Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study. METHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-µm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. RESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. CONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

Active-passive path-length encoded (APPLE) Doppler OCT.

We present a novel active-passive path-length encoded (APPLE) swept source Doppler optical coherence tomography (DOCT) approach, enabling three-dimensional velocity vector reconstruction of moving particles without prior knowledge of the orientation of motion. The developed APPLE DOCT setup allows for non-invasive blood flow measurements in vivo and was primarily designed for quantitative human ocular blood flow investigations. The system's performance was demonstrated by in vitro flow phantom as well as in vivo retinal vessel bifurcation measurements. Furthermore, total retinal blood flow - a biomarker aiding in diagnosis and monitoring of major ocular diseases such as glaucoma, diabetic retinopathy or central/branch retinal vein occlusion - was determined in the eyes of healthy human volunteers.

Total retinal blood flow measurement by three beam Doppler optical coherence tomography.

We present measurements of total retinal blood flow in healthy volunteers using a three beam Doppler optical coherence tomography (D-OCT) technique. This technology has the advantage of a precise determination of the flow vector without the use of any a-priori information on the vessel geometry. Circular D-OCT scans around the optic disc were recorded and venous as well as arterial total blood flow was determined and compared for each subject. The reproducibility of the method was assessed in 6 subjects by repeated measurements. Only small deviations of around 6% between the measurements were found which indicates the high precision of the proposed method.

Single input state polarization sensitive swept source optical coherence tomography based on an all single mode fiber interferometer.

We present a newly developed single mode fiber based swept source polarization sensitive optical coherence tomography system using a single input state at 1040 nm. Two non-polarizing fiber based beam splitters are combined to form a Mach-Zehnder interferometer, while two polarizing beam splitters are used to obtain a polarization sensitive detection. Both types of beam splitters solely feature conventional single mode fibers. Polarization control paddles are used to set and maintain the polarization states in the fibers of the interferometer and detection unit. By use of a special paddle alignment scheme we are able to eliminate any bulk optic wave plates and polarization maintaining fibers in the interferometer and detection paths while preserving the advantages of a single input state system that illuminates the sample with circularly polarized light. To demonstrate the capabilities of our system, we performed retinal measurements on healthy human volunteers.

In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography.

We developed a three-beam Doppler optical coherence tomography (OCT) system that enables measurement of the velocity vector of moving particles in three-dimensions (3-D). The spatial orientation as well as the magnitude of motion can be determined without prior knowledge of the geometry of motion. The system combines three spectral-domain OCT interferometers whose sample beams are focused at the sample by a common focusing lens at three different angles. This provides three spatially independent velocity components simultaneously from which the velocity vector can be reconstructed. We demonstrate the system in a simple test object (rotating disc), a flow phantom, and for blood flow measurements in the retina of a healthy human subject. Measurements of blood flow at a venous bifurcation achieve a good agreement between in- and outflow and demonstrate the reliability of the method.

Retinal polarization-sensitive optical coherence tomography at 1060 nm with 350 kHz A-scan rate using an Fourier domain mode locked laser.

We present a novel, high-speed, polarization-sensitive, optical coherence tomography set-up for retinal imaging operating at a central wavelength of 1060 nm which was tested for in vivo imaging in healthy human volunteers. We use the system in combination with a Fourier domain mode locked laser with active spectral shaping which enables the use of forward and backward sweep in order to double the imaging speed without a buffering stage. With this approach and with a custom designed data acquisition system, we show polarization-sensitive imaging with an A-scan rate of 350 kHz. The acquired three-dimensional data sets of healthy human volunteers show different polarization characteristics in the eye, such as depolarization in the retinal pigment epithelium and birefringence in retinal nerve fiber layer and sclera. The increased speed allows imaging of large volumes with reduced motion artifacts. Moreover, averaging several two-dimensional frames allows the generation of high-definition B-scans without the use of an eye-tracking system. The increased penetration depth of the system, which is caused by the longer probing beam wavelength, is beneficial for imaging choroidal and scleral structures and allows automated segmentation of these layers based on their polarization characteristics.

Large-field high-speed polarization sensitive spectral domain OCT and its applications in ophthalmology.

We present a novel spectral domain polarization sensitive OCT system (PS-OCT) that operates at an A-scan rate of 70 kHz and supports scan angles of up to 40° × 40°. The high-speed imaging allows the acquisition of up to 1024 × 250 A-scans per 3D scan, which, together with the large field of view, considerably increases the informative value of the images. To demonstrate the excellent performance of the new PS-OCT system, we imaged several healthy volunteers and patients with various diseases such as glaucoma, AMD, Stargardt's disease, and albinism. The results are compared with clinically established methods such as scanning laser polarimetry and autofluorescence.