Blood Vessel Tortuosity Research Articles

OCTA-ReVA: an open-source toolbox for comprehensive retinal vessel feature analysis in optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) has significantly advanced the study and diagnosis of eye diseases. However, current clinical OCTA systems and software tools lack comprehensive quantitative analysis capabilities, limiting their full clinical utility. This paper introduces the OCTA Retinal Vessel Analyzer (OCTA-ReVA), a versatile open-source platform featuring a user-friendly graphical interface designed for the automated extraction and quantitative analysis of OCTA features. OCTA-ReVA includes traditional established OCTA features based on binary vascular image processing, such as blood vessel density (BVD), foveal avascular zone area (FAZ-A), blood vessel tortuosity (BVT), and blood vessel caliber (BVC). Additionally, it introduces new features based on blood perfusion intensity processing, such as perfusion intensity density (PID), vessel area flux (VAF), and normalized blood flow index (NBFI), which provide deeper insights into retinal perfusion conditions. These additional capabilities are crucial for the early detection and monitoring of retinal diseases. OCTA-ReVA demystifies the intricate task of retinal vasculature quantification, offering a robust tool for researchers and clinicians to objectively evaluate eye diseases and enhance the precision of retinal health assessments.

Immersive Photorealistic Three-Dimensional Neurosurgical Anatomy of the Cerebral Arteries: A Photogrammetry-Based Anatomic Study.

Neurosurgeons need a profound knowledge of the surgical anatomy of the cerebral arteries to safely treat patients. This is a challenge because of numerous branches, segments, and tortuosity of the main blood vessels that supply the brain. The objective of this study was to create high-quality three-dimensional (3D) anatomic photorealistic models based on dissections of the brain arterial anatomy and to incorporate this data into a virtual reality (VR) environment. Two formaldehyde-fixed heads were used. The vessels were injected with radiopaque material and colored silicone and latex. Before the dissections, the specimens were computed tomography scanned. Stratigraphical anatomic dissection of the neck and brain was performed to present the relevant vascular anatomy. A simplified surface scanning method using a mobile phone-based photogrammetry application was used, and the data were incorporated into a VR 3D modeling software for post-processing and presentation. Fifteen detailed layered photorealistic and two computed tomography angiography-based 3D models were generated. The models allow manipulation in VR environment with sufficient photographic detail to present the structures of interest. Topographical relevant anatomic structures and landmarks were annotated and uploaded for web-viewing and in VR. Despite that the VR application is a dedicated 3D modeling platform, it provided all necessary tools to be suitable for self-VR study and multiplayer scenarios with several participants in one immersive environment. Cerebral vascular anatomy presented with photogrammetry surface scanning method allows sufficient detail to present individual vessel's course and even small perforating arteries in photorealistic 3D models. These features, including VR visualization, provide new teaching prospects. The whole study was done with simplified algorithms and free or open-source software platforms allowing creation of 3D databases especially useful in cases with limited body donor-based dissection training availability.

Computational analysis of cancer cell adhesion in curved vessels affected by wall shear stress for prediction of metastatic spreading.

