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Laser-induced autofluorescence for medical diagnosis

Journal of Fluorescence volume 4, pages 17–40 (1994)Cite this article

Abstract

The naturally occurring autofluorescence of cells and tissues is based on biomolecules containing intrinsic fluorophores, such as porphyrins, the amino acids tryptophan and tyrosine, and the coenzymes NADH, NADPH, and flavins. Coenzymes fluoresce in the blue/green spectral region (fluorecence lifetimes: 0.5–6 ns) and are highly sensitive indicators of metabolic function. Steadystate and time-resolved blue-green autofluorescence is, therefore, an appropriate measure of the function of the respiratory chain as well as of cellular and tissue damage. Autofluorescence in the yellow/red spectral region is based mainly on endogenous porphyrins and metalloporphyrins, such as coproporphyrin, protoporphyrin (fluorescence lifetime of porphyrin monomers: >10 ns), and Zn-protoporphyrin (2 ns). Various pathological microorganisms such asPropionibacterium acnes, Pseudomonas aeruginosa, Actinomyces odontolyticus, Bacteroides intermedius, andSaccharomyces cerevisiae are able to synthesize large amounts of these fluorophores and can therefore be located. This permits fluorescence-based detection of a variety of diseases, including early-stage dental caries, dental plaque, acne vulgaris, otitis externa, and squamous cell carcinoma. The sensitivity of noninvasive autofluorescence diagnostics can be enhanced by time-gated fluorescence measurements using an appropriate time delay between ultrashort laser excitation and detection. For example, videocameras with ultrafast shutters, in the nanosecond region, can be used to create “caries images” of the teeth. Alternatively, autofluorescence can be enhanced by stimulating protoporphyrin biosynthesis with the exogenously administered porphyrin precursor 5-aminolevulinic acid (ALA). The fluorophore protoporphyrin IX (PP IX) is photolabile and photodynamically active. Irradiation of PP IX-containing tissue results in cytotoxic reactions which correlate with modifications in fluorescence due to photobleaching and singlet oxygen-dependent photoproduct formation. Therefore, on-line autofluorescence measurements during the phototreatment can yield information on the efficiency of ALA-based photodynamic therapy.

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References

  1. D. Creed (1984)Photochem. Photobiol. 39, 537–562.

    Google Scholar 

  2. D. Creed (1984)Photochem. Photobiol. 39, 563–575.

    Google Scholar 

  3. A. White et al. (1978)Principles of Biochemistry, McGraw-Hill, New York.

    Google Scholar 

  4. National Academy of Sciences (1984)Specifications and Criteria of Biochemical Compounds, 3rd ed., Sigma Chemical Company, St. Louis, MO.

