Abstract

In this study we present a novel imaging method that combines high resolution cerebral blood flow imaging with a highly flexible map of absolute pO2. In vivo measurements of pO2 in animals using phosphorescence quenching is a well established method, and is preferable over electrical probes which are inherently invasive and are limited to single point measurements. However, spatially resolved pO2 measurements using phosphorescence lifetime quenching typically require expensive cameras to obtain images of pO2 and often suffer from poor signal to noise. Our approach enables us to retain the high temporal resolution and sensitivity of single point detection of phosphorescence by using a digital micromirror device (DMD) to selectively illuminate arbitrarily shaped regions of tissue. In addition, by simultaneously using Laser Speckle Contrast Imaging (LSCI) to measure relative blood flow, we can better examine the relationship between blood flow and absolute pO2. We successfully used this instrument to study changes that occur during ischemic conditions in the brain with enough spatial resolution to clearly distinguish different regions. This novel instrument will provide researchers with an inexpensive and improved technique to examine multiple hemodynamic parameters simultaneously in the brain as well as other tissues.

© 2010 OSA

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    [CrossRef] [PubMed]
  3. A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
    [CrossRef] [PubMed]
  4. A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  6. N. Prakash, J. D. Biag, S. A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A. W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37(Suppl 1), S27–S36 (2007).
    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
  30. V. Rozhkov, D. F. Wilson, and S. A. Vinogradov, “Phosphorescent Pd porphyrin-dendrimers: Tuning core accessibility by varying the hydrophobicity of the dendritic matrix,” Macromolecules 35(6), 1991–1993 (2002).
    [CrossRef]
  31. W. L. Rumsey, J. M. Vanderkooi, and D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241(4873), 1649–1651 (1988).
    [CrossRef] [PubMed]
  32. I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002).
    [CrossRef] [PubMed]
  33. D. L. Adkins, A. C. Voorhies, and T. A. Jones, “Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions,” Neuroscience 128(3), 473–486 (2004).
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    [CrossRef] [PubMed]
  36. B. D. Watson, R. Prado, A. Veloso, J. Brunschwig, and W. D. Dietrich, “Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke,” Stroke 33, 428–434 (2002).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  39. J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).
  40. A. A. P. Leao, “Spreading depression of activity in the cerebral cortex,” J. Neurophysiol. 7, 359–390 (1944).
  41. A. Mayevsky and H. R. Weiss, “Cerebral blood flow and oxygen consumption in cortical spreading depression,” J. Cereb. Blood Flow Metab. 11(5), 829–836 (1991).
    [CrossRef] [PubMed]
  42. P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
    [CrossRef] [PubMed]
  43. A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).
  44. H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).
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    [CrossRef] [PubMed]
  47. J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
    [CrossRef] [PubMed]

2009

2008

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging 27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

A. D. Estrada, A. Ponticorvo, T. N. Ford, and A. K. Dunn, “Microvascular oxygen quantification using two-photon microscopy,” Opt. Lett. 33(10), 1038–1040 (2008).
[CrossRef] [PubMed]

A. Bednarkiewicz and M. P. Whelan, “Global analysis of microscopic fluorescence lifetime images using spectral segmentation and a digital micromirror spatial illuminator,” J. Biomed. Opt. 13(4), 041316 (2008).
[CrossRef] [PubMed]

A. Bednarkiewicz, M. Bouhifd, and M. P. Whelan, “Digital micromirror device as a spatial illuminator for fluorescence lifetime and hyperspectral imaging,” Appl. Opt. 47(9), 1193–1199 (2008).
[CrossRef] [PubMed]

P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

2007

A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

S. H. Chao, M. R. Holl, S. C. McQuaide, T. T. H. Ren, S. A. Gales, and D. R. Meldrum, “Phosphorescence lifetime based oxygen micro-sensing using a digital micromirror device,” Opt. Express 15(17), 10681–10689 (2007).
[CrossRef] [PubMed]

N. Prakash, J. D. Biag, S. A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A. W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37(Suppl 1), S27–S36 (2007).
[CrossRef] [PubMed]

2006

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron 50(6), 823–839 (2006).
[CrossRef] [PubMed]

R. K. Miyake, H. D. Zeman, F. H. Duarte, R. Kikuchi, E. Ramacciotti, G. Lovhoiden, and C. Vrancken, “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” Dermatol. Surg. 32(8), 1031–1038 (2006).
[CrossRef] [PubMed]

