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Nonlinear Multimodal Optical Imaging

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Handbook of Photonics for Biomedical Engineering

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Abstract

The constant evolution of optical microscopy over the past century has been driven by the desire to improve the spatial resolution and image contrast, with the goal to achieve a better characterization of smaller biological specimens. The innovation of optical microscopy technology has been proven to be a driving force in the development of biology and medicine. In particular, advanced nonlinear optical microscopes have unique advantages over traditional microscopy approaches: intrinsic three-dimensional (3D) imaging with <1 um lateral resolution reduces photodamage to tissue samples, decreases photo-bleaching to fluorescent molecules, and gives a deep penetration depth with the usage of near-infrared lasers. In the past two decades, much effort has been devoted to develop nonlinear optical microscopy based on different kinds of nonlinear optical contrast mechanisms. In particular, the intrinsic nonlinear optical signals of two-photon excitation fluorescence (TPEF), second harmonic generation (SHG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS) have become the most popular contrast mechanisms for imaging a variety of biomedical specimens in vivo. Specifically, the recently developed spectral- and time-resolved fluorescence detection technology further enables investigating biochemical functions, such as energy metabolism, protein alteration, cellular acidification, etc., during the study of biological processes. This chapter focuses on introducing label-free and multimodal nonlinear optical microscopies and their potential biomedical applications.

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References

  1. Karamanou M, Poulakou-Rebelakou E, Tzetis M, Androutsos G (2010) Anton van leeuwenhoek (1632–1723): father of micromorphology and discoverer of spermatozoa. Rev Argent Microbiol 42(4):311–314. doi:10.1590/S0325-75412010000400013

    Google Scholar 

  2. (2009) Milestones in light microscopy. Nat Cell Biol 11(10):1165. doi:10.1038/ncb1009-1165

    Google Scholar 

  3. Masters BR (2008) History of the optical microscope in cell biology and medicine. In: Encyclopedia of life science. John Wiley & Sons, doi:10.1002/9780470015902.a0003082

    Google Scholar 

  4. Boyd RW (2008) Nonlinear optics, 3rd edn. Academic, Amsterdam

    Google Scholar 

  5. Lakowicz JR (2007) Principles of fluorescence spectroscopy. Springer

    Google Scholar 

  6. Suzuki T, Matsuzaki T, Hagiwara H, Aoki T, Takata K (2007) Recent advances in fluorescent labeling techniques for fluorescence microscopy. Acta Histochem Cytochem 40(5):131–137. doi:10.1267/ahc.07023

    Article  Google Scholar 

  7. Richards-Kortum R, Sevick-Muraca E (1996) Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem 47:555–606. doi:10.1146/annurev.physchem.47.1.555

    Article  Google Scholar 

  8. Finklea H, Meyers R (2000) In: Meyers RA (ed) Encyclopedia of analytical chemistry. Self-assembled monolayers on electrodes, John Wiley & Sons

    Google Scholar 

  9. Zheng W, Li D, Zeng Y, Luo Y, Qu JY (2010) Two-photon excited hemoglobin fluorescence. Biomed Opt Express 2(1):71–79. doi:10.1364/BOE.2.000071

    Article  Google Scholar 

  10. Li D, Zheng W, Zeng Y, Luo Y, Qu JY (2011) Two-photon excited hemoglobin fluorescence provides contrast mechanism for label-free imaging of microvasculature in vivo. Opt Lett 36(6):834–836. doi:10.1364/OL.36.000834

    Article  Google Scholar 

  11. Kleinman D (1962) Nonlinear dielectric polarization in optical media. Phys Rev 126(6):1977. doi:10.1103/PhysRev.126.1977

    Article  Google Scholar 

  12. Hsieh C, Grange R, Pu Y, Psaltis D (2009) Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging. Opt Express 17(4):2880–2891. doi:10.1364/OE.17.002880

    Article  Google Scholar 

  13. Aartsma TJ, Matysik J (2008) Biophysical techniques in photosynthesis. Springer

    Google Scholar 

  14. Born M, Wolf E (1999) Principles of optics: electromagnetic theory of propagation, interference and diffraction of light, 7th expa edn. Cambridge University Press, Cambridge

    Google Scholar 

  15. Barad Y, Eisenberg H, Horowitz M, Silberberg Y (1997) Nonlinear scanning laser microscopy by third harmonic generation. Appl Phys Lett 70(8):922–924. doi:10.1063/1.118442

    Article  Google Scholar 

  16. Zumbusch A, Holtom GR, Xie XS (1999) Three-dimensional vibrational imaging by coherent anti-stokes Raman scattering. Phys Rev Lett 82(20):4142–4145. doi:10.1103/PhysRevLett.82.4142

    Article  Google Scholar 

  17. Evans CL, Xie XS (2008) Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine. Annu Rev Anal Chem 1:883–909. doi:10.1146/annurev.anchem.1.031207.112754

    Article  Google Scholar 

  18. Movasaghi Z, Rehman S, Rehman IU (2007) Raman spectroscopy of biological tissues. Appl Spectrosc Rev 42(5):493–541. doi:10.1080/05704920701551530

    Article  Google Scholar 

  19. Masia F, Glen A, Stephens P, Borri P, Langbein W (2013) Quantitative chemical imaging and unsupervised analysis using hyperspectral coherent anti-stokes Raman scattering microscopy. Anal Chem 85(22):10820–10828. doi:10.1021/ac402303g

    Article  Google Scholar 

  20. Zharov VP (2011) Ultrasharp nonlinear photothermal and photoacoustic resonances and holes beyond the spectral limit. Nat Photonics 5(2):110–116. doi:10.1038/nphoton.2010.280

    Article  Google Scholar 

  21. Wang LV (2009) Multiscale photoacoustic microscopy and computed tomography. Nat Photonics 3(9):503–509. doi:10.1038/nphoton.2009.157

    Article  Google Scholar 

  22. Levi J, Kothapalli SR, Ma TJ, Hartman K, Khuri-Yakub BT, Gambhir SS (2010) Design, synthesis, and imaging of an activatable photoacoustic probe. J Am Chem Soc 132(32):11264–11269. doi:10.1021/ja104000a

    Article  Google Scholar 

  23. Min W, Lu S, Chong S, Roy R, Holtom GR, Xie XS (2009) Imaging chromophores with undetectable fluorescence by stimulated emission microscopy. Nature 461(7267):1105–1109. doi:10.1038/nature08438

    Article  Google Scholar 

  24. Konig K (2000) Multiphoton microscopy in life sciences. J Microsc 200(Pt 2):83–104. doi:10.1046/j.1365-2818.2000.00738.x

    Article  Google Scholar 

  25. Centonze VE, White JG (1998) Multiphoton excitation provides optical sections from deeper within scattering specimens than confocal imaging. Biophys J 75(4):2015–2024. doi:10.1016/S0006-3495(98)77643-X

    Article  Google Scholar 

  26. So PT, Dong CY, Masters BR, Berland KM (2000) Two-photon excitation fluorescence microscopy. Annu Rev Biomed Eng 2:399–429. doi:10.1146/annurev.bioeng.2.1.399

    Article  Google Scholar 

  27. Nan X, Cheng JX, Xie XS (2003) Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-stokes Raman scattering microscopy. J Lipid Res 44(11):2202–2208. doi:10.1194/jlr.D300022-JLR200

    Article  Google Scholar 

  28. Zuber TJ (2002) Punch biopsy of the skin. Am Fam Physician 65(6):1155–1158, 1161–1162, 1164

    Google Scholar 

  29. Diaspro A, Chirico G, Collini M (2005) Two-photon fluorescence excitation and related techniques in biological microscopy. Q Rev Biophys 38(2):97–166. doi:10.1017/S0033583505004129

    Article  Google Scholar 

  30. Rulliere C (1998) Femtosecond laser pulses. Springer

    Google Scholar 

  31. Hilligsoe KM, Andersen T, Paulsen H, Nielsen C, Molmer K, Keiding S et al (2004) Supercontinuum generation in a photonic crystal fiber with two zero dispersion wavelengths. Opt Express 12(6):1045–1054. doi:10.1364/OPEX.12.001045

    Article  Google Scholar 

  32. Prism compressor for ultrashort laser pulses – app note 29. https://assets.newport.com/webDocuments-EN/images/12243.pdf

  33. Fork RL, Martinez OE, Gordon JP (1984) Negative dispersion using pairs of prisms. Opt Lett 9(5):150–152. doi:10.1364/OL.9.000150

    Article  Google Scholar 

  34. Li D, Zheng W, Qu JY (2009) Two-photon autofluorescence microscopy of multicolor excitation. Opt Lett 34(2):202–204. doi:10.1364/OL.34.000202

    Article  Google Scholar 

  35. Becker W (2008) The bh TCSPC handbook. Becker & Hickl GmbH

    Google Scholar 

  36. Gudgin E, Lopez-Delgado R, Ware WR (1981) The tryptophan fluorescence lifetime puzzle. A study of decay times in aqueous solution as a function of pH and buffer composition. Can J Chem 59(7):1037–1044

    Article  Google Scholar 

  37. Li D, Zheng W, Qu JY (2008) Time-resolved spectroscopic imaging reveals the fundamentals of cellular NADH fluorescence. Opt Lett 33(20):2365–2367. doi:10.1364/OL.33.002365

    Article  Google Scholar 

  38. Wu Y, Zheng W, Qu JY (2006) Sensing cell metabolism by time-resolved autofluorescence. Opt Lett 31(21):3122–3124. doi:10.1364/OL.31.003122

    Article  Google Scholar 

  39. Li D, Zheng W, Qu JY (2009) Imaging of epithelial tissue in vivo based on excitation of multiple endogenous nonlinear optical signals. Opt Lett 34(18):2853–2855. doi:10.1364/OL.34.002853

    Article  Google Scholar 

  40. Cheng J, Xie XS (2004) Coherent anti-stokes Raman scattering microscopy: instrumentation, theory, and applications. J Phys Chem B 108(3):827–840. doi:10.1021/jp035693v

    Article  MathSciNet  Google Scholar 

  41. Burkacky O, Zumbusch A, Brackmann C, Enejder A (2006) Dual-pump coherent anti-stokes-Raman scattering microscopy. Opt Lett 31(24):3656–3658. doi:10.1364/OL.31.003656

    Article  Google Scholar 

  42. Li D, Zheng W, Zeng Y, Qu JY (2010) In vivo and simultaneous multimodal imaging: integrated multiplex coherent anti-stokes Raman scattering and two photon microscopy. Appl Phys Lett 97(22):223702. doi:10.1063/1.3521415

    Article  Google Scholar 

  43. Clokey GV, Jacobson LA (1986) The autofluorescent “lipofuscin granules” in the intestinal cells of Caenorhabditis elegans are secondary lysosomes. Mech Ageing Dev 35(1):79–94. doi:10.1016/0047-6374(86)90068-0

    Article  Google Scholar 

  44. Le TT, Duren HM, Slipchenko MN, Hu CD, Cheng JX (2010) Label-free quantitative analysis of lipid metabolism in living Caenorhabditis elegans. J Lipid Res 51(3):672–677. doi:10.1194/jlr.D000638

    Article  Google Scholar 

  45. De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T (2009) Mitochondrial (dys) function in adipocyte (de) differentiation and systemic metabolic alterations. Am J Pathol 175(3):927–939. doi:10.2353/ajpath.2009.081155

    Article  Google Scholar 

  46. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7(12):885–896. doi:10.1038/nrm2066

    Article  Google Scholar 

  47. Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Nicoloro S et al (2003) Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol 23(3):1085–1094. doi:10.1128/MCB.23.3.1085-1094.2003

    Article  Google Scholar 

  48. Hu E, Tontonoz P, Spiegelman BM (1995) Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc Natl Acad Sci U S A 92(21):9856–9860

    Article  Google Scholar 

  49. Nugent C, Prins JB, Whitehead JP, Savage D, Wentworth JM, Chatterjee VK, O’Rahilly S (2001) Potentiation of glucose uptake in 3T3-L1 adipocytes by PPARγ agonists is maintained in cells expressing a PPARγ dominant-negative mutant: evidence for selectivity in the downstream responses to PPARγ activation. Mol Endocrinol 15(10):1729–1738. doi:10.1210/mend.15.10.0715

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Electronic and Computer Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People’s Republic of China

    Yan Zeng, Qiqi Sun & Jianan Y. Qu

Authors
  1. Yan Zeng
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  2. Qiqi Sun
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  3. Jianan Y. Qu
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Corresponding author

Correspondence to Yan Zeng .

Editor information

Editors and Affiliations

  1. Department of Electronic Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong

    Aaron Ho-Pui Ho

  2. School of Electrical and Electronic Engineering, Yonsei University, Seoul, Korea (Republic of)

    Donghyun Kim

  3. Department of Electronic and Information Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

    Michael G. Somekh

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Zeng, Y., Sun, Q., Qu, J.Y. (2017). Nonlinear Multimodal Optical Imaging. In: Ho, AP., Kim, D., Somekh, M. (eds) Handbook of Photonics for Biomedical Engineering. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5052-4_9

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