Abstract

To date, two main categories of OCT techniques have been described for imaging hemodynamics: Doppler OCT and OCT angiography. Doppler OCT can measure axial velocity profiles and flow in arteries and veins, while OCT angiography can determine vascular morphology, tone, and presence or absence of red blood cell (RBC) perfusion. However, neither method can quantify RBC velocity in capillaries, where RBC flow is typically transverse to the probe beam and single-file. Here, we describe new methods that potentially address these limitations. Firstly, we describe a complex-valued OCT signal in terms of a static scattering component, dynamic scattering component, and noise. Secondly, we propose that the time scale of random fluctuations in the dynamic scattering component are related to red blood cell velocity. Analysis was performed along the slow axis of repeated B-scans to parallelize measurements. We correlate our purported velocity measurements against two-photon microscopy measurements of RBC velocity, and investigate changes during hypercapnia. Finally, we image the ischemic stroke penumbra during distal middle cerebral artery occlusion (dMCAO), where OCT velocimetry methods provide additional insight that is not afforded by either Doppler OCT or OCT angiography.

© 2012 OSA

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2011 (1)

S. Yousefi, Z. Zhi, and R. Wang, “Eigendecomposition-based clutter filtering technique for optical micro-angiography,” IEEE Trans. Biomed. Eng.58(8), 2316–2323 (2011).
[CrossRef] [PubMed]

2010 (7)

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

J. Kalkman, R. Sprik, and T. G. van Leeuwen, “Path-length-resolved diffusive particle dynamics in spectral-domain optical coherence tomography,” Phys. Rev. Lett.105(19), 198302 (2010).
[CrossRef] [PubMed]

Y. Wang and R. Wang, “Autocorrelation optical coherence tomography for mapping transverse particle-flow velocity,” Opt. Lett.35(21), 3538–3540 (2010).
[CrossRef] [PubMed]

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[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]

A. Mariampillai, M. K. Leung, M. Jarvi, B. A. Standish, K. Lee, B. C. Wilson, A. Vitkin, and V. X. Yang, “Optimized speckle variance OCT imaging of microvasculature,” Opt. Lett.35(8), 1257–1259 (2010).
[CrossRef] [PubMed]

V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Quantitative cerebral blood flow with optical coherence tomography,” Opt. Express18(3), 2477–2494 (2010).
[CrossRef] [PubMed]

2009 (4)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
[CrossRef] [PubMed]

T. Schmoll, C. Kolbitsch, and R. A. Leitgeb, “Ultra-high-speed volumetric tomography of human retinal blood flow,” Opt. Express17(5), 4166–4176 (2009).
[CrossRef] [PubMed]

J. Fingler, R. J. Zawadzki, J. S. Werner, D. Schwartz, and S. E. Fraser, “Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique,” Opt. Express17(24), 22190–22200 (2009).
[CrossRef] [PubMed]

2008 (2)

2007 (4)

2006 (3)

2005 (1)

H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation12(1), 5–15 (2005).
[CrossRef] [PubMed]

2004 (1)

2003 (4)

2002 (1)

2001 (1)

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab.21(3), 195–201 (2001).
[CrossRef] [PubMed]

1999 (1)

1998 (1)

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]

1997 (3)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1989 (1)

U. Dirnagl, B. Kaplan, M. Jacewicz, and W. Pulsinelli, “Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model,” J. Cereb. Blood Flow Metab.9(5), 589–596 (1989).
[CrossRef] [PubMed]

1986 (1)

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,” Nature324(6095), 361–364 (1986).
[CrossRef] [PubMed]

1981 (1)

1979 (1)

H. L. Goldsmith and J. C. Marlow, “Flow behavior of erythrocytes. 2. Particle motions in concentrated suspensions of ghost cells,” J. Colloid Interface Sci.71(2), 383–407 (1979).
[CrossRef]

1978 (1)

T. M. Fischer, M. Stöhr-Lissen, and H. Schmid-Schönbein, “The red cell as a fluid droplet: tank tread-like motion of the human erythrocyte membrane in shear flow,” Science202(4370), 894–896 (1978).
[CrossRef] [PubMed]

Akassoglou, K.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Barman, I.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Barry, S.

Bartlett, L. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Barton, J. K.

Blinder, P.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Boas, D. A.

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(3), 195–201 (2001).
[CrossRef] [PubMed]

Bonner, R.

Bouma, B. E.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express11(25), 3490–3497 (2003).
[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]

Brecke, K. M.

Burns, L. D.

B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
[CrossRef] [PubMed]

Cable, A.

Cable, A. E.

Cense, B.

Chance, B.

A. Villringer and B. Chance, “Non-invasive optical spectroscopy and imaging of human brain function,” Trends Neurosci.20(10), 435–442 (1997).
[CrossRef] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, T. C.

Chen, Z.

Choi, W.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Cobb, M. J.

Dale, A. M.

Davalos, D.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Dave, D.

Davis, A. M.

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]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Diez-Silva, M.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Ding, Z.

Dirnagl, U.

U. Dirnagl, B. Kaplan, M. Jacewicz, and W. Pulsinelli, “Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model,” J. Cereb. Blood Flow Metab.9(5), 589–596 (1989).
[CrossRef] [PubMed]

Drew, P. J.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Driscoll, J. D.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Dunn, A. K.

E. M. Hillman, D. A. Boas, A. M. Dale, and A. K. Dunn, “Laminar optical tomography: demonstration of millimeter-scale depth-resolved imaging in turbid media,” Opt. Lett.29(14), 1650–1652 (2004).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab.21(3), 195–201 (2001).
[CrossRef] [PubMed]

et,

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Feld, M. S.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Fercher, A. F.

Fingler, J.

Fischer, T. M.

T. M. Fischer, M. Stöhr-Lissen, and H. Schmid-Schönbein, “The red cell as a fluid droplet: tank tread-like motion of the human erythrocyte membrane in shear flow,” Science202(4370), 894–896 (1978).
[CrossRef] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Fraser, S. E.

Friebel, M.

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,” Nature324(6095), 361–364 (1986).
[CrossRef] [PubMed]

Fu, D.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Fujimoto, J. G.

Fukumura, D.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
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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,” Nature324(6095), 361–364 (1986).
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H. L. Goldsmith and J. C. Marlow, “Flow behavior of erythrocytes. 2. Particle motions in concentrated suspensions of ghost cells,” J. Colloid Interface Sci.71(2), 383–407 (1979).
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Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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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,” Nature324(6095), 361–364 (1986).
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Hanson, S. R.

He, Y.

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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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).
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Hitzenberger, C. K.

Hong, Y.

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]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Hutchinson, E. B.

E. B. Hutchinson, B. Stefanovic, A. P. Koretsky, and A. C. Silva, “Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia,” Neuroimage32(2), 520–530 (2006).
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Izatt, J. A.

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U. Dirnagl, B. Kaplan, M. Jacewicz, and W. Pulsinelli, “Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model,” J. Cereb. Blood Flow Metab.9(5), 589–596 (1989).
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Jain, R. K.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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Jiang, J.

Jiang, J. Y.

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J. Kalkman, R. Sprik, and T. G. van Leeuwen, “Path-length-resolved diffusive particle dynamics in spectral-domain optical coherence tomography,” Phys. Rev. Lett.105(19), 198302 (2010).
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P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
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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).
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P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
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Koretsky, A. P.

E. B. Hutchinson, B. Stefanovic, A. P. Koretsky, and A. C. Silva, “Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia,” Neuroimage32(2), 520–530 (2006).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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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,” Nature324(6095), 361–364 (1986).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation12(1), 5–15 (2005).
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H. L. Goldsmith and J. C. Marlow, “Flow behavior of erythrocytes. 2. Particle motions in concentrated suspensions of ghost cells,” J. Colloid Interface Sci.71(2), 383–407 (1979).
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Milner, T. E.

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).
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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(3), 195–201 (2001).
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B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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Park, Y.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
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Popescu, G.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
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Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Pulsinelli, W.

U. Dirnagl, B. Kaplan, M. Jacewicz, and W. Pulsinelli, “Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model,” J. Cereb. Blood Flow Metab.9(5), 589–596 (1989).
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T. M. Fischer, M. Stöhr-Lissen, and H. Schmid-Schönbein, “The red cell as a fluid droplet: tank tread-like motion of the human erythrocyte membrane in shear flow,” Science202(4370), 894–896 (1978).
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Schnitzer, M. J.

B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Schwartz, D.

Shih, A. Y.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
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E. B. Hutchinson, B. Stefanovic, A. P. Koretsky, and A. C. Silva, “Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia,” Neuroimage32(2), 520–530 (2006).
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J. Kalkman, R. Sprik, and T. G. van Leeuwen, “Path-length-resolved diffusive particle dynamics in spectral-domain optical coherence tomography,” Phys. Rev. Lett.105(19), 198302 (2010).
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Standish, B. A.

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E. B. Hutchinson, B. Stefanovic, A. P. Koretsky, and A. C. Silva, “Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia,” Neuroimage32(2), 520–530 (2006).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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T. M. Fischer, M. Stöhr-Lissen, and H. Schmid-Schönbein, “The red cell as a fluid droplet: tank tread-like motion of the human erythrocyte membrane in shear flow,” Science202(4370), 894–896 (1978).
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W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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Sun, T.

