Abstract

Stimulated Raman scattering (SRS) microscopy is a promising technique for studying tissue structure, physiology, and function. Similar to other nonlinear optical imaging techniques, SRS is severely limited in imaging depth due to the turbidity and heterogeneity of tissue, regardless of whether imaging in the transmissive or epi mode. While this challenge is well known, important imaging parameters (namely maximum imaging depth and imaging signal to noise ratio) have rarely been reported in the literature. It is also important to compare epi mode and transmissive mode imaging to determine the best geometry for many tissue imaging applications. In this manuscript we report the achievable signal sizes and imaging depths using a simultaneous epi/transmissive imaging approach in four different murine tissues; brain, lung, kidney, and liver. For all four cases we report maximum signal sizes, scattering lengths, and achievable imaging depths as a function of tissue type and sample thickness. We report that for murine brain samples thinner than 2 mm transmissive imaging provides better results, while samples 2 mm and thicker are best imaged with epi imaging. We also demonstrate the use of a CNN-based denoising algorithm to yield a 40 µm (24%) increase in achievable imaging depth.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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    [Crossref]

2019 (9)

A. H. Hill and D. Fu, “Cellular Imaging Using Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(15), 9333–9342 (2019).
[Crossref]

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

B. Sarri, F. Poizat, S. Heuke, J. Wojak, F. Franchi, F. Caillol, M. Giovannini, and H. Rigneault, “Stimulated Raman histology: one to one comparison with standard hematoxylin and eosin staining,” Biomed. Opt. Express 10(10), 5378–5384 (2019).
[Crossref]

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
[Crossref]

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
[Crossref]

B. Manifold, E. Thomas, A. T. Francis, A. H. Hill, and D. Fu, “Denoising of stimulated Raman scattering microscopy images via deep learning,” Biomed. Opt. Express 10(8), 3860–3874 (2019).
[Crossref]

M. J. B. Moester, L. Zada, B. Fokker, F. Ariese, and J. F. de Boer, “Stimulated Raman scattering microscopy with long wavelengths for improved imaging depth,” J. Raman Spectrosc. 50(9), 1321–1328 (2019).
[Crossref]

J. Li, P. Lin, Y. Tan, and J.-X. Cheng, “Volumetric stimulated Raman scattering imaging of cleared tissues towards three-dimensional chemical histopathology,” Biomed. Opt. Express 10(8), 4329–4339 (2019).
[Crossref]

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

2018 (5)

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

C. Ounkomol, S. Seshamani, M. M. Maleckar, F. Collman, and G. R. Johnson, “Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy,” Nat. Methods 15(11), 917–920 (2018).
[Crossref]

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

M. Wang, C. Wu, D. Sinefeld, B. Li, F. Xia, and C. Xu, “Comparing the effective attenuation lengths for long wavelength in vivo imaging of the mouse brain,” Biomed. Opt. Express 9(8), 3534–3543 (2018).
[Crossref]

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
[Crossref]

2017 (3)

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

D. Fu, W. L. Yang, and X. L. S. Xie, “Label-free Imaging of Neurotransmitter Acetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering,” J. Am. Chem. Soc. 139(2), 583–586 (2017).
[Crossref]

D. Fu, “Quantitative chemical imaging with stimulated Raman scattering microscopy,” Curr. Opin. Chem. Biol. 39, 24–31 (2017).
[Crossref]

2016 (1)

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

2015 (3)

J.-X. Cheng and X. S. Xie, “Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine,” Science 350(6264), aaa8870 (2015).
[Crossref]

C. Zhang, D. Zhang, and J.-X. Cheng, “Coherent Raman Scattering Microscopy in Biology and Medicine,” Annu. Rev. Biomed. Eng. 17(1), 415–445 (2015).
[Crossref]

D. S. Richardson and J. W. Lichtman, “Clarifying Tissue Clearing,” Cell 162(2), 246–257 (2015).
[Crossref]

2014 (5)

