Abstract

Time-domain fluorescence imaging is a powerful new technique that adds a rich amount of information to conventional fluorescence imaging. Specifically, time-domain fluorescence can be used to remove autofluorescence from signals, resolve multiple fluorophore concentrations, provide information about tissue microenvironments, and, for reflectance-based imaging systems, resolve inclusion depth. The present study provides the theory behind an improved method of analyzing reflectance-based time-domain data that is capable of accurately recovering mixed concentration ratios of multiple fluorescent agents while also recovering the depth of the inclusion. The utility of the approach was demonstrated in a number of simulations and in tissuelike phantom experiments using a short source–detector separation system. The major findings of this study were (1) both depth of an inclusion and accurate ratios of two-fluorophore concentrations can be recovered accurately up to depths of approximately 1cm with only the optical properties of the medium as prior knowledge, (2) resolving the depth and accounting for the dispersion effects on fluorescent lifetimes is crucial to the accuracy of recovered ratios, and (3) ratios of three-fluorophore concentrations can be resolved at depth but only if the lifetimes of the three fluorophores are used as prior knowledge. By accurately resolving the concentration ratios of two to three fluorophores, it may be possible to remove autofluorescence or carry out quantitative techniques, such as reference tracer kinetic modeling or ratiometric approaches, to determine receptor binding or microenvironment parameters in point-based time-domain fluorescence applications.

© 2011 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef]
  31. S. H. Han, S. Farshchi-Heydari, and D. J. Hall, “Analysis of the fluorescence temporal point-spread function in a turbid medium and its application to optical imaging,” J. Biomed. Opt. 13, 064038 (2008).
    [CrossRef]
  32. D. J. Hall, U. Sunar, S. Farshchi-Heydari, and S. H. Han, “In vivo simultaneous monitoring of two fluorophores with lifetime contrast using a full-field time domain system,” Appl. Opt. 48, D74–D78 (2009).
    [CrossRef] [PubMed]
  33. C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
    [CrossRef]
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    [CrossRef]

2011

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

2010

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation,” Mol. Imaging 9, 237–255 (2010).
[PubMed]

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

2009

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, 024004 (2009).
[CrossRef] [PubMed]

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

D. J. Hall, U. Sunar, S. Farshchi-Heydari, and S. H. Han, “In vivo simultaneous monitoring of two fluorophores with lifetime contrast using a full-field time domain system,” Appl. Opt. 48, D74–D78 (2009).
[CrossRef] [PubMed]

2008

C. D. Salthouse, R. Weissleder, and U. Mahmood, “Development of a time domain fluorimeter for fluorescent lifetime multiplexing analysis,” IEEE Trans. Biomed. Circuits Syst. 2, 204–211 (2008).
[CrossRef]

S. H. Han, S. Farshchi-Heydari, and D. J. Hall, “Analysis of the fluorescence temporal point-spread function in a turbid medium and its application to optical imaging,” J. Biomed. Opt. 13, 064038 (2008).
[CrossRef]

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13, 041304 (2008).
[CrossRef] [PubMed]

S. H. Han and D. J. Hall, “Estimating the depth and lifetime of a fluorescent inclusion in a turbid medium using a simple time-domain optical method,” Opt. Lett. 33, 1035–1037 (2008).
[CrossRef] [PubMed]

L. Zhang, F. Gao, H. He, and H. Zhao, “Three-dimensional scheme for time-domain fluorescence molecular tomography based on Laplace transforms with noise-robust factors,” Opt. Express 16, 7214–7223 (2008).
[CrossRef] [PubMed]

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(2008).
[CrossRef] [PubMed]

2007

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotechnol. 18, 17–25 (2007).
[CrossRef] [PubMed]

R. S. DaCosta, B. C. Wilson, and N. E. Marcon, “Fluorescence and spectral imaging,” Scientific World J. 7, 2046–2071 (2007).
[CrossRef]

V. Y. Soloviev, K. B. Tahir, J. McGinty, D. S. Elson, M. A. Neil, P. M. French, and S. R. Arridge, “Fluorescence lifetime imaging by using time-gated data acquisition,” Appl. Opt. 46, 7384–7391 (2007).
[CrossRef] [PubMed]

2006

2005

S. Lam, F. Lesage, and X. Intes, “Time domain fluorescent diffuse optical tomography: analytical expressions,” Opt. Express 13, 2263–2275 (2005).
[CrossRef] [PubMed]

A. T. Kumar, J. Skoch, B. J. Bacskai, D. A. Boas, and A. K. Dunn, “Fluorescence-lifetime-based tomography for turbid media,” Opt. Lett. 30, 3347–3349 (2005).
[CrossRef]

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, “Three-dimensional fluorescence lifetime tomography,” Med. Phys. 32, 992–1000 (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, 313–320 (2005).
[CrossRef] [PubMed]

2004

2002

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

E. Kuwana and E. M. Sevick-Muraca, “Fluorescence lifetime spectroscopy in multiply scattering media with dyes exhibiting multiexponential decay kinetics,” Biophys. J. 83, 1165–1176 (2002).
[CrossRef] [PubMed]

K. Vishwanath, B. Pogue, and M. A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47, 3387–3405 (2002).
[CrossRef] [PubMed]

2001

V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28, 1115–1124 (2001).
[CrossRef] [PubMed]

1997

1995

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

1989

1943

S. Chandrasekhar, “Stochastic problems in physics and astronomy,” Rev. Mod. Phys. 15, 1–89 (1943).
[CrossRef]

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, 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, 024004 (2009).
[CrossRef] [PubMed]

Alerstam, E.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13, 041304 (2008).
[CrossRef] [PubMed]

Alford, R.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

Andersson-Engels, S.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13, 041304 (2008).
[CrossRef] [PubMed]

Arridge, S. R.

Bacskai, B. J.

Berg, M.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Boas, D. A.

Boverman, G.

Bressel, L.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Chance, B.

V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28, 1115–1124 (2001).
[CrossRef] [PubMed]

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 28, 2331–2336(1989).
[CrossRef] [PubMed]

Chandrasekhar, S.

S. Chandrasekhar, “Stochastic problems in physics and astronomy,” Rev. Mod. Phys. 15, 1–89 (1943).
[CrossRef]

Chernova, S. P.

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

Choi, H. S.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation,” Mol. Imaging 9, 237–255 (2010).
[PubMed]

Choyke, P. L.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

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, 024004 (2009).
[CrossRef] [PubMed]

DaCosta, R. S.

R. S. DaCosta, B. C. Wilson, and N. E. Marcon, “Fluorescence and spectral imaging,” Scientific World J. 7, 2046–2071 (2007).
[CrossRef]

Dadani, F. N.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

Davis, S. C.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

Diop, M.

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Dosche, C.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Dragulescu-Andrasi, A.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotechnol. 18, 17–25 (2007).
[CrossRef] [PubMed]

Dunn, A. K.

Elliott, J. T.

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Elson, D. S.

Eppstein, M. J.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, “Three-dimensional fluorescence lifetime tomography,” Med. Phys. 32, 992–1000 (2005).
[CrossRef] [PubMed]

Farshchi-Heydari, S.

D. J. Hall, U. Sunar, S. Farshchi-Heydari, and S. H. Han, “In vivo simultaneous monitoring of two fluorophores with lifetime contrast using a full-field time domain system,” Appl. Opt. 48, D74–D78 (2009).
[CrossRef] [PubMed]

S. H. Han, S. Farshchi-Heydari, and D. J. Hall, “Analysis of the fluorescence temporal point-spread function in a turbid medium and its application to optical imaging,” J. Biomed. Opt. 13, 064038 (2008).
[CrossRef]

Frangioni, J. V.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation,” Mol. Imaging 9, 237–255 (2010).
[PubMed]

French, P. M.

Gandjbakhche, A. H.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

Gao, F.

Gioux, S.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation,” Mol. Imaging 9, 237–255 (2010).
[PubMed]

Godavarty, A.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, “Three-dimensional fluorescence lifetime tomography,” Med. Phys. 32, 992–1000 (2005).
[CrossRef] [PubMed]

Hall, D.

Hall, D. J.

Han, S. H.

Hasan, T.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

Hassan, M.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

He, H.

Hextrum, S.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

Hilderbrand, S. A.

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(2008).
[CrossRef] [PubMed]

Hille, C.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Intes, X.

Jermyn, M.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

Josephson, L.

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

Kelly, K. A.

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(2008).
[CrossRef] [PubMed]

Kienle, A.

Kim, A.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

Kobayashi, H.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

Kumar, A. T.

Kuwana, E.

E. Kuwana and E. M. Sevick-Muraca, “Fluorescence lifetime spectroscopy in multiply scattering media with dyes exhibiting multiexponential decay kinetics,” Biophys. J. 83, 1165–1176 (2002).
[CrossRef] [PubMed]

Lam, S.

Leblond, F.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

Lee, T.-Y.

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Lesage, F.

Liu, H.

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Lohmannsroben, H. G.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Ma, G.

Mahmood, U.

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

C. D. Salthouse, R. Weissleder, and U. Mahmood, “Development of a time domain fluorimeter for fluorescent lifetime multiplexing analysis,” IEEE Trans. Biomed. Circuits Syst. 2, 204–211 (2008).
[CrossRef]

Marcon, N. E.

R. S. DaCosta, B. C. Wilson, and N. E. Marcon, “Fluorescence and spectral imaging,” Scientific World J. 7, 2046–2071 (2007).
[CrossRef]

McGinty, J.

Migueis, M.

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Munzke, D.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Mycek, M. A.

K. Vishwanath, B. Pogue, and M. A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47, 3387–3405 (2002).
[CrossRef] [PubMed]

Neil, M. A.

Niedre, M.

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(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, 024004 (2009).
[CrossRef] [PubMed]

Ntziachristos, 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, 313–320 (2005).
[CrossRef] [PubMed]

V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28, 1115–1124 (2001).
[CrossRef] [PubMed]

O’Hara, J. A.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

Ogawa, M.

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

Papazoglou, T. G.

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

Patterson, M. S.

Patwardhan, S. V.

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, 024004 (2009).
[CrossRef] [PubMed]

Pogue, B.

K. Vishwanath, B. Pogue, and M. A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47, 3387–3405 (2002).
[CrossRef] [PubMed]

Pogue, B. W.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

Pravdin, A. B.

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

Primus, P.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Rao, J.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotechnol. 18, 17–25 (2007).
[CrossRef] [PubMed]

Raymond, S. B.

Reynolds, F.

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

Ripoll, J.

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, 313–320 (2005).
[CrossRef] [PubMed]

Roy, M.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

Salthouse, C. D.

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

C. D. Salthouse, R. Weissleder, and U. Mahmood, “Development of a time domain fluorimeter for fluorescent lifetime multiplexing analysis,” IEEE Trans. Biomed. Circuits Syst. 2, 204–211 (2008).
[CrossRef]

Samkoe, K. S.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, “Three-dimensional fluorescence lifetime tomography,” Med. Phys. 32, 992–1000 (2005).
[CrossRef] [PubMed]

E. Kuwana and E. M. Sevick-Muraca, “Fluorescence lifetime spectroscopy in multiply scattering media with dyes exhibiting multiexponential decay kinetics,” Biophys. J. 83, 1165–1176 (2002).
[CrossRef] [PubMed]

Skoch, J.

Soloviev, V. Y.

Srinivasan, S.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

St. Lawrence, K.

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Sunar, U.

Svensson, T.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13, 041304 (2008).
[CrossRef] [PubMed]

Tahir, K. B.

Tam, J. M.

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

Tichauer, K. M.

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

Tuchin, V. V.

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

Valdes, P. A.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

Vishwanath, K.

K. Vishwanath, B. Pogue, and M. A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47, 3387–3405 (2002).
[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, 313–320 (2005).
[CrossRef] [PubMed]

Wang, Y.

Weissleder, R.

C. D. Salthouse, R. Weissleder, and U. Mahmood, “Development of a time domain fluorimeter for fluorescent lifetime multiplexing analysis,” IEEE Trans. Biomed. Circuits Syst. 2, 204–211 (2008).
[CrossRef]

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(2008).
[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, 313–320 (2005).
[CrossRef] [PubMed]

Wilson, B. C.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

R. S. DaCosta, B. C. Wilson, and N. E. Marcon, “Fluorescence and spectral imaging,” Scientific World J. 7, 2046–2071 (2007).
[CrossRef]

M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 28, 2331–2336(1989).
[CrossRef] [PubMed]

Yao, H.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotechnol. 18, 17–25 (2007).
[CrossRef] [PubMed]

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, 024004 (2009).
[CrossRef] [PubMed]

Yodh, A. G.

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Zhang, L.

Zhang, Y.

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Zhao, H.

Anal. Bioanal. Chem.

C. Hille, M. Berg, L. Bressel, D. Munzke, P. Primus, H. G. Lohmannsroben, and C. Dosche, “Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues,” Anal. Bioanal. Chem. 391, 1871–1879 (2008).
[CrossRef] [PubMed]

Appl. Opt.

Bioconjug. Chem.

S. A. Hilderbrand, K. A. Kelly, M. Niedre, and R. Weissleder, “Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging,” Bioconjug. Chem. 19, 1635–1639(2008).
[CrossRef] [PubMed]

Biophys. J.

E. Kuwana and E. M. Sevick-Muraca, “Fluorescence lifetime spectroscopy in multiply scattering media with dyes exhibiting multiexponential decay kinetics,” Biophys. J. 83, 1165–1176 (2002).
[CrossRef] [PubMed]

Contrast Media Mol. Imaging

R. Alford, M. Ogawa, M. Hassan, A. H. Gandjbakhche, P. L. Choyke, and H. Kobayashi, “Fluorescence lifetime imaging of activatable target specific molecular probes,” Contrast Media Mol. Imaging 5, 1–8 (2010).
[PubMed]

Curr. Opin. Biotechnol.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: recent advances,” Curr. Opin. Biotechnol. 18, 17–25 (2007).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Circuits Syst.

C. D. Salthouse, R. Weissleder, and U. Mahmood, “Development of a time domain fluorimeter for fluorescent lifetime multiplexing analysis,” IEEE Trans. Biomed. Circuits Syst. 2, 204–211 (2008).
[CrossRef]

J. Biomed. Opt.

E. Alerstam, S. Andersson-Engels, and T. Svensson, “White Monte Carlo for time-resolved photon migration,” J. Biomed. Opt. 13, 041304 (2008).
[CrossRef] [PubMed]

S. H. Han, S. Farshchi-Heydari, and D. J. Hall, “Analysis of the fluorescence temporal point-spread function in a turbid medium and its application to optical imaging,” J. Biomed. Opt. 13, 064038 (2008).
[CrossRef]

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, 024004 (2009).
[CrossRef] [PubMed]

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15, 066026 (2010).
[CrossRef]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15, 030513 (2010).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

J. Photochem. Photobiol. B

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: review of instruments, methods and applications,” J. Photochem. Photobiol. B 98, 77–94 (2010).
[CrossRef]

Med. Phys.

A. Godavarty, E. M. Sevick-Muraca, and M. J. Eppstein, “Three-dimensional fluorescence lifetime tomography,” Med. Phys. 32, 992–1000 (2005).
[CrossRef] [PubMed]

V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28, 1115–1124 (2001).
[CrossRef] [PubMed]

Mol. Imaging

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation,” Mol. Imaging 9, 237–255 (2010).
[PubMed]

Nat. Biotechnol.

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, 313–320 (2005).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Med. Biol.

H. Liu, D. A. Boas, Y. Zhang, A. G. Yodh, and B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

K. Vishwanath, B. Pogue, and M. A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47, 3387–3405 (2002).
[CrossRef] [PubMed]

Proc. SPIE

M. Diop, K. M. Tichauer, J. T. Elliott, M. Migueis, T.-Y. Lee, and K. St. Lawrence, “Time-resolved near-infrared technique for bedside monitoring of absolute cerebral blood flow” Proc. SPIE 7555, 75550Z (2010).
[CrossRef]

J. T. Elliott, K. M. Tichauer, M. Diop, and K. St. Lawrence, “Fast Monte Carlo fitting of two-layered tissue structures for short source–detector distances,” Proc. SPIE 7896, 789611(2011).
[CrossRef]

Rev. Mod. Phys.

S. Chandrasekhar, “Stochastic problems in physics and astronomy,” Rev. Mod. Phys. 15, 1–89 (1943).
[CrossRef]

Scientific World J.

R. S. DaCosta, B. C. Wilson, and N. E. Marcon, “Fluorescence and spectral imaging,” Scientific World J. 7, 2046–2071 (2007).
[CrossRef]

Sens. Actuators B

C. D. Salthouse, F. Reynolds, J. M. Tam, L. Josephson, and U. Mahmood, “Quantitative measurement of protease-activity with correction of probe delivery and tissue absorption effects,” Sens. Actuators B 138, 591–597 (2009).
[CrossRef]

Other

A. B. Pravdin, S. P. Chernova, T. G. Papazoglou, and V. V. Tuchin, “Tissue Phantoms,” in Handbook of Optical Biomedical Diagnostics, V.V.Tuchin, ed. (SPIE, 2002), pp. 311–354.

