Abstract

Long-lived near-infrared phosphors with high quantum yields have recently become available, making it possible to image oxygen distributions in tissue in three dimensions. By numerical simulations we demonstrate that, by using phosphorescent probes with appropriate oxygen quenching constants, one can image hypoxic phantoms in scattering media with adequate spatial resolution, employing simple time-gated measurements. The approach developed will guide experimental imaging of phosphorescence lifetime and oxygen pressure in living tissue.

© 2006 Optical Society of America

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References

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  1. A. H. Hielscher, Curr. Opin. Biotechnol. 16, 79 (2005), and references therein.
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  12. Optical parameters of the prototype probe, Pd tetrabenzoporphyrin dendrimer: λmax(abs)=636nm, ϵ=82,000M−1cm−1, λmax(emiss)=810nm, phivphos=0.2, Kq=718mmHg−1s−1, τ0=246μs.
  13. S. R. Arridge, Inverse Probl. 15, R41 (1999).
    [CrossRef]
  14. SNR here is defined as the ratio of the signal at the start of the decay (before integration) to the amplitude of the noise. The SNR of a data set (decays for all source-detector pairs) is the SNR of the decay with maximal initial intensity. In the shot-noise limit and for the model experiment described, a SNR of 50 can easily be achieved by use of, e.g., 1μs excitation pulses of 1W LED and detection over an ∼5mm2 boundary area.
  15. S. A. Vinogradov and D. F. Wilson, Appl. Spectrosc. 54, 849 (2000).
    [CrossRef]

2005

A. H. Hielscher, Curr. Opin. Biotechnol. 16, 79 (2005), and references therein.
[CrossRef] [PubMed]

2004

2003

I. B. Rietveld, E. Kim, and S. A. Vinogradov, Tetrahedron 59, 3821 (2003).
[CrossRef]

2002

E. Shives, Y. Xu, and H. Jiang, Opt. Express 10, 1557 (2002).
[PubMed]

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

K. Licha, Top. Curr. Chem. 222, 1 (2002).
[CrossRef]

2000

1999

S. R. Arridge, Inverse Probl. 15, R41 (1999).
[CrossRef]

1998

1997

A. Chen and E. M. Sevic-Muraca, in Proc. SPIE 2979, 129 (1997).
[CrossRef]

1996

1994

Arridge, S. R.

S. R. Arridge, Inverse Probl. 15, R41 (1999).
[CrossRef]

Boas, D. A.

Bremer, C.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

Burch, C. L.

Chance, B.

Chen, A.

A. Chen and E. M. Sevic-Muraca, in Proc. SPIE 2979, 129 (1997).
[CrossRef]

Hielscher, A. H.

A. H. Hielscher, Curr. Opin. Biotechnol. 16, 79 (2005), and references therein.
[CrossRef] [PubMed]

Jiang, H.

Kim, E.

I. B. Rietveld, E. Kim, and S. A. Vinogradov, Tetrahedron 59, 3821 (2003).
[CrossRef]

Li, X. D.

Licha, K.

K. Licha, Top. Curr. Chem. 222, 1 (2002).
[CrossRef]

Ntziachristos, V.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

O'Leary, M. A.

Rietveld, I. B.

I. B. Rietveld, E. Kim, and S. A. Vinogradov, Tetrahedron 59, 3821 (2003).
[CrossRef]

Sevick-Muraca, E. M.

Sevic-Muraca, E. M.

A. Chen and E. M. Sevic-Muraca, in Proc. SPIE 2979, 129 (1997).
[CrossRef]

Shives, E.

Soloviev, V. Y.

Tung, C.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

Vinogradov, S. A.

V. Y. Soloviev, D. F. Wilson, and S. A. Vinogradov, Appl. Opt. 43, 564 (2004).
[CrossRef] [PubMed]

I. B. Rietveld, E. Kim, and S. A. Vinogradov, Tetrahedron 59, 3821 (2003).
[CrossRef]

S. A. Vinogradov and D. F. Wilson, Appl. Spectrosc. 54, 849 (2000).
[CrossRef]

D. F. Wilson and S. A. Vinogradov, in Handbook of Biomedical Fluorescence, M.-AMycek and B.W.Pogue, eds. (Marcel Dekker, 2003), pp. 637-662.

Weissleder, R.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

Wilson, D. F.

