Abstract

There is an increasing need for quantitative and computationally affordable models for analyzing tissue metabolism and hemodynamics in microvascular networks. In this work, we develop a hybrid model to solve for the time-varying oxygen advection-diffusion equation in the vessels and tissue. To obtain a three-dimensional temporal evolution of tissue oxygen concentration for realistic complex vessel networks, we used a graph-based advection model combined with a finite-element based diffusion model and an implicit time-advancing scheme. We validated this algorithm for both static and dynamic conditions. We also applied it to a complex vascular network obtained from a rodent somatosensory cortex. Qualitative agreement was found with in-vivo experiments.

© 2008 Optical Society of America

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  29. M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2008

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]

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

2007

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

R. K. Wang, S. Jacques, Z. Ma, S. Hurst, S. Hanson, and A. Gruber, " Three dimensional optical angiography," Opt. Express 15,4083-4097 (2007).
[CrossRef] [PubMed]

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

2006

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

P. Herman, H. K. Trubel, and F. Hyder, "A multiparametric assessment of oxygen efflux from the brain," J. Cereb. Blood Flow Metab. 26,79-91 (2006).
[CrossRef]

2005

H. H. Lipowsky, "Microvascular rheology and hemodynamics," Microcirculation 12, 5-15 (2005).
[CrossRef] [PubMed]

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffuse optical imaging," Phys. Med. Biol. 50,R1-R43 (2005).
[CrossRef] [PubMed]

2004

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

2002

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

2001

D. A. Beard and J. B. Bassingthwaighte, "Modeling advection and diffusion of oxygen in complex vascular networks," Ann. Biomed. Eng. 29,298-310 (2001).
[CrossRef] [PubMed]

J. D. Briers, "Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging," Physiol. Meas. 22,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. 21,195-201 (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. 437,617-623 (1999).
[CrossRef] [PubMed]

1998

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

1997

A. Villringer and B. Chance, "Non-invasive optical spectroscopy and imaging of human brain function," Trends Neurosci. 20,435-442 (1997).
[CrossRef] [PubMed]

1994

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

1993

1989

A. S. Popel, R. N. Pittman, and M. L. Ellsworth, "Rate of oxygen loss from arterioles is an order of magnitude higher than expected." Am. J. Physiol. Heart Circ. Physiol. 256,H921-H924 (1989).

1988

M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood flow and tissue oxygenation on newborn infants by infra-red transillumination," Med. Biol. Eng. Comput. 26,289-294 (1988).
[CrossRef] [PubMed]

1986

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

1985

H. S. Orbach, L. B. Cohen, and A. Grinvald, "Optical mapping of electrical activity in rat somatosensory and visual cortex," J. Neurosci. 5,1886-1895 (1985).
[PubMed]

1981

D. D. Lobdell, "An invertible simple equation for computation of blood O2 dissociation relations," J. Appl. Physiol. 50,971-973 (1981).
[PubMed]

1971

B. Chance, N. Graham, and D. Mayer, "A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein," Rev. Sci. Instrum. 42,951-957 (1971).
[CrossRef] [PubMed]

Allen, M. S.

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

T. J. Huppert, M. S. Allen, G. S. Diamond, and D. A. Boas, "Inferring cerebral oxygen metabolism from fMRI with a dynamic multi-compartment Windkessel model," Human Brain Mapping (to be published).

Andersson, C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Arridge, S. R.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffuse optical imaging," Phys. Med. Biol. 50,R1-R43 (2005).
[CrossRef] [PubMed]

Arvin, K.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Austin, T.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Baker, B. J.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Bassingthwaighte, J. B.

D. A. Beard and J. B. Bassingthwaighte, "Modeling advection and diffusion of oxygen in complex vascular networks," Ann. Biomed. Eng. 29,298-310 (2001).
[CrossRef] [PubMed]

Beard, D. A.

D. A. Beard and J. B. Bassingthwaighte, "Modeling advection and diffusion of oxygen in complex vascular networks," Ann. Biomed. Eng. 29,298-310 (2001).
[CrossRef] [PubMed]

Benav, H.

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

Berwick, J.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Bigio, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Billings, S.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[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]

T. J. Huppert, M. S. Allen, G. S. Diamond, and D. A. Boas, "Inferring cerebral oxygen metabolism from fMRI with a dynamic multi-compartment Windkessel model," Human Brain Mapping (to be published).

