Abstract

We present a novel optical coherence tomography (OCT)-based technique for rapid volumetric imaging of red blood cell (RBC) flux in capillary networks. Previously we reported that OCT can capture individual RBC passage within a capillary, where the OCT intensity signal at a voxel fluctuates when an RBC passes the voxel. Based on this finding, we defined a metric of statistical intensity variation (SIV) and validated that the mean SIV is proportional to the RBC flux [RBC/s] through simulations and measurements. From rapidly scanned volume data, we used Hessian matrix analysis to vectorize a segment path of each capillary and estimate its flux from the mean of the SIVs gathered along the path. Repeating this process led to a 3D flux map of the capillary network. The present technique enabled us to trace the RBC flux changes over hundreds of capillaries with a temporal resolution of ~1 s during functional activation.

© 2014 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2013 (9)

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab.33(11), 1707–1710 (2013).
[CrossRef] [PubMed]

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt.18(8), 086004 (2013).
[CrossRef] [PubMed]

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

X. Liu, Y. Huang, J. C. Ramella-Roman, S. A. Mathews, and J. U. Kang, “Quantitative transverse flow measurement using optical coherence tomography speckle decorrelation analysis,” Opt. Lett.38(5), 805–807 (2013).
[CrossRef] [PubMed]

H. Radhakrishnan and V. J. Srinivasan, “Compartment-resolved imaging of cortical functional hyperemia with OCT angiography,” Biomed. Opt. Express4(8), 1255–1268 (2013).
[CrossRef] [PubMed]

A. Bouwens, D. Szlag, M. Szkulmowski, T. Bolmont, M. Wojtkowski, and T. Lasser, “Quantitative lateral and axial flow imaging with optical coherence microscopy and tomography,” Opt. Express21(15), 17711–17729 (2013).
[CrossRef] [PubMed]

J. Tokayer, Y. Jia, A.-H. Dhalla, and D. Huang, “Blood flow velocity quantification using split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Biomed. Opt. Express4(10), 1909–1924 (2013).
[CrossRef] [PubMed]

2012 (3)

2011 (3)

N. Mohan and B. Vakoc, “Principal-component-analysis-based estimation of blood flow velocities using optical coherence tomography intensity signals,” Opt. Lett.36(11), 2068–2070 (2011).
[CrossRef] [PubMed]

J. Tokayer and D. Huang, “Effect of blood vessel diameter on relative blood flow estimates in Doppler optical coherence tomography algorithms,” Proc. SPIE 7889, Optical Coherence Tomography and Coherence Domain Optical Methods in BiomedicineXV, 78892X (2011).
[CrossRef]

M. Tomita, Y. Tomita, M. Unekawa, H. Toriumi, and N. Suzuki, “Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries,” Neuroimage56(3), 1001–1010 (2011).
[CrossRef] [PubMed]

2010 (2)

2009 (1)

2008 (2)

A. Mariampillai, B. A. Standish, E. H. Moriyama, M. Khurana, N. R. Munce, M. K. K. Leung, J. Jiang, A. Cable, B. C. Wilson, I. A. Vitkin, and V. X. D. Yang, “Speckle variance detection of microvasculature using swept-source optical coherence tomography,” Opt. Lett.33(13), 1530–1532 (2008).
[CrossRef] [PubMed]

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

2005 (1)

2000 (1)

1998 (2)

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

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. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

1994 (1)

A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
[CrossRef] [PubMed]

1976 (1)

J. Ohtsubo and T. Asakura, “Velocity measurement of a diffuse object by using time-varying speckles,” Opt. Quantum Electron.8(6), 523–529 (1976).
[CrossRef]

An, L.

Asakura, T.

J. Ohtsubo and T. Asakura, “Velocity measurement of a diffuse object by using time-varying speckles,” Opt. Quantum Electron.8(6), 523–529 (1976).
[CrossRef]

Atsumi, H.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

Ayata, C.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

Barry, S.

Belluscio, L.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Boas, D. A.

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab.33(11), 1707–1710 (2013).
[CrossRef] [PubMed]

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, “Dynamic light scattering optical coherence tomography,” Opt. Express20(20), 22262–22277 (2012).
[CrossRef] [PubMed]

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett.35(1), 43–45 (2010).
[CrossRef] [PubMed]

Bolmont, T.

Bouwens, A.

Cable, A.

Cable, A. E.

Chen, Z.

Climov, M.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

Daneshmand, A.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

de Boer, J. F.

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. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Dhalla, A.-H.

Dirnagl, U.

A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
[CrossRef] [PubMed]

Dunn, A. K.

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

Einhäupl, K.

A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
[CrossRef] [PubMed]

Gerig, G.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[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. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Huang, D.

