Abstract

We present three-dimensional (3D) in vivo images of human breast cancer based on fluorescence diffuse optical tomography (FDOT). To our knowledge, this work represents the first reported 3D fluorescence tomography of human breast cancer in vivo. In our protocol, the fluorophore Indocyanine Green (ICG) is injected intravenously. Fluorescence excitation and detection are accomplished in the soft-compression, parallel-plane, transmission geometry using laser sources at 786 nm and spectrally filtered CCD detection. Phantom and in vivo studies confirm the signals are due to ICG fluorescence, rather than tissue autofluorescence and excitation light leakage. Fluorescence images of breast tumors were in good agreement with those of MRI, and with DOT based on endogenous contrast. Tumor-to-normal tissue contrast based on ICG fluorescence was two-to-four-fold higher than contrast based on hemoglobin and scattering parameters. In total the measurements demonstrate that FDOT of breast cancer is feasible and promising.

© 2007 Optical Society of America

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2007

2006

2005

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

S. V. Patwardhan, S. R. Bloch, S. Achilefu, and J. P. Culver, Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice, Opt. Express 13, 2564-2577 (2005).
[CrossRef] [PubMed]

K. Hwang, J. P. Houston, J. C. Rasmussen, A. Joshi, S. Ke, C. Li, and E. M. Sevick-Muraca, Improved excitation light rejection enhances small-animal fluorescent optical imaging, Mol. Imaging 4, 194-204 (2005).
[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. of Biomed. Opt. 10, 54003-54003 (2005).
[CrossRef]

A. Liebert, H. Wabnitz, J. Steinbrink, M. Moller, R. Macdonald, H. Rinneberg, A. Villringer, and H. Obrig, Bed-side assessment of cerebral perfusion in stroke patients based on optical monitoring of a dye bolus by timeresolved diffuse reflectance, Neuroimage 24, 426-35 (2005).
[CrossRef] [PubMed]

A. Corlu, R. Choe, T. Durduran, K. Lee,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Diffuse optical tomography with spectral constraints and wavelength optimization, Appl. Opt. 44, 2082-2093 (2005).
[CrossRef] [PubMed]

M. Schweiger, S. R. Arridge, and I. Nissilä, Gauss-Newton method for image reconstruction in diffuse optical tomography, Phys. Med. Biol. 50, 2365-2386 (2005).
[CrossRef] [PubMed]

D. Grosenick, H. Wabnitz, K. T. Moesta, J. Mucke, P. M. Schlag, and H. Rinneberg, Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas, Phys. Med. Biol 50, 2451- 2468 (2005).
[CrossRef] [PubMed]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Grosicka-Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. A. Rosen, and A. G. Yodh, Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI, Med. Phys. 32, 1128-1139 (2005).
[CrossRef] [PubMed]

A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, E. Stathopoulos, M. Kafousi, J. Ripoll, and TG Papazoglou, Optical characterization of thin female breast biopsies based on the reduced scattering coefficient, Phys. Med. Biol 50, 2583-2596 (2005).
[CrossRef] [PubMed]

A. Bogaards, A. Varma, K. Zhang, D. Zach, S. K. Bisland, E. H. Moriyama, L. Lilge, P. J. Muller, and B. C. Wilson, Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development, Photochem. Photobiol. Sci. 4, 438-442 (2005).
[CrossRef] [PubMed]

T. H. Foster, B. D. Pearson, S. Mitra, and C. E. Bigelow, Fluorescence anisotropy imaging reveals localization of meso-tetrahydroxyphenyl chlorin in the nuclear envelope, Photochem. Photobiol. 81, 1544-1547 (2005).
[CrossRef] [PubMed]

S. Kwon, S. Ke, J. P. Houston, W. Wang, Q. Wu, C. Li, and E. M. Sevick-Muraca, Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to alpha v beta 3 receptor expressed in Kaposi’s sarcoma, Mol. Imaging 4, 75-87 (2005).
[PubMed]

2004

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Fluorescence imaging in vivo: raster scanned pointsource imaging provides more accurate quantification than broad beam geometries, Technol. Cancer Res. Treat. 3, 15-21 (2004).
[PubMed]

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies, J. Biomed. Opt. 9, 488-496 (2004).
[CrossRef] [PubMed]

2003

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, A submillimeter resolution fluorescence molecular imaging system for small animal imaging, Med. Phys. 30, 901 (2003).
[CrossRef] [PubMed]

Y. Chen, C. Mu, X. Intes, D. Blessington, and B. Chance, Near-infrared phase cancellation instrument for fast and accurate localization of fluorescent heterogeneity, Rev. Sci. Instrum. 74, 3466-3473 (2003).
[CrossRef]

