With the aim of developing a more effective tool for early cancer screening, Adam Wax, professor of biomedical engineering at Duke University’s Pratt School of Engineering (Durham, NC), and colleagues have developed a frequency-domain angle-resolved low-coherence-interferometry (fa/LCI) system that collects data from live tissue in real time through an endoscopically compatible fiber probe. According to Wax, the light-based device can acquire, process, analyze, and report data on atypical cells in one second, while eliminating artifacts. The procedure does not require the removal of tissue for screening and surveillance.
Most cancers start in the body’s epithelial cells, which line the mucous membranes in the lungs, esophagus, and gut. “Being able to detect precancer in epithelial tissues-cells that line the internal organs-would therefore help prevent all types of cancer by catching it early, before it has a chance to develop further or spread,” Wax said.
Similar to optical-coherence tomography, fa/LCI uses low-coherence interferometry to achieve depth resolution. While OCT produces a depth-resolved image of a sample, fa/LCI records the depth-resolved angular-scattering distribution. This information is used to determine the size and the density of scattered particles as a function of depth beneath the probe tip. The tip has an illumination fiber to deliver the near-IR light of a superluminescent diode at 830 nm to the sample and a coherent fiber bundle to collect the angular-scattering distribution from the sample (see figure).
The probe overlaps the angular-scattering distribution with a reference field, and an imaging spectrograph detects the mixed signal. The detected signal is processed in real time to produce the angular-scattering distribution versus depth in less than 100 ms. Processed data are compared with theoretical predictions to determine the nuclear diameter and density. The fa/LCI device detects irregularities in the nucleus of cells through changes in the way laser light scatters.
“The size and shape of cell nuclei are powerful indicators of a precancerous condition called dysplasia,” Wax said. “Typically, nuclei are a fairly consistent size. However, when you go down the road toward cancer, you get irregular and enlarged cell nuclei.”
In a recent study supported by the National Cancer Institute and the National Science Foundation, the Duke researchers demonstrated the probe’s effectiveness on human tissue. Wax’s fiber-optic device instantly and 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. In less than a second, the fa/LCI-enhanced version of an endoscope provided the clinical information required for diagnosis.
Wax and his colleagues looked at tissue removed from several patients and were able to get 100% sensitivity. They could detect precancer in the esophagus and distinguish it from normal tissue. If the preliminary success of the “optical biopsy” technique is confirmed through clinical trials supported by the National Cancer Institute later this year, it could ultimately provide a particular advantage for early diagnosis, treatment, and prevention of many types of cancer, according to Wax. His team also is conducting animal studies to test the feasibility of incorporating fa/LCI into instruments for examining the colon, lung, and other organs. The technique might also be used in the identification of early lung cancer.
Wax and his colleagues have licensed the technology from Duke and launched a company called Oncoscope to pursue the commercial development of fa/LCI devices. If all goes well, a new and improved endoscope might be ready for clinical use in three to five years, he said.