Abstract

We derive a novel algorithm to recover the in vivo distributions of fluorophores based on an asymptotic lifetime analysis of time-domain fluorescence measurements with turbid tissue. We experimentally demonstrate the advantage offered by this method in localizing fluorophores with distinct lifetimes. This algorithm has wide applicability for diagnostic fluorescence imaging in the presence of several-centimeter-thick biological tissue, since fluorescence lifetime is a sensitive indicator of local tissue environment and interactions at the molecular level.

© 2005 Optical Society of America

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References

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2005

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

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, Nat. Biotechnol. 23, 314 (2005).
[CrossRef]

2003

2001

2000

P. R. Selvin, Nat. Struct. Biol. 7, 730 (2000).
[CrossRef] [PubMed]

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

1999

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

P. I.H. Bastiaens and A. Squire, Trends Cell Biol. 9, 48 (1999).
[CrossRef] [PubMed]

1996

1994

1989

Alfano, R. R.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

Alrubaiee, M.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

Barton, G.

G. Barton, Elements of Green's Functions and Propagation (Oxford U. Press, 1989).

Bastiaens, P. I.H.

P. I.H. Bastiaens and A. Squire, Trends Cell Biol. 9, 48 (1999).
[CrossRef] [PubMed]

Boas, D. A.

Chance, B.

Chen, K.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Das, B. B.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

Dasari, R. R.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Eppstein, M. J.

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

Feld, M. S.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Gayen, S. K.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

Godavarty, A.

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

Li, X. D.

Matthews, J.

J. Matthews and R. L. Walker, Mathematical Methods of Physics, 2nd ed. (Addison-Wesley, 1970).

Ntziachristos, V.

Oleary, M. A.

Patterson, M. S.

Perelman, L. T.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Pogue, B. W.

Ripoll, J.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, Nat. Biotechnol. 23, 314 (2005).
[CrossRef]

G. M. Turner, G Zacharakis, A. Sourbet, J. Ripoll, and V. Ntziachristos, Opt. Lett. 30, 409 (2003).
[CrossRef]

Selvin, P. R.

P. R. Selvin, Nat. Struct. Biol. 7, 730 (2000).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

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

Sourbet, A.

Squire, A.

P. I.H. Bastiaens and A. Squire, Trends Cell Biol. 9, 48 (1999).
[CrossRef] [PubMed]

Turner, G. M.

Walker, R. L.

J. Matthews and R. L. Walker, Mathematical Methods of Physics, 2nd ed. (Addison-Wesley, 1970).

Wang, L. V.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, Nat. Biotechnol. 23, 314 (2005).
[CrossRef]

Weissleder, R.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, Nat. Biotechnol. 23, 314 (2005).
[CrossRef]

Wessleder, R

Wilson, B. C.

Yodh, A. G.

Zacharakis, G

Zevallos, M. E.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

Zhang, Q. G.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Appl. Opt.

IEEE J. Sel. Top. Quantum Electron.

M. E. Zevallos, S. K. Gayen, B. B. Das, M. Alrubaiee, and R. R. Alfano, IEEE J. Sel. Top. Quantum Electron. 5, 916 (1999).
[CrossRef]

J. Biomed. Opt.

K. Chen, L. T. Perelman, Q. G. Zhang, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 5, 144 (2000).
[CrossRef] [PubMed]

Med. Phys.

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

Nat. Biotechnol.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, Nat. Biotechnol. 23, 314 (2005).
[CrossRef]

Nat. Struct. Biol.

P. R. Selvin, Nat. Struct. Biol. 7, 730 (2000).
[CrossRef] [PubMed]

Opt. Lett.

Trends Cell Biol.

P. I.H. Bastiaens and A. Squire, Trends Cell Biol. 9, 48 (1999).
[CrossRef] [PubMed]

Other

J. Matthews and R. L. Walker, Mathematical Methods of Physics, 2nd ed. (Addison-Wesley, 1970).

G. Barton, Elements of Green's Functions and Propagation (Oxford U. Press, 1989).

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Figures (2)

Fig. 1
Fig. 1

Simulated contours of constant asymptotic decay time of TD diffuse signals as a function of absorption and reduced scattering. The simulations assumed a perturbation at the center of a homogeneous slab, with a single-source–detector pair in the transmission geometry. Slab thickness (a) 2 cm, (b) 10 cm. The darker shaded region to the right of each contour gives the optical properties for which a fluorescence decay with lifetime corresponding to the contour lifetime can be recovered asymptotically from TD measurements.

Fig. 2
Fig. 2

Demonstration of lifetime-based tomography with experimental data. (a) Measurement geometry, with two tubes (0.5 mm inner diameter) immersed at depths 1.2 and 0.7 cm in an Intralipid + ink solution ( μ a = 0.1 cm 1 , μ s = 10 cm 1 ) in a phantom, and filled with fluorophores of lifetimes 0.5 and 0.8 ns, respectively. (b) Reconstruction of fluorescence yield by using the FD diffusion model. (c) (d), Reconstruction using the amplitudes of the 0.5 and the 0.8 ns decay components in Eq. (3). The + signs are the true fluorophore locations for reference.

Equations (5)

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

U F ( r d , r s , t ) = n d ω e i ω t
× V d 3 r [ G ̃ m ( r d , r , ω ) i Γ n η n ( r ) ω + i Γ n Φ ̃ x ( r , r s , ω ) ] ,
U F ( r d , r s , t ) = n a F n ( r d , r s ) exp ( Γ n t ) + a D ( r d , r s , t ) exp ( v μ a t ) ,
a F n ( r d , r s ) = V d 3 r W n ( r s , r d , r ) η n ( r ) ,
W n = Γ n G ̃ m ( r d , r , ω = i Γ n ) Φ ̃ x ( r , r s , ω = i Γ n ) .

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