OSA's Digital Library

Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editors: Andrew Dunn and Anthony Durkin
  • Vol. 7, Iss. 1 — Jan. 4, 2012

Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue

Emmanuelle Chaigneau, Amanda J. Wright, Simon P. Poland, John M. Girkin, and R. Angus Silver  »View Author Affiliations


Optics Express, Vol. 19, Issue 23, pp. 22755-22774 (2011)
http://dx.doi.org/10.1364/OE.19.022755


View Full Text Article

Enhanced HTML    Acrobat PDF (4787 KB) Open Access





Browse Journals / Lookup Meetings

Browse by Journal and Year


   


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools

Share
Citations

Abstract

Two-photon (2P) microscopy is widely used in neuroscience, but the optical properties of brain tissue are poorly understood. We have investigated the effect of brain tissue on the 2P point spread function (PSF2P) by imaging fluorescent beads through living cortical slices. By combining this with measurements of the mean free path of the excitation light, adaptive optics and vector-based modeling that includes phase modulation and scattering, we show that tissue-induced wavefront distortions are the main determinant of enlargement and distortion of the PSF2P at intermediate imaging depths. Furthermore, they generate surrounding lobes that contain more than half of the 2P excitation. These effects reduce the resolution of fine structures and contrast and they, together with scattering, limit 2P excitation. Our results disentangle the contributions of scattering and wavefront distortion in shaping the cortical PSF2P, thereby providing a basis for improved 2P microscopy.

© 2011 OSA

OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(180.2520) Microscopy : Fluorescence microscopy
(220.1000) Optical design and fabrication : Aberration compensation
(290.0290) Scattering : Scattering
(180.4315) Microscopy : Nonlinear microscopy
(110.1080) Imaging systems : Active or adaptive optics

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: August 26, 2011
Revised Manuscript: October 7, 2011
Manuscript Accepted: October 9, 2011
Published: October 26, 2011

Virtual Issues
Vol. 7, Iss. 1 Virtual Journal for Biomedical Optics

Citation
Emmanuelle Chaigneau, Amanda J. Wright, Simon P. Poland, John M. Girkin, and R. Angus Silver, "Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue," Opt. Express 19, 22755-22774 (2011)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-19-23-22755


