The design and characterization of a time-resolved functional imager using a wide-field excitation scheme for small animal imaging is described. The optimal operation parameters are established based on phantom studies. The performance of the platform for functional imaging and the simultaneous 3D reconstruction of absorption and scattering coefficients is investigated in vitro.

© 2010 OSA

1. A. H. Hielscher, “Optical tomographic imaging of small animals,” Curr. Opin. Biotechnol. 16(1), 79–88 (2005). [CrossRef] [PubMed]
2. S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000). [CrossRef] [PubMed]
3. C. H. Contag and M. H. Bachmann, “Advances in in vivo bioluminescence imaging of gene expression,” Annu. Rev. Biomed. Eng. 4(1), 235–260 (2002). [CrossRef] [PubMed]
4. R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003). [CrossRef] [PubMed]
5. G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Effect of optical property estimation accuracy on tomographic bioluminescence imaging: simulation of a combined optical-PET (OPET) system,” Phys. Med. Biol. 51(8), 2045–2053 (2006). [CrossRef] [PubMed]
6. X. Zhang, C. T. Badea, and G. A. Johnson, “Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy,” J. Biomed. Opt. 14(6), 064010 (2009). [CrossRef] [PubMed]
7. Y. Lin, H. Yan, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography with functional and structural a priori information,” Appl. Opt. 48(7), 1328–1336 (2009). [CrossRef] [PubMed]
8. X. Intes and B. Chance, “Non-PET functional imaging techniques: optical,” Radiol. Clin. North Am. 43(1), 221–234, xii (2005). [CrossRef] [PubMed]
9. W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990). [CrossRef]
10. S. R. Arridge and W. R. Lionheart, “Nonuniqueness in diffusion-based optical tomography,” Opt. Lett. 23(11), 882–884 (1998). [CrossRef] [PubMed]
11. X. F. Cheng and D. A. Boas, “Systematic diffuse optical image errors resulting from uncertainty in the background optical properties,” Opt. Express 4(8), 299–307 (1999). [CrossRef] [PubMed]
12. U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum. 79(3), 034301 (2008). [CrossRef] [PubMed]
13. E. M. C. Hillman, J. C. Hebden, F. E. W. Schmidt, S. Arridge, M. Schweiger, H. Dehghani, and D. T. Delpy, “Calibration techniques and datatype extraction for time-resolved optical tomography,” Rev. Sci. Instrum. 71(9), 3415 (2000). [CrossRef]
14. S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008). [CrossRef] [PubMed]
15. A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008). [CrossRef] [PubMed]
16. A. Liebert, H. Wabnitz, D. Grosenick, and R. Macdonald, “Fiber dispersion in time domain measurements compromising the accuracy of determination of optical properties of strongly scattering media,” J. Biomed. Opt. 8(3), 512–516 (2003). [CrossRef] [PubMed]
17. A. Corlu, R. Choe, T. Durduran, K. Lee, M. Schweiger, S. R. Arridge, E. M. C. Hillman, and A. G. Yodh, “Diffuse optical tomography with spectral constraints and wavelength optimization,” Appl. Opt. 44(11), 2082–2093 (2005). [CrossRef] [PubMed]
18. G. Gulsen, B. Xiong, O. Birgul, and O. Nalcioglu, “Design and implementation of a multifrequency near-infrared diffuse optical tomography system,” J. Biomed. Opt. 11(1), 014020 (2006). [CrossRef] [PubMed]
19. S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005). [CrossRef] [PubMed]
20. S. D. Konecky, G. Y. Panasyuk, K. Lee, V. Markel, A. G. Yodh, and J. C. Schotland, “Imaging complex structures with diffuse light,” Opt. Express 16(7), 5048–5060 (2008). [CrossRef] [PubMed]
21. A. B. Thompson, D. J. Hawrysz, and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with area illumination and area detection: the forward imaging problem,” Appl. Opt. 42(19), 4125–4136 (2003). [CrossRef] [PubMed]
22. V. Lukic, V. A. Markel, and J. C. Schotland, “Optical tomography with structured illumination,” Opt. Lett. 34(7), 983–985 (2009). [CrossRef] [PubMed]
23. S. D. Konecky, A. Mazhar, D. J. Cuccia, A. J. Durkin, J. C. Schotland, and B. J. Tromberg, “Quantitative optical tomography of sub-surface heterogeneities using spatially modulated structured light,” Opt. Express 17(17), 14780–14790 (2009). [CrossRef] [PubMed]
24. D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009). [CrossRef] [PubMed]
25. R. B. Saager, D. J. Cuccia, and A. J. Durkin, “Determination of optical properties of turbid media spanning visible and near-infrared regimes via spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 15(1), 017012 (2010). [CrossRef] [PubMed]
26. A. Bassi, C. D’Andrea, G. Valentini, R. Cubeddu, and S. Arridge, “Detection of inhomogeneities in diffusive media using spatially modulated light,” Opt. Lett. 34(14), 2156–2158 (2009). [CrossRef] [PubMed]
27. S. Gioux, A. Mazhar, D. J. Cuccia, A. J. Durkin, B. J. Tromberg, and J. V. Frangioni, “Three-dimensional surface profile intensity correction for spatially modulated imaging,” J. Biomed. Opt. 14(3), 034045 (2009). [CrossRef] [PubMed]
28. S. Bélanger, M. Abran, X. Intes, C. Casanova, and F. Lesage, “Real-time diffuse optical tomography based on structured illumination,” J. Biomed. Opt. 15(1), 016006 (2010). [CrossRef] [PubMed]
29. J. Chen, V. Venugopal, F. Lesage, and X. Intes, “Time-resolved diffuse optical tomography with patterned-light illumination and detection,” Opt. Lett. 35(13), 2121–2123 (2010). [CrossRef] [PubMed]
30. M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl. Opt. 28(12), 2331–2336 (1989). [CrossRef] [PubMed]
31. 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(10), 2727–2741 (1994). [CrossRef] [PubMed]
32. M. J. Niedre and V. Ntziachristos, “Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons,” Opt. Lett. 35(3), 369–371 (2010). [CrossRef] [PubMed]
33. J. Chen and X. Intes, “Time-gated perturbation Monte Carlo for whole body functional imaging in small animals,” Opt. Express 17(22), 19566–19579 (2009). [CrossRef] [PubMed]
34. J. Dutta, S. Ahn, A. A. Joshi, and R. M. Leahy, “Illumination pattern optimization for fluorescence tomography: theory and simulation studies,” Phys. Med. Biol. 55(10), 2961–2982 (2010). [CrossRef] [PubMed]
35. V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28(6), 1115–1124 (2001). [CrossRef] [PubMed]
36. Using Lasers with DLP® DMD technology, http://focus.ti.com/pdfs/dlpdmd/Using_Lasers_with_DLP(r)_Technology.pdf
37. J. Selb, J. J. Stott, M. A. Franceschini, A. G. Sorensen, and D. A. Boas, “Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system: analytical model and experimental validation,” J. Biomed. Opt. 10(1), 011013 (2005). [CrossRef] [PubMed]
38. C. D'Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003). [CrossRef]
39. X. Intes and B. Chance, “Multi-frequency diffuse optical tomography,” J. Mod. Opt. 52(15), 2139–2159 (2005). [CrossRef]
40. B. W. Pogue, T. O. McBride, J. Prewitt, U. L. Österberg, and K. D. Paulsen, “Spatially variant regularization improves diffuse optical tomography,” Appl. Opt. 38(13), 2950–2961 (1999). [CrossRef] [PubMed]
41. X. Intes, C. Maloux, M. Guven, B. Yazici, and B. Chance, “Diffuse optical tomography with physiological and spatial a priori constraints,” Phys. Med. Biol. 49(12), N155–N163 (2004). [CrossRef] [PubMed]

Annu. Rev. Biomed. Eng.

• C. H. Contag and M. H. Bachmann, “Advances in in vivo bioluminescence imaging of gene expression,” Annu. Rev. Biomed. Eng. 4(1), 235–260 (2002). [CrossRef] [PubMed]

Appl. Opt.

• Y. Lin, H. Yan, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography with functional and structural a priori information,” Appl. Opt. 48(7), 1328–1336 (2009). [CrossRef] [PubMed]
• A. Corlu, R. Choe, T. Durduran, K. Lee, M. Schweiger, S. R. Arridge, E. M. C. Hillman, and A. G. Yodh, “Diffuse optical tomography with spectral constraints and wavelength optimization,” Appl. Opt. 44(11), 2082–2093 (2005). [CrossRef] [PubMed]
• S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction,” Appl. Opt. 44(10), 1858–1869 (2005). [CrossRef] [PubMed]
• A. B. Thompson, D. J. Hawrysz, and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with area illumination and area detection: the forward imaging problem,” Appl. Opt. 42(19), 4125–4136 (2003). [CrossRef] [PubMed]
• M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl. Opt. 28(12), 2331–2336 (1989). [CrossRef] [PubMed]
• B. W. Pogue, T. O. McBride, J. Prewitt, U. L. Österberg, and K. D. Paulsen, “Spatially variant regularization improves diffuse optical tomography,” Appl. Opt. 38(13), 2950–2961 (1999). [CrossRef] [PubMed]

Curr. Opin. Biotechnol.

• A. H. Hielscher, “Optical tomographic imaging of small animals,” Curr. Opin. Biotechnol. 16(1), 79–88 (2005). [CrossRef] [PubMed]

IEEE J. Quantum Electron.

• W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990). [CrossRef]

IEEE Trans. Med. Imaging

• A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27(8), 1152–1163 (2008). [CrossRef] [PubMed]

Invest. Radiol.

• S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, “Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging,” Invest. Radiol. 35(8), 479–485 (2000). [CrossRef] [PubMed]

J. Biomed. Opt.

• A. Liebert, H. Wabnitz, D. Grosenick, and R. Macdonald, “Fiber dispersion in time domain measurements compromising the accuracy of determination of optical properties of strongly scattering media,” J. Biomed. Opt. 8(3), 512–516 (2003). [CrossRef] [PubMed]
• G. Gulsen, B. Xiong, O. Birgul, and O. Nalcioglu, “Design and implementation of a multifrequency near-infrared diffuse optical tomography system,” J. Biomed. Opt. 11(1), 014020 (2006). [CrossRef] [PubMed]
• X. Zhang, C. T. Badea, and G. A. Johnson, “Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy,” J. Biomed. Opt. 14(6), 064010 (2009). [CrossRef] [PubMed]
• S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008). [CrossRef] [PubMed]
• J. Selb, J. J. Stott, M. A. Franceschini, A. G. Sorensen, and D. A. Boas, “Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system: analytical model and experimental validation,” J. Biomed. Opt. 10(1), 011013 (2005). [CrossRef] [PubMed]
• D. J. Cuccia, F. Bevilacqua, A. J. Durkin, F. R. Ayers, and B. J. Tromberg, “Quantitation and mapping of tissue optical properties using modulated imaging,” J. Biomed. Opt. 14(2), 024012 (2009). [CrossRef] [PubMed]
• R. B. Saager, D. J. Cuccia, and A. J. Durkin, “Determination of optical properties of turbid media spanning visible and near-infrared regimes via spatially modulated quantitative spectroscopy,” J. Biomed. Opt. 15(1), 017012 (2010). [CrossRef] [PubMed]
• S. Gioux, A. Mazhar, D. J. Cuccia, A. J. Durkin, B. J. Tromberg, and J. V. Frangioni, “Three-dimensional surface profile intensity correction for spatially modulated imaging,” J. Biomed. Opt. 14(3), 034045 (2009). [CrossRef] [PubMed]
• S. Bélanger, M. Abran, X. Intes, C. Casanova, and F. Lesage, “Real-time diffuse optical tomography based on structured illumination,” J. Biomed. Opt. 15(1), 016006 (2010). [CrossRef] [PubMed]

J. Mod. Opt.

• X. Intes and B. Chance, “Multi-frequency diffuse optical tomography,” J. Mod. Opt. 52(15), 2139–2159 (2005). [CrossRef]

J. Opt. Soc. Am. A

• 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(10), 2727–2741 (1994). [CrossRef] [PubMed]

J. Phys. D Appl. Phys.

• C. D'Andrea, D. Comelli, A. Pifferi, A. Torricelli, G. Valentini, and R. Cubeddu, “Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera,” J. Phys. D Appl. Phys. 36(14), 1675–1681 (2003). [CrossRef]

Med. Phys.

• V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28(6), 1115–1124 (2001). [CrossRef] [PubMed]

Nat. Med.

• R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003). [CrossRef] [PubMed]

Opt. Express

• X. F. Cheng and D. A. Boas, “Systematic diffuse optical image errors resulting from uncertainty in the background optical properties,” Opt. Express 4(8), 299–307 (1999). [CrossRef] [PubMed]
• J. Chen and X. Intes, “Time-gated perturbation Monte Carlo for whole body functional imaging in small animals,” Opt. Express 17(22), 19566–19579 (2009). [CrossRef] [PubMed]
• S. D. Konecky, G. Y. Panasyuk, K. Lee, V. Markel, A. G. Yodh, and J. C. Schotland, “Imaging complex structures with diffuse light,” Opt. Express 16(7), 5048–5060 (2008). [CrossRef] [PubMed]
• S. D. Konecky, A. Mazhar, D. J. Cuccia, A. J. Durkin, J. C. Schotland, and B. J. Tromberg, “Quantitative optical tomography of sub-surface heterogeneities using spatially modulated structured light,” Opt. Express 17(17), 14780–14790 (2009). [CrossRef] [PubMed]

Opt. Lett.

• V. Lukic, V. A. Markel, and J. C. Schotland, “Optical tomography with structured illumination,” Opt. Lett. 34(7), 983–985 (2009). [CrossRef] [PubMed]
• J. Chen, V. Venugopal, F. Lesage, and X. Intes, “Time-resolved diffuse optical tomography with patterned-light illumination and detection,” Opt. Lett. 35(13), 2121–2123 (2010). [CrossRef] [PubMed]
• A. Bassi, C. D’Andrea, G. Valentini, R. Cubeddu, and S. Arridge, “Detection of inhomogeneities in diffusive media using spatially modulated light,” Opt. Lett. 34(14), 2156–2158 (2009). [CrossRef] [PubMed]
• M. J. Niedre and V. Ntziachristos, “Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons,” Opt. Lett. 35(3), 369–371 (2010). [CrossRef] [PubMed]
• S. R. Arridge and W. R. Lionheart, “Nonuniqueness in diffusion-based optical tomography,” Opt. Lett. 23(11), 882–884 (1998). [CrossRef] [PubMed]

Phys. Med. Biol.

• G. Alexandrakis, F. R. Rannou, and A. F. Chatziioannou, “Effect of optical property estimation accuracy on tomographic bioluminescence imaging: simulation of a combined optical-PET (OPET) system,” Phys. Med. Biol. 51(8), 2045–2053 (2006). [CrossRef] [PubMed]
• J. Dutta, S. Ahn, A. A. Joshi, and R. M. Leahy, “Illumination pattern optimization for fluorescence tomography: theory and simulation studies,” Phys. Med. Biol. 55(10), 2961–2982 (2010). [CrossRef] [PubMed]
• X. Intes, C. Maloux, M. Guven, B. Yazici, and B. Chance, “Diffuse optical tomography with physiological and spatial a priori constraints,” Phys. Med. Biol. 49(12), N155–N163 (2004). [CrossRef] [PubMed]

Radiol. Clin. North Am.

• X. Intes and B. Chance, “Non-PET functional imaging techniques: optical,” Radiol. Clin. North Am. 43(1), 221–234, xii (2005). [CrossRef] [PubMed]

Rev. Sci. Instrum.

• U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum. 79(3), 034301 (2008). [CrossRef] [PubMed]
• E. M. C. Hillman, J. C. Hebden, F. E. W. Schmidt, S. Arridge, M. Schweiger, H. Dehghani, and D. T. Delpy, “Calibration techniques and datatype extraction for time-resolved optical tomography,” Rev. Sci. Instrum. 71(9), 3415 (2000). [CrossRef]

Other

• Using Lasers with DLP® DMD technology, http://focus.ti.com/pdfs/dlpdmd/Using_Lasers_with_DLP(r)_Technology.pdf

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