Abstract

As a new modality of molecular imaging, bioluminescence imaging has been widely used in tumor detection and drug evaluation. However, BLI cannot present the depth of information for internal diseases such as a liver tumor in situ or a lung tumor in situ. In this paper, we describe a bioluminescence tomography (BLT) method based on the bioluminescent intensity attenuation calibration and applied it to the early detection of liver cancer in situ. In comparison with BLT without calibration, this method could improve the reconstruction accuracy by more than 10%. In comparison with micro-computed tomography and other traditional imaging modalities, this method can detect a liver tumor at a very early stage and provide reliable location information.

© 2011 Optical Society of America

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2010 (3)

2009 (1)

2008 (5)

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

J. Zhao, L. Dong, and B. Lu, “Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis,” Gastroenterology 135, 956–968 (2008).
[CrossRef] [PubMed]

J. Zhao, B. Lu, and H. Xu, “Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,” Hepatology 48, 265–275 (2008).
[CrossRef] [PubMed]

J. Tian, J. Xue, and Y. Dai, “A novel software platform for medical image processing and analyzing,” IEEE Trans. Inf. Technol. Biomed. 12, 800–812 (2008).
[CrossRef] [PubMed]

G. Yan, J. Tian, S. Zhu, Y. Dai, and C. Qin, “Fast cone beam CT image reconstruction using GPU hardware,” J. X-Ray Sci. Technol. 16, 225–234 (2008), http://www.3dmed.net/paper/YanGR_XRay_Fast%20cone-beam%20CT%20image%20reconstruction%20using%20GPU%20hardware.pdf.

2006 (6)

M. Safran, W. Kim, and F. O’Connell, “Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production,” Proc. Natl. Acad. Sci. USA 103, 105–110 (2006).
[CrossRef]

W. Cong and K. Durairaj, “A Born-type approximation method for bioluminescence tomography,” Med. Phys. 33, 679–686(2006).
[CrossRef] [PubMed]

I. Remy and S. Michnick, “A highly sensitive protein-protein interaction assay based on Gaussia luciferase,” Nat. Methods 3, 977–979 (2006).
[CrossRef] [PubMed]

G. Wang, W. Cong, K. Durairaj, and M. Henry, “In vivo mouse studies with bioluminescence tomography,” Opt. Express 14, 7801–7809 (2006).
[CrossRef] [PubMed]

G. Wang, H. Shen, and W. Cong, “Temperature-modulated bioluminescence tomography,” Opt. Express 14, 7852–7871(2006).
[CrossRef] [PubMed]

Y. Lv, J. Tian, W. Cong, G. Wang, J. Luo, W. Yang, and H. Li, “A multilevel adaptive finite element algorithm for bioluminescence tomography,” Opt. Express 14, 8211–8223 (2006).
[CrossRef] [PubMed]

2005 (5)

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

R. Paulmurugan and S. Gambhir, “Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals,” Cancer Res. 65, 7413–7420 (2005).
[CrossRef] [PubMed]

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

J. Grimm, D. Kirsch, and D. Windsor, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. USA 102, 14404–14409 (2005).
[CrossRef] [PubMed]

G. Alexandrakis, F. Rannou, and A. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50, 4225–4242 (2005).
[CrossRef] [PubMed]

2004 (3)

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

G. Zhang, M. Safran, and W. Wei, “Bioluminescent imaging of Cdk2 inhibition in vivo,” Nat. Med. 10, 643–648 (2004).
[CrossRef] [PubMed]

2003 (4)

M. Funovics, R. Weissleder, and C. Tung, “Protease sensors for bioimaging,” Anal. Bioanal. Chem. 377, 956–963 (2003).
[CrossRef] [PubMed]

R. Paulmurugan and S. Gambhir, “Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation,” Anal. Chem. 75, 1584–1589 (2003).
[CrossRef] [PubMed]

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

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

1995 (1)

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

Alexandrakis, G.

G. Alexandrakis, F. Rannou, and A. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50, 4225–4242 (2005).
[CrossRef] [PubMed]

Arridge, S. R.

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

Bruggen, N.

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

Cao, F.

Chatziioannou, A.

G. Alexandrakis, F. Rannou, and A. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50, 4225–4242 (2005).
[CrossRef] [PubMed]

Chen, D.

Chen, X.

Cong, A.

Cong, W.

Dai, Y.

G. Yan, J. Tian, S. Zhu, Y. Dai, and C. Qin, “Fast cone beam CT image reconstruction using GPU hardware,” J. X-Ray Sci. Technol. 16, 225–234 (2008), http://www.3dmed.net/paper/YanGR_XRay_Fast%20cone-beam%20CT%20image%20reconstruction%20using%20GPU%20hardware.pdf.

J. Tian, J. Xue, and Y. Dai, “A novel software platform for medical image processing and analyzing,” IEEE Trans. Inf. Technol. Biomed. 12, 800–812 (2008).
[CrossRef] [PubMed]

Delpy, D. T.

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

Dinkelborg, L.

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

Dong, L.

J. Zhao, L. Dong, and B. Lu, “Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis,” Gastroenterology 135, 956–968 (2008).
[CrossRef] [PubMed]

Durairaj, K.

W. Cong and K. Durairaj, “A Born-type approximation method for bioluminescence tomography,” Med. Phys. 33, 679–686(2006).
[CrossRef] [PubMed]

G. Wang, W. Cong, K. Durairaj, and M. Henry, “In vivo mouse studies with bioluminescence tomography,” Opt. Express 14, 7801–7809 (2006).
[CrossRef] [PubMed]

Feng, J.

Funovics, M.

M. Funovics, R. Weissleder, and C. Tung, “Protease sensors for bioimaging,” Anal. Bioanal. Chem. 377, 956–963 (2003).
[CrossRef] [PubMed]

Gambhir, S.

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

R. Paulmurugan and S. Gambhir, “Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals,” Cancer Res. 65, 7413–7420 (2005).
[CrossRef] [PubMed]

R. Paulmurugan and S. Gambhir, “Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation,” Anal. Chem. 75, 1584–1589 (2003).
[CrossRef] [PubMed]

Gammon, S.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

Grimm, J.

J. Grimm, D. Kirsch, and D. Windsor, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. USA 102, 14404–14409 (2005).
[CrossRef] [PubMed]

Han, R.

Henry, M.

Hiraoka, M.

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

Hoffman, E. A.

Hu, Z.

Jennings, P.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Jia, K.

Jiang, M.

Jiang, T.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Kim, W.

M. Safran, W. Kim, and F. O’Connell, “Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production,” Proc. Natl. Acad. Sci. USA 103, 105–110 (2006).
[CrossRef]

Kirsch, D.

J. Grimm, D. Kirsch, and D. Windsor, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. USA 102, 14404–14409 (2005).
[CrossRef] [PubMed]

Kumar, D.

Li, H.

Li, X.

Liang, J.

Liu, D.

Liu, J.

Liu, K.

Liu, Y.

Liu, Z.

X. Ma, Z. Liu, J. Tian, and F. Wang, “Dual-modality monitoring of tumor response to cyclophosphamide therapy in mice with bioluminescence imaging and small-animal positron emission tomography,” Mol. Imaging (to be published).
[PubMed]

Lu, B.

J. Zhao, L. Dong, and B. Lu, “Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis,” Gastroenterology 135, 956–968 (2008).
[CrossRef] [PubMed]

J. Zhao, B. Lu, and H. Xu, “Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,” Hepatology 48, 265–275 (2008).
[CrossRef] [PubMed]

Lu, Y.

Luker, G.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

Luker, K.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

Luo, J.

Lv, Y.

Ma, X.

X. Qu, X. Li, X. Ma, R. Han, Z. Hu, X. Chen, D. Sun, R. Zhang, D. Chen, D. Chen, X. Chen, J. Liang, F. Cao, and J. Tian, “In vivo quantitative bioluminescence tomography using heterogenous and homogeneous mouse models,” Opt. Express 18, 13102–13113 (2010).
[CrossRef] [PubMed]

X. Ma, Z. Liu, J. Tian, and F. Wang, “Dual-modality monitoring of tumor response to cyclophosphamide therapy in mice with bioluminescence imaging and small-animal positron emission tomography,” Mol. Imaging (to be published).
[PubMed]

McCray, P. B.

McLennan, G.

Michnick, S.

I. Remy and S. Michnick, “A highly sensitive protein-protein interaction assay based on Gaussia luciferase,” Nat. Methods 3, 977–979 (2006).
[CrossRef] [PubMed]

Nguyen, Q.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Ntziachristos, V.

