Measurement of a multi-layered tear film phantom using optical coherence tomography and statistical decision theory

To extend our understanding of tear film dynamics for the management of dry eye disease, we propose a method to optically sense the tear film and estimate simultaneously the thicknesses of the lipid and aqueous layers. The proposed method, SDT-OCT, combines ultra-high axial resolution optical coherence tomography (OCT) and a robust estimator based on statistical decision theory (SDT) to achieve thickness measurements at the nanometer scale. Unlike conventional Fourier-domain OCT where peak detection of layers occurs in Fourier space, in SDT-OCT thickness is estimated using statistical decision theory directly on the raw spectra acquired with the OCT system. In this paper, we demonstrate in simulation that a customized OCT system tailored to ~1 µm axial point spread function (FWHM) in the corneal tissue, combined with the maximum-likelihood estimator, can estimate thicknesses of the nanometer-scale lipid and micron-scale aqueous layers of the tear film, simultaneously, with nanometer precision. This capability was validated in experiments using a physical phantom that consists of two layers of optical coatings that mimic the lipid and aqueous layers of the tear film.OCIS codes: (170.4500) Optical coherence tomography, (030.0030) Coherence and statistical optics, (110.3000) Image quality assessment, (120.0120) Instrumentation, measurement, and metrology, (120.4290) Nondestructive testing, (330.7327) Visual optics, ophthalmic instrumentation     

Maximum-likelihood estimation in Optical Coherence Tomography in the context of the tear film dynamics

Understanding tear film dynamics is a prerequisite for advancing the management of Dry Eye Disease (DED). In this paper, we discuss the use of optical coherence tomography (OCT) and statistical decision theory to analyze the tear film dynamics of a digital phantom. We implement a maximum-likelihood (ML) estimator to interpret OCT data based on mathematical models of Fourier-Domain OCT and the tear film. With the methodology of task-based assessment, we quantify the tradeoffs among key imaging system parameters. We find, on the assumption that the broadband light source is characterized by circular Gaussian statistics, ML estimates of 40 nm +/− 4 nm for an axial resolution of 1 μm and an integration time of 5 μs. Finally, the estimator is validated with a digital phantom of tear film dynamics, which reveals estimates of nanometer precision.OCIS codes: (030.0030) Coherence and statistical optics, (110.3000) Image quality assessment     

Multilayer thin-film phantoms for axial contrast transfer function measurement in optical coherence tomography

In optical coherence tomography (OCT), axial resolution is one of the most critical parameters impacting image quality. It is commonly measured by determining the point spread function (PSF) based on a specular surface reflection. The contrast transfer function (CTF) provides more insights into an imaging system’s resolving characteristics and can be readily generated in a system-independent manner, without consideration for image pixel size. In this study, we developed a test method for determination of CTF based on multi-layer, thin-film phantoms, evaluated using spectral- and time-domain OCT platforms with different axial resolution values. Phantoms representing six spatial frequencies were fabricated and imaged. The fabrication process involved spin coating silicone films with precise thicknesses in the 8-40 μm range. Alternating layers were doped with a specified concentration of scattering particles. Validation of layer optical properties and thicknesses were achieved with spectrophotometry and stylus profilometry, respectively. OCT B-scans were used to calculate CTFs and results were compared with convetional PSF measurements based on specular reflections. Testing of these phantoms indicated that our approach can provide direct access to axial resolution characteristics highly relevant to image quality. Furthermore, tissue phantoms based on our thin-film fabrication approach may have a wide range of additional applications in optical imaging and spectroscopy.OCIS codes: (170.4500) Optical coherence tomography, (110.3000) Image quality assessment, (110.4850) Optical transfer functions, (350.4800) Optical standards and testing     

