Wall Shear Stress Measured with 4D Flow CMR Correlates with Biomarkers of Inflammation and Collagen Synthesis in Mild-to-Moderate Ascending Aortic Dilation and Tricuspid Aortic Valves.

AIMS: Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic hemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow CMR), and circulating biomarkers in aortic dilation. METHODS AND RESULTS: Forty-seven cases with aortic dilation (diameter ≥40 mm) and 50 sex-and age-matched controls (diameter <40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D Flow CMR, and biomarkers including interleukin-6, collagen type I α1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared to controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between hemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, p < 0.001), and maximum oscillatory shear index and collagen type I α1 chain (r = -0.575, p < 0.001 in cases). CONCLUSION: Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between hemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.

Oscillatory shear stress is elevated in patients with bicuspid aortic valve and aortic regurgitation: a 4D flow cardiovascular magnetic resonance cross-sectional study.

AIMS: Patients with bicuspid aortic valve (BAV) and aortic regurgitation have higher rate of aortic complications compared with patients with BAV and stenosis, as well as BAV without valvular disease. Aortic regurgitation alters blood haemodynamics not only in systole but also during diastole. We therefore sought to investigate wall shear stress (WSS) during the whole cardiac cycle in BAV with aortic regurgitation. METHODS AND RESULTS: Fifty-seven subjects that underwent 4D flow cardiovascular magnetic resonance imaging were included: 13 patients with BAVs without valve disease, 14 BAVs with aortic regurgitation, 15 BAVs with aortic stenosis, and 22 normal controls with tricuspid aortic valve. Peak and time averaged WSS in systole and diastole and the oscillatory shear index (OSI) in the ascending aorta were computed. Student's t-tests were used to compare values between the four groups where the data were normally distributed, and the non-parametric Wilcoxon rank sum tests were used otherwise. BAVs with regurgitation had similar peak and time averaged WSS compared with the patients with BAV without valve disease and with stenosis, and no regions of elevated WSS were found. BAV with aortic regurgitation had twice as high OSI as the other groups (P ≤ 0.001), and mainly in the outer mid-to-distal ascending aorta. CONCLUSION: OSI uniquely characterizes altered WSS patterns in BAVs with aortic regurgitation, and thus could be a haemodynamic marker specific for this specific group that is at higher risk of aortic complications. Future longitudinal studies are needed to verify this hypothesis.

Regional and Global Aortic Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is commonly defined as localised aortic dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA. METHODS: Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with an AAA > 30 mm (range 36 - 70 mm, all male, age range 65 - 76 years) and 27 age and sex matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as a 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured. RESULTS: Global aortic PWV was greater in men with an AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls. CONCLUSION: PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.

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

Haemodynamic effects of hypertension and type 2 diabetes: Insights from a 4D flow MRI-based personalized cardiovascular mathematical model.

Type 2 diabetes (T2D) and hypertension increase the risk of cardiovascular diseases mediated by whole-body changes to metabolism, cardiovascular structure and haemodynamics. The haemodynamic changes related to hypertension and T2D are complex and subject-specific, however, and not fully understood. We aimed to investigate the haemodynamic mechanisms in T2D and hypertension by comparing the haemodynamics between healthy controls and subjects with T2D, hypertension, or both. For all subjects, we combined 4D flow magnetic resonance imaging data, brachial blood pressure and a cardiovascular mathematical model to create a comprehensive subject-specific analysis of central haemodynamics. When comparing the subject-specific haemodynamic parameters between the four groups, the predominant haemodynamic difference is impaired left ventricular relaxation in subjects with both T2D and hypertension compared to subjects with only T2D, only hypertension and controls. The impaired relaxation indicates that, in this cohort, the long-term changes in haemodynamic load of co-existing T2D and hypertension cause diastolic dysfunction demonstrable at rest, whereas either disease on its own does not. However, through subject-specific predictions of impaired relaxation, we show that altered relaxation alone is not enough to explain the subject-specific and group-related differences; instead, a combination of parameters is affected in T2D and hypertension. These results confirm previous studies that reported more adverse effects from the combination of T2D and hypertension compared to either disease on its own. Furthermore, this shows the potential of personalized cardiovascular models in providing haemodynamic mechanistic insights and subject-specific predictions that could aid in the understanding and treatment planning of patients with T2D and hypertension. KEY POINTS: The combination of 4D flow magnetic resonance imaging data and a cardiovascular mathematical model allows for a comprehensive analysis of subject-specific haemodynamic parameters that otherwise cannot be derived non-invasively. Using this combination, we show that diastolic dysfunction in subjects with both type 2 diabetes (T2D) and hypertension is the main group-level difference between controls, subjects with T2D, subjects with hypertension, and subjects with both T2D and hypertension. These results suggest that, in this relatively healthy population, the additional load of both hypertension and T2D affects the haemodynamic function of the left ventricle, whereas each disease on its own is not enough to cause significant effects under resting conditions. Finally, using the subject-specific model, we show that the haemodynamic effects of diastolic dysfunction alone are not sufficient to explain all the observed haemodynamic differences. Instead, additional subject-specific variations in cardiac and vascular function combine to explain the complex haemodynamics of subjects affected by hypertension and/or T2D.

Helical flow in tortuous aortas and its relationship to turbulence: A whole-aorta 4D flow MRI study.

Background: Increased vascular tortuosity is a hallmark of ageing of the vascular system, including the aorta. However, the impact of tortuosity on aortic blood flow is unknown. We hypothesized that increased tortuosity would be associated with increased blood flow helicity and with decreased degree of blood flow turbulence as measured by the turbulent kinetic energy (TKE). Methods: 4D Flow MR images covering the entire aorta from the aortic valve to the iliac bifurcation were acquired in 23 normal volunteers aged 18-30 years ("Young") and 23 normal volunteers aged 66-76 years ("Old") without aortic disease. The aorta was segmented and divided into four regions: the ascending, descending, suprarenal abdominal and infrarenal abdominal aorta. Tortuosity, helicity, TKE, flow velocity, and Reynolds number were computed for the whole aorta and for each section. Results: Tortuosity and helicity were higher whereas TKE, velocity, and Reynolds number were lower in Old than in Young, for all aortic regions (p < 0.05) except for helicity in the descending aorta. Tortuosity correlated positively with helicity and negatively with TKE for all aortic regions (Spearman rho=±0.45-±0.72, p < =0.002) except for TKE in the ascending aorta. Further, helicity correlated with TKE in the descending, suprarenal abdominal and infrarenal abdominal aorta (Spearman rho=-0.56--0.77). Conclusion: Tortuosity increases with age and blood flow in tortuous aortas is more helical. Increasing helicity, in turn, is associated with decreasing TKE.

Impact of dobutamine stress on diastolic energetic efficiency of healthy left ventricle: an in vivo kinetic energy analysis.

The total kinetic energy (KE) of blood can be decomposed into mean KE (MKE) and turbulent KE (TKE), which are associated with the phase-averaged fluid velocity field and the instantaneous velocity fluctuations, respectively. The aim of this study was to explore the effects of pharmacologically induced stress on MKE and TKE in the left ventricle (LV) in a cohort of healthy volunteers. 4D Flow MRI data were acquired in eleven subjects at rest and after dobutamine infusion, at a heart rate that was ∼60% higher than the one in rest conditions. MKE and TKE were computed as volume integrals over the whole LV and as data mapped to functional LV flow components, i.e., direct flow, retained inflow, delayed ejection flow and residual volume. Diastolic MKE and TKE increased under stress, in particular at peak early filling and peak atrial contraction. Augmented LV inotropy and cardiac frequency also caused an increase in direct flow and retained inflow MKE and TKE. However, the TKE/KE ratio remained comparable between rest and stress conditions, suggesting that LV intracavitary fluid dynamics can adapt to stress conditions without altering the TKE to KE balance of the normal left ventricle at rest.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis.

BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Turbulent Intensity of Blood Flow in the Healthy Aorta Increases With Dobutamine Stress and is Related to Cardiac Output.