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

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

O’Connell, F.

M. Safran, W. Kim, and F. O’Connell, “Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production,” Proc. Natl. Acad. Sci. USA 103, 105–110 (2006).
[CrossRef]

Olson, E.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Paulmurugan, R.

R. Paulmurugan and S. Gambhir, “Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals,” Cancer Res. 65, 7413–7420 (2005).
[CrossRef] [PubMed]

R. Paulmurugan and S. Gambhir, “Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation,” Anal. Chem. 75, 1584–1589 (2003).
[CrossRef] [PubMed]

Pica, C.

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

Piwnica-Worms, D.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

Piwnica-Worms, H.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

Qin, C.

Qu, X.

Rannou, F.

G. Alexandrakis, F. Rannou, and A. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50, 4225–4242 (2005).
[CrossRef] [PubMed]

Rao, S. S.

S. S. Rao, The Finite Element Method in Engineering(Butterworth-Heinemann, 1999).

Remy, I.

I. Remy and S. Michnick, “A highly sensitive protein-protein interaction assay based on Gaussia luciferase,” Nat. Methods 3, 977–979 (2006).
[CrossRef] [PubMed]

Ripoll, J.

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

Roy, M.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Safran, M.

M. Safran, W. Kim, and F. O’Connell, “Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production,” Proc. Natl. Acad. Sci. USA 103, 105–110 (2006).
[CrossRef]

G. Zhang, M. Safran, and W. Wei, “Bioluminescent imaging of Cdk2 inhibition in vivo,” Nat. Med. 10, 643–648 (2004).
[CrossRef] [PubMed]

Schweiger, M.

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

Shen, H.

Smith, M.

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

Song, J.

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

Sun, D.

Tian, J.

X. Qu, X. Li, X. Ma, R. Han, Z. Hu, X. Chen, D. Sun, R. Zhang, D. Chen, D. Chen, X. Chen, J. Liang, F. Cao, and J. Tian, “In vivo quantitative bioluminescence tomography using heterogenous and homogeneous mouse models,” Opt. Express 18, 13102–13113 (2010).
[CrossRef] [PubMed]

B. Zhang, X. Yang, C. Qin, D. Liu, S. Zhu, J. Feng, and J. Tian, “A trust region method in adaptive finite element framework for bioluminescence tomography,” Opt. Express 18, 6477–6491(2010).
[CrossRef] [PubMed]

K. Liu, J. Tian, X. Yang, Y. Lu, C. Qin, S. Zhu, and X. Zhang, “A fast bioluminescent source localization method based on generalized graph cuts with mouse model validations,” Opt. Express 18, 3732–3745 (2010).
[CrossRef] [PubMed]

J. Feng, K. Jia, C. Qin, G. Yan, S. Zhu, X. Zhang, J. Liu, and J. Tian, “Three-dimensional bioluminescence tomography based on Bayesian approach,” Opt. Express 17, 16834–16848(2009).
[CrossRef] [PubMed]

J. Tian, J. Xue, and Y. Dai, “A novel software platform for medical image processing and analyzing,” IEEE Trans. Inf. Technol. Biomed. 12, 800–812 (2008).
[CrossRef] [PubMed]

G. Yan, J. Tian, S. Zhu, Y. Dai, and C. Qin, “Fast cone beam CT image reconstruction using GPU hardware,” J. X-Ray Sci. Technol. 16, 225–234 (2008), http://www.3dmed.net/paper/YanGR_XRay_Fast%20cone-beam%20CT%20image%20reconstruction%20using%20GPU%20hardware.pdf.

Y. Lv, J. Tian, W. Cong, G. Wang, J. Luo, W. Yang, and H. Li, “A multilevel adaptive finite element algorithm for bioluminescence tomography,” Opt. Express 14, 8211–8223 (2006).
[CrossRef] [PubMed]

X. Ma, Z. Liu, J. Tian, and F. Wang, “Dual-modality monitoring of tumor response to cyclophosphamide therapy in mice with bioluminescence imaging and small-animal positron emission tomography,” Mol. Imaging (to be published).
[PubMed]

Tsien, R.

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Tung, C.

M. Funovics, R. Weissleder, and C. Tung, “Protease sensors for bioimaging,” Anal. Bioanal. Chem. 377, 956–963 (2003).
[CrossRef] [PubMed]

Wang, F.

