Low-coherent backscattering spectroscopy for tissue characterization.

Although the phenomenon of coherent backscattering (CBS) in nonbiological media has generated substantial research interest, observing CBS in biological tissue has been extremely difficult. Here we show that the combination of low-spatial-coherence, broadband illumination, and low-temporal-coherence, spectrally resolved detection significantly facilitates CBS observation in biological tissue and other random media with long-transport mean-free path lengths, which have been previously beyond the reach of conventional CBS investigations. Furthermore, we demonstrate that depth-selective, speckle-free, low-coherent backscattering spectroscopy has the potential to diagnose the earliest, previously undetectable, precancerous alterations in the colon by means of probing short light paths.

Investigation of depth selectivity of polarization gating for tissue characterization.

Polarization gating has been widely used to selectively probe the structure of superficial biological tissue. However, the penetration depth selectivity of polarization gating has not been well understood. Using polarized light Monte Carlo simulations, we investigated how the optical properties of a scattering medium and light collection geometry affect the penetration depth of polarization gating.

Optical analysis of nanoparticles via enhanced backscattering facilitated by 3-D photonic nanojets.

We report the phenomenon of ultra-enhanced backscattering of visible light by nanoparticles facilitated by the 3-D photonic nanojet - a sub-diffraction light beam appearing at the shadow side of a plane-waveilluminated dielectric microsphere. Our rigorous numerical simulations show that backscattering intensity of nanoparticles can be enhanced up to eight orders of magnitude when locating in the nanojet. As a result, the enhanced backscattering from a nanoparticle with diameter on the order of 10 nm is well above the background signal generated by the dielectric microsphere itself.

Exact solution of Maxwell's equations for optical interactions with a macroscopic random medium: addendum.

This Addendum provides a revised set of figures containing converged numerical data for total scattering cross section (TSCS), replacing the figures in our recent publication [Opt. Lett. 29, 1393 (2004)].

Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles.

We report the development and validation of the equiphase-sphere (EPS) approximation for calculating the total-scattering cross-section (TSCS) spectra of inhomogeneous microparticles having complex interior structures. We show that this closed-form, analytical approximation can accurately model the TSCS of randomly inhomogeneous spherical particles having internal refractive index variations with geometrical scales spanning from nanometers (i.e.

Equiphase-sphere approximation for analysis of light scattering by arbitrarily shaped nonspherical particles.

We extend the previously proposed concept of equiphase sphere (EPS) to analyze light-scattering properties of arbitrarily shaped particles. Our analyses based on the Wentzel-Kramers-Brillouin technique and numerical studies based on the finite-difference time-domain method demonstrate that a wide range of irregularly shaped particles can be approximated as their equivalent equiphase ellipsoids to determine their total scattering cross-section (TSCS) spectra. As a result, a simple expression given by the EPS approximation can be used to calculate the TSCS spectra of these particles.

Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension.

Objectives: Emerging evidence implicates the SNAIL family of transcriptional repressors in cancer development; however, the role of SNAIL in colorectal cancer has not been established. To investigate the importance of SNAIL in colorectal carcinogenesis, we examined the phenotypic and cellular consequences of SNAIL down-regulation in the MIN mouse.

Methods: Twenty-eight male MIN mice were randomized to treatment with an antisense phosphorodiamidate morpholino oligomer (AS-PMO) to SNAIL, saline, or a scrambled sequence control for 6 weeks.

Coherent backscattering spectroscopy.

Coherent backscattering (CBS) of light in random media has been previously investigated by use of coherent light sources. Here we report a novel method of CBS measurement that combines low spatial coherence, broadband illumination, and spectrally resolved detection. We show that low spatial coherence illumination leads to an anomalously broad CBS peak and a dramatic speckle reduction; the latter is further facilitated by low temporal coherence detection.

Exact solution of Maxwell's equations for optical interactions with a macroscopic random medium.

We report what we believe to be the first rigorous numerical solution of the two-dimensional Maxwell equations for optical propagation within, and scattering by, a random medium of macroscopic dimensions. Our solution is based on the pseudospectral time-domain technique, which provides essentially exact results for electromagnetic field spatial modes sampled at the Nyquist rate or better. The results point toward the emerging feasibility of direct, exact Maxwell equations modeling of light propagation through many millimeters of biological tissues.

Analytical techniques for addressing forward and inverse problems of light scattering by irregularly shaped particles.

Understanding light scattering by nonspherical particles is crucial in modeling the transport of light in realistic structures such as biological tissues. We report the application of novel analytical approaches based on modified Wentzel-Kramers-Brillouin and equiphase-sphere methods that facilitate accurate characterization of light scattering by a wide range of irregularly shaped dielectric particles. We also demonstrate that these approaches have the potential to address the inverse-scattering problem by means of a spectral analysis of the total scattering cross section of arbitrarily shaped particles.

Photonic nanojet enhancement of backscattering of light by nanoparticles: a potential novel visible-light ultramicroscopy technique.

We report what we believe to be the first evidence of localized nanoscale photonic jets generated at the shadow-side surfaces of micronscale, circular dielectric cylinders illuminated by a plane wave. These photonic nanojets have waists smaller than the diffraction limit and propagate over several optical wavelengths without significant diffraction. We have found that such nanojets can enhance the backscattering of visible light by nanometer-scale dielectric particles located within the nanojets by several orders of magnitude.

Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis.

Background & Aims: Identification of preneoplastic changes in histologically normal epithelium (the "field effect") could provide a powerful screening tool for colorectal cancer. However, to date, reliable detection has not been possible. We have recently developed a new generation of optical technology, 4-dimensional elastic light-scattering fingerprinting (4D-ELF), which enables us to probe the nanoscale/microscale architecture of living cells.

Spectroscopic diagnosis and imaging of invisible pre-cancer.

The theme of this paper is the use of optical spectroscopy to diagnose invisible pre-cancer in patients undergoing endoscopy and similar medical procedures. We describe three techniques that provide diagnostic information and two instruments to implement them, the FastEEM for studying small regions of tissue and the LSS (light scattering spectroscopy) imaging system for wide-area surveillance. The FastEEM is an optical fiber clinical device that collects spectra of reflected light and fluorescence at multiple excitation wavelengths from the tissue, all in a fraction of a second.

Concept of the equiphase sphere for light scattering by nonspherical dielectric particles.

We introduce the concept of the equiphase sphere for light scattering by nonspherical dielectric particles. This concept facilitates the derivation of a simple analytical expression for the total scattering cross section of such particles. We tested this concept for spheroidal particles and obtained a bound on the minor-to-major axis ratio for the valid application of this technique.

Equivalent volume-averaged light scattering behavior of randomly inhomogeneous dielectric spheres in the resonant range.

Finite-difference time-domain numerical experiments and supporting analyses demonstrate that the spectral dependence of the total scattering cross sections of randomly inhomogeneous dielectric spheres of sizes in the resonant range closely resemble those of their homogeneous counterparts that have a volume-averaged refractive index. This result holds even for the extreme case in which the refractive index within an inhomogeneous sphere varies randomly over the range 1.0-2.

Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma.

Background: Understanding the development and progression of head and neck squamous cell carcinoma is key in the quest for the early diagnosis and prevention of this type of malignancy. The current study correlated early biochemical and histologic changes in oral tissue with spectral features in fluorescence, reflectance, and light scattering spectra acquired in vivo to diagnose early stages of oral malignancies.

Methods: A total of 91 tissue sites from 15 patients with varying degrees of malignancy (normal, dysplastic, and cancerous sites) and 8 healthy volunteers were analyzed with 3 spectroscopic techniques.

Determination of particle size by using the angular distribution of backscattered light as measured with low-coherence interferometry.

We employ a novel interferometer to measure the angular distribution of light backscattered by a turbid medium. Through comparison of the measured data with the predictions of Mie theory, we are able to determine the size of the scatterers comprising the medium with subwavelength precision. As the technique is based on low-coherence interferometry, we are able to examine the evolution of the angular distribution of scattered light as it propagates into the medium.

Cellular organization and substructure measured using angle-resolved low-coherence interferometry.

We measure the organization and substructure of HT29 epithelial cells in a monolayer using angle-resolved low-coherence interferometry. This new technique probes cellular structure by measuring scattered light, as in flow cytometry, but offers an advantage in that the structure can be examined in situ, avoiding the need to disrupt the cell monolayer. We determine the size distribution of the cell nuclei by fitting measured light-scattering spectra to the predictions of Mie theory.

Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo.

Objective: The objective of this study was to assess the potential of 3 spectroscopic techniques (intrinsic fluorescence, diffuse reflectance, and light scattering) individually and in combination (trimodal spectroscopy) for the detection of cervical squamous intraepithelial lesions.

Study Design: The study was conducted with 44 patients who underwent colposcopy for the evaluation of an abnormal Papanicolaou smear. Fluorescence and reflectance spectra were collected from colposcopically normal and abnormal sites and analyzed to extract quantitative information about tissue biochemistry and morphologic condition.

Imaging human epithelial properties with polarized light-scattering spectroscopy.

Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology developed to probe the structure of living epithelial cells in situ without need for tissue removal. LSS makes it possible to distinguish between single backscattering from epithelial-cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative information about the epithelial-cell nuclei such as nuclear size, degree of pleomorphism, degree of hyperchromasia and amount of chromatin.

Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus.

Background & Aims: The aim of this study was to assess the potential of 3 spectroscopic techniques (fluorescence, reflectance, and light-scattering spectroscopy) individually and in combination, for evaluating low- and high-grade dysplasia in patients with Barrett's esophagus (BE).

Methods: Fluorescence spectra at 11 excitation wavelengths and a reflectance spectrum were acquired in approximately 1 second from each site before biopsy using an optical fiber probe. The measured fluorescence spectra were combined with the reflectance spectra to extract the intrinsic tissue fluorescence.

Endoscopic detection of dysplasia in patients with Barrett's esophagus using light-scattering spectroscopy.

Background & Aims: We conducted a study to assess the potential of light-scattering spectroscopy (LSS), which can measure epithelial nuclear enlargement and crowding, for in situ detection of dysplasia in patients with Barrett's esophagus.

Methods: Consecutive patients with suspected Barrett's esophagus underwent endoscopy and systematic biopsy. Before biopsy, each site was sampled by LSS using a fiberoptic probe.

Determination of dimethylated arginines in human plasma by high-performance liquid chromatography.

Using high-performance liquid chromatography (HPLC) with multigradient elution, N(G),N(G)-dimethyl-L-arginine (asymmetric-DMA, ADMA) and N(G),N'(G)-dimethyl-L-arginine (symmetric-DMA, SDMA) can be separated from human plasma samples. The dimethylarginine compounds in plasma, after extraction with a cation-exchange column, are converted to fluorescent derivatives with o-phthaldialdehyde (OPA) in an alkaline medium and the derivatives are separated simultaneously within 50 min on a reversed-phase column (Ultracarb 3 ODS(20)). The recoveries of ADMA and SDMA are over 80% and the method permits quantitative determination of dimethylated arginines at concentrations as low as 0.