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The next frontier

University imaging and neuroscience expert Noam Harel, Ph.D., pushes the limits of magnetic resonance technology. (Photo: Scott Streble)

U’s Center for Magnetic Resonance Research to play a leading role in $30 million project to map connections in the human brain

Rumors were flying that the National Institutes of Health (NIH) was thinking big. Science’s next great frontier would aim to unlock mysteries of the brain, and the NIH was ready to put up big money to make it happen.

Kamil Ugurbil, Ph.D., knew that the University of Minnesota’s Center for Magnetic Resonance Research (CMRR) had to be a part of that study.

“We’ve developed a track record [of] pushing the limits of brain imaging technology,” he says of the world-renowned research entity he has led since 1991.

So when the news came last October that the CMRR and collaborators at Washington University in St. Louis had been selected to receive a $30 million grant to co-lead the breathtaking enterprise known as the Human Connectome Project, Ugurbil couldn’t have been more pleased.

Over the next five years, researchers involved in the high-profile project will use magnetic resonance imaging (MRI) techniques and additional brain imaging and genetics to map neural connectivity in the brain, all the while advancing the MR technology available for research and patient care.

“There’s undoubtedly a lot to do in a relatively short period of time,” Ugurbil says.

But it’s a challenge worth accepting. Investigators expect that the Human Connectome Project will have a transformative impact on science and health, leading to a much more detailed understanding of how brain circuitry changes as people age and how it differs in people who have psychiatric and neurologic illnesses.

A robust collection

The research plan for the University of Minnesota/Washington University portion of the Human Connectome Project looks like this: CMRR researchers will begin scanning the brains of 1,200 healthy volunteers with a 3 Tesla MRI magnet. Most hospitals’ MRI scanners are 1.5 Tesla.

The volunteers will be sets of twins (identical and fraternal) and their siblings, two degrees of relatedness that will help to reveal how genes and the environment shape brain circuitry and to pinpoint genetic variations between relatives.

After University faculty refine the imaging process and technology, the 3 Tesla machine will be moved down the highway to St. Louis, where the bulk of volunteers will undergo scans. There, researchers at Washington University will continue to amass data, creating a robust database of information about neural structures and connectivity.

Back at the CMRR, scientists will continue to focus on developing and optimizing brain imaging. MRI machines can be programmed in various modalities, so volunteers’ brain scans will cover several types of images. One type is the standard MR image, like that used in hospitals, revealing anatomical structures of the brain. Researchers also will capture functional MRI (fMRI) images that reveal regions of the brain “lighting up” as they become active, both when volunteers are resting and performing small tasks like tapping their fingers.

Yet another type of imaging, diffusion-weighted MRI, will provide detailed maps of nerve bundles in the brain; areas showing dense bundles of nerves indicate more significant connections. These scans can offer critical clinical information, for instance, for neurosurgeons who want to intervene in one region of the brain without disturbing neural connections to another area, explains University imaging expert Noam Harel, Ph.D. Ultimately, the technique may even provide neurosurgeons with individualized maps of each patient’s brain, making brain surgery quicker and more precise.

Significantly, the vast trove of information produced through the Human Connectome Project will be available to the public. Even the algorithms developed to interpret signals from the MR data will be publicly available, notes University electrical engineer and signal processing expert Guillermo Sapiro, Ph.D.

“Any scientist at any institution will have the opportunity to use the data for further research,” Harel adds.

This diffusion spectrum image shows brain wiring in a healthy adult. The thread-like structures are nerve bundles, each containing hundreds of thousands of nerve fibers. (Image courtesy of Van J. Wedeen, M.D., MGH/Harvard University.)

Early progress

Even as it begins to launch formal studies through the Human Connectome Project, the CMRR already has made important advances in how imaging is done. The group and its collaborators began investigating whether it would be possible to reduce the time, typically 30 to 40 minutes, needed for an imaging session. They found that they could accelerate scanning time many times over, both reducing how long a person might need to lie very still in the scanner and exponentially increasing the number of images of living tissue they can get in that timeframe.

“That gives us much better statistical power and new insights about what might be going on in the brain over time,” says Ugurbil of the finding, which his team published in the online journal PLoS ONE. “And we expect many more developments like that along the way.”

The first in the world to have a 7 Tesla scanner and now the only institution to have two of them, the CMRR also will use its 7 Tesla magnets to scan the brains of 200 volunteers through the Human Connectome Project.

The NIH is taking note of every step along the way.

“There’s huge enthusiasm for this project, which was evident from the beginning with the investment of such resources at a time when NIH funding is relatively tight,” Ugurbil says.

The enthusiasm for the field itself is pushing the scientists, too, he adds. The fundamental information they gather about healthy brains may someday provide a useful comparison in studies of disease, for example, in patients with Alzheimer’s or Parkinson’s.

Says Ugurbil, “We know that this project is going to be a prelude to all kinds of research in the future.”

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