Abstract

We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75° to 90°. We demonstrate in vivo detection of blood flow in vessels as small as 25μm in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.

© 2008 Optical Society of America

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2007 (4)

R. K. Wang, Phys. Med. Biol. 52, N531 (2007).
[CrossRef] [PubMed]

A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, Opt. Express 15, 408 (2007).
[CrossRef] [PubMed]

J. Fingler, D. Schwartz, C. Yang, and S. E. Fraser, Opt. Express 15, 12636 (2007).
[CrossRef] [PubMed]

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

2006 (2)

2005 (4)

2004 (1)

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

2003 (2)

2002 (2)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

1949 (1)

G. H. Algire and F. Y. Legallais, J. Natl. Cancer Inst. (1940-1978) 10, 225 (1949).

Adler, D. C.

Algire, G. H.

G. H. Algire and F. Y. Legallais, J. Natl. Cancer Inst. (1940-1978) 10, 225 (1949).

Bachmann, A. H.

Barton, J. K.

Blatter, C.

Bouma, B.

Bouma, B. E.

Brezinski, M. E.

M. E. Brezinski, Optical Coherence Tomography: Principles and Applications (Academic, 2006).

Brown, A. S.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Cable, A. E.

Cense, B.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Chen, T.

Chen, Z.

Cheung, A. M.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Cucevic, V.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

de Boer, J.

Ding, Z.

Fingler, J.

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Foster, F. S.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Foster, S.

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

Fraser, S. E.

Fujimoto, J. G.

R. Huber, D. C. Adler, and J. G. Fujimoto, Opt. Lett. 31, 2975 (2006).
[CrossRef] [PubMed]

R. Huber, M. Wojtkowski, J. G. Fujimoto, J. Y. Jiang, and A. E. Cable, Opt. Express 13, 10523 (2005).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Gordon, M.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Hicklin, D. J.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Hong, Y.

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Huber, R.

Izatt, J. A.

Jiang, J. Y.

Kerbel, R. S.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Lasser, T.

Legallais, F. Y.

G. H. Algire and F. Y. Legallais, J. Natl. Cancer Inst. (1940-1978) 10, 225 (1949).

Leitgeb, R. A.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Lo, S.

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

V. Yang, M. Gordon, B. Qi, J. Pekar, S. Lo, E. Seng-Yue, A. Mok, B. Wilson, and I. Vitkin, Opt. Express 11, 794 (2003).
[CrossRef] [PubMed]

Makita, S.

Mok, A.

Nassif, N.

Needles, A.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

Nelson, J.

Oh, W. Y.

Park, B.

Pekar, J.

Pierce, M.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Qi, B.

Ren, H.

Rollins, A. M.

Roy, M.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Schwartz, D.

Seng-Yue, E.

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Stromski, S.

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Tearney, G.

Tearney, G. J.

Vakoc, B.

Villiger, M. L.

Vitkin, I.

Vitkin, I. A.

V. X. D. Yang and I. A. Vitkin, in Handbook of Optical Coherence Tomography in Cardiology (Marcel Dekker, 2006).

Vray, D.

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

Wang, R. K.

R. K. Wang, Phys. Med. Biol. 52, N531 (2007).
[CrossRef] [PubMed]

Westphal, V.

White, B.

Wilson, B.

Wilson, B. C.

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

Wojtkowski, M.

Yamanari, M.

Yang, C.

Yang, V.

Yang, V. X. D.

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

V. X. D. Yang and I. A. Vitkin, in Handbook of Optical Coherence Tomography in Cardiology (Marcel Dekker, 2006).

Yasuno, Y.

Yatagai, T.

Yazdanfar, S.

Yun, S.

Yun, S. H.

Zhao, Y.

J. Natl. Cancer Inst. (1940-1978) (1)

G. H. Algire and F. Y. Legallais, J. Natl. Cancer Inst. (1940-1978) 10, 225 (1949).

Opt. Express (9)

Opt. Lett. (3)

Phys. Med. Biol. (1)

R. K. Wang, Phys. Med. Biol. 52, N531 (2007).
[CrossRef] [PubMed]

Proc.-IEEE Ultrason. Symp. (1)

V. X. D. Yang, A. Needles, D. Vray, S. Lo, B. C. Wilson, and S. Foster, Proc.-IEEE Ultrason. Symp. 1, 453 (2004).

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Ultrasound Med. Biol. (1)

A. M. Cheung, A. S. Brown, V. Cucevic, M. Roy, A. Needles, V. X. D. Yang, D. J. Hicklin, R. S. Kerbel, and F. S. Foster, Ultrasound Med. Biol. 33, 1259 (2007).
[CrossRef] [PubMed]

Other (2)

V. X. D. Yang and I. A. Vitkin, in Handbook of Optical Coherence Tomography in Cardiology (Marcel Dekker, 2006).

M. E. Brezinski, Optical Coherence Tomography: Principles and Applications (Academic, 2006).

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Figures (4)

Fig. 1
Fig. 1

Schematic of the FDML SS-OCT system. SOA, semiconductor optical amplifier; PC, polarization controller; C, collimator; FBG, fiber Bragg grating; MZI, Mach–Zehnder interferometer; D, detector; DB, dual balanced detector.

Fig. 2
Fig. 2

a, Doppler phase shift measured for stationary Intralipid within a 600 μ m tube at an 80° Doppler angle. b–e, Doppler phase shift measured from Intralipid moving through the tube at a rate of 12 ml h for Doppler angles of 75°, 80°, 85°, 89.5°, respectively. f–g, Corresponding normalized (to fixed value for all images) speckle variance images.

Fig. 3
Fig. 3

a, Dorsal skinfold WCM. b, White light microscopy of entire window. The white box represents the approximate location of confocal and OCT imaging. c, Maximum intensity projection image of a fluorescence confocal z stack obtained using 500 kD fluorescein labeled dextran ( 1.8 × 1.8 mm ) . d, Speckle variance OCT en face projection image of vasculature without the use of any external contrast agents ( 1.8 mm × 1.8 mm ) .

Fig. 4
Fig. 4

Speckle variance OCT imaging of Visudyne-mediated PDT within a 1 mm × 1 mm region of the dorsal skinfold window chamber mouse model (fluence rate = 42 mW cm 2 , total fluence = 25 J cm 2 , treatment time = 10 min ). a, Vasculature prior to laser irradiation. b, One minute after start of laser irradiation. c, Total shutdown of right branch. d, Reperfusion of right branch with imaging artifact. e, Reperfusion of right branch without imaging artifact. f, 10 min postend of laser irradiation showing reperfusion, but main vessels still appear to be constricted.

Equations (1)

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S V i j k = 1 N i = 1 N ( I i j k I mean ) 2 ,

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