Automatic dynamic tear meniscus measurement in optical coherence tomography

An image processing algorithm is developed for quantitative assessment of tear meniscus dynamics from continuous optical coherence tomography (OCT) measurements. Clinical utility of dynamic OCT tear meniscus measurement is assessed in studies of tear meniscus parameters. The results indicate that any apparent changes in the early post-blink phase meniscus parameters are essentially related to the longitudinal movements of the eye and not to the formation of tear meniscus corresponding to tear film build-up. Dynamic acquisition of tear film meniscus is essential for providing reliable estimates of its parameters such as height, depth, and area.OCIS codes: (100.0100) Image processing, (100.2960) Image analysis, (170.4500) Optical coherence tomography, (170.4470) Ophthalmology     

Micrometer axial resolution OCT for corneal imaging

An optical coherence tomography (OCT) for high axial resolution corneal imaging is presented. The system uses 375 nm bandwidth (625 to 1000 nm) from a broadband supercontinuum light source. The system was developed in free space to minimize image quality degradation due to dispersion. A custom-designed spectrometer based on a Czerny Turner configuration was implemented to achieve an imaging depth of 1 mm. Experimentally measured axial resolution was 1.1 μm in corneal tissue and had a good agreement with the theoretically calculated resolution from the envelope of the spectral interference fringes. In vivo imaging was carried out and thin corneal layers such as the tear film and the Bowman's layer were quantified in normal, keratoconus, and contact lens wearing eyes, indicating the system's suitability for several ophthalmic applications.     

Tissue thickness calculation in ocular optical coherence tomography

Thickness measurements derived from optical coherence tomography (OCT) images of the eye are a fundamental clinical and research metric, since they provide valuable information regarding the eye’s anatomical and physiological characteristics, and can assist in the diagnosis and monitoring of numerous ocular conditions. Despite the importance of these measurements, limited attention has been given to the methods used to estimate thickness in OCT images of the eye. Most current studies employing OCT use an axial thickness metric, but there is evidence that axial thickness measures may be biased by tilt and curvature of the image. In this paper, standard axial thickness calculations are compared with a variety of alternative metrics for estimating tissue thickness. These methods were tested on a data set of wide-field chorio-retinal OCT scans (field of view (FOV) 60° x 25°) to examine their performance across a wide region of interest and to demonstrate the potential effect of curvature of the posterior segment of the eye on the thickness estimates. Similarly, the effect of image tilt was systematically examined with the same range of proposed metrics. The results demonstrate that image tilt and curvature of the posterior segment can affect axial tissue thickness calculations, while alternative metrics, which are not biased by these effects, should be considered. This study demonstrates the need to consider alternative methods to calculate tissue thickness in order to avoid measurement error due to image tilt and curvature.OCIS codes: (100.0100) Image processing, (100.2960) Image analysis, (110.4500) Optical coherence tomography, (170.4470) Ophthalmology     

Segregation of neuronal-vascular components in a retinal nerve fiber layer for thickness measurement using OCT and OCT angiography

Assessment of the circumpapillary retinal nerve fiber layer (RNFL) provides crucial knowledge on the status of the optic nerve. Current circumpapillary RNFL measurements consider only thickness, but an accurate evaluation should also consider blood vessel contribution. Previous studies considered the presence of major vessels in RNFL thickness measurements from optical coherence tomography (OCT). However, such quantitative measurements do not account for smaller vessels, which could also affect circumpapillary RNFL measurements. We present an approach to automatically segregate the neuronal and vascular components in circumpapillary RNFL by combining vascular information from OCT angiography (OCTA) and structural data from OCT. Automated segmentation of the circumpapillary RNFL using a state-of-the-art deep learning network is first performed and followed by the lateral and depth-resolved localization of the vascular component by vertically projecting the vessels along the circular scan from OCTA vessels map onto the segmented RNFL. Using this proposed approach, we compare the correlations of circumpapillary RNFL thicknesses with age at different levels of vessel exclusion (exclusion of major vessels only vs both major- and micro-vessels) and also evaluate the thickness variability in 75 healthy eyes. Our results show that the ratio of major- and micro-vessels to circumpapillary RNFL achieved a stronger correlation with aging (r = 0.478, P < .001) than the ratio with only major vessels to circumpapillary RNFL (r = 0.027, P = .820). Exclusion of blood vessels from circumpapillary RNFL thickness using OCTA imaging provides a better measure of the neuronal components and could potentially improve the diagnostic performance for disease detection.     

Master slave en-face OCT/SLO

Master Slave optical coherence tomography (MS-OCT) is an OCT method that does not require resampling of data and can be used to deliver en-face images from several depths simultaneously. As the MS-OCT method requires important computational resources, the number of multiple depth en-face images that can be produced in real-time is limited. Here, we demonstrate progress in taking advantage of the parallel processing feature of the MS-OCT technology. Harnessing the capabilities of graphics processing units (GPU)s, information from 384 depth positions is acquired in one raster with real time display of up to 40 en-face OCT images. These exhibit comparable resolution and sensitivity to the images produced using the conventional Fourier domain based method. The GPU facilitates versatile real time selection of parameters, such as the depth positions of the 40 images out of the set of 384 depth locations, as well as their axial resolution. In each updated displayed frame, in parallel with the 40 en-face OCT images, a scanning laser ophthalmoscopy (SLO) lookalike image is presented together with two B-scan OCT images oriented along rectangular directions. The thickness of the SLO lookalike image is dynamically determined by the choice of number of en-face OCT images displayed in the frame and the choice of differential axial distance between them.OCIS codes: (110.4500) Optical coherence tomography, (170.0110) Imaging systems, (330.4460) Ophthalmic optics and devices, (120.3890) Medical optics instrumentation, (200.4960) Parallel processing     

Intracoronary optical coherence tomography,basic theory and image acquisition techniques

Optical coherence tomography (OCT) imaging is showing great potential as an alternative or complementary tool to intravascular ultrasound (IVUS) for aiding in stent procedures and future diagnosis/treatment of atherosclerosis. Here, we describe the basic theory behind OCT imaging and explain important parameters such as axial resolution, lateral resolution and sensitivity. Also, we describe several image acquisition techniques that have been adopted for OCT imaging.     

Complex differential variance algorithm for optical coherence tomography angiography

We describe a complex differential variance (CDV) algorithm for optical coherence tomography based angiography. The algorithm exploits both the intensity and phase changes of optical coherence tomography (OCT) signals from flowing blood to achieve high vascular contrast, and also intrinsically reject undesirable phase signals originating from small displacement axial bulk tissue motion and instrument synchronization errors. We present this algorithm within a broader discussion of the properties of OCT signal dynamics. The performance of the algorithm is compared against two other existing algorithms using both phantom measurements and in vivo data. We show that the algorithm provides better contrast for a given number of measurements and equivalent spatial averaging.OCIS codes: (170.4500) Optical coherence tomography, (170.3010) Image reconstruction techniques     

Optical Coherence Tomography and Fibrous Cap Characterization

The pathophysiology of acute coronary syndromes has long been associated with atherosclerotic plaque rupture. Inflammation, thinning, and disruption of the fibrous cap have been implicated with the final processes leading to plaque rupture, but confirmation of these mechanisms of coronary thrombosis in humans has been hampered by the lack of imaging methods with sufficient resolution to resolve fibrous cap characterization and thickness in vivo. Intravascular optical coherence tomography (OCT) provides images with micron-level axial and lateral resolution, enabling detailed visualization of micro-structural changes of the arterial wall. The present article provides an overview of the potential role of OCT in identifying and characterizing fibrous cap morphology, thickness, and inflammation in human coronary plaques.     

In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo.OCIS codes: (170.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.1610) Clinical applications, (170.4580) Optical diagnostics for medicine     

Imaging of retinal vasculature using adaptive optics SLO/OCT

We use our previously developed adaptive optics (AO) scanning laser ophthalmoscope (SLO)/ optical coherence tomography (OCT) instrument to investigate its capability for imaging retinal vasculature. The system records SLO and OCT images simultaneously with a pixel to pixel correspondence which allows a direct comparison between those imaging modalities. Different field of views ranging from 0.8°x0.8° up to 4°x4° are supported by the instrument. In addition a dynamic focus scheme was developed for the AO-SLO/OCT system in order to maintain the high transverse resolution throughout imaging depth. The active axial eye tracking that is implemented in the OCT channel allows time resolved measurements of the retinal vasculature in the en-face imaging plane. Vessel walls and structures that we believe correspond to individual erythrocytes could be visualized with the system.OCIS codes: (170.3890) Medical optics instrumentation, (110.1080) Active or adaptive optics, (170.4470) Ophthalmology, (330.5310) Vision - photoreceptors, (110.4500) Optical coherence tomography     

Characterizing the point spread function of retinal OCT devices with a model eye-based phantom

We have designed, fabricated, and tested a nanoparticle-embedded phantom (NEP) incorporated into a model eye in order to characterize the point spread function (PSF) of retinal optical coherence tomography (OCT) devices in three dimensions under realistic imaging conditions. The NEP comprises a sparse distribution of highly backscattering silica-gold nanoshells embedded in a transparent UV-curing epoxy. The commercially-available model eye replicates the key optical structures and focusing power of the human eye. We imaged the model eye-NEP combination with a research-grade spectral domain OCT system designed for in vivo retinal imaging and quantified the lateral and axial PSF dimensions across the field of view in the OCT images. We also imaged the model eye-NEP in a clinical OCT system. Subtle features in the PSF and its dimensions were consistent with independent measurements of lateral and axial resolution. This model eye-based phantom can provide retinal OCT device developers and users a means to rapidly, objectively, and consistently assess the PSF, a fundamental imaging performance metric.     

Ultrahigh speed endoscopic optical coherence tomography for gastroenterology

We describe an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor imaging catheter. The system had a 600 kHz axial scan rate and 8 µm axial resolution in tissue. Imaging was performed with a 3.2 mm diameter imaging catheter at 400 frames per second with a 12 µm spot size. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing upper and lower endoscopy. The use of distally actuated imaging catheters enabled OCT imaging with more flexibility, such as volumetric imaging in the small intestine and the assessment of hiatal hernia using retroflex imaging. The high rotational scanning stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face OCT and cross-sectional imaging, as well as OCT angiography (OCTA) for 3D visualization of subsurface microvasculature. The ability to perform both structural and functional 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies and enhance the sensitivity and specificity of OCT for detecting pathology.OCIS codes: (110.2350) Fiber optics imaging, (120.3890) Medical optics instrumentation, (120.5800) Scanners, (110.6880) Three-dimensional image acquisition, (140.7260) Vertical cavity surface emitting lasers, (170.2150) Endoscopic imaging, (170.2680) Gastrointestinal, (170.3880) Medical and biological imaging, (170.4500) Optical coherence tomography     

In vivo volumetric analysis of coronary stent using optical coherence tomography with a novel balloon occlusion-flushing catheter: a comparison with intravascular ultrasound

Optical coherence tomography (OCT) is limited as an intravascular imaging tool because of interference with blood. This study tested a new balloon occlusion-flushing catheter for OCT scanning of stented coronary arteries and compared stent measurements between OCT and intravascular ultrasound (IVUS). Motorized pullback with OCT and IVUS was examined in coronary stents deployed in swine. Quantitative measurements were obtained and compared between both groups. In addition, stent strut thickness was compared among OCT, IVUS and actual measurement. The occlusion catheter successfully provided motorized pullback OCT images in the stented coronary arteries without any complications. There were no differences in calculated lumen volume. However, stent volumes were significantly smaller with OCT than with IVUS (p < 0.05). OCT significantly underestimated the stent strut thickness compared with the actual measurement. Although OCT underestimates the stent strut thickness, motorized pullback OCT imaging with the occlusion catheter can provide appropriate in-stent images in the porcine coronary arteries.     

