Abstract

We present a novel non-contact small animal fluorescent molecular tomography (FMT) imaging system. At the heart of the system is a new mirror-based imaging head that was designed to provide 360-degree measurement data from an entire animal surface in one step. This imaging head consists of two conical mirrors, which considerably reduce multiple back reflections between the animal and mirror surfaces. These back reflections are common in existing mirror-based imaging heads and tend to degrade the quality of raw measurement data. In addition, the introduction of a novel ray-transfer operator allows for the inclusion of the angular dependent data in the image reconstruction process, which results in higher image resolution. We describe in detail the system design and implementation of the hardware components as well as the transport-theory-based image reconstruction algorithm. Using numerical simulations, measurements on a well-defined phantom and a live animal, we evaluate the system performance and show the advantages of our approach.

© 2014 Optical Society of America

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    [CrossRef]
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    [CrossRef]
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    [CrossRef] [PubMed]

2013 (3)

R. W. Holt, F. Leblond, and B. W. Pogue, “Toward ideal imaging geometry for recovery independence fluorescence molecular tomography,” Proc. SPIE8574, 857403 (2013).
[CrossRef]

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

2012 (4)

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

E. Lapointe, J. Pichette, and Y. Bérubé-Lauzière, “A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging,” Rev. Sci. Instrum.83(6), 063703 (2012).
[CrossRef] [PubMed]

D. Kang and M. A. Kupinski, “Noise characteristics of heterodyne/homodyne frequency-domain measurements,” J. Biomed. Opt.17(1), 015002 (2012).
[CrossRef] [PubMed]

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

2010 (4)

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

H. K. Kim, J. H. Lee, and A. H. Hielscher, “PDE-constrained fluorescence tomography with the frequency-domain equation of radiative transfer,” IEEE J. Sel. Top. Quantum Electron.16(4), 793–803 (2010).
[CrossRef]

H. Gao and H. Zhao, “Multilevel bioluminescence tomography based on radiative transfer equation Part 1: l1 regularization,” Opt. Express18(3), 1854–1871 (2010).
[CrossRef] [PubMed]

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

2009 (2)

C. Li, G. S. Mitchell, J. Dutta, S. Ahn, R. M. Leahy, and S. R. Cherry, “A three-dimensional multispectral fluorescence optical tomography imaging system for small animals based on a conical mirror design,” Opt. Express17(9), 7571–7585 (2009).
[CrossRef] [PubMed]

H. K. Kim and A. H. Hielscher, “A PDE-constrained reduced Hessian SQP method for optical tomography based on the frequency domain equation of radiative transfer,” Inv. Probl.25, 015010 (2009).
[CrossRef]

2008 (1)

U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum.79(3), 034301 (2008).
[CrossRef] [PubMed]

2007 (1)

2006 (2)

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

2005 (1)

2003 (2)

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

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

2002 (1)

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

1997 (1)

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multipixel techniques for frequency-domain photon migration imaging,” Biotechnol. Prog.13(5), 669–680 (1997).
[CrossRef] [PubMed]

Achilefu, S.

Ahn, S.

Ale, A.

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

Barber, W. C.

Basevi, H. R. A.

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Bérubé-Lauzière, Y.

E. Lapointe, J. Pichette, and Y. Bérubé-Lauzière, “A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging,” Rev. Sci. Instrum.83(6), 063703 (2012).
[CrossRef] [PubMed]

Beuthan, J.

U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum.79(3), 034301 (2008).
[CrossRef] [PubMed]

Birgul, O.

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Bloch, S. R.

Borden, M. A.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Bremer, C.

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

Chandhanayingyong, C.

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Cherry, S. R.

Cong, W.

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Culver, J. P.

Dehghani, H.

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Deliolanis, N.

Durairaj, K.

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Dutta, J.

Flexman, M. L.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Frampton, J.

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Gander, J. W.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Gao, H.

Graves, E. E.

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

Guggenheim, J. A.

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Gulsen, G.

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Hahn, C.

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Hernandez, S. L.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Hielscher, A. H.

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

H. K. Kim, J. H. Lee, and A. H. Hielscher, “PDE-constrained fluorescence tomography with the frequency-domain equation of radiative transfer,” IEEE J. Sel. Top. Quantum Electron.16(4), 793–803 (2010).
[CrossRef]

H. K. Kim and A. H. Hielscher, “A PDE-constrained reduced Hessian SQP method for optical tomography based on the frequency domain equation of radiative transfer,” Inv. Probl.25, 015010 (2009).
[CrossRef]

U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum.79(3), 034301 (2008).
[CrossRef] [PubMed]

Holt, R. W.

R. W. Holt, F. Leblond, and B. W. Pogue, “Toward ideal imaging geometry for recovery independence fluorescence molecular tomography,” Proc. SPIE8574, 857403 (2013).
[CrossRef]

Huang, J.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Hyde, D.

Iwanczyk, J. S.

Jia, J.

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

Johung, T. B.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Kandel, J. J.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Kang, D.

D. Kang and M. A. Kupinski, “Noise characteristics of heterodyne/homodyne frequency-domain measurements,” J. Biomed. Opt.17(1), 015002 (2012).
[CrossRef] [PubMed]

Kim, H. K.

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

H. K. Kim, J. H. Lee, and A. H. Hielscher, “PDE-constrained fluorescence tomography with the frequency-domain equation of radiative transfer,” IEEE J. Sel. Top. Quantum Electron.16(4), 793–803 (2010).
[CrossRef]

H. K. Kim and A. H. Hielscher, “A PDE-constrained reduced Hessian SQP method for optical tomography based on the frequency domain equation of radiative transfer,” Inv. Probl.25, 015010 (2009).
[CrossRef]

Kim, Y.

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Kupinski, M. A.

D. Kang and M. A. Kupinski, “Noise characteristics of heterodyne/homodyne frequency-domain measurements,” J. Biomed. Opt.17(1), 015002 (2012).
[CrossRef] [PubMed]

Lampl, B. S.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Lapointe, E.

E. Lapointe, J. Pichette, and Y. Bérubé-Lauzière, “A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging,” Rev. Sci. Instrum.83(6), 063703 (2012).
[CrossRef] [PubMed]

Lasser, T.

Leahy, R. M.

Leblond, F.

R. W. Holt, F. Leblond, and B. W. Pogue, “Toward ideal imaging geometry for recovery independence fluorescence molecular tomography,” Proc. SPIE8574, 857403 (2013).
[CrossRef]

Lee, F. Y.

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Lee, J. H.

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

H. K. Kim, J. H. Lee, and A. H. Hielscher, “PDE-constrained fluorescence tomography with the frequency-domain equation of radiative transfer,” IEEE J. Sel. Top. Quantum Electron.16(4), 793–803 (2010).
[CrossRef]

Li, C.

Lin, Y.

Mitchell, G. S.

Montejo, L. D.

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

Nalcioglu, O.

Y. Lin, W. C. Barber, J. S. Iwanczyk, W. Roeck, O. Nalcioglu, and G. Gulsen, “Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system,” Opt. Express18(8), 7835–7850 (2010).
[CrossRef] [PubMed]

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Netz, U. J.

U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum.79(3), 034301 (2008).
[CrossRef] [PubMed]

Ntziachristos, V.

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, and V. Ntziachristos, “Free-space fluorescence molecular tomography utilizing 360 ° geometry projections,” Opt. Lett.32(4), 382–384 (2007).
[CrossRef] [PubMed]

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

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

Patwardhan, S. V.

Pichette, J.

E. Lapointe, J. Pichette, and Y. Bérubé-Lauzière, “A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging,” Rev. Sci. Instrum.83(6), 063703 (2012).
[CrossRef] [PubMed]

Pogue, B. W.

R. W. Holt, F. Leblond, and B. W. Pogue, “Toward ideal imaging geometry for recovery independence fluorescence molecular tomography,” Proc. SPIE8574, 857403 (2013).
[CrossRef]

Qian, X.

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Reichstein, A. R.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Reynolds, J. S.

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multipixel techniques for frequency-domain photon migration imaging,” Biotechnol. Prog.13(5), 669–680 (1997).
[CrossRef] [PubMed]

Ripoll, J.

N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, and V. Ntziachristos, “Free-space fluorescence molecular tomography utilizing 360 ° geometry projections,” Opt. Lett.32(4), 382–384 (2007).
[CrossRef] [PubMed]

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

Roeck, W.

Sarantopoulos, A.

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

Schulz, R. B.

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multipixel techniques for frequency-domain photon migration imaging,” Biotechnol. Prog.13(5), 669–680 (1997).
[CrossRef] [PubMed]

Shafiiha, R.

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Shen, H.

