Abstract

Cone-beam X-ray luminescence computed tomography (CB-XLCT) has been proposed as a new molecular imaging modality recently. It can obtain both anatomical and functional tomographic images of an object efficiently, with the excitation of nanophosphors in vivo or in vitro by cone-beam X-rays. However, the ill-posedness of the CB-XLCT inverse problem degrades the image quality and makes it difficult to resolve adjacent luminescent targets with different concentrations, which is essential in the monitoring of nanoparticle metabolism and drug delivery. To address this problem, a multi-voltage excitation imaging scheme combined with principal component analysis is proposed in this study. Imaging experiments performed on physical phantoms by a custom-made CB-XLCT system demonstrate that two adjacent targets, with different concentrations and an edge-to-edge distance of 0 mm, can be effectively resolved.

© 2017 Optical Society of America

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2017 (1)

G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

2016 (1)

2015 (1)

X. Liu, Q. Liao, H. Wang, and Z. Yan, “Excitation-resolved cone-beam x-ray luminescence tomography,” J. Biomed. Opt. 20(7), 070501 (2015).
[Crossref] [PubMed]

2014 (8)

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
[Crossref] [PubMed]

W. Cong and G. Wang, “X-ray fan-beam luminescence tomography,” Austin J. Biomed. Eng. 1(5), 1024 (2014).

X. Liu, Q. Liao, and H. Wang, “Fast X-ray luminescence computed tomography imaging,” IEEE Trans. Biomed. Eng. 61(6), 1621–1627 (2014).
[Crossref] [PubMed]

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
[Crossref] [PubMed]

M. Ahmad, G. Pratx, M. Bazalova, and L. Xing, “X-ray luminescence and x-ray fluorescence computed tomography: new molecular imaging modalities,” IEEE Access 2, 1051–1061 (2014).
[Crossref]

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
[Crossref] [PubMed]

X. Liu, H. Wang, M. Xu, S. Nie, and H. Lu, “A wavelet-based single-view reconstruction approach for cone beam x-ray luminescence tomography imaging,” Biomed. Opt. Express 5(11), 3848–3858 (2014).
[Crossref] [PubMed]

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

2013 (5)

H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
[Crossref] [PubMed]

X. Liu, Q. Liao, and H. Wang, “In vivo x-ray luminescence tomographic imaging with single-view data,” Opt. Lett. 38(22), 4530–4533 (2013).
[Crossref] [PubMed]

Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
[Crossref] [PubMed]

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
[Crossref] [PubMed]

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

2012 (1)

Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
[Crossref] [PubMed]

2010 (7)

C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
[Crossref] [PubMed]

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
[Crossref] [PubMed]

L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

H. Abdi and L. J. Williams, “Principal component analysis,” Wiley Interdiscip. Rev. Comput. Stat. 2(4), 433–459 (2010).
[Crossref]

X. Liu, D. Wang, F. Liu, and J. Bai, “Principal component analysis of dynamic fluorescence diffuse optical tomography images,” Opt. Express 18(6), 6300–6314 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

2008 (1)

2006 (2)

G. Wang, W. Cong, K. Durairaj, X. Qian, H. Shen, P. Sinn, E. Hoffman, G. McLennan, and M. Henry, “In vivo mouse studies with bioluminescence tomography,” Opt. Express 14(17), 7801–7809 (2006).
[Crossref] [PubMed]

A. Soubret and V. Ntziachristos, “Fluorescence molecular tomography in the presence of background fluorescence,” Phys. Med. Biol. 51(16), 3983–4001 (2006).
[Crossref] [PubMed]

2005 (2)

W. Cong, G. Wang, D. Kumar, Y. Liu, M. Jiang, L. Wang, E. Hoffman, G. McLennan, P. McCray, J. Zabner, and A. Cong, “Practical reconstruction method for bioluminescence tomography,” Opt. Express 13(18), 6756–6771 (2005).
[Crossref] [PubMed]

A. D. Klose, V. Ntziachristos, and A. H. Hielscher, “The inverse source problem based on the radiative transfer equation in optical molecular imaging,” J. Comput. Phys. 202(1), 323–345 (2005).
[Crossref]

1996 (1)

I. Kandarakis, D. Cavouras, G. Panayiotakis, T. Agelis, C. Nomicos, and G. Giakoumakis, “X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens,” Phys. Med. Biol. 41(2), 297–307 (1996).
[Crossref] [PubMed]

1984 (1)

Abdi, H.

