High-resolution multimodal flexible coherent Raman endoscope

Alberto Lombardini; Vasyl Mytskaniuk; Siddharth Sivankutty; Esben Ravn Andresen; Xueqin Chen; Jérôme Wenger; Marc Fabert; Nicolas Joly; Frédéric Louradour; Alexandre Kudlinski; Hervé Rigneault

doi:10.1038/s41377-018-0003-3

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High-resolution multimodal flexible coherent Raman endoscope

Original Articles

- High-resolution multimodal flexible coherent Raman endoscope
- Light: Science & Applications Vol. 7, Issue 4, Pages: 87-94(2018)
- Affiliations：
  
  1.Aix-Marseille Univ, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France
  2.Laboratoire de Physique des Lasers Atomes et Molécules, UMR 8523, CNRS, Université Lille, 59000 Lille, France
  3.CNRS, XLIM, UMR 7252, Université de Limoges, 87060 Limoges, France
  4.Department of Physics, Max Planck Institute for the Science of Light, University of Erlangen Nuremberg, 91058 Erlangen, Germany
- Author bio：
  
  Hervé. Rigneault (herve.rigneault@fresnel.fr)
- Funds：
- DOI：10.1038/s41377-018-0003-3
  CLC：
- Published：2018，
  
  Published Online：30 May 2018，
  
  Received：21 September 2017，
  
  Revised：12 February 2018，
  
  Accepted：12 February 2018
- Accepted：
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Lombardini, A. et al. High-resolution multimodal flexible coherent Raman endoscope. Light: Science & Applications, 5, 87-94 (2018).
DOI：

Lombardini, A. et al. High-resolution multimodal flexible coherent Raman endoscope. Light: Science & Applications, 5, 87-94 (2018). DOI： 10.1038/s41377-018-0003-3.

摘要

Abstract

Coherent Raman scattering microscopy is a fast

label-free

and chemically specific imaging technique that shows high potential for future in vivo optical histology. However

the imaging depth in tissues is limited to the sub-millimeter range because of absorption and scattering. Realization of coherent Raman imaging using a fiber endoscope system is a crucial step towards imaging deep inside living tissues and providing information that is inaccessible with current microscopy tools. Until now

the development of coherent Raman endoscopy has been hampered by several issues

mainly related to the fiber delivery of the excitation pulses and signal collection. Here

we present a flexible

compact

coherent Raman

and multimodal nonlinear endoscope (4.2 mm outer diameter

71 mm rigid length) based on a resonantly scanned hollow-core Kagomé-lattice double-clad fiber. The fiber design enables distortion-less

background-free delivery of femtosecond excitation pulses and back-collection of nonlinear signals through the same fiber. Sub-micrometer spatial resolution over a large field of view is obtained by combination of a miniature objective lens with a silica microsphere lens inserted into the fiber core. We demonstrate high-resolution

high-contrast coherent anti-Stokes Raman scattering

and second harmonic generation endoscopic imaging of biological tissues over a field of view of 320 µm at a rate of 0.8 frames per second. These results pave the way for intraoperative label-free imaging applied to real-time histopathology diagnosis and surgery guidance.

关键词

Keywords

references

Cheng, J. X.&Xie, X. S. Vibrational spectroscopic imaging of living systems: an emerging platform for biology and medicine.Science350, aaa8870 (2015)..

Camp, C. H. Jr.&Cicerone, M. T. Chemically sensitive bioimaging with coherent Raman scattering.Nat. Photonics9, 295–305 (2015)..

Gao, L. S. et al. On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification.J. Biomed. Opt.16, 096004 (2011)..

Ji, M. B. et al. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.Sci. Transl. Med7, 309ra163 (2015)..

Orringer, D. A. et al. Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.Nat. Biomed. Eng.1, 0027 (2017)..

Helmchen, F.&Denk, W. Deep tissue two-photon microscopy.Nat. Methods2, 932–940 (2005)..

Ding, H. et al. In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy.Biomed. Opt. Express8, 3426–3439 (2017)..

Paidi, S. K. et al. Label-free raman spectroscopy detects stromal adaptations in premetastatic lungs primed by breast cancer.Cancer Res.77, 247–256 (2017)..

Balu, M., Liu, G. J., Chen, Z. P., Tromberg, B. J.&Potma, E. O. Fiber delivered probe for efficient CARS imaging of tissues.Opt. Express18, 2380–2388 (2010)..

Chen, X., Xu, X. Y., McCormick, D. T., Wong, K.&Wong, S. T. C. Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging.Biomed. Opt. Express6, 2283–2293 (2015)..

Deladurantaye, P. et al. Advances in engineering of high contrast CARS imaging endoscopes.Opt. Express22, 25053–25064 (2014)..

Légaré, F., Evans, C. L., Ganikhanov, F.&Xie, X. S. Towards CARS endoscopy.Opt. Express14, 4427–4432 (2006)..

Lukic, A. et al. Endoscopic fiber probe for nonlinear spectroscopic imaging.Optica4, 496–501 (2017)..

Saar, B. G., Johnston, R. S., Freudiger, C. W., Xie, X. S.&Seibel, E. J. Coherent Raman scanning fiber endoscopy.Opt. Lett.36, 2396–2398 (2011)..

Smith, B. et al. Portable, miniaturized, fibre delivered, multimodal CARS exoscope.Opt. Express21, 17161–17175 (2013)..

Flusberg, B. A. et al. Fiber-optic fluorescence imaging.Nat. Methods2, 941–950 (2005)..

Rivera, D. R. et al. Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue.Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011)..

Liang, W. X., Hall, G., Messerschmidt, B., Li, M. J.&Li, X. D. Nonlinear optical endomicroscopy for label-free functional histology in vivo.Light Sci. Appl.6, e17082 (2017)..

Agrawal, G. P.Nonlinear Fiber Optics, 5th edn (Academic Press, San Diego, 2012).

Cregan, R. F. et al. Single-mode photonic band gap guidance of light in air.Science285, 1537–1539 (1999)..

Couny, F., Benabid, F., Roberts, P. J., Light, P. S.&Raymer, M. G. Generation and photonic guidance of multi-octave optical-frequency combs.Science318, 1118–1121 (2007)..

Ferrand, P. et al. Direct imaging of photonic nanojets.Opt. Express16, 6930–6940 (2008)..

Ghenuche, P., Rigneault, H.&Wenger, J. Photonic nanojet focusing for hollow-core photonic crystal fiber probes.Appl. Opt.51, 8637–8640 (2012)..

Göbel, W., Nimmerjahn, A.&Helmchen, F. Distortion-free delivery of nanojoule femtosecond pulses from a Ti: sapphire laser through a hollow-core photonic crystal fiber.Opt. Lett.29, 1285–1287 (2004)..

Lefort, C., Mansuryan, T., Louradour, F.&Barthelemy, A. Pulse compression and fiber delivery of 45 fs Fourier transform limited pulses at 830 nm.Opt. Lett.36, 292–294 (2011)..

Couny, F., Benabid, F.&Light, P. S. Large-pitch kagome-structured hollow-core photonic crystal fiber.Opt. Lett.31, 3574–3576 (2006)..

Brustlein, S. et al. Double-clad hollow core photonic crystal fiber for coherent Raman endoscope.Opt. Express19, 12562–12568 (2011)..

Ducourthial, G. et al. Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal.Sci. Rep.5, 18303 (2015)..

Lombardini, A., Andresen, E. R., Kudlinski, A., Rimke, I.&Rigneault, H. Origin and suppression of parasitic signals in Kagomé lattice hollow core fibers used for SRS microscopy and endoscopy.Opt. Lett.42, 1824–1827 (2017)..

Ozeki, Y. et al. High-speed molecular spectral imaging of tissue with stimulated Raman scattering.Nat. Photonics6, 845–851 (2012)..

Freudiger, C. W. et al. Stimulated Raman scattering microscopy with a robust fibre laser source.Nat. Photonics8, 153–159 (2014)..

Mukamel, S.Principles of Nonlinear Optical Spectroscopy(Oxford University Press, New York, 1995).

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