Author:
Mirsanaye Kamdin,Uribe Castaño Leonardo,Kamaliddin Yasmeen,Golaraei Ahmad,Augulis Renaldas,Kontenis Lukas,Done Susan J.,Žurauskas Edvardas,Stambolic Vuk,Wilson Brian C.,Barzda Virginijus
Abstract
AbstractThe extracellular matrix (ECM) collagen undergoes major remodeling during tumorigenesis. However, alterations to the ECM are not widely considered in cancer diagnostics, due to mostly uniform appearance of collagen fibers in white light images of hematoxylin and eosin-stained (H&E) tissue sections. Polarimetric second-harmonic generation (P-SHG) microscopy enables label-free visualization and ultrastructural investigation of non-centrosymmetric molecules, which, when combined with texture analysis, provides multiparameter characterization of tissue collagen. This paper demonstrates whole slide imaging of breast tissue microarrays using high-throughput widefield P-SHG microscopy. The resulting P-SHG parameters are used in classification to differentiate tumor from normal tissue, resulting in 94.2% for both accuracy and F1-score, and 6.3% false discovery rate. Subsequently, the trained classifier is employed to predict tumor tissue with 91.3% accuracy, 90.7% F1-score, and 13.8% false omission rate. As such, we show that widefield P-SHG microscopy reveals collagen ultrastructure over large tissue regions and can be utilized as a sensitive biomarker for cancer diagnostics and prognostics studies.
Funder
Natural Sciences and Engineering Research Council of Canada
Canadian Institutes of Health Research
European Regional Development Fund with the Research Council of Lithuania
Publisher
Springer Science and Business Media LLC
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