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.

In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry.

BACKGROUND: Monitoring of patients with Barrett's esophagus (BE) for dysplasia, currently done by systematic biopsy, can be improved through increasing the proportion of at-risk tissue examined. OBJECTIVE: Optical biopsy techniques, which do not remove the tissue but interrogate the tissue with light, offer a potential method to improve the monitoring of BE. Frequency-domain angle resolved low-coherence interferometry (fa/LCI) is an optical spectroscopic technique applied through an endoscopic fiber bundle and measures the depth-resolved nuclear morphology of tissue, a key biomarker for identifying dysplasia. The aim of the study was to assess the diagnostic capability of fa/LCI for differentiating healthy and dysplastic tissue in patients with BE. METHODS: Depth-resolved angular scattering data are acquired by using fa/LCI from tissue excised from 3 patients who had esophagogastrectomy. The data are processed to determine the average nuclear size and density as a function of depth beneath the tissue surface. These data are compared with the pathologic classification of the tissue. MAIN OUTCOME MEASUREMENTS: Average of depth-resolved nuclear diameter and nuclear density measurements in tissue samples. RESULTS: Upon comparison to pathologic diagnosis, the fa/LCI data results report the nuclear atypia characteristic of dysplasia in the epithelial tissue. Examination of the average nuclear morphology over the superficial 150 mum results in complete separation between healthy columnar and BE dysplastic tissues. LIMITATIONS: Lack of in vivo data; lack of nondysplastic BE data because of limited sample size. CONCLUSIONS: In complicated tissue structures, such as BE, depth-resolved nuclear morphology measurements provided an excellent means to identify dysplasia. The preliminary results demonstrate the great potential for the in vivo application of fa/LCI as a targeting mechanism for physical biopsy in patients with BE.

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.