Abstract

This paper presents the design and evaluation of a reflectance confocal laser endomicroscope using a miniature objective lens within a rigid probe in conjunction with an electrically tunable lens for axial scanning. The miniature lens was characterized alone as well as in the endoscope across a 200 µm axial scan range using the tunable lens. The ability of the confocal endoscope to probe the human oral cavity is demonstrated by imaging of the oral mucosa in vivo. The results indicate that reflectance confocal endomicroscopy has the potential to be used in a clinical setting and guide diagnostic evaluation of biological tissue.

© 2014 Optical Society of America

Full Article  |  PDF Article
OSA Recommended Articles
Optical axial scanning in confocal microscopy using an electrically tunable lens

Joey M. Jabbour, Bilal H. Malik, Cory Olsovsky, Rodrigo Cuenca, Shuna Cheng, Javier A. Jo, Yi-Shing Lisa Cheng, John M. Wright, and Kristen C. Maitland
Biomed. Opt. Express 5(2) 645-652 (2014)

In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens

Kristen Carlson, Matthew Chidley, Kung-Bin Sung, Michael Descour, Ann Gillenwater, Michele Follen, and Rebecca Richards-Kortum
Appl. Opt. 44(10) 1792-1797 (2005)

Fiber confocal reflectance microscope (FCRM) for in-vivo imaging

Chen Liang, Michael R. Descour, Kung-Bin Sung, and Rebecca Richards-Kortum
Opt. Express 9(13) 821-830 (2001)

References

  • View by:
  • |
  • |
  • |

  1. J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
    [Crossref] [PubMed]
  2. J. B. Pawley, Handbook of biological confocal microscopy (Springer, New York, NY, 2006).
  3. J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
    [Crossref] [PubMed]
  4. I. D. Caliber, VivaCam, http://www.caliberid.com/vivacam-Overview.html .
  5. S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
    [Crossref] [PubMed]
  6. R. T. Kester, T. S. Tkaczyk, M. R. Descour, T. Christenson, and R. Richards-Kortum, “High numerical aperture microendoscope objective for a fiber confocal reflectance microscope,” Opt. Express 15(5), 2409–2420 (2007).
    [Crossref] [PubMed]
  7. K. Carlson, M. Chidley, K. B. Sung, M. Descour, A. Gillenwater, M. Follen, and R. Richards-Kortum, “In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens,” Appl. Opt. 44(10), 1792–1797 (2005).
    [Crossref] [PubMed]
  8. M. Kyrish, U. Utzinger, M. R. Descour, B. K. Baggett, and T. S. Tkaczyk, “Ultra-slim plastic endomicroscope objective for non-linear microscopy,” Opt. Express 19(8), 7603–7615 (2011).
    [Crossref] [PubMed]
  9. 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]
  10. D. T. Moore, “Gradient-Index Optics: a Review,” Appl. Opt. 19(7), 1035–1038 (1980).
    [Crossref] [PubMed]
  11. J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
    [Crossref] [PubMed]
  12. 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]
  13. 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]
  14. B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
    [Crossref] [PubMed]
  15. J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
    [Crossref] [PubMed]
  16. K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
    [Crossref] [PubMed]
  17. C. Olsovsky, R. Shelton, O. Carrasco-Zevallos, B. E. Applegate, and K. C. Maitland, “Chromatic confocal microscopy for multi-depth imaging of epithelial tissue,” Biomed. Opt. Express 4(5), 732–740 (2013).
    [Crossref] [PubMed]
  18. E. J. Botcherby, R. Juskaitis, M. J. Booth, and T. Wilson, “Aberration-free optical refocusing in high numerical aperture microscopy,” Opt. Lett. 32(14), 2007–2009 (2007).
    [Crossref] [PubMed]
  19. B. Li, H. Qin, S. Yang, and D. Xing, “In vivo fast variable focus photoacoustic microscopy using an electrically tunable lens,” Opt. Express 22(17), 20130–20137 (2014).
    [Crossref]
  20. B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
    [Crossref] [PubMed]
  21. J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
    [Crossref] [PubMed]
  22. R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
    [Crossref] [PubMed]
  23. M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
    [Crossref] [PubMed]
  24. A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
    [PubMed]

2014 (2)

2013 (3)

C. Olsovsky, R. Shelton, O. Carrasco-Zevallos, B. E. Applegate, and K. C. Maitland, “Chromatic confocal microscopy for multi-depth imaging of epithelial tissue,” Biomed. Opt. Express 4(5), 732–740 (2013).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

2012 (2)

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

2011 (2)

2010 (1)

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

2009 (1)

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]

2007 (2)

2005 (2)

K. Carlson, M. Chidley, K. B. Sung, M. Descour, A. Gillenwater, M. Follen, and R. Richards-Kortum, “In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens,” Appl. Opt. 44(10), 1792–1797 (2005).
[Crossref] [PubMed]

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

2004 (1)

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]

2003 (2)

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

2002 (1)

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

2001 (1)

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]

2000 (1)

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

1980 (1)

Aksay, E.

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]

Alizadeh-Naderi, R.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Applegate, B. E.

Baggett, B. K.

Barretto, R. P. J.

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]

Begnami, M. D.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Bixler, J. N.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

Booth, M. J.

Botcherby, E. J.

Braga, J. C. T.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Brookner, C. K.

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Buess, G.

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]

Carlson, K.

Carrasco-Zevallos, O.

Cheng, S. N.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Cheng, Y. S. L.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Chidley, M.

Choi, M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Christenson, T.

Clark, A. L.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Collier, T.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Collier, T. G.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Cuenca, R.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Descour, M.

K. Carlson, M. Chidley, K. B. Sung, M. Descour, A. Gillenwater, M. Follen, and R. Richards-Kortum, “In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens,” Appl. Opt. 44(10), 1792–1797 (2005).
[Crossref] [PubMed]

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

Descour, M. R.

Drezek, R. A.

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Duprat, J.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Eickhoff, J. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Eliceiri, K. W.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

El-Naggar, A. K.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Follen, M.

K. Carlson, M. Chidley, K. B. Sung, M. Descour, A. Gillenwater, M. Follen, and R. Richards-Kortum, “In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens,” Appl. Opt. 44(10), 1792–1797 (2005).
[Crossref] [PubMed]

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Gillenwater, A.

Gillenwater, A. M.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

González, S.

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

Grewe, B. F.

B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
[Crossref] [PubMed]

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

Helmchen, F.

B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
[Crossref] [PubMed]

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

Jabbour, J. M.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

Jo, J. A.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Jung, J. C.

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]

Jung, K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Juskaitis, R.

Kampa, B. M.

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

Kasper, H.

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

Kester, R. T.

Kim, J. K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, P.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, S.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Knittel, J.

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]

Kyrish, M.

Langer, D.

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

Lee, W. M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Li, B.

Liang, C. N.

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

Lotan, R.

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Macedo, M. P.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Maitland, K. C.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

C. Olsovsky, R. Shelton, O. Carrasco-Zevallos, B. E. Applegate, and K. C. Maitland, “Chromatic confocal microscopy for multi-depth imaging of epithelial tissue,” Biomed. Opt. Express 4(5), 732–740 (2013).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

Malik, B. H.

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. N. Cheng, J. A. Jo, Y. S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref] [PubMed]

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Malpica, A.

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Mehta, A. D.

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]

Messerschmidt, B.

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]

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]

Moore, D. T.

Olsovsky, C.

Pellacani, G.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Pinto, C.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Possner, T.

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]

Qin, H.

Rajadhyaksha, M.

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

Ramanujam, N.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Rezze, G. G.

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Richards-Kortum, R.

Richards-Kortum, R. R.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Saldua, M. A.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

Schnieder, L.

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]

Schnitzer, M. J.

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]

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]

Shelton, R.

Skala, M. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Squirrell, J. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Stepnoski, R.

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]

Sung, K. B.

K. Carlson, M. Chidley, K. B. Sung, M. Descour, A. Gillenwater, M. Follen, and R. Richards-Kortum, “In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens,” Appl. Opt. 44(10), 1792–1797 (2005).
[Crossref] [PubMed]

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

Swindells, K.

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

Tkaczyk, T. S.

Torres, A.

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

Utzinger, U.

van ’t Hoff, M.

Voigt, F. F.

Vrotsos, K. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Wilson, T.

Wright, J.

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

Wright, J. M.

Xing, D.

Yang, S.

