Abstract

We describe a method that combines fluorescence molecular tomography (FMT) with diffuse optical tomography (DOT), which allows us to study the impact of heterogeneous optical property distribution on FMT, an issue that has not been systemically studied. Both numerical simulations and phantom experiments were performed based on our finite-element reconstruction algorithms. The experiments were conducted using a noncontact optical fiber free, multiangle transmission system. In both the simulations and experiments, a fluorescent target was embedded in an optically heterogeneous background medium. The simulation results clearly suggest the necessity of considering the absorption coefficient (μa) and reduced scattering coefficient (μs) distributions for quantitatively accurate FMT, especially in terms of the accuracy of reconstructed fluorophore absorption coefficient (μaxm). Subsequent phantom experiments with an indocyanine green (ICG)-containing target confirm the simulation findings. In addition, we performed a series of phantom experiments with low ICG concentration (0.1, 0.2, 0.4, 0.6 and 1.0μM) in the target to systematically evaluate the quantitative accuracy of our FMT approach. The results indicate that, with the knowledge of optical property distribution, the accuracy of the recovered fluorophore concentration is improved significantly over that without such a priori information. In particular absolute value of μaxm from our DOT guided FMT are quantitatively consistent with that obtained using spectroscopic methods.

© 2008 Optical Society of America

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  1. J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Imaging of spontaneous canine mammary tumors using fluorescent contrast agents,” Photochem. Photobiol. 70, 87-94(1999).
  2. V. Ntziachristos, T. Jacks, R. Weissleder, J. Grimm, D. G. Kirsch, S. D. Windsor, C. F. Bender Kim, and P. M. Santiago, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. U.S.A. 102, 14404-14409 (2005).
  3. A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grotzinger, “Receptor targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327-331 (2001).
    [CrossRef]
  4. X. Montet, J. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242, 751-758 (2007).
    [CrossRef]
  5. H. Jiang, “Frequency-domain fluorescent diffusion tomography: a finite-element-based algorithm and simulations,” Appl. Opt. 37, 5337-5343 (1998).
  6. A. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall, and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Opt. Express 15, 6696-6716 (2007).
    [CrossRef]
  7. M. S. Patterson and B. W. Pogue, “Mathematical model for time-resolved and frequency-domain fluorescence spectroscopy in biological tissues,” Appl. Opt. 33, 1963-1974 (1994).
  8. E. M. Sevick-Muraca, G. Lopez, J. S. Reynolds, T. L. Troy, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency domain techniques,” Photochem. Photobiol. 66, 55-64 (1997).
    [CrossRef]
  9. V. Ntziachristos, A. H. Hielscher, A. G. Yodh, and B. Chance, “Diffuse optical tomography of highly heterogeneous media,” IEEE Trans. Med. Imaging 20, 470-478 (2001).
  10. 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]
  11. R. Roy, A. Godavarty, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical tomography using referenced measurements of heterogeneous media,” IEEE. T. Med. Imaging. 22, 824-836 (2003).
  12. A. K. Sahu, R. Roy, A. Joshi, and E. M. Sevick-Muraca, “Evaluation of anatomical structure and non-uniform distribution of imaging agent in near-infrared, fluorescence-enhanced optical tomography,” Opt. Express 13, 10182-10199 (2005).
    [CrossRef]
  13. J. P. Rolland and H. H. Barrett, “Effect of random background inhomogeneity on observer detection performance,” J. Opt. Soc. Am. A 9, 649-658 (1992).
  14. A. B. Milstein, S. Oh, K. J. Webb, C. A. Bouman, Q. Zhang, D. A. Boas, and R. P. Millane, “Fluorescence optical diffusion tomography,” Appl. Opt. 42, 3081-3094 (2003).
    [CrossRef]
  15. M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional Bayesian optical image reconstruction with domain decomposition,” IEEE. T. Med. Imaging. 20, 147-163 (2001).
  16. E. Shives, Y. Xu, and H. Jiang, “Fluorescence lifetime tomography of turbid media based on an oxygen-sensitive dye,” Opt. Express 10, 1557-1562 (2002).
  17. C. Wu, H. Barnhill, X. Liang, Q. Wang, and Huabei Jiang, “A new probe using hybrid virus-dye nanoparticles for near-infrared fluorescence tomography,” Opt. Commun. 255, 366-374 (2005).
    [CrossRef]
  18. R. Roy, A. B. Thompson, A. Godavarty, and E. M. Sevick-Muraca, “Tomographic fluorescence imaging in tissue phantoms: a novel reconstruction algorithm and imaging geometry,” IEEE. T. Med. Imaging. 24, 137-154 (2005).
  19. A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE. T. Med. Imaging. 24, 1377-1386 (2005).
  20. L. Hervé, A. Koenig, A. Da Silva, M. Berger, J. Boutet, J. M. Dinten, P. Peltié, and P. Rizo, “Noncontact fluorescence diffuse optical tomography of heterogeneous media,” Appl. Opt. 46, 4896-4906 (2007).
    [CrossRef]
  21. H. Jiang, K. D. Paulsen, U. L. Osterberg, B. W. Pogue, and M. S. Patterson, “Optical image reconstruction using frequency domain data: simulations and experiments,” J. Opt. Soc. Am. A 13, 253-266 (1996).
  22. R. Philip, A. Penzkofer, W. Biiumler, R. M. Szeimies, and C. Abels, “Absorption and fluorescence spectroscopic investigation of indocyanine green,” Photochem. Photobiol. 96, 137-148(1996).
    [CrossRef]
  23. B. Yuan, N. Chen, and Q. Zhu, “Emission and absorption properties of indocyanine green in intralipid solution,” J. Biomed. Opt. 9, 497-503 (2004).
  24. S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. V. Gemert, “Optical properties of intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510-519(1992).
    [CrossRef]
  25. H. G. Staveren, C. J. Moes, J. V. Marle, S. A. Prahl, and M. V. Gemert, “Light scattering in Intralipid-10% in the wavelength range of 400-1100 nanometers,” Appl. Opt. 30, 4507-4514(1991).
  26. E. L. Hully, M. G. Nicholsyz, and Thomas H Fosteryxk, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381-3404 (1998).
    [CrossRef]
  27. M. L. J. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light- absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40, 575-583(1976).
  28. C. Li and H. Jiang, “A calibration method in diffuse optical tomography,” J. Opt. A: Pure Appl. Opt. 6, 844-852 (2004).

2007 (3)

2005 (5)

A. K. Sahu, R. Roy, A. Joshi, and E. M. Sevick-Muraca, “Evaluation of anatomical structure and non-uniform distribution of imaging agent in near-infrared, fluorescence-enhanced optical tomography,” Opt. Express 13, 10182-10199 (2005).
[CrossRef]

V. Ntziachristos, T. Jacks, R. Weissleder, J. Grimm, D. G. Kirsch, S. D. Windsor, C. F. Bender Kim, and P. M. Santiago, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. U.S.A. 102, 14404-14409 (2005).

C. Wu, H. Barnhill, X. Liang, Q. Wang, and Huabei Jiang, “A new probe using hybrid virus-dye nanoparticles for near-infrared fluorescence tomography,” Opt. Commun. 255, 366-374 (2005).
[CrossRef]

R. Roy, A. B. Thompson, A. Godavarty, and E. M. Sevick-Muraca, “Tomographic fluorescence imaging in tissue phantoms: a novel reconstruction algorithm and imaging geometry,” IEEE. T. Med. Imaging. 24, 137-154 (2005).

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE. T. Med. Imaging. 24, 1377-1386 (2005).

2004 (2)

B. Yuan, N. Chen, and Q. Zhu, “Emission and absorption properties of indocyanine green in intralipid solution,” J. Biomed. Opt. 9, 497-503 (2004).

C. Li and H. Jiang, “A calibration method in diffuse optical tomography,” J. Opt. A: Pure Appl. Opt. 6, 844-852 (2004).

2003 (2)

A. B. Milstein, S. Oh, K. J. Webb, C. A. Bouman, Q. Zhang, D. A. Boas, and R. P. Millane, “Fluorescence optical diffusion tomography,” Appl. Opt. 42, 3081-3094 (2003).
[CrossRef]

R. Roy, A. Godavarty, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical tomography using referenced measurements of heterogeneous media,” IEEE. T. Med. Imaging. 22, 824-836 (2003).

2002 (1)

2001 (4)

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]

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional Bayesian optical image reconstruction with domain decomposition,” IEEE. T. Med. Imaging. 20, 147-163 (2001).

V. Ntziachristos, A. H. Hielscher, A. G. Yodh, and B. Chance, “Diffuse optical tomography of highly heterogeneous media,” IEEE Trans. Med. Imaging 20, 470-478 (2001).

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grotzinger, “Receptor targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327-331 (2001).
[CrossRef]

1999 (1)

J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Imaging of spontaneous canine mammary tumors using fluorescent contrast agents,” Photochem. Photobiol. 70, 87-94(1999).

1998 (2)

E. L. Hully, M. G. Nicholsyz, and Thomas H Fosteryxk, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381-3404 (1998).
[CrossRef]

H. Jiang, “Frequency-domain fluorescent diffusion tomography: a finite-element-based algorithm and simulations,” Appl. Opt. 37, 5337-5343 (1998).

1997 (1)

E. M. Sevick-Muraca, G. Lopez, J. S. Reynolds, T. L. Troy, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency domain techniques,” Photochem. Photobiol. 66, 55-64 (1997).
[CrossRef]

1996 (2)

R. Philip, A. Penzkofer, W. Biiumler, R. M. Szeimies, and C. Abels, “Absorption and fluorescence spectroscopic investigation of indocyanine green,” Photochem. Photobiol. 96, 137-148(1996).
[CrossRef]

H. Jiang, K. D. Paulsen, U. L. Osterberg, B. W. Pogue, and M. S. Patterson, “Optical image reconstruction using frequency domain data: simulations and experiments,” J. Opt. Soc. Am. A 13, 253-266 (1996).

1994 (1)

1992 (2)

J. P. Rolland and H. H. Barrett, “Effect of random background inhomogeneity on observer detection performance,” J. Opt. Soc. Am. A 9, 649-658 (1992).

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

1991 (1)

1976 (1)

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

Appl. Opt. (5)

IEEE Trans. Med. Imaging (1)

V. Ntziachristos, A. H. Hielscher, A. G. Yodh, and B. Chance, “Diffuse optical tomography of highly heterogeneous media,” IEEE Trans. Med. Imaging 20, 470-478 (2001).

IEEE. T. Med. Imaging. (4)

R. Roy, A. Godavarty, and E. M. Sevick-Muraca, “Fluorescence-enhanced optical tomography using referenced measurements of heterogeneous media,” IEEE. T. Med. Imaging. 22, 824-836 (2003).

M. J. Eppstein, D. E. Dougherty, D. J. Hawrysz, and E. M. Sevick-Muraca, “Three-dimensional Bayesian optical image reconstruction with domain decomposition,” IEEE. T. Med. Imaging. 20, 147-163 (2001).

R. Roy, A. B. Thompson, A. Godavarty, and E. M. Sevick-Muraca, “Tomographic fluorescence imaging in tissue phantoms: a novel reconstruction algorithm and imaging geometry,” IEEE. T. Med. Imaging. 24, 137-154 (2005).

A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio,” IEEE. T. Med. Imaging. 24, 1377-1386 (2005).

J. Appl. Physiol. (1)

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

J. Biomed. Opt. (1)

B. Yuan, N. Chen, and Q. Zhu, “Emission and absorption properties of indocyanine green in intralipid solution,” J. Biomed. Opt. 9, 497-503 (2004).

J. Opt. A: Pure Appl. Opt. (1)

C. Li and H. Jiang, “A calibration method in diffuse optical tomography,” J. Opt. A: Pure Appl. Opt. 6, 844-852 (2004).

J. Opt. Soc. Am. A (2)

Lasers Surg. Med. (1)

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

Nat. Biotechnol. (1)

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grotzinger, “Receptor targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19, 327-331 (2001).
[CrossRef]

Opt. Commun. (1)

C. Wu, H. Barnhill, X. Liang, Q. Wang, and Huabei Jiang, “A new probe using hybrid virus-dye nanoparticles for near-infrared fluorescence tomography,” Opt. Commun. 255, 366-374 (2005).
[CrossRef]

Opt. Express (3)

Opt. Lett. (1)

Photochem. Photobiol. (3)

E. M. Sevick-Muraca, G. Lopez, J. S. Reynolds, T. L. Troy, and C. L. Hutchinson, “Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency domain techniques,” Photochem. Photobiol. 66, 55-64 (1997).
[CrossRef]

J. S. Reynolds, T. L. Troy, R. H. Mayer, A. B. Thompson, D. J. Waters, K. K. Cornell, P. W. Snyder, and E. M. Sevick-Muraca, “Imaging of spontaneous canine mammary tumors using fluorescent contrast agents,” Photochem. Photobiol. 70, 87-94(1999).

R. Philip, A. Penzkofer, W. Biiumler, R. M. Szeimies, and C. Abels, “Absorption and fluorescence spectroscopic investigation of indocyanine green,” Photochem. Photobiol. 96, 137-148(1996).
[CrossRef]

Phys. Med. Biol. (1)

E. L. Hully, M. G. Nicholsyz, and Thomas H Fosteryxk, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381-3404 (1998).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A. (1)

V. Ntziachristos, T. Jacks, R. Weissleder, J. Grimm, D. G. Kirsch, S. D. Windsor, C. F. Bender Kim, and P. M. Santiago, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. U.S.A. 102, 14404-14409 (2005).

Radiology (1)

X. Montet, J. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder, “Tomographic fluorescence imaging of tumor vascular volume in mice,” Radiology 242, 751-758 (2007).
[CrossRef]

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Figures (5)

Fig. 1
Fig. 1

Photograph of the CCD based CW DOT and FMT system.

Fig. 2
Fig. 2

Simulation results: Reconstructed μ a x m image without (a) and with (b) a priori μ a and μ s knowledge. The axes (left and bottom) illustrate the spatial scale (mm), whereas the color scale (right) records the value of recovered μ a x m ( mm 1 ). The circle indicates the exact size/shape of the target.

Fig. 3
Fig. 3

Reconstructed μ a , μ s , and μ a x m images for a representative experimental case. (a)  μ a image, (b)  μ s image, (c)  μ a x m with DOT recovered μ a and μ s distributions, (d)  μ a x m with uniform μ s but DOT recovered μ a distributions, (e)  μ a x m with uniform μ a but DOT recovered μ s distributions, and (f)  μ a x m with uniform μ a and μ s distributions.

Fig. 4
Fig. 4

Reconstructed μ a x m values in the target with and without DOT recovered μ a and μ s distributions when different ICG concentration was used. The μ a x m value from literature (0.1,0.2,0.4 and 0.6 μM ) were obtained by spectroscopic methods [21], while the μ a x m literature value ( 1 μM ) was obtained by a micromolar aqueous solution with a spectrofluorometer [8].

Fig. 5
Fig. 5

Reconstructed 3D images for a representative case (ICG concentration in the target = 1 μM ).

Equations (5)

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· [ D x ( r ) Φ x ( r ) ] μ a x ( r ) Φ x ( r ) + S x ( r ) = 0 ,
· [ D m ( r ) Φ m ( r ) ] μ a m ( r ) Φ m ( r ) + η μ a x m ( r ) Φ x ( r ) = 0 ,
[ A x , m ] { Φ x , m } = { b x , m } ,
[ A x , m ] { Φ x , m χ } = { b x , m χ } [ A x , m χ ] { Φ x , m } ,
( I x , m T I x , m + λ I ) Δ χ = I x , m T ( Φ x , m o Φ x , m c ) ,

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