Abstract

A diffuse fluorescence tomography system, based upon time-correlated single photon counting, is presented with an automated algorithm to allow dynamic range variation through exposure control. This automated exposure control allows the upper and lower detection levels of fluorophore to be extended by an order of magnitude beyond the previously published performance and benefits in a slight decrease in system effective noise. The effective noise level is used as a metric to characterize the system performance, integrating both model-mismatch and calibration bias errors into a single parameter. This effective error is near 7% of the reconstructed fluorescent yield value, when imaging in just few minutes. Quantifying protoporphyrin IX concentrations down to 50 ng/ml is possible, for tumor-sized regions. This fluorophore has very low fluorescence yield, but high biological relevance for tumor imaging, given that it is produced in the mitochondria, and upregulated in many tumor types.

© 2009 OSA

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2009

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

2008

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

2007

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

H. Meyer, A. Garofalakis, G. Zacharakis, S. Psycharakis, C. Mamalaki, D. Kioussis, E. N. Economou, V. Ntziachristos, and J. Ripoll, “Noncontact optical imaging in mice with full angular coverage and automatic surface extraction,” Appl. Opt. 46(17), 3617–3627 (2007).
[CrossRef] [PubMed]

2005

W. Becker, “Advanced Time-Correlated Single Photon Counting Techniques,” Springer Ser. Chem. Phys. 81, 359 (2005).

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

2003

2002

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

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]

1999

1998

V. Ntziachristos, X. H. Ma, and B. Chance, “Time-correlated single photon counting imager for simultaneous magnetic resonance and near-infrared mammography,” Rev. Sci. Instrum. 69(12), 4221–4233 (1998).
[CrossRef]

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

1997

J. H. Chang, H. L. Graber, and R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44(9), 810–822 (1997).
[CrossRef] [PubMed]

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light reemitted from random media,” Appl. Opt. 36(10), 2260–2272 (1997).
[CrossRef] [PubMed]

1996

1986

D. V. O'Connor and D. Phillips, “Time-correlated single photon counting,” Appl. Opt. 25, 460–463 (1986).

Aikawa, E.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Barbour, R. L.

J. H. Chang, H. L. Graber, and R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44(9), 810–822 (1997).
[CrossRef] [PubMed]

Becker, W.

W. Becker, “Advanced Time-Correlated Single Photon Counting Techniques,” Springer Ser. Chem. Phys. 81, 359 (2005).

Boas, D. A.

Bremer, C.

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

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]

Canti, G.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Chance, B.

V. Ntziachristos, X. H. Ma, and B. Chance, “Time-correlated single photon counting imager for simultaneous magnetic resonance and near-infrared mammography,” Rev. Sci. Instrum. 69(12), 4221–4233 (1998).
[CrossRef]

M. A. O’Leary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, “Fluorescence lifetime imaging in turbid media,” Opt. Lett. 21(2), 158–160 (1996).
[CrossRef] [PubMed]

Chang, J. H.

J. H. Chang, H. L. Graber, and R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44(9), 810–822 (1997).
[CrossRef] [PubMed]

Chen, A. U.

Cubeddu, R.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Davis, S. C.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

de Kleine, R. H.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Dehghani, H.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

Deliolanis, N.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Economou, E. N.

Eppstein, M. J.

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

Garofalakis, A.

Gibbs-Strauss, S. L.

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

Godavarty, A.

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

Graber, H. L.

J. H. Chang, H. L. Graber, and R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44(9), 810–822 (1997).
[CrossRef] [PubMed]

Graves, E. E.

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (2002).
[CrossRef] [PubMed]

Gruber, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Hawrysz, D. J.

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

Hutchins, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

Hypnarowski, J.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Jiang, S.

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

Jiang, S. S.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

Josephson, L.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Kepshire, D.

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Khayat, M.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

Kioussis, D.

Kirsch, D. G.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Leblond, F.

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

Leussler, C.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

Li, X. D.

Lopez, G.

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

Ma, X. H.

V. Ntziachristos, X. H. Ma, and B. Chance, “Time-correlated single photon counting imager for simultaneous magnetic resonance and near-infrared mammography,” Rev. Sci. Instrum. 69(12), 4221–4233 (1998).
[CrossRef]

Mamalaki, C.

Mazurkewitz, P.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

McBride, T. O.

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

Meyer, H.

Mincu, N.

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

Nahrendorf, M.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Niedre, M. J.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

Novikov, M.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Ntziachristos, V.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

H. Meyer, A. Garofalakis, G. Zacharakis, S. Psycharakis, C. Mamalaki, D. Kioussis, E. N. Economou, V. Ntziachristos, and J. Ripoll, “Noncontact optical imaging in mice with full angular coverage and automatic surface extraction,” Appl. Opt. 46(17), 3617–3627 (2007).
[CrossRef] [PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, “Noncontact optical tomography of turbid media,” Opt. Lett. 28(18), 1701–1703 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (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]

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

V. Ntziachristos, X. H. Ma, and B. Chance, “Time-correlated single photon counting imager for simultaneous magnetic resonance and near-infrared mammography,” Rev. Sci. Instrum. 69(12), 4221–4233 (1998).
[CrossRef]

O’Leary, M. A.

O'Connor, D. V.

D. V. O'Connor and D. Phillips, “Time-correlated single photon counting,” Appl. Opt. 25, 460–463 (1986).

Paithankar, D. Y.

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light reemitted from random media,” Appl. Opt. 36(10), 2260–2272 (1997).
[CrossRef] [PubMed]

Patterson, M. S.

Paulsen, K. D.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

Phillips, D.

D. V. O'Connor and D. Phillips, “Time-correlated single photon counting,” Appl. Opt. 25, 460–463 (1986).

Pifferi, A.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Pogue, B. W.

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80(4), 043701 (2009).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue, and K. D. Paulsen, “Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization,” Opt. Express 15(7), 4066–4082 (2007).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light reemitted from random media,” Appl. Opt. 36(10), 2260–2272 (1997).
[CrossRef] [PubMed]

Psycharakis, S.

Reynolds, J. S.

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

Ripoll, J.

Rosenzweig, A.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Roy, R.

Schulz, R. B.

Sevick-Muraca, E. M.

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s optimization scheme for absorption and fluorescence optical tomography: Part II Reconstruction from synthetic measurements,” Opt. Express 4(10), 372–382 (1999).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, and E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light reemitted from random media,” Appl. Opt. 36(10), 2260–2272 (1997).
[CrossRef] [PubMed]

Song, X.

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

Sosnovik, D. E.

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

Springett, R.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

Srinivasan, S.

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

Taroni, P.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Tosteson, T. D.

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

Troy, T. L.

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

Tung, C.

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

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, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
[CrossRef] [PubMed]

Valentini, G.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Wang, J.

Weissleder, R.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (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]

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

Yodh, A. G.

Zacharakis, G.

Acad. Radiol.

V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, 2:5323-5 (2002).

Ann. N. Y. Acad. Sci.

E. M. Sevick-Muraca, J. S. Reynolds, T. L. Troy, G. Lopez, and D. Y. Paithankar, “Fluorescence lifetime spectroscopic imaging with measurements of photon migration,” Ann. N. Y. Acad. Sci. 838(1 ADVANCES IN O), 46–57 (1998).
[CrossRef] [PubMed]

Appl. Opt.

Circulation

D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115(11), 1384–1391 (2007).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng.

J. H. Chang, H. L. Graber, and R. L. Barbour, “Imaging of fluorescence in highly scattering media,” IEEE Trans. Biomed. Eng. 44(9), 810–822 (1997).
[CrossRef] [PubMed]

IEEE Trans. Med. Imaging

B. W. Pogue, X. Song, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations,” IEEE Trans. Med. Imaging 21(7), 755–763 (2002).
[CrossRef] [PubMed]

X. Song, B. W. Pogue, T. D. Tosteson, T. O. McBride, S. Jiang, and K. D. Paulsen, “Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation,” IEEE Trans. Med. Imaging 21(7), 764–772 (2002).
[CrossRef] [PubMed]

J. Biomed. Opt.

X. Song, B. W. Pogue, H. Dehghani, S. Jiang, K. D. Paulsen, and T. D. Tosteson, “Receiver operating characteristic and location analysis of simulated near-infrared tomography images,” J. Biomed. Opt. 12(5), 054013 (2007).
[CrossRef] [PubMed]

S. C. Davis, B. W. Pogue, H. Dehghani, and K. D. Paulsen, “Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction,” J. Biomed. Opt. 10(5), 050501 (2005).
[CrossRef] [PubMed]

Mol. Imaging

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging 1(2), 82–88 (2002).
[CrossRef] [PubMed]

Nat. Med.

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]

Opt. Express

Opt. Lett.

