Abstract

We have developed a fiber-based, video-rate fluorescence diffuse optical tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN) mapping. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was imaged in the region of the SLN following intradermal injection into the forepaw of rats. These results suggest that video-rate fluorescence DOT has significant potential as a clinical tool for noninvasive mapping of SLN.

© 2011 OSA

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2010 (6)

T. Hojo, T. Nagao, M. Kikuyama, S. Akashi, and T. Kinoshita, “Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer,” Breast19(3), 210–213 (2010).
[CrossRef] [PubMed]

S. T. Proulx, P. Luciani, S. Derzsi, M. Rinderknecht, V. Mumprecht, J. C. Leroux, and M. Detmar, “Quantitative imaging of lymphatic function with liposomal indocyanine green,” Cancer Res.70(18), 7053–7062 (2010).
[CrossRef] [PubMed]

B. T. Lee, M. Hutteman, S. Gioux, A. Stockdale, S. J. Lin, L. H. Ngo, and J. V. Frangioni, “The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in perforator flap breast reconstruction,” Plast. Reconstr. Surg.126(5), 1472–1481 (2010).
[CrossRef] [PubMed]

L. Cao, M. Breithaupt, and J. Peter, “Geometrical co-calibration of a tomographic optical system with CT for intrinsically co-registered imaging,” Phys. Med. Biol.55(6), 1591–1606 (2010).
[CrossRef] [PubMed]

L. Cao and J. Peter, “Bayesian reconstruction strategy of fluorescence-mediated tomography using an integrated SPECT-CT-OT system,” Phys. Med. Biol.55(9), 2693–2708 (2010).
[CrossRef] [PubMed]

W. C. Barber, Y. Lin, O. Nalcioglu, J. S. Iwanczyk, N. E. Hartsough, and G. Gulsen, “Combined fluorescence and x-ray tomography for quantitative in vivo detection of fluorophore,” Technol. Cancer Res. Treat.9(1), 45–52 (2010).
[PubMed]

2009 (2)

S. L. Troyan, V. Kianzad, S. L. Gibbs-Strauss, S. Gioux, A. Matsui, R. Oketokoun, L. Ngo, A. Khamene, F. Azar, and J. V. Frangioni, “The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping,” Ann. Surg. Oncol.16(10), 2943–2952 (2009).
[CrossRef] [PubMed]

B. R. White, A. Z. Snyder, A. L. Cohen, S. E. Petersen, M. E. Raichle, B. L. Schlaggar, and J. P. Culver, “Resting-state functional connectivity in the human brain revealed with diffuse optical tomography,” Neuroimage47(1), 148–156 (2009).
[CrossRef] [PubMed]

2008 (4)

L. Sampath, W. Wang, and E. M. Sevick-Muraca, “Near infrared fluorescent optical imaging for nodal staging,” J. Biomed. Opt.13(4), 041312 (2008).
[CrossRef] [PubMed]

R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
[CrossRef] [PubMed]

S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt.13(1), 011009 (2008).
[CrossRef] [PubMed]

2007 (4)

B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
[CrossRef] [PubMed]

J. V. Frangioni, S. W. Kim, S. Ohnishi, S. Kim, and M. G. Bawendi, “Sentinel lymph node mapping with type-II quantum dots,” Methods Mol. Biol.374, 147–159 (2007).
[PubMed]

R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
[CrossRef] [PubMed]

B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
[CrossRef] [PubMed]

2006 (3)

W. Rzyman, O. M. Hagen, R. Dziadziuszko, G. Kobierska-Gulida, A. Karmolinski, M. I. Lothe, W. Paleczka, M. Murawski, T. Jastrzebski, A. Kopacz, J. Jassem, and J. Skokowski, “Blue-dye intraoperative sentinel lymph node mapping in early non-small cell lung cancer,” Eur. J. Surg. Oncol.32(4), 462–465 (2006).
[CrossRef] [PubMed]

D. K. Joseph, T. J. Huppert, M. A. Franceschini, and D. A. Boas, “Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging,” Appl. Opt.45(31), 8142–8151 (2006).
[CrossRef] [PubMed]

T. Austin, A. P. Gibson, G. Branco, R. M. Yusof, S. R. Arridge, J. H. Meek, J. S. Wyatt, D. T. Delpy, and J. C. Hebden, “Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain,” Neuroimage31(4), 1426–1433 (2006).
[CrossRef] [PubMed]

2005 (6)

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(4), 1128–1139 (2005).
[CrossRef] [PubMed]

Q. Zhang, T. J. Brukilacchio, A. Li, J. J. Stott, T. Chaves, E. Hillman, T. Wu, M. Chorlton, E. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Coregistered tomographic x-ray and optical breast imaging: initial results,” J. Biomed. Opt.10(2), 024033 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, G. Turner, J. Dunham, S. Windsor, A. Soubret, J. Ripoll, and H. A. Shih, “Planar fluorescence imaging using normalized data,” J. Biomed. Opt.10(6), 064007 (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. Express13(7), 2564–2577 (2005).
[CrossRef] [PubMed]

Q. Zhu, “Optical tomography with ultrasound localization: initial clinical results and technical challenges,” Technol. Cancer Res. Treat.4(3), 235–244 (2005).
[PubMed]

Q. Zhu, E. B. Cronin, A. A. Currier, H. S. Vine, M. Huang, N. Chen, and C. Xu, “Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction,” Radiology237(1), 57–66 (2005).
[CrossRef] [PubMed]

2004 (1)

M. A. Franceschini and D. A. Boas, “Noninvasive measurement of neuronal activity with near-infrared optical imaging,” Neuroimage21(1), 372–386 (2004).
[CrossRef] [PubMed]

2003 (3)

J. P. Culver, A. M. Siegel, J. J. Stott, and D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett.28(21), 2061–2063 (2003).
[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys.30(2), 235–247 (2003).
[CrossRef] [PubMed]

A. Li, E. L. Miller, M. E. Kilmer, T. J. Brukilacchio, T. Chaves, J. Stott, Q. Zhang, T. Wu, M. Chorlton, R. H. Moore, D. B. Kopans, and D. A. Boas, “Tomographic optical breast imaging guided by three-dimensional mammography,” Appl. Opt.42(25), 5181–5190 (2003).
[CrossRef] [PubMed]

2002 (3)

X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol.47(1), N1–N10 (2002).
[CrossRef] [PubMed]

T. M. Tuttle, M. Colbert, R. Christensen, K. J. Ose, T. Jones, R. Wetherille, J. Friedman, K. Swenson, and K. M. McMasters, “Subareolar injection of 99mTc facilitates sentinel lymph node identification,” Ann. Surg. Oncol.9(1), 77–81 (2002).
[CrossRef] [PubMed]

V. Ntziachristos and R. Weissleder, “Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media,” Med. Phys.29(5), 803–809 (2002).
[CrossRef] [PubMed]

2001 (3)

2000 (1)

A. N. Bashkatov, E. A. Genina, I. V. Korovina, V. I. Kochubey, Yu. P. Sinichkin, and V. V. Tuchin, “In vivo and in vitro study of control of rat skin optical properties by acting of osmotical liquid,” Proc. SPIE4224, 300–311 (2000).
[CrossRef]

1999 (1)

1998 (1)

1995 (1)

1992 (1)

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
[CrossRef] [PubMed]

1990 (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A Review of the Optical-Properties of Biological Tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

Achilefu, S.

Adams, K. E.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
[CrossRef] [PubMed]

R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
[CrossRef] [PubMed]

R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
[CrossRef] [PubMed]

Akashi, S.

T. Hojo, T. Nagao, M. Kikuyama, S. Akashi, and T. Kinoshita, “Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer,” Breast19(3), 210–213 (2010).
[CrossRef] [PubMed]

Andersson-Engels, S.

Arridge, S. R.

