Abstract

We proposed to measure the metabolic rate of oxygen (MRO2) in small animals in vivo using a multimodal imaging system that combines laser-scanning optical-resolution photoacoustic microscopy (LSOR-PAM) and spectral-domain optical coherence tomography (SD-OCT). We first tested the capability of the multimodal system to measure flow rate in a phantom made of two capillary tubes of different diameters. We then demonstrated the capability of measuring MRO2 by imaging two parallel vessels selected from the ear of a Swiss Webster mouse. The hemoglobin oxygen saturation (sO2) and the vessel diameter were measured by the LSOR-PAM and the blood flow velocity was measured by the SD-OCT, from which blood flow rate and MRO2 were further calculated. The measured blood flow rates in the two vessels agreed with each other.

© 2011 OSA

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2011 (1)

2010 (4)

H. F. Zhang, J. Wang, Q. Wei, T. Liu, S. Jiao, and C. A. Puliafito, “Collecting back-reflected photons in photoacoustic microscopy,” Opt. Express 18(2), 1278–1282 (2010).
[CrossRef] [PubMed]

N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt. 15(2), 021304 (2010).
[CrossRef] [PubMed]

S. Jiao, M. Jiang, J. Hu, A. Fawzi, Q. Zhou, K. K. Shung, C. A. Puliafito, and H. F. Zhang, “Photoacoustic ophthalmoscopy for in vivo retinal imaging,” Opt. Express 18(4), 3967–3972 (2010).
[CrossRef] [PubMed]

2009 (4)

2008 (3)

2007 (7)

M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (2007).
[CrossRef] [PubMed]

H. Wehbe, M. Ruggeri, S. Jiao, G. Gregori, C. A. Puliafito, and W. Zhao, “Automatic retinal blood flow calculation using spectral domain optical coherence tomography,” Opt. Express 15(23), 15193–15206 (2007).
[CrossRef] [PubMed]

A. Laugier and J. Garai, “Derivation of the Ideal Gas Law,” J. Chem. Educ. 84(11), 1832–1833 (2007).
[CrossRef]

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99(18), 184501 (2007).
[CrossRef] [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(4), 041215 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, and L. V. Wang, “In vivo imaging of subcutaneous structures using functional photoacoustic microscopy,” Nat. Protoc. 2(4), 797–804 (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]

2006 (3)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

2003 (1)

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

1997 (1)

V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
[CrossRef] [PubMed]

1996 (1)

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Alder, V. A.

V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
[CrossRef] [PubMed]

Bajraszewski, T.

Beach, J.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Benediktsson, J. A.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

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(4), 041215 (2007).
[CrossRef] [PubMed]

Cepurna, W.

Chan-Ling, T.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Chen, W.

N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

Cringle, S. J.

V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
[CrossRef] [PubMed]

deCharms, R. C.

R. C. deCharms, “Applications of real-time fMRI,” Nat. Rev. Neurosci. 9(9), 720–729 (2008).
[CrossRef] [PubMed]

Dinn, R. B.

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

Dragostinoff, N.

Eysteinsson, T.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Fang, H.

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99(18), 184501 (2007).
[CrossRef] [PubMed]

Fawzi, A.

Garai, J.

A. Laugier and J. Garai, “Derivation of the Ideal Gas Law,” J. Chem. Educ. 84(11), 1832–1833 (2007).
[CrossRef]

Giuliano, E.

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

Gnessin, H.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Götzinger, E.

Gregori, G.

Halldorsson, G. H.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Hardarson, S. H.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Harris, A.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

Hitzenberger, C. K.

Hu, J.

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(4), 041215 (2007).
[CrossRef] [PubMed]

Itin, A.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Izatt, J. A.

Y. K. Tao, K. M. Kennedy, and J. A. Izatt, “Velocity-resolved 3D retinal microvessel imaging using single-pass flow imaging spectral domain optical coherence tomography,” Opt. Express 17(5), 4177–4188 (2009).
[CrossRef] [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(4), 041215 (2007).
[CrossRef] [PubMed]

Jensen, P. K.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Jiang, M.

