Abstract

We used single-photon counting (SPC) detection for diffuse fluorescence tomography to image nanomolar (nM) concentrations of reporter dyes through a rat. Detailed phantom data are presented to show that every centimeter increase in tissue thickness leads to 1 order of magnitude decrease in the minimum fluorophore concentration detectable for a given detector sensitivity. Specifically, here, detection of Alexa Fluor 647 dyes is shown to be achievable for concentrations as low as 1nM (<200fM) through more than 5cm in tissue phantoms, which indicates that this is feasible in larger rodent models. Because it is possible to detect sub-nM fluorescent inclusions with SPC technology in rats, it follows that it is possible to localize subpicomolar fluorophore concentrations in mice, putting the concentration sensitivity limits on the same order as nuclear medicine methods.

© 2011 Optical Society of America

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References

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  1. F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
    [CrossRef]
  2. 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]
  3. V. Ntziachristos and R. Weissleder, Opt. Lett. 26, 893(2001).
    [CrossRef]
  4. H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
    [CrossRef]
  5. D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, Opt. Express 17, 23272 (2009).
    [CrossRef]

2010 (1)

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

2009 (3)

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]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, Opt. Express 17, 23272 (2009).
[CrossRef]

2001 (1)

Carpenter, C. M.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Davis, S. C.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Dehghani, H.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

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]

D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, Opt. Express 17, 23272 (2009).
[CrossRef]

Eames, M. E.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

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]

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]

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]

Kepshire, D. L.

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.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

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]

D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, Opt. Express 17, 23272 (2009).
[CrossRef]

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.

Paulsen, K. D.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Pogue, B. W.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

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]

D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, Opt. Express 17, 23272 (2009).
[CrossRef]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Srinivasan, S.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Valdes, P. A.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

Weissleder, R.

Yalavarthy, P. K.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

Commun. Num. Meth. Eng. (1)

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, Commun. Num. Meth. Eng. 25, 711 (2009).
[CrossRef]

J. Photochem. Photobiol. B (1)

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, J. Photochem. Photobiol. B 98, 77 (2010).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

Rev. Sci. Instrum. (1)

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]

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Figures (6)

Fig. 1
Fig. 1

Noncontact SPC FT system.

Fig. 2
Fig. 2

Rear and side views of the tissue- simulating wedge phantom designed to emulate different interrogated thicknesses.

Fig. 3
Fig. 3

Fluorescence SBR as a function of thickness for four different AF647 concentrations. The line of detectability is at an SBR of 1.

Fig. 4
Fig. 4

FT images where an inclusion was filled with an AF647 solution of (a) 70 and (b)  0.7 nM .

Fig. 5
Fig. 5

Born-normalized fluorescence as a function of dye concentration.

Fig. 6
Fig. 6

FT-CT image of a rat cranium acquired postmortem where a 5 mm diameter fluorescent tube has been inserted.

Equations (1)

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SBR = I F I F bg D . N . ,

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