T. Austin, A. P. Gibson, G. Branco, R. M. Yusof, S. R. Arridge, J. H. Meek, J. S. Wyatt, D. T. Delpy, and J. C. Hebden, “Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain,” Neuroimage31(4), 1426–1433 (2006).
[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(4), 1128–1139 (2005).
[CrossRef] [PubMed]

Austin, T.

T. Austin, A. P. Gibson, G. Branco, R. M. Yusof, S. R. Arridge, J. H. Meek, J. S. Wyatt, D. T. Delpy, and J. C. Hebden, “Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain,” Neuroimage31(4), 1426–1433 (2006).
[CrossRef] [PubMed]

Azar, F.

S. L. Troyan, V. Kianzad, S. L. Gibbs-Strauss, S. Gioux, A. Matsui, R. Oketokoun, L. Ngo, A. Khamene, F. Azar, and J. V. Frangioni, “The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping,” Ann. Surg. Oncol.16(10), 2943–2952 (2009).
[CrossRef] [PubMed]

Barber, W. C.

W. C. Barber, Y. Lin, O. Nalcioglu, J. S. Iwanczyk, N. E. Hartsough, and G. Gulsen, “Combined fluorescence and x-ray tomography for quantitative in vivo detection of fluorophore,” Technol. Cancer Res. Treat.9(1), 45–52 (2010).
[PubMed]

Bashkatov, A. N.

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Q. Zhang, T. J. Brukilacchio, A. Li, J. J. Stott, T. Chaves, E. Hillman, T. Wu, M. Chorlton, E. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Coregistered tomographic x-ray and optical breast imaging: initial results,” J. Biomed. Opt.10(2), 024033 (2005).
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B. R. White, A. Z. Snyder, A. L. Cohen, S. E. Petersen, M. E. Raichle, B. L. Schlaggar, and J. P. Culver, “Resting-state functional connectivity in the human brain revealed with diffuse optical tomography,” Neuroimage47(1), 148–156 (2009).
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R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
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E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
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R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
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S. T. Proulx, P. Luciani, S. Derzsi, M. Rinderknecht, V. Mumprecht, J. C. Leroux, and M. Detmar, “Quantitative imaging of lymphatic function with liposomal indocyanine green,” Cancer Res.70(18), 7053–7062 (2010).
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V. Ntziachristos, G. Turner, J. Dunham, S. Windsor, A. Soubret, J. Ripoll, and H. A. Shih, “Planar fluorescence imaging using normalized data,” J. Biomed. Opt.10(6), 064007 (2005).
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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(4), 1128–1139 (2005).
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Sampath, L.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
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L. Sampath, W. Wang, and E. M. Sevick-Muraca, “Near infrared fluorescent optical imaging for nodal staging,” J. Biomed. Opt.13(4), 041312 (2008).
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B. R. White, A. Z. Snyder, A. L. Cohen, S. E. Petersen, M. E. Raichle, B. L. Schlaggar, and J. P. Culver, “Resting-state functional connectivity in the human brain revealed with diffuse optical tomography,” Neuroimage47(1), 148–156 (2009).
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B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
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B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
[CrossRef] [PubMed]

Schwartz, J. A.

Sevick-Muraca, E. M.

R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
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L. Sampath, W. Wang, and E. M. Sevick-Muraca, “Near infrared fluorescent optical imaging for nodal staging,” J. Biomed. Opt.13(4), 041312 (2008).
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R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
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E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
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R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
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B. R. White, A. Z. Snyder, A. L. Cohen, S. E. Petersen, M. E. Raichle, B. L. Schlaggar, and J. P. Culver, “Resting-state functional connectivity in the human brain revealed with diffuse optical tomography,” Neuroimage47(1), 148–156 (2009).
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V. Ntziachristos, G. Turner, J. Dunham, S. Windsor, A. Soubret, J. Ripoll, and H. A. Shih, “Planar fluorescence imaging using normalized data,” J. Biomed. Opt.10(6), 064007 (2005).
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Stott, J. J.

