Abstract
The state of the art in fluorescence imaging for biomedical applications is demonstrated. 2-dimensional profiles of fluorophores gained with non-contact techniques show the quantitative distribution of endogenous NADH in the UV and synthetic markers in the NIR spectral range. The biomedical use extends from basic research investigations on the metabolism in mitochondria to clinical applications when differentiating the tumor border zone.
One of the outstanding advantages of near infrared so-called Optical Molecular Imaging (OMI) is bright fluorescence of the markers by specific molecular interaction with tumor specific enzymes. For the in vivo tests of the dyes an experimental NIR imager was used. NIR fluorescence of the entire body of small animals can be imaged.
The analysis of fluorescences from the interior of the probes shows strong intensity distortion due to tissue optics. Rescaling as the physical basis for image processing taking into account biochemical and biooptical methods result in the real concentration of the fluorophore under consideration. For example, the diameter of the fluorescent volume is apparently larger without rescaling. This new interpretation of fluorescence pictures has useful applications in biomedicine now and in the future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Paul H (ed.): Lexikon der Optik Spektruumm Akademischer Verlag, Heidelberg, Berlin, 1999
Chance B, Legallais V, Schoener B: Metabolically linked changes in fluorescence emission spectra of cortex of rat brain, kidney and adrenal. Nature 195 (1962) 1073–1075
Chance B, Schoener B, Oshino R, Itshak F, Nakase Y: Oxidation-Reduction Ratio studies of mitichondria in freeze-trapped samples. J. Biol. Chem. 254 (1979) 4766–4771
Renault G, Raynal E, Sinet M, Berthier JP, Godard B, Cornillault J: A laser fluorimeter for direct cardiac metabolism monitoring. Opt. Laser Technol. 14 (1982) 143–148
Renault G, Sinet M, Muffat-Joly M, Fourati T, Polianski J, Meric P, Weiser M, Pocidalo J: Evaluation in situ du métabolisme tissulaire par fluorimétrie laser. La Presse Médicale 13 (1984) 2381–2385
Richards-Kortum, R, Raya R, Fitzmaurice M, Tong L, Ratliff N, Kramer J: A one-layer model of laserinduced fluorescence for diagnosis in human tissue: Applications to artheroscleroris. IEEE Trans. Biomed. Eng. 36 (1989) 1222–1232
Beuthan J, Zur C, Hofmann H: Quantitative (in vivo) NADH-Messung — ein methodisch klinischer Anssatz zur biologischen Äquivalentdosimetrie. Adv. Laser Medicine 5 (1990) 253–260
Beuthan J, Minet O, Müller G: Observations of the fluorescence response of the coenzyme NADH in biological samples, Opt. Lett 18 (1993) 1098–1099
Lohmann W, Schill WB, Bucher D, Peters T, Nilles M, Schulz A, Bohle R, Schramm W: Tissue diagnosis using autofluorescence. Proc. SPIE 2081 (1993) 10–24
Wu J, Field S, Raya RP: Analytical model for extracting intrinsic fluorescence in turbid media. Appl. Opt. 32 (1993) 3285–3295
Beuthan J, Weber A, Minet O, Hagemann R, Roggan A, Schmitt I, Müller G, Germer C, Albrecht D, Bocher T: Untersuchungen zur NADH-Konzentrationsbestimmung mittels optischer Biopsie. Lasermedizin 10 (1994) 57–63
Beuthan J, Bocher T, Minet O, Roggan A, Schmitt I, Weber A, Müller G: Investigations concerning the determination of NADH-concentrations using optical biopsy. Proc. SPIE 2135 (1994) 147–156
Chung YG, Schwartz J, Gardner C, Sawaya R, Jacques SL: Fluorescence of normal and cancerous brain tissues: the excitation/emission matrix. Proc. SPIE 2135 (1994) 66–75
Gandjbakhche A, Ganmot I: Quantitative fluorescent imaging of specific markers of diseased tissue. IEEE Sel. Topics QE 2 (1996) 914–921
Pogue BW, Hasan T: Fluorophore quantition in tissue-simulating media with confocal detection. IEEE SeL Topics QE 2 (1996) 959–964
