Abstract

In conventional phase-resolved OCT blood flow is detected from phase changes between successive A-scans. Especially in high-speed OCT systems this results in a short evaluation time interval. This method is therefore often unable to visualize complete vascular networks since low flow velocities cause insufficient phase changes. This problem was solved by comparing B-scans instead of successive A-scans to enlarge the time interval. In this paper a detailed phase-noise analysis of our OCT system is presented in order to calculate the optimal time intervals for visualization of the vasculature of the human retina and choroid. High-resolution images of the vasculature of a healthy volunteer taken with various time intervals are presented to confirm this analysis. The imaging was performed with a backstitched B-scan in which pairs of small repeated B-scans are stitched together to independently control the time interval and the imaged lateral field size. A time interval of ≥2.5 ms was found effective to image the retinal vasculature down to the capillary level. The higher flow velocities of the choroid allowed a time interval of 0.64 ms to reveal its dense vasculature. Finally we analyzed depth-resolved histograms of volumetric phase-difference data to assess changes in amount of blood flow with depth. This analysis indicated different flow regimes in the retina and the choroid.

© 2012 OSA

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2012 (2)

2011 (6)

V. F. Duma, K. S. Lee, P. Meemon, and J. P. Rolland, “Experimental investigations of the scanning functions of galvanometer-based scanners with applications in OCT,” Appl. Opt. 50(29), 5735–5749 (2011).
[Crossref] [PubMed]

D. Y. Kim, J. Fingler, J. S. Werner, D. M. Schwartz, S. E. Fraser, and R. J. Zawadzki, “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express 2(6), 1504–1513 (2011).
[Crossref] [PubMed]

B. Braaf, K. A. Vermeer, V. A. Sicam, E. van Zeeburg, J. C. van Meurs, and J. F. de Boer, “Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid,” Opt. Express 19(21), 20886–20903 (2011).
[Crossref] [PubMed]

S. Makita, J. Franck, M. Yamanari, M. Miura, and Y. Yasuno, “Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography,” Opt. Express 19(2), 1271–1283 (2011).
[Crossref] [PubMed]

S. Zotter, M. Pircher, T. Torzicky, M. Bonesi, E. Götzinger, R. A. Leitgeb, and C. K. Hitzenberger, “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).
[Crossref] [PubMed]

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

2010 (5)

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

L. Yu and Z. Chen, “Doppler variance imaging for three-dimensional retina and choroid angiography,” J. Biomed. Opt. 15(1), 016029 (2010).
[Crossref] [PubMed]

A. S. Singh, C. Kolbitsch, T. Schmoll, and R. A. Leitgeb, “Stable absolute flow estimation with Doppler OCT based on virtual circumpapillary scans,” Biomed. Opt. Express 1(4), 1047–1058 (2010).
[Crossref] [PubMed]

L. An, H. M. Subhush, D. J. Wilson, and R. K. Wang, “High-resolution wide-field imaging of retinal and choroidal blood perfusion with optical microangiography,” J. Biomed. Opt. 15(2), 026011 (2010).
[Crossref] [PubMed]

Q. Yang, D. W. Arathorn, P. Tiruveedhula, C. R. Vogel, and A. Roorda, “Design of an integrated hardware interface for AOSLO image capture and cone-targeted stimulus delivery,” Opt. Express 18(17), 17841–17858 (2010).
[Crossref] [PubMed]

2009 (5)

E. Koch, J. Walther, and M. Cuevas, “Limits of Fourier domain Doppler-OCT at high velocities,” Sens. Actuators A-Phys. 156(1), 8–13 (2009).
[Crossref]

M. K. Leung, A. Mariampillai, B. A. Standish, K. K. Lee, N. R. Munce, I. A. Vitkin, and V. X. Yang, “High-power wavelength-swept laser in Littman telescope-less polygon filter and dual-amplifier configuration for multichannel optical coherence tomography,” Opt. Lett. 34(18), 2814–2816 (2009).
[Crossref] [PubMed]