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J. P. Culver, A. M. Siegel, J. J. Stott, and D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett.28(21), 2061–2063 (2003).
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Troyan, S. L.

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A. N. Bashkatov, E. A. Genina, I. V. Korovina, V. I. Kochubey, Yu. P. Sinichkin, and V. V. Tuchin, “In vivo and in vitro study of control of rat skin optical properties by acting of osmotical liquid,” Proc. SPIE4224, 300–311 (2000).
[CrossRef]

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V. Ntziachristos, G. Turner, J. Dunham, S. Windsor, A. Soubret, J. Ripoll, and H. A. Shih, “Planar fluorescence imaging using normalized data,” J. Biomed. Opt.10(6), 064007 (2005).
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T. M. Tuttle, M. Colbert, R. Christensen, K. J. Ose, T. Jones, R. Wetherille, J. Friedman, K. Swenson, and K. M. McMasters, “Subareolar injection of 99mTc facilitates sentinel lymph node identification,” Ann. Surg. Oncol.9(1), 77–81 (2002).
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S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
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Q. Zhu, E. B. Cronin, A. A. Currier, H. S. Vine, M. Huang, N. Chen, and C. Xu, “Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction,” Radiology237(1), 57–66 (2005).
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Wang, L. V.

Wang, W.

L. Sampath, W. Wang, and E. M. Sevick-Muraca, “Near infrared fluorescent optical imaging for nodal staging,” J. Biomed. Opt.13(4), 041312 (2008).
[CrossRef] [PubMed]

R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
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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,” Radiology218(1), 261–266 (2001).
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R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
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E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology246(3), 734–741 (2008).
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T. M. Tuttle, M. Colbert, R. Christensen, K. J. Ose, T. Jones, R. Wetherille, J. Friedman, K. Swenson, and K. M. McMasters, “Subareolar injection of 99mTc facilitates sentinel lymph node identification,” Ann. Surg. Oncol.9(1), 77–81 (2002).
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B. R. White, A. Z. Snyder, A. L. Cohen, S. E. Petersen, M. E. Raichle, B. L. Schlaggar, and J. P. Culver, “Resting-state functional connectivity in the human brain revealed with diffuse optical tomography,” Neuroimage47(1), 148–156 (2009).
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B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
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B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
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V. Ntziachristos, G. Turner, J. Dunham, S. Windsor, A. Soubret, J. Ripoll, and H. A. Shih, “Planar fluorescence imaging using normalized data,” J. Biomed. Opt.10(6), 064007 (2005).
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Q. Zhang, T. J. Brukilacchio, A. Li, J. J. Stott, T. Chaves, E. Hillman, T. Wu, M. Chorlton, E. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Coregistered tomographic x-ray and optical breast imaging: initial results,” J. Biomed. Opt.10(2), 024033 (2005).
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A. Li, E. L. Miller, M. E. Kilmer, T. J. Brukilacchio, T. Chaves, J. Stott, Q. Zhang, T. Wu, M. Chorlton, R. H. Moore, D. B. Kopans, and D. A. Boas, “Tomographic optical breast imaging guided by three-dimensional mammography,” Appl. Opt.42(25), 5181–5190 (2003).
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T. Austin, A. P. Gibson, G. Branco, R. M. Yusof, S. R. Arridge, J. H. Meek, J. S. Wyatt, D. T. Delpy, and J. C. Hebden, “Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain,” Neuroimage31(4), 1426–1433 (2006).
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Xu, C.

Q. Zhu, E. B. Cronin, A. A. Currier, H. S. Vine, M. Huang, N. Chen, and C. Xu, “Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction,” Radiology237(1), 57–66 (2005).
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X. Intes, V. Ntziachristos, J. P. Culver, A. Yodh, and B. Chance, “Projection access order in algebraic reconstruction technique for diffuse optical tomography,” Phys. Med. Biol.47(1), N1–N10 (2002).
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[CrossRef] [PubMed]

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys.30(2), 235–247 (2003).
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J. P. Culver, V. Ntziachristos, M. J. Holboke, and A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis,” Opt. Lett.26(10), 701–703 (2001).
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Q. Zhu, T. Durduran, V. Ntziachristos, M. Holboke, and A. G. Yodh, “Imager that combines near-infrared diffusive light and ultrasound,” Opt. Lett.24(15), 1050–1052 (1999).
[CrossRef] [PubMed]

Yusof, R. M.

