Abstract

In this study, several key optimization steps are outlined for a non-contact, time-correlated single photon counting small animal optical tomography system, using simultaneous collection of both fluorescence and transmittance data. The system is presented for time-domain image reconstruction in vivo, illustrating the sensitivity from single photon counting and the calibration steps needed to accurately process the data. In particular, laser time- and amplitude-referencing, detector and filter calibrations, and collection of a suitable instrument response function are all presented in the context of time-domain fluorescence tomography and a fully automated workflow is described. Preliminary phantom time-domain reconstructed images demonstrate the fidelity of the workflow for fluorescence tomography based on signal from multiple time gates.

© 2011 OSA

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    [CrossRef] [PubMed]

2011 (6)

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
[CrossRef] [PubMed]

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
[CrossRef]

A. Laidevant, L. Hervé, M. Debourdeau, J. Boutet, N. Grenier, and J. M. Dinten, “Fluorescence time-resolved imaging system embedded in an ultrasound prostate probe,” Biomed. Opt. Express2(1), 194–206 (2011).
[CrossRef] [PubMed]

X. Zhang, C. Badea, G. Hood, A. Wetzel, Y. Qi, J. Stiles, and G. A. Johnson, “High-resolution reconstruction of fluorescent inclusion in mouse thorax using anatomically guided sampling and parallel Monte Carlo computing,” Biomed. Opt. Express2(9), 2449–2460 (2011).
[CrossRef]

2010 (10)

J. B. Domínguez and Y. Bérubé-Lauzière, “Diffuse light propagation in biological media by a time-domain parabolic simplified spherical harmonics approximation with ray-divergence effects,” Appl. Opt.49(8), 1414–1429 (2010).
[CrossRef] [PubMed]

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

F. Gao, J. Li, L. Zhang, P. Poulet, H. Zhao, and Y. Yamada, “Simultaneous fluorescence yield and lifetime tomography from time-resolved transmittances of small-animal-sized phantom,” Appl. Opt.49(16), 3163–3172 (2010).
[CrossRef] [PubMed]

V. Venugopal, J. Chen, F. Lesage, and X. Intes, “Full-field time-resolved fluorescence tomography of small animals,” Opt. Lett.35(19), 3189–3191 (2010).
[CrossRef] [PubMed]

F. Leblond, K. M. Tichauer, and B. W. Pogue, “Singular value decomposition metrics show limitations of detector design in diffuse fluorescence tomography,” Biomed. Opt. Express1(5), 1514–1531 (2010).
[CrossRef] [PubMed]

X. Yang, H. Gong, G. Quan, Y. Deng, and Q. Luo, “Combined system of fluorescence diffuse optical tomography and microcomputed tomography for small animal imaging,” Rev. Sci. Instrum.81(5), 054304 (2010).
[CrossRef] [PubMed]

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
[CrossRef] [PubMed]

J. Cao, A. Moosman, and V. E. Johnson, “A Bayesian chi-squared goodness-of-fit test for censored data models,” Biometrics66(2), 426–434 (2010).
[CrossRef] [PubMed]

2009 (7)

A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

A. Da Silva, M. Leabad, C. Driol, T. Bordy, M. Debourdeau, J. M. Dinten, P. Peltié, and P. Rizo, “Optical calibration protocol for an x-ray and optical multimodality tomography system dedicated to small-animal examination,” Appl. Opt.48(10), D151–D162 (2009).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, “Automatic exposure control and estimation of effective system noise in diffuse fluorescence tomography,” Opt. Express17(25), 23272–23283 (2009).
[CrossRef] [PubMed]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
[CrossRef] [PubMed]

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. 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 (4)

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

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. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (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 (3)

2006 (1)

B. Montcel and P. Poulet, “An instrument for small-animal imaging using time-resolved diffuse and fluorescence optical methods,” Nucl. Instrum. Meth. Phys. Res. Sec. A569(2), 551–556 (2006).
[CrossRef]

2005 (4)

M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

M. Rudin, M. Rausch, and M. Stoeckli, “Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods,” Mol. Imaging Biol.7(1), 5–13 (2005).
[CrossRef] [PubMed]

2003 (2)

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol.13(1), 195–208 (2003).
[PubMed]

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol.7(5), 626–634 (2003).
[CrossRef] [PubMed]

2001 (1)

2000 (1)

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

1999 (2)

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
[CrossRef]

S. Arridge, “Optical tomography in medical imaging,” Inverse Probl.15(2), R41–R93 (1999).
[CrossRef]

1996 (1)

1995 (1)

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]

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

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]

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]

Ale, A.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

Arridge, S.

S. Arridge, “Optical tomography in medical imaging,” Inverse Probl.15(2), R41–R93 (1999).
[CrossRef]

Arridge, S. R.

Bacskai, B. J.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

Badea, C.

Bai, J.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Baltes, C.

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

Barber, W. C.

Bérubé-Lauzière, Y.

Bhaumik, S.

A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

Bloch, S.

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

Boas, D. A.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

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]

Bordy, T.

Boutet, J.

Brambilla, M.

M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (2008).
[CrossRef] [PubMed]

Bremer, C.

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol.13(1), 195–208 (2003).
[PubMed]

Cao, J.

J. Cao, A. Moosman, and V. E. Johnson, “A Bayesian chi-squared goodness-of-fit test for censored data models,” Biometrics66(2), 426–434 (2010).
[CrossRef] [PubMed]

Capala, J.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Carpenter, C. M.

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M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
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V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
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F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
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Chernomordik, V.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
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Da Silva, A.

Dasari, R. R.

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F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
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H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
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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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D. S. Kepshire, S. C. Davis, H. Dehghani, K. D. Paulsen, and B. W. Pogue, “Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth,” Appl. Opt.46(10), 1669–1678 (2007).
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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).
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Dehghani, H.

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
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D. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, “Automatic exposure control and estimation of effective system noise in diffuse fluorescence tomography,” Opt. Express17(25), 23272–23283 (2009).
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F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A26(6), 1444–1457 (2009).
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H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
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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).
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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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D. S. Kepshire, S. C. Davis, H. Dehghani, K. D. Paulsen, and B. W. Pogue, “Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth,” Appl. Opt.46(10), 1669–1678 (2007).
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F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
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F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
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Domínguez, J. B.

Driol, C.

Dunn, A. K.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
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H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
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El-Ghussein, F.

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
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Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
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Feld, M. S.

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Freyer, M.

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F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

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A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
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Gandjbakhche, A.

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
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Gandjbakhche, A. H.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Gao, F.

Gao, H.

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
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Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
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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]

Gong, H.

X. Yang, H. Gong, G. Quan, Y. Deng, and Q. Luo, “Combined system of fluorescence diffuse optical tomography and microcomputed tomography for small animal imaging,” Rev. Sci. Instrum.81(5), 054304 (2010).
[CrossRef] [PubMed]

Grenier, N.

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).
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Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
[CrossRef] [PubMed]

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

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X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

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M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
[CrossRef] [PubMed]

Hassan, M.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Hebden, J. C.

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

Hervé, L.

Hillman, E. M. C.

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

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R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

Hood, G.

Hu, G.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[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]

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).
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V. Venugopal, J. Chen, F. Lesage, and X. Intes, “Full-field time-resolved fluorescence tomography of small animals,” Opt. Lett.35(19), 3189–3191 (2010).
[CrossRef] [PubMed]

M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
[CrossRef] [PubMed]

Itzkan, I.

Iwanczyk, J. S.

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]

Johnson, G. A.

Johnson, V. E.

J. Cao, A. Moosman, and V. E. Johnson, “A Bayesian chi-squared goodness-of-fit test for censored data models,” Biometrics66(2), 426–434 (2010).
[CrossRef] [PubMed]

Kepshire, D.

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]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

Kepshire, D. L.

Kepshire, D. S.

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]

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]

Kumar, A. T.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

Laidevant, A.

Leabad, M.

Leblond, F.

