Coherent Raman scattering (CRS) microscopy is a high-speed vibrational imaging platform with the ability to visualize the chemical content of a living specimen by using molecular vibrational fingerprints. We review technical advances and biological applications of CRS microscopy. The basic theory of CRS and the state-of-the-art instrumentation of a CRS microscope are presented. We further summarize and compare the algorithms that are used to separate the Raman signal from the nonresonant background, to denoise a CRS image, and to decompose a hyperspectral CRS image into concentration maps of principal components. Important applications of single-frequency and hyperspectral CRS microscopy are highlighted. Potential directions of CRS microscopy are discussed.


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Literature Cited

  1. Whitesides GM. 1.  2013. Is the focus on “molecules” obsolete?. Annu. Rev. Anal. Chem. 6:1–29 [Google Scholar]
  2. Raman CV, Krishnan KS. 2.  1928. A new type of secondary radiation. Nature 121:501–2 [Google Scholar]
  3. Abraham JL, Etz ES. 3.  1979. Molecular microanalysis of pathological specimens in situ with a laser-Raman microprobe. Science 206:716–18 [Google Scholar]
  4. Cheng J-X, Xie XS. 4.  2013. Coherent Raman Scattering Microscopy Boca Raton, FL: CRC Press
  5. Terhune RW, Maker PD, Savage CM. 5.  1965. Measurements of nonlinear light scattering. Phys. Rev. Lett. 14:681–84 [Google Scholar]
  6. Régnier PR, Taran JPE. 6.  1973. On the possibility of measuring gas concentrations by stimulated anti-Stokes scattering. Appl. Phys. Lett. 23:240–42 [Google Scholar]
  7. Gord JR, Meyer TR, Roy S. 7.  2008. Applications of ultrafast lasers for optical measurements in combusting flows. Annu. Rev. Anal. Chem. 1:663–87 [Google Scholar]
  8. Duncan MD, Reintjes J, Manuccia TJ. 8.  1982. Scanning coherent anti-Stokes Raman microscope. Opt. Lett. 7:350–52 [Google Scholar]
  9. Zumbusch A, Holtom GR, Xie XS. 9.  1999. Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys. Rev. Lett. 82:4142–45 [Google Scholar]
  10. Cheng J-X, Book LD, Xie XS. 10.  2001. Polarization coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 26:1341–43 [Google Scholar]
  11. Cheng J-X, Volkmer A, Book LD, Xie XS. 11.  2001. An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity. J. Phys. Chem. B 105:1277–80 [Google Scholar]
  12. Volkmer A, Book LD, Xie XS. 12.  2002. Time-resolved coherent anti-Stokes Raman scattering microscopy: imaging based on Raman free induction decay. Appl. Phys. Lett. 80:1505–7 [Google Scholar]
  13. Potma EO, Evans CL, Xie XS. 13.  2006. Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging. Opt. Lett. 31:241–43 [Google Scholar]
  14. Ganikhanov F, Evans CL, Saar BG, Xie XS. 14.  2006. High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy. Opt. Lett. 31:1872–74 [Google Scholar]
  15. Evans CL, Potma EO, Puoris'haag M, Côté D, Lin CP, Xie XS. 15.  2005. Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy. PNAS 102:16807–12 [Google Scholar]
  16. Brustlein S, Ferrand P, Walther N, Brasselet S, Billaudeau C. 16.  et al. 2011. Optical parametric oscillator-based light source for coherent Raman scattering microscopy: practical overview. J. Biomed. Opt. 16:021106 [Google Scholar]
  17. Hellerer T, Enejder AMK, Zumbusch A. 17.  2004. Spectral focusing: high spectral resolution spectroscopy with broad-bandwidth laser pulses. Appl. Phys. Lett. 85:25–27 [Google Scholar]
  18. Bonn M, Müller M, Rinia HA, Burger KNJ. 18.  2009. Imaging of chemical and physical state of individual cellular lipid droplets using multiplex CARS microscopy. J. Raman Spectrosc. 40:763–69 [Google Scholar]
  19. Parekh SH, Lee YJ, Aamer KA, Cicerone MT. 19.  2010. Label-free cellular imaging by broadband coherent anti-stokes Raman scattering microscopy. Biophys. J. 99:2695–704 [Google Scholar]
  20. Kee TW, Cicerone MT. 20.  2004. Simple approach to one-laser, broadband coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 29:2701–3 [Google Scholar]
  21. Camp CH, Lee YJ, Heddleston JM, Hartshorn CM, Walker ARH. 21.  et al. 2014. High-speed coherent Raman fingerprint imaging of biological tissues. Nat. Photonics 8:627–34 [Google Scholar]
  22. Woodbury EJ, Ng WK. 22.  1962. Ruby laser operation in the near IR. Proc. IRE 50:2367 [Google Scholar]
  23. Kukura P, Yoon S, Mathies RA. 23.  2006. Femtosecond stimulated Raman spectroscopy. Anal. Chem. 78:5952–59 [Google Scholar]
  24. Ploetz E, Laimgruber S, Berner S, Zinth W, Gilch P. 24.  2007. Femtosecond stimulated Raman microscopy. Appl. Phys. B 87:389–93 [Google Scholar]
  25. Freudiger CW, Min W, Saar BG, Lu S, Holtom GR. 25.  et al. 2008. Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322:1857–61 [Google Scholar]
  26. Suhalim JL, Chung CY, Lilledahl MB, Lim RS, Levi M. 26.  et al. 2012. Characterization of cholesterol crystals in atherosclerotic plaques using stimulated Raman scattering and second-harmonic generation microscopy. Biophys. J. 102:1988–95 [Google Scholar]
  27. Zhang D, Wang P, Slipchenko MN, Ben-Amotz D, Weiner AM. 27.  et al. 2012. Quantitative vibrational imaging by hyperspectral stimulated Raman scattering microscopy and multivariate curve resolution analysis. Anal. Chem. 85:98–106 [Google Scholar]
  28. Fu D, Holtom G, Freudiger C, Zhang X, Xie XS. 28.  2012. Hyperspectral imaging with stimulated Raman scattering by chirped femtosecond lasers. J. Phys. Chem. B 117:4634–40 [Google Scholar]
  29. Ozeki Y, Umemura W, Otsuka Y, Satoh S, Hashimoto H. 29.  et al. 2012. High-speed molecular spectral imaging of tissue with stimulated Raman scattering. Nat. Photonics 6:845–51 [Google Scholar]
  30. Slipchenko MN, Oglesbee RA, Zhang DL, Wu W, Cheng J-X. 30.  2012. Heterodyne detected nonlinear optical imaging in a lock-in free manner. J. Biophotonics 5:801–7 [Google Scholar]
  31. Liao C-S, Slipchenko MN, Wang P, Li J, Lee S-Y. 31.  et al. 2015. Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy. Light Sci. Appl. 4:e265 [Google Scholar]
  32. Masia F, Glen A, Stephens P, Borri P, Langbein W. 32.  2013. Quantitative chemical imaging and unsupervised analysis using hyperspectral coherent anti-Stokes Raman scattering microscopy. Anal. Chem. 85:10820–28 [Google Scholar]
  33. Fu D, Xie XS. 33.  2014. Reliable cell segmentation based on spectral phasor analysis of hyperspectral stimulated Raman scattering imaging data. Anal. Chem. 86:4115–19 [Google Scholar]
  34. Onogi C, Hamaguchi HO. 34.  2009. Photobleaching of the “Raman spectroscopic signature of life” and mitochondrial activity in Rho budding yeast cells. J. Phys. Chem. B 113:10942–45 [Google Scholar]
  35. Uzunbajakava N, Lenferink A, Kraan Y, Volokhina E, Vrensen G. 35.  et al. 2003. Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells. Biophys. J. 84:3968–81 [Google Scholar]
  36. Hartshorn CM, Lee YJ, Camp CH, Liu Z, Heddleston J. 36.  et al. 2013. Multicomponent chemical imaging of pharmaceutical solid dosage forms with broadband CARS microscopy. Anal. Chem. 85:8102–11 [Google Scholar]
  37. Liao C-S, Choi JH, Zhang D, Chan SH, Cheng J-X. 37.  2015. Denoising stimulated Raman spectroscopic images by total variation minimization. J. Phys. Chem. Lett. C 119:19397–403 [Google Scholar]
  38. Vartiainen EM, Peiponen KE, Asakura T. 38.  1996. Phase retrieval in optical spectroscopy: resolving optical constants from power spectra. Appl. Spectrosc. 50:1283–89 [Google Scholar]
  39. Vartiainen EM, Rinia HA, Müller M, Bonn M. 39.  2006. Direct extraction of Raman line-shapes from congested CARS spectra. Opt. Express 14:3622–30 [Google Scholar]
  40. Rinia HA, Bonn M, Müller M, Vartiainen EM. 40.  2007. Quantitative CARS spectroscopy using the maximum entropy method: the main lipid phase transition. Chemphyschem 8:279–87 [Google Scholar]
  41. Liu YX, Lee YJ, Cicerone MT. 41.  2009. Broadband CARS spectral phase retrieval using a time-domain Kramers-Kronig transform. Opt. Lett. 34:1363–65 [Google Scholar]
  42. Cicerone MT, Aamer KA, Lee YJ, Vartiainen E. 42.  2012. Maximum entropy and time-domain Kramers-Kronig phase retrieval approaches are functionally equivalent for CARS microspectroscopy. J. Raman Spectrosc. 43:637–43 [Google Scholar]
  43. Evans CL, Xie XS. 43.  2008. Coherent anti-Stokes Raman scattering microscopy: chemical imaging for biology and medicine. Annu. Rev. Anal. Chem. 1:883–909 [Google Scholar]
  44. Le TT, Yue S, Cheng J-X. 44.  2010. Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy. J. Lipid Res. 51:3091–102 [Google Scholar]
  45. Yue S, Slipchenko MN, Cheng J-X. 45.  2011. Multimodal nonlinear optical microscopy. Laser Photonics Rev. 5:496–512 [Google Scholar]
  46. Min W, Freudiger CW, Lu S, Xie XS. 46.  2011. Coherent nonlinear optical imaging: beyond fluorescence microscopy. Annu. Rev. Phys. Chem. 62:507–30 [Google Scholar]
  47. Pezacki JP, Blake JA, Danielson DC, Kennedy DC, Lyn RK. 47.  et al. 2011. Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy. Nat. Chem. Biol. 7:137–45 [Google Scholar]
  48. Suhalim JL, Boik JC, Tromberg BJ, Potma EO. 48.  2012. The need for speed. J. Biophotonics 5:387–95 [Google Scholar]
  49. Chung C-Y, Boik J, Potma EO. 49.  2013. Biomolecular imaging with coherent nonlinear vibrational microscopy. Annu. Rev. Phys. Chem. 64:77–99 [Google Scholar]
  50. Zhang D, Wang P, Slipchenko MN, Cheng J-X. 50.  2014. Fast vibrational imaging of single cells and tissues by stimulated Raman scattering microscopy. Acc. Chem. Res. 47:2282–90 [Google Scholar]
  51. Zhang C, Zhang D, Cheng J-X. 51.  2015. Coherent Raman scattering microscopy in biology and medicine. Annu. Rev. Biomed. Eng. 17:415–45 [Google Scholar]
  52. Levenson MD, Kano SS. 52.  1988. Introduction to Nonlinear Laser Spectroscopy San Diego, CA: Academic
  53. Shen YR. 53.  1984. The Principles of Nonlinear Optics New York: Wiley
  54. Jones DJ, Potma EO, Cheng J-X, Burfeindt B, Pang Y. 54.  et al. 2002. Synchronization of two passively mode-locked, picosecond lasers within 20 fs for coherent anti-Stokes Raman scattering microscopy. Rev. Sci. Instrum. 73:2843–48 [Google Scholar]
  55. Ganikhanov F, Carrasco S, Xie XS, Katz M, Seitz W. 55.  et al. 2006. Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 31:1292–94 [Google Scholar]
  56. Ozeki Y, Dake F, Kajiyama S, Fukui K, Itoh K. 56.  2009. Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy. Opt. Express 17:3651–58 [Google Scholar]
  57. Cheng J-X, Volkmer A, Book LD, Xie XS. 57.  2002. Multiplex coherent anti-Stokes Raman scattering microspectroscopy and study of lipid vesicles. J. Phys. Chem. B 106:8493–98 [Google Scholar]
  58. Müller M, Schins JM. 58.  2002. Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy. J. Phys. Chem. B 106:3715–23 [Google Scholar]
  59. Kano H, Hamaguchi H. 59.  2005. Ultrabroadband (>2500 cm−1) multiplex coherent anti-Stokes Raman scattering microspectroscopy using a supercontinuum generated from a photonic crystal fiber. Appl. Phys. Lett. 86:121113 [Google Scholar]
  60. von Vacano B, Meyer L, Motzkus M. 60.  2007. Rapid polymer blend imaging with quantitative broadband multiplex CARS microscopy. J. Raman Spectrosc. 38:916–26 [Google Scholar]
  61. Okuno M, Kano H, Leproux P, Couderc V, Hamaguchi HO. 61.  2008. Ultrabroadband multiplex CARS microspectroscopy and imaging using a subnanosecond supercontinuum light source in the deep near infrared. Opt. Lett. 33:923–25 [Google Scholar]
  62. Marx B, Czerwinski L, Light R, Somekh M, Gilch P. 62.  2014. Multichannel detectors for femtosecond stimulated Raman microscopy—ideal and real ones. J. Raman Spectrosc. 45:521–27 [Google Scholar]
  63. Rock W, Bonn M, Parekh SH. 63.  2013. Near shot-noise limited hyperspectral stimulated Raman scattering spectroscopy using low energy lasers and a fast CMOS array. Opt. Express 21:15113–20 [Google Scholar]
  64. Seto K, Okuda Y, Tokunaga E, Kobayashi T. 64.  2013. Development of a multiplex stimulated Raman microscope for spectral imaging through multi-channel lock-in detection. Rev. Sci. Instrum. 84:083705 [Google Scholar]
  65. Paris S, Durand F. 65.  2009. A fast approximation of the bilateral filter using a signal processing approach. Int. J. Comput. Vis. 81:24–52 [Google Scholar]
  66. Chan SH, Zickler T, Lu YM. 66.  2014. Monte Carlo non-local means: random sampling for large-scale image filtering. IEEE Trans. Image Process. 23:3711–25 [Google Scholar]
  67. Haq I, Chowdhury BZ, Chaires JB. 67.  1997. Singular value decomposition of 3-D DNA melting curves reveals complexity in the melting process. Eur. Biophys. J. Biophys. Lett. 26:419–26 [Google Scholar]
  68. Lee YJ, Moon D, Migler KB, Cicerone MT. 68.  2011. Quantitative image analysis of broadband CARS hyperspectral images of polymer blends. Anal. Chem. 83:2733–39 [Google Scholar]
  69. Peterson CW, Knight BW. 69.  1973. Causality calculations in time domain—efficient alternative to Kramers-Kronig method. J. Opt. Soc. Am. 63:1238–42 [Google Scholar]
  70. Vartiainen EM. 70.  1992. Phase retrieval approach for coherent anti-Stokes-Raman scattering spectrum analysis. J. Opt. Soc. Am. B 9:1209–14 [Google Scholar]
  71. Fu D, Holtom G, Freudiger C, Zhang X, Xie XS. 71.  2013. Hyperspectral imaging with stimulated Raman scattering by chirped femtosecond lasers. J. Phys. Chem. B 117:4634–40 [Google Scholar]
  72. Lin CY, Suhalim JL, Nien CL, Miljkovic MD, Diem M. 72.  et al. 2011. Picosecond spectral coherent anti-Stokes Raman scattering imaging with principal component analysis of meibomian glands. J. Biomed. Opt. 16:021104 [Google Scholar]
  73. Masia F, Karuna A, Borri P, Langbein W. 73.  2015. Hyperspectral image analysis for CARS, SRS, and Raman data. J. Raman Spectrosc. 46:727–34 [Google Scholar]
  74. Wang P, Li J, Wang P, Hu C-R, Zhang D. 74.  et al. 2013. Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral stimulated Raman scattering microscopy. Angew. Chem. Int. Ed. Engl. 52:13042–46 [Google Scholar]
  75. Wang P, Liu B, Zhang DL, Belew MY, Tissenbaum HA, Cheng JX. 75.  2014. Imaging lipid metabolism in live Caenorhabditis elegans using fingerprint vibrations. Angew. Chem. Int. Ed. Engl. 53:11787–92 [Google Scholar]
  76. de Juan A, Tauler R. 76.  2006. Multivariate curve resolution (MCR) from 2000: progress in concepts and applications. Crit. Rev. Anal. Chem. 36:163–76 [Google Scholar]
  77. Jaumot J, Tauler R. 77.  2010. MCR-BANDS: a user friendly MATLAB program for the evaluation of rotation ambiguities in Multivariate Curve Resolution. Chemo. Intell. Lab. Syst. 103:96–107 [Google Scholar]
  78. Saar BG, Freudiger CW, Reichman J, Stanley CM, Holtom GR. 78.  et al. 2010. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330:1368–70 [Google Scholar]
  79. Chen HT, Wang HF, Slipchenko MN, Jung YK, Shi YZ. 79.  et al. 2009. A multimodal platform for nonlinear optical microscopy and microspectroscopy. Opt. Express 17:1282–90 [Google Scholar]
  80. Pegoraro AF, Slepkov AD, Ridsdale A, Pezacki JP, Stolow A. 80.  2010. Single laser source for multimodal coherent anti-Stokes Raman scattering microscopy. Appl. Opt. 49:F10–17 [Google Scholar]
  81. Pegoraro AF, Ridsdale A, Moffatt DJ, Jia YW, Pezacki JP. 81.  et al. 2009. Optimally chirped multimodal CARS microscopy based on a single Ti: Sapphire oscillator. Opt. Express 17:2984–96 [Google Scholar]
  82. Zhang DL, Slipchenko MN, Cheng J-X. 82.  2011. Highly sensitive vibrational imaging by femtosecond pulse stimulated Raman loss. J. Phys. Chem. Lett. 2:1248–53 [Google Scholar]
  83. Akhmanov SA, Bunkin AF, Ivanov SG, Koroteev NI. 83.  1978. Polarization coherent active Raman-spectroscopy and coherent Raman ellipsometry. Zh. Eksp. Teor. Fiz. 4:1272–94 [Google Scholar]
  84. Levine BF, Bethea CG. 84.  1980. Frequency-modulated shot noise limited stimulated Raman gain spectroscopy. Appl. Phys. Lett. 36:245–47 [Google Scholar]
  85. Levenson MD, Moerner WE, Horne DE. 85.  1983. FM spectroscopy detection of stimulated Raman gain. Opt. Lett. 8:108–10 [Google Scholar]
  86. Zhang DL, Slipchenko MN, Leaird DE, Weiner AM, Cheng J-X. 86.  2013. Spectrally modulated stimulated Raman scattering imaging with an angle-to-wavelength pulse shaper. Opt. Express 21:13864–74 [Google Scholar]
  87. Berto P, Andresen ER, Rigneault H. 87.  2014. Background-free stimulated Raman spectroscopy and microscopy. Phys. Rev. Lett. 112:053905 [Google Scholar]
  88. Freudiger CW, Min W, Holtom GR, Xu BW, Dantus M. 88.  et al. 2011. Highly specific label-free molecular imaging with spectrally tailored excitation-stimulated Raman scattering (STE-SRS) microscopy. Nat. Photonics 5:103–9 [Google Scholar]
  89. Freudiger CW, Pfannl R, Orringer DA, Saar BG, Ji MB. 89.  et al. 2012. Multicolored stain-free histopathology with coherent Raman imaging. Lab. Investig. 92:1661–61 [Google Scholar]
  90. Nan X, Cheng J-X, Xie XS. 90.  2003. Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy. J. Lipid Res. 44:2202–8 [Google Scholar]
  91. Paar M, Jüngst C, Steiner NA, Magnes C, Sinner F. 91.  et al. 2012. Remodeling of lipid droplets during lipolysis and growth in adipocytes. J. Biol. Chem. 287:11164–73 [Google Scholar]
  92. Le TT, Huff TB, Cheng J-X. 92.  2009. Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis. BMC Cancer 9:42 [Google Scholar]
  93. Dou W, Zhang D, Jung Y, Cheng J-X, Umulis DM. 93.  2012. Label-free imaging of lipid-droplet intracellular motion in early Drosophila embryos using femtosecond-stimulated Raman loss microscopy. Biophys. J. 102:1666–75 [Google Scholar]
  94. Mitra R, Chao O, Urasaki Y, Goodman OB, Le TT. 94.  2012. Detection of lipid-rich prostate circulating tumour cells with coherent anti-Stokes Raman scattering microscopy. BMC Cancer 12:540 [Google Scholar]
  95. Zhang X, Roeffaers MBJ, Basu S, Daniele JR, Fu D. 95.  et al. 2012. Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy. Chemphyschem 13:1054–59 [Google Scholar]
  96. Hellerer T, Axäng C, Brackmann C, Hillertz P, Pilon M. 96.  et al. 2007. Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy. PNAS 104:14658–63 [Google Scholar]
  97. Yen K, Le TT, Bansal A, Narasimhan SD, Cheng J-X. 97.  et al. 2010. A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLOS ONE 5:e12810 [Google Scholar]
  98. Wang MC, Min W, Freudiger CW, Ruvkun G, Xie XS. 98.  2011. RNAi screening for fat regulatory genes with SRS microscopy. Nat. Methods 8:135–38 [Google Scholar]
  99. Wang H, Fu Y, Zickmund P, Shi R, Cheng J-X. 99.  2005. Coherent anti-stokes Raman scattering imaging of axonal myelin in live spinal tissues. Biophys. J. 89:581–91 [Google Scholar]
  100. Fu Y, Wang H, Huff TB, Shi R, Cheng J-X. 100.  2007. Coherent anti-stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination. J. Neurosci. Res. 85:2870–81 [Google Scholar]
  101. Shi Y, Kim S, Huff TB, Borgens RB, Park K. 101.  et al. 2010. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles. Nat. Nanotechnol. 5:80–87 [Google Scholar]
  102. Bélanger E, Henry FP, Vallée R, Randolph MA, Kochevar IE. 102.  et al. 2011. In vivo evaluation of demyelination and remyelination in a nerve crush injury model. Biomed. Opt. Express 2:2698–708 [Google Scholar]
  103. Shi Y, Zhang D, Huff TB, Wang X, Shi R. 103.  et al. 2011. Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord. J. Biomed. Opt. 16:1060121 [Google Scholar]
  104. Huff TB, Cheng J-X. 104.  2007. In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue. J. Microsc. 225:175–82 [Google Scholar]
  105. Jung Y, Ng JH, Keating CP, Senthil-Kumar P, Zhao J. 105.  et al. 2014. Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model. PLOS ONE 9:e94054 [Google Scholar]
  106. Ji M, Orringer DA, Freudiger CW, Ramkissoon S, Liu X. 106.  et al. 2013. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci. Transl. Med. 5:201ra119 [Google Scholar]
  107. Wei L, Yu Y, Shen YH, Wang MC, Min W. 107.  2013. Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy. PNAS 110:11226–31 [Google Scholar]
  108. Wei L, Hu FH, Shen YH, Chen ZX, Yu Y. 108.  et al. 2014. Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering. Nat. Methods 11:410–12 [Google Scholar]
  109. Hong SL, Chen T, Zhu YT, Li A, Huang YY. 109.  et al. 2014. Live-cell stimulated Raman scattering imaging of alkyne-tagged biomolecules. Angew. Chem. Int. Ed. Engl. 53:5827–31 [Google Scholar]
  110. Lee HJ, Zhang WD, Zhang DL, Yang Y, Liu B. 110.  et al. 2015. Assessing cholesterol storage in live cells and C. elegans by stimulated Raman scattering imaging of phenyl-diyne cholesterol. Sci. Rep. 5:7930 [Google Scholar]
  111. Li JJ, Cheng J-X. 111.  2014. Direct visualization of de novo lipogenesis in single living cells. Sci. Rep. 4:6807 [Google Scholar]
  112. Saar BG, Contreras-Rojas LR, Xie XS, Guy RH. 112.  2011. Imaging drug delivery to skin with stimulated Raman scattering microscopy. Mol. Pharm. 8:969–75 [Google Scholar]
  113. Saar BG, Zeng YN, Freudiger CW, Liu YS, Himmel ME. 113.  et al. 2010. Label-free, real-time monitoring of biomass processing with stimulated Raman scattering microscopy. Angew. Chem. Int. Ed. Engl. 49:5476–79 [Google Scholar]
  114. Slipchenko MN, Le TT, Chen H, Cheng J-X. 114.  2009. High-speed vibrational imaging and spectral analysis of lipid bodies by compound Raman microscopy. J. Phys. Chem. B 113:7681–86 [Google Scholar]
  115. Le TT, Duren HM, Slipchenko MN, Hu C-D, Cheng J-X. 115.  2010. Label-free quantitative analysis of lipid metabolism in living Caenorhabditis elegans. J. Lipid Res. 51:672–77 [Google Scholar]
  116. Yue S, Li J, Lee S-Y, Lee HJ, Shao T. 116.  et al. 2014. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 19:393–406 [Google Scholar]
  117. Mansfield JC, Littlejohn GR, Seymour MP, Lind RJ, Perfect S. 117.  et al. 2013. Label-free chemically specific imaging in planta with stimulated Raman scattering microscopy. Anal. Chem. 85:5055–63 [Google Scholar]
  118. Garbacik ET, Herek JL, Otto C, Offerhaus HL. 118.  2012. Rapid identification of heterogeneous mixture components with hyperspectral coherent anti-Stokes Raman scattering imaging. J. Raman Spectrosc. 43:651–55 [Google Scholar]
  119. Kong LJ, Ji MB, Holtom GR, Fu D, Freudiger CW. 119.  et al. 2013. Multicolor stimulated Raman scattering microscopy with a rapidly tunable optical parametric oscillator. Opt. Lett. 38:145–47 [Google Scholar]
  120. Ozeki Y, Umemura W, Sumimura K, Nishizawa N, Fukui K. 120.  et al. 2012. Stimulated Raman hyperspectral imaging based on spectral filtering of broadband fiber laser pulses. Opt. Lett. 37:431–33 [Google Scholar]
  121. Beier HT, Noojin GD, Rockwell BA. 121.  2011. Stimulated Raman scattering using a single femtosecond oscillator with flexibility for imaging and spectral applications. Opt. Express 19:18885–92 [Google Scholar]
  122. Andresen ER, Berto P, Rigneault H. 122.  2011. Stimulated Raman scattering microscopy by spectral focusing and fiber-generated soliton as Stokes pulse. Opt. Lett. 36:2387–89 [Google Scholar]
  123. Di Napoli C, Pope I, Masia F, Watson P, Langbein W. 123.  et al. 2014. Hyperspectral and differential CARS microscopy for quantitative chemical imaging in human adipocytes. Biomed. Opt. Express 5:1378–90 [Google Scholar]
  124. Fu D, Yu Y, Folick A, Currie E, Farese RV. 124.  et al. 2014. In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy. J. Am. Chem. Soc. 136:8820–28 [Google Scholar]
  125. Billecke N, Rago G, Bosma M, Eijkel G, Gemmink A. 125.  et al. 2014. Chemical imaging of lipid droplets in muscle tissues using hyperspectral coherent Raman microscopy. Histochem. Cell Biol. 141:263–73 [Google Scholar]
  126. Lim RS, Suhalim JL, Miyazaki-Anzai S, Miyazaki M, Levi M. 126.  et al. 2011. Identification of cholesterol crystals in plaques of atherosclerotic mice using hyperspectral CARS imaging. J. Lipid Res. 52:2177–86 [Google Scholar]
  127. Fussell A, Garbacik E, Offerhaus H, Kleinebudde P, Strachan C. 127.  2013. In situ dissolution analysis using coherent anti-Stokes Raman scattering (CARS) and hyperspectral CARS microscopy. Eur. J. Pharm. Biopharm. 85:1141–47 [Google Scholar]
  128. Fu D, Zhou J, Zhu WS, Manley PW, Wang YK. 128.  et al. 2014. Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering. Nat. Chem. 6:615–23 [Google Scholar]
  129. Liu B, Wang P, Kim JI, Zhang D, Xia Y. 129.  et al. 2015. Vibrational fingerprint mapping reveals spatial distribution of functional groups of lignin in plant cell wall. Anal. Chem. 87:9436–42 [Google Scholar]
  130. Evans CL, Potma EO, Xie XSN. 130.  2004. Coherent anti-Stokes Raman scattering spectral interferometry: determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy. Opt. Lett. 29:2923–25 [Google Scholar]
  131. Lim SH, Caster AG, Leone SR. 131.  2005. Single-pulse phase-control interferometric coherent anti-Stokes Raman scattering spectroscopy. Phys. Rev. A 72:041803 [Google Scholar]
  132. Lim SH, Caster AG, Leone SR. 132.  2007. Fourier transform spectral interferometric coherent anti-Stokes Raman scattering (FTSI-CARS) spectroscopy. Opt. Lett. 32:1332–34 [Google Scholar]
  133. Lu FK, Ji MB, Fu D, Ni XH, Freudiger CW. 133.  et al. 2012. Multicolor stimulated Raman scattering microscopy. Mol. Phys. 110:1927–32 [Google Scholar]
  134. Weiner AM, Leaird DE, Wiederrecht GP, Nelson KA. 134.  1991. Femtosecond multiple-pulse impulsive stimulated Raman-scattering spectroscopy. J. Opt. Soc. Am. B 8:1264–75 [Google Scholar]
  135. Ogilvie JP, Beaurepaire E, Alexandrou A, Joffre M. 135.  2006. Fourier-transform coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 31:480–82 [Google Scholar]
  136. Ideguchi T, Holzner S, Bernhardt B, Guelachvili G, Picqué N, Hänsch W. 136.  2013. Coherent Raman spectro-imaging with laser frequency combs. Nature 502:355–58 [Google Scholar]
  137. Fu D, Lu FK, Zhang X, Freudiger C, Pernik DR. 137.  et al. 2012. Quantitative chemical imaging with multiplex stimulated Raman scattering microscopy. J. Am. Chem. Soc. 134:3623–26 [Google Scholar]
  138. Liao C-S, Wang P, Wang P, Li J, Lee HJ. 138.  et al. 2015. Spectrometer-free vibrational imaging by retrieving stimulated Raman signal from highly scattered photons. Sci. Adv. 1:e1500738 [Google Scholar]
  139. Müller M, Schins JM, Nastase N, Wurpel GWH, Brakenhoff GJ. 139.  2002. Imaging the chemical composition and thermodynamic state of lipid membranes with multiplex CARS microscopy. Biophys. J. 82:175a [Google Scholar]
  140. Rinia HA, Bonn M, Müller M. 140.  2006. Quantitative multiplex CARS spectroscopy in congested spectral regions. J. Phys. Chem. B 110:4472–79 [Google Scholar]
  141. Wurpel GWH, Müller M. 141.  2006. Water confined by lipid bilayers: a multiplex CARS study. Chem. Phys. Lett. 425:336–41 [Google Scholar]
  142. Wurpel GWH, Rinia HA, Müller M. 142.  2005. Imaging orientational order and lipid density in multilamellar vesicles with multiplex CARS microscopy. J. Microsc. 218:37–45 [Google Scholar]
  143. Okuno M, Kano H, Leproux P, Couderc V, Day JPR. 143.  et al. 2010. Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method. Angew. Chem. Int. Ed. Engl. 49:6773–77 [Google Scholar]
  144. Kano H, Hamaguchi H. 144.  2006. In-vivo multi-nonlinear optical imaging of a living cell using a supercontinuum light source generated from a photonic crystal fiber. Opt. Express 14:2798–804 [Google Scholar]
  145. Rinia HA, Burger KNJ, Bonn M, Müller M. 145.  2008. Quantitative label-free imaging of lipid composition and packing of individual cellular lipid droplets using multiplex CARS microscopy. Biophys. J. 95:4908–14 [Google Scholar]
  146. Pohling C, Buckup T, Pagenstecher A, Motzkus M. 146.  2011. Chemoselective imaging of mouse brain tissue via multiplex CARS microscopy. Biomed. Opt. Express 2:2110–16 [Google Scholar]
  147. Murugkar S, Smith B, Srivastava P, Moica A, Naji M. 147.  et al. 2010. Miniaturized multimodal CARS microscope based on MEMS scanning and a single laser source. Opt. Express 18:23796–804 [Google Scholar]
  148. Legare F, Evans CL, Ganikhanov F, Xie XS. 148.  2006. Towards CARS endoscopy. Opt. Express 14:4427–32 [Google Scholar]
  149. Wang ZY, Liu YJ, Gao L, Chen YX, Luo PF. 149.  et al. 2011. Use of multimode optical fibers for fiber-based coherent anti-Stokes Raman scattering microendoscopy imaging. Opt. Lett. 36:2967–69 [Google Scholar]
  150. Freudiger CW, Yang WL, Holtom GR, Peyghambarian N, Xie XS. 150.  et al. 2014. Stimulated Raman scattering microscopy with a robust fibre laser source. Nat. Photonics 8:153–59 [Google Scholar]

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