T. Austin, A. P. Gibson, G. Branco, R. M. Yusof, S. R. Arridge, J. H. Meek, J. S. Wyatt, D. T. Delpy, and J. C. Hebden, “Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain,” Neuroimage31(4), 1426–1433 (2006).
[CrossRef] [PubMed]

Zeff, B. W.

B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
[CrossRef] [PubMed]

B. W. Zeff, B. R. White, H. Dehghani, B. L. Schlaggar, and J. P. Culver, “Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” Proc. Natl. Acad. Sci. U.S.A.104(29), 12169–12174 (2007).
[CrossRef] [PubMed]

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Q. Zhang, T. J. Brukilacchio, A. Li, J. J. Stott, T. Chaves, E. Hillman, T. Wu, M. Chorlton, E. Rafferty, R. H. Moore, D. B. Kopans, and D. A. Boas, “Coregistered tomographic x-ray and optical breast imaging: initial results,” J. Biomed. Opt.10(2), 024033 (2005).
[CrossRef] [PubMed]

A. Li, E. L. Miller, M. E. Kilmer, T. J. Brukilacchio, T. Chaves, J. Stott, Q. Zhang, T. Wu, M. Chorlton, R. H. Moore, D. B. Kopans, and D. A. Boas, “Tomographic optical breast imaging guided by three-dimensional mammography,” Appl. Opt.42(25), 5181–5190 (2003).
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[PubMed]

Q. Zhu, E. B. Cronin, A. A. Currier, H. S. Vine, M. Huang, N. Chen, and C. Xu, “Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction,” Radiology237(1), 57–66 (2005).
[CrossRef] [PubMed]

Q. Zhu, T. Durduran, V. Ntziachristos, M. Holboke, and A. G. Yodh, “Imager that combines near-infrared diffusive light and ultrasound,” Opt. Lett.24(15), 1050–1052 (1999).
[CrossRef] [PubMed]

Zubkov, L.

J. P. Culver, R. Choe, M. J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance, and A. G. Yodh, “Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging,” Med. Phys.30(2), 235–247 (2003).
[CrossRef] [PubMed]

Am. J. Physiol. Heart Circ. Physiol. (1)

R. Sharma, W. Wang, J. C. Rasmussen, A. Joshi, J. P. Houston, K. E. Adams, A. Cameron, S. Ke, S. Kwon, M. E. Mawad, and E. M. Sevick-Muraca, “Quantitative imaging of lymph function,” Am. J. Physiol. Heart Circ. Physiol.292(6), H3109–H3118 (2007).
[CrossRef] [PubMed]

Ann. N. Y. Acad. Sci. (1)

R. Sharma, J. A. Wendt, J. C. Rasmussen, K. E. Adams, M. V. Marshall, and E. M. Sevick-Muraca, “New horizons for imaging lymphatic function,” Ann. N. Y. Acad. Sci.1131(1), 13–36 (2008).
[CrossRef] [PubMed]

Ann. Surg. Oncol. (2)

T. M. Tuttle, M. Colbert, R. Christensen, K. J. Ose, T. Jones, R. Wetherille, J. Friedman, K. Swenson, and K. M. McMasters, “Subareolar injection of 99mTc facilitates sentinel lymph node identification,” Ann. Surg. Oncol.9(1), 77–81 (2002).
[CrossRef] [PubMed]

S. L. Troyan, V. Kianzad, S. L. Gibbs-Strauss, S. Gioux, A. Matsui, R. Oketokoun, L. Ngo, A. Khamene, F. Azar, and J. V. Frangioni, “The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping,” Ann. Surg. Oncol.16(10), 2943–2952 (2009).
[CrossRef] [PubMed]

