Abstract

We developed a novel imaging technique that provides real-time two-dimensional maps of the absolute partial pressure of oxygen and relative cerebral blood flow in rats by combining phosphorescence lifetime imaging with laser speckle contrast imaging. Direct measurement of blood oxygenation based on phosphorescence lifetime is not significantly affected by changes in the optical parameters of the tissue during the experiment. The potential of the system as a novel tool for quantitative analysis of the dynamic delivery of oxygen to support brain metabolism was demonstrated in rats by imaging cortical responses to forepaw stimulation and the propagation of cortical spreading depression waves. This new instrument will enable further study of neurovascular coupling in normal and diseased brain.

© 2009 Optical Society of America

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2008

N. K. Logothetis, “What we can do and what we cannot do with fMRI,” Nature 453, 869-878 (2008).
[CrossRef] [PubMed]

H. K. Shin, M. Nishimura, P. B. Jones, H. Ay, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia,” Stroke 39, 1548-1555 (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, 44007 (2008).
[CrossRef]

A. S. Golub and R. N. Pittman, “PO2 measurements in the microcirculation using phosphorescence quenching microscopy at high magnification,” Am. J. Physiol.-Heart. C. 294, H2905-2916 (2008).
[CrossRef]

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” Chemphyschem 9, 1673-1679 (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, 1038-1040 (2008).
[CrossRef] [PubMed]

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, 754-762 (2007).
[CrossRef] [PubMed]

K. Masamoto, J. Kershaw, M. Ureshi, N. Takizawa, H. Kobayashi, K. Tanishita, and I. Kanno, “Apparent diffusion time of oxygen from blood to tissue in rat cerebral cortex: Implication for tissue oxygen dynamics during brain functions,” J. Appl. Physiol. 103, 1352-1358 (2007).
[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 130, 1631-1642 (2007).
[CrossRef] [PubMed]

2006

D. F. Wilson, W. M. Lee, S. Makonnen, O. Finikova, S. Apreleva, and S. A. Vinogradov, “Oxygen pressures in the interstitial space and their relationship to those in the blood plasma in resting skeletal muscle,” J. Appl. Physiol. 101, 1648-1656 (2006).
[CrossRef] [PubMed]

X. Wang, X. Xie, G. Ku, L. V. Wang, and G. Stoica, “Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography,” J. Biomed. Opt. 11, 024015 (2006).
[CrossRef] [PubMed]

H. Girouard and C. Iadecola, “Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease,” J. Appl. Physiol. 100, 328-335 (2006).
[CrossRef]

2005

C. Humpel and J. Marksteiner, “Cerebrovascular damage as a cause for Alzheimer's disease,” Curr. Neurovasc. Res. 2, 341-347 (2005).
[CrossRef] [PubMed]

G. De Visscher, S. Rooker, P. Jorens, J. Verlooy, M. Borgers, R. S. Reneman, K. Van Rossem, and W. Flameng, “Pentobarbital fails to reduce cerebral oxygen consumption early after non-hemorrhagic closed head injury in rats,” J. Neurotrauma 22, 793-806 (2005).
[CrossRef] [PubMed]

P. Frykholm, L. Hillered, B. Langstrom, L. Persson, J. Valtysson, and P. Enblad, “Relationship between cerebral blood flow and oxygen metabolism, and extracellular glucose and lactate concentrations during middle cerebral artery occlusion and reperfusion: a microdialysis and positron emission tomography study in nonhuman primates,” J. Neurosurg. 102, 1076-1084 (2005).
[CrossRef] [PubMed]

J. V. Guadagno, E. A. Warburton, P. S. Jones, T. D. Fryer, D. J. Day, J. H. Gillard, T. A. Carpenter, F. I. Aigbirhio, C. J. Price, and J. C. Baron, “The diffusion-weighted lesion in acute stroke: Heterogeneous patterns of flow/metabolism uncoupling as assessed by quantitative positron emission tomography,” Cerebrovasc. Dis. 19, 239-246 (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, 279-290 (2005).
[CrossRef] [PubMed]

K. M. Sicard and T. Q. Duong, “Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals,” Neuroimage 25, 850-858 (2005).
[CrossRef] [PubMed]

