Nuclear Morphology Measurements with Angle-Resolved Low Coherence Interferometry For Application To Cell Biology And Early Cancer Detection

Abstract

Abstract. The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents.

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

“…A significant contribution from nuclear backscattering and clear correlation of dysplasia with nuclear size has been demonstrated in earlier studies 12–16,22–24 . Direct comparison of the nuclear size distribution extracted from the backscattering signal to that of histological examination of the corresponding H&E stained sections was also demonstrated 17,18 .…”

“…The largest is a diffuse background signal from submucosal tissue, next is scattering by small organelles and lastly a relatively small backscattered component from epithelial cell nuclei. The submucosal background can be excluded by one of various gating techniques 12–18 and the smaller organelles have a very different scattering spectral dependence than that of the nuclei. Elastic light scattering can also be used to measure other cellular compartments, such as mitochondria 19 , whose spectra 20 are sufficiently different from that of nuclei to be distinguished 21 .…”

Phase-function corrected diffusion model for diffuse reflectance of a pencil beam obliquely incident on a semi-infinite turbid medium

“…In this paper, we extend their work to include a pencil beam obliquely incident on a semi-infinite turbid medium and investigate the accuracy of the models by comparing with Monte Carlo simulations. The case of oblique incidence is of noteworthy importance as a number of techniques rely on angled illumination, including oblique incidence reflectometry (1-3, 22-24), angled low-coherence interferometry (25,26), among others (8). In this article, we focus on applications to oblique-incidence reflectometry, a technique which has seen great success in some clinical studies (3,27).…”

Phase-function corrected diffusion model for diffuse reflectance of a pencil beam obliquely incident on a semi-infinite turbid medium

“…In this paper, we extend their work to include a pencil beam obliquely incident on a semi-infinite turbid medium, and investigate the accuracy of the models by comparing them with Monte Carlo simulations. The case of oblique incidence is of noteworthy importance as a number of techniques rely on angled illumination, including oblique incidence reflectometry (OIR) and [1][2][3][4][5][6][29][30][31] angled low-coherence interferometry, [32][33][34][35][36][37][38] among others. 11 In this article, we focus on the applications of OIR, a technique that has seen great success in some clinical studies.…”