Abstract

A fast 3-D optical imaging method with use of exogenous fluorescence agent is proposed and demonstrated by simulation in a model tissue. After administration of fluorescent agent, ultrashort near-infrared laser pulses are used to illuminate the tissue and excite fluorescence emission. The transient fluorescence signals are detected on the tissue boundaries and employed to reconstruct a 3-D image of relative fluorescence emission distribution inside the tissue. A region with greater fluorescence emission represents a diseased tissue if the fluorescent agent has a close affinity with the disease. We successfully demonstrated the feasibility of this method in the imaging of a small cubic tumor embedded in a cubical tissue phantom with a preassigned uptake distribution of fluorescent indocyanine green dye. The image reconstruction does not involve any inverse optimization. It took less than 5 minutes in a general PC for the two model imaging problems.

© 2004 Optical Society of America

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  1. M. A. O’Leary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, “Fluorescence Lifetime Imaging in Turbid Media,” Opt. Lett. 21, 158–160 (1996).
    [CrossRef]
  2. V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
    [CrossRef] [PubMed]
  3. R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s Optimization Scheme for Absorption and Fluorescence Optical Tomography: Part 1 Theory and Formulation,” Opt. Express 4, 353–371 (1999).
    [CrossRef] [PubMed]
  4. A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
    [CrossRef] [PubMed]
  5. J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
    [CrossRef] [PubMed]
  6. J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
  9. Z. Guo and K.-H. Kim, “Ultrafast-Laser-Radiation Transfer in Heterogeneous Tissues With the Discrete-Ordinates Method,” Appl. Opt. 42, 2897–2905 (2003).
    [CrossRef] [PubMed]
  10. Z. Guo and S. Kumar, “Radiation Element Method for Transient Hyperbolic Radiative Transfer in Plane-Parallel Inhomogeneous Media,” Numerical Heat Transfer B 39, 371–387 (2001).
    [CrossRef]
  11. B. Valeur, Molecular Fluorescence: Principles and Applications (Wiley-VCH, Weinheim, New York, 2002).
  12. K. R. Castleman, Digital Image Processing (Prentice Hall, New Jersey, USA, 1996).
  13. S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
    [CrossRef]

2004 (1)

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

2003 (3)

2001 (2)

Z. Guo and S. Kumar, “Radiation Element Method for Transient Hyperbolic Radiative Transfer in Plane-Parallel Inhomogeneous Media,” Numerical Heat Transfer B 39, 371–387 (2001).
[CrossRef]

Z. Guo and S. Kumar, “Discrete Ordinates Solution of Short Pulse Laser Transport in Two-Dimensional Turbid Media,” Appl. Opt. 40, 3156–3163 (2001).
[CrossRef]

2000 (1)

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

1999 (1)

1997 (2)

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

1996 (1)

Aber, J.

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Barbour, R.L.

J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Boas, D. A.

Castleman, K. R.

K. R. Castleman, Digital Image Processing (Prentice Hall, New Jersey, USA, 1996).

Chance, B.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

M. A. O’Leary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, “Fluorescence Lifetime Imaging in Turbid Media,” Opt. Lett. 21, 158–160 (1996).
[CrossRef]

Chang, J.

J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Dasari, R. R.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

Eppstein, M. J.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Feld, M. S.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

Garetz, B. A.

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Godavarty, A.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Graber, H. L.

J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

Guo, Z.

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Z. Guo and K.-H. Kim, “Ultrafast-Laser-Radiation Transfer in Heterogeneous Tissues With the Discrete-Ordinates Method,” Appl. Opt. 42, 2897–2905 (2003).
[CrossRef] [PubMed]

Z. Guo and S. Kumar, “Discrete Ordinates Solution of Short Pulse Laser Transport in Two-Dimensional Turbid Media,” Appl. Opt. 40, 3156–3163 (2001).
[CrossRef]

Z. Guo and S. Kumar, “Radiation Element Method for Transient Hyperbolic Radiative Transfer in Plane-Parallel Inhomogeneous Media,” Numerical Heat Transfer B 39, 371–387 (2001).
[CrossRef]

Gurfinkel, M.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Hielscher, A. H.

Kim, K.-H.

Klose, A. D.

Kumar, S.

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Z. Guo and S. Kumar, “Radiation Element Method for Transient Hyperbolic Radiative Transfer in Plane-Parallel Inhomogeneous Media,” Numerical Heat Transfer B 39, 371–387 (2001).
[CrossRef]

Z. Guo and S. Kumar, “Discrete Ordinates Solution of Short Pulse Laser Transport in Two-Dimensional Turbid Media,” Appl. Opt. 40, 3156–3163 (2001).
[CrossRef]

Li, X. D.

Ntziachristos, V.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

O’Leary, M. A.

Perelman, L.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

Roy, R.

Schnall, M.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

R. Roy and E. M. Sevick-Muraca, “Truncated Newton’s Optimization Scheme for Absorption and Fluorescence Optical Tomography: Part 1 Theory and Formulation,” Opt. Express 4, 353–371 (1999).
[CrossRef] [PubMed]

Theru, S.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Thompson, A. B.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Valeur, B.

B. Valeur, Molecular Fluorescence: Principles and Applications (Wiley-VCH, Weinheim, New York, 2002).

Wan, S. K.

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Wu, J.

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

Yodh, A. G.

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

M. A. O’Leary, D. A. Boas, X. D. Li, B. Chance, and A. G. Yodh, “Fluorescence Lifetime Imaging in Turbid Media,” Opt. Lett. 21, 158–160 (1996).
[CrossRef]

Zhang, C.

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Appl. Opt. (2)

IEEE Trans. Biomed. Eng. (1)

J. Chang, H. L. Graber, and R.L. Barbour, “Imaging of Fluorescence in Highly Scattering Media,” IEEE Trans. Biomed. Eng. 44, 810–822 (1997).
[CrossRef] [PubMed]

JQSRT (1)

S. K. Wan, Z. Guo, S. Kumar, J. Aber, and B. A. Garetz, “Noninvasive Detection of Inhomogeneities in Turbid Media with Time-Resolved Log-Slope Analysis,” JQSRT 84, 493–500 (2004).
[CrossRef]

Numerical Heat Transfer B (1)

Z. Guo and S. Kumar, “Radiation Element Method for Transient Hyperbolic Radiative Transfer in Plane-Parallel Inhomogeneous Media,” Numerical Heat Transfer B 39, 371–387 (2001).
[CrossRef]

Opt. Express (1)

Opt. Lett. (2)

Phys. Med. Biol. (1)

A. Godavarty, M. J. Eppstein, C. Zhang, S. Theru, A. B. Thompson, M. Gurfinkel, and E. M. Sevick-Muraca, “Fluorescence-Enhanced Optical Imaging in Large Tissue Volumes Using a Gain-Modulated ICCD Camera,” Phys. Med. Biol. 48, 1701–1720 (2003).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA (2)

J. Wu, L. Perelman, R. R. Dasari, and M. S. Feld, “Fluorescence Tomographic Imaging in Turbid Media Using Early-Arriving Photons and Laplace Transforms,” Proc. Natl. Acad. Sci. USA 94, 8783–8788 (1997).
[CrossRef] [PubMed]

V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and Diffuse Optical Tomography of Breast After Indocyanine Green Enhancement,” Proc. Natl. Acad. Sci. USA 97, 2767–2772 (2000).
[CrossRef] [PubMed]

Other (2)

B. Valeur, Molecular Fluorescence: Principles and Applications (Wiley-VCH, Weinheim, New York, 2002).

K. R. Castleman, Digital Image Processing (Prentice Hall, New Jersey, USA, 1996).

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Figures (6)

Fig. 1.
Fig. 1.

Sketch of a model imaging system.

Fig. 2.
Fig. 2.

A representative fluorescence signal.

Fig. 3.
Fig. 3.

Reconstructed 3-D tumor image.

Fig. 4.
Fig. 4.

Projections of the 3-D tumor image: (a) on the Y-Z plane, (b) on the X-Z plane, (c) on the X-Y plane.

Fig 5.
Fig 5.

Tomographic images: (a) along the X-direction, (b) along the Y-direction, (c) along the Z-direction.

Fig. 6.
Fig. 6.

Reconstructed 3-D image for a small tumor embedded at off-center of the tissue.

Equations (14)

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

1 c I 1 l t + ξ l I 1 l X + η l I 1 l Y + μ l I 1 l Z + σ e 1 I 1 l = σ e 1 ( S 1 l + S c l )
1 c I 2 l t + ξ l I 2 l X + η l I 2 l Y + μ l I 2 l Z + σ e 2 I 2 l = σ e 2 ( S 2 l + S F l )
S j l = ω j 4 π i = 1 n w j i Φ i l ( s i s l ) I j i , j = 1 , 2
S c l = ω 1 4 π I 0 [ X = 0 , Y , Z , t X ( c ξ c ) ] · exp ( σ e X ξ c ) · δ ( ξ c 1 ) · Φ cl
S F l = ω 2 4 π v 2 v 1 α F σ a 1 τ 0 t C v C v 0 e ( t t ) τ i = 1 n w i I 1 i ( t ) d t
T i , j , k C = T i , j , k T 0 2 , T m i , j , k C = T m i , j , k T m 0 2
P ( T i , j , k ) = 1 2 π σ exp [ ( T i , j , k T m i , j , k C ) 2 2 σ 2 ]
σ = ( T m i , j , k C T i , j , k C ) 2 ln 2 .
T i , j , k F = T m i , j , k C 2 σ 2 ln ( 2 π σ P ) .
R i , j , k = c T i , j , k F .
( X D i ) 2 + ( Y D j ) 2 + ( Z D k ) 2 = R i , j , k 2
Z = V k 1 = D k + R i , j , k 2 ( V i D i ) 2 ( V j D j ) 2 ,
or Z = V k 2 = D k R i , j , k 2 ( V i D i ) 2 ( V j D j ) 2 .
E ( V i , V j , V k ) = { i = 1 N k = 1 K [ I D ( D i , D 1 , D k ; V i , V j , V k ) + I D ( D i , D M , D k ; V i , V j , V k ) ] + j = 1 M k = 1 K [ I D ( D 1 , D j , D k ; V i , V j , V k ) + I D ( D N , D j , D k ; V i , V j , V k ) ] } { i = 1 N k = 1 K [ I max ( D i , D 1 , D k ) + I max ( D i , D M , D k ) ] + j = 1 M k = 1 K [ I max ( D 1 , D j , D k ) + I max ( D N , D j , D k ) ] }

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