Abstract

Noncontact optical tomography in reflection mode is often the only possible configuration when imaging the expression of green fluorescent protein (GFP) or other fluorescent proteins in live animals owing to the short penetration depth of visible light. When imaging in reflection mode using noncontact approaches (i.e., without the use of fibers coupled to tissue), correctly accounting for the intensity profile of the source at the surface is a difficult task, usually needing to fit for source positions and/or approximating these to point sources. In this Letter we present a rigorous theoretical approach that directly accounts for the source’s intensity profile and verify it using in vivo data from GFP-expressing mice. We show how this approach improves image quality and resolution, while considerably simplifying the forward and inverse problems of the image reconstruction process.

© 2009 Optical Society of America

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D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

2008

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

2006

J. Ripoll and V. Ntziachristos, Phys. Rev. Lett. 96, 173903 (2006).
[CrossRef] [PubMed]

2004

2003

R. B. Schulz, J. Ripoll, and V. Ntziachristos, Opt. Lett. 28, 1701 (2003).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

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A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

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Arridge, S. R.

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[CrossRef]

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Chance, B.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
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M. S. Patterson, B. Chance, and B. C. Wilson, Appl. Opt. 28, 2331 (1989).
[CrossRef] [PubMed]

Choe, R.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Culver, J. P.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Dale, A. M.

Dehghani, H.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Dunn, A. K.

Durduran, T.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Garofalakis, A.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Graves, E. E.

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

Gruber, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Hillman, E. M.

Holboke, M. J.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Hutchins, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Hypnarowski, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Ishimaru, A.

A. Ishimaru, Wave Propagation and Scattering in Random Media (Academic, 1978), Vol. 1.

Kepshire, D.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Khayat, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Leblond, F.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Mamalaki, C.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Martin, A.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Meyer, H.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Mincu, N.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Ntziachristos, V.

J. Ripoll and V. Ntziachristos, Phys. Rev. Lett. 96, 173903 (2006).
[CrossRef] [PubMed]

J. Ripoll and V. Ntziachristos, Mod. Phys. Lett. B 18, 1403 (2004).
[CrossRef]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, Opt. Lett. 28, 1701 (2003).
[CrossRef] [PubMed]

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

Patterson, M. S.

Planas, A. M.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Pogue, B. W.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Ripoll, J.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

J. Ripoll and V. Ntziachristos, Phys. Rev. Lett. 96, 173903 (2006).
[CrossRef] [PubMed]

J. Ripoll and V. Ntziachristos, Mod. Phys. Lett. B 18, 1403 (2004).
[CrossRef]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, Opt. Lett. 28, 1701 (2003).
[CrossRef] [PubMed]

Sarasa-Renedo, A.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Schotland, J.-C.

Schulz, R. B.

Slemp, A.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Tsoukatou, D.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Weissleder, R.

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

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

Wilson, B. C.

Yodh, A. G.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Zubkov, L.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

Appl. Opt.

Inverse Probl.

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

J. Opt. Soc. Am. A

Med. Phys.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, Med. Phys. 30, 235 (2003).
[CrossRef] [PubMed]

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

Mod. Phys. Lett. B

J. Ripoll and V. Ntziachristos, Mod. Phys. Lett. B 18, 1403 (2004).
[CrossRef]

Mol. Imaging

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, Mol. Imaging 7, 157 (2008).

Opt. Lett.

Phys. Rev. Lett.

J. Ripoll and V. Ntziachristos, Phys. Rev. Lett. 96, 173903 (2006).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, Rev. Sci. Instrum. 80, 043701 (2009).
[CrossRef] [PubMed]

Other

A. Ishimaru, Wave Propagation and Scattering in Random Media (Academic, 1978), Vol. 1.

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Figures (3)

Fig. 1
Fig. 1

Scattering geometry.

Fig. 2
Fig. 2

(a) Experimental geometry for in vivo imaging of lymph nodes with GFP expressing T cells. The average fluorescence over all source positions (shown as circles) is shown in gray scale where the lymph node is clearly visible. (b) Typical fluorescence measurement at 488 nm excitation for a single-source position. (c) Excitation measurement at 488 nm for the same source position as (b).

Fig. 3
Fig. 3

(a) 3D reconstruction of GFP concentration in vivo when accounting for the source intensity profile. The inset shows the first five slices from top (left) to bottom (right). (b) Same as (a) but when using the point-source assumption.

Equations (3)

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U ( inc ) ( r ) = 1 4 π D S [ C nd D g ( κ | r r | ) n + g ( κ | r r | ) ] J src ( r ) d S , r V ,
U ( r ) = 1 4 π D S [ C nd D g ( κ | r r | ) n + g ( κ | r r | ) ] { J n ( r ) + J src ( r ) } d S , r V ,
W ( r s , r ; r , r d ) = U meas ( r s , r ) G ( r , r d ) U meas ( r s , r d ) ,

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