Abstract

Detection of blood flow inside the tissue sample can be achieved by measuring the local change of complex signal over time in angiographic optical coherence tomography (OCT). In conventional angiographic OCT, the transverse displacement of the imaging beam during the time interval between a pair of OCT signal measurements must be significantly reduced to minimize the noise due to the beam scanning-induced phase decorrelation at the expense of the imaging speed. Recent introduction of dual-beam scan method either using polarization encoding or two identical imaging systems in spectral-domain (SD) OCT scheme shows potential for high-sensitivity vasculature imaging without suffering from spurious phase noise caused by the beam scanning-induced spatial decorrelation. In this paper, we present multi-functional angiographic optical frequency domain imaging (OFDI) using frequency-multiplexed dual-beam illumination. This frequency multiplexing scheme, utilizing unique features of OFDI, provides spatially separated dual imaging beams occupying distinct electrical frequency bands that can be demultiplexed in the frequency domain processing. We demonstrate the 3D multi-functional imaging of the normal mouse skin in the dorsal skin fold chamber visualizing distinct layer structures from the intensity imaging, information about mechanical integrity from the polarization-sensitive imaging, and depth-resolved microvasculature from the angiographic imaging that are simultaneously acquired and automatically co-registered.

© 2015 Optical Society of America

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  5. M. C. Pierce, B. Hyle Park, B. Cense, and J. F. de Boer, “Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography,” Opt. Lett. 27(17), 1534–1536 (2002).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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2014 (3)

2013 (2)

2012 (2)

2011 (3)

2010 (1)

2009 (2)

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]

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 (1)

2005 (3)

2004 (2)

2002 (2)

M. C. Pierce, B. Hyle Park, B. Cense, and J. F. de Boer, “Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography,” Opt. Lett. 27(17), 1534–1536 (2002).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

2000 (1)

1997 (2)

An, L.

Bajraszewski, T.

R. A. Leitgeb, L. Schmetterer, C. K. Hitzenberger, A. F. Fercher, F. Berisha, M. Wojtkowski, and T. Bajraszewski, “Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography,” Opt. Lett. 29(2), 171–173 (2004).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[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.

Baumann, B.

Berisha, F.

Bonesi, M.

Bouma, B.

Bouma, B. E.

Braaf, B.

Cable, A. E.

Carmeliet, P.

P. Carmeliet, “Angiogenesis in life, disease and medicine,” Nature 438(7070), 932–936 (2005).
[Crossref] [PubMed]

Cense, B.

Chen, Z.

Chico-Calero, I.

Cho, H. S.

Choi, W.

Dan-Chin-Yu, A. V.

Dave, D.

de Boer, J.

de Boer, J. F.

Desjardins, A. E.

Duker, J. S.

Duma, V.-F.

Fercher, A. F.

R. A. Leitgeb, L. Schmetterer, C. K. Hitzenberger, A. F. Fercher, F. Berisha, M. Wojtkowski, and T. Bajraszewski, “Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography,” Opt. Lett. 29(2), 171–173 (2004).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Francis, P.

Fujimoto, J. G.

Fukumura, D.

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

Gorczynska, I.

Götzinger, E.

Gruber, A.

Grulkowski, I.

Hanson, S. R.

Hitzenberger, C. K.

Hong, Y.

Huang, D.

Hurst, S.

Hyle Park, B.

Izatt, J. A.

Jacques, S. L.

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]

Jang, S. J.

Jayaraman, V.

Jun, C.

Kim, K.

Kowalczyk, A.

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]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [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]

Lee, K. S.

Leitgeb, R.

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Leitgeb, R. A.

Liu, J. J.

Lu, C. D.

Ma, Z.

Makita, S.

Meemon, P.

Milner, T. E.

Miura, M.

Mujat, M.

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]

Nam, A. S.

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]

Park, B.

Park, B. H.

Pierce, M. C.

Pircher, M.

Potsaid, B.

Radhakrishnan, H.

V. J. Srinivasan and H. Radhakrishnan, “Total average blood flow and angiography in the rat retina,” J. Biomed. Opt. 18(7), 076025 (2013).
[Crossref] [PubMed]

Rolland, J. P.

Saxer, C.

Schmetterer, L.

Shishkov, M.

Srinivasan, V. J.

V. J. Srinivasan and H. Radhakrishnan, “Total average blood flow and angiography in the rat retina,” J. Biomed. Opt. 18(7), 076025 (2013).
[Crossref] [PubMed]

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.

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]

W. Y. Oh, S. H. Yun, B. J. Vakoc, M. Shishkov, A. E. Desjardins, B. H. Park, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing,” Opt. Express 16(2), 1096–1103 (2008).
[Crossref] [PubMed]

Torzicky, T.

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.

Vermeer, K. A.

Vienola, K. V.

Villiger, M.

Wang, R. K.

Welch, A. J.