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
[CrossRef]

F. Leblond, K. M. Tichauer, and B. W. Pogue, “Singular value decomposition metrics show limitations of detector design in diffuse fluorescence tomography,” Biomed. Opt. Express1(5), 1514–1531 (2010).
[CrossRef] [PubMed]

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

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. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, “Automatic exposure control and estimation of effective system noise in diffuse fluorescence tomography,” Opt. Express17(25), 23272–23283 (2009).
[CrossRef] [PubMed]

Lee, S. B.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Lesage, F.

V. Venugopal, J. Chen, F. Lesage, and X. Intes, “Full-field time-resolved fluorescence tomography of small animals,” Opt. Lett.35(19), 3189–3191 (2010).
[CrossRef] [PubMed]

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

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, J.

Li, X. D.

Liang, K.

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

Lin, Y.

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
[CrossRef] [PubMed]

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

Liu, F.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Liu, N.

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
[CrossRef] [PubMed]

Liu, X.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Luo, Q.

X. Yang, H. Gong, G. Quan, Y. Deng, and Q. Luo, “Combined system of fluorescence diffuse optical tomography and microcomputed tomography for small animal imaging,” Rev. Sci. Instrum.81(5), 054304 (2010).
[CrossRef] [PubMed]

Ma, X. H.

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
[CrossRef]

May, A.

A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

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]

McGinty, J.

McIntosh, L.

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
[CrossRef] [PubMed]

Mincu, N.

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).
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B. Montcel and P. Poulet, “An instrument for small-animal imaging using time-resolved diffuse and fluorescence optical methods,” Nucl. Instrum. Meth. Phys. Res. Sec. A569(2), 551–556 (2006).
[CrossRef]

Moosman, A.

J. Cao, A. Moosman, and V. E. Johnson, “A Bayesian chi-squared goodness-of-fit test for censored data models,” Biometrics66(2), 426–434 (2010).
[CrossRef] [PubMed]

Nalcioglu, O.

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
[CrossRef] [PubMed]

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

Neil, M. A.

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]

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.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

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]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol.13(1), 195–208 (2003).
[PubMed]

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

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
[CrossRef]

O’Leary, M. A.

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(2), 024004 (2009).
[CrossRef] [PubMed]

Paulsen, K. D.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (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]

D. S. Kepshire, S. C. Davis, H. Dehghani, K. D. Paulsen, and B. W. Pogue, “Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth,” Appl. Opt.46(10), 1669–1678 (2007).
[CrossRef] [PubMed]

Peltié, P.

Perelman, L.

Pifferi, A.

M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (2008).
[CrossRef] [PubMed]

Pogue, B. W.

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
[CrossRef]

F. Leblond, K. M. Tichauer, and B. W. Pogue, “Singular value decomposition metrics show limitations of detector design in diffuse fluorescence tomography,” Biomed. Opt. Express1(5), 1514–1531 (2010).
[CrossRef] [PubMed]

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
[CrossRef] [PubMed]

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
[CrossRef] [PubMed]

F. Leblond, H. Dehghani, D. Kepshire, and B. W. Pogue, “Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations,” J. Opt. Soc. Am. A26(6), 1444–1457 (2009).
[CrossRef] [PubMed]

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. L. Kepshire, H. Dehghani, F. Leblond, and B. W. Pogue, “Automatic exposure control and estimation of effective system noise in diffuse fluorescence tomography,” Opt. Express17(25), 23272–23283 (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]

D. S. Kepshire, S. C. Davis, H. Dehghani, K. D. Paulsen, and B. W. Pogue, “Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth,” Appl. Opt.46(10), 1669–1678 (2007).
[CrossRef] [PubMed]

Poulet, P.

F. Gao, J. Li, L. Zhang, P. Poulet, H. Zhao, and Y. Yamada, “Simultaneous fluorescence yield and lifetime tomography from time-resolved transmittances of small-animal-sized phantom,” Appl. Opt.49(16), 3163–3172 (2010).
[CrossRef] [PubMed]

B. Montcel and P. Poulet, “An instrument for small-animal imaging using time-resolved diffuse and fluorescence optical methods,” Nucl. Instrum. Meth. Phys. Res. Sec. A569(2), 551–556 (2006).
[CrossRef]

Pursley, R.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Qi, Y.