Yun, S. H.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Am. J. Obstet. Gynecol. (1)

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182(5), 1135–1139 (2000).
[Crossref] [PubMed]

Ann. Biomed. Eng. (1)

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Ann. Biomed. Eng. 40(2), 378–397 (2012).
[Crossref] [PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (3)

Cancer Res. (1)

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005).
[Crossref] [PubMed]

Clin. Cancer Res. (1)

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal microscopy for real-time detection of oral cavity neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Clin. Dermatol. (1)

S. González, K. Swindells, M. Rajadhyaksha, and A. Torres, “Changing paradigms in dermatology: confocal microscopy in clinical and surgical dermatology,” Clin. Dermatol. 21(5), 359–369 (2003).
[Crossref] [PubMed]

IEEE Trans. Biomed. Eng. (1)

K. B. Sung, C. N. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. 49(10), 1168–1172 (2002).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

J. M. Jabbour, S. N. Cheng, B. H. Malik, R. Cuenca, J. A. Jo, J. Wright, Y. S. L. Cheng, and K. C. Maitland, “Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer,” J. Biomed. Opt. 18(4), 046012 (2013).
[Crossref] [PubMed]

J. Neurophysiol. (1)

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]

Nat. Methods (2)

B. F. Grewe, D. Langer, H. Kasper, B. M. Kampa, and F. Helmchen, “High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision,” Nat. Methods 7(5), 399–405 (2010).
[Crossref] [PubMed]

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]

Nat. Protoc. (1)

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Opt. Commun. (1)

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]

Opt. Express (3)

Opt. Lett. (1)

PLoS ONE (1)

J. C. T. Braga, M. P. Macedo, C. Pinto, J. Duprat, M. D. Begnami, G. Pellacani, and G. G. Rezze, “Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections,” PLoS ONE 8(12), e81205 (2013).
[Crossref] [PubMed]

Other (2)

I. D. Caliber, VivaCam, http://www.caliberid.com/vivacam-Overview.html .

J. B. Pawley, Handbook of biological confocal microscopy (Springer, New York, NY, 2006).

Supplementary Material (2)

» Media 1: AVI (1314 KB)     
» Media 2: AVI (1174 KB)     

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (8)

Fig. 1
Fig. 1 (a) CAD model of the rCLE system illustrating the optical setup. (b) CAD model and (c) photo of the clinical handheld rCLE system.
Fig. 2
Fig. 2 Optical design of the miniature objective lens.
Fig. 3
Fig. 3 (a) Field curvature and (b) distortion of the miniature objective lens design for wavelengths of 0.806 µm (blue), 0.811 µm (green), and 0.816 µm (red). Maximum field is 4 degrees. (c) RMS wavefront error across field. (d) Polychromatic diffraction modulation transfer function of the miniature objective lens design for the fields above and for wavelengths from 0.806 to 0.816 µm.
Fig. 4
Fig. 4 Photographs showing the assembled miniature objective next to a ruler and a United States penny.
Fig. 5
Fig. 5 Schematic diagram of the Twyman interferometry setup used for evaluation of the miniature objective lens.
Fig. 6
Fig. 6 Zernike 2D plot showing the wave aberration of the miniature objective lens.
Fig. 7
Fig. 7 (a) Ronchi ruling showing 550 µm FOV of the rCLE with miniature objective lens. (b) Groups 8, 9 and 7 (to the right) of USAF target at 0 mA ETL current. (c) Axial response plot showing a FWHM of 5 μm at 0 mA ETL current.
Fig. 8
Fig. 8 rCLE images from human volunteers in vivo of (a-h, Media 1) buccal mucosa/cheek and (i-p, Media 2) inner lip tissue. (b,d,f,h) are zoomed in images from the corresponding dashed boxes in (a,c,e,g), and (j,l,n,p) are zoomed in images from the corresponding dashed boxes in (i,k,m,o), respectively. Arrows point to individual nuclei. Cell borders can be identified in (e,f). Scale bars: 100 µm in (a,i) and 50 µm in (b,j) for zoom in versions.

Tables (3)

Tables Icon

Table 2 Miniature objective lens prescription. CX: Convex, CC: Concave, L: Lens, S: Surface.

Tables Icon

Table 3 Lens system tolerances for miniature lens design

Tables Icon

Table 4 Imaging parameters as a function of current applied to the ETL

Metrics