Vascular Regions Research Articles

Measurement of Wall Shear Rate Across the Entire Vascular Wall Using Ultrasound Speckle Decorrelation

ObjectiveThe accurate measurement of the wall shear rate (WSR) plays a crucial role in the early diagnosis of cardiovascular disease progression and acute events such as aneurysms and atherosclerotic plaque ruptures. To address this need, the speckle decorrelation (SDC) technique has been used to measure WSR based on the 2-D out-of-plane blood flow speed. This technique is particularly advantageous because it enables the use of a 1-D array transducer to measure WSR over the entire luminal area. This study aims to develop a region-based singular value decomposition (SVD) filtering technique that selectively suppresses clutter noise in the vascular region to measure WSR using SDC. MethodUltrasound simulations, in-vitro flow experiments, and an in-vivo human study were conducted to evaluate the feasibility of this method's clinical application. ResultsThe results demonstrated that WSR can be effectively measured across entire vascular walls using a conventional 1-D array transducer along with the proposed methodology. ConclusionThis study successfully demonstrates a noninvasive and accurate SDC-based method for measuring vital vascular WSR. This approach holds significant promise for assessing vascular WSR in both healthy individuals and high-risk cardiovascular disease patients.

Laser speckle contrast imaging versus microvascular Doppler sonography in aneurysm surgery: A prospective study

ObjectiveThis study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. MethodsMDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). ResultsAgreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. ConclusionsLSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.

A vasculature based nanocryosurgical model for tumor destruction

The vascular model built on porous media approach is a more realistic representation of biological tissue. A vasculature system based axisymmetric cryosurgical model is proposed here for cryosurgery of lung tumor based on the freezing of the vascular region of the biological tissue. A two-temperature model is developed based on the porous medium approach considering the thermal non-equilibrium between the tissue and the blood region. Bioheat transfer phenomenon between tissue and blood involves interfacial heat transfer, perfusion heat transfer and metabolic heat generation in tissue cylinder. To improve the cryothermal penetration inside the tumor tissue, high conductive nanoparticles are injected into it which increases the local freezing rate of tumor region with minimum damage to the surrounding healthy tissue. The blood phase change in the vascular network is modelled through a source based implicit enthalpy method. The proposed model is utilized to simulate cryosurgery for lung lesion. It is observed that the solidification time for 99.9% tumor using Pennes model and Vascular model (ε=0.01) are 414 s and 512 s respectively, which shows that Pennes model overpredicts the freezing of tumor during cryosurgery. The freezing necrosis is found to reduce by 13.95% at 0.05 (volume fraction) nanoparticle concentration.

A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease

Background: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. Methods: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. Results: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. Conclusions: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.

Differences in vocal brain areas and astrocytes between the house wren and the rufous-tailed hummingbird.

The house wren shows complex song, and the rufous-tailed hummingbird has a simple song. The location of vocal brain areas supports the song's complexity; however, these still need to be studied. The astrocytic population in songbirds appears to be associated with change in vocal control nuclei; however, astrocytic distribution and morphology have not been described in these species. Consequently, we compared the distribution and volume of the vocal brain areas: HVC, RA, Area X, and LMAN, cell density, and the morphology of astrocytes in the house wren and the rufous-tailed hummingbird. Individuals of the two species were collected, and their brains were analyzed using serial Nissl- NeuN- and MAP2-stained tissue scanner imaging, followed by 3D reconstructions of the vocal areas; and GFAP and S100β astrocytes were analyzed in both species. We found that vocal areas were located close to the cerebral midline in the house wren and a more lateralized position in the rufous-tailed hummingbird. The LMAN occupied a larger volume in the rufous-tailed hummingbird, while the RA and HVC were larger in the house wren. While Area X showed higher cell density in the house wren than the rufous-tailed hummingbird, the LMAN showed a higher density in the rufous-tailed hummingbird. In the house wren, GFAP astrocytes in the same bregma where the vocal areas were located were observed at the laminar edge of the pallium (LEP) and in the vascular region, as well as in vocal motor relay regions in the pallidum and mesencephalon. In contrast, GFAP astrocytes were found in LEP, but not in the pallidum and mesencephalon in hummingbirds. Finally, when comparing GFAP astrocytes in the LEP region of both species, house wren astrocytes exhibited significantly more complex morphology than those of the rufous-tailed hummingbird. These findings suggest a difference in the location and cellular density of vocal circuits, as well as morphology of GFAP astrocytes between the house wren and the rufous-tailed hummingbird.