J. Tokayer, Y. Jia, A.-H. Dhalla, and D. Huang, “Blood flow velocity quantification using split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Biomed. Opt. Express4(10), 1909–1924 (2013).
[CrossRef] [PubMed]

J. Tokayer and D. Huang, “Effect of blood vessel diameter on relative blood flow estimates in Doppler optical coherence tomography algorithms,” Proc. SPIE 7889, Optical Coherence Tomography and Coherence Domain Optical Methods in BiomedicineXV, 78892X (2011).
[CrossRef]

Huang, Y.

Hutchinson, E.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Jia, Y.

Jiang, J.

Jiang, J. Y.

Jones, T. A.

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

Kalkman, J.

N. Weiss, T. G. van Leeuwen, and J. Kalkman, “Localized measurement of longitudinal and transverse flow velocities in colloidal suspensions using optical coherence tomography,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.88(4), 042312 (2013).
[CrossRef] [PubMed]

Kang, J. U.

Kazmi, S. M. S.

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

Khurana, M.

Kikinis, R.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[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. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Koller, T.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

Koretsky, A. P.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Lasser, T.

Lee, J.

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab.33(11), 1707–1710 (2013).
[CrossRef] [PubMed]

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab.33(6), 819–825 (2013).
[CrossRef] [PubMed]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, “Dynamic light scattering optical coherence tomography,” Opt. Express20(20), 22262–22277 (2012).
[CrossRef] [PubMed]

Lesage, F.

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab.33(11), 1707–1710 (2013).
[CrossRef] [PubMed]

Leung, M. K. K.

Lin, A. J.

Lindauer, U.

A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
[CrossRef] [PubMed]

Liu, G.

Liu, X.

Lo, E. H.

Mandeville, E. T.

Mariampillai, A.

Mathews, S. A.

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. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Mohan, N.

Moriyama, E. H.

Munce, N. R.

Nakajima, S.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

Nelson, J. S.

Ohtsubo, J.

J. Ohtsubo and T. Asakura, “Velocity measurement of a diffuse object by using time-varying speckles,” Opt. Quantum Electron.8(6), 523–529 (1976).
[CrossRef]

Parthasarthy, A. B.

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

Qin, J.

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt.18(8), 086004 (2013).
[CrossRef] [PubMed]

Radhakrishnan, H.

Ramella-Roman, J. C.

Russell, J. T.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Sato, Y.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

Saxer, C.

Schram, V.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Serov, A.

Shiraga, N.

Y. Sato, S. Nakajima, N. Shiraga, H. Atsumi, S. Yoshida, T. Koller, G. Gerig, and R. Kikinis, “Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images,” Med. Image Anal.2(2), 143–168 (1998).
[CrossRef] [PubMed]

Silva, A. C.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Song, N. E.

S. M. S. Kazmi, A. B. Parthasarthy, N. E. Song, T. A. Jones, and A. K. Dunn, “Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging,” J. Cereb. Blood Flow Metab.33(6), 798–808 (2013).
[CrossRef] [PubMed]

Srinivasan, V. J.

Standish, B. A.

Stefanovic, B.

B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
[CrossRef] [PubMed]

Steinacher, B.

Suzuki, N.

M. Tomita, Y. Tomita, M. Unekawa, H. Toriumi, and N. Suzuki, “Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries,” Neuroimage56(3), 1001–1010 (2011).
[CrossRef] [PubMed]

Szkulmowski, M.

Szlag, D.

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M. Tomita, Y. Tomita, M. Unekawa, H. Toriumi, and N. Suzuki, “Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries,” Neuroimage56(3), 1001–1010 (2011).
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Unekawa, M.

M. Tomita, Y. Tomita, M. Unekawa, H. Toriumi, and N. Suzuki, “Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries,” Neuroimage56(3), 1001–1010 (2011).
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A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
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Biomed. Opt. Express (4)

Circ. Res. (1)

A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt.18(8), 086004 (2013).
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B. Stefanovic, E. Hutchinson, V. Yakovleva, V. Schram, J. T. Russell, L. Belluscio, A. P. Koretsky, and A. C. Silva, “Functional reactivity of cerebral capillaries,” J. Cereb. Blood Flow Metab.28(5), 961–972 (2008).
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J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab.33(11), 1707–1710 (2013).
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Opt. Express (4)

Opt. Lett. (6)

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Phys. Rev. E Stat. Nonlin. Soft Matter Phys. (1)

N. Weiss, T. G. van Leeuwen, and J. Kalkman, “Localized measurement of longitudinal and transverse flow velocities in colloidal suspensions using optical coherence tomography,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.88(4), 042312 (2013).
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Proc. Natl. Acad. Sci. U.S.A. (1)

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Proc. SPIE 7889, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine (1)

J. Tokayer and D. Huang, “Effect of blood vessel diameter on relative blood flow estimates in Doppler optical coherence tomography algorithms,” Proc. SPIE 7889, Optical Coherence Tomography and Coherence Domain Optical Methods in BiomedicineXV, 78892X (2011).
[CrossRef]

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Figures (8)

Fig. 1
Fig. 1

(A) Mie scattering calculation. The reduced scattering coefficient (μs’) is presented as a function of the scatterer diameter. The black arrow indicates the diameter of RBCs (~6.5 μm). The refractive index of medium, the refractive index of scatterers and the volume fraction of scatterers in medium were assumed to be 1.33, 1.57 and 0.05, respectively. (B) Cross-sectional OCT angiogram of the rodent cerebral cortex. Scale bar, 100 μm. (C) RBC passage captured in OCT intensity time courses. Each line presents the time course of relative changes in the OCT intensity at the center of each capillary indicted by the color circles in (B). Each peak (overlaid black pieces) represents single RBC passage. The peaks were localized with a spatial extent consistent with RBC size and peaks moved through a capillary when the scanning line was aligned to the capillary (data shown in [12]). Reprinted from the authors’ previous publication [12]. (D) A schematic of the dynamic OCT imaging sequence to capture individual RBC passage as in (C). (E) A schematic of the scanning sequence for SIV imaging. Only two B-scans were repeated for each Y-position, and SIV values will be gathered along the capillary segment path.

Fig. 2
Fig. 2

Numerical simulation and experimental validation of the SIV relation to the RBC flux. (A) Examples of the synthesized time courses for various RBC speeds and densities. (B) Numerical simulation result. (C) Experiment result. 22 capillaries were analyzed. Data are presented as mean ± SD.

Fig. 3
Fig. 3

A diagram of data processing.

Fig. 4
Fig. 4

Volumetric SIV imaging. (A) CCD image of the brain cortex through the cranial window. (B) En face maximum intensity projection (MIP) of the OCT angiogram. Ten volumes were averaged. (C) En face MIP of the SIV volume data.

Fig. 5
Fig. 5

Vectorization of capillary segments. (A) En face MIP of the tubeness. (B) For an example of vectorization indicated by the red curve in (A), the tubeness and SIV are plotted versus the path length. This segment consisted of 75 points and its length was 169 μm. The tubeness exhibited relatively smaller values at the branch while the SIV did not. (C) For all 75 points of the exemplary segment, slices of the SIV map were obtained over the cross-sectional planes normal to the capillary direction and then averaged (left). The diameter of the capillary segment can be estimated from the mean cross-section, where the mean SIV as a function of the distance from the center (i.e., radius) was fit with a Gaussian function (right). The diameter of this segment was 6.3 μm. Scale bar, 5 μm. (D) En face and inclined views of the vectorized capillary segments with random color (n = 178). The bar graph in the right side presents the histogram of the diameter.

Fig. 6
Fig. 6

3D flux map of the capillary network. The bar graph in the right side presents the RBC flux histogram of the identified 178 capillaries.

Fig. 7
Fig. 7

Scanning and stimulation protocols for SIV imaging of capillary network flux response to functional activation. For each sub-volume, ten runs of electrical stimulation (3 Hz for 4 s in the middle of a 22-s resting period) were applied to the contralateral forepaw while SIV imaging was repeated 220 volumes.

Fig. 8
Fig. 8

SIV imaging of capillary network flux responses. (A) A CCD image of the rodent somatosensory cortex. (B) IOS imaging of the hemodynamic response of the cortical surface. As we used 570-nm illumination, a decrease in the CCD intensity (red color) represents an increase in the blood volume. Scale bar, 500 μm. (C) En face MIP of SIV at T = 0 s. A temporal series of 20 SIV volumes like this were obtained. We located the OCT focus at a slightly deeper area to include the capillaries near the neurons of the somatosensory cortex. Scale bar, 100 μm. (D) Capillary network flux map at T = 0 s. A temporal series of 20 flux maps like this were obtained. (E) Time courses of RBC flux changes of the 196 capillaries during functional activation. A change in the mean flux averaged across capillaries is presented by the thick black curve. The peak change was 2.2% and highly significant (p < 10−8). The black bar in the bottom indicates the duration of forepaw stimulation (3 Hz for T = 0 – 4 s).

Equations (2)

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SIV(z,x,y) E[ {I(z,x, t 2 ;y)I(z,x, t 1 ;y)} 2 ] E[ 1 2 { I 2 (z,x, t 2 ;y)+ I 2 (z,x, t 1 ;y)}]
T={ | λ 3 | ( λ 2 λ 3 ) γ 23 ( 1+ λ 1 | λ 2 | ) γ 12 , λ 3 < λ 2 < λ 1 0 | λ 3 | ( λ 2 λ 3 ) γ 23 ( 1α λ 1 | λ 2 | ) γ 12 , λ 3 < λ 2 <0< λ 1 < | λ 2 | α 0,otherwise.

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