    Google Scholar 

  5. J. Lakowicz (1986)Principles of Fluorescence Spectroscopy, Plenum Press, New York.

    Google Scholar 

  6. S. D. Kozikowski, L. J. Wolfram, and R. R. Alfano (1984)IEEE-QE 12, 1379–1382.

    Google Scholar 

  7. J. H. Aiken and C. W. Hui (1991)Anal. Lett. 24, 167–180.

    Google Scholar 

  8. R. R. Alfano et al. (1984)IEEE-QE 20, 1507–1511.

    Google Scholar 

  9. A. R. Holzwarth and T. A. Roelofs (1992)J. Photochem. Photobiol. B 15, 45–62.

    Google Scholar 

  10. H. Schneckenburger and W. Schmidt (1992)J. Photochem. Photobiol. B 13, 190–193.

    Google Scholar 

  11. C. Lee (1974)Biochem. Biophys. Res. Commun. 60, 838–843.

    Google Scholar 

  12. J. M. Salmon et al. (1982)Photochem. Photobiol. 36, 585–593.

    Google Scholar 

  13. P. Galland and H. Senger (1988)J. Photochem. Photobiol. B 1, 277–294.

    Google Scholar 

  14. M. Sun, T. A. Moore, and P. S. Song (1972)J. Am. Chem. Soc. 94, 1730–1740.

    Google Scholar 

  15. K. Koeniget al. (1994) In W. Waidelich (Ed.),Laser. Optoelectronics in Medicine (in press).

  16. H. Schneckenburger and K. Koenig (1992)Opt. Eng. 31, 1447–1451.

    Google Scholar 

  17. B. Chance et al. (1962)Science 137, 499–508.

    Google Scholar 

  18. B. Chance and F. F. Josis (1959)Nature 184, 195–196.

    Google Scholar 

  19. C. Y. Guezennec et al. (1991)Eur. J. Appl. Physiol. 63, 36.

    Google Scholar 

  20. A. Mayevski (1984)Brain Res. Rev. 7, 49–68.

    Google Scholar 

  21. W. Lohmann and E. Paul (1988)Naturwissenschaften 75, 201–202.

    Google Scholar 

  22. W. Lohmann et al. (1990)Z. Naturforsch. 45c, 1063–1066.

    Google Scholar 

  23. H. Schneckenburger, A. Rueck, and O. Haferkamp (1989)Anal. Chim. Acta 227, 227–233.

    Google Scholar 

  24. H. Schneckenburger, P. Gessler, and I. Pavenstaedt-Grupp (1992)J. Histchem. Cytochem. 40, 1573–1578.

    Google Scholar 

  25. P. S. Song (1980) in H. Senger (Ed.),The Blue Light Syndrome, Springer, Berlin, pp. 157–171.

    Google Scholar 

  26. K. Koeniget al. (1994)SPIE Budapest 2086 (in press).

  27. D. R. Doiron and O. J. Gomer (1983)Porphyrin Localization and Treatment of Tumours, Alan R Liss, New York.

    Google Scholar 

  28. J. C. Kennedy and R. H. Pottier (1992)J. Photochem. Photobiol. B 14, 275–292.

    Google Scholar 

  29. A. K. Gupta and T. F. Anderson (1987)J. Am. Acad. Dermatol. 17, 703–734.

    Google Scholar 

  30. J. W. Young and E. T. Conte (1991)Int. J. Dermatol. 30, 399–404.

    Google Scholar 

  31. D. Fuchs et al. (1990)AIDS 4, 341–344.

    Google Scholar 

  32. H. N. Shah et al. (1979)Biochem. J. 180, 45–50.

    Google Scholar 

  33. C. E. Cornelius and G. D. Ludwig (1967)J. Invest. Derm. 49, 368–370.

    Google Scholar 

  34. B. Kjeldstad, A. Johnsson, and S. Sandberg (1984)Arch. Dermatol. Res. 276, 396–400.

    Google Scholar 

  35. A. Johnsson, B. Kjeldstad, and T. B. Melo (1987)Arch. Dermatol. Res. 279, 190–193.

    Google Scholar 

  36. J. S. Brazier (1986)J. Appl. Bacteriol. 60, 121–126.

    Google Scholar 

  37. R. L. Harms, D. R. Martinez, and V. M. Griego (1986)Appl. Eviron. Microbiol. 51, 481–486.

    Google Scholar 

  38. R. de la Fuente et al. (1986)FEMS Microbiol Lett. 35, 183–188.

    Google Scholar 

  39. K. Koenig, W. Dietel, and H. Schubert (1989)Neoplasma 36, 135–138.

    Google Scholar 

  40. G. Weagle et al. (1988)J. Photochem. Photobiol. B 2, 313–320.

    Google Scholar 

  41. K. Koeniget al. (1994)SPIE Budapest 2078 (in press).

  42. B. A. Tapper et al. (1975)J. Sci. Food Agr. 26, 277–284.

    Google Scholar 

  43. A. Policard (1924)C.R. Soc. Biol. 91, 1423–1424.

    Google Scholar 

  44. S. Bommer (1927)Klin. Wochenschr. 24, 1142–1144.

    Google Scholar 

  45. H. Gougerot and A. Patte (1939)Bull. Soc. Franc. Derm. Syph. 46, 288–295.

    Google Scholar 

  46. F. Rochese (1954)Oral Surg. Oral Med. Oral Pathol. 7, 353–362.

    Google Scholar 

  47. D. Sharvill (1955)Trans. St. John's Hosp. Derm. Soc. (London) 34, 32–36.

    Google Scholar 

  48. F. N. Ghadially (1960)J. Pathol. Bact. 80, 345–361.

    Google Scholar 

  49. F. N. Ghadially and W. J. P. Neish (1960)Nature 188, 1124.

    Google Scholar 

  50. F. N. Ghadially, W. J. P. Neish, and H. C. Dawkins (1963)J. Pathol. Bact. 85, 77–92.

    Google Scholar 

  51. D. M. Harris and J. Werkhaven (1987)Lasers Surg. Med. 7, 467–472.

    Google Scholar 

  52. Y. Yuanlong et al. (1987)Lasers Surg. Med. 7, 528–532.

    Google Scholar 

  53. W. Dietel, K. Koenig,and P. Dorn (1988)Laser-Induced Autofluorescence of Tumors, PDT School, Berlin.

    Google Scholar 

  54. K. Koenig, J. Hemmer, and H. Schneckenburger (1992) in P. Spinelli, M. DalFante, and R. Marchesini (Eds.),Photodynamic Therapy and Biomedical Lasers, Elsevier, Amsterdam, pp. 903–906.

    Google Scholar 

  55. R. Margalit and S. Cohnes (1985)J. Inorg. Biochem. 25, 187–195.

    Google Scholar 

  56. S. Sommer, C. Rimington, and J. Moan (1984)FEBS 172, 267–271.

    Google Scholar 

  57. S. Montan and L. G. Stroemblad (1987)Lasers Life Sci. 1, 275–285.

    Google Scholar 

  58. J. Hung et al. (1991)Lasers Surg. Med. 11, 99–105.

    Google Scholar 

  59. G. C. Tang and R. R. Alfano (1989)Lasers Surg. Med. 9, 290–295.

    Google Scholar 

  60. S. Svanberget al. (1994)SPIE Budapest 2081 (in press).

  61. I. Formanek et al. (1977)Arch. Dermatol. Res. 259, 169–176.

    Google Scholar 

  62. D. Fanta et al. (1981)Arch. Dermatol. Res. 271, 127–133.

    Google Scholar 

  63. D. Fanta et al. (1978)Arch. Dermatol. Res. 261, 175–179.

    Google Scholar 

  64. W. S. Lee, A. R. Shalita, and M. B. Poh-Fitzpatrick (1978)J. Bacteriol. 133, 811–815.

    Google Scholar 

  65. K. Koenig, A. Rueck, and H. Schneckenburger (1992)Opt. Eng. 31, 1470–1474.

    Google Scholar 

  66. H. Meffert. Personal communication.

  67. A. V. Lassus et al. (1983)Dermatol. Monatsschr. 169, 376–379.

    Google Scholar 

  68. H. C. Benedict (1928)Science 67, 442.

    Google Scholar 

  69. R. L. Hartles and A. G. Leaver (1953)Biochem. J. 54, 632–638.

    Google Scholar 

  70. W. G. Armstrong (1963)Arch. Oral Biol. 8, 79–90.

    Google Scholar 

  71. R. R. Alfano and S. S. Yao (1981)J. Dent. Res. 80, 120–122.

    Google Scholar 

  72. H. Bjelkhagen (1981)IEEE-QE 17, 226–228.

    Google Scholar 

  73. H. Bjelkhagen et al. (1982)Swed. Dent. J. 6, 1–7.

    Google Scholar 

  74. R. R. Alfano et al. (1984)IEEE-QE 20, 1512–1515.

    Google Scholar 

  75. S. Albin, C. E. Byvik, and A. M. Buonchristini (1988)SPIE 907, 96–98.

    Google Scholar 

  76. U. Hafstocm-Bjoerkman et al. (1991)Acta Odontol. Scand. 49, 27.

    Google Scholar 

  77. K. Koenig et al. (1993)SPIE 907, 125–131.

    Google Scholar 

  78. K. Koeniget al. (1994)SPIE Budapest 2080 (in press).

  79. J. M. Hardie and G. H. Bowden (1974) in F. A. Skinner and J. G. Carr (Eds.),Microbial Flora of Man, Academic Press, New York, p. 58.

    Google Scholar 

  80. J. M. Li et al. (1989)J. Bacteriol. 171, 2547–2552.

    Google Scholar 

  81. I. Z. Ades (1990)Int. J. Biochem. 22, 565–578.

    Google Scholar 

  82. J. Z. Yang et al. (1993)Photochem. Photobiol. 57, 803–807.

    Google Scholar 

  83. Z. Malik and M. Djaldetti (1979)Cell. Different. 8, 223–233.

    Google Scholar 

  84. R. Baumgaertneret al. (1994)SPIE Budapest (in press).

  85. H. Schneckenburgeret al. (1994)Opt. Eng. (in press).

  86. K. Koenig, F. Genze, and K. Miller (1993)Dermatol. Monatsschr. 179, 132–134.

    Google Scholar 

  87. F. DcMatteis and B. E. Prior (1962)Biochem. J. 83, 1–8.

    Google Scholar 

  88. F. DeMatteis and C. Remmington (1963)Br. J. Dermatol. 75, 91–104.

    Google Scholar 

  89. A. M. Brady and E. F. Lock (1992)Arch. Toxicol. 66, 175–181.

    Google Scholar 

  90. Z. Maliket al. (1994)SPIE Budapest 2078 (in press).

  91. G. T. Javor and E. F. Febre (1992)J. Bacteriol. 174, 1072–1075.

    Google Scholar 

  92. M. Doss and W. K. P. Dormston (1971)Hoppe-Seyler Physiol. Chem. 352, 725–733.

    Google Scholar 

  93. W. K. Philipp-Dormston and M. Doss (1975) Overproduction of porphyrins and heme in heterotrophic bacteria.Z. Naturforsch. 30, 425–426.

    Google Scholar 

  94. A. Andreoni et al. (1982)Chem. Phys. Lett. 88, 33–36.

    Google Scholar 

  95. M. Yamashita et al. (1984)IEEE-QE 20, 1363–1369.

    Google Scholar 

  96. H. Schneckenburger, H. K. Seidlitz, and J. Eberz (1988)J. Photochem. Photobiol. B 2, 1–19.

    Google Scholar 

  97. K. Koenig, H. Wabnitz, and W. Dietel (1990)J. Photochem. Photobiol. B 8, 103–111.

    Google Scholar 

  98. H. Schneckenburger et al. (1994) in W. Waidelich (Ed.),Laser '93-Optoelectronics in Medicine, Springer, Berlin-Heidelberg (in press).

    Google Scholar 

  99. R. Pottier and T. G. Truscott (1986)Int. J. Radiat. Biol. 50, 421–452.

    Google Scholar 

  100. P. Valat, G. D. Reinhardt, and D. M. Jameson (1988)Photochem. Photobiol. 47, 787–790.

    Google Scholar 

  101. W. Dietel, K. Koenig, and E. Zenkevich (1990)Lasers Life Sci. 3, 197–203.

    Google Scholar 

  102. H. K. Scidlitz et al. (1992)Opt. Eng. 31, 1482–1486.

    Google Scholar 

  103. K. Koenig et al. (1993)J. Photochem. Photobiol. B 18, 287–290.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Lasertechnology in Medicine, Ulm, Germany

    K. Koenig & H. Schneckenburger

  2. Beckman Laser Institute and Medical Clinic, Irvine, California

    K. Koenig

  3. Department of Optoelectronics, Fachhochschule Aalen, Aalen, Germany

    H. Schneckenburger

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  1. K. Koenig
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  2. H. Schneckenburger
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Koenig, K., Schneckenburger, H. Laser-induced autofluorescence for medical diagnosis. J Fluoresc 4, 17–40 (1994). https://doi.org/10.1007/BF01876650

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  • DOI: https://doi.org/10.1007/BF01876650

Key words

  • Autofluorescence
  • medical diagnosis
  • fluorophores
  • NADH
  • flavins
  • porphyrins
  • ALA