Quan, G.

X. Yang, H. Gong, G. Quan, Y. Deng, and Q. Luo, “Combined system of fluorescence diffuse optical tomography and microcomputed tomography for small animal imaging,” Rev. Sci. Instrum.81(5), 054304 (2010).
[CrossRef] [PubMed]

Rausch, M.

M. Rudin, M. Rausch, and M. Stoeckli, “Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods,” Mol. Imaging Biol.7(1), 5–13 (2005).
[CrossRef] [PubMed]

Raymond, S. B.

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

Riley, J.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Ripoll, J.

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

Rizo, P.

Roeck, W.

Rudin, M.

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

M. Rudin, M. Rausch, and M. Stoeckli, “Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods,” Mol. Imaging Biol.7(1), 5–13 (2005).
[CrossRef] [PubMed]

Sarantopoulos, A.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

Schmidt, F. E. W.

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

Schulz, R. B.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

Smith, P.

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Soehngen, E.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

Soloviev, V. Y.

Soubret, A.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

Spinelli, L.

M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (2008).
[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.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
[CrossRef] [PubMed]

Stiles, J.

Stoeckli, M.

M. Rudin, M. Rausch, and M. Stoeckli, “Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods,” Mol. Imaging Biol.7(1), 5–13 (2005).
[CrossRef] [PubMed]

Stuker, F.

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

Tahir, K. B.

Tian, F.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Tichauer, K. M.

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

F. Leblond, K. M. Tichauer, and B. W. Pogue, “Singular value decomposition metrics show limitations of detector design in diffuse fluorescence tomography,” Biomed. Opt. Express1(5), 1514–1531 (2010).
[CrossRef] [PubMed]

Torricelli, A.

M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (2008).
[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]

Valdés, P. A.

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
[CrossRef] [PubMed]

Vats, D.

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

Venugopal, V.

Wang, X.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Wang, Y.

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]

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol.13(1), 195–208 (2003).
[PubMed]

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

Wetzel, A.

Wu, J.

Yalavarthy, P. K.

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
[CrossRef] [PubMed]

Yamada, Y.

Yang, X.

X. Yang, H. Gong, G. Quan, Y. Deng, and Q. Luo, “Combined system of fluorescence diffuse optical tomography and microcomputed tomography for small animal imaging,” Rev. Sci. Instrum.81(5), 054304 (2010).
[CrossRef] [PubMed]

Yazdanfar, S.

A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

Yazici, B.

M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
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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]

Yodh, A. G.

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
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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).
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A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

Zhang, B.

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

Zhang, L.

Zhang, X.

Zhao, H.

Zhu, Q.

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
[CrossRef]

Zientkowska, M.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

Appl. Opt. (5)

Biomed. Opt. Express (3)

Biometrics (1)

J. Cao, A. Moosman, and V. E. Johnson, “A Bayesian chi-squared goodness-of-fit test for censored data models,” Biometrics66(2), 426–434 (2010).
[CrossRef] [PubMed]

Commun. Numer. Methods Eng. (1)

H. Dehghani, M. E. Eames, P. K. Yalavarthy, S. C. Davis, S. Srinivasan, C. M. Carpenter, B. W. Pogue, and K. D. Paulsen, “Near infrared optical tomography using NIRFAST: algorithm for numerical model and image reconstruction,” Commun. Numer. Methods Eng.25(6), 711–732 (2009).
[CrossRef] [PubMed]

Curr. Opin. Chem. Biol. (1)

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol.7(5), 626–634 (2003).
[CrossRef] [PubMed]

Eur. Radiol. (1)

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol.13(1), 195–208 (2003).
[PubMed]

IEEE Trans. Biomed. Eng. (1)

X. Guo, X. Liu, X. Wang, F. Tian, F. Liu, B. Zhang, G. Hu, and J. Bai, “A combined fluorescence and microcomputed tomography system for small animal imaging,” IEEE Trans. Biomed. Eng.57(12), 2876–2883 (2010).
[CrossRef] [PubMed]

