Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

SSN2V: unsupervised OCT denoising using speckle split.

Denoising in optical coherence tomography (OCT) is important to compensate the low signal-to-noise ratio originating from laser speckle. In recent years learning algorithms have been established as the most powerful denoising approach. Especially unsupervised denoising is an interesting topic since it is not possible to acquire noise free scans with OCT. However, speckle in in-vivo OCT images contains not only noise but also information about blood flow. Existing OCT denoising algorithms treat all speckle equally and do not distinguish between the noise component and the flow information component of speckle. Consequently they either tend to either remove all speckle or denoise insufficiently. Unsupervised denoising methods tend to remove all speckle but create results that have a blurry impression which is not desired in a clinical application. To this end we propose the concept, that an OCT denoising method should, besides reducing uninformative noise, additionally preserve the flow-related speckle information. In this work, we present a fully unsupervised algorithm for single-frame OCT denoising (SSN2V) that fulfills these goals by incorporating known operators into our network. This additional constraint greatly improves the denoising capability compared to a network without. Quantitative and qualitative results show that the proposed method can effectively reduce the speckle noise in OCT B-scans of the human retina while maintaining a sharp impression outperforming the compared methods.

Maximum a posteriori signal recovery for optical coherence tomography angiography image generation and denoising.

Optical coherence tomography angiography (OCTA) is a novel and clinically promising imaging modality to image retinal and sub-retinal vasculature. Based on repeated optical coherence tomography (OCT) scans, intensity changes are observed over time and used to compute OCTA image data. OCTA data are prone to noise and artifacts caused by variations in flow speed and patient movement. We propose a novel iterative maximum a posteriori signal recovery algorithm in order to generate OCTA volumes with reduced noise and increased image quality. This algorithm is based on previous work on probabilistic OCTA signal models and maximum likelihood estimates. Reconstruction results using total variation minimization and wavelet shrinkage for regularization were compared against an OCTA ground truth volume, merged from six co-registered single OCTA volumes. The results show a significant improvement in peak signal-to-noise ratio and structural similarity. The presented algorithm brings together OCTA image generation and Bayesian statistics and can be developed into new OCTA image generation and denoising algorithms.

Efficient and high accuracy 3-D OCT angiography motion correction in pathology.

We describe a novel method for non-rigid 3-D motion correction of orthogonally raster-scanned optical coherence tomography angiography volumes. This is the first approach that aligns predominantly axial structural features such as retinal layers as well as transverse angiographic vascular features in a joint optimization. Combined with orthogonal scanning and favorization of kinematically more plausible displacements, subpixel alignment and micrometer-scale distortion correction is achieved in all 3 dimensions. As no specific structures are segmented, the method is by design robust to pathologic changes. Furthermore, the method is designed for highly parallel implementation and short runtime, allowing its integration into clinical workflow even for high density or wide-field scans. We evaluated the algorithm with metrics related to clinically relevant features in an extensive quantitative evaluation based on 204 volumetric scans of 17 subjects, including patients with diverse pathologies and healthy controls. Using this method, we achieve state-of-the-art axial motion correction and show significant advances in both transverse co-alignment and distortion correction, especially in the subgroup with pathology.

OCT-OCTA segmentation: combining structural and blood flow information to segment Bruch's membrane.

In this paper we present a fully automated graph-based segmentation algorithm that jointly uses optical coherence tomography (OCT) and OCT angiography (OCTA) data to segment Bruch's membrane (BM). This is especially valuable in cases where the spatial correlation between BM, which is usually not visible on OCT scans, and the retinal pigment epithelium (RPE), which is often used as a surrogate for segmenting BM, is distorted by pathology. We validated the performance of our proposed algorithm against manual segmentation in a total of 18 eyes from healthy controls and patients with diabetic retinopathy (DR), non-exudative age-related macular degeneration (AMD) (early/intermediate AMD, nascent geographic atrophy (nGA) and drusen-associated geographic atrophy (DAGA) and geographic atrophy (GA)), and choroidal neovascularization (CNV) with a mean absolute error of ∼0.91 pixel (∼4.1 µm). This paper suggests that OCT-OCTA segmentation may be a useful framework to complement the growing usage of OCTA in ophthalmic research and clinical communities.

Glaucoma classification in 3 x 3 mm en face macular scans using deep learning in a different plexus.

Glaucoma is among the leading causes of irreversible blindness worldwide. If diagnosed and treated early enough, the disease progression can be stopped or slowed down. Therefore, it would be very valuable to detect early stages of glaucoma, which are mostly asymptomatic, by broad screening. This study examines different computational features that can be automatically deduced from images and their performance on the classification task of differentiating glaucoma patients and healthy controls. Data used for this study are 3 x 3 mm en face optical coherence tomography angiography (OCTA) images of different retinal projections (of the whole retina, the superficial vascular plexus (SVP), the intermediate capillary plexus (ICP) and the deep capillary plexus (DCP)) centered around the fovea. Our results show quantitatively that the automatically extracted features from convolutional neural networks (CNNs) perform similarly well or better than handcrafted ones when used to distinguish glaucoma patients from healthy controls. On the whole retina projection and the SVP projection, CNNs outperform the handcrafted features presented in the literature. Area under receiver operating characteristics (AUROC) on the SVP projection is 0.967, which is comparable to the best reported values in the literature. This is achieved despite using the small 3 × 3 mm field of view, which has been reported as disadvantageous for handcrafted vessel density features in previous works. A detailed analysis of our CNN method, using attention maps, suggests that this performance increase can be partially explained by the CNN automatically relying more on areas of higher relevance for feature extraction.

SPATIAL DISTRIBUTION OF CHORIOCAPILLARIS IMPAIRMENT IN EYES WITH CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Quantitative OCT Angiography Study.

PURPOSE: To develop an optical coherence tomography angiography (OCTA)-based framework for quantitatively analyzing the spatial distribution of choriocapillaris (CC) impairment around choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: In a retrospective, cross-sectional study, 400-kHz swept-source OCTA images from 7 eyes of 6 patients with CNV secondary to age-related macular degeneration were quantitatively analyzed using custom software. A lesion-centered zonal OCTA analysis technique-which portioned the field-of-view into zones relative to CNV boundaries-was developed to quantify the spatial dependence of CC flow deficits. RESULTS: Quantitative, lesion-centered zonal analysis of CC OCTA images revealed highest flow-deficit percentages near CNV boundaries, decreasing in zones farther from the boundaries. Optical coherence tomography angiography using shorter (1.5 ms) interscan times revealed more severe flow deficits than OCTA using longer (3.0 ms) interscan times; however, spatial trends were similar for both interscan times. A detailed description of the OCTA processing steps and parameters was provided so as to elucidate their influence on quantitative measurements. CONCLUSION: Impairment of the CC, assessed by flow-deficit percentages, was most prominent closest to CNV boundaries. The lesion-centered zonal analysis technique enabled quantitative CC measurements relative to focal lesions. Understanding how processing steps, imaging/processing parameters, and artifacts can affect quantitative CC measurements is important for longitudinal, OCTA-based studies of disease progression, and treatment response.

Temporal and volumetric denoising via quantile sparse image prior.

This paper introduces an universal and structure-preserving regularization term, called quantile sparse image (QuaSI) prior. The prior is suitable for denoising images from various medical imaging modalities. We demonstrate its effectiveness on volumetric optical coherence tomography (OCT) and computed tomography (CT) data, which show different noise and image characteristics. OCT offers high-resolution scans of the human retina but is inherently impaired by speckle noise. CT on the other hand has a lower resolution and shows high-frequency noise. For the purpose of denoising, we propose a variational framework based on the QuaSI prior and a Huber data fidelity model that can handle 3-D and 3-D+t data. Efficient optimization is facilitated through the use of an alternating direction method of multipliers (ADMM) scheme and the linearization of the quantile filter. Experiments on multiple datasets emphasize the excellent performance of the proposed method.

Analyzing Relative Blood Flow Speeds in Choroidal Neovascularization Using Variable Interscan Time Analysis OCT Angiography.

PURPOSE: Longitudinally visualizing relative blood flow speeds within choroidal neovascularization (CNV) may provide valuable information regarding the evolution of CNV and the response to vascular endothelial growth factor (VEGF) inhibitors. DESIGN: Retrospective, longitudinal case series conducted at the New England Eye Center. PARTICIPANTS: Patients with either treatment-naïve or previously treated CNV secondary to neovascular age-related macular degeneration. METHODS: Optical coherence tomography angiography (OCTA) was performed using a 400-kHz, 1050-nm swept-source OCT system with a 5-repeat B-scan protocol. Variable interscan time analysis (VISTA) was used to compute relative flow speeds from pairs of B-scans having 1.5- and 3.0-ms separations; VISTA signals then were mapped to a color space for display. MAIN OUTCOME MEASURES: Quantitative outcomes included OCTA-based area and volume measurements of CNV at initial and follow-up visits. Qualitative outcomes included VISTA OCTA analysis of relative blood flow speeds, along with analysis of contraction, expansion, densification, and rarefication of CNV. RESULTS: Seven eyes of 6 patients (4 women and 2 men) with neovascular age-related macular degeneration were evaluated. Two eyes were treatment naïve at the initial visit. Choroidal neovascularization in all eyes at each visit showed relatively higher flow speeds in the trunk, central, and larger vessels and lower flow speed in the small vessels, which generally were located at the periphery of the CNV complex. Overall, the CNV appeared to expand over time despite retention of good visual acuity in all patients. In the treatment-naïve patients, slower-flow-speed vessels contracted with treatment, whereas the larger vessels with higher flow speed remained constant. CONCLUSIONS: Variable interscan time analysis OCTA allows for longitudinal observations of relative blood flow speeds in CNV treated with anti-VEGF intravitreal injections. A common finding in this study is that the main trunk and larger vessels seem to have relatively faster blood flow speeds compared with the lesions' peripheral vasculature. Moreover, an overall growth of chronically treated CNV was seen despite retention of good visual acuity. The VISTA framework may prove useful for developing clinical end points, as well as for studying hemodynamics, disease pathogenesis, and treatment response.

The Definition, Rationale, and Effects of Thresholding in OCT Angiography.

PURPOSE: To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). DESIGN: A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. PARTICIPANTS: Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. MAIN OUTCOME MEASURES: A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. RESULTS: Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS: Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images.

Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors.

PURPOSE: To evaluate tumor vasculature with optical coherence tomography angiography (OCTA) in malignant iris melanomas and benign iris lesions. DESIGN: Cross-sectional observational clinical study. PARTICIPANTS: Patients with iris lesions and healthy volunteers. METHODS: Eyes were imaged using OCTA systems operating at 1050- and 840-nm wavelengths. Three-dimensional OCTA scans were acquired. Iris melanoma patients treated with radiation therapy were imaged again after I-125 plaque brachytherapy at 6 and 18 months. MAIN OUTCOME MEASURES: OCT and OCTA images, qualitative evaluation of iris and tumor vasculature, and quantitative vessel density. RESULTS: One eye each of 8 normal volunteers and 9 patients with iris melanomas or benign iris lesions, including freckles, nevi, and an iris pigment epithelial (IPE) cyst, were imaged. The normal iris has radially oriented vessels within the stroma on OCTA. Penetration of flow signal in normal iris depended on iris color, with best penetration seen in light to moderately pigmented irides. Iris melanomas demonstrated tortuous and disorganized intratumoral vasculature. In 2 eyes with nevi there was no increased vascularity; in another, fine vascular loops were noted near an area of ectropion uveae. Iris freckles and the IPE cyst did not have intrinsic vascularity. The vessel density was significantly higher within iris melanomas (34.5%±9.8%, P < 0.05) than in benign iris nevi (8.0%±1.4%) or normal irides (8.0%±1.2%). Tumor regression after radiation therapy for melanomas was associated with decreased vessel density. OCTA at 1050 nm provided better visualization of tumor vasculature and penetration through thicker tumors than at 840 nm. But in very thick tumors and highly pigmented lesions even 1050-nm OCTA could not visualize their full thickness. Interpretable OCTA images were obtained in 82% of participants in whom imaging was attempted. CONCLUSIONS: This is the first demonstration of OCTA in iris tumors. OCTA may provide a dye-free, no-injection, cost-effective method for monitoring a variety of tumors, including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field.

AN AUTOMATIC, INTERCAPILLARY AREA-BASED ALGORITHM FOR QUANTIFYING DIABETES-RELATED CAPILLARY DROPOUT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To develop a robust, sensitive, and fully automatic algorithm to quantify diabetes-related capillary dropout using optical coherence tomography (OCT) angiography (OCTA). METHODS: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography imaging over 3 mm × 3 mm fields in normal controls (n = 5), patients with diabetes without diabetic retinopathy (DR) (n = 7), patients with nonproliferative diabetic retinopathy (NPDR) (n = 9), and patients with proliferative diabetic retinopathy (PDR) (n = 5); for each patient, one eye was imaged. A fully automatic algorithm to quantify intercapillary areas was developed. RESULTS: Of the 26 evaluated eyes, the segmentation was successful in 22 eyes (85%). The mean values of the 10 and 20 largest intercapillary areas, either including or excluding the foveal avascular zone, showed a consistent trend of increasing size from normal control eyes, to eyes with diabetic retinopathy but without diabetic retinopathy, to nonproliferative diabetic retinopathy eyes, and finally to PDR eyes. CONCLUSION: Optical coherence tomography angiography-based screening and monitoring of patients with diabetic retinopathy is critically dependent on automated vessel analysis. The algorithm presented was able to automatically extract an intercapillary area-based metric in patients having various stages of diabetic retinopathy. Intercapillary area-based approaches are likely more sensitive to early stage capillary dropout than vascular density-based methods.

TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis.

PURPOSE: Currently available optical coherence tomography angiography systems provide information about blood flux but only limited information about blood flow speed. The authors develop a method for mapping the previously proposed variable interscan time analysis (VISTA) algorithm into a color display that encodes relative blood flow speed. METHODS: Optical coherence tomography angiography was performed with a 1,050 nm, 400 kHz A-scan rate, swept source optical coherence tomography system using a 5 repeated B-scan protocol. Variable interscan time analysis was used to compute the optical coherence tomography angiography signal from B-scan pairs having 1.5 millisecond and 3.0 milliseconds interscan times. The resulting VISTA data were then mapped to a color space for display. RESULTS: The authors evaluated the VISTA visualization algorithm in normal eyes (n = 2), nonproliferative diabetic retinopathy eyes (n = 6), proliferative diabetic retinopathy eyes (n = 3), geographic atrophy eyes (n = 4), and exudative age-related macular degeneration eyes (n = 2). All eyes showed blood flow speed variations, and all eyes with pathology showed abnormal blood flow speeds compared with controls. CONCLUSION: The authors developed a novel method for mapping VISTA into a color display, allowing visualization of relative blood flow speeds. The method was found useful, in a small case series, for visualizing blood flow speeds in a variety of ocular diseases and serves as a step toward quantitative optical coherence tomography angiography.

Visualizing the Choriocapillaris Under Drusen: Comparing 1050-nm Swept-Source Versus 840-nm Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: To investigate the appearance of choriocapillaris (CC) flow under drusen by comparing long-wavelength (1050 nm) swept-source optical coherence tomography (SS-OCT) angiography with shorter-wavelength (840 nm) spectral-domain (SD) OCT angiography. METHODS: Patients with drusen imaged on both devices on the same day were selected and graded. Ambiguous OCT angiography (OCTA) signal loss was defined as low OCTA signal on the en face OCTA CC image that also had low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. Unambiguous OCTA signal loss was defined as low OCTA signal on the en face OCTA CC image that did not have low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. False-positive flow impairment on SS-OCTA was defined as ambiguous OCTA signal loss on SS-OCTA but no OCTA signal loss on SD-OCTA. False-positive flow impairment on SD-OCTA was defined as ambiguous OCTA signal loss on SD-OCTA but no OCTA signal loss on SS-OCTA. RESULTS: Nine eyes from seven patients were enrolled, 23 drusen were analyzed. On 840-nm SD-OCTA, 17 drusen (73.9%) exhibited OCTA signal loss. Fourteen (82.4%) were classified as ambiguous, and three (17.6%) were classified as unambiguous; 10 (58.8%) were classified as having false-positive flow impairment. On 1050-nm SS-OCTA, seven drusen (30.4%) exhibited OCTA signal loss and were classified as unambiguous; none were classified as having false-positive flow impairment. CONCLUSIONS: Results showed that 1050-nm SS-OCTA appears less prone to producing areas of false-positive flow impairment under drusen.

Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging.

We derive a physically realistic model for the generation of virtual transillumination, white light microscopy images using epi-fluorescence measurements from thick, unsectioned tissue. We demonstrate this technique by generating virtual transillumination H&E images of unsectioned human breast tissue from epi-fluorescence multiphoton microscopy data. The virtual transillumination algorithm is shown to enable improved contrast and color accuracy compared with previous color mapping methods. Finally, we present an open source implementation of the algorithm in OpenGL, enabling real-time GPU-based generation of virtual transillumination microscopy images using conventional fluorescence microscopy systems.

Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. DESIGN: Comparative analysis of diagnostic instruments. METHODS: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant. RESULTS: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm(2) and 0.340 ± 0.301 mm(2), respectively (P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm(2) and 0.604 ± 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively). CONCLUSION: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature.