OSA's Digital Library

Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics


  • Editor: Gregory W. Faris
  • Vol. 4, Iss. 8 — Jul. 30, 2009

Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations

Frederic Leblond, Hamid Dehghani, Dax Kepshire, and Brian W. Pogue  »View Author Affiliations

JOSA A, Vol. 26, Issue 6, pp. 1444-1457 (2009)

View Full Text Article

Enhanced HTML    Acrobat PDF (826 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



In vivo tissue imaging using near-infrared light suffers from low spatial resolution and poor contrast recovery because of highly scattered photon transport. For diffuse optical tomography (DOT) and fluorescence molecular tomography (FMT), the resolution is limited to about 5–10% of the diameter of the tissue being imaged, which puts it in the range of performance seen in nuclear medicine. This paper introduces the mathematical formalism explaining why the resolution of FMT can be significantly improved when using instruments acquiring fast time-domain optical signals. This is achieved through singular-value analysis of the time-gated inverse problem based on weakly diffused photons. Simulations relevant to mouse imaging are presented showing that, in stark contrast to steady-state imaging, early time-gated intensities (within 200 ps or 400 ps ) can in principle be used to resolve small fluorescent targets (radii from 1.5 to 2.5 mm ) separated by less than 1.5 mm .

© 2009 Optical Society of America

OCIS Codes
(170.3010) Medical optics and biotechnology : Image reconstruction techniques
(170.3660) Medical optics and biotechnology : Light propagation in tissues
(170.6920) Medical optics and biotechnology : Time-resolved imaging
(170.6960) Medical optics and biotechnology : Tomography
(260.2510) Physical optics : Fluorescence

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: March 3, 2009
Manuscript Accepted: April 27, 2009
Published: May 27, 2009