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Sirsi, S. R.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Soubret, A.

Staples, J. R.

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Styles, I. B.

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Thompson, A. B.

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

Troy, T. L.

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multipixel techniques for frequency-domain photon migration imaging,” Biotechnol. Prog.13(5), 669–680 (1997).
[CrossRef] [PubMed]

Tung, C. H.

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

Unlu, M. B.

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Vlachos, F.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Wang, A.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Wang, G.

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Weissleder, R.

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

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

Yamashiro, D. J.

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Zhao, H.

Biotechnol. Prog. (1)

J. S. Reynolds, T. L. Troy, and E. M. Sevick-Muraca, “Multipixel techniques for frequency-domain photon migration imaging,” Biotechnol. Prog.13(5), 669–680 (1997).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

H. K. Kim, J. H. Lee, and A. H. Hielscher, “PDE-constrained fluorescence tomography with the frequency-domain equation of radiative transfer,” IEEE J. Sel. Top. Quantum Electron.16(4), 793–803 (2010).
[CrossRef]

Int. J. Biomed. Imag. (1)

G. Wang, H. Shen, K. Durairaj, X. Qian, and W. Cong, “The first bioluminescence tomography system for simultaneous acquisition of multiview and multispectral data,” Int. J. Biomed. Imag.2006, 58601 (2006).

Inv. Probl. (1)

H. K. Kim and A. H. Hielscher, “A PDE-constrained reduced Hessian SQP method for optical tomography based on the frequency domain equation of radiative transfer,” Inv. Probl.25, 015010 (2009).
[CrossRef]

J. Biomed. Opt. (3)

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt.8(1), 111–120 (2003).
[CrossRef] [PubMed]

D. Kang and M. A. Kupinski, “Noise characteristics of heterodyne/homodyne frequency-domain measurements,” J. Biomed. Opt.17(1), 015002 (2012).
[CrossRef] [PubMed]

M. L. Flexman, F. Vlachos, H. K. Kim, S. R. Sirsi, J. Huang, S. L. Hernandez, T. B. Johung, J. W. Gander, A. R. Reichstein, B. S. Lampl, A. Wang, M. A. Borden, D. J. Yamashiro, J. J. Kandel, and A. H. Hielscher, “Monitoring early tumor response to drug therapy with diffuse optical tomography,” J. Biomed. Opt.17(1), 016014 (2012).
[CrossRef] [PubMed]

Meas. Sci. Technol. (1)

J. A. Guggenheim, H. R. A. Basevi, J. Frampton, I. B. Styles, and H. Dehghani, “Multi-modal molecular diffuse optical tomography system for small animal imaging,” Meas. Sci. Technol.24(10), 105405 (2013).
[CrossRef]

Med. Phys. (2)

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

A. Ale, R. B. Schulz, A. Sarantopoulos, and V. Ntziachristos, “Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors,” Med. Phys.37(5), 1976–1986 (2010).
[CrossRef] [PubMed]

Nat. Med. (1)

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

Opt. Express (4)

Opt. Lett. (1)

Proc. SPIE (2)

J. Jia, J. H. Lee, L. D. Montejo, H. K. Kim, and A. H. Hielscher, “Measurement operator for angular dependent photon propagation in contact-free optical tomography,” Proc. SPIE8578, 857815 (2013).
[CrossRef]

R. W. Holt, F. Leblond, and B. W. Pogue, “Toward ideal imaging geometry for recovery independence fluorescence molecular tomography,” Proc. SPIE8574, 857403 (2013).
[CrossRef]

Rev. Sci. Instrum. (2)

U. J. Netz, J. Beuthan, and A. H. Hielscher, “Multipixel system for gigahertz frequency-domain optical imaging of finger joints,” Rev. Sci. Instrum.79(3), 034301 (2008).
[CrossRef] [PubMed]

E. Lapointe, J. Pichette, and Y. Bérubé-Lauzière, “A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging,” Rev. Sci. Instrum.83(6), 063703 (2012).
[CrossRef] [PubMed]

Sarcoma (1)

C. Chandhanayingyong, Y. Kim, J. R. Staples, C. Hahn, and F. Y. Lee, “MAPK/ERK signaling in osteosarcomas, Ewing sarcoma and Chondrosarcomas: therapeutic implications and future directions,” Sarcoma2012, 404810 (2012).
[CrossRef] [PubMed]

Technol. Cancer Res. Treat. (1)

