Molecular Imaging and Biology

, Volume 12, Issue 5, pp 500–508 | Cite as

A Comparison Between Time Domain and Spectral Imaging Systems for Imaging Quantum Dots in Small Living Animals

  • Adam de la Zerda
  • Sunil Bodapati
  • Robert Teed
  • Meike L. Schipper
  • Shay Keren
  • Bryan R. Smith
  • Johnny S. T. Ng
  • Sanjiv Sam Gambhir
Research Article

Abstract

Purpose

We quantified the performance of time-domain imaging (TDI) and spectral imaging (SI) for fluorescence imaging of quantum dots (QDs) in three distinct imaging instruments: eXplore Optix (TDI, Advanced Research Technologies Inc.), Maestro (SI, CRi Inc.), and IVIS-Spectrum (SI, Caliper Life Sciences Inc.).

Procedure

The instruments were compared for their sensitivity in phantoms and living mice, multiplexing capabilities (ability to resolve the signal of one QD type in the presence of another), and the dependence of contrast and spatial resolution as a function of depth.

Results

In phantoms, eXplore Optix had an order of magnitude better sensitivity compared to the SI systems, detecting QD concentrations of ~40 pM in vitro. Maestro was the best instrument for multiplexing QDs. Reduction of contrast and resolution as a function of depth was smallest with eXplore Optix for depth of 2–6 mm, while other depths gave comparable results in all systems. Sensitivity experiments in living mice showed that the eXplore Optix and Maestro systems outperformed the IVIS-Spectrum.

Conclusion

TDI was found to be an order of magnitude more sensitive than SI at the expense of speed and very limited multiplexing capabilities. For deep tissue QD imaging, TDI is most applicable for depths between 2 and 6 mm, as its contrast and resolution degrade the least at these depths.

Key words

Time-domain imaging Frequency-domain imaging Quantum dots imaging Optical tomography Small animal imaging Molecular imaging 

References

  1. 1.
    Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580CrossRefPubMedGoogle Scholar
  2. 2.
    Lee J, Sevick-Muraca EM (2002) Three-dimensional fluorescence enhanced optical tomography using referenced frequency-domain photon migration measurements at emission and excitation wavelengths. J Opt Soc Am A, Opt Image Sci Vis 19:759–771CrossRefGoogle Scholar
  3. 3.
    Godavarty A, Eppstein MJ, Zhang C, Theru S, Thompson AB, Gurfinkel M, Sevick-Muraca EM (2003) Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera. Phys Med Biol 48:1701–1720CrossRefPubMedGoogle Scholar
  4. 4.
    McCormack E, Micklem DR, Pindard LE, Silden E, Gallant P, Belenkov A, Lorens JB, Gjertsen BT (2007) In vivo optical imaging of acute myeloid leukemia by green fluorescent protein: time-domain autofluorescence decoupling, fluorophore quantification, and localization. Mol Imaging 6:193–204PubMedGoogle Scholar
  5. 5.
    Kumar AT, Skoch J, Bacskai BJ, Boas DA, Dunn AK (2005) Fluorescence-lifetime-based tomography for turbid media. Opt Lett 30:3347–3349CrossRefPubMedGoogle Scholar
  6. 6.
    Arridge SR, Hebden JC (1997) Optical imaging in medicine: II. Modelling and reconstruction. Phys Med Biol 42:841–853CrossRefPubMedGoogle Scholar
  7. 7.
    Elson D, Requejo-Isidro J, Munro I, Reavell F, Siegel J, Suhling K, Tadrous P, Benninger R, Lanigan P, McGinty J, Talbot C, Treanor B, Webb S, Sandison A, Wallace A, Davis D, Lever J, Neil M, Phillips D, Stamp G, French P (2004) Time-domain fluorescence lifetime imaging applied to biological tissue. Photochem Photobiol Sci 3:795–801CrossRefPubMedGoogle Scholar
  8. 8.
    Cai W, Shin DW, Chen K, Gheysens K, Cao Q, Wang SX, Gambhir SS, Chen X (2006) Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett 6:669–676CrossRefPubMedGoogle Scholar
  9. 9.
    Li ZB, Cai W, Chen W (2007) Semiconductor quantum dots for in vivo imaging. J Nanosci Nanotechnol 7:2567–2581CrossRefPubMedGoogle Scholar
  10. 10.
    Gao X, Chung LW, Nie S (2007) Quantum dots for in vivo molecular and cellular imaging. Methods Mol Biol 374:135–145PubMedGoogle Scholar
  11. 11.
    Kim S, Lim Y,Soltesz E, De Grand A, Lee J, Nakayama A, Parker J, Mihaljevic T, Laurence R, Dor D, Cohn L, Bawendi M, Frangioni J (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22:93–97CrossRefPubMedGoogle Scholar
  12. 12.
    Cai W, Chen X (2008) Preparation of peptide-conjugated quantum dots for tumor vasculature-targeted imaging. Nat Protoc 3:89–96CrossRefPubMedGoogle Scholar
  13. 13.
    Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9:123–128CrossRefPubMedGoogle Scholar
  14. 14.
    Soo Choi H, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170CrossRefGoogle Scholar
  15. 15.
    Keren S, Gheysens O, Levin CS, Gambhir SS (2008) A comparison between a time domain and continuous wave small animal optical imaging system. Medical Imaging, IEEE Transactions on 27:58–63CrossRefGoogle Scholar
  16. 16.
    Lam S, Lesage F, Intes X (2005) Time domain fluorescent diffuse optical tomography: analytical expressions. Opt Express 13:2263–2275CrossRefPubMedGoogle Scholar
  17. 17.
    Miller PJ, Hoyt CC (1995) Multispectral imaging with a liquid crystal tunable filter. Presented at Optics in Agriculture, Forestry, and Biological Processing, Boston, MAGoogle Scholar
  18. 18.
    Levenson RM, Lynch DT, Kobayashi H, Backer JM, Backer MV (2008) Multiplexing with multispectral imaging: from mice to microscopy. Ilar J 49:78–88PubMedGoogle Scholar
  19. 19.
    Mansfield JR, Gossage KW, Hoyt CC, Levenson RM (2005) Autofluorescence removal, multiplexing, and automated analysis methods for in vivo fluorescence imaging. J Biomed Opt 10:41207CrossRefPubMedGoogle Scholar
  20. 20.
    Godavarty A, Sevick-Muraca EM, Eppstein MJ (2005) Three-dimensional fluorescence lifetime tomography. Med Phys 32:992–1000CrossRefPubMedGoogle Scholar
  21. 21.
    Chernomordik V, Gandjbakhche A, Lepore M, Esposito R, Delfino I (2001) Depth dependence of the analytical expression for the width of the point spread function (spatial resolution) in time-resolved transillumination. J Biomed Opt 6:441–445CrossRefPubMedGoogle Scholar

Copyright information

© Academy of Molecular Imaging 2009

Authors and Affiliations

  • Adam de la Zerda
    • 1
    • 2
  • Sunil Bodapati
    • 1
  • Robert Teed
    • 1
  • Meike L. Schipper
    • 1
  • Shay Keren
    • 1
  • Bryan R. Smith
    • 1
  • Johnny S. T. Ng
    • 4
  • Sanjiv Sam Gambhir
    • 1
    • 3
  1. 1.Department of RadiologyMolecular Imaging Program at Stanford (MIPS), The Bio-X ProgramStanfordUSA
  2. 2.Department of Electrical EngineeringStanford UniversityStanfordUSA
  3. 3.Department of BioengineeringStanford UniversityStanfordUSA
  4. 4.Stanford Linear Accelerator CenterStanford UniversityStanfordUSA

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