IEEE Trans. Med. Imaging (4)

A. T. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging27(8), 1152–1163 (2008).
[CrossRef] [PubMed]

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging29(2), 465–473 (2010).
[CrossRef] [PubMed]

F. Stuker, C. Baltes, K. Dikaiou, D. Vats, L. Carrara, E. Charbon, J. Ripoll, and M. Rudin, “Hybrid small animal imaging system combining magnetic resonance imaging with fluorescence tomography using single photon avalanche diode detectors,” IEEE Trans. Med. Imaging30(6), 1265–1273 (2011).
[CrossRef] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging24(10), 1377–1386 (2005).
[CrossRef] [PubMed]

Inverse Probl. (1)

S. Arridge, “Optical tomography in medical imaging,” Inverse Probl.15(2), R41–R93 (1999).
[CrossRef]

J. Biomed. Opt. (3)

A. May, S. Bhaumik, S. S. Gambhir, C. Zhan, and S. Yazdanfar, “Whole-body, real-time preclinical imaging of quantum dot fluorescence with time-gated detection,” J. Biomed. Opt.14(6), 060504 (2009).
[CrossRef] [PubMed]

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]

S. Bloch, F. Lesage, L. McIntosh, A. Gandjbakhche, K. Liang, and S. Achilefu, “Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice,” J. Biomed. Opt.10(5), 054003 (2005).
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J. Opt. Soc. Am. A (1)

J. Photochem. Photobiol. B (1)

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B98(1), 77–94 (2010).
[CrossRef] [PubMed]

Mol. Imaging (1)

M. Hassan, J. Riley, V. Chernomordik, P. Smith, R. Pursley, S. B. Lee, J. Capala, and A. H. Gandjbakhche, “Fluorescence lifetime imaging system for in vivo studies,” Mol. Imaging6(4), 229–236 (2007).
[PubMed]

Mol. Imaging Biol. (1)

M. Rudin, M. Rausch, and M. Stoeckli, “Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods,” Mol. Imaging Biol.7(1), 5–13 (2005).
[CrossRef] [PubMed]

Nucl. Instrum. Meth. Phys. Res. Sec. A (1)

B. Montcel and P. Poulet, “An instrument for small-animal imaging using time-resolved diffuse and fluorescence optical methods,” Nucl. Instrum. Meth. Phys. Res. Sec. A569(2), 551–556 (2006).
[CrossRef]

Opt. Express (2)

Opt. Lett. (4)

Phys. Med. Biol. (2)

M. Guven, B. Yazici, X. Intes, and B. Chance, “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol.50(12), 2837–2858 (2005).
[CrossRef] [PubMed]

Y. Lin, M. T. Ghijsen, H. Gao, N. Liu, O. Nalcioglu, and G. Gulsen, “A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging,” Phys. Med. Biol.56(15), 4731–4747 (2011).
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Proc. Natl. Acad. Sci. U.S.A. (1)

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]

Proc. SPIE (2)

Q. Zhu, F. Leblond, F. El-Ghussein, B. W. Pogue, and H. Dehghani, “Development and evaluation of a time-resolved near-infrared fluorescence finite element model,” Proc. SPIE7896, 78960T, 78960T-13 (2011).
[CrossRef]

R. Holt, F. El-Ghussein, K. M. Tichauer, F. Leblond, and B. W. Pogue, “Hybrid approach combining microCT and fluorescence tomography: imaging workflow and system of coordinate registration,” Proc. SPIE7892, 789213, 789213-8 (2011).
[CrossRef]

Rev. Sci. Instrum. (6)

F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, J. C. Hebden, and D. T. Delpy, “A 32-channel time-resolved instrument for medical optical tomography,” Rev. Sci. Instrum.71(1), 256–265 (2000).
[CrossRef]

V. Ntziachristos, X. H. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum.70(1), 193–201 (1999).
[CrossRef]

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]

M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum.79(1), 013103 (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]

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[CrossRef] [PubMed]

Supplementary Material (1)

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Figures (7)

Fig. 1
Fig. 1

Frame from a video (Media 1) of the system that portrays the motorized linear stage and motorized rotational imaging gantry in action. The five detection fibers (capped in green) can be seen at the top of the screen at the beginning of the video with the single source fiber at the bottom (capped in red). The specimen attached to the phantom bed is a mouse-shaped phantom from Caliper Life Sciences Inc.

