Abstract

Ratiometric approaches to quantifying molecular concentrations have been used for decades in microscopy, but have rarely been exploited in vivo until recently. One dual-tracer approach can utilize an untargeted reference tracer to account for non-specific uptake of a receptor-targeted tracer, and ultimately estimate receptor binding potential quantitatively. However, interpretation of the relative dynamic distribution kinetics is confounded by differences in local tissue absorption at the wavelengths used for each tracer. This study simulated the influence of absorption on fluorescence emission intensity and depth sensitivity at typical near-infrared fluorophore wavelength bands near 700 and 800 nm in mouse skin in order to correct for these tissue optical differences in signal detection. Changes in blood volume [1-3%] and hemoglobin oxygen saturation [0-100%] were demonstrated to introduce substantial distortions to receptor binding estimates (error > 30%), whereas sampled depth was relatively insensitive to wavelength (error < 6%). In response, a pixel-by-pixel normalization of tracer inputs immediately post-injection was found to account for spatial heterogeneities in local absorption properties. Application of the pixel-based normalization method to an in vivo imaging study demonstrated significant improvement, as compared with a reference tissue normalization approach.

© 2014 Optical Society of America

Full Article  |  PDF Article
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    [Crossref] [PubMed]

2014 (3)

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

2013 (2)

2012 (2)

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

2010 (3)

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation,” Mol. Imaging 9(5), 237–255 (2010).
[PubMed]

2009 (1)

S. C. Kanick, D. J. Robinson, H. J. Sterenborg, and A. Amelink, “Monte Carlo analysis of single fiber reflectance spectroscopy: photon path length and sampling depth,” Phys. Med. Biol. 54(22), 6991–7008 (2009).
[Crossref] [PubMed]

2008 (1)

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[Crossref] [PubMed]

2007 (1)

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

2005 (3)

J. W. Lichtman and J. A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
[Crossref] [PubMed]

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[Crossref] [PubMed]

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

2003 (2)

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

2002 (1)

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas. 23(4), 741–753 (2002).
[Crossref] [PubMed]

2000 (1)

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

1996 (2)

A. A. Lammertsma and S. P. Hume, “Simplified reference tissue model for PET receptor studies,” Neuroimage 4(3), 153–158 (1996).
[Crossref] [PubMed]

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

1993 (1)

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

1990 (1)

R. K. Jain, “Vascular and interstitial barriers to delivery of therapeutic agents in tumors,” Cancer Metastasis Rev. 9(3), 253–266 (1990).
[Crossref] [PubMed]

1951 (1)

S. S. Kety, “The theory and applications of the exchange of inert gas at the lungs and tissues,” Pharmacol. Rev. 3(1), 1–41 (1951).
[PubMed]

Amelink, A.

S. C. Kanick, D. J. Robinson, H. J. Sterenborg, and A. Amelink, “Monte Carlo analysis of single fiber reflectance spectroscopy: photon path length and sampling depth,” Phys. Med. Biol. 54(22), 6991–7008 (2009).
[Crossref] [PubMed]

Arce, P.

Backes, W. H.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Beets-Tan, R. G.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Bench, C. J.

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Brooks, D. J.

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Carson, R. E.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Choi, H. S.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation,” Mol. Imaging 9(5), 237–255 (2010).
[PubMed]

Conchello, J. A.

J. W. Lichtman and J. A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
[Crossref] [PubMed]

Cunningham, V. J.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Davis, S. C.

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

de Lussanet, Q. G.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Delforge, J.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Diop, M.

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

Elliott, J. T.

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

Felder, S.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Frackowiak, R. S.

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Frangioni, J. V.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation,” Mol. Imaging 9(5), 237–255 (2010).
[PubMed]

Fujita, M.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Gioux, S.

S. Gioux, H. S. Choi, and J. V. Frangioni, “Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation,” Mol. Imaging 9(5), 237–255 (2010).
[PubMed]

Girard, E. J.

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

Gjedde, A.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Glaser, A. K.

Griffioen, A. W.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Gunn, J. R.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

Gunn, K.

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Gunn, R. N.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Hamzei, N.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

Hasan, T.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Hashimoto, D.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Hextrum, S.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Hextrum, S. K.

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

Holden, J.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Holt, R. W.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

Hoopes, P. J.

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

Hori, K.

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

Hou, V. W.

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

Houle, S.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Huang, S. C.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Hume, S. P.

A. A. Lammertsma and S. P. Hume, “Simplified reference tissue model for PET receptor studies,” Neuroimage 4(3), 153–158 (1996).
[Crossref] [PubMed]

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Hurwitz, D. R.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Ichise, M.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Iida, H.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Innis, R. B.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Ito, H.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Jacques, S. L.

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

Jain, R. K.

R. K. Jain, “Vascular and interstitial barriers to delivery of therapeutic agents in tumors,” Cancer Metastasis Rev. 9(3), 253–266 (1990).
[Crossref] [PubMed]

Jermyn, M.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Kanick, S. C.

A. K. Glaser, S. C. Kanick, R. Zhang, P. Arce, and B. W. Pogue, “A GAMOS plug-in for GEANT4 based Monte Carlo simulation of radiation-induced light transport in biological media,” Biomed. Opt. Express 4(5), 741–759 (2013).
[Crossref] [PubMed]

S. C. Kanick, D. J. Robinson, H. J. Sterenborg, and A. Amelink, “Monte Carlo analysis of single fiber reflectance spectroscopy: photon path length and sampling depth,” Phys. Med. Biol. 54(22), 6991–7008 (2009).
[Crossref] [PubMed]

Kety, S. S.

S. S. Kety, “The theory and applications of the exchange of inert gas at the lungs and tissues,” Pharmacol. Rev. 3(1), 1–41 (1951).
[PubMed]

Khurana, M.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Kim, A.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Kimura, Y.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Klubben, W. S.

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

Knudsen, G. M.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Knuuti, J.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Kobayashi, H.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Koeppe, R. A.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Lammertsma, A. A.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

A. A. Lammertsma and S. P. Hume, “Simplified reference tissue model for PET receptor studies,” Neuroimage 4(3), 153–158 (1996).
[Crossref] [PubMed]

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Langereis, S.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Laruelle, M.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Lax, I.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Lee, T. Y.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

Lichtman, J. W.

J. W. Lichtman and J. A. Conchello, “Fluorescence microscopy,” Nat. Methods 2(12), 910–919 (2005).
[Crossref] [PubMed]

Liow, J. S.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Logan, J.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Lu, J. Q.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Maeda, H.

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

Maguire, R. P.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Matcher, S. J.

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas. 23(4), 741–753 (2002).
[Crossref] [PubMed]

Matsumura, Y.

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

Meglinski, I. V.

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas. 23(4), 741–753 (2002).
[Crossref] [PubMed]

Mintun, M. A.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Model, K.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Moriyama, Y.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Morris, E. D.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Nelson, L. Y.

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

Ntziachristos, V.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[Crossref] [PubMed]

O’Hara, J. A.

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Osman, S.

A. A. Lammertsma, C. J. Bench, S. P. Hume, S. Osman, K. Gunn, D. J. Brooks, and R. S. Frackowiak, “Comparison of methods for analysis of clinical [11C]raclopride studies,” J. Cereb. Blood Flow Metab. 16(1), 42–52 (1996).
[Crossref] [PubMed]

Pardesi, O.

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

Parsey, R.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Pittet, M. J.

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[Crossref] [PubMed]

Pogue, B. W.

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

A. K. Glaser, S. C. Kanick, R. Zhang, P. Arce, and B. W. Pogue, “A GAMOS plug-in for GEANT4 based Monte Carlo simulation of radiation-induced light transport in biological media,” Biomed. Opt. Express 4(5), 741–759 (2013).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Price, J. C.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Ripoll, J.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[Crossref] [PubMed]

Robinson, D. J.

S. C. Kanick, D. J. Robinson, H. J. Sterenborg, and A. Amelink, “Monte Carlo analysis of single fiber reflectance spectroscopy: photon path length and sampling depth,” Phys. Med. Biol. 54(22), 6991–7008 (2009).
[Crossref] [PubMed]

Rubinstein, M.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Samkoe, K. S.

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

Sawa, T.

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

Schlessinger, J.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Seibel, E. J.

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

Sexton, K.

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

Sexton, K. J.

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

Shimizu, A.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Shirakawa, K.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Slifstein, M.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Sobajima, J.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Sossi, V.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Soubret, A.

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[Crossref] [PubMed]

Srinivasan, S.

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

St. Lawrence, K.

