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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