title: Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy.
abstract: We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.
authors.affiliation: State University of Campinas (UNICAMP), "Gleb Wataghin" Institute of Physics, Optics and Photonics Research Center, Biomedical Lasers Application Laboratory, Brazil. jadur@bioingenieria.edu.ar
authors.forename: Javier
authors.initials: J
authors.lastname: Adur
authors.forename: Vitor B
authors.initials: VB
authors.lastname: Pelegati
authors.forename: Andre A
authors.initials: AA
authors.lastname: de Thomaz
authors.forename: Lilia
authors.initials: L
authors.lastname: D'Souza-Li
authors.forename: Maria do Carmo
authors.initials: Mdo C
authors.lastname: Assunção
authors.forename: Fátima
authors.initials: F
authors.lastname: Bottcher-Luiz
authors.forename: Liliana A L A
authors.initials: LA
authors.lastname: Andrade
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Cesar
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000473:pathology*; D017711:Nonlinear Dynamics; D010013:Osteogenesis Imperfecta / Q000150:complications* / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity