Brain Imaging Breakthrough: 64 Million Times Sharper

Coronal TDI

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An excellent-powerful MRI merged with light-sheet microscopy permits researchers to create a high-definition wiring diagram of the whole mind in mice. Credit: Duke Center for In Vivo Microscopy

MRI expertise from Duke-led effort reveals the whole mouse mind within the highest decision.

Researchers from a number of universities have made a breakthrough in MRI expertise, capturing the sharpest pictures ever of a mouse mind. This refined MRI, mixed with mild sheet microscopy, supplies an unprecedented method to visualize the mind’s connectivity, doubtlessly resulting in a greater understanding of neurodegenerative illnesses in people.

Magnetic resonance imaging (MRI) is how we visualize mushy, watery tissue that’s arduous to picture with X-rays. But whereas an MRI supplies adequate decision to identify a mind tumor, it must be so much sharper to visualise microscopic particulars inside the mind that reveal its group.

In a decades-long technical tour de pressure led by Duke’s Center for In Vivo Microscopy with colleagues on the University of Tennessee Health Science Center, University of Pennsylvania, University of Pittsburgh and Indiana University, researchers took up the gauntlet and improved the decision of MRI resulting in the sharpest pictures ever captured of a mouse mind.

Coinciding with the 50th anniversary of the primary MRI, the researchers generated scans of a mouse mind which can be dramatically crisper than a typical scientific MRI for people, the scientific equal of going from a pixelated 8-bit graphic to the hyper-realistic element of a Chuck Close portray.

A single voxel of the brand new pictures – consider it as a cubic pixel – measures simply 5 microns. That’s 64 million instances smaller than a scientific MRI voxel.

Mouse Brain MRI

Duke MRI pictures whole mouse mind at decision 64 million instances higher than scientific MRI, providing hope of understanding Parkinson’s, Alzheimer’s and different illnesses. Credit: Duke Center for In Vivo Microscopy

Although the researchers centered their magnets on mice as a substitute of people, the refined MRI supplies an essential new method to visualize the connectivity of the whole mind at record-breaking decision. The researchers say new insights from mouse imaging will in flip result in a greater understanding of circumstances in people, akin to how the mind adjustments with age, food regimen, and even with neurodegenerative illnesses like Alzheimer’s.

“It is something that is truly enabling. We can start looking at neurodegenerative diseases in an entirely different way,” said G. Allan Johnson, Ph.D., the lead author of the new paper and the Charles E. Putman University Distinguished professor of radiology, physics and biomedical engineering at Duke.

Johnson’s excitement is a long time coming. The team’s new work, published on April 17 in the Proceedings of the National Academy of Sciences, is the culmination of nearly 40 years of research at the Duke Center for In Vivo Microscopy.

Over the four decades, Johnson, his engineering graduate students and his many collaborators at Duke and afar refined many elements that, when all combined, made the revolutionary MRI resolution possible.

Horizontal TDI Mouse Brain

A super-powerful MRI merged with light-sheet microscopy allows researchers to create a high-definition wiring diagram of the entire brain in mice. Credit: Duke Center for In Vivo Microscopy

Some of the key ingredients include an incredibly powerful magnet (most clinical MRIs rely on a 1.5 to 3 Tesla magnet; Johnson’s team uses a 9.4 Tesla magnet), a special set of gradient coils that are 100 times stronger than those in a clinical MRI and help generate the brain image, and a high-performance computer equivalent to nearly 800 laptops all cranking away to image one brain.

After Johnson and his team “scan the daylights out of it,” they send off the tissue to be imaged using a different technique called light sheet microscopy. This complementary technique gives them the ability to label specific groups of cells across the brain, such as dopamine-issuing cells to watch the progression of Parkinson’s disease.

The team then maps the light sheet pictures, which give a highly accurate look at brain cells, onto the original MRI scan, which is much more anatomically accurate and provides a vivid view of cells and circuits throughout the entire brain.

With this combined whole brain data imagery, researchers can now peer into the microscopic mysteries of the brain in ways never possible before.

One set of MRI images shows how brain-wide connectivity changes as mice age, as well as how specific regions, like the memory-involved subiculum, change more than the rest of the mouse’s brain.

Another set of images showcases a spool of rainbow-colored brain connections that highlight the remarkable deterioration of neural networks in a mouse model of Alzheimer’s disease.

The hope is that by making the MRI an even higher-powered microscope, Johnson and others can better understand mouse models of human diseases, such as Huntington’s disease, Alzheimer’s, and others. And that should lead to a better understanding of how similar things function or go awry in people.

“Research supported by the National Institute of Aging uncovered that modest dietary and drug interventions can lead to animals living 25% longer,” Johnson said. “So, the question is, is their brain still intact during this extended lifespan? Could they still do crossword puzzles? Are they going to be able to do Sudoku even though they’re living 25% longer? And we have the capacity now to look at it. And as we do so, we can translate that directly into the human condition.”

Reference: “Merged magnetic resonance and light sheet microscopy of the whole mouse brain” by G. Allan Johnson, Yuqi Tian, David G. Ashbrook, Gary P. Cofer, James J. Cook, James C. Gee, Adam Hall, Kathryn Hornburg, Yi Qi, Fang-Cheng Yeh, Nian Wang, Leonard E. White and Robert W. Williams, 17 April 2023, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2218617120

This research was supported by the National Institutes of Health (R01-AG070913391, R01-NS096729, P41EB015897, S10OD010683).