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Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model

Lezlee Coghlan, Urs Utzinger, Rebekah Drezek, Douglas Heintzelman, Andres Zuluaga, Carrie Brookner, Rebecca Richards-Kortum, Irma Gimenez-Conti, and Michele Follen

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Abstract

Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350–370 nm and 410 nm excitation and decreased fluorescence near 450–470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350–370 nm excitation and 400–450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.

©2000 Optical Society of America

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Supplementary Material (1)

Media 1: MOV (1458 KB)     

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Figures (6)
Fig. 1.
Fig. 1. Block diagram of system used to measure fluorescence EEMs.

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Table 1a.
Table 1a. Study design for the DMBA treated and control group animals. Colored boxes indicate measurement events. Histopathologic diagnoses are shown with abbreviations, where N=normal, INF=inflammation, U=ulceration, H=hyperplasia, I=grade I dysplasia, II=grade II dysplasia, III=grade III dysplasia, CIS=carcinoma in situ, and SCC=squamous cell carcinoma. Discrepant diagnoses are indicated with D. Yellow shaded boxes indicate those non-neoplastic measurements used in algorithm development; orange shaded boxes indicate those neoplastic measurements used in algorithm development; pink shaded boxes indicate those measurements with fluorescence EEMs discarded during data review. Light blue shaded boxes indicate measurement where diagnosis was undetermined and therefore not used for algorithm development.

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Table 1b.
Table 1b. Table 1, part 2. Study design for the DMBA treated and control group animals. Colored boxes indicate measurement events. Histopathologic diagnoses are shown with abbreviations, where N=normal, INF=inflammation, U=ulceration, H=hyperplasia, I=grade I dysplasia, II=grade II dysplasia, III=grade III dysplasia, CIS=carcinoma in situ, and SCC=squamous cell carcinoma. Discrepant diagnoses are indicated with D. Yellow shaded boxes indicate those non-neoplastic measurements used in algorithm development; orange shaded boxes indicate those neoplastic measurements used in algorithm development; pink shaded boxes indicate those measurements with fluorescence EEMs discarded during data review. Light blue shaded boxes indicate measurement where diagnosis was undetermined and therefore not used for algorithm development.

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Fig. 2.
Fig. 2. Fluorescence EEMs of (left) non-neoplastic and (right) neoplastic hamster cheek pouch.

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Fig. 3.
Fig. 3. Video illustrating fluorescence EEMs each week for a hamster treated with DMBA. Biopsy at week 10 showed grade II dysplasia and histology at week 17 showed squamous cell carcinoma (1.459 KB).

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Fig. 4.
Fig. 4. Histograms depicting the frequency of occurrence of each excitation wavelength in the 25 top performing combinations of 3 excitation wavelengths under cross-validation using (a) normalization method 1 and (b) normalization method 2.

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Tables (1)

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Table 2. Algorithm results for top performing combinations of 1, 2 and 3 excitation wavelengths (λex) using cross validation and both normalization methods.

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