Abnormal accumulation of amyloid-β (Aβ) plaques in the brain is one of the major characteristics of Alzheimer’s disease and there is a possibility that the degree of plaque toxicity is related to the distribution of nanoscale oligomeric aggregates in plaques. Here, by super-resolution fluorescence imaging, we visualized that anti-Aβ oligomer antibodies localized differently to plaques compared to anti-Aβ monomer antibodies and characteristic plaque shapes in brain tissues were classified. These differences in nanoscale distribution were hard to be discerned by conventional fluorescence imaging, implying that super-resolution imaging has the potential to reveal the detailed features of oligomeric aggregates in plaques.
Artificial intelligence is attracting attention as a promising tool to create new clinical value from big data acquired by medical instruments. Here, I introduce results of employing deep learning while analyzing data of biological samples. In the classification of cell images acquired by imaging flow cytometer, deep learning enabled the rapid discrimination of a few cancer cells with an accuracy of 99% or more, in a milieu of thousands of normal blood cells. In addition, the application of AI to vibrational spectroscopy for the identification of amino acids or peptides with high sensitivity and accuracy, is also introduced.
KEYWORDS: Signal detection, Super resolution, Brain, Luminescence, Visualization, Spatial resolution, Signal attenuation, Proteins, Molecules, Microscopy
Abnormal deposition of amyloid-β (Aβ) causes the formation of senile plaques, which is one of the main pathological features of Alzheimer disease. To visualize the plaques at nanometer resolution, single-molecule localization microscopy (SMLM) is promising. It is also essential to develop a method for suppressing autofluorescence especially under high-magnifications used for detecting single molecules. Here, we report a novel method to reduce autofluorescence in mouse brains which is applicable to visualize the structure of Aβ plaques by SMLM. The super-resolution images of Aβ plaques showed fibrous structures that were not able to be discerned by conventional fluorescence imaging.
Amino acids and peptides are basic components of proteins and have vital importance in various biological functions and diseases. In this research, we have attempted to detect and distinguish 20 kinds of amino acids and 39 kinds of peptides without any labeling. By using Raman microscopy, more than two thousand Raman spectra were obtained within five minutes from each analyte, at femtomolecular levels. Furthermore, deep learning analyses of the spectra yielded accuracies greater than 96 percent in discriminating between the amino acids and the peptides.
We have attempted to image three-dimensional distribution of fluorescence beads embedded within gels in a glass capillary using light-sheet illumination, as a primary step towards developing a three-dimensional molecular imaging flow cytometer. An illumination and a detection path were arranged orthogonal to the longer axis of the capillary. The light-sheet illumination was tilted with respect to the illumination axis to image a projection of a section of the sample by a CCD. Different sections of the sample were imaged through scanning the capillary itself, along its length. By stacking the images after inverse transformation, the three-dimensional distribution of the fluorescence beads was imaged.
KEYWORDS: Luminescence, Breast, Super resolution, Microscopy, Point spread functions, Spatial resolution, Tissues, 3D image processing, Tissue optics, Breast cancer
HER2 positive breast cancer is currently examined by counting HER2 genes using fluorescence in situ hybridization (FISH)-stained breast carcinoma samples. In this research, two-dimensional super resolution fluorescence microscopy based on stochastic optical reconstruction microscopy (STORM), with a spatial resolution of approximately 20 nm in the lateral direction, was used to more precisely distinguish and count HER2 genes in a FISH-stained tissue section. Furthermore, by introducing double-helix point spread function (DH-PSF), an optical phase modulation technique, to super resolution microscopy, three-dimensional images were obtained of HER2 in a breast carcinoma sample approximately 4 μm thick.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.