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, 5239-5248 (2005).
[CrossRef] [PubMed]

2004

C. Ayata, H. K. Shin, S. Salomone, Y. Ozdemir-Gursoy, D. A. Boas, A. K. Dunn, and M. A. Moskowitz, “Pronounced hypoperfusion during spreading depression in mouse cortex,” J. Cereb. Blood Flow Metab. 24, 1172-1182 (2004).
[CrossRef] [PubMed]

S. A. Sheth, M. Nemoto, M. Guiou, M. Walker, N. Pouratian, and A. W. Toga, “Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses,” Neuron 42, 347-355 (2004).
[CrossRef] [PubMed]

A. Kharlamov, B. R. Brown, K. A. Easley, and S. C. Jones, “Heterogeneous response of cerebral blood flow to hypotension demonstrated by laser speckle imaging flowmetry in rats,” Neurosci. Lett. 368, 151-156 (2004).
[CrossRef] [PubMed]

C. Ayata, A. K. Dunn, O. Y. Gursoy, Z. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab. 24, 744-755 (2004).
[CrossRef] [PubMed]

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2003

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2002

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dupan, and D. F. Wilson, “A method for measuring oxygen distributions in tissue using frequency domain phosphorometry,” Comp. Biochem. Phys. A 132, 147-152 (2002).
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2001

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2000

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1999

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J. J. A. Marota, C. Ayata, M. A. Moskowitz, R. M. Weisskoff, B. R. Rosen, and J. B. Mandeville, “Investigation of the early response to rat forepaw stimulation,” Magn. Reson. Med. 41, 247-252 (1999).
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I. Vanzetta and A. Grinvald, “Increased cortical oxidative metabolism due to sensory stimulation: Implications for functional brain imaging,” Science 286, 1555-1558 (1999).
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J. B. Mandeville, J. J. A. Marota, C. Ayata, G. Zaharchuk, M. A. Moskowitz, B. R. Rosen, and R. M. Weisskoff, “Evidence of a cerebrovascular post-arteriole Windkessel with delayed compliance,” J. Cereb. Blood Flow Metab. 19, 679-689 (1999).
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M. Nemoto, Y. Nomura, C. Sato, M. Tamura, K. Houkin, I. Koyanagi, and H. Abe, “Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: Dynamic changes in hemoglobin concentration and oxygenation,” J. Cereb. Blood Flow Metab. 19, 246-259 (1999).
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1998

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1997

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1996

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1994

L. M. Gault, C. W. Lin, J. C. Lamanna, and W. D. Lust, “Changes in energy metabolites, cGMP and intracellular pH during cortical spreading depression,” Brain Res. 641, 176-180 (1994).
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1993

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1991

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1990

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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, 1649-1651(1988).
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P. T. Fox, M. E. Raichle, M. A. Mintun, and C. Dence, “Nonoxidative glucose consumption during focal physiologic neural activity,” Science 241, 462-464 (1988).
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1987

J. M. Vanderkooi, G. Maniara, T. J. Green, and D. F. Wilson, “An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence,” J. Biol. Chem. 262, 5476-5482 (1987).
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1986

P. T. Fox and M. E. Raichle, “Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects,” Proc. Natl. Acad. Sci. USA 83, 1140-1144 (1986).
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1984

W. A. Mutch and A. J. Hansen, “Extracellular pH changes during spreading depression and cerebral ischemia: Mechanisms of brain pH regulation,” J. Cereb. Blood Flow Metab. 4, 17-27 (1984).
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1983

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1981

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1979

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1975

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1959

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1944

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Abe, H.

M. Nemoto, Y. Nomura, C. Sato, M. Tamura, K. Houkin, I. Koyanagi, and H. Abe, “Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: Dynamic changes in hemoglobin concentration and oxygenation,” J. Cereb. Blood Flow Metab. 19, 246-259 (1999).
[CrossRef] [PubMed]

Aigbirhio, F. I.

