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Researchers Say Laser Technique May Help Doctors Avoid Biopsies - 2003-08-05

Lasers, tightly focused beams of light, are used in medicine for many things from treating cancer to correcting vision. Now a laser technique for viewing tissue may replace surgery to help doctors diagnose disease. It takes advantage of the body's natural ability to glow.

Every day, by knife or needle, doctors perform biopsies to remove small samples of patients' tissue and view them under microscopes to see if they are diseased. But biopsies are invasive, take days to complete, and require dyes potentially harmful to laboratory workers.

Now, a recent study in the Proceedings of the U.S. National Academy of Sciences describes a non-surgical laser technique that can see individual cells as well as biopsies can, but takes only minutes. It pairs a laser with a special microscope.

The Cornell and Harvard University researchers who wrote the paper are applying this technique in animal and human experiments, observing everything from brain functioning to cancer.

"We can see a lot of detail and we're able to do this without adding extra stains to the tissue," said physicist Watt Webb. "That means that this is a minimally invasive process."

The Cornell physicist and engineer is one of the inventors of this method, which allows scientists to see nearly one millimeter deep into tissue.

"We can look through the skin, see the circulation, see the collagen structures below the skin, all sorts of nice things like that, which give a very useful diagnostic feature for research and we believe soon for medical applications," he said.

How does this new laser process work?

Some molecules in our body glow when viewed under certain kinds of light. Normally, the high energy needed to make these molecules light up might damage tissue.

But lower energy light, such as infrared, is much less harmful and is very good at looking through tissue. So the researchers use a laser that emits infrared light in very short pulses, as many as 80 million per second. They focus the beams through a microscope onto a tiny area of tissue, less than one hundredth the width of a human hair.

"They're very, very short pulses in time, but within that pulse there's a very large number of photons, particles of light," he said.

Cornell researcher Warren Zipfel says it takes the combined energy of at least two light particles to cause certain molecules in the body to glow. This is where laser pulses, with their higher density of photons, work better than natural light. They offer a greater chance that two photons will hit a molecule at the same time. The chemicals react as if they had been hit with a single photon of more damaging higher energy light and glow.

"Normally with sunlight, there's never a high probability that there will be two photons exactly in the same place at the same time," he said. "It's only with an intense pulse you can get from modern lasers can this actually happen."

The resulting multicolored image is scanned by the microscope and processed by a computer. Mr. Zipfel says a highly detailed, three dimensional picture of living cells emerges.

"We can form images of very high resolution. It's actually analogous, for example, to looking at page 100 of a book without opening the book," he said.

University of Wisconsin optical techniques expert John White, who did not take part in the study, is excited that these colorful pictures show different features of the tissue simultaneously, a result that normally requires multiple dyes in surgical biopsies.

"They're just using the optical properties of the tissue itself and reading out the information from that," he said.

Warren Zipfel and his associates are working to improve the technique. They are attaching their laser to thin, flexible glass fibers, which transmit light. By inserting these optical fibers into the body, they hope to see deeper than just one millimeter in order for the procedure to become a useful alternative to biopsies.