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Precise characterization and analysis of corneal nerve fiber tortuosity are of great importance in facilitating examination and diagnosis of many eye-related diseases. In this paper we propose a fully automated method for image-level tortuosity estimation, comprising image enhancement, exponential curvature estimation, and tortuosity level classification. The image enhancement component is based on an extended Retinex model, which not only corrects imbalanced illumination and improves image contrast in an image, but also models noise explicitly to aid removal of imaging noise. Afterwards, we take advantage of exponential curvature estimation in the 3D space of positions and orientations to directly measure curvature based on the enhanced images, rather than relying on the explicit segmentation and skeletonization steps in a conventional pipeline usually with accumulated pre-processing errors. The proposed method has been applied over two corneal nerve microscopy datasets for the estimation of a tortuosity level for each image. The experimental results show that it performs better than several selected state-of-the-art methods. Furthermore, we have performed manual gradings at tortuosity level of four hundred and three corneal nerve microscopic images, and this dataset has been released for public access to facilitate other researchers in the community in carrying out further research on the same and related topics. [ABSTRACT FROM AUTHOR]

3D optical coherence tomography angiography (OCT-A) is a novel and non-invasive imaging modality for analyzing retinal diseases. The studies of microvasculature in 2D en face projection images have been widely implemented, but comprehensive 3D analysis of OCT-A images with rich depth-resolved microvascular information is rarely considered. In this paper, we propose a robust, effective, and automatic 3D shape modeling framework to provide a high-quality 3D vessel representation and to preserve valuable 3D geometric and topological information for vessel analysis. Effective vessel enhancement and extraction steps by means of curvelet denoising and optimally oriented flux (OOF) filtering are first designed to produce 3D microvascular networks. Afterwards, a novel 3D data representation of OCT-A microvasculature is reconstructed via advanced mesh reconstruction techniques. Based on the 3D surfaces, shape analysis is established to extract novel shape-based microvascular area distortion via the Laplace-Beltrami eigen-projection. The extracted feature is integrated into a graph-cut segmentation system to categorize large vessels and small capillaries for more precise shape analysis. The proposed framework is validated on a dedicated repeated scan dataset including 260 volume images and shows high repeatability. Statistical analysis using the surface area biomarker is performed on small capillaries to avoid the effect of tailing artifact from large vessels. It shows significant differences ($p< 0.001$) between DR stages on 100 subjects in a OCTA-DR dataset. The proposed shape modeling and analysis framework opens the possibility for further investigating OCT-A microvasculature in a new perspective. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a significant microvascular complication of diabetes mellitus and a leading cause of vision impairment in working age adults. Optical coherence tomography (OCT) is a routinely used clinical tool to observe retinal structural and thickness alterations in DR. Pathological changes that alter the normal anatomy of the retina, such as intraretinal edema, pose great challenges for conventional layer-based analysis of OCT images. We present an alternative approach for the automated analysis of OCT volumes in DR research based on nonlinear registration. In this paper, we first obtain an anatomically consistent volume of interest (VOI) in different OCT images via carefully designed masking and affine registration. After that, efficient B-spline transformations are computed using stochastic gradient descent optimization. Using the OCT volumes of normal controls, for which layer-based segmentation works well, we demonstrate the accuracy of our registration-based analysis in aligning layer boundaries. By nonlinearly registering the OCT volumes of DR subjects to an atlas constructed from normal controls and measuring the Jacobian determinant of the deformation, we can simultaneously visualize tissue contraction and expansion due to DR pathology. Tensor-based morphometry (TBM) can also be performed for quantitative analysis of local structural changes. In our experimental results, we apply our method to a dataset of 105 subjects and demonstrate that volumetric OCT registration and TBM analysis can successfully detect local retinal structural alterations due to DR. [ABSTRACT FROM AUTHOR]

This paper presents a robust and fully automatic filter-based approach for retinal vessel segmentation. We propose new filters based on 3D rotating frames in so-called orientation scores, which are functions on the Lie-group domain of positions and orientations \mathbb R^2 \rtimes S^1 . By means of a wavelet-type transform, a 2D image is lifted to a 3D orientation score, where elongated structures are disentangled into their corresponding orientation planes. In the lifted domain \mathbb R^2 \rtimes S^1 , vessels are enhanced by means of multi-scale second-order Gaussian derivatives perpendicular to the line structures. More precisely, we use a left-invariant rotating derivative (LID) frame, and a locally adaptive derivative (LAD) frame. The LAD is adaptive to the local line structures and is found by eigensystem analysis of the left-invariant Hessian matrix (computed with the LID). After multi-scale filtering via the LID or LAD in the orientation score domain, the results are projected back to the 2D image plane giving us the enhanced vessels. Then a binary segmentation is obtained through thresholding. The proposed methods are validated on six retinal image datasets with different image types, on which competitive segmentation performances are achieved. In particular, the proposed algorithm of applying the LAD filter on orientation scores (LAD-OS) outperforms most of the state-of-the-art methods. The LAD-OS is capable of dealing with typically difficult cases like crossings, central arterial reflex, closely parallel and tiny vessels. The high computational speed of the proposed methods allows processing of large datasets in a screening setting. [ABSTRACT FROM PUBLISHER]

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Automated detection of retinal structures, such as retinal vessels (RV), the foveal avascular zone (FAZ), and retinal vascular junctions (RVJ), are of great importance for understanding diseases of the eye and clinical decision-making. In this paper, we propose a novel Voting-based Adaptive Feature Fusion multi-task network (VAFF-Net) for joint segmentation, detection, and classification of RV, FAZ, and RVJ in optical coherence tomography angiography (OCTA). A task-specific voting gate module is proposed to adaptively extract and fuse different features for specific tasks at two levels: features at different spatial positions from a single encoder, and features from multiple encoders. In particular, since the complexity of the microvasculature in OCTA images makes simultaneous precise localization and classification of retinal vascular junctions into bifurcation/crossing a challenging task, we specifically design a task head by combining the heatmap regression and grid classification. We take advantage of three different en face angiograms from various retinal layers, rather than following existing methods that use only a single en face. We carry out extensive experiments on three OCTA datasets acquired using different imaging devices, and the results demonstrate that the proposed method performs on the whole better than either the state-of-the-art single-purpose methods or existing multi-task learning solutions. We also demonstrate that our multi-task learning method generalizes across other imaging modalities, such as color fundus photography, and may potentially be used as a general multi-task learning tool. We also construct three datasets for multiple structure detection, and part of these datasets with the source code and evaluation benchmark have been released for public access. [ABSTRACT FROM AUTHOR]

Accurate estimation and quantification of the corneal nerve fiber tortuosity in corneal confocal microscopy (CCM) is of great importance for disease understanding and clinical decision-making. However, the grading of corneal nerve tortuosity remains a great challenge due to the lack of agreements on the definition and quantification of tortuosity. In this paper, we propose a fully automated deep learning method that performs image-level tortuosity grading of corneal nerves, which is based on CCM images and segmented corneal nerves to further improve the grading accuracy with interpretability principles. The proposed method consists of two stages: 1) A pre-trained feature extraction backbone over ImageNet is fine-tuned with a proposed novel bilinear attention (BA) module for the prediction of the regions of interest (ROIs) and coarse grading of the image. The BA module enhances the ability of the network to model long-range dependencies and global contexts of nerve fibers by capturing second-order statistics of high-level features. 2) An auxiliary tortuosity grading network (AuxNet) is proposed to obtain an auxiliary grading over the identified ROIs, enabling the coarse and additional gradings to be finally fused together for more accurate final results. The experimental results show that our method surpasses existing methods in tortuosity grading, and achieves an overall accuracy of 85.64% in four-level classification. We also validate it over a clinical dataset, and the statistical analysis demonstrates a significant difference of tortuosity levels between healthy control and diabetes group. We have released a dataset with 1500 CCM images and their manual annotations of four tortuosity levels for public access. The code is available at: https://github.com/iMED-Lab/TortuosityGrading. [ABSTRACT FROM AUTHOR]

The segmentation of pathological fluid lesions in optical coherence tomography (OCT), including intraretinal fluid, subretinal fluid, and pigment epithelial detachment, is of great importance for the diagnosis and treatment of various eye diseases such as neovascular age-related macular degeneration and diabetic macular edema. Although significant progress has been achieved with the rapid development of fully convolutional neural networks (FCN) in recent years, some important issues remain unsolved. First, pathological fluid lesions in OCT show large variations in location, size, and shape, imposing challenges on the design of FCN architecture. Second, fluid lesions should be continuous regions without holes inside. But the current architectures lack the capability to preserve the shape prior information. In this study, we introduce an FCN architecture for the simultaneous segmentation of three types of pathological fluid lesions in OCT. First, attention gate and spatial pyramid pooling modules are employed to improve the ability of the network to extract multi-scale objects. Then, we introduce a novel curvature regularization term in the loss function to incorporate shape prior information. The proposed method was extensively evaluated on public and clinical datasets with significantly improved performance compared with the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

The development of medical imaging techniques has greatly supported clinical decision making. However, poor imaging quality, such as non-uniform illumination or imbalanced intensity, brings challenges for automated screening, analysis and diagnosis of diseases. Previously, bi-directional GANs (e.g., CycleGAN), have been proposed to improve the quality of input images without the requirement of paired images. However, these methods focus on global appearance, without imposing constraints on structure or illumination, which are essential features for medical image interpretation. In this paper, we propose a novel and versatile bi-directional GAN, named Structure and illumination constrained GAN (StillGAN), for medical image quality enhancement. Our StillGAN treats low- and high-quality images as two distinct domains, and introduces local structure and illumination constraints for learning both overall characteristics and local details. Extensive experiments on three medical image datasets (e.g., corneal confocal microscopy, retinal color fundus and endoscopy images) demonstrate that our method performs better than both conventional methods and other deep learning-based methods. In addition, we have investigated the impact of the proposed method on different medical image analysis and clinical tasks such as nerve segmentation, tortuosity grading, fovea localization and disease classification. [ABSTRACT FROM AUTHOR]

Optical Coherence Tomography Angiography (OCTA) is a non-invasive imaging technique that has been increasingly used to image the retinal vasculature at capillary level resolution. However, automated segmentation of retinal vessels in OCTA has been under-studied due to various challenges such as low capillary visibility and high vessel complexity, despite its significance in understanding many vision-related diseases. In addition, there is no publicly available OCTA dataset with manually graded vessels for training and validation of segmentation algorithms. To address these issues, for the first time in the field of retinal image analysis we construct a dedicated Retinal OCTA SEgmentation dataset (ROSE), which consists of 229 OCTA images with vessel annotations at either centerline-level or pixel level. This dataset with the source code has been released for public access to assist researchers in the community in undertaking research in related topics. Secondly, we introduce a novel split-based coarse-to-fine vessel segmentation network for OCTA images (OCTA-Net), with the ability to detect thick and thin vessels separately. In the OCTA-Net, a split-based coarse segmentation module is first utilized to produce a preliminary confidence map of vessels, and a split-based refined segmentation module is then used to optimize the shape/contour of the retinal microvasculature. We perform a thorough evaluation of the state-of-the-art vessel segmentation models and our OCTA-Net on the constructed ROSE dataset. The experimental results demonstrate that our OCTA-Net yields better vessel segmentation performance in OCTA than both traditional and other deep learning methods. In addition, we provide a fractal dimension analysis on the segmented microvasculature, and the statistical analysis demonstrates significant differences between the healthy control and Alzheimer’s Disease group. This consolidates that the analysis of retinal microvasculature may offer a new scheme to study various neurodegenerative diseases. [ABSTRACT FROM AUTHOR]