Introduction: The blood flow in the normal cardiovascular system is predominately laminar but operates close to the threshold to turbulence. Morphological distortions such as vascular and valvular stenosis can cause transition into turbulent blood flow, which in turn may cause damage to tissues in the cardiovascular system. A growing number of studies have used magnetic resonance imaging (MRI) to estimate the extent and degree of turbulent flow in different cardiovascular diseases. However, the way in which heart rate and inotropy affect turbulent flow has not been investigated. In this study we hypothesized that dobutamine stress would result in higher turbulence intensity in the healthy thoracic aorta. Method: 4D flow MRI data were acquired in twelve healthy subjects at rest and with dobutamine, which was infused until the heart rate increased by 60% when compared to rest. A semi-automatic segmentation method was used to segment the thoracic aorta in the 4D flow MR images. Subsequently, flow velocity and several turbulent kinetic energy (TKE) parameters were calculated in the ascending aorta, aortic arch, descending aorta and whole thoracic aorta. Results: With dobutamine infusion there was an increase in heart rate (66 ± 9 vs. 108 ± 13 bpm, p < 0.001) and stroke volume (88 ± 13 vs. 102 ± 25 ml, p < 0.01). Additionally, there was an increase in Peak Average velocity (0.7 ± 0.1 vs. 1.2 ± 0.2 m/s, p < 0.001, Peak Max velocity (1.3 ± 0.1 vs. 2.0 ± 0.2 m/s, p < 0.001), Peak Total TKE (2.9 ± 0.7 vs. 8.0 ± 2.2 mJ, p < 0.001), Peak Median TKE (36 ± 7 vs. 93 ± 24 J/m3, p = 0.002) and Peak Max TKE (176 ± 33 vs. 334 ± 69 J/m3, p < 0.001). The relation between cardiac output and Peak Total TKE in the whole thoracic aorta was very strong (R2 = 0.90, p < 0.001). Conclusion: TKE of blood flow in the healthy thoracic aorta increases with dobutamine stress and is strongly related to cardiac output. Quantification of such turbulence intensity parameters with cardiac stress may serve as a risk assessment of aortic disease development.

Wall shear stress and relative residence time as potential risk factors for abdominal aortic aneurysms in males: a 4D flow cardiovascular magnetic resonance case-control study.

BACKGROUND: Abdominal aortic aneurysms (AAA) can lead to catastrophic events such as dissection or rupture, and are an expression of general aortic disease. Low wall shear stress (WSS), high oscillatory shear index (OSI), and high relative residence time (RRT) have been correlated against increased uptake of inflammatory markers in the vessel wall and may improve risk stratification of AAA. We sought to obtain a comprehensive view of WSS, OSI, and RRT in the whole aorta for patients with AAA and age-matched elderly controls and young normal controls. METHODS: 4D Flow cardiovascular magnetic resonance images of the whole aorta were acquired in 18 AAA patients (70.8 ± 3.4 years), 22 age-matched controls (71.4 ± 3.4 years), and 23 young subjects (23.3 ± 3.1 years), all males. Three-dimensional segmentations of the whole aorta were created for all timeframes using a semi-automatic approach. The aorta was divided into five segments: ascending aorta, arch, descending aorta, suprarenal and infrarenal abdominal aorta. For each segment, average values of peak WSS, OSI, and RRT were computed. Student's t-tests were used to compare values between the three cohorts (AAA patients vs elderly controls, and elderly controls vs young controls) where the data were normally distributed, and the non-parametric Wilcoxon rank sum tests were used otherwise. RESULTS: AAA patients had lower peak WSS in the descending aorta as well as in the abdominal aorta compared to elderly controls (p ≤ 0.001), similar OSI, but higher RRT in the descending and abdominal aorta (p ≤ 0.001). Elderly controls had lower peak WSS compared to young controls throughout the aorta (p < 0.001), higher OSI in all segments except for the infrarenal aorta (p < 0.001), and higher RRT throughout the aorta, except the infrarenal aorta (p < 0.001). CONCLUSIONS: This study provides novel insights into WSS, OSI, and RRT in patients with AAA in relation to normal ageing, highlighting how AAA patients have markedly abnormal hemodynamic stresses not only in the infrarenal, but in the entire aorta. Moreover, we identified RRT as a marker for abnormal AAA hemodynamics. Further investigations are needed to explore if RRT or other measures of hemodynamics stresses best predict AAA growth and/or rupture.

Quantitative Magnetic Resonance Imaging Assessment of the Relationships Between Fat Fraction and R2* Inside Carotid Plaques, and Circulating Lipoproteins.

BACKGROUND: Lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) are morphological features of high-risk atherosclerotic plaques. However, their relationship to circulating lipoproteins is unclear. PURPOSE: To study associations between changes in lipoproteins vs. changes in LRNC (represented by fat fraction [FF]) and IPH (represented by R2*). STUDY TYPE: Prospective. SUBJECTS: Fifty-two patients with carotid plaques, 33 males (63.5%), mean age 72 (±5). FIELD STRENGTH/SEQUENCE: Four-point fast gradient Dixon magnetic resonance imaging (MRI) was used to quantify FF and R2* (to measure IPH) inside plaques and in vessel wall. Turbo-spin echo was used for T1 weighted sequences to guide manual segmentation. ASSESSMENT: Carotid MRI and serum lipid levels were assessed at baseline and at 1-year follow-up. For patients, lipid-lowering therapy was customized to reduce low-density lipoprotein (LDL) levels below 1.8 mmol/L. Segmentation was performed with one set of regions of interest for the plaque and one for the vessel wall at the location of the plaque. Thereby MRI data for FF, R2*, and volumes in plaque- and vessel-wall segmentations could be obtained from baseline and follow-up, as well as changes over the study year. STATISTICAL TESTS: Pearson correlation coefficient for correlations. Paired samples t-test for changes over time. Significance at P < 0.05, 95% confidence interval. RESULTS: LDL decreased significantly (2.19-1.88 mmol/L, Z - 2.9), without correlation to changes in plaque composition, nor to the significant reduction in vessel-wall volume (-106.3 mm3 ). Plaque composition remained unchanged, FF +8.5% (P = 0.366) and R2* +3.5% (P = 0.304). Compared to plaque segmentations, R2* was significantly lower in the vessel-wall segmentations both at baseline (-9.3%) and at follow-up (-9.1%). DATA CONCLUSION: The absence of correlations between changes in lipoproteins and changes in plaque composition indicates more complex relationships between these parameters than previously anticipated. The significant differences in both R2* and volume dynamics comparing plaque segmentations and vessel-wall segmentations suggest differences in their pathobiology of atherosclerosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

In-vitro and In-Vivo Assessment of 4D Flow MRI Reynolds Stress Mapping for Pulsatile Blood Flow.

Imaging hemodynamics play an important role in the diagnosis of abnormal blood flow due to vascular and valvular diseases as well as in monitoring the recovery of normal blood flow after surgical or interventional treatment. Recently, characterization of turbulent blood flow using 4D flow magnetic resonance imaging (MRI) has been demonstrated by utilizing the changes in signal magnitude depending on intravoxel spin distribution. The imaging sequence was extended with a six-directional icosahedral (ICOSA6) flow-encoding to characterize all elements of the Reynolds stress tensor (RST) in turbulent blood flow. In the present study, we aimed to demonstrate the feasibility of full RST analysis using ICOSA6 4D flow MRI under physiological conditions. First, the turbulence analysis was performed through in vitro experiments with a physiological pulsatile flow condition. Second, a total of 12 normal subjects and one patient with severe aortic stenosis were analyzed using the same sequence. The in-vitro study showed that total turbulent kinetic energy (TKE) was less affected by the signal-to-noise ratio (SNR), however, maximum principal turbulence shear stress (MPTSS) and total turbulence production (TP) had a noise-induced bias. Smaller degree of the bias was observed for TP compared to MPTSS. In-vivo study showed that the subject-variability on turbulence quantification was relatively low for the consistent scan protocol. The in vivo demonstration of the stenosis patient showed that the turbulence analysis could clearly distinguish the difference in all turbulence parameters as they were at least an order of magnitude larger than those from the normal subjects.

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study.

Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s-1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was - 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.

Automated segmentation of the individual branches of the carotid arteries in contrast-enhanced MR angiography using DeepMedic.

BACKGROUND: Non-invasive imaging is of interest for tracking the progression of atherosclerosis in the carotid bifurcation, and segmenting this region into its constituent branch arteries is necessary for analyses. The purpose of this study was to validate and demonstrate a method for segmenting the carotid bifurcation into the common, internal, and external carotid arteries (CCA, ICA, ECA) in contrast-enhanced MR angiography (CE-MRA) data. METHODS: A segmentation pipeline utilizing a convolutional neural network (DeepMedic) was tailored and trained for multi-class segmentation of the carotid arteries in CE-MRA data from the Swedish CardioPulmonsary bioImage Study (SCAPIS). Segmentation quality was quantitatively assessed using the Dice similarity coefficient (DSC), Matthews Correlation Coefficient (MCC), F2, F0.5, and True Positive Ratio (TPR). Segmentations were also assessed qualitatively, by three observers using visual inspection. Finally, geometric descriptions of the carotid bifurcations were generated for each subject to demonstrate the utility of the proposed segmentation method. RESULTS: Branch-level segmentations scored DSC = 0.80 ± 0.13, MCC = 0.80 ± 0.12, F2 = 0.82 ± 0.14, F0.5 = 0.78 ± 0.13, and TPR = 0.84 ± 0.16, on average in a testing cohort of 46 carotid bifurcations. Qualitatively, 61% of segmentations were judged to be usable for analyses without adjustments in a cohort of 336 carotid bifurcations without ground-truth. Carotid artery geometry showed wide variation within the whole cohort, with CCA diameter 8.6 ± 1.1 mm, ICA 7.5 ± 1.4 mm, ECA 5.7 ± 1.0 mm and bifurcation angle 41 ± 21°. CONCLUSION: The proposed segmentation method automatically generates branch-level segmentations of the carotid arteries that are suitable for use in further analyses and help enable large-cohort investigations.

In vitro experiments on ICOSA6 4D flow MRI measurement for the quantification of velocity and turbulence parameters.

PURPOSE: To perform comprehensive in vitro experiments using six-directional icosahedral flow encoding (ICOSA6) 4D flow magnetic resonance imaging (MRI) under various scan conditions to analyze the robustness of velocity and turbulence quantification. MATERIALS AND METHODS: In vitro flow phantoms with steady flow rates of 10 and 20 L/min were scanned using both conventional 4D flow MRI and ICOSA6. Experiments focused on comparisons between ICOSA6 and conventional four point (4P) methods, and the effects of contrast agents, velocity encoding range (Venc), and scan direction on velocity and turbulence quantification. RESULTS: The results demonstrated that 1) ICOSA6 improves the velocity-to-noise ratio (VNR) of velocity estimation by 33% (on average) and results in similar turbulent kinetic energy (TKE) estimation as the 4P method. 2) Measurements with a contrast agent resulted in more than a 2.5 fold increase in average VNR. However, the improvement of total TKE quantification was not obvious. 3) TKE estimation was less affected by Venc and the scan direction, whereas turbulence production (TP) estimation was largely affected by these measurement conditions. The effects of Venc and scan direction accounted for less than 11.63% of TKE estimation, but up to 33.89% of TP estimation. CONCLUSION: The ICOSA6 scheme is compatible with conventional 4D flow MRI for velocity and TKE measurement. Contrast agents are effective at increasing VNR, but not signal-to-noise ratio for TKE quantification. The effects of Venc and scan direction influence total TP more than total TKE.

Towards Automated Quantification of Vessel Wall Composition Using MRI.

BACKGROUND: MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. PURPOSE: To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. STUDY TYPE: Prospective. SUBJECTS: 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). FIELD STRENGTH/SEQUENCES: T1 -weighted (T1 W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. ASSESSMENT: The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T1 w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. STATISTICAL TESTS: Two-tailed t-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss' kappa. RESULTS: Automated segmentation of the CA using SVM had a Dice score of 0.89 ± 0.02 and true-positive ratio 0.93 ± 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 ± 2.5% considering FF and 1.1 ± 5.7[1/s] for R2*. LEVEL OF EVIDENCE: 1. TECHNICAL EFFICACY STAGE: 1. J. Magn. Reson. Imaging 2020;52:710-719.

Exploring the Relationships Between Hemodynamic Stresses in the Carotid Arteries.

Background: Atherosclerosis manifests as a focal disease, often affecting areas with complex hemodynamics such as the carotid bifurcation. The magnitude and regularity of the hemodynamic shear stresses acting on the vessel wall are thought to generate risk patterns unique to each patient and play a role in the pathogenesis of atherosclerosis. The involvement of different expressions of shear stress in the pathogenesis of carotid atherosclerosis highlights the need to characterize and compare the differential impact of the various expressions of shear stress in the atherosclerotic carotid bifurcation. Therefore, the aim of this study is to characterize and compare hemodynamic wall shear stresses (WSS) in the carotid arteries of subjects with asymptomatic atherosclerotic plaques. Shear stresses were also compared against vessel diameter and bifurcation angle to examine the relationships with the geometry of the carotid bifurcation. Methods: 4D Flow MRI and contrast-enhanced MRA data were acquired for 245 subjects with atherosclerotic plaques of at least 2.7 mm in conjunction with the Swedish CArdioPulmonary bioImage Study (SCAPIS). Following automatic segmentation and geometric analysis, time-resolved WSS and near-wall turbulent kinetic energy (nwTKE) were derived from the 4D Flow data. Whole-cycle parameters including time-averaged WSS and nwTKE, and the oscillatory shear index (OSI) were calculated. Pairwise Spearman rank-correlation analyses were used to investigate relationships among the hemodynamic as well as geometric parameters. Results: One hundred and seventy nine subjects were successfully segmented using automated tools and subsequently geometric and hemodynamic analyses were performed. Temporally resolved WSS and nwTKE were strongly correlated, ρ = 0.64. Cycle-averaged WSS and nwTKE were moderately correlated, ρ = 0.57. Cycle-average nwTKE was weakly correlated to OSI (ρ = -0.273), revealing that nwTKE provides information about disturbed flow on the vessel wall that OSI does not. In this cohort, there was large inter-individual variation for both WSS and nwTKE. Both WSS and nwTKE varied most within the external carotid artery. WSS, nwTKE, and OSI were weakly correlated to vessel diameter and bifurcation angle. Conclusion: The turbulent and mean component of WSS were examined together in vivo for the first time, and a strong correlation was found between them. nwTKE presents the opportunity to quantify turbulent wall stresses in vivo and gain insight into the effects of disturbed flow on the vessel wall. Neither vessel diameter nor bifurcation angle were found to be strongly correlated to the turbulent or mean component of WSS in this cohort.

Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI.

BACKGROUND: A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation. PURPOSE: To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order. STUDY TYPE: Retrospective. SUBJECTS: Eighteen healthy subjects (eight female, mean age 32 ± 5 years). FIELD STRENGTH AND SEQUENCE: 1.5 T. [Correction added on July 26, 2019, after first online publication: The preceding field strength was corrected.] SGRE and EPI-based 4D Flow MRI. ASSESSMENT: Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis. STATISTICAL TESTS: Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Student's t-test was used for comparison of flow volumes. RESULTS: No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R2 = 0.86-0.94 SGRE; 0.71-0.79 EPI, BC0-4). LV and right ventricular (RV) outflows and LV pathline flows were very strongly associated (R2 = 0.93-0.95 SGRE; 0.88-0.91 EPI, R2 = 0.91-0.95 SGRE; 0.91-0.93 EPI, BC1-4). EPI LV outflow was lower than the short-axis-based stroke volume. EPI RV outflow and proximal descending aortic flow were lower than SGREs. DATA CONCLUSION: Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2020;51:885-896.