Skip to main content
SpringerLink
Log in

A Nonparametric Method for Analysis of Fluorescence Emission in Combined Time and Wavelength Dimensions

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

We report a method for accurate recovery of tissue intrinsic fluorescence emission characteristics, including fluorescence lifetimes and spectral profiles, from complex two-dimensional (spectro-temporal) emission waveforms. Most algorithms for analysis of fluorescence data address separately the characteristics of either spectral emission or fluorescence relaxation time. We developed a novel nonparametric analytical method that allows for identification and estimation of the intrinsic Fluorescent Impulse Response Kernel (FIRK) simultaneously in time and wavelength dimensions. Modeling of FIRK was based on the characteristics of spectro-temporal fluorescence waveforms. Due to the decaying behavior of the fluorescence, a linear combination of discrete Laguerre functions was used to model the fluorescence response in time. To address the large variability of spectral profiles of distinct fluorophores, a discrete Fourier series expansion was used to model the variation of fluorescence intensity across wavelength. The proposed method was validated on synthetic fluorescence data and data measured from fluorescence lifetime standards and tissue endogenous fluorescent biomolecules. We determined that this method provides a direct recovery of the two-dimensional FIRK and accurate estimation (residual error < 6%) of a broad range of fluorescence lifetimes including the sub-nanosecond range. The FIRK retrieved using this method can further facilitate modeling and recognition of pathological and physiological conditions in tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Andersson-Engels, S., J. Johansson, and S. Svanberg. The use of time-resolved fluorescence for diagnosis of atherosclerotic plaque and malignant tumors. Spectrochim. Acta 40A:1203–1210, 1990.

    Google Scholar 

  2. Badea, M., and L. Brand. Time resolved fluorescence measurements. Methods Enzymol. 61:378–425, 1979.

    CAS  PubMed  Google Scholar 

  3. Baraga, J. J., P. Taroni, Y. D. Park, K. An, A. Maestri, L. L. Tong, R. P. Rava, C. Kittrell, R. R. Dasari, and M. S. Feld. Ultraviolet laser induced fluorescence of human aorta. Spectrochim. Acta 45:95–99, 1989.

    Article  Google Scholar 

  4. Beechem, J. M., E. Gratton, M. Ameloot, J. R. Knutson, and L. Brand. The global analysis of fluorescence intensity and anisotropy decay data: Second-generation theory and programs. In: Topics in Fluorescence Spectroscopy, edited by J. R. Lakowicz. New York: Plenum Press, 1991, pp. 241–305.

    Google Scholar 

  5. Bruce, E. N. Biomedical Signal Processing and Signal Modeling. New York: Wiley Series in Telecommunications and Signal Processing, 2001.

    Google Scholar 

  6. Cubeddu, R., D. Comelli, D. C. D’Andrea, P. Taroni, and G. Valentini. Time-resolved fluorescence imaging in biology and medicine. J. Phys. D: Appl. Phys. 35:61–76, 2002.

    Article  Google Scholar 

  7. Faddeev, D. K., and V. N. Faddeeva, Computational Methods of Linear Algebra. San Francisco: W.H. Freeman, 1963.

    Google Scholar 

  8. Fang, Q., T. Papaioannou, J. A. Jo, R. Vaitha, and K. Shastry. Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics. Rev. Sci. Instrum. 75:151–162, 2004.

    Article  CAS  Google Scholar 

  9. Gafni, A., R. L. Modlin, and L. Brand. Analysis of fluorescent decay curves by means of the Laplace transformation. Biophys. J. 15:263–280, 1975.

    CAS  PubMed  Google Scholar 

  10. Grinvald, A. The use of standards in the analysis of fluorescence decay data. Anal. Biochem. 30:261–279, 1976.

    Google Scholar 

  11. Grinvald, A., and I. Z. Steinberg. On the analysis of fluorescence decay kinetics by the method of least squares. Anal. Biochem. 59:583–598, 1974.

    Article  CAS  PubMed  Google Scholar 

  12. Glanzmann, T., J. P. Ballini, H. van den Bergh, and G. Wagnieres. Time-resolved spectrofluorometer for clinical tissue characterization during endoscopy. Rev. Sci. Instrum. 70:4067–4077, 1999.

    Article  CAS  Google Scholar 

  13. Golub, G. H., and C. F. Van Loan. Matrix Computations. Baltimore: The Johns Hopkins University Press, 1983.

    Google Scholar 

  14. Jo, J. A., Q. Fang, T. Papaioannou, and L. Marcu. Fast model-free deconvolution of fluorescence decay for analysis of biological systems. J. Biomed. Opt. 9(4):743–752, 2004.

    Article  CAS  PubMed  Google Scholar 

  15. Khoo, M. Physiological Control Systems: Analysis, Simulation and Estimation. New York: IEEE Press Series in Biomedical Engineering, 2000.

    Google Scholar 

  16. Kalaba, R. E., and N. Rasakhoo. Algorithms for generalized inverses. J. Opt. Th. Appl. 48:427–435, 1986.

    Google Scholar 

  17. Kalaba, R. E., and K. Springarn. Control, Identification and Input Optimization. New York: Plenum Press, 1982.

    Google Scholar 

  18. Lakowicz, J. R. Principles of Fluorescent Spectroscopy, 2nd ed. New York: Kluwer Academic/Plenum, 1999.

    Google Scholar 

  19. Lampert, R. A., L. A. Chewter, and D. Phillips. Standards for nanosecond fluorescence decay time measurement. Anal. Chem. 55:68–73, 1983.

    CAS  Google Scholar 

  20. Maarek, J. M. I., L. Marcu, W. J. Snyder, and W. S. Grundfest. Time-resolved fluorescence spectra of arterial fluorescent compounds reconstruction with Laguerre expansion technique. Photochem. Photobiol. 71:178–187, 2000.

    CAS  PubMed  Google Scholar 

  21. Marcu, L., M. C. Fishbein, J. M. Maarek, and W. S. Grundfest. Discrimination of human coronary artery atherosclerotic lipid-rich lesions by time-resolved laser-induced fluorescence spectroscopy. Atheroscl. Thromb. Vasc. Biol. 21:1244–1250, 2001.

    CAS  Google Scholar 

  22. Marcu, L., W. S. Grundfest, and M. C. Fishbein. Time-resolved laser-induced fluorescence spectroscopy for staging atherosclerotic lesions. In: Fluorescence in Biomedicine, edited by M. A. Mycek, and B. Pogue. New York: Marcel Dekker, 2003, pp. 397–430.

    Google Scholar 

  23. Manly, B. F. J. Randomization, Bootstrap, and Monte Carlo Methods in Biology. New York: Wiley, 1997.

    Google Scholar 

  24. Marmarelis, V. Z. Identification of nonlinear biological systems using Laguerre expansion of kernels. Ann. Biomed. Eng. 21:573–589, 1993.

    CAS  PubMed  Google Scholar 

  25. Marmarelis, V. Z. Modeling methodology for nonlinear physiological systems. Ann. Biomed. Eng. 25:239–251, 1997.

    CAS  PubMed  Google Scholar 

  26. McGown, L. B. Fluorescence lifetime filtering. Anal. Chem. 61:839–847, 1989.

    Google Scholar 

  27. O’Connor, D. V., and D. Phillips. Time-Correlated Single Photon Counting. London: Academic Press, 1984.

    Google Scholar 

  28. O’Connor, D. V., W. R. Ware, and J. C. Andre. Deconvolution of fluorescence decay curves. A critical comparison of techniques. J. Phys. Chem. 83:1333–1343, 1979.

    CAS  Google Scholar 

  29. Proakis, J. G., and D. G. Manolakis. Digital Signal Processing. Principles, Algorithms, and Applications. Upper Saddle River: Prentice Hall, 1996.

    Google Scholar 

  30. Proakis, J. G. Digital Communications, 4th ed. McGraw-Hill, 2001.

  31. Stavridi, M., V. Z. Marmarelis, and W. S. Grundfest. Spectro-temporal studies of Xe–Cl excimer laser induced arterial wall fluorescence. Med. Eng. Phys. 17:595–601, 1995.

    CAS  PubMed  Google Scholar 

  32. Tellinghuisen, J., and C. W. Wilkerson, Jr. Bias and precision in the estimation of exponential decay parameters from sparse data. Anal. Chem. 65:1240–1246, 1993.

    CAS  Google Scholar 

  33. Vallotton, P., and R. Vogel. Parameter recovery in frequency-domain time-resolved fluorescent spectroscopy; resolution off the prototropic forms of 5-carboxyfluorescein in the physiological pH range. J. Fluoresc. 10:325–332, 2000.

    CAS  Google Scholar 

  34. Ware, W. R., L. J. Doemeny, and T. L. Nemzek. Deconvolution of fluorescence and phosphorescence decay curves. A least squares method. J. Phys. Chem. 77:2038–2048, 1973.

    CAS  Google Scholar 

  35. Webb, S. E. D., Y. Gu, S. Leveque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, and P. M. W. French. A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning. Rev. Sci. Instrum. 73:1898–1907, 2002.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089

    V. Ivanova Olga, Laura Marcu PhD & C. K. Khoo Michael

  2. Biophotonics Research and Technology Development, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048

    V. Ivanova Olga & Laura Marcu PhD

  3. Department of Electrical-Engineering, University of Southern California, Los Angeles, CA, 90089

    Laura Marcu PhD

  4. Biophotonics Research Lab., Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd. Davis G149A, Los Angeles, CA, 90048

    Laura Marcu PhD

Authors
  1. V. Ivanova Olga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Marcu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. K. Khoo Michael
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura Marcu PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olga, V.I., Marcu, L. & Michael, C.K.K. A Nonparametric Method for Analysis of Fluorescence Emission in Combined Time and Wavelength Dimensions. Ann Biomed Eng 33, 531–544 (2005). https://doi.org/10.1007/s10439-005-2512-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-005-2512-5

Keywords

Search

Navigation