Medical Device Daily

The first laboratory tests on human tissue using a light-based probe, developed by researchers at the Pratt School of Engineering at Duke University (Durham, North Carolina), have demonstrated that the technology can detect the earliest signs of cancer in epithelial cells, those cells that line internal organs such as the lungs, esophagus and colon.

According to Adam Wax, PhD, the Duke researcher leading the study, the next step will be the development of a clinical trial, funded by the National Cancer Institute, in collaboration with researchers at Duke University Medical Center.

The patients will be those "undergoing their regular surveillance procedure," that is, they will be visiting the medical center to undergo a biopsy, Wax said.

"It's really encouraging to go forward with a larger study," Wax, assistant professor of biomedical engineering at Duke, told Medical Device Daily.

According to Wax, about 85% of all cancers start in the epithelium, so that while a patient may die of brain cancer, the cancer may have begun in the lining of the colon.

"Being able to detect precancer in epithelial tissues would therefore help prevent all types of cancer by catching it early, before it has a chance to develop further or spread," he said.

Wax and John Pyhtila, his former graduate student, reported in the March 2007 issue of Gastrointestinal Endoscopy that their fiber-optic device reliably differentiated between healthy and precancerous digestive tissue taken from the stomach and esophagus of three patients known to have a precancerous form of a condition called Barrett's esophagus. The technique is known as fa/LCl (for frequency-domain angle-resolved low coherence interferometry).

Wax called that initial study "very promising" because after only a "handful of patients," the researchers were able to get 100% sensitivity, translating to the ability to actually detect precancerous cells in the esophagus.

"Right now we're focusing on the esophagus," Wax said. "We think the colon is the next best target, and we see the bladder, cervix and the lungs as follow-ons."

Using the "regular biopsy channel," the researchers' probe is attached to a typical port on a typical endoscope. Rather than using one of the ports to collect tissue to be sent to a lab for examination, the fa/LCl technique would scan the tissue with the Duke researchers' so-called optical probe.

In studying the technique, researchers then compare their results with those of a pathologist.

The technique involves using laser light, which scatters off the cell nuclei, creating scattering or light diffraction when held against tissue. Providing some basics of physics, Wax said that when light goes through a very small hole, it diffracts, creating so-called "diffraction rings."

"The angle of the rings tells us about the size of the nuclei [in cells of the tissue] very accurately," he told MDD, noting that it tells the physician operating the probe the average size of the cell nuclei in the probed area.

"This is an important parameter, because this is what pathologists actually look at when they're doing a physical biopsy. We feel this will help aid adoption and acceptance by the physicians."

An advantage that light-scattering technology has over fluorescence is that rather than only providing a "non-specific parameter," the device is "actually relating it to a physical property of the tissue," Wax said.

The fiber-optic probe carries the light back to a spectrometer, and the measurements of the cell nuclei are analyzed using a computer. The researchers employ software "where algorithms give you the size of the cell nuclei based on the scattering pattern."

The computer actually provides a numerical measurement on the computer screen. If the cell nuclei are less than 10 microns, this would be considered in the safe range. From 10-15 microns is considered precancerous, and the measurements can be as large as 30, Wax said.

Although ultimately the fiber-optic device may be the answer to often difficult and painful biopsies, Wax said, "Initially, we're selling it as a guide to biopsy. Right now, when they do random biopsies, you typically only get about 3% to 5% of tissue coverage. With our device, since it's only a second per point, you can cover a much larger area, so when you find a suspicious area [with the probe], you can do the biopsy there."

Based on a study in hamsters, Wax and Duke postdoctoral researcher Kevin Chalut reported in the February 2007 issue of Cancer Epidemiology Biomarkers & Prevention that the technique might also be used in the identification of early lung cancer.

The National Science Foundation also funded the preliminary study.

Wax and colleagues have also formed a company, named Oncoscope, to pursue commercial development of the fa/LCl devices, and the company has received an SBIR grant from the government.

It also has secured some patents on the device, with others pending.

If the clinical trial confirms the findings of the preliminary research, the researchers expect that the device could be ready for clinical use within three to five years.