Suresh, S.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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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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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express11(25), 3490–3497 (2003).
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P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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J. Kalkman, R. Sprik, and T. G. van Leeuwen, “Path-length-resolved diffusive particle dynamics in spectral-domain optical coherence tomography,” Phys. Rev. Lett.105(19), 198302 (2010).
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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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W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
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B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
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Werner, J. S.

White, B. R.

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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,” Nature324(6095), 361–364 (1986).
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Wilson, B. C.

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B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
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Annu. Rev. Neurosci. (1)

B. A. Wilt, L. D. Burns, E. T. Wei Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in light microscopy for neuroscience,” Annu. Rev. Neurosci.32(1), 435–506 (2009).
[CrossRef] [PubMed]

Appl. Opt. (2)

IEEE Trans. Biomed. Eng. (1)

S. Yousefi, Z. Zhi, and R. Wang, “Eigendecomposition-based clutter filtering technique for optical micro-angiography,” IEEE Trans. Biomed. Eng.58(8), 2316–2323 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

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]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (2)

U. Dirnagl, B. Kaplan, M. Jacewicz, and W. Pulsinelli, “Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model,” J. Cereb. Blood Flow Metab.9(5), 589–596 (1989).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab.21(3), 195–201 (2001).
[CrossRef] [PubMed]

J. Colloid Interface Sci. (1)

H. L. Goldsmith and J. C. Marlow, “Flow behavior of erythrocytes. 2. Particle motions in concentrated suspensions of ghost cells,” J. Colloid Interface Sci.71(2), 383–407 (1979).
[CrossRef]

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

Microcirculation (1)

H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation12(1), 5–15 (2005).
[CrossRef] [PubMed]

Nat. Med. (1)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Nat. Methods (1)

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Nature (1)

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,” Nature324(6095), 361–364 (1986).
[CrossRef] [PubMed]

Neuroimage (1)

E. B. Hutchinson, B. Stefanovic, A. P. Koretsky, and A. C. Silva, “Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia,” Neuroimage32(2), 520–530 (2006).
[CrossRef] [PubMed]

Opt. Express (9)

J. Fingler, R. J. Zawadzki, J. S. Werner, D. Schwartz, and S. E. Fraser, “Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique,” Opt. Express17(24), 22190–22200 (2009).
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R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, “Performance of Fourier domain vs. time domain optical coherence tomography,” Opt. Express11(8), 889–894 (2003).
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B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express11(25), 3490–3497 (2003).
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S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express14(17), 7821–7840 (2006).
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R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express15(7), 4083–4097 (2007).
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Y. K. Tao, A. M. Davis, and J. A. Izatt, “Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform,” Opt. Express16(16), 12350–12361 (2008).
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Figures (7)

Fig. 1
Fig. 1

Frequency domain comparison of Doppler OCT (a), OCT angiography (b), and the proposed method of OCT velocimetry (c). (a) In Doppler OCT, the center frequency of the dynamic scattering component of the power spectral density is estimated, and used to determine the axial projection of velocity, vz. (b) In conventional OCT angiography, a high-pass filter is applied to suppress static scattering, and visualize only the dynamic scattering component. (c) In the method of OCT velocimetry presented here, the spectral width of the dynamic scattering component is estimated.

Fig. 2
Fig. 2

The autocorrelation function / power spectral density are superpositions of static (blue) and dynamic (red) scattering components. (a) Magnitude and phase of the autocorrelation function components. Due to coherent interference of the static and dynamic components, the autocorrelation magnitude exhibits oscillations (black line). (b) Power spectral density, obtained from Fourier transformation of the autocorrelation function, showing static and dynamic components. (c) En face image of total scattering from 250 to 300 µm depth in the rat somatosensory cortex. Static (d) and dynamic (e) scattering components can be estimated. Note that (c) and (d) are displayed on the same grayscale, while (e) is rescaled due to the lower dynamic scattering power. These components can be overlaid (f) to show the contributions of scattering from static tissue (blue) and dynamic red blood cells (red). For simplicity, noise sources have been neglected.

Fig. 3
Fig. 3

Examples of autocorrelation function estimates from vasculature. En face OCT angiogram of the rat somatosensory cortex through a cranial window. (b) OCT Δf map, showing bandwidth in color scale. Cross-sectional slice through the angiogram (c) and Δf map (d) are shown, along with 4 labeled points where the autocorrelation function is estimated. (e) Plot of autocorrelation function estimate magnitudes at the 4 labeled points. The Δf values shown in the legend are proportional to the rate of autocorrelation decay.

