Abstract

We present a study of the dynamics of optical contrast agents indocyanine green (ICG) and methylene blue (MB) in an adenocarcinoma rat tumor model. Measurements are conducted with a combined frequency-domain and steady-state optical technique that facilitates rapid measurement of tissue absorption in the 650–1000-nm spectral region. Tumors were also imaged by use of contrast-enhanced magnetic resonance imaging (MRI) and coregistered with the location of the optical probe. The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin, and water are measured simultaneously each second for approximately 10 min. The differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise from differences in their effective molecular weights. ICG, because of its binding to plasma proteins, behaves as a macromolecular contrast agent with a low vascular permeability. A compartmental model describing ICG dynamics is used to quantify physiologic parameters related to capillary permeability. In contrast, MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the vasculature into the extravascular, extracellular space, and is sensitive to blood flow and the arterial input function.

© 2003 Optical Society of America

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  25. N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
    [CrossRef]
  26. M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
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  28. D. L. Buckley, “Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced T1-weighted MRI,” Magn. Reson. Med. 47, 601–606 (2002).
    [CrossRef] [PubMed]

2003

2002

M. K. Pugsley, V. Kalra, S. Froebel-Wilson, “Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle,” Life Sci. 72(3), 293–305 (2002).
[CrossRef]

D. L. Buckley, “Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced T1-weighted MRI,” Magn. Reson. Med. 47, 601–606 (2002).
[CrossRef] [PubMed]

2001

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

R. Springett, Y. Sakata, D. T. Delpy, “Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green,” Phys. Med. Biol. 46, 2209–2225 (2001).
[CrossRef] [PubMed]

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

2000

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

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

F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39, 6498–6507 (2000).
[CrossRef]

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

1999

N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
[CrossRef]

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

1998

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

1997

J. B. Fishkin, O. Coquoz, E. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Opt. 36, 10–20 (1997).
[CrossRef] [PubMed]

P. S. Tofts, “Modeling tracer kinetics in dynamic Gd-DTPA MR imaging,” J. Magn. Reson. Imag. 7, 91–101 (1997).
[CrossRef]

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

1996

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

1994

M. Y. Su, J. C. Jao, O. Nalcioglu, “Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI,” Magn. Reson. Med. 32, 714–724 (1994).
[CrossRef] [PubMed]

J. Fishbaugh, “Retina: indocyanine green (ICG) angiography,” Insight 19(3), 30–32 (1994).

1992

1987

R. K. Jain, “Transport of molecules across tumor vasculature,” Cancer Metastasis Rev. 6, 559–593 (1987).
[CrossRef] [PubMed]

1983

M. S. Yates, C. J. Bowmer, J. Emmerson, “The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration,” Biochem. Pharmacol. 32, 3109–3114 (1983).
[CrossRef] [PubMed]

1976

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

Aarnoudse, J. G.

Anderson, E.

Becker, A.

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Berger, A. J.

Bevilacqua, F.

Bornhop, D. J.

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

Bowmer, C. J.

M. S. Yates, C. J. Bowmer, J. Emmerson, “The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration,” Biochem. Pharmacol. 32, 3109–3114 (1983).
[CrossRef] [PubMed]

Brenner, M.

Buckley, D. L.

D. L. Buckley, “Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced T1-weighted MRI,” Magn. Reson. Med. 47, 601–606 (2002).
[CrossRef] [PubMed]

Carpenter, P. M.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

Cerussi, A. E.

Chance, B.

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

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Comet, M.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Contag, C. H.

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

Coquoz, O.

Cuccia, D. J.

de Mul, F. F. M.

de Vries, A.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Delpy, D. T.

R. Springett, Y. Sakata, D. T. Delpy, “Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green,” Phys. Med. Biol. 46, 2209–2225 (2001).
[CrossRef] [PubMed]

Diamond, K. R.

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

Durkin, A. J.

Emmerson, J.

M. S. Yates, C. J. Bowmer, J. Emmerson, “The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration,” Biochem. Pharmacol. 32, 3109–3114 (1983).
[CrossRef] [PubMed]

Essig, M.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Evelhoch, J. L.

N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
[CrossRef]

Fishbaugh, J.

J. Fishbaugh, “Retina: indocyanine green (ICG) angiography,” Insight 19(3), 30–32 (1994).

Fishkin, J. B.

Fritz-Hansen, T.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Froebel-Wilson, S.

M. K. Pugsley, V. Kalra, S. Froebel-Wilson, “Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle,” Life Sci. 72(3), 293–305 (2002).
[CrossRef]

Geddes, L. A.

L. A. Geddes, “Cardiac output measurement,” in The Biomedical Engineering Handbook (CRC Press, Boca Raton, Fla., 1995), pp. 1212–1213.

Geoffray, B.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Gneiting, T.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Graaff, R.

Greve, J.

Griebel, J.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Gulsen, G.

Gurfinkel, M.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Gust, J. D.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Hawighorst, H.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Hawrysz, D. J.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Hayward, J. E.

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

He, Z.

N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
[CrossRef]

Henriksen, O.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Holtz, J. Z.

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Island, T. C.

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Jacquot, C.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Jain, R. K.

R. K. Jain, “Transport of molecules across tumor vasculature,” Cancer Metastasis Rev. 6, 559–593 (1987).
[CrossRef] [PubMed]

Jakubowski, D.

Jakubowski, D. J.

D. J. Jakubowski, “Development of broadband quantitative tissue optical spectroscopy for the non-invasive characterization of breast disease,” (Beckman Laser Institute, University of California, Irvine, Irvine, Calif., 2002).

Jao, J. C.

M. Y. Su, J. C. Jao, O. Nalcioglu, “Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI,” Magn. Reson. Med. 32, 714–724 (1994).
[CrossRef] [PubMed]

Kalra, V.

M. K. Pugsley, V. Kalra, S. Froebel-Wilson, “Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle,” Life Sci. 72(3), 293–305 (2002).
[CrossRef]

Klavuhn, K. G.

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Knopp, M. V.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Koelink, H. M.

Kremser, C.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Kwant, G.

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

Lafond, J. L.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Landsman, M. L.

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

Lanning, R.

Lao, X.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

Larsson, H. B.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Law, E. J.

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Licha, K.

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Lukas, P. H.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Mayer, R. H.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Mayr, N. A.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Merritt, S.

Mook, G. A.

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

Moore, A. L.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Moore, T. A.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Muggenburg, B.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Muhler, A.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

Murphy, C. J.

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

Nalcioglu, O.

S. Merritt, F. Bevilacqua, A. J. Durkin, D. J. Cuccia, R. Lanning, B. J. Tromberg, G. Gulsen, H. Yu, J. Wang, O. Nalcioglu, “Monitoring tumor physiology using near-infrared spectroscopy and MRI coregistration,” Appl. Opt. 42, 2951–2959 (2003).
[CrossRef] [PubMed]

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

M. Y. Su, J. C. Jao, O. Nalcioglu, “Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI,” Magn. Reson. Med. 32, 714–724 (1994).
[CrossRef] [PubMed]

Nikula, K.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Ntziachristos, V.

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

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Pandey, R.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Patterson, M. S.

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

Payen, J. F.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Pugsley, M. K.

M. K. Pugsley, V. Kalra, S. Froebel-Wilson, “Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle,” Life Sci. 72(3), 293–305 (2002).
[CrossRef]

Ralston, W.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Reynolds, J. S.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Riefke, B.

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Ring, P.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Rostrup, E.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Sakata, Y.

R. Springett, Y. Sakata, D. T. Delpy, “Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green,” Phys. Med. Biol. 46, 2209–2225 (2001).
[CrossRef] [PubMed]

Schnall, M.

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

Semmler, W.

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Simpson, N. E.

N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
[CrossRef]

Sloot, P. M. A.

Sondergaard, L.

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Springett, R.

R. Springett, Y. Sakata, D. T. Delpy, “Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green,” Phys. Med. Biol. 46, 2209–2225 (2001).
[CrossRef] [PubMed]

Stieglitz, P.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Still, J. M.

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Su, M. Y.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

M. Y. Su, J. C. Jao, O. Nalcioglu, “Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI,” Magn. Reson. Med. 32, 714–724 (1994).
[CrossRef] [PubMed]

Tatman, D.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Thompson, A. B.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Tofts, P. S.