Introduction: The dynamics of circulating tumor cells (CTCs) within blood vessels play a pivotal role in predicting metastatic spreading of cancer within the body. However, the limited understanding and method to quantitatively investigate the influence of vascular architecture on CTC dynamics hinders our ability to predict metastatic process effectively. To address this limitation, the present study was conducted to investigate the influence of blood vessel tortuosity on the behaviour of CTCs, focusing specifically on establishing methods and examining the role of shear stress in CTC-vessel wall interactions and its subsequent impact on metastasis. Methods: We computationally simulated CTC behaviour under various shear stress conditions induced by vessel tortuosity. Our computational model, based on the lattice Boltzmann method (LBM) and a coarse-grained spectrin-link membrane model, efficiently simulates blood plasma dynamics and CTC deformability. The model incorporates fluid-structure interactions and receptor-ligand interactions crucial for CTC adhesion using the immersed boundary method (IBM). Results: Our findings reveal that uniform shear stress in straight vessels leads to predictable CTC-vessel interactions, whereas in curved vessels, asymmetrical flow patterns and altered shear stress create distinct adhesion dynamics, potentially influencing CTC extravasation. Quantitative analysis shows a 25% decrease in the wall shear stress in low-shear regions and a 58.5% increase in the high-shear region. We observed high-shear regions in curved vessels to be potential sites for increased CTC adhesion and extravasation, facilitated by elevated endothelial expression of adhesion molecules. This phenomenon correlates with the increased number of adhesion bonds, which rises to approximately 40 in high-shear regions, compared to around 12 for straight vessels and approximately 5-6 in low-shear regions. The findings also indicate an optimal cellular stiffness necessary for successful CTC extravasation in curved vessels. Discussion: By the quantitative assessment of the risk of CTC extravasation as a function of vessel tortuosity, our study offers a novel tool for the prediction of metastasis risk to support the development of personalized therapeutic interventions based on individual vascular characteristics and tumor cell properties.

Differential artery-vein analysis improves the OCTA classification of diabetic retinopathy.

This study investigates the impact of differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) on machine learning classification of diabetic retinopathy (DR). Leveraging deep learning for arterial-venous area (AVA) segmentation, six quantitative features, including perfusion intensity density (PID), blood vessel density (BVD), vessel area flux (VAF), blood vessel caliber (BVC), blood vessel tortuosity (BVT), and vessel perimeter index (VPI) features, were derived from OCTA images before and after AV differentiation. A support vector machine (SVM) classifier was utilized to assess both binary and multiclass classifications of control, diabetic patients without DR (NoDR), mild DR, moderate DR, and severe DR groups. Initially, one-region features, i.e., quantitative features extracted from the entire OCTA, were evaluated for DR classification. Differential AV analysis improved classification accuracies from 78.86% to 87.63% and from 79.62% to 85.66% for binary and multiclass classifications, respectively. Additionally, three-region features derived from the entire image, parafovea, and perifovea, were incorporated for DR classification. Differential AV analysis further enhanced classification accuracies from 84.43% to 93.33% and from 83.40% to 89.25% for binary and multiclass classifications, respectively. These findings highlight the potential of differential AV analysis in augmenting disease diagnosis and treatment assessment using OCTA.

Scanning optoacoustic angiography for assessing structural and functional alterations in superficial vasculature of patients with post-thrombotic syndrome: A pilot study

This study highlights the potential of scanning optoacoustic angiography (OA) in identifying alterations of superficial vasculature in patients with post-thrombotic syndrome (PTS) of the foot, a venous stress disorder associated with significant morbidity developing from long-term effects of deep venous thrombosis. The traditional angiography methods available in the clinics are not capable of reliably assessing the state of peripheral veins that provide blood outflow from the skin, a key hallmark of personalized risks of PTS formation after venous thrombosis. Our findings indicate that OA can detect an increase in blood volume, diameter, and tortuosity of superficial blood vessels. The inability to spatially separate vascular plexuses of the dermis and subcutaneous adipose tissue serves as a crucial criterion for distinguishing PTS from normal vasculature. Furthermore, our study demonstrates the ability of scanning optoacoustic angiography to detect blood filling decrease in an elevated limb position versus increase in a lowered position.

Mechanobiological tortuosity of blood vessels with stress-modulated growth and remodeling

The stability of blood vessels is essential for maintaining their functions, while severe blood vessel tortuosity leads to various clinical complications. The growth and remodeling of blood vessels, which are regulated by mechanical and biochemical cues, cause residual stresses that affect vessel stability. In this paper, we combine theory and simulations to study the mechanobiological behavior of blood vessels with stress-modulated growth and remodeling. Effects of the volumetric growth of the matrix and the turnover and reorientation of collagen fibers are accounted for. Linear stability analysis is first carried out to investigate the mechanobiological stability of blood vessels. By developing a finite element method that incorporates stress-modulated growth and remodeling, we validate the theoretical solution of the critical state and further capture the postbuckling evolution of blood vessels. Our results show that an increased internal pressure can lead to the thickening of the vessel wall, which stabilizes the blood vessels mechanically, whereas the effect of internal pressure on the mechanobiological buckling is nonmonotonic. Compared to the mechanical instability, the mechanobiological buckling results in a larger mode number and a shorter wavelength, as usually observed in varicose veins. Vessels during postbuckling may exhibit non-uniform wall thicknesses, in consistency with the experimental observation on tortuous aortas. These findings highlight the crucial role of mechanical remodeling in tissue morphogenesis and could deepen the understanding of mechanobiological mechanisms underlying the formation and development of blood vessel tortuosity.

Dolichoectasia of the ophthalmic artery: a case report on the treatment strategy in endovascular therapy and literature review

BackgroundDolichoectasia is a rare arterial condition characterized by the dilatation, tortuosity, and elongation of cerebral blood vessels. The vertebrobasilar artery and internal carotid artery are the common sites of dolichoectasia. However, dolichoectasia of the branch arteries, such as the ophthalmic artery (OA), is extremely rare. To the best of our knowledge, this is the first case of ophthalmic dolichoectasia that was successfully treated with endovascular internal coil trapping.Case presentationA 54-year-old female patient presented with transient left ophthalmalgia and visual disturbance. Magnetic resonance imaging revealed a dilated and elongated left OA compressing the optic nerve at the entrance of the optic canal. However, a previous image that was taken 17 years back revealed that the OA was normal, which suggested the change in dolichoectasia was acquired. Cerebral angiography showed that the dilated and tortuous OA was running from the ophthalmic segment of the left internal carotid artery into the orbit. The symptoms could have been attributed to the direct compression of the dolichoectatic OA in the optic canal. A sufficient anastomosis between the central retinal artery and the middle meningeal artery was identified on external carotid angiography with balloon occlusion of the internal carotid artery. Endovascular treatment with internal trapping of the OA was performed due to ophthalmic symptom progression. Internal coil trapping of the OA was performed at the short segment between the OA bifurcation and the entrance of the optic canal. As expected, the central retinal artery was supplied via the middle meningeal artery after the treatment. The transient visual disturbance was immediately resolved. Ophthalmalgia worsened temporarily after the treatment. However, it completely resolved after several days of oral corticosteroid therapy. Postoperative angiography showed that the origin of the OA was occluded and that the OA in the optic canal was shrunk. The flow of the central retinal arteries via the middle meningeal artery was preserved.ConclusionsOA dolichoectasia is rare, and its pathogenesis and long-term visual prognosis are still unknown. However, endovascular therapy can improve symptom by releasing the pressure site in the optic canal.

Innovative Macula Capillaries Plexuses Visualization with OCTA B-Scan Graph Representation: Transforming OCTA B-Scan into OCTA Graph Representation.

The aim of this study is to transform optical coherence tomography angiography (OCTA) scans into innovative OCTA graphs, serving as novel biomarkers representing the macular vasculature. The study included 90 healthy subjects and 39 subjects with various abnormalities (29 with diabetic retinopathy, 5 with age-related macular degeneration, and 5 with choroid neovascularization). OCTA 5µm macular coronal views (MCVs) were generated for each subject, followed by blood vessel segmentation and skeleton processing. Subsequently, the blood vessel density index, blood vessel skeleton index, and blood vessel tortuosity index were computed. The graphs of each metric were plotted against the axial axes of the OCTA B-scan, representing the integrity of vasculature at successive 5µm macular depths. The results revealed two significant findings. First, the B-scans from OCTA can be transformed into OCTA graphs, yielding three specific OCTA graphs in this study. These graphs provide new biomarkers for assessing the integrity of deep vascular complex (DVC) and superficial vascular complex (SVC) within the macula. Second, a statistically significant difference was observed between normal (n=90) and abnormal (n=39) subjects, with a t-test p-value significantly lower than 0.001. The Mann-Whitney u-test also yielded significant difference but only between the 90 normal and 29 DR subjects. The novel OCTA graphs offer a unique representation of the macula's SVC and DVC, suggesting their potential in aiding physicians in the diagnosis of eye health within OCTA clinics. Further research is warranted to finalize the shape of these newly derived OCTA graphs and establish their clinical relevance and utility.

