Abstract

Fluorescence diffuse imaging (FDI) suffers from limited spatial resolution. In this Letter, we report a scanning imaging approach to increase the resolution of FDI using nonlinear fluorophores. The resolution of a linear fluorophore was compared with nonlinear upconverting nanoparticles (NaYF4:Yb3+/Tm3+) in a tissue phantom. A resolution improvement of a factor of 1.3 was found experimentally. Simulations suggested a maximum resolution improvement of a factor of 1.45. Usage of nonlinear fluorophores is a promising method for increasing the spatial resolution in FDI.

© 2010 Optical Society of America

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C. T. Xu, J. Axelsson, and S. Andersson-Engels, Appl. Phys. Lett. 94, 251107 (2009).
[CrossRef]

2008

E. Alerstam, T. Svensson, and S. Andersson-Engels, J. Biomed. Opt. 13, 060504 (2008).
[CrossRef]

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

E. Alerstam, S. Andersson-Engels, and T. Svensson, Opt. Express 16, 10440 (2008).
[CrossRef] [PubMed]

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

2007

G. S. Yi and G. M. Chow, Chem. Mater. 19, 341 (2007).
[CrossRef]

2006

V. Ntziachristos, Annu. Rev. Biomed. Eng. 8, 1 (2006).
[CrossRef] [PubMed]

2005

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

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

2004

F. Auzel, Chem. Rev. 104, 139 (2004).
[CrossRef] [PubMed]

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

1996

1991

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

1990

Aikawa, E.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Alerstam, E.

E. Alerstam, T. Svensson, and S. Andersson-Engels, J. Biomed. Opt. 13, 060504 (2008).
[CrossRef]

E. Alerstam, S. Andersson-Engels, and T. Svensson, Opt. Express 16, 10440 (2008).
[CrossRef] [PubMed]

Alfano, R. R.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Andersson-Engels, S.

C. T. Xu, J. Axelsson, and S. Andersson-Engels, Appl. Phys. Lett. 94, 251107 (2009).
[CrossRef]

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

E. Alerstam, S. Andersson-Engels, and T. Svensson, Opt. Express 16, 10440 (2008).
[CrossRef] [PubMed]

E. Alerstam, T. Svensson, and S. Andersson-Engels, J. Biomed. Opt. 13, 060504 (2008).
[CrossRef]

S. Andersson-Engels, R. Berg, S. Svanberg, and O. Jarlman, Opt. Lett. 15, 1179 (1990).
[CrossRef] [PubMed]

Auzel, F.

F. Auzel, Chem. Rev. 104, 139 (2004).
[CrossRef] [PubMed]

Axelsson, J.

C. T. Xu, J. Axelsson, and S. Andersson-Engels, Appl. Phys. Lett. 94, 251107 (2009).
[CrossRef]

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Berg, R.

Chen, B.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

Chen, G.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Chow, G. M.

G. S. Yi and G. M. Chow, Chem. Mater. 19, 341 (2007).
[CrossRef]

de Kleine, R. H.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Gibbs, S.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

Gudel, H. U.

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

Haase, M.

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

Heer, S.

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

Hielscher, A. H.

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

Ho, P. P.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Jarlman, O.

Kirsch, D. G.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Kompe, K.

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

Liang, H.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Liu, C.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Liu, H.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Niedre, M. J.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Ntziachristos, V.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

V. Ntziachristos, Annu. Rev. Biomed. Eng. 8, 1 (2006).
[CrossRef] [PubMed]

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

Pogue, B. W.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

Ripoll, J.

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

Savellano, M.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

Somesfalean, G.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Svanberg, S.

Svenmarker, P.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Svensson, N.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Svensson, T.

E. Alerstam, S. Andersson-Engels, and T. Svensson, Opt. Express 16, 10440 (2008).
[CrossRef] [PubMed]

E. Alerstam, T. Svensson, and S. Andersson-Engels, J. Biomed. Opt. 13, 060504 (2008).
[CrossRef]

Wang, L.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Wang, L. V.

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

Webb, W. W.

Weissleder, R.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

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

Xu, C.

Xu, C. T.

C. T. Xu, J. Axelsson, and S. Andersson-Engels, Appl. Phys. Lett. 94, 251107 (2009).
[CrossRef]

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Yi, G. S.

G. S. Yi and G. M. Chow, Chem. Mater. 19, 341 (2007).
[CrossRef]

Zhang, G.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Zhang, Z.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

Adv. Mater.

S. Heer, K. Kompe, H. U. Gudel, and M. Haase, Adv. Mater. 16, 2102 (2004).
[CrossRef]

Annu. Rev. Biomed. Eng.

V. Ntziachristos, Annu. Rev. Biomed. Eng. 8, 1 (2006).
[CrossRef] [PubMed]

Appl. Phys. Lett.

C. T. Xu, N. Svensson, J. Axelsson, P. Svenmarker, G. Somesfalean, G. Chen, H. Liang, H. Liu, Z. Zhang, and S. Andersson-Engels, Appl. Phys. Lett. 93, 171103(2008).
[CrossRef]

C. T. Xu, J. Axelsson, and S. Andersson-Engels, Appl. Phys. Lett. 94, 251107 (2009).
[CrossRef]

Chem. Mater.

G. S. Yi and G. M. Chow, Chem. Mater. 19, 341 (2007).
[CrossRef]

Chem. Rev.

F. Auzel, Chem. Rev. 104, 139 (2004).
[CrossRef] [PubMed]

Curr. Opin. Biotechnol.

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

J. Biomed. Opt.

E. Alerstam, T. Svensson, and S. Andersson-Engels, J. Biomed. Opt. 13, 060504 (2008).
[CrossRef]

J. Opt. Soc. Am. B

Nat. Biotechnol.

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

Opt. Express

Opt. Lett.

Proc. Natl. Acad. Sci. USA

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, Proc. Natl. Acad. Sci. USA 105, 19126 (2008).
[CrossRef] [PubMed]

Science

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, Science 253, 769 (1991).
[CrossRef] [PubMed]

Technol. Cancer. Res. Treat.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Technol. Cancer. Res. Treat. 3, 15 (2004).
[PubMed]

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Figures (3)

Fig. 1
Fig. 1

Monte Carlo simulation of light propagation modeling the resolution using the scanning imaging method for upconverting nanoparticles and conventional linear fluorescent dyes: (a) image cross section for a transmission geometry with the fluorophore located at a 7 mm depth from the excitation side, (b) ratio of the FWHM of the linear fluorescent dye to the FWHM of the upconverting nanoparticles versus depth locations of the simulated rod inclusion.

Fig. 2
Fig. 2

Schematic of the experimental setup. The excitation laser was scanned in four rows according to the black dots indicated. One fluorescent rod was submerged into a tissue phantom. Fluorescence was collected through the 800 nm bandpass filter and recorded by a camera.

Fig. 3
Fig. 3

Fluorescence images using the scanning imaging technique. Each pixel in the image correspond to the fluorescence induced by a single excitation point. Here the excitation source was scanned in a 40 × 40 grid, thus generating an image of 40 × 40 pixels. (a) Linear conventional fluorescence dye, (b) upconverting nanoparticles. A cross section of images (a) and (b) is displayed in (c).

Equations (2)

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F l ( r d ) = V U x ( r s , r ) η l ( r ) U f * ( r d , r ) d V ,
F nl ( r d ) = V U x γ ( r s , r ) η nl ( r ) U f * ( r d , r ) d V ,

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