Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry

Abstract

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.

Rapid, depth-resolved light scattering measurements using Fourier domain, angle-resolved low coherence interferometry

“…We note that faLCI is a new data acquisition technique for a/LCI. As such the introduction of faLCI does not impact the efficacy of the analysis method used to determine structure from a/LCI measurements, a proven process for determining structure based on elastic scattering properties [2][3][4][5][6], including accounting for a distribution in the size of scatterers [2][3][4] and determining the size of sub-surface epithelial cell nuclei [3][4][5]. We emphasize that it is the decreased data acquisition time of faLCI which opens the possibility of clinical application.…”

“…The a/LCI technique combines the ability of low coherence interferometry to detect singly scattered light from sub-surface sites with the capability of light scattering methods to obtain structural information with sub-wavelength precision and accuracy [2,4]. a/LCI has been successfully applied to measuring cellular morphology in tissues [3] and in vitro [4] as well as diagnosing intraepithelial neoplasia [5] and assessing the efficacy of chemopreventive agents [6] in an animal model of carcinogenesis. The latter study was significant because it used a/ LCI to prospectively grade tissue samples without tissue processing, demonstrating the potential of the technique as a biomedical diagnostic.…”

Comparative study of the angle-resolved backscattering properties of collagen fibers in bovine tendon and cartilage

“…The measurement of angle-resolved backscatter has generated considerable interest when applied to cells as it offers the potential to estimate the size of spherical scatterers such as the cell nuclei. 7 Our study has been to extend this approach to wide angles of optical backscattering from fibrous connective tissues containing collagen fibers of different size and to demonstrate significant differences between scattering profiles of bovine tendon and cartilage. We hypothesize that the differences in the angle-resolved backscattering profiles arise due to differences in the collagen fiber diameter and packing arrangement.…”

“…5 More details on quantitative studies on polarized light interaction in tissues is given here. 6 It has been demonstrated that angle-resolved backscatter can accurately size the spherical scatterers, with applications, e.g., in detecting abnormal cell nuclei as reported by Wax et al 7 The nature of the optical backscattering differences between different types of collagen molecules arise due to the difference in the underlying molecular organization: Type I collagen fibers in tendon and Type II collagen fibers in articular cartilage. 8 In this paper, we present a comparative study of the optical backscattering properties obtained using an OCT system over different angles of illumination, of the different scatterers type involved in the collagen fiber networks of bovine tendon and cartilage samples.…”

Nuclear morphology measurements using Fourier domain low coherence interferometry

“…Elastic light scattering has been previously demonstrated as a means of probing cellular morphology [1,2] and diagnosing dysplasia [3][4][5], a pre-cancerous tissue state. Low-coherence interferometry (LCI) has been employed as a means for detecting singly scattered light from sub-surface sites for light scattering spectroscopy.…”