Abstract

The eye offers a unique opportunity for the non-invasive exploration of cardiovascular diseases. Optical angiography in the retina requires sensitive measurements, which hinders conventional full-field laser Doppler imaging schemes. To overcome this limitation, we used digital holography to perform laser Doppler perfusion imaging of human retina with near-infrared light. Two imaging channels with a slow and a fast CMOS camera were used simultaneously for real-time narrowband measurements, and offline wideband measurements, respectively. The beat frequency spectrum of optical interferograms recorded with the fast (up to 75 kHz) CMOS camera was analyzed by short-time Fourier transformation. Power Doppler images drawn from the Doppler power spectrum density qualitatively revealed blood flow in retinal vessels over 512 × 512 pixels covering 2.4 × 2.4 mm2 on the retina with a temporal resolution down to 1.6 ms. The sensitivity to lateral motion as well as the requirements in terms of sampling frequency are discussed.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2018 (1)

2016 (3)

H. Sudkamp, P. Koch, H. Spahr, D. Hillmann, G. Franke, M. Münst, F. Reinholz, R. Birngruber, and G. Hüttmann, “In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography,” Opt. Lett. 41, 4987–4990 (2016).
[Crossref] [PubMed]

M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
[Crossref]

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
[Crossref]

2015 (4)

J. F. Polak, J. M. Alessi-Chinetti, A. R. Patel, and J. M. Estes, “Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction,” J. Ultrasound Medicine 34, 461–467 (2015).
[Crossref]

H. Spahr, D. Hillmann, C. Hain, C. Pfäffle, H. Sudkamp, G. Franke, and G. Hüttmann, “Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography,” Opt. letters 40, 4771–4774 (2015).
[Crossref]

Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
[Crossref] [PubMed]

D. J. Fechtig, B. Grajciar, T. Schmoll, C. Blatter, R. M. Werkmeister, W. Drexler, and R. A. Leitgeb, “Line-field parallel swept source MHz OCT for structural and functional retinal imaging,” Biomed. Opt. Express 6, 716–735 (2015).
[Crossref] [PubMed]

2014 (3)

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

V. Doblhoff-Dier, L. Schmetterer, W. Vilser, G. Garhöfer, M. Gröschl, R. A. Leitgeb, and R. M. Werkmeister, “Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes,” Biomed. Opt. Express 5, 630–642 (2014).
[Crossref] [PubMed]

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

2013 (2)

A. P. Cherecheanu, G. Garhofer, D. Schmidl, R. Werkmeister, and L. Schmetterer, “Ocular perfusion pressure and ocular blood flow in glaucoma,” Curr. Opin. Pharmacol. 13, 36–42 (2013).
[Crossref]

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
[Crossref] [PubMed]

2012 (2)

2010 (2)

R. K. Wang, L. An, P. Francis, and D. J. Wilson, “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35, 1467–1469 (2010).
[Crossref] [PubMed]

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
[Crossref]

2009 (2)

C. E. Riva, M. Geiser, and B. L. Petrig, “Ocular blood flow assessment using continuous laser Doppler flowmetry,” Acta Ophthalmol. 88, 622–629 (2009).
[Crossref] [PubMed]

V. Rajan, B. Varghese, T. G. van Leeuwen, and W. Steenbergen, “Review of methodological developments in laser Doppler flowmetry,” Lasers Med. Sci. 24, 269–283 (2009).
[Crossref]

2008 (3)

2007 (1)

L. Schmetterer and G. Garhofer, “How can blood flow be measured?” Surv. Ophthalmol. 52, S134–S138 (2007).
[Crossref] [PubMed]

2004 (1)

L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
[Crossref] [PubMed]

2003 (1)

2002 (1)

2000 (1)

1999 (1)

M. Leahy, F. De Mul, G. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Heal. Care 7, 143–162 (1999).

1997 (2)

1996 (1)

G. Michelson, B. Schmauss, M. Langhans, J. Harazny, and M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma. 5, 99–105 (1996).
[Crossref] [PubMed]

1995 (1)

J. A. Briers and S. Webster, “Quasi real-time digital version of single-exposure speckle photography for full-field monitoring of velocity or flow fields,” Opt. Comm. 116, 36–42 (1995).
[Crossref]

1994 (1)

H. Fujii, “Visualisation of retinal blood flow by laser speckle flowgraphy,” Med. Biol. Eng. Comput. 32, 302–304 (1994).
[Crossref] [PubMed]

1992 (2)

1985 (1)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. & Vis. Sci. 26, 1124–1132 (1985).