J. V. Guadagno, E. A. Warburton, P. S. Jones, T. D. Fryer, D. J. Day, J. H. Gillard, T. A. Carpenter, F. I. Aigbirhio, C. J. Price, and J. C. Baron, “The diffusion-weighted lesion in acute stroke: Heterogeneous patterns of flow/metabolism uncoupling as assessed by quantitative positron emission tomography,” Cerebrovasc. Dis. 19, 239-246 (2005).
[CrossRef] [PubMed]

Ances, B. M.

B. M. Ances, D. F. Wilson, J. H. Greenberg, and J. A. Detre, “Dynamic changes in cerebral blood flow, O2 tension, and calculated cerebral metabolic rate of O2 during functional activation using oxygen phosphorescence quenching,” J. Cereb. Blood Flow Metab. 21, 511-516 (2001).
[CrossRef] [PubMed]

B. M. Ances, D. G. Buerk, J. H. Greenberg, and J. A. Detre, “Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats,” Neurosci. Lett. 306, 106-110 (2001).
[CrossRef] [PubMed]

Andermann, M. L.

Aprelev, A.

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” Chemphyschem 9, 1673-1679 (2008).
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D. F. Wilson, W. M. Lee, S. Makonnen, O. Finikova, S. Apreleva, and S. A. Vinogradov, “Oxygen pressures in the interstitial space and their relationship to those in the blood plasma in resting skeletal muscle,” J. Appl. Physiol. 101, 1648-1656 (2006).
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Arthurs, O. J.

O. J. Arthurs and S. Boniface, “How well do we understand the neural origins of the fMRI BOLD signal?,” Trends Neurosci. 25, 27-31 (2002).
[CrossRef] [PubMed]

Asiedu, J. K.

J. K. Asiedu, J. Ji, M. Nguyen, N. Rosenzweig, and Z. Rosenzweig, “Development of a digital fluorescence sensing technique to monitor the response of macrophages to external hypoxia,” J. Biomed. Opt. 6, 116-121 (2001).
[CrossRef] [PubMed]

Augath, M.

N. K. Logothetis, J. Pauls, M. Augath, T. Trinath, and A. Oeltermann, “Neurophysiological investigation of the basis of the fMRI signal,” Nature 412, 150-157 (2001).
[CrossRef] [PubMed]

Ay, H.

H. K. Shin, M. Nishimura, P. B. Jones, H. Ay, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia,” Stroke 39, 1548-1555 (2008).
[CrossRef] [PubMed]

Ayata, C.

H. K. Shin, M. Nishimura, P. B. Jones, H. Ay, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia,” Stroke 39, 1548-1555 (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, 44007 (2008).
[CrossRef]

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 130, 1631-1642 (2007).
[CrossRef] [PubMed]

C. Ayata, A. K. Dunn, O. Y. Gursoy, Z. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab. 24, 744-755 (2004).
[CrossRef] [PubMed]

C. Ayata, H. K. Shin, S. Salomone, Y. Ozdemir-Gursoy, D. A. Boas, A. K. Dunn, and M. A. Moskowitz, “Pronounced hypoperfusion during spreading depression in mouse cortex,” J. Cereb. Blood Flow Metab. 24, 1172-1182 (2004).
[CrossRef] [PubMed]

J. B. Mandeville, J. J. A. Marota, C. Ayata, G. Zaharchuk, M. A. Moskowitz, B. R. Rosen, and R. M. Weisskoff, “Evidence of a cerebrovascular post-arteriole Windkessel with delayed compliance,” J. Cereb. Blood Flow Metab. 19, 679-689 (1999).
[CrossRef] [PubMed]

J. J. A. Marota, C. Ayata, M. A. Moskowitz, R. M. Weisskoff, B. R. Rosen, and J. B. Mandeville, “Investigation of the early response to rat forepaw stimulation,” Magn. Reson. Med. 41, 247-252 (1999).
[CrossRef] [PubMed]

Bacon, J. R.

E. R. Carraway, J. N. Demas, B. A. Degraff, and J. R. Bacon, “Photophysics and photochemistry of oxygen sensors based on luminescent transition-metal complexes,” Anal. Chem. 63, 337-342 (1991).
[CrossRef]

Bakker, D.

N. Hadjikhani, M. S. Del Rio, O. Wu, D. Schwartz, D. Bakker, B. Fischl, K. K. Kwong, F. M. Cutrer, B. R. Rosen, R. B. Tootell, A. G. Sorensen, and M. A. Moskowitz, “Mechanisms of migraine aura revealed by functional MRI in human visual cortex,” Proc. Natl. Acad. Sci. USA 98, 4687-4692(2001).
[CrossRef] [PubMed]

Baron, J. C.

J. V. Guadagno, E. A. Warburton, P. S. Jones, T. D. Fryer, D. J. Day, J. H. Gillard, T. A. Carpenter, F. I. Aigbirhio, C. J. Price, and J. C. Baron, “The diffusion-weighted lesion in acute stroke: Heterogeneous patterns of flow/metabolism uncoupling as assessed by quantitative positron emission tomography,” Cerebrovasc. Dis. 19, 239-246 (2005).
[CrossRef] [PubMed]

Bennett, J.

Berwick, J.

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, 1002-1015(2001).
[CrossRef] [PubMed]

Boas, D. A.

H. K. Shin, M. Nishimura, P. B. Jones, H. Ay, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia,” Stroke 39, 1548-1555 (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, 44007 (2008).
[CrossRef]

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 130, 1631-1642 (2007).
[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, 279-290 (2005).
[CrossRef] [PubMed]

C. Ayata, A. K. Dunn, O. Y. Gursoy, Z. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab. 24, 744-755 (2004).
[CrossRef] [PubMed]

C. Ayata, H. K. Shin, S. Salomone, Y. Ozdemir-Gursoy, D. A. Boas, A. K. Dunn, and M. A. Moskowitz, “Pronounced hypoperfusion during spreading depression in mouse cortex,” J. Cereb. Blood Flow Metab. 24, 1172-1182 (2004).
[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, 28-30 (2003).
[CrossRef] [PubMed]

H. Bolay, U. Reuter, A. K. Dunn, Z. Huang, D. A. Boas, and M. A. Moskowitz, “Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model,” Nat. Med. 8, 136-142 (2002).
[CrossRef] [PubMed]

G. Strangman, D. A. Boas, and J. P. Sutton, “Non-invasive neuroimaging using near-infrared light,” Biol. Psychiatry 52, 679-693 (2002).
[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, 195-201 (2001).
[CrossRef] [PubMed]

Bolay, H.

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, 28-30 (2003).
[CrossRef] [PubMed]

H. Bolay, U. Reuter, A. K. Dunn, Z. Huang, D. A. Boas, and M. A. Moskowitz, “Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model,” Nat. Med. 8, 136-142 (2002).
[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, 195-201 (2001).
[CrossRef] [PubMed]

Boniface, S.

O. J. Arthurs and S. Boniface, “How well do we understand the neural origins of the fMRI BOLD signal?,” Trends Neurosci. 25, 27-31 (2002).
[CrossRef] [PubMed]

Borgers, M.

G. De Visscher, S. Rooker, P. Jorens, J. Verlooy, M. Borgers, R. S. Reneman, K. Van Rossem, and W. Flameng, “Pentobarbital fails to reduce cerebral oxygen consumption early after non-hemorrhagic closed head injury in rats,” J. Neurotrauma 22, 793-806 (2005).
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Briers, J. D.

A. F. Fercher and J. D. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37, 326-330 (1981).
[CrossRef]

Brown, B. R.

A. Kharlamov, B. R. Brown, K. A. Easley, and S. C. Jones, “Heterogeneous response of cerebral blood flow to hypotension demonstrated by laser speckle imaging flowmetry in rats,” Neurosci. Lett. 368, 151-156 (2004).
[CrossRef] [PubMed]

Buerk, D. G.

B. M. Ances, D. G. Buerk, J. H. Greenberg, and J. A. Detre, “Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats,” Neurosci. Lett. 306, 106-110 (2001).
[CrossRef] [PubMed]

Burnett, M. G.

