Depth-resolved vascular profile features for artery-vein classification in OCT and OCT angiography of human retina

This study is to characterize reflectance profiles of retinal blood vessels in optical coherence tomography (OCT), and to test the potential of using these vascular features to guide artery-vein classification in OCT angiography (OCTA) of the human retina. Depth-resolved OCT reveals unique features of retinal arteries and veins. Retinal arteries show hyper-reflective boundaries at both upper (inner side towards the vitreous) and lower (outer side towards the choroid) walls. In contrast, retinal veins reveal hyper-reflectivity at the upper boundary only. Uniform lumen intensity was observed in both small and large arteries. However, the venous lumen intensity was dependent on the vessel size. Small veins exhibit a hyper-reflective zone at the bottom half of the lumen, while large veins show a hypo-reflective zone at the bottom half of the lumen.     

High-speed and widefield handheld swept-source OCT angiography with a VCSEL light source

Optical coherence tomography (OCT) and OCT angiography (OCTA) enable noninvasive structural and angiographic imaging of the eye. Portable handheld OCT/OCTA systems are required for imaging patients in the supine position. Examples include infants in the neonatal intensive care unit (NICU) and operating room (OR). The speed of image acquisition plays a pivotal role in acquiring high-quality OCT/OCTA images, particularly with the handheld system, since both the operator hand tremor and subject motion can cause significant motion artifacts. In addition, having a large field of view and the ability of real-time data visualization are critical elements in rapid disease screening, reducing imaging time, and detecting peripheral retinal pathologies. The arrangement of optical components is less flexible in the handheld system due to the limitation of size and weight. In this paper, we introduce a 400-kHz, 55-degree field of view handheld OCT/OCTA system that has overcome many technical challenges as a portable OCT system as well as a high-speed OCTA system. We demonstrate imaging premature infants with retinopathy of prematurity (ROP) in the NICU, a patient with incontinentia pigmenti (IP), and a patient with X-linked retinoschisis (XLRS) in the OR using our handheld OCT system. Our design may have the potential for improving the diagnosis of retinal diseases and help provide a practical guideline for designing a flexible and portable OCT system.     

Dynamic inverse SNR-decorrelation OCT angiography with GPU acceleration

Dynamic OCT angiography (OCTA) is an attractive approach for monitoring stimulus-evoked hemodynamics; however, a 4D (3D space and time) dataset requires a long acquisition time and has a large data size, thereby posing a great challenge to data processing. This study proposed a GPU-based real-time data processing pipeline for dynamic inverse SNR-decorrelation OCTA (ID-OCTA), offering a measured line-process rate of 133 kHz for displaying OCT and OCTA cross-sections in real time. Real-time processing enabled automatic optimization of angiogram quality, which improved the vessel SNR, contrast-to-noise ratio, and connectivity by 14.37, 14.08, and 9.76%, respectively. Furthermore, motion-contrast 4D angiographic imaging of stimulus-evoked hemodynamics was achieved within a single trail in the mouse retina. Consequently, a flicker light stimulus evoked an apparent dilation of the retinal arterioles and venules and an elevation of the decorrelation value in the retinal plexuses. Therefore, GPU ID-OCTA enables real-time and high-quality angiographic imaging and is particularly suitable for hemodynamic studies.     

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.     

In vivo imaging of retinal hemodynamics with OCT angiography and Doppler OCT

Retinal hemodynamics is important for early diagnosis and precise monitoring in retinal vascular diseases. We propose a novel method for measuring absolute retinal blood flow in vivo using the combined techniques of optical coherence tomography (OCT) angiography and Doppler OCT. Doppler values can be corrected by Doppler angles extracted from OCT angiography images. A three-dimensional (3D) segmentation algorithm based on dynamic programming was developed to extract the 3D boundaries of optic disc vessels, and Doppler angles were calculated from 3D vessel geometry. The accuracy of blood flow from the Doppler OCT was validated using a flow phantom. The feasibility of the method was tested on a subject in vivo. The pulsatile retinal blood flow and the parameters for retinal hemodynamics were successfully obtained.OCIS codes: (100.2960) Image analysis, (100.6890) Three-dimensional image processing, (170.4500) Optical coherence tomography, (170.4460) Ophthalmic optics and devices     

Phase-stabilized complex-decorrelation angiography

In this study, we developed a novel phase-stabilized complex-decorrelation (PSCD) optical coherence tomography (OCT) angiography (OCTA) method that can generate high quality OCTA images. This method has been validated using three different types of OCT systems and compared with conventional complex- and amplitude-based OCTA algorithms. Our results suggest that in combination with a pre-processing phase stabilization method, the PSCD method is insensitive to bulk motion phase shifts, less dependent on OCT reflectance than conventional complex methods and demonstrates extended dynamic range of flow signal, in contrast to other two methods.     

Functional optoretinography: concurrent OCT monitoring of intrinsic signal amplitude and phase dynamics in human photoreceptors

Intrinsic optical signal (IOS) imaging promises a noninvasive method for objective assessment of retinal function. This study demonstrates concurrent optical coherence tomography (OCT) of amplitude-IOS and phase-IOS changes in human photoreceptors. A new procedure for differential-phase-mapping (DPM) is validated to enable depth-resolved phase-IOS imaging. Dynamic OCT revealed rapid amplitude-IOS and phase-IOS changes, which occur almost right away after the stimulus onset. These IOS changes were predominantly observed within the photoreceptor outer segment (OS), particularly two boundaries connecting to the inner segment and retinal pigment epithelium. The comparative analysis supports that both amplitude-IOS and phase-IOS attribute to transient OS morphological change associated with phototransduction activation in retinal photoreceptors. A simulation modeling is proposed to discuss the relationship between the photoreceptor OS length and phase-IOS changes.     

Optical coherence tomography angiography characteristics in Waldenström macroglobulinemia retinopathy: A case report

BACKGROUNDWaldenström macroglobulinemia (WM) is a distinct clinicopathologic entity characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM) in the blood, and patients may present with symptoms related to the infiltration of the hematopoietic tissues or the effects of monoclonal IgM in the blood. Funduscopic abnormalities were noted in some of the patients due to hyperviscosity or other retinal lesions. Optical coherence tomography angiography (OCTA) as a non-invasive imaging tool can give qualitative and quantitative information about the status of retinal and choroidal vessels, which might be useful for diagnosing patients with WM-associated retinopathy.CASE SUMMARYThe patient was a 67-year-old man who presented with sudden visual disturbance in both eyes. Ophthalmic tests showed that best corrected visual acuity (BCVA) for this patient was 20/100 in the right eye and 20/1000 in the left eye. Fundus examination, optical coherence tomography (OCT), and OCTA revealed substantial bilateral optic disc edema, dilated and tortuous retinal veins, and diffuse intraretinal blot hemorrhages and edema which were consistent with bilateral central retinal vein occlusion (CRVO). Meanwhile, remarkable bilateral serous macular detachments (SMD) were noticed on OCT. Systemic examinations showed that the patient had anemia and extremely high level of monoclonal IgM and infiltration of clonal lymphoplasmacytic cells in bone marrow. The diagnosis of WM with hyperviscosity and retinopathy was made based on the clinical manifestation and laboratory findings. He was subsequently treated with intravitreal ranibizumab injection, plasmapheresis, and bortezomib plus rituximab with dexamethasone. Six months after treatments, the central macular volume decreased by 16.1% in the right eye and 28.6% in the left eye on OCT, and the patient’s BCVA was improved to 20/60 in the right eye and 20/400 in the left eye. Very good partial response was obtained after systemic treatment.CONCLUSIONWM may affect visual function and present as bilateral CRVO. OCTA can show characteristic changes in both retina and choroid vasculatures, which might be of great value for diagnosing or following patients with WM retinopathy. Intravitreal anti-vascular endothelial growth factor treatment combined with systemic therapy might be beneficial for WM patients with retinopathy (SMD and CRVO).     

Quantitative multi-contrast in vivo mouse imaging with polarization diversity optical coherence tomography and angiography

Retinal microvasculature and the retinal pigment epithelium (RPE) play vital roles in maintaining the health and metabolic activity of the eye. Visualization of these retina structures is essential for pre-clinical studies of vision-robbing diseases, such as age-related macular degeneration (AMD). We have developed a quantitative multi-contrast polarization diversity OCT and angiography (QMC-PD-OCTA) system for imaging and visualizing pigment in the RPE using degree of polarization uniformity (DOPU), along with flow in the retinal capillaries using OCT angiography (OCTA). An adaptive DOPU averaging kernel was developed to increase quantifiable values from visual data, and QMC en face images permit simultaneous visualization of vessel location, depth, melanin region thickness, and mean DOPU values, allowing rapid identification and differentiation of disease symptoms. The retina of five different mice strains were measured in vivo, with results demonstrating potential for pre-clinical studies of retinal disorders.     

Effect of A-scan rate and interscan interval on optical coherence angiography

Optical coherence tomography angiography (OCTA) can provide rapid, volumetric, and noninvasive imaging of tissue microvasculature without the requirement of exogenous contrast agents. To investigate how A-scan rate and interscan time affected the contrast and dynamic range of OCTA, we developed a 1.06-µm swept-source OCT system enabling 100-kHz or 200-kHz OCT using two light sources. After system settings were carefully adjusted, almost the same detection sensitivity was achieved between the 100-kHz and 200-kHz modalities. OCTA of ear skin was performed on five mice. We used the variable interscan time analysis algorithm (VISTA) and the designated scanning protocol with OCTA images reconstructed through the correlation mapping method. With a relatively long interscan time (e.g., 12.5 ms vs. 6.25 ms for 200-kHz OCT), OCTA can identify more intricate microvascular networks. OCTA image sets with the same interscan time (e.g., 12.5 ms) were compared. OCTA images acquired with a 100-kHz A-scan rate showed finer microvasculature than did other imaging modalities. We performed quantitative analysis on the contrast from OCTA images reconstructed with different A-scan rates and interscan time intervals in terms of vessel area, total vessel length, and junction density.     

视网膜分支静脉阻塞患者的脉络膜厚度及血流密度分析

目的分析视网膜分支静脉阻塞(BRVO)患者的脉络膜厚度及血流密度。方法选取2019年1月至2019年9月于重庆市中医院眼科门诊确诊为非缺血型BRVO的20例患者作为研究对象,均为单侧眼睛非缺血型BRVO。将20只患眼纳入A组,20只对侧眼纳入B组。采用光学相干断层扫描血流成像(OCTA)技术测定视网膜脉络膜血流密度,采用增强深部成像(EDI)-OCT技术测定脉络膜厚度。比较两组的脉络膜厚度、视网膜脉络膜血流密度及最佳矫正视力(BCVA);分析BCVA与脉络膜厚度及视网膜脉络膜血流密度的相关性。结果A组中央脉络膜厚度、中心凹上、下方4.5 mm脉络膜厚度均厚于B组,差异具有统计学意义(P<0.05)。A组LogMAR BCVA高于B组,差异具有统计学意义(P<0.05)。A组、B组BCVA与脉络膜厚度呈负相关,与视网膜脉络膜血流密度呈低负相关(P<0.05)。结论BRVO患者的脉络膜厚度、视网膜脉络膜血流密度与患者视力预后紧密相关,OCTA技术在BRVO的诊疗中具有一定的意义。     

Developing a normative database for retinal perfusion using optical coherence tomography angiography

Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual’s data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12×12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and >69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12×12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma.     

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.     

An end-to-end network for segmenting the vasculature of three retinal capillary plexuses from OCT angiographic volumes

The segmentation of en face retinal capillary angiograms from volumetric optical coherence tomographic angiography (OCTA) usually relies on retinal layer segmentation, which is time-consuming and error-prone. In this study, we developed a deep-learning-based method to segment vessels in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) directly from volumetric OCTA data. The method contains a three-dimensional convolutional neural network (CNN) for extracting distinct retinal layers, a custom projection module to generate three vascular plexuses from OCTA data, and three parallel CNNs to segment vasculature. Experimental results on OCTA data from rat eyes demonstrated the feasibility of the proposed method. This end-to-end network has the potential to simplify OCTA data processing on retinal vasculature segmentation. The main contribution of this study is that we propose a custom projection module to connect retinal layer segmentation and vasculature segmentation modules and automatically convert data from three to two dimensions, thus establishing an end-to-end method to segment three retinal capillary plexuses from volumetric OCTA without any human intervention.     

视网膜静脉阻塞性黄斑水肿OCT和FFA的对比分析

目的探讨视网膜静脉阻塞性黄斑水肿相干光断层扫描（OCT）和眼底荧光素血管造影（FFA）的相互关系。方法分别对视网膜静脉阻塞性黄斑水肿患者进行OCT及FFA检查,观察两种分类之间的相互关系,并与中心凹中心厚度、最佳矫正视力等临床资料进行对比分析。结果FFA分类的局限水肿型在OCT1型中所占的比例高于弥漫水肿型和囊样水肿型。FFA弥漫水肿型在OCT2型中占的比例明显高于局限水肿型和囊样水肿型。FFA分类的囊样水肿型在OCT3型（3A型＋3B型）中占的比例明显高于局限水肿型和弥漫水肿型。OCT1型及FFA局限水肿型的矫正视力最好,黄斑中心凹中心厚度值最小（p〈0．05）。结论视网膜静脉阻塞性黄斑水肿患者结合OCT与FFA两种检查方法,可更加全面地反映视网膜静脉阻塞性黄斑水肿患者黄斑区视网膜的变化,为揭示视网膜静脉阻塞性黄斑水肿的病理机制、寻求每种类型的最佳治疗方案提供参考。     

Analysis of macular OCT images using deformable registration

Optical coherence tomography (OCT) of the macula has become increasingly important in the investigation of retinal pathology. However, deformable image registration, which is used for aligning subjects for pairwise comparisons, population averaging, and atlas label transfer, has not been well–developed and demonstrated on OCT images. In this paper, we present a deformable image registration approach designed specifically for macular OCT images. The approach begins with an initial translation to align the fovea of each subject, followed by a linear rescaling to align the top and bottom retinal boundaries. Finally, the layers within the retina are aligned by a deformable registration using one-dimensional radial basis functions. The algorithm was validated using manual delineations of retinal layers in OCT images from a cohort consisting of healthy controls and patients diagnosed with multiple sclerosis (MS). We show that the algorithm overcomes the shortcomings of existing generic registration methods, which cannot be readily applied to OCT images. A successful deformable image registration algorithm for macular OCT opens up a variety of population based analysis techniques that are regularly used in other imaging modalities, such as spatial normalization, statistical atlas creation, and voxel based morphometry. Examples of these applications are provided to demonstrate the potential benefits such techniques can have on our understanding of retinal disease. In particular, included is a pilot study of localized volumetric changes between healthy controls and MS patients using the proposed registration algorithm.OCIS codes: (100.0100) Image processing, (170.4470) Ophthalmology, (170.4500) Optical coherence tomography     

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.     

Automatic segmentation of up to ten layer boundaries in SD-OCT images of the mouse retina with and without missing layers due to pathology

Accurate quantification of retinal layer thicknesses in mice as seen on optical coherence tomography (OCT) is crucial for the study of numerous ocular and neurological diseases. However, manual segmentation is time-consuming and subjective. Previous attempts to automate this process were limited to high-quality scans from mice with no missing layers or visible pathology. This paper presents an automatic approach for segmenting retinal layers in spectral domain OCT images using sparsity based denoising, support vector machines, graph theory, and dynamic programming (S-GTDP). Results show that this method accurately segments all present retinal layer boundaries, which can range from seven to ten, in wild-type and rhodopsin knockout mice as compared to manual segmentation and has a more accurate performance as compared to the commercial automated Diver segmentation software.OCIS codes: (100.0100) Image processing, (170.4470) Ophthalmology, (100.2960) Image analysis, (100.5010) Pattern recognition, (110.4500) Optical coherence tomography     

光学相干断层成像技术对视网膜病变时视力与神经上皮层关系及预后的评估作用

背景光学相干断层成像(optical coherence tomography,OCT)是一种新型的非接触性、非损伤性的视网膜断层扫描技术,可分辨显示微小的视网膜神经上皮层的浆液性脱离,并能定量测量视网膜神经上皮层或色素上皮层下液的范围,以评估视力恢复情况.目的光学相干断层成像技术在评估特发性中心性浆液性脉络膜视网膜病变(idiopathic central serous chorioretinopathy,ICSC)时视力与神经上皮层关系及其预后中的应用价值.设计单一样本研究.单位一所大学医院的眼科中心.对象1999-01/2003-06暨南大学医学院深圳眼科中心初诊的ICSC患者.男32例,女8例;年龄平均(36.2±5.6)岁.干预采用Zeiss-Humphrey OCT成像仪进行检查.对ICSC的浆液性脱离区分别测量其最大脱离范围和最大脱离高度,并计算平均值和标准差.主要观察指标视力、浆液性脱离的最大脱离范围和最大脱离高度.结果40例(41眼)ICSC的OCT图像均表现为黄斑中心的视网膜神经上皮层局限性脱离,脱离范围在705～5 720μm[平均(3 051±1 338)μm],高度55～491 μm[平均(270±114)μm].4眼合并有色素上皮层浆液性脱离.并经统计表明脱离范围、高度与视力相关.结论OCT作为一种客观的无损伤的视网膜断层扫描技术,其高分辨率的特性在ICSC的诊断、定量分析和病程视功能评估检测随访中具有重要的价值和特别的优势.     

Initial color Doppler findings in retinal vein occlusion

PURPOSE: We assessed early hemodynamic characteristics of various types of retinal vein occlusion using color Doppler imaging and spectral analysis. METHODS: We measured the maximum systolic and diastolic blood flow velocities and the resistance index (RI) in the central retinal artery and the maximum and minimum blood flow velocities in the central retinal vein of affected eyes and contralateral unaffected eyes in 102 adults (63 men and 39 women; mean age, 61 +/- 14.6 years) who presented with retinal vein occlusion. Sixty-three control subjects (27 men and 36 women; mean age, 50 +/- 22.1 years) were also investigated. RESULTS: No significant differences in hemodynamic characteristics were found between the control subjects' eyes and the patients' unaffected eyes. In the 18 cases of ischemic central retinal vein occlusion, the mean diastolic arterial flow velocity (p = 0.005) and venous flow velocity (p < 0.04) were lower and the mean RI was higher (p = 0. 0002) in the affected eyes than in the unaffected contralateral eyes. In the 51 cases of nonischemic central retinal vein occlusion, the mean diastolic arterial flow velocity (p < 0.0001) and venous flow velocity (p < 0.0001) also were lower and the mean RI (p < 0.0001) was higher in the affected eyes than in the unaffected contralateral eyes. These variables were different in the ischemic versus nonischemic types of central retinal vein occlusion. In the 33 cases of branch retinal vein occlusion, no significant differences were observed in arterial or venous blood flow velocities in the affected versus unaffected eyes. The mean RI in the affected eyes was significantly higher (p = 0.009) in patients with central versus branch retinal vein occlusion. CONCLUSIONS: These results suggest that previous arterial disorders were not involved in the pathogenesis of central retinal vein occlusion in these patients. The findings also support the value of Doppler imaging and spectral analysis in the diagnosis and evaluation of retinal vein occlusion and confirm the involvement of arterial flow in venous occlusion.