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Automatic segmentation of retinal blood vessels from fundus images is of great importance in assessing the condition of vascular network in human eyes. The task is primary challenging due to the low contrast of images, the variety of vessels and potential pathology. Previous studies have proposed shallow machine learning based methods to tackle the problem. However, these methods require specific domain knowledge, and the efficiency and robustness of these methods are not satisfactory for medical diagnosis. In recent years, deep learning models have made great progress in various segmentation tasks. In particular, Fully Convolutional Network and U-net have achieved promising results in end-to-end dense prediction tasks. In this study, we propose a novel encoder-decoder architecture based on the vanilla U-net architecture for retinal blood vessels segmentation. The proposed deep learning architecture integrates hybrid dilation convolutions and pixel transposed convolutions in the encoder-decoder model. Such design enables global dense feature extraction and resolves the common “gridding” and “checkerboard” issues in the regular U-net. Furthermore, the proposed network can be efficiently and directly implemented for any semantic segmentation applications. We evaluate the proposed network on two retinal blood vessels data sets. The experimental results show that our proposed model outperforms the baseline U-net model.

The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.

This paper aims to trace retinal blood vessel trees in fundus images. This task is far from being trivial as the crossover of vessels are commonly encountered in image-based vessel networks. Meanwhile it is often crucial to separate the vessel tree structures in applications such as diabetic retinopathy analysis. In this work, a novel directed graph based approach is proposed to cast the task as label propagation over directed graphs, such that the graph is to be partitioned into disjoint sub-graphs, or equivalently, each of the vessel trees is traced and separated from the rest of the vessel network. Then the tracing problem is addressed by making novel usage of the matrix-forest theorem in algebraic graph theory. Empirical experiments on synthetic as well as publicly available fundus image datasets demonstrate the applicability of our approach.

Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor (VEGF) in retinal ischemia. Retinal ischemia was induced in porcine eyes by applying an intraocular pressure, followed by 12 h of reperfusion. HIF-1α mRNA expression was not affected by ischemia, while immunofluorescence staining was higher after ischemia in the neuroretina. HIF-1β immunoreactivity and mRNA expression were unaffected. VEGF protein levels in the vitreous humor and VEGF staining in the neuroretina were more pronounced in eyes subjected to ischemia than in the sham eyes. VEGF may be activated downstream of HIF-1 and is known to stimulate retinal neovascularization, which causes sight-threatening complications. These results emphasize the need for pharmacological treatment to block the HIF and VEGF signaling pathways in retinal ischemia.

We present a method for automatically segmenting the blood vessels in optic nerve head (ONH) centered spectral-domain optical coherence tomography (SD-OCT) volumes, with a focus on the ability to segment the vessels in the region near the neural canal opening (NCO). The algorithm first pre-segments the NCO using a graph-theoretic approach. Oriented Gabor wavelets rotated around the center of the NCO are applied to extract features in a 2-D vessel-aimed projection image. Corresponding oriented NCO-based templates are utilized to help suppress the false positive tendency near the NCO boundary. The vessels are identified in a vessel-aimed projection image using a pixel classification algorithm. Based on the 2-D vessel profiles, 3-D vessel segmentation is performed by a triangular-mesh-based graph search approach in the SD-OCT volume. The segmentation method is trained on 5 and is tested on 10 randomly chosen independent ONH-centered SD-OCT volumes from 15 subjects with glaucoma. Using ROC analysis, for the 2-D vessel segmentation, we demonstrate an improvement over the closest previous work with an area under the curve (AUC) of 0.81 (0.72 for previously reported approach) for the region around the NCO and 0.84 for the region outside the NCO (0.81 for previously reported approach).

In this paper, segmentation of blood vessels from colour retinal images using a novel clustering algorithm with a partial supervision strategy is proposed. The proposed clustering algorithm, which is a RAdius based Clustering ALgorithm (RACAL), uses a distance based principle to map the distributions of the data by utilising the premise that clusters are determined by a distance parameter, without having to specify the number of clusters. Additionally, the proposed clustering algorithm is enhanced with a partial supervision strategy and it is demonstrated that it is able to segment blood vessels of small diameters and low contrasts. Results are compared with those from the KNN classifier and show that the proposed RACAL performs better than the KNN in case of abnormal images as it succeeds in segmenting small and low contrast blood vessels, while it achieves comparable results for normal images. For automation process, RACAL can be used as a classifier and results show that it performs better than the KNN classifier in both normal and abnormal images.

