Abstract

One limitation of fluorescence molecular imaging that can limit clinical implementation and hamper small animal imaging is the inability to eliminate ambient light. Herein, we demonstrate the ability to conduct rapid non-invasive, far-red and near-infrared fluorescence imaging in living animals and a phantom under ambient light conditions using a modulated image intensified CCD (ICCD) and a laser diode operated in homodyne detection. By mapping AC amplitude from three planar images at varying phase delays, we show improvement in target-to-background ratios (TBR) and reasonable signal-to-noise ratios (SNR) over continuous wave measurements. The rapid approach can be used to accurately collect fluorescence in situations where ambient light cannot be spectrally conditioned or controlled, such as in the case of fluorescent molecular image-guided surgery.

© 2014 Optical Society of America

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  1. B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
    [CrossRef] [PubMed]
  2. B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
    [CrossRef] [PubMed]
  3. B. Zhu and E. M. Sevick-Muraca, “Minimizing excitation light leakage and maximizing measurement sensitivity for molecular imaging with near-infrared fluorescence,” J. Innovative Opt. Health Sci.4(03), 301–307 (2011).
    [CrossRef]
  4. A. M. De Grand and J. V. Frangioni, “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat.2(6), 553–562 (2003).
    [PubMed]
  5. G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).
  6. C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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  19. K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
    [PubMed]
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    [CrossRef]

2014

2013

K. Sexton, S. C. Davis, D. McClatchy, P. A. Valdes, S. C. Kanick, K. D. Paulsen, D. W. Roberts, and B. W. Pogue, “Pulsed-light imaging for fluorescence guided surgery under normal room lighting,” Opt. Lett.38(17), 3249–3252 (2013).
[CrossRef] [PubMed]

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

2012

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

2011

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

B. Zhu and E. M. Sevick-Muraca, “Minimizing excitation light leakage and maximizing measurement sensitivity for molecular imaging with near-infrared fluorescence,” J. Innovative Opt. Health Sci.4(03), 301–307 (2011).
[CrossRef]

2010

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

2009

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

2008

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt.13, 041303 (2008).

2005

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

2003

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

A. M. De Grand and J. V. Frangioni, “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat.2(6), 553–562 (2003).
[PubMed]

2000

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Arts, H. J. G.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Azhdarinia, A.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Aznar, M.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Baatenburg de Jong, R. J.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Babiera, G. V.

Bart, J.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Beck, L. N.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Crane, L. M. A.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Darne, C. D.

C. D. Darne, Y. Lu, and E. M. Sevick-Muraca, “Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update,” Phys. Med. Biol.59(1), R1–R64 (2014).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

Davis, S. C.

Day, K. E.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

De Grand, A. M.

A. M. De Grand and J. V. Frangioni, “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat.2(6), 553–562 (2003).
[PubMed]

de Jong, J. S.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Deep, N. L.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Eppstein, M. J.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

Filonov, G. S.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Frangioni, J. V.

A. M. De Grand and J. V. Frangioni, “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat.2(6), 553–562 (2003).
[PubMed]

Gagnon, J. H.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Ghosh, S. C.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Godavarty, A.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

Gurfinkel, M.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

Hall, M. A.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Harlaar, N. J.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Harvey, B. R.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Heath, C. H.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Houston, J. P.

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

Huang, C. C.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Hutteman, M.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Kaijzel, E. L.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Kanick, S. C.

Ke, S.

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

Keereweer, S.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Kelder, W.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Kerrebijn, J. D. F.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Kim, K.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Krishnamurthy, S.

Li, C.

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

Lisbona, R.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Loutfi, A.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Low, P. S.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Löwik, C. W.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Löwik, C. W. G. M.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

Lu, Y.

C. D. Darne, Y. Lu, and E. M. Sevick-Muraca, “Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update,” Phys. Med. Biol.59(1), R1–R64 (2014).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

McClatchy, D.

Meric-Bernstam, F.

Mieog, J. S. D.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Mittendorf, E. A.

Murthy, K.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Ntziachristos, V.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

Paulsen, K. D.

Piatkevich, K. D.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Pinkston, K. L.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Pleijhuis, R. G.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Pogue, B. W.

Que, I.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Rasmussen, J. C.

F. Meric-Bernstam, J. C. Rasmussen, S. Krishnamurthy, I. Tan, B. Zhu, J. L. Wagner, G. V. Babiera, E. A. Mittendorf, and E. M. Sevick-Muraca, “Toward nodal staging of axillary lymph node basins through intradermal administration of fluorescent imaging agents,” Biomed. Opt. Express5(1), 183–196 (2014).
[CrossRef]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt.13, 041303 (2008).

Roberts, D. W.

Robinson, H.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Rosenthal, E. L.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Sarantopoulos, A.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Schulz, R.

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

Sevick-Muraca, E. M.

F. Meric-Bernstam, J. C. Rasmussen, S. Krishnamurthy, I. Tan, B. Zhu, J. L. Wagner, G. V. Babiera, E. A. Mittendorf, and E. M. Sevick-Muraca, “Toward nodal staging of axillary lymph node basins through intradermal administration of fluorescent imaging agents,” Biomed. Opt. Express5(1), 183–196 (2014).
[CrossRef]

C. D. Darne, Y. Lu, and E. M. Sevick-Muraca, “Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update,” Phys. Med. Biol.59(1), R1–R64 (2014).
[CrossRef] [PubMed]

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

B. Zhu and E. M. Sevick-Muraca, “Minimizing excitation light leakage and maximizing measurement sensitivity for molecular imaging with near-infrared fluorescence,” J. Innovative Opt. Health Sci.4(03), 301–307 (2011).
[CrossRef]

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt.13, 041303 (2008).

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

Sexton, K.

Smith, A. M.

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

Snoeks, T. J. A.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Soh, K.-S.

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

Sterenborg, H. J. C. M.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

Sweeny, L.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Tan, I.

Tan, I. C.

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

Themelis, G.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

Theru, S.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

Thompson, A. B.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

Thompson, C. J.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Ting, L.-M.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Vahrmeijer, A. L.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Valdes, P. A.

van Dam, G. M.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

van de Velde, C. J.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

van der Vorst, J. R.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

van der Zee, A. G. J.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Van Driel, P. B. A. A.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Verkhusha, V. V.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Wagner, J. L.

Wang, W.

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

Wilganowski, N.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Wu, G.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

Xie, B.

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Yan, S.

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

Yoo, J. S.

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

Zhang, C.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

Zhang, J.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Zhu, B.

F. Meric-Bernstam, J. C. Rasmussen, S. Krishnamurthy, I. Tan, B. Zhu, J. L. Wagner, G. V. Babiera, E. A. Mittendorf, and E. M. Sevick-Muraca, “Toward nodal staging of axillary lymph node basins through intradermal administration of fluorescent imaging agents,” Biomed. Opt. Express5(1), 183–196 (2014).
[CrossRef]

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

B. Zhu and E. M. Sevick-Muraca, “Minimizing excitation light leakage and maximizing measurement sensitivity for molecular imaging with near-infrared fluorescence,” J. Innovative Opt. Health Sci.4(03), 301–307 (2011).
[CrossRef]

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

Zinn, K. R.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Biomed. Opt. Express

Clin. Cancer Res.

S. Keereweer, P. B. A. A. Van Driel, T. J. A. Snoeks, J. D. F. Kerrebijn, R. J. Baatenburg de Jong, A. L. Vahrmeijer, H. J. C. M. Sterenborg, and C. W. G. M. Löwik, “Optical Image-Guided Cancer Surgery: Challenges and Limitations,” Clin. Cancer Res.19(14), 3745–3754 (2013), doi:.
[CrossRef] [PubMed]

J. Biomed. Opt

G. Themelis, J. S. Yoo, K.-S. Soh, R. Schulz, and V. Ntziachristos, “Real-time intraoperative fluorescence imaging system using light-absorption correction,” J. Biomed. Opt, 14, 064012 (2009).

J. Biomed. Opt.

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt.13, 041303 (2008).

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt.10, 054010 (2005).

J. Innovative Opt. Health Sci.

B. Zhu and E. M. Sevick-Muraca, “Minimizing excitation light leakage and maximizing measurement sensitivity for molecular imaging with near-infrared fluorescence,” J. Innovative Opt. Health Sci.4(03), 301–307 (2011).
[CrossRef]

J. Nucl. Med.

K. Murthy, M. Aznar, C. J. Thompson, A. Loutfi, R. Lisbona, and J. H. Gagnon, “Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG,” J. Nucl. Med.41(11), 1851–1858 (2000).
[PubMed]

Med. Phys.

B. Zhu, J. C. Rasmussen, Y. Lu, and E. M. Sevick-Muraca, “Reduction of excitation light leakage to improve near-infrared fluorescence imaging for tissue surface and deep tissue imaging,” Med. Phys.37(11), 5961–5970 (2010).
[CrossRef] [PubMed]

Mol. Imaging Biol.

B. Zhu, G. Wu, H. Robinson, N. Wilganowski, M. A. Hall, S. C. Ghosh, K. L. Pinkston, A. Azhdarinia, B. R. Harvey, and E. M. Sevick-Muraca, “Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP,” Mol. Imaging Biol.15(5), 560–568 (2013).
[CrossRef] [PubMed]

S. Keereweer, J. D. F. Kerrebijn, P. B. A. A. van Driel, B. Xie, E. L. Kaijzel, T. J. A. Snoeks, I. Que, M. Hutteman, J. R. van der Vorst, J. S. D. Mieog, A. L. Vahrmeijer, C. J. van de Velde, R. J. Baatenburg de Jong, and C. W. Löwik, “Optical image-guided surgery--where do we stand?” Mol. Imaging Biol.13(2), 199–207 (2011).
[CrossRef] [PubMed]

Nat. Biotechnol.

G. S. Filonov, K. D. Piatkevich, L.-M. Ting, J. Zhang, K. Kim, and V. V. Verkhusha, “Bright and stable near-infrared fluorescent protein for in vivo imaging,” Nat. Biotechnol.29(8), 757–761 (2011).
[CrossRef] [PubMed]

Nat. Med.

G. M. van Dam, G. Themelis, L. M. A. Crane, N. J. Harlaar, R. G. Pleijhuis, W. Kelder, A. Sarantopoulos, J. S. de Jong, H. J. G. Arts, A. G. J. van der Zee, J. Bart, P. S. Low, and V. Ntziachristos, “Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results,” Nat. Med.17(10), 1315–1319 (2011).
[CrossRef] [PubMed]

Opt. Lett.

Otolaryngol. Head Neck Surg.

C. H. Heath, N. L. Deep, L. N. Beck, K. E. Day, L. Sweeny, K. R. Zinn, C. C. Huang, and E. L. Rosenthal, “Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice,” Otolaryngol. Head Neck Surg.148(6), 982–990 (2013).
[CrossRef] [PubMed]

Photochem. Photobiol.

J. P. Houston, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-Infrared Fluorescence Contrast-Enhanced Imaging,” Photochem. Photobiol.77(4), 420–430 (2003).
[CrossRef] [PubMed]

Phys. Med. Biol.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Phys. Med. Biol.48(12), 1701–1720 (2003).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, I. C. Tan, B. Zhu, J. C. Rasmussen, A. M. Smith, S. Yan, and E. M. Sevick-Muraca, “A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography,” Phys. Med. Biol.57(24), 8135–8152 (2012).
[CrossRef] [PubMed]

C. D. Darne, Y. Lu, and E. M. Sevick-Muraca, “Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update,” Phys. Med. Biol.59(1), R1–R64 (2014).
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A. M. De Grand and J. V. Frangioni, “An operational near-infrared fluorescence imaging system prototype for large animal surgery,” Technol. Cancer Res. Treat.2(6), 553–562 (2003).
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Figures (4)

Fig. 1
Fig. 1

Schematic of fluorescence imaging device using a modulated ICCD camera and laser diode.

Fig. 2
Fig. 2

(a) Data depicting the sinusoidal variation of detected phase-sensitive intensity for a randomly chosen pixel at three representative modulation frequencies, where a.u. represents the arbitrary unit. (b) Modulation depth (M) at various modulation frequencies.

Fig. 3
Fig. 3

iRFP fluorescence images acquired at the phase delay (a) 0°, (b) 90° and (c) 180° from a representative mouse. (d) The extracted image of AC amplitude. (e) CW Image of DC. (f) Spectra of the fluorescent room lights acquired in the surgical suite showing far red spectral. The arrows point to the breast cancer location and the dashed circles represent the background (BK) ROIs.

Fig. 4
Fig. 4

NIRF images acquired at the phase delay (a) 0°, (b) 90° and (c) 180° from a mouse-shaped phantom. (d) The extracted image of AC amplitude. (e) CW image of DC. (f) Spectra of the surgical lights and the surgeon’s head lamp in the operating room showing interference in the NIR wavelength region. The arrows point to the rod tips containing AF750 fluorophore and the dashed circles represent the background (BK) ROIs.

Tables (3)

Tables Icon

Table 1 Comparison of the PT, PB, σ, TBR and SNR of AC amplitude and DC intensity in mouse depicted in Fig. 3, where a.u. represents arbitrary unit.

Tables Icon

Table 2 Comparison of TBR and SNR of AC amplitude and DC intensity in five mice

Tables Icon

Table 3 Comparison of the PT, PB, σ, TBR and SNR of AC amplitude and DC intensity in mouse-shaped phantom depicted in Fig. 4, where a.u. represents arbitrary unit.

Equations (7)

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

L( x,y )= L DC ( x,y )+ L AC ( x,y )cos[ ωt+θ( x,y ) ]
G= G DC + G AC cos( ωt+ θ inst )
S(x,y)=L(x,y)×G= L DC (x,y) G DC + L DC (x,y) G AC cos[ωt+ θ instr +η] + G DC L AC (x,y)cos[ ωt+θ(x,y) ] + L AC (x,y) G AC 2 cos(θ(x,y)+ θ inst +η) + L AC (x,y) G AC 2 cos[ 2ωt+ θ inst +θ(x,y) ]
S(x,y)=DC(x,y)+AC(x,y)cos(θ(x,y)+ θ inst +η)
AC(x,y)= 1 2 ( 2 S 90 S 0 S 180 ) 2 + ( S 180 S 0 ) 2
TBR= P T P B
SNR=20 log 10 P T P B σ

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