H. Abdi and L. J. Williams, “Principal component analysis,” Wiley Interdiscip. Rev. Comput. Stat. 2(4), 433–459 (2010).
[Crossref]

Agelis, T.

I. Kandarakis, D. Cavouras, G. Panayiotakis, T. Agelis, C. Nomicos, and G. Giakoumakis, “X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens,” Phys. Med. Biol. 41(2), 297–307 (1996).
[Crossref] [PubMed]

Ahmad, M.

M. Ahmad, G. Pratx, M. Bazalova, and L. Xing, “X-ray luminescence and x-ray fluorescence computed tomography: new molecular imaging modalities,” IEEE Access 2, 1051–1061 (2014).
[Crossref]

Ale, A.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
[Crossref] [PubMed]

Bai, J.

G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
[Crossref] [PubMed]

H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
[Crossref] [PubMed]

X. Liu, D. Wang, F. Liu, and J. Bai, “Principal component analysis of dynamic fluorescence diffuse optical tomography images,” Opt. Express 18(6), 6300–6314 (2010).
[Crossref] [PubMed]

Bazalova, M.

M. Ahmad, G. Pratx, M. Bazalova, and L. Xing, “X-ray luminescence and x-ray fluorescence computed tomography: new molecular imaging modalities,” IEEE Access 2, 1051–1061 (2014).
[Crossref]

Carpenter, C. M.

C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

Cavouras, D.

I. Kandarakis, D. Cavouras, G. Panayiotakis, T. Agelis, C. Nomicos, and G. Giakoumakis, “X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens,” Phys. Med. Biol. 41(2), 297–307 (1996).
[Crossref] [PubMed]

Cena, J.

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

Chen, D.

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
[Crossref] [PubMed]

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

Cherry, S.

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

Cherry, S. R.

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
[Crossref] [PubMed]

Cong, A.

Cong, W.

Das, G. K.

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

Davis, L.

Deng, L.

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
[Crossref] [PubMed]

Durairaj, K.

Feldkamp, L.

Feng, J.

Freyer, M.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
[Crossref] [PubMed]

Giakoumakis, G.

I. Kandarakis, D. Cavouras, G. Panayiotakis, T. Agelis, C. Nomicos, and G. Giakoumakis, “X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens,” Phys. Med. Biol. 41(2), 297–307 (1996).
[Crossref] [PubMed]

Gu, S.

Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
[Crossref] [PubMed]

Guang, H.

Y. Zhou, H. Guang, H. Pu, J. Zhang, and J. Luo, “Unmixing multiple adjacent fluorescent targets with multispectral excited fluorescence molecular tomography,” Appl. Opt. 55(18), 4843–4849 (2016).
[Crossref] [PubMed]

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
[Crossref] [PubMed]

He, W.

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
[Crossref] [PubMed]

H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
[Crossref] [PubMed]

Henry, M.

Hielscher, A. H.

A. D. Klose, V. Ntziachristos, and A. H. Hielscher, “The inverse source problem based on the radiative transfer equation in optical molecular imaging,” J. Comput. Phys. 202(1), 323–345 (2005).
[Crossref]

Hoffman, E.

Huang, S.

Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
[Crossref] [PubMed]

Jia, K.

Jiang, M.

Kandarakis, I.

I. Kandarakis, D. Cavouras, G. Panayiotakis, T. Agelis, C. Nomicos, and G. Giakoumakis, “X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens,” Phys. Med. Biol. 41(2), 297–307 (1996).
[Crossref] [PubMed]

Kennedy, I. M.

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

Klose, A. D.

A. D. Klose, V. Ntziachristos, and A. H. Hielscher, “The inverse source problem based on the radiative transfer equation in optical molecular imaging,” J. Comput. Phys. 202(1), 323–345 (2005).
[Crossref]

Kress, J.

Kumar, D.

Li, C.

L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
[Crossref] [PubMed]

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L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
[Crossref] [PubMed]

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H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
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Liang, J.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
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H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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X. Liu, Q. Liao, H. Wang, and Z. Yan, “Excitation-resolved cone-beam x-ray luminescence tomography,” J. Biomed. Opt. 20(7), 070501 (2015).
[Crossref] [PubMed]

X. Liu, Q. Liao, and H. Wang, “Fast X-ray luminescence computed tomography imaging,” IEEE Trans. Biomed. Eng. 61(6), 1621–1627 (2014).
[Crossref] [PubMed]

X. Liu, Q. Liao, and H. Wang, “In vivo x-ray luminescence tomographic imaging with single-view data,” Opt. Lett. 38(22), 4530–4533 (2013).
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G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
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H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
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Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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Liu, J.

G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
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Liu, Y.

Liu, Z.

Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
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Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
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Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
[Crossref] [PubMed]

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G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
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H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
[Crossref] [PubMed]

Lv, Y.

Martínez-Dávalos, A.

C. Li, A. Martínez-Dávalos, and S. R. Cherry, “Numerical simulation of x-ray luminescence optical tomography for small-animal imaging,” J. Biomed. Opt. 19(4), 046002 (2014).
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M. Ahmad, G. Pratx, M. Bazalova, and L. Xing, “X-ray luminescence and x-ray fluorescence computed tomography: new molecular imaging modalities,” IEEE Access 2, 1051–1061 (2014).
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C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
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G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
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G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
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Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
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Qian, C.

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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Qin, C.

Qu, X.

Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
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Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
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Ren, J.

Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
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R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
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R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
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Sinn, P.

Soehngen, E.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
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A. Soubret and V. Ntziachristos, “Fluorescence molecular tomography in the presence of background fluorescence,” Phys. Med. Biol. 51(16), 3983–4001 (2006).
[Crossref] [PubMed]

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L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
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L. Sudheendra, G. K. Das, C. Li, D. Stark, J. Cena, S. Cherry, and I. M. Kennedy, “Nagdf4: Eu3+ nanoparticles for enhanced x-ray excited optical imaging,” Chem. Mater. 26(5), 1881–1888 (2014).
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G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
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C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

Tian, J.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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J. Feng, K. Jia, G. Yan, S. Zhu, C. Qin, Y. Lv, and J. Tian, “An optimal permissible source region strategy for multispectral bioluminescence tomography,” Opt. Express 16(20), 15640–15654 (2008).
[Crossref] [PubMed]

Wang, D.

Wang, G.

Wang, H.

X. Liu, Q. Liao, H. Wang, and Z. Yan, “Excitation-resolved cone-beam x-ray luminescence tomography,” J. Biomed. Opt. 20(7), 070501 (2015).
[Crossref] [PubMed]

X. Liu, Q. Liao, and H. Wang, “Fast X-ray luminescence computed tomography imaging,” IEEE Trans. Biomed. Eng. 61(6), 1621–1627 (2014).
[Crossref] [PubMed]

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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X. Liu, H. Wang, M. Xu, S. Nie, and H. Lu, “A wavelet-based single-view reconstruction approach for cone beam x-ray luminescence tomography imaging,” Biomed. Opt. Express 5(11), 3848–3858 (2014).
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X. Liu, Q. Liao, and H. Wang, “In vivo x-ray luminescence tomographic imaging with single-view data,” Opt. Lett. 38(22), 4530–4533 (2013).
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Wang, X.