Computational Fluid Dynamic Assessment of Patients with Congenital Heart Disease from 3D Rotational Angiography.

For congenital heart disease patients, multiple imaging modalities are needed to discern anatomy and functional information such as differential blood flow. During cardiac catheterization, 3D rotational angiography (3DRA) can provide CTA-like images, enabling anatomical information and intraprocedural guidance. We seek to establish whether unique aspects of this technique can also generate quantitative functional blood flow information. We propose that systematic integration of 3DRA imaging, catheter hemodynamic information, and computational fluid dynamics (CFD), can provide quantitative information regarding blood flow dynamics and energetics, without additional imaging or procedures. We report a single center retrospective feasibility study comprising four patients with 3DRA imaging and a complete set of hemodynamic data. 3DRA was processed and segmented to reconstruct vascular regions of interest (ROI), and a computational grid for CFD modeling of blood flow through the ROI was generated. Blood flow was simulated by integrating catheter hemodynamic data to devise boundary conditions at vascular ROI inlets and outlets. The 3DRA-based workflow successfully generated key computational outputs commonly used for cardiovascular applications, including flow patterns, distribution fractions, wall shear stress. Computational outputs obtained were as detailed and resolved as those obtained from more commonly used CT or MR angiography. Accuracy was confirmed by comparing computed flow distributions with measurements for 2 cases, showing less than 2.0% error from the measured data. Systematic integration of catheter hemodynamic information, 3DRA imaging, and CFD modeling, provides an effective and feasible alternative to obtain important quantitative blood flow information and visualization, without additional imaging.

Cytological assessments and a methodological approach to observe the apoptotic effect of nickel sulfate (NiSO4) on Allium cepa L. root germination using EB/AO fluorescence staining

Ethidium bromide–acridine orange (EB/AO) is one of the fastest, most economically valid methods for separating living and dead cells in plant root tips. The present study aimed to investigate the apoptotic effect, nuclear abnormalities and cell division index using an Allium cepa test assay with EB/AO staining and an ImageJ program. Nickel sulphate (NiSO4) concentrations (1.75, 3.5, 7 and 14 ppm) were exposed to the root germination of A. cepa for 48 and 72 h to observe mitotic abnormalities, cytotoxic effects and 5-day exposure to apoptotic effects. It was found that amorphous nuclei, vacuolisation and C-mitosis were the most observed abnormalities, which increased at 14 ppm NiSO4 exposure after 48 and 72 h. The total number of nuclear abnormalities significantly increased at all concentrations and exposure periods. The ImageJ program was used to determine apoptosis rates. The data obtained showed that high concentrations of NiSO4 caused significantly more cell death in root tips than in the control group, resulting in root growth inhibition and increased apoptosis with increased concentration and exposure period. NiSO4 caused toxic activity on root growth, identified as apoptosis, especially at the cortex and vascular region in the root tips. The study found affected damaged and apoptotic areas on the root tips using an EB/AO staining method, which can be used as a marker of damaged tissue areas.

Are hemodynamics responsible for inflammatory changes in venous vessel walls? A quantitative study of wall-enhancing intracranial arteriovenous malformation draining veins.

Signal enhancement of vascular walls on vessel wall MRI might be a biomarker for inflammation. It has been theorized that contrast enhancement on vessel wall imaging (VWI) in draining veins of intracranial arteriovenous malformations (AVMs) may be associated with disease progression and development of venous stenosis. The aim of this study was to investigate the relationship between vessel wall enhancement and hemodynamic stressors along AVM draining veins. Eight AVM patients with 15 draining veins visualized on VWI were included. Based on MR venography data, patient-specific 3D surface models of the venous anatomy distal to the nidus were segmented. The enhanced vascular wall regions were manually extracted and mapped onto the venous surface models after registration of image data. Using image-based blood flow simulations applying patient-specific boundary conditions based on phase-contrast quantitative MR angiography, hemodynamics were investigated in the enhanced vasculature. For the shear-related parameters, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated. Velocity, oscillatory velocity index (OVI), and vorticity were extracted for the intraluminal flow-related hemodynamics. Visual observations demonstrated overlap of enhancement with local lower shear stresses resulting from decreased velocities. Thus, higher RRT values were measured in the enhanced areas. Furthermore, nonenhancing draining veins showed on average slightly higher flow velocities and TAWSS. Significant decreases of 55% (p = 0.03) for TAWSS and of 24% (p = 0.03) for vorticity were identified in enhanced areas compared with near distal and proximal domains. Velocity magnitude in the enhanced region showed a nonsignificant decrease of 14% (p = 0.06). Furthermore, increases were present in the OSI (32%, p = 0.3), RRT (25%, p = 0.15), and OVI (26%, p = 0.3) in enhanced vessel sections, although the differences were not significant. This novel multimodal investigation of hemodynamics in AVM draining veins allows for precise prediction of occurring shear- and flow-related phenomena in enhanced vessel walls. These findings may suggest low shear to be a local predisposing factor for venous stenosis in AVMs.

