Abstract

Time-resolved fluorescence optical tomography allows 3-dimensional localization of multiple fluorophores based on lifetime contrast while providing a unique data set for improved resolution. However, to employ the full fluorescence time measurements, a light propagation model that accurately simulates weakly diffused and multiple scattered photons is required. In this article, we derive a computationally efficient Monte Carlo based method to compute time-gated fluorescence Jacobians for the simultaneous imaging of two fluorophores with lifetime contrast. The Monte Carlo based formulation is validated on a synthetic murine model simulating the uptake in the kidneys of two distinct fluorophores with lifetime contrast. Experimentally, the method is validated using capillaries filled with 2.5nmol of ICG and IRDye™800CW respectively embedded in a diffuse media mimicking the average optical properties of mice. Combining multiple time gates in one inverse problem allows the simultaneous reconstruction of multiple fluorophores with increased resolution and minimal crosstalk using the proposed formulation.

© 2011 OSA

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2008

L. Zhang, F. Gao, H. He, and H. Zhao, “Three-dimensional scheme for time-domain fluorescence molecular tomography based on Laplace transforms with noise-robust factors,” Opt. Express 16(10), 7214–7223 (2008).
[CrossRef] [PubMed]

A. Liebert, H. Wabnitz, N. Zołek, and R. Macdonald, “Monte Carlo algorithm for efficient simulation of time-resolved fluorescence in layered turbid media,” Opt. Express 16(17), 13188–13202 (2008).
[CrossRef] [PubMed]

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

2007

B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

2006

2005

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

A. H. Hielscher, “Optical tomographic imaging of small animals,” Curr. Opin. Biotechnol. 16(1), 79–88 (2005).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

S. Lam, F. Lesage, and X. Intes, “Time domain fluorescent diffuse optical tomography: analytical expressions,” Opt. Express 13(7), 2263–2275 (2005).
[CrossRef] [PubMed]

2003

J. Swartling, A. Pifferi, A. M. K. Enejder, and S. Andersson-Engels, “Accelerated Monte Carlo models to simulate fluorescence spectra from layered tissues,” J. Opt. Soc. Am. A 20(4), 714–727 (2003).
[CrossRef] [PubMed]

W. Cai, M. Xu, and R. R. Alfano, “X. M, and R. Alfano, “Three-dimensional radiative transfer tomography for turbid media,” IEEE J. Sel. Top. Quantum Electron. 9(2), 189–198 (2003).
[CrossRef]

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

2002

M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

D. A. Boas, J. P. Culver, J. J. Stott, and A. K. Dunn, “Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head,” Opt. Express 10(3), 159–170 (2002).
[PubMed]

M. Sakami, K. Mitra, and T. Vo-Dinh, “Analysis of short-pulse laser photon transport through tissues for optical tomography,” Opt. Lett. 27(5), 336–338 (2002).
[CrossRef] [PubMed]

1999

1998

1997

I. V. Yaroslavsky, A. N. Yaroslavsky, V. V. Tuchin, and H.-J. Schwarzmaier, “Effect of the scattering delay on time-dependent photon migration in turbid media,” Appl. Opt. 36(25), 6529–6538 (1997).
[CrossRef] [PubMed]

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

1995

1993

1992

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200(1-2), 199–204 (1992).
[CrossRef]

Aikawa, E.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Alerstam, E.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[CrossRef] [PubMed]

Alfano, R. R.

W. Cai, M. Xu, and R. R. Alfano, “X. M, and R. Alfano, “Three-dimensional radiative transfer tomography for turbid media,” IEEE J. Sel. Top. Quantum Electron. 9(2), 189–198 (2003).
[CrossRef]

M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

L. Wang, X. Liang, P. Galland, P. P. Ho, and R. R. Alfano, “True scattering coefficients of turbid matter measured by early-time gating,” Opt. Lett. 20(8), 913–915 (1995).
[CrossRef] [PubMed]

F. Liu, K. M. Yoo, and R. R. Alfano, “Ultrafast laser-pulse transmission and imaging through biological tissues,” Appl. Opt. 32(4), 554–558 (1993).
[CrossRef] [PubMed]

Andersson-Engels, S.

Arridge, S. R.

Bacskai, B. J.

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, “Time resolved fluorescence tomography of turbid media based on lifetime contrast,” Opt. Express 14(25), 12255–12270 (2006).
[CrossRef] [PubMed]

Boas, D.

Boas, D. A.

Boverman, G.

Cai, W.

W. Cai, M. Xu, and R. R. Alfano, “X. M, and R. Alfano, “Three-dimensional radiative transfer tomography for turbid media,” IEEE J. Sel. Top. Quantum Electron. 9(2), 189–198 (2003).
[CrossRef]

M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

Chan, E.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Chatziioannou, A. F.

B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

Chen, J.

Cheng, X.

Comelli, D.

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

Criswell, G.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Cubeddu, R.