1981 (1)

1978 (1)

H. N. Sabbah and P. D. Stein, “Valve origin of the aortic incisura,” Am. J. Cardiol. 41, 32–38 (1978).
[Crossref] [PubMed]

1977 (1)

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Albrecht, H.

H. Albrecht, M. Borys, N. Damaschke, and C. Tropea, Laser Doppler and Phase Doppler Measurement Techniques (Springer, 2003).
[Crossref]

Alessi-Chinetti, J. M.

J. F. Polak, J. M. Alessi-Chinetti, A. R. Patel, and J. M. Estes, “Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction,” J. Ultrasound Medicine 34, 461–467 (2015).
[Crossref]

An, L.

Araie, M.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
[Crossref]

Atlan, M.

M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
[Crossref]

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

Bailey, S. T.

Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
[Crossref] [PubMed]

Barton, J. K.

Baumann, B.

Birngruber, R.

Blatter, C.

Bonner, R.

Bonner, R. F.

R. F. Bonner and R. Nossal, “Principles of laser-Doppler flowmetry,” in “Laser-Doppler Blood Flowmetry,” (Springer, 1990), pp. 17–45.
[Crossref]

Borys, M.

H. Albrecht, M. Borys, N. Damaschke, and C. Tropea, Laser Doppler and Phase Doppler Measurement Techniques (Springer, 2003).
[Crossref]

Boucneau, T.

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

Bouma, B. E.

Bowen, P.

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Bowman, R.

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Briers, J. A.

J. A. Briers and S. Webster, “Quasi real-time digital version of single-exposure speckle photography for full-field monitoring of velocity or flow fields,” Opt. Comm. 116, 36–42 (1995).
[Crossref]

Burns, S. A.

Cable, A. E.

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
[Crossref] [PubMed]

Castel, A.

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

Cense, B.

Chen, C.-L.

A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
[Crossref] [PubMed]

Chen, T. C.

Chen, Z.

Cherecheanu, A. P.

A. P. Cherecheanu, G. Garhofer, D. Schmidl, R. Werkmeister, and L. Schmetterer, “Ocular perfusion pressure and ocular blood flow in glaucoma,” Curr. Opin. Pharmacol. 13, 36–42 (2013).
[Crossref]

Chimosky, J.

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Choi, W.

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
[Crossref] [PubMed]

Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3, 3127–3137 (2012).
[Crossref] [PubMed]

Damaschke, N.

H. Albrecht, M. Borys, N. Damaschke, and C. Tropea, Laser Doppler and Phase Doppler Measurement Techniques (Springer, 2003).
[Crossref]

de Boer, J. F.

de Mul, F.

A. Serov, W. Steenbergen, and F. de Mul, “Laser Doppler perfusion imaging with complementary metal oxide semiconductor image sensor,” Opt. Lett. 27, 300–302 (2002).
[Crossref]

M. Leahy, F. De Mul, G. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Heal. Care 7, 143–162 (1999).

Degardin, J.

M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
[Crossref]

Doblhoff-Dier, V.

Drexler, W.

Duker, J. S.

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
[Crossref] [PubMed]

Estes, J. M.

J. F. Polak, J. M. Alessi-Chinetti, A. R. Patel, and J. M. Estes, “Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction,” J. Ultrasound Medicine 34, 461–467 (2015).
[Crossref]

Fechtig, D. J.

Ferezou, I.

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Grunwald, J. E.

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Hain, C.

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
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D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
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D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
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H. Sudkamp, P. Koch, H. Spahr, D. Hillmann, G. Franke, M. Münst, F. Reinholz, R. Birngruber, and G. Hüttmann, “In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography,” Opt. Lett. 41, 4987–4990 (2016).
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Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
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Jayaraman, V.