M. A. O’Leary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, “Fluorescence lifetime imaging in turbid media,” Opt. Lett. 21(2), 158–160 (1996).
[CrossRef] [PubMed]

R. B. Schulz, J. Ripoll, and V. Ntziachristos, “Noncontact optical tomography of turbid media,” Opt. Lett. 28(18), 1701–1703 (2003).
[CrossRef] [PubMed]

D. Kepshire, S. L. Gibbs-Strauss, M. Hutchins, N. Mincu, F. Leblond, M. Khayat, H. Dehghani, S. Srinivasan, and B. W. Pogue, “Imaging of glioma tumor with endogenous fluorescence tomography,” Opt. Lett. 14, 030501 (2009).

Photochem. Photobiol.

R. Cubeddu, G. Canti, A. Pifferi, P. Taroni, and G. Valentini, “Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice,” Photochem. Photobiol. 66(2), 229–236 (1997).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

M. J. Niedre, R. H. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105(49), 19126–19131 (2008).
[CrossRef] [PubMed]

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, “Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography,” Proc. Natl. Acad. Sci. U.S.A. 99(15), 9619–9624 (2002).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

S. C. Davis, B. W. Pogue, R. Springett, C. Leussler, P. Mazurkewitz, S. B. Tuttle, S. L. Gibbs-Strauss, S. S. Jiang, H. Dehghani, and K. D. Paulsen, “Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue,” Rev. Sci. Instrum. 79(6), 064302 (2008).
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Figures (6)

Fig. 1
Fig. 1

(a) The underlying principal of TCSPC is illustrated, adapted from Ref. [24], where individual photon pulses analog amplified, and time referenced from a separate PMT signal. The time to amplitude conversion (TAC) is used for analog to digital conversion (ADC) and the temporal data points are summed together and used to construct a histogram of the photon arrival time in TCSPC data memory. In (b) a typical TCSPC data set is shown where the secondary peaks are artifacts from the pulsed laser shape. Note that the y-axis is logarithmic, so that the first peak is actually substantially larger than the 2nd pear. After 500 on the x-axis, the signal is dark noise.

Fig. 2
Fig. 2

Flow chart illustrating the logical flow of steps in the automatic exposure control (AEC) process, to ensure the TPSF has optimal signal. In the lower move attenuator box, the target counts are subtracted by the measure counts, b, and divided by a known slope value, m, which relates counts to attenuator position.

Fig. 3
Fig. 3

Flowchart illustrating the steps required to generate images following data acquisition. The choice of calibration method, either difference-based or calibration simulating the in vivo situation where there is no data set which can be used as an exact reference. The choice of calibration approach affects the accuracy in recovery.

Fig. 4
Fig. 4

In (a) the calibrated measured data are shown for both techniques (with and without the AEC) and clearly illustrates a breakdown in the SNR, without AEC. In (b) the AEC calibrated data and the reconstructed fit data are shown, illustrating a good fit in the reconstruction. In (c), the performance comparison between the “No AEC” and “AEC” data sets, reconstructing a single fluorescent region in the top center of the phantom with PpIX. This was at 62.5 ng/ml concentration, the previously determined floor with the “No AEC” technique. In the latter case, the recovered region at top is larger, and more representative of the true region size. In (d) the reconvened values in the region for different concentrations of PpIX is shown, with both AEC and no AEC in the data acquisition. For the no AEC data, useful images could not be obtained at concentrations above and below the range shown in the plot (circles).

Fig. 5
Fig. 5

Experimental sets of 20 images were reconstructed from phantom data obtained without AEC and with AEC, and representative images from each are shown in (a) and (b), respectively. Estimating the error in recovering the fluorescence yield could then be compared to simulations done with a range of forward data error values. In simulations, repeated reconstructions were used to estimate the standard deviation in the recovery, which is plotted in (c). This graph shows the concentration error vs. forward modeled data noise that was used in the reconstruction, and can be used to estimate the effective system error based upon the reconstructed concentrations (shown by arrows).

Fig. 6
Fig. 6

A systematic series of reconstructions are shown with decreasing concentration of PpIX in the top region (a). Then the recovered values for images are shown in (b), generated from (i) simulated data with appropriate amount of system noise (ii) the difference calibration technique and (iii) the in-vivo calibration routine used with animals (IVC).

Equations (3)

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φ r a w i = ( φ T P S F i d t φ D a r k i d t t int ) × 10 O D S o u r c e + O D D e t e c t i o n
φ f l i = ( φ m e a s ( h e t e r o _ f l ) i ( φ m e a s ( h e t e r o _ t r ) i × 10 O D r e j e c t i o n _ f l ) )
φ c a l _ f l i = φ f l i φ m e a s ( h e t e r o _ t r ) i × φ c a l c ( hom o _ t r ) i

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