Abstract

We describe a complex differential variance (CDV) algorithm for optical coherence tomography based angiography. The algorithm exploits both the intensity and phase changes of optical coherence tomography (OCT) signals from flowing blood to achieve high vascular contrast, and also intrinsically reject undesirable phase signals originating from small displacement axial bulk tissue motion and instrument synchronization errors. We present this algorithm within a broader discussion of the properties of OCT signal dynamics. The performance of the algorithm is compared against two other existing algorithms using both phantom measurements and in vivo data. We show that the algorithm provides better contrast for a given number of measurements and equivalent spatial averaging.

© 2014 Optical Society of America

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References

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  1. T. Misgeld and M. Kerschensteiner, “In vivo imaging of the diseased nervous system,” Nat. Rev. Neurosci. 7(6), 449–463 (2006).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  4. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  10. A. Szkulmowska, M. Szkulmowski, D. Szlag, A. Kowalczyk, and M. Wojtkowski, “Three-dimensional quantitative imaging of retinal and choroidal blood flow velocity using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 17(13), 10584–10598 (2009).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  15. B. Braaf, K. A. Vermeer, V. A. D. P. 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]
  16. J. Fingler, D. Schwartz, C. Yang, and S. E. Fraser, “Mobility and transverse flow visualization using phase variance contrast with spectral domain optical coherence tomography,” Opt. Express 15(20), 12636–12653 (2007).
    [Crossref] [PubMed]
  17. G. Liu, L. Chou, W. Jia, W. Qi, B. Choi, and Z. Chen, “Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems,” Opt. Express 19(12), 11429–11440 (2011).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  20. L. Yu and Z. Chen, “Doppler variance imaging for three-dimensional retina and choroid angiography,” J. Biomed. Opt. 15(1), 016029 (2010).
    [Crossref] [PubMed]
  21. S. H. Yun, C. Boudoux, G. J. Tearney, and B. E. Bouma, “High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter,” Opt. Lett. 28(20), 1981–1983 (2003).
    [Crossref] [PubMed]
  22. W. Y. Oh, S. H. Yun, G. J. Tearney, and B. E. Bouma, “115 kHz tuning repetition rate ultrahigh-speed wavelength-swept semiconductor laser,” Opt. Lett. 30(23), 3159–3161 (2005).
    [Crossref] [PubMed]
  23. S. H. Yun, G. J. Tearney, J. F. de Boer, and B. E. Bouma, “Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting,” Opt. Express 12(20), 4822–4828 (2004).
    [Crossref] [PubMed]

2012 (4)

2011 (3)

2010 (2)

2009 (3)

A. Szkulmowska, M. Szkulmowski, D. Szlag, A. Kowalczyk, and M. Wojtkowski, “Three-dimensional quantitative imaging of retinal and choroidal blood flow velocity using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 17(13), 10584–10598 (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]

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[Crossref] [PubMed]

2008 (1)

2007 (2)

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]

T. Misgeld and M. Kerschensteiner, “In vivo imaging of the diseased nervous system,” Nat. Rev. Neurosci. 7(6), 449–463 (2006).
[Crossref] [PubMed]

2005 (2)

2004 (1)

2003 (2)

2000 (1)

Ahlers, C.

Alex, A.

An, L.

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]

Blatter, C.

Boudoux, C.

Bouma, B. E.

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

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[Crossref] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5493 (2005).
[Crossref] [PubMed]

W. Y. Oh, S. H. Yun, G. J. Tearney, and B. E. Bouma, “115 kHz tuning repetition rate ultrahigh-speed wavelength-swept semiconductor laser,” Opt. Lett. 30(23), 3159–3161 (2005).
[Crossref] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, and B. E. Bouma, “Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting,” Opt. Express 12(20), 4822–4828 (2004).
[Crossref] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, and B. E. Bouma, “High-speed optical frequency-domain imaging,” Opt. Express 11(22), 2953–2963 (2003).
[Crossref] [PubMed]

S. H. Yun, C. Boudoux, G. J. Tearney, and B. E. Bouma, “High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter,” Opt. Lett. 28(20), 1981–1983 (2003).
[Crossref] [PubMed]

Braaf, B.

Cable, A. E.

Chen, Z.

Choi, B.

Chou, L.

de Boer, J. F.

Drexler, W.

Fingler, J.

Fraser, S. E.

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]

Grajciar, B.

Gruber, A.

Hanson, S. R.

Hong, Y.

Huber, R.

Hurst, S.

Iftimia, N.

Jacques, S. L.

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]

Jia, W.

Jiang, J.

Kerschensteiner, M.

T. Misgeld and M. Kerschensteiner, “In vivo imaging of the diseased nervous system,” Nat. Rev. Neurosci. 7(6), 449–463 (2006).
[Crossref] [PubMed]

Khurana, M.

Kowalczyk, A.

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]

Leitgeb, R. A.

Leung, M. K. K.

Lin, A. J.

Liu, G.

Ma, Z.

Makita, S.

Mariampillai, A. A.

Misgeld, T.

T. Misgeld and M. Kerschensteiner, “In vivo imaging of the diseased nervous system,” Nat. Rev. Neurosci. 7(6), 449–463 (2006).
[Crossref] [PubMed]

Moriyama, E. H.

Motaghiannezam, R.

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]

Nelson, J. S.

Oh, W. Y.

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]

Qi, W.

Qin, J.

Saxer, C.

Schmidt-Erfurth, U.

Schmoll, T.

Schriefl, S.

Schwartz, D.

Shen, Q.

Sicam, V. A. D. P.

Singh, A. S. G.

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]

Szkulmowska, A.

Szkulmowski, M.

Szlag, D.

