroimage 58(4), 984–992 (2011).

2010

2009

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).

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. Express 17(16), 13354–13364 (2009).

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. Cortex 19(10), 2380–2395 (2009).

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol. 102(2), 1310–1314 (2009).

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).

2008

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).

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).

2007

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).

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).

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).

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

2005

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).

2004

2003

2002

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).

2001

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun. 188(1-4), 25–29 (2001).

1999

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).

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).

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,” Methods 18(2), 91–103 (1999).

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).

R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods 18(2), 185–196, 179 (1999).

1998

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).

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).

1997

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).

1995

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).

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).

1994

P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J. 66(1), 259–267 (1994).

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).

1991

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).

1990

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).

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,” Radiology 176(2), 439–445 (1990).

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).

1974

Aalders, M. C. G.

Abosch, A.

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,” Neuroimage 58(4), 984–992 (2011).

Aitken, P. G.

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,” Methods 18(2), 91–103 (1999).

Akkin, T.

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,” Neuroimage 58(4), 984–992 (2011).

Al-Qaisi, M. K.

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,” Neuroimage 58(4), 984–992 (2011).

Andrew, R. D.

R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods 18(2), 185–196, 179 (1999).

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).

Asgari, H. S.

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,” Radiology 176(2), 439–445 (1990).

Backman, V.

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).

Badizadegan, K.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Barry, S.

Bartlett, L. A.

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).

Basser, P. J.

P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J. 66(1), 259–267 (1994).

Beaurepaire, E.

E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun. 188(1-4), 25–29 (2001).

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

Ben Arous, J.

Binding, J.

Black, A. J.

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,” Neuroimage 58(4), 984–992 (2011).

Blonder, G. E.

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).

Boas, D. A.

Boccara, C.

Boppart, S. A.

Bouma, B. E.

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).

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).

Bourdieu, L.

Brezinski, M. E.

Burgess, R. W.

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).

Burns, L. D.

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).

Cable, A. E.

Campagnola, P.

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).

Chaigneau, E.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

Charpak, S.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

Chia, T. H.

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol. 102(2), 1310–1314 (2009).

Chileuitt, L.

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).

Choi, W.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Clascá, F.

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. Cortex 19(10), 2380–2395 (2009).

Cohen, Y.

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).

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,” Radiology 176(2), 439–445 (1990).

Crawford, J. M.

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).

Dasari, R. R.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Denk, W.

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).

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).

Drexler, W.

Duker, J. S.

Durst, M. E.

Enright, L. E.

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).

Faber, D. J.

Fang-Yen, C.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Fayuk, D.

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,” Methods 18(2), 91–103 (1999).

Feld, M. S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

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).

Foster, T. H.

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).

Fujimoto, J. G.

Fukumura, D.

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).

Galazo, M. J.

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. Cortex 19(10), 2380–2395 (2009).

Gelbard, H. A.

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).

Ghosh, K. K.

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).

Gigan, S.

Gorczynska, I.

Goto, T.

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).

Gruber, A.

Hagmann, P.

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).

Hamano, T.

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).

Hansen, A. J.

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).

Hanson, S. R.

Hasan, M. T.

Hatanaka, R.

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).

Hee, M. R.

Helmchen, F.

A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).

Hoehn-Berlage, M.

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).

Hossmann, K. A.

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).

Hrabetová, S.

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).

Hurst, S.

Ippen, E. P.

Itzkan, I.

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).

Izatt, J. A.

Jacques, S. L.

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).

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).

Jain, R. K.

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).

Jarvis, C. R.

R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods 18(2), 185–196, 179 (1999).

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).

Jiang, J. Y.

Kärtner, F. X.

Kasischke, K. A.

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).

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).

Kawashima, R.

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).

Kerr, J. N.

A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).

Kirchhoff, F.

A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).

Kleinfeld, D.

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).

Ko, T. H.

Kobat, D.

Kohno, K.

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).

Kowalczyk, A.

Kreisman, N. R.

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).

Kucharczyk, J.

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,” Radiology 176(2), 439–445 (1990).

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).

LaManna, J. C.

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).

Lambert, E. M.

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).

Lanning, R. M.

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).

LaPorta, A.

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).

LeBihan, D.

P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J. 66(1), 259–267 (1994).

Léger, J. F.

Leibfritz, D.

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).

Levene, M. J.

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol. 102(2), 1310–1314 (2009).

Li, X. D.

Lima, C.

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).

Lou, N.

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).

Lovatt, D.

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).

