Abstract

We have built a video-rate confocal scanning laser microscope for reflectance imaging of human skin and oral mucosa in vivo. Design and imaging parameters were determined for optimum resolution and contrast. Mechanical skin-holding fixtures and oral tissue clamps were made for stable objective lens-to-tissue contact such that gross tissue motion relative to the microscope was minimized. Confocal imaging was possible to maximum depths of 350 µm in human skin and 450 µm in oral mucosa, with measured lateral resolution of 0.5–1 µm and axial resolution (section thickness) of 3–5 µm at the 1064-nm wavelength. This resolution is comparable with that of conventional microscopy of excised biopsies (histology). Normal and abnormal tissue morphology and dynamic processes were observed.

© 1999 Optical Society of America

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    [CrossRef]

1998

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

1997

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
[CrossRef] [PubMed]

B. R. Masters, G. Gonnord, P. Corcuff, “Three-dimensional microscopic biopsy of in vivo human skin: a new technique based on a flexible confocal microscope,” J. Microsc. 185, 329–338 (1997).
[CrossRef] [PubMed]

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
[CrossRef] [PubMed]

1996

R. H. Webb, “Confocal optical microscopy,” Rep. Prog. Phys. 59, 427–471 (1996).
[CrossRef]

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

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Sources of contrast in confocal reflectance imaging,” Appl. Opt. 35, 3441–3446 (1996).
[CrossRef] [PubMed]

1995

D. R. Sandison, D. W. Piston, R. M. Williams, W. W. Webb, “Quantitative comparison of background rejection, signal-to-noise ratio, and resolution in confocal and full-field scanning microscopes,” Appl. Opt. 34, 3576–3588 (1995).
[CrossRef] [PubMed]

G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett. 20, 2258–2260 (1995).
[CrossRef] [PubMed]

S. C. Kaufman, R. W. Beuerman, D. L. Greer, “Confocal microscopy: a new tool for the study of the nail unit,” J. Am. Acad. Dermatol. 32, 668–670 (1995).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

1994

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

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

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

M. H. Koelink, F. F. M. de Mul, J. Greve, R. Graaff, A. C. M. Dassel, J. G. Aardnouse, “Laser Doppler blood flowmetry using two wavelengths: Monte Carlo simulations and measurements,” Appl. Opt. 33, 3549–3558 (1994).
[CrossRef] [PubMed]

1993

C. J. Koester, J. D. Auran, H. D. Rosskothen, G. J. Florakis, R. B. Tackaberry, “Clinical microscopy of the cornea utilizing optical sectioning and a high numerical aperture objective,” J. Opt. Soc. Am. A 10, 1670–1679 (1993).
[CrossRef] [PubMed]

R. H. Webb, G. W. Hughes, “Detectors for scanning video imagers,” Appl. Opt. 32, 6227–6235 (1993).
[CrossRef] [PubMed]

S. Hell, G. Reiner, C. Cremer, E. H. K. Stelzer, “Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index,” J. Microsc. 169, 391–405 (1993).
[CrossRef]

G. E. Pierard, “In vivo confocal microscopy: a new paradigm in dermatology,” Dermatology 186, 4–5 (1993).
[CrossRef]

P. Corcuff, J. L. Leveque, “In vivo vision of the human skin with the tandem scanning microscope,” Dermatology 186, 50–54 (1993).
[CrossRef]

P. Corcuff, C. Bertrand, J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res. 285, 475–481 (1993).
[CrossRef] [PubMed]

1992

1991

C. J. R. Sheppard, C. J. Cogswell, “Effects of aberrating layers and tube length on confocal imaging properties,” Optik 87, 34–38 (1991).