Adaptive optics SLO/OCT for 3D imaging of human photoreceptors in vivo

We present a new instrument that is capable of imaging human photoreceptors in three dimensions. To achieve high lateral resolution, the system incorporates an adaptive optics system. The high axial resolution is achieved through the implementation of optical coherence tomography (OCT). The instrument records simultaneously both, scanning laser ophthalmoscope (SLO) and OCT en-face images, with a pixel to pixel correspondence. The information provided by the SLO is used to correct for transverse eye motion in post-processing. In order to correct for axial eye motion, the instrument is equipped with a high speed axial eye tracker. In vivo images of foveal cones as well as images recorded at an eccentricity from the fovea showing cones and rods are presented.OCIS codes: (170.3890) Medical optics instrumentation, (110.1080) Active or adaptive optics, (170.4470) Ophthalmology, (330.5310) Vision - photoreceptors, (110.4500) Optical coherence tomography     

Toward Clinical μOCT—A Review of Resolution-Enhancing Technical Advances

Intravascular optical coherence tomography (IVOCT) has made significant clinical impact, providing a method of visualizing coronary plaques, optimizing percutaneous coronary intervention, and monitoring treatment results. Achieving cellular resolution in cardiovascular optical coherence tomography (OCT) adds even greater utility; thin-cap fibroatheromas (TCFA) that include microcalcifications, cholesterol crystals, and macrophages are hypothesized to correlate with rupture potential, yet are too small to be imaged by conventional OCT. In this review, we survey new developments in the optical technology that may contribute to the advancement of IVOCT into the microscopic domain, including new light sources and optical configurations. We also describe recent progress in micro-OCT (μOCT), a high-resolution OCT implementation developed in our laboratory that utilizes many of these advances to achieve 1-μm resolution.     

Quantitative characterization of human breast tissue based on deep learning segmentation of 3D optical coherence tomography images

In this study, we performed dual-modality optical coherence tomography (OCT) characterization (volumetric OCT imaging and quantitative optical coherence elastography) on human breast tissue specimens. We trained and validated a U-Net for automatic image segmentation. Our results demonstrated that U-Net segmentation can be used to assist clinical diagnosis for breast cancer, and is a powerful enabling tool to advance our understanding of the characteristics for breast tissue. Based on the results obtained from U-Net segmentation of 3D OCT images, we demonstrated significant morphological heterogeneity in small breast specimens acquired through diagnostic biopsy. We also found that breast specimens affected by different pathologies had different structural characteristics. By correlating U-Net analysis of structural OCT images with mechanical measurement provided by quantitative optical coherence elastography, we showed that the change of mechanical properties in breast tissue is not directly due to the change in the amount of dense or porous tissue.     

Improved measurement of vibration amplitude in dynamic optical coherence elastography

Abstract: Optical coherence elastography employs optical coherence tomography (OCT) to measure the displacement of tissues under load and, thus, maps the resulting strain into an image, known as an elastogram. We present a new improved method to measure vibration amplitude in dynamic optical coherence elastography. The tissue vibration amplitude caused by sinusoidal loading is measured from the spread of the Doppler spectrum, which is extracted using joint spectral and time domain signal processing. At low OCT signal-to-noise ratio (SNR), the method provides more accurate vibration amplitude measurements than the currently used phase-sensitive method. For measurements performed on a mirror at OCT SNR = 5 dB, our method introduces <3% error, compared to >20% using the phase-sensitive method. We present elastograms of a tissue-mimicking phantom and excised porcine tissue that demonstrate improvements, including a 50% increase in the depth range of reliable vibration amplitude measurement.OCIS codes: (110.4500) Optical coherence tomography, (290.5820) Scattering measurements, (170.6935) Tissue characterization