Lue, N.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Ma, Z.

Manoharan, R.

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).

Masri, D.

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).

Mattiello, J.

P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J. 66(1), 259–267 (1994).

Mertz, J.

E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun. 188(1-4), 25–29 (2001).

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

Mies, G.

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).

Mintorovitch, J.

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).

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,” Radiology 176(2), 439–445 (1990).

Morgner, U.

Moseley, M. E.

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,” Radiology 176(2), 439–445 (1990).

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).

Mukamel, E. A.

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).

Müller, M.

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).

Munn, L. L.

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).

Murphy, T. H.

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).

Nedergaard, M.

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).

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).

Netoff, T. I.

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,” Neuroimage 58(4), 984–992 (2011).

Nicholson, C.

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).

Nimmerjahn, A.

A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).

Nishimura, N.

Norman, D.

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,” Radiology 176(2), 439–445 (1990).

Norris, D. G.

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).

Nusrat, A.

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).

Obeidat, A. S.

R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods 18(2), 185–196, 179 (1999).

Ogawa, T.

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).

Oh, S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

Oheim, M.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun. 188(1-4), 25–29 (2001).

Owen, G. M.

Padera, T. P.

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).

Palmer, K. F.

Panepento, B.

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).

Peng, W.

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).

Perelman, L. T.

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).

Pérez-de-Manzo, F.

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. Cortex 19(10), 2380–2395 (2009).

Pitris, C.

Polischuk, T. M.

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).

Porrero, C.

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. Cortex 19(10), 2380–2395 (2009).

Raccuia-Behling, F.

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).

Radhakrishnan, H.

Reese, T. G.

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).

Riera, J.

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).

Rubio-Garrido, P.

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. Cortex 19(10), 2380–2395 (2009).

Ruvinskaya, S.

Sakadzic, S.

Samatham, R.

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).

Schaffer, C. B.

Schnitzer, M. J.

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).

Seiler, M.

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).

Shields, S.

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).

Shimizu, H.

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).

Slusher, R. E.

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).

Somjen, G. G.

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).

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,” Methods 18(2), 91–103 (1999).

Southern, J. F.

Srinivasan, V. J.

Stepnoski, R. A.

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).

Stigen, T. W.

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,” Neuroimage 58(4), 984–992 (2011).

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).

Stylianopoulos, T.

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).

Sumiyoshi, A.

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).

Sun, A.

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).

Svoboda, K.

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).

Swanson, E. A.

Takano, T.

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).

Tao, L.

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).

Tearney, G. J.

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).

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).

Theer, P.

Tian, G. F.

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).

Tseng, W. Y. I.

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).

Tsuruda, J.

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,” Radiology 176(2), 439–445 (1990).

Tuch, D. S.

D. S. Tuch, “Q-ball imaging,” Magn. Reson. Med. 52(6), 1358–1372 (2004).

Turner, D. A.

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,” Methods 18(2), 91–103 (1999).

Tyrrell, J. A.

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).

Vakoc, B. J.

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).

Van Dam, J.

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).

van der Meer, F. J.

van Leeuwen, T.

Wallace, M.

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).

Wang, H.

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,” Neuroimage 58(4), 984–992 (2011).

Wang, R. K.

Webb, W. W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).

Wedeen, V. J.

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).

Wei Ho, E. T.

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).

Weinstein, P. R.

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).

Weisskoff, R. M.

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).

Wendland, M. F.

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,” Radiology 176(2), 439–445 (1990).

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).

Williams, D.

Wilt, B. A.

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).

Wojtkowski, M.

Wong, A. W.

Wu, W.

Xu, C.

Yaseen, M. A.

Zhang, S.

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).

Zhu, J. F.

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,” Neuroimage 58(4), 984–992 (2011).

Zonios, G.

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).

Annu. Rev. Neurosci.

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).

Biophys. J.

P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophys. J. 66(1), 259–267 (1994).

Brain Res.

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).

Cereb. Cortex

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. Cortex 19(10), 2380–2395 (2009).

J. Biomed. Opt.

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).

J. Cereb. Blood Flow Metab.

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).

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).

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).

J. Neurophysiol.

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).

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol. 102(2), 1310–1314 (2009).

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).

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).

J. Neurosci. Methods

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods 111(1), 29–37 (2001).

J. Opt. Soc. Am.

Magn. Reson. Med.

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).

D. S. Tuch, “Q-ball imaging,” Magn. Reson. Med. 52(6), 1358–1372 (2004).

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).

