Abstract

The performance of small animal photonic imaging has been considerably improved since the development of fluorescence diffuse optical tomography (fDOT), which can reconstruct fluorescent probe distribution inside tissue. However, the quantification capabilities of this new technology are still a topic of debate, especially in comparison to classical nuclear imaging techniques. Here, we present a method to in vivo calibrate the quantity and localization of a probe provided by free-space fDOT (where no plate is compressing the mouse) with positron emission tomography (PET) and x-ray computed tomography, respectively. This methodology allowed us to demonstrate a strong linear correlation (R2=0.95) between fDOT and PET for probe concentrations ranging from 3nM to 1μM in a deep-seated organ.

© 2010 Optical Society of America

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References

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2010 (3)

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

2009 (2)

D. Hyde, R. Schulz, D. Brooks, E. Miller, and V. Ntziachristos, J. Opt. Soc. Am. A 26, 919 (2009).
[CrossRef]

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

2008 (3)

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

R. Weissleder and M. J. Pittet, Nature 452, 580 (2008).
[CrossRef] [PubMed]

2007 (1)

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

2005 (1)

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

2004 (1)

R. B. Schulz, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 23, 492 (2004).
[CrossRef] [PubMed]

2002 (1)

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

1996 (1)

Bacharach, S. L.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Barber, W. C.

Berger, M.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Boas, D. A.

Boisgard, R.

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Boutet, J.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Bremer, C.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

Brooks, D.

Cathier, P.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Chance, B.

Coll, J.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Comtat, C.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Dinten, J.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Dollé, F.

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Duchesnay, E.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Ducongé, F.

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

Economou, E. N.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Feruglio, P. F.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Fexon, L.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Frouin, V.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Garofalakis, A.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Gonon, G.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Graves, E. E.

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

Gulsen, G.

Hadi, M.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Hasegawa, B. H.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Hervé, L.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Hyde, D.

Iwanczyk, J. S.

Josserand, V.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Keliher, E.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Kioussis, D.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Koenig, A.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Li, X. D.

Lin, Y.

Mamalaki, C.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Marinelli, B.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Maroy, R.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Meyer, H.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Miller, E.

Nahrendorf, M.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Nalcioglu, O.

Nielsen, P. E.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Ntziachristos, V.

D. Hyde, R. Schulz, D. Brooks, E. Miller, and V. Ntziachristos, J. Opt. Soc. Am. A 26, 919 (2009).
[CrossRef]

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 23, 492 (2004).
[CrossRef] [PubMed]

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

O’Leary, M. A.

Papamatheakis, J.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Peltié, P.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Pittet, M. J.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

R. Weissleder and M. J. Pittet, Nature 452, 580 (2008).
[CrossRef] [PubMed]

Pivovarov, M.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Ripoll, J.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 23, 492 (2004).
[CrossRef] [PubMed]

Rizo, P.

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

Roeck, W.

Schreck, C.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Schulz, R.

Schulz, R. B.

R. B. Schulz, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 23, 492 (2004).
[CrossRef] [PubMed]

Seo, Y.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Swirski, F. K.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Tavitian, B.

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Teo, B.

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Trébossen, R.

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

Tung, C.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

Turner, G.

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

Vinegoni, C.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Waterman, P.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Weissleder, R.

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

R. Weissleder and M. J. Pittet, Nature 452, 580 (2008).
[CrossRef] [PubMed]

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

Yessayan, D.

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

Yodh, A. G.

Zacharakis, G.

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

IEEE Trans. Med. Imaging (2)

R. Maroy, R. Boisgard, C. Comtat, V. Frouin, P. Cathier, E. Duchesnay, F. Dollé, P. E. Nielsen, R. Trébossen, and B. Tavitian, IEEE Trans. Med. Imaging 27, 342 (2008).
[CrossRef] [PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, IEEE Trans. Med. Imaging 23, 492 (2004).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

E. E. Graves, D. Yessayan, G. Turner, R. Weissleder, and V. Ntziachristos, J. Biomed. Opt. 10, 044019 (2005).
[CrossRef]

A. Koenig, L. Hervé, G. Gonon, V. Josserand, M. Berger, J. Dinten, J. Boutet, P. Peltié, J. Coll, and P. Rizo, J. Biomed. Opt. 15, 016016 (2010).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (1)

Med. Phys. (1)

Y. Seo, B. Teo, M. Hadi, C. Schreck, S. L. Bacharach, and B. H. Hasegawa, Med. Phys. 35, 3086 (2008).
[CrossRef] [PubMed]

Methods Mol. Biol. (1)

B. Tavitian, F. Ducongé, R. Boisgard, and F. Dollé, Methods Mol. Biol. 535, 241 (2009).
[PubMed]

Mol. Imaging (1)

A. Garofalakis, G. Zacharakis, H. Meyer, E. N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, Mol. Imaging 6, 96 (2007).
[PubMed]

Nat. Med. (1)

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Nat. Med. 8, 757 (2002).
[CrossRef] [PubMed]

Nature (1)

R. Weissleder and M. J. Pittet, Nature 452, 580 (2008).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Proc. Natl. Acad. Sci. USA (1)

M. Nahrendorf, E. Keliher, B. Marinelli, P. Waterman, P. F. Feruglio, L. Fexon, M. Pivovarov, F. K. Swirski, M. J. Pittet, C. Vinegoni, and R. Weissleder, Proc. Natl. Acad. Sci. USA 107, 7910 (2010).
[CrossRef] [PubMed]

Supplementary Material (1)

» Media 1: AVI (12826 KB)     

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Figures (3)

Fig. 1
Fig. 1

Timing of the different imaging acquisitions. In the top row, typical reconstructed images of each modality are shown. The graph points below illustrate the variation of the probe quantity residing inside the two kidneys as calculated by two separate dynamic PET scans on the same mouse. The gap under the two PET scans was filled by a nonlinear regression, and the fitted line served for extracting the probe value that corresponds to the time point of the fDOT measurement. The vertical dotted lines indicate the repositioning of the mouse bed from the one modality to the other (Media 1).

Fig. 2
Fig. 2

(a) Probe quantities in picomoles as calculated by PET correlated with the optical reconstructed signal, in arbitrary units (a.u.) and plotted in logarithmic axes. The errors in the points correspond to the regression errors of the extrapolation process of Fig. 1. The equation of the linear regression is [ pmol ] = ( 0.0045 ± 0.0002 ) × [ a . u . ] ( 1.0074 ± 5.7776 ) with R 2 = 0.95 . (b) Correlation of concentrations between PET and fDOT. The equation of the linear regression is [ C ] = ( 0.0099 ± 0.0005 ) × [ a . u . ] ( 0.0002 ± 0.0244 ) with R 2 = 0.95 .

Fig. 3
Fig. 3

(a) and (b) present the axial and the coronal views of fused mesh volumes occupied by the reconstructed signal in the kidneys. The optical reconstructed mesh is depicted with green (b), the PET with red (a), and the CT with granular gray [(a) and (b)]. The mesh volumes of the organs are rendered to the mesh volume of the mouse body region corresponding to the optical scanning frame.

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