Abstract

We present a novel procedure for localizing fluorescing-tagged objects embedded in turbid slab media from fluorescent intensity profiles acquired along a surface of interest. Using a numerical model based on a finite element code, we firstly develop a method devoted to lateral detection by varying the laser source position along one face of the tissue slab. Next, we mainly demonstrate the possibility to accurately assess the depth location by alternately changing the position of the source and the detector at the both sides of the slab. The dimensionless depth indicator derived from this procedure remains independent, over a wide range, on both the optical properties of the host tissue and the probe concentration. The overall findings validate the method in situations involving moderate size object-like tumors tagged with a new smart contrast agent (Cy 5.5) that offers high tumor-to-background contrast and great interest in early cancer diagnostic.

© 2006 Optical Society of America

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2006 (3)

X. Deulin and J. P. L’Huillier, "Finite element approach to photon propagation modelling in semi-infinite homogeneous and multilayered tissue structures," Eur. Phys. J. Appl. Phys. 33, 133 - 146 (2006).
[CrossRef]

A. M. Zysk, E. J. Chaney and S. A. Boppart, "Refractive index of carcinogen-induced rat mammary tumours, Phys. Med. Biol. 51, 2165-2177 (2006).
[CrossRef] [PubMed]

B. Yuan and Q. Zhu, "Separately reconstructing the structural and functional parameters of a fluorescent inclusion embedded in a turbid medium," Opt. Express 14, 7172-7187 (2006).
[CrossRef]

2005 (7)

2004 (5)

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

M. Pfister and B. Scholz, "Localization of fluorescent spots with space-space MUSIC for mammography-like measurements system," J. Biomed. Opt. 9, 481-487 (2004).
[CrossRef] [PubMed]

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

S. Achilefu, "Lighting up tumors with receptor-specific optical molecular probes," Technol. Cancer Res. Treat. 3, 393-409 (2004)
[PubMed]

H. Quan and Z. Guo, "Fast 3-D optical imaging with transient fluorescence signals" Opt. Express 12, 449-457 (2004).
[CrossRef] [PubMed]

2003 (3)

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

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

V. Ntziachristos, C. Bremer, and R. Weissleder, "Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging," Eur. Radiol. 13, 195-208 (2003).
[PubMed]

2002 (3)

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, and R. Weissleder, "Would near infrared fluorescence signals propagate through large human organs for clinical studies?" Opt. Lett. 27, 333-335 (2002).
[CrossRef]

2001 (3)

1998 (3)

K. A. Kang, D. F. Bruley, J. M. Londono, and B. Chance, "Localization of a fluorescent object in highly scattering media via frequency response analysis of near infrared-time resolved spectroscopy spectra," Ann. Biomed. Eng. 26, 138-145 (1998).
[CrossRef]

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

E. L. Hull, M. G. Nichols and T. H. Foster, "Localization of luminescent inhomogeneities in turbid media with spatially resolved measurement of cw diffuse luminescence emittance," Appl. Opt. 37, 2755-2765 (1998).
[CrossRef]

1997 (1)

1996 (1)

H. Heusmann, J. Kölzer and G. Mitic, "Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy," J. Biomed. Opt. 1, 425-434 (1996).
[CrossRef]

1995 (2)

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

J. Wu, Y. Wang, L. Perelman, I. Itzkan, R. R. Dasari and M. S. Feld, "Three-dimensional imaging of objects embedded in turbid media with fluorescence and Raman spectroscopy," Appl. Opt. 34, 3425-3430 (1995).
[CrossRef] [PubMed]

1994 (2)

M. S. Patterson and B. W. Pogue, "Mathematical models for time-resolved and frequency domain fluorescence spectroscopy in biological tissues," Appl. Opt. 33, 1963 - 1974 (1994).
[CrossRef] [PubMed]

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

1992 (1)

T. J. Farrell, M. S. Patterson and B. C. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[CrossRef] [PubMed]

1989 (1)

Achilefu, S.

Andersson-Engels, S.

Arridge, S. R.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffusive optical imaging," Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

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

Bengtsson, D.

Bloch, S. R.

Boas, D. A.

Bolin, F. P.

Bonner, R. F.

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Boppart, S. A.

A. M. Zysk, E. J. Chaney and S. A. Boppart, "Refractive index of carcinogen-induced rat mammary tumours, Phys. Med. Biol. 51, 2165-2177 (2006).
[CrossRef] [PubMed]

Bouman, C. A.

Bremer, C.

V. Ntziachristos, C. Bremer, and R. Weissleder, "Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging," Eur. Radiol. 13, 195-208 (2003).
[PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

Bruley, D. F.

K. A. Kang, D. F. Bruley, J. M. Londono, and B. Chance, "Localization of a fluorescent object in highly scattering media via frequency response analysis of near infrared-time resolved spectroscopy spectra," Ann. Biomed. Eng. 26, 138-145 (1998).
[CrossRef]

Buchner, A.

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

Chance, B.

Chaney, E. J.

A. M. Zysk, E. J. Chaney and S. A. Boppart, "Refractive index of carcinogen-induced rat mammary tumours, Phys. Med. Biol. 51, 2165-2177 (2006).
[CrossRef] [PubMed]

Chernomordik, V.

Comelli, D.

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

Cubeddu, R.

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Culver, J. P.

D’Andrea, C.

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

Danesini, G. M.

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Dasari, R. R.

Delpy, D. T.

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

Deulin, X.

X. Deulin and J. P. L’Huillier, "Finite element approach to photon propagation modelling in semi-infinite homogeneous and multilayered tissue structures," Eur. Phys. J. Appl. Phys. 33, 133 - 146 (2006).
[CrossRef]

Eppstein, M. J.

A. Godavarty, M. J. Eppstein, C. Zhang, E. M. Sevick-Muraca, "Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

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

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

Farrell, T. J.

T. J. Farrell, M. S. Patterson and B. C. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[CrossRef] [PubMed]

Feld, M. S.

Feng, T. C.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Ference, R. J.

Foster, T. H.

Fox, P. C.

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Gandjbakhche, A.

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

Gandjbakhche, A. H.

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Gannot, G.

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Gannot, I.

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Garashi, A.

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

Gibson, A. P.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffusive optical imaging," Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

Godavarty, A.

A. Godavarty, M. J. Eppstein, C. Zhang, E. M. Sevick-Muraca, "Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

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

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

Guo, Z.

Gurfinkel, M.

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

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

Haskell, R. C.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Hebden, J. C.

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffusive optical imaging," Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

Heusmann, H.

H. Heusmann, J. Kölzer and G. Mitic, "Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy," J. Biomed. Opt. 1, 425-434 (1996).
[CrossRef]

Hiroaka, M.

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

Holboke, M. J.

Hull, E. L.

Intes, X.

Itzkan, I.

Kang, K. A.

K. A. Kang, D. F. Bruley, J. M. Londono, and B. Chance, "Localization of a fluorescent object in highly scattering media via frequency response analysis of near infrared-time resolved spectroscopy spectra," Ann. Biomed. Eng. 26, 138-145 (1998).
[CrossRef]

Keisari, Y.

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

Kennedy, M. D.

Kölzer, J.

H. Heusmann, J. Kölzer and G. Mitic, "Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy," J. Biomed. Opt. 1, 425-434 (1996).
[CrossRef]

Kumar, S.

M. Sadoqi, P. Riseborough and S. Kumar, "Analytical models for time-resolved fluorescence spectroscopy in tissues," Phys. Med. Biol. 46, 2725 - 2743 (2001).
[CrossRef] [PubMed]

L’Huillier, J. P.

X. Deulin and J. P. L’Huillier, "Finite element approach to photon propagation modelling in semi-infinite homogeneous and multilayered tissue structures," Eur. Phys. J. Appl. Phys. 33, 133 - 146 (2006).
[CrossRef]

Londono, J. M.

K. A. Kang, D. F. Bruley, J. M. Londono, and B. Chance, "Localization of a fluorescent object in highly scattering media via frequency response analysis of near infrared-time resolved spectroscopy spectra," Ann. Biomed. Eng. 26, 138-145 (1998).
[CrossRef]

Low, P. S.

McAdams, M. S.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Milstein, A. B.

Mitic, G.

H. Heusmann, J. Kölzer and G. Mitic, "Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy," J. Biomed. Opt. 1, 425-434 (1996).
[CrossRef]

Nichols, M. G.

Ntziachristos, V.

