Angle-resolved low-coherence interferometry ͑a/LCI͒ is used to obtain quantitative, depth-resolved nuclear morphology measurements. We compare the average diameter and texture of cell nuclei in rat esophagus epithelial tissue to grading criteria established in a previous a/LCI study to prospectively grade neoplastic progression. We exploit the depth resolution of a/LCI to exclusively examine the basal layer of the epithelium, approximately 50 to 100 m beneath the tissue surface, without the need for exogenous contrast agents, tissue sectioning, or fixation. The results of two studies are presented that compare the performance of two a/LCI modalities. Overall, the combined studies show 91% sensitivity and 97% specificity for detecting dysplasia, using histopathology as the standard. In addition, the studies enable the effects of dietary chemopreventive agents, difluoromethylornithine ͑DFMO͒ and curcumin, to be assessed by observing modulation in the incidence of neoplastic change. We demonstrate that a/LCI is highly effective for monitoring neoplastic change and can be applied to assessing the efficacy of chemopreventive agents in the rat esophagus.

We outline the process for determining the morphology of subsurface epithelial cell nuclei using depth-resolved light scattering measurements. The measurements are accomplished using a second generation angle-resolved low coherence interferometry system. The new system greatly improves data acquisition and analysis times compared to the initial prototype system. The calibration of the new system is demonstrated in scattering studies to determine the size distribution of polystyrene microspheres in a turbid sample. The process for determining the size of cell nuclei is discussed by analyzing measurements of basal cells in a sub-surface layer of intact, unstained epithelial tissue.

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