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Biomedical subjects

Adam Wax

Publications and source records attributed to Adam Wax.

14 recordsLinked to original sources
PubMed2006

Fourier-domain angle-resolved low coherence interferometry through an endoscopic fiber bundle for light-scattering spectroscopy.

We present a novel endoscopic fiber bundle probe incorporated in a Fourier-domain angle-resolved low coherence interferometry system for the measurement of depth-resolved angular scattering distributions to permit the determination of scatterer size via elastic scattering properties. Depth resolution is achieved with a superluminescent diode via a Mach-Zehnder interferometer. The sample is illuminated with a collimated beam, and a Fourier plane image of the backscattered light is collected by a coherent fiber bundle. The angular scattering distribution relayed by the fiber bundle is mixed with the reference field and made to coincide with the input slit of an imaging spectrograph. The data collected are processed in real time, producing a depth-resolved angular scattering distribution in 0.37 s. The data are used to determine the sizes of polystyrene microspheres with subwavelength precision and accuracy.

Endoscopes↗
PubMed2005

Nuclear morphology measurements using Fourier domain low coherence interferometry.

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.

Journal Article↗
PubMed2005

Low-cost, scalable laser scanning module for real-time reflectance and fluorescence confocal microscopy.

We present a low-cost, high-speed, retrofitted laser scanning module for microscopy. The cage-mounted system, with various available fiber-coupled sources, offers a real-time imaging alternative to costly commercial systems with capabilities for conventional or confocal reflectance and fluorescence applications as well as advanced laser scanning microscopy implementations. Reflectance images of a resolution target and confocal images of fluorescent polystyrene beads are presented for system characterization. Confocal fluorescence image stacks of T84 epithelial cancer cells are presented to demonstrate application to biological studies. This laser scanning module is a flexible, scalable, high-speed alternative to commercial laser scanning systems suitable for applications requiring a simple imaging tool and for teaching laboratories.

Algorithms↗
PubMed2005

Improved interferometric detection of scattered light with a 4f imaging system.

We analyze the performance of three imaging systems to detect near-forward scattered light interferometrically by using a Mach-Zehnder geometry. The alignment of each system is demonstrated by measurement of the heterodyne efficiency and correlation of the angular width and field 1/e radius measurements of the sample beam. Measurements of angular-scattering data demonstrate the range of angles over which each system is effective. Of the three systems analyzed, the 4f imaging system is determined to be most effective, because it accurately reproduces both the phase and the amplitude of the scattered field at the detector.

Equipment Design↗
PubMed2005

Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer.

Harmonic phase-dispersion microscopy (PDM) is a new imaging technique in which contrast is provided by differences in refractive index at two harmonically related wavelengths. We report a new configuration of the harmonic phase-dispersion microscope in a Mach-Zehnder geometry as an instrument for imaging biological samples. Several improvements on the earlier design are demonstrated, including a single-pass configuration and acousto-optic modulators for generating the heterodyne signals without mechanical arm scanning. We demonstrate quantitative phase-dispersion images of test structures and biological samples.

Equipment Design↗
PubMed2005

Low-coherence light-scattering calculations for polydisperse size distributions.

The calculation of angular light-scattering distributions is considered for low-coherence light incident on a polydisperse particle size distribution of scatterers. As low-coherence light is now commonly used in interferometry schemes when applied to biomedical imaging, the difference between detecting scattered intensity and interferometrically detecting the scattered field is examined. An expression is derived that allows the presence of multiple wavelengths lambda and particle sizes d to be described by a single distribution in the size parameter x = pi d/lambda, which simplifies numerical calculations. The applicability of this expression is examined numerically.

Journal Article↗
PubMed2003

Fourier-domain low-coherence interferometry for light-scattering spectroscopy.

We present a novel method for obtaining depth-resolved spectra for determining scatterer size through elastic-scattering properties. Depth resolution is achieved with a white-light source in a Michelson interferometer with the mixed signal and reference fields dispersed by a spectrograph. The spectrum is Fourier transformed to yield the axial spatial cross correlation between the signal and reference fields with near 1-microm depth resolution. Spectral information is obtained by windowing to yield the scattering amplitude as a function of wave number. The technique is demonstrated by determination of the size of polystyrene microspheres in a subsurface layer with subwavelength accuracy. Application of the technique to probing the size of cell nuclei in living epithelial tissues is discussed.

Fourier Analysis↗
PubMed2003

In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry.

We present a quantitative study of the nuclear morphometry of epithelial cells in an animal model of esophageal carcinogenesis. Changes in the size and texture of cell nuclei as a result of neoplastic transformation and chemopreventive action are observed in situ using a new optical technique, angle-resolved low-coherence interferometry (a/LCI). The capabilities of a/LCI are demonstrated via quantitative in situ measurements of the nuclear morphometry of basal epithelial cells, approximately 50-100 microm beneath the tissue surface without the need for exogenous contrast agents or tissue fixation. The measurements quantify changes in nuclear size, characterized by average diameter, and nuclear texture, characterized by fractal dimension of the subcellular structures. Using this technique, we observed changes in the morphometry of rat esophageal epithelial cells in response to treatment with the carcinogen N-nitrosomethylbenzylamine. In addition, morphometric changes were observed in the esophagi of rats treated with N-nitrosomethylbenzylamine and two chemopreventive agents, difluoromethylornithine and perillyl alcohol. These agents induced either apoptosis in the basal epithelium (difluoromethylornithine) or both apoptosis and vacuolation of basal epithelial cells (perillyl alcohol). Vacuolation was associated with cellular toxicity. The light-scattering measurements were compared with histological images of the same tissues. The potential of a/LCI as a noninvasive means to investigate the development of epithelial neoplasia and for tracking the efficacy of chemopreventive agents appears high. This technique also may provide a new screening tool for intraepithelial neoplasia.

Animals↗
PubMed2002

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. In addition, we obtain information about the cellular organization and substructure by examining the spatial correlations within the monolayer. A remarkable finding is that the spatial correlations over small length scales take the form of an inverse power law, indicating the fractal nature of the packing of the subcellular structures. We also identify spatial correlations on a scale large compared with the size of a cell, indicating an overlying order within the monolayer.

Biophysics↗
PubMed2002

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. The effects of multiple scattering as a function of penetration depth in the medium are analyzed. We also present various considerations for extending this technique to determining structural information in biological tissues, such as the effects of a distribution of particle sizes and the need to average out speckle contributions.

Interferometry↗
PubMedDate not supplied

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

Angle-resolved low-coherence interferometry (a/LCI) 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 microm 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 (DFMO) 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.

Animals↗
PubMedDate not supplied

Label-free measurement of microbicidal gel thickness using low-coherence interferometry.

Spectral-domain low-coherence interferometry (LCI) was used to measure the thickness of microbicidal gels applied to a cylindrical calibration test socket. Microbicides are topical formulations containing active ingredients targeted to inhibit specific pathogens that are currently under development for application to the epithelial lining of the lower female reproductive tract to combat sexually transmitted infections such as HIV. Understanding the deployment and drug delivery of these formulations is vital to maximizing their effectiveness. Previously, in vivo measurements of microbicidal formulation thickness were assessed using fluorescence measurements of fluorescein-labeled gels via an optical endoscope-based device. Here we present an LCI-based device that measures the thickness of a formulation without the use of any exogenous agents by analyzing the interference pattern generated between the reflections from the front and back surface of the sample. Results are presented that validate the effectiveness and performance of the LCI measurement in a clinically relevant system as compared to an existing fluorescence-based method. The impact of the new LCI-based design on in vivo measurements is discussed.

Anti-Infective Agents↗
PubMedDate not supplied

Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) enables depth-resolved measurements of scattered light that can be used to recover subsurface structural information, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed angular data, based on the justification that the coherent scattering must necessarily occur over length scales greater than the cell size. To fully study this effect, results of experiments designed to test the validity of this approach are now presented. The a/LCI technique is used to examine light scattered by regular cell arrays, created using stamped adhesive micropatterned substrates. By varying the array spacing, it is demonstrated that cell-to-cell correlations have a predictable effect on light scattering distributions. These results are compared to image analysis of fluorescence micrographs of the cell array samples. The a/LCI results show that the impact of coherent scattering on nuclear morphology measurements can be eliminated through data filtering.

Algorithms↗