V. Ntziachristos, C. Bremer, and R. Weissleder, "Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging," Eur. Radiol. 13, 195-208 (2003).
[PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, and R. Weissleder, "Would near infrared fluorescence signals propagate through large human organs for clinical studies?" Opt. Lett. 27, 333-335 (2002).
[CrossRef]

V. Ntziachristos and R. Weissleder, "Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation," Opt. Lett. 26, 893-895 (2001).
[CrossRef]

O’Leary, M. A.

Patterson, M. S.

M. S. Patterson and B. W. Pogue, "Mathematical models for time-resolved and frequency domain fluorescence spectroscopy in biological tissues," Appl. Opt. 33, 1963 - 1974 (1994).
[CrossRef] [PubMed]

T. J. Farrell, M. S. Patterson and B. C. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[CrossRef] [PubMed]

Patwardhan, S. V.

Perelman, L.

Pfister, M.

M. Pfister and B. Scholz, "Localization of fluorescent spots with space-space MUSIC for mammography-like measurements system," J. Biomed. Opt. 9, 481-487 (2004).
[CrossRef] [PubMed]

Pifferi, A.

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Pogue, B. W.

Preuss, L. E.

Quan, H.

Ripoll, J.

Riseborough, P.

M. Sadoqi, P. Riseborough and S. Kumar, "Analytical models for time-resolved fluorescence spectroscopy in tissues," Phys. Med. Biol. 46, 2725 - 2743 (2001).
[CrossRef] [PubMed]

Roy, R.

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

Sadoqi, M.

M. Sadoqi, P. Riseborough and S. Kumar, "Analytical models for time-resolved fluorescence spectroscopy in tissues," Phys. Med. Biol. 46, 2725 - 2743 (2001).
[CrossRef] [PubMed]

Scholz, B.

M. Pfister and B. Scholz, "Localization of fluorescent spots with space-space MUSIC for mammography-like measurements system," J. Biomed. Opt. 9, 481-487 (2004).
[CrossRef] [PubMed]

Schweiger, M.

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

Sevick-Muraca, E. M.

A. Godavarty, M. J. Eppstein, C. Zhang, E. M. Sevick-Muraca, "Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

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

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

Smith, P. D.

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Spinelli, L.

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Svaasand, L. O.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Svensson, J.

Swartling, J.

Taroni, P.

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Taylor, R. C.

Terike, K.

Theru, S.

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

Thompson, A. B.

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

Thomson, A. B.

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

Toricelli, A.

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

Tromberg, B. J.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Tsay, T. T.

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Tung, C. H.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

Valentini, G.

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

Wang, Y.

Webb, K. J.

Weissleder, R.

V. Ntziachristos, C. Bremer, and R. Weissleder, "Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging," Eur. Radiol. 13, 195-208 (2003).
[PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, and R. Weissleder, "Would near infrared fluorescence signals propagate through large human organs for clinical studies?" Opt. Lett. 27, 333-335 (2002).
[CrossRef]

V. Ntziachristos and R. Weissleder, "Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation," Opt. Lett. 26, 893-895 (2001).
[CrossRef]

Wilson, B. C.

T. J. Farrell, M. S. Patterson and B. C. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[CrossRef] [PubMed]

Wu, J.

Yodh, A. G.

Yuan, B.

Zhang, C.

A. Godavarty, M. J. Eppstein, C. Zhang, E. M. Sevick-Muraca, "Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

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

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

Zhu, Q.

Zysk, A. M.

A. M. Zysk, E. J. Chaney and S. A. Boppart, "Refractive index of carcinogen-induced rat mammary tumours, Phys. Med. Biol. 51, 2165-2177 (2006).
[CrossRef] [PubMed]

Ann. Biomed. Eng. (1)

K. A. Kang, D. F. Bruley, J. M. Londono, and B. Chance, "Localization of a fluorescent object in highly scattering media via frequency response analysis of near infrared-time resolved spectroscopy spectra," Ann. Biomed. Eng. 26, 138-145 (1998).
[CrossRef]

Appl. Opt. (8)

F. P. Bolin, L. E. Preuss, R. C. Taylor, and R. J. Ference, "Refractive index of some mammalian tissues using a fiber optic cladding method," Appl. Opt. 28, 2297-2303 (1989).
[CrossRef] [PubMed]

M. S. Patterson and B. W. Pogue, "Mathematical models for time-resolved and frequency domain fluorescence spectroscopy in biological tissues," Appl. Opt. 33, 1963 - 1974 (1994).
[CrossRef] [PubMed]

J. Wu, Y. Wang, L. Perelman, I. Itzkan, R. R. Dasari and M. S. Feld, "Three-dimensional imaging of objects embedded in turbid media with fluorescence and Raman spectroscopy," Appl. Opt. 34, 3425-3430 (1995).
[CrossRef] [PubMed]

D. A. Boas, M. A. O’Leary, B. Chance, and A. G. Yodh, "Detection and characterization of optical inhomogeneities with diffuse photon density waves: a signal-to-noise analysis," Appl. Opt. 36, 75-92 (1997).
[CrossRef] [PubMed]

E. L. Hull, M. G. Nichols and T. H. Foster, "Localization of luminescent inhomogeneities in turbid media with spatially resolved measurement of cw diffuse luminescence emittance," Appl. Opt. 37, 2755-2765 (1998).
[CrossRef]

I. Gannot, A. Garashi, G. Gannot, V. Chernomordik, and A. Gandjbakhche, "In vivo quantitative three dimensional localization of tumor labelled with exogenous specific fluorescence markers," Appl. Opt. 42, 3073-3080 (2003).
[CrossRef] [PubMed]

J. Swartling, J. Svensson, D. Bengtsson, K. Terike, and S. Andersson-Engels, "Fluorescence spectra provide information on the depth of fluorescent lesions in tissues," Appl. Opt. 44,1934-1941 (2005).
[CrossRef] [PubMed]

A. B. Milstein, M. D. Kennedy, P. S. Low, C. A. Bouman and K. J. Webb, "Statistical approach for detection and localization of a fluorescing mouse tumor in intralipid," Appl. Opt. 44, 2300-2310 (2005).
[CrossRef] [PubMed]

Eur. Phys. J. Appl. Phys. (1)

X. Deulin and J. P. L’Huillier, "Finite element approach to photon propagation modelling in semi-infinite homogeneous and multilayered tissue structures," Eur. Phys. J. Appl. Phys. 33, 133 - 146 (2006).
[CrossRef]

Eur. Radiol. (1)

V. Ntziachristos, C. Bremer, and R. Weissleder, "Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging," Eur. Radiol. 13, 195-208 (2003).
[PubMed]

J. Biomed. Opt. (5)

L. Spinelli, A. Toricelli, A. Pifferi, P. Taroni, G. M. Danesini, and R. Cubeddu, "Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography," J. Biomed. Opt. 9, 1137-1142 (2004).
[CrossRef] [PubMed]

H. Heusmann, J. Kölzer and G. Mitic, "Characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy," J. Biomed. Opt. 1, 425-434 (1996).
[CrossRef]

I. Gannot, G. Gannot, A. Garashi, A. Gandjbakhche, A. Buchner and Y. Keisari, "Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers," J. Biomed. Opt. 7, 14-19 (2002).
[CrossRef] [PubMed]

M. Pfister and B. Scholz, "Localization of fluorescent spots with space-space MUSIC for mammography-like measurements system," J. Biomed. Opt. 9, 481-487 (2004).
[CrossRef] [PubMed]

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

J. Opt. Soc. Am. A. (1)

R. C. Haskell, L. O. Svaasand, T. T. Tsay, T. C. Feng, M. S. McAdams and B. J. Tromberg, "Boundary conditions for the diffusion equation in radiative transfer," J. Opt. Soc. Am. A. 11, 2727-2741 (1994).
[CrossRef]

Med. Phys. (3)

T. J. Farrell, M. S. Patterson and B. C. Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties in vivo," Med. Phys. 19, 879-888 (1992).
[CrossRef] [PubMed]

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

I. Gannot, R. F. Bonner, G. Gannot, P. C. Fox, P. D. Smith and A. H. Gandjbakhche, "Optical simulations of a non-invasive technique for the diagnosis of diseased salivary glands in situ,"Med. Phys. 25, 1139-1144 (1998).
[CrossRef] [PubMed]

Nature Med. (1)

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, "Fluorescence mediated tomographic imaging system," Nature Med. 8, 757-760 (2002).
[CrossRef] [PubMed]

Opt. Express (5)

Opt. Lett. (2)

Phys. Med. Biol. (5)

A. P. Gibson, J. C. Hebden, and S. R. Arridge, "Recent advances in diffusive optical imaging," Phys. Med. Biol. 50, R1-R43 (2005).
[CrossRef] [PubMed]

M. Sadoqi, P. Riseborough and S. Kumar, "Analytical models for time-resolved fluorescence spectroscopy in tissues," Phys. Med. Biol. 46, 2725 - 2743 (2001).
[CrossRef] [PubMed]

C. D’Andrea, L. Spinelli, D. Comelli, G. Valentini and R. Cubeddu, "Localization and quantification of fluorescent inclusions embedded in a turbid medium," Phys. Med. Biol. 50, 2313-2327 (2005).
[CrossRef] [PubMed]

A. M. Zysk, E. J. Chaney and S. A. Boppart, "Refractive index of carcinogen-induced rat mammary tumours, Phys. Med. Biol. 51, 2165-2177 (2006).
[CrossRef] [PubMed]

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

Radiology (1)

A. Godavarty, M. J. Eppstein, C. Zhang, E. M. Sevick-Muraca, "Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study," Radiology 235, 148-154 (2005).
[CrossRef] [PubMed]

Technol. Cancer Res. Treat. (1)

S. Achilefu, "Lighting up tumors with receptor-specific optical molecular probes," Technol. Cancer Res. Treat. 3, 393-409 (2004)
[PubMed]

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FlexPDE , "A Flexible Solution System for Partial Differential Equations," PDE Inc.

A. E. Cerrusi, S. Fantini, J. S. Maier, W. W. Mantulin and E. Gratton, "Chromophore detection by fluorescence spectroscopy in tissue-like phantoms," in Optical Tomography and Spectroscopy of Tissue: Theory, Instrumentation, Model, and Human Studies II, B. Chance, R. R. Alfano, eds., Proc. SPIE 2979, 139-150 (1997).
[CrossRef]

G. G. Guilbault, "Practical Fluorescence," (Marcel Dekker, Inc., New-York 1973).

M. Born and E. Wolf, "Principles of Optics," (MacMillan, N.Y., 1964).

D. S. Burnett, "Finite Element Analysis. from concepts to applications," (Addison-Wesley, 1987).

E. M. Sevick-Muraca, E. Kuwana, A. Godavarty, J. P. Houston, A. B. Thomson, and R. Roy, Near-infrared fluorescence imaging and spectroscopy in random media and tissues, in Biomedical photonics handbook, T. Vo Dinh ed., (CRC Press, 2003).

T. H. Foster, E. L. Hull, M. G. Nichols, D. S. Rifkin and N. Schwartz, "Two steady-state methods for localizing a fluorescent inhomogeneity in a turbid medium," in Optical Tomography and spectroscopy of Tissue :Theory, Instrumentation, Model, and Human studies II, B. Chance and R. R. Alfano, eds., Proc. SPIE 2979, 741-749 (1997).
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J. P. L’Huillier and A. Humeau, "A computationally efficient model for simulating time-resolved fluorescence spectroscopy of thick biological tissues, in Photon Management, F. Wyrowski, ed., Proc. SPIE 5456, 1-10 (2004).
[CrossRef]

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Figures (9)

Fig. 1.
Fig. 1.

Sketch of the photon propagation in a turbid slab medium with a fluorescent object and geometry of the system under investigation with L=100mm and d=40mm or 60mm. The fluorescing-tagged object was positioned at L/2, but displaced along z at different depths Zt. At each source location Y0, a fluorescence intensity profile can be computed and used to assess the localization of the object. The numbers 1, 1′, 2 and 2′ refer to the segments along which the boundary conditions were applied.

Fig. 2.
Fig. 2.

Principle of the lateral detection of a fluorophore probe (rt=3 mm, Zt=20 mm, C=1µM) by varying the position of the laser source over the top of a tissue slab surface, and probing. the fluorescence intensity profile at the opposite side. The optical parameters used for the simulations are the following: µax =µam= =0.015 mm-1, µ′sx =µ′sm =0.8 mm-1, µfx =µfm =0 for the scattering slab of thickness d=40 mm, and µfx =0.023 mm-1, µfm =0.0115 mm-1 for the inclusion (rt=3 mm)

Fig. 3.
Fig. 3.