K. Carlsson, “The influence of specimen refractive index, detector signal integration, and non-uniform scan speed on the imaging properties in confocal microscopy,” J. Microsc. 163, 167–178 (1991).
[CrossRef]

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

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

P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
[CrossRef] [PubMed]

C. J. R. Sheppard, M. Gu, “Aberration compensation in confocal microscopy,” Appl. Opt. 30, 3563–3568 (1991).
[CrossRef] [PubMed]

H. J. van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl, M. J. C. van Gemert, “Light scattering in Intralipid-10% in the wavelength range of 400–1100 nm,” Appl. Opt. 30, 4507–4514 (1991).
[CrossRef] [PubMed]

1990

H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2199 (1990).
[CrossRef]

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

E. Peli, “Contrast in complex images,” J. Opt. Soc. Am. A 7, 2032–2040 (1990).
[CrossRef] [PubMed]

1989

M. J. C. van Gemert, S. L. Jacques, H. J. C. M. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[CrossRef] [PubMed]

1988

T. Wilson, A. R. Carlini, “Three-dimensional imaging in confocal imaging systems with finite sized detectors,” J. Microsc. 149, 51–66 (1988).
[CrossRef]

1987

1986

T. R. Corle, C. H. Chou, G. S. Kino, “Depth response of confocal optical microscopes,” Opt. Lett. 11, 770–772 (1986).
[CrossRef] [PubMed]

M. Petran, M. Hadravsky, J. Benes, A. Boyde, “In vivo microscopy using the tandem scanning microscope,” Ann. N.Y. Acad. Sci. 483, 440–447 (1986).
[CrossRef]

1981

R. R. Anderson, J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[CrossRef] [PubMed]

R. H. Webb, G. W. Hughes, “Scanning laser ophthalmoscope,” IEEE Trans. Biomed. Eng. BME-28, 488–492 (1981).
[CrossRef]

S. Wan, R. R. Anderson, J. A. Parrish, “Analytical modeling for the optical properties of the skin with in vitro and in vivo applications,” Photochem. Photobiol. 34, 493–499 (1981).
[PubMed]

1978

1974

P. P. Webb, R. J. McIntyre, J. Conradi, “Properties of avalanche photodiodes,” RCA Rev. 35, 234–278 (1974).

1972

K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

1969

G. Szabo, A. B. Gerald, M. A. Pathak, T. B. Fitzpatrick, “Racial differences in the fate of melanosomes in human epidermis,” Nature (London) 222, 1081–1082 (1969).
[CrossRef]

Aardnouse, J. G.

Anderson, R. R.

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

R. R. Anderson, J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[CrossRef] [PubMed]

S. Wan, R. R. Anderson, J. A. Parrish, “Analytical modeling for the optical properties of the skin with in vitro and in vivo applications,” Photochem. Photobiol. 34, 493–499 (1981).
[PubMed]

Andrews, P. M.

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

P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
[CrossRef] [PubMed]

Auran, J. D.

Aziz, D. J.

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
[CrossRef] [PubMed]

Benes, J.

M. Petran, M. Hadravsky, J. Benes, A. Boyde, “In vivo microscopy using the tandem scanning microscope,” Ann. N.Y. Acad. Sci. 483, 440–447 (1986).
[CrossRef]

Bertrand, C.

C. Bertrand, 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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S. C. Kaufman, R. W. Beuerman, D. L. Greer, “Confocal microscopy: a new tool for the study of the nail unit,” J. Am. Acad. Dermatol. 32, 668–670 (1995).
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J. V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, H. D. Cavanagh, “In vivo, real-time confocal imaging,” J. Electron Microsc. 18, 50–60 (1991).
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K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
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P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
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B. R. Masters, G. Gonnord, P. Corcuff, “Three-dimensional microscopic biopsy of in vivo human skin: a new technique based on a flexible confocal microscope,” J. Microsc. 185, 329–338 (1997).
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P. Corcuff, G. Gonnord, G. E. Pierard, J. L. Leveque, “In vivo confocal microscopy of human skin: a new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
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C. Bertrand, P. Corcuff, “In vivo spatio-temporal visualization of the human skin by real-time confocal microscopy,” Scanning 16, 150–154 (1994).
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P. Corcuff, C. Bertrand, J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res. 285, 475–481 (1993).
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P. Corcuff, J. L. Leveque, “In vivo vision of the human skin with the tandem scanning microscope,” Dermatology 186, 50–54 (1993).
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K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
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Cremer, C.

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de Mul, F. F. M.

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A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
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R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

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H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

J. V. Jester, H. D. Cavanagh, J. Essepian, W. J. Shields, M. A. Lemp, “Real-time confocal imaging of the living eye,” in New Methods in Light Microscopy and Low Light Imaging, J. E. Wampler, ed., Proc. SPIE1161, 366–376 (1989).
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M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
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W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

Fewkes, J. L.

