Abstract

Simultaneous detection of several biological processes in vivo is a common requirement in biomedical and biological applications, and in order to address this issue the use of multiple fluorophores is usually the method of choice. Existing methodologies however, do not provide quantitative feedback of multiple fluorophore concentrations in small animals in vivo when their spectra overlap, especially when imaging the whole body in 3D. Here we present an approach where a spectroscopic module has been implemented into a custom-built Fluorescence Molecular Tomography (FMT) system. In contrast with other multispectral approaches, this multimodal imaging system is capable of recording the fluorescence spectra from each illumination point during a tomographic measurement. In situ spectral information can thus be extracted and used to improve the separation of overlapping signals associated with different fluorophores. The results of this new approach tested on both in vitro and in vivo experiments are presented, proving that accurate recovery of fluorophore concentrations can be obtained from multispectral tomography data even in the presence of high autofluorescence.

© 2011 OSA

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    [CrossRef] [PubMed]
  32. A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2010 (1)

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]

2009 (3)

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

A. D. Zacharopoulos, P. Svenmarker, J. Axelsson, M. Schweiger, S. R. Arridge, and S. Andersson-Engels, “A matrix-free algorithm for multiple wavelength fluorescence tomography,” Opt. Express 17(5), 3042–3052 (2009).
[CrossRef] [PubMed]

2008 (3)

G. Themelis, J. S. Yoo, and V. Ntziachristos, “Multispectral imaging using multiple-bandpass filters,” Opt. Lett. 33(9), 1023–1025 (2008).
[CrossRef] [PubMed]

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[CrossRef] [PubMed]

2007 (1)

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

2006 (2)

V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng. 8(1), 1–33 (2006).
[CrossRef] [PubMed]

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

2005 (8)

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[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]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

J. Swartling, J. Svensson, D. Bengtsson, K. Terike, and S. Andersson-Engels, “Fluorescence spectra provide information on the depth of fluorescent lesions in tissue,” Appl. Opt. 44(10), 1934–1941 (2005).
[CrossRef] [PubMed]

B. Brooksby, S. Srinivasan, S. Jiang, H. Dehghani, B. W. Pogue, K. D. Paulsen, J. Weaver, C. Kogel, and S. P. Poplack, “Spectral priors improve near-infrared diffuse tomography more than spatial priors,” Opt. Lett. 30(15), 1968–1970 (2005).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

2004 (6)

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

J. Ripoll and V. Ntziachristos, “Imaging scattering media from a distance: Theory and applications of non-contact optical tomography,” Mod. Phys. Lett. B 18(28 & 29), 1403–1431 (2004).
[CrossRef]

S. R. Cherry, “In vivo molecular and genomic imaging: new challenges for imaging physics,” Phys. Med. Biol. 49(3), R13–R48 (2004).
[CrossRef] [PubMed]

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

V. V. Verkhusha and K. A. Lukyanov, “The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins,” Nat. Biotechnol. 22(3), 289–296 (2004).
[CrossRef] [PubMed]

2003 (5)

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

J. P. Culver, A. M. Siegel, J. J. Stott, and D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett. 28(21), 2061–2063 (2003).
[CrossRef] [PubMed]

2002 (2)

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

2001 (3)

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation,” Opt. Lett. 26(12), 893–895 (2001).
[CrossRef] [PubMed]

Aguirre, J.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Alencar, H.

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

Andersson-Engels, S.

Arridge, S. R.

Axelsson, J.

Balas, C.

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

Bengtsson, D.

Berberides, K.

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

Boas, D. A.

J. P. Culver, A. M. Siegel, J. J. Stott, and D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett. 28(21), 2061–2063 (2003).
[CrossRef] [PubMed]

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Bogdanov, A.

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Bremer, C.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

Brooks, D. H.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Brooksby, B.

Campbell, R. E.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Chance, B.

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Cherry, S. R.

S. R. Cherry, “In vivo molecular and genomic imaging: new challenges for imaging physics,” Phys. Med. Biol. 49(3), R13–R48 (2004).
[CrossRef] [PubMed]

Cheung, C.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

Choe, R.

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Culver, J. P.

