When scientists need to understand the effects of new ingredients in infant formula on brain development, it is rarely possible for them to conduct initial safety studies in human subjects. After all, few parents are willing to hand over their newborn baby to test unproven ingredients.
Enter the domestic pig. Her brain and intestinal development is surprisingly similar to that of human infants – much more so than traditional laboratory animals, rats and mice. And, like infants, young pigs can be scanned using equipment available in the clinic, including non-invasive magnetic resonance imaging or MRI. This means researchers can test nutritional interventions in pigs, examine their effects on brain development via MRI, and make educated predictions about how these same nutrients will affect human infants.
For nearly a decade, scientists have relied on an MRI-based map, or atlas, of the pig’s brain – developed at the University of Illinois using 4-week-old pigs – to understand where and how nutrients and other interventions affect the developing brain. . Now, scientists in Illinois have updated this atlas, increasing its resolution by a factor of four, and they’ve also added a new atlas for 12-week-old adolescent pigs.
The new atlases are available for free download at pigmri.illinois.edu.
“This improvement in spatial resolution makes a huge difference when you look at the development of a small pig brain and try to see how your intervention changes the structure, size or even function in the brain,” says Brad Sutton, professor. at the Department of Bioengineering, technical director of the Biomedical Imaging Center at the Illinois Beckman Institute, and co-author of the brain atlas study, published in the Journal of Neuroscience Methods.
Ryan Dilger, associate professor in the Department of Animal Sciences and lead author of the Atlas study, adds, “It’s about our ability to discern one part of the brain from another. The higher the resolution, the more reliably we can say that this part is the hippocampus, for example. Part of the need for an atlas is for every research group working in this area to consistently reference the same parts or regions of the brain. We need to have common terms and infrastructure to speak the same language. “
To build the updated atlas, researchers anesthetized and scanned 4- and 12-week-old pigs at the Beckman Biomedical Imaging Center using a state-of-the-art Siemens Prisma 3 T MRI scanner. . Scans of several pigs from each age class were averaged into a single atlas for each age, to account for variations between individuals. Subsequently, the researchers identified and numerically isolated 26 regions of interest, such as the cerebellum, marrow, right and left cortex, and others, and provided volumetric standards for each in the pig.
“We provide the absolute and relative volumes not only for the whole brain, but also for tissues such as gray matter, white matter, cerebrospinal fluid, as well as all the different regions of interest. This normative data can serve as a benchmark for others who might be interested in seeing how a particular intervention influences brain growth or development in pigs, ”says Joanne Fil, doctoral student in the Illinois Neuroscience Program and author. principal of the study of the atlas. .
The previous Pig Brain Atlas has been used by researchers to advance neuroscience around the world, with some 450 downloads to date. The collective findings made possible by the atlas go far beyond pediatric nutrition to include a deeper understanding of the microbiota-gut-brain axis, which appears to relate to common clinical situations.
Dilger says the new atlas will give researchers an even more precise view of the brain, allowing for more advanced discoveries. And with the addition of the atlas for older pigs, they will be able to extend their discoveries even further.
“At 24 weeks, or six months, the pig is sexually mature. We would expect the pig by this age to have completed most, if not all, of its brain development, ”says Fil. “So now we are able to see how our interventions impact development not only at an early age, but also in adulthood in pigs. “
Fil adds that the study also provides a detailed account of the process used to create the atlas, giving researchers the blueprints to create additional atlases for other animals.
But there is a lot to be said for pigs as an important animal for biomedical research.
“You can study brain development in a mouse, but for some studies the mouse brain is not similar to a human brain in some important respects. Also, you can’t really study the effects of an intervention on the brain directly in humans, because although we can put people through the scanner, we can’t always change their diet and test different components ” , explains Sutton.
“So the pig is in this perfect place: its brain is the right size to use human MRI scans, and the pig’s brain development closely matches that of humans. And we have the tools to be able to study it in detail, especially on this campus, and do great things with it. The pig is perfect for studying the brain.
Dilger adds, “We are using real human clinical equipment in pigs. In fact, non-invasively, we take a microscope into the pig’s brain while it is still alive. This is the advantage. We can take a virtual peek inside the pig’s brain multiple times throughout the life of the pig to see how the brain is developing structurally.
Reference: “High-resolution magnetic resonance imaging-based atlases for young and adolescent domestic pigs (Sus scrofa) ”By Joanne E. Fil, Sangyun Joung, Benjamin J. Zimmerman, Bradley P. Sutton and Ryan N. Dilger, March 3, 2021, Journal of Neuroscience Methods.
DOI: 10.1016 / j.jneumeth.2021.109107
The Department of Animal Sciences is part of the College of Agricultural, Consumer, and Environmental Sciences at the University of Illinois.