Abstract

Depth-resolved three-dimensional (3D) reconstruction of fluorophore-tagged inclusions in fluorescence tomography (FT) poses a highly ill-conditioned problem as depth information must be extracted from boundary data. Due to the ill-posed nature of the FT inverse problem, noise and errors in the data can severely impair the accuracy of the 3D reconstructions. The signal-to-noise ratio (SNR) of the FT data strongly affects the quality of the reconstructions. Additionally, in FT scenarios where the fluorescent signal is weak, data acquisition requires lengthy integration times that result in excessive FT scan periods. Enhancing the SNR of FT data contributes to the robustness of the 3D reconstructions as well as the speed of FT scans. A major deciding factor in the SNR of the FT data is the power of the radiation illuminating the subject to excite the administered fluorescent reagents. In existing single-point illumination FT systems, the source power level is limited by the skin maximum radiation exposure levels. In this paper, we introduce and study the performance of a multiplexed fluorescence tomography system with orders-of-magnitude enhanced data SNR over existing systems. The proposed system allows for multi-point illumination of the subject without jeopardizing the information content of the FT measurements and results in highly robust reconstructions of fluorescent inclusions from noisy FT data. Improvements offered by the proposed system are validated by numerical and experimental studies.

© 2014 Optical Society of America

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2013 (2)

A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
[CrossRef] [PubMed]

V. Venugopal and X. Intes, “Adaptive wide-field optical tomography,” J. Biomed. Opt.18(3), 036006 (2013).
[CrossRef] [PubMed]

2012 (1)

2010 (8)

J. C. Baritaux, K. Hassler, and M. Unser, “An efficient numerical method for general Lp regularization in fluorescence molecular tomography,” IEEE Trans. Med. Imaging29(4), 1075–1087 (2010).
[CrossRef] [PubMed]

D. Han, J. Tian, S. Zhu, J. Feng, C. Qin, B. Zhang, and X. Yang, “A fast reconstruction algorithm for fluorescence molecular tomography with sparsity regularization,” Opt. Express18(8), 8630–8646 (2010).
[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]

V. Venugopal, J. Chen, and X. Intes, “Development of an optical imaging platform for functional imaging of small animals using wide-field excitation,” Biomed. Opt. Express1(1), 143–156 (2010).
[CrossRef] [PubMed]

A. Mazhar, D. J. Cuccia, S. Gioux, A. J. Durkin, J. V. Frangioni, and B. J. Tromberg, “Structured illumination enhances resolution and contrast in thick tissue fluorescence imaging,” J. Biomed. Opt.15(1), 010506 (2010).
[CrossRef] [PubMed]

N. Ducros, C. D’andrea, G. Valentini, T. Rudge, S. Arridge, and A. Bassi, “Full-wavelet approach for fluorescence diffuse optical tomography with structured illumination,” Opt. Lett.35(21), 3676–3678 (2010).
[CrossRef] [PubMed]

C. D’Andrea, N. Ducros, A. Bassi, S. Arridge, and G. Valentini, “Fast 3D optical reconstruction in turbid media using spatially modulated light,” Biomed. Opt. Express1(2), 471–481 (2010).
[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]

2009 (2)

2007 (3)

2006 (3)

V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng.8(1), 1–33 (2006).
[CrossRef] [PubMed]

A. Joshi, W. Bangerth, and E. M. Sevick-Muraca, “Non-contact fluorescence optical tomography with scanning patterned illumination,” Opt. Express14(14), 6516–6534 (2006).
[CrossRef] [PubMed]

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, “Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection,” Med. Phys.33(5), 1299–1310 (2006).
[CrossRef] [PubMed]

2005 (1)

2003 (1)

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

2002 (2)

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
[CrossRef] [PubMed]

2001 (2)

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized born approximation,” Opt. Lett.26(12), 893–895 (2001).
[CrossRef] [PubMed]

1999 (1)

R. A. DeVerse, R. M. Hammaker, and W. G. Fateley, “Hadamard transform Raman imagery with a digital micro-mirror array,” Vib. Spectrosc.19(2), 177–186 (1999).
[CrossRef]

1998 (1)

1997 (2)

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol.42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

S. R. Arridge and J. C. Hebden, “Optical imaging in medicine: II. Modelling and reconstruction,” Phys. Med. Biol.42(5), 841–853 (1997).
[CrossRef] [PubMed]

1992 (1)

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
[CrossRef] [PubMed]

1970 (1)

R. Gordon, R. Bender, and G. T. Herman, “Algebraic reconstruction techniques (ART) for three-dimensional electron microscopy and x-ray photography,” J. Theor. Biol.29(3), 471–481 (1970).
[CrossRef] [PubMed]

Abran, M.

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]

Adibi, A.

Ahn, S.

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]

Arridge, S.

Arridge, S. R.

Bangerth, W.

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, “Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection,” Med. Phys.33(5), 1299–1310 (2006).
[CrossRef] [PubMed]

A. Joshi, W. Bangerth, and E. M. Sevick-Muraca, “Non-contact fluorescence optical tomography with scanning patterned illumination,” Opt. Express14(14), 6516–6534 (2006).
[CrossRef] [PubMed]

Baritaux, J. C.

J. C. Baritaux, K. Hassler, and M. Unser, “An efficient numerical method for general Lp regularization in fluorescence molecular tomography,” IEEE Trans. Med. Imaging29(4), 1075–1087 (2010).
[CrossRef] [PubMed]

Bassi, A.

Behrooz, A.

A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
[CrossRef] [PubMed]

A. Behrooz, H. M. Zhou, A. A. Eftekhar, and A. Adibi, “Total variation regularization for 3D reconstruction in fluorescence tomography: experimental phantom studies,” Appl. Opt.51(34), 8216–8227 (2012).
[CrossRef] [PubMed]

Bélanger, S.

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]

Bender, R.

R. Gordon, R. Bender, and G. T. Herman, “Algebraic reconstruction techniques (ART) for three-dimensional electron microscopy and x-ray photography,” J. Theor. Biol.29(3), 471–481 (1970).
[CrossRef] [PubMed]

Bevilacqua, F.

Boas, D. A.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

Bremer, C.

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

Brooks, D. H.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

Burling-Claridge, G. R.

Casanova, C.

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]

Chen, J.

Choe, R.

Corlu, A.

Cree, M. J.

Cubeddu, R.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol.42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Cuccia, D.

Cuccia, D. J.

A. Mazhar, D. J. Cuccia, S. Gioux, A. J. Durkin, J. V. Frangioni, and B. J. Tromberg, “Structured illumination enhances resolution and contrast in thick tissue fluorescence imaging,” J. Biomed. Opt.15(1), 010506 (2010).
[CrossRef] [PubMed]

D. J. Cuccia, F. Bevilacqua, A. J. Durkin, and B. J. Tromberg, “Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain,” Opt. Lett.30(11), 1354–1356 (2005).
[CrossRef] [PubMed]

D’Andrea, C.

Davis, S. C.

Dehghani, H.

DeVerse, R. A.

R. A. DeVerse, R. M. Hammaker, and W. G. Fateley, “Hadamard transform Raman imagery with a digital micro-mirror array,” Vib. Spectrosc.19(2), 177–186 (1999).
[CrossRef]

DiMarzio, C. A.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

Ducros, N.

Durduran, T.

Durkin, A. J.

Dutta, J.

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]

Eftekhar, A. A.

Fateley, W. G.

R. A. DeVerse, R. M. Hammaker, and W. G. Fateley, “Hadamard transform Raman imagery with a digital micro-mirror array,” Vib. Spectrosc.19(2), 177–186 (1999).
[CrossRef]

Feng, J.

Flock, S. T.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
[CrossRef] [PubMed]

Frangioni, J. V.

A. Mazhar, D. J. Cuccia, S. Gioux, A. J. Durkin, J. V. Frangioni, and B. J. Tromberg, “Structured illumination enhances resolution and contrast in thick tissue fluorescence imaging,” J. Biomed. Opt.15(1), 010506 (2010).
[CrossRef] [PubMed]

Gaudette, R. J.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

Gioux, S.

A. Mazhar, D. J. Cuccia, S. Gioux, A. J. Durkin, J. V. Frangioni, and B. J. Tromberg, “Structured illumination enhances resolution and contrast in thick tissue fluorescence imaging,” J. Biomed. Opt.15(1), 010506 (2010).
[CrossRef] [PubMed]

Gordon, R.

R. Gordon, R. Bender, and G. T. Herman, “Algebraic reconstruction techniques (ART) for three-dimensional electron microscopy and x-ray photography,” J. Theor. Biol.29(3), 471–481 (1970).
[CrossRef] [PubMed]

Graves, E. E.

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

Hammaker, R. M.

R. A. DeVerse, R. M. Hammaker, and W. G. Fateley, “Hadamard transform Raman imagery with a digital micro-mirror array,” Vib. Spectrosc.19(2), 177–186 (1999).
[CrossRef]

Han, D.

Hassler, K.

J. C. Baritaux, K. Hassler, and M. Unser, “An efficient numerical method for general Lp regularization in fluorescence molecular tomography,” IEEE Trans. Med. Imaging29(4), 1075–1087 (2010).
[CrossRef] [PubMed]

Hebden, J. C.

S. R. Arridge and J. C. Hebden, “Optical imaging in medicine: II. Modelling and reconstruction,” Phys. Med. Biol.42(5), 841–853 (1997).
[CrossRef] [PubMed]

Herman, G. T.

R. Gordon, R. Bender, and G. T. Herman, “Algebraic reconstruction techniques (ART) for three-dimensional electron microscopy and x-ray photography,” J. Theor. Biol.29(3), 471–481 (1970).
[CrossRef] [PubMed]

Huang, J.

Hwang, K.

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, “Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection,” Med. Phys.33(5), 1299–1310 (2006).
[CrossRef] [PubMed]

Intes, X.

V. Venugopal and X. Intes, “Adaptive wide-field optical tomography,” J. Biomed. Opt.18(3), 036006 (2013).
[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]

V. Venugopal, J. Chen, and X. Intes, “Development of an optical imaging platform for functional imaging of small animals using wide-field excitation,” Biomed. Opt. Express1(1), 143–156 (2010).
[CrossRef] [PubMed]

Jacques, S. L.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
[CrossRef] [PubMed]

Jiang, H.

Jiang, S.

Joshi, A.

A. Joshi, W. Bangerth, and E. M. Sevick-Muraca, “Non-contact fluorescence optical tomography with scanning patterned illumination,” Opt. Express14(14), 6516–6534 (2006).
[CrossRef] [PubMed]

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, “Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection,” Med. Phys.33(5), 1299–1310 (2006).
[CrossRef] [PubMed]

Joshi, A. A.

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]

Kilmer, M.

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

Konecky, S. D.

Künnemeyer, R.

Kuo, C.

A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
[CrossRef] [PubMed]

Leahy, R. M.

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]

Lesage, F.

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]

Mazhar, A.

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[CrossRef]

Mohajerani, P.

Ntziachristos, V.

V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng.8(1), 1–33 (2006).
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E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
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V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized born approximation,” Opt. Lett.26(12), 893–895 (2001).
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A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
[CrossRef] [PubMed]

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E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

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Rudge, T.

Schnall, M. D.

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Schweiger, M.

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A. Joshi, W. Bangerth, and E. M. Sevick-Muraca, “Non-contact fluorescence optical tomography with scanning patterned illumination,” Opt. Express14(14), 6516–6534 (2006).
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R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol.42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

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R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol.42(10), 1971–1979 (1997).
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V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
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Wang, J.

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E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
[CrossRef] [PubMed]

V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992).
[CrossRef] [PubMed]

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A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
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[CrossRef] [PubMed]

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Biomed. Opt. Express (2)

IEEE Signal Process. Mag. (1)

D. A. Boas, D. H. Brooks, E. L. Miller, C. A. DiMarzio, M. Kilmer, R. J. Gaudette, and Q. Zhang, “Imaging the body with diffuse optical tomography,” IEEE Signal Process. Mag.18(6), 57–75 (2001).
[CrossRef]

IEEE Trans. Med. Imaging (1)

J. C. Baritaux, K. Hassler, and M. Unser, “An efficient numerical method for general Lp regularization in fluorescence molecular tomography,” IEEE Trans. Med. Imaging29(4), 1075–1087 (2010).
[CrossRef] [PubMed]

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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).
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V. Venugopal and X. Intes, “Adaptive wide-field optical tomography,” J. Biomed. Opt.18(3), 036006 (2013).
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A. Mazhar, D. J. Cuccia, S. Gioux, A. J. Durkin, J. V. Frangioni, and B. J. Tromberg, “Structured illumination enhances resolution and contrast in thick tissue fluorescence imaging,” J. Biomed. Opt.15(1), 010506 (2010).
[CrossRef] [PubMed]

A. Behrooz, C. Kuo, H. Xu, and B. W. Rice, “Adaptive row-action inverse solver for fast noise-robust 3D reconstructions in bioluminescence tomography: theory and dual-modality optical/CT in vivo studies,” J. Biomed. Opt.18(7), 076010 (2013).
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[CrossRef] [PubMed]

Med. Phys. (2)

