MRI has set the standard for imaging in clinical diagnosis and biomedical research, thanks in large part to the availability of contrast agents that highlight areas of interest within the body. But the contrast provided by these agents, and by MRI in general, is still essentially monochrome. Unlike optical imaging, where different color tags or labels allow multifunctional imaging, MRI contrast depends essentially on stronger and weaker signals.Investigators with the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Md., and the National Institute of Standards and Technology in Boulder, Colo., who employ MRI techniques in their studies, understood how researchers in other areas of biology were benefiting from use of colored tags for optical biomaging, including fluorophores and quantum dots. Struck by the potential, they began exploring ways to achieve multifunctional imaging with MRI.They recently reported a novel type of contrast agent that enables them to do just that. Their approach takes advantage of the physical shapes of the nanoparticles to generate characteristic spectral signals. Using various shapes and geometries will yield distinct spectral signals. Thus, investigators can achieve “multicolor,” multifunctional imaging simply by using various versions of the nanoparticles.Researchers have reported a novel contrast agent that enables “multicolor,” multifunctional imaging with MRI. They showed that they can generate unique spectral signals by using nanoparticles of various shapes and geometries. The signals can be converted to a range of colors, and the nanoparticles can be used to tag specific cells and tissues.The nanoparticles consist of two round magnetic discs stacked on top of one another, with a small open gap between them. Researchers can vary the magnetic field — and, thus, the characteristic spectral signal — either by using different materials to fabricate the particles or by modifying the geometry: by narrowing the distance between the discs, for example, or by changing the discs’ diameters. Specialized software then can convert the signals into myriad colors, providing multicolor magnetic resonance imaging.Using different versions of the nanoparticles, therefore, researchers can tag specific cells, tissues or even physiological conditions, much as they can with optical imaging. In this way, the probes could contribute to a range of applications in medical research as well as in diagnostic imaging.Contrast agents produce magnetic fields that fluctuate in time, causing faster relaxation of water molecules in the vicinity following radio-frequency excitation and, therefore, an enhanced nuclear magnetic resonance signal. The disc nanoparticles do not rely on relaxation effects but operate instead by changing the frequency of the detected radio signals. The nanoparticles, which are compatible with standard MRI systems, can be made using conventional microfabrication techniques. Shown are grids of nanoparticles on a wafer on which they were made, with light scattering from the nanoparticles.Besides playing a potential role in multifunctional imaging, the nanoparticles can serve as highly sensitive MRI contrast agents. The design of the aforementioned probes leads to water flowing between the discs, and this diffusion produces a signal that may be thousands of times stronger than that measured with similar volumes of stationary water.The researchers envision a range of potential applications of the new MRI contrast agent, from identifying cancerous cells in vivo to facilitating radio-frequency ID tag-based microfluidic devices for biotechnology and handheld medical diagnostic toolkits. But first, “a lot of basic engineering has to be done,” said Gary Zabow, the first author of the paper. The investigators hope to reduce the size of the nanoparticles to less than a micron, for example. They also must assess various materials for use in the probes. The prototypes used in the study were made of nickel, which is easy to work with but toxic in humans. Zabow noted that other, nontoxic magnetic materials, such as iron, readily could replace the nickel in the nanoparticles.The researchers also are planning a series of safety tests both in vitro and in animal studies. Only after they have completed these would they consider moving on to clinical trials to test the efficacy of the probes in humans.Nature, June 19, 2008, pp. 1058-1063.