The difference between slightly abnormal tissue and precancerous tissue can be subtle. Because the changeover may not be visible to the naked eye, surgeons exploring questionable tissue remove a tiny sample for a biopsy–a detailed examination by a trained pathologist. If some biomedical researchers have it their way, physicians will one day be able to scout for precancerous cells by simply shining light on them.
Boston-area researchers are developing a new technology that could become the basis for such optical biopsies. In less than 1 second, the device these scientists have built beams 12 colors of light sequentially down a cable of optical fibers and onto the tissue the fibers are touching. Each pulse excites certain chemicals in the tissue. The chemicals instantly respond by emitting characteristic fluorescent flashes, which the cable transmits back to a central processor.
The new system not only identifies precancerous tissue, but it also offers some measure of how much the tissue had transformed.
Kamran Badizadegan of Harvard Medical School in Boston presented his team’s findings this week in Orlando, Fla., at Experimental Biology 2001, the joint annual meeting for dozens of scientific societies.
Devices that rely on fluorescent signatures from tissues to detect some malignancies, such as lung cancer, are already on the market, notes Badizadegan’s coworker Irene Georgakoudi. However, she points out, the presence of blood can seriously distort the fluorescence signals those systems pick up. That, in turn, can undermine the tools’ diagnostic value.
Last year, a group at the Massachusetts Institute of Technology (MIT) now including Georgakoudi, found a way to compensate for this distortion by adding white light to the array of colored flashes shone on tissue. The white light sends back a reference reflection that helps the processor interpret the fluorescent signals even when blood interferes with those signals.
“By combining information from this together with the measured fluorescence, we recover the
undistorted–or intrinsic–fluorescence [of the tissue],” Georgakoudi explains. The MIT team detailed the development in the Oct. 1, 2000 Optical Letters.
This week, the Boston-area team together report that just two cellular substances emit the bulk of the fluorescence: collagen, a major structural protein, and a form of nicotinamide adenine dinucleotide (NADH), which is part of cells’ energy-making machinery. As cells become precancerous, the scientists report, their collagen content drops and their NADH supply climbs.
Badizadegan, Georgakoudi, and their colleagues tested the experimental system on people with a high risk of contracting esophageal or uterine cancer. To survey for precancerous changes in esophageal tissue that’s been damaged by gastric-reflux disease, gastroenterologists today “blindly sample every couple centimeters” along the damaged area of a person’s esophagus, explains Badizadegan, a gastrointestinal pathologist.
Among the 29 esophageal sites tested in 12 patients, fluorescence correctly identified 22 as harmless and 7 as highly transformed precancerous tissue, according to biopsies of tissue taken from the same sites during the examinations. In 35 women who had abnormal Pap smears, the fluorescence system correctly identified 10 highly precancerous sites and 43 harmless ones in uterine tissue.
As Badizadegan’s group begins testing the technique on a larger group of women, Georgakoudi’s MIT team is looking to make the system more versatile. The MIT researchers want to enlarge the area that the new device can survey–now only
1 square millimeter–at one time. They’re also interested in converting the analyzed signals into a pictorial display that pathologists could read at a glance as they move the optical probe over tissue.
“To validate this for any potential clinical application, one has got to see some very solid statistical [proof] that it’s truly quantitative and reproducible,” notes Donald C. Malins of the Pacific Northwest Research Institute in Seattle. For that, the researchers must examine more people and tissue samples, he says.
If the technique passes such further testing, Malin adds, “it may be a significant advance” as an adjunct or an alternative to surgical biopsy in tissues accessible to optical fibers.