Pulse
Power House
Tenacious scientists at the University of Minnesota continuously redefine what’s possible in magnetic resonance imaging.
Last year, papers published in the Journal of Neuroscience and Magnetic Resonance in Medicine described the use of magnetic resonance microimaging to detect Alzheimer’s amyloid plaques in the brains of mice. The papers, one of which was named Best Paper Published between 2004-2006 by the Alzheimer’s Association, are in a long line of groundbreaking studies that have come out of the University of Minnesota’s Center for Magnetic Resonance Research (CMRR). The authors, who hailed from Mayo Clinic and the University of Minnesota, used the center’s 9.4-Tesla magnetic resonance imaging (MRI) equipment and new imaging approaches developed by the CMRR faculty. (The field strength of an average hospital MRI unit is 1.5 Tesla.)
The center, which is housed in a low-slung brick building on the university campus in Minneapolis, is responsible for many such milestones in magnetic resonance imaging. In 1991, a paper by center founder and head Kamil Ugurbil, Ph.D., and others described what was then a new method for imaging activity in the brain: functional magnetic resonance imaging (fMRI).
“Yes, that is true,” Ugurbil says of having developed fMRI. But he quickly qualifies the statement, explaining that another group from Massachusetts General Hospital published a paper on it about the same time. So like many scientific firsts, fMRI was developed by two groups working independently.
Pushing the Envelope
Still, Ugurbil insists that the CMRR has been ahead of its time since its inception in 1990. He attributes this to the center’s focus on the process of imaging, not just the end result, and to its faculty. The physicists, chemists, radiologists, and engineers who work there not only understand physics and physiology, they can assemble the hardware bits and pieces that eventually become the new research instruments. The parts that enable imaging at strengths as high as 9.4 Tesla—the magnet, transmitter and receiver coils, power supply and switches, radiofrequency signal generators, amplifiers, and cables—are configured onsite. “This is one of the secrets of the success of the center,” he says. “We bring together a lot of people with talent in physics or technology so that we can advance the technology ourselves. We are not relying on other groups or instrument manufacturers,” he says. “We build new hardware, we advance hardware, we advance methodology.”
That sort of can-do attitude has enabled the group to work with ever-stronger magnets and ever-more-complicated organisms.
In the early 1990s, high magnetic fields were actually considered a detriment for imaging the human head. And for many years, a field strength of 3 or 4 Tesla was considered the practical limit for imaging humans.
The problem had to do with the radiofrequency coils inside the magnet that send signals into the object being imaged. Those signals stimulate a response that produces the signals that generate images. Stronger magnets require higher frequency electromagnetic waves, which many people thought didn’t penetrate biological objects as well as lower frequency waves. Ugurbil cites the example of daylight, which has a very high frequency and can hardly penetrate the skin, to illustrate the concept. Complicating matters was the human body itself, which with multiple structures was less uniformly conductive as, say, a simple vessel of water.
So the conventional thinking was that using high magnetic fields to image the head couldn’t work. But CMRR investigators questioned that thinking because it was based on modeling and assumptions rather than experimentation. “We were not facing something like the second law of thermodynamics, which you cannot violate,” he says. “It was an opinion.”
There were, however, many technical problems to overcome. Among the new imaging strategies they arrived at were new designs for coils, with many small transmitters and detectors rather than one large one. As manufacturers have seen the clarity of and information generated by the images and the data on the feasibility of the high-field systems, they have begun to produce them. Siemens, Philips, and GE, for example, now manufacture 7-Tesla scanners.
Today, the center does MRI of the human brain at the 9.4-Tesla level, which enabled the Mayo and University of Minnesota researchers to obtain images of Alzheimer’s plaques in the brains of mice. The center is exploring the possibility of imaging other parts of the body such as the heart at high magnetic fields, and faculty are in talks with a manufacturer about producing a 16-Tesla magnet that could be used in animal imaging.
Again, they’re in uncharted technological territory. But that seems to be exactly where Ugurbil and the center like to be.
Having their Heads Examined
Researchers are using the university’s high-powered scanners to understand how children’s brains develop
University of Minnesota developmental psychologist Kathleen Thomas, Ph.D., gets to do what every parent or teacher has wished they could at some point in their lives: look inside the brains of kids.
A few years ago, that might have required her to spend long hours observing them from the screened booths that overlook the Institute of Child Development’s Laboratory preschool, where researchers surreptitiously watch kids at play. Today, the director of the institute’s cognitive developmental neuroimaging laboratory has at her disposal a
3-Tesla magnetic resonance imaging machine at the Center for Magnetic Resonance Research. Thomas is one of the many faculty on campus who use the facility to do their research.
One of Thomas’s interests is cognitive regulation in children, their ability to control their behavior. “We’re understanding how that changes, what the normal process is, why 4-year-olds have trouble regulating their behavior and cognition and 10-year-olds are quite good at it, and what happens between 4 and 10,” she says.
Functional MRI studies have shown that in very young children, the brain is activating many different regions as it performs a task. “Some of them are not very efficient. At least, that’s our interpretation,” Thomas says. Over time, the activity becomes more focal or localized. A preschooler, for example, might exhibit activity across the whole frontal lobe when performing a task. By age 10, he might exhibit activity in only one specific area of the frontal lobe. “It’s as though the brain has identified the key area that it needs to engage in order to complete the task,” she explains.
Thomas sees this as an evolutionary asset. “If everything were very focal and specific early on in development, then if there were some sort of major brain insult or the environment wasn’t what was expected, the brain wouldn’t be able to adapt to it.”
Her research suggests that this localization of brain activity occurs fairly late in childhood. In one study, the brains of 7- to 10-year-olds were still activating more diffusely than those of adults. “I would imagine it comes at different times for different tasks,” Thomas says. “Certainly, there’s a lot of individual variability.”
Not surprising, Thomas has found that the patterns on the MRIs of children with attention-deficit hyperactivity disorder (ADHD), who are notoriously poor at regulating their behavior, are different than those of other kids. Areas of the brain, such as the basal ganglia, that appear to be necessary for kids to perform a task aren’t activated, and some new regions that aren’t helpful are activated.
One goal of Thomas’s research is to gain a better understanding of how medications for conditions such as ADHD affect the brain.
The horizon for neuroimaging research is certainly vast. Yet one very practical concern limits it for researchers such as Thomas: the fact that kids squirm. So Thomas spends part of her grant money and part of her time training 3- and 4-year-olds to lie still in a mock scanner that replicates everything about MRI except the magnetic field. The big challenge, she says, “is being sensitive to how long kids can stay in the scanner without getting antsy."
—C. Peota