2005

D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005).
[CrossRef] [PubMed]

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

R. P. Briñas, T. Troxler, R. M. Hochstrasser, and S. A. Vinogradov, “Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna,” J. Am. Chem. Soc. 127(33), 11851–11862 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

2004

D. L. Adkins, A. C. Voorhies, and T. A. Jones, “Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions,” Neuroscience 128(3), 473–486 (2004).
[CrossRef] [PubMed]

2003

T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt. 42(19), 4119–4124 (2003).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

A. G. Tsai, P. C. Johnson, and M. Intaglietta, “Oxygen gradients in the microcirculation,” Physiol. Rev. 83(3), 933–963 (2003).
[PubMed]

R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31(9), 1084–1096 (2003).
[CrossRef] [PubMed]

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
[CrossRef] [PubMed]

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
[CrossRef] [PubMed]

2002

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

B. D. Watson, R. Prado, A. Veloso, J. Brunschwig, and W. D. Dietrich, “Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke,” Stroke 33, 428–434 (2002).
[CrossRef] [PubMed]

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002).
[CrossRef] [PubMed]

V. Rozhkov, D. F. Wilson, and S. A. Vinogradov, “Phosphorescent Pd porphyrin-dendrimers: Tuning core accessibility by varying the hydrophobicity of the dendritic matrix,” Macromolecules 35(6), 1991–1993 (2002).
[CrossRef]

2001

S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
[CrossRef]

J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas. 22(4), R35–R66 (2001).
[CrossRef]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage 13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
[CrossRef] [PubMed]

1999

E. Vovenko, “Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in normoxia: an experimental study on rats,” Pflugers Arch. 437(4), 617–623 (1999).
[CrossRef] [PubMed]

I. Vanzetta and A. Grinvald, “Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging,” Science 286(5444), 1555–1558 (1999).
[CrossRef] [PubMed]

S. A. Vinogradov, L. W. Lo, and D. F. Wilson, “Dendritic polyglutamic porphyrins: Probing porphyrin protection by oxygen dependent quenching of phosphorescence,” Chemistry 5(4), 1338–1347 (1999).
[CrossRef]

1997

R. D. Shonat and P. C. Johnson, “Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study,” Am. J. Physiol. 272(5 Pt 2), H2233–H2240 (1997).
[PubMed]

G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
[CrossRef] [PubMed]

R. D. Shonat, E. S. Wachman, W. Niu, A. P. Koretsky, and D. L. Farkas, “Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope,” Biophys. J. 73(3), 1223–1231 (1997).
[CrossRef] [PubMed]

1991

A. Mayevsky and H. R. Weiss, “Cerebral blood flow and oxygen consumption in cortical spreading depression,” J. Cereb. Blood Flow Metab. 11(5), 829–836 (1991).
[CrossRef] [PubMed]

1988

W. L. Rumsey, J. M. Vanderkooi, and D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241(4873), 1649–1651 (1988).
[CrossRef] [PubMed]

1985

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[CrossRef] [PubMed]

1967

W. J. Whalen, J. Riley, and P. Nair, “A microelectrode for measuring intracellular PO2,” J. Appl. Physiol. 23(5), 798–801 (1967).
[PubMed]

1944

A. A. P. Leao, “Spreading depression of activity in the cerebral cortex,” J. Neurophysiol. 7, 359–390 (1944).

Adkins, D. L.

D. L. Adkins, A. C. Voorhies, and T. A. Jones, “Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions,” Neuroscience 128(3), 473–486 (2004).
[CrossRef] [PubMed]

Alam, M.

J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

Andermann, M. L.

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

Anderson, P. J.

A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

Ayata, C.

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Appl. Opt. 48(10), D169–D177 (2009).
[CrossRef] [PubMed]

P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

Bednarkiewicz, A.

A. Bednarkiewicz and M. P. Whelan, “Global analysis of microscopic fluorescence lifetime images using spectral segmentation and a digital micromirror spatial illuminator,” J. Biomed. Opt. 13(4), 041316 (2008).
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A. Bednarkiewicz, M. Bouhifd, and M. P. Whelan, “Digital micromirror device as a spatial illuminator for fluorescence lifetime and hyperspectral imaging,” Appl. Opt. 47(9), 1193–1199 (2008).
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Berwick, J.