K. R. Diamond, T. J. Farrell, and M. S. Patterson, Measurement of fluorophore concentrations and fluorescence quantum yield in tissue-simulating phantoms using three diffusion models of steady-state spatially resolved fluorescence, Phys. Med. Biol. 48, 4135-4149 (2003).
[CrossRef]

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, 1701-1720 (2003).
[CrossRef] [PubMed]

H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results, Appl. Opt 42, 135-145 (2003).
[CrossRef] [PubMed]

A. Corlu, T. Durduran, R. Choe,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Uniqueness and wavelength optimization in continous-wave multispectral diffuse optical tomography, Opt. Lett. 28, 2339-2341 (2003).
[CrossRef] [PubMed]

A. Tsourkas and G. Bao, Shedding light on health and disease using molecular beacons.Brief Funct. Genomic. Proteomic. 1, 372-384 (2003).
[CrossRef]

E. Kuwana and E. M. Sevick-Muraca, Fluorescence lifetime spectroscopy for pH sensing in scattering media, Anal. Chem. 75, 4325-4329 (2003).
[CrossRef] [PubMed]

A. D. Klose and A. H. Hielscher, Fluorescence tomography with simulated data based on the equation of radiative transfer, Opt. Lett. 28, 1019-1021 (2003).
[CrossRef] [PubMed]

R. Cheung, M. Solonenko, T. M. Busch, F. Del Piero, M. E. Putt, S. M. Hahn, and A. G. Yodh, Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model, J. Of Biomed. Opt. 8, 248-252 (2003).
[CrossRef]

S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li, Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts, Cancer Res. 63, 7870-7875 (2003).
[PubMed]

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, In vivo continuous-wave optical breast imaging enhanced with indocyanine green, Med. Phys. 30, 1039-1047 (2003).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, D. N. Pattanayak, B. Chance, and A. G. Yodh, 3D diffuse optical tomography in the plane parallel transmission geometry: Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging, Med. Phys. 30, 235-247 (2003).
[CrossRef] [PubMed]

2002

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, Bulk optical properties of healthy female breast tissue, Phys. Med. Biol. 47, 2847-2861 (2002).
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V. Ntziachristos and R. Weissleder, CCD-based scanner for three-dimensional fluorescence-mediated diffuse optical tomography of small animals, Med. Phys. 29, 803-809 (2002).
[CrossRef] [PubMed]

E. Shives, Y. Xu, and H. Jiang, Fluorescence lifetime tomography of turbid media based on an oxygen-sensitive dye, Opt. Express 10, 1557-1562 (2002).
[PubMed]

M. J. Eppstein, D. J. Hawrysz, A. Godavarty, and E. M. Sevick-Muraca, Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: Near-infrared fluorescence tomography, Proc. Natl. Acad. Sci. 99, 9619-9624 (2002).
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A. R. Padhani, Dynamic contrast-enhanced mri in clinical oncology: current status and future directions, J. Magn. Reson. Imaging 16, 407-422 (2002).
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V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Fluorescence molecular tomography resolves protease activity in vivo, Nat. Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

2001

E. Bombardieri and F. Crippa. PET imaging in breast cancer, Q. J. of Nucl. Med. 45, 245-55 (2001).

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
[CrossRef] [PubMed]

T. O. McBride B. W. Pogue, S. D. Jiang, and U. L. Osterberg, A parallel-detection frequency-domain nearinfrared tomography system for hemoglobin imaging of the breast in vivo, Rev. Sci. Instrum. 72, 1817-1824 (2001).
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V. Ntziachristos and B. Chance, Probing physiology and molecular function using optical imaging: applications to breast cancer, Breast Cancer Res. 3, 41-46 (2001).
[CrossRef] [PubMed]

B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: Pilot results in the breast, Radiology 218, 261-266 (2001).
[PubMed]

N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, Noninvasive functional optical spectroscopy of human breast tissue, Proc. Natl. Acad. Sci. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

V. Ntziachristos and R. Weissleder, Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized born approximation, Opt. Lett. 26, 893-895 (2001).
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D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations, Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

2000

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Concurrent mri and diffuse optical tomography of breast after indocyanine green enhancement, Proc. Natl. Acad. Sci. 97, 2767-2772 (2000).
[CrossRef] [PubMed]

D. J. Hawrysz and E. M. Sevick-Muraca, Developments Toward Diagnostic Breast Cancer Imaging Using Near- Infrared Optical Measurements and Fluorescent Contrast Agents, Neoplasia 2, 388-417 (2000).
[CrossRef]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging, Invest. Radiol. 35, 479-485 (2000).
[CrossRef] [PubMed]

1999

R. Weissleder, C. H. Tung, U. Mahmood, and A. Bogdanov, In vivo imaging of tumors with protease-activated near-infrared fluorescent probes, Nat. Biotechnol. 17, 375-378 (1999).
[CrossRef] [PubMed]

