Abstract

Spectrally encoded flow cytometry (SEFC) is a promising technique for noninvasive in vivo microscopy of blood cells. Here, we introduce a novel SEFC system for label-free confocal imaging of blood cells flowing at velocities of up to 10mm/s within 65 μm-diameter vessels. The new system employs interferometric Fourier-domain detection and a high-speed wavelength-swept source, allowing 100 kHz line rate, sufficient for sampling the rapidly flowing cells 80 μm below the tissue surface. The large data sets obtained by this technique would improve diagnosis accuracy, reduce imaging time, and open new possibilities for noninvasive monitoring of blood in patients.

© 2012 Optical Society of America

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2012 (1)

2010 (1)

2009 (1)

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

2007 (2)

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

D. Yelin, W. M. White, J. T. Motz, S. H. Yun, B. E. Bouma, and G. J. Tearney, Opt. Express 15, 2432 (2007).
[CrossRef]

2006 (1)

2005 (1)

2004 (1)

1998 (1)

1997 (1)

1996 (1)

1992 (1)

1981 (1)

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

1969 (1)

R. Skalak and P. I. Branemark, Science 164, 717 (1969).
[CrossRef]

Boudoux, C.

Bouma, B.

Bouma, B. E.

Branemark, P. I.

R. Skalak and P. I. Branemark, Science 164, 717 (1969).
[CrossRef]

Briers, J. D.

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

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A. C. Burton, Phyisiology and Biophyisics of the Circulation, 2nd ed. (Year Book Medical Publishers, Inc., 1972).

Chapman, J. V.

J. V. Chapman, Noninvasive Evaluation of Hemodynamics in Congenital Heart Disease (Kluwer, 1990).

Chen, Z.

Chim, S. S. C.

Dann, E. J.

Fercher, A. F.

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Fujimoto, J. G.

Georgakoudi, I.

Golan, L.

Huber, R.

Iftimia, N.

Intaglietta, M.

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Johnson, P. C.

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Kim, S.

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Kino, G. S.

Kong, R. L.

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Larkin, K. G.

Lin, C. P.

Malekafzali, A.

Milner, T. E.

Minai, L.

Motz, J. T.

Nelson, J. S.

Novak, J.

Oh, W.

Popel, A. S.

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Prossin, A.

Shishkov, M.

Skalak, R.

R. Skalak and P. I. Branemark, Science 164, 717 (1969).
[CrossRef]

Srinivas, S.

Tearney, G.

Tearney, G. J.

van Gemert, M. J. C.

Wang, L. V.

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

Wang, X.

Webb, R. H.

Wei, X.

White, W.

White, W. M.

Wojtkowski, M.

Yeheskely-Hayon, D.

Yelin, D.

Yun, S.

Yun, S. H.

Am. J. Physiol. (1)

S. Kim, R. L. Kong, A. S. Popel, M. Intaglietta, and P. C. Johnson, Am. J. Physiol. 293, H1526 (2007).
[CrossRef]

Appl. Opt. (1)

Biomed. Opt. Express (1)

J. Opt. Soc. Am. A (1)

Nat. Photonics (1)

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

Opt. Commun. (1)

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Opt. Express (3)

Opt. Lett. (4)

Science (1)

R. Skalak and P. I. Branemark, Science 164, 717 (1969).
[CrossRef]

Other (3)

A. C. Burton, Phyisiology and Biophyisics of the Circulation, 2nd ed. (Year Book Medical Publishers, Inc., 1972).

J. V. Chapman, Noninvasive Evaluation of Hemodynamics in Congenital Heart Disease (Kluwer, 1990).

T. Wilson, ed., Confocal Microscopy (Academic, 1990).

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Figures (4)

Fig. 1.
Fig. 1.

SEFC system layout.

Fig. 2.
Fig. 2.

(a) Intensity profiles obtained from a resolution target before (solid curve) and after demodulation (dashed curve). Circle markers indicate sampling points, (b) schematic illustration of the power spectrum of a modulated signal, (c) 2D SEFC raw (before demodulation) image of a resolution target scanned at 50mm/s, (d) demodulated image using discrete Hilbert transform. Dashed white lines in (c) and (d) indicate the location of the signal profile in (a).

Fig. 3.
Fig. 3.

In vitro high-speed SEFC image of diluted whole blood. A white blood cell flowing at 12mm/s is marked by an arrow. Horizontal scale bar, 1 ms; vertical scale bar, 10 um.

Fig. 4.
Fig. 4.

(a) In vivo SEFC image of cells flowing within a 65 μm diameter vessel, acquired using a broadband source at 1.3 kHz line rate acquisition, (b) SEFC image of the same vessel (at slightly different location) captured using Fourier-domain interferometry and a wavelength-swept source at 100 kHz line rate. Insets: green widefield images of the vessel; dashed red lines mark the position of the spectrally encoded imaging lines in (a)–(c). In vivo imaging of a white blood cell flowing at 4.5mm/s. (d) In vivo imaging of slipper-shaped red blood cells flowing at 7mm/s.

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