P. S. Tofts, “Modeling tracer kinetics in dynamic Gd-DTPA MR imaging,” J. Magn. Reson. Imag. 7, 91–101 (1997).
[CrossRef]

Tromberg, B. J.

Troy, T. L.

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

Vuillez, J. P.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Wang, J.

Wang, Z.

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

Weersink, R. A.

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

Yates, M. S.

M. S. Yates, C. J. Bowmer, J. Emmerson, “The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration,” Biochem. Pharmacol. 32, 3109–3114 (1983).
[CrossRef] [PubMed]

Yodh, A. G.

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

Yu, H.

Yuh, W. T.

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

Zijlstra, W. G.

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

Zijp, J. R.

Appl. Opt.

Biochem. Pharmacol.

M. S. Yates, C. J. Bowmer, J. Emmerson, “The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration,” Biochem. Pharmacol. 32, 3109–3114 (1983).
[CrossRef] [PubMed]

Burns

J. M. Still, E. J. Law, K. G. Klavuhn, T. C. Island, J. Z. Holtz, “Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial,” Burns 27, 364–371 (2001).
[CrossRef] [PubMed]

Cancer Metastasis Rev.

R. K. Jain, “Transport of molecules across tumor vasculature,” Cancer Metastasis Rev. 6, 559–593 (1987).
[CrossRef] [PubMed]

Crit. Care Med.

J. F. Payen, J. P. Vuillez, B. Geoffray, J. L. Lafond, M. Comet, P. Stieglitz, C. Jacquot, “Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid,” Crit. Care Med. 25, 243–248 (1997).
[CrossRef] [PubMed]

Insight

J. Fishbaugh, “Retina: indocyanine green (ICG) angiography,” Insight 19(3), 30–32 (1994).

J. Appl. Physiol.

M. L. Landsman, G. Kwant, G. A. Mook, W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575–583 (1976).
[PubMed]

J. Biomed. Opt.

D. J. Bornhop, C. H. Contag, K. Licha, C. J. Murphy, “Advance in contrast agents, reporters, and detection,” J. Biomed. Opt. 6, 106–110 (2001).
[CrossRef] [PubMed]

J. Magn. Reson. Imag.

P. S. Tofts, “Modeling tracer kinetics in dynamic Gd-DTPA MR imaging,” J. Magn. Reson. Imag. 7, 91–101 (1997).
[CrossRef]

J. Griebel, N. A. Mayr, A. de Vries, M. V. Knopp, T. Gneiting, C. Kremser, M. Essig, H. Hawighorst, P. H. Lukas, W. T. Yuh, “Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging,” J. Magn. Reson. Imag. 7(1), 111–119 (1997).
[CrossRef]

M. Y. Su, Z. Wang, P. M. Carpenter, X. Lao, A. Muhler, O. Nalcioglu, “Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents,” J. Magn. Reson. Imag. 9, 177–186 (1999).
[CrossRef]

Life Sci.

M. K. Pugsley, V. Kalra, S. Froebel-Wilson, “Protamine is a low molecular weight polycationic amine that produces actions on cardiac muscle,” Life Sci. 72(3), 293–305 (2002).
[CrossRef]

Magn. Reson. Med.

M. Y. Su, A. Muhler, X. Lao, O. Nalcioglu, “Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights,” Magn. Reson. Med. 39, 259–269 (1998).
[CrossRef] [PubMed]

N. E. Simpson, Z. He, J. L. Evelhoch, “Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods,” Magn. Reson. Med. 42(1), 42–52 (1999).
[CrossRef]

D. L. Buckley, “Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced T1-weighted MRI,” Magn. Reson. Med. 47, 601–606 (2002).
[CrossRef] [PubMed]

M. Y. Su, J. C. Jao, O. Nalcioglu, “Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI,” Magn. Reson. Med. 32, 714–724 (1994).
[CrossRef] [PubMed]

H. B. Larsson, T. Fritz-Hansen, E. Rostrup, L. Sondergaard, P. Ring, O. Henriksen, “Myocardial perfusion modeling using MRI,” Magn. Reson. Med. 35, 716–726 (1996).
[CrossRef] [PubMed]

Photochem. Photobiol.