J. P. Culver, A. M. Siegel, J. J. Stott, and D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett. 28(21), 2061–2063 (2003).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Davis, S. C.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

Dehghani, H.

Delides, G.

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

DiMarzio, C. A.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Durduran, T.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Dustin, M. L.

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

Favicchio, R.

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

Figueiredo, J. L.

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

Filippidis, G.

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Furuya, D.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (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, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Gaudette, R. J.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Germain, R. N.

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

Giammarco, J.

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Giepmans, B. N. G.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Gossage, K. W.

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

Graves, E. E.

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Greenberg, J. H.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

Grimm, J.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

Holboke, M. J.

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Hoyt, C. C.

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

Jiang, S.

Josephson, L.

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Kambara, H.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

Kilmer, M.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Kogel, C.

Levenson, R. M.

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

Lukyanov, K. A.

V. V. Verkhusha and K. A. Lukyanov, “The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins,” Nat. Biotechnol. 22(3), 289–296 (2004).
[CrossRef] [PubMed]

Mahmood, U.

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[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, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

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]

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

Martin, A.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

McBride, T. O.

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Meyer, H.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Miller, E. L.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Miller, M. J.

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

Montet, X.

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

Nikiforidis, G.

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

Ntziachristos, V.

G. Themelis, J. S. Yoo, and V. Ntziachristos, “Multispectral imaging using multiple-bandpass filters,” Opt. Lett. 33(9), 1023–1025 (2008).
[CrossRef] [PubMed]

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng. 8(1), 1–33 (2006).
[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]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

J. Ripoll and V. Ntziachristos, “Imaging scattering media from a distance: Theory and applications of non-contact optical tomography,” Mod. Phys. Lett. B 18(28 & 29), 1403–1431 (2004).
[CrossRef]

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation,” Opt. Lett. 26(12), 893–895 (2001).
[CrossRef] [PubMed]

Nussenzweig, M. C.

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

Osterberg, U. L.

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Osterman, K. S.

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Palmer, A. E.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Papadakis, A.

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

Papazoglou, T. G.

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Paulsen, K. D.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

B. Brooksby, S. Srinivasan, S. Jiang, H. Dehghani, B. W. Pogue, K. D. Paulsen, J. Weaver, C. Kogel, and S. P. Poplack, “Spectral priors improve near-infrared diffuse tomography more than spatial priors,” Opt. Lett. 30(15), 1968–1970 (2005).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Pepperkok, R.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Pittet, M. J.

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[CrossRef] [PubMed]

Planas, A. M.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Pogue, B. W.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005).
[CrossRef] [PubMed]

B. Brooksby, S. Srinivasan, S. Jiang, H. Dehghani, B. W. Pogue, K. D. Paulsen, J. Weaver, C. Kogel, and S. P. Poplack, “Spectral priors improve near-infrared diffuse tomography more than spatial priors,” Opt. Lett. 30(15), 1968–1970 (2005).
[CrossRef] [PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Poplack, S. P.

B. Brooksby, S. Srinivasan, S. Jiang, H. Dehghani, B. W. Pogue, K. D. Paulsen, J. Weaver, C. Kogel, and S. P. Poplack, “Spectral priors improve near-infrared diffuse tomography more than spatial priors,” Opt. Lett. 30(15), 1968–1970 (2005).
[CrossRef] [PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Psycharakis, S.

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

Rietdorf, J.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Ripoll, J.

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[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]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

J. Ripoll and V. Ntziachristos, “Imaging scattering media from a distance: Theory and applications of non-contact optical tomography,” Mod. Phys. Lett. B 18(28 & 29), 1403–1431 (2004).
[CrossRef]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Saeki, Y.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

Sanidas, E.

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Sarasa-Renedo, A.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Schellenberger, E. A.

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Schweiger, M.

Shaner, N. C.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Shih, H.

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

Siegel, A. M.

Simantiraki, M.

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

Srinivasan, S.

Stathopoulos, E.

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

Steinbach, P. A.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Stott, J. J.

Svenmarker, P.

Svensson, J.

Swartling, J.

Terike, K.

Themelis, G.

Tsien, R. Y.

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

Tsiftsis, D. D.

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Tsoukatou, D.