Associations between retinal microvascular flow, geometry, and progression of diabetic retinopathy in type 2 diabetes: a 2-year longitudinal study.

To determine the association between retinal blood vessel flow and geometric parameters and the risk of diabetic retinopathy (DR) progression through a 2-year prospective cohort study. Patients with type 2 diabetes mellitus (T2DM) were recruited from a diabetic registry between November 2017 and March 2019. All participants underwent standardized examinations at the baseline and 2-year follow-up visit, and the presence and severity of DR were assessed based on standard seven-field color fundus photographs. They also underwent swept-source optical coherence tomography angiography (OCTA) imaging to obtain measurements of foveal avascular zone area, blood vessel density (VD), fractal dimension (FD), blood vessel tortuosity (BVT) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). A total of 233 eyes of 125 patients were included, and 40 eyes (17.17%) experienced DR progression within 2years. DR progression was significantly associated with lower baseline VD (odds ratio [OR] 2.323 per SD decrease; 95% confidence interval [CI] 1.456-3.708; P < 0.001), lower FD (OR, 2.484 per SD decrease; 95% CI 1.268-4.867; P = 0.008), and higher BVT (OR, 2.076 per SD increase; 95% CI 1.382-3.121; P < 0.001) of the DCP after adjusting for confounding factors. The addition of OCTA metrics improved the predictive ability of the original model for DR progression (area under the curve [AUC] from 0.725 to 0.805; P = 0.022). OCTA-derived VD, FD and BVT in the DCP were independent predictors of DR progression and showed additive value when added to established risk models predicting DR progression.

A novel deep learning framework for the identification of tortuous vessels in plus diseased infant retinal images

Retinopathy of prematurity (ROP), sometimes known as Terry syndrome, is an ophthalmic condition that affects premature babies. It is the main cause of childhood blindness and morbidity of vision throughout life. ROP frequently coexists with a disease stage known as Plus disease, which is marked by severe tortuosity and dilated retinal blood vessels. The goal of this research is to create a diagnostic technique that can discriminate between infants with Plus disease from healthy subjects. Blood vascular tortuosity is used as a prognostic indicator for the diagnosis. We examine the quantification of retinal blood vessel tortuosity and propose a computer-aided diagnosis system that can be used as a tool for ROP identification. Deep neural networks are used in the proposed approach to segment retinal blood vessels, which is followed by the prediction of tortuous vessel pixels in the segmented vessel map. Digital fundus images obtained from Retcam3TM is used for screening. We use a proprietary data set of 289 infant retinal images (89 with Plus disease and 200 healthy) from Narayana Nethralaya in Bangalore, India, to illustrate the efficacy of our methodology. The findings of this study demonstrate the reliability of the proposed method as a computer-aided diagnostic tool that can help medical professionals make an early diagnosis of ROP.

Image harmonization and deep learning automated classification of plus disease in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a retinal vascular disease affecting premature infants that can culminate in blindness within days if not monitored and treated. A disease stage for scrutiny and administration of treatment within ROP is "plus disease" characterized by increased tortuosity and dilation of posterior retinal blood vessels. The monitoring of ROP occurs via routine imaging, typically using expensive instruments ($50 to $140K) that are unavailable in low-resource settings at the point of care. As part of the smartphone-ROP program to enable referrals to expert physicians, fundus images are acquired using smartphone cameras and inexpensive lenses. We developed methods for artificial intelligence determination of plus disease, consisting of a preprocessing pipeline to enhance vessels and harmonize images followed by deep learning classification. A deep learning binary classifier (plus disease versus no plus disease) was developed using GoogLeNet. Vessel contrast was enhanced by 90% after preprocessing as assessed by the contrast improvement index. In an image quality evaluation, preprocessed and original images were evaluated by pediatric ophthalmologists from the US and South America with years of experience diagnosing ROP and plus disease. All participating ophthalmologists agreed or strongly agreed that vessel visibility was improved with preprocessing. Using images from various smartphones, harmonized via preprocessing (e.g., vessel enhancement and size normalization) and augmented in physically reasonable ways (e.g., image rotation), we achieved an area under the ROC curve of 0.9754 for plus disease on a limited dataset. Promising results indicate the potential for developing algorithms and software to facilitate the usage of cell phone images for staging of plus disease.

A Comparison of the Tortuosity Phenomenon in Retinal Arteries and Veins Using Digital Image Processing and Statistical Methods

The tortuosity of retinal blood vessels is an important phenomenon, and it can act as a biomarker in the diagnosis of several eye diseases. The study of abnormalities in the tortuosity of retinal arteries and veins provides ophthalmologists with important information for disease diagnosis. Our study aims to compare the tortuosity relation between retinal arteries and veins by quantifying the vessels’ tortuosity in the retina using 14 tortuosity measures applied to the AV-classification retinal dataset. Two feature sets are created, one for arteries and the other for veins. The comparison between the tortuosity of arteries and veins is based on a two-sample T-test statistical method, a regression analysis between the quantified tortuosity features, principal component analysis at the dataset level, and the introduction of the arteriovenous length ratios concept to compare the variations in these new ratios to see the tortuosity behavior in each image. The methods’ results have shown that the tortuosity of retinal arteries and veins is similar. The result of the two-sample T-test supports the research hypothesis, as the P-value obtained was greater than 0.05. Furthermore, the regression analysis between arteries and veins features showed a high correlation (r2 = 89.39% and 89.11%) for arteries and veins, respectively. The study concludes that the retinal vessel type has no statistical significance in the tortuosity calculation results.

Molecular and environmental contributors to neurological complications in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which affected hemoglobin polymerizes under hypoxic conditions resulting in red cell distortion and chronic hemolytic anemia. SCD affects millions of people worldwide, primarily in Sub-Saharan Africa and the Indian subcontinent. Due to vaso-occlusion of sickled red cells within the microvasculature, SCD affects virtually every organ system and causes significant morbidity and early mortality. The neurological complications of SCD are particularly devastating and diverse, ranging from overt stroke to covert cerebral injury, including silent cerebral infarctions and blood vessel tortuosity. However, even individuals without evidence of neuroanatomical changes in brain imaging have evidence of cognitive deficits compared to matched healthy controls likely due to chronic cerebral hypoxemia and neuroinflammation. In this review, we first examined the biological contributors to SCD-related neurological complications and then discussed the equally important socioenvironmental contributors. We then discuss the evidence for neuroprotection from the two primary disease-modifying therapies, chronic monthly blood transfusions and hydroxyurea, and end with several experimental therapies designed to specifically target these complications.

Using Mean Arterial Pressure in Hypertension Diagnosis versus Using Either Systolic or Diastolic Blood Pressure Measurements.

Hypertension is a severe and highly prevalent disease. It is considered a leading contributor to mortality worldwide. Diagnosis guidelines for hypertension use systolic and diastolic blood pressure (BP) together. Mean arterial pressure (MAP), which refers to the average of the arterial blood pressure through a single cardiac cycle, can be an alternative index that may capture the overall exposure of the person to a heightened pressure. A clinical hypothesis, however, suggests that in patients over 50 years old in age, systolic BP may be more predictive of adverse events, while in patients under 50 years old, diastolic BP may be slightly more predictive. In this study, we investigated the correlation between cerebrovascular changes, (impacted by hypertension), and MAP, systolic BP, and diastolic BP separately. Several experiments were conducted using real and synthetic magnetic resonance angiography (MRA) data, along with corresponding BP measurements. Each experiment employs the following methodology: First, MRA data were processed to remove noise, bias, or inhomogeneity. Second, the cerebrovasculature was delineated for MRA subjects using a 3D adaptive region growing connected components algorithm. Third, vascular features (changes in blood vessel's diameters and tortuosity) that describe cerebrovascular alterations that occur prior to and during the development of hypertension were extracted. Finally, feature vectors were constructed, and data were classified using different classifiers, such as SVM, KNN, linear discriminant, and logistic regression, into either normotensives or hypertensives according to the cerebral vascular alterations and the BP measurements. The initial results showed that MAP would be more beneficial and accurate in identifying the cerebrovascular impact of hypertension (accuracy up to 95.2%) than just using either systolic BP (accuracy up to 89.3%) or diastolic BP (accuracy up to 88.9%). This result emphasizes the pathophysiological significance of MAP and supports prior views that this simple measure may be a superior index for the definition of hypertension and research on hypertension.

Retinal Vessel Local Tortuosity under a Macula-to-Optic Disc Central-Framing Change

Some ocular and cardiovascular diseases can be detected through the increased tortuosity of retinal blood vessels. Objective tortuosity measures can be obtained from digital image analysis of a retinography. This study tested a set of local tortuosity indices under a change in the frame center (macula, optic disc) of the eye fundus image. We illustrate the effects of such a change on 40 pairs of vessels evaluated with eight tortuosity indices. We show that the frame center change caused significant differences in the mean values of the vast majority of the tortuosity indices analyzed. The index defined as the ratio of the curvature to the arc length of a vessel segment proved to be the most robust in relation to a frame center change. Experimental results obtained from the analysis of clinical images are provided and discussed.

Retinal vessel caliber and tortuosity and prediction of 5-year incidence of hypertension.

With arterial hypertension as a global risk factor for cerebrovascular and cardiovascular diseases, we examined whether retinal blood vessel caliber and tortuosity assessed by a vessel-constraint network model can predict the incidence of hypertension. The community-based prospective study included 9230 individuals who were followed for 5 years. Ocular fundus photographs taken at baseline were analyzed by a vessel-constraint network model. Within the 5-year follow-up, 1279 (18.8%) and 474 (7.0%) participants out of 6813 individuals free of hypertension at baseline developed hypertension and severe hypertension, respectively. In multivariable analysis, a higher incidence of hypertension was related to a narrower retinal arteriolar diameter ( P < 0.001), wider venular diameter ( P = 0.005), and a smaller arteriole-to-venule diameter ratio ( P < 0.001) at baseline. Individuals with the 5% narrowest arteriole or the 5% widest venule diameter had a 17.1-fold [95% confidence interval (CI):7.9, 37.2] or 2.3-fold (95% CI: 1.4, 3.7) increased risk for developing hypertension, as compared with those with the 5% widest arteriole or the 5% narrowest venule. The area under the receiver operator characteristic curve for predicting the 5-year incidence of hypertension and severe hypertension was 0.791 (95% CI: 0.778, 0.804) and 0.839 (95% CI: 0.821, 0.856), respectively. Although the venular tortuosity was positively associated with the presence of hypertension at baseline ( P = 0.01), neither arteriolar tortuosity nor venular tortuosity was associated with incident hypertension (both P ≥ 0.10). Narrower retinal arterioles and wider venules indicate an increased risk for incident hypertension within 5 years, while tortuous retinal venules are associated with the presence rather than the incidence of hypertension. The automatic assessment of retinal vessel features performed well in identifying individuals at risk of developing hypertension.

Numerical Analysis of Tortuosity of Blood Vessels Considering Mechanical Constraints of Surrounding Tissues

Numerical Analysis of Tortuosity of Blood Vessels Considering Mechanical Constraints of Surrounding Tissues

Macular Vascular Complexity Analysis of Diabetes Mellitus by Swept-Source Optical Coherence Tomographic Angiography

Purpose: This study was designed to evaluate the associations between retinal vascular complexity features, including fractal dimension (FD) and blood vessel tortuosity (BVT), and the severity of diabetic retinopathy (DR) by using optical coherence tomographic angiography (OCTA). Methods: In this prospective cross-sectional study, 1,282 ocular-treatment-naive patients with type 2 diabetes mellitus (DM) (1,059 without DR and 223 with DR) registered in the community of Guangzhou, China, were enrolled. OCTA was used to measure FD and BVT in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Univariate and multivariate linear regression analyses were performed to analyze the correlation of FD and BVT in different layers with DR severity. Results: In this study, 1,282 patients with DM (1,282 eyes), with a mean age of 64.2 ± 7.8 years, were included. FD in the DCP decreased and BVT in the DCP increased in patients with DR compared with those in patients without DR, even after adjusting for confounding factors (p < 0.05). Trend analysis showed a significant decrease in the FD values as the DR progressed, whereas the BVT progressively increased with worsening DR severity (p < 0.01). The FD in DCP had a statistically significant positive correlation with FD in SCP and a negative correlation with BVT in SCP and BVT in DCP in all of the participants, including the non-DR group, moderate DR group, and severe DR group (p < 0.01). Conclusions: FD and BVT determined using OCTA might be useful parameters for objectively distinguishing DR from non-DR and indicating DR progression.

Sustained Upregulation of Endothelial Nox4 Mediates Retinal Vascular Pathology in Type 1 Diabetes.

NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in retinal endothelial cells (ECs) and is upregulated under hyperglycemic and hypoxic conditions. However, the role of endothelial Nox4 upregulation in long-term retinal blood vessel damage in diabetic retinopathy (DR) remains undefined. Here, we attempted to address this question using humanized EC-specific Nox4 transgenic (hNox4EC-Tg) and EC-specific Nox4 knockout (Nox4EC-KO) mouse models. Our results show that hNox4EC-Tg mice at age of 10-12 months exhibited increased tortuosity of retinal blood vessels, focal vascular leakage, and acellular capillary formation. In vitro study revealed enhanced apoptosis in brain microvascular ECs derived from hNox4EC-Tg mice, concomitant with increased mitochondrial ROS, elevated lipid peroxidation, decreased mitochondrial membrane potential, and reduced mitochondrial respiratory function. In contrast, EC-specific deletion of Nox4 decreased mitochondrial ROS generation, alleviated mitochondrial damage, reduced EC apoptosis, and protected the retina from acellular capillary formation and vascular hyperpermeability in a streptozotocin-induced diabetes mouse model. These findings suggest that sustained upregulation of Nox4 in the endothelium contributes to retinal vascular pathology in diabetes, at least in part, through impairing mitochondrial function. Normalization of Nox4 expression in ECs may provide a new approach for prevention of vascular injury in DR.

Ultrasound examination of the upper extremity vessels in the early diagnosis of peripheral angiodystonic syndrome of occupational etiology

Introduction. The cardiovascular system reacts to almost all occupational hazards. Various methods for diagnostics, in particular ultrasound, may help to identify preclinical forms of the disease. The study aims to development of criteria for early diagnosis of occupational diseases of the vessels of the upper extremities in machine-building workers. Materials and methods. One hundred twenty-six workers of a machine-building plant were examined using standard clinical and laboratory methods, ultrasound examination of the vessels of the upper extremities and X-ray examination of the hands. Results. Laboring job, hand-arm and whole-body vibration, and noise with an average work experience of 21 years are risk factors for spastic changes in the vessels of the upper extremities in workers of machine-building production. X-ray changes in the hands are determined in 83% of cases and manifest themselves as a violation of local blood circulation, cystic restructuring in the bones of the wrists, and peri-articular osteopenia. Characteristic signs of vascular pathology detected by ultrasound are an increase in the resistance index with the preservation of speed indices (in 100%), impaired venous outflow (in 82%), and pathological tortuosity of blood vessels (in 76%). Limitations. We did not standardize workers depending on tobacco smoking due to the low number of workers in certain occupations. Conclusion. The results of ultrasound examination of the main vessels of the upper extremities in power engineering workers showed the presence of spastic vascular changes, which, with further exposure to occupational hazards, develop into angiodystonic syndrome, which is one of the syndromes of effects of vibration or polyneuropathy.