Arterial pulsation dependence of perivascular cerebrospinal fluid flow measured by dynamic diffusion tensor imaging in the human brain.

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17-28 years; seven men, one woman) underwent dynDTIlow-b using a 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7 % and 4.94 %, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5 % of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of apparent diffusivity in pCSF was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

An extended phase graph-based framework for DANTE-SPACE simulations including physiological, temporal, and spatial variations.

PURPOSE: The delay alternating with nutation for tailored excitation (DANTE)-sampling perfection with application-optimized contrasts (SPACE) sequence facilitates 3D intracranial vessel wall imaging with simultaneous suppression of blood and CSF. However, the achieved image contrast depends closely on the selected sequence parameters, and the clinical use of the sequence is limited in vivo by observed signal variations in the vessel wall, CSF, and blood. This paper introduces a comprehensive DANTE-SPACE simulation framework, with the aim of providing a better understanding of the underlying contrast mechanisms and facilitating improved parameter selection and contrast optimization. METHODS: An extended phase graph formalism was developed for efficient spin ensemble simulation of the DANTE-SPACE sequence. Physiological processes such as pulsatile flow velocity variation, varying flow directions, intravoxel velocity variation, diffusion, and B 1 + $$ {\mathrm{B}}_1^{+} $$ effects were included in the framework to represent the mechanisms behind the achieved signal levels accurately. RESULTS: Intravoxel velocity variation improved temporal stability and robustness against small velocity changes. Time-varying pulsatile velocity variation affected CSF simulations, introducing periods of near-zero velocity and partial rephasing. Inclusion of diffusion effects was found to substantially reduce the CSF signal. Blood flow trajectory variations had minor effects, but B 1 + $$ {\mathrm{B}}_1^{+} $$ differences along the trajectory reduced DANTE efficiency in low- B 1 + $$ {\mathrm{B}}_1^{+} $$ areas. Introducing low-velocity pulsatility of both CSF and vessel wall helped explain the in vivo observed signal heterogeneity in both tissue types. CONCLUSION: The presented simulation framework facilitates a more comprehensive optimization of DANTE-SPACE sequence parameters. Furthermore, the simulation framework helps to explain observed contrasts in acquired data.

Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

Pulsative venous return from the branchial vessels to the heart of the bivalve Mytilus galloprovincialis supports the constant-volume mechanism.

In bivalves and gastropods, ventricle contraction causes a negative pressure in the auricles and increases venous return from the afferent oblique vein (AOV): the constant-volume (CV) mechanism. The flow in the AOV should be a pulsative flow synchronized with the ventricular contraction. The flow in the heart and adjacent vessels of Mytilus galloprovincialis were measured by magnetic resonance imaging to confirm this hypothesis. Under a regular heartbeat, pulsative flows in the AOV and branchial vessels (BVs) were almost completely synchronized with the flow in the aorta, while filling of the ventricle was in the opposite phase. Flows in the BVs were directed to the posterior direction, and a pair of BVs in the gill axes (the efferent BVs) were connected to the AOV. Based on the images of the whole pathway of the AOV in an oblique slice, we confirmed that haemolymph flow was evoked from the efferent BVs and flow into the ventricle via the auricle was completed in a single heartbeat. Therefore, the walls of the AOV and BVs could resist negative transmural pressure caused by the ventricular contraction. In conclusion, the auricle, the AOV and the BVs, including the gill filaments, act as a suction pump. The pulsative venous return is driven by the negative pressure of the AOV as in the CV mechanism, and the negative pressure in the efferent BVs could draw haemolymph from the sinus via the gill and the afferent BVs. Therefore, Mytilus can start and stop its heartbeat as necessary.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Validation of machine-learning model for first-trimester prediction of pre-eclampsia using cohort from PREVAL study.

OBJECTIVE: Effective first-trimester screening for pre-eclampsia (PE) can be achieved using a competing-risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine-learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. METHODS: Previously, a machine-learning model derived with the use of a fully connected neural network for first-trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first-trimester PE validation (PREVAL) study, in which first-trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing-risks model. The performance of screening was assessed by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% screen-positive rate (SPR). These indices were compared with those derived from the application of the FMF competing-risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. RESULTS: The DRs at 10% SPR for early, preterm and all PE with the machine-learning model were 84.4% (95% CI, 67.2-94.7%), 77.8% (95% CI, 66.4-86.7%) and 55.7% (95% CI, 49.0-62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864-0.975), 0.913 (95% CI, 0.882-0.944) and 0.846 (95% CI, 0.820-0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA-PI and PlGF); inclusion of PAPP-A did not provide significant improvement in DR. The machine-learning model had similar performance to that achieved by the FMF competing-risks model (DR at 10% SPR, 82.7% (95% CI, 69.6-95.8%) for early PE, 72.7% (95% CI, 62.9-82.6%) for preterm PE and 55.1% (95% CI, 48.8-61.4%) for all PE) without requiring specific adaptations to the population. CONCLUSIONS: A machine-learning model for first-trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Pulsatile Femoral Vein Doppler Pattern is a Parameter of Venous Congestion in ICU Patients.

OBJECTIVES: The aim of this study was to evaluate if the presence of a pulsatile femoral vein pattern is an indicator of venous congestion in the intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Three medico-surgical university-affiliated ICUs. PARTICIPANTS: Adult patients who had an ultrasound evaluation at several time points during their ICU stay: at baseline (within 24 hours of admission to ICU), daily during their ICU stay, and within 24 hours before ICU discharge. INTERVENTIONS: At each time point, the hemodynamic, respiratory, and cardiac ultrasound parameters were recorded. The common femoral vein was studied with pulsed-wave Doppler at the level of the femoral trigonum, with high frequency (5-13 MHz) linear array vascular probe and venous vascular mode, in supine patients. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who underwent 400 ultrasound evaluations (3.7 ± 1 ultrasound evaluations per patient) during their ICU stay were included. Seventy-nine of 108 patients (73%) had a pulsatile femoral vein pattern at least at 1 time point. The multivariable mixed effects logistic regression model demonstrated an association among pulsatile femoral vein pattern, body mass index (OR: 0.91[95% CI 0.85-0.96], p = 0.002), inferior vena cava mean diameter (OR: 2.35 [95% CI 1.18-4.66], p = 0.014), portal vein pulsatility (OR: 2.3 [95% CI 1.2-4.4], p = 0.012), and congestive renal vein flow pattern (OR: 4.02 [95% CI 2.01-8.03], p < 0.001). The results were confirmed by principal component analysis. CONCLUSION: In the ICU, a pulsatile femoral vein pattern is associated with parameters of venous congestion, independently of the patient's volume status, and ventilatory treatment. These results suggest the femoral vein Doppler pulsatility as a parameter of congestion in ICU patients.

Evaluation of Automated Finger Compression for Capillary Refill Time Measurement in Pediatrics.

OBJECTIVES: Early shock reversal is crucial to improve patient outcomes. Capillary refill time (CRT) is clinically important to identify and monitor shock in children but has issues with inconsistency. To minimize inconsistency, we evaluated a CRT monitoring system using an automated compression device. Our objective was to determine proper compression pressure in children. METHODS: Clinician force for CRT was collected during manual CRT measurement as a reference for automated compression in a previous study (12.9 N, 95% confidence interval, 12.5-13.4; n = 454). An automated compression device with a soft inflation bladder was fitted with a force sensor. We evaluated the effectiveness of the automated pressure to eliminate pulsatile blood flow from the distal phalange. Median and variance of CRT analysis at each pressure was compared. RESULTS: A comparison of pressures at 300 to 500 mm Hg on a simulated finger yielded a force of 5 to 10 N, and these pressures were subsequently used for automated compression for CRT. Automated compression was tested in 44 subjects (median age, 33 months; interquartile range [IQR], 14-56 months). At interim analysis of 17 subjects, there was significant difference in the waveform with residual pulsatile blood flow (9/50: 18% at 300 mm Hg, 5/50:10% at 400 mm Hg, 0/51: 0% at 500 mm Hg, P = 0.008). With subsequent enrollment of 27 subjects at 400 and 500 mm Hg, none had residual pulsatile blood flow. There was no difference in the CRT: median 1.8 (IQR, 1.06-2.875) in 400 mm Hg vs median 1.87 (IQR, 1.25-2.8325) in 500 mm Hg, P = 0.81. The variance of CRT was significantly larger in 400 mm Hg: 2.99 in 400 mm Hg vs. 1.35 in 500 mm Hg, P = 0.02, Levene's test. Intraclass correlation coefficient for automated CRT was 0.56 at 400 mm Hg and 0.78 at 500 mm Hg. CONCLUSIONS: Using clinician CRT measurement data, we determined either 400 or 500 mm Hg is an appropriate pressure for automated CRT, although 500 mm Hg demonstrates superior consistency.

A new Doppler index, cerebro-placental-uterine ratio, and fetal cardiac parameters in early onset preeclampsia.

OBJECTIVE: Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. STUDY DESIGN: Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. RESULTS: The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CONCLUSION: CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.

[Fluid-solid coupling model and analysis on pulse wave propagation properties of iliac artery].

In this work, we investigated the influence of the bifurcation geometry of the iliac artery on the propagation properties of the pulse wave, and applied software to establish the straight bifurcation and curved bifurcation bi-directional fluid-solid coupling finite element analysis models based on the iliac artery, and compared and analyzed the influence of the bifurcation angle of the blood vessel on the propagation characteristics of the pulse wave. It was found that the bifurcation geometry had a significant effect on the pulse wave propagation in the iliac arteries, and the pressure and velocity pulse wave amplitudes predicted by these two models had a good agreement with that before the vessel bifurcation in a cardiac cycle. The curvilinear bifurcation model predicted the pulse wave amplitude to be lower and the pressure drop to be smaller after the bifurcation, which was more in line with the actual situation of the human body. In addition, the bifurcation point is accompanied by the stress concentration phenomenon in the vessel wall, and there is a transient increase in the velocity pulse waveform amplitude, which was consistent with the fact that the bifurcation site is prone to phenomena such as arterial stenosis and hardening. The preliminary results of this paper will provide some reference for the use of pulse waveforms in the diagnosis of arterial diseases.

Continuous versus Pulsatile Flow in 24-Hour Vascularized Composite Allograft Machine Perfusion in Swine: A Pilot Study.

INTRODUCTION: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. METHODS: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. RESULTS: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. CONCLUSIONS: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.

ASPRE trial: effects of aspirin on mean arterial blood pressure and uterine artery pulsatility index trajectories in pregnancy.

OBJECTIVES: The mechanism by which aspirin prevents pre-eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. We aimed to investigate the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI) using repeated measures from women at increased risk of preterm pre-eclampsia. METHODS: This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Pre-eclampsia Prevention (ASPRE) trial using repeated measures of MAP and UtA-PI. In the trial, 1620 women at increased risk of preterm pre-eclampsia were identified using the Fetal Medicine Foundation algorithm at 11 + 0 to 13 + 6 weeks, of whom 798 were randomly assigned to receive 150 mg/day aspirin and 822 were assigned to receive placebo daily from 11-14 weeks to 36 weeks of gestation or delivery, whichever came first. MAP and UtA-PI were measured at baseline and follow-up visits at 19-24, 32-34 and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effects of aspirin on MAP and UtA-PI trajectories over time. RESULTS: Among 798 participants in the aspirin group and 822 in the placebo group, there were 5951 MAP and 5942 UtA-PI measurements. Trajectories of raw and multiples of the median (MoM) values of MAP did not differ significantly between the two groups (MAP MoM analysis: P-value for treatment by gestational age interaction, 0.340). In contrast, trajectories of raw and MoM values of UtA-PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation (UtA-PI MoM analysis: P-value for treatment by gestational age interaction, 0.006). CONCLUSIONS: In women at increased risk of preterm pre-eclampsia, 150 mg/day aspirin initiated in the first trimester does not affect MAP but is associated with a significant decrease in mean UtA-PI, particularly before 20 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A novel pulsatile blood pump design for cardiothoracic surgery: Proof-of-concept in a mock circulation.

BACKGROUND: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation. METHODS: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically. RESULTS: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. CONCLUSIONS: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion.

A Universal Device to Convert a Continuous Flow Assist Device to a Pulsatile Flow Device to Simulate Normal Blood Flow and Pressure Patterns.

BACKGROUND: Continuous follow assist devices (CFAD) are the most commonly used mechanical circulatory support devices. Compared to Pulsatile flow assist devices (PFAD), CFADs deliver a non-physiologic type of flow, which might contribute to complications related to lack of pulsatility in these devices. Moreover, lack of pulsatility complicates the clinical management of these patients who often present with good perfusion but with no palpable pulse and none or a negligible pulse pressure on blood pressure measurement. METHODS AND RESULTS: Presented here is a concept of a universal converter device that can be added inline other CFADs to convert the flow from continuous to pulsatile, simulating a normal flow and pressure pattern. After initial implantation and stabilization with a CFAD, adding this converter might potentially provide the benefits of pulsatile physiologic flow. The device is made of 2 components connected in parallel, working in tandem in user determined cycles. The continuous flow through a specifically positioned openings create a smooth conversion to a pulsatile flow. This device can convert a continuous flow to a physiologic pulsatile flow to achieve a native-like flow pattern and potentially prevent some CFAD complications. CONCLUSION: This paper presents the concept of pulsatility generation and simulation for other assist devices. Such a device can be a universal add-on or a supplemental option for CFADs.

Autonomic arousals contribute to brain fluid pulsations during sleep.

During sleep, slow waves of neuro-electrical activity engulf the human brain and aid in the consolidation of memories. Recent research suggests that these slow waves may also promote brain health by facilitating the removal of metabolic waste, possibly by orchestrating the pulsatile flow of cerebrospinal fluid (CSF) through local neural control over vascular tone. To investigate the role of slow waves in the generation of CSF pulsations, we analyzed functional MRI data obtained across the full sleep-wake cycle and during a waking respiratory task. This revealed a novel generating mechanism that relies on the autonomic regulation of cerebral vascular tone without requiring slow electrocortical activity or even sleep. Therefore, the role of CSF pulsations in brain waste clearance may, in part, depend on proper autoregulatory control of cerebral blood flow.

Cerebrovascular activity is a major factor in the cerebrospinal fluid flow dynamics.

Cerebrospinal fluid (CSF) provides physical protection to the central nervous system as well as an essential homeostatic environment for the normal functioning of neurons. Additionally, it has been proposed that the pulsatile movement of CSF may assist in glymphatic clearance of brain metabolic waste products implicated in neurodegeneration. In awake humans, CSF flow dynamics are thought to be driven primarily by cerebral blood volume fluctuations resulting from a number of mechanisms, including a passive vascular response to blood pressure variations associated with cardiac and respiratory cycles. Recent research has shown that mechanisms that rely on the action of vascular smooth muscle cells ("cerebrovascular activity") such as neuronal activity, changes in intravascular CO2, and autonomic activation from the brainstem, may lead to CSF pulsations as well. Nevertheless, the relative contribution of these mechanisms to CSF flow remains unclear. To investigate this further, we developed an MRI approach capable of disentangling and quantifying CSF flow components of different time scales associated with these mechanisms. This approach was evaluated on human control subjects (n = 12) performing intermittent voluntary deep inspirations, by determining peak flow velocities and displaced volumes between these mechanisms in the fourth ventricle. We found that peak flow velocities were similar between the different mechanisms, while displaced volumes per cycle were about a magnitude larger for deep inspirations. CSF flow velocity peaked at around 10.4 s (range 7.1-14.8 s, n = 12) following deep inspiration, consistent with known cerebrovascular activation delays for this autonomic challenge. These findings point to an important role of cerebrovascular activity in the genesis of CSF pulsations. Other regulatory triggers for cerebral blood flow such as autonomic arousal and orthostatic challenges may create major CSF pulsatile movement as well. Future quantitative comparison of these and possibly additional types of CSF pulsations with the proposed approach may help clarify the conditions that affect CSF flow dynamics.

The essential role of arterial pulse in venous return.

The close proximity of arteries and veins is a well-known anatomical finding documented in the extremities of all vertebrates. However, the physiological consequences of this arrangement are rarely given proper consideration nor are they covered in the textbook list of mechanisms that aid blood flow. We hypothesized that arterial pressure pulsations can significantly increase blood flow in the adjacent valve-containing vein segments. To demonstrate the existence of this mechanism, 10- to 15-cm sections of the bovine forelimb neurovascular bundle were isolated. The proximal and distal ends of the median artery and adjacent veins were cannulated, their tributaries were tied off, and the dissected bundle was then inserted into an airtight enclosure to mimic in vivo encasement by surrounding muscle. Pulsatile pressure was subsequently applied to the arterial segment while recording venous flow. At pressure settings mimicking physiological scenarios, arterial pulsations caused a highly significant increase in venous return. The amplitude of this effect was dependent on the arterial pulsation rate, stroke volume, and pressure gradient across the vein segment.

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

Midgestation cardiovascular phenotype in women who develop gestational diabetes and hypertensive disorders of pregnancy: comparative study.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests. RESULTS: The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain. CONCLUSIONS: In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler at 19-23 weeks' gestation in pregnancies that deliver small-for-gestational-age neonates.

OBJECTIVES: First, to explore hemodynamic differences between pregnancies delivering a small-for-gestational-age (SGA) neonate in the absence of hypertensive disorders and those that develop pre-eclampsia (PE) or gestational hypertension (GH), by comparing the ophthalmic artery peak systolic velocity (PSV) ratio and first (PSV1) and second (PSV2) PSV at 19-23 weeks' gestation, and second, to compare these pregnancies for markers of placental perfusion and function. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for assessment of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, PSV1, PSV2, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). The values of PSV ratio, PSV1, PSV2, MAP, UtA-PI and PlGF were converted to multiples of the median (MoM) or deltas. Mean MoMs or deltas of these biomarkers in the SGA, PE and GH groups were compared with those in the unaffected group. The definition of SGA was birth weight below the 10th percentile in the absence of PE or GH. RESULTS: The study population of 5214 pregnancies contained 4375 (83.9%) that were unaffected by SGA, PE or GH, 563 (10.8%) complicated by SGA, 157 (3.0%) with PE and 119 (2.3%) with GH. There were three main findings of the study. First, in the SGA, PE and GH groups, compared with unaffected pregnancies, the PSV ratio delta, PSV2 MoM, MAP MoM and UtA-PI MoM were increased and PlGF MoM was decreased; however, the magnitude of most changes was smaller in the SGA group than in PE and GH groups. Second, in the PE and GH groups, but not in the SGA group, PSV1 MoM was increased. Third, in general, in the pathological pregnancies, the magnitude of deviation of biomarkers from unaffected pregnancies was greater for those delivering at < 37 than at ≥ 37 weeks' gestation. CONCLUSION: In mid-gestation, pregnancies that subsequently develop hypertensive disorders and those delivering a SGA neonate, compared with unaffected pregnancies, have abnormal uteroplacental measurements and increased maternal ophthalmic artery PSV ratio. These data suggest similar pathophysiology in the two conditions, with evidence of placental dysfunction and increased peripheral vascular resistance, but the magnitude of abnormalities is greater in hypertensive disorders. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.