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
[CrossRef] [PubMed]

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage 13(6), 1002–1015 (2001).
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N. Prakash, J. D. Biag, S. A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A. W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37(Suppl 1), S27–S36 (2007).
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S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Appl. Opt. 48(10), D169–D177 (2009).
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P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
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R. P. Briñas, T. Troxler, R. M. Hochstrasser, and S. A. Vinogradov, “Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna,” J. Am. Chem. Soc. 127(33), 11851–11862 (2005).
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B. D. Watson, R. Prado, A. Veloso, J. Brunschwig, and W. D. Dietrich, “Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke,” Stroke 33, 428–434 (2002).
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B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
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Chao, S. H.

Dale, A. M.

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

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G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
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Devor, A.

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

Dietrich, W. D.

B. D. Watson, R. Prado, A. Veloso, J. Brunschwig, and W. D. Dietrich, “Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke,” Stroke 33, 428–434 (2002).
[CrossRef] [PubMed]

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
[CrossRef] [PubMed]

Dilekoz, E.

Dirnagl, U.

J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
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J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

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R. K. Miyake, H. D. Zeman, F. H. Duarte, R. Kikuchi, E. Ramacciotti, G. Lovhoiden, and C. Vrancken, “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” Dermatol. Surg. 32(8), 1031–1038 (2006).
[CrossRef] [PubMed]

Dugan, B. W.

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
[CrossRef] [PubMed]

S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
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W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging 27(12), 1728–1738 (2008).
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A. D. Estrada, A. Ponticorvo, T. N. Ford, and A. K. Dunn, “Microvascular oxygen quantification using two-photon microscopy,” Opt. Lett. 33(10), 1038–1040 (2008).
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P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Dunphy, I.

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
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I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002).
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J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
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Evans, S.

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
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R. D. Shonat, E. S. Wachman, W. Niu, A. P. Koretsky, and D. L. Farkas, “Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope,” Biophys. J. 73(3), 1223–1231 (1997).
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S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
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Fukano, T.

Fukuda, K.

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
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Gales, S. A.

Ginsberg, M. D.

B. D. Watson, W. D. Dietrich, R. Busto, M. S. Wachtel, and M. D. Ginsberg, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Ann. Neurol. 17(5), 497–504 (1985).
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A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

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I. Vanzetta and A. Grinvald, “Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging,” Science 286(5444), 1555–1558 (1999).
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D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005).
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S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
[CrossRef] [PubMed]

Heinemann, U.

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

Helmlinger, G.

G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
[CrossRef] [PubMed]

Hochstrasser, R. M.

R. P. Briñas, T. Troxler, R. M. Hochstrasser, and S. A. Vinogradov, “Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna,” J. Am. Chem. Soc. 127(33), 11851–11862 (2005).
[CrossRef] [PubMed]

Holl, M. R.

Hyman, B. T.

P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

Ibayashi, S.

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
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Iida, M.

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
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A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

Jain, R. K.

G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
[CrossRef] [PubMed]

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A. G. Tsai, P. C. Johnson, and M. Intaglietta, “Oxygen gradients in the microcirculation,” Physiol. Rev. 83(3), 933–963 (2003).
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R. D. Shonat and P. C. Johnson, “Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study,” Am. J. Physiol. 272(5 Pt 2), H2233–H2240 (1997).
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M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage 13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
[CrossRef] [PubMed]

Jones, M.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage 13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
[CrossRef] [PubMed]

Jones, P. B.

P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

Jones, S. R.

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
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R. K. Miyake, H. D. Zeman, F. H. Duarte, R. Kikuchi, E. Ramacciotti, G. Lovhoiden, and C. Vrancken, “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” Dermatol. Surg. 32(8), 1031–1038 (2006).
[CrossRef] [PubMed]

Kitazono, T.

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
[CrossRef] [PubMed]

Kleeberg, J.

J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

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J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

Koretsky, A. P.

R. D. Shonat, E. S. Wachman, W. Niu, A. P. Koretsky, and D. L. Farkas, “Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope,” Biophys. J. 73(3), 1223–1231 (1997).
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J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

Lloyd, A.

A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

Lo, E. H.

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

Lo, L. W.

