Purpose:To demonstrate high-resolution, motion-corrected, volume-fused optical coherence tomography (OCT) for assessing longitudinal changes in macular dot form subretinal drusenoid deposits (SDDs). Methods:Six consecutive isotropic volume raster scans over 6 × 6 mm (500 × 500 A-scans) were acquired using a high-resolution (2.7 µm axial resolution) spectral domain OCT prototype instrument. OCT volumes were computationally motion-corrected and fused. The distribution and longitudinal changes in dot SDDs were evaluated using en face OCT in a 50-µm-thick slab, from 27 µm above Bruch's membrane. Results:Computational motion correction and volume fusion methods improve visibility of small en face features and compensate for motion artifacts to facilitate longitudinal assessment. In total, 326 SDDs were identified in a representative series of four eyes from four patients with intermediate age-related macular degeneration (AMD) and assessed with a 3- to 12-month follow-up. Of the SDDs, 85.3% remained stable over the follow-up, while 9.8% regressed, 3.4% fused, and 1.5% new SDDs appeared. Conclusions:Computational motion correction and volume fusion combined with high-resolution OCT B-scans and en face slabs facilitate visualization and longitudinal tracking of focal pathologies, such as SDDs. Translational Relevance:The methods presented have the potential to improve OCT analysis of focal features, such as quantification of SDDs and other AMD biomarkers.

Purpose: To investigate retinal capillary plexus capillary flow speed and vessel density in diabetic retinopathy and normal subjects using variable interscan time analysis optical coherence tomography angiography (OCTA). Methods: High speed swept source OCTA imaging using multiple interscan times was performed over a 5 mm × 5 mm field-of-view with 600 kHz A-scan rate. Second-generation variable interscan time analysis OCTA was used to measure a surrogate marker for capillary blood flow speed, variable interscan time analysis flow speed (VFS), in the superficial and intermediate capillary plexusesVFS, and deep capillary plexusVFS. Vessel density was measured using OCTA. Results: Fifty-seven eyes with different diabetic retinopathy severity and 37 normal eyes were analyzed. Variable interscan time analysis OCTA provided diverse blood flow speed information, including pseudo-color OCTA and mean flow speed in different regions. Both deep capillary plexusVFS and deep capillary plexusVFS/(superficial and intermediate capillary plexuses)VFS were higher in diabetic retinopathy compared with normal eyes. Elevated deep capillary plexusVFS correlated with decreased deep capillary plexus vessel density in nonproliferative diabetic retinopathy. Conclusion: Variable interscan time analysis OCTA can measure a quantitative biomarker for blood flow speed alterations in diabetic retinopathy and normal eyes as well as the association with vessel density in different capillary plexuses. Variable interscan time analysis OCTA is promising for studies of pathogenesis and early flow alterations, which may precede nonperfusion.

Purpose:To evaluate visibility of a sub-band posterior to the external limiting membrane (ELM) and assess its age-associated variation. Methods:In a retrospective cross-sectional study, normal eyes were imaged using a high-resolution spectral-domain optical coherence tomography (SD-OCT) prototype (2.7-µm axial resolution). Volume fusion of six sequential scans (each 500 × 500 A-scans over 6 mm × 6 mm) was performed in the motion correction and volume reconstruction in OCT (MoReOCT) framework to enhance feature visibility in OCT. The subjects were divided into three groups: young (21-40 years old), middle (41-60 years old), and older (>60 years old). Three expert graders assessed the visibility of the sub-band on B-scans, and its A-scan intensity relative to ELM intensity (peak intensity ratio) was measured. Results:Forty-four eyes of 44 subjects were imaged. The sub-band, tentatively attributed to the photoreceptor myoid, can be visualized under high-resolution OCT. The B-scan gradings showed that sub-band visibility increased with age (visible in 16.7%, 47.2%, and 66.7% of the young, middle, and older age groups, respectively). The gradings were statistically different among age groups at 1 mm and 2 mm nasal and 1 mm and 2 mm temporal (P < 0.04) from the foveal center. Similarly, the mean peak intensity ratios of the sub-band to the ELM were 71.6%, 77.5%, and 85.2% in the young, middle, and older age groups, respectively, and were positively correlated with age at 1 mm temporal (P = 0.012) and 2 mm temporal (P < 0.001). Conclusions:High-resolution OCT, combined with advanced volume fusion, enables visualization of the photoreceptor myoid and investigation of its age-associated variations. Translational Relevance:Investigating the sub-band can advance our understanding of photoreceptors and their association with aging and disease pathogenesis.

Purpose: To quantify the blood flow speed within retinal microaneurysms (MAs) and investigate the relationship between blood flow speed and clinical characteristics in eyes with diabetic retinopathy (DR). Methods: Variable interscan time analysis (VISTA) quantifies blood flow speed in the vasculature by measuring how fast optical coherence tomography (OCT) angiography (OCTA) saturates for different interscan times. Macular OCTA imaging was performed in eyes with DR using a high-speed swept-source OCT prototype instrument operating at a 600-kHz A-scan rate. The presence of MAs was determined using OCT B-scans, and three-dimensional MA masks were generated. VISTA flow speed (VFS) was determined within MAs and the retinal capillary plexus (RCP). Intraluminal reflectivity, axial location within the RCP, and the presence of intraretinal fluid (IRF) around the MAs were evaluated. Results: A total of 123 MAs were detected from 24 eyes of 20 patients with DR. Mean VFS was 1.26 ms(-1) (95% confidence interval, 1.16-1.35). MAs with medium and high intraluminal reflectivity had slower VFS than those with low intraluminal reflectivity (P < 0.01) and often had slower VFS than the RCP (P < 0.01). Sixty-six MAs were located near IRF and had slower VFS than the other 57 MAs without surrounding IRF (1.16 ms(-1) vs. 1.37 ms(-1); P = 0.03). Conclusions: VISTA OCTA can assess blood flow speed of MAs in relation to other structural features in DR. Decreased blood flow speed in MAs is correlated with the presence of IRF around MAs.

Purpose:A micrometer scale hyporeflective band within the retinal pigment epithelium basal lamina - Bruch's membrane complex (RPE-BL-BrM) was topographically measured in aging and age-related macular degeneration (AMD). Methods:In a prospective cross-sectional study, 90 normal eyes from 76 subjects (range = 23-90 years) and 53 dry AMD eyes from 47 subjects (range = 62-91 years) were enrolled. Isotropic volume raster scans over 6 mm × 6 mm (500 × 500 A-scans) were acquired using a high-resolution (2.7 µm axial resolution) spectral-domain optical coherence tomography (SD-OCT) prototype instrument. Six consecutive optical coherence tomography (OCT) volumes were computationally motion-corrected and fused to improve feature visibility. A boundary regression neural network was developed to measure hyporeflective band thickness. Topographic dependence was evaluated over a 6-mm-diameter Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Results:The hyporeflective band thickness map (median of 4.3 µm and 7.8 µm in normal and AMD eyes, respectively) is thicker below and radially symmetric around the fovea. In normal eyes, age-associated differences occur within 0.7 to 2.3 mm from the foveal center (P < 0.05). In AMD eyes, the hyporeflective band is hypothesized to be basal laminar deposits (BLamDs) and is thicker within the 3-mm ETDRS circle (P < 0.0002) compared with normal eyes. The inner ring is the most sensitive location to detect age versus AMD-associated changes within the RPE-BL-BrM. AMD eyes with subretinal drusenoid deposits (SDDs) have a significantly thicker hyporeflective band (P < 0.001) than those without SDDs. Conclusions:The hyporeflective band is a quantifiable biomarker which differentiates AMD from aging. Longitudinal studies are warranted. The hyporeflective band may be a useful biomarker for risk stratification and disease progression.

Vision is essential for quality of life, but is threatened by visionimpairing diseases like age-related macular degeneration (AMD). A recently proposed biomarker potentially to distinguish normal aging from AMD is the gap visualized between the retinal pigment epithelium (RPE) and the Bruch’s membrane. Due to lack of automated processing, to date, this gap was only described sparsely in histologic data or on optical coherence tomography (OCT) B-scans. By segmenting the posterior RPE boundary automatically for the first time, we enable fully-automatic quantification of the thickness of this gap in vivo across whole volumetric OCT images. Our novel processing pipeline leverages advancements in motion correction, volumetric image merging, and high resolution OCT. A novel 3D boundary regression network named depth map regression network (DMR-Net) estimates the gap thickness in the volume. As 3D networks require full-volume ground truth boundary labels, which are labor-intensive, we developed a novel semi-automatic labeling approach to refine existing labels based on the visibility of the gap with minimal user input. We demonstrate thickness maps across a wide age range of healthy participants (23 – 79 years). The median absolute error in the test set is 0.161 μm, which is well below the axial pixel spacing (0.89 μm). For the first time, our results allow spatially resolved analysis to investigate pathologic deviations in normal aging and AMD.

Optical coherence tomography (OCT) is a non-invasive, micrometer-scale imaging modality that has become a clinical standard in ophthalmology. By raster-scanning the retina, sequential cross-sectional image slices are acquired to generate volumetric data. In-vivo imaging suffers from discontinuities between slices that show up as motion and illumination artifacts. We present a new illumination model that exploits continuity in orthogonally raster-scanned volume data. Our novel spatiotemporal parametrization adheres to illumination continuity both temporally, along the imaged slices, as well as spatially, in the transverse directions. Yet, our formulation does not make inter-slice assumptions, which could have discontinuities. This is the first optimization of a 3D inverse model in an image reconstruction context in OCT. Evaluation in 68 volumes from eyes with pathology showed reduction of illumination artifacts in 88% of the data, and only 6% showed moderate residual illumination artifacts. The method enables the use of forward-warped motion corrected data, which is more accurate, and enables supersampling and advanced 3D image reconstruction in OCT.

Optical coherence tomography angiography (OCTA) can visualize vasculature structures, but provides limited information about blood flow speed. Here, we present a second generation variable interscan time analysis (VISTA) OCTA, which evaluates a quantitative surrogate marker for blood flow speed in vasculature. At the capillary level, spatially compiled OCTA and a simple temporal autocorrelation model, ρ(τ) = exp(-ατ), were used to evaluate a temporal autocorrelation decay constant, α, as the blood flow speed marker. A 600 kHz A-scan rate swept-source OCT prototype instrument provides short interscan time OCTA and fine A-scan spacing acquisition, while maintaining multi mm2 field of views for human retinal imaging. We demonstrate the cardiac pulsatility and assess repeatability of α measured with VISTA. We show different α for different retinal capillary plexuses in healthy eyes and present representative VISTA OCTA in eyes with diabetic retinopathy.

Biofilms, a porous matrix of cells aggregated with extracellular polymeric substances under the influence of chemical constituents in the feed water, can develop a viscoelastic response to mechanical stresses. In this study, the roles of phosphate and silicate, common additives in corrosion control and meat processing, on the stiffness, viscoelasticity, porous structure networks, and chemical properties of biofilm were investigated. Three-year biofilms on PVC coupons were grown from sand-filtered groundwater with or without one of the non-nutrient (silicate) or nutrient additives (phosphate or phosphate blends). Compared with non-nutrient additives, the phosphate and phosphate-blend additives led to a biofilm with the lowest stiffness, most viscoelastic, and more porous structure, including more connecting throats with greater equivalent radii. The phosphate-based additives also led to more organic species in the biofilm matrix than the silicate additive did. This work demonstrated that nutrient additives could promote biomass accumulation but also reduce mechanical stability.

Disinfectant decay by biofilms in distribution networks during stagnation can allow opportunistic pathogens' transmission and thus compromise drinking water safety. Applying phosphate-based corrosion inhibitors to the system can exacerbate disinfectant decay by providing nutrients to biofilms growing inside premise plumbings. In this study, we evaluate the impacts of corrosion inhibitors on biofilms' structural and chemical properties that form in premise plumbing, and the resulting implications for disinfectant decay. Two commonly used phosphate-based (phosphate blends and phosphate) corrosion inhibitors were added separately to simulated drinking water for biofilm development over 1 to 2 years. Optical coherence tomography (OCT) imaging showed that the studied biofilms' thickness, porosity, and porous structure did not change after exposure to free chlorine for 24 h or monochloramine for 120 h. Compared with groundwater biofilms, phosphate-based biofilms had the highest overall porosity due to their many connecting channels. The phosphate-based biofilms consumed free chlorine or monochloramine at a faster rate than groundwater biofilms. Experimental results showed that phosphate-based biofilms consumed more monochloramine after 96 h of contact than other biofilms. A separate set of experiments involving disinfectant decay with suspended biomass material, together with the OCT results, provided parameters for a simplified quasi-first-order reaction-diffusion model so that predictive modeling of decay in biofilms under stagnation conditions could be attempted without parameter fitting. The biofilm modeling results provided a close estimate for free chlorine decay while underestimating monochloramine decay. In agreement with the experimental results, the model results indicate that the phosphate-based biofilms led to slightly faster free chlorine consumption and monochloramine consumption than groundwater biofilms and indicate that diffusion limitation imposed by biofilm pore structure on disinfectant decay is important. The study results suggest that using phosphate-based corrosion inhibitors may lead to a rapid depletion of residual disinfectant during stagnation in the presence of biofilms.

Otitis media (OM), a common ear infection, is characterized by the presence of an accumulated middle ear effusion (MEE) in a normally air-filled middle ear cavity. While assessing the MEE plays a critical role in the overall management of OM, identifying and examining the MEE is challenging with the current diagnostic tools since the MEE is located behind the semi-opaque eardrum. The objective of this cross-sectional, observational study is to non-invasively visualize and characterize MEEs and bacterial biofilms in the middle ear. A portable, handheld, otoscope-integrated optical coherence tomography (OCT) system combined with novel analytical methods has been developed. In vivo middle ear OCT images were acquired from 53 pediatric subjects (average age of 3.9 years; all awake during OCT imaging) diagnosed with OM and undergoing a surgical procedure (ear tube surgery) to aspirate the MEE and aerate the middle ear. In vivo middle ear OCT acquired prior to the surgery was compared with OCT of the freshly extracted MEEs, clinical diagnosis, and post-operative evaluations. Among the subjects who were identified with the presence of MEEs, 89.6% showed the presence of the TM-adherent biofilm in in vivo OCT. This study provides an atlas of middle ear OCT images exhibiting a range of depth-resolved MEE features, which can only be visualized and assessed non-invasively through OCT. Quantitative metrics of OCT images acquired prior to the surgery were statistically correlated with surgical evaluations of MEEs. Measurements of MEE characteristics will provide new readily available information that can lead to improved diagnosis and management strategies for the highly prevalent OM in children.

Optical coherence tomography (OCT) is a micrometer-scale, volumetric imaging modality that has become a clinical standard in ophthalmology. OCT instruments image by raster-scanning a focused light spot across the retina, acquiring sequential cross-sectional images to generate volumetric data. Patient eye motion during the acquisition poses unique challenges: Non-rigid, discontinuous distortions can occur, leading to gaps in data and distorted topographic measurements. We present a new distortion model and a corresponding fully-automatic, reference-free optimization strategy for computational motion correction in orthogonally raster-scanned, retinal OCT volumes. Using a novel, domain-specific spatiotemporal parametrization of forward-warping displacements, eye motion can be corrected continuously for the first time. Parameter estimation with temporal regularization improves robustness and accuracy over previous spatial approaches.We correct each A-scan individually in 3D in a single mapping, including repeated acquisitions used in OCT angiography protocols. Specialized 3D forward image warping reduces median runtime to < 9 s, fast enough for clinical use. We present a quantitative evaluation on 18 subjects with ocular pathology and demonstrate accurate correction during microsaccades. Transverse correction is limited only by ocular tremor, whereas submicron repeatability is achieved axially (0.51 µm median of medians), representing a dramatic improvement over previous work. This allows assessing longitudinal changes in focal retinal pathologies as a marker of disease progression or treatment response, and promises to enable multiple new capabilities such as supersampled/super-resolution volume reconstruction and analysis of pathological eye motion occuring in neurological diseases. This paper was accepted and presented at medical image computing and computer assisted intervention (MICCAI) 2022 [1].

Recent advances in optical coherence tomography such as the development of high speed ultrahigh resolution scanners and corresponding signal processing techniques may reveal new potential biomarkers in retinal diseases. Newly visible features are, for example, small hyperreflective specks in age-related macular degeneration. Identifying these new markers is crucial to investigate potential association with disease progression and treatment outcomes. Therefore, it is necessary to reliably detect these features in 3D volumetric scans. Because manual labeling of entire volumes is infeasible a need for automatic detection arises. Labeled datasets are often not publicly available and there are usually large variations in scan protocols and scanner types. Thus, this work focuses on an unsupervised approach that is based on local peak-detection and random walker segmentation to detect small features on each B-scan of the volume.