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]

I. Grulkowski, I. Gorczynska, M. Szkulmowski, D. Szlag, A. Szkulmowska, R. A. Leitgeb, A. Kowalczyk, and M. Wojtkowski, “Scanning protocols dedicated to smart velocity ranging in spectral OCT,” Opt. Express 17(26), 23736–23754 (2009).
[Crossref] [PubMed]

S. Ricco, M. Chen, H. Ishikawa, G. Wollstein, and J. Schuman, “Correcting motion artifacts in retinal spectral domain optical coherence tomography via image registration,” Med. Image Comput. Comput. Assist. Interv. 12(Pt 1), 100–107 (2009).
[PubMed]

2008 (3)

2007 (3)

2006 (2)

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
[Crossref] [PubMed]

L. Zhu, Y. Zheng, C. H. von Kerczek, L. D. Topoleski, and R. W. Flower, “Feasibility of extracting velocity distribution in choriocapillaris in human eyes from ICG dye angiograms,” J. Biomech. Eng. 128(2), 203–209 (2006).
[Crossref] [PubMed]

2005 (4)

2004 (1)

2003 (3)

2002 (2)

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[Crossref]

H. Ren, K. M. Brecke, Z. Ding, Y. Zhao, J. S. Nelson, and Z. Chen, “Imaging and quantifying transverse flow velocity with the Doppler bandwidth in a phase-resolved functional optical coherence tomography,” Opt. Lett. 27(6), 409–411 (2002).
[Crossref] [PubMed]

2000 (4)

1998 (1)

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

1997 (2)

1995 (2)

X. J. Wang, T. E. Milner, and J. S. Nelson, “Characterization of fluid flow velocity by optical Doppler tomography,” Opt. Lett. 20(11), 1337–1339 (1995).
[Crossref] [PubMed]

R. W. Flower, A. W. Fryczkowski, and D. S. McLeod, “Variability in choriocapillaris blood flow distribution,” Invest. Ophthalmol. Vis. Sci. 36(7), 1247–1258 (1995).
[PubMed]

1994 (1)

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

1988 (1)

A. W. Fryczkowski and M. D. Sherman, “Scanning electron microscopy of human ocular vascular casts: the submacular choriocapillaris,” Acta Anat. (Basel) 132(4), 265–269 (1988).
[Crossref] [PubMed]

1986 (2)

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

T. J. Fallon, P. Chowiencyzk, and E. M. Kohner, “Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon,” Br. J. Ophthalmol. 70(1), 43–46 (1986).
[Crossref] [PubMed]

An, L.

L. An, H. M. Subhush, D. J. Wilson, and R. K. Wang, “High-resolution wide-field imaging of retinal and choroidal blood perfusion with optical microangiography,” J. Biomed. Opt. 15(2), 026011 (2010).
[Crossref] [PubMed]

Arathorn, D. W.

Bachmann, A. H.

Bajraszewski, T.

Barak, A.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

Bar-Tal, O. P.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

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.

Beaton, S.

Blatter, C.

Bonesi, M.

Bouma, B.

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]

Bower, B. A.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 13(6), 064003 (2008).
[Crossref] [PubMed]

Braaf, B.

Brecke, K. M.

Brown, G. C.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Burgansky-Eliash, Z.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

Cense, B.

Chen, M.

S. Ricco, M. Chen, H. Ishikawa, G. Wollstein, and J. Schuman, “Correcting motion artifacts in retinal spectral domain optical coherence tomography via image registration,” Med. Image Comput. Comput. Assist. Interv. 12(Pt 1), 100–107 (2009).
[PubMed]

Chen, T.

Chen, Z.

Chen, Z. P.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[Crossref]

Chowiencyzk, P.