Morphological and Immunohistochemical Differentiation of Neuronal and Glial Cells of the Vascular and Avascular Regions of the Donkey’s Paurangiotic Retina

Introduction: Ocular diseases pose a significant health concern for donkeys. However, studies examining the microanatomy and cell populations of the donkey retina are scarce. The current study aimed to describe the vascular pattern of the donkey retina and document its cellular components. Methods: The donkey retina specimens were obtained from different retinal regions and prepared for semithin sectioning and immunohistochemistry. Results: The donkey has a paurangiotic retina in which retinal vessels are confined to a narrow area around the optic disc. Glial cells coexist with the blood vessels being very numerous in the vascular region and become scanty in the avascular ones. S-100-positive astrocytes could be observed in these avascular areas. Ganglion cells are organized in a single layer with the least population existing in the peripheral retina. Acidic fibroblast growth factor (AFGF) is immunoreactive in amacrine and ganglion cells. A subpopulation of amacrine cells reacted strongly to tyrosine hydroxylase (TH), and others reacted positively to S-100 protein. Ganglion cell nuclei exhibited a strong immunoreactivity to S-100 protein as well. Furthermore, glial fibrillary acidic protein (GFAP) is used to identify Müller cells that extend their processes across the retina from the inner to the outer limiting membrane. Conclusions: In conclusion, our findings provide novel insights into the normal retinal organization. The donkey retina shows the characteristic expression of immunohistochemical markers for the major cell types. In addition, the distribution of glial cells is comparable between the vascular and avascular regions.

Abstract 75: Validation of Vascular Location Subcodes for Acute Ischemic Stroke by the International Classification of Diseases-10

Background: The affected vascular region is included in the International Classification of Diseases-10 (ICD-10) coding scheme for stroke. These data have the potential to enable studies of vascular and regional location. For example, differentiating anterior versus posterior circulation stroke. However, the coding in real world practice has not been validated. The purpose of this study was to evaluate the validity of these subcodes. Methods: We identified all hospitalizations for ischemic stroke at a single center from 2018-2022. We selected a random sample of 100 hospitalizations with vascular region subcoding specifying 50 with anterior circulation subcodes (carotid, anterior cerebral artery [CA], middle CA) and 50 with posterior circulation subcodes (vertebral, basilar, cerebellar, posterior CA). The gold standard classification for the primary infarct vascular distribution was made by the study team, blinded to the subcode, after review of the available imaging studies and the medical record. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the administrative data posterior circulation subcodes versus anterior circulation subcodes with the gold standard classification. We also calculated the kappa statistic for overall agreement of the 7 vascular regions. Results: The final study population was 50 ICD-10 anterior circulation ischemic stroke hospitalizations and 50 ICD-10 posterior circulation ischemic stroke hospitalizations. Mean age was 68 (SD, 15) and 44% (44/100) were female. Mean NIHSS was 8 (SD, 8). Neuroimaging was performed in 100% (100/100): Head CT, 95% (95/100); MRI brain, 77% (77/100). The accuracy of the ICD-10 classification for primary posterior circulation stroke was as follows: sensitivity 89% (49/55); specificity 98% (44/45); PPV 98% (49/50); NPV 88% (44/50), respectively. The reliability of the 7-region classification was excellent (kappa statistic, 0.85). Conclusions: We found that the ICD-10 subcode classification for vascular location used in clinical practice had excellent agreement with our gold standard based on medical review. These data validate the use of these subcodes for anterior versus posterior circulation stroke studies.