E. E. Graves, J. Ripoll, R. Weissleder, and V. Ntziachristos, “A submillimeter resolution fluorescence molecular imaging system for small animal imaging,” Med. Phys.30(5), 901–911 (2003).
[CrossRef] [PubMed]

A. Joshi, W. Bangerth, K. Hwang, J. C. Rasmussen, and E. M. Sevick-Muraca, “Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection,” Med. Phys.33(5), 1299–1310 (2006).
[CrossRef] [PubMed]

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V. Ntziachristos, C. Bremer, E. E. Graves, J. Ripoll, and R. Weissleder, “In vivo tomographic imaging of near-infrared fluorescent probes,” Mol. Imaging1(2), 82–88 (2002).
[CrossRef] [PubMed]

Nat. Med. (1)

V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med.8(7), 757–761 (2002).
[CrossRef] [PubMed]

Opt. Express (5)

Opt. Lett. (3)

Phys. Med. Biol. (3)

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol.42(10), 1971–1979 (1997).
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Figures (7)

Fig. 1
Fig. 1

In a conventional FT system depicted in row (a), in each measurement one source illuminates the box-shaped turbid medium housing two fluorescent rods. In Hadamard-multiplexed FT, depicted in row (b), multiple sources (four out of seven) illuminate the medium in each measurement. A total of seven measurements are performed in each configuration. The S-matrix Hadamard encodings are based on the S-matrix formulated in Eq. (5).

Fig. 2
Fig. 2

2D numerical studies with (a) 7, (b) 11, (c) 15, (d) 19, and (e) 23 sources illuminating a turbid medium with μ s = 1 mm−1 and μ a = 0.01 mm−1. The ground-truth fluorophore distribution is shown in rows labeled (i). The 2D reconstructions from (ii) conventional single-source illumination, and (iii) Hadamard-multiplexed data were performed using MLS-ART for data contaminated with noise levels equivalent to single-point illumination data SNRs of 60, 50, 40, 30, 20, 10, and 0 dB and are shown in corresponding rows ordered from left to right, respectively.

Fig. 3
Fig. 3

The relative mean-square errors (ε) of the MLS-ART reconstructions presented in Fig. 2 versus the data SNR.

Fig. 4
Fig. 4

Schematic of the non-contact Hadamard-multiplexed FT system. Visible or NIR radiation from a laser source is collimated and directed onto a lenslet array with an S-matrix mask mounted on it. The phantom is placed at the focal plane of the lenslet array. The non-masked lenslets form multi-point Hadamard S-matrix illumination patterns on the phantom. The radiation diffuses through the liquid phantom, excites the fluorescent inclusions (two rods) whose emission is imaged to a cooled CCD camera by an objective lens.

Fig. 5
Fig. 5

The phantom-based Hadamard-multiplexed FT system: a) Picture of the experimental system. b) A Hadamard S-matrix mask mounted on a lenslet array is illuminated with collimated beam of laser radiation. c) The S-matrix mask produces the desired excitation source pattern on the phantom surface.

Fig. 6
Fig. 6

Phantom-based experimental results: (i) the double-tube configuration of the fluorescent inclusions in the slab-shaped phantom. 3D reconstructions are performed by MLS-ART on (ii) conventional single-point illumination phantom FT data, and (iii) Hadamard-multiplexed FT data, where the depth of the pair of fluorescent tubes is (a) 3 mm, (b) 6 mm, and (c) 9 mm from the phantom surface facing the camera.

Fig. 7
Fig. 7

The relative mean-square errors (ε) of the 3D MLS-ART reconstructions presented in Fig. 6 are plotted versus the depth of the fluorescent inclusions for single-point illumination and Hadamard multiplexed FT architectures.

Equations (8)

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

D(r)Φ(r)+ μ a (r)Φ(r)=q(r),
D(r) Φ exc (r)+ μ a (r) Φ exc (r)= q exc (r),
D(r) Φ em (r)+ μ a (r) Φ em (r)=η μ fl c(r) Φ exc (r),
y=Mx.
S=[ 1 1 1 0 1 0 0 1 1 0 1 0 0 1 1 0 1 0 0 1 1 0 1 0 0 1 1 1 1 0 0 1 1 1 0 0 0 1 1 1 0 1 0 1 1 1 0 1 0 ].
y=WMx,
W=[ dia g n d ( S 11 ) dia g n d ( S 1 n s ) dia g n d ( S n s 1 ) dia g n d ( S n s n s ) ],
ε= x- x ^ 2 x 2 ,

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