X. Ma, Z. Liu, J. Tian, and F. Wang, “Dual-modality monitoring of tumor response to cyclophosphamide therapy in mice with bioluminescence imaging and small-animal positron emission tomography,” Mol. Imaging (to be published).
[PubMed]

Wang, G.

Wang, L. H. V.

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

Wang, L. V.

Wei, W.

G. Zhang, M. Safran, and W. Wei, “Bioluminescent imaging of Cdk2 inhibition in vivo,” Nat. Med. 10, 643–648 (2004).
[CrossRef] [PubMed]

Weissleder, R.

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

M. Funovics, R. Weissleder, and C. Tung, “Protease sensors for bioimaging,” Anal. Bioanal. Chem. 377, 956–963 (2003).
[CrossRef] [PubMed]

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

Willmann, J.

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

Windsor, D.

J. Grimm, D. Kirsch, and D. Windsor, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. USA 102, 14404–14409 (2005).
[CrossRef] [PubMed]

Xu, H.

J. Zhao, B. Lu, and H. Xu, “Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,” Hepatology 48, 265–275 (2008).
[CrossRef] [PubMed]

Xue, J.

J. Tian, J. Xue, and Y. Dai, “A novel software platform for medical image processing and analyzing,” IEEE Trans. Inf. Technol. Biomed. 12, 800–812 (2008).
[CrossRef] [PubMed]

Yan, G.

J. Feng, K. Jia, C. Qin, G. Yan, S. Zhu, X. Zhang, J. Liu, and J. Tian, “Three-dimensional bioluminescence tomography based on Bayesian approach,” Opt. Express 17, 16834–16848(2009).
[CrossRef] [PubMed]

G. Yan, J. Tian, S. Zhu, Y. Dai, and C. Qin, “Fast cone beam CT image reconstruction using GPU hardware,” J. X-Ray Sci. Technol. 16, 225–234 (2008), http://www.3dmed.net/paper/YanGR_XRay_Fast%20cone-beam%20CT%20image%20reconstruction%20using%20GPU%20hardware.pdf.

Yang, W.

Yang, X.

Zabner, J.

Zhang, B.

Zhang, G.

G. Zhang, M. Safran, and W. Wei, “Bioluminescent imaging of Cdk2 inhibition in vivo,” Nat. Med. 10, 643–648 (2004).
[CrossRef] [PubMed]

Zhang, R.

Zhang, X.

Zhao, J.

J. Zhao, L. Dong, and B. Lu, “Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis,” Gastroenterology 135, 956–968 (2008).
[CrossRef] [PubMed]

J. Zhao, B. Lu, and H. Xu, “Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,” Hepatology 48, 265–275 (2008).
[CrossRef] [PubMed]

Zhu, S.

Anal. Bioanal. Chem. (1)

M. Funovics, R. Weissleder, and C. Tung, “Protease sensors for bioimaging,” Anal. Bioanal. Chem. 377, 956–963 (2003).
[CrossRef] [PubMed]

Anal. Chem. (1)

R. Paulmurugan and S. Gambhir, “Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation,” Anal. Chem. 75, 1584–1589 (2003).
[CrossRef] [PubMed]

Cancer Res. (1)

R. Paulmurugan and S. Gambhir, “Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals,” Cancer Res. 65, 7413–7420 (2005).
[CrossRef] [PubMed]

Gastroenterology (1)

J. Zhao, L. Dong, and B. Lu, “Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis,” Gastroenterology 135, 956–968 (2008).
[CrossRef] [PubMed]

Hepatology (1)

J. Zhao, B. Lu, and H. Xu, “Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,” Hepatology 48, 265–275 (2008).
[CrossRef] [PubMed]

IEEE Trans. Inf. Technol. Biomed. (1)

J. Tian, J. Xue, and Y. Dai, “A novel software platform for medical image processing and analyzing,” IEEE Trans. Inf. Technol. Biomed. 12, 800–812 (2008).
[CrossRef] [PubMed]

J. X-Ray Sci. Technol. (1)

G. Yan, J. Tian, S. Zhu, Y. Dai, and C. Qin, “Fast cone beam CT image reconstruction using GPU hardware,” J. X-Ray Sci. Technol. 16, 225–234 (2008), http://www.3dmed.net/paper/YanGR_XRay_Fast%20cone-beam%20CT%20image%20reconstruction%20using%20GPU%20hardware.pdf.

Med. Phys. (2)

M. Schweiger, S. R. Arridge, M. Hiraoka, and D. T. Delpy, “The finite element method for the propagation of light in scattering media: boundary and source conditions,” Med. Phys. 22, 1779–1792 (1995).
[CrossRef] [PubMed]

W. Cong and K. Durairaj, “A Born-type approximation method for bioluminescence tomography,” Med. Phys. 33, 679–686(2006).
[CrossRef] [PubMed]

Mol. Imaging (1)

X. Ma, Z. Liu, J. Tian, and F. Wang, “Dual-modality monitoring of tumor response to cyclophosphamide therapy in mice with bioluminescence imaging and small-animal positron emission tomography,” Mol. Imaging (to be published).
[PubMed]

Nat. Biotechnol. (1)

V. Ntziachristos, J. Ripoll, L. H. V. Wang, and R. Weissleder, “Looking and listening to light: the evolution of whole-body photonic imaging,” Nat. Biotechnol. 23, 313–320 (2005).
[CrossRef] [PubMed]

Nat. Med. (3)

G. Luker, C. Pica, J. Song, K. Luker, and D. Piwnica-Worms, “Imaging 26S proteasome activity and inhibition in living mice,” Nat. Med. 9, 969–973 (2003).
[CrossRef] [PubMed]

G. Zhang, M. Safran, and W. Wei, “Bioluminescent imaging of Cdk2 inhibition in vivo,” Nat. Med. 10, 643–648 (2004).
[CrossRef] [PubMed]

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

Nat. Methods (1)

I. Remy and S. Michnick, “A highly sensitive protein-protein interaction assay based on Gaussia luciferase,” Nat. Methods 3, 977–979 (2006).
[CrossRef] [PubMed]

Nature (1)

J. Willmann, N. Bruggen, L. Dinkelborg, and S. Gambhir, “Molecular imaging in drug development,” Nature 7, 591–606(2008).
[CrossRef]

Opt. Express (8)

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

G. Wang, W. Cong, K. Durairaj, and M. Henry, “In vivo mouse studies with bioluminescence tomography,” Opt. Express 14, 7801–7809 (2006).
[CrossRef] [PubMed]

G. Wang, H. Shen, and W. Cong, “Temperature-modulated bioluminescence tomography,” Opt. Express 14, 7852–7871(2006).
[CrossRef] [PubMed]

Y. Lv, J. Tian, W. Cong, G. Wang, J. Luo, W. Yang, and H. Li, “A multilevel adaptive finite element algorithm for bioluminescence tomography,” Opt. Express 14, 8211–8223 (2006).
[CrossRef] [PubMed]

J. Feng, K. Jia, C. Qin, G. Yan, S. Zhu, X. Zhang, J. Liu, and J. Tian, “Three-dimensional bioluminescence tomography based on Bayesian approach,” Opt. Express 17, 16834–16848(2009).
[CrossRef] [PubMed]

K. Liu, J. Tian, X. Yang, Y. Lu, C. Qin, S. Zhu, and X. Zhang, “A fast bioluminescent source localization method based on generalized graph cuts with mouse model validations,” Opt. Express 18, 3732–3745 (2010).
[CrossRef] [PubMed]

B. Zhang, X. Yang, C. Qin, D. Liu, S. Zhu, J. Feng, and J. Tian, “A trust region method in adaptive finite element framework for bioluminescence tomography,” Opt. Express 18, 6477–6491(2010).
[CrossRef] [PubMed]

X. Qu, X. Li, X. Ma, R. Han, Z. Hu, X. Chen, D. Sun, R. Zhang, D. Chen, D. Chen, X. Chen, J. Liang, F. Cao, and J. Tian, “In vivo quantitative bioluminescence tomography using heterogenous and homogeneous mouse models,” Opt. Express 18, 13102–13113 (2010).
[CrossRef] [PubMed]

Phys. Med. Biol. (1)

G. Alexandrakis, F. Rannou, and A. Chatziioannou, “Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study,” Phys. Med. Biol. 50, 4225–4242 (2005).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA (4)

M. Safran, W. Kim, and F. O’Connell, “Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production,” Proc. Natl. Acad. Sci. USA 103, 105–110 (2006).
[CrossRef]

K. Luker, M. Smith, G. Luker, S. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms, “Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals,” Proc. Natl. Acad. Sci. USA 101, 12288–12293 (2004).
[CrossRef] [PubMed]

J. Grimm, D. Kirsch, and D. Windsor, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. USA 102, 14404–14409 (2005).
[CrossRef] [PubMed]

T. Jiang, E. Olson, Q. Nguyen, M. Roy, P. Jennings, and R. Tsien, “Tumor imaging by means of proteolytic activation of cell-penetrating peptides,” Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
[CrossRef] [PubMed]

Other (1)

S. S. Rao, The Finite Element Method in Engineering(Butterworth-Heinemann, 1999).

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Figures (7)

Fig. 1
Fig. 1

Our prototype BLT/micro-CT dual modality imaging system. 1, CCD camera; 2, x-ray detector; 3, mouse bed; 4, X-ray tube; 5, anesthesia machine; 6, rotation stage.

Fig. 2
Fig. 2

(a) Four view overlay images from bioluminescent images and corresponding photographs of the HCC-LM3-fLuc-bearing nude mouse without calibration. 0 ° , anterior– posterior; 90 ° , left lateral; 180 ° , posterior–anterior; 270 ° , right lateral image. (b) Absolute irradiance distribution on the mouse surface after mapping from two-dimensional bioluminescence data.

Fig. 3
Fig. 3

Time-dependent bioluminescent intensity decay curve.

Fig. 4
Fig. 4

(a) Four view overlay images from bioluminescent images and corresponding photographs of the HCC-LM3-fLuc bearing nude mouse after calibrating the bioluminescent intensity. 0 ° , anterior–posterior; 90 ° , left lateral; 180 ° , posterior– anterior; 270 ° , right lateral image. (b) Absolute irradiance distribution on the mouse surface after mapping from two-dimensional bioluminescence data with intensity calibration.

Fig. 5
Fig. 5

Micro-CT volume data of the HCC-LM3-fLuc-bearing nude mouse: (a) coronal image; (b) transect image; (c) sagittal image.

Fig. 6
Fig. 6

Four subfigures that are the reconstructed bioluminescence distribution at different angles based on the heterogeneous mouse without calibrating the bioluminescent intensity. The dark blue (half-moon-shaped) area is the liver. Numbers 1–4 label the prominent differences between the two reconstruction results.

Fig. 7
Fig. 7

Four subfigures that are the reconstructed bioluminescence distribution at different angles based on the heterogeneous mouse after calibrating the bioluminescent intensity. The dark blue (half-moon-shaped) area is the liver.

Tables (3)

Tables Icon

Table 1 Optical Parameters of Different Heterogeneous Mouse Tissues

Tables Icon

Table 2 Reconstruction Results With Calibration and Without Calibration

Tables Icon

Table 3 Reconstruction Results from Three Mice With Calibration and Without Calibration

Equations (12)

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

( D ( x ) Φ ( x ) ) + μ a ( x ) Φ ( x ) = S ( x ) ( x Ω ) ,
Φ ( x ) + 2 A ( x ; n , n ) D ( x ) ( v ( x ) · Φ ( x ) ) = 0 ( x Ω ) ,
A ( x ; n , n ) = 1 + R ( x ; n , n ) 1 R ( x ; n , n ) .
Q ( x ) = D ( x ) ( v · Φ ( x ) ) = Φ ( x ) 2 A ( x ; n , n ) ( x Ω ) .
A S p = Φ m
d ( x j ) = 1 N n = 1 N | Φ m ( x j ) Φ m ( x n ) | , x n Ω B ¯ r ( x j ) .
Φ C m ( x j ) = 1 N n = 1 N Φ m ( x n ) , x n Ω B ¯ r ( x j ) .
A S p = Φ C m .
min s inf S p s sup { A S p Φ C m Λ + λ η ( S p ) } ,
PS = { ( x , y , z ) | 12 < x < 24 , 14 < y < 24 , 28 < z < 40 , ( x , y , z ) Ω } .
1 6 | x 1 y 1 z 1 1 x 2 y 2 z 2 1 x 3 y 3 z 3 1 x 4 y 4 z 4 1 | ,
RA = i = 1 M V virtual i / j = 1 N V total j ,

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