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Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3, 3127–3137 (2012).
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M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
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M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
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Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
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L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
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W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
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Lu, C. D.

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
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Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3, 3127–3137 (2012).
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Maniewski, R.

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Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
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Mohler, K. J.

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
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M. Leahy, F. De Mul, G. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Heal. Care 7, 143–162 (1999).

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M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
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C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
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M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
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C. Riva, S. Harino, B. Petrig, and R. Shonat, “Laser Doppler flowmetry in the optic nerve,” Exp. Eye Res. 55, 499–506 (1992).
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C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. & Vis. Sci. 26, 1124–1132 (1985).

Petrig, B. L.

Pfäffle, C.

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
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H. Spahr, D. Hillmann, C. Hain, C. Pfäffle, H. Sudkamp, G. Franke, and G. Hüttmann, “Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography,” Opt. letters 40, 4771–4774 (2015).
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Polak, J. F.

J. F. Polak, J. M. Alessi-Chinetti, A. R. Patel, and J. M. Estes, “Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction,” J. Ultrasound Medicine 34, 461–467 (2015).
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W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
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A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
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T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
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C. E. Riva, M. Geiser, and B. L. Petrig, “Ocular blood flow assessment using continuous laser Doppler flowmetry,” Acta Ophthalmol. 88, 622–629 (2009).
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L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
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A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
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C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
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L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
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G. Michelson, B. Schmauss, M. Langhans, J. Harazny, and M. Groh, “Principle, validity, and reliability of scanning laser Doppler flowmetry,” J. Glaucoma. 5, 99–105 (1996).
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T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
[Crossref]

B. Pemp and L. Schmetterer, “Ocular blood flow in diabetes and age-related macular degeneration,” Can. J. Ophthalmol. Can. d’Ophtalmologie 43, 295–301 (2008).
[Crossref]

L. Schmetterer and G. Garhofer, “How can blood flow be measured?” Surv. Ophthalmol. 52, S134–S138 (2007).
[Crossref] [PubMed]

Schmidl, D.

A. P. Cherecheanu, G. Garhofer, D. Schmidl, R. Werkmeister, and L. Schmetterer, “Ocular perfusion pressure and ocular blood flow in glaucoma,” Curr. Opin. Pharmacol. 13, 36–42 (2013).
[Crossref]

Schmitt, J.

Schmoll, T.

Schurtenberger, P.

L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
[Crossref] [PubMed]

Serov, A.

Shi, Y.

A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
[Crossref] [PubMed]

Shonat, R.

C. Riva, S. Harino, B. Petrig, and R. Shonat, “Laser Doppler flowmetry in the optic nerve,” Exp. Eye Res. 55, 499–506 (1992).
[Crossref] [PubMed]

Simonutti, M.

M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
[Crossref]

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

Sinclair, S. H.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. & Vis. Sci. 26, 1124–1132 (1985).

Spahr, H.

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
[Crossref]

H. Sudkamp, P. Koch, H. Spahr, D. Hillmann, G. Franke, M. Münst, F. Reinholz, R. Birngruber, and G. Hüttmann, “In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography,” Opt. Lett. 41, 4987–4990 (2016).
[Crossref] [PubMed]

H. Spahr, D. Hillmann, C. Hain, C. Pfäffle, H. Sudkamp, G. Franke, and G. Hüttmann, “Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography,” Opt. letters 40, 4771–4774 (2015).
[Crossref]

Srinivas, S.

Steenbergen, W.

V. Rajan, B. Varghese, T. G. van Leeuwen, and W. Steenbergen, “Review of methodological developments in laser Doppler flowmetry,” Lasers Med. Sci. 24, 269–283 (2009).
[Crossref]

A. Serov, W. Steenbergen, and F. de Mul, “Laser Doppler perfusion imaging with complementary metal oxide semiconductor image sensor,” Opt. Lett. 27, 300–302 (2002).
[Crossref]

Stefánsson, E.

