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Modern functional imaging techniques of the brain measure local hemodynamic responses evoked by neuronal activity. Capillary pericytes recently were suggested to mediate neurovascular coupling in brain slices, but their role in vivo remains unexplored. We used two-photon microscopy to study in real time pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized mice, as well as in brain slices. The thromboxane A₂ analog, 9,11-dideoxy-9α, 11α-methanoepoxy Prostaglandin F2α (U46619), induced constrictions in the vicinity of pericytes in a fraction of capillaries, whereas others dilated. The changes in vessel diameter resulted in changes in capillary red blood cell (RBC) flow. In contrast, during brief epochs of seizure activity elicited by local administration of the GABA A receptor antagonist, bicuculline, capillary RBC flow increased without pericyte-induced capillary diameter changes. Precapillary arterioles were the smallest vessels to dilate, together with penetrating and pial arterioles. Our results provide in vivo evidence that pericytes can modulate capillary blood flow in the brain, which may be important under pathological conditions. However, our data suggest that precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity.

Summary Background For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. Methods TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov , number NCT01425307. Findings Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10−16 ) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). Interpretation For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. Funding National Heart, Lung, and Blood Institute, National Institutes of Health.

Image velocimetry has proven to be a promising technique for monitoring river flows using remotely operated platforms such as Unmanned Aerial Systems (UAS). However, the application of various image velocimetry algorithms has not been extensively assessed. Therefore, a sensitivity analysis has been conducted on five different image velocimetry algorithms including Large Scale Particle Image Velocimetry (LSPIV), Large-Scale Particle Tracking Velocimetry (LSPTV), Kanade–Lucas Tomasi Image Velocimetry (KLT-IV or KLT), Optical Tracking Velocimetry (OTV) and Surface Structure Image Velocimetry (SSIV), during low river flow conditions (average surface velocities of 0.12–0.14 m s − 1 , Q60) on the River Kolubara, Central Serbia. A DJI Phantom 4 Pro UAS was used to collect two 30-second videos of the surface flow. Artificial seeding material was distributed homogeneously across the rivers surface, to enhance the conditions for image velocimetry techniques. The sensitivity analysis was performed on comparable parameters between the different algorithms, including the particle identification area parameters (such as Interrogation Area (LSPIV, LSPTV and SSIV), Block Size (KLT-IV) and Trajectory Length (OTV)) and the feature extraction rate. Results highlighted that KLT and SSIV were sensitive to changing the feature extraction rate; however, changing the particle identification area did not affect the surface velocity results significantly. OTV and LSPTV, on the other hand, highlighted that changing the particle identification area presented higher variability in the results, while changing the feature extraction rate did not affect the surface velocity outputs. LSPIV proved to be sensitive to changing both the feature extraction rate and the particle identification area. This analysis has led to the conclusions that for surface velocities of approximately 0.12 m s − 1 image velocimetry techniques can provide results comparable to traditional techniques such as ADCPs. However, LSPIV, LSPTV and OTV require additional effort for calibration and selecting the appropriate parameters when compared to KLT-IV and SSIV. Despite the varying levels of sensitivity of each algorithm to changing parameters, all configuration image velocimetry algorithms provided results that were within 0.05 m s − 1 of the ADCP measurements, on average.

The vasculature undergoes changes in diameter, permeability and blood flow in response to specific stimuli. The dynamics and interdependence of these responses in different vessels are largely unknown. Here we report a non-invasive technique to study dynamic events in different vessel categories by multi-photon microscopy and an image analysis tool, RVDM (relative velocity, direction, and morphology) allowing the identification of vessel categories by their red blood cell (RBC) parameters. Moreover, Claudin5 promoter-driven green fluorescent protein (GFP) expression is used to distinguish capillary subtypes. Intradermal injection of vascular endothelial growth factor A (VEGFA) is shown to induce leakage of circulating dextran, with vessel-type-dependent kinetics, from capillaries and venules devoid of GFP expression. VEGFA-induced leakage in capillaries coincides with vessel dilation and reduced flow velocity. Thus, intravital imaging of non-invasive stimulation combined with RVDM analysis allows for recording and quantification of very rapid events in the vasculature.

Volumetric imaging of a mouse brain in vivo with one-photon and two-photon ultralong anti-diffracting (UAD) beam illumination was performed. The three-dimensional (3D) structure of blood vessels in the mouse brain were mapped to a two-dimensional (2D) image. The speed of volumetric imaging was significantly improved due to the long focal length of the UAD beam. Comparing one-photon and two-photon UAD beam volumetric imaging, we found that the imaging depth of two-photon volumetric imaging (80 μm) is better than that of one-photon volumetric imaging (60 μm), and the signal-to-background ratio (SBR) of two-photon volumetric imaging is two times that of one-photon volumetric imaging. Therefore, we used two-photon UAD volumetric imaging to perform dynamic volumetric imaging of mouse brain blood vessels in vivo, and obtained the blood flow velocity.

Aortic Dissection (AD) is a complex pathology that affects the aorta. Diagnosis, management and treatment remain a challenge as it is a highly patient-specific pathology and there is still a limited understanding of the fluid-mechanics phenomena underlying clinical outcomes. Although in vitro models can allow the accurate study of AD flow fields in physical phantoms, they are currently scarce and almost exclusively rely on over simplifying assumptions. In this work, we present the first experimental study of a patient-specific case of AD. An anatomically correct phantom was produced and combined with a state-of-the-art in vitro platform, informed by clinical data, employed to accurately reproduce personalised conditions. The complex AD haemodynamics reproduced by the platform was characterised by flow rate and pressure acquisitions as well as Particle Image Velocimetry (PIV) derived velocity fields. Clinically relevant haemodynamic indices, that can be correlated with AD prognosis – such as velocity, shear rate, turbulent kinetic energy distributions – were extracted in two regions of interest in the aortic domain. The acquired data highlighted the complex nature of the flow (e.g. recirculation regions, low shear rate in the false lumen) and was in very good agreement with the available clinical data and the CFD results of a study conducted alongside, demonstrating the accuracy of the findings. These results demonstrate that the described platform constitutes a powerful, unique tool to reproduce in vitro personalised haemodynamic conditions, which can be used to support the evaluation of surgical procedures, medical devices testing and to validate state-of-the-art numerical models.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 ‘4D Flow CMR Consensus Statement’. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Purpose It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. Methods Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin ( n  = 100) or non-statin users ( n  = 112). Results MCAv and cerebrovascular conductance were significantly higher in statin users ( p  = 0.047; p  = 0.04), and pulsatility index (PI) was significantly lower in statin users ( p  < 0.01). An interaction effect between statin use and sex was present for PI ( p  = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. Conclusion In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer’s disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.

ObjectiveWe sought to evaluate prognostic markers of clinical outcome in asymptomatic patients with moderate to severe aortic stenosis (AS).DesignProspective follow-up of asymptomatic patients with moderate to severe AS. The patients underwent clinical and Doppler echocardiographic evaluation.SettingDepartment of Cardiology.Patients163 patients with moderate to severe AS (aortic valve area ≤0.6 cm2/m2).Main outcome measuresRisk stratification. Predefined endpoints for assessing the outcome were the occurrence during follow-up of symptoms, aortic valve replacement or death.ResultsDuring follow-up (mean, 20 (19) months), 11 patients developed symptoms but were not operated on, 57 required aortic valve replacement and six patients died. In multivariable Cox regression analysis, four parameters that were associated with the outcome were identified: peak aortic jet velocity, left ventricular systolic (LV) longitudinal deformation, valvulo-arterial impedance and indexed left atrial area. Using receiver−operator characteristic curve analysis, a peak aortic jet velocity ≥4.4 m/s, a LV longitudinal myocardial deformation ≤15.9%, a valvular-arterial impedance ≥4.9 mm Hg/ml per m2 and an indexed left atrial area ≥12.2 cm2/m2 were identified as the best cut-off values to be associated with events.ConclusionsIn asymptomatic patients with moderate to severe AS, measurements that integrate the ventricular, vascular and valvular components of the disease improve risk stratification.

In vitro aortic flow simulators allow studying hemodynamics with a wider range of flow visualization techniques compared to in vivo medical imaging and without the limitations of invasive examinations. This work aims to develop an experimental bench to emulate the pulsatile circulation in a realistic aortic phantom. To mimic the blood shear thinning behavior, a non-Newtonian aqueous solution is prepared with glycerin and xanthan gum polymer. The flow is compared to a reference flow of Newtonian fluid. Particle image velocimetry is carried out to visualize 2D velocity fields in a phantom section. The experimental loop accurately recreates flowrates and pressure conditions and preserves the shear-thinning properties of the non-Newtonian fluid. Velocity profiles, shear rate, and shear stress distribution maps show that the Newtonian fluid tends to dampen the observed velocities. Preferential asymmetrical flow paths are observed in a diameter narrowing region and amplified in the non-Newtonian case. Wall shear stresses are about twice higher in the non-Newtonian case. This study shows new insights on flow patterns, velocity and shear stress distributions compared to rigid and simplified geometry aorta phantom with Newtonian fluid flows studies. The use of a non-Newtonian blood analog shows clear differences in flows compared to the Newtonian one in this compliant patient-specific geometry. The development of this aortic simulator is a promising tool to better analyze and understand aortic hemodynamics and to aid in clinical decision-making.