NU research to improve cell imaging techniques

Technology offers access, insight to elusive body, brain membranes

By Andy Kim

The Daily Northwestern

A team of Northwestern chemists recently developed a break-through technology that could give doctors the ability to explore the environments inside living cells without harming them.

The development will significantly improve techniques for magnetic resonance imaging — commonly called MRI.

The team, led by chemistry Prof. Thomas J. Meade, published the study in the March issue of the Journal of Chemistry and Biology. The research in this area has been ongoing for more than 14 years.

“It’s like finding a piece of a very, very big puzzle,” he said. “You get a piece that’s been kicking your butt for a while. It feels good, but you know that although it’s an important piece, it’s not the final piece.”

Physicians and biologists frequently use MRI to obtain images of anatomical structure for use in research and diagnoses.

MRIs currently rely on the use of contrast agents, Meade said, which function like the method a plumber would use to fix a leaky septic tank. By pouring fluorescent dye into the tank and waiting for the dye to flow out of the puncture, the location of the leak is revealed.

Although current MRI techniques have been helpful, Meade said, there are many areas in the body where a contrast agent or dye cannot enter — namely through cellular membranes and certain barriers in the brain.

The NU team set out to create a way to transport molecules that could take contrast agents to hard-to-reach areas yet to be explored in living organisms.

The newly developed transport method involves a tiny metal complex that can penetrate both cells and many areas of the brain. In effect, Meade said, it delivers the contrast agent to places it naturally could not enter.

“It’s the key master that can get into all the doors,” he said.

Meade said the team’s next step will be to find an effective way to combine the new transport methods with “smart dyes,” which his team developed in 2000. Smart dyes are special contrast agents that can change behavior depending on the presence of certain enzymes.

The use of the new techniques could potentially help doctors in checking for tumors or diseases, many of which are associated with particular enzymes.

Some of the other possibilities for the new delivery technology include the ability to more closely observe the development of cells in the embryonic stage. Because of the agent’s cell-permeable quality, it can effectively track and monitor cells through their membranes from the very earliest stages of embryonic development.

In what Meade calls “fate-mapping,” the methods could help inform biologists how cells in the early embryonic stages differentiate as they mature.

Dianna Bardo, professor of radiology and neurology at the University of Chicago Medical School, said that while the new developments may eventually be beneficial for her work, they would also require doctors and radiologists to devise completely new methods of observing brain tissue, a process she said would require years of animal research.

“If we all become trained to see enhancement of the brain tissue (from the transporter), it could help,” she said. “But is there a need for that? I’m not 100 percent certain.”

Meade said that any potential application to humans and clinical research was “very much downstream,” and emphasized that while he is satisfied and excited about the research, it is a considerable work in progress.

“(The research) is drawing international attention and it’s a big deal,” Meade said. “But it’s certainly not the whole deal.”