Abstract

We show that asymptotic lifetime-based fluorescence tomography can localize multiple-lifetime targets separated well below the diffuse point spread function of a turbid medium. This is made possible due to a complete diagonalization of the time domain forward problem in the asymptotic limit. We also show that continuous wave or direct time gate approaches to fluorescence tomography are unable to achieve this separation, indicating the unique advantage of a decay-amplitude-based approach for tomographic lifetime multiplexing with time domain data.

© 2013 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
    [CrossRef]
  2. X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
    [CrossRef]
  3. A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
    [CrossRef]
  4. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, 2006), pp. 157–199.
  5. S. B. Raymond, D. A. Boas, B. J. Bacskai, and A. T. N. Kumar, J. Biomed. Opt. 15, 046011 (2010).
    [CrossRef]
  6. R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
    [CrossRef]
  7. Z. Li and M. Niedre, Biomed. Opt. Express 2665 (2011).
    [CrossRef]
  8. F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, J. Opt. Soc. Am. A 26, 1444 (2009).
    [CrossRef]
  9. A. T. N. Kumar, E. Chung, S. B. Raymond, J. A. J. M. van de Water, K. Shah, D. Fukumura, R. K. Jain, B. J. Bacskai, and D. A. Boas, Opt. Lett. 34, 2066 (2009).
    [CrossRef]
  10. A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, IEEE Trans. Med. Imaging 27, 1152 (2008).
    [CrossRef]
  11. A. T. N. Kumar, S. B. Raymond, B. J. Bacskai, and D. A. Boas, Opt. Lett. 33, 470 (2008).
    [CrossRef]
  12. A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, Opt. Express 14, 12255 (2006).
    [CrossRef]
  13. B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
    [CrossRef]
  14. J. Chen, V. Venugopal, and X. Intes, Biomed. Opt. Express 2, 871 (2011).
    [CrossRef]

2011

2010

S. B. Raymond, D. A. Boas, B. J. Bacskai, and A. T. N. Kumar, J. Biomed. Opt. 15, 046011 (2010).
[CrossRef]

2009

2008

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, IEEE Trans. Med. Imaging 27, 1152 (2008).
[CrossRef]

A. T. N. Kumar, S. B. Raymond, B. J. Bacskai, and D. A. Boas, Opt. Lett. 33, 470 (2008).
[CrossRef]

2006

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, Opt. Express 14, 12255 (2006).
[CrossRef]

2005

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
[CrossRef]

2004

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

2003

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

Achilefu, S.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Akers, W.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Bacskai, B. J.

Boas, D. A.

Boverman, G.

Brooksby, B. A.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

Chen, J.

Chung, E.

Chung, L. W. K.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Cui, Y.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Culver, J. P.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Davis, S. C.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

Dehghani, H.

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, J. Opt. Soc. Am. A 26, 1444 (2009).
[CrossRef]

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

Dunn, A. K.

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, IEEE Trans. Med. Imaging 27, 1152 (2008).
[CrossRef]

Eppstein, M. J.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
[CrossRef]

Fukumura, D.

Gao, X.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Godavarty, A.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
[CrossRef]

Graves, E. E.

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

Intes, X.

Jain, R. K.

Kepshire, D.

Kumar, A. T. N.

Lakowicz, J. R.

J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, 2006), pp. 157–199.

Leblond, F.

Levenson, R. M.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Li, Z.

Nie, S.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Niedre, M.

Nothdurft, R. E.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Ntziachristos, V.

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

Patwardhan, S. V.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Paulsen, K. D.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

Pogue, B. W.

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, J. Opt. Soc. Am. A 26, 1444 (2009).
[CrossRef]

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

Raymond, S. B.

Ripoll, J.

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

Sevick-Muraca, E. M.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
[CrossRef]

Shah, K.

Song, X.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

van de Water, J. A. J. M.

Venugopal, V.

Weissleder, R.

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

Ye, Y.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

Biomed. Opt. Express

IEEE Trans. Med. Imaging

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, IEEE Trans. Med. Imaging 27, 1152 (2008).
[CrossRef]

J. Biomed. Opt.

B. W. Pogue, S. C. Davis, X. Song, B. A. Brooksby, H. Dehghani, and K. D. Paulsen, J. Biomed. Opt. 11, 33001 (2006).
[CrossRef]

S. B. Raymond, D. A. Boas, B. J. Bacskai, and A. T. N. Kumar, J. Biomed. Opt. 15, 046011 (2010).
[CrossRef]

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, J. Biomed. Opt. 14, 024004 (2009).
[CrossRef]

J. Opt. Soc. Am. A

Med. Phys.

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

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, Med. Phys. 32, 992 (2005).
[CrossRef]

Nat. Biotechnol.

X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie, Nat. Biotechnol. 22, 969 (2004).
[CrossRef]

Opt. Express

Opt. Lett.

Other

J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, 2006), pp. 157–199.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (3)

Fig. 1.
Fig. 1.

Dish phantom filled with intralipid and nigrosin solution to a depth of 1.7 cm, shown with the tubes. Parallel dye-filled tubes have a center-to-center separation of 5.6 (shown), 2, or 1.4 mm. Also shown are source and detector positions (o) overlaid on top of the total CW fluorescence intensity distribution for all sources.

Fig. 2.
Fig. 2.

Fluorescence lifetime amplitude maps and line profiles for each phantom measurement. The peak of the amplitude distribution for the long (aL, τL=1.27ns, red) component and the short (aS, τS=0.88ns, green) component reveals the correct position of the corresponding dye-filled tube (indicated by gray bars). The individual tube positions are not evident from the CW (integrated TD) fluorescence (black dash–dotted line).

Fig. 3.
Fig. 3.

3D fluorescence reconstructions using CW, DTD, and ATD approaches for three tube separations. Top three rows: xz projections of the reconstructions along a central slice through the phantom. The ATD and DTD yield distributions are shown for the long (ηL) and short (ηS) lifetimes as the red and green components of an RGB image. Bottom row: corresponding normalized profiles of CW and ATD yield reconstructions along a line at a depth of 8.5 mm.

Equations (1)

Equations on this page are rendered with MathJax. Learn more.

(a1ja2j)=(W¯1j00W¯2j)(η1(r)η2(r)),

Metrics