Angle-resolved low-coherence interferometry (a/LCI) is an optical technique which uses inverse models of light scattering to predict the size and density of cell nuclei, a significant biomarker of precancer. In recent years, substantial progress has occurred in a/LCI technology, particularly in novel instrumentation for the detection of dysplasia in the cervix and the esophagus. This abstract summarizes recent developments in a/LCI, with a focus on developments over the previous four years. Clinical studies in the cervix, novel optical instrumentation addressing the cervix and esophagus, and novel applications related to Alzheimer’s disease are discussed.
Optical coherence tomography (OCT) is currently recognized as the gold standard for identifying retinal structural abnormalities in ophthalmology. However, its availability is often limited to large eye centers and research labs due to its high cost and lack of portability. We present a low-cost, portable spectral-domain OCT system with a total cost of materials under $6,000. Compared to current commercial systems, our design offers 50% size reduction and over 80% cost reduction. Image acquisition interface is incorporated and displayed onto a mounted 7-inch touchscreen. Human retinal imaging is demonstrated, and performance is compared with a commercial OCT system. Based on contrast-to-noise ratio analysis, the low-cost OCT demonstrates comparable imaging capabilities.
Video endoscopy remains the most common means of examining the upper gastrointestinal tract. However, white-light widefield imagery is limited in diagnostic sensitivity and specificity for conditions such as Barrett’s esophagus. To provide cross-sectional imaging that yields more accurate diagnosis, optical coherence tomography (OCT) has been implemented for upper GI screening and diagnosis in several form factors, such as inflatable balloons and tethered capsules.
We now present an alternative configuration for esophageal OCT. Our OCT probe is contained within an articulating paddle that attaches to the end of an upper GI endoscope via flexible cuff. This arrangement allows regions of interest to be visually identified by the physician operating the endoscope and targeted for OCT imaging by application of the paddle.
The probe housing was 3D printed using biocompatible dental resin. The flexible cuff was also 3D printed using a silicone-based resin to allow a tight fit to the endoscope. The optical probe was a rotating fiber-optic design, consisting of a gradient-index lens and prism on the distal end, wound steel torque coil, a polymer sheath, and a fiber-optic rotary junction. The OCT system was a spectral domain configuration with custom spectrometer operating at 20,000 A-lines per second. The illumination source was a superluminescent diode centered at 1310 nm.
A clinical pilot study at the University of North Carolina Endoscopy Center is scheduled to begin imminently.
The early detection of cervical dysplasia enables early treatment, a critical factor in cancer prevention. In the United States, cervical cancer screening is age-based and includes cervical cytology with human papilloma virus (HPV) testing with referral to colposcopy for abnormal results. Colposcopy is used to visualize changes in the appearance of the transformation zone to direct biopsies which can confirm a diagnosis of dysplasia or cancer. Directed biopsies can be limited in detection of abnormalities because they represent a small area of the transformation zone and can be limited by provider expertise. Additionally, biopsies contribute to patient discomfort and anxiety awaiting for results.
We recently reported the first in vivo cervical data from angle-resolved low-coherence interferometry (a/LCI), an optical technique that measures nuclear size as a biomarker for dysplasia, which is well-suited for screening due to its high sensitivity and specificity and its non-invasive utilization. However, in order to target the single-point measurements of the a/LCI instrument, we aimed to construct a probe capable of mapping the cervical epithelium to identify the transformation zone between the ectocervical and endocervical epithelia, the location at which dysplasia is most likely to develop.
We termed this complementary technology multiplexed low-coherence interferometer (m/LCI). Thirty-six parallel fiber-optic interferometers were constructed to obtain optical depth profiles using spectral-domain LCI. Light from each channel is delivered to the cervix via a 6x6 fiber-optic bundle and a custom endoscopic probe. The depth-profile from each optical channel enables the identification of the ectocervix and endocervix.
A pilot study at Duke University (n=5) was followed by an ongoing clinical study at New York City Health + Hospitals/Jacobi (Bronx, New York) (current n=20, target n=50). We present the results from these first studies to demonstrate the feasibility of m/LCI as a means of identifying the transformation zone for screening of dysplasia.
The cervix is primarily composed of two types of epithelium: stratified squamous ectocervix and simple columnar endocervix. In between these two layers lies a metaplastic squamocolumnar junction commonly referred to as the transformation zone (T-zone). During puberty, the cervical epithelium undergoes dynamic changes including cervical ectropion and increased area and rates of metaplasia. Although these metaplastic changes have been linked to higher incidence of cervical cancer among young women, research in this field has been limited to surface analysis using computerized planimetry of colopophotographs.
Here, we present a novel multiplexed low coherence interferometry (mLCI) system for interrogating the cervical epithelium. The system is comprised of 6 parallel Mach-Zehnder interferometers in a time-multiplexed configuration that increases throughput by 6-fold to realize a combined 36-channel acquisition. A custom designed endoscopic handheld probe is used to collect sparsely sampled, depth-resolved scattering intensity profiles (A-scans) from a large field of view (25 x 25 mm) on the cervical epithelium in vivo. The instrument incorporates white light imaging through a plastic fiber bundle to co-register the mLCI A-scans to colpophotographs which are analyzed by a clinician to manually segment the cervical epithelium. Our preliminary data shows significant differences in characteristic A-scans from endocervical and ectocervical epithelium. These results demonstrate the feasibility of using mLCI as both a research tool for studying the relationship between cervical ectopy and cancer as well as a clinical instrument for identifying the at-risk T-zone on the cervix in vivo as a means to improve biopsy targeting. Further analysis will be performed to develop an algorithm for distinguishing the mLCI A-scans of endocervical, ectocervical, and metaplastic epithelium in real time.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.