V. Y. Soloviev, C. D’Andrea, G. Valentini, R. Cubeddu, and S. R. Arridge, “Combined reconstruction of fluorescent and optical parameters using time-resolved data,” Appl. Opt. 48(1), 28–36 (2009).
[CrossRef] [PubMed]

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

Culver, J. P.

D’Andrea, C.

V. Y. Soloviev, C. D’Andrea, G. Valentini, R. Cubeddu, and S. R. Arridge, “Combined reconstruction of fluorescent and optical parameters using time-resolved data,” Appl. Opt. 48(1), 28–36 (2009).
[CrossRef] [PubMed]

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

Dasari, R. R.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

de Kleine, R. H.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Dogdas, B.

B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

Dunn, A. K.

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

D. A. Boas, J. P. Culver, J. J. Stott, and A. K. Dunn, “Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head,” Opt. Express 10(3), 159–170 (2002).
[PubMed]

Eick, A. A.

Enejder, A. M. K.

Feld, M. S.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

Figueiredo, J.-L.

French, P. M.

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Freyer, J. P.

Galland, P.

Gao, F.

Gardner, C. M.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

He, H.

Hielscher, A. H.

Ho, P. P.

Intes, X.

Johnson, T. M.

Kirsch, D. G.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Köllner, M.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200(1-2), 199–204 (1992).
[CrossRef]

Kumar, A. T. N.

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, “Time resolved fluorescence tomography of turbid media based on lifetime contrast,” Opt. Express 14(25), 12255–12270 (2006).
[CrossRef] [PubMed]

Kumar, S.

Lam, S.

Lax, M.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

Leahy, R. M.

B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

Lesage, F.

Liang, X.

Liebert, A.

Liu, F.

Macdonald, R.

Mansfield, J. R.

J. R. Mansfield, “Distinguished photons: a review of in vivo spectral fluorescence imaging in small animals,” Curr. Pharm. Biotechnol. 11(6), 628–638 (2010).
[CrossRef] [PubMed]

McBride, T. O.

Mitra, K.

Mourant, J. R.

Nahrendorf, M.

Niedre, M.

Niedre, M. J.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

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M. Niedre and V. Ntziachristos, “Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons,” Opt. Lett. 35(3), 369–371 (2010).
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[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

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Paulsen, K. D.

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J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

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A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
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K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
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J. Swartling, A. Pifferi, A. M. K. Enejder, and S. Andersson-Engels, “Accelerated Monte Carlo models to simulate fluorescence spectra from layered tissues,” J. Opt. Soc. Am. A 20(4), 714–727 (2003).
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[CrossRef]

Pogue, B. W.

Prewitt, J.

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E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

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A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
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A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

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A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

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E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

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Soubret, A.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

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B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

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K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

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E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
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R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

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C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

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Valentini, G.

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[CrossRef] [PubMed]

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

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Vinegoni, C.

Vo-Dinh, T.

Wabnitz, H.

Wang, L.

Wang, L. V.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

Warren, S.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Weissleder, R.

C. Vinegoni, D. Razansky, J.-L. Figueiredo, M. Nahrendorf, V. Ntziachristos, and R. Weissleder, “Normalized Born ratio for fluorescence optical projection tomography,” Opt. Lett. 34(3), 319–321 (2009).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

Welch, A. J.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
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M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

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Yaroslavsky, I. V.

Yoo, K. M.

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Appl. Opt.

Biomed. Opt. Express

Chem. Phys. Lett.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett. 200(1-2), 199–204 (1992).
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J. R. Mansfield, “Distinguished photons: a review of in vivo spectral fluorescence imaging in small animals,” Curr. Pharm. Biotechnol. 11(6), 628–638 (2010).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron.

W. Cai, M. Xu, and R. R. Alfano, “X. M, and R. Alfano, “Three-dimensional radiative transfer tomography for turbid media,” IEEE J. Sel. Top. Quantum Electron. 9(2), 189–198 (2003).
[CrossRef]

IEEE Trans. Med. Imaging

A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

J. Biomed. Opt.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13(4), 041304 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

J. Phys. D Appl. Phys.

C. D’Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003).
[CrossRef]

R. Cubeddu, D. Comelli, C. D’Andrea, P. Taroni, and G. Valentini, “Time-resolved fluorescence imaging in biology and medicine,” J. Phys. D Appl. Phys. 35(9), R61–R76 (2002).
[CrossRef]

Lasers Surg. Med.

A. J. Welch, C. M. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, and S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21(2), 166–178 (1997).
[CrossRef] [PubMed]

Nat. Biotechnol.

V. Ntziachristos, J. Ripoll, L. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23(3), 313–320 (2005).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Photochem. Photobiol. Sci.

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[CrossRef] [PubMed]

Phys. Med. Biol.

B. Dogdas, D. Stout, A. F. Chatziioannou, and R. M. Leahy, “Digimouse: a 3D whole body mouse atlas from CT and cryosection data,” Phys. Med. Biol. 52(3), 577–587 (2007).
[CrossRef] [PubMed]

Phys. Rev. E Stat. Nonlin. Soft Matter Phys.