A. Alfonso-García, R. Mittal, E. S. Lee, and E. O. Potma, “Biological imaging with coherent Raman scattering microscopy: a tutorial,” J. Biomed. Opt. 19(7), 071407 (2014).
[Crossref]

D. Zhang, P. Wang, M. N. Slipchenko, and J.-X. Cheng, “Fast Vibrational Imaging of Single Cells and Tissues by Stimulated Raman Scattering Microscopy,” Acc. Chem. Res. 47(8), 2282–2290 (2014).
[Crossref]

L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
[Crossref]

S. Hong, T. Chen, Y. Zhu, A. Li, Y. Huang, and X. Chen, “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules,” Angew. Chem., Int. Ed. 53(23), 5827–5831 (2014).
[Crossref]

D. M. Drutis, T. M. Hancewicz, E. Pashkovski, L. Feng, D. Mihalov, G. R. Holtom, K. P. Ananthapadmanabhan, X. S. Xie, and M. Misra, “Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy,” J. Biomed. Opt. 19(11), 111604 (2014).
[Crossref]

2013 (1)

L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
[Crossref]

2011 (1)

2010 (2)

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
[Crossref]

V. Chauhan, P. Bowlan, J. Cohen, and R. Trebino, “Single-diffraction-grating and grism pulse compressors,” J. Opt. Soc. Am. B 27(4), 619–624 (2010).
[Crossref]

2007 (2)

2005 (2)

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 102(46), 16807–16812 (2005).
[Crossref]

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

Agar, N. Y. R.

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

Alfonso-García, A.

A. Alfonso-García, R. Mittal, E. S. Lee, and E. O. Potma, “Biological imaging with coherent Raman scattering microscopy: a tutorial,” J. Biomed. Opt. 19(7), 071407 (2014).
[Crossref]

Ananthapadmanabhan, K. P.

D. M. Drutis, T. M. Hancewicz, E. Pashkovski, L. Feng, D. Mihalov, G. R. Holtom, K. P. Ananthapadmanabhan, X. S. Xie, and M. Misra, “Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy,” J. Biomed. Opt. 19(11), 111604 (2014).
[Crossref]

Ariese, F.

M. J. B. Moester, L. Zada, B. Fokker, F. Ariese, and J. F. de Boer, “Stimulated Raman scattering microscopy with long wavelengths for improved imaging depth,” J. Raman Spectrosc. 50(9), 1321–1328 (2019).
[Crossref]

Boothe, T.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Bowlan, P.

Boyle, J.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

Broaddus, C.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Caillol, F.

Calligaris, D.

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

Camelo-Piragua, S.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

Chaigneau, E.

Chauhan, V.

Chen, C. P.

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
[Crossref]

Chen, L.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Chen, T.

S. Hong, T. Chen, Y. Zhu, A. Li, Y. Huang, and X. Chen, “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules,” Angew. Chem., Int. Ed. 53(23), 5827–5831 (2014).
[Crossref]

Chen, X.

S. Hong, T. Chen, Y. Zhu, A. Li, Y. Huang, and X. Chen, “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules,” Angew. Chem., Int. Ed. 53(23), 5827–5831 (2014).
[Crossref]

Chen, Y.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Chen, Z. X.

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M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
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Li, H.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
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Liu, C.

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F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
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Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
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D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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Mao, X.-J.

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Mao, Y.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
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L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
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D. M. Drutis, T. M. Hancewicz, E. Pashkovski, L. Feng, D. Mihalov, G. R. Holtom, K. P. Ananthapadmanabhan, X. S. Xie, and M. Misra, “Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy,” J. Biomed. Opt. 19(11), 111604 (2014).
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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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C. Ounkomol, S. Seshamani, M. M. Maleckar, F. Collman, and G. R. Johnson, “Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy,” Nat. Methods 15(11), 917–920 (2018).
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D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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Poland, S. P.

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Qu, J. A. Y.

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
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D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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Reichman, J.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
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D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
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Schmidt, D.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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C. Ounkomol, S. Seshamani, M. M. Maleckar, F. Collman, and G. R. Johnson, “Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy,” Nat. Methods 15(11), 917–920 (2018).
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Shen, Y.

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
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L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
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L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
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Shi, L.

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
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Sinefeld, D.

Slipchenko, M. N.

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M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
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L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
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Tan, Y.

Tang, B. Z.

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
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Tang, H.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
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Targoff, K.

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
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Thomas, E.

Tomancak, P.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
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Tong, S.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
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Trautman, J. K.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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Trebino, R.

Venneti, S.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
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Wang, H.

Wang, K.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
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Wang, M.

Wang, M. C.

L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
[Crossref]

L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
[Crossref]

Wang, P.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

D. Zhang, P. Wang, M. N. Slipchenko, and J.-X. Cheng, “Fast Vibrational Imaging of Single Cells and Tissues by Stimulated Raman Scattering Microscopy,” Acc. Chem. Res. 47(8), 2282–2290 (2014).
[Crossref]

Wei, L.

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
[Crossref]

L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
[Crossref]

L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
[Crossref]

Wei, M.

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
[Crossref]

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
[Crossref]

Weigert, M.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Wilhelm, B.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Wilkinson, D. A.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

Wojak, J.

Wright, A. J.

Wu, C.

Wu, W. J.

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
[Crossref]

Wu, Y. Z.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Xia, F.

Xie, X. L. S.

D. Fu, W. L. Yang, and X. L. S. Xie, “Label-free Imaging of Neurotransmitter Acetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering,” J. Am. Chem. Soc. 139(2), 583–586 (2017).
[Crossref]

Xie, X. S.

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

J.-X. Cheng and X. S. Xie, “Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine,” Science 350(6264), aaa8870 (2015).
[Crossref]

D. M. Drutis, T. M. Hancewicz, E. Pashkovski, L. Feng, D. Mihalov, G. R. Holtom, K. P. Ananthapadmanabhan, X. S. Xie, and M. Misra, “Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy,” J. Biomed. Opt. 19(11), 111604 (2014).
[Crossref]

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
[Crossref]

A. J. Wright, S. P. Poland, J. M. Girkin, C. W. Freudiger, C. L. Evans, and X. S. Xie, “Adaptive optics for enhanced signal in CARS microscopy,” Opt. Express 15(26), 18209–18219 (2007).
[Crossref]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 102(46), 16807–16812 (2005).
[Crossref]

Xu, C.

Xu, T.-H.

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

Yan, S.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Yang, G.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Yang, W.

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

Yang, W. L.

D. Fu, W. L. Yang, and X. L. S. Xie, “Label-free Imaging of Neurotransmitter Acetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering,” J. Am. Chem. Soc. 139(2), 583–586 (2017).
[Crossref]

Yang, Y. L.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Yang, Y.-B.

X.-J. Mao, C. Shen, and Y.-B. Yang, “Image restoration using very deep convolutional encoder-decoder networks with symmetric skip connections,” in Proceedings of the 30th International Conference on Neural Information Processing Systems, pp. 2810–2818, Curran Associates Inc., Barcelona, Spain (2016).

Yao, L.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Yu, T.-T.

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

Yu, Y.

L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
[Crossref]

L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
[Crossref]

Zada, L.

M. J. B. Moester, L. Zada, B. Fokker, F. Ariese, and J. F. de Boer, “Stimulated Raman scattering microscopy with long wavelengths for improved imaging depth,” J. Raman Spectrosc. 50(9), 1321–1328 (2019).
[Crossref]

Zerial, M.

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Zhang, C.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

C. Zhang, D. Zhang, and J.-X. Cheng, “Coherent Raman Scattering Microscopy in Biology and Medicine,” Annu. Rev. Biomed. Eng. 17(1), 415–445 (2015).
[Crossref]

Zhang, D.

C. Zhang, D. Zhang, and J.-X. Cheng, “Coherent Raman Scattering Microscopy in Biology and Medicine,” Annu. Rev. Biomed. Eng. 17(1), 415–445 (2015).
[Crossref]

D. Zhang, P. Wang, M. N. Slipchenko, and J.-X. Cheng, “Fast Vibrational Imaging of Single Cells and Tissues by Stimulated Raman Scattering Microscopy,” Acc. Chem. Res. 47(8), 2282–2290 (2014).
[Crossref]

Zhang, L. L.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Zhang, L. Y.

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
[Crossref]

Zhao, Y.-J.

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

Zhao, Z.

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
[Crossref]

Zheng, B.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Zheng, C. G.

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
[Crossref]

Zhu, D.

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

Zhu, Y.

S. Hong, T. Chen, Y. Zhu, A. Li, Y. Huang, and X. Chen, “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules,” Angew. Chem., Int. Ed. 53(23), 5827–5831 (2014).
[Crossref]

Zou, X.

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Acc. Chem. Res. (1)

D. Zhang, P. Wang, M. N. Slipchenko, and J.-X. Cheng, “Fast Vibrational Imaging of Single Cells and Tissues by Stimulated Raman Scattering Microscopy,” Acc. Chem. Res. 47(8), 2282–2290 (2014).
[Crossref]

Anal. Chem. (3)

A. H. Hill and D. Fu, “Cellular Imaging Using Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(15), 9333–9342 (2019).
[Crossref]

X. S. Li, Y. Li, M. J. Jiang, W. J. Wu, S. C. He, C. P. Chen, Z. Y. Qin, B. Z. Tang, H. Y. Mak, and J. A. Y. Qu, “Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy,” Anal. Chem. 91(3), 2279–2287 (2019).
[Crossref]

Y. Chen, S. Liu, H. Liu, S. Tong, H. Tang, C. Zhang, S. Yan, H. Li, G. Yang, D. Zhu, K. Wang, and P. Wang, “Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging,” Anal. Chem. 91(15), 9371–9375 (2019).
[Crossref]

Angew. Chem., Int. Ed. (1)

S. Hong, T. Chen, Y. Zhu, A. Li, Y. Huang, and X. Chen, “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules,” Angew. Chem., Int. Ed. 53(23), 5827–5831 (2014).
[Crossref]

Annu. Rev. Biomed. Eng. (1)

C. Zhang, D. Zhang, and J.-X. Cheng, “Coherent Raman Scattering Microscopy in Biology and Medicine,” Annu. Rev. Biomed. Eng. 17(1), 415–445 (2015).
[Crossref]

Biomed. Opt. Express (4)

Cancer Res. (1)

F.-K. Lu, D. Calligaris, O. I. Olubiyi, I. Norton, W. Yang, S. Santagata, X. S. Xie, A. J. Golby, and N. Y. R. Agar, “Label-Free Neurosurgical Pathology with Stimulated Raman Imaging,” Cancer Res. 76(12), 3451–3462 (2016).
[Crossref]

Cell (1)

D. S. Richardson and J. W. Lichtman, “Clarifying Tissue Clearing,” Cell 162(2), 246–257 (2015).
[Crossref]

Curr. Opin. Chem. Biol. (1)

D. Fu, “Quantitative chemical imaging with stimulated Raman scattering microscopy,” Curr. Opin. Chem. Biol. 39, 24–31 (2017).
[Crossref]

J. Am. Chem. Soc. (1)

D. Fu, W. L. Yang, and X. L. S. Xie, “Label-free Imaging of Neurotransmitter Acetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering,” J. Am. Chem. Soc. 139(2), 583–586 (2017).
[Crossref]

J. Biomed. Opt. (2)

D. M. Drutis, T. M. Hancewicz, E. Pashkovski, L. Feng, D. Mihalov, G. R. Holtom, K. P. Ananthapadmanabhan, X. S. Xie, and M. Misra, “Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy,” J. Biomed. Opt. 19(11), 111604 (2014).
[Crossref]

A. Alfonso-García, R. Mittal, E. S. Lee, and E. O. Potma, “Biological imaging with coherent Raman scattering microscopy: a tutorial,” J. Biomed. Opt. 19(7), 071407 (2014).
[Crossref]

J. Opt. Soc. Am. B (1)

J. Raman Spectrosc. (1)

M. J. B. Moester, L. Zada, B. Fokker, F. Ariese, and J. F. de Boer, “Stimulated Raman scattering microscopy with long wavelengths for improved imaging depth,” J. Raman Spectrosc. 50(9), 1321–1328 (2019).
[Crossref]

Light: Sci. Appl. (1)

Y.-J. Zhao, T.-T. Yu, C. Zhang, Z. Li, Q.-M. Luo, T.-H. Xu, and D. Zhu, “Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution,” Light: Sci. Appl. 7(2), 17153 (2018).
[Crossref]

Nat. Biomed. Eng. (1)

D. A. Orringer, B. Pandian, Y. S. Niknafs, T. C. Hollon, J. Boyle, S. Lewis, M. Garrard, S. L. Hervey-Jumper, H. J. L. Garton, C. O. Maher, J. A. Heth, O. Sagher, D. A. Wilkinson, M. Snuderl, S. Venneti, S. H. Ramkissoon, K. A. McFadden, A. Fisher-Hubbard, A. P. Lieberman, T. D. Johnson, X. S. Xie, J. K. Trautman, C. W. Freudiger, and S. Camelo-Piragua, “Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy,” Nat. Biomed. Eng. 1(2), 0027 (2017).
[Crossref]

Nat. Commun. (1)

L. Y. Shi, C. G. Zheng, Y. H. Shen, Z. X. Chen, E. S. Silveira, L. Y. Zhang, M. Wei, C. Liu, C. de Sena-Tomas, K. Targoff, and W. Min, “Optical imaging of metabolic dynamics in animals,” Nat. Commun. 9(1), 17 (2018).
[Crossref]

Nat. Methods (4)

L. Wei, F. H. Hu, Y. H. Shen, Z. X. Chen, Y. Yu, C. C. Lin, M. C. Wang, and W. Min, “Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering,” Nat. Methods 11(4), 410–412 (2014).
[Crossref]

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

C. Ounkomol, S. Seshamani, M. M. Maleckar, F. Collman, and G. R. Johnson, “Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy,” Nat. Methods 15(11), 917–920 (2018).
[Crossref]

M. Weigert, U. Schmidt, T. Boothe, A. Müller, A. Dibrov, A. Jain, B. Wilhelm, D. Schmidt, C. Broaddus, S. Culley, M. Rocha-Martins, F. Segovia-Miranda, C. Norden, R. Henriques, M. Zerial, M. Solimena, J. Rink, P. Tomancak, L. Royer, F. Jug, and E. W. Myers, “Content-aware image restoration: pushing the limits of fluorescence microscopy,” Nat. Methods 15(12), 1090–1097 (2018).
[Crossref]

Opt. Express (2)

Opt. Lett. (1)

Proc. Natl. Acad. Sci. U. S. A. (3)

L. Wei, Y. Yu, Y. H. Shen, M. C. Wang, and W. Min, “Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 110(28), 11226–11231 (2013).
[Crossref]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 102(46), 16807–16812 (2005).
[Crossref]

M. Wei, L. Shi, Y. Shen, Z. Zhao, A. Guzman, L. J. Kaufman, L. Wei, and W. Min, “Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy,” Proc. Natl. Acad. Sci. U. S. A. 116(14), 6608–6617 (2019).
[Crossref]

Science (2)

J.-X. Cheng and X. S. Xie, “Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine,” Science 350(6264), aaa8870 (2015).
[Crossref]

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering,” Science 330(6009), 1368–1370 (2010).
[Crossref]

Theranostics (1)

L. L. Zhang, Y. Z. Wu, B. Zheng, L. Z. Su, Y. Chen, S. Ma, Q. Q. Hu, X. Zou, L. Yao, Y. L. Yang, L. Chen, Y. Mao, Y. Chen, and M. B. Ji, “Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy,” Theranostics 9(9), 2541–2554 (2019).
[Crossref]

Other (1)

X.-J. Mao, C. Shen, and Y.-B. Yang, “Image restoration using very deep convolutional encoder-decoder networks with symmetric skip connections,” in Proceedings of the 30th International Conference on Neural Information Processing Systems, pp. 2810–2818, Curran Associates Inc., Barcelona, Spain (2016).

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Figures (6)

Fig. 1.
Fig. 1. Home built SRS microscope used for biological imaging. Acronyms defined in inset.
Fig. 2.
Fig. 2. DC and SRS signal sizes for epi and transmissive images as a function of brain tissue thickness. (A) Transmissive DC signal size as a function of depth for four different tissue thicknesses. (B) Epi DC signal size as a function of depth for four different tissue thicknesses. (C) Transmissive SRS signal sizes as a function of depth for four different tissue thicknesses. (D) Epi SRS signal sizes as a function of depth for four different tissue thicknesses. X’s and lines correspond to three-trial averages while shaded areas correspond to standard deviations.
Fig. 3.
Fig. 3. SNR as a function of depth for murine brain images collected in epi and transmissive mode from samples of varying thickness. (A) SNR as a function of depth for a 250 µm thick tissue sample. (B) SNR as a function of depth for a 500 µm thick tissue sample. (C) SNR as a function of depth for a 1 mm thick sample. (D) SNR as a function of depth for a 2 mm thick sample. All curves shown are averages over three fields of view. Shaded areas reflect standard deviation within those datasets.
Fig. 4.
Fig. 4. Transmissive and epi signal sizes and image SNR as a function of depth for a variety of murine tissues. (A) Transmissive DC signal size as a function of depth in murine kidney, lung, and liver tissue. (B) Epi DC signal size as a function of depth in murine kidney, liver, and lung tissue. Dashed lines reflect fitting to Eq. 1. (C) Transmissive SRS signal size as a function of depth in murine kidney, lung, and liver tissue. (D) Epi SRS signal size as a function of depth in murine kidney, liver, and lung tissue. Dashed lines reflect fitting to Eq. 1.
Fig. 5.
Fig. 5. Demonstration of CNN-based denoising leading to increases in maximum imaging depth. (A) Epi SRS image collected at 0 µm depth. (B) Epi SRS image collected at 100 µm depth. (C) Epi SRS image collected at 165 µm depth, defined as the maximum imaging depth based on SNR. (D) Epi SRS image collected at 210 µm depth. (E) CNN denoised version of image in A. (F) CNN denoised version of image in B. (G) CNN denoised version of image in C. (H) CNN denoised version of image in D.
Fig. 6.
Fig. 6. Raw and denoised data collected at a depth of 210 µm. (A) Raw image collected at 210 µm deep in the murine cortex. (B) Line plot of area depicted by dashed line in panel A. Background used in SBR calculation collected from area encompassed by red square. (C) Denoised image of image A. (D) Line plot of area depicted by dashed line in panel C. Background used in SBR calculation collected from area encompassed by red square.

Tables (3)

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Table 1. Maximum DC and SRS Signal Sizes as a Function of Tissue Thickness and SRS Imaging Geometry in Murine Brain Tissue

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Table 2. Epi and Transmissive SRS Image Peak SNR and Imaging Depth for Murine Brain Tissue Samples of Varying Thickness

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Table 3. Epi and Transmissive Scattering Lengths SRS Image Peak SNR and Imaging Depth for Various Murine Tissues

Equations (1)

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I S R S = A e 2 z / 2 z L s L s

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