P. I. Bastiaens and A. Squire, Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell, Trends Cell Biol. 9, 48-52 (1999).
[CrossRef] [PubMed]

J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, Imaging of spontaneous canine mammary tumors using fluorescent contrast agents, Photochem. Photobiol. 70, 87-94 (1999).
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S. R. Arridge, Optical tomography in medical imaging, Inverse Problems 15, R41-R93 (1999).
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1998

1997

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplacetransforms.Proc. Natl. Acad. Sci. 94, 8783-8788 (1997).
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B. B. Das, F. Liu, and R. R. Alfano, Time-resolved fluorescence and photon migration studies in biomedical and model random media.Rep. Prog. Phys. 60, 227-292 (1997).
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T. Durduran, A. G. Yodh, B. Chance, and D. A. Boas, Does the photon diffusion coefficient depend on absorption?J. Opt. Soc. Am. 14, 3358-3365 (1997).
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E. M. Sevick-Muraca, G. Lopez, J. S. Reynolds, T. L. Troy, and C. L. Hutchinson, Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques, Photochem. Photobiol. 66, 55-64 (1997).
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1996

1995

B. Ballou, G.W. Fisher, A. S. Waggoner, D. L. Farkas, J. M. Reiland, R. Jaffe, R. B. Mujumdar, S. R. Mujumdar, and T. R. Hakala, Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies, Cancer Immunol. Immunother 41, 257-263 (1995).
[CrossRef] [PubMed]

A. G. Yodh and B. Chance, Spectroscopy and imaging with diffusing light, Phys. Today 48, 34-40 (1995).
[CrossRef]

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, The finite element model for the propagation of light in scattering media: Boundary and source conditions, Med. Phys. 22, 1779-1792 (1995).
[CrossRef] [PubMed]

1994

M. A. O’Leary, D. A. Boas, B. Chance, and A. G. Yodh, Reradiation and imaging of diffuse photon density waves using fluorescent inhomogeneities.J. Lumin. 60-1, 281-286 (1994).
[CrossRef]

1993

S. R. Arridge, M. Schweiger, M. Hiraoka, and D. T. Delpy, A finite element approach for modeling photon transport in tissue, Med. Phys. 20, 299-309 (1993).
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Achilefu, S.

S. V. Patwardhan, S. R. Bloch, S. Achilefu, and J. P. Culver, Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice, Opt. Express 13, 2564-2577 (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. of Biomed. Opt. 10, 54003-54003 (2005).
[CrossRef]

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging, Invest. Radiol. 35, 479-485 (2000).
[CrossRef] [PubMed]

Alfano, R. R.

B. B. Das, F. Liu, and R. R. Alfano, Time-resolved fluorescence and photon migration studies in biomedical and model random media.Rep. Prog. Phys. 60, 227-292 (1997).
[CrossRef]

Apreleva, S. V.

Arridge, S. R.

A. Corlu, R. Choe, T. Durduran, K. Lee,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Diffuse optical tomography with spectral constraints and wavelength optimization, Appl. Opt. 44, 2082-2093 (2005).
[CrossRef] [PubMed]

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Grosicka-Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. A. Rosen, and A. G. Yodh, Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI, Med. Phys. 32, 1128-1139 (2005).
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M. Schweiger, S. R. Arridge, and I. Nissilä, Gauss-Newton method for image reconstruction in diffuse optical tomography, Phys. Med. Biol. 50, 2365-2386 (2005).
[CrossRef] [PubMed]

A. Corlu, T. Durduran, R. Choe,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Uniqueness and wavelength optimization in continous-wave multispectral diffuse optical tomography, Opt. Lett. 28, 2339-2341 (2003).
[CrossRef] [PubMed]

S. R. Arridge, Optical tomography in medical imaging, Inverse Problems 15, R41-R93 (1999).
[CrossRef]

S. R. Arridge and M. Schweiger, A gradient-based optimisation scheme for optical tomography, Opt. Express 2, 213-226 (1998).
[CrossRef] [PubMed]

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, The finite element model for the propagation of light in scattering media: Boundary and source conditions, Med. Phys. 22, 1779-1792 (1995).
[CrossRef] [PubMed]

S. R. Arridge, M. Schweiger, M. Hiraoka, and D. T. Delpy, A finite element approach for modeling photon transport in tissue, Med. Phys. 20, 299-309 (1993).
[CrossRef] [PubMed]

Bacskai, B. J.

Ballou, B.

B. Ballou, G.W. Fisher, A. S. Waggoner, D. L. Farkas, J. M. Reiland, R. Jaffe, R. B. Mujumdar, S. R. Mujumdar, and T. R. Hakala, Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies, Cancer Immunol. Immunother 41, 257-263 (1995).
[CrossRef] [PubMed]

Bangerth, W.

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection, Med. Phys. 33, 1299-1310 (2006).
[CrossRef] [PubMed]

Bao, G.

A. Tsourkas and G. Bao, Shedding light on health and disease using molecular beacons.Brief Funct. Genomic. Proteomic. 1, 372-384 (2003).
[CrossRef]

Bastiaens, P. I.

P. I. Bastiaens and A. Squire, Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell, Trends Cell Biol. 9, 48-52 (1999).
[CrossRef] [PubMed]

Berger, A. J.

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
[CrossRef] [PubMed]

Bevilacqua, F.

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
[CrossRef] [PubMed]

Bigelow, C. E.

T. H. Foster, B. D. Pearson, S. Mitra, and C. E. Bigelow, Fluorescence anisotropy imaging reveals localization of meso-tetrahydroxyphenyl chlorin in the nuclear envelope, Photochem. Photobiol. 81, 1544-1547 (2005).
[CrossRef] [PubMed]

Bisland, S. K.

A. Bogaards, A. Varma, K. Zhang, D. Zach, S. K. Bisland, E. H. Moriyama, L. Lilge, P. J. Muller, and B. C. Wilson, Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development, Photochem. Photobiol. Sci. 4, 438-442 (2005).
[CrossRef] [PubMed]

Blessington, D.

Y. Chen, C. Mu, X. Intes, D. Blessington, and B. Chance, Near-infrared phase cancellation instrument for fast and accurate localization of fluorescent heterogeneity, Rev. Sci. Instrum. 74, 3466-3473 (2003).
[CrossRef]

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. of Biomed. Opt. 10, 54003-54003 (2005).
[CrossRef]

Bloch, S. R.

Boas, D. A.

A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, Time resolved fluorescence tomography of turbid media based on lifetime contrast, Opt. Express 14, 12255-12270 (2006).
[CrossRef] [PubMed]

T. Durduran, A. G. Yodh, B. Chance, and D. A. Boas, Does the photon diffusion coefficient depend on absorption?J. Opt. Soc. Am. 14, 3358-3365 (1997).
[CrossRef]

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

M. A. O’Leary, D. A. Boas, B. Chance, and A. G. Yodh, Reradiation and imaging of diffuse photon density waves using fluorescent inhomogeneities.J. Lumin. 60-1, 281-286 (1994).
[CrossRef]

Bogaards, A.

A. Bogaards, A. Varma, K. Zhang, D. Zach, S. K. Bisland, E. H. Moriyama, L. Lilge, P. J. Muller, and B. C. Wilson, Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development, Photochem. Photobiol. Sci. 4, 438-442 (2005).
[CrossRef] [PubMed]

Bogdanov, A.

R. Weissleder, C. H. Tung, U. Mahmood, and A. Bogdanov, In vivo imaging of tumors with protease-activated near-infrared fluorescent probes, Nat. Biotechnol. 17, 375-378 (1999).
[CrossRef] [PubMed]

Bombardieri, E.

E. Bombardieri and F. Crippa. PET imaging in breast cancer, Q. J. of Nucl. Med. 45, 245-55 (2001).

Boverman, G.

Bremer, C.

V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Fluorescence molecular tomography resolves protease activity in vivo, Nat. Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

Bugaj, J. E.

S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging, Invest. Radiol. 35, 479-485 (2000).
[CrossRef] [PubMed]

Busch, T. M.

R. Cheung, M. Solonenko, T. M. Busch, F. Del Piero, M. E. Putt, S. M. Hahn, and A. G. Yodh, Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model, J. Of Biomed. Opt. 8, 248-252 (2003).
[CrossRef]

Butler, J.

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
[CrossRef] [PubMed]

N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, Noninvasive functional optical spectroscopy of human breast tissue, Proc. Natl. Acad. Sci. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

Cerussi, A.

N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, Noninvasive functional optical spectroscopy of human breast tissue, Proc. Natl. Acad. Sci. 98, 4420-4425 (2001).
[CrossRef] [PubMed]

Cerussi, A. E.

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
[CrossRef] [PubMed]

Chance, B.

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Grosicka-Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. A. Rosen, and A. G. Yodh, Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI, Med. Phys. 32, 1128-1139 (2005).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, D. N. Pattanayak, B. Chance, and A. G. Yodh, 3D diffuse optical tomography in the plane parallel transmission geometry: Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging, Med. Phys. 30, 235-247 (2003).
[CrossRef] [PubMed]

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, In vivo continuous-wave optical breast imaging enhanced with indocyanine green, Med. Phys. 30, 1039-1047 (2003).
[CrossRef] [PubMed]

Y. Chen, C. Mu, X. Intes, D. Blessington, and B. Chance, Near-infrared phase cancellation instrument for fast and accurate localization of fluorescent heterogeneity, Rev. Sci. Instrum. 74, 3466-3473 (2003).
[CrossRef]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, Bulk optical properties of healthy female breast tissue, Phys. Med. Biol. 47, 2847-2861 (2002).
[CrossRef] [PubMed]

V. Ntziachristos and B. Chance, Probing physiology and molecular function using optical imaging: applications to breast cancer, Breast Cancer Res. 3, 41-46 (2001).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Concurrent mri and diffuse optical tomography of breast after indocyanine green enhancement, Proc. Natl. Acad. Sci. 97, 2767-2772 (2000).
[CrossRef] [PubMed]

X. D. Li, B. Chance, and A. G. Yodh, Fluorescent heterogeneities in turbid media: limits for detection, characterization, and comparison with absorption, Applied Optics 37, 6833-6844 (1998).
[CrossRef]

T. Durduran, A. G. Yodh, B. Chance, and D. A. Boas, Does the photon diffusion coefficient depend on absorption?J. Opt. Soc. Am. 14, 3358-3365 (1997).
[CrossRef]

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

A. G. Yodh and B. Chance, Spectroscopy and imaging with diffusing light, Phys. Today 48, 34-40 (1995).
[CrossRef]

M. A. O’Leary, D. A. Boas, B. Chance, and A. G. Yodh, Reradiation and imaging of diffuse photon density waves using fluorescent inhomogeneities.J. Lumin. 60-1, 281-286 (1994).
[CrossRef]

Charnsangavej, C.

S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li, Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts, Cancer Res. 63, 7870-7875 (2003).
[PubMed]

Chen, B.

B. W. Pogue, S. L. Gibbs, B. Chen, and M. Savellano, Fluorescence imaging in vivo: raster scanned pointsource imaging provides more accurate quantification than broad beam geometries, Technol. Cancer Res. Treat. 3, 15-21 (2004).
[PubMed]

Chen, Y.

Y. Chen, C. Mu, X. Intes, D. Blessington, and B. Chance, Near-infrared phase cancellation instrument for fast and accurate localization of fluorescent heterogeneity, Rev. Sci. Instrum. 74, 3466-3473 (2003).
[CrossRef]

X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, In vivo continuous-wave optical breast imaging enhanced with indocyanine green, Med. Phys. 30, 1039-1047 (2003).
[CrossRef] [PubMed]

Cheung, R.

R. Cheung, M. Solonenko, T. M. Busch, F. Del Piero, M. E. Putt, S. M. Hahn, and A. G. Yodh, Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model, J. Of Biomed. Opt. 8, 248-252 (2003).
[CrossRef]

Choe, R.

R. Choe, A. Corlu, K. Lee, T. Durduran, S. D. Konecky, M. Grosicka-Koptyra, S. R. Arridge, B. J. Czerniecki, D. L. Fraker, A. DeMichele, B. Chance, M. A. Rosen, and A. G. Yodh, Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI, Med. Phys. 32, 1128-1139 (2005).
[CrossRef] [PubMed]

A. Corlu, R. Choe, T. Durduran, K. Lee,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Diffuse optical tomography with spectral constraints and wavelength optimization, Appl. Opt. 44, 2082-2093 (2005).
[CrossRef] [PubMed]

