Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI.

Background/Aims: In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Methods: This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. Results: A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. Conclusion: The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Hemodynamic Assessment of Infants With Congenital Heart Disease Using Ferumoxytol-Enhanced 4D Flow Cardiac Magnetic Resonance.

In complex congenital heart disease, characterization of the circulation is necessary to anticipate the clinical course. Four-dimensional cardiac magnetic resonance imaging enhanced by superparamagnetic iron oxide contrast agents (ferumoxytol) enables detailed and efficient assessment of both anatomy and physiology in neonates. We demonstrate this impact in 3 cases of neonates with congenital heart disease.

Assessment of abnormal transvalvular flow and wall shear stress direction for pediatric/young adults with bicuspid aortic valve: a cross-sectional 4D flow study.

BACKGROUND: Aortic dilation is seen in pediatric/young adult patients with bicuspid aortic valve (BAV), and hemodynamic markers to predict aortic dilation are necessary for monitoring. Although promising hemodynamic metrics, such as abnormal wall shear stress (WSS) magnitude, have been proposed for adult BAV patients using 4D flow cardiovascular magnetic resonance, those for pediatric BAV patients have less frequently been reported, partly due to scarcity of data to define normal WSS range. To circumvent this challenge, this study aims to investigate if a recently proposed 4D flow-based hemodynamic measurement, abnormal flow directionality, is associated with aortic dilation in pediatric/young adult BAV patients. METHODS: 4D flow scans for BAV patients (<20 years old) and age-matched controls were retrospectively enrolled. Static segmentation for the aorta and pulmonary arteries was obtained to quantify peak systolic hemodynamics and diameters in the proximal aorta. In addition to peak velocity, wall shear stress (WSS), vorticity, helicity, and viscous energy loss, direction of aortic velocity and WSS in BAV patients was compared with that of control atlas using registration technique; angle differences of >60deg and >120deg were defined as moderately and severely abnormal, respectively. Association between the obtained metrics and normalized diameters (Z-scores) were evaluated at the sinotubular junction, mid ascending aorta, and distal ascending aorta. RESULTS: Fifty-three BAV patients, including eighteen with history of repaired aortic coarctation, and seventeen controls were enrolled. Correlation between moderately abnormal velocity/WSS direction and aortic Z-scores was moderate to strong at the sinotubular junction and mid ascending aorta (R=0.62-0.81; p<0.001) while conventional measurements exhibited weaker correlation (|R|=0.003-0.47, p=0.009-0.99) in all subdomains. Multivariable regression analysis found moderately abnormal velocity direction and existence of aortic regurgitation (only for isolated BAV group) were independently associated with mid ascending aortic Z-scores. CONCLUSION: Abnormal velocity and WSS directionality in the proximal aorta was strongly associated with aortic Z-scores in pediatric/young adult BAV patients.

Porto-mesenteric four-dimensional flow MRI: a novel non-invasive technique for assessment of gastro-oesophageal varices.

OBJECTIVES: To assess the role of 4D flow MRI in the assessment of gastro-oesophageal varices and in the prediction of high-risk varices in patients with chronic liver disease. METHODS: Thirty-eight patients diagnosed with either oesophageal or gastric varices were included in this single-centre prospective study. 4D flow MRI was used to calculate peak flow, average flow and peak velocity at the portal vein confluence (PV1) and hilum (PV2), splenic vein hilum (SV1) and confluence (SV2), and superior mesenteric vein (SMV). PV and SV fractional flow changes were also measured. RESULTS: ROC analysis revealed that both PV2 average flow and PV fractional average flow change had 100% sensitivity to predict high-risk patients with the PV fractional peak flow change having the widest area under the curve (AUC) and the highest specificity (92.3%). SV1 average flow, SV2 average flow, SV2 peak flow, and SV2 peak velocity increased significantly in patients with oesophageal compared to gastric varices included (p = 0.022, < 0.001, < 0.001 and 0.001, respectively). CONCLUSION: Based on certain porto-mesenteric blood flow, velocity, and fractional flow change parameters, 4D flow MRI showed excellent performance in identifying high-risk patients and giving an idea about the grade and location of varices. CRITICAL RELEVANCE STATEMENT: Variceal bleeding is a major consequence of unidentified risky upper GI varices. Thus, by identifying and locating high-risk varices early, either oesophageal or gastric, using a non-invasive method like MRI, adverse events might be avoided. KEY POINTS: 4D flow MRI can be used as a potential alternative for endoscopy to predict patients with high-risk varices. Based on portal vein fractional flow change, splenic flow and velocity, 4D MRI can predict and locate high-risk varices. Earlier identification of high-risk varices can allow for interventions to prevent adverse events.

Intracranial aneurysm stiffness assessment using 4D Flow MRI.

BACKGROUND: Although arterial stiffness is known as a biomarker for cardiovascular events and stroke, there is limited information in the literature regarding the stiffness of intracranial aneurysms. In this study, we aim to assess the stiffness of intracranial aneurysms using 4D Flow MRI. METHODS: A total of 27 aneurysms in 25 patients with internal carotid artery aneurysms were included in this study. Using 4D Flow MRI, we measured the arterial pulse wave form during a cardiac cycle at planes proximal and distal to the target aneurysm. The damping of these waveforms through the aneurysm was defined as the aneurysm damping index (ADI) and compared to the contralateral side. We also investigated the clinical factors related to the ADI. RESULTS: ADI assessment was successful in all cases. The average ADI was 1.18±0.28, which was significantly larger than 1.0 (P = 0.0027 [t-test]). The ADI on the aneurysm side was larger than on the contralateral side (1.19±0.30 vs 1.05±0.17, P = 0.029 [t-test]). On multivariate analysis, the use of beta-blockers (ß=0.46, P = 0.015) and smoking history (ß=-0.22, P = 0.024) showed a significant correlation with ADI. CONCLUSION: We have proposed a novel method to observe arterial pulse wave dumping through intracranial aneurysm using 4D Flow MRI. The damping can be quantitatively observed, and the ADI has correlations with clinical factors such as antihypertensive drugs and smoking. Further studies should focus more on evaluating aneurysm stiffness and its clinical applications.

Flow quantification within the aortic ejection tract using 4D flow cardiac MRI in patients with bicuspid aortic valve: Implications for the assessment of aortic regurgitation.

PURPOSE: The purpose of this study was to evaluate the performance of four-dimensional (4D) flow cardiac MRI in quantifying aortic flow in patients with bicuspid aortic valve (BAV). MATERIALS AND METHODS: Patients with BAV who underwent transthoracic echocardiography (TTE) and 4D flow cardiac MRI were prospectively included. Aortic flow was quantified using two-dimensional phase contrast velocimetry at the sinotubular junction and in the ascending aorta and using 4D flow in the regurgitant jet, in the left ventricular outflow tract, at the aortic annulus, the sinotubular junction, and the ascending aorta, with or without anatomical tracking. Flow quantification was compared with ventricular volumes, pulmonary flow using Pearson correlation test, bias and limits of agreement (LOA) using Bland Altman method, and with multiparametric transthoracic echocardiography quantification using weighted kappa test. RESULTS: Eighty-eight patients (63 men, 25 women) with a mean age of 50.5 ± 14.8 (standard deviation) years (age range: 20.8-78.3) were included. Changes in flow with or without tracking were modest (< 5 mL). The best correlation was obtained at the aortic annulus for forward volume (r = 0.84; LOA [-28.4; 25.3] mL) and at the regurgitant jet and sinotubular junction for regurgitant volume (r = 0.68; LOA [-27.8; 33.8] and r = 0.69; LOA [-28.6; 24.2] mL). A combined approach for regurgitant fraction and net volume calculations using forward volume measured at ANN and regurgitant volume at sinotubular junction performed better than each level taken separately (r = 0.90; LOA [-20.7; 10.0] mL and r = 0.48, LOA [-33.8; 33.4] %). The agreement between transthoracic echocardiography and 4D flow cardiac MRI for aortic regurgitation grading was poor (kappa, 0.13 to 0.42). CONCLUSION: In patients with BAV, aortic flow quantification by 4D flow cardiac MRI is the most accurate at the annulus for the forward volume, and at the sinotubular junction or directly in the jet for the regurgitant volume.

Comparing flow and pulmonary artery growth post-patent ductus arteriosus stenting in patients with ductal-dependent pulmonary flow using 4D magnetic resonance imaging.

Aims: The 4D magnetic resonance imaging (4D-flow MRI) provides a qualitative and quantitative assessment of cardiovascular structures and processes. 4D-flow MRI was used to study pulmonary flow in post-patent ductus arteriosus (PDA) stent insertion in duct-dependent pulmonary flow neonates at baseline (PDA stent insertion) and after 6 months, and also, to evaluate the effect of flow dynamics on the growth of pulmonary arteries (PAs). Methods and results: This prospective observational study included neonates with ductus arteriosus-dependent pulmonary circulation who underwent ductal stenting between June 2021 and November 2022. Cardiac 4D-flow MRI and magnetic resonance angiography were conducted in two phases; after the deployment of the PDA stent during the neonatal period and after 6 months from stent deployment. Eight neonates were recruited, but only five completed both scans. A total of 10 PAs were evaluated during each phase. The median left PA (LPA) and right PA (RPA) diameters and indexed flow for LPA and RPA were evaluated. The growth rate of LPA was observed to be lower than that of RPA (percentage diameter increase: 74 vs. 153%). LPA Z-score was lower than RPA. Indexed flow in both LPA and RPA showed a reduction in the 6-month scan, which was consistent with reduced stent patency. Conclusion: 4D-flow cardiac MRI showed different growth rates and reduced flow between LPA and RPA post-PDA stent. These insights can aid in future management decisions.

High-Frame-Rate Ultrasound Velocimetry in the Healthy Femoral Bifurcation: A Comparative Study Against 4-D Flow Magnetic Resonance Imaging.

OBJECTIVE: Local flow dynamics impact atherosclerosis yet are difficult to quantify with conventional ultrasound techniques. This study investigates the performance of ultrasound vector flow imaging (US-VFI) with and without ultrasound contrast agents in the healthy femoral bifurcation. METHODS: High-frame-rate ultrasound data with incremental acoustic outputs were acquired in the femoral bifurcations of 20 healthy subjects before (50V) and after contrast injection (2V, 5V and 10V). 2-D blood-velocity profiles were obtained through native blood speckle tracking (BST) and contrast tracking (echo particle image velocimetry [echoPIV]). As a reference, 4-D flow magnetic resonance imaging (4-D flow MRI) was acquired. Contrast-to-background ratio and vector correlation were used to assess the quality of the US-VFI acquisitions. Spatiotemporal velocity profiles were extracted, from which peak velocities (PSV) were compared between the modalities. Furthermore, root-mean-square error analysis was performed. RESULTS: US-VFI was successful in 99% of the cases and optimal VFI quality was established with the 10V echoPIV and BST settings. A good correspondence between 10V echoPIV and BST was found, with a mean PSV difference of -0.5 cm/s (limits of agreement: -14.1-13.2). Both US-VFI techniques compared well with 4-D flow MRI, with a mean PSV difference of 1.4 cm/s (-18.7-21.6) between 10V echoPIV and MRI, and 0.3 cm/s (-23.8-24.4) between BST and MRI. Similar complex flow patterns among all modalities were observed. CONCLUSION: 2-D blood-flow quantification of femoral bifurcation is feasible with echoPIV and BST. Both modalities showed good agreement compared to 4-D flow MRI. For the femoral tract the administration of contrast was not needed to increase the echogenicity of the blood for optimal image quality.

Super-Resolving and Denoising 4D flow MRI of Neurofluids Using Physics-Guided Neural Networks.

PURPOSE: To obtain high-resolution velocity fields of cerebrospinal fluid (CSF) and cerebral blood flow by applying a physics-guided neural network (div-mDCSRN-Flow) to 4D flow MRI. METHODS: The div-mDCSRN-Flow network was developed to improve spatial resolution and denoise 4D flow MRI. The network was trained with patches of paired high-resolution and low-resolution synthetic 4D flow MRI data derived from computational fluid dynamic simulations of CSF flow within the cerebral ventricles of five healthy cases and five Alzheimer's disease cases. The loss function combined mean squared error with a binary cross-entropy term for segmentation and a divergence-based regularization term for the conservation of mass. Performance was assessed using synthetic 4D flow MRI in one healthy and one Alzheimer' disease cases, an in vitro study of healthy cerebral ventricles, and in vivo 4D flow imaging of CSF as well as flow in arterial and venous blood vessels. Comparison was performed to trilinear interpolation, divergence-free radial basis functions, divergence-free wavelets, 4DFlowNet, and our network without divergence constraints. RESULTS: The proposed network div-mDCSRN-Flow outperformed other methods in reconstructing high-resolution velocity fields from synthetic 4D flow MRI in healthy and AD cases. The div-mDCSRN-Flow network reduced error by 22.5% relative to linear interpolation for in vitro core voxels and by 49.5% in edge voxels. CONCLUSION: The results demonstrate generalizability of our 4D flow MRI super-resolution and denoising approach due to network training using flow patches and physics-based constraints. The mDCSRN-Flow network can facilitate MRI studies involving CSF flow measurements in cerebral ventricles and association of MRI-based flow metrics with cerebrovascular health.

Cluster analysis of 100 Marfan patients based on aortic 4D flow MRI and Z-score: insights into disease heterogeneity and stratification of subgroups.

OBJECTIVES: 4D flow MRI-derived variables from Marfan patients are highly heterogeneous. Our aim was to identify distinct Marfan patient subgroups based on aortic 4D flow MRI and Z-score for stratification of distinct hemodynamic profiles and clinical features by means of hierarchical cluster analysis. MATERIALS AND METHODS: One hundred Marfan patients underwent baseline aortic 4D flow MRI at 3 T. Z-scores, degree of helical and vortical flow, wall shear stress, flow displacement, and peak velocity were determined in the ascending aorta. Sex, age, BMI, antihypertensive medication, and dural ectasia were recorded. Hierarchical cluster analysis was performed using 4D flow MRI variables and Z-scores as input. RESULTS: Cluster analysis resulted in three distinct clusters characterized by different Z-scores (mean ± SD); cluster 1: 0.4 ± 1.1 vs. cluster 2: 3.1 ± 1.1 vs. cluster 3: 3.6 ± 1.9. The three clusters delivered differences in helical and vortical flow patterns (global p = 0.003 and p < 0.001, respectively), wall shear stress (0.49 ± 0.11 vs. 0.44 ± 0.12 vs. 0.37 ± 0.09 N/m2, global p < 0.001), flow displacement (0.11 ± 0.05 vs. 0.16 ± 0.08 vs. 0.15 ± 0.07, global p = 0.006), and peak velocity (76.3 ± 9.0 vs. 60.1 ± 7.3 vs. 56.0 ± 7.8 cm/s, global p < 0.001). Patients in cluster 1 and 2 were relevantly younger than in cluster 3 (32.3 ± 13.8 vs. 32.8 ± 12.6 vs. 40.2 ± 15.0 years, all pairwise ∆p < 0.0297). CONCLUSION: Hierarchical cluster analysis based on aortic 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients, each characterized by specific hemodynamic profiles and clinical features. Follow-up of our patients is warranted to assess if 4D flow MRI- and Z-score-based stratification can predict future aortic diameter growth and ultimately improve outcomes. CLINICAL RELEVANCE STATEMENT: A combination of Z-score and 4D flow MRI-derived parameters may help identify subgroups of Marfan patients representing different stages or phenotypes of aortic disease, which require specific management strategies. KEY POINTS: Four-dimensional (4D) flow MRI-derived variables of Marfan patients are highly heterogeneous across varying Z-scores. Cluster analysis based on 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients. A combination of Z-score and 4D flow MRI-derived parameters may identify different stages of aortic disease in Marfan patients.

Interactive effect of hemodynamics in transverse sigmoid sinus and bone morphology on venous pulsatile tinnitus: a four-dimensional (4D) flow magnetic resonance imaging (MRI) study.

Background: The hemodynamic pathogenesis of venous pulsatile tinnitus (VPT) is still unclear. This study aimed to explore the mechanism of bone morphology and hemodynamic changes in transverse sigmoid sinus (TSS) on VPT patients. Methods: 49 patients with unilateral VPT, 26 patients with subjective tinnitus and 36 healthy controls were included in this retrospective clinical trial. Four-dimensional (4D) flow magnetic resonance imaging (MRI) was used to evaluate the hemodynamics of the TSS. High-resolution computed tomography was used to assess the perivenous bone structures. All images were independently assessed for each participant by two trained neuroradiologists. Kolmogorov-Smirnov test was used to determine the normal distribution of the data. Chi-square test and nonparametric test were used to compare classified or continuous variables. Stepwise linear regression and mediation effect analysis was used to explore the relationship between bone dehiscence (BD), hemodynamic factors and VPT symptoms. Results: Peak velocity (P=0.001) and maximum energy loss (P=0.041) in VPT group were risk factors for the severity of tinnitus. Energy loss [indirect effect =0.692, P<0.005, 95% confidence interval (CI): 0.201-1.377] and peak velocity (indirect effect =0.899, P<0.005, 95% CI: 0.406-1.582) demonstrated the complete mediation effect between the BD and VPT. BD showed a complete mediation effect between the wall shear stress (WSS) and VPT (indirect effect =15.181, P<0.005, 95% CI: 3.448-35.493). Conclusions: Cross-talk between the hemodynamic changes of TSS and BD can regulate the VPT symptoms. This type of analysis might be helpful in establishing the possible occurrence and development mechanism of the hemodynamics and bone morphology of the VPT.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease.

OBJECTIVES: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). METHODS: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). RESULTS: All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. CONCLUSIONS: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

The New Frontiers of Fetal Imaging: MRI Insights into Cardiovascular and Thoracic Structures.

Fetal magnetic resonance imaging (fMRI) represents a second-line imaging modality that provides multiparametric and multiplanar views that are crucial for confirming diagnoses, detecting associated pathologies, and resolving inconclusive ultrasound findings. The introduction of high-field magnets and new imaging sequences has expanded MRI's role in pregnancy management. Recent innovations in ECG-gating techniques have revolutionized the prenatal evaluation of congenital heart disease by synchronizing imaging with the fetal heartbeat, thus addressing traditional challenges in cardiac imaging. Fetal cardiac MRI (fCMR) is particularly valuable for assessing congenital heart diseases, especially when ultrasound is limited by poor imaging conditions. fCMR allows for detailed anatomical and functional evaluation of the heart and great vessels and is also useful for diagnosing additional anomalies and analyzing blood flow patterns, which can aid in understanding abnormal fetal brain growth and placental perfusion. This review emphasizes fMRI's potential in evaluating cardiac and thoracic structures, including various gating techniques like metric optimized gating, self-gating, and Doppler ultrasound gating. The review also covers the use of static and cine images for structural and functional assessments and discusses advanced techniques like 4D-flow MRI and T1 or T2 mapping for comprehensive flow quantification and tissue characterization.

Optimizing encoding strategies for 4D Flow MRI of mean and turbulent flow.

For 4D Flow MRI of mean and turbulent flow a compromise between spatiotemporal undersampling and velocity encodings needs to be found. Assuming a fixed scan time budget, the impact of trading off spatiotemporal undersampling versus velocity encodings on quantification of velocity and turbulence for aortic 4D Flow MRI was investigated. For this purpose, patient-specific mean and turbulent aortic flow data were generated using computational fluid dynamics which were embedded into the patient-specific background image data to generate synthetic MRI data with corresponding ground truth flow. Cardiac and respiratory motion were included. Using the synthetic MRI data as input, 4D Flow MRI was subsequently simulated with undersampling along pseudo-spiral Golden angle Cartesian trajectories for various velocity encoding schemes. Data were reconstructed using a locally low rank approach to obtain mean and turbulent flow fields to be compared to ground truth. Results show that, for a 15-min scan, velocity magnitudes can be reconstructed with good accuracy relatively independent of the velocity encoding scheme ( S S I M U = 0.938 ± 0.003 ) , good accuracy ( S S I M U ≥ 0.933 ) and with peak velocity errors limited to 10%. Turbulence maps on the other hand suffer from both lower reconstruction quality ( S S I M TKE ≥ 0.323 ) and larger sensitivity to undersampling, motion and velocity encoding strengths ( S S I M TKE = 0.570 ± 0.110 ) when compared to velocity maps. The best compromise to measure unwrapped velocity maps and turbulent kinetic energy given a fixed 15-min scan budget was found to be a 7-point multi- V enc acquisition with a low V enc tuned for best sensitivity to the range of expected intra-voxel standard deviations and a high V enc larger than the expected peak velocity.

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.

Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI.

BACKGROUND AND OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Impact of training data composition on the generalizability of convolutional neural network aortic cross-section segmentation in four-dimensional magnetic resonance flow imaging.

