Smart molecules may enhance images.

In medicine, a good picture is often worth more than a thousand words.

For that reason, physicians have invested heavily in high-tech systems to image the body's interior by means of X rays, magnetic resonance imaging (MRI), and positron emission tomography (PET).

Today, such systems provide three-dimensional color images of living tissues without the need to cut into a patient's tender flesh. What remains tricky, though, is producing detailed images that show how organs perform their biological duties.

To enhance MRI's capacity to track biological activities as they happen, Thomas J. Meade, a chemist at the California Institute of Technology, and his colleagues are developing a series of what they call smart contrast agents.

They hope to make injectable compounds that can light up specific biological actions during MRI, Meade said in Baltimore this week at the annual meeting of the American Association for the Advancement of Science.

"These contrast agents could allow researchers to get the same kind of functional data about a person that they usually obtain with PET, except that MRI has higher resolution and is easier to use than PET," Meade says.

PET excels in observation of biological processes, but it requires radioactive materials and particle accelerators, making the technique clinically unwieldy.

MRI, on the other hand, is highly effective at structural imaging and has found widespread clinical use, but it is less effective at gathering live-action information.

The new contrast agents offer the potential to help physicians identify disease processes as they occur-highlighting, for example, tissues damaged during a heart attack or stroke, says Meade. Such timely data could give physicians a head start in treatment, increasing a patient's chances of benefiting from speedy intervention.

The prototype contrast agents use gadolinium atoms encased in molecular shells tailored to trigger a specific enzyme, Meade says. Inside the body, the enzyme takes a bite out of the shell. This enzymatic chomp exposes the gadolinium atom within, enabling the MRI to pinpoint enzymatic activity.

The effect, he adds, is to illuminate the image of body tissues where specific metabolic processes are taking place. Though gadolinium on its own has toxic effects, it shows no toxicity in mice when processed this way, Meade says.

"These agents could also prove useful for mapping the brain and identifying hard-to-diagnose diseases," Meade says. Patients suffering from Alzheimer's disease, schizophrenia, and manic depression, for example, often present similar symptoms despite their vastly different brain disorders. Meade's team thinks that the smart agents could someday help clinicians distinguish such diseases on the basis of crisp brain images rather than interpretations of symptoms.

"Contrast agents have a lot of potential," says James V. Haxby, a neuroscientist at the National Institute of Mental Health in Bethesda, Md., "though they need to be tested carefully to make sure they don't have unwanted pharmacological activities."

Moreover, the contrast agents can help researchers track cell and neuron growth as organisms develop, Meade says, perhaps replacing the "slice-and-dice" methods required when using a microscope to follow embryonic development.