Sort:  Author  |  Year  |  Journal  |  Reset  

References

  1. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990). [CrossRef] [PubMed]
  2. 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]
  3. K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006). [CrossRef] [PubMed]
  4. F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods2(12), 932–940 (2005). [CrossRef] [PubMed]
  5. J. Herz, V. Siffrin, A. E. Hauser, A. U. Brandt, T. Leuenberger, H. Radbruch, F. Zipp, and R. A. Niesner, “Expanding two-photon intravital microscopy to the infrared by means of optical parametric oscillator,” Biophys. J.98(4), 715–723 (2010). [CrossRef] [PubMed]
  6. N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010). [CrossRef] [PubMed]
  7. O. Katz, E. Small, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics5(6), 372–377 (2011). [CrossRef]
  8. C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1998).
  9. M. Born and E. Wolf, Principles of Optics, 7th ed. (Cambridge, 2001).
  10. W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990). [CrossRef]
  11. A. N. Yaroslavsky, P. C. Schulze, I. V. Yaroslavsky, R. Schober, F. Ulrich, and H. J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol.47(12), 2059–2073 (2002). [CrossRef] [PubMed]
  12. P. Theer and W. Denk, “On the fundamental imaging-depth limit in two-photon microscopy,” J. Opt. Soc. Am. A23(12), 3139–3149 (2006). [CrossRef] [PubMed]
  13. M. Schwertner, M. J. Booth, and T. Wilson, “Characterizing specimen induced aberrations for high NA adaptive optical microscopy,” Opt. Express12(26), 6540–6552 (2004). [CrossRef] [PubMed]
  14. R. K. Tyson, Principles of Adaptive Optics (Academic, 1998).
  15. J. M. Girkin, S. Poland, and A. J. Wright, “Adaptive optics for deeper imaging of biological samples,” Curr. Opin. Biotechnol.20(1), 106–110 (2009). [CrossRef] [PubMed]
  16. M. J. Booth, “Adaptive optics in microscopy,” Philos. Transact. A Math. Phys. Eng. Sci.365(1861), 2829–2843 (2007). [CrossRef] [PubMed]
  17. M. A. Neil, R. Juskaitis, M. J. Booth, T. Wilson, T. Tanaka, and S. Kawata, “Adaptive aberration correction in a two-photon microscope,” J. Microsc.200(2), 105–108 (2000). [CrossRef] [PubMed]
  18. L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, “Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror,” J. Microsc.206(1), 65–71 (2002). [CrossRef] [PubMed]
  19. P. Marsh, D. Burns, and J. Girkin, “Practical implementation of adaptive optics in multiphoton microscopy,” Opt. Express11(10), 1123–1130 (2003). [CrossRef] [PubMed]
  20. M. Rueckel, J. A. Mack-Bucher, and W. Denk, “Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing,” Proc. Natl. Acad. Sci. U.S.A.103(46), 17137–17142 (2006). [CrossRef] [PubMed]
  21. D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett.34(16), 2495–2497 (2009). [CrossRef] [PubMed]
  22. Y. P. Zhou, T. Bifano, and C. Lin, “Adaptive optics two-photon fluorescence microscopy ” Proc. SPIE6467, 646705 (2007).
  23. N. Ji, D. E. Milkie, and E. Betzig, “Pupil-segmentation-based adaptive optics for microscopy,” Proc. SPIE7931, 79310I (2011)
  24. A. Leray, K. Lillis, and J. Mertz, “Enhanced background rejection in thick tissue with differential-aberration two-photon microscopy,” Biophys. J.94(4), 1449–1458 (2008). [CrossRef] [PubMed]
  25. E. W. Weisstein, “Gaussian integral,” Wolfram MathWorld, (1999), http://mathworld.wolfram.com/GaussianIntegral.html.
  26. H. U. Dodt, M. Eder, A. Schierloh, and W. Zieglgänsberger, “Infrared-guided laser stimulation of neurons in brain slices,” Sci. STKE2002(120), 2pl (2002). [CrossRef] [PubMed]
  27. E. Chaigneau and R. A. Silver, University College London, London, UK, are preparing a manuscript entitled “Refractive index mismatch effects at edges: theory and application to two-photon imaging of biological samples.”
  28. M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz, and S. Charpak, “Two-photon microscopy in brain tissue: parameters influencing the imaging depth,” J. Neurosci. Methods111(1), 29–37 (2001). [CrossRef] [PubMed]
  29. D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998). [CrossRef] [PubMed]
  30. B. Richards and E. Wolf, “Electromagnetic diffraction in optical systems. 2. Structure of the image field in an aplanatic system,” Proc. R. Soc. London A Math. Phys. Eng. Sci.253(1274), 358–379 (1959). [CrossRef]
  31. S. P. Poland, A. J. Wright, and J. M. Girkin, “Evaluation of fitness parameters used in an iterative approach to aberration correction in optical sectioning microscopy,” Appl. Opt.47(6), 731–736 (2008). [CrossRef] [PubMed]
  32. A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, “Exploration of the optimisation algorithms used in the implementation of adaptive optics in confocal and multiphoton microscopy,” Microsc. Res. Tech.67(1), 36–44 (2005). [CrossRef] [PubMed]
  33. E. Wolf, “Electromagnetic diffraction in optical systems. 1. An integral representation of the image field,” Proc. R. Soc. London A Math. Phys. Eng. Sci.253(1274), 349–357 (1959). [CrossRef]
  34. M. Schwertner, M. J. Booth, M. A. A. Neil, and T. Wilson, “Measurement of specimen-induced aberrations of biological samples using phase stepping interferometry,” J. Microsc.213(1), 11–19 (2004). [CrossRef] [PubMed]
  35. F. P. Bolin, L. E. Preuss, R. C. Taylor, and R. J. Ference, “Refractive index of some mammalian tissues using a fiber optic cladding method,” Appl. Opt.28(12), 2297–2303 (1989). [CrossRef] [PubMed]
  36. J. W. Cha, J. Ballesta, and P. T. C. So, “Shack-Hartmann wavefront-sensor-based adaptive optics system for multiphoton microscopy,” J. Biomed. Opt.15(4), 046022 (2010). [CrossRef] [PubMed]
  37. M. Schwertner, M. J. Booth, and T. Wilson, “Simulation of specimen-induced aberrations for objects with spherical and cylindrical symmetry,” J. Microsc.215(3), 271–280 (2004). [CrossRef] [PubMed]
  38. 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. Express15(26), 18209–18219 (2007). [CrossRef] [PubMed]
  39. S. P. Poland, A. J. Wright, S. Cobb, J. C. Vijverberg, and J. M. Girkin, “A demonstration of the effectiveness of a single aberration correction per optical slice in beam scanned optically sectioning microscopes,” Micron42(4), 318–323 (2011). [CrossRef]
  40. I. M. Vellekoop and C. M. Aegerter, “Scattered light fluorescence microscopy: imaging through turbid layers,” Opt. Lett.35(8), 1245–1247 (2010). [CrossRef] [PubMed]

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.


« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited