Abstract

We report on a systematic study of upconverting fluorescence signal generation within turbid phantoms and real tissues. An accurate three-point Green’s function, describing the forward model of photon propagation, is established and experimentally validated. We further demonstrate, for the first time to our knowledge, autofluorescence-free transillumination imaging of mice that have received biocompatible upconverting nanoparticles. The method holds great promise for artifact-free whole-body visualization of optical molecular probes.

© 2009 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
    [PubMed]
  2. G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
    [CrossRef] [PubMed]
  3. V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
    [CrossRef] [PubMed]
  4. A. Soubret and V. Ntziachristos, Phys. Med. Biol. 51, 3983 (2006).
    [CrossRef] [PubMed]
  5. S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
    [CrossRef]

2009 (1)

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

2006 (2)

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

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

2005 (2)

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

Grimm, J.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Hilderbrand, S. A.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

Kambara, H.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Mahmood, U.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

Ntziachristos, V.

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

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

Ripoll, J.

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Saekl, Y.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Salthouse, C.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

Shao, F.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

Shih, H.

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Soubret, A.

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

Wang, L.

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

Weissleder, R.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Zacharakis, G.

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

Chem. Commun. (1)

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, Chem. Commun. 28, 4188 (2009).
[CrossRef]

Mol. Imaging (1)

G. Zacharakis, H. Shih, J. Ripoll, R. Weissleder, and V. Ntziachristos, Mol. Imaging 5, 153 (2006).
[PubMed]

Nat. Biotechnol. (1)

V. Ntziachristos, J. Ripoll, L. Wang, and R. Weissleder, Nat. Biotechnol. 23, 313 (2005).
[CrossRef] [PubMed]

Phys. Med. Biol. (1)

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

Proc. Natl. Acad. Sci. USA (1)

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saekl, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 102, 18252 (2005).
[CrossRef] [PubMed]

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 (2)

Fig. 1
Fig. 1

(a) Cy5.5 fluorescence signal as a function of the excitation power (open circles). Thick and thin lines represent the theoretical dependence and the best fit, respectively. (b) Upconverting nanoparticle fluorescence signal (squares). The line represents the best fit, demonstrating a nonlinear dependence (slope n = 2.26 ) of the fluorescence intensity on the excitation intensity For the Cy5.5 fluorescence signal (linear dependence), n = 0.97 . (c) Intensity of the fluorescence signal at fixed excitation illumination for a 500 μ m diameter glass tube filled with a drop of Cy5.5 or UNP (top and bottom lines respectively). The signal is measured in transillumination mode as a function of depth within a chamber filled with an optically tissue-equivalent phantom that consists of intralipid and black India ink. Fluorescence detected at 710 nm after excitation at 680 nm for Cy5.5 (open circles) and upconverting fluorescence detected at 670 nm after excitation at 980 nm for UNP (filled squares) is plotted. Inset, the geometry of the experiment.

Fig. 2
Fig. 2

(a) White-light epi-illumination images of the mouse with a glass capillary tube inserted into the esophagus. The tube is filled with either Cy5.5 (upper row, excited at 680 nm ) or upconverting nanoparticles (lower row, excited at 980 nm ). Transillumination images averaged over all 36 sources are presented for (b) the intrinsic (c) the autofluorescence, and (d) the fluorescence signals. The transillumination signal is overlaid on top of the corresponding white image after color mapping.

Equations (3)

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

G exc NP ( r s , r ) = ( e k 1 | r s r | | r s r | ) n = e n k 1 | r s r | | r s r | n ,
G fluo NP ( r , r d ) = e k 2 | r r d | | r r d | ,
U ( r s , r ) G exc NP ( r s , r ) A ( r ) G fluo NP ( r , r d ) d S ,

Metrics