T. J. Fallon, P. Chowiencyzk, and E. M. Kohner, “Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon,” Br. J. Ophthalmol. 70(1), 43–46 (1986).
[Crossref] [PubMed]

Cobbold, R. S. C.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[Crossref]

Costanza, M. A.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Cree, M. J.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Cuevas, M.

E. Koch, J. Walther, and M. Cuevas, “Limits of Fourier domain Doppler-OCT at high velocities,” Sens. Actuators A-Phys. 156(1), 8–13 (2009).
[Crossref]

Dave, D.

de Boer, J.

de Boer, J. F.

de Kinkelder, R.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Ding, Z.

Drexler, W.

Duma, V. F.

Dupont, J. C.

J. E. Grunwald, T. I. Metelitsina, J. C. Dupont, G. S. Ying, and M. G. Maguire, “Reduced foveolar choroidal blood flow in eyes with increasing AMD severity,” Invest. Ophthalmol. Vis. Sci. 46(3), 1033–1038 (2005).
[Crossref] [PubMed]

Faber, D. J.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Fabritius, T.

Fallon, T. J.

T. J. Fallon, P. Chowiencyzk, and E. M. Kohner, “Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon,” Br. J. Ophthalmol. 70(1), 43–46 (1986).
[Crossref] [PubMed]

Fercher, A.

Ferguson, R. D.

Fingler, J.

Flower, R. W.

L. Zhu, Y. Zheng, C. H. von Kerczek, L. D. Topoleski, and R. W. Flower, “Feasibility of extracting velocity distribution in choriocapillaris in human eyes from ICG dye angiograms,” J. Biomech. Eng. 128(2), 203–209 (2006).
[Crossref] [PubMed]

R. W. Flower, A. W. Fryczkowski, and D. S. McLeod, “Variability in choriocapillaris blood flow distribution,” Invest. Ophthalmol. Vis. Sci. 36(7), 1247–1258 (1995).
[PubMed]

Forrester, J. V.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Franck, J.

Fraser, S. E.

Fryczkowski, A. W.

R. W. Flower, A. W. Fryczkowski, and D. S. McLeod, “Variability in choriocapillaris blood flow distribution,” Invest. Ophthalmol. Vis. Sci. 36(7), 1247–1258 (1995).
[PubMed]

A. W. Fryczkowski and M. D. Sherman, “Scanning electron microscopy of human ocular vascular casts: the submacular choriocapillaris,” Acta Anat. (Basel) 132(4), 265–269 (1988).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Gorczynska, I.

Gordon, M. L.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[Crossref]

Götzinger, E.

Gragoudas, E. S.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Gregori, G.

Grinvald, A.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

Grulkowski, I.

Grunwald, J. E.

J. E. Grunwald, T. I. Metelitsina, J. C. Dupont, G. S. Ying, and M. G. Maguire, “Reduced foveolar choroidal blood flow in eyes with increasing AMD severity,” Invest. Ophthalmol. Vis. Sci. 46(3), 1033–1038 (2005).
[Crossref] [PubMed]

Guyer, D. R.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Hammer, D. X.

Hitzenberger, C. K.

Hong, Y.

Hope-Ross, M.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Hossain, P.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Huang, D.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 13(6), 064003 (2008).
[Crossref] [PubMed]

Huang, X.

Hurst, S.

Ishikawa, H.

S. Ricco, M. Chen, H. Ishikawa, G. Wollstein, and J. Schuman, “Correcting motion artifacts in retinal spectral domain optical coherence tomography via image registration,” Med. Image Comput. Comput. Assist. Interv. 12(Pt 1), 100–107 (2009).
[PubMed]

Izatt, J. A.

Jaillon, F.

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).
[Crossref] [PubMed]

Jiao, S.

Kalkman, J.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Kim, D. Y.

Knighton, R.

Koch, E.

E. Koch, J. Walther, and M. Cuevas, “Limits of Fourier domain Doppler-OCT at high velocities,” Sens. Actuators A-Phys. 156(1), 8–13 (2009).
[Crossref]

Kohner, E. M.

T. J. Fallon, P. Chowiencyzk, and E. M. Kohner, “Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon,” Br. J. Ophthalmol. 70(1), 43–46 (1986).
[Crossref] [PubMed]

Kok, P. H.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Kolbitsch, C.

Kowalczyk, A.

Krupsky, S.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Kulkarni, M. D.

Lanning, R. M.

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]

Lasser, T.

Lee, K. K.

Lee, K. S.

Leitgeb, R.

Leitgeb, R. A.

Leung, M. K.

Liversidge, J.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Lowenstein, A.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

Maguire, M. G.

J. E. Grunwald, T. I. Metelitsina, J. C. Dupont, G. S. Ying, and M. G. Maguire, “Reduced foveolar choroidal blood flow in eyes with increasing AMD severity,” Invest. Ophthalmol. Vis. Sci. 46(3), 1033–1038 (2005).
[Crossref] [PubMed]

Makita, S.

Manivannan, A.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Mariampillai, A.

McLeod, D. S.

R. W. Flower, A. W. Fryczkowski, and D. S. McLeod, “Variability in choriocapillaris blood flow distribution,” Invest. Ophthalmol. Vis. Sci. 36(7), 1247–1258 (1995).
[PubMed]

Meemon, P.

Metelitsina, T. I.

J. E. Grunwald, T. I. Metelitsina, J. C. Dupont, G. S. Ying, and M. G. Maguire, “Reduced foveolar choroidal blood flow in eyes with increasing AMD severity,” Invest. Ophthalmol. Vis. Sci. 46(3), 1033–1038 (2005).
[Crossref] [PubMed]

Milner, T. E.

Miura, M.

Mok, A.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[Crossref]

Mujat, M.

Munce, N. R.

Munn, L. L.

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]

Nassif, N.

Nelson, D. A.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref] [PubMed]

Nelson, J. S.

Ohtsuki, H.

T. Okanouchi, F. Shiraga, I. Takasu, Y. Tsuchida, and H. Ohtsuki, “Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes,” Jpn. J. Ophthalmol. 47(6), 572–577 (2003).
[Crossref] [PubMed]

I. Takasu, F. Shiraga, T. Okanouchi, Y. Tsuchida, and H. Ohtsuki, “Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes,” Invest. Ophthalmol. Vis. Sci. 41(10), 2844–2848 (2000).
[PubMed]

Okanouchi, T.

T. Okanouchi, F. Shiraga, I. Takasu, Y. Tsuchida, and H. Ohtsuki, “Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes,” Jpn. J. Ophthalmol. 47(6), 572–577 (2003).
[Crossref] [PubMed]

I. Takasu, F. Shiraga, T. Okanouchi, Y. Tsuchida, and H. Ohtsuki, “Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes,” Invest. Ophthalmol. Vis. Sci. 41(10), 2844–2848 (2000).
[PubMed]

Orlock, D. A.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Padera, T. P.

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]

Park, B.

Paunescu, L. A.

Pierce, M.

Pierce, M. C.

Pircher, M.

Puliafito, C.

Puliafito, C. A.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Ren, H.

Ricco, S.

S. Ricco, M. Chen, H. Ishikawa, G. Wollstein, and J. Schuman, “Correcting motion artifacts in retinal spectral domain optical coherence tomography via image registration,” Med. Image Comput. Comput. Assist. Interv. 12(Pt 1), 100–107 (2009).
[PubMed]

Rohrer, K. T.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Rolland, J. P.

Rollins, A. M.

Roorda, A.

Saxer, C.

Schmetterer, L.

Schmoll, T.

Schraa, O.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Schuman, J.

S. Ricco, M. Chen, H. Ishikawa, G. Wollstein, and J. Schuman, “Correcting motion artifacts in retinal spectral domain optical coherence tomography via image registration,” Med. Image Comput. Comput. Assist. Interv. 12(Pt 1), 100–107 (2009).
[PubMed]

Schuman, J. S.

Schwartz, D.

Schwartz, D. M.

Sharp, P. F.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
[PubMed]

Shen, Q.

Sherman, M. D.

A. W. Fryczkowski and M. D. Sherman, “Scanning electron microscopy of human ocular vascular casts: the submacular choriocapillaris,” Acta Anat. (Basel) 132(4), 265–269 (1988).
[Crossref] [PubMed]

Shields, W.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Shiraga, F.

T. Okanouchi, F. Shiraga, I. Takasu, Y. Tsuchida, and H. Ohtsuki, “Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes,” Jpn. J. Ophthalmol. 47(6), 572–577 (2003).
[Crossref] [PubMed]

I. Takasu, F. Shiraga, T. Okanouchi, Y. Tsuchida, and H. Ohtsuki, “Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes,” Invest. Ophthalmol. Vis. Sci. 41(10), 2844–2848 (2000).
[PubMed]

Sicam, V. A.

Singh, A. S.

Slakter, J. S.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Sobel, R. S.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Sorenson, J. A.

M. Hope-Ross, L. A. Yannuzzi, E. S. Gragoudas, D. R. Guyer, J. S. Slakter, J. A. Sorenson, S. Krupsky, D. A. Orlock, and C. A. Puliafito, “Adverse reactions due to indocyanine green,” Ophthalmology 101(3), 529–533 (1994).
[PubMed]

Standish, B. A.

Stylianopoulos, T.

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]

Subhush, H. M.

L. An, H. M. Subhush, D. J. Wilson, and R. K. Wang, “High-resolution wide-field imaging of retinal and choroidal blood perfusion with optical microangiography,” J. Biomed. Opt. 15(2), 026011 (2010).
[Crossref] [PubMed]

Sylwestrzak, M.

Szkulmowska, A.

Szkulmowski, M.

Szlag, D.

Takasu, I.

T. Okanouchi, F. Shiraga, I. Takasu, Y. Tsuchida, and H. Ohtsuki, “Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes,” Jpn. J. Ophthalmol. 47(6), 572–577 (2003).
[Crossref] [PubMed]

I. Takasu, F. Shiraga, T. Okanouchi, Y. Tsuchida, and H. Ohtsuki, “Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes,” Invest. Ophthalmol. Vis. Sci. 41(10), 2844–2848 (2000).
[PubMed]

Tan, O.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 13(6), 064003 (2008).
[Crossref] [PubMed]

Tearney, G.

Tearney, G. J.

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]

Tindel, L. J.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Tiruveedhula, P.

Topoleski, L. D.

L. Zhu, Y. Zheng, C. H. von Kerczek, L. D. Topoleski, and R. W. Flower, “Feasibility of extracting velocity distribution in choriocapillaris in human eyes from ICG dye angiograms,” J. Biomech. Eng. 128(2), 203–209 (2006).
[Crossref] [PubMed]

Torzicky, T.

Tsuchida, Y.

T. Okanouchi, F. Shiraga, I. Takasu, Y. Tsuchida, and H. Ohtsuki, “Evaluation of the dynamics of choroidal circulation in experimental acute hypertensionusing indocyanine green-stained leukocytes,” Jpn. J. Ophthalmol. 47(6), 572–577 (2003).
[Crossref] [PubMed]

I. Takasu, F. Shiraga, T. Okanouchi, Y. Tsuchida, and H. Ohtsuki, “Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes,” Invest. Ophthalmol. Vis. Sci. 41(10), 2844–2848 (2000).
[PubMed]

Tyrrell, J. 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]

Vakoc, B.

Vakoc, B. J.

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]

van Leeuwen, T. G.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

van Meurs, J. C.

van Zeeburg, E.

Verbraak, F. D.