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Figures (7)

Fig. 1
Fig. 1

Partial derivative sensitivities, with respect to lifetime (dashed curve) and distance of fluorescence inclusion from source and detection (dotted curve), of a theoretical FTPSF (solid curve) in a turbid medium ( μ a = 0.02 mm 1 , μ s = 1.0 mm 1 , d = 8 mm , τ = 0.5 ns ). All curves are normalized to their maximum height.

Fig. 2
Fig. 2

(a) Sensitivities of the decay constant, τ, of a theoretical FTPSF tail (75–5% of curve peak) to changes in distance and (b) sensitivities of the Green’s function distance parameter, d, of FTPSF rise (5–60% of curve peak) to changes in distance lifetime in a turbid medium ( μ a = 0.02 mm 1 , μ s = 1.0 mm 1 ).

Fig. 3
Fig. 3

(a), (c), (e) Distance and (b), (d), (f) lifetime histograms of weighting terms from the FTPSF analysis algorithm (Subsection 2C) applied to simulated data with 1% noise of (a), (b) a one-fluorophore inclusion of lifetime = 0.5 ns , at a depth of 8 mm and of (c), (d) a two-fluorophore inclusion consisting of 25% 0.3 ns lifetime and 75% 0.85 ns lifetime and (e), (f) vice versa at a depth of 8 mm .

Fig. 4
Fig. 4

Theoretical sensitivities of (a), (b) the decay constant (lifetime) fitting and (c), (d) the fitted distance over a range of optical properties: scattering (left) and absorption (right). In all cases the inputted distances and lifetimes were 8 mm and 0.5 ns , respectively.

Fig. 5
Fig. 5

Depth cross sections of agarose/Intralipid/ink phantoms with 1 mm diameter, spherical inclusions of ICG at depths of 2, 4, 6, 8, 10, 15, and 20 mm (from left to right), positioned centrally in the horizontal plane. The pixel size is 1 mm , isotropic, and each image corresponds to a width of 12 mm and height of 20 mm .

Fig. 6
Fig. 6

Measured ratios of fluorophore concentrations from phantoms with a range of mixed-fluorophore inclusions at a depth of 8 mm . (a) Example histogram of FTPSF analysis algorithm lifetime weighting terms from a phantom with 25% ICG and 75% DTTCI (percent by fluorescence intensity). (b) Average measured percent ratios of ICG to DTTCI (solid curve), determined from the lifetime histogram peak at 0.3 ns divided by the sum of the 0.75 ns peak and the 0.3 ns peak, and vice versa (dashed curve) compared to the actual ICG contribution ( n = 3 ).

Fig. 7
Fig. 7

Example of a typical fit of the model to experimental data [the same data depicted in Fig. 6a]. (a) Model fit (solid black curve) of the fluorescence data (small circles) in a 5 ns time interval. (b) Log-scale plot of the fit depicted in (a). (c) Residuals of the fit. The chi square associated with this fit was 0.004.

Tables (2)

Tables Icon

Table 1 Errors in Biexponential Fitting Approach If Depth of Inclusion Is Not Accounted For

Tables Icon

Table 2 Recovered Ratios of Three-Fluorophore Mixed Inclusions

Equations (5)

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

· [ D ϕ ( r , t ) ] + 1 v t ϕ ( r , t ) + μ a ϕ ( r , t ) = S ( r s , t ) ,
G ( | r r s | , t ) = 1 ( 4 π D v t ) 3 / 2 exp ( | r r s | 2 4 D v t μ a v t ) .
ϕ λ 2 ( r d , t ) = G λ 1 ( | r r s | , t ) * η τ exp ( t / τ ) * G λ 2 ( | r d r | , t ) ,
ϕ ( r d , t ) = G ( d , t ) * η τ exp ( t / τ ) * G ( d , t ) ,
Φ ( r d , t ) = i , j α i , j G ( d i , t ) * η j τ j exp ( t / τ j ) * G ( d i , t ) * I ( t ) ,

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