V. Y. Soloviev, D. F. Wilson, and S. A. Vinogradov, Appl. Opt. 43, 564 (2004).
[CrossRef] [PubMed]

S. A. Vinogradov and D. F. Wilson, Appl. Spectrosc. 54, 849 (2000).
[CrossRef]

D. F. Wilson and S. A. Vinogradov, in Handbook of Biomedical Fluorescence, M.-AMycek and B.W.Pogue, eds. (Marcel Dekker, 2003), pp. 637-662.

Xu, Y.

Yodh, A. G.

Appl. Opt.

Appl. Spectrosc.

Curr. Opin. Biotechnol.

A. H. Hielscher, Curr. Opin. Biotechnol. 16, 79 (2005), and references therein.
[CrossRef] [PubMed]

Inverse Probl.

S. R. Arridge, Inverse Probl. 15, R41 (1999).
[CrossRef]

Nat. Med. (N.Y.)

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. (N.Y.) 8, 757 (2002).

Opt. Express

Opt. Lett.

Proc. SPIE

A. Chen and E. M. Sevic-Muraca, in Proc. SPIE 2979, 129 (1997).
[CrossRef]

Tetrahedron

I. B. Rietveld, E. Kim, and S. A. Vinogradov, Tetrahedron 59, 3821 (2003).
[CrossRef]

Top. Curr. Chem.

K. Licha, Top. Curr. Chem. 222, 1 (2002).
[CrossRef]

Other

SNR here is defined as the ratio of the signal at the start of the decay (before integration) to the amplitude of the noise. The SNR of a data set (decays for all source-detector pairs) is the SNR of the decay with maximal initial intensity. In the shot-noise limit and for the model experiment described, a SNR of 50 can easily be achieved by use of, e.g., 1μs excitation pulses of 1W LED and detection over an ∼5mm2 boundary area.

D. F. Wilson and S. A. Vinogradov, in Handbook of Biomedical Fluorescence, M.-AMycek and B.W.Pogue, eds. (Marcel Dekker, 2003), pp. 637-662.

Optical parameters of the prototype probe, Pd tetrabenzoporphyrin dendrimer: λmax(abs)=636nm, ϵ=82,000M−1cm−1, λmax(emiss)=810nm, phivphos=0.2, Kq=718mmHg−1s−1, τ0=246μs.

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Figures (4)

Fig. 1
Fig. 1

(Color online) a, Dependence of contrast C on k q for two equally excited volumes with continuous-wave excitation; b, dependence of contrast C ( t n ) on index n for which t n = τ 2 ln ( n ) ; t n , start of data integration values of k q for the curves are given in units of mm Hg 1 s 1 ( 1 mm Hg = 1 Torr ) .

Fig. 2
Fig. 2

(Color online) a, Distribution of excitation density and c–f, individually normalized distributions of phosphorescence density (log scale) after delays t n in a two-dimensional object: μ s = 0.5 mm 1 , μ a = 0.006 mm 1 (excitation), p O 2 = 50 mm Hg (hypoxic region, p O 2 = 10 mm Hg). b, Changes in fraction of the τ 2 signal in detectors d1–d3 and relative changes in total photons (lighter shading).

Fig. 3
Fig. 3

Images of a hypoxic phantom ( τ 2 = 90 μ s ) , a, in a normoxic volume ( τ 1 = 25 μ s ; Fig. 2) and, b–d, reconstructed from boundary data acquired after delays t n = τ 2 ln ( n ) .

Fig. 4
Fig. 4

(Color online) a, Scattering object ( 6 cm , p O 2 = 50 mm Hg ) with two hypoxic regions: p O 2 = 15 mm Hg ( τ 2 = 70 μ s ) and p O 2 = 15 mm Hg ( τ 3 = 133 μ s ) . Lifetime images (microseconds), b, reconstructed from the whole sequence of intensity images (lower row) or, c, from the intensity images acquired at higher delays ( t n > 50 μ s ) . d, Oxygen images (in millimeters of mercury) obtained from lifetime image. b, Bottom row, phosphorescence intensity images collected at difference delays t n and normalized by the maximal intensity in the first image ( t n = 15 μ s ) . Same color scheme as for a–d.

Equations (3)

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τ 0 τ = I 0 I = 1 + k q × τ 0 × p O 2 ,
C ( t n ) = I 2 ( t n ) I 1 ( t n ) = τ 2 τ 1 exp ( τ 2 τ 1 τ 1 τ 2 t n ) .
f ( r , t n ) = t n I 0 ( r ) exp [ t τ ( r ) ] d t = I 0 ( r ) τ ( r ) exp [ t n τ ( r ) ] ,

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