Methods

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,” Methods 18(2), 91–103 (1999).

R. D. Andrew, C. R. Jarvis, and A. S. Obeidat, “Potential sources of intrinsic optical signals imaged in live brain slices,” Methods 18(2), 185–196, 179 (1999).

Nat. Med.

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).

Nat. Methods

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).

A. Nimmerjahn, F. Kirchhoff, J. N. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).

Nat. Neurosci.

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).

Neurobiol. Dis.

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).

Neuroimage

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,” Neuroimage 58(4), 984–992 (2011).

Neuron

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).

Opt. Commun.

E. Beaurepaire, M. Oheim, and J. Mertz, “Ultra-deep two-photon fluorescence excitation in turbid media,” Opt. Commun. 188(1-4), 25–29 (2001).

Opt. Express

Opt. Lett.

Phys. Rev. Lett.

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).

Proc. Natl. Acad. Sci. U.S.A.

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).

Prog. Retin. Eye Res.

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).

Radiology

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,” Radiology 176(2), 439–445 (1990).

Science

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).

Supplementary Material (5)

» Media 1: AVI (5450 KB)     
» Media 2: AVI (17154 KB)     
» Media 3: AVI (5934 KB)     
» Media 4: AVI (2686 KB)     
» Media 5: AVI (1909 KB)     

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (12)

Fig. 1
Fig. 1

Optical Coherence Microscopy (OCM) system for deep tissue brain imaging. (a) OCM system schematic. (b) Zoom of ray optics diagram. (c) Two dimensional cross-sectional images with focus fit. By successive application of Snell's law at each interface, it is possible to determine the derivative of the path length to the focus (zfocus) with respect to the objective assembly translation (Z), in terms of the local brain refractive index, as described in the Experimental methods.

Fig. 2
Fig. 2

OCM neuronal imaging. (a) OCM cellular images at different cortical depths, showing expected laminar differences between cortical layers. (b) A virtual coronal section of the rat somatosensory S1 cortex shows clear delineation of layers. This includes a thin layer near the cortical surface with few neurons, as well as supragranular, granular, and infragranular layers. (c) Maximum intensity projection image of a 20 micron coronal slice from two-photon microscopy data with SR101-staining, showing astrocytes as bright regions. (d) Minimum intensity projection image of a 20 micron coronal slice from two-photon microscopy data with SR101-staining, showing neurons as dark quasi-spherical regions. (e) Minimum intensity projection image of OCM data from the same 20 micron coronal slice, showing dark regions that correspond closely with those in (d). A red box is drawn around a region in cortical layer I, and neurons are circled. (f) OCM performs in vivo “histology”. A volumetric, dynamically focused data set (5 micron steps), is used to extract coronal sections (slices) of different thicknesses, without actually cutting the tissue.

Fig. 3
Fig. 3

(a) 8.5 micron minimum intensity projection OCM slice with a white rectangle drawn around a region of interest approximately 300 microns beneath the cortical surface. (b) zoom of raw OCM image around region of interest (above), with red rays drawn from origin of a spherical coordinate system to locations where the interpolated OCM data first exceeds an empirically set threshold (below). (c) Parametric surface plot using a spherical coordinate system, showing a neuron-like morphology, and possible visualization of a portion of the apical dendrite (Media 1).

Fig. 4
Fig. 4

OCM myelin imaging. (a) Imaging of myelination in different cortical layers shows the expected laminar characteristics, with increased myelination in layer IV and below. In addition, myelinated axons exhibit orientation-dependent backscattering characteristics, so that only orientations perpendicular to the incident light are visualized. To investigate this phenomenon, a microprism was used to rotate the imaging geometry by 90 degrees (b, incident light from the x-direction). In addition, imaging in the conventional geometry was performed (b, incident light from the z-direction). By comparison of axial and coronal slices in the two different imaging geometries, it is evident that the visualization of myelinated axons is highly orientation dependent. In particular, processes with orientations in the en face plane (perpendicular to the incident light) are well visualized, whereas others are not (c). The direction of incident light (opposite to the direction of backscattered light) is shown in red.

Fig. 5
Fig. 5

Laminar distribution of myelination in the rat visual (V1) cortex. Images of myelination at different cortical depths. In particular, a reduction in myelination is seen in layer II-III (b) compared to the other cortical layers.

Fig. 6
Fig. 6

Laminar distribution of myelination in layer I (Media 2). Thinner myelinated processes are found more superficially (a) while thicker myelinated processes are observed at greater depths (c).

Fig. 7
Fig. 7

Backscattering from myelin processes shows no polarization dependence. The contrast with light polarized along the x-axis (a) is virtually identical to the contrast with light polarized along the y-axis (b). The polarization is shown in red, and was achieved by placing a polarizer before the objective lens (Fig. 2(a)).

Fig. 8
Fig. 8

OCM quantification of optical properties. (a) A piecewise linear fit of the OCM signal from the focus automatically detected 5 regions with different attenuation coefficients, demarcated by dashed lines. (b) Index of refraction measurements were also performed in these 5 regions, based on dzfocus/dZ (see Experimental methods). (c) The 5 regions with different attenuation coefficients corresponded well to layers IA, IB, II/III, IV, and V. In order to better appreciate the relationship between morphology and attenuation coefficient, a color overlay is shown, with neuronal cell bodies in green, and myelin in red. In general layers with more myelin and fewer cell bodies had a higher attenuation coefficient, while layers with more cell bodies had a lower attenuation coefficient.

Fig. 9
Fig. 9

Changes in optical properties correspond with changes in tissue cellular architecture. (a) OCM signal slope clearly shows a discontinuity at approximately 140 microns, as detected by maximum likelihood fitting, as described in the main text. (b) The refractive index (determined from dzfocus/dZ) also shows a discontinuity at 140 microns. (c-e) The images of myelination (above) and cell bodies (below) show a corresponding transition to less myelination and more cell bodies at 140 microns (d), which may explain the discontinuity in optical properties.

Fig. 10
Fig. 10

Attenuation coefficient (a) and refractive index (b), obtained from n = 17 rats. Mean ± standard errors for different cortical layers are shown. Layer I had a significantly greater attenuation coefficient than all of the other measured layers, while layer IV had a significantly greater attenuation coefficient than layer II/III, as determined by one-way ANOVA followed by Tukey's honestly significant differences test (* α < 0.05, ** α < 0.01). There were no statistically significant differences between the refractive indices of the different cortical layers. As tissue refractive index is known to exceed the water refractive index by a few percent, the vertical axis in a has been shortened in (b) to display only the expected range of tissue refractive indices.

Fig. 11
Fig. 11

OCM angiography. OCM angiography visualizes microvasculature using intrinsic contrast (Media 3). (a) Maximum intensity projection image of OCM angiogram from an 80 g Sprague Dawley rat. (b) A maximum intensity projection coronal image of a 50 micron slice is shown, centered at the location of the arrow shown in (a). In particular, the absence of capillaries is notable in the vicinity of the diving arteriole at the center of the coronal image.

Fig. 12
Fig. 12

OCM imaging of cell viability. OCM has the capability to image cell viability in vivo based on intrinsic scattering signatures. (a-d) OCM in layer II (Media 4) shows that depolarization causes transient swelling (b) and increased scattering (d) during cortical spreading depression (CSD). (e-h) OCM in layer II (Media 5) shows that depolarization causes permanent loss of contrast (g) and increased scattering (h) during anoxic depolarization (AD). These results suggest that OCM may be able to distinguish viable cells from non-viable cells based on intrinsic contrast.

Equations (11)

Equations on this page are rendered with MathJax. Learn more.

z(d brain ,Z)=z 0 + z'=0 d brain fn brain (z')dz' -fn water Z
dz=fn brain Δd brain -fn water dZ
dz focus =fn brain Δ d focus -fn water dZ
Δd focus =dZ n brain n water
dz focus =f( dZ n brain 2 -n water 2 n water )
A(x,y,z,Z) B[d brain (x,y,z,Z)] ( z-z focus (x,y,Z) z R ) 2 +1 exp[-2 0 d brain (x,y,z,Z) μ t (z')fn brain (z')dz' ]
A(x,y,z focus (Z),Z) B[d focus (x,y,Z)] exp[- 0 d focus (x,y,Z) μ t (z')fn brain (z')dz' ]
log[ A(x,y,z focus (Z),Z) ]log[ B[d focus (x,y,Z)] ]- 0 d focus (x,y,Z) μ t (z')fn brain (z')dz'
d dZ { log[ A(x,y,z focus (Z),Z) ] } d dZ { log[ B[d focus (x,y,Z)] ] } t [ d focus (x,y,Z) ]f { n brain [ d focus (x,y,Z) ] } 2 n water
μ t =a(g)μ s
A ^ (x,y, d brain )= i w[z( d brain , Z i )- z focus (x,y, Z i )]A[x,y,z( d brain , Z i ), Z i ]

Metrics