Validation of Vascular Location Subcodes for Acute Ischemic Stroke by the International Classification of Diseases-10

BackgroundVascular region of infarct is part of the International Classification of Diseases-10 (ICD-10) coding scheme for ischemic stroke. These data could potentially be used for studies about vascular location, such as comparisons of anterior versus posterior circulation stroke. The objective of this study was to evaluate the validity of these subcodes. MethodsWe selected a random sample of 100 hospitalizations specifying 50 with anterior circulation ICD-10 ischemic stroke (carotid, anterior cerebral artery [CA], middle CA) and 50 with posterior circulation stroke (vertebral, basilar, cerebellar, posterior CA). The gold standard primary vascular distribution was scored using imaging studies and reports, blinded to the subcode. We compared gold-standard distribution to coded distribution and calculated the operating characteristics of ICD-10 posterior circulation versus anterior circulation codes with the gold standard. We also calculated the kappa statistic for agreement across all 7 vascular regions. ResultsIn our population of 100 strokes, mean NIHSS was 8 (SD, 8). Head CT was performed in 95 % (95/100) and MRI in 77 % (77/100). The gold standard classified 55 primary posterior circulation strokes (26 PCA, 16 cerebellar, 8 basilar, 5 vertebral), 44 primary anterior circulation strokes (35 MCA, 6 carotid, 3 ACA), and 1 stroke with no infarct on imaging. The accuracy of the ICD-10 classification for primary posterior circulation stroke versus anterior circulation/no infarct was: sensitivity 89 % (49/55); specificity 98 % (44/45); positive predictive value 98 % (49/50); negative predictive value 88 % (44/50). The reliability of the 7-region classification was excellent (kappa 0.85). ConclusionsWe found that ICD-10 classification of vascular location in routine practice correlates strongly with gold-standard localization for hospitalized ischemic stroke and supports validity in differentiating posterior versus anterior circulation. At a more granular vascular level, the location reliability was excellent, although limited data were available for some subcodes.

Siamese model for collateral score prediction from computed tomography angiography images in acute ischemic stroke.

Imaging biomarkers, such as the collateral score as determined from Computed Tomography Angiography (CTA) images, play a role in treatment decision making for acute stroke patients. In this manuscript, we present an end-to-end learning approach for automatic determination of a collateral score from a CTA image. Our aim was to investigate whether such end-to-end learning approaches can be used for this classification task, and whether the resulting classification can be used in existing outcome prediction models. The method consists of a preprocessing step, where the CTA image is aligned to an atlas and divided in the two hemispheres: the affected side and the healthy side. Subsequently, a VoxResNet based convolutional neural network is used to extract features at various resolutions from the input images. This is done by using a Siamese model, such that the classification is driven by the comparison between the affected and healthy using a unique set of features for both hemispheres. After masking the resulting features for both sides with the vascular region and global average pooling (per hemisphere) and concatenation of the resulting features, a fully connected layer is used to determine the categorized collateral score. Several experiments have been performed to optimize the model hyperparameters and training procedure, and to validate the final model performance. The hyperparameter optimization and subsequent model training was done using CTA images from the MR CLEAN Registry, a Dutch multi-center multi-vendor registry of acute stroke patients that underwent endovascular treatment. A separate set of images, from the MR CLEAN Trial, served as an external validation set, where collateral scoring was assessed and compared with both human observers and a recent more traditional model. In addition, the automated collateral scores have been used in an existing functional outcome prediction model that uses both imaging and non-imaging clinical parameters. The results show that end-to-end learning of collateral scoring in CTA images is feasible, and does perform similar to more traditional methods, and the performance also is within the inter-observer variation. Furthermore, the results demonstrate that the end-to-end classification results also can be used in an existing functional outcome prediction model.

The expert's knowledge combined with AI outperforms AI alone in seizure onset zone localization using resting state fMRI.

We evaluated whether integration of expert guidance on seizure onset zone (SOZ) identification from resting state functional MRI (rs-fMRI) connectomics combined with deep learning (DL) techniques enhances the SOZ delineation in patients with refractory epilepsy (RE), compared to utilizing DL alone. Rs-fMRI was collected from 52 children with RE who had subsequently undergone ic-EEG and then, if indicated, surgery for seizure control (n = 25). The resting state functional connectomics data were previously independently classified by two expert epileptologists, as indicative of measurement noise, typical resting state network connectivity, or SOZ. An expert knowledge integrated deep network was trained on functional connectomics data to identify SOZ. Expert knowledge integrated with DL showed a SOZ localization accuracy of 84.8 ± 4.5% and F1 score, harmonic mean of positive predictive value and sensitivity, of 91.7 ± 2.6%. Conversely, a DL only model yielded an accuracy of <50% (F1 score 63%). Activations that initiate in gray matter, extend through white matter, and end in vascular regions are seen as the most discriminative expert-identified SOZ characteristics. Integration of expert knowledge of functional connectomics can not only enhance the performance of DL in localizing SOZ in RE but also lead toward potentially useful explanations of prevalent co-activation patterns in SOZ. RE with surgical outcomes and preoperative rs-fMRI studies can yield expert knowledge most salient for SOZ identification.

Photocrosslinkable silk-based bioinks embedded with growth factor loaded microspheres towards cell-free 3D printing approach for biomimetic regeneration of meniscal tissue

Fibrocartilaginous meniscal tear regeneration is a major challenge due to the large avascular regions which suffer several injuries among all age-groups. Mostly, meniscus implants are focused on the development of multi-layered meniscus constructs and scaffolds that mimic the macro-architecture, functionality and mechanical strength. The native human menisci consist of vascular and avascular regions that contain different cellular phenotypes and are hence composed of a gradient of extracellular matrix (ECM) components. The biochemical composition of the inner, middle and outer regions of the knee menisci plays a significant role in the mechanical behavior and its overall functionality. We have developed a photo-polymerizing mulberry and non-mulberry silk-based biomaterial ink which is laden with growth factor loaded gelMA microspheres for the zone-specific regeneration of full thickness meniscus tears using three-dimensional (3D) fabrication. We have fabricated growth factor loaded gelMA microspheres and encapsulated them within the biomaterial ink for controlled release of Connective Tissue Growth Factor (CTGF) and Transforming Growth Factor-beta3 (TGF-β3) from the different zones of the meniscus constructs. The growth factor releasing constructs demonstrate the requisite mechanical resilience, degradability and release behaviour for regeneration of meniscal tissue. The developed growth factor loaded constructs demonstrate zone specific phenotypic differentiation of adipose derived stem cells and extracellular matrix deposition by the differentiated stem cells in vitro. The microsphere loaded constructs were found to be immuno-compatible as well. Therefore, these bioactive microsphere-laden 3D printed meniscus constructs would potentially promote regeneration and integration of meniscal tissue in vivo.

Changes in Optic Nerve Head Blood Flow During Horizontal Ocular Duction.

In this study, we aimed to compare blood flow changes in the optic nerve head (ONH) during horizontal ocular duction among normal, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG) eyes. In this cross-sectional study, we included 90 eyes from 90 participants (30 control eyes, 30 POAG eyes, and 30 NTG eyes). ONH blood flow was measured with laser speckle flowgraphy using an external fixation light to induce central gaze, abduction, and adduction at 30 degrees for each eye. The mean blur rate (MBR) of the entire ONH area (MA), vascular region (MV), and tissue region (MT), and the change ratio were analyzed. The change ratio was defined as abduction or adduction value/central gaze value. In the control group, MA significantly decreased during adduction (22.9 ± 3.7) compared with that during central gaze (23.6 ± 3.9, P < 0.05). In the POAG group, MA (adduction = 17.4 ± 3.8 and abduction = 17.3 ± 3.6) and MV (adduction = 37.9 ± 5.6 and abduction = 38.0 ± 5.6) significantly decreased during adduction and abduction compared with those during central gaze (18.0 ± 4.1 and 39.5 ± 6.3, respectively, P < 0.05). In the NTG group, MA significantly decreased during adduction (17.4 ± 4.2) compared with that during central gaze (18.1 ± 4.6) and abduction (18.1 ± 4.8, P < 0.05). The change ratio did not differ between the glaucoma and control groups. ONH blood flow decreased during horizontal ocular duction regardless of normal or glaucoma states; however, the change ratio was comparable between the normal and glaucoma groups.

Localization of matrix metalloproteinases in the placenta of cows with complicated pregnancy by placental insufficiency

The placenta of 8 cows with physiological (PP) and placental insufficiency pregnancy (FPI) served as the material for the study. Analysis of the content of glycosaminoglycans (GAG) in the tissue of the uterine part of the placenta in cows with FPI indicated the degradation of the connective tissue matrix of cotyledons of chorionic villi and crypts of caruncles, due to the lack of interstitial substance structuring. Hyperplasia of crypts of caruncles is observed, which form glandular-like structures, with reduction in cotyledon chorionic villi in cotyledons. The level of MMP-3 metalloproteinase was detected in the structure of defragmented maternal crypts, and the presence of immunopositive cells was recorded only in the vascular region with active hyperplasia of crypt epithelial cells. The level of MMP-3 metalloproteinase was detected in the structure of defragmented maternal crypts, and the presence of immunopositive cells was recorded only in the vascular region with active hyperplasia of crypt epithelial cells. A decrease in the level of MMP-3 metalloproteinase in cotyledons of placental structures of cows was clearly noted in samples obtained from cows with placental insufficiency (FPI). Morphological changes in the placenta in cows with FPI, manifested before childbirth, are characterized by the free arrangement of cotyledons of chorionic villi in the crypts of caruncles formed by branches of uterine septa. Translocation of metalloproteinases of the MMR-3 type was found in the cotyledon space between the villi of the cotiledon chorion and the epithelium of the crypts of caruncles, especially in places where the villi are completely reduced. The conducted research may contribute to the development of enzyme immunoassay (ELISA) for the diagnosis of reproductive pathologies in mothers and newborns.

Potentiation of anti-angiogenic eNOS-siRNA transfection by ultrasound-mediated microbubble destruction in ex vivo rat aortic rings.

Nitric oxide (NO) regulates vascular homeostasis and plays a key role in revascularization and angiogenesis. The endothelial nitric oxide synthase (eNOS) enzyme catalyzes NO production in endothelial cells. Overexpression of the eNOS gene has been implicated in pathologies with dysfunctional angiogenic processes, such as cancer. Therefore, modulating eNOS gene expression using small interfering RNAs (siRNAs) represents a viable strategy for antitumor therapy. siRNAs are highly specific to the target gene, thus reducing off-target effects. Given the widespread distribution of endothelium and the crucial physiological role of eNOS, localized delivery of nucleic acid to the affected area is essential. Therefore, the development of an efficient eNOS-siRNA delivery carrier capable of controlled release is imperative for targeting specific vascular regions, particularly those associated with tumor vascular growth. Thus, this study aims to utilize ultrasound-mediated microbubble destruction (UMMD) technology with cationic microbubbles loaded with eNOS-siRNA to enhance transfection efficiency and improve siRNA delivery, thereby preventing sprouting angiogenesis. The efficiency of eNOS-siRNA transfection facilitated by UMMD was assessed using bEnd.3 cells. Synthesis of nitric oxide and eNOS protein expression were also evaluated. The silencing of eNOS gene in a model of angiogenesis was assayed using the rat aortic ring assay. The results showed that from 6 to 24 h, the transfection of fluorescent siRNA with UMMD was twice as high as that of lipofection. Moreover, transfection of eNOS-siRNA with UMMD enhanced the knockdown level (65.40 ± 4.50%) compared to lipofectamine (40 ± 1.70%). Silencing of eNOS gene with UMMD required less amount of eNOS-siRNA (42 ng) to decrease the level of eNOS protein expression (52.30 ± 0.08%) to the same extent as 79 ng of eNOS-siRNA using lipofectamine (56.30 ± 0.10%). NO production assisted by UMMD was reduced by 81% compared to 67% reduction transfecting with lipofectamine. This diminished NO production led to higher attenuation of aortic ring outgrowth. Three-fold reduction compared to lipofectamine transfection. In conclusion, we propose the combination of eNOS-siRNA and UMMD as an efficient, safe, non-viral nucleic acid transfection strategy for inhibition of tumor progression.

MR2-Net: Retinal OCTA Image Stitching via Multi-Scale Representation Learning and Dynamic Location Guidance.

Optical coherence tomography angiography (OCTA) plays a crucial role in quantifying and analyzing retinal vascular diseases. However, the limited field of view (FOV) inherent in most commercial OCTA imaging systems poses a significant challenge for clinicians, restricting the possibility to analyze larger retinal regions of high resolution. Automatic stitching of OCTA scans in adjacent regions may provide a promising solution to extend the region of interest. However, commonly-used stitching algorithms face difficulties in achieving effective alignment due to noise, artifacts and dense vasculature present in OCTA images. To address these challenges, we propose a novel retinal OCTA image stitching network, named MR2-Net, which integrates multi-scale representation learning and dynamic location guidance. In the first stage, an image registration network with a progressive multi-resolution feature fusion is proposed to derive deep semantic information effectively. Additionally, we introduce a dynamic guidance strategy to locate the foveal avascular zone (FAZ) and constrain registration errors in overlapping vascular regions. In the second stage, an image fusion network based on multiple mask constraints and adjacent image aggregation (AIA) strategies is developed to further eliminate the artifacts in the overlapping areas of stitched images, thereby achieving precise vessel alignment. To validate the effectiveness of our method, we conduct a series of experiments on two delicately constructed datasets, i.e., OPTOVUE-OCTA and SVision-OCTA. Experimental results demonstrate that our method outperforms other image stitching methods and effectively generates high-quality wide-field OCTA images, achieving a structural similarity index (SSIM) score of 0.8264 and 0.8014 on the two datasets, respectively.

Central stress pathways in the development of cardiovascular disease.

Mental stress is of essential consideration when assessing cardiovascular pathophysiology in all patient populations. Substantial evidence indicates associations among stress, cardiovascular disease and aberrant brain-body communication. However, our understanding of the flow of stress information in humans, is limited, despite the crucial insights this area may offer into future therapeutic targets for clinical intervention. Key terms including mental stress, cardiovascular disease and central control, were searched in PubMed, ScienceDirect and Scopus databases. Articles indicative of heart rate and blood pressure regulation, or central control of cardiovascular disease through direct neural innervation of the cardiac, splanchnic and vascular regions were included. Focus on human neuroimaging research and the flow of stress information is described, before brain-body connectivity, via pre-motor brainstem intermediates is discussed. Lastly, we review current understandings of pathophysiological stress and cardiovascular disease aetiology. Structural and functional changes to corticolimbic circuitry encode stress information, integrated by the hypothalamus and amygdala. Pre-autonomic brain-body relays to brainstem and spinal cord nuclei establish dysautonomia and lead to alterations in baroreflex functioning, firing of the sympathetic fibres, cellular reuptake of norepinephrine and withdrawal of the parasympathetic reflex. The combined result is profoundly adrenergic and increases the likelihood of cardiac myopathy, arrhythmogenesis, coronary ischaemia, hypertension and the overall risk of future sudden stress-induced heart failure. There is undeniable support that mental stress contributes to the development of cardiovascular disease. The emerging accumulation of large-scale multimodal neuroimaging data analytics to assess this relationship promises exciting novel therapeutic targets for future cardiovascular disease detection and prevention.

Osobennosti tserebral'nogo krovoobrashcheniya studentov-pervokursnikov severnogo regiona

Relevance. Intense psycho-emotional and intellectual loads during the period of higher education, combined with climatic and environmental pressure, living in the northern regions, cause enormous stress for the emerging organism and can lead to violations of the functional state of the organism as a whole and cerebral hemodynamics in particular. In this regard, early identification of students with risk factors of circulatory system dysfunction for timely assistance and correction of their lifestyle is relevant. The purpose of the study was to analyze the features of cerebral circulation of first-year students of the northern region. Materials and Methods. Within the framework of the pilot study, first-year students (n = 30; 13 girls and 17 boys, average age 18 ± 0.6 years) of Surgut State Pedagogical University living in the territory equated to the conditions of the Far North took part. Indicators of cerebral circulation of the examined patients were diagnosed using the rheographic complex «Reo-Spectrum» (LLC «Neurosoft», Ivanovo) in four standard leads: front-mastoid (FM) on the left and right, and occipito-mastoid (OM) on the left and right. The diagnosis was carried out in accordance with bioethical norms with the voluntary written consent to conduct the study. Results and Discussion. In the course of the study, it was found that rheoencephalography indicators in the majority of the examined young men reveal insufficient blood filling in all the diagnosed arterial basins of the brain. At the same time, the tone of the arteries of different calibers correspondes to the normative indicators. Cerebral blood flow in them is provided mainly by increasing the tone of arterioles. An adequate blood outflow was diagnosed against the background of normal tone of venous vessels In young men. The tone of small vessels of girls was increased in all brain leads, in the carotid artery basin there was an increase in volumetric blood filling of brain vessels against the background of increased tone of large vessels, which can be considered as a regulatory mechanism for normalizing reduced blood filling of the corresponding vascular region. The outflow of blood from arterioles and vein tone was increased only on the left. Conclusion. To identify the peculiarities of cerebral circulation of first-year students of the northern region, it is necessary further to study the hemodynamic mechanisms of regulation of vascular tone, as well as the relationship with central circulation.