Abstract

High resolution, in vivo confocal imaging of amelanotic epithelial tissue may offer a clinically useful adjunct to standard histopathologic techniques. Application of acetic acid has been shown to enhance contrast in confocal images of these tissues. In this study, we record the time course of aceto-whitening at the cellular level and determine whether the contrast provided enables quantitative feature analysis. Confocal images and videos of cervical specimens were obtained throughout the epithelium before, during and post-acetic acid after the application of 6% acetic acid. Aceto-whitening occurs within seconds after the application. The confocal imaging system resolved sub-cellular detail throughout the entire epithelial thickness and provided sufficient contrast to enable quantitative feature analysis.

©2000 Optical Society of America

Full Article  |  PDF Article
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References

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  1. D.M. Parkin, P. Pisani, and J. Ferlay Estimates of the Worldwide Incidence of Eighteen Major Cancers in 1985. Int. J. Cancer1993; 54,594–606
    [Crossref] [PubMed]
  2. G. Dallen Bach-Hellueg and H. Doulson, Histopathology of the Cervix Uteri, (Springer-Verlag New York Inc., 1990)
  3. V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
    [Crossref]
  4. J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
    [Crossref]
  5. B. Masters and A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” AppI. Opt. 33, 695–701 (1994).
    [Crossref]
  6. C. Bertrand and P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real time confocal microscopy,” Scanning 16, 150–154 (1994).
    [Crossref] [PubMed]
  7. P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
    [Crossref] [PubMed]
  8. M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
    [Crossref]
  9. B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).
  10. C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
    [Crossref]
  11. C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
    [Crossref]
  12. R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.
  13. L. Burke, D. Antonioli, and B. Durcatman, Colposcopy Text and Atlas, (Appleton and Lange., 1991)
  14. J. Thiran and B. Macq, “Morphological Feature Extraction for the Classification of Digital Images of Cancerous Tissues,” IEEE Trans. Biomed.,  43, 1011–1020, (1996)
    [Crossref]
  15. A. Gmitro and D. Aziz, “Confocal microscopy through a fiber-optic imaging bundle,” Opt. Lett. 18, 565–567 (1993).
    [Crossref] [PubMed]
  16. R. Juskaitis, T. Wilson, and T.F. Watson, “Real time white light reflection confocal microscopy using a fiber-optic bundle,” Scanning. 19,15–19 (1997).
    [Crossref]
  17. T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,” Appi. Opt 31,3030–3035 (1992).
    [Crossref]
  18. L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
    [Crossref]
  19. D.L. Dickensheets and G.S. Kino, “Micro-machined scanning confocal optical microscope,” Opt. Lett. 21, 764–766 (1996).
    [Crossref] [PubMed]

1998 (3)

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

1997 (1)

R. Juskaitis, T. Wilson, and T.F. Watson, “Real time white light reflection confocal microscopy using a fiber-optic bundle,” Scanning. 19,15–19 (1997).
[Crossref]

1996 (3)

P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
[Crossref] [PubMed]

D.L. Dickensheets and G.S. Kino, “Micro-machined scanning confocal optical microscope,” Opt. Lett. 21, 764–766 (1996).
[Crossref] [PubMed]

J. Thiran and B. Macq, “Morphological Feature Extraction for the Classification of Digital Images of Cancerous Tissues,” IEEE Trans. Biomed.,  43, 1011–1020, (1996)
[Crossref]

1995 (1)

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

1994 (2)

B. Masters and A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” AppI. Opt. 33, 695–701 (1994).
[Crossref]

C. Bertrand and P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real time confocal microscopy,” Scanning 16, 150–154 (1994).
[Crossref] [PubMed]

1993 (2)

A. Gmitro and D. Aziz, “Confocal microscopy through a fiber-optic imaging bundle,” Opt. Lett. 18, 565–567 (1993).
[Crossref] [PubMed]

L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
[Crossref]

1992 (2)

T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,” Appi. Opt 31,3030–3035 (1992).
[Crossref]

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

1991 (1)

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Anderson,

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

Andrews, P. M.

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Antonioli, D.

L. Burke, D. Antonioli, and B. Durcatman, Colposcopy Text and Atlas, (Appleton and Lange., 1991)

Aziz, D.

Aziz, U. I.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

Bertrand, C.

C. Bertrand and P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real time confocal microscopy,” Scanning 16, 150–154 (1994).
[Crossref] [PubMed]

Brookner, C.

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Burke, L.

L. Burke, D. Antonioli, and B. Durcatman, Colposcopy Text and Atlas, (Appleton and Lange., 1991)

Cavanaugh, H. D.

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Collier, T.

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Corcuff, P.

P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
[Crossref] [PubMed]

C. Bertrand and P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real time confocal microscopy,” Scanning 16, 150–154 (1994).
[Crossref] [PubMed]

Dabbs, T.

T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,” Appi. Opt 31,3030–3035 (1992).
[Crossref]

Dallen Bach-Hellueg, G.

G. Dallen Bach-Hellueg and H. Doulson, Histopathology of the Cervix Uteri, (Springer-Verlag New York Inc., 1990)

Dickensheets, D.L.

Doulson, H.

G. Dallen Bach-Hellueg and H. Doulson, Histopathology of the Cervix Uteri, (Springer-Verlag New York Inc., 1990)

Dresek, R.

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Drezek, R.

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

Dunn, A.

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

Dunn, A. K.

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

Durcatman, B.

L. Burke, D. Antonioli, and B. Durcatman, Colposcopy Text and Atlas, (Appleton and Lange., 1991)

Esterowitz, R. H.

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

Ferlay, J.

D.M. Parkin, P. Pisani, and J. Ferlay Estimates of the Worldwide Incidence of Eighteen Major Cancers in 1985. Int. J. Cancer1993; 54,594–606
[Crossref] [PubMed]

Follen, M.

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Garana, R. M.

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

Giniunas, L.

L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
[Crossref]

Glass, M.

T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,” Appi. Opt 31,3030–3035 (1992).
[Crossref]

Gmitro, A.

Gmitro, A. F.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

Goldman, L.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

Gonnord, G.

P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
[Crossref] [PubMed]

Grossman, D.

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

Jester, J. V.

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

Jester, V.

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Juskaitis, R.

R. Juskaitis, T. Wilson, and T.F. Watson, “Real time white light reflection confocal microscopy using a fiber-optic bundle,” Scanning. 19,15–19 (1997).
[Crossref]

L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
[Crossref]

Kerr, J. H.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

Kino, G.S.

Lemp, M. A.

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Leveque, J. L.

P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
[Crossref] [PubMed]

Lotan, R.

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Macq, B.

J. Thiran and B. Macq, “Morphological Feature Extraction for the Classification of Digital Images of Cancerous Tissues,” IEEE Trans. Biomed.,  43, 1011–1020, (1996)
[Crossref]

Malpica, A.

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Masters, B.

B. Masters and A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” AppI. Opt. 33, 695–701 (1994).
[Crossref]

Masters, B. R.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

O’Grady, T. C.

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

Parkin, D.M.

D.M. Parkin, P. Pisani, and J. Ferlay Estimates of the Worldwide Incidence of Eighteen Major Cancers in 1985. Int. J. Cancer1993; 54,594–606
[Crossref] [PubMed]

Petroll, W. M.

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Petrull, W. M.

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

Pierard, G.E.

P. Corcuff, G. Gonnord, G.E. Pierard, and J. L. Leveque, “In vivo microscopy of human skin: A new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
[Crossref] [PubMed]

Pisani, P.

D.M. Parkin, P. Pisani, and J. Ferlay Estimates of the Worldwide Incidence of Eighteen Major Cancers in 1985. Int. J. Cancer1993; 54,594–606
[Crossref] [PubMed]

Rajadhyaksha, M.

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

Richards-Kortum, R.

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

R. Dresek, T. Collier, C. Brookner, R. Lotan, A. Malpica, R. Richards-Kortum, and M. Follen, “Laser Scanning Confocal Microscopy of Cervical Tissue, Before and After Application of Acetic Acid,” Am. J. of Obstetrics and Gynecology, paper under review.

Shatalin, S.V.

L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
[Crossref]

Smithpeter, C. L.

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

Thaer, A. A.

B. Masters and A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” AppI. Opt. 33, 695–701 (1994).
[Crossref]

Thiran, J.

J. Thiran and B. Macq, “Morphological Feature Extraction for the Classification of Digital Images of Cancerous Tissues,” IEEE Trans. Biomed.,  43, 1011–1020, (1996)
[Crossref]

Watson, T.F.

R. Juskaitis, T. Wilson, and T.F. Watson, “Real time white light reflection confocal microscopy using a fiber-optic bundle,” Scanning. 19,15–19 (1997).
[Crossref]

Webb, R. R.

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

Welch, A. I.

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

Wilson, T.

R. Juskaitis, T. Wilson, and T.F. Watson, “Real time white light reflection confocal microscopy using a fiber-optic bundle,” Scanning. 19,15–19 (1997).
[Crossref]

Appi. Opt (1)

T. Dabbs and M. Glass, “Fiber-optic confocal microscope: FOCON,” Appi. Opt 31,3030–3035 (1992).
[Crossref]

Appi. Opt. (1)

L. Giniunas, R. Juskaitis, and S.V. Shatalin, “Endoscope with optical sectioning capability,” Appi. Opt. 32, 2888–2890 (1993).
[Crossref]

C. L. Smithpeter, A. K. Dunn, A. I. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” AppI. Opt. 37, 2749–2754 (1998).
[Crossref]

B. Masters and A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” AppI. Opt. 33, 695–701 (1994).
[Crossref]

I. Invest. Dermatol. (1)

M. Rajadhyaksha, D. Grossman, R. H. Esterowitz, R. R. Webb, and Anderson, “In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast,” I. Invest. Dermatol. 104, 946952 (1995).
[Crossref]

I. Microsc. (1)

J. V. Jester, W. M. Petrull, R. M. Garana, M. A. Lemp, and H. D. Cavanaugh, “Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy,” I. Microsc. 165, 169–181 (1992).
[Crossref]

IEEE Trans. Biomed. (1)

J. Thiran and B. Macq, “Morphological Feature Extraction for the Classification of Digital Images of Cancerous Tissues,” IEEE Trans. Biomed.,  43, 1011–1020, (1996)
[Crossref]

J, Biom. Opt. (1)

C. L. Smithpeter, A. Dunn, R. Drezek, T. Collier, and R. Richards-Kortum, “Near Real Time Confocal Microscopy of Cultured Amelanotic Cells: Sources of Signal, Contrast Agents and Limits of Contrast,” J, Biom. Opt.,  3,429–436, (1998)
[Crossref]

L Biomed. Opt. (1)

B. R. Masters, U. I. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, and L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” L Biomed. Opt. 2, 437~5 (1998).

L Electron Microsc. Tech. (1)

V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, and H. D. Cavanaugh, “In vivo, real-time confocal imaging,” L Electron Microsc. Tech. 18, 50–60 (1991).
[Crossref]

Opt. Lett. (2)

Scanning (2)

C. Bertrand and P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real time confocal microscopy,” Scanning 16, 150–154 (1994).
[Crossref] [PubMed]

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Supplementary Material (3)

» Media 1: MOV (3130 KB)     
» Media 2: MOV (3098 KB)     
» Media 3: MOV (2470 KB)     

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Figures (8)

Figure 1.
Figure 1. Set up of epi-illumination confocal microscope used to collect the images and video.
Figure 2.
Figure 2. Images of cervical biopsy obtained prior to the application of acetic acid. a). Image taken with confocal microscope with the image plane parallel to the epithelial surface and the focus 20 microns below the surface. b). Same as (a), but with the focus 100 microns below the surface. c). Image of hemotoxylin and eosin stained transverse section using bright field microscopy. Contrast has been reversed in this black and white image to aid in comparing confocal and histologic images. Lines a and b indicate the approximate depth at which the confocal images in (a) and (b) were obtained.
Figure 3.
Figure 3. Images of cervical biopsy obtained after the application of acetic acid. a). Image taken with confocal microscope with the image plane parallel to the epithelial surface and the focus 50 microns below the surface. b). Same as (a) but with the focus 100 microns beneath the surface. c). Same as (a) but with the focus 200 microns beneath the surface. d). Image of hemotoxylin and eosin stained transverse section using bright field microscopy. Contrast has been reversed in this black and white image to aid in comparing confocal and histologic images. Lines a, b and c indicate the approximate depth at which the confocal images in (a), (b) and (c) were obtained.
Figure 4.
Figure 4. 3.1 MB Quicktime video of confocal images obtained as the image plane was translated from the epithelial surface to the basement membrane approximately 5 minutes after the application of acetic. The field of view is approximately 200 um.
Figure 5.
Figure 5. 3.1 MB Quicktime video of confocal images from a fixed image plane approximately 50 um below the epithelial surface as acetic acid is applied. The field of view is approximately 150 um.
Figure 6.
Figure 6. 2.4 MB Quicktime video of three dimensional rendering viewed from various angles. The rendering was created from 30 images taken at 1 um increments through 3 cell layers.
Figure 7.
Figure 7. Segmentations of cell features with the feature detection algorithm on images taken without application of acetic acid. a). Unprocessed image of cervical biopsy. b). Same image as (a) with features outlined in yellow.
Figure 8.
Figure 8. Segmentation of cell nuclei with our feature detection algorithm on images taken with the use of acetic acid. a). Unprocessed image of cervical biopsy. b). Same image as (a) with nuclei highlighted in yellow.

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