Abstract

The most common and lethal birth defects affect the cardiovascular (CV) system. The mouse is a superior model for identifying and understanding mammalian CV birth defects, but there is a great need for tools that can detect early and subtle deficiencies in cardiac function in mouse embryos. We combined swept source optical coherence tomography (SS-OCT) with live mouse embryo culture protocols to generate structural two-dimensional and three-dimensional imaging and hemodynamic measurements in a live 8.5  day embryo just a few hours after the beginning of a heartbeat. Our data show that individual circulating blood cells can be visualized with structural SS-OCT, and using Doppler SS-OCT the velocity of single moving blood cells were measured during different phases of the heartbeat cycle. These results demonstrate that Doppler SS-OCT is an extremely useful tool for structural and hemodynamic analysis at the earliest stages of mammalian blood circulation.

© 2009 Optical Society of America

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  1. M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
    [CrossRef] [PubMed]
  2. A. Mariampillai, B. A. Standish, N. R. Munce, C. Randall, G. Liu, J. Y. Jiang, A. E. Cable, I. A. Vitkin, and V. X. D. Yang, Opt. Express 15, 1627 (2007).
    [CrossRef] [PubMed]
  3. S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
    [CrossRef] [PubMed]
  4. M. W. Jenkins, O. Q. Chughtai, A. N. Basavanhally, M. Watanabe, and A. M. Rollins, J. Biomed. Opt. 12, 030505 (2007).
    [CrossRef] [PubMed]
  5. M. W. Jenkins, D. C. Adler, M. Gargesha, R. Huber, F. Rothenberg, J. Belding, M. Watanabe, D. L. Wilson, J. G. Fujimoto, and A. M. Rollins, Opt. Express 15, 6251 (2007).
    [CrossRef] [PubMed]
  6. M. W. Jenkins, F. Rothenberg, D. Roy, V. P. Nikolski, Z. Hu, M. Watanabe, D. L. Wilson, I. R. Efimov, and A. M. Rollins, Opt. Express 14, 736 (2006).
    [CrossRef] [PubMed]
  7. W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
    [CrossRef] [PubMed]
  8. E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
    [CrossRef] [PubMed]
  9. J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
    [CrossRef] [PubMed]
  10. I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
    [CrossRef]
  11. B. Vakoc, S. Yun, J. de Boer, G. Tearney, and B. Bouma, Opt. Express 13, 5483 (2005).
    [CrossRef] [PubMed]
  12. E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
    [CrossRef] [PubMed]

2008 (1)

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

2007 (4)

2006 (3)

M. W. Jenkins, F. Rothenberg, D. Roy, V. P. Nikolski, Z. Hu, M. Watanabe, D. L. Wilson, I. R. Efimov, and A. M. Rollins, Opt. Express 14, 736 (2006).
[CrossRef] [PubMed]

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

2005 (1)

2004 (1)

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

2002 (1)

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

1997 (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Adler, D. C.

Baron, M. H.

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Basavanhally, A. N.

M. W. Jenkins, O. Q. Chughtai, A. N. Basavanhally, M. Watanabe, and A. M. Rollins, J. Biomed. Opt. 12, 030505 (2007).
[CrossRef] [PubMed]

Belding, J.

Bodmer, R.

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Boppart, S. A.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Bouma, B.

Bouma, B. E.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Brezinski, M. E.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Cable, A.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Cable, A. E.

Chen, J.

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

Choma, M. A.

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Chughtai, O. Q.

M. W. Jenkins, O. Q. Chughtai, A. N. Basavanhally, M. Watanabe, and A. M. Rollins, J. Biomed. Opt. 12, 030505 (2007).
[CrossRef] [PubMed]

Crotty, D.

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

de Boer, J.

Dickinson, M. E.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Efimov, I. R.

Fraser, S. E.

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Fujimoto, J. G.

M. W. Jenkins, D. C. Adler, M. Gargesha, R. Huber, F. Rothenberg, J. Belding, M. Watanabe, D. L. Wilson, J. G. Fujimoto, and A. M. Rollins, Opt. Express 15, 6251 (2007).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Gargesha, M.

Ghosn, M.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Hu, Z.

Huang, C.

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

Huber, R.

Izatt, J. A.

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Izatt, S. D.

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Jenkins, M. W.

Jiang, J.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Jiang, J. Y.

Jones, E. A. V.

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Kulesa, P. M.

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Larin, K. V.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Larina, I. V.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Liu, G.

Lucitti, J. L.

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

Luo, W.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Mariampillai, A.

Marks, D. L.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Munce, N. R.

Nikolski, V. P.

Ralston, T. S.

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Randall, C.

Rollins, A. M.

Rothenberg, F.

Roy, D.

Southern, J. F.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Standish, B. A.

Sudheendran, N.

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

Tearney, G.

Tearney, G. J.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

Vakoc, B.

Vitkin, I. A.

Watanabe, M.

Waters, C. W.

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

Wessells, R. J.

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Wilson, D. L.

Yang, V. X. D.

Yun, S.

Am. J. Physiol. Heart Circ. Physiol. (1)

E. A. V. Jones, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Am. J. Physiol. Heart Circ. Physiol. 287, H1561 (2004).
[CrossRef] [PubMed]

Circulation (1)

M. A. Choma, S. D. Izatt, R. J. Wessells, R. Bodmer, and J. A. Izatt, Circulation 114, e35 (2006).
[CrossRef] [PubMed]

Development (1)

J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson, Development 134, 3317 (2007).
[CrossRef] [PubMed]

Genesis (1)

E. A. V. Jones, D. Crotty, P. M. Kulesa, C. W. Waters, M. H. Baron, S. E. Fraser, and M. E. Dickinson, Genesis 34, 228 (2002).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

I. V. Larina, N. Sudheendran, M. Ghosn, J. Jiang, A. Cable, K. V. Larin, and M. E. Dickinson, J. Biomed. Opt. 13, 060506 (2008).
[CrossRef]

M. W. Jenkins, O. Q. Chughtai, A. N. Basavanhally, M. Watanabe, and A. M. Rollins, J. Biomed. Opt. 12, 030505 (2007).
[CrossRef] [PubMed]

W. Luo, D. L. Marks, T. S. Ralston, and S. A. Boppart, J. Biomed. Opt. 11, 021014 (2006).
[CrossRef] [PubMed]

Opt. Express (4)

Proc. Natl. Acad. Sci. U.S.A. (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Proc. Natl. Acad. Sci. U.S.A. 94, 4256 (1997).
[CrossRef] [PubMed]

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Figures (3)

Fig. 1
Fig. 1

Live structural imaging of 8.5   day mouse embryo with SS-OCT. A, Typical 3D reconstruction of the whole embryo with the yolk sac. B, SS-OCT image depicting a cross section of a heart and a fragment of vitelline vein with individual circulating blood cells. The scale bars correspond to 100 μ m .

Fig. 2
Fig. 2

Doppler OCT velocity signals from blood cells on the embryonic day 8.5. A, Structural and corresponding color coded Doppler velocity images acquired at different phases of the heartbeat cycle. Green corresponds to zero velocity. Individual blood cells are distinguishable in the dorsal aorta. B, Magnified view of the same area showing Doppler signal from single cells as well as a small group of cells.

Fig. 3
Fig. 3

Blood flow measurements at different phases of the cardiac cycle. A, Average blood flow velocity as a function of time in the corresponding area of the dorsal aorta. Each data point corresponds to the Doppler OCT velocity measurement from an individual cell. The data points were regressed using a parabolic fit. B, Blood flow velocity profiles. Each data point corresponds to the Doppler OCT velocity measurement from an individual cell. The data points were regressed using a parabolic fit.

Equations (1)

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v = Δ φ ( 2 n k τ cos ( β ) ) ,

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