New MRI technique could picture disease metabolism in action

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Duke University chemists are using a modified polarization technique that produces stronger MRI signals to better see molecular changes that could signal health problems such as cancer, according to research published in the March 27 issue of Science.

The new method makes more of the body's chemistry visible by MRI, said Warren Warren, MD, a professor of chemistry at Duke in Durham, N.C.

Standard MRI and the functional MRI used for brain imaging enlist the hydrogen atoms in water to create a graphic display in response to magnetic pulses and radio waves. But, the authors noted that a huge array of water molecules are needed to accomplish that.

"Only one out of every 100,000 water molecules in the body will actually contribute any useful signal to build that image," Warren said. "The water signal is not much different between tumors and normal tissue, but the other internal chemistry is different. So detecting other molecules, and how they change, would aid diagnosis."

The researchers have seen these other molecules with MRI by ‘hyperpolarizing' some atoms in a sample, adjusting the spins of their nuclei to drastically increase their signal. This creates large imbalances among the populations of those spin states, making the molecules into more powerful magnets.

Unlike normal MRI, hyperpolarization and a technique, called dynamic nuclear polarization (DNP), which was used for this research, can produce strong MRI signals from a variety of other kinds of atoms besides water, the researchers reported. Without hyperpolarization, detecting signals from atoms besides water is exceedingly difficult because the signal size is so small.

However, "these signals are strong enough to see, even though the molecules are much more complex than water," Warren said.

The investigators used Duke's Small Molecule Synthesis Facility to create custom molecular architectures. "You thus have a signal that, at least transiently, can be thousands or ten thousands times stronger than regular hydrogen in an MRI," Warren said. "It lets you turn molecules you are interested in into MRI lightbulbs."

Duke's hyperpolarizer includes a superconducting magnet, a cryogenic cooling system that initially plunges temperatures to a scant 1.4 Kelvin degrees while microwave radiation transfers spin polarization from electrons to nuclei, and a heating system to rapidly reheat the molecules.

Hyperpolarized spin states do not last for long inside the body, but ways have been found to lengthen them. Several years ago, another group discovered a method to make DNP work at room temperature in some biological molecules by substituting carbon-13 atoms for some of those molecules' normal carbon-12s. Unlike carbon-12, carbon-13 emits an NMR signal like hydrogen atoms do.

Using this room-temperature DNP, the biological molecule pyruvate can retain its MRI signal for as long as 40 seconds-long enough to observe it undergoing rapid chemical change. "So you can watch pyruvate metabolize to produce lactate, acetic acid and bicarbonate-all breakdown products that might correlate with cancer," Warren said.

The researchers described a new method that can further extend the signals of molecules carrying swapped carbon-13s. It works by temporarily bottling-up the hyperpolarization in the longest-lived spin states -- called "singlet eigenstates" -- within specially designed molecular architectures. "You can actually use their own chemistries to get the molecules in and out of those protected states," Warren said.