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Brain imaging method will unravel mysteries of neural processes

Researchers from the National Institute for Physiological Sciences (NIPS), along with various collaborators, have pioneered an innovative technique for observing the brain’s intricate workings in living mice. 

This breakthrough, known as the “nanosheet incorporated into light-curable resin” (NIRE) method, allows for unprecedented large-scale and prolonged imaging of neuronal activities and structures in mice that are awake, bridging gaps left by traditional brain imaging methods.

Brain imaging limitations

Conventional brain imaging tools, such as functional magnetic resonance imaging (fMRI) and two-photon microscopy, each have limitations in terms of the spatial and temporal resolution they can achieve or the size of the area they can observe simultaneously. 

The NIRE method overcomes these hurdles by employing a unique combination of fluoropolymer nanosheets and light-curable resin to create expansive cranial windows, enabling researchers to examine broad brain regions concurrently.

Superior brain imaging method

“The NIRE method is superior to previous methods because it produces larger cranial windows than previously possible, extending from the parietal cortex to the cerebellum, utilizing the biocompatible nanosheet and the transparent light-curable resin that changes in form from liquid to solid,” said study lead author Taiga Takahash, a researcher at the Tokyo University of Science and the Exploratory Research Center on Life and Living Systems (ExCELLS).

By affixing polyethylene-oxide–coated CYTOP (PEO-CYTOP) nanosheets to the brain’s surface with light-curable resin, the researchers created a durable, transparent window that closely conforms to the brain’s contours, including the highly curved cerebellum. 

This method not only enhances the window’s strength and transparency but also significantly reduces motion artifacts, which are distortions in images caused by the movements of awake mice.

Studying fine neural structures

The cranial windows developed through the NIRE method enable high-resolution imaging with sub-micrometer accuracy. This level of detail is crucial for studying the morphology and activity of fine neural structures. 

“Importantly, the NIRE method enables imaging to be performed for a longer period of more than 6 months with minimal impact on transparency,” explained corresponding author Tomomi Nemoto, an expert in brain sciences at ExCELLS and NIPS. 

“This should make it possible to conduct longer-term research on neuroplasticity at various levels – from the network level to the cellular level – as well as during maturation, learning, and neurodegeneration.” 

This breakthrough in neuroimaging opens up new avenues for research into complex neural processes related to development, cognition, and various neurological conditions. 

Broader implications 

The NIRE method’s ability to facilitate large-scale, long-term, and multi-scale in vivo brain imaging holds significant promise for advancing our understanding of how neural networks operate and interact across different brain regions.

“The method holds promise for unraveling the mysteries of neural processes associated with growth and development, learning, and neurological disorders. Potential applications include investigations into neural population coding, neural circuit remodeling, and higher-order brain functions that depend on coordinated activity across widely distributed regions,” Nemoto said.

In conclusion, the development of the NIRE method represents a significant leap forward in the field of neuroimaging, offering researchers a powerful tool to explore the brain’s complexities in ways that were previously out of reach. This innovative approach promises to deepen our understanding of the brain’s structure and function, paving the way for new insights into the neural basis of behavior and disease.

The study is published in the journal Communications Biology.


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