• Head-mounted microscope reaches deeper i

    From ScienceDaily@1:317/3 to All on Tue Mar 29 22:30:40 2022
    Head-mounted microscope reaches deeper into mouse brains
    Detailed time-lapse images of brain cells could lead to new insights for neurological disorders

    Date:
    March 29, 2022
    Source:
    Optica
    Summary:
    Researchers have developed a miniature microscope that is designed
    for high-resolution 3D images inside the brains of living mice. The
    new, lightweight design could help scientists understand how brain
    cells operate by imaging deeper into the brain than previously
    possible with miniature widefield microscopes.



    FULL STORY ========================================================================== Researchers have developed a miniature microscope that is designed for
    high- resolution 3D images inside the brains of living mice. By imaging
    deeper into the brain than previously possible with miniature widefield microscopes, the new lightweight microscope could help scientists better understand how brain cells and circuits operate.


    ========================================================================== "With further development, our microscope will be able to image neural
    activity over time while an animal is in a naturalistic environment or performing different tasks," said lead author Omkar Supekar from the
    University of Colorado Boulder. "We show that it can be used to study
    cells that play an important role in neurological disorders such as
    multiple sclerosis." In the Optica Publishing Group journal Biomedical
    Optics Express, the researchers describe their new SIMscope3D, which
    images fluorescence emitted from tissue or fluorescent tags after the
    sample is exposed to certain wavelengths of light. The new device is
    the first miniature microscope to use structured illumination to remove out-of-focus and scattered light, which allowed imaging as deep as 260
    microns on fixed brain tissue with an LED light source.

    "Developing new treatments for neurological disorders requires
    understanding the brain at the cellular and circuit-level," said
    research team lead Emily Gibson from the University of Colorado
    Anschutz Medical Campus. "New optical imaging tools -- particularly
    those that can image deep into brain tissue like the microscope our
    team developed -- are important for achieving this goal." Seeing deeper
    Head mounted microscopes are used to image the brains of small rodents
    through transparent windows implanted into their skulls. Researchers have previously developed head-mounted widefield fluorescence microscopes, but
    light scattered by tissue prevents imaging deep into the brain. Miniature two-photon microscopes can overcome this drawback by eliminating
    out-of-focus light in each focal plane -- a process known as optical
    sectioning -- but typically require expensive pulsed lasers and complex mechanical scanning components.



    ==========================================================================
    To design the new microscope, Andrew Sias, Sean Hansen, Gabriel Martinez
    and Emily Gibson from the Department of Bioengineering at the University
    of Colorado Anschutz Medical Campus; Douglas Shepherd from the Department
    of Physics at Arizona State University; Omkar Supekar and Juliet Gopinath
    from the Department of Electrical, Computer and Energy Engineering,
    and Victor Bright from the Department of Mechanical Engineering at the University of Colorado Boulder collaborated closely with neuroscientists
    Graham Peet, Diego Restrepo and Ethan Hughes from the Department of Cell
    and Developmental Biology and Xiaoyu Peng and Cristin Welle from the
    Department of Physiology and Biophysics at the University of Colorado
    Anschutz Medical Campus to optimize it for studying the brain.

    Volumetric imaging is accomplished by using an imaging fiber to deliver spatially patterned light to the miniature microscope objective. This
    process also removes out-of-focus light, enabling optical sectioning
    similar to that accomplished with two-photon approaches but without the
    complex components or expensive laser.

    The microscope includes a compact tunable electrowetting lens that allows
    3D visualization of brain structures by changing the microscope's focal
    depth without requiring any moving parts. The researchers also integrated
    a CMOS camera directly into the microscope. This enables imaging with
    high lateral resolution while avoiding artifacts that might be induced if
    the images traveled through the fiber bundle. Using an LED light source,
    the new microscope can produce sharp contrast even when imaging deeply
    into highly scattering tissue.

    Capturing glial cells The researchers demonstrated their new system
    by imaging oligodendrocytes and microglia labeled with a fluorescent
    protein in mice that were awake but placed in a device that kept their
    head stationary. In people with multiple sclerosis, oligodendrocytes
    -- which form an insulating layer around axons -- are destroyed. This
    causes the connections in the brain to slow down, leading to impairment
    of vision, motor skills and other problems.

    "We used our miniature microscope to record a time series of glial
    cell dynamics in awake mice at depths up to 120 microns in the brain,"
    said Supekar.

    "Scientists don't fully understand exactly how these cells work
    or their repair processes. Our microscope opens the possibility of
    long-term studies examining how these cells migrate and are repaired."
    The researchers are now working to improve the microscope's acquisition
    speed and weight. With minor upgrades, the microscope will be able to
    image faster dynamics, such as neuronal electrical activity, while the
    mouse performs different tasks. The researchers say that because the
    microscope does not require expensive components it could be easily
    developed into a commercial system for use in neuroscience labs.


    ========================================================================== Story Source: Materials provided by Optica. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Omkar D. Supekar, Andrew Sias, Sean R. Hansen, Gabriel Martinez,
    Graham
    C. Peet, Xiaoyu Peng, Victor M. Bright, Ethan G. Hughes, Diego
    Restrepo, Douglas P. Shepherd, Cristin G. Welle, Juliet T. Gopinath,
    Emily A.

    Gibson. Miniature structured illumination microscope for in vivo
    3D imaging of brain structures with optical sectioning. Biomedical
    Optics Express, 2022; 13 (4): 2530 DOI: 10.1364/BOE.449533 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220329142540.htm

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