Dependence of the on-axis maximum fluorescence signal detected at the surface of the slab on the fluorophore concentration for three different locations of the inclusion (Zt=5, 20 and 35 mm): (a) reflectance mode, (b) transmittance mode. The different simulations refer to µax =µam =0.003 mm-1, µ′sx =µ′sm =1 mm-1, µfx =µfm =0 for the scattering slab of thickness d=40 mm, while µfx =2 µfm was varied in the inclusion of radius rt=3 mm, from 0 (C=0 µM) to 0.23 mm-1 (C=10 µM).

Fig. 4.
Fig. 4.

Contour plots y-z of fluorescence photon flux density at emission wavelength. The computations refer to the same parameters as those used in Fig. 3 except that the fluorophore concentration in the inclusion was fixed at (a) 0.1 µM, (b) 1 µM, and (c) 10 µM, respectively.

Fig. 5.
Fig. 5.

Examples of simulated transmittance measurement of a fluorescing-tagged object of various radii rt and located at different depths Zt inside a turbid slab medium of thickness d=40 mm, (a) plot of normalized scan intensity profiles for a small object of radius rt=1 mm located at four different depths Zt=2, 20, 30 and 36 mm, (b) plot of normalized scan intensity profiles for five different sized objects rt=1, 3, 5, 6, and 10 mm located at Zt=20 mm. The simulations are based on the same optical parameters as those used in Fig. 2.

Fig. 6.
Fig. 6.

Contour plot y-z of fluorescence photon flux density at emission wavelength, for two different sized objects containing 1µM of ICG and embedded in the middle plane of a turbid slab medium of thickness d=40 mm. (a) radius rt=2 mm, (b) rt=6 mm.

Fig. 7.
Fig. 7.

(a). Plot of the depth indicator Fw (Zt) against depth location Zt, for a fluorescent object of radius 3 mm embedded in turbid slab media having different optical properties: -µax =µam =0.015 mm-1, µs x,m=0.8 mm-1 and 1.6 mm-1, -µax =µam =0.0015 mm-1, µs x,m=0.8 mm-1. (b) Plot of the depth indicator Fw (Zt) against depth location Zt, for three different sized objects (rt=1, 3 and 5mm) embedded in a turbid slab medium with µax =µam =0.015 mm-1, and µs x,m=0.8 mm-1. In both cases the fluorophore concentration inside the object is equal to 1µM.

Fig. 8.
Fig. 8.

Plot of the dimensionless indicator Fw(β) against the dimensionless depth β=Zt/d for a probe of radius 3mm containing various concentrations of markers and embedded inside a turbid slab of different thicknesses. (a) ICG/C=0.1µM, 1µM, and 3µM, Cy5.5/C=0.1µM, d=40mm. (b) Cy5.5/0.1µM, d=40mm and 60mm.

Fig. 9.
Fig. 9.

Plot of the dimensionless indicator Fw(β) against the dimensionless depth β=Zt/d for a probe of radius rt=3mm embedded inside a turbid slab of thickness d=40mm with three typical concentration contrasts equal to 1:0, 1:0.01 and 1:0.005.

Equations (10)

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. ( D x Φ x ( y , z ) ) + k x Φ x ( y , z ) = q x ( y , z )
. ( D m Φ m ( y , z ) ) + k m Φ m ( y , z ) = q m ( y , z )
q m ( y , z ) = ϕ μ fx Φ x ( y , z )
q x ( y 0 , z ) = μ sx L 0 e μ tx z ( 1 + g μ tx μ trx )
Φ m ( ξ ) + 2 A . n ̂ . D m . Φ m ( ξ ) = 0
A = 1 + R eff 1 R eff
Φ x ( ξ ) + 2 A . n ̂ . D x . Φ x ( ξ ) = g μ sx μ trx L 0
J m ( R ) ( y , z ) = D m Φ m ( y , z ) | z = 0
J m ( T ) ( y , z ) = D m Φ m ( y , z ) | z = d
F W ( Z t ) = FWHM ( Z t ) FWHM ( d Z t ) FWHM ( Z t ) + FWHM ( d Z t )

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