S. A. Vinogradov, L. W. Lo, and D. F. Wilson, “Dendritic polyglutamic porphyrins: Probing porphyrin protection by oxygen dependent quenching of phosphorescence,” Chemistry 5(4), 1338–1347 (1999).
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A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

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H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
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J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

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S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
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S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
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A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

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A. Mayevsky and H. R. Weiss, “Cerebral blood flow and oxygen consumption in cortical spreading depression,” J. Cereb. Blood Flow Metab. 11(5), 829–836 (1991).
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W. J. Whalen, J. Riley, and P. Nair, “A microelectrode for measuring intracellular PO2,” J. Appl. Physiol. 23(5), 798–801 (1967).
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D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44(25), 5239–5248 (2005).
[CrossRef] [PubMed]

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
[CrossRef] [PubMed]

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002).
[CrossRef] [PubMed]

V. Rozhkov, D. F. Wilson, and S. A. Vinogradov, “Phosphorescent Pd porphyrin-dendrimers: Tuning core accessibility by varying the hydrophobicity of the dendritic matrix,” Macromolecules 35(6), 1991–1993 (2002).
[CrossRef]

S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
[CrossRef]

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[CrossRef]

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J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
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Yao, H.

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
[CrossRef] [PubMed]

Yasuda, R.

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron 50(6), 823–839 (2006).
[CrossRef] [PubMed]

Yuan, F.

G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
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Yuan, S.

Zeman, H. D.

R. K. Miyake, H. D. Zeman, F. H. Duarte, R. Kikuchi, E. Ramacciotti, G. Lovhoiden, and C. Vrancken, “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” Dermatol. Surg. 32(8), 1031–1038 (2006).
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Zheng, Y.

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
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Adv. Exp. Med. Biol.

S. A. Vinogradov, P. Grosul, V. Rozhkov, I. Dunphy, L. Shuman, B. W. Dugan, S. Evans, and D. F. Wilson, “Oxygen distributions in tissue measured by phosphorescence quenching,” Adv. Exp. Med. Biol. 510, 181–185 (2003).
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Am. J. Physiol.

R. D. Shonat and P. C. Johnson, “Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study,” Am. J. Physiol. 272(5 Pt 2), H2233–H2240 (1997).
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Anal. Biochem.

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Anal. Biochem. 310(2), 191–198 (2002).
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Ann. Biomed. Eng.

R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31(9), 1084–1096 (2003).
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Ann. Neurol.

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[CrossRef] [PubMed]

Brain

J. P. Dreier, J. Kleeberg, G. Petzold, J. Priller, O. Windmüller, H. D. Orzechowski, U. Lindauer, U. Heinemann, K. M. Einhäupl, and U. Dirnagl, “Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?” Brain 125(1), 102–112 (2002).
[CrossRef] [PubMed]

Chemistry

S. A. Vinogradov, L. W. Lo, and D. F. Wilson, “Dendritic polyglutamic porphyrins: Probing porphyrin protection by oxygen dependent quenching of phosphorescence,” Chemistry 5(4), 1338–1347 (1999).
[CrossRef]

Dermatol. Surg.

R. K. Miyake, H. D. Zeman, F. H. Duarte, R. Kikuchi, E. Ramacciotti, G. Lovhoiden, and C. Vrancken, “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” Dermatol. Surg. 32(8), 1031–1038 (2006).
[CrossRef] [PubMed]

Exp. Biol. Med. (Maywood)

J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller, “Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis,” Exp. Biol. Med. (Maywood) 232(2), 204–213 (2007).

IEEE Trans. Med. Imaging

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging 27(12), 1728–1738 (2008).
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J. Am. Chem. Soc.

R. P. Briñas, T. Troxler, R. M. Hochstrasser, and S. A. Vinogradov, “Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna,” J. Am. Chem. Soc. 127(33), 11851–11862 (2005).
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[CrossRef] [PubMed]

P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt. 13(4), 044007 (2008).
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A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
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A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, and R. Graf, ““Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex,” Brain,” J. Neurol. 130, 995–1008 (2007).

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, E. H. Lo, M. A. Moskowitz, and C. Ayata, ““Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia,” Brain,” J. Neurol. 130, 1631–1642 (2007).

