Evaluation of blood vessel network formation and visual field defect in optic disc melanocytoma

AimTo investigate the association between visual field defects and blood vessel network (BVN) formation in optic disc melanocytomas (ODMs) using optical coherence tomography angiography (OCTA).MethodsSingle-centre, retrospective case series of 32 eyes of 32 patients with ODM, in which eyes were divided into two groups based on complete and incomplete BVN formations.ResultsOCTA revealed incomplete BVN formation in 16 of 32 ODMs. The location of BVN absence corresponded to the location of hypofluorescence from fluorescein angiography (FA) in 12 (75%) and to the location of visual field defect in 13 (81%) ODMs in the incomplete BVN group. Perimetric indices were significantly worse in the incomplete BVN group than in the complete BVN group. Linear regression of mean deviation (MD) and Visual Field Index (VFI) on the area of BVN absence were statistically significant (p=0.01 and p=0.003, respectively), whereas linear regressions of MD and VFI on the tumour area were not statistically significant (both p=0.09) in the incomplete BVN group.ConclusionThe location of BVN absence within ODMs corresponded to the location of visual field defect and the location of FA hypofluorescence. Visual field defect was more severe in the incomplete BVN group than in the complete BVN group. Visual field defect was more significantly associated with the area of BVN absence than the tumour area.

Automated Detection and Tortuosity Characterization of Retinal Vascular Networks

Automated retinal vascular network detection and analysis using digital retinal images continue to play a major role in the field of biomedicine for the diagnosis and management of various forms of human ailments like hypertension, diabetic retinopathy, retinopathy of prematurity, glaucoma and cardiovascular diseases. Although several literature have implemented different automatic approaches of detecting blood vessels in the retinal and also determining their tortuous states, the results obtained show that there are needs for further investigation on more efficient ways to detect and characterize the blood vessel network tortuosity states. This paper implements the use of an adaptive thresholding method based on local spatial relational variance (LSRV) for the detection of the retinal vascular networks. The suitability of a multi-layer perceptron artificial neural network (MLP-ANN) technique for the tortuosity characterization of retinal blood vascular networks is also presented in this paper. Some vessel geometric features of detected vessels are fed into ANN classifier for the automatic classification of the retinal vascular networks as being tortuous vessels or normal vessels. Experimental studies conducted on DRIVE and STARE databases show that the vascular network detection results obtained from the method implemented in this paper detects large and thin vascular networks in the retina. In comparison to preious methods in the literature, the proposed method for vascular network segmentation achieved better performance than several methods in the literature with a mean accuracy value of 95.04% and mean sensitivity value of 75.16% on DRIVE and mean accuracy value of 94.02% and average sensitivity value of 76.55% on STARE with computational processing time of 4.5 seconds and 9.4 seconds on DRIVE and STARE respectively. The MLP-ANN method proposed for the vascular network tortuosity characterization achieves promising accuracy rates of 77.5%, 80%, 83.33%, 85%, 86.67% and 100% for varying training sample sizes.

SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis

Fluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-induced flow misalignment. Endothelial cells depleted for SMAD6 had defective barrier function accompanied by upregulation of proliferation-associated genes and down regulation of junction-associated genes. The vascular protocadherin PCDH12 was upregulated by SMAD6 and required for proper flow-mediated endothelial cell alignment, placing it downstream of SMAD6. Thus, SMAD6 is a required transducer of flow-mediated signaling inputs downstream of Notch1 and upstream of PCDH12, as vessels transition from an angiogenic phenotype to maintenance of a homeostatic phenotype.

A fast numerical method for oxygen supply in tissue with complex blood vessel network

Oxygen field evaluation is important in modeling and simulation of many important physiological processes of animals, such as angiogenesis. However, numerical simulation of the oxygen field in animal tissue is usually limited by the unusual coupling of different mechanisms, the nonlinearity of the model, and the complex geometry of refined blood vessel networks. In this work, a fast numerical method is designed for the simulation of oxygen supply in tissue with a large-scale complex vessel network. This method employs an implicit finite-difference scheme to compute the oxygen field. By virtue of an oxygen source distribution technique from vessel center lines to mesh points and a corresponding post-processing technique that eliminate the local numerical error induced by source distribution, square mesh with relatively large mesh sizes can be applied while sufficient numerical accuracy is maintained. The new method has computational complexity which is slightly higher than linear with respect to the number of mesh points and has a convergence order which is slightly lower than second order with respect to the mesh size. As an example, the oxygen field of a tissue irrigated by a blood vessel network with more than four thousand blood vessels can be accurately computed within one minute with our new method. The new method will definitely promote further researches based on evaluation of oxygen field, such as modeling of angiogenesis and pathogenesis of many cardiovascular diseases.

Changes in the Expression Profile of VEGF-A, VEGF-B, VEGFR-1, VEGFR-2 in Different Grades of Endometrial Cancer

Background: VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 are important proteins involved in the induction and development of a new blood vessel network through which the tumor is properly nourished and oxygenated. Objective: The aim of the study was to evaluate changes in VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 expression in endometrial cancer depending on its grade and to determine the VEGFR-1 to VEGFR-2 concentration ratio. Methods: The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, Cracow, Poland). It included the one-way ANOVA and Tukey's post-hoc test (p<0.05). Results: Statistically significant differences in the level of VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 were observed between the majority of analyzed groups (except for VEGF-B; G3 vs. G1, p=0.997700). The expression pattern of VEGF-A, VEGF-R1, VEGFR-2 was as follows: G3>G2>G1>C; VEGF-B: G2> G3> G1>C. A lower concentration of VEGFR-1 than VEGFR-2 was found regardless of the cancer grade. Conclusion: VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 are key proteins involved in tumor angiogenesis. The analysis of the entire panel of proteins participating in a given process is an important element of modern diagnostics. The concentration ratio of VEGFR-1 to VEGFR-2 appears to be a determining factor in the patients' survival prognosis.

“Open-top” microfluidic device for in vitro three-dimensional capillary beds

We introduce a novel microfluidic device to co-culture a blood vessel network and cell tissues in an in vivo-like niche.