T. Durduran, M. G. Burnett, G. Yu, C. Zhou, D. Furuya, A. G. Yodh, J. A. Detre, and J. H. Greenberg, “Spatiotemporal quantification of cerebral blood flow during functional activation in rat somatosensory cortex using laser-speckle flowmetry,” J. Cereb. Blood Flow Metab. 24, 518-525 (2004).
[CrossRef] [PubMed]

Buxton, R. B.

R. B. Buxton, Introduction to Functional Magnetic Resonance Imaging: Principles and Techniques (Cambridge U. Press, 2002).

Carpenter, T. A.

J. V. Guadagno, E. A. Warburton, P. S. Jones, T. D. Fryer, D. J. Day, J. H. Gillard, T. A. Carpenter, F. I. Aigbirhio, C. J. Price, and J. C. Baron, “The diffusion-weighted lesion in acute stroke: Heterogeneous patterns of flow/metabolism uncoupling as assessed by quantitative positron emission tomography,” Cerebrovasc. Dis. 19, 239-246 (2005).
[CrossRef] [PubMed]

Carraway, E. R.

E. R. Carraway, J. N. Demas, B. A. Degraff, and J. R. Bacon, “Photophysics and photochemistry of oxygen sensors based on luminescent transition-metal complexes,” Anal. Chem. 63, 337-342 (1991).
[CrossRef]

Cen, J.

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, and H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8, 559-564 (2003).
[CrossRef] [PubMed]

Chen, S.

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, and H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8, 559-564 (2003).
[CrossRef] [PubMed]

Cheng, H.

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, and H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8, 559-564 (2003).
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Figures (4)

Fig. 1
Fig. 1

Experimental setup. Two personal computers (PC1 and PC2) control triggering signals and image acquisition. CCD, charge-coupled device; BS, beam sampler; CL, collimating lens; FL, focusing lens; DAQ, data acquisition board.

Fig. 2
Fig. 2

Formation of the p O 2 image. (a)–(c) Phosphorescence intensity images at different time delays with respect to the laser pulse. (d) Measurement and single exponential decay lifetime (τ) fit of the phosphorescence intensity at point A marked with an x in (a). (e) In vitro calibration of 4 × 10 5 M blood concentration of Oxypor R2. (f) p O 2 image obtained based on dye calibration and calculated lifetime values at each CCD pixel. Arterial p O 2 measured during the experiment was 106 mm Hg . The scale bar is 1 mm .

Fig. 3
Fig. 3

Imaging of the brain activation during forepaw stimulation. (a) Position of the cranial window and photograph of the cortical vasculature. (b) 2D p O 2 map during the resting period of activation sequence. (c) Composite image consisting of phosphorescence intensity (gray) and activation area (color). The activation area was obtained by estimating the percent change in p O 2 during the stimulus, relative to baseline, and applying a 50% threshold. (d) Speckle contrast image during the resting period of activation sequence. (e) Time courses of p O 2 (solid curve) and rCBF (dashed curve) during several stimulation sequences. Both p O 2 and rCBF values were averaged over the area marked with the windows in (b) and (d). Duration of the stimulus within each stimulation sequence was marked with the horizontal bars in (e) and (f). (f) Average p O 2 , rCBF, and rCMRO 2 responses during one stimulation sequence obtained from the six individual sequences in (e). Arterial p O 2 measured during the experiment was 102 mm Hg . The scale bar is 1 mm .

Fig. 4
Fig. 4

Imaging of CSD. (a) and (b) Phosphorescence intensity image and p O 2 image at the arrival of the CSD [ t = 46 s , marked by an arrow in (f)]. (c) and (d) Laser speckle contrast image and rCBF image at the arrival of the CSD (Media 1). (e) Positions of the cranial window and the location of KCl injection were marked on the schematic of the rat skull. Photograph of the cortical vasculature was taken through the microscope eyepieces. (f) Temporal evolutions of p O 2 (upper solid curve), rCBF (upper dashed curve), and rCMRO 2 averaged over the rectangular area marked on (b) and (d). rCMRO 2 was calculated assuming a constant pH (lower solid curve) and a variable pH (lower dotted curve) with transients centered around CSD-induced peaks in rCBF. Arterial p O 2 measured at the beginning of the experiment was 81 mm Hg . The scale bar is 1 mm .

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