S. H. Hardarson and E. Stefánsson, “Retinal oxygen saturation is altered in diabetic retinopathy,” Br. J. Ophthalmol. 96, 560–563 (2012).
[Crossref]

Stein, P. D.

H. N. Sabbah and P. D. Stein, “Valve origin of the aortic incisura,” Am. J. Cardiol. 41, 32–38 (1978).
[Crossref] [PubMed]

Stern, M.

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Sudkamp, H.

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
[Crossref]

H. Sudkamp, P. Koch, H. Spahr, D. Hillmann, G. Franke, M. Münst, F. Reinholz, R. Birngruber, and G. Hüttmann, “In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography,” Opt. Lett. 41, 4987–4990 (2016).
[Crossref] [PubMed]

H. Spahr, D. Hillmann, C. Hain, C. Pfäffle, H. Sudkamp, G. Franke, and G. Hüttmann, “Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography,” Opt. letters 40, 4771–4774 (2015).
[Crossref]

Sugiyama, T.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
[Crossref]

Tan, O.

Tearney, G. J.

Thurman, S. T.

Tokayer, J.

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H. Albrecht, M. Borys, N. Damaschke, and C. Tropea, Laser Doppler and Phase Doppler Measurement Techniques (Springer, 2003).
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van Leeuwen, T. G.

V. Rajan, B. Varghese, T. G. van Leeuwen, and W. Steenbergen, “Review of methodological developments in laser Doppler flowmetry,” Lasers Med. Sci. 24, 269–283 (2009).
[Crossref]

Varghese, B.

V. Rajan, B. Varghese, T. G. van Leeuwen, and W. Steenbergen, “Review of methodological developments in laser Doppler flowmetry,” Lasers Med. Sci. 24, 269–283 (2009).
[Crossref]

Vilser, W.

Vitalis, T.

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
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Wang, R. K.

R. K. Wang, L. An, P. Francis, and D. J. Wilson, “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35, 1467–1469 (2010).
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A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
[Crossref] [PubMed]

Wang, X.

Webster, S.

J. A. Briers and S. Webster, “Quasi real-time digital version of single-exposure speckle photography for full-field monitoring of velocity or flow fields,” Opt. Comm. 116, 36–42 (1995).
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Welch, A. J.

Werkmeister, R.

A. P. Cherecheanu, G. Garhofer, D. Schmidl, R. Werkmeister, and L. Schmetterer, “Ocular perfusion pressure and ocular blood flow in glaucoma,” Curr. Opin. Pharmacol. 13, 36–42 (2013).
[Crossref]

Werkmeister, R. M.

White, B. R.

Wilson, D. J.

Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
[Crossref] [PubMed]

R. K. Wang, L. An, P. Francis, and D. J. Wilson, “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35, 1467–1469 (2010).
[Crossref] [PubMed]

Winter, C.

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
[Crossref]

Wurster, L. M.

Xiang, S.

Yazdanfar, S.

Zhao, Y.

Zheng, F.

A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
[Crossref] [PubMed]

Zhong, Z.

Acta Ophthalmol. (2)

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88, 723–729 (2010).
[Crossref]

C. E. Riva, M. Geiser, and B. L. Petrig, “Ocular blood flow assessment using continuous laser Doppler flowmetry,” Acta Ophthalmol. 88, 622–629 (2009).
[Crossref] [PubMed]

Am. J. Cardiol. (1)

H. N. Sabbah and P. D. Stein, “Valve origin of the aortic incisura,” Am. J. Cardiol. 41, 32–38 (1978).
[Crossref] [PubMed]

Am. J. Physiol. (1)

M. Stern, D. Lappe, P. Bowen, J. Chimosky, G. Holloway, H. Keiser, and R. Bowman, “Continuous measurement of tissue blood flow by laser-Doppler spectroscopy,” Am. J. Physiol. 232, H441–H448 (1977).
[PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (4)

Br. J. Ophthalmol. (1)

S. H. Hardarson and E. Stefánsson, “Retinal oxygen saturation is altered in diabetic retinopathy,” Br. J. Ophthalmol. 96, 560–563 (2012).
[Crossref]

Can. J. Ophthalmol. Can. d’Ophtalmologie (1)

B. Pemp and L. Schmetterer, “Ocular blood flow in diabetes and age-related macular degeneration,” Can. J. Ophthalmol. Can. d’Ophtalmologie 43, 295–301 (2008).
[Crossref]

Curr. Opin. Pharmacol. (1)

A. P. Cherecheanu, G. Garhofer, D. Schmidl, R. Werkmeister, and L. Schmetterer, “Ocular perfusion pressure and ocular blood flow in glaucoma,” Curr. Opin. Pharmacol. 13, 36–42 (2013).
[Crossref]

Exp. Eye Res. (1)

C. Riva, S. Harino, B. Petrig, and R. Shonat, “Laser Doppler flowmetry in the optic nerve,” Exp. Eye Res. 55, 499–506 (1992).
[Crossref] [PubMed]

Investig. Ophthalmol. & Vis. Sci. (1)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. & Vis. Sci. 26, 1124–1132 (1985).

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J. F. Polak, J. M. Alessi-Chinetti, A. R. Patel, and J. M. Estes, “Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction,” J. Ultrasound Medicine 34, 461–467 (2015).
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JOSA A (2)

L. F. Rojas-Ochoa, D. Lacoste, R. Lenke, P. Schurtenberger, and F. Scheffold, “Depolarization of backscattered linearly polarized light,” JOSA A 21, 1799–1804 (2004).
[Crossref] [PubMed]

C. Magnain, A. Castel, T. Boucneau, M. Simonutti, I. Ferezou, A. Rancillac, T. Vitalis, J.-A. Sahel, M. Paques, and M. Atlan, “Holographic laser Doppler imaging of microvascular blood flow,” JOSA A 31, 2723–2735 (2014).
[Crossref]

Lasers Med. Sci. (1)

V. Rajan, B. Varghese, T. G. van Leeuwen, and W. Steenbergen, “Review of methodological developments in laser Doppler flowmetry,” Lasers Med. Sci. 24, 269–283 (2009).
[Crossref]

Med. Biol. Eng. Comput. (1)

H. Fujii, “Visualisation of retinal blood flow by laser speckle flowgraphy,” Med. Biol. Eng. Comput. 32, 302–304 (1994).
[Crossref] [PubMed]

Opt. Comm. (1)

J. A. Briers and S. Webster, “Quasi real-time digital version of single-exposure speckle photography for full-field monitoring of velocity or flow fields,” Opt. Comm. 116, 36–42 (1995).
[Crossref]

Opt. Express (2)

Opt. Lett. (7)

R. K. Wang, L. An, P. Francis, and D. J. Wilson, “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35, 1467–1469 (2010).
[Crossref] [PubMed]

M. Guizar-Sicairos, S. T. Thurman, and J. R. Fienup, “Efficient subpixel image registration algorithms,” Opt. Lett. 33, 156–158 (2008).
[Crossref] [PubMed]

A. Serov, W. Steenbergen, and F. de Mul, “Laser Doppler perfusion imaging with complementary metal oxide semiconductor image sensor,” Opt. Lett. 27, 300–302 (2002).
[Crossref]

H. Sudkamp, P. Koch, H. Spahr, D. Hillmann, G. Franke, M. Münst, F. Reinholz, R. Birngruber, and G. Hüttmann, “In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography,” Opt. Lett. 41, 4987–4990 (2016).
[Crossref] [PubMed]

Y. Zhao, Z. Chen, C. Saxer, S. Xiang, J. F. de Boer, and J. S. Nelson, “Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity,” Opt. Lett. 25, 114–116 (2000).
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J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22, 1439–1441 (1997).
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Opt. letters (2)

H. Spahr, D. Hillmann, C. Hain, C. Pfäffle, H. Sudkamp, G. Franke, and G. Hüttmann, “Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography,” Opt. letters 40, 4771–4774 (2015).
[Crossref]

M. Pellizzari, M. Simonutti, J. Degardin, J.-A. Sahel, M. Fink, M. Paques, and M. Atlan, “High speed optical holography of retinal blood flow,” Opt. letters 41, 3503–3506 (2016).
[Crossref]

PloS One (1)

W. Choi, K. J. Mohler, B. Potsaid, C. D. Lu, J. J. Liu, V. Jayaraman, A. E. Cable, J. S. Duker, R. Huber, and J. G. Fujimoto, “Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography,” PloS One 8, e81499 (2013).
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Proc. Natl. Acad. Sci. (1)

Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. 112, E2395–E2402 (2015).
[Crossref] [PubMed]

Prog. Retin. Eye Res. (1)

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
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Sci. Reports (1)

D. Hillmann, H. Spahr, C. Hain, H. Sudkamp, G. Franke, C. Pfäffle, C. Winter, and G. Hüttmann, “Aberration-free volumetric high-speed imaging of in vivo retina,” Sci. Reports 6, 35209 (2016).
[Crossref]

Surv. Ophthalmol. (1)

L. Schmetterer and G. Garhofer, “How can blood flow be measured?” Surv. Ophthalmol. 52, S134–S138 (2007).
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M. Leahy, F. De Mul, G. Nilsson, and R. Maniewski, “Principles and practice of the laser-Doppler perfusion technique,” Technol. Heal. Care 7, 143–162 (1999).

Other (4)

A. H. Kashani, C.-L. Chen, J. K. Gahm, F. Zheng, G. M. Richter, P. J. Rosenfeld, Y. Shi, and R. K. Wang, “Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications,” Prog. Retin. Eye Res. (2017).
[Crossref] [PubMed]

H. Albrecht, M. Borys, N. Damaschke, and C. Tropea, Laser Doppler and Phase Doppler Measurement Techniques (Springer, 2003).
[Crossref]

J. W. Goodman, Introduction to Fourier Optics (Roberts and Company Publishers, 2005).

R. F. Bonner and R. Nossal, “Principles of laser-Doppler flowmetry,” in “Laser-Doppler Blood Flowmetry,” (Springer, 1990), pp. 17–45.
[Crossref]

Supplementary Material (3)

NameDescription
» Visualization 1       Laser Doppler holography of human retina showing blood flow in the optic nerve head.
» Visualization 2       Laser Doppler holography of human retina showing blood flow in an artery intertwinned with a vein
» Visualization 3       Laser Doppler holography of human retina showing the Doppler power spectrum density as a function of frequency

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Figures (9)

Fig. 1
Fig. 1 Optical setup. L1, L2 and L3 are converging lenses. PBS: Polarizing Beam Splitter. BS: Beam Splitter. The light source is a single wavelength laser diode (SWL-7513-H-P, Newport). The 90% output of the fiber coupler is used for the object arm. The Doppler broadened light backscattered by the retina is combined with the reference field and interferograms are recorded on the two imaging channels to study the Doppler beat frequency. The data from the fast CMOS camera is processed offline while the 80 Hz camera is used for real-time monitoring.
Fig. 2
Fig. 2 Short-Time Fourier Transform analysis. A 3D sliding window of consecutive holograms is moved along the full hologram stack; for each window, the Doppler Power Spectral Density (DPSD) is estimated from the squared magnitude of the Fourier Transform in Eq. (3). A single image with blood flow contrast is obtained by integrating the DPSD over [ω1, ω2] in Eq. (4), and the resulting image M0+ is referred to as power Doppler image. Examples of non-averaged power Doppler images are shown in Fig. 5, and examples of averaged power Doppler images are shown in Fig. 3(c) and Fig. 4(c).
Fig. 3
Fig. 3 Optic Nerve Head (ONH) region imaged with commercialized instruments and Laser Doppler holography. (a) Scanning laser ophthalmoscope (Spectralis, Heidelberg). (b) Adaptive optics flood illumination (rtx1, Imagine Eyes). (c) Power Doppler images M0+ calculated from holograms recorded at fS = 39 kHz; S(ω) is integrated over [ f1, f2] = 4–19.5 kHz. Multiple power Doppler images M0+ are averaged over a total time of 80 ms (see Visualization 1 for blood flow movie). The peri-papillary crescent is visible on the edge of the ONH. (d) Asymmetry of the DPSD M0 (averaged over the same period of time) illustrating the resultant flow direction with respect to the optical axis.
Fig. 4
Fig. 4 An artery intertwined with a vein is imaged with commercialized instruments and Laser Doppler holography.(a) Scanning laser ophthalmoscope (Spectralis, Heidelberg). (b) Adaptive optics flood illumination (rtx1, Imagine Eyes). (c) Power Doppler images M0+ calculated from holograms recorded at fS = 39 kHz; S(ω) is integrated over [f1, f2] = 7–19.5 kHz. Multiple power Doppler images M0+ are averaged over a total time of 0.66 s (see Visualization 2 for blood flow movie). (d) Asymmetry of the DPSD M0 (averaged over the same period of time) illustrating the resultant flow direction with respect to the optical axis.
Fig. 5
Fig. 5 Comparison in Signal to Noise Ratio (SNR) of power Doppler images M0+ and M0 calculated with jwin = 64 and 512 holograms (i.e. σwin = 1.6 ms and 13.1 ms, respectively). The four images are non-averaged power Doppler images calculated from raw holograms acquired at 39 kHz: (a) M0+, jwin = 64. (b) M0+, jwin = 512. (c) M0, jwin = 64. (d) M0, jwin = 512. The SNR dramatically improves with the duration of the short-time window.
Fig. 6
Fig. 6 Comparison of pulsatile flow measurements in a vein and an artery for two STFT analysis performed on the same dataset with (a) jwin = 64 and (b) jwin = 512 holograms. For each analysis, a time averaged power Doppler images M0+ is displayed on the left hand side and shows a red, blue and green ROI which mark an artery (A), a vein (V), and the background tissues (B), respectively. These regions are used to spatially average the power Doppler signal for the plots on the right hand side. Although noisier, the pulsatility signal is already well visible when using jwin = 64.
Fig. 7
Fig. 7 Cases of spectral asymmetry between the positive and negative parts of the DPSD calculated according to Eq. (3). (a, b) Schematic illustrating the sign of the Doppler frequency shift for the direct backscatter (cf. Eq. (6)). (c) M0 showing the two regions where the spectra are calculated. (d) Negative and positive part of the DPSD measured in the ROI 1. (e) Negative and positive part of the DPSD measured in the ROI 2. For the range of frequencies 4–19.5 kHz used to calculate PDIs, S1(ω) > S1(−ω) and on the contrary S2(ω) < S2(−ω) depending on the vessel geometry.
Fig. 8
Fig. 8 Multiple laser Doppler holography measurements of a same region are made with different sampling frequencies. For each of these sampling frequencies, PDIs M0+ are calculated for different frequency bands indicated below the images. (a) fS = 10 kHz. (b) fS = 20 kHz. (c) fS = 39 kHz. (d) fS = 75 kHz.
Fig. 9
Fig. 9 Requirements in terms of sampling frequency for laser Doppler holography in the central retinal artery. For each sampling frequency, power Doppler images are spatially averaged over the depicted ROIs on the left hand side and the result is displayed in the associated plot. The STFT parameters used for each acquisition are displayed on the left and have been chosen to have σwin ≈ 13 ms for all acquisitions. (a) fS = 10 kHz, (b) fS = 20 kHz, (c) fS = 39 kHz, (d) fS = 75 kHz. Visualization 3 shows PDIs as a function of the frequency for the acquisition with fS = 75 kHz.

Equations (6)

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H ( x , y , z ) I ^ ( k x , k y ) exp ( i k z z ) exp ( i k x x + i k y y ) d k x d k y
σ win = j win f S
S ( x , y , t n , ω ) = | t n t n + σ win H ( x , y , τ ) exp ( i ω τ ) d τ | 2
M 0 ± ( x , y , t n ) = ω 1 ω 2 S ( x , y , t n , ω ) ± S ( x , y , t n , ω ) d ω
M 0 ( x , y , t n ) = ω 1 ω 2 S ( x , y , t n , ω ) S ( x , y , t n , ω ) d ω
ω D = ( k s k i ) . v

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