When Alan Koretsky, scientific director of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, and Gary Zabow began to think about developing new contrast agents for magnetic resonance imaging (MRI), they took their design cues from the colourful world of molecular imaging. "It was looking at what existed and then figuring out some way to copy the idea of quantum dots," says Zabow, a physicist at the National Institute of Standards and Technology in Boulder, Colorado.
In molecular imaging, a quantum dot can generate a range of possible emission spectra simply by varying the size of the dot's inner core shell. This is a stark contrast to the traditional agents used in MRI, such as gadolinium or iron oxide, which are magnetic materials that alter the signal from the protons in the surrounding water, appearing as either darker or brighter spots on images. "It is sometimes difficult to tell the different agents apart from one another or from artefacts that make something brighter or darker," says Zabow. (At present, colour in MRI scans — such as those in this article — is assigned to shades of grey and added during processing.)
"One of the areas of MRI that has exploded over the past 5 or 6 years is the ability to track cells as they move around," says Koretsky. Although MRI cannot achieve single-cell resolution, a single cell can have sufficient magnetic-resonance contrast to be detected. But for researchers interested in tracking two or three cells at once, this level of differentiation is not enough.
So Zabow and Koretsky microfabricated specific magnetic shapes that would create different magnetic fields and so shift the nuclear magnetic resonance frequency. "The existing magnetic particles do not shift the frequency — they just broaden it out," says Zabow. But the very precise shape of these new agents generates a corresponding precise frequency shift, similar to quantum dots, giving Zabow and Koretsky the possibility of creating different colours through different shapes and their specific frequency shifts.
The initial work consists of two discs with a gap between them in which the magnetic field can be generated. By varying the thickness or diameter of the discs, or the gap, different fields can be obtained so that when water passes between the discs the magnetic resonance of the water molecules flowing through the gap shifts (G. Zabow et al. Nature 453, 1058–1063; 2008).
Although the possible range of new colours is still to be determined, that is not the primary focus at the moment, says Zabow. They are working to improve the fabrication process and make the magnetic particles smaller and more robust. "We are working first on that. The idea of having as many colours as possible falls out from there because in improving the fabrication we are getting the geometry more precise," he says.
Koretsky sees these new contrasting agents as adding a unique ability to MRI that no other radiological imaging technique possesses.