R. de Kinkelder, J. Kalkman, D. J. Faber, O. Schraa, P. H. Kok, F. D. Verbraak, and T. G. van Leeuwen, “Heartbeat-induced axial motion artifacts in optical coherence tomography measurements of the retina,” Invest. Ophthalmol. Vis. Sci. 52(6), 3908–3913 (2011).
[Crossref] [PubMed]

Vermeer, K. A.

Vieira, P.

P. Hossain, J. Liversidge, M. J. Cree, A. Manivannan, P. Vieira, P. F. Sharp, G. C. Brown, and J. V. Forrester, “In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics,” Invest. Ophthalmol. Vis. Sci. 39(10), 1879–1887 (1998).
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Supplementary Material (2)

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Figures (11)

Fig. 1
Fig. 1

Phase-noise measurement in a model eye. (A) The static galvanometer scanner noise was measured without scanning the OCT beam. (B) The dynamic galvanometer scanner noise was determined by measuring the phase-noise from inter-B-scan phase-difference values from successive B-scans. In both (A) and (B) examples of the experiment are shown with the intensity image at the top and the phase-difference image at the bottom. (C) The phase-noise as a function of the time interval and lateral scan width. The phase-noise is plotted when the galvanometer scanners are switched off (red), switched on but kept still (blue), and scanned over three lateral scan widths: 1.05 mm (black), 4.21 mm (green), and 8.56 mm (orange). The galvanometer scanners cause a significant amount of phase-noise which is attributed to electrical noise and scanning errors.

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Fig. 2
Fig. 2

In vivo phase-noise measurement due to sample motion. (A) The scanners were off and A-scans were acquired for a period of 0.1s (10,000 A-scans). The top figure shows the intensity image, the bottom figure shows the phase-difference image for a time interval of 1.0 ms (100 A-scans). The phase-noise was analyzed from the RPE layer (red box) to avoid interference with blood flow. (B) The phase-noise due to sample motion (black) and the static galvanometer scanner phase-noise (blue) from Fig. 1 as a function of the time interval. The phase-noise due to sample motion becomes dominant for time intervals above 0.25 ms (25 A-scans).

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Fig. 3
Fig. 3

The SNRs-levels as a function of the time interval that give an equivalent amount of phase-noise as the combined phase-noise of the galvanometer scanners and sample motion. The phase-noise is dominated by the SNRs if the SNR of a measurement falls below the red line.

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Fig. 4
Fig. 4

Observable flow velocities as a function of the time interval for Doppler angles of 85° (A) and 89° (B). The blue areas indicate observable flow velocities for which the wrapped phase-difference signals exceed the phase-noise. The white areas indicate unobservable flow velocities that are buried in the phase-noise.

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Fig. 5
Fig. 5

(A) An example of the backstitched B-scan (in blue) that is used for inter-B-scan phase-resolved OFDI imaging with a time interval of 2.5 ms (250 A-scans). The corresponding intensity image is plotted in the background. An example of a single B-scan is marked by the solid orange box. The subsequent B-scan without flyback is marked by the dashed orange box. In order to prevent gaps in between successive sets of repeated B-scans a small overlap is used as shown in green in the inset. The backstitched B-scan returns to its initial location with a long flyback as shown right from the yellow line. (B&C) The B-scans over the full lateral scan width as reconstructed from the backstitched B-scan corresponding respectively to the first (B) and second (C) B-scan of each set.

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Fig. 6
Fig. 6

Pre-processing of inter-B-scan phase-difference images. (A) The inter-B-scan phase-difference image as calculated from Fig. 5(B) and 5(C). (B) The absolute phase-difference is calculated to avoid cancellation of positive and negative flows. (C) A threshold on the SNR is applied to reject noise from low SNR regions. (D) Median filtering and a threshold on the absolute phase-difference are used to minimize remaining phase-noise. Flow in the retinal vessels are visible as white dots, flow in the choroid is visible as a dense white band.

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Fig. 7
Fig. 7

En-face flow images of the retina in the macular area for a 2.1 x 2.1 mm2 area. Increasing time intervals of 0.01 ms (A), 0.64 ms (B), 1.25 ms (C), 2.50 ms (D), 3.75 ms (E), and 5.00 ms (F) were used to improve the visualization of the capillary network, which is optimal for time intervals ≥2.50 ms. White horizontal lines indicate eye motion artifacts.

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Fig. 8
Fig. 8

En-face flow images of the choroid in the macular area for a 2.1 x 2.1 mm2 area. Increasing time intervals of 0.01 ms (A), 0.64 ms (B), 1.25 ms (C) were used for a better visualization of the blood flow. The shown images were derived from the same data sets as for Figs. 7(A)–7(C). The fast flow of the choroid is only partly visible with the shortest time interval while longer time intervals reveal a dense vessel network.

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Fig. 9
Fig. 9

Wide-field en-face images of blood flow in the retina for a 6.0 x 7.9 mm2 (20° x 26.3°) area. Increasing time intervals of 0.01 ms (A), 0.64 ms (B), 1.25 ms (C) and 2.50 ms (D) were used to improve the visualization of the vasculature. For comparison the retinal intensity shadowgram is shown in (E). It can be seen that the shortest time interval shows only the central retinal arteries and veins. The flow signal is however discontinuous along the vessels due to the cardiac cycle and vessel orientation changes. Increasing the time interval gradually shows more of the vasculature including small arteries and veins, arterioles and venules, and capillaries. Although the shadowgram gives a clear view on the central arteries and veins, smaller vasculature cannot be resolved. High-resolution versions of the images can be downloaded here in PDF. (Media 1)

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Fig. 10
Fig. 10

Wide-field en-face images of blood flow in the choroid for a 6.0 x 7.9 mm2 (20° x 26.3°) area. Increasing time intervals of 0.01 ms (A), 0.64 ms (B), and 1.25 ms (C) were used to improve the visualization of the vasculature. For comparison the choroidal intensity en-face image is shown in (D). The shortest time interval shows individual vessels within the choroid, but the flow signal is often discontinuous due to the cardiac cycle and vessel orientation changes. Further several localized spot of flow are seen that are likely due to vertically oriented vessels. Increasing the time interval shows a very dense vascular network. Although individual vessels can be seen it is not possible to distinctly observe the different vascular types. In the integrated intensity en-face image it is hard to identify individual vessels due to insufficient intensity contrast between vessels and surrounding tissues. High-resolution versions of the images can be downloaded here in PDF. (Media 2)

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Fig. 11
Fig. 11

Schematic description of the proposed flow analysis on volumetric phase-difference data. (Inset) Histogram analysis was performed on the phase-difference values of single-pixel layers. Each layer shows a Gaussian distribution for which the standard deviation, σΔϕ group, is a measure of the amount of blood flow. (Main) A graph of σΔϕ group as a function of depth which shows absence of flow in the RPE (low values) compared to the rest of the retina (moderate increase) and the choroid (significant increase).

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Tables (2)

Tables Icon

Table 1 Flow velocity ranges for the retinal and the choroidal vasculature and the corresponding time intervals that are required for imaging phase-resolved OCT. The time intervals are given for Doppler angles of 85° and 89° that are expected to reside within the macular region. *Partially obtained from animal studies.

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Table 2 Backstitched B-scan parameters for the time intervals used in this study. All backstitched B-scans covered a width of 2.1 mm on the retinal surface. The time interval 0.01 ms used conventional phase-resolved OCT without backstitched B-scans. All numbers that are expressed in #A-scans can be converted to time by division through the swept-source repetition rate: 100,000 A-scans/s. The predicted phase-noise was obtained in section 3.3 in which spot-overlap mismatch was minimal.

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Δϕ= 4 π n τ  v flow λ 0  cos( α ),
σ Δϕ = ( 1 SN R s )+( 4π 3 )( 1−exp( −2 ( Δ x d ) 2 ) )  .

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