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Tung, C. H.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

Tuttle, S. B.

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

Verkhusha, V. V.

V. V. Verkhusha and K. A. Lukyanov, “The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins,” Nat. Biotechnol. 22(3), 289–296 (2004).
[CrossRef] [PubMed]

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]

Weaver, J.

Weissleder, R.

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[CrossRef] [PubMed]

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (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]

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation,” Opt. Lett. 26(12), 893–895 (2001).
[CrossRef] [PubMed]

Wells, W. A.

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Yessayan, D.

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Yodh, A. G.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Yoo, J. S.

Zacharakis, G.

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Zacharopoulos, A. D.

Zhang, Q.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

Zimmermann, T.

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[PubMed]

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Zubkov, L.

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

Adv. Biochem. Eng. Biotechnol. (1)

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[PubMed]

Annu. Rev. Biomed. Eng. (1)

V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng. 8(1), 1–33 (2006).
[CrossRef] [PubMed]

Appl. Opt. (2)

Curr. Pharm. Biotechnol. (1)

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]

FEBS Lett. (1)

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

IEEE Signal Process. Mag. (1)

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag. 18(6), 57–75 (2001).
[CrossRef]

IEEE Trans. Biomed. Eng. (1)

A. Papadakis, E. Stathopoulos, G. Delides, K. Berberides, G. Nikiforidis, and C. Balas, “A novel spectral microscope system: application in quantitative pathology,” IEEE Trans. Biomed. Eng. 50(2), 207–217 (2003).
[CrossRef] [PubMed]

J. Appl. Phys. (1)

S. C. Davis, B. W. Pogue, S. B. Tuttle, H. Dehghani, and K. D. Paulsen, “Spectral distortion in diffuse molecular luminescence tomography in turbid media,” J. Appl. Phys. 105(10), 102024 (2009).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

J. R. Mansfield, K. W. Gossage, C. C. Hoyt, and R. M. Levenson, “Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging,” J. Biomed. Opt. 10(4), 041207 (2005).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (1)

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23(8), 911–924 (2003).
[CrossRef] [PubMed]

J. Innovative Optical Health Science (1)

M. Simantiraki, R. Favicchio, S. Psycharakis, G. Zacharakis, and J. Ripoll, “Multispectral unmixing of fluorescence molecular tomography data,” J. Innovative Optical Health Science 2(4), 353–364 (2009).
[CrossRef]

J. Opt. A, Pure Appl. Opt. (1)

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, V. Ntziachristos, T. G. Papazoglou, and J. Ripoll, “Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments,” J. Opt. A, Pure Appl. Opt. 6(7), 725–735 (2004).
[CrossRef]

Mod. Phys. Lett. B (1)

J. Ripoll and V. Ntziachristos, “Imaging scattering media from a distance: Theory and applications of non-contact optical tomography,” Mod. Phys. Lett. B 18(28 & 29), 1403–1431 (2004).
[CrossRef]

Mol. Imaging (1)

A. Martin, J. Aguirre, A. Sarasa-Renedo, D. Tsoukatou, A. Garofalakis, H. Meyer, C. Mamalaki, J. Ripoll, and A. M. Planas, “Imaging changes in lymphoid organs in vivo after brain ischemia with three-dimensional fluorescence molecular tomography in transgenic mice expressing green fluorescent protein in T lymphocytes,” Mol. Imaging 7(4), 157–167 (2008).
[PubMed]

Nat. Biotechnol. (3)

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]

N. C. Shaner, R. E. Campbell, P. A. Steinbach, B. N. G. Giepmans, A. E. Palmer, and R. Y. Tsien, “Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein,” Nat. Biotechnol. 22(12), 1567–1572 (2004).
[CrossRef] [PubMed]

V. V. Verkhusha and K. A. Lukyanov, “The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins,” Nat. Biotechnol. 22(3), 289–296 (2004).
[CrossRef] [PubMed]

Nat. Med. (2)

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8(7), 757–761 (2002).
[CrossRef] [PubMed]

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[CrossRef] [PubMed]

Nat. Rev. Immunol. (1)

R. N. Germain, M. J. Miller, M. L. Dustin, and M. C. Nussenzweig, “Dynamic imaging of the immune system: progress, pitfalls and promise,” Nat. Rev. Immunol. 6(7), 497–507 (2006).
[CrossRef] [PubMed]

Nature (1)

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (4)

Phys. Med. Biol. (3)

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, “Bulk optical properties of healthy female breast tissue,” Phys. Med. Biol. 47(16), 2847–2861 (2002).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, and E. Stathopoulos, “M. kafousi, J. Ripoll and T. G. Papazoglou,” Phys. Med. Biol. 50(1), 1–11 (2005).
[PubMed]

S. R. Cherry, “In vivo molecular and genomic imaging: new challenges for imaging physics,” Phys. Med. Biol. 49(3), R13–R48 (2004).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

G. Zacharakis, H. Kambara, H. Shih, J. Ripoll, J. Grimm, Y. Saeki, R. Weissleder, and V. Ntziachristos, “Volumetric tomography of fluorescent proteins through small animals in vivo,” Proc. Natl. Acad. Sci. U.S.A. 102(51), 18252–18257 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. E. Graves, A. Bogdanov, L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101(33), 12294–12299 (2004).
[CrossRef] [PubMed]

Radiology (2)

X. Montet, J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242(3), 751–758 (2007).
[CrossRef] [PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001).
[PubMed]

Other (1)

C. Kak, and M. Slaney, Principles of Computerized Tomographic Imaging (IEEE, New York, 1988).

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Figures (5)

Fig. 1
Fig. 1

The Spectral/FMT experimental setup. R and T stand for the position of the mirror for Reflection or Transmission geometries.

Fig. 2
Fig. 2

Characteristic spectra obtained with our Spectral/FMT system and the corresponding fittings for the calculation of the spectral contributions of the two fluorophores. (a) A schematic of the measurement geometry with the positions where the spectra were collected (solid stars) in respect to the position of the tubes (green for CFSE and red for ATTO590). (b) and (c) Spectra for 488nm and 514nm excitation respectively (green and red triangles) and the corresponding fittings (black squares).

Fig. 3
Fig. 3

(a) Quantification results from the phantom study for the recovered concentrations of ATTO590 and CFSE for the two methods of obtaining the spectral strengths (see text for details). (b) Ratios of the recovered concentrations of ATTO590 over CFSE (see text for details). (c) and (d) Axial views of the unmixed 3D reconstruction for CFSE and ATTO590 respectively.

Fig. 4
Fig. 4

(a) Quantification results for the recovered concentrations of ATTO590 and CFSE for the two methods of obtaining the spectral strengths (see text for details). (b) Ratios of the recovered concentrations of ATTO590 over CFSE (see text for details).

Fig. 5
Fig. 5

Coronal views of the 3D reconstructions of the CFSE and ATTO590 fluorescence signal overlaid on a schematic outline of the mouse. The inset shows the axial view of the same reconstructions. (a) the mixed reconstructions, (b) the unmixed ATTO590 reconstruction and (c) the unmixed CFSE reconstruction.

Equations (8)

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U f i t i = g i ( λ ) G i ( λ ) + r i ( λ ) R i ( λ ) + b k g r d i
e r r = n ( U i U f i t i ) 2 N n
g C F S E ( λ min , λ max ) = 520 n m 560 n m g 488 ( λ ) G 488 d λ   and  r C F S E ( λ min , λ max ) = 570 n m 660 n m g 514 ( λ ) G 514 d λ
g A T T O 590 ( λ min , λ max ) = 520 n m 560 n m r 488 ( λ ) R 488 d λ   and  r A T T O 590 ( λ min , λ max ) = 570 n m 660 n m r 514 ( λ ) R 514 d λ
[ U ] = [ s ] × [ C ]
U g = g C F S E C C F S E + g A T T O 590 C A T T O 590 U r = r C F S E C C F S E + r A T T O 590 C A T T O 590
[ U g U r ] = [ g C F S E g A T T O 590 r C F S E r A T T O 590 ] × [ C C F S E C A T T O 590 ]
[ C C F S E C A T T O 590 ] = [ g C F S E g A T T O 590 r C F S E r A T T O 590 ] 1 × [ U g U r ]

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