Abstract

We predict the capacity of near-infrared fluorescent signals to propagate through human tissue for non-invasive medical imaging. This analysis employs experimental measurements of a biologically relevant local fluorochrome embedded in tissuelike media and predicts the equivalent photon counts expected from breast, lung, brain, and muscle as a function of diameter by use of an analytical solution of the diffusion equation that can take into account large arbitrary geometries. The findings address feasibility issues for clinical studies and are relevant to recent development of near-infrared fluorescent probes and molecular beacons for in vivo applications.

© 2002 Optical Society of America

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  1. R. Weissleder, Nat. Biotechnol. 19, 316 (2001).
    [CrossRef] [PubMed]
  2. V. Ntziachristos and R. Weissleder, Opt. Lett. 26, 893 (2001).
    [CrossRef]
  3. A. Kak and M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, New York, 1988).
  4. M. A. Oleary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, Opt. Lett. 21, 158 (1996).
    [CrossRef]
  5. J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
    [CrossRef]
  6. V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
    [CrossRef]
  7. J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
    [CrossRef] [PubMed]
  8. A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
    [CrossRef] [PubMed]
  9. V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
    [CrossRef]
  10. E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
    [CrossRef]
  11. J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
    [CrossRef]
  12. J. Culver, V. Ntziachristos, M. Holboke, and A. Yodh, Opt. Lett. 26, 701 (2001).
    [CrossRef]
  13. M. J. Eppstein, D. E. Dougherty, T. L. Troy, and E. M. Sevick-Muraca, Appl. Opt. 38, 2138 (1999).
    [CrossRef]
  14. S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
    [CrossRef]

2001 (5)

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

R. Weissleder, Nat. Biotechnol. 19, 316 (2001).
[CrossRef] [PubMed]

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

J. Culver, V. Ntziachristos, M. Holboke, and A. Yodh, Opt. Lett. 26, 701 (2001).
[CrossRef]

V. Ntziachristos and R. Weissleder, Opt. Lett. 26, 893 (2001).
[CrossRef]

2000 (2)

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
[CrossRef]

1999 (2)

M. J. Eppstein, D. E. Dougherty, T. L. Troy, and E. M. Sevick-Muraca, Appl. Opt. 38, 2138 (1999).
[CrossRef]

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

1998 (1)

E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
[CrossRef]

1997 (2)

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

1996 (1)

Beek, J. F.

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

Boas, D. A.

Bogdanoy, A.

E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
[CrossRef]

Carminati, R.

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

Chance, B.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

M. A. Oleary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, Opt. Lett. 21, 158 (1996).
[CrossRef]

Cubeddu, R.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Culver, J.

Dasari, R. R.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

Dougherty, D. E.

Eppstein, M. J.

Feld, M. S.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

Giambattistelli, E.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Holboke, M.

Kak, A.

A. Kak and M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, New York, 1988).

Kramer, F. R.

S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
[CrossRef]

Li, X. D.

Ma, X. H.

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

Marecos, E.

E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
[CrossRef]

Marras, S. A. E.

S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
[CrossRef]

Nieto-Vesperinas, M.

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

Ntziachristos, V.

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

J. Culver, V. Ntziachristos, M. Holboke, and A. Yodh, Opt. Lett. 26, 701 (2001).
[CrossRef]

V. Ntziachristos and R. Weissleder, Opt. Lett. 26, 893 (2001).
[CrossRef]

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

Oleary, M. A.

Perelman, L.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

Pifferi, A.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Posthumus, P.

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

Ripoll, J.

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

Schnall, M.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

Sevick-Muraca, E. M.

Slaney, M.

A. Kak and M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, New York, 1988).

Sterenborg, H. J. C. M.

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

Taroni, P.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Torricelli, A.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Troy, T. L.

Tyagi, S.

S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
[CrossRef]

van Gemert, M. J. C.

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

van Staveren, H. J.

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

Weissleder, R.

V. Ntziachristos and R. Weissleder, Opt. Lett. 26, 893 (2001).
[CrossRef]

R. Weissleder, Nat. Biotechnol. 19, 316 (2001).
[CrossRef] [PubMed]

E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
[CrossRef]

Wu, J.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

Yodh, A.

Yodh, A. G.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

M. A. Oleary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, Opt. Lett. 21, 158 (1996).
[CrossRef]

Appl. Opt. (1)

Bioconjugate Chem. (1)

E. Marecos, R. Weissleder, and A. Bogdanoy, Bioconjugate Chem. 9, 184 (1998).
[CrossRef]

Nat. Biotechnol. (1)

R. Weissleder, Nat. Biotechnol. 19, 316 (2001).
[CrossRef] [PubMed]

Nature Biotechnol. (1)

S. Tyagi, S. A. E. Marras, and F. R. Kramer, Nature Biotechnol. 18, 1191 (2000).
[CrossRef]

Opt. Lett. (3)

Phys. Med. Biol. (2)

J. F. Beek, H. J. van Staveren, P. Posthumus, H. J. C. M. Sterenborg, and M. J. C. van Gemert, Phys. Med. Biol. 42, 2263 (1997).
[CrossRef] [PubMed]

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, and R. Cubeddu, Phys. Med. Biol. 46, 2227 (2001).
[CrossRef] [PubMed]

Phys. Rev. E (1)

J. Ripoll, V. Ntziachristos, R. Carminati, and M. Nieto-Vesperinas, Phys. Rev. E 64, 051917 (2001).
[CrossRef]

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

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Proc. Nat. Acad. Sci. U.S.A. 94, 8783 (1997).
[CrossRef]

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

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Proc. Natl. Acad. Sci. U.S.A. 97, 2767 (2000).
[CrossRef]

Rev. Sci. Instrum. (1)

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, Rev. Sci. Instrum. 70, 193 (1999).
[CrossRef]

Other (1)

A. Kak and M. Slaney, Principles of Computerized Tomographic Imaging (IEEE Press, New York, 1988).

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Figures (2)

Fig. 1
Fig. 1

(a) Middle slice (top view) through the center of the three-dimensional geometry used in the simulations and the experimental measurements. The diameter varied from 4 to 20 cm for the simulations and was set to 2.5 cm for the experimental measurements. The small circle represents a fluorochrome of 100µL volume.

Fig. 2
Fig. 2

(a) Average fluorescent photon counts expected at the peripheries of different organs as a result of the fluorochrome shown in Fig. 1, as a function of diameter. (b) Average fluorescent photon counts predicted for 2-orders-of-magnitude improvement in detection technology. Three signal-to-noise ratio levels for shot-noise-limited detection are also plotted (dashed lines).

Tables (1)

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Table 1 Optical Properties Used in the Simulations

Equations (1)

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Uflrs,rd=S0γ·Fr·Gr,rs,rd·V,

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