Light-based Device Probes For Early Cancer Signs

The team has reported the first clinically practical version of their "angle-resolved low coherence interferometry" (a/LCI) technology designed to diagnose incipient cancer in the esophagus. Adam Wax, professor of biomedical engineering at the Pratt School, and graduate student John Pyhtila, lead author of the study, reported tests of their device in the March 15, 2006, Optics Letters. The work was supported by the National Institutes of Health and the National Science Foundation.

Preliminary results of a further study of the latest a/LCI device in human esophageal tissue look promising, Wax said. The next step will be to test the device in human trials.

In principle, the researchers said their technology could be adapted to detect pre-cancerous cells on the surfaces of any organ, where the disease most often begins.

"The majority of all cancers -- some 80 percent -- start in the epithelium," Wax said. "Fiber-optic probes have the potential to test for early evidence of cancer in seconds, providing biopsy-type information without removing tissue. They could also serve as a guide to biopsy, directing physicians to suspicious sites to increase the likelihood that cancer will be detected." Biopsy surveillance in the esophagus removes tissue at random, he said.

Acid reflux can lead to changes in the esophageal lining as the organ attempts to adapt to acids normally limited to the stomach, a condition called Barrett's esophagus, he explained. The condition raises the risk of esophageal cancer, and patients are generally tested for cancer periodically through random biopsy.

Previous studies by Wax's team used a/LCI to identify pre-cancer in animal tissue. Pre-cancerous cells are characterized by an enlarged nucleus, the structure that houses the cell's genetic material. It is such cellular changes that pathologists rely on to identify cancer in biopsied tissue, Wax said.

The a/LCI device emits light that scatters when it hits the cell nucleus. To enable a/LCI to be used as a diagnostic technology, the researchers developed a model of how light is scattered by the nucleus of healthy cells versus cancerous ones.

"What really sets a/LCI apart is its ability to focus on light scattered from a single cell layer," Wax said.

The device is also fast, he added. While early versions of the technology required up to 30 minutes to scan a 1 millimeter point, further development led to a "Fourier-domain" device (faLCI) that captures the same information in a fraction of a second, Wax said.

The researchers now have devised an endoscopic fiber bundle probe incorporated into the faLCI system. Endoscopes are thin, flexible tools used to examine the inner lining of the esophagus. In laboratory tests, the endoscopic faLCI probe could precisely and accurately determine the size of tiny polystyrene beads in solution, the team found. The beads represented a clinically relevant size range comparable to the dimensions of nuclei found in normal to cancerous tissue.

"The clinical diagnosis of cancer today is a slow process, requiring a physician to remove tissue and send it off to pathology." Wax said. "Furthermore, cancer often isn't identified until a full-blown mass develops.

"In contrast, our device lends itself to almost instant diagnosis of pre-cancer." In the esophagus, the speed of the technology could allow physicians to examine perhaps 100 more tissue sites than biopsy currently allows, an advance that should help to make cancer harder to miss, he said.

Collaborators on the study include Jeffrey Boyer and Kevin Chalut, both at Duke's Pratt School of Engineering.