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

M. Ahmad, G. Pratx, M. Bazalova, and L. Xing, “X-ray luminescence and x-ray fluorescence computed tomography: new molecular imaging modalities,” IEEE Access 2, 1051–1061 (2014).
[Crossref]

G. Pratx, C. M. Carpenter, C. Sun, and L. Xing, “X-ray luminescence computed tomography via selective excitation: a feasibility study,” IEEE Trans. Med. Imaging 29(12), 1992–1999 (2010).
[Crossref] [PubMed]

C. M. Carpenter, C. Sun, G. Pratx, R. Rao, and L. Xing, “Hybrid x-ray/optical luminescence imaging: Characterization of experimental conditions,” Med. Phys. 37(8), 4011–4018 (2010).
[Crossref] [PubMed]

G. Pratx, C. M. Carpenter, C. Sun, R. P. Rao, and L. Xing, “Tomographic molecular imaging of x-ray-excitable nanoparticles,” Opt. Lett. 35(20), 3345–3347 (2010).
[Crossref] [PubMed]

Xiong, L.

L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
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L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
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[Crossref] [PubMed]

Yan, G.

Yan, Z.

X. Liu, Q. Liao, H. Wang, and Z. Yan, “Excitation-resolved cone-beam x-ray luminescence tomography,” J. Biomed. Opt. 20(7), 070501 (2015).
[Crossref] [PubMed]

Yang, J.

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
[Crossref] [PubMed]

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L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
[Crossref] [PubMed]

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L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
[Crossref] [PubMed]

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D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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Z. Liu, F. Pu, S. Huang, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Gd2O3:Yb3+, Er3+ up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging,” Biomaterials 34(6), 1712–1721 (2013).
[Crossref] [PubMed]

Z. Liu, Z. Li, J. Liu, S. Gu, Q. Yuan, J. Ren, and X. Qu, “Long-circulating Er3+-doped Yb2O3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent,” Biomaterials 33(28), 6748–6757 (2012).
[Crossref] [PubMed]

Zabner, J.

Zeng, S.

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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Zeng, T.

Z. Yi, W. Lu, Y. Xu, J. Yang, L. Deng, C. Qian, T. Zeng, H. Wang, L. Rao, H. Liu, and S. Zeng, “PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking,” Biomaterials 35(36), 9689–9697 (2014).
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Zhang, B.

Zhang, G.

G. Zhang, F. Liu, J. Liu, J. Luo, Y. Xie, J. Bai, and L. Xing, “Cone Beam X-ray Luminescence Computed Tomography Based on Bayesian Method,” IEEE Trans. Med. Imaging 36(1), 225–235 (2017).
[Crossref] [PubMed]

H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
[Crossref] [PubMed]

H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
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Zhang, J.

Zhang, X.

D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
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H. Pu, G. Zhang, W. He, F. Liu, H. Guang, Y. Zhang, J. Bai, and J. Luo, “Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis,” Phys. Med. Biol. 59(17), 5025–5042 (2014).
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H. Pu, W. He, G. Zhang, B. Zhang, F. Liu, Y. Zhang, J. Luo, and J. Bai, “Separating structures of different fluorophore concentrations by principal component analysis on multispectral excitation-resolved fluorescence tomography images,” Biomed. Opt. Express 4(10), 1829–1845 (2013).
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Zhou, Y.

Zhu, S.

H. Yi, D. Chen, W. Li, S. Zhu, X. Wang, J. Liang, and J. Tian, “Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study,” J. Biomed. Opt. 18(5), 056013 (2013).
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D. Chen, S. Zhu, H. Yi, X. Zhang, D. Chen, J. Liang, and J. Tian, “Cone beam x-ray luminescence computed tomography: A feasibility study,” Med. Phys. 40(3), 031111 (2013).
[Crossref] [PubMed]

J. Feng, K. Jia, G. Yan, S. Zhu, C. Qin, Y. Lv, and J. Tian, “An optimal permissible source region strategy for multispectral bioluminescence tomography,” Opt. Express 16(20), 15640–15654 (2008).
[Crossref] [PubMed]

Zientkowska, M.