Bolay, H.

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]

Bortfeld, H.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Bouma, B. E.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Bower, B. A.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

Brady, T.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Briers, J. D.

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

Burns, D. H.

Cense, B.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Chance, B.

A. Villringer and B. Chance, "Non-invasive optical spectroscopy and imaging of human brain function," Trends Neurosci. 20,435-442 (1997).
[CrossRef] [PubMed]

B. Chance, N. Graham, and D. Mayer, "A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein," Rev. Sci. Instrum. 42,951-957 (1971).
[CrossRef] [PubMed]

Chen, D.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Chen, T. C.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Cipolloni, P. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Cohen, L. B.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

H. S. Orbach, L. B. Cohen, and A. Grinvald, "Optical mapping of electrical activity in rat somatosensory and visual cortex," J. Neurosci. 5,1886-1895 (1985).
[PubMed]

Cope, M.

M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood flow and tissue oxygenation on newborn infants by infra-red transillumination," Med. Biol. Eng. Comput. 26,289-294 (1988).
[CrossRef] [PubMed]

Dale, A. M.

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

de Boer, J. F.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Delpy, D. T.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood flow and tissue oxygenation on newborn infants by infra-red transillumination," Med. Biol. Eng. Comput. 26,289-294 (1988).
[CrossRef] [PubMed]

Denk, W.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

Devor, A.

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

Diamond, G. S.

T. J. Huppert, M. S. Allen, G. S. Diamond, and D. A. Boas, "Inferring cerebral oxygen metabolism from fMRI with a dynamic multi-compartment Windkessel model," Human Brain Mapping (to be published).

Diamond, S. G.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Dirnagl, U.

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Djurisic, M.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Dunn, A. K.

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]

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]

Einhaupl, K.

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Ellsworth, M. L.

A. S. Popel, R. N. Pittman, and M. L. Ellsworth, "Rate of oxygen loss from arterioles is an order of magnitude higher than expected." Am. J. Physiol. Heart Circ. Physiol. 256,H921-H924 (1989).

Elwell, C. E.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Estrada, A. D.

Falk, C. X.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Fang, H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Fisher, P. J.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Ford, T. N.

Franceschini, M. A.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Frangos, J. A.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Freedman, S. D.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Frostig, R. D.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

Ghiran, I. C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Gibson, A. P.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffuse optical imaging," Phys. Med. Biol. 50,R1-R43 (2005).
[CrossRef] [PubMed]

Gilbert, C. D.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

Graham, N.

B. Chance, N. Graham, and D. Mayer, "A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein," Rev. Sci. Instrum. 42,951-957 (1971).
[CrossRef] [PubMed]

Grant, P. E.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Grinvald, A.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

H. S. Orbach, L. B. Cohen, and A. Grinvald, "Optical mapping of electrical activity in rat somatosensory and visual cortex," J. Neurosci. 5,1886-1895 (1985).
[PubMed]

Gruber, A.

Haidekker, M. A.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Hanlon, E. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Hanson, S.

Hebden, J. C.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffuse optical imaging," Phys. Med. Biol. 50,R1-R43 (2005).
[CrossRef] [PubMed]

Helmchen, F.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

Henty, J. R.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Herman, P.

P. Herman, H. K. Trubel, and F. Hyder, "A multiparametric assessment of oxygen efflux from the brain," J. Cereb. Blood Flow Metab. 26,79-91 (2006).
[CrossRef]

Huang, D.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

Huppert, T. J.

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

T. J. Huppert, M. S. Allen, G. S. Diamond, and D. A. Boas, "Inferring cerebral oxygen metabolism from fMRI with a dynamic multi-compartment Windkessel model," Human Brain Mapping (to be published).

Hurst, S.

Hyder, F.

P. Herman, H. K. Trubel, and F. Hyder, "A multiparametric assessment of oxygen efflux from the brain," J. Cereb. Blood Flow Metab. 26,79-91 (2006).
[CrossRef]

Intaglietta, M.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Itzkan, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Izatt, J. A.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

Jacques, S.

Johnston, D.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Jones, P. B.

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

Jones, S. R.

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

Kasischke, K. A.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Kimerer, L. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Kleinfeld, D.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

Kosmidis, E. K.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Krishnamoorthy, K. K.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Leung, T. S.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Lieke, E.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

Lim, K. H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Lindauer, U.

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Lipowsky, H. H.

H. H. Lipowsky, "Microvascular rheology and hemodynamics," Microcirculation 12, 5-15 (2005).
[CrossRef] [PubMed]

Lobdell, D. D.

D. D. Lobdell, "An invertible simple equation for computation of blood O2 dissociation relations," J. Appl. Physiol. 50,971-973 (1981).
[PubMed]

Ma, Z.

Mayer, D.

B. Chance, N. Graham, and D. Mayer, "A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein," Rev. Sci. Instrum. 42,951-957 (1971).
[CrossRef] [PubMed]

Mayhew, J.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Meek, J. H.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Mitra, P. P.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

Modell, M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Moskowitz, M. A.

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]

Nassif, N.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Orbach, H. S.

H. S. Orbach, L. B. Cohen, and A. Grinvald, "Optical mapping of electrical activity in rat somatosensory and visual cortex," J. Neurosci. 5,1886-1895 (1985).
[PubMed]

Park, B. H.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Perelman, L. T.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Pierce, M. C.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Pittman, R. N.

A. S. Popel, R. N. Pittman, and M. L. Ellsworth, "Rate of oxygen loss from arterioles is an order of magnitude higher than expected." Am. J. Physiol. Heart Circ. Physiol. 256,H921-H924 (1989).

Plant, R. L.

Ponticorvo, A.

Popel, A. S.

A. S. Popel, R. N. Pittman, and M. L. Ellsworth, "Rate of oxygen loss from arterioles is an order of magnitude higher than expected." Am. J. Physiol. Heart Circ. Physiol. 256,H921-H924 (1989).

Qiu, L.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Sachs, B. P.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Salahuddin, S.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Stevens, H. Y.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Tan, O.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

Tearney, G. J.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Thaker, S.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Them, A.

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Themelis, G.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Theodorakis, E.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Trubel, H. K.

P. Herman, H. K. Trubel, and F. Hyder, "A multiparametric assessment of oxygen efflux from the brain," J. Cereb. Blood Flow Metab. 26,79-91 (2006).
[CrossRef]

Tsai, A. G.

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Villringer, A.

A. Villringer and B. Chance, "Non-invasive optical spectroscopy and imaging of human brain function," Trends Neurosci. 20,435-442 (1997).
[CrossRef] [PubMed]

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Vishwasrao, H. D.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Vitkin, E.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Vovenko, E.

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. 437,617-623 (1999).
[CrossRef] [PubMed]

Vucinic, D.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Wang, R. K.

Wang, Y.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

Webb, W. W.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Wiesel, T. N.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

Wyatt, J. S.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Yun, S. H.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Zaman, M. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
[CrossRef] [PubMed]

Zecevic, D.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Zheng, Y.

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Zipfel, W. R.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Adv. Exp. Med. Biol.

C. E. Elwell, J. R. Henty, T. S. Leung, T. Austin, J. H. Meek, D. T. Delpy, and J. S. Wyatt, "Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy," Adv. Exp. Med. Biol. 566,263-268 (2005).
[CrossRef]

Am. J. Physiol. Heart Circ. Physiol.

A. S. Popel, R. N. Pittman, and M. L. Ellsworth, "Rate of oxygen loss from arterioles is an order of magnitude higher than expected." Am. J. Physiol. Heart Circ. Physiol. 256,H921-H924 (1989).

M. A. Haidekker, A. G. Tsai, T. Brady, H. Y. Stevens, J. A. Frangos, E. Theodorakis, and M. Intaglietta, "A novel approach to blood plasma viscosity measurement using fluorescent molecular rotors," Am. J. Physiol. Heart Circ. Physiol. 282,H1609-H1614. (2002).
[PubMed]

Ann. Biomed. Eng.

D. A. Beard and J. B. Bassingthwaighte, "Modeling advection and diffusion of oxygen in complex vascular networks," Ann. Biomed. Eng. 29,298-310 (2001).
[CrossRef] [PubMed]

Appl. Spectrosc.

Bull. Soc. Belg. Ophtalmol.

B. Cense, T. C. Chen, N. Nassif, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology," Bull. Soc. Belg. Ophtalmol.123-132 (2006).

Cell. Mol. Neurobiol.

B. J. Baker, E. K. Kosmidis, D. Vucinic, C. X. Falk, L. B. Cohen, M. Djurisic, and D. Zecevic, "Imaging brain activity with voltage- and calcium-sensitive dyes," Cell. Mol. Neurobiol. 25,245-282 (2005).
[CrossRef] [PubMed]

Circ. Res.

A. Villringer, A. Them, U. Lindauer, K. Einhaupl, and U. Dirnagl, "Capillary perfusion of the rat brain cortex," Circ. Res. 75,55-62 (1994).
[PubMed]

Human Brain Mapping

T. J. Huppert, M. S. Allen, G. S. Diamond, and D. A. Boas, "Inferring cerebral oxygen metabolism from fMRI with a dynamic multi-compartment Windkessel model," Human Brain Mapping (to be published).

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D. D. Lobdell, "An invertible simple equation for computation of blood O2 dissociation relations," J. Appl. Physiol. 50,971-973 (1981).
[PubMed]

J. Biomed. Opt.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, "In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography," J. Biomed. Opt. 12,041215 (2007).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab.

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]

T. J. Huppert, M. S. Allen, H. Benav, P. B. Jones, and D. A. Boas, "A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation," J. Cereb. Blood Flow Metab. 27,1262-1279 (2007).
[CrossRef] [PubMed]

P. Herman, H. K. Trubel, and F. Hyder, "A multiparametric assessment of oxygen efflux from the brain," J. Cereb. Blood Flow Metab. 26,79-91 (2006).
[CrossRef]

J. Neurosci.

H. S. Orbach, L. B. Cohen, and A. Grinvald, "Optical mapping of electrical activity in rat somatosensory and visual cortex," J. Neurosci. 5,1886-1895 (1985).
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Med. Biol. Eng. Comput.

M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood flow and tissue oxygenation on newborn infants by infra-red transillumination," Med. Biol. Eng. Comput. 26,289-294 (1988).
[CrossRef] [PubMed]

Microcirculation

H. H. Lipowsky, "Microvascular rheology and hemodynamics," Microcirculation 12, 5-15 (2005).
[CrossRef] [PubMed]

Nature

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324,361-364 (1986).
[CrossRef] [PubMed]

NeuroImage

D. A. Boas, S. R. Jones, A. Devor, T. J. Huppert, and A. M. Dale, "A vascular anatomical network model of the spatio-temporal response to brain activation," NeuroImage 40,1116-1129 (2008).
[CrossRef] [PubMed]

Y. Zheng, D. Johnston, J. Berwick, D. Chen, S. Billings, and J. Mayhew, "A three-compartment model of the hemodynamic response and oxygen delivery to brain," NeuroImage 28,925-939 (2005).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Pediatr. Res.

M. A. Franceschini, S. Thaker, G. Themelis, K. K. Krishnamoorthy, H. Bortfeld, S. G. Diamond, D. A. Boas, K. Arvin, and P. E. Grant, "Assessment of infant brain development with frequency-domain near-infrared spectroscopy," Pediatr. Res. 61,546-551 (2007).
[PubMed]

Pflugers Arch.

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. 437,617-623 (1999).
[CrossRef] [PubMed]

Phys. Med. Biol.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffuse optical imaging," Phys. Med. Biol. 50,R1-R43 (2005).
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J. D. Briers, "Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging," Physiol. Meas. 22,R35-R66 (2001).
[CrossRef]

Proc. Natl. Acad. Sci. USA

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, "Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex," Proc. Natl. Acad. Sci. USA 95,15741-15746 (1998).
[CrossRef] [PubMed]

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, "Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels," Proc. Natl. Acad. Sci. USA 104,17255-17260 (2007).
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Science

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305,99-103 (2004).
[CrossRef] [PubMed]

Trends Neurosci.

A. Villringer and B. Chance, "Non-invasive optical spectroscopy and imaging of human brain function," Trends Neurosci. 20,435-442 (1997).
[CrossRef] [PubMed]

Other

G. Arfken, Mathematical Methods for Physicists, 3rd ed. (Academic, 1985).

D. R. Lynch, Computational Partial Differential Equations for Environmental Scientists and Engineers - A First Practical Course (Springer, 2005).
[PubMed]

C. Godsil and G. Royle, Algebraic Graph Theory (Springer-Verlag, 2001).
[CrossRef]

Supplementary Material (3)

» Media 1: AVI (16292 KB)     
» Media 2: AVI (9329 KB)     
» Media 3: AVI (12431 KB)     

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Figures (7)

Fig. 1.
Fig. 1.

The decomposition of the problem domain.

Fig. 2.
Fig. 2.

Model validations with a single vessel: (a) PO2 distribution across an X-Y plane along the vessel; (b–d) PO2 along the vessel for different values of (b) blood velocity, (c) hematocrit, and (d) oxygen consumption.

Fig. 3.
Fig. 3.

Validation of dynamic processes with a single vessel. (a) PO2 profiles along the vessel at 20 ms intervals for isolated advection. The modeled PO2 profile is given by the solid line. The star represents the expected advancement of oxygen pressure profile of 8 µm/s. (b) Tissue PO2 evolution for validation of vessel wall permeability. The dots and dashed line show our model results for Kw and Kw /2 respectively, and the solid line is the analytic prediction. (c) Tissue PO2 profiles at different times for validation of diffusion (see text for more details). The solid line is the analytic solution of the diffusion equation and dots and dashed line are our model results for DO2 and DO2 /2 respectively.

Fig. 4.
Fig. 4.

Anatomical vessel network extracted from two-photon scans of a rodent somatosensory cortex. (a) Raw image (Media 1, View 1). (b–d) Top view projections of the 3D maps of (b) vessel types: arterioles - red, venules - blue, and capillaries - green, (c) blood velocity, and (d) PO2 inside the vessel network (Media 2).

Fig. 5.
Fig. 5.

The (a) median velocity, (b) blood pressure and (c) partial pressure of oxygen versus vessel diameter compared with experimental data from the literature. The experimental data in panel (a–b) were derived from Ref. [33] and (c) from Ref. [34].

Fig. 6.
Fig. 6.

The 3D rendering (left, Media 3, View 2) and cross-sections (right) of the PO2 distributions in the vessel and tissue.

Fig. 7.
Fig. 7.

The tissue PO2 versus distance from a vessel wall of a few selected (a) arterioles, (b) capillaries and (c) venules. Different colors represent different vessels selected for this test.

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Equations (25)

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

C T t = v · C F v · C B + · ( D O 2 C F ) O C ,
C B = 4 C H b H S O 2 ( C F ) ,
C F t = v · C F ,
C B t = v · C B ,
C B = 4 C H b H S O 2 ( C F ) .
C F , i t V i = J i A i ,
J i = K w ( C F , i C F , i 0 ) α w ,
C F t = · ( D O 2 C F ) O C ,
C i t V i = - j = 1 N v k i , j v i , j C i V i C j V j d i , j ,
1 Δ t V i C i n + 1 + j θ k i , j v i , j d i , j ( V i C i n + 1 V j C j n + 1 ) = 1 Δ t V i C i n j ( 1 θ ) k i , j v i , j d i , j ( V i C i n V j C j n ) ,
A a C F n + 1 = B a C F n ,
A a C B n + 1 = B a C B n .
C B n + 1 = 4 C H b H S O 2 ( C F n + 1 ) ,
C F , i t = K w ( C F , i C F , i 0 ) A i α w V i ,
1 Δ t C F , i n + 1 + θ K w A i a w V i ( C F , i n + 1 C F , i 0 n + 1 ) = 1 Δ t C i n ( 1 θ ) K w A i a w V i ( C F , i n C F , i 0 n ) ,
A f C F n + 1 = B f C F n .
i = 1 4 C i t ϕ i , ϕ j + i = 1 4 C i D O 2 ϕ i , ϕ j = Ω D O 2 C · n ̂ ϕ i d s + O C , ϕ i ,
A d C F n + 1 = B d C F n + R ,
a i , j = < φ i , φ j > + θ < D O 2 φ i , φ j > , b i , j = < φ i , φ j > + ( 1 θ ) < D O 2 φ i , φ j > , r i = k k + 1 ( Ω D O 2 C φ i n ^ d s + < O C , φ i > ) d t .
( A f + A d ) C n + 1 = ( B f + B d ) C n + R .
C Ω = 0 .
R = 128 η l π d 4 ,
( π 4 d 2 υ ) ( C T , i n C T , out ) = V tis OC ,
N O 2 , t i s t = π d l K w w ( N O 2 , ves N O 2 , tis ) ,
P O 2 , x = N O 2 , x α V x ,

Metrics