BACKGROUND: Four-dimensional cardiovascular magnetic resonance flow imaging (4D flow CMR) plays an important role in assessing cardiovascular diseases. However, the manual or semi-automatic segmentation of aortic vessel boundaries in 4D flow data introduces variability and limits the reproducibility of aortic hemodynamics visualization and quantitative flow-related parameter computation. This paper explores the potential of deep learning to improve 4D flow CMR segmentation by developing models for automatic segmentation and analyzes the impact of the training data on the generalization of the model across different sites, scanner vendors, sequences, and pathologies. METHODS: The study population consists of 260 4D flow CMR datasets, including subjects without known aortic pathology, healthy volunteers, and patients with bicuspid aortic valve (BAV) examined at different hospitals. The dataset was split to train segmentation models on subsets with different representations of characteristics, such as pathology, gender, age, scanner model, vendor, and field strength. An enhanced three-dimensional U-net convolutional neural network (CNN) architecture with residual units was trained for time-resolved two-dimensional aortic cross-sectional segmentation. Model performance was evaluated using Dice score, Hausdorff distance, and average symmetric surface distance on test data, datasets with characteristics not represented in the training set (model-specific), and an overall evaluation set. Standard diagnostic flow parameters were computed and compared with manual segmentation results using Bland-Altman analysis and interclass correlation. RESULTS: The representation of technical factors, such as scanner vendor and field strength, in the training dataset had the strongest influence on the overall segmentation performance. Age had a greater impact than gender. Models solely trained on BAV patients' datasets performed well on datasets of healthy subjects but not vice versa. CONCLUSION: This study highlights the importance of considering a heterogeneous dataset for the training of widely applicable automatic CNN segmentations in 4D flow CMR, with a particular focus on the inclusion of different pathologies and technical aspects of data acquisition.

Regional aortic wall shear stress increases over time in patients with a bicuspid aortic valve.

BACKGROUND: Aortic wall shear stress (WSS) is a known predictor of ascending aortic growth in patients with a bicuspid aortic valve (BAV). The aim of this study was to study regional WSS and changes over time in BAV patients. METHODS: BAV patients and age-matched healthy controls underwent four-dimensional (4D) flow cardiovascular magnetic resonance (CMR). Regional, peak systolic ascending aortic WSS, aortic valve function, aortic stiffness measures, and aortic dimensions were assessed. In BAV patients, 4D flow CMR was repeated after 3 years of follow-up and both at baseline and follow-up computed tomography angiography (CTA) were acquired. Aortic growth (volume increase of ≥5%) was measured on CTA. Regional WSS differences within patients' aorta and WSS changes over time were analyzed using linear mixed-effect models and were associated with clinical parameters. RESULTS: Thirty BAV patients (aged 34 years [interquartile range (IQR) 25-41]) were included in the follow-up analysis. Additionally, another 16 BAV patients and 32 healthy controls (aged 33 years [IQR 28-48]) were included for other regional analyses. Magnitude, axial, and circumferential WSS increased over time (all p < 0.001) irrespective of aortic growth. The percentage of regions exposed to a magnitude WSS >95th percentile of healthy controls increased from 21% (baseline 506/2400 regions) to 31% (follow-up 734/2400 regions) (p < 0.001). WSS angle, a measure of helicity near the aortic wall, decreased during follow-up. Magnitude WSS changes over time were associated with systolic blood pressure, peak aortic valve velocity, aortic valve regurgitation fraction, aortic stiffness indexes, and normalized flow displacement (all p < 0.05). CONCLUSION: An increase in regional WSS over time was observed in BAV patients, irrespective of aortic growth. The increasing WSSs, comprising a larger area of the aorta, warrant further research to investigate the possible predictive value for aortic dissection.

Prerequisites for Clinical Implementation of Whole-Heart 4D-Flow MRI: A Delphi Analysis.

Whole-heart 4D-flow MRI is a valuable tool for advanced visualization and quantification of blood flow in cardiovascular imaging. Despite advantages over 2D-phase-contrast flow, clinical implementation remains only partially exploited due to many hurdles in all steps, from image acquisition, reconstruction, postprocessing and analysis, clinical embedment, reporting, legislation, and regulation to data storage. The intent of this manuscript was 1) to evaluate the extent of clinical implementation of whole-heart 4D-flow MRI, 2) to identify hurdles hampering clinical implementation, and 3) to reach consensus on requirements for clinical implementation of whole-heart 4D-flow MRI. This study is based on Delphi analysis. This study involves a panel of 18 experts in the field on whole-heart 4D-flow MRI. The experience with and opinions of experts (mean 13 years of experience, interquartile range 6) in the field were aggregated. This study showed that among experts in the cardiovascular field, whole-heart 4D-flow MRI is currently used for both clinical and research purposes. Overall, the panelists agreed that major hurdles currently hamper implementation and utilization. The sequence-specific hurdles identified were long scan time and lack of standardization. Further hurdles included cumbersome and time-consuming segmentation and postprocessing. The study concludes that implementation of whole-heart 4D-flow MRI in clinical routine is feasible, but the implementation process is complex and requires a dedicated, multidisciplinary team. A predefined plan, including risk assessment and technique validation, is essential. The reported consensus statements may guide further tool development and facilitate broader implementation and clinical use. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 5.