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Biomedicine

Multicolor MRI for Molecular Imaging

Injectable magnets could let doctors watch diseases at work.

Magnetic resonance imaging (MRI) is a clinical workhorse, producing exquisitely detailed 3-D pictures of tumors, blood vessels, bones, and structures deep inside the body. MRI images are in shades of gray, and their contrast is based on how much water is in the part of the body under study. Now physicists have fabricated miniature magnetic particles that could brighten MRI with a rainbow of colors that convey a wealth of information about the disease states and behavior of tissues in the body.

Mini magnets: Injected into the body, microscale magnetic particles (top) could yield colored magnetic resonance images that let doctors examine the molecular underpinnings of diseases, including cancer. At bottom is a grid of mini magnets before they’re removed from the semiconductor wafer on which they’re manufactured using standard techniques from the computer industry.

Research on these particles, under way at the National Institute of Standards and Technology, in Boulder, CO, is in its early stages, and the particles haven’t been tested in animals. But if multicolor MRI lives up to its promise, it could provide visual information at the level of genes, proteins, and other molecules. Researchers hope that such “molecular imaging” will eventually become part of personalized medicine, allowing doctors to literally see the processes underlying an individual patient’s inflammation or tumor growth and then prescribe the right therapy with less guesswork. Most molecular-imaging techniques are optical and involve fluorescent tags such as the tiny particles of semiconductor material known as quantum dots. But the light emitted by these tags can travel through only about a centimeter of tissue, so they’re not very useful for imaging organs. MRI provides a noninvasive look below the surface.

Magnetic resonance images are generated from radio frequency signals emitted by water molecules inside the body. When the strong circular magnet that surrounds the patient is turned on, the nuclei of hydrogen atoms inside the patient’s body align with the magnetic field. A radio frequency pulse knocks them out of alignment, and as they snap back into position, they release their excess energy as radio waves.

The particles designed by the National Institute of Standards and Technology (NIST) act like miniature magnets, causing a predictable shift in the frequency of the radio waves emitted by water flowing through them. The magnitude of this shift is directly related to the size and shape of the particles, which consist of two disc-shaped nickel magnets held together by nonmagnetic posts. The varied radio frequency shifts can be mapped onto the spectrum of colors of visible light.

“We can engineer whatever color we want,” says Gary Zabow, a physicist in NIST’s electromagnetics division who is leading the particles’ development. Using microfabrication techniques that are standard in the computer industry, he says, “we get these colors by controlling the particles’ exact shape.”

The micromagnets shift the frequency of only those radio waves emitted by water traveling between their constituent discs. If this space is blocked off, says Zabow, the particles have no effect on the MRI signal. Consequently, the micromagnets could act as miniature chemical sensors. “You could purposely block the space with a material that melts at a certain temperature or that is in some way reactive, expanding or shrinking” under specific conditions inside the body, says Zabow.

Contrast agents for MRI already exist, and some of them can even be targeted to particular tissues or cell types. Like the NIST micromagnets, these agents make part of the image look brighter or darker by shifting the radio frequencies emitted by protons. Unlike the NIST particles, however, they’re made using chemical techniques, so the dimensions of their particles can’t be carefully controlled. As a consequence, they shift the frequencies of the protons’ signals unpredictably. On average, they provide a contrast to the standard MRI signal, but they can’t offer more-precise, local distinctions.

“If you were to put in two [such agents], you couldn’t tell the difference between them,” says Richard Bowtell, a professor of physics at the Institute of Neuroscience at the University of Nottingham, in England. Each NIST particle, though, produces a distinct signature. “If you put them all in simultaneously, you could see which signal belongs to which one,” Bowtell says.

The micromagnets, described this week in the journal Nature, have so far been made from nickel, which is toxic. But Zabow says that they could easily be made from iron, which is nontoxic and magnetic. The researchers are exploring the idea of using the particles as “sensors of physiological conditions inside the body,” says Zabow, but he cautions that they are only now taking the first step in that direction, planning tests in cells.

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