Abstract

A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood flow in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood flow during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood flow and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains.

© 2003 Optical Society of America

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  1. D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
    [CrossRef] [PubMed]
  2. T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
    [CrossRef] [PubMed]
  3. M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
    [CrossRef] [PubMed]
  4. D. Malonek and A. Grinvald, Science 272, 551 (1996).
    [CrossRef] [PubMed]
  5. J. Briers, Physiol. Meas. 22, R35 (2001).
    [CrossRef]
  6. A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
    [CrossRef] [PubMed]
  7. H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
    [CrossRef]
  8. Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
    [PubMed]
  9. J. Briers and S. Webster, J. Biomed. Opt. 1, 174 (1996).
    [CrossRef] [PubMed]
  10. R. Bonner and R. Nossal, Appl. Opt. 20, 2097 (1981).
    [CrossRef] [PubMed]
  11. M. Lauritzen, Cephalalgia 21, 757 (2001).
    [CrossRef] [PubMed]
  12. A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
    [CrossRef] [PubMed]
  13. M. Kohl, U. Lindauer, U. Dirnagl, and A. Villringer, Opt. Lett. 23, 555 (1998).
    [CrossRef]
  14. M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
    [CrossRef] [PubMed]
  15. P. Fox and M. Raichle, Proc. Natl. Acad. Sci. USA 83, 1140 (1986).
    [CrossRef]
  16. J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
    [CrossRef] [PubMed]
  17. H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

2002

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

2001

J. Briers, Physiol. Meas. 22, R35 (2001).
[CrossRef]

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

M. Lauritzen, Cephalalgia 21, 757 (2001).
[CrossRef] [PubMed]

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

2000

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

1999

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

1998

1996

J. Briers and S. Webster, J. Biomed. Opt. 1, 174 (1996).
[CrossRef] [PubMed]

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

D. Malonek and A. Grinvald, Science 272, 551 (1996).
[CrossRef] [PubMed]

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

1994

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

1990

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

1986

P. Fox and M. Raichle, Proc. Natl. Acad. Sci. USA 83, 1140 (1986).
[CrossRef]

1981

Araie, M.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

Ayata, C.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Berwick, J.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

Boas, D.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

Bolay, H.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

Bonner, R.

Briers, J.

J. Briers, Physiol. Meas. 22, R35 (2001).
[CrossRef]

J. Briers and S. Webster, J. Biomed. Opt. 1, 174 (1996).
[CrossRef] [PubMed]

Cannestra, A.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Chen, J.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Cox, S.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Dirnagl, U.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

M. Kohl, U. Lindauer, U. Dirnagl, and A. Villringer, Opt. Lett. 23, 555 (1998).
[CrossRef]

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Doge, C.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Dunn, A.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

Eguchi, S.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

Fox, P.

P. Fox and M. Raichle, Proc. Natl. Acad. Sci. USA 83, 1140 (1986).
[CrossRef]

Frostig, R.

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

Fuji, H.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

Gold, L.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

Grinvald, A.

D. Malonek and A. Grinvald, Science 272, 551 (1996).
[CrossRef] [PubMed]

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

Henegar, M.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Hirth, C.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Huang, Z.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

Johnston, D.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

Jones, M.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

Junge-Hulsing, J.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Kawamoto, E.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

Kohl, M.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

M. Kohl, U. Lindauer, U. Dirnagl, and A. Villringer, Opt. Lett. 23, 555 (1998).
[CrossRef]

Kuhl, M.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

Lauritzen, M.

M. Lauritzen, Cephalalgia 21, 757 (2001).
[CrossRef] [PubMed]

Liang, G.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Lieke, E.

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

Lindauer, U.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

M. Kohl, U. Lindauer, U. Dirnagl, and A. Villringer, Opt. Lett. 23, 555 (1998).
[CrossRef]

Liu, D.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Malonek, D.

D. Malonek and A. Grinvald, Science 272, 551 (1996).
[CrossRef] [PubMed]

Mandeville, J.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Marota, J.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Mayhew, J.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

Moskalenko, Y.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Moskowitz, M.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Muthialu, A.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Nossal, R.