R. A. Weersink, J. E. Hayward, K. R. Diamond, M. S. Patterson, “Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy,” Photochem. Photobiol. 66, 326–335 (1997).
[CrossRef] [PubMed]

M. Gurfinkel, A. B. Thompson, W. Ralston, T. L. Troy, A. L. Moore, T. A. Moore, J. D. Gust, D. Tatman, J. S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R. H. Mayer, D. J. Hawrysz, E. M. Sevick-Muraca, “Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study,” Photochem. Photobiol. 72, 94–102 (2000).
[CrossRef] [PubMed]

K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, “Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization,” Photochem. Photobiol. 72, 392–398 (2000).
[CrossRef] [PubMed]

Phys. Med. Biol.

R. Springett, Y. Sakata, D. T. Delpy, “Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green,” Phys. Med. Biol. 46, 2209–2225 (2001).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA

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

Other

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S. Prahl, “Tabulated molar extinction coefficient for methylene blue in water,” (1998), http://omlc.ogi.edu/spectra/mb/mb-water.html .

D. J. Jakubowski, “Development of broadband quantitative tissue optical spectroscopy for the non-invasive characterization of breast disease,” (Beckman Laser Institute, University of California, Irvine, Irvine, Calif., 2002).

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Figures (9)

Fig. 1
Fig. 1

SS-FDPM and MRI instrumentation diagram showing optical probe placement inside the animal coils of a 3.0-tesla magnet.

Fig. 2
Fig. 2

T2-weighted MR image of the optical probe placement on a rat tumor. Copper sulfate tubes mark the location of the fiber probe, allowing coregistration of optical and MR data.

Fig. 3
Fig. 3

(a) Preinjection frequency-domain absorption measurements (black bars), broadband absorption measurement (gray squares), and fit (black curve) versus wavelength. (b) Preinjection tissue scattering measurements (black bars) and broadband fit (black curve) versus wavelength.

Fig. 4
Fig. 4

(a) Pre- and postinjection absorption spectra of MB versus wavelength. (b) Pre- and postinjection absorption spectra of ICG versus wavelength.

Fig. 5
Fig. 5

(a) Absolute concentrations of Hb, HbO2, H2O, and contrast agent (ICG) versus time calculated with a least-squares fit to absorption coefficient as determined from the broadband component of SS-FDPM. The error bars have been removed for clarity but are typically 10%. Note that little coupling between the chromophores is observed. (b) Similar plots for MB. MB demonstrates a rapid wash-in wash-out behavior during the first pass through the circulation, whereas ICG shows a very slow tissue uptake and removal behavior.

Fig. 6
Fig. 6

(a) MRI Gd-DTPA enhancement map with MB peak information located above each region. (b) MB concentration during short times for quickly enhanced (solid curve) and slowly enhanced (dotted curve) regions of the tumor.

Fig. 7
Fig. 7

MB time dynamics for two different rats. The initial pulse shapes are similar, demonstrating the bolus pulse. However the MB in Rat 2 decays away, whereas that for Rat 3 begins to rise again, displaying behavior of hindered diffusion across the capillary membrane. Second, the peak concentration of Rat 3 is much smaller than that of Rat 2, supporting the idea of hindered diffusion.

Fig. 8
Fig. 8

Representation of the two-compartment pharmacokinetic model. v p and v e represent the plamas and EES compartments, respectively. kinPSρ and koutPSρ represent the leakage into and the drainage out of the EES, respectively. α1 and α2 are the exponents of the terms that describe the biexponential removal of ICG by metabolic processes.

Fig. 9
Fig. 9

Plot of ICG concentration versus time (points) and the corresponding pharmacokinetic fit (solid curve).

Tables (2)

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Table 1 Extracted Pharmacokinetic Parameters from ICG Curve Fitting

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Table 2 Qualitative Summary of Results from MRI, DOS, MB and ICG

Equations (5)

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dCedt=kinPSρCp-koutPSρCe,
Cpt=A1 exp-α1t+A2 exp-α2t.
Ct=vpCp+veCe.
Ctt=A1vp+vekinPSρkoutPSρ-α1exp-α1t+A2vp+vekinPSρkoutPSρ-α2exp-α2t-A1vekinPSρkoutPSρ-α1+A2vekinPSρkoutPSρ-α2exp-koutPSρt.
vp=HbTHbB100-HctHct2.415×10-4×HbTμM.

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