Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

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 w...

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Bibliographic Details
Published in:Journal of Biomedical Optics 2012-08, Vol.17 (8), p.081407-081401
Main Authors: Adur, Javier, Pelegati, Vitor B, de Thomaz, Andre A, D'Souza-Li, Lilia, Assunc¸a˜o, Maria do Carmo, Bottcher-Luiz, Fa´tima, Andrade, Liliana A. L. A, Cesar, Carlos L
Format: Article
Language:English
Subjects:
Adult
Aged
Biomedical materials
Breast
breast cancer
Breast Neoplasms - etiology
Breast Neoplasms - pathology
Cancer
collagen
Entropy
extracellular matrix
Female
Fluorescence
Human
Humans
Microscopy
Microscopy, Fluorescence, Multiphoton - methods
Middle Aged
Neoplasms, Glandular and Epithelial - etiology
Neoplasms, Glandular and Epithelial - pathology
Nonlinear Dynamics
nonlinear microscopy
Nonlinearity
osteogenesis imperfecta
Osteogenesis Imperfecta - complications
Osteogenesis Imperfecta - pathology
ovarian cancer
Precancerous Conditions - pathology
Reproducibility of Results
Sensitivity and Specificity
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Summary: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.
ISSN:1083-3668
1560-2281
DOI:10.1117/1.JBO.17.8.081407