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Abstract

Imaging techniques greatly facilitate the comprehensive knowledge of biological systems. Although imaging methodology for biomacromolecules such as protein and nucleic acids has been long established, microscopic techniques and contrast mechanisms are relatively limited for small biomolecules, which are equally important participants in biological processes. Recent developments in Raman imaging, including both microscopy and tailored vibrational tags, have created exciting opportunities for noninvasive imaging of small biomolecules in living cells, tissues, and organisms. Here, we summarize the principle and workflow of small-biomolecule imaging by Raman microscopy. Then, we review recent efforts in imaging, for example, lipids, metabolites, and drugs. The unique advantage of Raman imaging has been manifested in a variety of applications that have provided novel biological insights.

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2019-05-06
2024-03-29
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Literature Cited

  1. 1.
    Alfonso-García A, Mittal R, Lee ES, Potma EO 2014. Biological imaging with coherent Raman scattering microscopy: a tutorial. J. Biomed. Opt. 19:771407
    [Google Scholar]
  2. 2.
    Alfonso-García A, Pfisterer SG, Riezman H, Ikonen E, Potma EO 2016. D38-cholesterol as a Raman active probe for imaging intracellular cholesterol storage. J. Biomed. Opt. 21:661003
    [Google Scholar]
  3. 3.
    Aljakouch K, Lechtonen T, Yosef HK, Hammoud MK, Alsaidi W et al. 2018. Raman microspectroscopic evidence for the metabolism of a tyrosine kinase inhibitor, neratinib, in cancer cells. Angew. Chem. Int. Ed. 57:247250–54
    [Google Scholar]
  4. 4.
    Ametamey SM, Honer M, Schubiger PA 2008. Molecular imaging with PET. Chem. Rev. 108:51501–16
    [Google Scholar]
  5. 5.
    Ando J, Kinoshita M, Cui J, Yamakoshi H, Dodo K et al. 2015. Sphingomyelin distribution in lipid rafts of artificial monolayer membranes visualized by Raman microscopy. PNAS 112:154558–63
    [Google Scholar]
  6. 6.
    Ashtikar M, Matthäus C, Schmitt M, Krafft C, Fahr A, Popp J 2013. Non-invasive depth profile imaging of the stratum corneum using confocal Raman microscopy: first insights into the method. Eur. J. Pharm. Sci. 50:5601–8
    [Google Scholar]
  7. 7.
    Baumgart T, Hunt G, Farkas ER, Webb WW, Feigenson GW 2007. Fluorescence probe partitioning between Lo/Ld phases in lipid membranes. Biochim. Biophys. Acta 1768:92182–94
    [Google Scholar]
  8. 8.
    Beattie JR, Maguire C, Gilchrist S, Barrett LJ, Cross CE et al. 2007. The use of Raman microscopy to determine and localize vitamin E in biological samples. FASEB J 21:3766–76
    [Google Scholar]
  9. 9.
    Beatty KE, Liu JC, Xie F, Dieterich DC, Schuman EM et al. 2006. Fluorescence visualization of newly synthesized proteins in mammalian cells. Angew. Chem. Int. Ed. 45:447364–67
    [Google Scholar]
  10. 10.
    Brozek-Pluska B, Musial J, Kordek R, Bailo E, Dieing T, Abramczyk H 2012. Raman spectroscopy and imaging: applications in human breast cancer diagnosis. Analyst 137:163773–80
    [Google Scholar]
  11. 11.
    Camp CH, Lee YJ, Heddleston JM, Hartshorn CM, Walker ARH et al. 2014. High-speed coherent Raman fingerprint imaging of biological tissues. Nat. Photon. 8:8627–34
    [Google Scholar]
  12. 12.
    Chen AJ, Li J, Jannasch A, Mutlu AS, Wang MC, Cheng J-X 2018. Fingerprint stimulated Raman scattering imaging reveals retinoid coupling lipid metabolism and survival. Chemphyschem 19:192500–6
    [Google Scholar]
  13. 13.
    Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W et al. 2013. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155:71479–91
    [Google Scholar]
  14. 14.
    Chen YJ, Huang X, Mahieu NG, Cho K, Schaefer J, Patti GJ 2014. Differential incorporation of glucose into biomass during Warburg metabolism. Biochemistry 53:294755–57
    [Google Scholar]
  15. 15.
    Chen Z, Paley DW, Wei L, Weisman AL, Friesner RA et al. 2014. Multicolor live-cell chemical imaging by isotopically edited alkyne vibrational palette. J. Am. Chem. Soc. 136:228027–33
    [Google Scholar]
  16. 16.
    Cheng J-X, Xie XS 2013. Coherent Raman Scattering Microscopy Boca Raton, FL: CRC Press
  17. 17.
    Cheng J-X, Xie XS 2015. Vibrational spectroscopic imaging of living systems: an emerging platform for biology and medicine. Science 350:6264aaa8870
    [Google Scholar]
  18. 18.
    Chung C-Y, Potma EO 2013. Biomolecular imaging with coherent nonlinear vibrational microscopy. Annu. Rev. Phys. Chem. 64:77–99
    [Google Scholar]
  19. 19.
    Crawford JM, Portmann C, Zhang X, Roeffaers MBJ, Clardy J 2012. Small molecule perimeter defense in entomopathogenic bacteria. PNAS 109:2710821–26
    [Google Scholar]
  20. 20.
    Cullis PR, Fenske DB, Hope MJ 2008. Physical properties and functional roles of lipids in membranes. Biochemistry of Lipids, Lipoproteins and Membranes DE Vance, JE Vance 1–37 Elsevier. , 5th ed..
    [Google Scholar]
  21. 21.
    Donaldson SH, de Aguiar HB 2018. Molecular imaging of cholesterol and lipid distributions in model membranes. J. Phys. Chem. Lett. 9:71528–33
    [Google Scholar]
  22. 22.
    Drozdz MM, Jiang H, Pytowski L, Grovenor C, Vaux DJ 2017. Formation of a nucleoplasmic reticulum requires de novo assembly of nascent phospholipids and shows preferential incorporation of nascent lamins. Sci. Rep. 7:17454
    [Google Scholar]
  23. 23.
    Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:72931357–61
    [Google Scholar]
  24. 24.
    Duncan MD, Reintjes J, Manuccia TJ 1982. Scanning coherent anti-Stokes Raman microscope. Opt. Lett. 7:8350–52
    [Google Scholar]
  25. 25.
    El-Mashtoly SF, Petersen D, Yosef HK, Mosig A, Reinacher-Schick A et al. 2014. Label-free imaging of drug distribution and metabolism in colon cancer cells by Raman microscopy. Analyst 139:51155–61
    [Google Scholar]
  26. 26.
    Freudiger CW, Min W, Saar BG, Lu S, Holtom GR et al. 2008. Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322:59091857–61
    [Google Scholar]
  27. 27.
    Fu D, Xie XS 2014. Reliable cell segmentation based on spectral phasor analysis of hyperspectral stimulated Raman scattering imaging data. Anal. Chem. 86:94115–19
    [Google Scholar]
  28. 28.
    Fu D, Yang W, Xie XS 2017. Label-free imaging of neurotransmitter acetylcholine at neuromuscular junctions with stimulated Raman scattering. J. Am. Chem. Soc. 139:2583–86
    [Google Scholar]
  29. 29.
    Fu D, Yu Y, Folick A, Currie E, Farese RV Jr et al. 2014. In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy. J. Am. Chem. Soc. 136:248820–28
    [Google Scholar]
  30. 30.
    Fu D, Zhou J, Zhu WS, Manley PW, Wang YK et al. 2014. Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering. Nat. Chem. 6:7614–22
    [Google Scholar]
  31. 31.
    Gambhir SS 2002. Molecular imaging of cancer with positron emission tomography. Nat. Rev. Cancer 2:9683–93
    [Google Scholar]
  32. 32.
    Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR 2018. Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis. ACS Chem. Biol. 13:41013–20
    [Google Scholar]
  33. 33.
    Glunde K, Artemov D, Penet M-F, Jacobs MA, Bhujwalla ZM 2010. Magnetic resonance spectroscopy in metabolic and molecular imaging and diagnosis of cancer. Chem. Rev. 110:53043–59
    [Google Scholar]
  34. 34.
    Grammel M, Hang HC 2013. Chemical reporters for biological discovery. Nat. Chem. Biol. 9:8475–84
    [Google Scholar]
  35. 35.
    Guillermier C, Poczatek JC, Taylor WR, Steinhauser ML 2017. Quantitative imaging of deuterated metabolic tracers in biological tissues with nanoscale secondary ion mass spectrometry. Int. J. Mass Spectrom. 422:42–50
    [Google Scholar]
  36. 36.
    Hashimoto A, Yamaguchi Y, Chiu L-d, Morimoto C, Fujita K et al. 2015. Time-lapse Raman imaging of osteoblast differentiation. Sci. Rep. 5:12529
    [Google Scholar]
  37. 37.
    He C, Weston TA, Jung RS, Heizer P, Larsson M et al. 2018. NanoSIMS analysis of intravascular lipolysis and lipid movement across capillaries and into cardiomyocytes. Cell Metab 27:51055–66.e3
    [Google Scholar]
  38. 38.
    Hofer M, Balla NK, Brasselet S 2017. High-speed polarization-resolved coherent Raman scattering imaging. Optica 4:7795–801
    [Google Scholar]
  39. 39.
    Hong S, Chen T, Zhu Y, Li A, Huang Y, Chen X 2014. Live-cell stimulated Raman scattering imaging of alkyne-tagged biomolecules. Angew. Chem. Int. Ed. 53:235827–31
    [Google Scholar]
  40. 40.
    Hu F, Chen Z, Zhang L, Shen Y, Wei L, Min W 2015. Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering. Angew. Chem. Int. Ed. 54:349821–25
    [Google Scholar]
  41. 41.
    Hu F, Lamprecht MR, Wei L, Morrison B, Min W 2016. Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering. Sci. Rep. 6:139660
    [Google Scholar]
  42. 42.
    Hu F, Wei L, Zheng C, Shen Y, Min W 2014. Live-cell vibrational imaging of choline metabolites by stimulated Raman scattering coupled with isotope-based metabolic labeling. Analyst 139:102312–17
    [Google Scholar]
  43. 43.
    Hu F, Zeng C, Long R, Miao Y, Wei L et al. 2018. Supermultiplexed optical imaging and barcoding with engineered polyynes. Nat. Methods 15:3194–200
    [Google Scholar]
  44. 44.
    Huang B, Bates M, Zhuang X 2009. Super-resolution fluorescence microscopy. Annu. Rev. Biochem. 78:993–1016
    [Google Scholar]
  45. 45.
    Ishitsuka K, Koide M, Yoshida M, Segawa H, Leproux P et al. 2017. Identification of intracellular squalene in living algae, Aurantiochytrium mangrovei with hyper-spectral coherent anti-Stokes Raman microscopy using a sub-nanosecond supercontinuum laser source. J. Raman Spectrosc. 48:8–15
    [Google Scholar]
  46. 46.
    Jamieson LE, Greaves J, McLellan JA, Munro KR, Tomkinson NCO et al. 2018. Tracking intracellular uptake and localisation of alkyne tagged fatty acids using Raman spectroscopy. Spectrochim. Acta A Mol. Biomol. Spectrosc. 197:30–36
    [Google Scholar]
  47. 47.
    Jiang H, Goulbourne CN, Tatar A, Turlo K, Wu D et al. 2014. High-resolution imaging of dietary lipids in cells and tissues by NanoSIMS analysis. J. Lipid Res. 55:102156–66
    [Google Scholar]
  48. 48.
    Kim H, Bryant GW, Stranick SJ 2012. Superresolution four-wave mixing microscopy. Opt. Express 20:66042–51
    [Google Scholar]
  49. 49.
    Kim MM, Parolia A, Dunphy MP, Venneti S 2016. Non-invasive metabolic imaging of brain tumours in the era of precision medicine. Nat. Rev. Clin. Oncol. 13:12725–39
    [Google Scholar]
  50. 50.
    Kim SH, Lee ES, Lee JY, Lee ES, Lee BS et al. 2010. Multiplex coherent anti-Stokes Raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids. Circ. Res. 106:81332–41
    [Google Scholar]
  51. 51.
    Klymchenko AS, Kreder R 2014. Fluorescent probes for lipid rafts: from model membranes to living cells. Chem. Biol. 21:197–113
    [Google Scholar]
  52. 52.
    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 51:3672–77
    [Google Scholar]
  53. 53.
    Leamy AK, Egnatchik RA, Young JD 2013. Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog. Lipid Res. 52:1165–74
    [Google Scholar]
  54. 54.
    Lee HJ, Zhang W, Zhang D, Yang Y, Liu B 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]
  55. 55.
    Levsky JM, Singer RH 2003. Fluorescence in situ hybridization: past, present and future. J. Cell Sci. 116:142833–38
    [Google Scholar]
  56. 56.
    Li J, Cheng J-X 2015. Direct visualization of de novo lipogenesis in single living cells. Sci. Rep. 4:16807
    [Google Scholar]
  57. 57.
    Li J, Condello S, Thomes-Pepin J, Ma X, Xia Y et al. 2017. Lipid desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell 20:3303–14.e5
    [Google Scholar]
  58. 58.
    Li L, Cheng JX 2008. Label-free coherent anti-Stokes Raman scattering imaging of coexisting lipid domains in single bilayers. J. Phys. Chem. B 112:61576–79
    [Google Scholar]
  59. 59.
    Li L, Wang H, Cheng J-X 2005. Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in coexisting domains. Biophys. J. 89:53480–90
    [Google Scholar]
  60. 60.
    Li X, Jiang M, Lam JWY, Tang BZ, Qu JY 2017. Mitochondrial imaging with combined fluorescence and stimulated Raman scattering microscopy using a probe of the aggregation-induced emission characteristic. J. Am. Chem. Soc. 139:4717022–30
    [Google Scholar]
  61. 61.
    Liao C-S, Cheng J-X 2016. In situ and in vivo molecular analysis by coherent Raman scattering microscopy. Annu. Rev. Anal. Chem. 9:69–93
    [Google Scholar]
  62. 62.
    Liao C-S, Slipchenko MN, Wang P, Li J, Lee S-Y et al. 2015. Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy. Light Sci. Appl. 4:e265
    [Google Scholar]
  63. 63.
    Liao CS, Wang P, Wang P, Li J, Lee HJ et al. 2015. Spectrometer-free vibrational imaging by retrieving stimulated Raman signal from highly scattered photons. Sci. Adv. 1:9e1500738
    [Google Scholar]
  64. 64.
    Lietz CB, Gemperline E, Li L 2013. Qualitative and quantitative mass spectrometry imaging of drugs and metabolites. Adv. Drug Deliv. Rev. 65:81074–85
    [Google Scholar]
  65. 65.
    Lim RS, Suhalim JL, Miyazaki-Anzai S, Miyazaki M, Levi M et al. 2011. Identification of cholesterol crystals in plaques of atherosclerotic mice using hyperspectral CARS imaging. J. Lipid Res. 52:122177–86
    [Google Scholar]
  66. 66.
    Lombardini A, Mytskaniuk V, Sivankutty S, Andresen ER, Chen X et al. 2018. High-resolution multimodal flexible coherent Raman endoscope. Light Sci. Appl. 7:10
    [Google Scholar]
  67. 67.
    Long R, Zhang L, Shi L, Shen Y, Hu F et al. 2018. Two-color vibrational imaging of glucose metabolism by stimulated Raman scattering. Chem. Commun. 54:2152–55
    [Google Scholar]
  68. 68.
    Marty F, Rago G, Smith DF, Gao X, Eijkel GB et al. 2017. Combining time-of-flight secondary ion mass spectrometry imaging mass spectrometry and CARS microspectroscopy reveals lipid patterns reminiscent of gene expression patterns in the wing imaginal disc of Drosophila melanogaster. Anal. Chem 89:189664–70
    [Google Scholar]
  69. 69.
    Matthäus C, Krafft C, Dietzek B, Brehm BR, Lorkowski S, Popp J 2012. Noninvasive imaging of intracellular lipid metabolism in macrophages by Raman microscopy in combination with stable isotopic labeling. Anal. Chem. 84:208549–56
    [Google Scholar]
  70. 70.
    Maxfield FR, Tabas I 2005. Role of cholesterol and lipid organization in disease. Nature 438:7068612–21
    [Google Scholar]
  71. 71.
    Maxfield FR, Wüstner D 2012. Analysis of cholesterol trafficking with fluorescent probes. Methods Cell Biol 108:367–93
    [Google Scholar]
  72. 72.
    Meister K, Niesel J, Schatzschneider U, Metzler-Nolte N, Schmidt DA, Havenith M 2010. Label-free imaging of metal-carbonyl complexes in live cells by Raman microspectroscopy. Angew. Chem. Int. Ed. 49:193310–12
    [Google Scholar]
  73. 73.
    Min W, Freudiger CW, Lu S, Xie XS 2011. Coherent nonlinear optical imaging: beyond fluorescence microscopy. Annu. Rev. Phys. Chem. 62:507–30
    [Google Scholar]
  74. 74.
    Morisaki T, Lyon K, DeLuca KF, DeLuca JG, English BP et al. 2016. Real-time quantification of single RNA translation dynamics in living cells. Science 352:62921425–29
    [Google Scholar]
  75. 75.
    Müller M, Schins JM 2002. Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy. J. Phys. Chem. B 106:143715–23
    [Google Scholar]
  76. 76.
    Nandakumar P, Kovalev A, Volkmer A 2009. Vibrational imaging based on stimulated Raman scattering microscopy. New J. Phys. 11:033026
    [Google Scholar]
  77. 77.
    Okada M, Smith NI, Palonpon AF, Endo H, Kawata S et al. 2012. Label-free Raman observation of cytochrome c dynamics during apoptosis. PNAS 109:128–32
    [Google Scholar]
  78. 78.
    Ozeki Y, Umemura W, Otsuka Y, Satoh S, Hashimoto H et al. 2012. High-speed molecular spectral imaging of tissue with stimulated Raman scattering. Nat. Photon. 6:12845–51
    [Google Scholar]
  79. 79.
    Paige JS, Wu KY, Jaffrey SR 2011. RNA mimics of green fluorescent protein. Science 333:6042642–46
    [Google Scholar]
  80. 80.
    Pawley JB, Masters BR 2008. Handbook of biological confocal microscopy. J. Biomed. Opt. 13:29902
    [Google Scholar]
  81. 81.
    Phelps ME 2000. Positron emission tomography provides molecular imaging of biological processes. PNAS 97:169226–33
    [Google Scholar]
  82. 82.
    Piez K, Eagle H 1958. The free amino acid pool of cultured human cells. J. Biol. Chem. 231:533–45
    [Google Scholar]
  83. 83.
    Ploetz E, Laimgruber S, Berner S, Zinth W, Gilch P 2007. Femtosecond stimulated Raman microscopy. Appl. Phys. B 87:3389–93
    [Google Scholar]
  84. 84.
    Potma EO, de Boeij WP, van Haastert PJM, Wiersma DA 2001. Real-time visualization of intracellular hydrodynamics in single living cells. PNAS 98:41577–82
    [Google Scholar]
  85. 85.
    Potma EO, Xie XS 2005. Direct visualization of lipid phase segregation in single lipid bilayers with coherent anti-Stokes Raman scattering microscopy. ChemPhysChem 6:177–79
    [Google Scholar]
  86. 86.
    Pully VV, Lenferink ATM, Otto C 2011. Time-lapse Raman imaging of single live lymphocytes. J. Raman Spectrosc. 42:2167–73
    [Google Scholar]
  87. 87.
    Radhakrishnan A, Goldstein JL, McDonald JG, Brown MS 2008. Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab 8:6512–21
    [Google Scholar]
  88. 88.
    Raman CV, Krishnan KS 1928. A new type of secondary radiation. Nature 121:3048501–2
    [Google Scholar]
  89. 89.
    Rinia HA, Burger KNJ, Bonn M, Müller M 2008. Quantitative label-free imaging of lipid composition and packing of individual cellular lipid droplets using multiplex CARS microscopy. Biophys. J. 95:104908–14
    [Google Scholar]
  90. 90.
    Rodrigues TB, Serrao EM, Kennedy BWC, Hu D-E, Kettunen MI, Brindle KM 2013. Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose. Nat. Med. 20:193–97
    [Google Scholar]
  91. 91.
    Saar BG, Freudiger CW, Reichman J, Stanley CM, Holtom GR, Xie XS 2010. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330:60091368–70
    [Google Scholar]
  92. 92.
    Saar BG, Johnston RS, Freudiger CW, Xie XS, Seibel EJ 2011. Coherent Raman scanning fiber endoscopy. Opt. Lett. 36:132396–98
    [Google Scholar]
  93. 93.
    Salzer R, Siesler HW, eds. 2009. Infrared Raman Spectroscopic Imaging Hoboken, NJ: Wiley
  94. 94.
    Schaffer JE 2016. Lipotoxicity: many roads to cell dysfunction and cell death: introduction to a thematic review series. J. Lipid Res. 57:81327–28
    [Google Scholar]
  95. 95.
    Shen Y, Xu F, Wei L, Hu F, Min W 2014. Live-cell quantitative imaging of proteome degradation by stimulated Raman scattering. Angew. Chem. Int. Ed. 53:225596–99
    [Google Scholar]
  96. 96.
    Shen Y, Zhao Z, Zhang L, Shi L, Shahriar S et al. 2017. Metabolic activity induces membrane phase separation in endoplasmic reticulum. PNAS 114:5113394–99
    [Google Scholar]
  97. 97.
    Shi L, Shen Y, Min W 2018. Visualizing protein synthesis in mice with in vivo labeling of deuterated amino acids using vibrational imaging. APL Photon 3:092401
    [Google Scholar]
  98. 98.
    Silva WR, Graefe CT, Frontiera RR 2016. Toward label-free super-resolution microscopy. ACS Photon 3:179–86
    [Google Scholar]
  99. 99.
    Simons K, Sampaio JL 2011. Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol. 3:10a004697
    [Google Scholar]
  100. 100.
    Simons K, Van Meer G 1988. Lipid sorting in epithelial cells. Biochemistry 27:176197–202
    [Google Scholar]
  101. 101.
    Singer S, Nicolson GL 1972. The fluid mosaic model of the structure of cell membranes. Science 175:23720–31
    [Google Scholar]
  102. 102.
    Stiebing C, Meyer T, Rimke I, Matthäus C, Schmitt M et al. 2017. Real-time Raman and SRS imaging of living human macrophages reveals cell-to-cell heterogeneity and dynamics of lipid uptake. J. Biophoton. 10:91217–26
    [Google Scholar]
  103. 103.
    Suhalim JL, Chung C-Y, Lilledahl MB, Lim RS, Levi M 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]
  104. 104.
    Surmacki J, Musial J, Kordek R, Abramczyk H 2013. Raman imaging at biological interfaces: applications in breast cancer diagnosis. Mol. Cancer 12:48
    [Google Scholar]
  105. 105.
    Syed A, Smith EA 2017. Raman imaging in cell membranes, lipid-rich organelles, and lipid bilayers. Annu. Rev. Anal. Chem. 10:271–91
    [Google Scholar]
  106. 106.
    Thurber GM, Yang KS, Reiner T, Kohler RH, Sorger P et al. 2013. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat. Commun. 4:1504
    [Google Scholar]
  107. 107.
    Tipping WJ, Lee M, Serrels A, Brunton VG, Hulme AN 2016. Stimulated Raman scattering microscopy: an emerging tool for drug discovery. Chem. Soc. Rev. 45:82075–89
    [Google Scholar]
  108. 108.
    Tipping WJ, Lee M, Serrels A, Brunton VG, Hulme AN 2017. Imaging drug uptake by bioorthogonal stimulated Raman scattering microscopy. Chem. Sci. 8:85606–15
    [Google Scholar]
  109. 109.
    Unger RH 2002. Lipotoxic diseases. Annu. Rev. Med. 53:319–36
    [Google Scholar]
  110. 110.
    van Manen H-J, Lenferink A, Otto C 2008. Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy. Anal. Chem. 80:249576–82
    [Google Scholar]
  111. 111.
    Villareal VA, Fu D, Costello DA, Xie XS, Yang PL 2016. Hepatitis C virus selectively alters the intracellular localization of desmosterol. ACS Chem. Biol. 11:71827–33
    [Google Scholar]
  112. 112.
    Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V et al. 2013. In vivo imaging of glucose uptake and metabolism in tumors. Nat. Med. 19:81067–72
    [Google Scholar]
  113. 113.
    Wang C, Han B, Zhou R, Zhuang X 2016. Real-time imaging of translation on single mRNA transcripts in live cells. Cell 165:4990–1001
    [Google Scholar]
  114. 114.
    Wang C-C, Moorhouse S, Stain C, Seymour M, Green E et al. 2018. In situ chemically specific mapping of agrochemical seed coatings using stimulated Raman scattering microscopy. J. Biophoton. 11:11e20180010
    [Google Scholar]
  115. 115.
    Wang P, Li J, Wang P, Hu C-R, Zhang D et al. 2013. Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral stimulated Raman scattering microscopy. Angew. Chem. Int. Ed. 52:4913042–46
    [Google Scholar]
  116. 116.
    Weeks T, Schie I, den Hartigh LJ, Rutledge JC, Huser T 2011. Lipid-cell interactions in human monocytes investigated by doubly-resonant coherent anti-Stokes Raman scattering microscopy. J. Biomed. Opt. 16:221117
    [Google Scholar]
  117. 117.
    Wei L, Chen Z, Shi L, Long R, Anzalone AV et al. 2017. Super-multiplex vibrational imaging. Nature 544:7651465–70
    [Google Scholar]
  118. 118.
    Wei L, Hu F, Chen Z, Shen Y, Zhang L, Min W 2016. Live-cell bioorthogonal chemical imaging: stimulated Raman scattering microscopy of vibrational probes. Acc. Chem. Res. 49:81494–502
    [Google Scholar]
  119. 119.
    Wei L, Hu F, Shen Y, Chen Z, Yu Y et al. 2014. Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering. Nat. Methods 11:4410–12
    [Google Scholar]
  120. 120.
    Wei L, Shen Y, Xu F, Hu F, Harrington JK et al. 2015. Imaging complex protein metabolism in live organisms by stimulated Raman scattering microscopy with isotope labeling. ACS Chem. Biol. 10:3901–8
    [Google Scholar]
  121. 121.
    Wei L, Yu Y, Shen Y, Wang MC, Min W 2013. Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy. PNAS 110:11226–31
    [Google Scholar]
  122. 122.
    Wenk MR 2005. The emerging field of lipidomics. Nat. Rev. Drug Discov. 4:7594–610
    [Google Scholar]
  123. 123.
    Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS 2008. Molecular imaging in drug development. Nat. Rev. Discov. 7:7591–607
    [Google Scholar]
  124. 124.
    Wu B, Eliscovich C, Yoon YJ, Singer RH 2016. Translation dynamics of single mRNAs in live cells and neurons. Science 352:6292aaf1084
    [Google Scholar]
  125. 125.
    Yamakoshi H, Dodo K, Okada M, Ando J, Palonpon A et al. 2011. Imaging of EdU, an alkyne-tagged cell proliferation probe, by Raman microscopy. J. Am. Chem. Soc. 133:166102–5
    [Google Scholar]
  126. 126.
    Yamakoshi H, Dodo K, Palonpon AF, Fujita K, Kawata S, Sodeoka M 2012. Alkyne-tag Raman imaging for visualization of mobile small molecules in live cells. J. Am. Chem. Soc. 134:5120681–89
    [Google Scholar]
  127. 127.
    Yamakoshi H, Palonpon AF, Dodo K, Ando J, Kawata S et al. 2014. Simultaneous imaging of protonated and deprotonated carbonylcyanide p-trifluoromethoxyphenylhydrazone in live cells by Raman microscopy. Chem. Commun. 50:111341–43
    [Google Scholar]
  128. 128.
    Yamakoshi H, Palonpon A, Dodo K, Ando J, Kawata S et al. 2015. A sensitive and specific Raman probe based on bisarylbutadiyne for live cell imaging of mitochondria. Bioorg. Med. Chem. Lett. 25:3664–67
    [Google Scholar]
  129. 129.
    Yan X, Hoek TA, Vale RD, Tanenbaum ME 2016. Dynamics of translation of single mRNA molecules in vivo. Cell 165:4976–89
    [Google Scholar]
  130. 130.
    Yu Y, Mutlu AS, Liu H, Wang MC 2017. High-throughput screens using photo-highlighting discover BMP signaling in mitochondrial lipid oxidation. Nat. Commun. 8:1865
    [Google Scholar]
  131. 131.
    Yu Y, Ramachandran PV, Wang MC 2014. Shedding new light on lipid functions with CARS and SRS microscopy. Biochim. Biophys. Acta 1841:81120–29
    [Google Scholar]
  132. 132.
    Yue S, Li J, Lee S-Y, Lee HJ, Shao T et al. 2014. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab 19:3393–406
    [Google Scholar]
  133. 133.
    Zeng C, Hu F, Long R, Min W 2018. A radiometric Raman probe for live-cell imaging of hydrogen sulfide in mitochondria by stimulated Raman scattering. Analyst 143:204844–48
    [Google Scholar]
  134. 134.
    Zenobi R 2013. Single-cell metabolomics: analytical and biological perspectives. Science 342:61631243259
    [Google Scholar]
  135. 135.
    Zhang C, Zhang D, Cheng J-X 2015. Coherent Raman scattering microscopy in biology and medicine. Annu. Rev. Biomed. Eng. 17:415–45
    [Google Scholar]
  136. 136.
    Zhang D, Slipchenko MN, Cheng J-X 2011. Highly sensitive vibrational imaging by femtosecond pulse stimulated Raman loss. J. Phys. Chem. Lett. 2:111248–53
    [Google Scholar]
  137. 137.
    Zhang D, Wang P, Slipchenko MN, Ben-Amotz D, Weiner AM, Cheng J-X 2013. Quantitative vibrational imaging by hyperspectral stimulated Raman scattering microscopy and multivariate curve resolution analysis. Anal. Chem. 85:198–106
    [Google Scholar]
  138. 138.
    Zhang D, Wang P, Slipchenko MN, Cheng J-X 2014. Fast vibrational imaging of single cells and tissues by stimulated Raman scattering microscopy. Acc. Chem. Res. 47:82282–90
    [Google Scholar]
  139. 139.
    Zhang D, Wang PP, Slipchenko MN, Cheng J, Leaird DE et al. 2014. Breaking the diffraction limit by saturation in stimulated-Raman-scattering microscopy: a theoretical study. Phys. Rev. A 11:12641–43
    [Google Scholar]
  140. 140.
    Zhang J, Yan S, He Z, Ding C, Zhai T et al. 2018. Small unnatural amino acid carried Raman tag for molecular imaging of genetically targeted proteins. J. Phys. Chem. Lett. 9:164679–85
    [Google Scholar]
  141. 141.
    Zhang L, Min W 2017. Bioorthogonal chemical imaging of metabolic changes during epithelial-mesenchymal transition of cancer cells by stimulated Raman scattering microscopy. J. Biomed. Opt. 22:101–7
    [Google Scholar]
  142. 142.
    Zhang X, de Juan A, Tauler R 2015. Multivariate curve resolution applied to hyperspectral imaging analysis of chocolate samples. Appl. Spectrosc. 69:8993–1003
    [Google Scholar]
  143. 143.
    Zhao Z, Shen Y, Hu F, Min W 2017. Applications of vibrational tags in biological imaging by Raman microscopy. Analyst 142:214018–29
    [Google Scholar]
  144. 144.
    Zumbusch A, Holtom GR, Xie XS 1999. Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys. Rev. Lett. 82:204142–45
    [Google Scholar]
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