O’Farrell, A.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Obrig, H.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Pouratian, N.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Raichle, M.

P. Fox and M. Raichle, Proc. Natl. Acad. Sci. USA 83, 1140 (1986).
[CrossRef]

Reuter, U.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

Rex, D.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Rosen, B.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Rovainen, C.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Royl, G.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

Sui, J.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Tamaki, Y.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

Toga, A.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Ts’o, D.

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

Villringer, A.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

M. Kohl, U. Lindauer, U. Dirnagl, and A. Villringer, Opt. Lett. 23, 555 (1998).
[CrossRef]

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Webster, S.

J. Briers and S. Webster, J. Biomed. Opt. 1, 174 (1996).
[CrossRef] [PubMed]

Wei, L.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Weisskoff, R.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Wolf, T.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

Wong, G.

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Woolsey, T.

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Zaharchuk, G.

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Appl. Opt.

Cephalalgia

M. Lauritzen, Cephalalgia 21, 757 (2001).
[CrossRef] [PubMed]

Cereb. Cortex

T. Woolsey, C. Rovainen, S. Cox, M. Henegar, G. Liang, D. Liu, Y. Moskalenko, J. Sui, and L. Wei, Cereb. Cortex 6, 647 (1996).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

Y. Tamaki, M. Araie, E. Kawamoto, S. Eguchi, and H. Fuji, Invest. Ophthalmol. Vis. Sci. 35, 3825 (1994).
[PubMed]

J. Appl. Physiol.

H. Obrig, C. Hirth, J. Junge-Hulsing, C. Doge, T. Wolf, U. Dirnagl, and A. Villringer, J. Appl. Physiol. 81, 1174 (1996).

J. Biomed. Opt.

J. Briers and S. Webster, J. Biomed. Opt. 1, 174 (1996).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab.

A. Dunn, H. Bolay, M. Moskowitz, and D. Boas, J. Cereb. Blood Flow Metab. 21, 195 (2001).
[CrossRef] [PubMed]

J. Mandeville, J. Marota, C. Ayata, G. Zaharchuk, M. Moskowitz, B. Rosen, and R. Weisskoff, J. Cereb. Blood Flow Metab. 19, 679 (1999).
[CrossRef] [PubMed]

Nature Med.

H. Bolay, U. Reuter, A. Dunn, Z. Huang, D. Boas, and M. Moskowitz, Nature Med. 8, 136 (2002).
[CrossRef]

Neuroimage

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, Neuroimage 13, 1002 (2001).
[CrossRef] [PubMed]

Neuroreport

A. O’Farrell, D. Rex, A. Muthialu, N. Pouratian, G. Wong, A. Cannestra, J. Chen, and A. Toga, Neuroreport 11, 2121 (2000).
[CrossRef] [PubMed]

Opt. Lett.

Phys. Med. Biol.

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl, Phys. Med. Biol. 45, 3749 (2000).
[CrossRef] [PubMed]

Physiol. Meas.

J. Briers, Physiol. Meas. 22, R35 (2001).
[CrossRef]

Proc. Natl. Acad. Sci. USA

P. Fox and M. Raichle, Proc. Natl. Acad. Sci. USA 83, 1140 (1986).
[CrossRef]

Science

D. Ts’o, R. Frostig, E. Lieke, and A. Grinvald, Science 249, 417 (1990).
[CrossRef] [PubMed]

D. Malonek and A. Grinvald, Science 272, 551 (1996).
[CrossRef] [PubMed]

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Figures (3)

Fig. 1
Fig. 1

Geometry for simultaneous laser speckle contrast imaging of blood flow and spectral imaging of hemoglobin oxygenation.

Fig. 2
Fig. 2

Changes in a, HbO, b, Hb, and c, CBF 1 min after induction of CSD. The boxes in a indicate the regions of interest for the time courses. d, Top left region, e, lower region. Scale bar, 1 mm.

Fig. 3
Fig. 3

Images of changes in a, HbO, b, Hb, and c, CBF following single whisker deflection. The time course, d, is the average response over the activated region. Scale bar, 0.5 mm.

Metrics