A. Corlu, T. Durduran, R. Choe,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Uniqueness and wavelength optimization in continous-wave multispectral diffuse optical tomography, Opt. Lett. 28, 2339-2341 (2003).
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A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, E. Stathopoulos, M. Kafousi, J. Ripoll, and TG Papazoglou, Optical characterization of thin female breast biopsies based on the reduced scattering coefficient, Phys. Med. Biol 50, 2583-2596 (2005).
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E. Kuwana and E. M. Sevick-Muraca, Fluorescence lifetime spectroscopy for pH sensing in scattering media, Anal. Chem. 75, 4325-4329 (2003).
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S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li, Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts, Cancer Res. 63, 7870-7875 (2003).
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Slemp, A.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, D. N. Pattanayak, B. Chance, and A. G. Yodh, 3D diffuse optical tomography in the plane parallel transmission geometry: Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging, Med. Phys. 30, 235-247 (2003).
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J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, Imaging of spontaneous canine mammary tumors using fluorescent contrast agents, Photochem. Photobiol. 70, 87-94 (1999).
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R. Cheung, M. Solonenko, T. M. Busch, F. Del Piero, M. E. Putt, S. M. Hahn, and A. G. Yodh, Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model, J. Of Biomed. Opt. 8, 248-252 (2003).
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A. Liebert, H. Wabnitz, J. Steinbrink, M. Moller, R. Macdonald, H. Rinneberg, A. Villringer, and H. Obrig, Bed-side assessment of cerebral perfusion in stroke patients based on optical monitoring of a dye bolus by timeresolved diffuse reflectance, Neuroimage 24, 426-35 (2005).
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A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies, J. Biomed. Opt. 9, 488-496 (2004).
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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, 1701-1720 (2003).
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J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, Imaging of spontaneous canine mammary tumors using fluorescent contrast agents, Photochem. Photobiol. 70, 87-94 (1999).
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N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, and B. Tromberg, Noninvasive functional optical spectroscopy of human breast tissue, Proc. Natl. Acad. Sci. 98, 4420-4425 (2001).
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A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
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J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, Imaging of spontaneous canine mammary tumors using fluorescent contrast agents, Photochem. Photobiol. 70, 87-94 (1999).
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E. M. Sevick-Muraca, G. Lopez, J. S. Reynolds, T. L. Troy, and C. L. Hutchinson, Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques, Photochem. Photobiol. 66, 55-64 (1997).
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A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, E. Stathopoulos, M. Kafousi, J. Ripoll, and TG Papazoglou, Optical characterization of thin female breast biopsies based on the reduced scattering coefficient, Phys. Med. Biol 50, 2583-2596 (2005).
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A. Tsourkas and G. Bao, Shedding light on health and disease using molecular beacons.Brief Funct. Genomic. Proteomic. 1, 372-384 (2003).
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V. Ntziachristos, C. Tung, C. Bremer, and R. Weissleder, Fluorescence molecular tomography resolves protease activity in vivo, Nat. Med. 8, 757-760 (2002).
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R. Weissleder, C. H. Tung, U. Mahmood, and A. Bogdanov, In vivo imaging of tumors with protease-activated near-infrared fluorescent probes, Nat. Biotechnol. 17, 375-378 (1999).
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A. Liebert, H. Wabnitz, J. Steinbrink, M. Moller, R. Macdonald, H. Rinneberg, A. Villringer, and H. Obrig, Bed-side assessment of cerebral perfusion in stroke patients based on optical monitoring of a dye bolus by timeresolved diffuse reflectance, Neuroimage 24, 426-35 (2005).
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A. Liebert, H. Wabnitz, J. Steinbrink, M. Moller, R. Macdonald, H. Rinneberg, A. Villringer, and H. Obrig, Bed-side assessment of cerebral perfusion in stroke patients based on optical monitoring of a dye bolus by timeresolved diffuse reflectance, Neuroimage 24, 426-35 (2005).
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S. Kwon, S. Ke, J. P. Houston, W. Wang, Q. Wu, C. Li, and E. M. Sevick-Muraca, Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to alpha v beta 3 receptor expressed in Kaposi’s sarcoma, Mol. Imaging 4, 75-87 (2005).
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J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, Imaging of spontaneous canine mammary tumors using fluorescent contrast agents, Photochem. Photobiol. 70, 87-94 (1999).
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B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, and K. D. Paulsen, Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: Pilot results in the breast, Radiology 218, 261-266 (2001).
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S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li, Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts, Cancer Res. 63, 7870-7875 (2003).
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A. Bogaards, A. Varma, K. Zhang, D. Zach, S. K. Bisland, E. H. Moriyama, L. Lilge, P. J. Muller, and B. C. Wilson, Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development, Photochem. Photobiol. Sci. 4, 438-442 (2005).
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Yodh, A. G.

A. Corlu, R. Choe, T. Durduran, K. Lee,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Diffuse optical tomography with spectral constraints and wavelength optimization, Appl. Opt. 44, 2082-2093 (2005).
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X. Intes, J. Ripoll, Y. Chen, S. Nioka, A. G. Yodh, and B. Chance, In vivo continuous-wave optical breast imaging enhanced with indocyanine green, Med. Phys. 30, 1039-1047 (2003).
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R. Cheung, M. Solonenko, T. M. Busch, F. Del Piero, M. E. Putt, S. M. Hahn, and A. G. Yodh, Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model, J. Of Biomed. Opt. 8, 248-252 (2003).
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A. Corlu, T. Durduran, R. Choe,M. Schweiger, E.M. C. Hillman, S. R. Arridge, and A. G. Yodh, Uniqueness and wavelength optimization in continous-wave multispectral diffuse optical tomography, Opt. Lett. 28, 2339-2341 (2003).
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T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, Bulk optical properties of healthy female breast tissue, Phys. Med. Biol. 47, 2847-2861 (2002).
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V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, Concurrent mri and diffuse optical tomography of breast after indocyanine green enhancement, Proc. Natl. Acad. Sci. 97, 2767-2772 (2000).
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A. Garofalakis, G. Zacharakis, G. Filippidis, E. Sanidas, D. D. Tsiftsis, E. Stathopoulos, M. Kafousi, J. Ripoll, and TG Papazoglou, Optical characterization of thin female breast biopsies based on the reduced scattering coefficient, Phys. Med. Biol 50, 2583-2596 (2005).
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Zhang, C.

A. Godavarty, A. B. Thompson, R. Roy, M. Gurfinkel, M. J. Eppstein, C. Zhang, and E. M. Sevick-Muraca, Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies, J. Biomed. Opt. 9, 488-496 (2004).
[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, 1701-1720 (2003).
[CrossRef] [PubMed]

Zhang, K.

A. Bogaards, A. Varma, K. Zhang, D. Zach, S. K. Bisland, E. H. Moriyama, L. Lilge, P. J. Muller, and B. C. Wilson, Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development, Photochem. Photobiol. Sci. 4, 438-442 (2005).
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Zubkov, L.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, D. N. Pattanayak, B. Chance, and A. G. Yodh, 3D diffuse optical tomography in the plane parallel transmission geometry: Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging, Med. Phys. 30, 235-247 (2003).
[CrossRef] [PubMed]

T. Durduran, R. Choe, J. P. Culver, L. Zubkov, M. J. Holboke, J. Giammarco, B. Chance, and A. G. Yodh, Bulk optical properties of healthy female breast tissue, Phys. Med. Biol. 47, 2847-2861 (2002).
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Acad. Radiol.

A. E. Cerussi, A. J. Berger, F. Bevilacqua, N. Shah, D. Jakubowski, J. Butler, R. F. Holcombe, and B. J. Tromberg, Sources of absorption and scattering contrast for near-infrared optical mammography, Acad. Radiol. 8, 211-218 (2001).
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Anal. Chem.

E. Kuwana and E. M. Sevick-Muraca, Fluorescence lifetime spectroscopy for pH sensing in scattering media, Anal. Chem. 75, 4325-4329 (2003).
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Appl. Opt

H. Dehghani, B. W. Pogue, S. P. Poplack, and K. D. Paulsen, Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results, Appl. Opt 42, 135-145 (2003).
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Appl. Opt.

Applied Optics

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Brief Funct. Genomic. Proteomic.

A. Tsourkas and G. Bao, Shedding light on health and disease using molecular beacons.Brief Funct. Genomic. Proteomic. 1, 372-384 (2003).
[CrossRef]

Cancer Immunol. Immunother

B. Ballou, G.W. Fisher, A. S. Waggoner, D. L. Farkas, J. M. Reiland, R. Jaffe, R. B. Mujumdar, S. R. Mujumdar, and T. R. Hakala, Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies, Cancer Immunol. Immunother 41, 257-263 (1995).
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Figures (16)

Fig. 1.
Fig. 1.

Schematic of parallel plate DOT instrument. (a) The subject lies in prone position with breasts suspended in the breast box. Continuous wave (CW) transmission and frequency-domain (FD) remission measurements are performed simultaneously. Spectral filters are introduced in front of the detectors for fluorescence measurements. 45 sources and 9 FD detectors are positioned on the compression plate in a 9×5 and 3×3 grid arrangement. A diode laser at 786 nm is utilized for excitation of ICG and fluorescence detection (b) Excitation and emission spectra of whole blood containing 0.05 mg/ml of sterile ICG [58] are shown together with the 785 nm notch filter (blue line) and 830 nm (red shading, FWHM = 10 nm) bandpass filter.

Fig. 2.
Fig. 2.

(a) Illustration of the phantom (CCD view). The tube ends are attached to a pump (not shown) in order to titrate the phantom with different ICG concentrations. (b) Timetable for the phantom measurement protocol.

Fig. 3.
Fig. 3.

Time-table for the in vivo measurements.

Fig. 4.
Fig. 4.

Reconstruction flowchart.

Fig. 5.
Fig. 5.

Outline of the phantom is drawn in pink color and white mark (*) shows the projection of the 43 rd source location onto the detector plane. The phantom has 1μM ICG concentration. (a) Transmission intensity at the excitation wavelength is centered at the source position. (b) Fluorescence signal originates within the object.

Fig. 6.
Fig. 6.

Image slices from 3D reconstructions of the phantom’s ICG concentration (a) and absorption at 786nm (b). Object location and size correlate well with both fluorescence and absorption images.

Fig. 7.
Fig. 7.

The different origin of excitation transmission and fluorescence signals are demonstrated with data acquired from a patient (case 2). The breast outline is drawn with red, and the white mark (*) shows the projection of the excitation source location onto the detector plane. Transmitted excitation light appears to come from the source position as shown in (a) and (b) for source 23 and 36, respectively. The fluorescence signal, on the other hand, is clearly contained inside the breast boundary, as demonstrated for sources 23 and 36 in (c) and (d), respectively.