Yova D, Atlamazoglou V, Davaris P, Kavantzas N, Loukas S: Colon cancer diagnosis using fluorescence spectroscopy and fluorescence imaging technique. Proc. SPIE 3197 (1997) 4–15
af Klinteberg C, Wang I, Lindquist C, Vaitkuviene A, Svanberg K: Laser-induced fluorescence studies of premalignant and benign lesions in the female genital tract. Proc. SPIE 3197 (1997) 34–40
Padilla-Ybarra JJ, Bourg-Heckly G, A’Amar O, Biais J, Etienne J, Guillemin F: UV induced autofluorescence spectroscopy in Barrett’s esophagus. Proc. SPIE 3197 (1997) 54–59
Lohmann W, Schill WB, Bohle RM, Dreyer T: Autofluorescence of seborrheic keratosis (warts) and of tissue surrrounding malignant tumors. Proc. SPIE 3197 (1997) 140–150
Beuthan J, Minet O, Müüller G: Optical Biopsy of Cytokeratin and NADH in the Tumor Border Zone. Ann. N.Y. Acad. SCi 838 (1998) 150–170
Beuthan J, Minet O: Fluorescence Diagnosis in the Border Zone of Liver Tumors. In: Rettig W. et al (eds.): Applied Fluorescence in Chemistry, Biology and Medicine. Springer, Berlin 1999, pp.537–551
Shehada REN, Marmarelis VZ, Mansour HN, Grundfest WS: Laser Induced Fluorescence Attenuation Spectroscopy: Detection of Hypoxia. IEEE Trans. Biomed. Eng. 47 (2000) 301–312
Schuchmann S, Kovacs R, Kann O, Heinemann U, Buchheim K: Monitoring NAD(P)H autofluorescence to assess mitochondrial metabolic functions in rat hippocampal-entorhinal cortex slices. Brain Res. Prot. 7 (2001) 267–276
Zeilweger M, Goujon D, Conde R, Forrer M, van den Bergh, H, Wagnières G: Absolute autofluorescence spectra of human healthy, metaplastic, and early cancerous bronchial tissue in vivo. Appl. Opt. 40 (2001) 3784–3791
Loetscher P, Alvarez-Gonsalez R, Althaus FR: Poly(ADP-ribose) may signal changing metabolic conditions to the chromatin of mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 84 (1987), 1286–1289
D’Amours D, Desnoyers S, D’Silva I, Poirier GG: Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 324 (1999) 249–268
Ziegler M: New functions of a long-known molecule. Emerging roles of NAD in cellular signalling. Eur. J. Biochem. 267(2000) 1550–1564
Skidmore CJ, Davies MI, Goodwin PM, Halldorsson H, Lewis PJ, Shall S, Zia’ee AA: The involvement of poly(ADP-ribose) polymerase in the degradation of NAD caused by gamma-radiation and N-methyl-N-nitrosourea. Eur. J. Biochem. 101 (1979) 135–142
Berger NA: Poly(ADP-ribose) in the cellular response to DNA damage. Radiat. Res. 101 (1985) 4–15
Ha HC, Snyder SH: Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc. NatL Acad Sci. U.S.A. 96 (1999) 13978–13982
Lee HC: Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers. Ann. Rev. Pharmacol. Toxicol. 41 (2001) 317–345
Guse AH: Cyclic ADP-ribose: a novel Ca2+-mobilising second messenger. Cell. Signal. 11 (1999) 309–316
Sahnan JM, Kohen E, Viallet P, Hirschberg JG, Wouters AW, Kohen C, Thorell B: Microspectrofluometric approach to the study of free/bound NAD(P)H ratio as metabolic indicator in various cell types. Photochem. Photobiol. 36 (1982) 585–593
Galeotti T, van Rossum GDV, Mayer DH, Chance B: On the fluorescence of NAD(P)H in Whole-Cell Preparations of Tumours and Normal Tissues. Eur. J. Biochem. 17 (1970) 485–496
Lakowicz JR, Szmacinski H, Nowaczyk K, Johnson ML: Fluorescence Lifetime Imaging of Free and Protein-Bound NADH. Proc. Natl. Acad. Sci. USA. 89 (1992) 1271–1275
Virag L, Szabo C: The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol. Rev. 54 (2002) 375–429
Tentorri L, Portarena I, Graziani G: Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors Phamnacol Res. 45 (2002) 73–85
Varadarajan SG, An J, Novalija E, Smart SC, Stowe DF: Changes in [Na i, compartmental [Ca2+], and NADH with dysfunction after global ischemia in intact hearts. Am. J. Physiol. Heart Circ. PhysioL 280 (2001) H280–293
Halmosi R, Berente Z, Osz E, Toth K, Literati-Nagy P, Sumegi B: Effect of Poly(ADP-Ribose) Polymerase Inhibitors on the Ischemia-Reperfusion-Induced Oxidative Cell Damage and Mitochondrial Metabolism in Langendorff Heart Perfusion System. Mol. Pharmacol. 59 (2001) 1479–1505
Kohen E, Santus R, Hirschberg JG: Fluorescence Probes in Oncology. Imperial College Press, London 2002
Mildažiene V, Baniene R: private communication July 2003
Gornal AG, Bardavill GJ, David MM: Determination of serum proteins by means of the biuret reaction. J. Biol. Chem. 177 (1949) 751–766
Fabiato A, Fabiato F: Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J. Physiol.(Paris), 75 (1979) 463–505
Roggan A, Minet O, Schröder C, Müller G: Measurements of optical tissue properties using integratinng sphere technique. In: Medical Optical Tomography. G. Müller et al. (eds.), SPIE IS 11, Bellingham 1993, pp. 149–165
Ishimaru I: Wave Propagation and Scattering in Random Media. Academic Press, San Diego, New York 1978
Tuchin V: Selected Papers on Tissue Optics. SPIE MS 102, Bellingham 1994
Bocher T, Luhmann T, Baier S, Dierolf M, Naumann M, Beuthan J, Berlien HP, Müller GJ: Multispectral fluorescence imaging device for malignancy detection. Proc. SPIE 3197 (1997) 60–67
Weissleder R: Molecular Imaging: Exploring the next frontier. Radiology 212 (1999) 609–614
Becker A, Hessenius C, Licha K, Ebert B, Sukowski U, Semmler W, Wiedenmnann B, Grötzinger C: Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nature Biotech. 19 (2001) 327–331
Bugaj JE, Achilefu S, Dorshow RB, Rajagopalan R: Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. J. Biomed Opt. 6 (2001) 122–133
Weissleder R, Tung C, Mahmood U, Bognanov A: In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nature Biotech. 17 (1999) 375–378
Weissleder R: Scaling down Imaging: Molecular Mapping of Cancer in Mice. Nature Rev. 2 (2002) 1–7
Adams JY, Johnson M, Sato M, Berger F, Gambhie SS, Carey M, Iruela-Arispe ML, Wu L: Visualization of advanced human prostate cancer lesions in mice by a targeted gene transfer vector and optical imaging. Nature Med. 8 (2002) 891–896
Licha K, Riefke B, Ntziachristos V, Becker A, Chance B, Semmler W: Hydrophilic Cyanine Dyes as Contrast Agents for Near-Infrrared Tumor Imaging: Synthesis, Photophysical Properties and Spectroscopic In Vivo Characterization. Photochem. Photobiol. 72 (2000) 392–398
Licha K: Contrast Agents for Optical imaging. In: Krause W (ed.): Contrast Agents II (Topics in Current Chemistry, Vol. 222). Springer, Berlin, Heidelberg, NY. 2002, pp. 1–29
Minet O, Beuthan J, Licha K, Mahnke C: The biomedical use of rescaling procedures in Optical Biopsy and Optical Molecular Imaging. In R. Kraayenhof, A.J.W.G. Visser, H.C. Germitsen, (ed): Fluorescence Spectroscopy, Imaging and Probes. Springer, Berlin, Heidelberg, NY. 2002, pp. 349–360
Riefke, B, Licha, K, Nolte, D, Ebert, B, Rinneberg, H, Semmler, W: In vivo characterization of cyanine dyes as contrast agents for near-infrared imaging. Proc. SPIE 2927 (1996) 199–208
Ebert B, Sukowski U, Grosenick D, Wabnitz H, Moesta KT, Licha K, Becker A, Semmler W, Schlag PM, Rinneberg H: Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments. J. Biomed. Opt 6 (2001) 134–40
Minet O: Zur Bestimmung der räumlichen Verteilung von Fluoreszenzzentren in streuenden Medien. Fortschritte in der Lasermedizin 12 (1995) 98
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer Science+Business Media New York
About this chapter
Cite this chapter
Minet, O., Beuthan, J., Mildažiene, V., Baniene, R. (2004). Fluorescence Techniques in Biomedicine: From the Monitoring of Cell Metabolism to Image Processing in Cancer Detection. In: Geddes, C.D., Lakowicz, J.R. (eds) Reviews in Fluorescence 2004. Reviews in Fluorescence 2004, vol 2004. Springer, Boston, MA. https://doi.org/10.1007/978-0-306-48672-2_10
Download citation
DOI: https://doi.org/10.1007/978-0-306-48672-2_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-0992-6
Online ISBN: 978-0-306-48672-2
eBook Packages: Springer Book Archive