3D Automatic Segmentation Method for Retinal Optical Coherence Tomography Volume Data Using Boundary Surface Enhancement

With the introduction of spectral-domain optical coherence tomography (SDOCT), much larger image datasets are routinely acquired compared to what was possible using the previous generation of time-domain OCT. Thus, there is a critical need for the development of 3D segmentation methods for processing these data. We present here a novel 3D automatic segmentation method for retinal OCT volume data. Briefly, to segment a boundary surface, two OCT volume datasets are obtained by using a 3D smoothing filter and a 3D differential filter. Their linear combination is then calculated to generate new volume data with an enhanced boundary surface, where pixel intensity, boundary position information, and intensity changes on both sides of the boundary surface are used simultaneously. Next, preliminary discrete boundary points are detected from the A-Scans of the volume data. Finally, surface smoothness constraints and a dynamic threshold are applied to obtain a smoothed boundary surface by correcting a small number of error points. Our method can extract retinal layer boundary surfaces sequentially with a decreasing search region of volume data. We performed automatic segmentation on eight human OCT volume datasets acquired from a commercial Spectralis OCT system, where each volume of data consisted of 97 OCT images with a resolution of 496 512; experimental results show that this method can accurately segment seven layer boundary surfaces in normal as well as some abnormal eyes.Comment: 27 pages, 19 figure

Superpixel guided active contour segmentation of retinal layers in OCT volumes

Retinal OCT image segmentation is a precursor to subsequent medical diagnosis by a clinician or machine learning algorithm. In the last decade, many algorithms have been proposed to detect retinal layer boundaries and simplify the image representation. Inspired by the recent success of superpixel methods for pre-processing natural images, we present a novel framework for segmentation of retinal layers in OCT volume data. In our framework, the region of interest (e.g. the fovea) is located using an adaptive-curve method. The cell layer boundaries are then robustly detected firstly using 1D superpixels, applied to A-scans, and then fitting active contours in B-scan images. Thereafter the 3D cell layer surfaces are efficiently segmented from the volume data. The framework was tested on healthy eye data and we show that it is capable of segmenting up to 12 layers. The experimental results imply the effectiveness of proposed method and indicate its robustness to low image resolution and intrinsic speckle noise

RETINAL OCT IMAGE ANALYSIS USING DEEP LEARNING

Optical coherence tomography (OCT) is a noninvasive imaging modality which uses low-coherence light waves to take cross-sectional images of optical scattering media. OCT has been widely used in diagnosing retinal and neural diseases by imaging the human retina. The thicknesses of retinal layers are important biomarkers for neurological diseases like multiple sclerosis (MS). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIP) thickness can be used to assess the global disease progression of MS patients. Automated OCT image analysis tools are critical for quantitatively monitoring disease progression and exploring biomarkers. With the development of more powerful computational resources, deep learning based methods have achieved much better performance in accuracy, speed, and algorithm flexibility for many image analysis tasks. However, without task-specific modifications, these emerging deep learning methods are not satisfactory if directly applied to tasks like retinal layer segmentation. In this thesis, we present a set of novel deep learning based methods for OCT image analysis. Specifically, we focus on automated retinal layer segmentation from macular OCT images. The first problem we address is that existing deep learning methods do not incorporate explicit anatomical rules and cannot guarantee the layer segmentation hierarchy~(pixels of the upper layers should have no overlap or gap with pixels of layers beneath it). To solve this, we developed an efficient fully convolutional network to generate structured layer surfaces with correct topology that is also able to perform retinal lesion~(cysts or edema) segmentation. The second problem we addressed is that the segmentation uncertainty reduces the sensitivity of detecting mild retinal changes in MS patients over time. To solve this, we developed a longitudinal deep learning pipeline that considers both inter-slice and longitudinal segmentation priors to achieve a more consistent segmentation for monitoring patient-specific retinal changes. The third problem we addressed is that the performance of the deep learning models will degrade when test data is generated from different scanners~(domain shift). We address this problem by developing a novel test-time domain adaptation method. Different from existing solutions, our model can dynamically adapt to each test subject during inference without time-consuming retraining. Our deep networks achieved state-of-the-art segmentation accuracy, speed, and flexibility compared to the existing methods

Simultaneous Multiple Surface Segmentation Using Deep Learning

The task of automatically segmenting 3-D surfaces representing boundaries of objects is important for quantitative analysis of volumetric images, and plays a vital role in biomedical image analysis. Recently, graph-based methods with a global optimization property have been developed and optimized for various medical imaging applications. Despite their widespread use, these require human experts to design transformations, image features, surface smoothness priors, and re-design for a different tissue, organ or imaging modality. Here, we propose a Deep Learning based approach for segmentation of the surfaces in volumetric medical images, by learning the essential features and transformations from training data, without any human expert intervention. We employ a regional approach to learn the local surface profiles. The proposed approach was evaluated on simultaneous intraretinal layer segmentation of optical coherence tomography (OCT) images of normal retinas and retinas affected by age related macular degeneration (AMD). The proposed approach was validated on 40 retina OCT volumes including 20 normal and 20 AMD subjects. The experiments showed statistically significant improvement in accuracy for our approach compared to state-of-the-art graph based optimal surface segmentation with convex priors (G-OSC). A single Convolution Neural Network (CNN) was used to learn the surfaces for both normal and diseased images. The mean unsigned surface positioning errors obtained by G-OSC method 2.31 voxels (95% CI 2.02-2.60 voxels) was improved to $1.27$ voxels (95% CI 1.14-1.40 voxels) using our new approach. On average, our approach takes 94.34 s, requiring 95.35 MB memory, which is much faster than the 2837.46 s and 6.87 GB memory required by the G-OSC method on the same computer system.Comment: 8 page

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE