3D printed transparent skull grants insight into Alzheimer’s disease development

Written by Georgi Makin (Future Science Group)

Research published in Nature Communications describes how a research team from the University of Minnesota (MN, USA) has designed a 3D printed, transparent implant to fit the skull of a mouse, creating a ‘window’ for real-time monitoring of the surface of the brain.
The device could allow for unique research opportunities into a variety of neurological conditions, including concussions as well as Alzheimer’s and Parkinson’s diseases.

Traditionally, the focus of research groups in these areas has been to examine small, isolated regions of the brain. More recently, however, researchers are finding that events occurring in some areas of the brain are likely to simultaneously affect other regions.

“What we are trying to do is to see if we can visualize and interact with large parts of the mouse brain surface, called the cortex, over long periods of time. This will give us new information about how the human brain works,” explained Suhasa Kodandaramaiah (University of Minnesota).

“This technology allows us to see most of the cortex in action with unprecedented control and precision while stimulating certain parts of the brain.”

Initial research using the device investigated how mild concussions in one part of the brain affect other parts of the brain as it structurally and functionally reorganizes. Due to the cross-species similarities between murine models and human brains, the team claims that the device offers new potential for similar studies into degenerative conditions, such as Alzheimer’s and Parkinson’s diseases.

Video footage of the brain’s surface activity exhibited changes in brightness of the mouse’s brain, corresponding to waxing and waning of neural activity. Subtle flashes represented periods when the whole brain was suddenly stimulated in ‘global coordinated activity’ – a phenomenon researchers are still reportedly trying to understand and relate to behavior.

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“These are studies we couldn’t do in humans, but they are extremely important in our understanding of how the brain works so we can improve treatments for people who experience brain injuries or diseases,” added Timothy Ebner (University of Minnesota Medical School).

Digitally scanning and subsequently 3D printing the transparent implant provided many advantages. The implant complemented the original skull of the mouse, matching the same contours and natural shape, easing the precise and intricate surgery required to replace the top of the mouse skull with the transparent ‘window’.

The implant was also not rejected by the mouse’s body, further benefitting the team with a study that could last several months. This allowed the researchers to study brain aging in a way which would have reportedly taken decades in humans.

“This new device allows us to look at the brain activity at the smallest level zooming in on specific neurons while getting a big picture view of a large part of the brain surface over time,” concluded Kodandaramaiah. “Developing the device and showing that it works is just the beginning of what we will be able to do to advance brain research.”


What’s next?

The team claim to be planning to commercialize the implant, under the name ‘See-Shell’, as a cost-effective, widely adoptable and highly flexible tool for similar laboratories.

The designs for the device could be adapted beyond skull implants to provide insights into more mobile structures, such as the spine, or for the real-time observation of a variety of organs including mammary glands and lungs.

The flexibility, optical clarity, and biocompatibility of PET as a 3D printed material paired with the endless possibilities for customization via digital imaging and CAD/CAM offer a truly unique potential for real time intravital observation.


Sources: Ghanbari L, Carter RE, Rynes ML et al. Cortex-wide neural interfacing via transparent polymer skulls. Nat. Commun. doi: 10.1038/s41467-019-09488-0 (2019) (Epub ahead of print); https://twin-cities.umn.edu/news-events/research-brief-3d-printed-transparent-skull-provides-window-brain