Abstract

Förster resonance energy transfer (FRET) is a powerful biological tool for reading out cell signaling processes. In vivo use of FRET is challenging because of the scattering properties of bulk tissue. By combining diffuse fluorescence tomography with fluorescence lifetime imaging (FLIM), implemented using wide-field time-gated detection of fluorescence excited by ultrashort laser pulses in a tomographic imaging system and applying inverse scattering algorithms, we can reconstruct the three dimensional spatial localization of fluorescence quantum efficiency and lifetime. We demonstrate in vivo spatial mapping of FRET between genetically expressed fluorescent proteins in live mice read out using FLIM. Following transfection by electroporation, mouse hind leg muscles were imaged in vivo and the emission of free donor (eGFP) in the presence of free acceptor (mCherry) could be clearly distinguished from the fluorescence of the donor when directly linked to the acceptor in a tandem (eGFP-mCherry) FRET construct.

© 2011 OSA

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2011

2010

V. Gaind, S. Kularatne, P. S. Low, and K. J. Webb, “Deep-tissue imaging of intramolecular fluorescence resonance energy-transfer parameters,” Opt. Lett. 35(9), 1314–1316 (2010).
[CrossRef] [PubMed]

V. Y. Soloviev, C. D’Andrea, P. S. Mohan, G. Valentini, R. Cubeddu, and S. R. Arridge, “Fluorescence lifetime optical tomography with Discontinuous Galerkin discretisation scheme,” Biomed. Opt. Express 1(3), 998–1013 (2010).
[CrossRef] [PubMed]

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

2009

2008

S. B. VanEngelenburg and A. E. Palmer, “Fluorescent biosensors of protein function,” Curr. Opin. Chem. Biol. 12(1), 60–65 (2008).
[CrossRef] [PubMed]

B. Ananthanarayanan, Q. Ni, and J. Zhang, “Chapter 2: Molecular sensors based on fluorescence resonance energy transfer to visualize cellular dynamics,” Methods Cell Biol. 89, 37–57 (2008).
[CrossRef] [PubMed]

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

2007

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

2006

S. S. Vogel, C. Thaler, and S. V. Koushik, “Fanciful FRET,” Sci. STKE 2006(331), re2 (2006).
[CrossRef] [PubMed]

E. A. Jares-Erijman and T. M. Jovin, “Imaging molecular interactions in living cells by FRET microscopy,” Curr. Opin. Chem. Biol. 10(5), 409–416 (2006).
[CrossRef] [PubMed]

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

2001

J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

1997

J. C. Hebden, S. R. Arridge, and D. T. Delpy, “Optical imaging in medicine: I. Experimental techniques,” Phys. Med. Biol. 42(5), 825–840 (1997).
[CrossRef] [PubMed]

1995

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Achilefu, S.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

Akers, W.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

Ananthanarayanan, B.

B. Ananthanarayanan, Q. Ni, and J. Zhang, “Chapter 2: Molecular sensors based on fluorescence resonance energy transfer to visualize cellular dynamics,” Methods Cell Biol. 89, 37–57 (2008).
[CrossRef] [PubMed]

Arridge, S. R.

V. Y. Soloviev, C. D’Andrea, P. S. Mohan, G. Valentini, R. Cubeddu, and S. R. Arridge, “Fluorescence lifetime optical tomography with Discontinuous Galerkin discretisation scheme,” Biomed. Opt. Express 1(3), 998–1013 (2010).
[CrossRef] [PubMed]

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

J. McGinty, V. Y. Soloviev, K. B. Tahir, R. Laine, D. W. Stuckey, J. V. Hajnal, A. Sardini, P. M. French, and S. R. Arridge, “Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging,” Opt. Lett. 34(18), 2772–2774 (2009).
[CrossRef] [PubMed]

J. C. Hebden, S. R. Arridge, and D. T. Delpy, “Optical imaging in medicine: I. Experimental techniques,” Phys. Med. Biol. 42(5), 825–840 (1997).
[CrossRef] [PubMed]

Bastiaens, P. I.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

Behr, J. P.

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Boussif, O.

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Breakefield, X. O.

Cubeddu, R.

Culver, J. P.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

D’Andrea, C.

Deliolanis, N. C.

Delpy, D. T.

J. C. Hebden, S. R. Arridge, and D. T. Delpy, “Optical imaging in medicine: I. Experimental techniques,” Phys. Med. Biol. 42(5), 825–840 (1997).
[CrossRef] [PubMed]

Demeneix, B.

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Dunsby, C.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Fazio, V. M.

J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

Fiks, I. I.

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

French, P. M.

J. McGinty, V. Y. Soloviev, K. B. Tahir, R. Laine, D. W. Stuckey, J. V. Hajnal, A. Sardini, P. M. French, and S. R. Arridge, “Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging,” Opt. Lett. 34(18), 2772–2774 (2009).
[CrossRef] [PubMed]

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

French, P. M. W.

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

Gaind, V.

Grant, D. M.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Hajnal, J. V.

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

J. McGinty, V. Y. Soloviev, K. B. Tahir, R. Laine, D. W. Stuckey, J. V. Hajnal, A. Sardini, P. M. French, and S. R. Arridge, “Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging,” Opt. Lett. 34(18), 2772–2774 (2009).
[CrossRef] [PubMed]

Hebden, J. C.

J. C. Hebden, S. R. Arridge, and D. T. Delpy, “Optical imaging in medicine: I. Experimental techniques,” Phys. Med. Biol. 42(5), 825–840 (1997).
[CrossRef] [PubMed]

Hink, M. A.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

Itoh, Y.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Ivashina, T. V.

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

Jares-Erijman, E. A.

E. A. Jares-Erijman and T. M. Jovin, “Imaging molecular interactions in living cells by FRET microscopy,” Curr. Opin. Chem. Biol. 10(5), 409–416 (2006).
[CrossRef] [PubMed]

Jovin, T. M.

E. A. Jares-Erijman and T. M. Jovin, “Imaging molecular interactions in living cells by FRET microscopy,” Curr. Opin. Chem. Biol. 10(5), 409–416 (2006).
[CrossRef] [PubMed]

Kennedy, G. T.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Kinkhabwala, A.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

Knop, M.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

Koushik, S. V.

S. S. Vogel, C. Thaler, and S. V. Koushik, “Fanciful FRET,” Sci. STKE 2006(331), re2 (2006).
[CrossRef] [PubMed]

Kularatne, S.

Laine, R.

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

J. McGinty, V. Y. Soloviev, K. B. Tahir, R. Laine, D. W. Stuckey, J. V. Hajnal, A. Sardini, P. M. French, and S. R. Arridge, “Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging,” Opt. Lett. 34(18), 2772–2774 (2009).
[CrossRef] [PubMed]

Lezoualc’h, F.

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Low, P. S.

Maeder, C. I.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

Magee, A. I.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Manning, H. B.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Mayr, R.

C. I. Maeder, M. A. Hink, A. Kinkhabwala, R. Mayr, P. I. Bastiaens, and M. Knop, “Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling,” Nat. Cell Biol. 9(11), 1319–1326 (2007).
[CrossRef] [PubMed]

McGinty, J.

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

J. McGinty, V. Y. Soloviev, K. B. Tahir, R. Laine, D. W. Stuckey, J. V. Hajnal, A. Sardini, P. M. French, and S. R. Arridge, “Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging,” Opt. Lett. 34(18), 2772–2774 (2009).
[CrossRef] [PubMed]

McMahon, J. M.

J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

Meerovich, I. G.

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

Mergny, M. D.

O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

Mohan, P. S.

V. Y. Soloviev, C. D’Andrea, P. S. Mohan, G. Valentini, R. Cubeddu, and S. R. Arridge, “Fluorescence lifetime optical tomography with Discontinuous Galerkin discretisation scheme,” Biomed. Opt. Express 1(3), 998–1013 (2010).
[CrossRef] [PubMed]

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

Neil, M. A.

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

Ni, Q.

B. Ananthanarayanan, Q. Ni, and J. Zhang, “Chapter 2: Molecular sensors based on fluorescence resonance energy transfer to visualize cellular dynamics,” Methods Cell Biol. 89, 37–57 (2008).
[CrossRef] [PubMed]

Nothdurft, R. E.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

Ntziachristos, V.

Orlova, A. G.

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

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H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

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S. B. VanEngelenburg and A. E. Palmer, “Fluorescent biosensors of protein function,” Curr. Opin. Chem. Biol. 12(1), 60–65 (2008).
[CrossRef] [PubMed]

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R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

Pike, L.

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A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

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V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
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A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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Stuckey, D. W.

V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

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[CrossRef]

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[CrossRef] [PubMed]

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S. S. Vogel, C. Thaler, and S. V. Koushik, “Fanciful FRET,” Sci. STKE 2006(331), re2 (2006).
[CrossRef] [PubMed]

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A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
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S. B. VanEngelenburg and A. E. Palmer, “Fluorescent biosensors of protein function,” Curr. Opin. Chem. Biol. 12(1), 60–65 (2008).
[CrossRef] [PubMed]

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A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

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J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

Wells, K. E.

J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

Wurdinger, T.

Ye, Y.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

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O. Boussif, F. Lezoualc’h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, “A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine,” Proc. Natl. Acad. Sci. U.S.A. 92(16), 7297–7301 (1995).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
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[CrossRef] [PubMed]

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J. M. McMahon, E. Signori, K. E. Wells, V. M. Fazio, and D. J. Wells, “Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage,” Gene Ther. 8(16), 1264–1270 (2001).
[CrossRef] [PubMed]

J Biophotonics

H. B. Manning, G. T. Kennedy, D. M. Owen, D. M. Grant, A. I. Magee, M. A. Neil, Y. Itoh, C. Dunsby, and P. M. French, “A compact, multidimensional spectrofluorometer exploiting supercontinuum generation,” J Biophotonics 1(6), 494–505 (2008).
[CrossRef] [PubMed]

A. L. Rusanov, T. V. Ivashina, L. M. Vinokurov, I. I. Fiks, A. G. Orlova, I. V. Turchin, I. G. Meerovich, V. V. Zherdeva, and A. P. Savitsky, “Lifetime imaging of FRET between red fluorescent proteins,” J Biophotonics 3(12), 774–783 (2010).
[CrossRef] [PubMed]

J. Biomed. Opt.

R. E. Nothdurft, S. V. Patwardhan, W. Akers, Y. Ye, S. Achilefu, and J. P. Culver, “In vivo fluorescence lifetime tomography,” J. Biomed. Opt. 14(2), 024004 (2009).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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V. Y. Soloviev, J. McGinty, K. B. Tahir, R. Laine, D. W. Stuckey, P. S. Mohan, J. V. Hajnal, A. Sardini, P. M. W. French, and S. R. Arridge, “Tomographic imaging of fluorescence resonance energy transfer in highly light scattering media,” Proc. SPIE 7573, 75730G, 75730G-10 (2010).
[CrossRef]

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Figures (5)

Fig. 1
Fig. 1

Schematic of the in vivo time-gated imaging setup. (a) Ultrashort pulses of radiation from a spectrally filtered supercontinuum laser were focused on the surface of the mouse leg. The emerging fluorescence light distribution was imaged onto the GOI and read out using the CCD. (b) The anaesthetized mouse was positioned on the imaging platform, which was set on a motorised rotation stage controlled by the PC. The target leg was held under slight tension by an elastic band. M, Mirror; F1, Filter 1; F2, Filter 2; L, Lens; IR1, Image Relay 1; IR2, Image Relay 2; GOI, Gated-Optical Intensifier; CCD, Charged-Couple Device camera; PC, Personal Computer.

Fig. 2
Fig. 2

Transverse sections from tomographic reconstructions of MRI and fluorescence lifetime from in vivo measurements of mouse hind legs. Panels show leg cross sections from (a) mouse 3 expressing GCLink and (b) mouse 4 co-expressing eGFP and mCherry, with left image: MRI; central image: reconstructed MAP lifetime distribution (τ); right image: merged. Panel (c) shows fluorescence lifetime histograms of tomographic reconstructions from mice 3 and 4. These values are extracted from a volume defined by the top 30% of the calculated quantum yield distribution.

Fig. 3
Fig. 3

Time-resolved fluorescence spectroscopy of cytosol preparations of eGFP, GCLink and eGFP + mCherry. The experimental data are displayed in blue, the fitting model in red and the Instrument Response Function (IRF) is displayed in black. At the bottom of the figure the residuals of the fits are shown.

Fig. 4
Fig. 4

Tomographic reconstructions of quantum yield distributions from in vivo FLIM of hind leg muscles. Leg cross sections expressing GCLink (a) and co-expressing eGFP and mCherry (b). Left side panel: MRI; central panel: reconstructed MAP quantum yield distribution (η); right panel: merged.

Fig. 5
Fig. 5

Co-location of transfected fluorophores. Panel (a) shows fluorescence microscope images of a whole leg section of a mouse transfected with GCLink with left image eGFP signal; central image: mCherry signal; right image: combined bright field and fluorescent images with overlay of two fluorescent signals in yellow. Panels (b) and (c) show confocal sections of TA muscles from mice transfected either with GCLink (b) or eGFP and mCherry (c) respectively with left image: eGFP signal; central image: mCherry signal; right image: overlaid.

Tables (2)

Tables Icon

Table 1 Mean eGFP fluorescence lifetimes and quantum yields

Tables Icon

Table 2 Time-resolved fluorescence spectroscopy of cytosol preparations of eGFP, GCLink and eGFP + mCherry

Equations (2)

Equations on this page are rendered with MathJax. Learn more.

I ( t ) = p 1 e t τ 1 + p 2 e t τ 2
τ ¯ = p 1 τ 1 2 + p 2 τ 2 2 p 1 τ 1 + p 2 τ 2

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