Jiao, S.

Jiao, S. L.

Johnson, E.

Kagemann, L.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

Kang Derwent, J. J.

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

Karlsson, R. A.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Kennedy, K. M.

Keshet, E.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Kowalczyk, A.

Laugier, A.

A. Laugier and J. Garai, “Derivation of the Ideal Gas Law,” J. Chem. Educ. 84(11), 1832–1833 (2007).
[CrossRef]

Leitgeb, R. A.

Linsenmeier, R. A.

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

Liu, T.

Maslov, K.

E. W. Stein, K. Maslov, and L. V. Wang, “Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy,” J. Biomed. Opt. 14(2), 020502 (2009).
[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]

M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (2007).
[CrossRef] [PubMed]

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99(18), 184501 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, and L. V. Wang, “In vivo imaging of subcutaneous structures using functional photoacoustic microscopy,” Nat. Protoc. 2(4), 797–804 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Morrison, J.

Narfström, K.

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

Padnick-Silver, L.

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

Park, J. K.

N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

Pe’er, J.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

Pircher, M.

Puliafito, C. A.

Rechtman, E.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

Ruggeri, M.

Schmetterer, L.

Shen, T.

Shung, K. K.

Sivaramakrishnan, M.

M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (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]

Stefánsson, E.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

Stein, E. W.

E. W. Stein, K. Maslov, and L. V. Wang, “Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy,” J. Biomed. Opt. 14(2), 020502 (2009).
[CrossRef] [PubMed]

Stoica, G.

M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (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]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Stone, J.

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
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V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
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Szkulmowski, M.

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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(4), 041215 (2007).
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Thorsteinsson, A.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
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J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt. 15(2), 021304 (2010).
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E. W. Stein, K. Maslov, and L. V. Wang, “Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy,” J. Biomed. Opt. 14(2), 020502 (2009).
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M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (2007).
[CrossRef] [PubMed]

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99(18), 184501 (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]

H. F. Zhang, K. Maslov, and L. V. Wang, “In vivo imaging of subcutaneous structures using functional photoacoustic microscopy,” Nat. Protoc. 2(4), 797–804 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
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M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (2007).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, and L. V. Wang, “In vivo imaging of subcutaneous structures using functional photoacoustic microscopy,” Nat. Protoc. 2(4), 797–804 (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]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

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N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

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N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

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Zhi, Z.

Zhou, Q.

Zhu, X. H.

N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

Zoega, G. M.

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (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]

Biomed. Opt. Express (1)

Clin. Exp. Pharmacol. Physiol. (1)

V. A. Alder, E. N. Su, D. Y. Yu, S. J. Cringle, and P. K. Yu, “Diabetic retinopathy: early functional changes,” Clin. Exp. Pharmacol. Physiol. 24(9-10), 785–788 (1997).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci. (3)

J. Stone, T. Chan-Ling, J. Pe’er, A. Itin, H. Gnessin, and E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest. Ophthalmol. Vis. Sci. 37(2), 290–299 (1996).
[PubMed]

S. H. Hardarson, A. Harris, R. A. Karlsson, G. H. Halldorsson, L. Kagemann, E. Rechtman, G. M. Zoega, T. Eysteinsson, J. A. Benediktsson, A. Thorsteinsson, P. K. Jensen, J. Beach, and E. Stefánsson, “Automatic retinal oximetry,” Invest. Ophthalmol. Vis. Sci. 47(11), 5011–5016 (2006).
[CrossRef] [PubMed]

L. Padnick-Silver, J. J. Kang Derwent, E. Giuliano, K. Narfström, and R. A. Linsenmeier, “Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration,” Invest. Ophthalmol. Vis. Sci. 47(8), 3683–3689 (2006).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

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(4), 041215 (2007).
[CrossRef] [PubMed]

J. Yao and L. V. Wang, “Transverse flow imaging based on photoacoustic Doppler bandwidth broadening,” J. Biomed. Opt. 15(2), 021304 (2010).
[CrossRef] [PubMed]

E. W. Stein, K. Maslov, and L. V. Wang, “Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy,” J. Biomed. Opt. 14(2), 020502 (2009).
[CrossRef] [PubMed]

J. Chem. Educ. (1)

A. Laugier and J. Garai, “Derivation of the Ideal Gas Law,” J. Chem. Educ. 84(11), 1832–1833 (2007).
[CrossRef]

Nat. Biotechnol. (1)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Nat. Protoc. (1)

H. F. Zhang, K. Maslov, and L. V. Wang, “In vivo imaging of subcutaneous structures using functional photoacoustic microscopy,” Nat. Protoc. 2(4), 797–804 (2007).
[CrossRef] [PubMed]

Nat. Rev. Neurosci. (1)

R. C. deCharms, “Applications of real-time fMRI,” Nat. Rev. Neurosci. 9(9), 720–729 (2008).
[CrossRef] [PubMed]

Neuroimage (1)

N. Zhang, X. H. Zhu, Y. Zhang, J. K. Park, and W. Chen, “High-resolution fMRI mapping of ocular dominance layers in cat lateral geniculate nucleus,” Neuroimage 50(4), 1456–1463 (2010).
[CrossRef] [PubMed]

Ophthalmic Surg. Lasers Imaging (1)

A. Harris, R. B. Dinn, L. Kagemann, and E. Rechtman, “A review of methods for human retinal oximetry,” Ophthalmic Surg. Lasers Imaging 34(2), 152–164 (2003).
[PubMed]

Opt. Express (5)

Opt. Lett. (3)

Phys. Med. Biol. (1)

M. Sivaramakrishnan, K. Maslov, H. F. Zhang, G. Stoica, and L. V. Wang, “Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels,” Phys. Med. Biol. 52(5), 1349–1361 (2007).
[CrossRef] [PubMed]

Phys. Rev. Lett. (1)

H. Fang, K. Maslov, and L. V. Wang, “Photoacoustic Doppler effect from flowing small light-absorbing particles,” Phys. Rev. Lett. 99(18), 184501 (2007).
[CrossRef] [PubMed]

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Figures (4)

Fig. 1
Fig. 1

Schematics of the combined LSOR-PAM and SD-OCT. PD: photodiode; 2 × 2: 2 × 2 single-mode optical fiber coupler; HM: hot mirror; GM: 2D galvanometer; OBJ: objective lens; AMP: amplifier; UT: ultrasonic transducer; WT: water tank; SLED: superluminescent emitting diode; Ref: OCT reference arm.

Fig. 2
Fig. 2

Flow phantom imaging results. (a) LSOR-PAM image of the tubes (mean intensity projection); (b) PA amplitude profile along the dashed line in panel a; (c) flow velocity measured by Doppler OCT at the cross section marked in panel a; (d) the flow velocity profile at locations marked by the two dash lines in panel c. Bar: 250 µm.

Fig. 3
Fig. 3

Multimodal anatomic imaging of a mouse ear. (a) LSOR-PAM projection image of an artery-vein pair; (b) LSOR-PAM B-Scan image acquired at the 570-nm optical wavelength at the location marked by the dashed line in panel a; (c) OCT B-Scan image acquired at the same location. A: Artery; V: Vein; Ep, epidermis; De, dermis; Ca, cartilaginous backbone; Bar: 100 µm.

Fig. 4
Fig. 4

Multimodal functional imaging. (a) Imaged sO2 using LSOR-PAM; (b) Imaged blood flow velocity using SD-OCT. Bar: 100 µm.

Equations (3)

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MRO 2 = 60 4 W O2 W HbO2 [ [ HbT ¯ ] sO 2a ( π 4 d a 2 ) v ¯ a [ HbT ¯ ] sO 2v ( π 4 d v 2 ) v ¯ v ] = 60 π W O2 W HbO2 [ HbT ¯ ] ( sO 2a d a 2 v ¯ a sO 2v d v 2 v ¯ v ) ,
v ¯ = f sample λ 0 Δ ϕ 4 π n cos θ
V = n g R T / P

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