Fig. 4
Fig. 4

OCT velocimetry of the rat somatosensory cortex. (a) En face OCT angiogram of the rat somatosensory cortex through a cranial window. (b) OCT Δf map, showing bandwidth in color scale. (c-d) Zoom of branch points show heterogeneous, branch-specific dynamics. (e) Cross-section through a vein shows increased bandwidth at the center, as would be expected from a parabolic profile.

Fig. 5
Fig. 5

Comparison of OCT and two photon velocimetry. (a) OCT angiogram and (b) two-photon angiogram. The location of the two-photon angiogram is shown as a red box in (a). (c) OCT Δf map at the location of the red box in (b). with a capillary (above, black region-of-interest) and two-photon line scan (below, red arrow) at the same location. (d) The slope of the space-time plot from the line scan is inversely proportional to the velocity (e) Comparison of velocity measured by two-photon microscopy and Δf values measured by OCT at the same location. The black line shows a linear fit for capillaries and veins only.

Fig. 6
Fig. 6

Capillary velocimetry during a hypercapnic challenge. OCT angiograms under normocapnia (a) and hypercapnia (b) show no noticeable differences. However, OCT Δf map shows an apparent redistribution of capillary velocity during hypercapnia (d) compared to normocapnia (c). On average, the number of high-velocity capillaries is increased during hypercapnia.

Fig. 7
Fig. 7

OCT methods of velocimetry provide additional insight which is not obtained from conventional OCT angiograms. OCT angiograms of the mouse cortex before (a) and one day after (b) distal MCA occlusion are shown. Surface vessels (pial and dural) have been colored yellow, while deeper vessels are colored in green. Black and white OCT angiograms show a rarefaction of perfused capillaries after occlusion (d) compared to before occlusion (c). OCT Δf maps show a reduction in velocity in perfused capillaries after occlusion (f) compared to before occlusion (e). The Δf maps (e-f) provide novel information which is not contained in the angiograms (c-d), and show an increase in heterogeneity after stroke.

Equations (22)

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A(t)= A s (t)+ A d (t)+N(t)
R(τ)=E[ A * (t)A(t+τ)]= R s (τ)+ R d (τ)+ R N (τ)
P(f)= P s (f)+ P d (f)+ P N (f)
R s (τ)= I s P s (f)= I s δ(f)
R N (τ)= I N δ(τ)
I ^ s R(τ>>Δτ)
I d = R d (0)= -1/2 1/2 P d (f)df
I N = R N (0)= -1/2 1/2 P N (f)df
I=R(0)= R s (0)+ R d (0)+ R N (0)= I s + I d + I N
h(x,y,z)= 2K π w ix w iy e ( 2 x 2 w ix 2 ) e ( 2 y 2 w iy 2 ) e ( 2 z 2 w iz 2 ) e i( 4πn λ )z
p(t)=h( v x t, v y t, v z t)= 2K π w ix w iy e [ 2 ( v x t ) 2 w ix 2 ] e [ 2 ( v y t ) 2 w iy 2 ] e [ 2 ( v z t ) 2 w iz 2 ] e i( 4πn λ ) v z t
n A n p(t- t n ) =p(t)*A(t) where A(t)= n A n δ(t- t n )
R d (τ)= 2|K | 2 π 3/2 w ix 3/2 w iy 3/2 P A e [ ( v x τ ) 2 w ix 2 ] e [ ( v y τ ) 2 w iy 2 ] e [ ( v z τ ) 2 w iz 2 ] e i( 4πn λ ) v z τ
R d (τ)= 2|K | 2 π 3/2 w 0 3 P A e ( vτ w 0 ) 2 e i( 4πn v z λ )τ
P d (f)= 2|K | 2 π w 0 2 v P A e π 2 w 0 2 v 2 ( f- 2n v z λ ) 2
R d (τ)= R RBC (x,y,z) | x= v x τ,y= v y τ,z= v z τ
R ^ (x,y,z,nT)= x z m=0 M-n-1 A * [x,y,z,mT] A corr [x,y,z,(m+n)T] M-n  for n=0...,N-1,N
R ^ (x,y,z,nT)= R ^ * (x,y,z,-nT) for n=-N,-N+1,...,-1
R ^ d (x,y,z,nT)= R ^ (x,y,z,nT)- I ^ s (x,y,z)
P ^ d,demod (x,y,z,f)= n=-N N | R ^ d (x,y,z,nT)|exp[-i2πf(nT)]
Δf= f |f| P ^ d,demod (x,y,z,f) f P ^ d,demod (x,y,z,f)
ΔA[x,y,z]= m=0 M-3 |A[x,y,z,mT]- A corr [x,y,z,(m+2)T]|

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