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Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

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ABSTRACT: We aimed to measure cerebral, splanchnic, and renal transit times and the associated blood volumes using contrast ultrasound. In healthy individuals, regional transit times were calculated from time-intensity curves generated as ultrasound contrast passed through the associated inflow and outflow vessels. These included the internal carotid artery and internal jugular vein (brain), the superior mesenteric artery and portal vein (intestines), and the renal artery and renal vein (kidney). An organ's blood volume relative to the stroke volume delivered to that organ with each cardiac cycle was calculated from the product of heart rate and transit time of contrast passage through the associated vascular bed. The fraction of systemic stroke volume received by each organ was calculated from the respective velocity-time integral and inflow vessel cross-sectional area and used to estimate absolute organ blood volume. The cohort consisted of 16 participants (age: 42 ± 13 years; 5 female) without known cerebrovascular, gastrointestinal, or renal disease. Cerebral, splanchnic, and renal transit times were obtained for 15, 14, and 8 individuals, respectively. Anatomic variability of the renal vessels confounded the acquisition of renal transit times. For all organs, transit times were reproducible and the associated blood volumes were generally comparable to reference values. Cerebral, gastrointestinal, and renal transit times/blood volumes can be reasonably acquired from contrast ultrasound, although the latter is less reliably available. Assessment of the impact on regional blood volumes of pharmacologic or other interventions is a next step toward clinical application of this technique.

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We introduce a new computational framework that utilises Pulse Wave Velocity (PWV) extracted directly from 4D flow MRI (4DMRI) to inform patient-specific compliant computational fluid dynamics (CFD) simulations of a Type-B aortic dissection (TBAD), post-thoracic endovascular aortic repair (TEVAR). The thoracic aortic geometry, a 3D inlet velocity profile (IVP) and dynamic outlet boundary conditions are derived from 4DMRI and brachial pressure patient data. A moving boundary method (MBM) is applied to simulate aortic wall displacement. The aortic wall stiffness is estimated through two methods: one relying on area-based distensibility and the other utilising regional pulse wave velocity (RPWV) distensibility, further fine-tuned to align with in vivo values. Predicted pressures and outlet flow rates were within 2.3 % of target values. RPWV-based simulations were more accurate in replicating in vivo hemodynamics than the area-based ones. RPWVs were closely predicted in most regions, except the endograft. Systolic flow reversal ratios (SFRR) were accurately captured, while differences above 60 % in in-plane rotational flow (IRF) between the simulations were observed. Significant disparities in predicted wall shear stress (WSS)-based indices were observed between the two approaches, especially the endothelial cell activation potential (ECAP). At the isthmus, the RPWV-driven simulation indicated a mean ECAP>1.4 Pa-1 (critical threshold), indicating areas potentially prone to thrombosis, not captured by the area-based simulation. RPWV-driven simulation results agree well with 4DMRI measurements, validating the proposed pipeline and facilitating a comprehensive assessment of surgical decision-making scenarios and potential complications, such as thrombosis and aortic growth.

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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters, including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV, are noninvasive markers of coronary microvascular circulation. The existing literature contains conflicting findings regarding these parameters in NAFLD patients. METHODS: A comprehensive systematic search was conducted on major electronic databases from inception until May 8, 2024, to identify relevant studies. We pooled the standardized mean differences (SMD) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at P < .05. RESULTS: Four studies with 1139 participants (226 with NAFLD and 913 as controls) were included. NAFLD was associated with a significantly lower CFRV (SMD: -0.77; 95% CI: -1.19, -0.36; P < .0002) and hyperemic DPFV (SMD: -0.73; 95% CI: -1.03, -0.44; P < .00001) than the controls. NAFLD demonstrated a statistically insignificant trend toward a reduction in baseline DPFV (SMD: -0.09; 95% CI: -0.38, 0.19; P = .52) compared to healthy controls. CONCLUSION: Patients with NAFLD are at a higher risk of coronary microvascular dysfunction, as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in patients with NAFLD provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions for impaired coronary flow reserve in subjects with NAFLD may lead to improvement in clinical outcomes.

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Numerical simulation of blood flow is a challenging topic due to the multiphase nature of this biological fluid. The choice of a specific method among the ones available in literature is often motivated by the physical scale of interest. Single-phase approximation allows for lower computational time, but does not consider this multiphase nature. Cell-level simulation, on the other hand, requires high computational resources and is limited to small scales. This work proposes a scale-up approach for cell-level simulation of blood flow, in the framework of unresolved CFD-DEM technique. This method offers the possibility to simulate hundreds of thousands of particles with limited computational effort, but requires specific models for fluid-particle interactions. Regarding blood flow, drag and lift force acting on the red blood cells (RBCs) are responsible for several macroscopic blood characteristics. Despite several correlations available for drag and lift force acting on rigid particles, specific force models for the simulation of deformable particles compatible with RBCs physics are missing. This study employs data obtained from cell-level simulations to derive equations then used in unresolved simulation of RBCs. The strategy followed during the modeling phase is presented, together with the model verification and validation. This approach returns satisfying results when used to simulate blood flow in large-scale channels. Up to half a million RBCs are considered, and computational effort is reported to allow a comparison with other existing methods. Future perspectives include further improvement of the model, such as a deeper understanding of particle-particle interactions.

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Platelet aggregation is a dynamic process that can obstruct blood flow, leading to cardiovascular diseases. While many studies have demonstrated clear connections between shear rate and platelet aggregation, the impact of flow-derived mechanical signals on this process is not fully understood. The objective of this work is to investigate the role of flow conditions on platelet aggregation dynamics, including effects on growth, shape, density composition, and their potential correlation with binding processes that are characterised by longer (e.g., via αIIbß3 integrin) and shorter (e.g., via VWF) initial binding times. In vitro blood perfusion experiments were conducted at wall shear rates of 800, 1600 and 4000 s-1. Detailed analysis of two modalities of experimental images was performed to offer insights into the morphology of platelet aggregates. A consistent structural pattern was observed across all samples: a high-density core enveloped by a low-density outer shell. An image-based 3D computational blood flow model was subsequently employed to study the local flow conditions, including binding availability time and flow-derived mechanical signals via shear rate and rate of elongation. The results show substantial dependence of the aggregation dynamics on these flow parameters. We found that the different binding mechanisms that prefer different flow regimes do not have a monotonic cross-over in efficiency as the flow increases. There is a significant dip in the cumulative aggregation potential in-between the preferred regimes. The results suggest that treatments targeting the biomechanical pathways could benefit from creating conditions that exploit these low-efficiency zones of aggregation.

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PURPOSE: Cardiogenic shock still has a high mortality. In order to correctly manage these patients, it is useful to have available haemodynamic parameters, invasive and non-invasive. The aim of this review is to show the current evidence on the use of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral. METHODS: Publications relevant to the discussion of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral and cardiogenic shock, were retrieved from PubMed®. RESULTS: Left ventricular outflow tract - velocity time integral is an easily sampled and reproducible parameter that has already been shown to have prognostic value in various cardiovascular pathologies, including myocardial infarction and heart failure. Although there are still few data available in the literature, the LVOT-VTI also seems to have an important role in CS from prognosis to guidance in the escalation/de-escalation of vasoactive therapy and to support devices by allowing an estimate of patient's probability of response to fluid administration. CONCLUSION: Aortic flow assessment can become a very useful invasive parameter in the management of cardiogenic shock.

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Hyperventilation-induced intracranial pressure reduction might be impaired in cerebral venous thrombosis (CVT) patients. Using transcranial Doppler, we assessed carbon dioxide-vasomotor reactivity (CO2-VMR) within 24 hours of admission in CVT patients and studied its correlation with patient outcomes. Adult moderate-severe CVT patients (participants of another large observational study) were included. CO2-VMR was calculated as the percentage change in peak flow velocities during maximal hypercapnia and hypocapnia. Outcome was assessed with the modified Rankin scale (mRS) at one - month post-discharge, dichotomized into favourable (mRS≤2) and unfavourable (mRS>2). Twenty patients' data was analysed. Impaired CO2-VMR (<70 %) was observed in 13 patients in the affected hemisphere; among them, 10 had impairments in both hemispheres. CO2-VMR correlated negatively with mRS (Rho = -0.688, p = 0.001). Odds for unfavourable outcomes were reduced by 92 % in patients with intact VMR on the ipsilateral hemisphere (Odds ratio (OR) 0.08, Confidence interval (CI) 0.006---0.636, p = 0.027) and by 94 % with VMR intact on the contralateral hemisphere (OR 0.063, CI 0.003---0.569, p = 0.03). Thus, impaired CO2-VMR in moderate to severe CVT patients is associated with unfavourable outcomes, and has the potential to prognosticate CVT patients objectively.

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OBJECTIVES: Cardiac surgery associated-acute kidney injury is a common and serious postoperative complication of cardiac surgery, which is associated with increased postoperative morbidity and mortality. This study aimed to explore the association between cardiopulmonary bypass (CPB) blood flow rate (BFR), and major adverse kidney events (MAKEs) at day 30. DESIGN: Retrospective single-center before-after observational study. Patients were divided in 2 groups according to CPB flow rates: a first group with an institutional protocol targeting a CPB-BFR of >2.2 L/min/m² (low CPB-BFR group), and a second group with a modified institutional protocol targeting a CPB-BFR of >2.4 L/min/m² (high CPB-BFR group). The primary outcome was MAKE at 30 days, defined as the composite of death, renal replacement therapy or persistent renal dysfunction. SETTING: The data were collected from clinical routines in university hospital. PARTICIPANTS: Adult patients who underwent elective and urgent cardiac surgery without severe chronic renal failure, for whom CPB duration was ≥90 minutes. INTERVENTIONS: We included 533 patients (low CPB-BFR group, n = 270; high CPB-BFR group, n = 263). MEASUREMENTS AND MAIN RESULTS: A significant decrease in MAKE at 30 days was observed in the high CPB-BFR group (3% v 8%; odds ratio [OR], 0.779; 95% confidence interval [CI], 0.661-0.919; p < 0.001) mainly mediated by a lower 30-day mortality in the high CPB-BFR group (1% v 5%; OR, 0.697; 95% CI, 0.595-0.817; p = 0.001), as was renal replacement therapy (1% v 4%; OR, 0.739; 95% CI, 0.604-0.904; p = 0.016). CONCLUSIONS: In patients undergoing cardiac surgery, increased CPB-BFR was associated with a decrease in MAKE at 30 days including mortality and renal replacement therapy.

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BACKGROUND: The pulmonary vein (PV) flow pattern is influenced by the presence of mitral regurgitation (MR). After a successful reduction in MR severity, the pattern is expected to be changed. We aimed to evaluate the prognostic value of a change in the PV flow pattern in patients with primary MR undergoing mitral valve repair (MVR). METHODS: The PV flow pattern was assessed with transthoracic echocardiography in 216 patients (age 65 [IQR 56-72] years, 70% male) with primary MR before and after surgical MVR. The population was divided according to a change in the PV flow pattern following MVR into 'improvers' and 'non-improvers'. RESULTS: Non-improvers (15%) had a higher prevalence of paroxysmal AF at baseline (46% vs. 22%, p = 0.004), left ventricular dysfunction (LVEF ≤60%) (39% vs. 21%, p = 0.020), and had lower systolic pulmonary artery pressure (28[IQR 25-38] vs. 35[IQR 26-48] mmHg, p = 0.018) compared to improvers (85%). After a median follow-up of 83[IQR 43-140] months, 26(12%) patients died. Non-improvers had higher mortality rates than improvers (p = 0.009). On multivariable Cox regression analysis, a lack of improvement in the PV flow pattern remained independently associated with all-cause mortality (HR 2.322, 95% CI 1.140 to 4.729, P = 0.020). CONCLUSION: A lack of improvement in the PV flow pattern is independently associated with worse long-term survival in patients with primary MR undergoing MVR.

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The choroid, which is a highly vascularized layer between the retina and sclera, is essential for supplying oxygen and nutrients to the outer retina. Choroidal vascular dysfunction has been implicated in numerous ocular diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and myopia. Traditionally, the in vivo assessment of choroidal blood flow relies on techniques such as laser Doppler flowmetry, laser speckle flowgraphy, pneumotonometry, laser interferometry, and ultrasonic color Doppler imaging. While the aforementioned methods have provided valuable insights into choroidal blood flow regulation, their clinical applications have been limited. Recent advancements in optical coherence tomography and optical coherence tomography angiography have expanded our understanding of the choroid, allowing detailed visualization of the larger choroidal vessels and choriocapillaris, respectively. This review provides an overview of the available techniques that can investigate the choroid and its blood flow in vivo. Future research should combine these techniques to comprehensively image the entire choroidal microcirculation and develop robust methods to quantify choroidal blood flow. The potential findings will provide a better picture of choroidal hemodynamics and its effect on ocular health and disease.

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Induced arterial pressure oscillation may improve the assessment of dynamic cerebral autoregulation (dCA) with transfer function analysis (TFA). This study investigated dCA during repeated handgrip exercise (RHE) compared with spontaneous rest and sit-stand maneuvers (SSM), often used in cerebrovascular research. After a 5-min rest, 20 healthy young adults (10 women and 10 men) underwent 5 min of RHE (30% maximal voluntary contraction) and SSM at 0.05 Hz and 0.10 Hz each in random order. Power spectral density (PSD) and TFA gain, phase, coherence of mean arterial pressure (MAP), and blood velocity in the middle cerebral artery (MCAvmean) were measured in very low (VLF: 0.02-0.07 Hz) and low (LF: 0.07-0.20 Hz) frequencies. End-tidal CO2 (EtCO2) was continuously recorded throughout data collection. Compared with rest, RHE increased the PSD of MAP and MCAvmean in VLF (444% and 273%, respectively) and LF (1,571% and 1,765%, respectively) (all P < 0.001). Coherence increased during RHE (VLF: 131%, LF: 128%) and SSM (VLF: 166%, LF: 136%) compared with rest (all P < 0.05). TFA gain and phase were similar between RHE and rest, but VLF gain was higher, whereas VLF and LF phases were lower during SSM than RHE (all P < 0.05). EtCO2 was higher during SSM than rest and RHE (both P < 0.05), with the individual EtCO2 changes positively correlated with VLF gain (r = 0.538, P < 0.001). These results indicate that RHE significantly increases arterial pressure oscillation and TFA coherence and may improve dCA assessment in individuals unable to perform repeated postural changes.NEW & NOTEWORTHY This is the first study investigating dynamic cerebral autoregulation (dCA) during light-intensity repeated handgrip exercise (RHE) compared with rest and sit-stand maneuvers (SSM) using transfer function analysis (TFA). Compared with rest, RHE significantly increased oscillations of arterial blood pressure and cerebral blood velocity and coherence, whereas SSM exhibited the highest oscillations and coherence. These findings suggest that RHE may serve as an alternative method for assessing dCA in individuals unable to perform repeated postural changes.

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BACKGROUND: In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. METHODS: We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. RESULTS: After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023). CONCLUSIONS: Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

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BACKGROUND: Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR). METHODS: Twenty healthy controls (10 young and 10 age-gender-matched old controls) and 20 patients with heart failure with preserved ejection fraction (HFpEF) were recruited. All had 4D flow CMR. Flow was quantified at the ascending and descending aorta levels. In addition, at the ascending aorta level, we quantified systolic flow displacement (FDs) and systolic flow reversal ratio (sFRR). The aortic conduit function was defined as the relative drop in systolic flow from the ascending to the descending aorta (∆Fs). Aortic reservoir function was defined as descending aortic diastolic stroke volume (DAo SVd). RESULTS: Both ∆Fs (R=0.51, p=0.001) and DAo SVd (R=-0.68, p=0.001) were significantly associated with ageing. Native T1 (R=0.51, p=0.001) and extracellular volume (R=0.51, p=0.001) showed maximum association with ∆Fs. ∆Fs significantly increased in HFpEF versus age-gender-matched controls (41±8% vs 52±12%, p=0.02). In multiple regression, only ∆Fs and DAo SVd were independent predictors of the estimated glomerular filtration rate (model R=0.77, p=0.0001). FDs was significantly associated with ∆Fs (R=0.4, p=0.01) and DAo SVd (R=-0.48, p=0.002), whereas sFRR was mainly associated with DAo SVd (R=-0.46, p=0.003). CONCLUSION: Both aortic conduit and reservoir function decline with age and this decline in aortic function is also independently associated with renal functional decline. Ascending aortic turbulent flow signatures are associated with loss of aortic conduit and reservoir functions. Finally, in HFpEF, aortic conduit and reservoir function demonstrate progressive decline. TRIALS REGISTRATION NUMBER: NCT05114785.

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OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO. METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared. RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt. CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

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Blood flow reconstruction in the vasculature is important for many clinical applications. However, in clinical settings, the available data are often quite limited. For instance, transcranial Doppler ultrasound is a non-invasive clinical tool that is commonly used in clinical settings to measure blood velocity waveforms at several locations. This amount of data is grossly insufficient for training machine learning surrogate models, such as deep neural networks or Gaussian process regression. In this work, we propose a Gaussian process regression approach based on empirical kernels constructed by data generated from physics-based simulations-enabling near-real-time reconstruction of blood flow in data-poor regimes. We introduce a novel methodology to reconstruct the kernel within the vascular network. The proposed kernel encodes both spatiotemporal and vessel-to-vessel correlations, thus enabling blood flow reconstruction in vessels that lack direct measurements. We demonstrate that any prediction made with the proposed kernel satisfies the conservation of mass principle. The kernel is constructed by running stochastic one-dimensional blood flow simulations, where the stochasticity captures the epistemic uncertainties, such as lack of knowledge about boundary conditions and uncertainties in vasculature geometries. We demonstrate the performance of the model on three test cases, namely, a simple Y-shaped bifurcation, abdominal aorta and the circle of Willis in the brain.

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The study of blood flow is becoming a new trend in cardiology and cardiovascular surgery. Based on the literature and our own data, a review is presented on the use of 4D flow in diseases of the heart and blood vessels. The main state of the question about the features of the application of the technique in various pathologies of the cardiovascular system is described in detail, the priorities, limitations and promising directions of the technique application are considered taking into account the goals of practical medicine. The review consists of two parts. The first is devoted to general issues, limitations of the technique, and issues of 4D flow mapping in patients with lesions of the great vessels. In the second part, the emphasis is on the use of 4D flow MRI in the study of intraventricular blood flow and the application of the technique in congenital heart and vascular diseases.

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