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

Sterenborg, H. J.

S. C. Kanick, D. J. Robinson, H. J. Sterenborg, and A. Amelink, “Monte Carlo analysis of single fiber reflectance spectroscopy: photon path length and sampling depth,” Phys. Med. Biol. 54(22), 6991–7008 (2009).
[Crossref] [PubMed]

Suhara, T.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Suzuki, K.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Takano, A.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Tichauer, K. M.

K. M. Tichauer, M. Diop, J. T. Elliott, K. S. Samkoe, T. Hasan, K. St. Lawrence, and B. W. Pogue, “Accounting for pharmacokinetic differences in dual-tracer receptor density imaging,” Phys. Med. Biol. 59(10), 2341–2351 (2014).
[Crossref] [PubMed]

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

K. S. Samkoe, K. Sexton, K. M. Tichauer, S. K. Hextrum, O. Pardesi, S. C. Davis, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas,” Mol. Imaging Biol. 14(4), 472–479 (2012).
[Crossref] [PubMed]

Toyama, H.

M. Ichise, J. S. Liow, J. Q. Lu, A. Takano, K. Model, H. Toyama, T. Suhara, K. Suzuki, R. B. Innis, and R. E. Carson, “Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain,” J. Cereb. Blood Flow Metab. 23(9), 1096–1112 (2003).
[Crossref] [PubMed]

Ullrich, A.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

van Engelshoven, J. M.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

van Genderen, M. H.

Q. G. de Lussanet, S. Langereis, R. G. Beets-Tan, M. H. van Genderen, A. W. Griffioen, J. M. van Engelshoven, and W. H. Backes, “Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice,” Radiology 235(1), 65–72 (2005).
[Crossref] [PubMed]

Votaw, J. R.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Wakasugi, H.

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Weissleder, R.

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[Crossref] [PubMed]

Wilson, B. C.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Wong, D. F.

R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S. C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, and R. E. Carson, “Consensus nomenclature for in vivo imaging of reversibly binding radioligands,” J. Cereb. Blood Flow Metab. 27(9), 1533–1539 (2007).
[Crossref] [PubMed]

Wu, J.

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review,” J. Control. Release 65(1-2), 271–284 (2000).
[Crossref] [PubMed]

Yang, C.

C. Yang, V. W. Hou, E. J. Girard, L. Y. Nelson, and E. J. Seibel, “Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging,” J. Biomed. Opt. 19(7), 076014 (2014).
[Crossref] [PubMed]

Yang, H. H.

K. M. Tichauer, K. S. Samkoe, K. J. Sexton, S. K. Hextrum, H. H. Yang, W. S. Klubben, J. R. Gunn, T. Hasan, and B. W. Pogue, “In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging,” Mol. Imaging Biol. 14(5), 584–592 (2012).
[Crossref] [PubMed]

Zhang, R.

Zhou, M.

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Austin J. Biomed. Eng. (1)

N. Hamzei, K. S. Samkoe, J. T. Elliott, R. W. Holt, J. R. Gunn, T. Y. Lee, T. Hasan, and B. W. Pogue, “Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors,” Austin J. Biomed. Eng. 1, 9 (2014).

Biochemistry (1)

M. Zhou, S. Felder, M. Rubinstein, D. R. Hurwitz, A. Ullrich, I. Lax, and J. Schlessinger, “Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation,” Biochemistry 32(32), 8193–8198 (1993).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Breast Cancer Res. (1)

K. Shirakawa, H. Kobayashi, J. Sobajima, D. Hashimoto, A. Shimizu, and H. Wakasugi, “Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model,” Breast Cancer Res. 5(3), 136–139 (2003).
[Crossref] [PubMed]

Cancer Metastasis Rev. (1)

R. K. Jain, “Vascular and interstitial barriers to delivery of therapeutic agents in tumors,” Cancer Metastasis Rev. 9(3), 253–266 (1990).
[Crossref] [PubMed]

IEEE Trans. Med. Imaging (1)

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24(10), 1377–1386 (2005).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

B. W. Pogue, K. S. Samkoe, S. Hextrum, J. A. O’Hara, M. Jermyn, S. Srinivasan, and T. Hasan, “Imaging targeted-agent binding in vivo with two probes,” J. Biomed. Opt. 15(3), 030513 (2010).
[Crossref] [PubMed]

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Figures (7)

Fig. 1
Fig. 1 In vivo dual-tracer compartment model for cell-surface receptors. ROIT(t) and ROIU(t) represent the measured uptake curves of the targeted and untargeted tracers, respectively, in any region of interest, as a function of time, t; ηT and ηU are the imaging system detection efficiencies for the targeted and untargeted tracers (see text for details); K1 and k2 are the rates of exchange of the tracers from the blood concentration (Cp) to the interstitial space (Cf,2 for the targeted tracer and Cf,1 for the untargeted tracer) and back, respectively; and k3 and k4 are the rates of association and dissociation of the targeted tracer to its receptor in a bound state (Cb), respectively. The fraction plasma volume in the tissue is represented by vp. The red circled fraction in the black bordered equation is the parameter attained by the pixel-by-pixel or reference tissue normalization approaches explored in this study. The BP, underlined in red, is known as the “binding potential” and is the key parameter of interest: it is equivalent to k3/k4 and proportional to the receptor concentration by the tracer affinity.
Fig. 2
Fig. 2 A gray-scale white light image of an exposed subcutaneous xenograph glioma tumor grown on the left flank of an athymic mouse is depicted in (a). Targeted and untargeted tracer uptakes at 2 min after tracer injection are presented in (b) and (c), respectively. The pixel-based normalization approach, wherein all untargeted tracer images are scaled by a normalization factor map that is determined by dividing, pixel-by-pixel, the uptake images of the targeted and untargeted tracers at 2-min post-injection, is depicted in (d). The reference tissue-based normalization approach, wherein all untargeted tracer images are scaled by a single normalization factor determined by the ratio of the uptakes of the targeted and untargeted tracers in a region devoid of receptor is depicted in (e).
Fig. 3
Fig. 3 a) Schematic of simulated measurement geometry. b) Absorption spectra for 2% blood volume at selected saturations and background absorption. c) Absorption (solid) and emission (dashed) spectra for dual tracers (i.e. IR700 and IR800). Vertical dashed lines in both panels represent integrated waveband for fluorescence intensity. d) Time-dependent concentrations of targeted and untargeted tracers for binding potential = 1.7.
Fig. 4
Fig. 4 a) IR700 emission spectra for various Sat (inset for IR800); b) Error in BP vs. Sat; c) Maximum error in BP vs. expected BP for various inclusion depths; d) Depth sensitivity for both tracers for BVF = 2% and Sat = 100%; e) Tracer depth mismatch vs. Sat; f) Mean sampling depth vs. inclusion depth. In b and e markers indicate BVF and colors indicate Sat.
Fig. 5
Fig. 5 a) Model geometry of a turbid medium containing two absorption inclusions (1) BVF = 25%, Sat = 50% and (2) BVF = 100%, Sat = 0%. b) and c) Show simulated fluorescence images with of IR700 and IR800 at 2 min, respectively. d) Shows the pixel-based normalization map. e) and f) Show simulated images of both tracers at 60 min. g) and h) Show binding potential maps for images in the presence of the absorption inclusions as estimated by both the reference tracer method and pixel-by-pixel normalization method, respectively.
Fig. 6
Fig. 6 Binding potential maps calculated using the reference tissue-based normalization (first column of images) and the pixel-based normalization approach (second column of images) are presented for 3 athymic mice with subcutaneous xenograph glioma tumors. The binding potential (BP) measured in each case within the tumor is displayed on the figure. For reference, the white-light image for Mouse 1 is depicted in Fig. 1(a). On the far right, the average targeted tracer uptake (red curve) in the tumor is presented along with the untargeted tracer uptake after normalization by the reference tissue-based approach (dotted green curve), and by the pixel-based approach (solid green curve).
Fig. 7
Fig. 7 Simulation study results to determine the optimal time-window in which to normalize targeted and untargeted tracer uptake curves to correct for optical property and detection efficiency mismatch between tracers. In (a), the various simulated targeted tracer uptake curves based on binding potentials (BP) between 0 and 5 are presented over 60 min. In (b), the same curves in (a) are re-plotted for just the first 10 min of uptake. The shaded regions demonstrate the ranges over which the 1-min (blue), 2-min (red), 5-min (green), and 10-min (purple) normalizations were carried out. The results of these normalizations and their affects on BP estimation are presented in (c) in the form of a Bland-Altman.

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