Ryan L. Shelton

Optical coherence tomography for advanced screening in the primary care office.

Optical coherence tomography (OCT) has long been used as a diagnostic tool in the field of ophthalmology. The ability to observe microstructural changes in the tissues of the eye has proved very effective in diagnosing ocular disease. However, this technology has yet to be introduced into the primary care office, where indications of disease are first encountered. We have developed a portable, handheld imaging probe for use in the primary care setting and evaluated its tissue site accessibility, ability to observe diseased tissue, and screening capabilities in in vivo human patients, particularly for pathologies related to the eye, ear and skin. Various stages of diabetic retinopathy were investigated using the handheld probe and early-stage diabetic retinopathy was flagged as abnormal from the OCT images. At such early stages of disease, it is difficult to observe abnormalities with the limited tools that are currently available to primary care physicians. These results indicate that OCT shows promise to transform from being a diagnostic technology in the medical and surgical specialities to a screening technology in the primary care office and at the front-line of healthcare.

Noninvasive depth‐resolved optical measurements of the tympanic membrane and middle ear for differentiating otitis media

In this study, optical coherence tomography (OCT) is used to noninvasively and quantitatively determine tympanic membrane (TM) thickness and the presence and thickness of any middle‐ear biofilm located behind the TM. These new metrics offer the potential to differentiate normal, acute, and chronic otitis media (OM) infections in pediatric subjects.

Intraoperative optical coherence tomography for assessing human lymph nodes for metastatic cancer

BackgroundEvaluation of lymph node (LN) status is an important factor for detecting metastasis and thereby staging breast cancer. Currently utilized clinical techniques involve the surgical disruption and resection of lymphatic structure, whether nodes or axillary contents, for histological examination. While reasonably effective at detection of macrometastasis, the majority of the resected lymph nodes are histologically negative. Improvements need to be made to better detect micrometastasis, minimize or eliminate lymphatic disruption complications, and provide immediate and accurate intraoperative feedback for in vivo cancer staging to better guide surgery.MethodsWe evaluated the use of optical coherence tomography (OCT), a high-resolution, real-time, label-free imaging modality for the intraoperative assessment of human LNs for metastatic disease in patients with breast cancer. We assessed the sensitivity and specificity of double-blinded trained readers who analyzed intraoperative OCT LN images for presence of metastatic disease, using co-registered post-operative histopathology as the gold standard.ResultsOur results suggest that intraoperative OCT examination of LNs is an appropriate real-time, label-free, non-destructive alternative to frozen-section analysis, potentially offering faster interpretation and results to empower superior intraoperative decision-making.ConclusionsIntraoperative OCT has strong potential to supplement current post-operative histopathology with real-time in situ assessment of LNs to preserve both non-cancerous nodes and their lymphatic vessels, and thus reduce the associated risks and complications from surgical disruption of lymphoid structures following biopsy.

Real-time automated thickness measurement of the in vivo human tympanic membrane using optical coherence tomography

BACKGROUND Otitis media (OM), an infection in the middle ear, is extremely common in the pediatric population. Current gold-standard methods for diagnosis include otoscopy for visualizing the surface features of the tympanic membrane (TM) and making qualitative assessments to determine middle ear content. OM typically presents as an acute infection, but can progress to chronic OM, and after numerous infections and antibiotic treatments over the course of many months, this disease is often treated by surgically inserting small tubes in the TM to relieve pressure, enable drainage, and provide aeration to the middle ear. Diagnosis and monitoring of OM is critical for successful management, but remains largely qualitative. METHODS We have developed an optical coherence tomography (OCT) system for high-resolution, depth-resolved, cross-sectional imaging of the TM and middle ear content, and for the quantitative assessment of in vivo TM thickness including the presence or absence of a middle ear biofilm. A novel algorithm was developed and demonstrated for automatic, real-time, and accurate measurement of TM thickness to aid in the diagnosis and monitoring of OM and other middle ear conditions. The segmentation algorithm applies a Hough transform to the OCT image data to determine the boundaries of the TM to calculate thickness. RESULTS The use of OCT and this segmentation algorithm is demonstrated first on layered phantoms and then during real-time acquisition of in vivo OCT from humans. For the layered phantoms, measured thicknesses varied by approximately 5 µm over time in the presence of large axial and rotational motion. In vivo data also demonstrated differences in thicknesses both spatially on a single TM, and across normal, acute, and chronic OM cases. CONCLUSIONS Real-time segmentation and thickness measurements of image data from both healthy subjects and those with acute and chronic OM demonstrate the use of OCT and this algorithm as a robust, quantitative, and accurate method for use during real-time in vivo human imaging.

Detection of retinal blood vessel changes in multiple sclerosis with optical coherence tomography

Although retinal vasculitis is common in multiple sclerosis (MS), it is not known if MS is associated with quantitative abnormalities in retinal blood vessels (BVs). Optical coherence tomography (OCT) is suitable for examining the integrity of the anterior visual pathways in MS. In this paper we have compared the size and number of retinal blood vessels in patients with MS, with and without a history of optic neuritis (ON), and control subjects from the cross-sectional retinal images from OCT. Blood vessel diameter (BVD), blood vessel number (BVN), and retinal nerve fiber layer thickness (RNFLT) were extracted from OCT images collected from around the optic nerves of 129 eyes (24 control, 24 MS + ON, 81 MS-ON) of 71 subjects. Associations between blood vessel metrics, MS diagnosis, MS disability, ON, and RNFLT were evaluated using generalized estimating equation (GEE) models. MS eyes had a lower total BVD and BVN than control eyes. The effect was more pronounced with increased MS disability, and persisted in multivariate models adjusting for RNFLT and ON history. Twenty-nine percent (29%) of MS subjects had fewer retinal blood vessels than all control subjects. MS diagnosis, disability, and ON history were not associated with average blood vessel size. The relationship between MS and lower total BVD/BVN is not accounted for by RNFLT or ON. Further study is needed to determine the relationship between OCT blood vessel metrics and qualitative retinal blood vessel abnormalities in MS.

Sensor-Based Technique for Manually Scanned Hand-Held Optical Coherence Tomography Imaging

Hand-held optical coherence tomography (OCT) imaging probes offer flexibility to image sites that are otherwise challenging to access. While the majority of hand-held imaging probes utilize galvanometer- or MEMS-scanning mirrors to transversely scan the imaging beam, these probes are commonly limited to lateral fields-of-view (FOV) of only a few millimeters. The use of a freehand manually scanned probe can significantly increase the lateral FOV. However, using the traditional fixed-rate triggering scheme for data acquisition in a manually scanned probe results in imaging artifacts due to variations in the scan velocity of the imaging probe. These artifacts result in a structurally inaccurate image of the sample. In this paper, we present a sensor-based manual scanning technique for OCT imaging, where real-time feedback from an optical motion sensor is used to trigger data acquisition. This technique is able to circumvent the problem of motion artifacts during manual scanning by adaptively altering the trigger rate based on the instantaneous scan velocity, enabling OCT imaging over a large lateral FOV. The feasibility of the proposed technique is demonstrated by imaging several biological and nonbiological samples.

A Mosaicking Approach for In Vivo Thickness Mapping of the Human Tympanic Membrane Using Low Coherence Interferometry.

The thickness of the human tympanic membrane (TM) is known to vary considerably across different regions of the TM. Quantitative determination of the thickness distribution and mapping of the TM is of significant importance in hearing research, particularly in mathematical modeling of middle-ear dynamics. Change in TM thickness is also associated with several middle-ear pathologies. Determination of the TM thickness distribution could therefore also enable a more comprehensive diagnosis of various otologic diseases. Despite its importance, very limited data on human TM thickness distribution, obtained almost exclusively from ex vivo samples, are available in the literature. In this study, the thickness distribution for the in vivo human TM is reported for the first time. A hand-held imaging system, which combines a low coherence interferometry (LCI) technique for single-point thickness measurement, with video-otoscopy for recording the image of the TM, was used to collect the data used in this study. Data were acquired by pointing the imaging probe over different regions of the TM, while simultaneously recording the LCI and concomitant TM surface video image data from an average of 500 locations on the TM. TM thickness distribution maps were obtained by mapping the LCI imaging sites onto an anatomically accurate wide-field image of the TM, which was generated by mosaicking the sequence of multiple small field-of-view video-otoscopy images. Descriptive statistics of the thickness measurements obtained from the different regions of the TM are presented, and the general thickness distribution trends are discussed.

Implementation and evaluation of Google Glass for visualizing real-time image and patient data in the primary care office

Primary care physicians must conduct a staggering number of comprehensive physical exams and medical record reviews, resulting in demanding daily schedules. Few commercial technologies have been marketed towards the primary care market, which has stifled improvements in disease screening and detection, work flow, and records management, taking time away from interactions with patients. In efforts to improve the quality of care in primary care medicine, we integrated our handheld primary care optical imaging system with Google Glass©, a commercial heads-up display (HUD). The integration of a HUD allows the physician to focus on the patient during the medical history review and during the patient exam, resulting in potential improvements to the quality of care and efficient access to real-time data for display and analysis.

Retinal imaging with en face and cross-sectional optical coherence tomography delineates outer retinal changes in cancer-associated retinopathy secondary to Merkel cell carcinoma

BackgroundThe study aims to correlate Fourier-domain optical coherence tomography (FD-OCT) with Goldmann visual field (GVF) to show the photoreceptor (PR) structure and function relationship in the first described case of cancer-associated retinopathy (CAR) from Merkel cell carcinoma.FindingsA case study of a patient with CAR who was imaged with serial GVF and FD-OCT over a 2-year period was carried out. En face images were created using a custom algorithm from the volumetric Fourier-domain OCT scans at the PR level. The areas of decreased PR reflectivity on the en face images were compared with GVF obtained at the same time point. Regions of reduced signal on en face scans corresponded with the position and shape of the GVF scotomas. Initially, the vision improved without PR changes. Cross-sectional OCTs showed early recovery of the outer nuclear layer and later improvement in the nerve fiber layer. Worsening vision corresponded with recurrence of the underlying cancer. Progressive global retinal atrophy was seen over time.ConclusionsMerkle cell carcinoma can cause CAR. Retinal function recovered without structural PR recovery. Transient vision improvements in treated CAR patients may be due to layers other than the PRs, but eventual vision decline results from significant progressive retinal atrophy.

Low-cost hand-held probe for depth-resolved low-coherence interferometry

We report on the development of a low-cost hand-held low-coherence interferometric imaging system based on the principle of linear optical coherence tomography (Linear OCT), a technique which was first proposed in the early 2000s as a simpler alternative to the conventional time-domain and Fourier-domain OCT. A bench-top implementation of the proposed technique is first presented and validated. The axial resolution, SNR, and sensitivity roll-of of the system was estimated to be 5.2 μm and 80 dB, and 3.7 dB over a depth of 0.15 mm, respectively. After validating the bench-top system, two hand-held probe implementations for contact-based imaging and in vivo human tympanic membrane imaging are presented. The performance of the proposed system was compared with a research-grade state-of-the-art Fourier-domain low coherence interferometry (LCI) system by imaging several biological and non-biological samples. The results of this study suggest that the proposed system might be a suitable choice for applications where imaging depth and SNR can be traded for lower cost and simpler optical design.