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Scientists Discover Cheap Contrast Agent That Could Lead To Cheap MRIs

May 2, 2018 By National High Magnetic Field Laboratory

Researchers at theNational High Magnetic Field Laboratory(National MagLab) have discovered a substance that could help MRI machines evolve from today’s bulky behemoths to hand-held scanners straight out of “Star Trek.”

The amazing substance they discovered: water.

Funded by the National Science Foundation, a research team led by Clifford “Russ” Bowers, a chemist at the University of Florida (UF) and the National MagLab, discovered a way to turn plain old H20 into a very effective contrast agent used in magnetic resonance imaging, or MRI. Contrast agents are a kind of dye administered orally or intravenously to make a patient’s organs, blood vessels or tissues easier to see on MRI scans.

Using a very simple technique, Bowers’ team polarized the protons of hydrogen atoms in water, effectively boosting its magnetic properties. The resulting “hyperpolarized water” is far more sensitive to MRI detection than regular water. Their findings, published in the journal Chem, suggest the liquid could be used to create MRI images using magnets that are far cheaper and smaller than what are currently needed.

“It’s a potentially transformative result,” said Bowers.

Doctors routinely use MRI machines to diagnose diseases. The machines feature a tube-shaped superconducting magnet that generates 1.5 or 3 teslas, a unit of magnetic field strength. (By contrast, the little magnets on your fridge are around 0.01 tesla and the Earth’s magnetic field is about 0.000025 tesla). The machine needs that high of a field in order to work. An MRI image is, in essence, a map of water in the body: The varying amounts of H20 in a backbone, organ, or tumor translate into different shades of gray in the MRI image. Like all atomic nuclei, the nuclei in hydrogen spin on an axis, a behavior that is manipulated by MRI machines to generate a signal indicating the atom’s location.

Contrast agents such as gadolinium help boost hydrogen’s signal in an MRI, increasing the contrast in the image. When done without contrast agents, MRI is not a particularly sensitive imaging method: It picks up on the body’s hydrogen in large part because there’s so much of it: Water makes up about 60 percent of the body.

But the type of hydrogen Bowers and his team at the MagLab’s AMRIS Facility learned to make—hyperpolarized hydrogen—is another story entirely.

The scientists discovered hyperpolarized water is relatively easy to make. They started with pure water, then added some platinum-tin nanoparticles that were synthesized in the lab of Iowa State University chemist Wenyu Huang by Raghu Maligal-Ganesh. Then they “bubbled” a special kind of hydrogen gas called parahydrogen into the liquid in much the same way you might blow air bubbles into a glass of water through a straw. The bubbling stirred up the suspension, causing the nanoparticles to spread throughout without dissolving in the water.

Then something cool happened at the atomic level: Whenever a parahydrogen atom floating in its little bubble bumped into one of the nanoparticles, the spin of that atom was transferred to a hydrogen atom in the adjacent water. This spin transfer, made possible by the surface properties of the catalyst nanoparticle, made the affected hydrogen atom far more sensitive to MRI.

Although the process may be a little hard for non-scientists to envision, it’s pretty straightforward chemistry, said Bowers.

“It’s an unbelievably simple experiment,” Bowers said. “That’s the beauty of it. The most significant discoveries are often those that are so simple and elegant.”

Because the nanoparticles settle out of the liquid, the end product of this process is simply water, albeit hyperpolarized. After testing it in one of the nuclear magnetic resonance (NMR) magnets at AMRIS, Bowers’ group confirmed it responded exceptionally well to a magnetic field. They created the first MRI image using the technique, which Bowers dubbed SWAMP (which stands for “surface waters are magnetized by parahydrogen” and is a nod to UF’s mascot, the Gators). It’s one of the first time scientists have hyperpolarized water, Bowers said, and the technique is far simpler than anything previously discovered, making it far more likely to lead to practical applications.

“It’s very fast and cheap,” said Bowers. “Anybody can do it with very little equipment. You just need a special catalyst—that’s the magic.”

Because the hyperpolarized water is so sensitive to magnetic fields, it could potentially work even in relatively weak magnetic fields. It might, Bowers suggested, be used one day with a mobile MRI machine in remote areas, on the battlefield or perhaps even in space—something Dr. Leonard McCoy might proudly wield.

The protons of liquid water (HDO) are hyperpolarized by spin transfer from co-adsorbed parahydrogen on the surface of platinum-tin nanoparticles. Parahydrogen (antiparallel arrows) is converted to orthohydrogen (parallel arrows) in this process. Credit: Russ Bowers

 

Science Serendipity

The project is a great example of the serendipity of science. The research team was actually conducting experiments on a different contrast agent to see how strong a signal it generated in an NMR magnet, which uses the same technology as MRI magnets. Before testing the contrast agent, UF postdoc Evan Wenbo Zhao, lead author on the resulting paper, did a control experiment using treated water, fully expecting it would generate no signal.

But it did. A meticulous Zhao took note.

“A lot of discoveries are made by very careful observation and a very systematic experiment and careful observations by the researcher,” Bowers explained. “A lot of things may happen that people don’t notice or dismiss. In this case, it was a very unexpected observation.”

Both Zhao and Bowers immediately saw the potential of the discovery: Hyperpolarized water would be a cheap and completely non-toxic contrast agent, and the parahydrogen used to make it is easy to prepare, ship and store.

Perhaps, they imagined, it could even work using just Earth’s own magnetic field, obviating any man-made magnet entirely.

“An MRI is a very expensive, large machine,” Bowers explained. “But the only reason you need that huge magnet is to orient the hydrogen protons to create the alignment of those spins. You can do MRI in zero field, or an ultra low field, or even in the Earth’s field if you had a way to pre-polarize the protons.”

Bowers said there’s a lot more research to do before those futuristic scanners could become a reality.

“But it’s just the beginning,” he said. “We can already think of ways to improve it.”

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