Abstract

In vivo surface imaging of fluorescently labeled vasculature has become a widely used tool for functional brain imaging studies. Techniques such as phosphorescence quenching for oxygen tension measurements and indocyanine green fluorescence for vessel perfusion monitoring rely on surface measurements of vascular fluorescence. However, the depth dependence of the measured fluorescence signals has not been modeled in great detail. In this paper, we investigate the depth dependence of the measured signals using a three-dimensional Monte Carlo model combined with high resolution vascular anatomy. We found that a bulk-vascularization assumption to modeling the depth dependence of the signal does not provide an accurate picture of penetration depth of the collected fluorescence signal in most cases. Instead the physical distribution of microvasculature, the degree of absorption difference between extravascular and intravascular space, and the overall difference in absorption at the excitation and emission wavelengths must be taken into account to determine the depth penetration of the fluorescence signal. Additionally, we found that using targeted illumination can provide for superior surface vessel sensitivity over wide-field illumination, with small area detection offering an even greater amount of sensitivity to surface vasculature. Depth sensitivity can be enhanced by either increasing the detector area or increasing the illumination area. Finally, we see that excitation wavelength and vessel size can affect intra-vessel sampling distribution, as well as the amount of signal that originates from inside the vessel under targeted illumination conditions.

© 2011 OSA

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    [CrossRef] [PubMed]
  7. M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  24. A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
    [CrossRef] [PubMed]
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    [CrossRef]

2011 (1)

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

2010 (3)

A. Ponticorvo and A. K. Dunn, “Simultaneous imaging of oxygen tension and blood flow in animals using a digital micromirror device,” Opt. Express18, 8160–8170 (2010).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Opt. Express1, 310–317 (2010).
[CrossRef]

2009 (1)

2007 (1)

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotech.18, 17–25 (2007).
[CrossRef] [PubMed]

2005 (2)

2004 (1)

2003 (2)

A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

V. Soloviev, D. Wilson, and S. Vinogradov, “Phosphorescence lifetime imaging in turbid media: the forward problem,” Appl. Opt.42, 113–123 (2003).
[CrossRef] [PubMed]

2002 (2)

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

A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

2001 (3)

S. A. Vinogradov, M. A. Fernandez-searra, B. W. Dugan, and D. A. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum.72, 3396–3406 (2001).
[CrossRef]

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

C. K. Hayakawa, J. Spanier, F. Bevilacqua, A. K. Dunn, J. S. You, B. J. Tromberg, and V. Venugopalan, “Perturbation Monte Carlo methods to solve inverse photon migration problems in heterogeneous tissues,” Opt. Lett.26, 1335–1337 (2001).
[CrossRef]

1999 (2)

F. Bevilacqua, D. Piguet, P. Marquet, J. D. Gross, B. J. Tromberg, and C. Depeursinge, “In vivo local determination of tissue optical properties: applications to human brain,” Appl. Opt.38, 4939–4950 (1999).
[CrossRef]

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

1998 (2)

1997 (1)

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

1996 (1)

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

1992 (1)

S. Arridge, M. Cope, and D. Delpy, “The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis,” Phys. Med. Biol.37, 1531–1560 (1992).
[CrossRef] [PubMed]

1978 (1)

L. Cohen and B. Salzberg, “Optical measurement of membrane potential,” Rev. Physiol. Biochem. Pharmacol.83, 36–77 (1978)..

1976 (1)

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
[PubMed]

Alianelli, L.

Arridge, S.

S. Arridge, M. Cope, and D. Delpy, “The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis,” Phys. Med. Biol.37, 1531–1560 (1992).
[CrossRef] [PubMed]

Bacskai, B.

Barton, J.

Beck, J.

A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

Bennett, J.

Berlin, D.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Bevilacqua, F.

Blumetti, C.

Boas, D.

Boas, D. A.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

M. A. Yaseen, V. J. Srinivasan, S. Sakadzić, W. Wu, S. Ruvinskaya, S. A. Vinogradov, and D. A. Boas, “Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy,” Opt. Express17, 22341–22350 (2009).
[CrossRef]

Boas, D.A.

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

Chan, E.

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Chernomordik, V.

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Chowdhury, S.

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Opt. Express1, 310–317 (2010).
[CrossRef]

Cohen, L.

L. Cohen and B. Salzberg, “Optical measurement of membrane potential,” Rev. Physiol. Biochem. Pharmacol.83, 36–77 (1978)..

Contini, D.

Cope, M.

S. Arridge, M. Cope, and D. Delpy, “The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis,” Phys. Med. Biol.37, 1531–1560 (1992).
[CrossRef] [PubMed]

Dale, A.M.

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

Delpy, D.

S. Arridge, M. Cope, and D. Delpy, “The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis,” Phys. Med. Biol.37, 1531–1560 (1992).
[CrossRef] [PubMed]

Depeursinge, C.

Devor, A.

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

Do, K.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Dragulescu-Andrasi, A.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotech.18, 17–25 (2007).
[CrossRef] [PubMed]

Ducros, M.

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Dugan, B. W.

S. A. Vinogradov, M. A. Fernandez-searra, B. W. Dugan, and D. A. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum.72, 3396–3406 (2001).
[CrossRef]

Dunn, A.

Dunn, A. K.

Dunphy, I.

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

Fernandez-searra, M. A.

S. A. Vinogradov, M. A. Fernandez-searra, B. W. Dugan, and D. A. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum.72, 3396–3406 (2001).
[CrossRef]

Friebel, M.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Fujimoto, J. G.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

Gandjbakhche, A.

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Gannot, I.

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Gerlach, R.

A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

Gorczynska, I.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

Gross, J. D.

Grosul, P.

Hahn, A.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Hattery, D.

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Hayakawa, C. K.

Ismaelli, A.

Johnson, P. C.

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

Kehlet Barton, J.

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Kumar, A.

Kuroki, A.

Kwant, G.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
[PubMed]

Landsman, M. L.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
[PubMed]

Loew, M.

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Marquet, P.

Martelli, F.

Medizin, L.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Milner, T.

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Mook, G. A.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
[PubMed]

Mu, G.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

Nelson, J.

J. Barton, T. Pfefer, A. Welch, D. Smithies, J. Nelson, and M. Van Gemert, “Optical Monte Carlo modeling of a true portwine stain anatomy,” Opt. Express2, 391–396 (1998).
[CrossRef] [PubMed]

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Pfefer, T.

J. Barton, T. Pfefer, A. Welch, D. Smithies, J. Nelson, and M. Van Gemert, “Optical Monte Carlo modeling of a true portwine stain anatomy,” Opt. Express2, 391–396 (1998).
[CrossRef] [PubMed]

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

Piguet, D.

Ponticorvo, A.

Raabe, A.

A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

Radhakrishnan, H.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

Rao, J.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotech.18, 17–25 (2007).
[CrossRef] [PubMed]

Robles, F. E.

F. E. Robles, S. Chowdhury, and A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Opt. Express1, 310–317 (2010).
[CrossRef]

Ruvinskaya, S.

Sakadzic, S.

Sakadžic, S.

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

Salzberg, B.

L. Cohen and B. Salzberg, “Optical measurement of membrane potential,” Rev. Physiol. Biochem. Pharmacol.83, 36–77 (1978)..

Sassaroli, A.

Schober, R.

A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

Schulze, P. C.

A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

Schwarzmaier, H. J.

A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

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A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

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[CrossRef]

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[CrossRef]

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[CrossRef]

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[CrossRef] [PubMed]

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A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

Universita, F.

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

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[CrossRef]

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[CrossRef]

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S. A. Vinogradov, M. A. Fernandez-searra, B. W. Dugan, and D. A. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum.72, 3396–3406 (2001).
[CrossRef]

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M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

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[CrossRef]

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J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotech.18, 17–25 (2007).
[CrossRef] [PubMed]

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A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

Yaroslavsky, I. V.

A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

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M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

M. A. Yaseen, V. J. Srinivasan, S. Sakadzić, W. Wu, S. Ruvinskaya, S. A. Vinogradov, and D. A. Boas, “Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy,” Opt. Express17, 22341–22350 (2009).
[CrossRef]

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[PubMed]

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A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

Am. J. Physiol. Heart. Ciculatory Physiol. (1)

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

Anal. Biochem. (1)

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

Appl. Opt. (5)

Curr. Opin. Biotech. (1)

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotech.18, 17–25 (2007).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

T. Pfefer, J. Kehlet Barton, E. Chan, M. Ducros, B. Sorg, T. Milner, J. Nelson, and A.J. Welch, “A three-dimensional modular adaptable grid numerical model for light propagation during laser irradiation of skin tissue,” IEEE J. Sel. Top. Quantum Electron.2, 934–942 (1996).
[CrossRef]

J. Appl. Physiol. (1)

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green.” J. Appl. Physiol.40, 575–583 (1976).
[PubMed]

J. Biomed. Opt. (2)

P. Tian, A. Devor, S. Sakadžić, A.M. Dale, and D.A. Boas, “Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain,” J. Biomed. Opt.16, 016006 (2011).
[CrossRef] [PubMed]

M. Friebel, K. Do, A. Hahn, G. Mu, D. Berlin, L. Medizin, and F. Universita, “Optical properties of circulating human blood in the wavelength range 400–2500 nm,” J. Biomed. Opt.4, 36–46 (1999).
[CrossRef]

J. Cerebr. Blood Flow Metabol. (1)

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cerebr. Blood Flow Metabol.31, 1051–1063 (2010).
[CrossRef]

J. Opt. Soc. Am. A. (1)

D. Hattery, V. Chernomordik, M. Loew, I. Gannot, and A. Gandjbakhche, “Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid medium such as tissue,” J. Opt. Soc. Am. A.18, 1523–1530 (2001).
[CrossRef]

Neurosurgery (1)

A. Raabe, J. Beck, R. Gerlach, M. Zimmerman, and V. Seirfert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52, 132–139 (2003).

Opt. Express (4)

Opt. Lett. (2)

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A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47, 2059–2073 (2002).
[CrossRef] [PubMed]

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L. Cohen and B. Salzberg, “Optical measurement of membrane potential,” Rev. Physiol. Biochem. Pharmacol.83, 36–77 (1978)..

Rev. Sci. Instrum. (1)

S. A. Vinogradov, M. A. Fernandez-searra, B. W. Dugan, and D. A. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum.72, 3396–3406 (2001).
[CrossRef]

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Figures (6)

Fig. 1
Fig. 1

(a) 500μm by 500μm by 400μm microvasculature image stack acquired in a CD-1 mouse brain by two-photon scanning microscopy. (b) Single vessel geometry. Red area represents vessel, blue area represents bulk-vascularized space.

Fig. 2
Fig. 2

f(z) and F(z) of collected signal using homogeneous, bulk-vascularized tissue assumption and comparison to the camera illumination and detection scheme using (a–b) 415 nm, (c–d) 524 nm and (e–f) 800 nm excitation. Note that the x-axis in (a–b) is different from (c–f).

Fig. 3
Fig. 3

f(z) and F(z) of collected signal using the camera illumination and detection scheme at different detector positions using (a–b) 415 nm, (c–d) 524 nm and (e–f) 800 nm excitation. Note that the x-axis in (a–b) is different from (c–f).

Fig. 4
Fig. 4

(a) Depth-dependent, f(z), and (b) depth-integrated, F(z), signal distribution for the targeted illumination and detection scheme; (c) and (d) are f(z) and F(z) using the camera scheme, and (e) and (f) are f(z) and F(z) using the confocal scheme.

Fig. 5
Fig. 5

3D rendering of fluorescence signal distribution using the camera illumination and detection scheme for (a) 415 nm, (b) 524 nm and (c) 800 nm excitation. Note that the scale bar in (c) is different from (a) and (b).

Fig. 6
Fig. 6

100μm single vessel geometry with (a) 415 nm targeted illumination and (b) 524 nm targeted illumination. Color represents the log of the signal distribution in each 1μm × 1μm pixel. (c) Amount of detected signal originating from inside the vessel as a function of vessel diameter.

Tables (1)

Tables Icon

Table 1 Optical properties for microvasculature geometry

Equations (3)

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I d ( x , y , z ) = j e i μ a i l i j
f ( z ) = I d ( x , y , z ) d x d y I d ( x , y , z ) d x d y d z
F ( z ) = 0 z f ( z ) d z

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