M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 65(6), 066609 (2002).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms,” Proc. Natl. Acad. Sci. U.S.A. 94(16), 8783–8788 (1997).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

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Figures (7)

Fig. 1.
Fig. 1.

Block diagram summarizing the steps to perform fluorescence reconstruction.

Fig. 2.
Fig. 2.

(a) The mouse model geometry and arrangement of sources (top) and detectors (bottom) used for the simulations. The fluorescent kidneys are marked as red and black, according to different lifetimes. (b) The illumination patterns (red: on, black: off).

Fig. 3.
Fig. 3.

(a) Representative simulated signals from the fluorophores with τ 1 = 0.5ns (blue) and τ 2 = 1ns (red), and the total fluorescence signal (black) used in the reconstructions. All the signals are generated using the mouse phantom and a single transmittance S-D pair as shown in (b) and (c). (b) Weight matrices for τ = 1ns at the 3 gates (gray) presented in (a). (c) The direct detector readings from the region of interest (black boxes) from the simulation on the mouse phantom. The bars in (b) and white boxes in (c) indicate the illumination pattern and the crosses in (b) and (c) indicate the detector used in (a).

Fig. 4.
Fig. 4.

Information content evaluation based on single gate reconstructions in terms of (a) quantification, (b) crosstalk and (c) resolution.

Fig. 5.
Fig. 5.

(a) Sets of time gates investigated in multi-gate reconstructions. (b) and (c) display the reconstructions using combined gates of set 1 and set 5, respectively.

Fig. 6.
Fig. 6.

(a) Schematic of the TD fluorescence tomography system. LS: laser; PC: power control; FBC: fiber-beam coupler; BE: beam expander; DMD: DmD-based DLP chip; IL: imaging lens; IC: imaging chamber; CCD: intensified CCD camera; HRI: high rate imager; TDU: trigger delay unit; TG: trigger generator. (b) Phantom setup. The red box shows the pattern illumination area. All dimensions are in mm.

Fig. 7.
Fig. 7.

Experiment results using (a) TD data and (b) CW data. The images are normalized to the maximum of the reconstruction.

Tables (1)

Tables Icon

Table 1. Quantitative Comparison of the Multi-Gate Reconstructions

Equations (17)

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η ( r ) = μ a f x ( r ) Φ μ a x ( r )
U F ( r s , r d , t ) = Ω d r 3 W ( r s , r d , r , t ) η ( r ) ,
W ( r s , r d , r , t ) = 0 t d t A ( r s , r , t ) E ( r , r d , t t ) .
U F ( r s , r d , t ) = 0 t d t U F ( r s , r d , t ) e ( t t ) τ .
U F ( r s , r d , t ) = Ω d r 3 W ( r s , r d , r , t ) η ( r ) ,
W ( r s , r d , r , t ) = 0 t d t W ( r s , r d , r , t ) e ( t t ) τ ,
w i x ( r s , r , t s , r ) = w i , 0 exp ( Σ j = 1 p i μ a x ( r j ) l ( r j ) ) ,
A i ( r s , r , t s , r ) = w i x ( r s , r , t s , r ) ( 1 exp ( μ a x ( r ) l i ( r ) ) ) .
w i m ( r , r d , t r , d ) = A i ( r s , r , t s , r ) η ( r ) exp ( Σ j = p i + 1 q i μ a m ( r j ) l i ( r j ) ) ,
w ( r s , r d , r , t ) = Σ i = 1 n A i ( r s , r , t ) exp ( Σ j = p i + 1 q i μ a m ( r j ) l i ( r j ) ) .
W ( r s , r d , r , t ) = Σ i = 1 n w i , 0 exp ( Σ j = 1 p i μ a x ( r j ) l i ( r j ) ) × ( 1 exp ( μ a x ( r ) l i ( r ) ) × exp ( Σ j = p i + 1 q i μ a m ( r j ) l i ( r j ) ) .
W ( r s , r d , r , t ) = Σ i = 1 n w i x ( r s , r d , t ) ( 1 exp ( μ a x ( r ) l i ( r ) ) ,
w i x ( r s , r d , t ) = w i , 0 exp ( Σ j = 1 q i μ a x ( r j ) l i ( r j ) ) .
W ( r s , r d , r , t ) = Σ i = 1 n w i x ( r s , r d , t ) μ a x ( r ) l i ( r ) .
M m ( r s , r d , t ) M x ( r s , r d ) = α U x ( r s , r d ) Σ k = 1 N F d 3 r W k ( r s , r d , r , t ) η k ( r ) ,
[ γ 1 γ N m ] = [ β 1 W 1 , 1 Ω β 1 W 1 , N F Ω β N m W N m , 1 Ω β N m W N m , N F Ω ] [ η 1 Ω η N F Ω ] ,
Ψ = A x b 2 + λ ( r ) x 2 ,

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