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

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K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
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Fujimoto, J. G.

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G. Szabo, A. B. Gerald, M. A. Pathak, T. B. Fitzpatrick, “Racial differences in the fate of melanosomes in human epidermis,” Nature (London) 222, 1081–1082 (1969).
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B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
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B. R. Masters, G. Gonnord, P. Corcuff, “Three-dimensional microscopic biopsy of in vivo human skin: a new technique based on a flexible confocal microscope,” J. Microsc. 185, 329–338 (1997).
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P. Corcuff, G. Gonnord, G. E. Pierard, J. L. Leveque, “In vivo confocal microscopy of human skin: a new design for cosmetology and dermatology,” Scanning 18, 351–355 (1996).
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González, E.

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

González, S.

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

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Greer, D. L.

S. C. Kaufman, R. W. Beuerman, D. L. Greer, “Confocal microscopy: a new tool for the study of the nail unit,” J. Am. Acad. Dermatol. 32, 668–670 (1995).
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Grossman, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
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M. Petran, M. Hadravsky, J. Benes, A. Boyde, “In vivo microscopy using the tandem scanning microscope,” Ann. N.Y. Acad. Sci. 483, 440–447 (1986).
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Hell, S.

S. Hell, G. Reiner, C. Cremer, E. H. K. Stelzer, “Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index,” J. Microsc. 169, 391–405 (1993).
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J. V. Jester, P. M. Andrews, W. M. Petroll, M. A. Lemp, H. D. Cavanagh, “In vivo, real-time confocal imaging,” J. Electron Microsc. 18, 50–60 (1991).
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K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
[CrossRef] [PubMed]

H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

J. V. Jester, H. D. Cavanagh, J. Essepian, W. J. Shields, M. A. Lemp, “Real-time confocal imaging of the living eye,” in New Methods in Light Microscopy and Low Light Imaging, J. E. Wampler, ed., Proc. SPIE1161, 366–376 (1989).
[CrossRef]

Kaufman, S. C.

S. C. Kaufman, R. W. Beuerman, D. L. Greer, “Confocal microscopy: a new tool for the study of the nail unit,” J. Am. Acad. Dermatol. 32, 668–670 (1995).
[CrossRef] [PubMed]

Kerr, J. H.

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
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Koelink, M. H.

Koester, C. J.

Kollias, N.

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

Langley, R. G. B.

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

Lanni, F.

Lemp, M. A.

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

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

H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

J. V. Jester, H. D. Cavanagh, J. Essepian, W. J. Shields, M. A. Lemp, “Real-time confocal imaging of the living eye,” in New Methods in Light Microscopy and Low Light Imaging, J. E. Wampler, ed., Proc. SPIE1161, 366–376 (1989).
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Leveque, J. L.

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

P. Corcuff, J. L. Leveque, “In vivo vision of the human skin with the tandem scanning microscope,” Dermatology 186, 50–54 (1993).
[CrossRef]

P. Corcuff, C. Bertrand, J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res. 285, 475–481 (1993).
[CrossRef] [PubMed]

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

Martin, L.

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

Masters, B. R.

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
[CrossRef] [PubMed]

B. R. Masters, G. Gonnord, P. Corcuff, “Three-dimensional microscopic biopsy of in vivo human skin: a new technique based on a flexible confocal microscope,” J. Microsc. 185, 329–338 (1997).
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B. R. Masters, A. A. Thaer, “Real-time scanning slit confocal microscopy of the in vivo human cornea,” Appl. Opt. 33, 695–701 (1994).
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New, K. C.

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

O’Grady, T. C.

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
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K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

Pathak, M. A.

K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

G. Szabo, A. B. Gerald, M. A. Pathak, T. B. Fitzpatrick, “Racial differences in the fate of melanosomes in human epidermis,” Nature (London) 222, 1081–1082 (1969).
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M. Petran, M. Hadravsky, J. Benes, A. Boyde, “In vivo microscopy using the tandem scanning microscope,” Ann. N.Y. Acad. Sci. 483, 440–447 (1986).
[CrossRef]

Petroll, W. M.

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

P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
[CrossRef] [PubMed]

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

Pierard, G. E.

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

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K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

Rajadhyaksha, M.

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

Reiner, G.

S. Hell, G. Reiner, C. Cremer, E. H. K. Stelzer, “Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index,” J. Microsc. 169, 391–405 (1993).
[CrossRef]

Richards-Kortum, R.

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
[CrossRef] [PubMed]

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Sources of contrast in confocal reflectance imaging,” Appl. Opt. 35, 3441–3446 (1996).
[CrossRef] [PubMed]

Rosskothen, H. D.

Rubinstein, G.

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

Sandison, D. R.

Sheppard, C. J. R.

Shields, W.

H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

Shields, W. J.

J. V. Jester, H. D. Cavanagh, J. Essepian, W. J. Shields, M. A. Lemp, “Real-time confocal imaging of the living eye,” in New Methods in Light Microscopy and Low Light Imaging, J. E. Wampler, ed., Proc. SPIE1161, 366–376 (1989).
[CrossRef]

Smithpeter, C.

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
[CrossRef] [PubMed]

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Sources of contrast in confocal reflectance imaging,” Appl. Opt. 35, 3441–3446 (1996).
[CrossRef] [PubMed]

Sober, A. J.

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

Southern, J. F.

Star, W. M.

M. J. C. van Gemert, S. L. Jacques, H. J. C. M. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[CrossRef] [PubMed]

Stelzer, E. H. K.

S. Hell, G. Reiner, C. Cremer, E. H. K. Stelzer, “Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index,” J. Microsc. 169, 391–405 (1993).
[CrossRef]

Sterenborg, H. J. C. M.

M. J. C. van Gemert, S. L. Jacques, H. J. C. M. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[CrossRef] [PubMed]

Szabo, G.

G. Szabo, A. B. Gerald, M. A. Pathak, T. B. Fitzpatrick, “Racial differences in the fate of melanosomes in human epidermis,” Nature (London) 222, 1081–1082 (1969).
[CrossRef]

Tackaberry, R. B.

Tearney, G. J.

Thaer, A. A.

Toda, K.

K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

Ugent, S. J.

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

van Gemert, M. J. C.

van Marle, J.

van Staveren, H. J.

Verdeyen, J. T.

J. T. Verdeyen, “Detection of optical radiation,” in Laser Electronics (Prentice-Hall, Englewood Cliffs, N.J., 1981), Chap. 14, pp. 399–418.

Vitkin, I. A.

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

Wan, S.

S. Wan, R. R. Anderson, J. A. Parrish, “Analytical modeling for the optical properties of the skin with in vitro and in vivo applications,” Photochem. Photobiol. 34, 493–499 (1981).
[PubMed]

Watson, A. B.

A. B. Watson, “Temporal sensitivity,” in Handbook of Perception and Human PerformanceK. R. Boff, L. Kaufman, J. P. Thomas, eds. (Wiley, New York, 1986), Vol. 1, Chap. 6, pp. 6.34–6.35.

Webb, P. P.

P. P. Webb, R. J. McIntyre, J. Conradi, “Properties of avalanche photodiodes,” RCA Rev. 35, 234–278 (1974).

Webb, R. H.

R. H. Webb, “Confocal optical microscopy,” Rep. Prog. Phys. 59, 427–471 (1996).
[CrossRef]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

R. H. Webb, G. W. Hughes, “Detectors for scanning video imagers,” Appl. Opt. 32, 6227–6235 (1993).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

R. H. Webb, G. W. Hughes, “Scanning laser ophthalmoscope,” IEEE Trans. Biomed. Eng. BME-28, 488–492 (1981).
[CrossRef]

O. Pomerantzeff, R. H. Webb, “Scanning ophthalmoscope for examining the fundus of the eye,” U.S. patent4,213,678 (22July1980).

R. H. Webb, G. W. Hughes, “Double scanning optical apparatus,” U.S. patents4,764,005, 4,765,730, and 4768873 (16August, 23August, and 6September1988).

Webb, W. W.

Welch, A. J.

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
[CrossRef] [PubMed]

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Sources of contrast in confocal reflectance imaging,” Appl. Opt. 35, 3441–3446 (1996).
[CrossRef] [PubMed]

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

White, W. M.

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

Williams, R. M.

Wilson, B. C.

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2199 (1990).
[CrossRef]

Wilson, T.

T. Wilson, A. R. Carlini, “Three-dimensional imaging in confocal imaging systems with finite sized detectors,” J. Microsc. 149, 51–66 (1988).
[CrossRef]

T. Wilson, A. R. Carlini, “Size of the detector in confocal imaging systems,” Opt. Lett. 12, 227–229 (1987).
[CrossRef] [PubMed]

C. J. R. Sheppard, T. Wilson, “Depth of field in the scanning microscope,” Opt. Lett. 3, 115–117 (1978).
[CrossRef] [PubMed]

T. Wilson, “The role of the pinhole in confocal imaging systems,” in Handbook of Biological Confocal Microscopy, 2nd ed., J. B. Pawley, Ed. (Plenum, New York, 1995), Chap. 11, pp. 167–182.
[CrossRef]

Wolf, E.

M. Born, E. Wolf, Principles of Optics, 6th ed. (Pergamon, New York, 1980), p. 437.

Woolsey, J.

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

Zavislan, J.

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

Am. J. Anat.

P. M. Andrews, W. M. Petroll, H. D. Cavanagh, J. V. Jester, “Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys,” Am. J. Anat. 191, 95–102 (1991).
[CrossRef] [PubMed]

Am. J. Contact Dermatitis

S. González, W. M. White, M. Rajadhyaksha, G. Rubinstein, R. R. Anderson, E. González, “Confocal imaging of acute contact dermatitis in vivo,” Am. J. Contact Dermatitis 9, 62 (1998).
[CrossRef]

Ann. N.Y. Acad. Sci.

M. Petran, M. Hadravsky, J. Benes, A. Boyde, “In vivo microscopy using the tandem scanning microscope,” Ann. N.Y. Acad. Sci. 483, 440–447 (1986).
[CrossRef]

Appl. Opt.

Arch. Dermatol. Res.

P. Corcuff, C. Bertrand, J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res. 285, 475–481 (1993).
[CrossRef] [PubMed]

Contact Lens Association of Ophthalmologists Journal

H. D. Cavanagh, J. V. Jester, J. Essepian, W. Shields, M. A. Lemp, “Confocal microscopy of the living eye,” Contact Lens Association of Ophthalmologists Journal 16, 65–73 (1990).

Dermatology

G. E. Pierard, “In vivo confocal microscopy: a new paradigm in dermatology,” Dermatology 186, 4–5 (1993).
[CrossRef]

P. Corcuff, J. L. Leveque, “In vivo vision of the human skin with the tandem scanning microscope,” Dermatology 186, 50–54 (1993).
[CrossRef]

IEEE J. Quantum Electron.

B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2199 (1990).
[CrossRef]

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

IEEE Trans. Biomed. Eng.

M. J. C. van Gemert, S. L. Jacques, H. J. C. M. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[CrossRef] [PubMed]

R. H. Webb, G. W. Hughes, “Scanning laser ophthalmoscope,” IEEE Trans. Biomed. Eng. BME-28, 488–492 (1981).
[CrossRef]

J. Am. Acad. Dermatol.

S. C. Kaufman, R. W. Beuerman, D. L. Greer, “Confocal microscopy: a new tool for the study of the nail unit,” J. Am. Acad. Dermatol. 32, 668–670 (1995).
[CrossRef] [PubMed]

J. Biomed. Opt.

B. R. Masters, D. J. Aziz, A. F. Gmitro, J. H. Kerr, T. C. O’Grady, L. Goldman, “Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization,” J. Biomed. Opt. 2, 437–445 (1997).
[CrossRef] [PubMed]

A. K. Dunn, C. Smithpeter, A. J. Welch, R. Richards-Kortum, “Finite-difference time-domain simulation of light scattering from single cells,” J. Biomed. Opt. 2, 262–266 (1997).
[CrossRef] [PubMed]

J. Electron Microsc.

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

J. Invest. Dermatol.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

R. R. Anderson, J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[CrossRef] [PubMed]

R. G. B. Langley, M. Rajadhyaksha, P. J. Dwyer, R. R. Anderson, A. J. Sober, “Confocal scanning laser microscopy of pigmented lesions,” J. Invest. Dermatol. 106, 836 (1996).

