Abstract

By integrating the clinically used endoscope with the emerging Cerenkov luminescence imaging (CLI) technology, a new endoscopic Cerenkov luminescence imaging (ECLI) system was developed. The aim is to demonstrate the potential of translating CLI to clinical studies of gastrointestinal (GI) tract diseases. We systematically evaluated the feasibility and performance of the developed ECLI system with a series of in vitro and pseudotumor experiments. The ECLI system is comprised of an electron multiplying charge coupled device (EMCCD) camera coupled with a clinically used endoscope via an optical adapter. A 1951-USAF test board was used to measure the white-light lateral resolution, while a homemade test chart filled with 68Ga was employed to measure the CL lateral resolution. Both in vitro and pseudotumor experiments were conducted to obtain the sensitivity of the ECLI system. The results were validated with that of CLI using EMCCD only, and the relative attenuation ratio of the ECLI system was calculated. Results showed that The white-light lateral resolution of the ECLI system was 198 µm, and the luminescent lateral resolution was better than 1 mm. Sensitivity experiments showed a theoretical sensitivity of 0.186KBq/μl (5.033×103μCi/μl) and 1.218KBq/μl (32.922×103μCi/μl) for the in vitro and pseudotumor studies, respectively. The relative attenuation ratio of ECLI to CLI was about 96%. The luminescent lateral resolution of the ECLI system was comparable with that of positron emission tomography (PET). The pseudotumor study illustrated the feasibility and applicability of the ECLI system in living organisms, indicating the potential for translating the CLI technology to the clinic.

© 2014 Optical Society of America

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References

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2013 (3)

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer J. Clin. 63(1), 11–30 (2013).
[Crossref] [PubMed]

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

2012 (4)

2011 (3)

Y. Xu, H. Liu, and Z. Cheng, “Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging,” J. Nucl. Med. 52(12), 2009–2018 (2011).
[Crossref] [PubMed]

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

2010 (3)

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

2009 (1)

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

2006 (1)

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

2005 (2)

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Y. Li, M. Jiang, and G. Wang, “Computational optical biopsy,” Biomed. Eng. Online 4(1), 36 (2005).
[Crossref] [PubMed]

2004 (1)

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

2000 (1)

Z. Zhang, “A flexible new technique for camera calibration,” IEEE Trans. Pattern Analysis Machine Intelligence 22(11), 1330–1334 (2000).
[Crossref]

Antoch, G.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Barghouth, G.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Bauer, S.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Beattie, B. J.

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

Bockisch, A.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Boschi, F.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Bossuyt, P. M.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

Bray, F.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Buchin, M. P.

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

Buckley, C.

Calandrino, R.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

Calderan, L.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Carpenter, C. M.

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

Center, M. M.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Cheng, Z.

S.-R. Kothapalli, H. Liu, J. C. Liao, Z. Cheng, and S. S. Gambhir, “Endoscopic imaging of Cerenkov luminescence,” Biomed. Opt. Express 3(6), 1215–1225 (2012).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

Y. Xu, H. Liu, and Z. Cheng, “Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging,” J. Nucl. Med. 52(12), 2009–2018 (2011).
[Crossref] [PubMed]

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

D’Ambrosio, D.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Debatin, J. F.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Dekker, E.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

Dizendorf, E.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Dobbs, J.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Dothager, R. S.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Fenzi, A.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

Ferlay, J.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Forman, D.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Freudenberg, L. S.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Gambhir, S. S.

S.-R. Kothapalli, H. Liu, J. C. Liao, Z. Cheng, and S. S. Gambhir, “Endoscopic imaging of Cerenkov luminescence,” Biomed. Opt. Express 3(6), 1215–1225 (2012).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Girkin, J. M.

Goerres, G. W.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Goiffon, R. J.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Grimm, J.

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

Han, P.

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Hany, T. F.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Harpstrite, S.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Jackson, E.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Jain, S.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Jemal, A.

R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer J. Clin. 63(1), 11–30 (2013).
[Crossref] [PubMed]

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Jiang, H.

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

Jiang, M.

Y. Li, M. Jiang, and G. Wang, “Computational optical biopsy,” Biomed. Eng. Online 4(1), 36 (2005).
[Crossref] [PubMed]

Kanja, J.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Kothapalli, S.-R.

Kuehl, H.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Kyrish, M.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Leyvraz, S.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Li, Y.

Y. Li, M. Jiang, and G. Wang, “Computational optical biopsy,” Biomed. Eng. Online 4(1), 36 (2005).
[Crossref] [PubMed]

Liao, J. C.

Liu, H.

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

S.-R. Kothapalli, H. Liu, J. C. Liao, Z. Cheng, and S. S. Gambhir, “Endoscopic imaging of Cerenkov luminescence,” Biomed. Opt. Express 3(6), 1215–1225 (2012).
[Crossref] [PubMed]

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

Y. Xu, H. Liu, and Z. Cheng, “Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging,” J. Nucl. Med. 52(12), 2009–2018 (2011).
[Crossref] [PubMed]

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Luthi, F.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Marengo, M.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Mullins, J.

Naishadham, D.

R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer J. Clin. 63(1), 11–30 (2013).
[Crossref] [PubMed]

Ogirala, A.

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

Pestalozzi, B.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Piwnica-Worms, D.

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Pratx, G.

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

Reitsma, J. B.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

Renzing-Koehler, K.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Richards-Kortum, R.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Saunter, C. D.

Sbarbati, A.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Schnyder, P.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Schuette, J.

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Semprini, S.

Siegel, R.

R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer J. Clin. 63(1), 11–30 (2013).
[Crossref] [PubMed]

Spinelli, A. E.

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

Stoker, J.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

Stupp, R.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Sun, C.

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

Thorek, D. L.

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

Tkaczyk, T. S.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

van Deventer, S. J.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

van Rijn, J. C.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

von Schulthess, G. K.

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

Wang, G.

Y. Li, M. Jiang, and G. Wang, “Computational optical biopsy,” Biomed. Eng. Online 4(1), 36 (2005).
[Crossref] [PubMed]

Wang, X.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Ward, E.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Xing, B.

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Xing, L.

C. M. Carpenter, C. Sun, G. Pratx, H. Liu, Z. Cheng, and L. Xing, “Radioluminescent nanophosphors enable multiplexed small-animal imaging,” Opt. Express 20(11), 11598–11604 (2012).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

Xu, Y.

Y. Xu, H. Liu, and Z. Cheng, “Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging,” J. Nucl. Med. 52(12), 2009–2018 (2011).
[Crossref] [PubMed]

Yu, D.

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

Zhang, X.

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Zhang, Z.

Z. Zhang, “A flexible new technique for camera calibration,” IEEE Trans. Pattern Analysis Machine Intelligence 22(11), 1330–1334 (2000).
[Crossref]

Am. J. Gastroenterol. (1)

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101(2), 343–350 (2006).
[Crossref] [PubMed]

Biomed. Eng. Online (1)

Y. Li, M. Jiang, and G. Wang, “Computational optical biopsy,” Biomed. Eng. Online 4(1), 36 (2005).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

CA Cancer J. Clin. (2)

R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer J. Clin. 63(1), 11–30 (2013).
[Crossref] [PubMed]

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer J. Clin. 61(2), 69–90 (2011).
[Crossref] [PubMed]

Eur. J. Nucl. Med. Mol. Imaging (2)

G. W. Goerres, R. Stupp, G. Barghouth, T. F. Hany, B. Pestalozzi, E. Dizendorf, P. Schnyder, F. Luthi, G. K. von Schulthess, and S. Leyvraz, “The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate,” Eur. J. Nucl. Med. Mol. Imaging 32(2), 153–162 (2005).
[Crossref] [PubMed]

F. Boschi, L. Calderan, D. D’Ambrosio, M. Marengo, A. Fenzi, R. Calandrino, A. Sbarbati, and A. E. Spinelli, “In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation,” Eur. J. Nucl. Med. Mol. Imaging 38(1), 120–127 (2011).
[Crossref] [PubMed]

IEEE Trans. Pattern Analysis Machine Intelligence (1)

Z. Zhang, “A flexible new technique for camera calibration,” IEEE Trans. Pattern Analysis Machine Intelligence 22(11), 1330–1334 (2000).
[Crossref]

J. Biomed. Opt. (1)

M. Kyrish, J. Dobbs, S. Jain, X. Wang, D. Yu, R. Richards-Kortum, and T. S. Tkaczyk, “Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective,” J. Biomed. Opt. 18(9), 096003 (2013).
[Crossref] [PubMed]

J. Nucl. Med. (3)

Y. Xu, H. Liu, and Z. Cheng, “Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging,” J. Nucl. Med. 52(12), 2009–2018 (2011).
[Crossref] [PubMed]