Appl. Opt. (4)

Breast (1)

T. Hojo, T. Nagao, M. Kikuyama, S. Akashi, and T. Kinoshita, “Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer,” Breast19(3), 210–213 (2010).
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Supplementary Material (2)

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Figures (5)

Fig. 1
Fig. 1

Schematic of the video-rate fluorescence DOT hardware. (A) Schematic demonstrating frequency-encoding of 830 nm and 785 nm laser diode sources. Both reference and excitation light (at distinct frequencies) are incident on the tissue. Light exiting consists of reference, excitation, and emission (fluorescent) light. After collimation, the light is passed through a narrow band optical filter (F) to block the excitation light (785 nm). The resulting detected light, a sum of the reference transmission (I2) and fluorescence emission (I3), is simultaneously detected by a single detector. (B) A Fourier transform of the sum of I2 and I3 provides identification of transmission and emission signals from a single detector.

Fig. 2
Fig. 2

Schematic of the video-rate fluorescence DOT experimental setup. (A) Schematic of our experimental setup with an imaging array and a 3 mm ICG tube embedded in a tissue mimicking phantom. (B) Schematic of the placement of the fiber array on a preclinical animal model using an 8-10 mm thick chicken breast to simulate a deep tissue imaging situation.

Fig. 3
Fig. 3

System sensitivity analysis with phantom studies. (A) Vertical x-z and y-z slices of reconstructed experimental data from a fluorescent 3 mm tube target whose center of mass is located at 7.5 mm, 10.5 mm, and 13.5 mm depths. The system accurately reconstructs the tube shape with some artifact at the optode positions. (B) Point-spread function analysis using a simulated image reconstruction. Half-maximum contours of responses for different depths are shown. (C) Evaluation of the depth localization accuracy of a phantom target. The system has accurate localization from 6 to 13.5 mm. (D) Sensitivity vs depth. The data demonstrate that the signal intensity falls off exponentially with depth. (E) The relation between the raw reconstructed value and the true concentration of the dye was characterized by titration of ICG from 1 nM to 1 uM concentrations in a 3 mm tube.

Fig. 4
Fig. 4

Shallow imaging of lymph dynamics. (A) DOT images of the fluorescence dynamics at 2 mm depth in a rat following injection of ICG into the left forepaw. (B) Time traces of the dynamics of ICG accumulation in the region of the sentinel lymph node (for comparison the mean background signal is shown). (C) Reflectance fluorescent imaging of the sentinel lymph node region demonstrating fluorescence from the injection site (paws) and the lymph vessels leading to axillary lymph nodes (arrow). (D) Reflectance fluorescent image of the rat after euthanasia and removal of overlying skin. Inset: fluorescence from ex vivo imaging shows ICG uptake in the lymph nodes.

Fig. 5
Fig. 5

Deep (>10 mm) imaging of lymph dynamics. The video rate fluorescence DOT was used to image the SLN region in rats through 8-10 mm of chicken breast following ICG injection into the rat forepaw. (A) The dynamics in a slice at 11 mm depth from a DOT reconstruction. (B) Time traces of the dynamics (for 2 representative rats) of a region around the SLN and of the mean of all background pixels. (C) Dynamics of ICG accumulation averaged over 5 rats.

Equations (3)

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y i =[ ϕ emi ( r s(i) , r d(i) , λ emi ) ϕ bleedthrough ( r s(i) , r d(i) ) ϕ ref ( r s(i) , r d(i) , λ ref ) ].
ϕ bleedthrough ( r s(i) , r d(i) )=α× ϕ exc ( r s(i) , λ exc )= α filter d(i) ×R× ϕ ref ( r s(i) , λ ref );whereR= ϕ exc ( r s(i) , λ exc ) ϕ ref ( r s(i) , λ ref ) ;
A i,j = s o v h 3 D o G( r s(i) , r j , λ ref )G( r j , r d(i) , λ emi ) G( r s(i) , r d(i) , λ ref ) ;  x j = N j

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