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UTHSC Researchers Part of Decades-Long Project to Drastically Improve Brain Imaging

An MRI scan with record-breaking resolution merged with light sheet microscopy allows researchers to visualize brain cells in unprecedented detail and to map connections between parts of the brain.

After nearly 40 years of research, a team including two researchers from the University of Tennessee Health Science Center has published a process for improving magnetic resonance imaging (MRI) capabilities, allowing the researchers to capture brain images at a higher resolution than ever before.

As a result of the study, scientists can now create images that show unprecedented details of cell types and connections between parts of a mouse’s brain. The researchers believe this can have broad applications in studies of aging and neurogenerative diseases, including Alzheimer’s disease, in humans.

Dr. Robert Williams

“The primary goal was to make sure we have the technology that allows us to do preclinical research more efficiently and at higher resolution, and we’re there now,” said Robert W. Williams, PhD, professor in the UTHSC College of Medicine’s Department of Genetics, Genomics, and Informatics.

More than 20 years ago, Dr. Williams joined forces with G. Allan Johnson, PhD, the leader of Duke University’s Center for In Vivo Microscopy, which started the research project more than a decade earlier. Dr. Williams and his UTHSC colleague David Ashbrook, PhD, were tasked with providing possible applications for Dr. Johnson’s work to devise higher resolution and higher throughput methods to image the brain in the areas of aging and neurodegenerative disease genetics. The study also included six other colleagues from Duke and one each from the University of Pennsylvania, University of Pittsburgh, Indiana University, and LifeCanvas Technologies.

In an article published recently in Proceedings of the National Academy of Sciences, Dr. Johnson, the lead author, describes the two-step process for obtaining such clear brain images. High-computing pipelines merge the improved MR scans, which allow scientists to map the circuits of the brain, with light sheet microscopy, which allows scientists to label groups of brain cells. Combining the complementary techniques is a groundbreaking method that provides a vivid view into what is going on inside the brain.

“By jacking up the resolution, as we have in both the MR and the light sheet, we’re getting closer to where everything is happening in the brain,” Dr. Johnson said. “We are not encumbered by having all of the rest of the population of the human brain to keep us from honing our focus down close to the operational units, whatever they happen to be, of the animal model of interest.”

Track density imaging shows the connecting fibers of the brain. The fibers are color coded to show their direction; green fibers span from the back to the front of the brain, red from left to right, and blue fibers run in and out of the plane.

Not only does the process allow for clearer images, but it also allows the researchers to have a much higher throughput. According to Dr. Williams, “If you tried to do this 10 years ago, it would have been one case a week. Dr. Johnson can process two cases a day, and that’s enough to do some serious, serious science.”

While the technology won’t be used to treat patients with neurogenerative diseases, it is already being used to study those illnesses. Dr. Williams has created mouse models of Alzheimer’s disease that meaningfully replicate the disease in humans. Using the models, the team is investigating whether dietary changes could extend the part of a person’s life in which cognition is intact. With the new imaging techniques, the disease can be studied in the mice in a way Dr. Johnson described as “gloriously simple, but gloriously robust.”

“If you do that study in a clinical population, you’re talking about tens to hundreds of millions of dollars,” he said. “We can now examine these diseases in a much more controlled environment, at orders of magnitude lower cost, and with orders of magnitude higher fidelity.”

The team’s success in improving brain imaging has opened the door for more advanced studying of neurogenetics and of “diseases that are important to all of us,” Dr. Williams said. It is the culmination of decades of work of people from multiple organizations and multiple disciplines — biomedical technology and neurogenetics.

“When you have two completely different areas of research, the sum is considerably more than the parts,” Dr. Johnson said. “The fact that we have two completely different views of the world, two completely different areas of research, but we’ve been able to merge them together, it gives us some capacity that others don’t have.”