Abstract

We present a multispectral digital colposcope (MDC) to measure multispectral autofluorescence and reflectance images of the cervix by using an inexpensive color CCD camera. The diagnostic ability of the MDC was evaluated by application of MDC spectral response to fluorescence and reflectance spectra measured from a large clinical trial. High diagnostic performance was achieved by use of only two excitation wavelengths: 330 and 440 nm. Good quality autofluorescence images of the human cervix were acquired in vivo with the MDC. Automated diagnostic algorithms correctly identified CIN (cervical intraepithelial neoplasia) lesions from MDC fluorescence images. The MDC has the potential to provide a cost-effective alternative to standard colposcopy and better direction of biopsies.

© 2003 Optical Society of America

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References

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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]

Appl. Opt. (1)

Appl. Spectrosc. (2)

Cancer Res. (1)

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, D. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, �??,�?? Cancer Res. 62, 682-687 (2002).
[PubMed]

Gastroenterology (1)

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M.G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. Thomas, L. T. Perelman, and M. S. Feld, �??Fluorescence, reflectance, and lightscattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,�?? Gastroenterology 120, 1620-1629 (2001).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng. (2)

U. Utzinger, V. Trujillo, N. Atkinson, M. F. Mitchell, S. Cantor, and R. Richards-Kortum, �??Performance estimation of diagnostic tests for cervical precancer based on fluorescence spectroscopy: effects on tissue type, sample size population, and signal to noise ratio,�?? IEEE Trans. Biomed. Eng. 49, 1293-1303 (1999).
[CrossRef]

S. K. Chang, M. Follen, A. Malpica, U. Utzinger, S. Gtaerkel, D. Cox, N. Atkinson, C. MacAulay, and R. Richards-Kortum, �??Optimal excitation wavelengths for discrimination of cervical neoplasia,�?? IEEE Trans. Biomed. Eng. 49, 1102-1111 (2002).
[CrossRef] [PubMed]

J. Am. Med. Assoc. (2)

L. G. Koss, �??The Papanicoloau test for cervical cancer detection: a triumph and a tragedy,�?? J. Am. Med. Assoc. 261, 737-743 (1989).
[CrossRef]

R. J. Kurman, D. E. Herison, A. L. Herbst, K. L. Noller, and M. H. Schiffman, �??Interim guidelines for management of abnormal cervical cytology,�?? J. Am. Med. Assoc. 271, 1866-1869 (1994).
[CrossRef]

J. Biomed. Opt. (2)

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, �??Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,�?? J. Biomed. Opt. 6, 385-396 (2001).
[CrossRef] [PubMed]

A. Bogaards, M.C.G. Aalders, C.C. Zeyl, S. de Blok, C. Dannecker, P. Hillemanns, H. Stepp, and H. J. C. M. Sterenborg, �??Localization and staging of cervical intraepithelial neoplasia using double ratio fluorescence imaging,�?? J. Biomed. Opt. 7(2), 215-220 (2002).
[CrossRef] [PubMed]

J. Lower Genital Tract Disease (1)

L. Burke, M. Modell, J. Niloff, M. Kobelin, G. Abu-Jawdeh, and A. Zelenchuk, �??Identification of squamous intraepithelial lesions: fluorescence of cervical tissue during colposcopy,�?? J. Lower Genital Tract Disease 3, 159-162 (1999).
[CrossRef]

J. of Lower Genital Tract Disease (1)

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. L. Faupel, �??Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,�?? J. of Lower Genital Tract Disease 5(2), 65-72 (2001).

Lasers Surg. Med. (4)

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, �??Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,�?? Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, A. Malpica, T. Wright, N. Atkinson, and R. Richards-Kortum, �??,�?? Lasers Surg. Med. 19, 46-62 (1996).
[CrossRef] [PubMed]

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, �??Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,�?? Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Thomsen, A. Malpica, T. C. Wright, N. Atkinson, and R. R. Richards-Kortum, �??Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser induced fluorescence spectra at multiple excitation wavelengths,�?? Lasers Surg. Med. 19, 63-74 (1996).
[CrossRef] [PubMed]

Obstet. Gynecol. (2)

S. B. Cantor, M. Follen-Mitchell, G. Tortolero-Luna, C. Bratka, D. Bodurka, and R. Richards-Kortum, �??Cost-effectiveness analysis of diagnosis and management of cervical squamous intraepithelial lesions,�?? Obstet. Gynecol. 91, 270-277 (1998).
[CrossRef] [PubMed]

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, R. and Richards-Kortum, �??Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta-analysis,�?? Obstet. Gynecol. 91, 626-631 (1998).
[CrossRef] [PubMed]

Opt. Express (1)

Photochem. Photobiol. (2)

G. A. Wagnieres, W. M. Star, and B. C. Wilson, �??In vivo fluorescence spectroscopy and imaging for oncological applications,�?? Photochem. Photobiol. 68, 603-32 (1998).
[PubMed]

N. Ramanujam, M. F. Mitchell, A. Mahadevan-Jansen, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards-Kortum, �??Cervical pre-cancer detection using a multivariate statistical algorithm based on laser induced fluorescence spectra at multiple excitation wavelengths,�?? Photochem. Photobiol. 6, 720-735 (1996).
[CrossRef]

Science (1)

A. Mayevsky, B. Chance, �??Intracellular oxidation-reduction state measured in situ by a multichannel fiberoptic surface fluorometer,�?? Science 217, 537-40 (1982).
[CrossRef] [PubMed]

Other (8)

I. Pavlova, K. Sokolov, A. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, �??Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser scanning fluorescence confocal microscopy,�?? submitted to Photochem. Photobiol. (2002).

N. Ramanujam, �??Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,�?? Neoplasia 2(1), 89- 117, (2000).
[CrossRef] [PubMed]

A. K. Dattamajumdar, D. Wells, J. Parnell, J. T. Lewis, D. Ganguly, and T. C. Jr. Wright, �??Preliminary experimental results from multi-center clinical trials for detection of cervical precancerous lesions using the Cerviscan system: a novel full-field evoked tissue fluorescence based imaging instruments,�?? in 23rd Annual Meeting of IEEE-Engineering in Medicine and Biology, Istanbul, Turkey, October 2001.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Thomsen, A. Malpica, T. C. Wright, N. Atkinson, and R. R. Richards-Kortum, �??In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laserinduced fluorescence,�?? Proc. Natl. Acad. Sci. USA 91, 10193-10197 (1994).
[CrossRef] [PubMed]

M. F. Mitchell, �??Preinvasive diseases of the female low genital track,�?? in Operative Gynecology D. M. Greshenson, A. DeCherney, and S. Curry, eds. (Saunders, Philadelphia, 1993), p. 231.

Cancer Facts and Figures, American Society of Cancer, 2001.

International Agency for Research in Cancer, 2002.

R. J. Kurman and D. Solomon, The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnosis (Springer-Verlag, New York, 1994).
[CrossRef]

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Figures (10)

Fig. 1.
Fig. 1.

System diagram of the MDC.

Fig. 2.
Fig. 2.

Picture of the MDC system.

Fig. 3.
Fig. 3.

Spectral response curves of the CV S3200 JAI color camera.

Fig. 4.
Fig. 4.

Se, Sp values for the classification algorithm when applied to simulated MDC data and the complete spectra at 330 nm and 440 nm excitation wavelengths.

Fig. 5.
Fig. 5.

Se and Sp of the four best performing excitation wavelengths and bandwidths combinations for the discrimination between SN and HGSIL. The fifth combination shows Se and Sp for the selected excitation wavelengths for the MDC.

Fig. 6.
Fig. 6.

(a) Fluorescence image of Exalite at 345 excitation, (b) red, (c) green, and (d) blue channels. (e) Intensity versus pixel number from the central horizontal cross section of images in (a) – (c) illustrating nonuniform illumination at edges of the field.

Fig. 7.
Fig. 7.

(a) Fluorescence image of FAD at 440 excitation, (b) red, (c) green, and (d) blue channels.

Fig. 8.
Fig. 8.

Background image measured with the room lights and the MDC light source off.

Fig. 9.
Fig. 9.

Frosted cuvette images at (a) 345 nm and (b) 440 nm excitation.

Fig. 10.
Fig. 10.

Reflectance and fluorescence images of a patient with both CIN I and CIN II lesions. (a) shows the reflectance image and (b) shows the pathology section code used to map the pathology diagnosis to the fluorescence images. (c) and (d) show the fluorescence images taken at 345nm and 440 nm respectively. These images were taken after the application of acetic acid. (e) shows the results from the classification algorithm for SN versus HG. Blue areas indicate SN tissue and red areas indicate HG tissue. (f) shows the areas classified as HG overlaid over the reflectance image.

Tables (1)

Tables Icon

Table 1. Selected bandpass and longpass filters for the two different imaging fluorescence modes.

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