Virtual Issues
Vol. 4, Iss. 8 Virtual Journal for Biomedical Optics

Frederic Leblond, Hamid Dehghani, Dax Kepshire, and Brian W. Pogue, "Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations," J. Opt. Soc. Am. A 26, 1444-1457 (2009)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. V. Ntziachristos, C. Bremer, C. Tung, and R. Weissleder, “Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT),” Acad. Radiol. 9, S323-S325 (2002). [CrossRef] [PubMed]
  2. V. Ntziachristos, C. H. Tung, C. Bremer, and R. Weissleder, “Fluorescence molecular tomography resolves protease activity in vivo,” Nat. Med. 8, 757-760 (2002). [CrossRef] [PubMed]
  3. V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging,” Eur. Radiol. 13, 195-208 (2003). [PubMed]
  4. R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9, 123-128 (2003). [CrossRef] [PubMed]
  5. Y. Chen, G. Zheng, Z. H. Zhang, D. Blessington, M. Zhang, H. Li, Q. Liu, L. Zhou, X. Intes, S. Achilefu, and B. Chance, “Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal studies,” Opt. Lett. 28, 2070-2072 (2003). [CrossRef] [PubMed]
  6. V. Ntziachristos, J. Ripoll, L. 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]
  7. E. E. Graves, R. Weissleder, and V. Ntziachristos, “Fluorescence molecular imaging of small animal tumor models,” Curr. Molec. Med. 4, 419-430 (2004). [CrossRef]
  8. V. Ntziachristos, E. A. Schellenberger, J. Ripoll, D. Yessayan, E. Graves, A. Bogdanov, Jr., L. Josephson, and R. Weissleder, “Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate,” Proc. Natl. Acad. Sci. U.S.A. 101, 12294-12299 (2004). [CrossRef] [PubMed]
  9. J. Grimm, D. G. Kirsch, S. D. Windsor, C. F. Bender Kim, P. M. Santiago, V. Ntziachristos, T. Jacks, and R. Weissleder, “Use of gene expression profiling to direct in vivo molecular imaging of lung cancer,” Proc. Natl. Acad. Sci. U.S.A. 102, 14404-14409 (2005). [CrossRef] [PubMed]
  10. X. Montet, V. Ntziachristos, J. Grimm, and R. Weissleder, “Tomographic fluorescence mapping of tumor targets,” Cancer Res. 65, 6330-6336 (2005). [CrossRef] [PubMed]
  11. V. Ntziachristos, “Fluorescence molecular imaging,” Annu. Rev. Biomed. Eng. 8, 1-33 (2006). [CrossRef] [PubMed]
  12. D. E. Sosnovik, M. Nahrendorf, N. Deliolanis, M. Novikov, E. Aikawa, L. Josephson, A. Rosenzweig, R. Weissleder, and V. Ntziachristos, “Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo,” Circulation 115, 1384-1391 (2007). [CrossRef] [PubMed]
  13. A. Garofalakis, G. Zacharakis, H. Meyer, N. Economou, C. Mamalaki, J. Papamatheakis, D. Kioussis, V. Ntziachristos, and J. Ripoll, “Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice with noncontact fluorescence molecular tomography,” Mol. Imaging 6, 96-107 (2007). [PubMed]
  14. A. C. Corlu, R. Choe, T. Durduran, M. A. Rosen, M. Schweiger, S. R. Arridge, M. D. Schnall, and A. G. Yodh, “Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans,” Opt. Express 15, 6696-6716 (2007). [CrossRef] [PubMed]
  15. C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45-47 (2008). [CrossRef]
  16. A. Koenig, L. Herve, V. Josserand, M. Berger, J. Boutet, A. Da Silva, J.-M. Dinten, P. Peltie, J.-L. Coll, and P. Rizo, “In vivo mice lung tumor follow-up with fluorescence diffuse optical tomography,” J. Biomed. Opt. 13, 011008 (2008). [CrossRef] [PubMed]
  17. M. A. O'Leary, D. A. Boas, B. Chance, and A. G. Yodh, “Experimental images of heterogeneous turbid media by frequency-domain diffusing-photon tomography,” Opt. Lett. 20, 426-428 (1995). [CrossRef] [PubMed]
  18. V. Ntziachristos, A. G. Yodh, M. Schnall, and B. Chance, “Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement,” Proc. Natl. Acad. Sci. U.S.A. 97, 2767-2772 (2000). [CrossRef] [PubMed]
  19. B. W. Pogue, M. S. Patterson, H. Jiang, and K. D. Paulsen, “Initial assessment of a simple system for frequency domain diffuse optical tomography,” Phys. Med. Biol. 40, 1709-1729 (1995). [CrossRef] [PubMed]
