Abstract

The highly diffuse nature of light propagation in biological tissue is a major challenge for obtaining high-fidelity fluorescence tomographic images. In this work we investigated the use of time-gated detection of early-arriving photons for reducing the effects of light scatter in mice relative to quasi-cw photons. When analyzing sinographic representations of the measured data, it was determined that early photons allowed a reduction in the measured FWHM of fluorescent targets by a factor of approximately 2–3, yielding a significant improvement in the tomographic image reconstruction quality.

© 2010 Optical Society of America

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  1. V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
    [CrossRef]
  2. E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
    [CrossRef] [PubMed]
  3. A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  6. W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  14. M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
    [CrossRef]

2009 (1)

2008 (1)

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

2007 (2)

2006 (3)

A. Soubret and V. Ntziachristos, Phys. Med. Biol. 51, 3983 (2006).
[CrossRef] [PubMed]

M. J. Niedre, G. M. Turner, and V. Ntziachristos, J. Biomed. Opt. 11, 064017 (2006).
[CrossRef]

B. W. Pogue and M. S. Patterson, J. Biomed. Opt. 11, 041102 (2006).
[CrossRef] [PubMed]

2005 (1)

A. Soubret, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 24, 1377 (2005).
[CrossRef] [PubMed]

2003 (1)

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

2002 (3)

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

1997 (1)

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

1996 (1)

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Abdoulaev, G. S.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Aikawa, E.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Alfano, R. R.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Beuthan, J.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Bluestone, A. Y.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Bremer, C.

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Cai, W.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Das, B. B.

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Dasari, R. R.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

de Kleine, R. H.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Dehghani, H.

Deliolanis, N.

Feld, M. S.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

Graves, E. E.

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Hielscher, A. H.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Hyde, D.

Kepshire, D.

Kirsch, D. G.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Klose, A. D.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Lasker, J.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Lasser, T.

Lax, M.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Leblond, F.

Liu, F.

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Netz, U.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Niedre, M. J.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

M. J. Niedre, G. M. Turner, and V. Ntziachristos, J. Biomed. Opt. 11, 064017 (2006).
[CrossRef]

Ntziachristos, V.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, and V. Ntziachristos, Opt. Lett. 32, 382 (2007).
[CrossRef] [PubMed]

G. M. Turner, A. Soubret, and V. Ntziachristos, Med. Phys. 34, 1405 (2007).
[CrossRef] [PubMed]

M. J. Niedre, G. M. Turner, and V. Ntziachristos, J. Biomed. Opt. 11, 064017 (2006).
[CrossRef]

A. Soubret and V. Ntziachristos, Phys. Med. Biol. 51, 3983 (2006).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 24, 1377 (2005).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Patterson, M. S.

B. W. Pogue and M. S. Patterson, J. Biomed. Opt. 11, 041102 (2006).
[CrossRef] [PubMed]

Perelman, L.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

Pogue, B. W.

Ripoll, J.

N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, and V. Ntziachristos, Opt. Lett. 32, 382 (2007).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 24, 1377 (2005).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Soubret, A.

G. M. Turner, A. Soubret, and V. Ntziachristos, Med. Phys. 34, 1405 (2007).
[CrossRef] [PubMed]

N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, and V. Ntziachristos, Opt. Lett. 32, 382 (2007).
[CrossRef] [PubMed]

A. Soubret and V. Ntziachristos, Phys. Med. Biol. 51, 3983 (2006).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 24, 1377 (2005).
[CrossRef] [PubMed]

Stewart, M.

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

Turner, G. M.

G. M. Turner, A. Soubret, and V. Ntziachristos, Med. Phys. 34, 1405 (2007).
[CrossRef] [PubMed]

M. J. Niedre, G. M. Turner, and V. Ntziachristos, J. Biomed. Opt. 11, 064017 (2006).
[CrossRef]

Weissleder, R.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Wu, J.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

Xu, M.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

Zevallos, M.

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

Dis. Markers (1)

A. H. Hielscher, A. Y. Bluestone, G. S. Abdoulaev, A. D. Klose, J. Lasker, M. Stewart, U. Netz, and J. Beuthan, Dis. Markers 18, 313 (2002).

IEEE Trans. Med. Imaging (1)

A. Soubret, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 24, 1377 (2005).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

M. J. Niedre, G. M. Turner, and V. Ntziachristos, J. Biomed. Opt. 11, 064017 (2006).
[CrossRef]

B. W. Pogue and M. S. Patterson, J. Biomed. Opt. 11, 041102 (2006).
[CrossRef] [PubMed]

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

Med. Phys. (2)

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

G. M. Turner, A. Soubret, and V. Ntziachristos, Med. Phys. 34, 1405 (2007).
[CrossRef] [PubMed]

Mol. Imaging (1)

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, Mol. Imaging 1, 82 (2002).
[CrossRef]

Opt. Lett. (1)

Phys. Med. Biol. (1)

A. Soubret and V. Ntziachristos, Phys. Med. Biol. 51, 3983 (2006).
[CrossRef] [PubMed]

Phys. Rev. E (1)

M. Xu, W. Cai, M. Lax, and R. R. Alfano, Phys. Rev. E 65, 066609 (2002).
[CrossRef]

Proc. Natl. Acad. Sci. USA (3)

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Natl. Acad. Sci. USA 94, 8783 (1997).
[CrossRef] [PubMed]

W. Cai, B. B. Das, F. Liu, M. Zevallos, M. Lax, and R. R. Alfano, Proc. Natl. Acad. Sci. USA 93, 13561 (1996).
[CrossRef] [PubMed]

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Figures (3)

Fig. 1
Fig. 1

Fluorescence tomographic imaging system used in these experiments. Early-arriving and quasi-cw photons from the pulsed femtosecond laser were detected with the gated ICCD.

Fig. 2
Fig. 2

Sinograms of the transmitted normalized fluorescence intensity at each lateral position as a function of rotation angle at (a) early and (d) quasi-cw time gates. Transmitted normalized intensity profiles with the mouse oriented at 0° rotation for (b) early and (e) quasi-cw time gates as well as (c),(f) the corresponding profiles for 90° rotation are shown. See text for detailed description of temporal gates.

Fig. 3
Fig. 3

(a),(d) X-ray computed tomography images of two axial slices through the torso of the animal, indicating the location of the implanted tubes (arrows) as well as the corresponding normalized reconstructed fluorescence tomographic images for (b),(e) early-arriving and (c),(f) quasi-cw time gates. The upper slice (a)–(c) corresponds to the data from Fig. 2 where both tubes were present, whereas in the lower slice (d)–(f) only the longer central tube was visible. A display threshold of 50% of the maximum reconstructed intensity was applied to each image.

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