title: Label-free imaging and quantitative chemical analysis of Alzheimer's disease brain samples with multimodal multiphoton nonlinear optical microspectroscopy.
abstract: We developed multimodal multiphoton microspectroscopy using a small-diameter probe with gradient-index lenses and applied it to unstained Alzheimer's disease (AD) brain samples. Our system maintained the image quality and spatial resolution of images obtained using an objective lens of similar numerical aperture. Multicolor images of AD brain samples were obtained simultaneously by integrating two-photon excited fluorescence and second-harmonic generation on a coherent anti-Stokes Raman scattering (CARS) microendoscope platform. Measurements of two hippocampal regions, the cornus ammonis-1 and dentate gyrus, revealed more lipids, amyloid fibers, and collagen in the AD samples than in the normal samples. Normal and AD brains were clearly distinguished by a large spectral difference and quantitative analysis of the CH mode using CARS microendoscope spectroscopy. We expect this system to be an important diagnosis tool in AD research
authors.affiliation: Gwangju Institute of Science and Technology, Department of Physics and Photon Science, Gwangju 500-712, Republic of Korea.
authors.forename: Jang Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 500-712, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 500-712, Republic of Korea.
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.affiliation: Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Myoung-Kyu
authors.initials: MK
authors.lastname: Oh
authors.affiliation: Gwangju Institute of Science and Technology, Department of Physics and Photon Science, Gwangju 500-712, Republic of Korea.
authors.forename: Do-Kyeong
authors.initials: DK
authors.lastname: Ko
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D019723:Endoscopes; D004867:Equipment Design; D019544:Equipment Failure Analysis; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000295:instrumentation*; D008904:Miniaturization; D055096:Optical Devices; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000295:instrumentation*; D013194:Staining and Labeling; D018511:Systems Integration
chemical_list: D015415:Biomarkers