Abstract

Complex differential variance (CDV) provides phase-sensitive angiographic imaging for optical coherence tomography (OCT) with immunity to phase-instabilities of the imaging system and small-scale axial bulk motion. However, like all angiographic methods, measurement noise can result in erroneous indications of blood flow that confuse the interpretation of angiographic images. In this paper, a modified CDV algorithm that corrects for this noise-bias is presented. This is achieved by normalizing the CDV signal by analytically derived upper and lower limits. The noise-bias corrected CDV algorithm was implemented into an experimental 1 μm wavelength OCT system for retinal imaging that used an eye tracking scanner laser ophthalmoscope at 815 nm for compensation of lateral eye motions. The noise-bias correction improved the CDV imaging of the blood flow in tissue layers with a low signal-to-noise ratio and suppressed false indications of blood flow outside the tissue. In addition, the CDV signal normalization suppressed noise induced by galvanometer scanning errors and small-scale lateral motion. High quality cross-section and motion-corrected en face angiograms of the retina and choroid are presented.

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

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2017 (3)

2016 (4)

K. V. Chalam and K. Sambhav, “Optical coherence tomography angiography in retinal diseases,” J. Ophthalmic Vis. Res. 11(1), 84–92 (2016).
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U. Baran, W. J. Choi, and R. K. Wang, “Potential use of OCT-based microangiography in clinical dermatology,” Skin Res. Technol. 22(2), 238–246 (2016).
[Crossref] [PubMed]

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2015 (2)

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

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[Crossref] [PubMed]

2014 (4)

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]

A. S. Nam, I. Chico-Calero, and B. J. Vakoc, “Complex differential variance algorithm for optical coherence tomography angiography,” Biomed. Opt. Express 5(11), 3822–3832 (2014).
[Crossref] [PubMed]

B. Braaf, K. A. Vermeer, M. de Groot, K. V. Vienola, and J. F. de Boer, “Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions,” Biomed. Opt. Express 5(8), 2736–2758 (2014).
[Crossref] [PubMed]

Y.-J. Hong, M. Miura, M. J. Ju, S. Makita, T. Iwasaki, and Y. Yasuno, “Simultaneous Investigation of Vascular and Retinal Pigment Epithelial Pathologies of Exudative Macular Diseases by Multifunctional Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 55(8), 5016–5031 (2014).
[Crossref] [PubMed]

2013 (4)

2012 (7)

Y. Lim, Y.-J. Hong, L. Duan, M. Yamanari, and Y. Yasuno, “Passive component based multifunctional Jones matrix swept source optical coherence tomography for Doppler and polarization imaging,” Opt. Lett. 37(11), 1958–1960 (2012).
[Crossref] [PubMed]

B. Baumann, W. Choi, B. Potsaid, D. Huang, J. S. Duker, and J. G. Fujimoto, “Swept source/Fourier domain polarization sensitive optical coherence tomography with a passive polarization delay unit,” Opt. Express 20(9), 10229–10241 (2012).
[Crossref] [PubMed]

Y.-J. Hong, S. Makita, F. Jaillon, M. J. Ju, E. J. Min, B. H. Lee, M. Itoh, M. Miura, and Y. Yasuno, “High-penetration swept source Doppler optical coherence angiography by fully numerical phase stabilization,” Opt. Express 20(3), 2740–2760 (2012).
[Crossref] [PubMed]

B. Braaf, K. A. Vermeer, K. V. Vienola, and J. F. de Boer, “Angiography of the retina and the choroid with phase-resolved OCT using interval-optimized backstitched B-scans,” Opt. Express 20(18), 20516–20534 (2012).
[Crossref] [PubMed]

B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
[Crossref] [PubMed]

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 4710–4725 (2012).
[Crossref] [PubMed]

C. Blatter, J. Weingast, A. Alex, B. Grajciar, W. Wieser, W. Drexler, R. Huber, and R. A. Leitgeb, “In situ structural and microangiographic assessment of human skin lesions with high-speed OCT,” Biomed. Opt. Express 3(10), 2636–2646 (2012).
[Crossref] [PubMed]

2011 (4)

2010 (1)

2009 (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]

2008 (1)

2007 (1)

2006 (2)

2005 (2)

2003 (2)

2002 (1)

1945 (1)

S. O. Rice, “Mathematical analysis of random noise,” Bell Syst. Tech. J. 24(1), 46–156 (1945).
[Crossref]

Alex, A.

Andersen, P. E.

Arathorn, D. W.

Baran, U.

U. Baran, W. J. Choi, and R. K. Wang, “Potential use of OCT-based microangiography in clinical dermatology,” Skin Res. Technol. 22(2), 238–246 (2016).
[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]

Baumann, B.

Berger, L.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
[Crossref] [PubMed]

Bigelow, C. E.

Blatter, C.

Bouma, B.

Bouma, B. E.

B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
[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]

Braaf, B.

Cable, A.

Cense, B.

Chalam, K. V.

K. V. Chalam and K. Sambhav, “Optical coherence tomography angiography in retinal diseases,” J. Ophthalmic Vis. Res. 11(1), 84–92 (2016).
[Crossref] [PubMed]

Chen, C.-L.

Chen, T.

Cheng, Y.

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

Chico-Calero, I.

Choi, W.

Choi, W. J.

U. Baran, W. J. Choi, and R. K. Wang, “Potential use of OCT-based microangiography in clinical dermatology,” Skin Res. Technol. 22(2), 238–246 (2016).
[Crossref] [PubMed]

Ciardo, S.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

de Boer, J.

de Boer, J. F.

de Carlo, T. E.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” Int J Retina Vitreous 1(1), 5 (2015).
[Crossref] [PubMed]

de Carvalho, N.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

de Groot, M.

Dhalla, A.-H.

Ding, Z.

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

Drexler, W.

Duan, L.

Duelk, M.

Duker, J. S.

Duma, V.-F.

Ebneter, A.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
[Crossref] [PubMed]

Esmaeelpour, M.

Ferguson, R. D.

Ferrante, A. A.

Fingler, J.

Fraser, S. E.

Fujimoto, J. G.

Fukumura, D.

B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
[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]

Giannakaki-Zimmermann, H.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
[Crossref] [PubMed]

Grajciar, B.

Grana, C.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

Guo, L.

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

Hammer, D. X.

Hendargo, H. C.

Holmes, J.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

Hong, T.

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

Hong, Y.

Hong, Y.-J.

Hornegger, J.

Huang, D.

Huber, R.

Huf, W.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
[Crossref] [PubMed]

Huo, L.

Hurst, S.

Iftimia, N.

Iftimia, N. V.

Itoh, M.

Iwasaki, T.

Y.-J. Hong, M. Miura, M. J. Ju, S. Makita, T. Iwasaki, and Y. Yasuno, “Simultaneous Investigation of Vascular and Retinal Pigment Epithelial Pathologies of Exudative Macular Diseases by Multifunctional Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 55(8), 5016–5031 (2014).
[Crossref] [PubMed]

Izatt, J. A.

Jaillon, F.

Jain, R. K.

B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
[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]

Jemec, G. B.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

Jensen, O. B.

Jia, Y.

Jiang, J.

Ju, M. J.

Y.-J. Hong, M. Miura, M. J. Ju, S. Makita, T. Iwasaki, and Y. Yasuno, “Simultaneous Investigation of Vascular and Retinal Pigment Epithelial Pathologies of Exudative Macular Diseases by Multifunctional Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 55(8), 5016–5031 (2014).
[Crossref] [PubMed]

Y.-J. Hong, S. Makita, F. Jaillon, M. J. Ju, E. J. Min, B. H. Lee, M. Itoh, M. Miura, and Y. Yasuno, “High-penetration swept source Doppler optical coherence angiography by fully numerical phase stabilization,” Opt. Express 20(3), 2740–2760 (2012).
[Crossref] [PubMed]

Kampik, A.

Kästle, R.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

Khazaeinezhad, R.

Khurana, M.

Kim, D. Y.

Klein, T.

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Kurokawa, K.

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]

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Lee, B. H.

Lee, K. S.

Leitgeb, R. A.

Leung, M. K.

Li, J.

Li, P.

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Li, X.

Lim, Y.

Liu, J. J.

Lu, T.

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

Makita, S.

Manfredi, M.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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Mariampillai, A.

McNabb, R. P.

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Min, E. J.

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Mujat, M.

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Munce, N. R.

Munk, M. R.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
[Crossref] [PubMed]

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).
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Nassif, N.

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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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Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
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M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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Potsaid, B.

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T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” Int J Retina Vitreous 1(1), 5 (2015).
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Roorda, A.

Rosen, D. I.

Sambhav, K.

K. V. Chalam and K. Sambhav, “Optical coherence tomography angiography in retinal diseases,” J. Ophthalmic Vis. Res. 11(1), 84–92 (2016).
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Schmetterer, L.

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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Sheehy, C. K.

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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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Tearney, G.

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M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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Tiruveedhula, P.

Tokayer, J.

Tripathi, R.

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).
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M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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Unterhuber, A.

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R. Khazaeinezhad, M. Siddiqui, and B. J. Vakoc, “16 MHz wavelength-swept and wavelength-stepped laser architectures based on stretched-pulse active mode locking with a single continuously chirped fiber Bragg grating,” Opt. Lett. 42(10), 2046–2049 (2017).
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A. S. Nam, I. Chico-Calero, and B. J. Vakoc, “Complex differential variance algorithm for optical coherence tomography angiography,” Biomed. Opt. Express 5(11), 3822–3832 (2014).
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B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
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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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van Zeeburg, E.

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Waheed, N. K.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” Int J Retina Vitreous 1(1), 5 (2015).
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Wang, R. K.

Wang, Y.

Weingast, J.

Welzel, J.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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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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White, B.

Whitehead, R.

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
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Wieser, W.

Wilson, B. C.

Wojtkowski, M.

Wolf, S.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
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Yamanari, M.

Yang, Q.

Yang, V. X.

Yasuno, Y.

Yatagai, T.

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Zinkernagel, M. S.

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
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Appl. Opt. (1)

Bell Syst. Tech. J. (1)

S. O. Rice, “Mathematical analysis of random noise,” Bell Syst. Tech. J. 24(1), 46–156 (1945).
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Biomed. Opt. Express (9)

A. S. Nam, I. Chico-Calero, and B. J. Vakoc, “Complex differential variance algorithm for optical coherence tomography angiography,” Biomed. Opt. Express 5(11), 3822–3832 (2014).
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S. Makita, K. Kurokawa, Y.-J. Hong, M. Miura, and Y. Yasuno, “Noise-immune complex correlation for optical coherence angiography based on standard and Jones matrix optical coherence tomography,” Biomed. Opt. Express 7(4), 1525–1548 (2016).
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H. C. Hendargo, R. P. McNabb, A.-H. Dhalla, N. Shepherd, and J. A. Izatt, “Doppler velocity detection limitations in spectrometer-based versus swept-source optical coherence tomography,” Biomed. Opt. Express 2(8), 2175–2188 (2011).
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C.-L. Chen and R. K. Wang, “Optical coherence tomography based angiography,” Biomed. Opt. Express 8(2), 1056–1082 (2017).
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C. Blatter, J. Weingast, A. Alex, B. Grajciar, W. Wieser, W. Drexler, R. Huber, and R. A. Leitgeb, “In situ structural and microangiographic assessment of human skin lesions with high-speed OCT,” Biomed. Opt. Express 3(10), 2636–2646 (2012).
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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).
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B. Braaf, K. A. Vermeer, M. de Groot, K. V. Vienola, and J. F. de Boer, “Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions,” Biomed. Opt. Express 5(8), 2736–2758 (2014).
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B. Braaf, K. V. Vienola, C. K. Sheehy, Q. Yang, K. A. Vermeer, P. Tiruveedhula, D. W. Arathorn, A. Roorda, and J. F. de Boer, “Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO,” Biomed. Opt. Express 4(1), 51–65 (2013).
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T. Klein, W. Wieser, L. Reznicek, A. Neubauer, A. Kampik, and R. Huber, “Multi-MHz retinal OCT,” Biomed. Opt. Express 4(10), 1890–1908 (2013).
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Dermatology (Basel) (1)

M. Ulrich, L. Themstrup, N. de Carvalho, M. Manfredi, C. Grana, S. Ciardo, R. Kästle, J. Holmes, R. Whitehead, G. B. Jemec, G. Pellacani, and J. Welzel, “Dynamic optical coherence tomography in dermatology,” Dermatology (Basel) 232(3), 298–311 (2016).
[Crossref] [PubMed]

Int J Retina Vitreous (1)

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” Int J Retina Vitreous 1(1), 5 (2015).
[Crossref] [PubMed]

Invest. Ophthalmol. Vis. Sci. (1)

Y.-J. Hong, M. Miura, M. J. Ju, S. Makita, T. Iwasaki, and Y. Yasuno, “Simultaneous Investigation of Vascular and Retinal Pigment Epithelial Pathologies of Exudative Macular Diseases by Multifunctional Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 55(8), 5016–5031 (2014).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

Y. Cheng, L. Guo, C. Pan, T. Lu, T. Hong, Z. Ding, and P. Li, “Statistical analysis of motion contrast in optical coherence tomography angiography,” J. Biomed. Opt. 20(11), 116004 (2015).
[Crossref] [PubMed]

J. Ophthalmic Vis. Res. (1)

K. V. Chalam and K. Sambhav, “Optical coherence tomography angiography in retinal diseases,” J. Ophthalmic Vis. Res. 11(1), 84–92 (2016).
[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. Rev. Cancer (1)

B. J. Vakoc, D. Fukumura, R. K. Jain, and B. E. Bouma, “Cancer imaging by optical coherence tomography: preclinical progress and clinical potential,” Nat. Rev. Cancer 12(5), 363–368 (2012).
[Crossref] [PubMed]

Opt. Express (14)

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 4710–4725 (2012).
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B. Braaf, K. A. Vermeer, K. V. Vienola, and J. F. de Boer, “Angiography of the retina and the choroid with phase-resolved OCT using interval-optimized backstitched B-scans,” Opt. Express 20(18), 20516–20534 (2012).
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B. White, M. Pierce, N. Nassif, B. Cense, B. Park, G. Tearney, B. Bouma, T. Chen, and J. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
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R. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 µm wavelength,” Opt. Express 15(18), 11402–11412 (2007).
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S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
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M. Szkulmowski and M. Wojtkowski, “Averaging techniques for OCT imaging,” Opt. Express 21(8), 9757–9773 (2013).
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S. Yun, G. Tearney, J. de Boer, N. Iftimia, and B. Bouma, “High-speed optical frequency-domain imaging,” Opt. Express 11(22), 2953–2963 (2003).
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N. V. Iftimia, D. X. Hammer, C. E. Bigelow, D. I. Rosen, T. Ustun, A. A. Ferrante, D. Vu, and R. D. Ferguson, “Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking,” Opt. Express 14(8), 3377–3388 (2006).
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B. Vakoc, S. Yun, J. de Boer, G. Tearney, and B. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5493 (2005).
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B. Braaf, K. A. Vermeer, V. A. D. 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).
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Y.-J. Hong, S. Makita, F. Jaillon, M. J. Ju, E. J. Min, B. H. Lee, M. Itoh, M. Miura, and Y. Yasuno, “High-penetration swept source Doppler optical coherence angiography by fully numerical phase stabilization,” Opt. Express 20(3), 2740–2760 (2012).
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J. Xi, L. Huo, J. Li, and X. Li, “Generic real-time uniform K-space sampling method for high-speed swept-Source optical coherence tomography,” Opt. Express 18(9), 9511–9517 (2010).
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PLoS One (1)

M. R. Munk, H. Giannakaki-Zimmermann, L. Berger, W. Huf, A. Ebneter, S. Wolf, and M. S. Zinkernagel, “OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices,” PLoS One 12(5), e0177059 (2017).
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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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Figures (9)

Fig. 1
Fig. 1 (a) OCT intensity image showing the structures of the retina. Several large blood vessels can be identified from the hyper-reflective spots within the upper layers of the retina as denoted by red arrows. (b) The retinal angiogram obtained with conventional CDV in which blood flow and stationary tissues are indicated in white and black respectively. The large blood vessels and several others are visible by their increased CDV value and their shadows cast onto deeper tissues. The noise-bias is seen as the SNR dependence of the conventional CDV method, which creates a layered appearance of the angiogram similar to the structural image. In addition, deep areas with limited SNR give a false indication of blood flow; this makes it difficult to appreciate the choroidal vasculature. Image sizes: 1.5 mm × 4.4 mm (height × width).
Fig. 2
Fig. 2 (a) Complex A-scan pairs E(z,x,tA) and E(z,x,tB) with their complex differential A-scan D(z,x,tA,tB) for stationary tissue (left) as well as tissue with blood flow (right). The complex A-scans pairs are denoted as blue and green vector arrows while the shot noise is visualized as red vector arrows. (b) In the coherent averaging step of Eq. (2) the phasors of the complex differential A-scans are summed and result in a long phasor path for stationary tissue due to the well aligned phasors, while in the case of blood flow the path is curved and the resulting phasor is significantly smaller in length. In both cases the shot noise results in a random ‘noise cloud’ around the phasor path end and introduces a bias in the measured length compared to the pure signal length as shown by the dashed lines. Im and Re indicate the imaginary and real axes of the phasor space.
Fig. 3
Fig. 3 The scalar factor β as a function of the length of Gaussian window w(k). The blue data points are the estimated values for β obtained with the simulation. The red curve is a polynomial fit to these data points to show the trend in the decay of β with an increasing length of w(k). It can be seen that β becomes smaller when w(k) includes more pixels in depth, but does not reach zero. The lower CDV limit Ĉflow(z,x) will therefore have a significant value.
Fig. 4
Fig. 4 Experimental setup and angiography imaging protocol. (a) PS-OFDI interferometer based on a passive-component depth-multiplexed PS-OCT design. (b) Ophthalmic interface for retinal imaging. The optical paths are indicated in red for OFDI, in orange for SLO and in blue for the fixation target. (c) Angiography imaging protocol. The bidirectional triangle waveform is plotted for two segments in blue on top of the corresponding OCT intensity image of retinal structures acquired near the optic nerve head. Red and green dashed boxes denote two waveform turning points that are magnified in the inset images. In the inset images the orange line sections indicate the position offset for the backward ramp sections of each triangle wave to match their measurement positions with the forward ramp sections. Component abbreviations: FBG: fiber Bragg grating, PC: polarization controller, PBC: fiber-based polarization beam combiner, BS: beam splitter, LP: linear polarizer, PBS: polarizing beam splitter, GP: glass plate, GS: galvanometer scanner, DM: dichroic mirror, FT: fixation target, LD: laser diode.
Fig. 5
Fig. 5 Cross-sectional CDV angiography in the macula. (a) OCT intensity showing the structures of the retina. (b) Conventional CDV angiogram. This angiogram suffers from noise-bias artifacts that hide all but the larger vessels denoted by red arrows. (c) Noise-bias corrected CDV angiogram. Correction of the noise-bias suppressed the artifacts of the conventional CDV angiogram and enabled a clear observation of the smaller retinal and the choroidal vasculature. (d) Noise-bias corrected CDV angiogram without the suppression of positioning errors. This lead to increased background noise, which made it hard to observe individual retinal capillaries. Image sizes: 1.5 mm (height) × 8.8 mm (width). (e)-(h) Zoomed in sections of Figs. (a)-(d) as denoted by the blue frames. Zoomed image sizes: 0.65 mm (height) × 1.1 mm (width).
Fig. 6
Fig. 6 Noise-bias corrected CDV angiography compared to phase variance angiography. (a) OCT intensity. (b) Phase variance angiography without axial bulk motion phase correction. Several motion artifacts are seen the oscillatory phase increases indicated by red arrows. (c) Phase variance angiography after axial bulk motion phase correction. Artifacts can still be seen such as an increased background noise from lateral motion (green arrows) and a local displacement of the tissue due to arterial pulsation (blue arrow). (d) Noise-bias corrected CDV angiogram. The artifacts observed with phase variance angiography are suppressed in the CDV method. Image sizes: 1.5 mm (height) × 8.8 mm (width).
Fig. 7
Fig. 7 Motion in retinal angiograms. (a) Motion distorted retinal en face angiogram. Saccadic motion decorrelated several line segments which appear completely white thereof. On the left a graph shows the horizontal (blue) and vertical (red) position of the retina as recorded by the SLO eye tracker. A threshold on the position change was used to reject the majority of the motion artifacts. (b) Retinal en face angiogram after the segments with motion artifacts were discarded. Image sizes: 8.8 mm × 8.8 mm.
Fig. 8
Fig. 8 Wide-field CDV angiography obtained with eye tracking for motion-correction and data set compounding (10 × ). (a) Retinal angiogram showing the vasculature from the large central arteries and veins down to the capillary level. (b) Choroidal angiogram showing a dense vascular network in which the larger vessels can be distinguished from their decrease in signal. Image sizes: 8.8 mm × 8.8 mm (29° × 29°).
Fig. 9
Fig. 9 Small-field CDV angiography of the retina with eye tracking for motion-correction and data set compounding (10 × ). (a) Superficial retinal vasculature with capillaries interconnecting the arterioles and venules. (b) Deeper retinal vasculature showing lobular patterns in the capillary network. Image sizes: 4.4 mm × 4.4 mm (15° × 15°).

Equations (20)

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f C D V c o n v ( z , x , t A , t B ) = 1 C ( z , x , t A , t B ) I ( z , x , t A , t B )
C ( z , x , t A , t B ) = | ( 1 2 L + 1 ) k = L L w ( k ) E ( z k , x , t A ) E * ( z k , x , t B ) | .
I ( z , x , t A , t B ) = ( 1 2 L + 1 ) k = L L w ( k ) 2 [ | E ( z k , x , t A ) | 2 + | E ( z k , x , t B ) | 2 ] .
f C D V c o r ( z , x , t A , t B ) = 1 C ( z , x , t A , t B ) C ^ f l o w ( z , x , t A , t B ) C ^ s t a t i o n a r y ( z , x , t A , t B ) C ^ f l o w ( z , x , t A , t B )
E ( z , x , t ) = s ( z , x , t ) p ( z , x , t ) + n ( z , x , t )
D ( z , x , t A , t B ) = E ( z , x , t A ) E * ( z , x , t B ) = s ( z , x , t A ) s * ( z , x , t B ) p ( z , x , t A ) p * ( z , x , t B ) + s ( z , x , t A ) p ( z , x , t A ) n * ( z , x , t B ) + s * ( z , x , t B ) p * ( z , x , t B ) n ( z , x , t A ) + n ( z , x , t A ) n * ( z , x , t B ) .
C ^ ( z , x , t A , t B ) = σ C ( z , x , t A , t B ) π 2 L 1 / 2 ( S 2 ( z , x , t A , t B ) 2 σ C 2 ( z , x , t A , t B ) )
S ( z , x , t A , t B ) = | ( 1 2 L + 1 ) k = L L w ( k ) s ( z k , x , t A ) s * ( z k , x , t B ) p ( z , x , t A ) p * ( z , x , t B ) | .
S ( z , x , t A , t B ) = | ( 1 2 L + 1 ) k = L L w ( k ) s ( z k , x , t A ) s * ( z k , x , t B ) | .
σ D ( z , x , t A , t B ) = ( | s ( z , x , t A ) | σ n ) 2 + ( | s ( z , x , t B ) | σ n ) 2 + σ AB 2
σ C ( z , x , t A , t B ) = k = L L { ( 1 2 L + 1 ) w ( k ) σ D ( z k , x , t A , t B ) } 2 .
S i d e a l ( z , x ) = ( 1 2 L + 1 ) k = L L w ( k ) | s ( z k , x , t ) | 2 .
S s t a t i o n a r y ( z , x , α ) α S i d e a l ( z , x ) .
C ^ s t a t i o n a r y ( z , x , t A , t B ) = σ C ( z , x , t A , t B ) π 2 L 1 / 2 ( S s t a t i o n a r y 2 ( z , x , α ) 2 σ C 2 ( z , x , t A , t B ) )
S f l o w ( z , x , β ) β S i d e a l ( z , x ) .
C ^ f l o w ( z , x , t A , t B ) = σ C ( z , x , t A , t B ) π 2 L 1 / 2 ( S f l o w 2 ( z , x , β ) 2 σ C 2 ( z , x , t A , t B ) ) .
C ( z , x ) = ( 1 M ) t = 1 M [ ( 1 2 O + 1 ) k = O O y ( k ) C ( z , x k , t A , t B ) ] .
f C D V i d e a l ( z , x , t A , t B ) = f C D V c o r ( z , x , t A , t B ) ρ ( S N R ( z , x ) , f C D V c o r ( z , x , t A , t B ) )
f C D V ( z , x , t A , t B ) ¯ = p { f C D V i d e a l ( z , x , t A , t B ) | s ( z , x , t ) | 2 } p p { | s ( z , x , t ) | 2 } p
| E ( z , x , t ) | 2 | s ( z , x , t ) | 2 + 2 σ n 2

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