H. Liu, C. M. Carpenter, H. Jiang, G. Pratx, C. Sun, M. P. Buchin, S. S. Gambhir, L. Xing, and Z. Cheng, “Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study,” J. Nucl. Med. 53(10), 1579–1584 (2012).
[Crossref] [PubMed]

G. Antoch, J. Kanja, S. Bauer, H. Kuehl, K. Renzing-Koehler, J. Schuette, A. Bockisch, J. F. Debatin, and L. S. Freudenberg, “Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors,” J. Nucl. Med. 45(3), 357–365 (2004).
[PubMed]

Nat. Med. (1)

D. L. Thorek, A. Ogirala, B. J. Beattie, and J. Grimm, “Quantitative imaging of disease signatures through radioactive decay signal conversion,” Nat. Med. 19(10), 1345–1350 (2013).
[Crossref] [PubMed]

Opt. Express (1)

Phys. Med. Biol. (2)

A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, A. Sbarbati, and F. Boschi, “Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers,” Phys. Med. Biol. 55(2), 483–495 (2010).
[Crossref] [PubMed]

F. Boschi, A. E. Spinelli, D. D’Ambrosio, L. Calderan, M. Marengo, and A. Sbarbati, “Combined optical and single photon emission imaging: preliminary results,” Phys. Med. Biol. 54(23), L57–L62 (2009).
[Crossref] [PubMed]

PLoS ONE (1)

R. S. Dothager, R. J. Goiffon, E. Jackson, S. Harpstrite, and D. Piwnica-Worms, “Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems,” PLoS ONE 5(10), e13300 (2010).
[Crossref] [PubMed]

Small (1)

H. Liu, X. Zhang, B. Xing, P. Han, S. S. Gambhir, and Z. Cheng, “Radiation-Luminescence-Excited Quantum Dots for in vivo Multiplexed Optical Imaging,” Small 6(10), 1087–1091 (2010).
[Crossref] [PubMed]

Other (3)

D. L. J Nucl MedJ Nucl MedThorek, C. Riedl, and J. Grimm, “Clinical Cerenkov Luminescence Imaging of 18F-FDG,” J. Nucl. Med., jnumed. 113.127266 (2014).

S. V. Hodgson, W. D. Foulkes, C. Eng, and E. R. Maher, “Gastrointestinal System,” in A Practical Guide to Human Cancer Genetics(Springer, 2014), pp. 47–87.

A. W. Glaudemans and A. Signore, “Nuclear Medicine Imaging Modalities: Bone Scintigraphy, PET-CT, SPECT-CT,” in Bone Metastases(Springer, 2014), pp. 71–94.

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Figures (6)

Fig. 1
Fig. 1 (a) Photograph of each component of the ECLI system; (b) Schematic diagram of the optical path of the ECLI system; (c) Photograph of the ECLI system; (d) Photograph of the traditional CLI system.
Fig. 2
Fig. 2 (a) Average intensities of each group; (b) Bhattacharyya factors of each group.
Fig. 3
Fig. 3 Results of the spatial lateral resolution evaluation experiment. (a) Photograph of the 1951 USAF test board; (b) Photographic image acquired by the ECLI system; (c) Calibrated image of (b); (d) Sketch of the homemade test board used in the CL resolution evaluation experiment; (e) Fusion images of each area in the test chart; (f) Quantitative line profile (red line in area 1).
Fig. 4
Fig. 4 Results of the in vitro sensitivity experiment and attenuation rate study. (a) Fusion images of the in vitro sensitivity experiment; (b) Linearity analysis between the average intensity of the region of interest versus the activity of 68Ga; (c) Fusion images acquired by the traditional CLI system; (d) Linearity analysis between the attenuation rates versus the activity of 68Ga.
Fig. 5
Fig. 5 Results of the mouse-bearing pseudotumor experiment. (a) Mouse was imaged by the traditional CLI system, and the pseudotumor area is outlined in red; (b) Regional image of the pseudotumor taken by the ECLI system (pseudo-colored). Left column depicts the white-light (WL) images, the middle shows the luminescent images (CL), and the fusion images with pseudo-color are on the right; (c) Linear relationship between the average intensity of ROIs versus the activity of 68Ga for the pseudotumor experiment.
Fig. 6
Fig. 6 Schematic sketch of the clinical application of the ECLI system in the future.

Equations (2)

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R= 1 2 i+(j1)/6
AR= | I E I T | I T

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