Fig. 8.
Fig. 8.

Fluorescence intensity (blue line) versus time, obtained from images acquired while excitation light at 786nm illuminates the medium from the 15 th source position. The green line shows the exponential fit to the fluorescence peak intensity values acquired after the 3 rd minute. The full fluorescence scan starts at t = 6.6 min and at t = 10.2 min, fluorescence intensity is recorded with the 15 th source. This data point serves as a reference to correct the full scan data.

Fig. 9.
Fig. 9.

Images acquired at different time points in a patient scan (case 2) while the excitation light at 786 nm illuminated the tissue from 15 th source position (marked with a white *). (a) At t = 0, before ICG injection, the detected intensity is essentially the system noise. (b) t = 2 min, fluorescence signal reaches its peak. (c) At later times the signal decreases as the ICG clears out of the tissue.

Fig. 10.
Fig. 10.

(a) Illustration of the tumor location for Case 1. (b) According to the gadolinium enhanced sagittal MR image slice the tumor is located around y = 5 cm position in the DOT configuration. (c) Fluorescence transillumination image obtained from patient (case 1).

Fig. 11.
Fig. 11.

Patient Case 1: Total hemoglobin concentration, blood oxygen saturation, μ′s (786nm) and fluorescence image slices at y = 5 cm are displayed (a) with their values along a horizontal line passing through the center of tumor (b).

Fig. 12.
Fig. 12.

Iso-surface plot of THC, μ′s (786nm) and fluorescence at iso-values of three standard deviations above their respective means correspond to tumor location. Outline designates the border of the breast modeled as an ellipsoid using the breast photo taken with the CCD camera.

Fig. 13.
Fig. 13.

(a) Illustration of the tumor location for Case 2. (b) Sagittal slice from gadolinium enhanced MR image shows a bright spot below the nipple area corresponding to the y = 4 cm axial slice in the DOT configuration. (c) Fluorescence transillumination picture obtained from patient (case 2).

Fig. 14.
Fig. 14.

Patient Case 2: Total hemoglobin concentration, blood oxygen saturation, μ′s (786nm) and fluorescence image slices at y = 4 cm are displayed (a) with their values along a horizontal line passing through the center of tumor location (b).

Fig. 15.
Fig. 15.

(a) Illustration of the tumor location for Case 3. (b) According to the gadolinium enhanced sagittal MR image slice the tumor is located around y = 5 cm position in the DOT configuration. (c) Fluorescence transillumination picture obtained from patient (case 3).

Fig. 16.
Fig. 16.

Patient Case 3: Total hemoglobin concentration, blood oxygen saturation, μ′s (786nm) and fluorescence image slices at y = 5 cm are displayed (a) with their values along a horizontal line passing through the center of tumor location (b).

Equations (11)

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

D ( λ ex , r ) Φ ( λ ex , ω , r ) + ( μ a ( λ ex , r ) + v ) Φ ( λ ex , ω , r ) = q 0 ( λ ex , ω , r s ) ,
D ( λ fl , r ) Φ ( λ fl , ω , r ) + ( μ a ( λ fl , r ) + v ) Φ ( λ fl , ω , r ) = n ( r ) 1 iωτ ( r ) Φ ( λ ex , ω , r ) .
n ( r ) = [ C ] × ε ( λ ex ) × η ,
Φ + D ( λ ) α d Φ d v ̂ = 0 ,
Φ c ( λ fl , r s , r d ) = d 3 r n ( r ) Φ c ( λ ex , r s , r ) G ( λ fl , r d , r ) ,
Φ m ( λ fl , r s , r d ) Φ m ( λ ex , r s , r d ) = Θ ( r s , r d , λ fl ) Φ c ( λ fl , r s , r d ) Θ ( r s , r d , λ ex ) Φ c ( λ ex , r s , r d ) ,
= 1 Φ c ( λ ex , r s , r d ) d 3 r n ( r ) Φ c ( λ ex , r s , r ) G ( λ fl , r d , r ) .
Φ m ( λ fl , r s , r d ) Φ m ( λ ex , r s , r d ) 1 Φ c ( λ ex , r s , r d ) j = 1 N h 3 n j Φ c ( λ ex , r s , r j ) G ( λ fl , r s , r j ) .
( J T J + Λ L ) n = J T y .
J i , j = h 3 Φ c ( λ ex , r si , r j ) G ( λ fl , r di , r j ) Φ c ( λ ex , r si , r di ) ,
T ( r d ) = log ( s N s Φ m fl ( r s , r d ) s N s Φ m ex ( r s , r d ) ) .

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