OSA's Digital Library

Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 19, Iss. 8 — Apr. 11, 2011
  • pp: 7213–7221

Deep-tissue access with confocal fluorescence microendoscopy through hypodermic needles

Rajesh S. Pillai, Dirk Lorenser, and David D. Sampson  »View Author Affiliations

Optics Express, Vol. 19, Issue 8, pp. 7213-7221 (2011)

View Full Text Article

Enhanced HTML    Acrobat PDF (1154 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



We report on the design and implementation of a gradient-index microendoscope suitable for accessing tissues deep within the body using confocal fluorescence imaging. The 350-μm diameter microendoscope has a length of 27 mm, which enables it to be inserted through a 22-gauge hypodermic needle. A prototype imaging system is demonstrated to obtain images of tissue samples at depths of ~15 mm with a lateral resolution of ~700 nm. To the best of our knowledge, this is the highest resolution and imaging depth reported for a confocal probe of these dimensions. We employ a scanning arrangement using a lensed fiber that can conveniently control the input beam parameters without causing off-axis aberrations typically present in the optical relay lenses used in galvanometer-mirror scanning systems.

© 2011 OSA

OCIS Codes
(110.2760) Imaging systems : Gradient-index lenses
(170.1790) Medical optics and biotechnology : Confocal microscopy
(170.2520) Medical optics and biotechnology : Fluorescence microscopy
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(220.2740) Optical design and fabrication : Geometric optical design

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: February 7, 2011
Revised Manuscript: March 21, 2011
Manuscript Accepted: March 21, 2011
Published: March 30, 2011

Virtual Issues
Vol. 6, Iss. 5 Virtual Journal for Biomedical Optics

Rajesh S. Pillai, Dirk Lorenser, and David D. Sampson, "Deep-tissue access with confocal fluorescence microendoscopy through hypodermic needles," Opt. Express 19, 7213-7221 (2011)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. J. Pawley, Handbook of biological confocal microscopy (Springer, New York, 2006).
  2. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990). [CrossRef] [PubMed]
  3. V. S. Erickson, M. L. Pearson, P. A. Ganz, J. Adams, and K. L. Kahn, “Arm edema in breast cancer patients,” J. Natl. Cancer Inst. 93(2), 96–111 (2001). [CrossRef] [PubMed]
  4. Y. Shapira, M. Katz, M. Ali, M. Kaplan, E. Brazowski, Z. Halpern, and E. Elinav, “Utilization of murine laparoscopy for continuous in-vivo assessment of the liver in multiple disease models,” PLoS ONE 4(3), e4776 (2009). [CrossRef] [PubMed]
  5. B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005). [CrossRef] [PubMed]
  6. P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt. 13(1), 010501 (2008). [CrossRef] [PubMed]
  7. A. F. Gmitro and D. Aziz, “Confocal microscopy through a fiber-optic imaging bundle,” Opt. Lett. 18(8), 565–567 (1993). [CrossRef] [PubMed]
  8. L. Thiberville, M. Salaün, S. Lachkar, S. Dominique, S. Moreno-Swirc, C. Vever-Bizet, and G. Bourg-Heckly, “Confocal fluorescence endomicroscopy of the human airways,” Proc. Am. Thorac. Soc. 6(5), 444–449 (2009). [CrossRef] [PubMed]
  9. J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, and C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010). [CrossRef] [PubMed]
  10. F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001). [CrossRef] [PubMed]
  11. E. J. Seibel and Q. Y. J. Smithwick, “Unique features of optical scanning, single fiber endoscopy,” Lasers Surg. Med. 30(3), 177–183 (2002). [CrossRef] [PubMed]
  12. A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005). [CrossRef] [PubMed]
  13. J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188(5-6), 267–273 (2001). [CrossRef]
  14. R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009). [CrossRef] [PubMed]
  15. J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003). [CrossRef] [PubMed]
  16. J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004). [CrossRef] [PubMed]
  17. M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004). [CrossRef]
  18. B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, “In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope,” Opt. Lett. 30(17), 2272–2274 (2005). [CrossRef] [PubMed]
  19. X. Li and W. Yu, “Deep tissue microscopic imaging of the kidney with a gradient-index lens system,” Opt. Commun. 281(7), 1833–1840 (2008). [CrossRef] [PubMed]
  20. W. Piyawattanametha, E. D. Cocker, L. D. Burns, R. P. J. Barretto, J. C. Jung, H. Ra, O. Solgaard, and M. J. Schnitzer, “In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror,” Opt. Lett. 34(15), 2309–2311 (2009). [CrossRef] [PubMed]
  21. B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008). [CrossRef] [PubMed]
  22. 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]
  23. J. M. Geary, Introduction to lens design with practical Zemax examples (Willmann-Bell, Inc., Richmond, 2007).
  24. W. L. Emkey and C. A. Jack, “Analysis and evaluation of graded-index fiber-lenses,” J. Lightwave Technol. 5(9), 1156–1164 (1987). [CrossRef]
  25. A. C. Ribes, S. Damaskinos, and A. E. Dixon, “Inexpensive, high-quality optical relay for use in confocal scanning beam imaging,” Scanning 22(5), 282–287 (2000). [CrossRef] [PubMed]
  26. X. Gan, M. Gu, and C. J. R. Sheppard, “Fluorescent image formation in the fibre-optical confocal scanning microscope,” J. Mod. Opt. 39(4), 825–834 (1992). [CrossRef]
  27. R. W. Wijnaendts-van-Resandt, H. J. B. Marsmann, R. Kaplan, J. Davoust, E. H. K. Stelzer, and R. Stricker, “Optical fluorescence microscopy in three dimensions: microtomoscopy,” J. Microsc. 138, 29–34 (1985). [CrossRef]
  28. H. K. Herring, R. G. Cassens, and E. J. Briskey, “Further studies on bovine muscle tenderness as influenced by carcass position, sarcomere length, and fiber diameter,” J. Food Sci. 30(6), 1049–1054 (1965). [CrossRef]
  29. M. Müller, Introduction to confocal fluorescence microscopy (SPIE- The International Society for Optical Engineering, Bellingham, 2006).

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