Stimulated Raman Scattering Microscopy for Brain Imaging: Basic Principle, Measurements, and Applications

Part of the Progress in Optical Science and Photonics book series (POSP, volume 5)


Stimulated Raman scattering (SRS) microscopy has proven to be a powerful imaging modality over the past decade due to its intrinsic capacity to provide a molecular fingerprint of the target specimen by detecting the vibrational energies associated with its chemical bonds. In fact, SRS automatically avoids the cumbersome process of attaching a fluorophore or fluorescence protein which may alter the intrinsic folding of the molecules due to its larger size and heavier molecular weight. Being a nonlinear imaging technique, SRS also enjoys other advantages such as pinhole-less three-dimensional optical sectioning, non-invasive observation, deep tissue penetration. Additionally, in contrast to coherent anti-Stokes Raman scattering (CARS), which is another coherent Raman technique, SRS signal is identical to spontaneous Raman spectra, linearly dependent on concentration, and free from non-resonant background. In this chapter, the basic principle of SRS microscopy and the corresponding advantages are elucidated. An overview of the advances in SRS measurements is also presented. Specifically, the recent progress in the instrumentation and chemistry related to both label-free and vibrational label-assisted SRS microscopy is reviewed with special emphasis on the brain imaging applications.


Stimulated Raman Gain Coherent anti-Stokes Raman Scattering (CARS) Stokes Beam Spectral Focus Raman Pump 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to acknowledge the Ministry of Science and Technology (MOST), Taiwan, and University Grants Commission (UGC), India, for their support to the biophotonics research projects at NYMU and JBC (UGC Grant No. F.5-376/2014-15/MRP/NERO/2181).


  1. 1.
    R. Chéreau, J. Tønnesen, U.V. Nägerl, STED microscopy for nanoscale imaging in living brain slices. Methods 88, 57–66 (2015)CrossRefGoogle Scholar
  2. 2.
    A. Dani, B. Huang, J. Bergan, C. Dulac, X. Zhuang, Superresolution imaging of chemical synapses in the brain. Neuron 68(5), 843–856 (2010)CrossRefGoogle Scholar
  3. 3.
    J. Vangindertael, I. Beets, S. Rocha, P. Dedecker, L. Schoofs, K. Vanhoorelbeeke, J. Hofkens, H. Mizuno, Super-resolution mapping of glutamate receptors in C. elegans by confocal correlated PALM. Sci. Rep. 5, 13532 (2015)CrossRefGoogle Scholar
  4. 4.
    K. Horisawa, Specific and quantitative labeling of biomolecules using click chemistry. Front. Physiol. 5, 457 (2014)CrossRefGoogle Scholar
  5. 5.
    H. Yamakoshi et al., Alkyne-tag Raman imaging for visualization of mobile small molecules in live cells. J. Am. Chem. Soc. 134(51), 20681–20689 (2012)CrossRefGoogle Scholar
  6. 6.
    Z. Chen et al., Multicolor live-cell chemical imaging by isotopically edited alkyne vibrational palette. J. Am. Chem. Soc. 136(22), 8027–8033 (2014)CrossRefGoogle Scholar
  7. 7.
    S. Hong et al., Live-cell stimulated Raman scattering imaging of alkyne-tagged biomolecules. Angew. Chem. Int. Edit. 53(23), 5827–5831 (2014)CrossRefGoogle Scholar
  8. 8.
    D.C. Dieterich et al., In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat. Nurosci. 13(7), 897–905 (2010)CrossRefGoogle Scholar
  9. 9.
    M. Boyce, C.R. Bertozzi, Bringing chemistry to life. Nat. Methods 8(8), 638–642 (2011)CrossRefGoogle Scholar
  10. 10.
    L. Wei et al., Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering. Nat. Methods 11(4), 410–412 (2014)CrossRefGoogle Scholar
  11. 11.
    H. Yamakoshi et al., Imaging of EdU, an alkyne-tagged cell proliferation probe, by Raman microscopy. J. Am. Chem. Soc. 133(16), 6102–6105 (2011)CrossRefGoogle Scholar
  12. 12.
    C.V. Raman, The molecular scattering of light. Nobel Lecture (11 Dec 1930)Google Scholar
  13. 13.
    C.V. Raman, The molecular scattering of light. Proc. Indian Acad. Sci.-Sect. A 37(3), 342–349 (1953)Google Scholar
  14. 14.
    J.X. Cheng, X.S. Xie, Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications. J. Phys. Chem. B 108, 827–840 (2004)CrossRefGoogle Scholar
  15. 15.
    J.X. Cheng, X.S. Xie, Vibrational spectroscopic imaging of living systems: an emerging platform for biology and medicine. Science 350 (6264), aaa8870 (2015)CrossRefGoogle Scholar
  16. 16.
    D. Fu, G. Holtom, C. Freudiger, X. Zhang, X.S. Xie, Hyperspectral imaging with stimulated Raman scattering by chirped femtosecond lasers. J. Phys. Chem. B 117(16), 4634–4640 (2013)CrossRefGoogle Scholar
  17. 17.
    A. Volkmer, Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering microscopy. J. Phys. D Appl. Phys. 38(5), R59 (2005)CrossRefGoogle Scholar
  18. 18.
    F.K. Lu et al., Label-free neurosurgical pathology with stimulated Raman imaging. Cancer Res. 76(12), 3451–3462 (2016)CrossRefGoogle Scholar
  19. 19.
    D.A. Orringer et al., Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy. Nat. Biomed. Eng. 1, 0027 (2017)CrossRefGoogle Scholar
  20. 20.
    M. Ji et al., Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy. Sci. Transl. Med. 309(7), 309ra163 (2015)CrossRefGoogle Scholar
  21. 21.
    M.A. Houle et al., Rapid 3D chemical-specific imaging of minerals using stimulated Raman scattering microscopy. J. Raman Spectros. 48(5), 726–735 (2017)CrossRefGoogle Scholar
  22. 22.
    W. Min, C.W. Freudiger, S. Lu, X.S. Xie, Coherent nonlinear optical imaging: beyond fluorescence microscopy. Annu. Rev. Phys. Chem. 62, 507–530 (2011)CrossRefGoogle Scholar
  23. 23.
    C.W. Freudiger, Stimulated Raman Scattering (SRS) Microscopy (Harvard University, ProQuest Dissertations Publishing, 2011)Google Scholar
  24. 24.
    L. Wei et al., Live-cell bioorthogonal chemical imaging: stimulated Raman scattering microscopy of vibrational probes. Acc. Chem. Res. 49(8), 1494–1502 (2016)CrossRefGoogle Scholar
  25. 25.
    A. Folick, W. Min, M.C. Wang, Label-free imaging of lipid dynamics using coherent anti-stokes Raman Scattering (CARS) and stimulated Raman scattering (SRS) microscopy. Curr. Opin. Genet. Dev. 21(5), 585–590 (2011)CrossRefGoogle Scholar
  26. 26.
    D. Zhang, P. Wang, M.N. Slipchenko, J.X. Cheng, Fast vibrational imaging of single cells and tissues by stimulated Raman scattering microscopy. Acc. Chem. Res. 47(8), 2282–2290 (2014)CrossRefGoogle Scholar
  27. 27.
    P. Nandakumar, A. Kovalev, A. Volkmer, Vibrational imaging based on stimulated Raman scattering microscopy. New J. Phys. 11(3), 033026 (2009)CrossRefGoogle Scholar
  28. 28.
    B. Mallick, A. Lakshmanna, V. Radhalakshmi, S. Umapathy, Design and development of stimulated Raman spectroscopy apparatus using a femtosecond laser system. Curr. Sci. 1551–1559 (2008)Google Scholar
  29. 29.
    C.W. Freudiger et al., Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322(5909), 1857–1861 (2008)CrossRefGoogle Scholar
  30. 30.
    M. Levenson, Introduction to Nonlinear Laser Spectroscopy (Elsevier, 2012)CrossRefGoogle Scholar
  31. 31.
    K. Wang, Y. Wang, R. Liang, J. Wang, P. Qiu, Contributed review: a new synchronized source solution for coherent Raman scattering microscopy. Rev. Sci. Instrum. 87(7), 071501 (2016)CrossRefGoogle Scholar
  32. 32.
    H.T. Beier, G.D. Noojin, B.A. Rockwell, Stimulated Raman scattering using a single femtosecond oscillator with flexibility for imaging and spectral applications. Opt. Express 19(20), 18885–18892 (2011)CrossRefGoogle Scholar
  33. 33.
    D.W.P. Zhang, M.N. Slipchenko, D. Ben-Amotz, A.M. Weiner, J.X. Cheng, Quantitative vibrational imaging by hyperspectral stimulated Raman scattering microscopy and multivariate curve resolution analysis. Anal. Chem. 85(1), 98–106 (2012)CrossRefGoogle Scholar
  34. 34.
    Q. Zhan, Y. Zhao, P. Lin, F. Kao, A facile supercontinuum-based method for broadband spectrally resolved stimulated Raman scattering microscopy, in Asia Communications and Photonics Conference, AF1 J-6 (Nov 2013)Google Scholar
  35. 35.
    E. Ploetz, S. Laimgruber, S. Berner, W. Zinth, P. Gilch, Femtosecond stimulated Raman microscopy. Appl. Phys. B: Lasers Opt. 87(3), 389–393 (2007)CrossRefGoogle Scholar
  36. 36.
    P. Kukura, S. Yoon, R.A. Mathies, Femtosecond stimulated Raman spectroscopy. Anal. Chem. 78(17), 5952–5959 (2006)CrossRefGoogle Scholar
  37. 37.
    P. Kukura, D.W. McCamant, R.A. Mathies, Femtosecond stimulated Raman spectroscopy. Annu. Rev. Phys. Chem. 58, 461–488 (2007)CrossRefGoogle Scholar
  38. 38.
    S. Shim, R.A. Mathies, Generation of narrow-bandwidth picosecond visible pulses from broadband femtosecond pulses for femtosecond stimulated Raman. Appl. Phys. Lett. 89(12), 121124 (2006)CrossRefGoogle Scholar
  39. 39.
    Y. Ozeki et al., High-speed molecular spectral imaging of tissue with stimulated Raman scattering. Nat. Photonics 6(12), 845–851 (2012)CrossRefGoogle Scholar
  40. 40.
    F. Dake, Y. Ozeki, K. Itoh, Principle Confirmation of Stimulated Raman Scattering Microscopy, presented at Optics & Photonics Japan (OPJ2008), 2008 (unpublished)Google Scholar
  41. 41.
    Y. Ozeki, F. Dake, S.I. Kajiyama, K. Fukui, K. Itoh, Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy. Opt. Express 17(5), 3651–3658 (2009)CrossRefGoogle Scholar
  42. 42.
    B.G. Saar et al., Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330(6009), 1368–1370 (2010)CrossRefGoogle Scholar
  43. 43.
    F. Saltarelli et al., Broadband stimulated Raman scattering spectroscopy by a photonic time stretcher. Opt. Express 24(19), 21264–21275 (2016)CrossRefGoogle Scholar
  44. 44.
    C.W. Freudiger et al., Highly specific label-free molecular imaging with spectrally tailored excitation-stimulated Raman scattering (STE-SRS) microscopy. Nat. Photonics 5(2), 103–109 (2011)CrossRefGoogle Scholar
  45. 45.
    F.K. Lu et al., Multicolor stimulated Raman scattering microscopy. Mol Phys 110((15-16)), 1927–1932 (2012)CrossRefGoogle Scholar
  46. 46.
    K. Seto, Y. Okuda, E. Tokunaga, T. Kobayashi, Development of a multiplex stimulated Raman microscope for spectral imaging through multi-channel lock-in detection. Rev. Sci. Instrum. 84(8), 083705 (2013)CrossRefGoogle Scholar
  47. 47.
    T. Hellerer, A.M. Enejder, A. Zumbusch, Spectral focusing: high spectral resolution spectroscopy with broad-bandwidth laser pulses. Appl. Phys. Lett. 85(1), 25–27 (2004)CrossRefGoogle Scholar
  48. 48.
    A.F. Pegoraro, A.D. Slepkov, A. Ridsdale, D.J. Moffatt, A. Stolow, Hyperspectral multimodal CARS microscopy in the fingerprint region. J. Biophotonics 7(1–2), 49–58 (2014)CrossRefGoogle Scholar
  49. 49.
    I. Pope, W. Langbein, P. Borri, P. Watson, Live cell imaging with chemical specificity using dual frequency CARS microscopy. Methods Enzymol. 504, 273–291 (2012)Google Scholar
  50. 50.
    E.R. Andresen, P. Berto, H. Rigneault, Stimulated Raman scattering microscopy by spectral focusing and fiber-generated soliton as Stokes pulse. Opt. Lett. 36(13), 2387–2389 (2011)CrossRefGoogle Scholar
  51. 51.
    M. Tani et al., in Vibrational Spectroscopy, ed. by D.d. Caro (InTech, 2012), pp. 153–168Google Scholar
  52. 52.
    I. Rocha-Mendoza, W. Langbein, P. Borri, Coherent anti-Stokes Raman microspectroscopy using spectral focusing with glass dispersion. Appl. Phys. Lett. 93(20), 201103 (2008)CrossRefGoogle Scholar
  53. 53.
    M. Andreana et al., Amplitude and polarization modulated hyperspectral stimulated Raman scattering microscopy. Opt. Express 23(22), 28119–28131 (2015)CrossRefGoogle Scholar
  54. 54.
    R. He et al., Stimulated Raman scattering microscopy and spectroscopy with a rapid scanning optical delay line. Opt. Lett. 42(4), 659–662 (2017)CrossRefGoogle Scholar
  55. 55.
    B. Figueroa, Y. Chen, K. Berry, A. Francis, D. Fu, Label-free chemical imaging of latent fingerprints with stimulated Raman Scattering microscopy. Anal. Chem. 89(8), 4468–4473 (2017)CrossRefGoogle Scholar
  56. 56.
    L. Zhang, S. Shen, Z. Liu, M. Ji, Label-free, quantitative imaging of MoS2-nanosheets in live cells with simultaneous stimulated Raman Scattering and transient absorption microscopy. Adv. Biosys. 1(4), 1700013 (2017)CrossRefGoogle Scholar
  57. 57.
    D. Fu, W. Yang, X.S. Xie, Label-free imaging of neurotransmitter acetylcholine at neuromuscular junctions with stimulated Raman Scattering. J. Am. Chem. Soc. 139(2), 583–586 (2016)CrossRefGoogle Scholar
  58. 58.
    D. Fu et al., Quantitative chemical imaging with multiplex stimulated Raman scattering microscopy. J. Am. Chem. Soc. 134(8), 3623–3626 (2012)CrossRefGoogle Scholar
  59. 59.
    C.S. Liao et al., Spectrometer-free vibrational imaging by retrieving stimulated Raman signal from highly scattered photons. Sci. Adv. 1(9), e1500738 (2015)CrossRefGoogle Scholar
  60. 60.
    C.S. Liao et al., Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy. Light: Sci Appl 4:e265 (2015)CrossRefGoogle Scholar
  61. 61.
    Y. Ozeki et al., Stimulated Raman hyperspectral imaging based on spectral filtering of broadband fiber laser pulses. Opt. Lett. 37(3), 431–433 (2012)CrossRefGoogle Scholar
  62. 62.
    Y. Ozeki et al., Label-free observation of tissues by high-speed stimulated Raman spectral microscopy and independent component analysis. Proc. SPIE 8588, 1–858806 (2013)Google Scholar
  63. 63.
    Y. Ozeki et al., Stimulated Raman scattering microscope with shot noise limited sensitivity using subharmonically synchronized laser pulses. Opt. Express 18(13), 13708–13719 (2010)CrossRefGoogle Scholar
  64. 64.
    J. Réhault et al., Broadband stimulated Raman scattering with Fourier-transform detection. Opt. Express 23(19), 25235–25246 (2015)CrossRefGoogle Scholar
  65. 65.
    K. Wang et al., Time-lens based hyperspectral stimulated Raman scattering imaging and quantitative spectral analysis. J. Biophotonics 6(10), 815–820 (2013)Google Scholar
  66. 66.
    C.W. Freudiger et al., Stimulated Raman scattering microscopy with a robust fibre laser source. Nat. Photonics 8(2), 153–159 (2014)CrossRefGoogle Scholar
  67. 67.
    T. Ito, Y. Obara, K. Misawa, Single-beam phase-modulated stimulated Raman scattering microscopy with spectrally focused detection. JOSA B 34(5), 1004–1015 (2017)CrossRefGoogle Scholar
  68. 68.
    M.J.B. Moester, F. Ariese, J.F. De Boer, Optimized signal-to-noise ratio with shot noise limited detection in Stimulated Raman Scattering microscopy. J. Eur. Opt. Soc.-Rapid Publ. 10, 15022 (2015)CrossRefGoogle Scholar
  69. 69.
    W. Min, Stimulated Raman Scattering Microscopy. Online material, (Date Accessed: 18 Oct 2017)
  70. 70.
    E.O. Potma, S. Mukamel, X.S. Xie, in Theory of Coherent Raman Scattering, ed. by J.X. Cheng, X.S. Xie (CRC Press/Taylor & Francis Group, LLC, 2013), pp. 3–42Google Scholar
  71. 71.
    N. Bloembergen, The stimulated Raman effect. Am. J. Phys. 35(11), 989–1023 (1967)CrossRefGoogle Scholar
  72. 72.
    About Lock-In Amplifiers. Stanford Research Systems,
  73. 73.
    R.L. McCreery, in Raman Spectroscopy for Chemical Analysis (Wiley, Hoboken, 2000), pp. 49–71Google Scholar
  74. 74.
    G. Keiser, Biophotonics: Concepts to Applications (Springer Nature, Singapore, 2016)CrossRefGoogle Scholar
  75. 75.
    A. Owyoung, Coherent Raman gain spectroscopy using CW laser sources. IEEE J. Quantum Elect. 14(3), 192–203 (1978)CrossRefGoogle Scholar
  76. 76.
    G. Eesley, M. Levenson, W. Tolles, Optically heterodyned coherent Raman spectroscopy. IEEE J. Quantum Elect. 14(1), 45–49 (1978)CrossRefGoogle Scholar
  77. 77.
    P.S. Venkataram, Johnson Noise and Shot Noise: The Boltzmann Constant, Absolute Zero, and the Electron Charge. (2012)
  78. 78.
    C.J. Sheppard, X. Gan, M. Gu, M. Roy, Handbook of Biological Confocal Microscopy (442–452, 2006)CrossRefGoogle Scholar
  79. 79.
    D.B. Murphy, Fundamentals of Light Microscopy and Electronic Imaging (Wiley, New York, 2002)Google Scholar
  80. 80.
    M.A. Houle, Amélioration de la microscopie “Stimulated Raman Scattering”(SRS) et applications aux sciences de la terre (Doctoral dissertation, Université du Québec, Institut national de la recherche scientifique,, 2017)
  81. 81.
    J. Art, Handbook of Biological Confocal Microscopy (Springer US, 2006), pp. 251–264CrossRefGoogle Scholar
  82. 82.
    C. Zhang, D. Zhang, J.X. Cheng, Coherent Raman scattering microscopy in biology and medicine. Annu. Rev. Biomed. Eng. 17, 415–445 (2015)CrossRefGoogle Scholar
  83. 83.
    Fundamental Noise and Fundamental Constants.
  84. 84.
    H. Nyquist, Thermal agitation of electric charge in conductors. Phys. Rev. 32(1), 110 (1928)CrossRefMathSciNetGoogle Scholar
  85. 85.
    M.N. Slipchenko, R.A. Oglesbee, D. Zhang, W. Wu, J.X. Cheng, Heterodyne detected nonlinear optical imaging in a lock-in free manner. J. Biophotonics 5(10), 801–807 (2012)CrossRefGoogle Scholar
  86. 86.
    Z. Wang, W. Zheng, Z. Huang, Lock-in-detection-free line-scan stimulated Raman scattering microscopy for near video-rate Raman imaging. Opt. Lett. 41(17), 3960–3963 (2016)CrossRefGoogle Scholar
  87. 87.
    G.M. Hieftje, Signal-to-noise enhancement through instrumental techniques. 1. Signals, noise, and S/N enhancement in the frequency domain. Anal. Chem. 44(6), 81A–88A (1972)Google Scholar
  88. 88.
    C. Freudiger, X.S. Xie, in Theory of Coherent Raman Scattering, ed. by J.X. Cheng, X.S. Xie (CRC Press/Taylor & Francis Group, LLC, 2013), pp. 99–120Google Scholar
  89. 89.
    D. Zhang, M.N. Slipchenko, J.X. Cheng, Highly sensitive vibrational imaging by femtosecond pulse stimulated Raman loss. J. Phys. Chem. Lett. 2(11), 1248–1253 (2011)CrossRefGoogle Scholar
  90. 90.
    P. Berto, E.R. Andresen, H. Rigneault, Background-free stimulated Raman spectroscopy and microscopy. Phys. Rev. Lett. 112(5), 053905 (2014)CrossRefGoogle Scholar
  91. 91.
    D. Zhang, M.N. Slipchenko, D.E. Leaird, A.M. Weiner, J.X. Cheng, Spectrally modulated stimulated Raman scattering imaging with an angle-to-wavelength pulse shaper. Opt. Express 21(11), 13864–13874 (2013)CrossRefGoogle Scholar
  92. 92.
    M. Rumi, J.W. Perry, Two-photon absorption: an overview of measurements and principles. Adv. Opt. Photonics 2(4), 451–518 (2010)CrossRefGoogle Scholar
  93. 93.
    D. Fu, T. Ye, T.E. Matthews, G. Yurtsever, W.S. Warren, Two-color, two-photon, and excited-state absorption microscopy. J. Biomed. Opt. 12(5), 054004–054004 (2007)CrossRefGoogle Scholar
  94. 94.
    T. Ye, D. Fu, W.S. Warren, Nonlinear absorption microscopy. Photochem. Photobiol. 85(3), 631–645 (2009)CrossRefGoogle Scholar
  95. 95.
    M.C. Fischer, J.W. Wilson, F.E. Robles, W.S. Warren, Invited review article: pump-probe microscopy. Rev. Sci. Instrum. 87(3), 031101 (2016)CrossRefGoogle Scholar
  96. 96.
    P. Samineni, B. Li, J.W. Wilson, W.S. Warren, M.C. Fischer, Cross-phase modulation imaging. Opt. Letters 37(5), 800–802 (2012)Google Scholar
  97. 97.
    G.P. Agrawal, P.L. Baldeck, R.R. Alfano, Temporal and spectral effects of cross-phase modulation on copropagating ultrashort pulses in optical fibers. Phys. Rev. A 40(9), 5063 (1989)CrossRefGoogle Scholar
  98. 98.
    R.R. Alfano, P.P. Ho, Self-, cross-, and induced-phase modulations of ultrashort laser pulse propagation. IEEE J. Quantum Elect. 24(2), 351–364 (1988)CrossRefGoogle Scholar
  99. 99.
    P.S. Spencer, K.A. Shore, Pump–probe propagation in a passive Kerr nonlinear optical medium. JOSA B 12(1), 67–71 (1995)CrossRefGoogle Scholar
  100. 100.
    K. Ekvall, P. Van der Meulen, C. Dhollande, L.E. Berg, S. Pommert, R. Naskrecki, J.C. Mialocq, Cross phase modulation artifact in liquid phase transient absorption spectroscopy. J. Appl. Phys. 87(5), 2340–2352 (2000)CrossRefGoogle Scholar
  101. 101.
    K. Mawatari, H. Shimizu, T. Kitamori, in Encyclopedia of Microfluidics and Nanofluidics, ed. by D. Li (Springer, Berlin, 2015), pp. 3246–3253Google Scholar
  102. 102.
    R. Rusconi, L. Isa, R. Piazza, Thermal-lensing measurement of particle thermophoresis in aqueous dispersions. JOSA B 21(3), 605–616 (2004)CrossRefGoogle Scholar
  103. 103.
    J.W. Wilson, P. Samineni, W.S. Warren, M.C. Fischer, Cross-phase modulation spectral shifting: nonlinear phase contrast in a pump-probe microscope. Biomed. Opt. Express. 3(5), 854–862 (2012)CrossRefGoogle Scholar
  104. 104.
    D. Fu, Quantitative chemical imaging with stimulated Raman scattering microscopy. Curr. Opin. Chem. Biol. 39, 24–31 (2017)CrossRefGoogle Scholar
  105. 105.
    W.J. Tipping, M. Lee, A. Serrels, V.G. Brunton, A.N. Hulme, Stimulated Raman scattering microscopy: an emerging tool for drug discovery. Chem. Soc. Rev. 45(8), 2075–2089 (2016)CrossRefGoogle Scholar
  106. 106.
    C.W. Freudiger et al., Multicolored stain-free histopathology with coherent Raman imaging. Lab. Invest. 92(10), 1492 (2012)CrossRefGoogle Scholar
  107. 107.
    W. Dou, D. Zhang, Y. Jung, J.X. Cheng, D.M. Umulis, Label-free imaging of lipid-droplet intracellular motion in early Drosophila embryos using femtosecond-stimulated Raman loss microscopy. Biophys. J. 102(7), 1666–1675 (2012)CrossRefGoogle Scholar
  108. 108.
    L. Wei et al., Super-multiplex vibrational imaging. Nature 544(7651), 465–470 (2017)CrossRefGoogle Scholar
  109. 109.
    C.R. Hu, D. Zhang, M.N. Slipchenko, J.X. Cheng, B. Hu, Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy. J. Biomed. Opt. 19(8), 086005 (2014)CrossRefGoogle Scholar
  110. 110.
    J.N. Bentley, M. Ji, X.S. Xie, D.A. Orringer, Real-time image guidance for brain tumor surgery through stimulated Raman scattering microscopy. Expert Rev. Anticancer Ther. 14(4), 359–361 (2014)CrossRefGoogle Scholar
  111. 111.
    H.J. Lee, J.X. Cheng, Imaging chemistry inside living cells by stimulated Raman Scattering microscopy. Methods (2017). Scholar
  112. 112.
    M. Ji et al., Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci. Transl. Med. 5 (201), 201ra119 (2013)CrossRefGoogle Scholar
  113. 113.
    A.H. Fischer, K.A. Jacobson, J. Rose, R. Zeller, Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harbor Protoc 5, pdb-prot4986 (2008)Google Scholar
  114. 114.
    W.E. Huang, R.I. Griffiths, I.P. Thompson, M.J. Bailey, A.S. Whiteley, Raman microscopic analysis of single microbial cells. Anal. Chem. 76(15), 4452–4458 (2004)CrossRefGoogle Scholar
  115. 115.
    H.J. van Manen, A. Lenferink, C. Otto, Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy. Anal. Chem. 80(24), 9576–9582 (2008)CrossRefGoogle Scholar
  116. 116.
    M. Bélanger, I. Allaman, P.J. Magistretti, Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14(6), 724–738 (2011)CrossRefGoogle Scholar
  117. 117.
    I.A. Silver, M. Erecinska, Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals. J. Neurosci. 14(8), 5068–5076 (1994)CrossRefGoogle Scholar
  118. 118.
    F. Hu et al., Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering. Angew. Chem. 127(34), 9959–9963 (2015)CrossRefGoogle Scholar
  119. 119.
    L. Wei et al., Imaging complex protein metabolism in live organisms by stimulated Raman scattering microscopy with isotope labeling. ACS Chem. Biol. 10(3), 901–908 (2015)CrossRefGoogle Scholar
  120. 120.
    F. Hu, L. Wei, C. Zheng, Y. Shen, W. Min, Live-cell vibrational imaging of choline metabolites by stimulated Raman scattering coupled with isotope-based metabolic labeling. Analyst 139(10), 2312–2317 (2014)CrossRefGoogle Scholar
  121. 121.
    L. Wei, Y. Yu, Y. Shen, M.C. Wang, W. Min, Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy. PNAS 110(28), 11226–11231 (2013)CrossRefGoogle Scholar
  122. 122.
    V.M. Ho, J.A. Lee, K.C. Martin, The cell biology of synaptic plasticity. Science 334(6056), 623–628 (2011)CrossRefGoogle Scholar
  123. 123.
    B. Alvarez-Castelao, E.M. Schuman, The regulation of synaptic protein turnover. J. Biol. Chem. 290(48), 28623–28630 (2015)CrossRefGoogle Scholar
  124. 124.
    M.P. Monopoli et al., Temporal proteomic profile of memory consolidation in the rat hippocampal dentate gyrus. Proteomics 11(21), 4189–4201 (2011)CrossRefGoogle Scholar
  125. 125.
    F. Hu, M.R. Lamprecht, L. Wei, B. Morrison, W. Min, Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering. Sci. Rep. 6, 39660 (2016)CrossRefGoogle Scholar
  126. 126.
    H.N.N. Venkata, S.A. Shigeto, Stable isotope-labeled Raman imaging reveals dynamic proteome localization to lipid droplets in single fission yeast cells. Chem. Biol. 19(11), 1373–1380 (2012)CrossRefGoogle Scholar
  127. 127.
    Y. Shen, F. Xu, L. Wei, F. Hu, W. Min, Live-cell quantitative imaging of proteome degradation by stimulated Raman Scattering. Angew. Chem. Int. Edit. 53(22), 5596–5599 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Institute of BiophotonicsNational Yang-Ming University, TaipeiTaipeiTaiwan
  2. 2.Department of PhysicsJagannath Barooah CollegeJorhatIndia
  3. 3.Department of Electrical and Computer EngineeringBoston UniversityBostonUSA

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