The posterior segment of the human eye complex contains two discrete microstructure and vasculature network systems, namely, the retina and choroid. We present a single segmentation framework technique for segmenting the entire layers present in the chorio-retinal complex of the human eye using optical coherence tomography (OCT) images. This automatic program is based on the graph theory method. This single program is capable of segmenting seven layers of the retina and choroid scleral interface. The graph theory was utilized to find the probability matrix and subsequent boundaries of different layers. The program was also implemented to segment angiographic maps of different chorio-retinal layers using "segmentation matrices." The method was tested and successfully validated on OCT images from six normal human eyes as well as eyes with non-exudative age-related macular degeneration (AMD). The thickness of microstructure and microvasculature for different layers located in the chorio-retinal segment of the eye was also generated and compared. A decent efficiency in terms of processing time, sensitivity, and accuracy was observed compared to the manual segmentation and other existing methods. The proposed method automatically segments whole OCT images of chorio-retinal complex with augmented probability maps generation in OCT volume dataset. We have also evaluated the segmentation results using quantitative metrics such as Dice coefficient and Hausdorff distance This method realizes a mean descent Dice similarity coefficient (DSC) value of 0.82 (range, 0.816-0.864) for RPE and CSI layer., (© 2024. International Federation for Medical and Biological Engineering.)

Segmenting retinal vessels plays a significant role in the diagnosis of fundus disorders. However, there are two problems in the retinal vessel segmentation methods. First, fine-grained features of fine blood vessels are difficult to be extracted. Second, it is easy to lose track of the details of blood vessel edges. To solve the problems above, the Residual SimAM Pyramid-Spatial Attention Unet (RSP-SA Unet) is proposed, in which the encoding, decoding, and upsampling layers of the Unet are mainly improved. Firstly, the RSP structure proposed in this paper approximates a residual structure combined with SimAM and Pyramid Segmentation Attention (PSA), which is applied to the encoding and decoding parts to extract multi-scale spatial information and important features across dimensions at a finer level. Secondly, the spatial attention (SA) is used in the upsampling layer to perform multi-attention mapping on the input feature map, which could enhance the segmentation effect of small blood vessels with low contrast. Finally, the RSP-SA Unet is verified on the CHASE_DB1, DRIVE, and STARE datasets, and the segmentation accuracy (ACC) of the RSP-SA Unet could reach 0.9763, 0.9704, and 0.9724, respectively. Area under the ROC curve (AUC) could reach 0.9896, 0.9858, and 0.9906, respectively. The RSP-SA Unet overall performance is better than the comparison methods., (© 2023. International Federation for Medical and Biological Engineering.)

Automated and accurate segmentation of retinal vessels in fundus images is an important step for screening and diagnosing various ophthalmologic diseases. However, many factors, including the variations of vessels in color, shape and size, make this task become an intricate challenge. One kind of the most popular methods for vessel segmentation is U-Net based methods. However, in the U-Net based methods, the size of the convolution kernels is generally fixed. As a result, the receptive field for an individual convolution operation is single, which is not conducive to the segmentation of retinal vessels with various thicknesses. To overcome this problem, in this paper, we employed self-calibrated convolutions to replace the traditional convolutions for the U-Net, which can make the U-Net learn discriminative representations from different receptive fields. Besides, we proposed an improved spatial attention module, instead of using traditional convolutions, to connect the encoding part and decoding part of the U-Net, which can improve the ability of the U-Net to detect thin vessels. The proposed method has been tested on Digital Retinal Images for Vessel Extraction (DRIVE) database and Child Heart and Health Study in England Database (CHASE DB1). The metrics used to evaluate the performance of the proposed method are accuracy (ACC), sensitivity (SE), specificity (SP), F1-score (F1) and the area under the receiver operating characteristic curve (AUC). The ACC, SE, SP, F1 and AUC obtained by the proposed method are 0.9680, 0.8036, 0.9840, 0.8138 and 0.9840 respectively on DRIVE database, and 0.9756, 0.8118, 0.9867, 0.8068 and 0.9888 respectively on CHASE DB1, which are better than those obtained by the traditional U-Net (the ACC, SE, SP, F1 and AUC obtained by U-Net are 0.9646, 0.7895, 0.9814, 0.7963 and 0.9791 respectively on DRIVE database, and 0.9733, 0.7817, 0.9862, 0.7870 and 0.9810 respectively on CHASE DB1). The experimental results indicate that the proposed modifications in the U-Net are effective for vessel segmentation. The structure of the proposed network., (© 2023. International Federation for Medical and Biological Engineering.)

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application., (© 2024. The Author(s).)

Many major diseases of the retina often show symptoms of lesions in the fundus of the eye. The extraction of blood vessels from retinal fundus images is essential to assist doctors. Some of the existing methods do not fully extract the detailed features of retinal images or lose some information, making it difficult to accurately segment capillaries located at the edges of the images. In this paper, we propose a multi-scale retinal vessel segmentation network (SCIE_Net) based on skip connection information enhancement. Firstly, the network processes retinal images at multiple scales to achieve network capture of features at different scales. Secondly, the feature aggregation module is proposed to aggregate the rich information of the shallow network. Further, the skip connection information enhancement module is proposed to take into account the detailed features of the shallow layer and the advanced features of the deeper network to avoid the problem of incomplete information interaction between the layers of the network. Finally, SCIE_Net achieves better vessel segmentation performance and results on the publicly available retinal image standard datasets DRIVE, CHASE_DB1, and STARE., (© 2024. International Federation for Medical and Biological Engineering.)

Diabetic retinopathy is a chronic disease of the eye that is precipitated via diabetes. As the disease progresses, the blood vessels in the retina are issue to modifications such as dilation, leakage, and new blood vessel formation. Early detection and treatment of the lesions are vital for the prevention and reduction of imaginative and prescient loss. A new dual-path multi-module network algorithm for diabetic retinopathy classification is proposed in this paper, aiming to accurately classify the diabetic retinopathy stage to facilitate early diagnosis and intervention. To obtain the purpose of fact augmentation, the algorithm first enhances retinal lesion features using color correcting and multi-scale fusion algorithms. It then optimizes the local records via a multi-path multiplexing structure with convolutional kernels of exclusive sizes. Finally, a multi-feature fusion module is used to improve the accuracy of the diabetic retinopathy classification model. Two public datasets and a real hospital dataset are used to validate the algorithm. The accuracy is 98.9%, 99.3%, and 98.3%, respectively. The experimental results not only confirm the advancement and practicability of the algorithm in the field of automatic DR diagnosis, but also foretell its broad application prospects in clinical settings, which is expected to provide strong technical support for the early screening and treatment of diabetic retinopathy., (© 2024. International Federation for Medical and Biological Engineering.)

Purpose: The morphological characteristics of retinal vessels are vital for the early diagnosis of pathological diseases such as diabetes and hypertension. However, the low contrast and complex morphology pose a challenge to automatic retinal vessel segmentation. To extract precise semantic features, more convolution and pooling operations are adopted, but some structural information is potentially ignored., Methods: In the paper, we propose a novel lightweight pyramid network (LPN) fusing multi-scale features with spatial attention mechanism to preserve the structure information of retinal vessels. The pyramid hierarchy model is constructed to generate multi-scale representations, and its semantic features are strengthened with the introduction of the attention mechanism. The combination of multi-scale features contributes to its accurate prediction., Results: The LPN is evaluated on benchmark datasets DRIVE, STARE and CHASE, and the results indicate its state-of-the-art performance (e.g., ACC of 97.09[Formula: see text]/97.49[Formula: see text]/97.48[Formula: see text], AUC of 98.79[Formula: see text]/99.01[Formula: see text]/98.91[Formula: see text] on the DRIVE, STARE and CHASE datasets, respectively). The robustness and generalization ability of the LPN are further proved in cross-training experiment., Conclusion: The visualization experiment reveals the semantic gap between various scales of the pyramid and verifies the effectiveness of the attention mechanism, which provide a potential basis for the pyramid hierarchy model in multi-scale vessel segmentation task. Furthermore, the number of model parameters is greatly reduced.

This chapter lays out the elementary principles of fractal geometry underpinning much of the rest of this book. It assumes a minimal mathematical background, defines the key principles and terms in context, and outlines the basics of a fractal analysis method known as box counting and how it is used to perform fractal, lacunarity, and multifractal analyses. As a standalone reference, this chapter grounds the reader to be able to understand, evaluate, and apply essential methods to appreciate and heal the exquisitely detailed fractal geometry of the brain., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

In recent years, eye disorders are an important health issue among older people. Generally, individuals with eye diseases are unaware of the gradual growth of symptoms. Therefore, routine eye examinations are required for early diagnosis. Usually, eye disorders are identified by an ophthalmologist via a slit-lamp investigation. Slit-lamp interpretations are inadequate due to the differences in the analytical skills of the ophthalmologist, inconsistency in eye disorder analysis, and record maintenance issues. Therefore, digital images of an eye and computational intelligence (CI)-based approaches are preferred as assistive methods for eye disease diagnosis. A comparative study of CI-based decision support models for eye disorder diagnosis is presented in this paper. The CI-based decision support systems used for eye abnormalities diagnosis were grouped as anterior and retinal eye abnormalities diagnostic systems, and numerous algorithms used for diagnosing the eye abnormalities were also briefed. Various eye imaging modalities, pre-processing methods such as reflection removal, contrast enhancement, region of interest segmentation methods, and public eye image databases used for CI-based eye disease diagnosis system development were also discussed in this paper. In this comparative study, the reliability of various CI-based systems used for anterior eye and retinal disorder diagnosis was compared based on the precision, sensitivity, and specificity in eye disease diagnosis. The outcomes of the comparative analysis indicate that the CI-based anterior and retinal disease diagnosis systems attained significant prediction accuracy. Hence, these CI-based diagnosis systems can be used in clinics to reduce the burden on physicians, minimize fatigue-related misdetection, and take precise clinical decisions., (© 2022. International Federation for Medical and Biological Engineering.)

Hypertensive retinopathy (HR) refers to changes in the morphological diameter of the retinal vessels due to persistent high blood pressure. Early detection of such changes helps in preventing blindness or even death due to stroke. These changes can be quantified by computing the arteriovenous ratio and the tortuosity severity in the retinal vasculature. This paper presents a decision support system for detecting and grading HR using morphometric analysis of retinal vasculature, particularly measuring the arteriovenous ratio (AVR) and retinal vessel tortuosity. In the first step, the retinal blood vessels are segmented and classified as arteries and veins. Then, the width of arteries and veins is measured within the region of interest around the optic disk. Next, a new iterative method is proposed to compute the AVR from the caliber measurements of arteries and veins using Parr-Hubbard and Knudtson methods. Moreover, the retinal vessel tortuosity severity index is computed for each image using 14 tortuosity severity metrics. In the end, a hybrid decision support system is proposed for the detection and grading of HR using AVR and tortuosity severity index. Furthermore, we present a new publicly available retinal vessel morphometry (RVM) dataset to evaluate the proposed methodology. The RVM dataset contains 504 retinal images with pixel-level annotations for vessel segmentation, artery/vein classification, and optic disk localization. The image-level labels for vessel tortuosity index and HR grade are also available. The proposed methods of iterative AVR measurement, tortuosity index, and HR grading are evaluated using the new RVM dataset. The results indicate that the proposed method gives superior performance than existing methods. The presented methodology is a novel advancement in automated detection and grading of HR, which can potentially be used as a clinical decision support system., (© 2021. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Patients with progressive neurodegenerative disorder retinitis pigmentosa (RP) are diagnosed in the midst of ongoing retinal degeneration and remodeling. Here, we used a Pde6b-deficient RP gene therapy mouse model to test whether treatment at late disease stages can halt photoreceptor degeneration and degradative remodeling, while sustaining constructive remodeling and restoring function. We demonstrated that when fewer than 13% of rods remain, our genetic rescue halts photoreceptor degeneration, electroretinography (ERG) functional decline and inner retinal remodeling. In addition, in a water maze test, the performance of mice treated at 16 weeks of age or earlier was indistinguishable from wild type. In contrast, no efficacy was apparent in mice treated at 24 weeks of age, suggesting the photoreceptors had reached a point of no return. Further, remodeling in the retinal pigment epithelium (RPE) and retinal vasculature was not halted at 16 or 24 weeks of age, although there appeared to be some slowing of blood vessel degradation. These data suggest a novel working model in which restoration of clinically significant visual function requires only modest threshold numbers of resilient photoreceptors, halting of destructive remodeling and sustained constructive remodeling. These novel findings define the potential and limitations of RP treatment and suggest possible nonphotoreceptor targets for gene therapy optimization., (© 2022. The Author(s).)

Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the inflammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 µg/mL) of sCT for 24 h. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 h and then exposed to glutamate for 24 h. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by flow cytometry method. sCT at all concentrations significantly improved the cell viability in C6 cells after glutamate-induced cytotoxicity (p < 0.001). Moreover, sCT significantly reduced the levels of NF-kB (p < 0.001), TNF-α, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the flow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting inflammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This paper proposes a deep image analysis-based model for glaucoma diagnosis that uses several features to detect the formation of glaucoma in retinal fundus. These features are combined with most extracted parameters like inferior, superior, nasal, and temporal region area, and cup-to-disc ratio that overall forms a deep image analysis. This proposed model is exercised to investigate the various aspects related to the prediction of glaucoma in retinal fundus images that help the ophthalmologist in making better decisions for the human eye. The proposed model is presented with the combination of four machine learning algorithms that provide the classification accuracy of 98.60% while other existing models like support vector machine (SVM), K-nearest neighbors (KNN), and Naïve Bayes provide individually with accuracies of 97.61%, 90.47%, and 95.23% respectively. These results clearly demonstrate that this proposed model offers the best methodology to an early diagnosis of glaucoma in retinal fundus.

Diabetic retinopathy (DR) is one of the severe eye conditions due to diabetes complication which can lead to vision loss if left untreated. In this paper, a computationally simple, yet very effective, DR detection method is proposed. First, a segmentation independent two-stage preprocessing based technique is proposed which can effectively extract DR pathognomonic signs; both bright and red lesions, and blood vessels from the eye fundus image. Then, the performance of Local Binary Patterns (LBP), Local Ternary Patterns (LTP), Dense Scale-Invariant Feature Transform (DSIFT) and Histogram of Oriented Gradients (HOG) as a feature descriptor for fundus images, is thoroughly analyzed. SVM kernel-based classifiers are trained and tested, using a 5-fold cross-validation scheme, on both newly acquired fundus image database from the local hospital and combined database created from the open-sourced available databases. The classification accuracy of 96.6% with 0.964 sensitivity and 0.969 specificity is achieved using a Cubic SVM classifier with LBP and LTP fused features for the local database. More importantly, in out-of-sample testing on the combined database, the model gives an accuracy of 95.21% with a sensitivity of 0.970 and specificity of 0.932. This indicates the proposed model is very well-fitted and generalized which is further corroborated by the presented train-test curves.

Pathological disorders may happen due to small changes in retinal blood vessels which may later turn into blindness. Hence, the accurate segmentation of blood vessels is becoming a challenging task for pathological analysis. This paper offers an unsupervised recursive method for extraction of blood vessels from ophthalmoscope images. First, a vessel-enhanced image is generated with the help of gamma correction and contrast-limited adaptive histogram equalization (CLAHE). Next, the vessels are extracted iteratively by applying an adaptive thresholding technique. At last, a final vessel segmented image is produced by applying a morphological cleaning operation. Evaluations are accompanied on the publicly available digital retinal images for vessel extraction (DRIVE) and Child Heart And Health Study in England (CHASE&#95;DB1) databases using nine different measurements. The proposed method achieves average accuracies of 0.957 and 0.952 on DRIVE and CHASE&#95;DB1 databases respectively.