◥Purpose: The ovarian cancer risk factors of age and ovulation are curious because ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased. To determine how age and ovulation underlie ovarian cancer risk, we assessed the effects of these risk factors on the ovarian microenvironment.Experimental Design: Aged C57/lcrfa mice (0-33 months old) were generated to assess the aged ovarian microenvironment. To expand our findings into human aging, we assembled a cohort of normal human ovaries (n ¼ 18, 21-71 years old). To validate our findings, an independent cohort of normal human ovaries was assembled (n ¼ 9, 41-82 years old).Results: We first validated the presence of age-associated murine ovarian fibrosis. Using interdisciplinary methodologies, we provide novel evidence that ovarian fibrosis also develops in human postmenopausal ovaries across two independent cohorts (n ¼ 27). Fibrotic ovaries have an increasedConclusions: These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis.
Histopathological image analysis of stained tissue slides is routinely used in tumor detection and classification. However, diagnosis requires a highly trained pathologist and can thus be time-consuming, labor-intensive, and potentially risk bias. Here, we demonstrate a potential complementary approach for diagnosis. We show that multiphoton microscopy images from unstained, reproductive tissues can be robustly classified using deep learning techniques. We fine-train four pretrained convolutional neural networks using over 200 murine tissue images based on combined second-harmonic generation and two-photon excitation fluorescence contrast, to classify the tissues either as healthy or associated with high-grade serous carcinoma with over 95% sensitivity and 97% specificity. Our approach shows promise for applications involving automated disease diagnosis. It could also be readily applied to other tissues, diseases, and related classification problems.
We demonstrate coherent anti-Stokes Raman scattering (CARS) microscopy of lipid-rich structures using a single unamplified femtosecond Ti:sapphire laser and a photonic crystal fiber (PCF) with two closely lying zero dispersion wavelengths (ZDW) for the Stokes source. The primary enabling factor for the fast data acquisition (84 micros per pixel) in the proof-of-principle CARS images, is the low noise supercontinuum (SC) generated in this type of PCF, in contrast to SC generated in a PCF with one ZDW. The dependence of the Stokes pulse on average input power, pump wavelength, pulse duration and polarization is experimentally characterized. We show that it is possible to control the spectral shape of the SC by tuning the pump wavelength of the input pulse and the consequence for CARS microscopy is discussed.
The actual Beld distribution in superlattices under electric field domain formation is investigated by photoluminescence and Raman spectroscopy. Prom the measured subband spacings, we determine the magnitude of the Beld that corresponds to resonant alignment of subbands in adjacent wells.The electron occupation of higher subbands is probed by photoluminescence (PL) measurements. Comparing the results of higher subband PL and the current-voltage characteristics, it is shown that the high-Beld domain is always nonresonantly coupled with a field strength below the resonance value. The sudden increase in the current when the high-field domain extends over the entire superlattice is explained. Calculations of the field distribution based on a microscopic model support our experimental observations.
We demonstrate a novel miniaturized multimodal coherent anti-Stokes Raman scattering (CARS) microscope based on microelectromechanical systems (MEMS) scanning mirrors and custom miniature optics. A single Ti:sapphire femtosecond pulsed laser is used as the light source to produce the CARS, two photon excitation fluorescence (TPEF) and second harmonic generation (SHG) images using this miniaturized microscope. The high resolution and distortion-free images obtained from various samples such as a USAF target, fluorescent and polystyrene microspheres and biological tissue successfully demonstrate proof of concept, and pave the path towards future integration of parts into a handheld multimodal CARS probe for non- or minimally-invasive in vivo imaging.
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