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Optical redox imaging of fixed unstained tissue slides to identify biomarkers for breast cancer diagnosis/prognosis: feasibility study
Author(s): He N. Xu; Julia Tchou; Yusheng Li; Min Feng; Paul Zhang; William J. Quinn; Joseph A. Baur; Lin Z. Li
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Paper Abstract

We previously showed that optical redox imaging (ORI) of snap-frozen breast biopsies by the Chance redox scanner readily discriminates cancer from normal tissue. Moreover, indices of redox heterogeneity differentiate among tumor xenografts with different metastatic potential. These observations suggest that ORI of fluorescence of NADH and oxidized flavoproteins (Fp) may provide diagnostic/prognostic value for clinical applications. In this work, we investigate whether ORI of formalin-fixed-paraffin-embedded (FFPE) unstained clinical tissue slides of breast tumors is feasible and comparable to ORI of snap-frozen tumors. If ORI of FFPE is validated, it will enhance the versatility of ORI as a novel diagnostic/prognostic assay as FFPE samples are readily available. ORI of fixed tissue slides was performed using a fluorescence microscope equipped with a precision automated stage and appropriate optical filters. We developed a vignette correction algorithm to remove the tiling effect of stitched-images. The preliminary data from imaging fixed slides of breast tumor xenografts showed intratumor redox heterogeneity patterns similar to that of the frozen tissues imaged by the Chance redox scanner. From ORI of human breast tissue slides we identified certain redox differences among normal, ductal carcinoma in situ, and invasive carcinoma. We found paraformaldehyde fixation causes no change in NADH signals but enhances Fp signals of fresh muscle fibers. We also investigated the stability of the fluorescence microscope and reproducibility of tissue slide fluorescence signals. We plan to validate the diagnostic/prognostic value of ORI using clinically annotated breast cancer sample set from patients with long-term follow-up data.

Paper Details

Date Published: 22 February 2018
PDF: 6 pages
Proc. SPIE 10472, Diagnosis and Treatment of Diseases in the Breast and Reproductive System IV, 104720U (22 February 2018); doi: 10.1117/12.2290845
Show Author Affiliations
He N. Xu, Univ. of Pennsylvania (United States)
Britton Chance Lab. of Redox Imaging (United States)
Julia Tchou, Univ. of Pennsylvania (United States)
Abramson Cancer Ctr. (United States)
Yusheng Li, Univ. of Pennsylvania (United States)
Min Feng, Univ. of Pennsylvania (United States)
Britton Chance Lab. of Redox Imaging (United States)
Paul Zhang, Univ. of Pennsylvania (United States)
William J. Quinn, Univ. of Pennsylvania (United States)
Joseph A. Baur, Perelman School of Medicine, Univ. of Pennsylvania (United States)
Lin Z. Li, Univ. of Pennsylvania (United States)
Britton Chance Lab. of Redox Imaging (United States)
Abramson Cancer Ctr. (United States)


Published in SPIE Proceedings Vol. 10472:
Diagnosis and Treatment of Diseases in the Breast and Reproductive System IV
Melissa C. Skala; Paul J. Campagnola, Editor(s)

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