R. B. Schulz, A. Ale, A. Sarantopoulos, M. Freyer, E. Soehngen, M. Zientkowska, and V. Ntziachristos, “Hybrid system for simultaneous fluorescence and x-ray computed tomography,” IEEE Trans. Med. Imaging 29(2), 465–473 (2010).
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Austin J. Biomed. Eng. (1)

W. Cong and G. Wang, “X-ray fan-beam luminescence tomography,” Austin J. Biomed. Eng. 1(5), 1024 (2014).

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Figures (9)

Fig. 1
Fig. 1 Schematic diagram of the CB-XLCT system.

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Fig. 2
Fig. 2 Illustration of the second phantom experiment. (a) Representative X-ray projection of the phantom. The region between the red and green lines was used for this study. (b) Representative CT image slice of the phantom, corresponding to the slice indicated by the blue line in (a). The nanophosphor concentration of the left tube was 50 mg/ml, and that of the right tube was 100 mg/ml, respectively.

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Fig. 3
Fig. 3 Illustration of three tube pairs used in the third experiment. Nanophosphor concentrations in (a), (b) and (c) were 50-50, 50-150, 50-200 mg/ml, respectively. The left tube in each image contained nanophosphors of 50 mg/ml.

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Fig. 4
Fig. 4 Optical photon counts excited under different X-ray tube voltages.

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Fig. 5
Fig. 5 Tomographic images of the nanophosphor distribution reconstructed from EMCCD measurements acquired at various tube voltages (from left to right, tube voltage is 40, 50, 60, 70, and 80 kV, respectively. z = 1.1 mm). The red curve in each image represents the outer boundary of the phantom acquired from white light images. All the XLCT images are displayed in the same range.

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Fig. 6
Fig. 6 Tomographic (z = 1.1 cm) and 3D results of PC2 obtained from different combinations of XLCT images acquired at various tube voltages. All the images are displayed in the same range. The values below 35% of the maximum are set as zero in the 3D results.

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Fig. 7
Fig. 7 Tomographic (z = 1.1 cm) results of PC2-XLCT obtained from combinations listed in Table 5. Images (a)-(c) correspond to case 1-3, respectively.

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Fig. 8
Fig. 8 Tomographic (z = 1.1 cm) results of the third experiment. The first two rows show the tomographic reconstruction results corresponding to each excitation X-ray tube voltage wavelength obtained by the ART algorithm. The last three rows show the PCs of each case obtained by PCA. The green parts indicate the negative PC2 and the red parts indicate the positive PC2.

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Fig. 9
Fig. 9 Tomographic (z = 1.1 cm) XLCT and PC2-XLCT results. Images in the first row were reconstructed from cone-beam imaging, while images in the second row were from fan-beam imaging.

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Tables (7)

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Table 1 Tube pairs of different concentrations used in the third experiment

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Table 2 Different combinations of XLCT images acquired at various X-ray voltages

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Table 3 The eigenvectors E1 and E2 for case 4

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Table 4 DOCs of the proposed method by using different combinations of multi-voltage XLCT images

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Table 5 DOCs of the proposed method with different two excitation voltages

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Table 6 DOCs of the proposed method with concentration pairs

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Table 7 DOCs of the proposed method for cone-beam and fan-beam imaging mode

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Equations (11)

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S(r)=εX(r)ρ(r)
X(r)=X( r 0 )exp{− ∫ r 0 r μ t (τ)d τ}
-∇[D(r)∇Φ(r)]+ μ a (r)Φ(r)=S(r) (r∈Ω)
Φ(r)+2αD(r)[ν∇Φ(r)]=0 (r∈∂Ω)
Aρ= Φ meas
P= X 0 ×E
L= 1 M−1 X 0 T X 0
L=EΛ E T
P j = X 0 × E j
u= 1 N ∑ x∈Q x
DOC= ‖ u pc2 − u ct ‖ 2

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