  20. B. W. Pogue, T. McBride, U. Osterberg, and K. Paulsen, “Comparison of imaging geometries for diffuse optical tomography of tissue,” Opt. Express 4, 270-286 (1999). [CrossRef] [PubMed]
  21. J. P. Culver, V. Ntziachristos, M. J. Holboke, and A. G. Yodh, “Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis,” Opt. Lett. 26, 701-703 (2001). [CrossRef]
  22. E. E. Graves, J. P. Culver, J. Ripoll, R. Weissleder, and V. Ntziachristos, “Singular-value analysis and optimization of experimental parameters in fluorescence molecular tomography,” J. Opt. Soc. Am. A 21, 231-241 (2004). [CrossRef]
  23. T. Lasser and V. Ntziachristos, “Optimization of360 degrees projection fluorescence molecular tomography,” Med. Image Anal. 11, 389-399 (2007). [CrossRef] [PubMed]
  24. H. Xu, H. Dehghani, B. W. Pogue, R. F. Springett, K. D. Paulsen, and J. F. Dunn, “Near-infrared imaging in the small animal brain: optimization of fiber positions,” J. Biomed. Opt. 8, 102-110 (2003). [CrossRef] [PubMed]
  25. S. R. Arridge and W. R. B. Lionheart, “Nonuniqueness in diffusion-based optical tomography,” Opt. Lett. 23, 882-884 (1998). [CrossRef]
  26. V. Ntziachristos, A. G. Yodh, M. D. Schnall, and B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347-354 (2002). [CrossRef] [PubMed]
  27. B. W. Pogue and K. D. Paulsen, “High-resolution near-infrared tomographic imaging simulations of rat cranium using a priori MRI structural information,” Opt. Lett. 23, 1716-1718 (1998). [CrossRef]
  28. B. Brooksby, H. Dehghani, B. W. Pogue, and K. D. Paulsen, “Near infrared (NIR) tomography breast image reconstruction with a priori structural information from MRI: algorithm development for reconstructing heterogeneities,” IEEE J. Sel. Top. Quantum Electron. 9, 199-209 (2003). [CrossRef]
  29. X. Intes, C. Maloux, M. Guven, T. Yazici, and B. Chance, “Diffuse optical tomography with physiological and spatial a priori constraints,” Phys. Med. Biol. 49, N155-N163 (2004). [CrossRef] [PubMed]
  30. P. K. Yalavarthy, B. W. Pogue, H. Dehghani, C. M. Carpenter, S. Jiang, and K. D. Paulsen, “Structural information within regularization matrices improves near infrared diffuse optical tomography,” Opt. Express 15, 8043-8058 (2007). [CrossRef] [PubMed]
  31. A. Corlu, R. Choe, T. Durduran, K. Lee, M. Schweiger, S. R. Arridge, E. M. C. Hillman, and A. G. Yodh, “Diffuse optical tomography with spectral constraints and wavelength optimization,” Appl. Opt. 44, 2082-2093 (2005). [CrossRef] [PubMed]
  32. S. Srinivasan, B. W. Pogue, S. Jiang, H. Dehghani, and K. D. Paulsen, “Spectrally constrained chromophore and scattering NIR tomography improves quantification and robustness of reconstruction,” Appl. Opt. 44, 1858-1869 (2004). [CrossRef]
  33. M. J. Niedre, R. de Kleine, E. Aikawa, D. G. Kirsch, R. Weissleder, and V. Ntziachristos, “Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo,” Proc. Natl. Acad. Sci. U.S.A. 105, 19126-19131 (2008). [CrossRef] [PubMed]
  34. J. C. J. Paasschens, “Solution of the time-dependent Boltzmann equation,” Phys. Rev. E 56, 1135-1141 (1997). [CrossRef]
  35. M. Xu, W. Cai, M. Lax, and R. R. Alfano, “Photon migration in turbid media using a cumulant approximation to radiative transfer,” Phys. Rev. E 65, 066609 (2002). [CrossRef]
  36. G. M. Turner, G. Zacharakis, A. Soubret, J. Ripoll, and V. Ntziachristos, “Complete-angle projection diffuse optical tomography by use of early photons,” Opt. Lett. 30, 409-411 (2005). [CrossRef] [PubMed]
  37. G. M. Turner, A. Soubret, and V. Ntziachristos, “Inversion with early photons,” Med. Phys. 34, 1405-1411 (2007). [CrossRef] [PubMed]
  38. D. Kepshire, N. Mincu, M. Hutchins, J. Gruber, H. Dehghani, J. Hypnarowski, F. Leblond, M. Khayat, and B. W. Pogue, “A microCT guided fluorescence tomography system for small animal molecular imaging,” Rev. Sci. Instrum. 80, 043701 (2009). [CrossRef] [PubMed]
  39. S. R. Arridge, “Optical tomography in medical imaging,” Inverse Probl. 15, R41-R93 (1999). [CrossRef]
  40. M. Brambilla, L. Spinelli, A. Pifferi, A. Torricelli, and R. Cubeddu, “Time-resolved scanning system for double reflectance and transmittance fluorescence imaging of diffusive media,” Rev. Sci. Instrum. 79, 013103 (2008). [CrossRef] [PubMed]
  41. V. Ntziachristos and R. Weissleder, “Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation,” Opt. Lett. 26, 893-895 (2001). [CrossRef]
  42. A. Soubret, J. Ripoll, and V. Ntziachristos, “Accuracy of fluorescent tomography in the presence of heterogeneities: Study of the normalized Born ratio,” IEEE Trans. Med. Imaging 24, 1377-1386 (2005). [CrossRef] [PubMed]
  43. F. Leblond, N. Mincu, N. Robitaille, S. Fortier, M. Khayat, and B. W. Pogue, “Why acquiring excitation data improves the quality of reconstructed fluorescence images for highly heterogeneous diffusive media,” in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2008), paper PDPBTuF9.
  44. F. Leblond, S. Fortier, and M. P. Friedlander, “Diffuse optical fluorescence tomography using data acquired in transmission,” Proc. SPIE 6431, 643106 (2007). [CrossRef]
  45. V. Ntziachristos, X. Ma, A. G. Yodh, and B. Chance, “Multichannel photon counting instrument for spatially resolved near infrared spectroscopy,” Rev. Sci. Instrum. 70, 193-201 (1999). [CrossRef]
  46. V. Ntziachristos and B. Chance, “Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy,” Med. Phys. 28, 1115-1124 (2001). [CrossRef] [PubMed]
  47. M. Niedre, G. M. Turner, and V. Ntziachristos, “Time-resolved imaging of optical coefficients through murine chest cavities,” J. Biomed. Opt. 11, 064017 (2006). [CrossRef]
  48. S. Lam, F. Lesage, and X. Intes, “Time domain fluorescent diffuse optical tomography: analytical expressions,” Opt. Express 13, 2263-2275 (2005). [CrossRef] [PubMed]
  49. A. T. N. Kumar, S. B. Raymond, G. Boverman, D. A. Boas, and B. J. Bacskai, “Time resolved fluorescence tomography of turbid media based on lifetime contrast,” Opt. Express 14, 12255-12270 (2006). [CrossRef] [PubMed]
  50. A. T. N. Kumar, S. B. Raymond, A. K. Dunn, B. J. Bacskai, and D. A. Boas, “A time domain fluorescence tomography system for small animal imaging,” IEEE Trans. Med. Imaging 27, 1152-1163 (2008). [CrossRef] [PubMed]
  51. V. Y. Soloviev, K. B. Tahir, J. McGinty, D. S. Elson, M. A. A. Neil, P. M. W. French, and S. R. Arridge, “Fluorescence lifetime imaging by using time-gated data acquisition,” Appl. Opt. 46, 7384-7391 (2007). [CrossRef] [PubMed]
  52. H. Dehghani, B. W. Pogue, J. Shudong, B. Brooksby, and K. D. Paulsen, “Three-dimensional optical tomography: resolution in small-object imaging,” Appl. Opt. 42, 3117-3128 (2003). [CrossRef] [PubMed]
  53. H. Dehghani, B. Brooksby, K. Vishwanath, B. W. Pogue, and K. D. Paulsen, “The effects of internal refractive index variation in near-infrared optical tomography: a finite element modelling approach,” Phys. Med. Biol. 48, 2713-2727 (2003). [CrossRef] [PubMed]
  54. E. M. Sevick-Muraca and C. L. Burch, “Origin of phosphorescence signals reemitted from tissues,” Opt. Lett. 19, 1928-1930 (1994). [CrossRef] [PubMed]
  55. J. Riley, M. Hassan, V. Chernomordik, and A. Gandjbakhche, “Choice of data types in time resolved fluorescence enhanced diffuse optical tomography,” Med. Phys. 34, 4890-4900 (2007). [CrossRef]
  56. M. P. Friedlander and K. Hatz, “Computing nonnegative tensor factorizations,” Optim. Methods Software 23, 631-647 (2008). [CrossRef]
  57. P. C. Hansen, Rank-Deficient and Discrete Ill-Posed Problems (Society for Industrial and Applied Mathematics, 1998). [CrossRef]
  58. H. Dehghani, B. W. Pogue, S. Jiang, B. Brooksby, and K. D. Paulsen, “Three dimensional optical tomography: resolution in small object imaging,” Appl. Opt. 42, 135-145 (2003). [CrossRef] [PubMed]
  59. M. Gao, G. Lewis, G. M. Turner, A. Soubret, and V. Ntziachristos, “Effects of background fluorescence in fluorescence molecular tomography,” Appl. Opt. 44, 5468-5474 (2005). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited