Development of a portable frequency-domain angle-resolved low coherence interferometry system

Abstract

Improved methods for detecting dysplasia, or pre-cancerous growth, are a current clinical need. Random biopsy and subsequent diagnosis through histological analysis is the current gold standard in endoscopic surveillance for dysplasia. However, this approach only allows limited examination of the at-risk tissue and has the drawback of a long delay in time-to-diagnosis. In contrast, optical scattering spectroscopy methods offer the potential to assess cellular structure and organization <i>in vivo</i>, thus allowing for instantaneous diagnosis and increased coverage of the at-risk tissue. Angle-resolved low coherence interferometry (a/LCI), a novel scattering spectroscopy technique, combines the ability of low-coherence interferometry to isolate scattered light from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales, specifically by analyzing the angular distribution of the backscattered light. In application to examining tissue, a/LCI enables depthresolved quantitative measurements of changes in the size and texture of cell nuclei, which are characteristic biomarkers of dysplasia. The capabilities of a/LCI were demonstrated initially by detecting pre-cancerous changes in epithelial cells within intact, unprocessed, animal tissues. Recently, we have developed a new frequency-domain a/LCI system, with sub-second acquisition time and a novel fiber optic probe. Preliminary results using the fa/LCI system to examine human esophageal tissue in Barrett's esophagus patients demonstrate the clinical viability of the approach. In this paper, we present a new portable system which improves upon the design of the fa/LCI system to allow for higher quality data to be collected in the clinic. Accurate sizing of polystyrene microspheres and cell nuclei from <i>ex vivo</i> human esophageal tissue is presented. These results demonstrate the promise of a/LCI as a clinically viable diagnostic tool.