Corrigendum: PI-YOLO: dynamic sparse attention and lightweight convolutional based YOLO for vessel detection in pathological images.

[This corrects the article DOI: 10.3389/fonc.2024.1347123.].

Potential therapeutic targets for pelvic organ prolapse: insights from key genes related to blood vessel development.

Objective: Pelvic organ prolapse (POP) is a disease in which pelvic floor support structures are dysfunctional due to disruption of the extracellular matrix (ECM). The vascular system is essential for maintaining ECM homeostasis. Therefore, this study explored the potential mechanism of blood vessel development-related genes (BVDRGs) in POP. Methods: POP-related datasets and BVDRGs were included in this study. Differentially expressed genes (DEGs) between the POP and control groups were first identified in the GSE12852 and GSE208271 datasets, and DE-BVDRGs were identified by determining the intersection of these DEGs and BVDRGs. Subsequently, the feature genes were evaluated by machine learning. Feature genes with consistent expression trends in the GSE12852 and GSE208271 datasets were considered key genes. Afterward, the overall diagnostic efficacy of key genes in POP was evaluated through receiver operating characteristic (ROC) curve analysis. Based on the key genes, enrichment analysis, immune infiltration analysis and regulatory network construction were performed to elucidate the molecular mechanisms underlying the functions of the key genes in POP. Results: A total of 888 DEGs1 and 643 DEGs2 were identified in the GSE12852 and GSE208271 datasets, and 26 candidate genes and 4 DE-BVDRGs were identified. Furthermore, Hyaluronan synthase 2 (HAS2), Matrix metalloproteinase 19 (MMP19) and Plexin Domain Containing 1 (PLXDC1) were identified as key genes in POP and had promising value for diagnosing POP (AUC > 0.8). Additional research revealed that the key genes were predominantly implicated in immune cell activation, chemotaxis, and cytokine release via the chemokine signaling pathway, the Nod-like receptor signaling pathway, and the Toll-like receptor signaling pathway. Analysis of immune cell infiltration confirmed a decrease in the proportion of plasma cells in POP, and MMP19 expression showed a significant negative correlation with plasma cell numbers. In addition, regulatory network analysis revealed that MALAT1 (a lncRNA) targeted hsa-miR-503-5p, hsa-miR-23a-3p and hsa-miR-129-5p to simultaneously regulate three key genes. Conclusion: We identified three key BVDRGs (HAS2, MMP19 and PLXDC1) related to the ECM in POP, providing markers for diagnostic studies and investigations of the molecular mechanism of POP.

Surgical management of extensive facial vascular malformation with skin graft: A multidisciplinary approach-Case report.

Vascular malformations are rare congenital abnormalities of blood vessels that persist throughout life. Large vascular malformations affecting the facial region can be distressing and require meticulous management to achieve satisfactory outcomes and prevent recurrence. Here, we present a case of a 40-year-old man with a progressively growing tumor-like mass on the right side of his face, extending from the periorbital region to the chin. He was diagnosed with vascular malformations, which was further confirmed with contrast-enhanced magnetic resonance imaging. Eventually, he underwent surgical excision of the lesion with a split-thickness skin graft. The surgical management of this case was challenging due to the large size and complexity of the lesion, particularly because it was located in the facial region. This unique case report highlights the importance of diagnostic imaging techniques and effective surgical management in addressing large vascular malformations, especially those affecting the facial region while prioritizing desirable cosmetic outcomes.

Exosomes derived from BMSCs in osteogenic differentiation promote type H blood vessel angiogenesis through miR-150-5p mediated metabolic reprogramming of endothelial cells.

Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.

3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study.

Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC50s ranging from ∼10 to 24 µM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. By using two inhibitors, activation of voltage-gated potassium channels (KV) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the KV7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.

PI-YOLO: dynamic sparse attention and lightweight convolutional based YOLO for vessel detection in pathological images.

Vessel density within tumor tissues strongly correlates with tumor proliferation and serves as a critical marker for tumor grading. Recognition of vessel density by pathologists is subject to a strong inter-rater bias, thus limiting its prognostic value. There are many challenges in the task of object detection in pathological images, including complex image backgrounds, dense distribution of small targets, and insignificant differences between the features of the target to be detected and the image background. To address these problems and thus help physicians quantify blood vessels in pathology images, we propose Pathological Images-YOLO (PI-YOLO), an enhanced detection network based on YOLOv7. PI-YOLO incorporates the BiFormer attention mechanism, enhancing global feature extraction and accelerating processing for regions with subtle differences. Additionally, it introduces the CARAFE upsampling module, which optimizes feature utilization and information retention for small targets. Furthermore, the GSConv module improves the ELAN module, reducing model parameters and enhancing inference speed while preserving detection accuracy. Experimental results show that our proposed PI-YOLO network has higher detection accuracy compared to Faster-RCNN, SSD, RetinaNet, YOLOv5 network, and the latest YOLOv7 network, with a mAP value of 87.48%, which is 2.83% higher than the original model. We also validated the performance of this network on the ICPR 2012 mitotic dataset with an F1 value of 0.8678, outperforming other methods, demonstrating the advantages of our network in the task of target detection in complex pathology images.

Correlations between blood vessel distribution, lung function and structural change in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Correlations between the image analysis of CT scan, lung function and quality of life in patients with idiopathic pulmonary fibrosis (IPF) remain unclear. This study aimed to investigate the impacts of pulmonary blood-vessel distribution and the extent of fibrosis on the lung function and quality of life of patients with IPF. METHODS: Patients were enrolled in an IPF registry and had completed pulmonary function tests, chest HRCT, St. George Respiratory Questionnaire (SGRQ) and echocardiography. Pulmonary blood-vessel distribution, specific image-derived airway volume (siVaw) and fibrosis extent (siVfib) were quantitatively calculated by functional respiratory imaging on HRCT. RESULTS: The study subjects were categorized into DLco <40% pred. (n = 40) and DLco ≥40% pred. (n = 19) groups. Patients with DLco <40% pred. had significantly higher scores of SGRQ, composite physiologic index (CPI), exercise oxygen desaturation (∆SpO2), siVaw, lower FVC% pred. and 6-minute walking distance% pred. The proportion of small blood vessels in the upper lobes (BV5PR-UL) was significantly correlated with CPI, DLco % Pred., FVC% pred., SGRQ and ∆SpO2. Only BV5PR-UL had a significant impact on all indices but not BV5PR in the lower lobes (BV5PR-LL). siVfib was significantly negatively correlated with BV5PR-UL, DLco% pred. and FVC% pred., as well as positively correlated with CPI, ∆SpO2 and siVaw. CONCLUSION: BV5PR-UL and siVfib had significant correlations with lung function and may become important indicators to assess the severity of IPF and the impact on quality of life.

SARC-UNet: A coronary artery segmentation method based on spatial attention and residual convolution.

BACKGROUND AND OBJECTIVE: Coronary artery segmentation is a pivotal field that has received increasing attention in recent years. However, this task remains challenging because of the inhomogeneous distributions of the contrast agent and dim light, resulting in noise, vascular breakages and small vessel losses in the obtained segmentation results. METHODS: To acquire better automatic blood vessel segmentation results for coronary angiography images, a UNet-based segmentation network (SARC-UNet) is constructed for coronary artery segmentation; this approach is based on residual convolution and spatial attention. First, we use the low-light image enhancement (LIME) approach to increase the contrast and clarity levels of coronary angiography images. Then, we design two residual convolution fusion modules (RCFM1 and RCFM2) that can successfully fuse the local and global information of coronary images while also capturing the characteristics of finer-grained blood vessels, hence preventing the loss of tiny blood vessels in the segmentation findings. Finally, using a cascaded waterfall structure, we create a new location-enhanced spatial attention (LESA) mechanism that can efficiently improve the long-distance dependencies between coronary vascular pixel features, eradicating vascular ruptures and noise in the segmentation results. RESULTS: This article subjectively and objectively evaluates the experimental results. This method has performed well on five general indicators. Furthermore, it outperforms the connectivity indicators proposed in this article. This method can effectively segment blood vessels and obtain higher accuracy results. CONCLUSIONS: Numerous experiments have shown that the suggested method outperforms the state-of-the-art approaches, particularly in terms of vessel connectivity and small blood vessel segmentation.

Neural Regulation of Vascular Development: Molecular Mechanisms and Interactions.

As a critical part of the circulatory system, blood vessels transport oxygen and nutrients to every corner of the body, nourishing each cell, and also remove waste and toxins. Defects in vascular development and function are closely associated with many diseases, such as heart disease, stroke, and atherosclerosis. In the nervous system, the nervous and vascular systems are intricately connected in both development and function. First, peripheral blood vessels and nerves exhibit parallel distribution patterns. In the central nervous system (CNS), nerves and blood vessels form a complex interface known as the neurovascular unit. Second, the vascular system employs similar cellular and molecular mechanisms as the nervous system for its development. Third, the development and function of CNS vasculature are tightly regulated by CNS-specific signaling pathways and neural activity. Additionally, vascular endothelial cells within the CNS are tightly connected and interact with pericytes, astrocytes, neurons, and microglia to form the blood-brain barrier (BBB). The BBB strictly controls material exchanges between the blood and brain, maintaining the brain's microenvironmental homeostasis, which is crucial for the normal development and function of the CNS. Here, we comprehensively summarize research on neural regulation of vascular and BBB development and propose directions for future research.

Spatial attention U-Net model with Harris hawks optimization for retinal blood vessel and optic disc segmentation in fundus images.

BACKGROUND: The state of the human eye's blood vessels is a crucial aspect in the diagnosis of ophthalmological illnesses. For many computer-aided diagnostic systems, precise retinal vessel segmentation is an essential job. However, it remains a difficult task due to the intricate vascular system of the eye. Although many different vascular segmentation techniques have already been presented, additional study is still required to address the problem of inadequate segmentation of thin and tiny vessels. METHODS: In this work, we introduce the Spatial Attention U-Net (SAU-Net) model with harris hawks' optimization (HHO), a lightweight network that can be applied as a data augmentation technique to improve the efficiency of the existing annotated samples without the need of thousands of training instances for Retinal Blood Vessel and Optic Disc Segmentation. The SAU-Net-HHO implementation uses a spatially inferred attention map multiplied by the input feature map for adaptive feature enhancement. U-Net convolutional blocks have been replaced with structured dropout blocks in the proposed network to prevent overfitting. Data from both vascular extraction (DRIVE) and structured analysis of the retina (STARE) are used to evaluate SAU-Net-HHO performance. RESULTS: The results show that the proposed SAU-Net-HHO performs well on both datasets. Analysing the obtained results, an average of 98.5% accuracy and Specificity 96.7% was achieved for DRIVE dataset and 97.8% accuracy and specificity 94.5% for STARE dataset. The proposed method yields numerical results with average values that are on par with those of state-of-the-art methods. CONCLUSION: Visual inspection has revealed that the suggested method can segment thin and tiny vessels with greater accuracy than previous methods. It also demonstrates its potential for real-life clinical application.

Imaging arterial and venous vessels using Iron Dextran enhanced multi-echo 3D gradient echo MRI at 7T.

Iron Dextran is a widely used iron oxide compound to treat iron-deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron-induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi-echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain. Phantom experiments were performed to measure the r2* relaxivity for Iron Dextran in blood, based on which the SWI sequence was optimized. Pre- and post-infusion MR images were acquired in human subjects from which maps of arteries and veins were extracted. The post-contrast SWI images showed enhanced susceptibility difference between blood and the surrounding tissue in both arteries and veins. Our results showed that the proposed Iron Dextran enhanced multi-echo SWI approach allowed the visualization of blood vessels with diameters down to ~100 µm, including small blood vessels supplying and draining small brain structures such as the hippocampus. We conclude that Iron Dextran can be an alternative iron-based MRI contrast agent for blood vessel imaging in the human brain.

Corrigendum: PI-YOLO: dynamic sparse attention and lightweight convolutional based YOLO for vessel detection in pathological images.

[This corrects the article DOI: 10.3389/fonc.2024.1347123.].

Epithelioid Hemangioendothelioma as a Dangerous, Easy to Miss, and Nearly Impossible to Clinically Diagnose Condition: Case Report.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with metastatic potential. EHE can have single- or multiorgan involvement, with presentations ranging from asymptomatic disease to pain and systemic symptoms. The extremely heterogeneous clinical presentation and disease progression complicates EHE diagnosis and management. We present the case of a 24-year-old woman with two periauricular erythematous papules, leading to the discovery of metastatic EHE through routine biopsy, despite a noncontributory medical history. Histology revealed the dermal proliferation of epithelioid cells and vacuoles containing red blood cells. Immunohistochemistry markers consistent with EHE solidified the diagnosis. Although extremely rare, prompt diagnosis of EHE is essential for informed decision-making and favorable outcomes. Key clinical and histopathological findings are highlighted to aid dermatologists in diagnosing and managing this uncommon condition.

Optical coherence tomography-measured blood vessel characteristics of port-wine birthmarks by depth: A cross-sectional study.

BACKGROUND: Port-Wine Birthmarks (PWB) are congenital capillary malformations requiring multiple treatments. Optical coherence tomography (OCT), a noninvasive imaging technique, characterizes vessels in cutaneous vascular lesions, including PWBs. OBJECTIVE: To assess variability in blood vessel characteristics within and between individual PWBs. METHODS: OCT was used to measure blood vessel density (%) and modal vessel diameter (micrometers) at increments of 0.05 mm from the skin surface to a depth of 0.50 mm at several adjacent spots of single PWBs in this cross-sectional study. Average ratios of vessel density and diameter in affected to control skin were obtained for each PWB by averaging data for all spots within a lesion. Statistical analysis was performed with a linear mixed effects model using SPSS software (IBM Corporation). RESULTS: There was great variability in vessel density and diameter within and between PWBs. Depths where average ratios of vessel density were consistently greater in affected to control skin were shallow, between 0.15 mm and 0.2 mm deep from the skin surface. LIMITATIONS: Small sample size and device's inability to measure diameters smaller than 20 micrometers. CONCLUSION: There is variability in vessel density and diameter within and between PWBs. Individualized treatment planning guided by OCT mapping should be studied further.

Biomimetic Approaches in Scaffold-Based Blood Vessel Tissue Engineering.

Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes. This review offers an updated picture of the state of the art in vascular tissue engineering, emphasising the design of scaffolds and dynamic culture conditions following a biomimetic approach. By emulating native vessel properties and, in particular, by mimicking the three-layer structure of the vascular wall, tissue-engineered grafts can improve long-term patency and clinical outcomes. Furthermore, ongoing research focuses on enhancing biomimicry through innovative scaffold materials, surface functionalisation strategies, and the use of bioreactors mimicking the physiological microenvironment. Through a multidisciplinary lens, this review provides insight into the latest advancements and future directions of vascular tissue engineering, with particular reference to employing biomimicry to create systems capable of reproducing the structure-function relationships present in the arterial wall. Despite the existence of a gap between benchtop innovation and clinical translation, it appears that the biomimetic technologies developed to date demonstrate promising results in preventing vascular occlusion due to blood clotting under laboratory conditions and in preclinical studies. Therefore, a multifaceted biomimetic approach could represent a winning strategy to ensure the translation of vascular tissue engineering into clinical practice.

Spatial transcriptomics of gastric cancer brain metastasis reveals atypical vasculature strategies with supportive immune profiles.

Background: Gastric cancer brain metastasis (GCBM) represents a rare but highly aggressive malignancy. Metastatic cancer cells are highly heterogeneous and differentially remodels brain vasculature and immune microenvironments, which affects the treatment effectiveness and patient outcome. This study aimed to investigate the spatial interactions among different cell components, especially the vasculature system and the brain microenvironment of GCBM patients. Methods: We used digital spatial profiling to examine 140 regions composing tumor, immune, and brain tissues from three GCBM patients. Transcriptomic data with spatial information were analyzed for tissue areas related to different blood recruitment strategies. For validation, independent analysis of patient bulk transcriptomic data and in vivo single-cell transcriptomic data were performed. Results: Angiogenesis and blood vessel co-option co-existed within the same GCBM lesion. Tumors with high epithelial-mesenchymal transition and an enhanced transcriptomic gene signature composed of CTNNB1, SPARC, VIM, SMAD3, SMAD4, TGFB1, TGFB2, and TGFB3 were more prone to adopt blood vessel co-option than angiogenesis. Enriched macrophage infiltration, angiogenic chemokines, and NAMPT were found in angiogenic areas, while increased T cells, T cell activating cytokines, and reduced NAMPT were found in vessel co-option regions. Spatially, angiogenesis was enriched at the tumor edge, which showed higher DMBT1 expression than the tumor center. Conclusions: This study mapped the orchestrated spatial characteristics of tumor and immunological compositions that support the conventional and atypical vascularization strategies in GCBM. Our data provided molecular insights for more effective combinations of anti-vascular and immune therapies.

Hybrid Repair of Infected Femoral Artery Pseudoaneurysm: Stent Graft Placement and Artificial Graft Replacement.

A femoral artery pseudoaneurysm is the most prevalent complication of femoral access due to the artery's accessibility and frequent use for catheterization and blood tests. An infected femoral artery pseudoaneurysm is often life-threatening and challenging to manage. A 70-year-old male with a history of tongue cancer treatments, including resection, lymph node dissection, and radiation chemotherapy, visited his previous physician for a fever and was prescribed oral antibiotics, but the fever persisted, accompanied by pain and a mass in the left groin. An enhanced CT revealed an infected pseudoaneurysm of the left femoral artery. The fever's etiology was unclear but likely stemmed from a blood draw from the femoral artery during a prior visit, resulting in a pseudoaneurysm that became infected. The patient was transferred to our hospital due to management challenges. Blood cultures from the previous hospital were positive, and laboratory tests indicated an active infection. The initial strategy was to continue antibiotic therapy to control the infection. After approximately a month of antibiotic treatment, blood cultures remained negative, and laboratory results improved significantly. However, the aneurysm had clearly enlarged, necessitating emergency surgery. Typically, surgical intervention requires opening the abdomen to replace the external iliac artery to its extent, a considerably invasive procedure for the patient. Thus, we opted for a hybrid treatment, implanting a stent graft from the external iliac artery to the proximal common femoral artery and replacing artificial blood vessels from there to the femoral artery bifurcation. The postoperative course was favorable. In this case, we provided the optimal treatment for the patient's condition, despite the impossibility of a radical cure due to the cancer's progression. We believe the infected pseudoaneurysm was adequately controlled, and the hybrid therapy is effective for patients who cannot endure more invasive treatments.

Automated thermographic detection of blood vessels for DIEP flap reconstructive surgery.

PURPOSE: Inadequate perfusion is the most common cause of partial flap loss in tissue transfer for post-mastectomy breast reconstruction. The current state-of-the-art uses computed tomography angiography (CTA) to locate the best perforators. Unfortunately, these techniques are expensive and time-consuming and not performed during surgery. Dynamic infrared thermography (DIRT) can offer a solution for these disadvantages. METHODS: The research presented couples thermographic examination during DIEP flap breast reconstruction with automatic segmentation approach using a convolutional neural network. Traditional segmentation techniques and annotations by surgeons are used to create automatic labels for the training. RESULTS: The network used for image annotation is able to label in real-time on minimal hardware and the labels created can be used to locate and quantify perforator candidates for selection with a dice score accuracy of 0.8 after 2 min and 0.9 after 4 min. CONCLUSIONS: These results allow for a computational system that can be used in place during surgery to improve surgical success. The ability to track and measure perforators and their perfused area allows for less subjective results and helps the surgeon to select the most suitable perforator for DIEP flap breast reconstruction.

Integrated transcriptomics of human blood vessels defines a spatially controlled niche for early mesenchymal progenitor cells.

Human blood vessel walls show concentric layers, with the outermost tunica adventitia harboring mesenchymal progenitor cells. These progenitor cells maintain vessel homeostasis and provide a robust cell source for cell-based therapies. However, human adventitial stem cell niche has not been studied in detail. Here, using spatial and single-cell transcriptomics, we characterized the phenotype, potential, and microanatomic distribution of human perivascular progenitors. Initially, spatial transcriptomics identified heterogeneity between perivascular layers of arteries and veins and delineated the tunica adventitia into inner and outer layers. From this spatial atlas, we inferred a hierarchy of mesenchymal progenitors dictated by a more primitive cell with a high surface expression of CD201 (PROCR). When isolated from humans and mice, CD201Low expression typified a mesodermal committed subset with higher osteogenesis and less proliferation than CD201High cells, with a downstream effect on canonical Wnt signaling through DACT2. CD201Low cells also displayed high translational potential for bone tissue generation.