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]

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[Crossref] [PubMed]

W. Y. Oh, S. H. Yun, G. J. Tearney, and B. E. Bouma, “115 kHz tuning repetition rate ultrahigh-speed wavelength-swept semiconductor laser,” Opt. Lett. 30(23), 3159–3161 (2005).
[Crossref] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5493 (2005).
[Crossref] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, and B. E. Bouma, “Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting,” Opt. Express 12(20), 4822–4828 (2004).
[Crossref] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, and B. E. Bouma, “High-speed optical frequency-domain imaging,” Opt. Express 11(22), 2953–2963 (2003).
[Crossref] [PubMed]

S. H. Yun, C. Boudoux, G. J. Tearney, and B. E. Bouma, “High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter,” Opt. Lett. 28(20), 1981–1983 (2003).
[Crossref] [PubMed]

Tromberg, B. J.

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. 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]

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[Crossref] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5493 (2005).
[Crossref] [PubMed]

van Meurs, J. C.

van Zeeburg, E.

Vermeer, K. A.

Vienola, K. V.

Vitkin, I. A.

Wang, R. K.

Weingast, J.

Wieser, W.

Wilson, B. C.

Wojtkowski, M.

Xiang, S.

Yamanari, M.

Yang, C.

Yang, V. X. D.

Yasuno, Y.

Yatagai, T.

Yu, L.

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

Yun, S. H.

Zhao, Y.

Biomed. Opt. Express (4)

IEEE Trans. Med. Imaging (1)

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical Properties of Phase-Decorrelation in Phase-Resolved Doppler Optical Coherence Tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

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

T. Misgeld and M. Kerschensteiner, “In vivo imaging of the diseased nervous system,” Nat. Rev. Neurosci. 7(6), 449–463 (2006).
[Crossref] [PubMed]

Opt. Express (11)

S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, and B. E. Bouma, “High-speed optical frequency-domain imaging,” Opt. Express 11(22), 2953–2963 (2003).
[Crossref] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5493 (2005).
[Crossref] [PubMed]

B. Braaf, K. A. Vermeer, V. A. D. P. 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]

J. Fingler, D. Schwartz, C. Yang, and S. E. Fraser, “Mobility and transverse flow visualization using phase variance contrast with spectral domain optical coherence tomography,” Opt. Express 15(20), 12636–12653 (2007).
[Crossref] [PubMed]

G. Liu, L. Chou, W. Jia, W. Qi, B. Choi, and Z. Chen, “Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems,” Opt. Express 19(12), 11429–11440 (2011).
[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]

L. An, J. Qin, and R. K. Wang, “Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds,” Opt. Express 18(8), 8220–8228 (2010).
[Crossref] [PubMed]

A. Szkulmowska, M. Szkulmowski, D. Szlag, A. Kowalczyk, and M. Wojtkowski, “Three-dimensional quantitative imaging of retinal and choroidal blood flow velocity using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 17(13), 10584–10598 (2009).
[Crossref] [PubMed]

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

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[Crossref] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, and B. E. Bouma, “Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting,” Opt. Express 12(20), 4822–4828 (2004).
[Crossref] [PubMed]

Opt. Lett. (4)

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Figures (5)

Fig. 1
Fig. 1 Time characteristic of OCT signals from (a) transverse and (b) axial flows presented at three depth locations as a function of time.
Fig. 2
Fig. 2 Illustration of the CDV algorithm for static and flow voxels. In the first column, the complex signal as a function of depth is illustrated for a first (purple) and second (grey) measurement. In the second column, the complex cross correlation between these measurements are presented. In (a), a static region undergoing bulk axial motion (or a static region acquired with DAQ synchronization errors) is presented. In (b), a flow region (large displacement, axial or transverse) is presented. In (a), the correlated phase shifts across depth do not significantly alter the summed vector length in the numerator (blue) relative to the denominator (red). In (b), the numerator sums to a smaller magnitude vector relative to the numerator due to uncorrelated phase signals across depth and variations in signal amplitude across time.
Fig. 3
Fig. 3 Cross-sectional OCT images of human skin. (a) Structural image. (b) Vascular contrast computed from CDV. (c) Vascular contrast computed from phase resolved Doppler Variance. The motion and DAQ synchronization artifacts show as vertical bands in (c). Both algorithms use phase data in angiographic processing but the CDV is insensitive to the depth-correlated phase signals induced by bulk motion and DAQ synchronization errors. Scale bars = 1 mm.
Fig. 4
Fig. 4 Phantom analysis: (a) a structural image and (b) a schematic of the phantom. (c, e, and g) contrast images with marked ROIs and (d, f, and h) the histograms of CDV, IBDV, and PID algorithms, respectively. The static ROI data is marked with a dashed line and the mobile ROI data with a solid line. Scale bars = 1 mm.
Fig. 5
Fig. 5 In vivo contrast comparison: (a, d, and g) single full-field en face plane vascular contrast images of a mouse dorsal skinfold chamber and the magnified view (b, e, and h) of the ROI - marked with black rectangles, and (c, f, and i) the histograms of manually segmented regions. Scale bars = 1 mm.

Tables (3)

Tables Icon

Table 1 Characteristics of OCT signal changes from varying sources.

Tables Icon

Table 2 Summary of OCT based angiography algorithms

Tables Icon

Table 3 Algorithm performance metrics for phantom analysis

Equations (2)

Equations on this page are rendered with MathJax. Learn more.

f CDV (z)= 1 | k=L L w(k)R(zk,1) R * (zk,2) | k=L L w(k) 1 2 [ | R(zk,1) | 2 + | R(zk,2) | 2 ] ,
f CDV (z)= 1 t=1 M1 | k=L L w(k)R(zk,t) R * (zk,t+1) | t=1 M1 k=L L w(k) 1 2 [ | R(zk,t) | 2 + | R(zk,t+1) | 2 ] ,

Metrics