Wilson, D. J.

Wojtkowski, M.

Xiang, S.

Yamanari, M.

Yasuno, Y.

Yatagai, T.

Yazdanfar, S.

Yun, S.

Yun, S. H.

Zhao, Y.

Zotter, S.

Appl. Opt. (1)

Biomed. Opt. Express (2)

J. Biomed. Opt. (2)

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

V. J. Srinivasan and H. Radhakrishnan, “Total average blood flow and angiography in the rat retina,” J. Biomed. Opt. 18(7), 076025 (2013).
[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]

Nature (1)

P. Carmeliet, “Angiogenesis in life, disease and medicine,” Nature 438(7070), 932–936 (2005).
[Crossref] [PubMed]

Opt. Express (12)

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]

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).
[Crossref] [PubMed]

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 µm,” Opt. Express 13(11), 3931–3944 (2005).
[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. Makita, F. Jaillon, 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. Makita, F. Jaillon, M. Yamanari, and Y. Yasuno, “Dual-beam-scan Doppler optical coherence angiography for birefringence-artifact-free vasculature imaging,” Opt. Express 20(3), 2681–2692 (2012).
[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]

W. Y. Oh, S. H. Yun, B. J. Vakoc, M. Shishkov, A. E. Desjardins, B. H. Park, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing,” Opt. Express 16(2), 1096–1103 (2008).
[Crossref] [PubMed]

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

C. Jun, M. Villiger, W. Y. Oh, and B. E. Bouma, “All-fiber wavelength swept ring laser based on Fabry-Perot filter for optical frequency domain imaging,” Opt. Express 22(21), 25805–25814 (2014).
[Crossref] [PubMed]

Opt. Lett. (7)

W. Choi, B. Potsaid, V. Jayaraman, B. Baumann, I. Grulkowski, J. J. Liu, C. D. Lu, A. E. Cable, D. Huang, J. S. Duker, and J. G. Fujimoto, “Phase-sensitive swept-source optical coherence tomography imaging of the human retina with a vertical cavity surface-emitting laser light source,” Opt. Lett. 38(3), 338–340 (2013).
[Crossref] [PubMed]

R. K. Wang, L. An, P. Francis, and D. J. Wilson, “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35(9), 1467–1469 (2010).
[Crossref] [PubMed]

R. A. Leitgeb, L. Schmetterer, C. K. Hitzenberger, A. F. Fercher, F. Berisha, M. Wojtkowski, and T. Bajraszewski, “Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography,” Opt. Lett. 29(2), 171–173 (2004).
[Crossref] [PubMed]

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, “Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media,” Opt. Lett. 22(1), 64–66 (1997).
[Crossref] [PubMed]

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[Crossref] [PubMed]

Y. Zhao, Z. Chen, C. Saxer, S. Xiang, J. F. de Boer, and J. S. Nelson, “Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity,” Opt. Lett. 25(2), 114–116 (2000).
[Crossref] [PubMed]

M. C. Pierce, B. Hyle Park, B. Cense, and J. F. de Boer, “Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography,” Opt. Lett. 27(17), 1534–1536 (2002).
[Crossref] [PubMed]

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Figures (6)

Fig. 1
Fig. 1 Principles of frequency-multiplexed dual-beam illumination. (a) Schematic of the reference arm and the sample arm of the system. (b) Frequency bands occupied by dual-beam OFDI signals: f1=2 f FS_ref and f2=2( f FS_ref + f FS_s ) .
Fig. 2
Fig. 2 System configuration. WSL, wavelength-swept laser; PM, polarization modulator; FBG, fiber Bragg grating; AFG, arbitrary function generator; Coll., collimator; BS, beam splitter; PBS, polarization beam splitter.
Fig. 3
Fig. 3 Decorrelation between the dual imaging beams due to the chromatic angular dispersion of the first-order diffracted beam caused by the sample arm frequency shifter. FS, sample arm frequency shifter; 2D GM, 2D galvanometric mirror scanner.
Fig. 4
Fig. 4 (a) Phase noise as a function of 3 dB optical bandwidth of the WSL and (b) phase noise as a function of depth in the homogeneous scattering phantom.
Fig. 5
Fig. 5 3D vasculatures of normal mouse skin in the dorsal skin fold chamber acquired with time interval of (a) 0.26 ms, (b) 2.08 ms, and (c) 8.32 ms between the two measurements by the frequency-multiplexed dual imaging beams. Depth is denoted by color: yellow (superficial) to red (deep). Scale bar, 500 μm.
Fig. 6
Fig. 6 3D multi-functional imaging. (a) Depth-projected vasculature in the dorsal skin fold of another mouse acquired with the time interval between the dual beams of 4.16 ms. (b)-(e) Cross-sectional intensity and local birefringence images at four different locations of the mouse skin on both sides of the angiographic image. Scale bar, 500 μm.

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