Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 μm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.
We present a novel Fourier-domain angle-resolved low-coherence interferometry (a /LCI) fiber probe designed for in vivo clinical application in gastrointestinal endoscopy. The a/LCI technique measures the depth-resolved angular scattering distribution to determine the size distribution and optical density of cell nuclei for assessing the health of epithelial tissues. Clinical application is enabled by an endoscopic fiber-optic probe that employs a 2.3-m-long coherent fiber bundle and is compatible with the standard 2.8-mm-diam biopsy channel of a gastroscope. The probe allows for real-time data acquisition by collecting the scattering from multiple angles in parallel, enabled by the Fourier domain approach. The performance of the probe is characterized through measurement of critical parameters. The depth-resolved sizing capability of the system is demonstrated using single- and double-layer microsphere phantoms with subwavelength sizing precision and accuracy achieved. Initial results from a clinical feasibility test are also presented to show in vivo application in the human esophagus.
Improved methods for detecting dysplasia, or pre-cancerous growth are a current clinical need, particularly in the
esophagus. The currently accepted method of random biopsy and histological analysis provides only a limited
examination of tissue in question while being coupled with a long time delay for diagnosis. Light scattering
spectroscopy, in contrast, allows for inspection of the cellular structure and organization of tissue in vivo.
Fourier-domain angle-resolved low-coherence interferometry (a/LCI) is a novel light scattering spectroscopy
technique that provides quantitative depth-resolved morphological measurements of the size and optical density of
the examined cell nuclei, which are characteristic biomarkers of dysplasia. Previously, clinical viability of the a/LCI
system was demonstrated through analysis of ex vivo human esophageal tissue in Barrett's esophagus patients using
a portable a/LCI, as was the development of a clinical a/LCI system. Data indicating the feasibility of the technique
in other organ sites (colon, oral cavity) will be presented.
We present an adaptation of the a/LCI system that will be used to investigate the presence of dysplasia in vivo in
Barrett's esophagus patients.
We propose a fiber-optic system for Fourier-domain angle-resolved low coherence interferometry. The system is
based on singlemode fiber couplers and employs a scanning fiber to collect the angular scattering distribution of the
sample. The measured distribution is then fitted to Mie theory to estimate the size of the scatterers. Depth resolution
is achieved with Fourier-domain low coherence Mach-Zehnder interferometry. The sample arm of the interferometer
illuminates the specimen with polarized light and collects back-scattered light from the sample. The probe's optical
performance is evaluated and its depth-resolved sizing capability is demonstrated with subwavelength accuracy
using a two-layer microsphere phantom.
Methods for the optimization of a/LCI for clinical use are presented. First, the use of the T-matrix light
scattering model to simulate scattering from spheroidal particles is presented as a more appropriate simulation of
cell nuclei scattering than the previously used Mie theory. In addition, the use of a broadband light source with a
bandwidth greater than 50nm similar to those utilized in OCT applications is demonstrated. Accurate sizing of
scatterers in tissue phantoms containing stretched and unstretched polystyrene microspheres along with
measurements of unstretched polystyrene microspheres in solution are presented, demonstrating advances in system
performance and design. In addition, preliminary human in vivo esophageal tissue data are presented.
Improved methods for detecting dysplasia, or pre-cancerous growth are a current clinical need, particularly in
the esophagus. The currently accepted method of random biopsy and histological analysis provides only a limited
examination of tissue in question while being coupled with a long time delay for diagnosis. Optical scattering
spectroscopy, in contrast, allows for inspection of the cellular structure and organization of tissue in vivo. Fourierdomain
angle-resolved low-coherence interferometry (a/LCI) is a novel scattering spectroscopy technique that provides
quantitative depth-resolved morphological measurements of the size and optical density of the examined cell nuclei,
which are characteristic biomarkers of dysplasia. Previously, the clinical viability of the a/LCI system was demonstrated
by analysis of ex vivo human esophageal tissue in Barrett's esophagus patients using a portable a/LCI system. We
present an adaptation of the portable a/LCI instrument that can be used in the accessory channel of a gastroscope,
allowing for in vivo measurements to be taken. Modifications to the previous generation system include the use of an
improved imaging spectrometer allowing for subsecond acquisition times and the redesign of the delivery fiber and
imaging optics in order to fit in the accessory channel of a gastroscope. Accurate sizing of polystyrene microspheres and
other preliminary results are presented, demonstrating promise as a clinically viable tool.
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