Cross-Domain Depth Estimation Network for 3D Vessel Reconstruction in OCT Angiography

Optical Coherence Tomography Angiography (OCTA) has been widely used by ophthalmologists for decision-making due to its superiority in providing caplillary details. Many of the OCTA imaging devices used in clinic provide high-quality 2D en face representations, while their 3D data quality are largely limited by low signal-to-noise ratio and strong projection artifacts, which restrict the performance of depth-resolved 3D analysis. In this paper, we propose a novel 2D-to-3D vessel reconstruction framework based on the 2D en face OCTA images. This framework takes advantage of the detailed 2D OCTA depth map for prediction and thus does not rely on any 3D volumetric data. Based on the data with available vessel depth labels, we first introduce a network with structure constraint blocks to estimate the depth map of blood vessels in other cross-domain en face OCTA data with unavailable labels. Afterwards, a depth adversarial adaptation module is proposed for better unsupervised cross-domain training, since images captured using different devices may suffer from varying image contrast and noise levels. Finally, vessels are reconstructed in 3D space by utilizing the estimated depth map and 2D vascular information. Experimental results demonstrate the effectiveness of our method and its potential to guide subsequent vascular analysis in 3D domain

Retinal vascular segmentation using superpixel-based line operator and its application to vascular topology estimation

Purpose: Automatic methods of analyzing of retinal vascular networks, such as retinal blood vessel detection, vascular network topology estimation, and arteries / veins classi cation are of great assistance to the ophthalmologist in terms of diagnosis and treatment of a wide spectrum of diseases. Methods: We propose a new framework for precisely segmenting retinal vasculatures, constructing retinal vascular network topology, and separating the arteries and veins. A non-local total variation inspired Retinex model is employed to remove the image intensity inhomogeneities and relatively poor contrast. For better generalizability and segmentation performance, a superpixel based line operator is proposed as to distinguish between lines and the edges, thus allowing more tolerance in the position of the respective contours. The concept of dominant sets clustering is adopted to estimate retinal vessel topology and classify the vessel network into arteries and veins. Results: The proposed segmentation method yields competitive results on three pub- lic datasets (STARE, DRIVE, and IOSTAR), and it has superior performance when com- pared with unsupervised segmentation methods, with accuracy of 0.954, 0.957, and 0.964, respectively. The topology estimation approach has been applied to ve public databases 1 (DRIVE,STARE, INSPIRE, IOSTAR, and VICAVR) and achieved high accuracy of 0.830, 0.910, 0.915, 0.928, and 0.889, respectively. The accuracies of arteries / veins classi cation based on the estimated vascular topology on three public databases (INSPIRE, DRIVE and VICAVR) are 0.90.9, 0.910, and 0.907, respectively. Conclusions: The experimental results show that the proposed framework has e ectively addressed crossover problem, a bottleneck issue in segmentation and vascular topology recon- struction. The vascular topology information signi cantly improves the accuracy on arteries / veins classi cation

Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity

TRPM6 is crucial for human Mg2+ homeostasis as patients carrying TRPM6 mutations develop hypomagnesemia and secondary hypocalcemia (HSH). However, the activation mechanism of TRPM6 has remained unknown. Here we demonstrate that phosphatidylinositol-4,5-bisphophate (PIP2) controls TRPM6 activation and Mg2+ influx. Stimulation of PLC-coupled M1-receptors to deplete PIP2 potently inactivates TRPM6. Translocation of over-expressed 5-phosphatase to cell membrane to specifically hydrolyze PIP2 also completely inhibits TRPM6. Moreover, depolarization-induced-activation of the voltage-sensitive-phosphatase (Ci-VSP) simultaneously depletes PIP2 and inhibits TRPM6. PLC-activation induced PIP2-depletion not only inhibits TRPM6, but also abolishes TRPM6-mediated Mg2+ influx. Furthermore, neutralization of basic residues in the TRP domain leads to nonfunctional or dysfunctional mutants with reduced activity by PIP2, suggesting that they are likely to participate in interactions with PIP2. Our data indicate that PIP2 is required for TRPM6 channel function; hydrolysis of PIP2 by PLC-coupled hormones/agonists may constitute an important pathway for TRPM6 gating, and perhaps Mg2+ homeostasis

Retinal Vascular Network Topology Reconstruction and Artery/Vein Classification via Dominant Set Clustering

The estimation of vascular network topology in complex networks is important in understanding the relationship between vascular changes and a wide spectrum of diseases. Automatic classification of the retinal vascular trees into arteries and veins is of direct assistance to the ophthalmologist in terms of diagnosis and treatment of eye disease. However, it is challenging due to their projective ambiguity and subtle changes in appearance, contrast and geometry in the imaging process. In this paper, we propose a novel method that is capable of making the artery/vein (A/V) distinction in retinal color fundus images based on vascular network topological properties. To this end, we adapt the concept of dominant set clustering and formalize the retinal blood vessel topology estimation and the A/V classification as a pairwise clustering problem. The graph is constructed through image segmentation, skeletonization and identification of significant nodes. The edge weight is defined as the inverse Euclidean distance between its two end points in the feature space of intensity, orientation, curvature, diameter, and entropy. The reconstructed vascular network is classified into arteries and veins based on their intensity and morphology. The proposed approach has been applied to five public databases, INSPIRE, IOSTAR, VICAVR, DRIVE and WIDE, and achieved high accuracies of 95.1%, 94.2%, 93.8%, 91.1%, and 91.0%, respectively. Furthermore, we have made manual annotations of the blood vessel topologies for INSPIRE, IOSTAR, VICAVR, and DRIVE datasets, and these annotations are released for public access so as to facilitate researchers in the community

Topology reconstruction of tree-like structure in images via structural similarity measure and dominant set clustering

The reconstruction and analysis of tree-like topological structures in the biomedical images is crucial for biologists and surgeons to understand biomedical conditions and plan surgical procedures. The underlying tree-structure topology reveals how different curvilinear components are anatomically connected to each other. Existing automated topology reconstruction methods have great difficulty in identifying the connectivity when two or more curvilinear components cross or bifurcate, due to their projection ambiguity, imaging noise and low contrast. In this paper, we propose a novel curvilinear structural similarity measure to guide a dominant-set clustering approach to address this indispensable issue. The novel similarity measure takes into account both intensity and geometric properties in representing the curvilinear structure locally and globally, and group curvilinear objects at crossover points into different connected branches by dominant-set clustering. The proposed method is applicable to different imaging modalities, and quantitative and qualitative results on retinal vessel, plant root, and neuronal network datasets show that our methodology is capable of advancing the current state-of-the-art techniques

3D VESSEL RECONSTRUCTION IN OCT-ANGIOGRAPHY VIA DEPTH MAP ESTIMATION

Optical Coherence Tomography Angiography (OCTA) has been increasingly used in the management of eye and systemic diseases in recent years. Manual or automatic analysis of blood vessel in 2D OCTA images (en face angiograms) is commonly used in clinical practice, however it may lose rich 3D spatial distribution information of blood vessels or capillaries that are useful for clinical decision-making. In this paper, we introduce a novel 3D vessel reconstruction framework based on the estimation of vessel depth maps from OCTA images. First, we design a network with structural constraints to predict the depth of blood vessels in OCTA images. In order to promote the accuracy of the predicted depth map at both the overall structure- and pixel- level, we combine MSE and SSIM loss as the training loss function. Finally, the 3D vessel reconstruction is achieved by utilizing the estimated depth map and 2D vessel segmentation results. Experimental results demonstrate that our method is effective in the depth prediction and 3D vessel reconstruction for OCTA images.% results may be used to guide subsequent vascular analysi

Deep Segmentation of OCTA for Evaluation and Association of Changes of Retinal Microvasculature with Alzheimer’s Disease and Mild Cognitive Impairment

BackgroundOptical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study.MethodsWe defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects.ResultsIn the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls.ConclusionOur study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI

ROSE: A Retinal OCT-Angiography Vessel Segmentation Dataset and New Model

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

Single-cell RNA sequencing reveals cancer stem-like cells and dynamics in tumor microenvironment during cholangiocarcinoma progression

Cholangiocarcinoma is a malignancy of the bile ducts that is driven by activities of cancer stem-like cells and characterized by a heterogeneous tumor microenvironment. To better understand the transcriptional profiles of cancer stem-like cells and dynamics in the tumor microenvironment during the progression of cholangiocarcinoma, we performed single-cell RNA analysis on cells collected from three different timepoints of tumorigenesis in a YAP/AKT mouse model. Bulk RNA sequencing data from TCGA (The Cancer Genome Atlas program) and ICGC cohorts were used to verify and support the finding. In vitro and in vivo experiments were performed to assess the stemness of cancer stem-like cells. We identified Tm4sf1high malignant cells as cancer stem-like cells. Across timepoints of cholangiocarcinoma formation in YAP/AKT mice, we found dynamic change in cancer stem-like cell/stromal/immune cell composition. Nevertheless, the dynamic interaction among cancer stem-like cells, immune cells, and stromal cells at different timepoints was elaborated. Collectively, these data serve as a useful resource for better understanding cancer stem-like cell and malignant cell heterogeneity, stromal cell remodeling, and immune cell reprogramming. It also sheds new light on transcriptomic dynamics during cholangiocarcinoma progression at single-cell resolution