Fig. 2
Fig. 2

The custom fluorescence tomography imaging bed is shown. (a) Side-view of the imaging bed. The system mount is at the bottom left of the picture and is attachable to the FT system and a microCT system. Above the system mount is an adjustable jack that can be used to adjust the height of the bed to help center various sizes of specimen. Attached to the jack and projecting to the right is the arm of the bed, supporting 2 or more fiberglass rods, which in turn are used to stabilize specimens while avoiding unnecessary blockage of source or detector during optical imaging. (b) Front view of the imaging bed: numerous holes were machined into the face of the imaging arm to adjust the spacing of the support rods or add additional rods depending on the logistics of the specimen. (c) The system and bed are set up with a gas anesthesia attachment, which includes a bite-bar to reduce subject motion during scanning.

Fig. 3
Fig. 3

A simplified workflow depicting the full experimental procedure for carrying out time-domain fluorescence tomography in small animals.

Fig. 4
Fig. 4

System calibration and instrument response function collection. (a) A cartoon layout of the fluorescence tomography imaging system depicting the arrangement used to calibrate the system and measure the instrument response functions. Specifically, a line diffuser is placed at the center of the imaging gantry to disperse the excitation beam evenly into each detection channel. (b) Raw temporal pulse spread functions collected at each detector. Each color denotes a different detection PMT. (c) The same curves as shown in (b) after applying amplitude and time shift calibrations to the detection channels.

Fig. 5
Fig. 5

Laser referencing is illustrated here, where changes in the detected signal intensity (a) & (b) and in mean time (c) & (d) for one detection channel (blue curves) and for the laser reference channel (red curves). In (b) the normalized intensity relative to the signal in (a) to either the assumed change in laser attenuation (blue curve) or to the intensity in the laser ref. channel (red curve). (d) The mean time in the detection channel (c, blue-line) after correction by using the drift observed in the laser reference (c red-line).

Fig. 6
Fig. 6

The finite-element model mesh was created as illustrated here, accounting for rod disturbance in the optical measurements. (a) A cross-sectional CT image of the optical mouse phantom shown in Fig. 2. The bright circles correspond to the cross-section of the fiberglass rods that hold the phantom in place and the dark circles are cylindrical holes in the phantom made to accommodate the addition of up to two fluorescence inclusions. (b) A mask (top) and finite element mesh with source-detector locations (bottom) of (a) if the rods are not accounted for. The blue lines are the boundaries of each finite element while the red circles represent the location of the sources and detectors projected on the surface of the specimen. (c) The three layered mask (top) and finite element mesh with source-detector locations (bottom) of (a) when the rods and all sources and detectors interfering with the rods are removed. A reconstruction of the mouse phantom with both inclusions filled with 100 nM of AlexaFluor 647 dye is presented (d).

Fig. 7
Fig. 7

Reconstructions of experimental data are shown using a pulse-integration reconstruction (a), and a seven-gate time-domain reconstruction (b), overlaid onto a CT image of the phantom. The comparison between the fluorescence cross-sections of both reconstructions (a vertical cross-section through (a) and (b)) is presented in (c). The green line corresponds to the pulse-integrated reconstruction, the blue line to the multi-time-gate reconstruction, and the black line to the expected fluorescence profile. Zero on the x-axis denotes the center of mass of the phantom. The fluorescence is normalized to the peak fluorescence in each cross-section.

Equations (3)

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χ= [ yF( μ ) ] μ min ,
μ a f = J T ( J J T +λI ) 1 Φ,
Φ=[ Φ t 2 t 1 Φ t 3 t 2 Φ t n t n1 ];    and   J=[ J t 2 t 1 J t 3 t 2 J t n t n1 ],

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