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K. A. Tennant and T. A. Jones, “Sensorimotor behavioral effects of endothelin-1 induced small cortical infarcts in C57BL/6 mice,” J. Neurosci. Methods 181(1), 18–26 (2009).
[CrossRef] [PubMed]

Macromolecules

V. Rozhkov, D. F. Wilson, and S. A. Vinogradov, “Phosphorescent Pd porphyrin-dendrimers: Tuning core accessibility by varying the hydrophobicity of the dendritic matrix,” Macromolecules 35(6), 1991–1993 (2002).
[CrossRef]

Nat. Med.

G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, “Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation,” Nat. Med. 3(2), 177–182 (1997).
[CrossRef] [PubMed]

Neuroimage

A. K. Dunn, A. Devor, A. M. Dale, and D. A. Boas, “Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex,” Neuroimage 27(2), 279–290 (2005).
[CrossRef] [PubMed]

N. Prakash, J. D. Biag, S. A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A. W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37(Suppl 1), S27–S36 (2007).
[CrossRef] [PubMed]

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage 13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

J. Mayhew, D. Johnston, J. Martindale, M. Jones, J. Berwick, and Y. Zheng, “Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex,” Neuroimage 13(6), 975–987 (2001).
[CrossRef] [PubMed]

Neuron

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron 50(6), 823–839 (2006).
[CrossRef] [PubMed]

Neuroscience

D. L. Adkins, A. C. Voorhies, and T. A. Jones, “Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions,” Neuroscience 128(3), 473–486 (2004).
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Opt. Express

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E. Vovenko, “Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in normoxia: an experimental study on rats,” Pflugers Arch. 437(4), 617–623 (1999).
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J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas. 22(4), R35–R66 (2001).
[CrossRef]

Physiol. Rev.

A. G. Tsai, P. C. Johnson, and M. Intaglietta, “Oxygen gradients in the microcirculation,” Physiol. Rev. 83(3), 933–963 (2003).
[PubMed]

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

A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A. 102(10), 3822–3827 (2005).
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Rev. Sci. Instrum.

S. A. Vinogradov, M. A. Fernandez-Searra, B. W. Dugan, and D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72(8), 3396 (2001).
[CrossRef]

Science

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Stroke

B. D. Watson, R. Prado, A. Veloso, J. Brunschwig, and W. D. Dietrich, “Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke,” Stroke 33, 428–434 (2002).
[CrossRef] [PubMed]

H. Yao, H. Sugimori, K. Fukuda, J. Takada, H. Ooboshi, T. Kitazono, S. Ibayashi, and M. Iida, “Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats,” Stroke 34(11), 2716–2721 (2003).
[CrossRef] [PubMed]

Other

H. Hou, O. Y. Grinberg, S. Taie, S. Leichtweis, M. Miyake, S. Grinberg, H. Xie, M. Csete, and H. M. Swartz, “Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats,” Anesthesia and Analgesia 96, 1467–72, table of contents (2003).

J. Suzurikawa, M. Nakao, Y. Jimbo, R. Kanzaki, and H. Takahashi, “Light-addressed Stimulation under Ca2+ Imaging of Cultured Neurons,” IEEE Transactions on Bio-Medical Engineering (2009).

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Figures (5)

Fig. 1
Fig. 1

(a) A schematic of the imaging setup. (b) An example transformation from DMD coordinates to the speckle contrast images. (c) Example decay curves and fitting from two regions.

Fig. 2
Fig. 2

(a) Location of the two craniotomies. ET-1 is applied to the lateral craniotomy and speckle contrast images are examined in the medial craniotomy (b) before and (c) 5 minutes after ET-1 application.

Fig. 3
Fig. 3

(a) Various regions are selected for analysis before a topical vasoconstricting agent is applied laterally to the field of view. The speckle contrast images were then used to calculate (b) relative blood flow while the DMD is simultaneously used to measure the (c) pO2 in the 8 regions.

Fig. 4
Fig. 4

(a) 6 regions are selected in a large field of view at various distances from an induced ischemia. The speckle contrast images were then used to calculate (b) relative blood flow while the DMD is simultaneously used to measure the (c) pO2 in the regions.

Fig. 5
Fig. 5

(a) 4 donut shaped regions were selected while the DMD was used to create an ischemic lesion in the center of the regions through photothrombosis. (b) Relative blood flow and pO2 were measured although pO2 measurements could not be made while the DMD was being used to induce the stroke.

Equations (2)

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K = σ s < I > .
1 τ = 1 τ 0 + k q [ p O 2 ] ,

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