OSA's Digital Library

Optics Express

Optics Express

  • Editor: Michael Duncan
  • Vol. 13, Iss. 7 — Apr. 4, 2005
  • pp: 2564–2577

Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice

Sachin V. Patwardhan, Sharon R. Bloch, Samuel Achilefu, and Joseph P. Culver  »View Author Affiliations

Optics Express, Vol. 13, Issue 7, pp. 2564-2577 (2005)

View Full Text Article

Enhanced HTML    Acrobat PDF (818 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



We present a fast scanning fluorescence optical tomography system for imaging the kinetics of probe distributions through out the whole body of small animals. Configured in a plane parallel geometry, the system scans a source laser using a galvanometer mirror pair (τswitch~1ms) over flexible source patterns, and detects excitation and emission light using a high frame rate low noise, 5 MHz electron multiplied charge-coupled device (EMCCD) camera. Phantom studies were used to evaluate resolution, linearity, and sensitivity. Time dependent (δt=2.2 min.) in vivo imaging of mice was performed following injections of a fluorescing probe (indocyanine green). The capability to detect differences in probe delivery route was demonstrated by comparing an intravenous injection, versus an injection into a fat pocket (retro orbital injection). Feasibility of imaging the distribution of tumor-targeted molecular probes was demonstrated by imaging a breast tumor-specific near infrared polypeptide in MDA MB 361 tumor bearing nude mice. A tomography scan, at 24 hour post injection, revealed preferential uptake in the tumor relative to surrounding tissue.

© 2005 Optical Society of America

OCIS Codes
(110.6960) Imaging systems : Tomography
(260.2510) Physical optics : Fluorescence

ToC Category:
Research Papers

Original Manuscript: January 20, 2005
Revised Manuscript: March 19, 2005
Published: April 4, 2005

Sachin Patwardhan, Sharon Bloch, Samuel Achilefu, and Joseph Culver, "Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice," Opt. Express 13, 2564-2577 (2005)

Sort:  Journal  |  Reset  


  1. Achilefu, S., R.B. Dorshow, J.E. Bugaj and R. Rajagopalan, "Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging," Invest. Radiol. 35, 479-485 (2000). [CrossRef] [PubMed]
  2. Bremer, C., S. Bredow, U. Mahmood, R. Weissleder and C.H. Tung, "Optical imaging of matrix metalloproteinase-2 activity in tumors: Feasibility study in a mouse model," Radiol. 221, 523-529 (2001). [CrossRef]
  3. Bugaj, J.E., S. Achilefu, R.B. Dorshow and R. Rajagopalan, "Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform," J. Biomed. Opt. 6, 122-133 (2001). [CrossRef] [PubMed]
  4. Pogue, B.W., S.L. Gibbs, B. Chen and M. Savellano, "Fluorescence imaging in vivo: Raster scanned point-source imaging provides more accurate quantification than broad beam geometries," Tech. in Cancer Research & Treatment 3, 15-21 (2004).
  5. Hebden, J.C. and K.S. Wong, "Time-Resolved Optical Tomography," Appl. Opt. 32, 372-380 (1993). [CrossRef] [PubMed]
  6. Barbour, R.L., H.L. Graber, J.W. Chang, S.L.S. Barbour, P.C. Koo and R. Aronson, "MRI-guided optical tomography: Prospects and computation for a new imaging method," IEEE Compu. Sc. & Engg. 2, 63-77 (1995). [CrossRef]
  7. Pogue, B.W., 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]
  8. Oleary, M.A., 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]
  9. Gonatas, C.P., M. Ishii, J.S. Leigh and J.C. Schotland, "Optical Diffusion Imaging Using a Direct Inversion Method," Phys. Rev. E 52, 4361-4365 (1995). [CrossRef]
  10. Ntziachristos, V. and R. Weissleder, "Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media," Med. Phys. 29, 803-809 (2000). [CrossRef]
  11. Ntziachristos, V., C.H. Tung, C. Bremer and R. Weissleder, "Fluorescence molecular tomography resolves protease activity in vivo," Nat. Med. 8, 757-760 (2002). [CrossRef] [PubMed]
  12. Ntziachristos, V., 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, 323-325 (2002). [CrossRef]
  13. Graves, E.E., J. Ripoll, R. Weissleder and V. Ntziachristos, "A submillimeter resolution fluorescence molecular imaging system for small animal imaging," Med. Phys. 30, 901-911 (2003). [CrossRef] [PubMed]
  14. Graves, E.E., R. Weissleder and V. Ntziachristos, "Fluorescence molecular imaging of small animal tumor models," Current Molecular Medicine 4, 419-430 (2004). [CrossRef] [PubMed]
  15. Ntziachristos, V., E.A. Schellenberger, J. Ripoll, D. Yessayan, E. Graves, A. Bogdanov, L. Josephson and R. Weissleder, "Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate," Proc. National Academy of Sciences of the United States of America 101, 12294-12299 (2004). [CrossRef]
  16. Culver, J.P., R. Choe, M.J. Holboke, L. Zubkov, T. Durduran, A. Slemp, V. Ntziachristos, B. Chance and A.G. Yodh, "Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging," Med. Phys. 30, 235-247 (2003). [CrossRef] [PubMed]
  17. Schulz, R.B., J. Ripoll and V. Ntziachristos, "Experimental fluorescence tomography of tissues with noncontact measurements," IEEE Trans. Med. Imaging 23, 492-500 (2004). [CrossRef] [PubMed]
  18. Godavarty, A., M.J. Eppstein, C.Y. Zhang, S. Theru, A.B. Thompson, M. Gurfinkel and E.M. Sevick-Muraca, "Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera," Phys. Med. Biol. 48, 1701-1720 (2003). [CrossRef] [PubMed]
  19. Godavarty, A., C. Zhang, M.J. Eppstein and E.M. Sevick-Muraca, "Fluorescence-enhanced optical imaging of large phantoms using single and simultaneous dual point illumination geometries," Med. Phys. 31, 183-190 (2004). [CrossRef] [PubMed]
  20. Schmitz, C.H., H.L. Graber, H.B. Luo, I. Arif, J. Hira, Y.L. Pei, A. Bluestone, S. Zhong, R. Andronica, I. Soller, N. Ramirez, S.L.S. Barbour and R.L. Barbour, "Instrumentation and calibration protocol for imaging dynamic features in dense-scattering media by optical tomography," Appl. Opt. 39, 6466-6486 (2000). [CrossRef]
  21. Ntziachristos, V. 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]
  22. Oleary, M.A., D.A. Boas, X.D. Li, B. Chance and A.G. Yodh, "Fluorescence lifetime imaging in turbid media," Opt. Lett. 21, 158-160 (1996). [CrossRef]
  23. Haskell, R.C., L.O. Svaasand, T.T. Tsay, T.C. Feng and M.S. McAdams, "Boundary-Conditions For the Diffusion Equation in Radiative- Transfer," J. Opt. Soc. Am. A - Optics Image Science and Vision 11, 2727-2741 (1994). [CrossRef]
  24. Patterson, M.S., B. Chance and B.C. Wilson, "Time resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties," Appl. Opt. 28, 2331-2336 (1989). [CrossRef] [PubMed]
  25. Kak, A.C. and M. Slaney, "Principles of Computerized Tomographic Imaging," New York: IEEE Press (1988).
  26. Eccles, S.A., W.J. Court, G.A. Box, C.J. Dean and R.G. Melton, "Regression of Established Breast-Carcinoma Xenografts with Antibody-Directed Enzyme Prodrug Therapy against C-Erbb2 P185," Cancer Res. 54, 5171-5177 (1994). [PubMed]
  27. Hillman, E.M.C., D.A. Boas, A.M. Dale and A.K. Dunn, "Laminar optical tomography: demonstration of millimeter-scale depth-resolved imaging in turbid media," Opt. Lett. 29, 1650-1652 (2004). [CrossRef] [PubMed]
  28. Dunn, A. and D. Boas, "Transport-based image reconstruction in turbid media with small source-detector separations," Opt. Lett. 25, 1777-1779 (2000). [CrossRef]
  29. Li, X.D., T. Durduran, A.G. Yodh, B. Chance and D.N. Pattanayak, "Diffraction tomography for biochemical imaging with diffuse- photon density waves," Optics Letters 22, 573-575 (1997). [CrossRef] [PubMed]
  30. Schotland, J.C., "Continuous-wave diffusion imaging," J. Opt. Soc. Am. A - Optics Image Science and Vision 14, 275-279 (1997). [CrossRef]
  31. Markel, V.A. and J.C. Schotland, "Inverse problem in optical diffusion tomography. I. Fourier- Laplace inversion formulas," J. Opt. Soc. Am. A - Optics Image Science and Vision 18, 1336-1347 (2001). [CrossRef]
  32. Matson, C.L., N. Clark, L. McMackin and J.S. Fender, "Three-dimensional tumor localization in thick tissue with the use of diffuse photon-density waves," Appl. Opt. 36, 214-220 (1997). [CrossRef] [PubMed]
  33. Durduran, T., J.P. Culver, M.J. Holboke, X.D. Li, L. Zubkov, B. Chance, D.N. Pattanayak and A.G. Yodh, "Algorithms for 3D localization and imaging using near-field diffraction tomography with diffuse light," Opt. Exp. 4, 247-262 (1999). [CrossRef]
  34. Achilefu, S. and R.B. Dorshow, "Dynamic and Continuous Monitoring of Renal and Hepatic Functions with Exogenous Markers," Topics in Current Chemistry. Springer-Verlag: Berlin Heidelberg (2002).
  35. Intes, X., J. Ripoll, Y. Chen, S. Nioka, A.G. Yodh and B. Chance, "In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green," Med. Phys. 30, 1039-1047 (2003). [CrossRef] [PubMed]
  36. Ntziachristos, V., A.G. Yodh, M. Schnall and B. Chance, "Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement," Proc. National Academy of Sciences of the United States of America 97, 2767-2772 (2000). [CrossRef]
  37. Cuccia, D.J., F. Bevilacqua, A.J. Durkin, S. Merritt, B.J. Tromberg, G. Gulsen, H. Yu, J. Wang and O. Nalcioglu, "In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration," Appl. Opt. 42, 2940-50 (2003). [CrossRef] [PubMed]
  38. Gurfinkel, M., A.B. Thompson, W. Ralston, T.L. Troy, A.L. Moore, T.A. Moore, J.D. Gust, D. Tatman, J.S. Reynolds, B. Muggenburg, K. Nikula, R. Pandey, R.H. Mayer, D.J. Hawrysz and E.M. Sevick-Muraca, "Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: A case study," Photochem. Photobiol. 72, 94-102 (2000). [CrossRef] [PubMed]
  39. Srinivasan, S., B.W. Pogue, H. Dehghani, S.D. Jiang, X.M. Song and K.D. Paulsen, "Improved quantification of small objects in near-infrared diffuse optical tomography," J. Biomed. Opt. 9, 1161-1171 (2004). [CrossRef] [PubMed]
  40. Pogue, B.W., C. Willscher, T.O. McBride, U.L. Osterberg and K.D. Paulsen, "Contrast-detail analysis for detection and characterization with near-infrared diffuse tomography," Med. Phys. 27, 2693-2700 (2000). [CrossRef]
  41. Dehghani, H., B.W. Pogue, S.D. Jiang, B. Brooksby and K.D. Paulsen, "Three-dimensional optical tomography: resolution in small-object imaging," Appl. Opt. 42, 3117-3128 (2003). [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