A technique perhaps best known for peering inside athletes' injured knees is now being tuned to tadpoles. A modified magnetic resonance imaging (MRI) procedure allows researchers to watch enzyme activity inside living creatures. In addition to generating new insights into embryonic development, the technique might someday be used to diagnose diseases and track therapy.
Typically, MRI detects the jiggling of hydrogen atoms perturbed by strong magnets. Slight differences in water content (most of the hydrogen atoms buzzed by the magnet are tied up in water) show up as shades of gray, revealing bone, cartilage, or clusters of neurons deep inside the brain. One extension of MRI called functional MRI can spot which brain areas are most active, but until now there hasn't been a high-resolution method for detecting enzyme activity--essentially a measure of what genes are turned on inside a cell.
A team led by chemist Thomas Meade of the California Institute of Technology in Pasadena figured out how to amplify the MRI's signal only in cells where a certain enzyme is active. The researchers used gadolinium, a metal that interacts with protons in water and boosts the intensity of MR images. They enclosed gadolinium in a chemical cage that normally keeps it from interacting with water, but they provided the cage with a gate that springs open when clipped by the enzyme. This exposes the gadolinium to water and ups the MRI signal wherever the enzyme is active.
The researchers tested their technique by injecting the caged gadolinium into both cells of a two-celled frog embryo. They then injected just one cell of the embryo with RNA or DNA that encodes the enzyme. When they created MR images of the tadpoles that grew from these embryos, bright spots indicated where the enzyme was active--in half the animal--and the spots correlated closely with standard stains of enzyme activity done by sectioning the tadpole, they report in the March Nature Biotechnology.
"They can see a measurable result in a living animal," says Claude Meares, a chemist at the University of California, Davis. "That's really quite exciting." What's more, the resolution--the highest so far in these types of studies--was good enough to discriminate structures as small as individual cells. Ultimately, experts hope, the technique will provide more sensitive methods for diagnosing diseases such as cancer and also help physicians measure how well therapies for cancer and other diseases are working.