A Peek At The Brain Through See-Through Skulls

Scientists in China have developed optical clearing agents that can make the skulls of living mice transparent, allowing high resolution imaging of brain structures.

AsianScientist (Mar. 13, 2018) – In a study published in Light: Science and Applications, scientists in China have developed a non-invasive approach for creating an optical window in the skull to enable the brains of living mice to be imaged.

Long term observation and manipulation of cells in the cortex of the brain is crucial for understanding brain structure and function. However, the strong scattering of light caused by the skull over the cortex limits the penetration depth of light in tissues, thus hindering the observation of fluorescently labeled neuronal structures and microvasculature.

In the present study, a research group led by Professor Zhu Dan and coworkers from Huazhong University of Science and Technology, China, tested the use of optical clearing agents (OCAs) that they applied to the bare skulls (hair and skin removed) of living mice.

Zhu was originally developing an in vivo optical clearing technique for skin tissue. She then realized through her interactions with her colleague, neuroscientist Professor Xu Tonghui, that imaging the turbid skull is a great bottleneck in the field of neuroscience. Hence, the two collaborated to develop optical clearing agents (OCAs) that could make skull tissue transparent.

The researchers optimized various OCAs consisting of an enzyme that digests collagen (collagenase), a decalcifying solution (EDTA disodium) and glycerol. They managed to find the right composition and treatment timings such that after treatment with OCAs, the skulls of mice became transparent within minutes, thus forming a visible window of the cortex.

Through this window, the image contrast and imaging depth of the brain were significantly improved. Combined with two-photon microscopy, this technique allowed the imaging of the fine structures of neurons, glia and the microvasculature in the mouse brain.

Given its easy handling, safety, reproducibility and performance, the researchers think that their method holds potential for wider applications in neuroscience research.


The article can be found at: Zhao et al. (2018) Skull Optical Clearing Window for in vivo Imaging of the Mouse Cortex at Synaptic Resolution.

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Source: Changchun Institute of Optics, Fine Mechanics and Physics; Photo: Shutterstock.
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