S. González, W. M. White, G. Rubinstein, M. Rajadhyaksha, J. Zavislan, J. L. Fewkes, R. R. Anderson, “In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms,” J. Invest. Dermatol. 110, 583 (1998).

W. M. White, M. Rajadhyaksha, S. González, R. L. Fabian, R. R. Anderson, “Clinical, real-time confocal imaging of human oral mucosa in vivo,” J. Invest. Dermatol. 110, 588 (1998).

S. González, M. Rajadhyaksha, G. Rubinstein, W. M. White, E. González, R. R. Anderson, “Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy,” J. Invest. Dermatol. 110, 580 (1998).

J. Microsc.

K. Carlsson, “The influence of specimen refractive index, detector signal integration, and non-uniform scan speed on the imaging properties in confocal microscopy,” J. Microsc. 163, 167–178 (1991).
[CrossRef]

S. Hell, G. Reiner, C. Cremer, E. H. K. Stelzer, “Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index,” J. Microsc. 169, 391–405 (1993).
[CrossRef]

T. Wilson, A. R. Carlini, “Three-dimensional imaging in confocal imaging systems with finite sized detectors,” J. Microsc. 149, 51–66 (1988).
[CrossRef]

B. R. Masters, G. Gonnord, P. Corcuff, “Three-dimensional microscopic biopsy of in vivo human skin: a new technique based on a flexible confocal microscope,” J. Microsc. 185, 329–338 (1997).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

Nature (London)

G. Szabo, A. B. Gerald, M. A. Pathak, T. B. Fitzpatrick, “Racial differences in the fate of melanosomes in human epidermis,” Nature (London) 222, 1081–1082 (1969).
[CrossRef]

Nature New Biology

K. Toda, M. A. Pathak, J. A. Parrish, T. B. Fitzpatrick, W. C. Quevedo, “Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light,” Nature New Biology 236, 143–145 (1972).
[CrossRef] [PubMed]

Opt. Lett.

Optik

C. J. R. Sheppard, C. J. Cogswell, “Effects of aberrating layers and tube length on confocal imaging properties,” Optik 87, 34–38 (1991).

Photochem. Photobiol.

S. Wan, R. R. Anderson, J. A. Parrish, “Analytical modeling for the optical properties of the skin with in vitro and in vivo applications,” Photochem. Photobiol. 34, 493–499 (1981).
[PubMed]

I. A. Vitkin, J. Woolsey, B. C. Wilson, R. R. Anderson, “Optical and thermal characterization of natural (sepia officinalis) melanin,” Photochem. Photobiol. 59, 455–462 (1994).
[CrossRef] [PubMed]

S. J. Ugent, M. Rajadhyaksha, N. Kollias, R. R. Anderson, “In vivo scanning laser confocal microscopy of UVB-irradiated human skin,” Photochem. Photobiol. 63, 50 (1996).

RCA Rev.

P. P. Webb, R. J. McIntyre, J. Conradi, “Properties of avalanche photodiodes,” RCA Rev. 35, 234–278 (1974).

Rep. Prog. Phys.

R. H. Webb, “Confocal optical microscopy,” Rep. Prog. Phys. 59, 427–471 (1996).
[CrossRef]

Scanning

K. C. New, W. M. Petroll, A. Boyde, L. Martin, P. Corcuff, J. L. Leveque, M. A. Lemp, H. D. Cavanagh, J. V. Jester, “In vivo imaging of human teeth and skin using real-time confocal microscopy,” Scanning 13, 369–372 (1991).
[CrossRef]

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

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

Other

J. B. Pawley, ed., Handbook of Biological Confocal Microscopy, 2nd ed. (Plenum, New York, 1995).

J. V. Jester, H. D. Cavanagh, J. Essepian, W. J. Shields, M. A. Lemp, “Real-time confocal imaging of the living eye,” in New Methods in Light Microscopy and Low Light Imaging, J. E. Wampler, ed., Proc. SPIE1161, 366–376 (1989).
[CrossRef]

J. T. Verdeyen, “Detection of optical radiation,” in Laser Electronics (Prentice-Hall, Englewood Cliffs, N.J., 1981), Chap. 14, pp. 399–418.

A. B. Watson, “Temporal sensitivity,” in Handbook of Perception and Human PerformanceK. R. Boff, L. Kaufman, J. P. Thomas, eds. (Wiley, New York, 1986), Vol. 1, Chap. 6, pp. 6.34–6.35.

S. Inoue, Video Microscopy (Plenum, New York, 1986).
[CrossRef]

E. Peli (Schepens Eye Research Institute, Boston, Mass. 02114 (personal communication, 1997).

M. Born, E. Wolf, Principles of Optics, 6th ed. (Pergamon, New York, 1980), p. 437.

T. Wilson, “The role of the pinhole in confocal imaging systems,” in Handbook of Biological Confocal Microscopy, 2nd ed., J. B. Pawley, Ed. (Plenum, New York, 1995), Chap. 11, pp. 167–182.
[CrossRef]

O. Pomerantzeff, R. H. Webb, “Scanning ophthalmoscope for examining the fundus of the eye,” U.S. patent4,213,678 (22July1980).

R. H. Webb, G. W. Hughes, “Double scanning optical apparatus,” U.S. patents4,764,005, 4,765,730, and 4768873 (16August, 23August, and 6September1988).

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Figures (6)

Fig. 1
Fig. 1

Optics of the video-rate CSLM for imaging human skin and oral mucosa in vivo.

Fig. 2
Fig. 2

Video-timing electronics of the CSLM: OP AMP, optical amplifier; other abbreviations defined in text.

Fig. 3
Fig. 3

Coefficient of variation, as a measure of image contrast, versus objective lens NA. The coefficient of variation for each NA was averaged over 15 grabbed images of human skin in vivo. The standard deviation may represent the biological variability of the skin. The reason for the large standard deviation for the 0.7-NA lens may be the fact that the imaging was performed at a different site than for the other lenses.

Fig. 4
Fig. 4

Mechanical arm and fixture to locate and minimize lateral skin motion. The optics following the galvanometric scanner were mounted upon the arm, and the microscope objective lens was enclosed in an aluminum housing. A brass ring-and-template assembly was attached to the skin with medical adhesive (either liquid or double-sided tape). The ring forms a well that holds the immersion medium. The site to be imaged was located with a hole in the template. Hole diameters ranged from 0.2 to 10 mm, permitting precise location of either small or large sites. By locking the ring-and template assembly into the housing of the objective lens, we obtained stable microscope-to-skin contact that effectively minimized gross lateral (XY) skin motion. The microscope objective lens was mounted upon a three-axis XYZ micrometer stage that allows the objective lens to be laterally (XY) and axially (Z) translated relative to the template.

Fig. 5
Fig. 5

Confocal reflectance images of human skin in vivo, showing (a) spinous cells, including a cluster of basal cells (arrow) at a depth of 100 µm in the epidermis; (b) circulating platelets and red and white blood cells (arrow) in a capillary at a depth of 125 µm in superficial dermis; (c) collagen bundles (arrows) at a depth of 200 µm in the superficial dermis. In the spinous and basal cells the bright areas are cytoplasm and the dark areas are the nuclei. Other structures that were clearly imaged were bright punctate outlines of spinous cells (which may be desmosomes), blood flow in the deeper vasculature, hair follicles, and sweat ducts. Objective lens: 100×; 1.2-NA water immersion; wavelength, 1064 nm. Scale bar, 25 µm.

Fig. 6
Fig. 6

Confocal reflectance images of human oral mucosa in vivo, showing (a) epithelial cells in the tongue at a depth of 50 µm; (b) epithelial cells in the lip at a depth of 100 µm; (c) connective tissue in the lip at a depth of 400 µm. Objective lens: (a), (b) 30×, 0.9-NA water immersion; (c) 60×, 0.85-NA water immersion. Wavelength, 1064 nm. Scale bar, 25 µm. The nuclei in the oral mucosa appear bright relative to the cytoplasm, whereas they appear dark in the skin. Other images showed structures such as salivary ducts and the rich network of blood vessels. Images provided by W. Matthew White, Wellman Laboratories, Massachusetts General Hospital, and Otolaryngology Department, Massachusetts Eye and Ear Infirmary.

Equations (3)

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Δx=0.46λNA,
Δz=1.4nλNA2,
vp=2πλNA rp,

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