Magnesium sulfate improves blood flow of uterine, umbilical, and fetal middle cerebral arteries in women with severe preeclampsia at 30-34 gestational weeks.

OBJECTIVES: Magnesium sulfate (MgSO4) is one of the most commonly used agents for the treatment and prophylaxis of eclampsia in patients with severe preeclampsia. However, there is no international consensus regarding the optimal gestational age for MgSO4 treatment. The aim of this study was to assess the effect of MgSO4 on uterine (UtA), umbilical, and fetal middle cerebral arteries (MCA) by calculating the SD ratio (S/D), resistance index (RI), and pulsatility index (PI) at different gestational weeks. METHODS: In total, 66 pregnant women as participants with severe preeclampsia were divided into two groups based on gestational age: Group 1 (n = 28, 26-30 weeks) and Group 2 (n = 38, 30-34 weeks). Color Doppler (Philip HD11) measurements were taken and compared before and after the MgSO4 loading dose. RESULTS: Within-group analysis revealed significant differences in RI-UtA, PI-UtA, and S/D in UtA before and after MgSO4 administration in Group 1. Furthermore, the RI-UA and RI-MCA decreased statistically significantly after MgSO4 treatment, whereas the pulsatility index and S/D did not change in either the umbilical or middle cerebral arteries. After MgSO4 treatment, all Doppler parameters in the uterine and umbilical arteries in Group 2 showed significant changes when compared to before MgSO4 administration. CONCLUSION: MgSO4 can effectively improve umbilical and MCA blood flow at 30-34 gestational weeks but not at 26-30w. Meanwhile, using MgSO4 can improve uterine blood flow in severe preeclampsia, which may contribute to the management of reducing adverse events in pregnant women who have preeclampsia and fetal growth restriction.

Comparison of the Effect of Pump Flow Type (Pulsatile or Non-Pulsatile) on Postoperative Neurocognitive Functions in Coronary Artery Surgery.

INTRODUCTION: The effect of pump flow type on perfusion in coronary surgery using cardiopulmonary bypass (CPB) is discussed. We aimed to evaluate the effect of pump flow type on cognitive functions with neurocognitive function tests. METHODS: One hundred patients who underwent isolated coronary artery bypass surgery between November 2020 and July 2021 were divided into two equa groups. Groups were formed according to pump flow type pulsatile (Group 1) and non-pulsatile (Group 2). Clock drawing test (CDT) and standardized mini mental test (SMMT) were performed on the patients in both groups in the preoperative period, on the 1st preoperative day, and on the day before discharge. Neurocognitive effects were compared with all follow-up parameters. RESULTS: There was no difference between the groups in terms of demographic data and in terms of neurocognitive tests performed before the operation. SMMT on postoperative day 1 (Group I: 27.64 ± 1.05; Group II: 24.44 ± 1.64; P=0.001) and CDT (Group I: 5.4 ± 0.54; Group II: 4 .66 ± 0.52; P=0.001), and SMMT on the day before discharge (Group I: 27.92 ± 1.16; Group II: 24.66 ± 1.22; P=0.001) and CDT (Group I: 5 It was calculated as .66 ± 0.48; Group II: 5.44 ± 0.5; P=0.001). The duration of intensive care and hospitalization were higher in the non-pulsatile group. CONCLUSION: We think that the type of pump flow used in coronary artery bypass surgery using CPB is effective in terms of neurocognitive functions and that pulsatile flow makes positive contributions to this issue.

Endovascular Treatment of Flow-Limiting Iliofemoral Stenosis Improves Left Ventricular Diastolic Function in Patients With HFpEF by Reducing Aortic Pulsatile Load.

BACKGROUND: Recent research indicates that there is a high prevalence of heart failure with preserved ejection fraction in patients with peripheral artery disease. We hypothesized that endovascular treatment (EVT) of flow-limiting peripheral stenosis improves left ventricular (LV) diastolic function. METHODS: Thirty patients with symptomatic peripheral artery disease and heart failure with preserved ejection fraction according to Heart Failure Association-preserved ejection fraction score who were scheduled for EVT or angiography were investigated at baseline, the day after EVT (n=25) or angiography (control, n=5), and at 4 months follow-up. Peripheral hemodynamics were determined by the total peripheral resistance, common femoral artery flow, and ankle brachial index. Aortic function was measured by arterial compliance, augmentation index, and pulse wave velocity. Aortic pulsatile load was estimated as the characteristic impedance of the proximal aorta and the magnitude of wave reflection (reflection coefficient). LV mass index, LV mean wall thickness, and systolic and diastolic function were assessed using echocardiography. Patient-centered outcomes were treadmill walking distance and New York Heart Association class. RESULTS: After EVT, peripheral hemodynamics changed significantly with a decrease in total peripheral resistance and an increase in common femoral artery flow and ankle brachial index. Aortic function improved after EVT, with significantly reduced augmentation index and pulse wave velocity and increased compliance immediately and at follow-up, resulting in a reduction in aortic pulsatile load (characteristic impedance of the proximal aorta and reflection coefficient). Concurrently, LV diastolic function improved after EVT compared with control, acutely and at follow-up, with increased septal and lateral e´ velocities and decreased E/e´ and left atrial volume index. The LV mass index and LV mean wall thickness decreased at follow-up. The New York Heart Association class and treadmill walking distance improved post-EVT at follow-up. Augmentation index, pulse wave velocity, and arterial compliance were identified as independent contributors to E/e´. CONCLUSIONS: Endovascular treatment of flow-limiting iliofemoral stenosis reduces aortic pulsatile load and concurrently lowers total peripheral resistance. This beneficial effect is associated with an acute and sustained improvement of left ventricular diastolic function. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT02728479.

Coupled pulsatile vascular and paravascular fluid dynamics in the human brain.

BACKGROUND: Cardiac pulsation propels blood through the cerebrovascular network to maintain cerebral homeostasis. The cerebrovascular network is uniquely surrounded by paravascular cerebrospinal fluid (pCSF), which plays a crucial role in waste removal, and its flow is suspected to be driven by arterial pulsations. Despite its importance, the relationship between vascular and paravascular fluid dynamics throughout the cardiac cycle remains poorly understood in humans. METHODS: In this study, we developed a non-invasive neuroimaging approach to investigate the coupling between pulsatile vascular and pCSF dynamics within the subarachnoid space of the human brain. Resting-state functional MRI (fMRI) and dynamic diffusion-weighted imaging (dynDWI) were retrospectively cardiac-aligned to represent cerebral hemodynamics and pCSF motion, respectively. We measured the time between peaks (∆TTP) in d d ϕ f M R I and dynDWI waveforms and measured their coupling by calculating the waveforms correlation after peak alignment (correlation at aligned peaks). We compared the ∆TTP and correlation at aligned peaks between younger [mean age: 27.9 (3.3) years, n = 9] and older adults [mean age: 70.5 (6.6) years, n = 20], and assessed their reproducibility within subjects and across different imaging protocols. RESULTS: Hemodynamic changes consistently precede pCSF motion. ∆TTP was significantly shorter in younger adults compared to older adults (-0.015 vs. -0.069, p < 0.05). The correlation at aligned peaks were high and did not differ between younger and older adults (0.833 vs. 0.776, p = 0.153). The ∆TTP and correlation at aligned peaks were robust across fMRI protocols (∆TTP: -0.15 vs. -0.053, p = 0.239; correlation at aligned peaks: 0.813 vs. 0.812, p = 0.985) and demonstrated good to excellent within-subject reproducibility (∆TTP: intraclass correlation coefficient = 0.36; correlation at aligned peaks: intraclass correlation coefficient = 0.89). CONCLUSION: This study proposes a non-invasive technique to evaluate vascular and paravascular fluid dynamics. Our findings reveal a consistent and robust cardiac pulsation-driven coupling between cerebral hemodynamics and pCSF dynamics in both younger and older adults.

Numerical assessment of using various outlet boundary conditions on the hemodynamics of an idealized left coronary artery model.

Vascular diseases are greatly influenced by the hemodynamic parameters and the accuracy of determining these parameters depends on the use of correct boundary conditions. The present work carries out a two-way fluid-structure interaction (FSI) simulation to investigate the effects of outlet pressure boundary conditions on the hemodynamics through the left coronary artery bifurcation with moderate stenosis (50%) in the left anterior descending (LAD) branch. The Carreau viscosity model is employed to characterise the shear-thinning behaviour of blood. The results of the study reveal that the employment of zero pressure at the outlet boundaries significantly overestimates the values of hemodynamic variables like wall shear stress (WSS), and time-averaged wall shear stress (TAWSS) compared with human healthy and pulsatile pressure outlet conditions. However, the difference between these variables is marginally low for human healthy and pulsatile pressure outlets. The oscillatory shear index (OSI) remains the same across all scenarios, indicating independence from the outlet boundary condition. Furthermore, the magnitude of negative axial velocity and pressure drop across the plaque are found to be higher at the zero pressure outlet boundary condition.

Quantifying irregular pulsation of intracranial aneurysms using 4D-CTA.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20±0.01 vs 0.16±0.02, p=0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment.

On flow fluctuations in ruptured and unruptured intracranial aneurysms: resolved numerical study.

Flow fluctuations have emerged as a promising hemodynamic metric for understanding of hemodynamics in intracranial aneurysms. Several investigations have reported flow instabilities using numerical tools. In this study, the occurrence of flow fluctuations is investigated using either Newtonian or non-Newtonian fluid models in five patient-specific intracranial aneurysms using high-resolution lattice Boltzmann simulation methods. Flow instabilities are quantified by computing power spectral density, proper orthogonal decomposition, and fluctuating kinetic energy of velocity fluctuations. Our simulations reveal substantial flow instabilities in two of the ruptured aneurysms, where the pulsatile inflow through the neck leads to hydrodynamic instability, particularly around the rupture position, throughout the entire cardiac cycle. In other monitoring points, the flow instability is primarily observed during the deceleration phase; typically, the fluctuations begin just after peak systole, gradually decay, and the flow returns to its original, laminar pulsatile state during diastole. Additionally, we assess the rheological impact on flow dynamics. The disparity between Newtonian and non-Newtonian outcomes remains minimal in unruptured aneurysms, with less than a 5% difference in key metrics. However, in ruptured cases, adopting a non-Newtonian model yields a substantial increase in the fluctuations within the aneurysm sac, with up to a 30% higher fluctuating kinetic energy compared to the Newtonian model. The study highlights the importance of using appropriate high-resolution simulations and non-Newtonian models to capture flow fluctuation characteristics that may be critical for assessing aneurysm rupture risk.

The role of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in patients with pregnancy-induced hypertension.

OBJECTIVES: To examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH). STUDY DESIGN: This prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated. MAIN OUTCOME MEASURE: The role of CPUR in predicting CAPO in preeclampsia and gestational hypertension. RESULTS: The CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001). CONCLUSION: CPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH.

Perfusion and pulsatile pressure: their relationship with target organ damage in the African-PREDICT study.

BACKGROUND: Hypertension is the leading risk factor for subclinical target-organ damage (TOD) and cardiovascular disease (CVD). Little is known about the relationship between different pressure measures and subclinical TOD, especially in young populations. We compared the strength of associations of subclinical TOD markers with perfusion and pulsatile pressure in young adults. METHODS: A total of 1 187 young adults from the African-PREDICT study were included. Ambulatory mean arterial pressure (MAP) and pulse pressure (PP) was obtained. Markers of subclinical TOD were measured and included left ventricular mass index (LVMi), carotid intimamedia thickness (cIMT), carotidfemoral pulse wave velocity (cfPWV), central retinal arteriolar equivalent (CRAE) and albumin to creatinine ratio (ACR). RESULTS: Measures of sub-clinical TOD (cIMT, cfPWV and CRAE), associated stronger with perfusion pressure (all p < 0.001) than pulsatile pressure in unadjusted models. Stronger associations were found between cfPWV (adjusted R2 = 0.26), CRAE (adjusted R2 = 0.12) and perfusion pressure (all p ≤ 0.001) than pulsatile pressure independent of several non-modifiable and modifiable risk factors. CONCLUSIONS: In young, healthy adults, perfusion pressure is more strongly associated with subclinical TOD markers than pulsatile pressure. These findings contribute to the understanding of the development of early cardiovascular changes and may guide future intervention strategies.

Computing pulsatile blood flow of coronary artery under incomplete boundary conditions.

BACKGROUND: Accurate measurement of pulsatile blood flow in the coronary arteries enables coronary wave intensity analysis, which can serve as an indicator for assessing coronary artery physiology and myocardial viability. Computational fluid dynamics (CFD) methods integrating coronary angiography images and fractional flow reserve (FFR) offer a novel approach for computing mean coronary blood flow. However, previous methods neglect the inertial effect of blood flow, which may have great impact on pulsatile blood flow calculation. To improve the accuracy of pulsatile blood flow calculation, a novel CFD based method considering the inertia term is proposed. METHODS: A flow resistance model based on Pressure-Flow vs.Time curves is proposed to model the resistance of the epicardial artery. The parameters of the flow resistance model can be fitted from the simulated pulsating flow rates and pressure drops of a specific mode. Then, pulsating blood flow can be calculated by combining the incomplete pressure boundary conditions under pulsating conditions which are easily obtained in clinic. Through simulation experiments, the effectiveness of the proposed method is validated in idealized and reconstructed 3D model of coronary artery. The impacts of key parameters for generating the simulated pulsating flow rates and pressure drops on the accuracy of pulsatile blood flow calculation are also investigated. RESULTS: For the idealized model, the previously proposed Pressure-Flow model has a significant leading effect on the computed blood flow waveform in the moderate model, and this leading effect disappears with the increase of the degree of stenosis. The improved model proposed in this paper has no leading effect, the root mean square error (RMSE) of the proposed model is low (the left coronary mode:≤0.0160, the right coronary mode:≤0.0065) for all simulated models, and the RMSE decreases with an increase of stenosis. The RMSE is consistently small (≤0.0217) as the key parameters of the proposed method vary in a large range. It is verified in the reconstructed model that the proposed model significantly reduces the RMSE of patients with moderate stenosis (the Pressure-Flow model:≤0.0683, the Pressure-Flow vs.Time model:≤0.0297), and the obtained blood flow waveform has a higher coincidence with the simulated reference waveform. CONCLUSIONS: This paper confirms that ignoring the effect of inertia term can significantly affect the accuracy of calculating pulsatile blood flow in moderate stenosis lesions, and the new method proposed in this paper can significantly improves the accuracy of calculating pulsatile blood flow in moderate stenosis lesions. The proposed method provides a convenient clinical method for obtaining pressure-synchronized blood flow, which is expected to facilitate the application of waveform analysis in the diagnosis of coronary artery disease.

CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age.

BACKGROUND: Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF dynamics could play a role in the accumulation of toxic waste in the CNS, with implications for Alzheimer's disease and other proteinopathies. Therefore, approaches that enable quantitative and volumetric assessment of CSF flow velocities could be of value. In this study we demonstrate the feasibility of 4D flow MRI for simultaneous assessment of CSF dynamics throughout the ventricular system, and evaluate associations to arterial pulsatility, ventricular volumes, and age. METHODS: In a cognitively unimpaired cohort (N = 43; age 41-83 years), cardiac-resolved 4D flow MRI CSF velocities were obtained in the lateral ventricles (LV), foramens of Monro, third and fourth ventricles (V3 and V4), the cerebral aqueduct (CA) and the spinal canal (SC), using a velocity encoding (venc) of 5 cm/s. Cerebral blood flow pulsatility was also assessed with 4D flow (venc = 80 cm/s), and CSF volumes were obtained from T1- and T2-weighted MRI. Multiple linear regression was used to assess effects of age, ventricular volumes, and arterial pulsatility on CSF velocities. RESULTS: Cardiac-driven CSF dynamics were observed in all CSF spaces, with region-averaged velocity range and root-mean-square (RMS) velocity encompassing from very low in the LVs (RMS 0.25 ± 0.08; range 0.85 ± 0.28 mm/s) to relatively high in the CA (RMS 6.29 ± 2.87; range 18.6 ± 15.2 mm/s). In the regression models, CSF velocity was significantly related to age in 5/6 regions, to CSF space volume in 2/3 regions, and to arterial pulsatility in 3/6 regions. Group-averaged waveforms indicated distinct CSF flow propagation delays throughout CSF spaces, particularly between the SC and LVs. CONCLUSIONS: Our findings show that 4D flow MRI enables assessment of CSF dynamics throughout the ventricular system, and captures independent effects of age, CSF space morphology, and arterial pulsatility on CSF motion.

Decoding pulsatile patterns of cerebrospinal fluid dynamics through enhancing interpretability in machine learning.

Analyses of complex behaviors of Cerebrospinal Fluid (CSF) have become increasingly important in diseases diagnosis. The changes of the phase-contrast magnetic resonance imaging (PC-MRI) signal formed by the velocity of flowing CSF are represented as a set of velocity-encoded images or maps, which can be thought of as signal data in the context of medical imaging, enabling the evaluation of pulsatile patterns throughout a cardiac cycle. However, automatic segmentation of the CSF region in a PC-MRI image is challenging, and implementing an explained ML method using pulsatile data as a feature remains unexplored. This paper presents lightweight machine learning (ML) algorithms to perform CSF lumen segmentation in spinal, utilizing sets of velocity-encoded images or maps as a feature. The Dataset contains 57 PC-MRI slabs by 3T MRI scanner from control and idiopathic scoliosis participants are involved to collect data. The ML models are trained with 2176 time series images. Different cardiac periods image (frame) numbers of PC-MRIs are interpolated in the preprocessing step to align to features of equal size. The fivefold cross-validation procedure is used to estimate the success of the ML models. Additionally, the study focusses on enhancing the interpretability of the highest-accuracy eXtreme gradient boosting (XGB) model by applying the shapley additive explanations (SHAP) technique. The XGB algorithm presented its highest accuracy, with an average fivefold accuracy of 0.99% precision, 0.95% recall, and 0.97% F1 score. We evaluated the significance of each pulsatile feature's contribution to predictions, offering a more profound understanding of the model's behavior in distinguishing CSF lumen pixels with SHAP. Introducing a novel approach in the field, develop ML models offer comprehension into feature extraction and selection from PC-MRI pulsatile data. Moreover, the explained ML model offers novel and valuable insights to domain experts, contributing to an enhanced scholarly understanding of CSF dynamics.

Comparison of Change in the Pulsatility Index before and after Ventriculoperitoneal Shunt Surgery in Adult Patients with Hydrocephalus.

BACKGROUND AND AIM: In hydrocephalus patients, after ventriculoperitoneal (VP) shunt, decrease in pulsatility index (PI) correlates with decrease in ventricle size. Also, increase in PI is noted in obstructed or malfunctioning VP shunts. However, previous studies were either done in infants and children or included patients of all age groups. Our aim was to compare PI before and after successful VP shunt surgery in adult patients and also the trend of transcranial Doppler (TCD) parameters for 3 days after surgery. MATERIALS AND METHODS: A prospective, observational study was done in 20 adult patients undergoing VP shunt. Clinical features, vitals, Evans index, and TCD parameters were noted in the preoperative period. A computed tomography (CT) head was repeated 4-6 h after surgery, and the position of ventricular end of shunt was confirmed and Evans index was calculated. The vitals and TCD parameters were noted at same time and for the next 2 days. Repeated measures analysis of variance (ANOVA) and paired t-test were uses for statistical analysis. RESULTS: A total of 18 patients were included for statistical analysis. The mean preoperative PI was 1.19 ± 0.24 and the postoperative PI after surgery was 0.97 ± 0.17, 0.97 ± 0.23, and 0.94 ± 0.21 (P = 0.0039) on postoperative day (POD) 1 (POD1), POD2, and POD3, respectively. The mean preoperative value of Evans index was 0.37 ± 0.06 and there was statistically significant (P = < 0.001) reduction to 0.33 ± 0.07 after VP shunt surgery. The change in PI and change in Evans index were found to be positively correlated (r = 0.34 and P = 0.0013). CONCLUSIONS: The decrease in PI after VP shunt surgery correlates with decrease in ventricular size. Any increase in PI in the postoperative period should raise the suspicion of malfunctioning of VP shunt.

Impact of Pulsatile Machine Perfusion on Posttransplant Recovery in Asystole Donation: Organ Optimization and the Future of Renal Transplantation.

OBJECTIVES: With the increase in life expectancy and the aging of the population, chronic kidney disease has become increasingly prevalent in our environment. Kidney transplantation remains the gold standard treatment for end-stage renal disease, but the supply of renal grafts has not been able to keep pace with growing demand. Because of this rationale, organ selection criteria have been extended (expanded criteria donation), and alternative donation types, such as donation after circulatory death, have been evaluated. These approaches aim to increase the pool of potential donors, albeit with organs of potentially lower quality. Various forms of donations, including donation after circulatory death, have also undergone assessment. This approach aims to augment the pool of potential donors, notwithstanding the compromised quality of organs associated with such methods. Diverse strategies have been explored to enhance graft function, with one of the most promising being the utilization of pulsatile machine perfusion. MATERIALS AND METHODS: We conducted a retrospective analysis on 28 transplant recipients who met the inclusion criterion of sharing the same donor, wherein one organ was preserved by cold storage and the other by pulsatile machine perfusion. We performed statistical analysis on posttransplant recovery parameters throughout the patients' hospitalization, including admission and discharge phases. RESULTS: Statistically significant differences were noted in delayed graft function (P = .04), blood transfusions requirements, and Clavien-Dindo complications. Furthermore, an overall trend of improvement in discharge parameters and hospital stay was in favor of the pulsatile machine perfusion group. CONCLUSIONS: The use of pulsatile machine perfusion as a method of renal preservation results in graft optimization, leading to earlier recovery and fewer complications compared with cold storage in the context of donation after circulatory death.

Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly.

Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( v p ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and v p from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (ß = - 2.9; p = 0.006), basal ganglia (ß = - 2.3; p = 0.04), white matter (ß = - 2.6; p = 0.04), whole-brain (ß = - 2.7; p = 0.04) and borderline-related for cortex (ß = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.

Turbulent blood flow in a cerebral artery with an aneurysm.

Unruptured intracranial aneurysms are common in the general population, and many uncertainties remain when predicting rupture risks and treatment outcomes. One of the cutting-edge tools used to investigate this condition is computational fluid dynamics (CFD). However, CFD is not yet mature enough to guide the clinical management of this disease. In addition, recent studies have reported significant flow instabilities when refined numerical methods are used. Questions remain as to how to properly simulate and evaluate this flow, and whether these instabilities are really turbulence. The purpose of the present study is to evaluate the impact of the simulation setup on the results and investigate the occurrence of turbulence in a cerebral artery with an aneurysm. For this purpose, direct numerical simulations were performed with up to 200 cardiac cycles and with data sampling rates of up to 100,000 times per cardiac cycle. Through phase-averaging or triple decomposition, the contributions of turbulence and of laminar pulsatile waves to the velocity, pressure and wall shear stress fluctuations were distinguished. For example, the commonly used oscillatory shear index was found to be closely related to the laminar waves introduced at the inlet, rather than turbulence. The turbulence energy cascade was evaluated through energy spectrum estimates, revealing that, despite the low flow rates and Reynolds number, the flow is turbulent near the aneurysm. Phase-averaging was shown to be an approach that can help researchers better understand this flow, although the results are highly dependent on simulation setup and post-processing choices.

On the use of steady flow rates for approximating flow instabilities and vibrations in intracranial aneurysms.

Recent computational and experimental studies of intracranial aneurysms have revealed potential mechanisms of aneurysm bruits and murmurs, driven by flow instabilities rather than by stable pulsatile flow. Some of these studies have been conducted under the assumption of constant flow rate (steady flow); however the validity of this assumption has not been evaluated for high-frequency flow instability, or vibrations from fluid-structure interaction (FSI) simulations. We evaluated the time-averaged wall shear stress, flow instability and vibration amplitude of steady flow simulations, performed at both cycle-averaged and peak-systolic flow rates, and compared these to recent pulsatile FSI simulations. Wall shear stress fields of pulsatile flow (time-averaged and peak values) were well-approximated by the respective steady-flow FSI simulations, and the spatial distribution and frequency content of flow instability and vibrations were reasonably approximated by the steady flow simulations at peak-systolic flow rates. However, the level of flow instability and vibration was generally over-predicted by the steady flow simulations at peak-systolic flow rates as flow remained unstable for longer than in the pulsatile simulation, while no flow instability was detected for steady flow at cycle-averaged flow rates. Additionally, the amplitude of flow instability and vibration fluctuated considerably in the steady flow simulations, while the pulsatile simulations exhibited consistent vibration amplitudes (less than 10 % variation at peak systole between cycles). Finally, steady flow simulations at peak-systolic conditions required 2-3x more compute time than the pulsatile simulations for the same time duration. Therefore, we recommend using pulsatile flow simulations when investigating vibrations and flow instabilities.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

Simulation of coronary fractional flow reserve and whole-cycle flow based on optical coherence tomography in individual patients with coronary artery disease.

Computer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was - 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75-0.95) with sensitivity 0.79 (0.58-0.93) and specificity 0.96 (0.79-1.00). The positive predictive value was 0.95 (0.75-1.00) and the negative predictive value was 0.82 (0.63-0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses.