OSA's Digital Library

Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics


  • Editor: Gregory W. Faris
  • Vol. 5, Iss. 3 — Feb. 10, 2010

Second harmonic generation imaging via nonlinear endomicroscopy

Hongchun Bao, Alex Boussioutas, Reynolds Jeremy, Sarah Russell, and Min Gu  »View Author Affiliations

Optics Express, Vol. 18, Issue 2, pp. 1255-1260 (2010)

View Full Text Article

Enhanced HTML    Acrobat PDF (208 KB) Open Access

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Abstract: A compact endomicroscope is the only solution for transferring second harmonic generation (SHG) imaging into in vivo imaging and real time monitoring the content and structure of collagen. This is important for early diagnoses of different diseases associated with collagen change. A compact nonlinear endomicroscope using a double clad fiber (DCF) is newly employed in SHG imaging. The experiment shows the core of the DCF can maintain the linear polarization of the excitation laser beam in particular directions, and the degree of polarization of the excitation laser beam directly affects signal to noise ratio of SHG imaging. The nonlinear endomicroscope can display clear three dimensional (3D) SHG images of mouse tail tendon without the aid of contrast agents, which reveals the collagen fiber structure at different depths. The high resolution of SHG imaging from the endomicroscope shows that SHG imaging can reveal additional information about the orientation and degree of organisation of proteins and collagen fibers than two-photon-excited fluorescence imaging. Therefore SHG imaging offers endomicroscopy with additional channel of imaging for understanding more about biological phenomena.

© 2010 OSA

OCIS Codes
(110.2350) Imaging systems : Fiber optics imaging
(110.3080) Imaging systems : Infrared imaging
(110.6880) Imaging systems : Three-dimensional image acquisition
(170.2150) Medical optics and biotechnology : Endoscopic imaging
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: November 12, 2009
Revised Manuscript: December 28, 2009
Manuscript Accepted: December 30, 2009
Published: January 11, 2010

Virtual Issues
Vol. 5, Iss. 3 Virtual Journal for Biomedical Optics

Hongchun Bao, Alex Boussioutas, Reynolds Jeremy, Sarah Russell, and Min Gu, "Second harmonic generation imaging via nonlinear endomicroscopy," Opt. Express 18, 1255-1260 (2010)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003). [CrossRef] [PubMed]
  2. L. Moreaux, O. Sandre, M. Blanchard-Desce, and J. Mertz, “Membrane imaging by simultaneous second-harmonic generation and two-photon microscopy,” Opt. Lett. 25(5), 320–322 (2000). [CrossRef]
  3. E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003). [CrossRef] [PubMed]
  4. M. Stroh, J. P. Zimmer, D. G. Duda, T. S. Levchenko, K. S. Cohen, E. B. Brown, D. T. Scadden, V. P. Torchilin, M. G. Bawendi, D. Fukumura, and R. K. Jain, “Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo,” Nat. Med. 11(6), 678–682 (2005). [CrossRef] [PubMed]
  5. P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003). [CrossRef] [PubMed]
  6. D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003). [CrossRef] [PubMed]
  7. N. Uldbjerg, A. Malmström, G. Ekman, and U. Ulmsten, “The integrity of cervical collagen during pregnancy and labor,” Gynecol. Obstet. Invest. 20(2), 68–73 (1985). [CrossRef] [PubMed]
  8. R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005). [CrossRef]
  9. L. Fu and M. Gu, “Polarization anisotropy in fiber-optic second harmonic generation microscopy,” Opt. Express 16(7), 5000–5006 (2008). [CrossRef] [PubMed]
  10. M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008). [PubMed]
  11. H. Bao and M. Gu, “Reduction of self-phase modulation in double-clad photonic crystal fiber for nonlinear optical endoscopy,” Opt. Lett. 34(2), 148–150 (2009). [CrossRef] [PubMed]
  12. D. Bird and M. Gu, “Compact two-photon fluorescence microscope based on a single-mode fiber coupler,” Opt. Lett. 27(12), 1031–1033 (2002). [CrossRef]
  13. L. Fu, X. Gan, and M. Gu, “Use of a single-mode fiber coupler for second-harmonic-generation microscopy,” Opt. Lett. 30(4), 385–387 (2005). [CrossRef] [PubMed]
  14. L. Fu and M. Gu, “Double-clad photonic crystal fiber coupler for compact nonlinear optical microscopy imaging,” Opt. Lett. 31(10), 1471–1473 (2006). [CrossRef] [PubMed]
  15. L. Fu, X. Gan, D. Bird, and M. Gu, “Polarization characteristics of a 1×2 fibre coupler under femtosecond pulsed and continuous wave illumination,” Opt. Laser Technol. 37(6), 494–497 (2005). [CrossRef]
  16. H. Bao, J. Allen, R. Pattie, R. Vance, and M. Gu, “A fast handheld two-photon fluorescence microendoscope with a 475µmx475µm field of view for in vivo imaging,” Opt. Lett. 33(12), 1333–1335 (2008). [CrossRef] [PubMed]
  17. M. Goetz, C. Fottner, E. Schirrmacher, P. Delaney, S. Gregor, C. Schneider, D. Strand, S. Kanzler, B. Memadathil, E. Weyand, M. Holtmann, R. Schirrmacher, M. M. Weber, M. Anlauf, G. Klöppel, M. Vieth, P. R. Galle, P. Bartenstein, M. F. Neurath, and R. Kiesslich, “In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases,” Endoscopy 39(4), 350–356 (2007). [CrossRef] [PubMed]
  18. R. Kiesslich, P. R. Galle, and M. F. Neurath, Atlas of endomicroscopy. Springer Medizin Verlag Heidelberg (2008).

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


Fig. 1 Fig. 2 Fig. 3
Fig. 4

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited