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Cancer Prevention Research
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Research Article

Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia

Mark C. Pierce, Richard A. Schwarz, Vijayashree S. Bhattar, Sharon Mondrik, Michelle D. Williams, J. Jack Lee, Rebecca Richards-Kortum and Ann M. Gillenwater
Mark C. Pierce
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Richard A. Schwarz
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Vijayashree S. Bhattar
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Sharon Mondrik
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Michelle D. Williams
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J. Jack Lee
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Rebecca Richards-Kortum
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Ann M. Gillenwater
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DOI: 10.1158/1940-6207.CAPR-11-0555 Published June 2012
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    Figure 1.

    Multimodal optical imaging in the oral cavity. A–D, a normal site on the anterior tongue. E–H, a site diagnosed with severe dysplasia on the left mid tongue in the same patient. A and E, WLE; B and F, AFI; C and G, high-resolution microendoscopy; and D and H, histopathology sections. In (E), scar tissue is apparent, with the smaller lesion alongside. In (B) and (F), arrows indicate the location of the microendoscope probe, as seen in (A) and (E). Scale bars represent 100 μm.

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    Figure 2.

    Multimodal optical imaging at the floor-of-mouth. A, the entire area appeared normal on clinical examination. B, AFI revealed a region with distinct loss of fluorescence intensity at the patient's right side. C and D, HRME images with the probe placed at sites “1” and “2” in panel (B), respectively. E and F, histopathology sections from sites “1” and “2” respectively in panel (B). Scale bars represent 100 μm.

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    Figure 3.

    Quantification of AFI and HRME images. Symbols represent the diagnosis for each site according to pathology. A, normalized ratio of red-to-green autofluorescence intensity at each of the 100 sites measured in the study. B, N/C area ratio for the same 100 sites shown in (A). C, classification of measurement sites using both wide-field autofluorescence and high-resolution morphology. Dashed lines represent linear threshold values to discriminate between normal sites, and those with mild/moderate/severe dysplasia or cancer.

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    Figure 4.

    Histopathology sections of tissue from 2 sites with a diagnosis of mild dysplasia. A–D, sections from a site which was classified as “normal” by optical measurement. E–H, sections from a site classified as “abnormal” by optical measurement. A and E, H&E-stained sections used by the study pathologist to classify each site as mild dysplasia. Immunostained sections from the same sites with (B) Ki-67, graded low, (C) p63, low (D) PHH3, low, (F) Ki-67, moderate, (G) p63, high, (H) PHH3, high. Scale bars represent 100 μm.

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    Figure 5.

    Analysis of immunohistochemical staining of sections from tissue sites with a pathology diagnosis of normal or dysplasia. A, mean IHC score (see main text for details) versus pathology grade established by H&E staining, for each of the markers Ki-67, PHH3, and p63. Error bars represent SEs. B, the fraction of tissue sites with a positive IHC score for either p63 alone, or for the complete panel of markers tested (see text for definition). Data are shown separated by the pathology grade established by H&E staining. C, plot of wide-field autofluorescence and high-resolution N/C ratio values for sites with a pathology diagnosis of mild dysplasia, stratified by p63 status. Note that only 15 of the original 17 measurement sites are displayed because of immunohistochemical processing artifacts in 2 cases. The dashed line represents the linear threshold shown in Fig. 3C to discriminate between normal sites, and those with mild/moderate/severe dysplasia or cancer.

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  • Table 1.

    Percentage of sites accurately classified by optical imaging for each pathologic grade

    Pathology grade
    Mild dysplasia
    Normal (%)Histopathology (%)IHC stratified (%)Mod. Dysplasia–Cancer (%)
    AFI alone76656797
    HRME alone71657392
    AFI + HRME (MMIS)98358795

    NOTE: Data are presented for sites with mild dysplasia by standard histopathology considered “abnormal,” and also following stratification of those mild dysplasia sites by biomarker status (p63− considered “normal,” p63+ considered abnormal).

    Additional Files

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    • Supplementary Data

      Files in this Data Supplement:

      • Supplementary Methods - PDF file - 27K
      • Supplementary Figures 1-2 - PDF file - 161K, Figure 1: Schematic diagrams of the imaging systems used in this study. Supplementary Figure 2: Multimodal imaging at the floor-of-mouth in a 73-year old female patient.
      • Supplementary Tables 1-4 - PDF file - 30K, Table 1: Criteria used by the surgeon to classify measurement sites Supplementary Table 2: Scoring criteria for IHC stained sites Supplementary Table 3: Distribution of measurement sites by anatomical location Supplementary Table 4: Distribution of measurement sites by clinical impression and pathology diagnosis
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    Cancer Prevention Research: 5 (6)
    June 2012
    Volume 5, Issue 6
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    Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia
    Mark C. Pierce, Richard A. Schwarz, Vijayashree S. Bhattar, Sharon Mondrik, Michelle D. Williams, J. Jack Lee, Rebecca Richards-Kortum and Ann M. Gillenwater
    Cancer Prev Res June 1 2012 (5) (6) 801-809; DOI: 10.1158/1940-6207.CAPR-11-0555

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    Accuracy of In Vivo Multimodal Optical Imaging for Detection of Oral Neoplasia
    Mark C. Pierce, Richard A. Schwarz, Vijayashree S. Bhattar, Sharon Mondrik, Michelle D. Williams, J. Jack Lee, Rebecca Richards-Kortum and Ann M. Gillenwater
    Cancer Prev Res June 1 2012 (5) (6) 801-809; DOI: 10.1158/1940-6207.CAPR-11-0555
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