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.

Current methods for analysis of spectroscopic optical coherence tomography (SOCT) signals suffer from an inherent tradeoff between time (depth) and frequency (wavelength) resolution. Here, we present a dual window (DW) method for reconstructing time frequency distributions (TFDs) that applies two orthogonal Gaussian windows that independently determine the spectral and temporal resolution. The effectiveness of the method is demonstrated in simulations and in processing of measured OCT signals that contain fields which vary in time and frequency. The DW method yields TFDs that maintain high spectral and temporal resolution and are free from the artifacts and limitations commonly observed with other processing methods.

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.

Abstract. We have developed a novel dual-window approach for spectroscopic optical coherence tomography ͑OCT͒ measurements and applied it to probe nuclear morphology in tissue samples drawn from the hamster cheek pouch carcinogenesis model. The dualwindow approach enables high spectral and depth resolution simultaneously, allowing detection of spectral oscillations, which we isolate to determine the structure of cell nuclei in the basal layer of the epithelium. The measurements were executed with our parallel frequency domain OCT system, which uses light from a thermal source, providing high bandwidth and access to the visible portion of the spectrum. The structural measurements show a highly statistically significant difference between untreated ͑normal͒ and treated ͑hyperplastic/dysplastic͒ tissues, indicating the potential utility of this approach as a diagnostic method.

We present a new common path configuration Fourier domain low coherence interferometry (fLCI) optical system and demonstrate its capabilities by presenting results which determine the size of cell nuclei in a monolayer of T84 epithelial cells. The optical system uses a white light source in a modified Michelson interferometer and a spectrograph for detection of the mixed signal and reference fields. Depth resolution is obtained from the Fourier transform of the measured spectrum which provides the axial spatial cross-correlation between the signal and reference fields. The spectral dependence of scattering by the samples is determined by windowing the spectrum to measure the scattering amplitude as a function of wavenumber. We present evidence that fLCI accurately measures the longitudinal profile of cell nuclei rather than the transverse profile.