Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy
Open accessAbstract
Imaging living organisms with molecular selectivity typically requires the introduction of specific labels. Many applications in biology and medicine, however, would significantly benefit from a noninvasive imaging technique that circumvents such exogenous probes. In vivo microscopy based on vibrational spectroscopic contrast offers a unique approach for visualizing tissue architecture with molecular specificity. We have developed a sensitive technique for vibrational imaging of tissues by combining coherent anti-Stokes Raman scattering (CARS) with video-rate microscopy. Backscattering of the intense forward-propagating CARS radiation in tissue gives rise to a strong epi-CARS signal that makes in vivo imaging possible. This substantially large signal allows for real-time monitoring of dynamic processes, such as the diffusion of chemical compounds, in tissues. By tuning into the CH 2 stretching vibrational band, we demonstrate CARS imaging and spectroscopy of lipid-rich tissue structures in the skin of a live mouse, including sebaceous glands, corneocytes, and adipocytes, with unprecedented contrast at subcellular resolution.
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CARS imaging has pixel dwell times in the range of microseconds and is significantly faster than spontaneous Raman imaging due to a 105 times higher CARS signal compared to spontaneous Raman scattering.
“Compared to spontaneous Raman imaging with typical pixel dwell times of several seconds181920, pixel dwell times in CARS imaging are in the range of microseconds21 and thus significantly faster due to a 105 times higher CARS signal compared to spontaneous Raman scattering22.”
From Label-free in vivo analysis of intracellular lipid droplets in the oleaginous microalga Monoraphidium neglectum by coherent Raman scattering microscopy (2016) · cites this paper as [21]
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Two-photon laser scanning fluorescence microscopy
Denk, W., Strickler, J. H., & Webb, W. W. (1990) · Science · doi:10.1126/science.2321027 · Cited by 9,488 · see citing works
MCML—Monte Carlo modeling of light transport in multi-layered tissues
Wang, L. V., Jacques, S. L., & Zheng, L. (1995) · Computer Methods and Programs in Biomedicine · doi:10.1016/0169-2607(95)01640-f · Cited by 3,330 · see citing works
Zipfel, W. R., Williams, R. M., Christie, R. H., Nikitin, A. Y., Hyman, B. T., & Webb, W. W. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832308100 · Cited by 1,691 · see citing works
Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering
Zumbusch, A., Holtom, G. R., & Xie, X. S. (1999) · Physical Review Letters · doi:10.1103/physrevlett.82.4142 · Cited by 1,610 · see citing works
Self-citationStudy of Optical Effects Due to an Induced Polarization Third Order in the Electric Field Strength
Maker, P. D., & Terhune, R. W. (1965) · Physical Review · doi:10.1103/physrev.137.a801 · Cited by 1,373 · see citing works
Campagnola, P. J., & Loew, L. M. (2003) · Nature Biotechnology · doi:10.1038/nbt894 · Cited by 1,326 · see citing works
Optical coherence tomography for ultrahigh resolution in vivo imaging
Fujimoto, J. G. (2003) · Nature Biotechnology · doi:10.1038/nbt892 · Cited by 1,036 · see citing works
Coherent Anti-Stokes Raman Scattering Microscopy: Instrumentation, Theory, and Applications
Cheng, J., & Xie, X. S. (2003) · The Journal of Physical Chemistry B · doi:10.1021/jp035693v · Cited by 962 · see citing works
Self-citationRajadhyaksha, M. M., González, S., Zavislan, J. M., Anderson, R. R., & Webb, R. H. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00690.x · Cited by 831 · see citing works
Optical properties of intralipid: A phantom medium for light propagation studies
Flock, S. T., Jacques, S. L., Wilson, B. C., Star, W. M., & van Gemert, M. J. C. (1992) · Lasers in Surgery and Medicine · doi:10.1002/lsm.1900120510 · Cited by 573 · see citing works
Two-photon tissue imaging: seeing the immune system in a fresh light
Cahalan, M. D., Parker, I., Wei, S. H., & Miller, M. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri935 · Cited by 486 · see citing works
Polarization coherent anti-Stokes Raman scattering microscopy
Cheng, J., Book, L. D., & Xie, X. S. (2001) · Optics Letters · doi:10.1364/ol.26.001341 · Cited by 402 · see citing works
Self-citationTheoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy
Cheng, J., Volkmer, A., & Xie, X. S. (2002) · Journal of the Optical Society of America B · doi:10.1364/josab.19.001363 · Cited by 380 · see citing works
Self-citationModel for photon migration in turbid biological media
Bonner, R. F., Nossal, R., Havlin, S., & Weiss, G. H. (1987) · Journal of the Optical Society of America A · doi:10.1364/josaa.4.000423 · Cited by 378 · see citing works
Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles
Cheng, J., Volkmer, A., Book, L. D., & Xie, X. S. (2002) · The Journal of Physical Chemistry B · doi:10.1021/jp025771z · Cited by 342 · see citing works
Self-citationCoherent Anti-Stokes Raman Scattering Imaging of Axonal Myelin in Live Spinal Tissues
Wang, H., Fu, Y., Zickmund, P., Shi, R., & Cheng, J. (2005) · Biophysical Journal · doi:10.1529/biophysj.105.061911 · Cited by 317 · see citing works
Nan, X., Cheng, J.-X., & Xie, X. S. (2003) · Journal of Lipid Research · doi:10.1194/jlr.d300022-jlr200 · Cited by 315 · see citing works
Self-citationVideo-rate confocal scanning laser microscope for imaging human tissues in vivo
Rajadhyaksha, M. M., Anderson, R. R., & Webb, R. H. (1999) · Applied Optics · doi:10.1364/ao.38.002105 · Cited by 300 · see citing works
Medical applications of Raman spectroscopy: From proof of principle to clinical implementation
Choo, L.-P., Edwards, H. G. M., Endtz, H. P., Kros, J. M., Heule, F., Barr, H., Robinson, J. S., Bruining, H. A., & Puppels, G. J. (2002) · Biopolymers · doi:10.1002/bip.10064 · Cited by 280 · see citing works
Composition and Morphology of Epidermal Cyst Lipids
Wertz, P. W., Swartzendruber, D. C., Madison, K. C., & Downing, D. T. (1987) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12471781 · Cited by 226 · see citing works
Real-time visualization of intracellular hydrodynamics in single living cells
Potma, E. O., de Boeij, W. P., Haastert, P. J. M. V., & Wiersma, D. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1577 · Cited by 192 · see citing works
Self-citationConfocal microscopy and multi-photon excitation microscopy of human skin in vivo
Masters, B. R., & So, P. T. C. (2001) · Optics Express · doi:10.1364/oe.8.000002 · Cited by 175 · see citing works
Detection of single lipid bilayers with coherent anti‐Stokes Raman scattering (CARS) microscopy
Potma, E. O., & Xie, X. S. (2003) · Journal of Raman Spectroscopy · doi:10.1002/jrs.1045 · Cited by 161 · see citing works
Self-citationUltra-deep two-photon fluorescence excitation in turbid media
Beaurepaire, E., Oheim, M., & Mertz, J. C. (2001) · Optics Communications · doi:10.1016/s0030-4018(00)01156-1 · Cited by 137 · see citing works
Direct Measurement of Chain Order in Single Phospholipid Mono- and Bilayers with Multiplex CARS
Wurpel, G. W. H., Schins, J. M., & Müller, M. (2004) · The Journal of Physical Chemistry B · doi:10.1021/jp037629j · Cited by 90 · see citing works
Chemistry and Function of Mammalian Sebaceous Lipids
Stewart, M. E., & Downing, D. T. (1991) · Advances in lipid research · doi:10.1016/b978-0-12-024924-4.50013-4 · Cited by 83 · see citing works
Miller, L. M., Smith, G. D., & Carr, G. L. (2003) · Journal of Biological Physics · doi:10.1023/a:1024401027599 · Cited by 64 · see citing works
Flagged first, then by citations
Research works printed but not linked: 29
- [1]Rajadhyaksha, M., Gonzalez, S., Zavislan, J. M., Anderson, R. R. & Webb, R. H. (1999) J. Invest. Dermatol. 113, 293-303. [DOI] [PubMed] [Google Scholar]
- [2]Fujimoto, J. G. (2003) Nat. Biotechnol. 21, 1361-1367. [DOI] [PubMed] [Google Scholar]
- [3]Masters, B. R. & So, P. T. C. (2001) Opt. Express 8, 2-10. [DOI] [PubMed] [Google Scholar]
- [4]Zipfel, W. R., Williams, R. M., Christie, R., Nikitin, A. Y., Hyman, B. T. & Webb, W. W. (2003) Proc. Natl. Acad. Sci. USA 100, 7075-7080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5]Campagnola, P. J. & Loew, L. M. (2003) Nat. Biotechnol. 21, 1356-1360. [DOI] [PubMed] [Google Scholar]
- [6]Miller, L. M., Smith, G. D. & Carr, G. L. (2003) Biol. Phys. 29, 219-230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7]Choo-Smith, L. P., Edwards, H. G. M., Endtz, H. P., Kros, J. M., Heule, F., Barr, H., Robinson, J. S., Bruining, H. A. & Puppels, G. J. (2002) Biopolymers 67, 1-9. [DOI] [PubMed] [Google Scholar]
- [8]Maker, P. D. & Terhune, R. W. (1965) Phys. Rev. 137, A801-A818. [Google Scholar]
- [9]Denk, W., Strickler, J. H. & Webb, W. W. (1990) Science 248, 73-76. [DOI] [PubMed] [Google Scholar]
- [10]Cheng, J. X. & Xie, X. S. (2004) J. Phys. Chem. B 108, 827-840. [Google Scholar]
- [11]Nan, X. L., Cheng, J. X. & Xie, X. S. (2003) J. Lipid Res. 44, 2202-2208. [DOI] [PubMed] [Google Scholar]
- [12]Cheng, J. X., Book, L. D. & Xie, X. S. (2001) Opt. Lett. 26, 1341-1343. [DOI] [PubMed] [Google Scholar]
- [13]Potma, E. O., de Boeij, W. P., van Haastert, P. J. M. & Wiersma, D. A. (2001) Proc. Natl. Acad. Sci. USA 98, 1577-1582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14]Potma, E. O. & Xie, X. S. (2003) J. Raman Spectrosc. 34, 642-650. [Google Scholar]
- [15]Wurpel, G. W. H., Schins, J. M. & Muller, M. (2004) J. Phys. Chem. B 108, 3400-3403. [Google Scholar]
- [16]Wang, H., Fu, Y., Zickmund, P., Shi, R. & Cheng, J. X. (2005) Biophys. J. 89, 581-591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17]Cheng, J. X., Volkmer, A. & Xie, X. S. (2002) J. Opt. Soc. Am. B 19, 1363-1375. [Google Scholar]
- [18]Cheng, J. X., Volkmer, A., Book, L. D. & Xie, X. S. (2002) J. Phys. Chem. B 106, 8493-8498. [Google Scholar]
- [19]Wang, L., Jacques, S. L. & Zheng, L. (1995) Comput. Meth. Prog. Biomed. 47, 131-146. [DOI] [PubMed] [Google Scholar]
- [20]Yodh, A. G., Tromberg, B., Sevick-Muraca, E. & Pine, D., eds. (1997) J. Opt. Soc. Am. A 14, 136-342. [Google Scholar]
- [21]Bonner, R. F., Nossal, R., Havlin, S. & Weiss, G. H. (1987) J. Opt. Soc. Am. A 4, 423-432. [DOI] [PubMed] [Google Scholar]
- [22]Flock, S. T., Jacques, S. L., Wilson, B. C., Star, W. M. & van Gemert, M. J. (1992) Lasers Surg. Med. 12, 510-519. [DOI] [PubMed] [Google Scholar]
- [23]Wertz, P. W., Schwartzendruber, D. C., Madison, K. C. & Downing, D. T. (1987) J. Invest. Dermatol. 89, 419-425. [DOI] [PubMed] [Google Scholar]
- [24]Stewart, M. E. & Downing, D. T. (1991) Adv. Lipid Res. 24, 263-301. [DOI] [PubMed] [Google Scholar]
- [25]Zumbusch, A., Holtom, G. & Xie, X. S. (1999) Phys. Rev. Lett. 82, 4142-4145. [Google Scholar]
- [26]Potma, E. O., Evans, C. L. & Xie, X. S. (2005) Opt. Lett., in press.
- [27]Beaurepaire, E., Oheim, M. & Mertz, J. (2001) Optics Comm. 188, 25-29. [Google Scholar]
- [28]Cahalan, M. D., Parker, I., Wei, S. H. & Miller, M. J. (2002) Nat. Rev. Immunol. 2, 872-880. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29]Rajadhyaksha, M., Anderson, R. R. & Webb, R. H. (1999) Appl. Opt. 38, 2105-2115. [DOI] [PubMed] [Google Scholar]
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Self-citationGanikhanov, F., Evans, C. L., Saar, B. G., & Xie, X. S. (2006) · Optics Letters · doi:10.1364/ol.31.001872 · Cited by 235 · see citing works
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Downes, A., & Elfick, A. P. D. (2010) · Sensors · doi:10.3390/s100301871 · Cited by 218 · see citing works
Chemical analysis in vivo and in vitro by Raman spectroscopy—from single cells to humans
Wachsmann‐Hogiu, S., Weeks, T. J., & Huser, T. R. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.02.006 · Cited by 201 · see citing works
Optical contrast agents and imaging systems for detection and diagnosis of cancer
Pierce, M. C., Javier, D. J., & Richards-Kortum, R. R. (2008) · International Journal of Cancer · doi:10.1002/ijc.23858 · Cited by 201 · see citing works
Characterization of photodamage in coherent anti-Stokes Raman scattering microscopy
Fu, Y., Wang, H., Shi, R., & Cheng, J. (2006) · Optics Express · doi:10.1364/oe.14.003942 · Cited by 200 · see citing works
Krafft, C., Schie, I. W., Meyer, T., Schmitt, M. P., & Popp, J. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00564g · Cited by 199 · see citing works
Ultrafast and nonlinear surface-enhanced Raman spectroscopy
Gruenke, N. L., Cardinal, M. F., McAnally, M. O., Frontiera, R. R., Schatz, G. C., & Duyne, R. P. V. (2016) · Chemical Society Reviews · doi:10.1039/c5cs00763a · Cited by 194 · see citing works
From molecular structure to tissue architecture: collagen organization probed by SHG microscopy
Cicchi, R., Vogler, N., Kapsokalyvas, D., Dietzek, B., Popp, J., & Pavone, F. S. (2012) · Journal of Biophotonics · doi:10.1002/jbio.201200092 · Cited by 191 · see citing works
Functional nano-systems for transdermal drug delivery and skin therapy
Liu, L., Wenbin, Z., Ma, Q., Gao, Y., Wang, W., Zhang, X., Dong, Y., Zhang, T., Liang, Y., Han, S., et al. (2023) · Nanoscale Advances · doi:10.1039/d2na00530a · Cited by 191 · see citing works
Label-free live brain imaging and targeted patching with third-harmonic generation microscopy
Witte, S. M., Negrean, A., Lodder, J. C., de Kock, C. P. J., Silva, G. T., Mansvelder, H. D., & Groot, M. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018743108 · Cited by 184 · see citing works
Stewart, S. D., Priore, R. J., Nelson, M. P., & Treado, P. J. (2012) · Annual Review of Analytical Chemistry · doi:10.1146/annurev-anchem-062011-143152 · Cited by 184 · see citing works
Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis
Le, T. T., Huff, T. B., & Cheng, J. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-42 · Cited by 183 · see citing works
Freudiger, C. W., Min, W., Holtom, G. R., Xu, B., Dantus, M. M., & Xie, X. S. (2011) · Nature Photonics · doi:10.1038/nphoton.2010.294 · Cited by 182 · see citing works
Self-citationMultimodal nonlinear optical microscopy
Yue, S., Slipchenko, M. N., & Cheng, J. (2011) · Laser & Photonics Review · doi:10.1002/lpor.201000027 · Cited by 181 · see citing works
Infrared multiphoton microscopy: subcellular-resolved deep tissue imaging
Andresen, V., Alexander, S., Heupel, W.-M., Hirschberg, M., Hoffman, R. M., & Friedl, P. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.02.008 · Cited by 179 · see citing works
Xu, L., Buldyrev, S. V., Angell, C. A., & Stanley, E. (2006) · Physical Review E · doi:10.1103/physreve.74.031108 · Cited by 172 · see citing works
Label‐Free Live‐Cell Imaging of Nucleic Acids Using Stimulated Raman Scattering Microscopy
Zhang, X., Roeffaers, M. B. J., Basu, S., Daniele, J. R., Fu, D., Freudiger, C. W., Holtom, G. R., & Xie, X. S. (2012) · ChemPhysChem · doi:10.1002/cphc.201100890 · Cited by 171 · see citing works
Self-citationCarriles, R., Schafer, D. N., Sheetz, K. E., Field, J. J., Cisek, R., Barzda, V., Sylvester, A. W., & Squier, J. A. (2009) · Review of Scientific Instruments · doi:10.1063/1.3184828 · Cited by 171 · see citing works
Super-Resolution Far-Field Infrared Imaging by Photothermal Heterodyne Imaging
Li, Z., Aleshire, K., Kuno, M. K., & Hartland, G. V. (2017) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.7b06065 · Cited by 170 · see citing works
Fu, Y., Huff, T. B., Wang, H.-W., Cheng, J., & Wang, H. (2008) · Optics Express · doi:10.1364/oe.16.019396 · Cited by 167 · see citing works
Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy
Le, T. T., Yue, S., & Cheng, J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r008730 · Cited by 166 · see citing works
Le, T. T., Langohr, I. M., Locker, M. J., Sturek, M. S., & Cheng, J. (2007) · Journal of Biomedical Optics · doi:10.1117/1.2795437 · Cited by 165 · see citing works
Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes
Kim, K., Lee, S., Yoon, J. W., Heo, J., Choi, C., & Park, Y. (2016) · Scientific Reports · doi:10.1038/srep36815 · Cited by 165 · see citing works
Raman and coherent anti-Stokes Raman scattering microspectroscopy for biomedical applications
Krafft, C., Dietzek, B., Popp, J., & Schmitt, M. (2012) · Journal of Biomedical Optics · doi:10.1117/1.jbo.17.4.040801 · Cited by 164 · see citing works
Nonlinear Interferometric Vibrational Imaging and Spectroscopy
Boppart, S. A. (2014) · CRC Press eBooks · doi:10.1201/b17288-14 · Cited by 163 · see citing works
Real-Time Fluorescence Image-Guided Oncologic Surgery
Mondal, S., Gao, S., Zhu, N., Liang, R., Gruev, V., & Achilefu, S. (2014) · Advances in cancer research · doi:10.1016/b978-0-12-411638-2.00005-7 · Cited by 163 · see citing works
Nonlinear microscopy, infrared, and Raman microspectroscopy for brain tumor analysis
Meyer, T., Bergner, N., Krafft, C., Akimov, D., Dietzek, B., Popp, J., Bielecki, C., Romeike, B. F. M., Reichart, R., & Kalff, R. (2011) · Journal of Biomedical Optics · doi:10.1117/1.3533268 · Cited by 156 · see citing works
Multicolored stain-free histopathology with coherent Raman imaging
Freudiger, C. W., Pfannl, R., Orringer, D. A., Saar, B. G., Ji, M., Zeng, Q., Ottoboni, L., Ying, W., Waeber, C., Sims, J. R., et al. (2012) · Laboratory Investigation · doi:10.1038/labinvest.2012.109 · Cited by 154 · see citing works
Self-citationFranzen, L., & Windbergs, M. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.04.002 · Cited by 153 · see citing works
Broadband Coherent Raman Scattering Microscopy
Polli, D., Kumar, V., Valensise, C. M., Marangoni, M., & Cerullo, G. (2018) · Laser & Photonics Review · doi:10.1002/lpor.201800020 · Cited by 151 · see citing works
Petrov, G. I., Arora, R., Yakovlev, V. V., Wang, X., Sokolov, A. V., & Scully, M. O. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702107104 · Cited by 151 · see citing works
Vogt, A., Wischke, C., Neffe, A. T., Ma, N., Alexiev, U., & Lendlein, A. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.07.027 · Cited by 150 · see citing works
Applications and future directions for optical coherence tomography in dermatology*
Wan, B., Ganier, C., Du‐Harpur, X., Harun, N., Watt, F. M., Patalay, R., & Lynch, M. D. (2021) · British Journal of Dermatology · doi:10.1111/bjd.19553 · Cited by 148 · see citing works
Bond-selective imaging by optically sensing the mid-infrared photothermal effect
Bai, Y., Yin, J., & Cheng, J. (2021) · Science Advances · doi:10.1126/sciadv.abg1559 · Cited by 147 · see citing works
Quantitative Coherent Anti-Stokes Raman Scattering (CARS) Microscopy
Day, J. P. R., Domke, K. F., Rago, G., Kano, H., Hamaguchi, H., Vartiainen∥, E. M., & Bonn, M. (2011) · The Journal of Physical Chemistry B · doi:10.1021/jp200606e · Cited by 146 · see citing works
Micro‐Raman spectroscopy of algae: Composition analysis and fluorescence background behavior
Huang, Y. Y., Beal, C. M., Cai, W. W., Ruoff, R. S., & Terentjev, E. M. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22617 · Cited by 145 · see citing works
Zhu, J., Lee, B., Buhman, K. K., & Cheng, J. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m800555-jlr200 · Cited by 145 · see citing works
Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology
Bhargava, R., & Madabhushi, A. (2016) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-112415-114722 · Cited by 145 · see citing works
Coherent Anti-Stokes Raman Scattering Microscopy
Cheng, J. (2007) · Applied Spectroscopy · doi:10.1366/000370207781746044 · Cited by 144 · see citing works
Four-wave mixing microscopy of nanostructures
Wang, Y., Lin, C., Nikolaenko, A., Raghunathan, V., & Potma, E. O. (2010) · Advances in Optics and Photonics · doi:10.1364/aop.3.000001 · Cited by 142 · see citing works
Self-citationPlasmon-enhanced stimulated Raman scattering microscopy with single-molecule detection sensitivity
Zong, C., Premasiri, R., Lin, H., Huang, Y., Zhang, C., Yang, C., Ren, B. W., Ziegler, L. D., & Cheng, J. (2019) · Nature Communications · doi:10.1038/s41467-019-13230-1 · Cited by 142 · see citing works
Advances in Imaging Plant Cell Walls
Zhao, Y., Man, Y., Wen, J., Guo, Y., & Lin, J. (2019) · Trends in Plant Science · doi:10.1016/j.tplants.2019.05.009 · Cited by 141 · see citing works
Coherent Raman scanning fiber endoscopy
Saar, B. G., Johnston, R. S., Freudiger, C. W., Xie, X. S., & Seibel, E. J. (2011) · Optics Letters · doi:10.1364/ol.36.002396 · Cited by 140 · see citing works
Self-citationSingle-shot detection of bacterial endospores via coherent Raman spectroscopy
Pestov, D., Wang, X., Ariunbold, G. O., Murawski, R. K., Sautenkov, V. A., Dogariu, A., Sokolov, A. V., & Scully, M. O. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710427105 · Cited by 138 · see citing works
Toward Label-Free Super-Resolution Microscopy
Silva, W. R., Graefe, C. T., & Frontiera, R. R. (2015) · ACS Photonics · doi:10.1021/acsphotonics.5b00467 · Cited by 137 · see citing works
High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman Spectroscopy
Horgan, C. C., Jensen, M., Nagelkerke, A., St‐Pierre, J., Vercauteren, T. K., Stevens, M. M., & Bergholt, M. S. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c02178 · Cited by 137 · see citing works
Kumar, S., Verma, T., Mukherjee, R., Ariese, F., Somasundaram, K., & Umapathy, S. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00540j · Cited by 136 · see citing works
Unveiling the Molecular Secrets: A Comprehensive Review of Raman Spectroscopy in Biological Research
Chandra, A., Kumar, V., Garnaik, U. C., Dada, R., Qamar, I., Goel, V. K., & Agarwal, S. (2024) · ACS Omega · doi:10.1021/acsomega.4c00591 · Cited by 136 · see citing works
High-Speed Vibrational Imaging and Spectral Analysis of Lipid Bodies by Compound Raman Microscopy
Slipchenko, M. N., Le, T. T., Chen, H., & Cheng, J. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp902231y · Cited by 136 · see citing works
Imaging with Raman Spectroscopy
Zhang, Y., Hong, H., & Cai, W. (2010) · Current Pharmaceutical Biotechnology · doi:10.2174/138920110792246483 · Cited by 133 · see citing works
- Authors
- Evans, C. L., Potma, E. O., Puoris'haag, M., Côté, D., Lin, C. P., & Xie, X. S.
- Affiliations
- Harvard University (US)
- Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138; and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-11
- Volume
- 102
- Issue
- 46
- Pages
- 16807-16812
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1283840
- OpenAlex
- W2148691803
- Cited by
- 957
- References
- 27
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 32 · 2023: 42 · 2022: 38 · 2021: 40 · 2020: 31 · 2019: 45 · 2018: 36 · 2017: 47 · 2016: 70 · 2015: 58 · 2014: 59 · 2013: 54 · 2012: 64
- FWCI
- 21.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Spectroscopy and Quantum Chemical Studies
- Keywords
- coherent anti-Stokes Raman scattering microscopy, in vivo tissue imaging, vibrational imaging, noninvasive molecular imaging, skin, sebaceous glands, corneocytes, adipocytes, mouse skin
- MeSH terms
- Animals, Diffusion, Female, Mice, Inbred BALB C, Mice, Hairless, Microscopy, Mineral Oil, Scattering, Radiation, Skin, Spectrum Analysis, Raman, Mice
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