Abstract
Background: Nonlinear optical (NLO) microscopy techniques have potential
to improve the early detection of epithelial ovarian cancer. In this
study we showed that multimodal NLO microscopies, including two-photon
excitation fluorescence (TPEF), second-harmonic generation (SHG),
third-harmonic generation (THG) and fluorescence lifetime imaging
microscopy (FLIM) can detect morphological and metabolic changes
associated with ovarian cancer progression.
Methodology/Principal Findings: We obtained strong TPEF + SHG + THG
signals from fixed samples stained with Hematoxylin & Eosin (H&E) and
robust FLIM signal from fixed unstained samples. Particularly, we imaged
34 ovarian biopsies from different patients (median age, 49 years)
including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous
tumors with the multimodal NLO platform developed in our laboratory. We
have been able to distinguish adenomas, borderline, and adenocarcinomas
specimens. Using a complete set of scoring methods we found significant
differences in the content, distribution and organization of collagen
fibrils in the stroma as well as in the morphology and fluorescence
lifetime from epithelial ovarian cells.
Conclusions/Significance: NLO microscopes provide complementary
information about tissue microstructure, showing distinctive patterns
for serous and mucinous ovarian tumors. The results provide a basis to
interpret future NLO images of ovarian tissue and lay the foundation for
future in vivo optical evaluation of premature ovarian lesions.
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