Abstract

Abstract: Imaging blood flow or oxygenation changes using optical techniques is useful for monitoring cortical activity in healthy subjects as well as in diseased states such as stroke or epilepsy. However, in order to gain a better understanding of hemodynamics in conscious, freely moving animals, these techniques must be implemented in a small scale, portable design that is adaptable to a wearable format. We demonstrate a novel system which combines the two techniques of laser speckle contrast imaging and intrinsic optical signal imaging simultaneously, using compact laser sources, to monitor induced cortical ischemia in a full field format with high temporal acquisition rates. We further demonstrate the advantages of using combined measurements of speckle contrast and oxygenation to establish absolute flow velocities, as well as to statistically distinguish between veins and arteries. We accomplish this system using coherence reduction techniques applied to Vertical Cavity Surface Emitting Lasers (VCSELs) operating at 680, 795 and 850 nm. This system uses minimal optical components and can easily be adapted into a portable format for continuous monitoring of cortical hemodynamics.

© 2012 OSA

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    [CrossRef] [PubMed]

2011 (7)

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011).
[CrossRef] [PubMed]

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011).
[CrossRef] [PubMed]

E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011).
[CrossRef] [PubMed]

2010 (2)

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[CrossRef] [PubMed]

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

2009 (2)

2008 (5)

J. C. Ramirez-San-Juan, R. Ramos-García, I. Guizar-Iturbide, G. Martínez-Niconoff, and B. Choi, “Impact of velocity distribution assumption on simplified laser speckle imaging equation,” Opt. Express16(5), 3197–3203 (2008).
[CrossRef] [PubMed]

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
[CrossRef] [PubMed]

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (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 (4)

C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007).
[CrossRef] [PubMed]

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

T. H. Schwartz, “Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset,” Epilepsy Curr.7(4), 91–94 (2007).
[CrossRef] [PubMed]

2006 (2)

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[CrossRef] [PubMed]

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

2005 (3)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (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]

2003 (1)

2002 (1)

F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002).
[PubMed]

2001 (1)

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]

1999 (1)

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

1998 (1)

A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998).
[CrossRef] [PubMed]

1996 (1)

K. A. Hossmann, “Periinfarct depolarizations,” Cerebrovasc. Brain Metab. Rev.8(3), 195–208 (1996).
[PubMed]

1976 (1)

Adhami, F.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Agoncillo, T.

C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007).
[CrossRef] [PubMed]

Allendorfer, J.

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
[CrossRef] [PubMed]

Amzica, F.

S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011).
[CrossRef] [PubMed]

F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002).
[PubMed]

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]

Ayata, C.

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, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[CrossRef] [PubMed]

Bagshaw, A. P.

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

Bénar, C.-G.

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

Bloch, O.

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Blood, A. J.

A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[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, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[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]

Boespflug, E. L.

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
[CrossRef] [PubMed]

Bolay, H.

Bonavita, S.

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

Bouchard, M. B.

Burgess, S. A.

Burns, L. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Chauvel, P.

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

Chen, B. R.

Chen-Bee, C. H.

C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007).
[CrossRef] [PubMed]

Cheung, E. L.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Chever, O.

S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011).
[CrossRef] [PubMed]

Choi, B.

O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011).
[CrossRef] [PubMed]

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

J. C. Ramirez-San-Juan, R. Ramos-García, I. Guizar-Iturbide, G. Martínez-Niconoff, and B. Choi, “Impact of velocity distribution assumption on simplified laser speckle imaging equation,” Opt. Express16(5), 3197–3203 (2008).
[CrossRef] [PubMed]

Chu, W. J.

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
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K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
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B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
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O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011).
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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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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).
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F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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Davis, R. J.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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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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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).
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F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
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D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
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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).
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W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[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]

Dunn, R. S.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
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B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
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F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
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[CrossRef] [PubMed]

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K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

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K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

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F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
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Guizar-Iturbide, I.

Hillman, E. M.

Holland, S. K.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

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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).
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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, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

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B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Kim, S. G.

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

Kim, T.

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

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F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
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J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
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Levi, O.

Levy, H.

Li, Y.

P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

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F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

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F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

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P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

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F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

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P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

Luo, Z.

Ma, H. T.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
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F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002).
[PubMed]

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P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Martínez-Niconoff, G.

Masamoto, K.

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

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H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
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Massimini, M.

F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002).
[PubMed]

Miao, P.

P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

Mizushima, N.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Morozov, Y. M.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Moskowitz, M. A.

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, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[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]

Muñoz-Lopez, J.

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

Munro, E. A.

Narayanan, S. N.

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]

Nguyen, J.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

Nimmerjahn, A.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Nishimura, N.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

O’Sullivan, T. D.

Padmawar, P.

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Pan, Y.

Pepino, A.

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

Piyawattanametha, W.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Ponticorvo, A.

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

Rakic, P.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Ramirez-San-Juan, J. C.

Ramírez-San-Juan, J. C.

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

Ramos-García, R.

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
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J. C. Ramirez-San-Juan, R. Ramos-García, I. Guizar-Iturbide, G. Martínez-Niconoff, and B. Choi, “Impact of velocity distribution assumption on simplified laser speckle imaging equation,” Opt. Express16(5), 3197–3203 (2008).
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Rector, D. M.

A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (2008).
[CrossRef] [PubMed]

Ringuette, D.

Rojas, M. J.

A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (2008).
[CrossRef] [PubMed]

Salazar-Hermenegildo, N.

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

Schaffer, C. B.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

Schei, J. L.

A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (2008).
[CrossRef] [PubMed]

Schloemer, A.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Schmithorst, V. J.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Schnitzer, M. J.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Schwartz, T. H.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

T. H. Schwartz, “Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset,” Epilepsy Curr.7(4), 91–94 (2007).
[CrossRef] [PubMed]

Sharp, F. R.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Shin, H. K.

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, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[CrossRef] [PubMed]

Sivaramakrishnan, M.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

Smaltino, F.

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

Stoica, G.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

Szaflarski, J. P.

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
[CrossRef] [PubMed]

Tedeschi, G.

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

Toga, A. W.

A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998).
[CrossRef] [PubMed]

Tom, W. J.

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

Tong, S. B.

P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

Ulbert, I.

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]

Vallée, R.

S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011).
[CrossRef] [PubMed]

Verkman, A. S.

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Vorhees, C. V.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Wang, L. V.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

Wang, P.

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

Wills-Karp, M.

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Xiong, Y.

C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007).
[CrossRef] [PubMed]

Yang, O.

O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011).
[CrossRef] [PubMed]

Yao, X.

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Yuan, Z.

Zhang, H. F.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

Zhao, M. R.

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

Ziv, Y.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Am. J. Pathol. (1)

F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006).
[CrossRef] [PubMed]

Appl. Phys. Lett. (1)

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007).
[CrossRef]

Cereb. Cortex (1)

K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007).
[CrossRef] [PubMed]

Cerebrovasc. Brain Metab. Rev. (1)

K. A. Hossmann, “Periinfarct depolarizations,” Cerebrovasc. Brain Metab. Rev.8(3), 195–208 (1996).
[PubMed]

Epilepsy Curr. (1)

T. H. Schwartz, “Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset,” Epilepsy Curr.7(4), 91–94 (2007).
[CrossRef] [PubMed]

Epilepsy Res. (1)

T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011).
[CrossRef] [PubMed]

Eur. J. Radiol. (1)

F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999).
[CrossRef] [PubMed]

IEEE Trans. Med. Imaging (1)

W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008).
[CrossRef] [PubMed]

J. Biomed. Opt. (5)

A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (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]

P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
[CrossRef] [PubMed]

O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011).
[CrossRef] [PubMed]

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (3)

A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998).
[CrossRef] [PubMed]

H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006).
[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]

J. Neurosci. (3)

C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007).
[CrossRef] [PubMed]

F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002).
[PubMed]

M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011).
[CrossRef] [PubMed]

J. Neurosci. Methods (1)

S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

Nat. Methods (3)

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005).
[CrossRef] [PubMed]

Opt. Express (3)

Opt. Lett. (2)

Phys. Med. Biol. (1)

J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

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]

Top. Stroke Rehabil. (1)

J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008).
[CrossRef] [PubMed]

Other (3)

R. Michalzik and K. J. Ebeling, “Operating Principles of VCSELs,” in Vertical-Cavity Surface-Emitting Laser Devices, H. Li, and K. Iga, eds. (Springer-Verlag, Berlin, 2003), pp. 53–98.

B. E. A. Saleh and M. C. Teich, Fundamentals of Photonics (Wiley, Hoboken, NJ, 2007).

R. Hebel and M. W. Stromberg, Anatomy and Embryology of the Laboratory Rat (BioMed Verlag, 1986).

Supplementary Material (1)

» Media 1: AVI (8575 KB)     

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Figures (6)

Fig. 1
Fig. 1

(a) Spectra for 680 nm, 795 nm, and 850 nm VCSELs. In each case, measurements were taken at threshold current (black), peak power (red), and current sweep operation (SW) through a range optimized for each device. (b) Interferogram envelopes for three wavelengths in SW operation, showing similar coherence lengths in each case. (c) Speckle contrast for 680 nm VCSEL near threshold, showing high contrast dropping off as power is increased

Fig. 2
Fig. 2

(a) Multiwavelength system schematic. The three wavelength VCSEL package is driven using two current sources, which are alternated along with a rapid switch synchronized by a camera trigger. Software and hardware control is accomplished with a customized frame grabber program. The trigger sequence is shown on the bottom right, with SW and SM waveforms. (b) and (c) Detail of multi-wavelength VCSEL package. In the center of (c), three 850 nm wafers are visible, as well as one multi-VCSEL wafer each for 795 nm and 680 nm wavelengths.

Fig. 3
Fig. 3

Processed image maps of flow and oxygenation (see Media 1). (a) Baseline LSCI map, showing speckle contrast values. (b)-(d) Percentage change in reflectance at peak of ischemia, for 680, 850 and 795 nm illumination respectively. Scale is matched to (a). (e) Montage of changing flow values during ischemia using relative flow index. 0 s indicates onset of ischemia. (f)-(h) Montage of concentration changes during ischemia for HbR, HbO and HbT respectively. Units are 10−5 M. Scale is matched to (e).

Fig. 4
Fig. 4

Time course plots of 3 different vessels showing changes in blood flow, HbR, HbO and HbT. Grayed region indicates duration of ischemic induction. Significantly stronger ischemic responses are seen in veins compared to arteries. Further, larger veins exhibit stronger response than smaller veins.

Fig. 5
Fig. 5

Line scan averaging for flow quantification in noisy data. (a) Averaged raw image shows vessels as seen with 680 illumination. Selected vessel flow convention is indicated by arrows. (b) Single line scan ‘carpet’ shows pixel intensities over time. (c) FFT averaged over several carpets shows preferred components with slope proportional to flow speed (d) Estimated flow speed map, based on LSCI image and calibration from single vessel line scan. Yellow arrows indicate flow direction. (e) Correlation between speckle flow index and flow velocity established from line scan. Measurements on vessels 1-6 as indicated in (d) are shown.

Fig. 6
Fig. 6

Classification of veins and arteries using principal component analysis. (a) Scatter plot of data projections on first two principal components, showing partition estimate. The final result is found to be independent of initial partition. (b) 3D scatter plot showing vessel data against vessel diameter, baseline flow speed and [HbO] changes. All units are normalized. Projections in x-y and y-z are shown to aid visualization. (c) Resulting vessel classification mapped onto calibrated LSCI flow map. Yellow vessels are arteries and cyan vessels are veins.

Tables (1)

Tables Icon

Table 1 Comparison of coherence lengths and resulting speckle pattern number for different VCSEL wavelengths

Equations (5)

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

δλ= λ c 2 2 σ s
n s = 2 σ s λ c 2 /Δλ
l c = 2ln2 π λ c 2 Δλ
n s = 4ln2 σ s π l c σ s l c
[ ln( R λ1 (0)/ R λ1 (t)) L λ1 ln( R λ2 (0)/ R λ2 (t)) L λ2 ln( R λ3 (0)/ R λ3 (t)) L λ3 ]  =  [ ε o λ1 ε r λ1 ε o λ2 ε r λ2 ε o λ3 ε r λ3 ][ Δ[HbO](t) Δ[HbR](t) ]

Metrics