G. Gulsen, O. Birgul, M. B. Unlu, R. Shafiiha, and O. Nalcioglu, “Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals,” Technol. Cancer Res. Treat.5(4), 351–363 (2006).
[PubMed]

Other (1)

M. F. Modest, Radiative Heat Transfer (Academic Press, USA, 2003).

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Figures (16)

Fig. 1
Fig. 1

Overview of the FMT small animal imaging system. The light input unit consists of a mirror adaptor, a rotational gantry, a linear translation stage, and laser diodes emitting light at various wavelengths (not presented in this view). The two conical mirrors are the main components of the imaging head that collect light from the animal and transfer it to the ICCD camera system. The detection unit is composed of filter sets, a lens, and the intensified CCD camera system. A line laser on the rotational gantry is the component of the surface scanner.

Fig. 2
Fig. 2

Laser source positioning subunit (a) front view, and (b) side view

Fig. 3
Fig. 3

Basic concept of the double reflection mirror scheme

Fig. 4
Fig. 4

Parameters for the conical mirror design

Fig. 5
Fig. 5

Assembled conical mirrors, (a) front view, (b) backside view, and (c) an obtained image using the conical mirror pair with a soda can

Fig. 6
Fig. 6

(a) Components on a movable platform, (b) two different operation modes (left: imaging mode, right: scan mode), (c) a photo of surface scanning, and (d) a generated mouse mesh together with the reference block

Fig. 7
Fig. 7

Photos of the FMT small animal imaging system. Figure (a) shows the overall appearance of the system and the imaging chamber. The imaging chamber was carefully designed for easy access to the animal and the system components and allows for convenient experiment environment. Figure (b) shows the inside of the imaging chamber.

Fig. 8
Fig. 8

(a) Calibration bar, (b) an image of the calibration bar obtained with the double-conical-mirror imaging head and the ICCD camera, and (c) laser spot alignment with a calibration bar.

Fig. 9
Fig. 9

Light propagation from an object’s surface to the aperture of the camera through optical components

Fig. 10
Fig. 10

Back reflection simulation setup, (a) a cylindrical phantom and displacement of a point source on the surface, (b) single conical mirror scheme, (c) double conical mirror scheme and (d) density distribution of returned photons on the phantom surface

Fig. 11
Fig. 11

Comparison of back reflection levels as a function of the location of a point source on the cylinder surface (see Fig. 10(a))

Fig. 12
Fig. 12

Simulation results of the single conical mirror scheme depending on a point source positions (black dot). For clear visualization, each result at different source positions is auto scaled based on the individual total returned photon results in Fig. 11.

Fig. 13
Fig. 13

Simulation results of the double conical mirror scheme depending on a point source positions (black dot). For clear visualization, each result at different source positions is auto scaled based on the individual total returned photon results in Fig. 11.

Fig. 14
Fig. 14

Comparison of reconstruction results using angular dependent and angular averaged data respectively: (a) true source position; (b) angular averaged data result; (c) angular dependent data result

Fig. 15
Fig. 15

(a) A polyurethane solid phantom with an insertion hole (red circle), (b) reconstruction results from the experiment using a fluorescein solution as a fluorophore.

Fig. 16
Fig. 16

In vivo imaging of a tumor-bearing mouse: in a clockwise direction, (a) perspective, side, top, and rear views of FMT reconstruction results; (b) axial, sagittal, coronal views of CT imaging. In CT images, the areas enclosed by a green line and a yellow line present a soft tissue part and a bony part of the tumor respectively.

Tables (1)

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Table 1 Summary of mirror design specification

Equations (5)

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dJ( r , s )=ψ( r , s ) n s dΩdA
J( r )=dA Ω A ( r ) ψ( r , s ) n s dΩ
z( r D )= J( r ) d A D = n dA d A D Ω A ( r ) ψ( r , s ) s dΩ =Q( r , s )ψ( r , s )
[ ( Ω )+ μ a x + μ s x + μ a xm + iϖ c ] ψ x ( r,Ω,ϖ )= 4π p( Ω ,Ω ) ψ x ( r, Ω ,ϖ )d Ω
[ ( Ω )+ μ a m + μ s m + iϖ c ] ψ m ( r,Ω,ϖ )= 4π p( Ω ,Ω ) ψ m ( r, Ω ,ϖ )d Ω + 1 4π η μ a xm ϕ( r,ϖ ) ( 1ϖτ( r ) )

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