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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 T-1-weighted (T1W) 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 T(1)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-tailedt-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.

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 p 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.

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.

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BackgroundNon-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.MethodsA 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), F-2, F-0.5, 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.ResultsBranch-level segmentations scored DSC=0.800.13, MCC=0.80 +/- 0.12, F-2=0.82 +/- 0.14, F-0.5=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 degrees .ConclusionThe 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. Funding Agencies|Linkoping University; Region Ostergotland; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Swedish Research CouncilSwedish Research CouncilEuropean Commission; VINNOVA (Swedens Innovation agency)Vinnova; University of Gothenburg; Sahlgrenska University Hospital; Stockholm County CouncilStockholm County Council; Linkoping University Hospital; Lund University; Skane University Hospital; Umea University; Umea University Hospital; Uppsala University; Uppsala University Hospital

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. Funding Agencies|National Research Foundation of Korea - Ministry of Education [2018R1D1A1A02043249]; National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2020R1A2C2003843]

Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated.Patients had reduced direct flow proportion and direct-flow average KE compared with controls ( P0.0001). The residual volume proportion and residual volume average KE were increased in patients ( P0.0001). Importantly, in a multiple linear regression model to predict the patient's 6-minute walk test, the independent predictors were age (β=-0.3015; P=0.019) and direct-flow average KE (β=0.280, P=0.035; RThis study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

Background: Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated. Results: Patients had reduced direct flow proportion and direct-flow average KE compared with controls ( P P P =0.019) and direct-flow average KE (β=0.280, P =0.035; R 2 model, 0.466, P =0.002). In contrast, neither ejection fraction nor left ventricular volumes were independently predictive. Conclusions: This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

Purpose: To assess valvular flow characteristics and pressure drop in a variety of normal and stenotic prosthetic heart valves (PHVs) using 4D Flow MRI. Materials and methods: In-vitro flow phantoms with four different PHVs were studied: Medtronic-Hall tilting disc, St. Jude Medical standard bileaflet (STJM), Medtronic CoreValve Evolut R and Edwards SAPIEN 3. The valvular flow characteristics were investigated in normal and stenotic PHVs by using 4D Flow MRI. Results: The results showed that each valve provided a different amount of signal loss in the 4D Flow MRI. The defect size of the signal loss from each valve was 37.5 mm, 39.0 mm, 37.5 mm and 51.0 mm for the Tilting disk, STJM, SAPIEN 3 and CoreValve, respectively. The 4D Flow MRI-based estimation of the elevation of the pressure drop through the stenotic PHV using both Bernoulli-based and turbulence-based methods correlated well with the true values for the Tilting disc, STJM and SAPIEN 3 valve. However, the obstructive hemodynamics in the stenotic CoreValve was not clearly identified due to the large signal void from the long struts, resulting in a severe underestimation of the pressure drop using 4D Flow MRI. Conclusion: The Tilting disc, STJM and SAPIEN 3 valves provided reasonable estimates of peak velocity, turbulence production and the corresponding pressure drop. In contrast, the large strut of the CoreValve and corresponding signal void prevented accurate measurements of the velocity and turbulence production; therefore, 4D Flow MRI prediction of the pressure drop through the CoreValve was not feasible. Funding Agencies|European Union Seventh Framework Programme, European-Union (FP7/2007-2013) [310612]; Swedish Research Council, Sweden [2013-6077, 2014-6191]; Basic Science Research Program through the National Research Foundation of Korea, South Korea (NRF) - Ministry of Education [2018R1D1A1A02043249]

Purpose To validate pressure drop measurements using 4D flow MRI-based turbulence production in various shapes of stenotic stenoses. Methods In vitro flow phantoms with seven different 3D-printed aortic valve geometries were constructed and scanned with 4D flow MRI with six-directional flow encoding (ICOSA6). The pressure drop through the valve was non-invasively predicted based on the simplified Bernoulli, the extended Bernoulli, the turbulence production, and the shear-scaling methods. Linear regression and agreement of the predictions with invasively measured pressure drop were analyzed. Results All pressure drop predictions using 4D Flow MRI were linearly correlated to the true pressure drop but resulted in different regression slopes. The regression slope and 95% limits of agreement for the simplified Bernoulli method were 1.35 and 11.99 ± 21.72 mm Hg. The regression slope and 95% limits of agreement for the extended Bernoulli method were 1.02 and 0.74 ± 8.48 mm Hg. The regression slope and 95% limits of agreement for the turbulence production method were 0.89 and 0.96 ± 8.01 mm Hg. The shear-scaling method presented good correlation with an invasively measured pressure drop, but the regression slope varied between 0.36 and 1.00 depending on the shear-scaling coefficient. Conclusion The pressure drop assessment based on the turbulence production method agrees well with the extended Bernoulli method and invasively measured pressure drop in various shapes of the aortic valve. Turbulence-based pressure drop estimation can, as a complement to the conventional Bernoulli method, play a role in the assessment of valve diseases.

Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. Methods: Patients scheduled for carotid enda ...

Purpose: To explore the use of MR-estimated turbulence quantities for the assessment of turbulent flow effects on the vessel wall. Methods: Numerical velocity data for two patient-derived models wa ...

To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI.Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization.VRT (RFlow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.

PurposeTo measure the Reynolds stress tensor using 4D flow MRI, and to evaluate its contribution to computed pressure maps. MethodsA method to assess both velocity and Reynolds stress using 4D flow MRI is presented and evaluated. The Reynolds stress is compared by cross-sectional integrals of the Reynolds stress invariants. Pressure maps are computed using the pressure Poisson equationboth including and neglecting the Reynolds stress. ResultGood agreement is seen for Reynolds stress between computational fluid dynamics, simulated MRI, and MRI experiment. The Reynolds stress can significantly influence the computed pressure loss for simulated (eg, -0.52% vs -15.34% error; Pamp;lt;0.001) and experimental (eg, 30611 vs 203 +/- 6 Pa; Pamp;lt;0.001) data. A 54% greater pressure loss is seen at the highest experimental flow rate when accounting for Reynolds stress (Pamp;lt;0.001). Conclusion4D flow MRI with extended motion-encoding enables quantification of both the velocity and the Reynolds stress tensor. The additional information provided by this method improves the assessment of pressure gradients across a stenosis in the presence of turbulence. Unlike conventional methods, which are only valid if the flow is laminar, the proposed method is valid for both laminar and disturbed flow, a common presentation in diseased vessels. Magn Reson Med 79:1962-1971, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. Funding Agencies|European Union [310612]; National Institutes of Health [HL114118, NS059944]

Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling. Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC). Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P < 0.01] and 93 6 15 ml/m2[healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P < 0.01] and 1.91 6 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002). Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair. Funding agencies: European Research Council [310612]; Swedish Heart and Lung Foundation [20140398]; County Council of Ostergotland; Medical Research Council of Southeast Sweden (FORSS); Swedish Research Council [2013-6077, 2014-6191]

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43–56% of the stroke volume, respectively. In conclusion, fixed-volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

Purpose To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease. Materials and Methods 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed. Results The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m2; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures “DF/EDV volume-ratio” and “DF/EDV KE-ratio at ED” were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups. Conclusion We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

Flow displacement quantifies eccentric flow, a potential risk factor for aneurysms in the ascending aorta, but only at a single anatomic location. The aim of this study is to extend flow displacement analysis to 3D in patients with aortic and aortic valve pathologies.43 individuals were studied with 4DFlow MRI in 6 groups: healthy, tricuspid aortic valve (TAV) with aortic stenosis (AS) but no dilatation, TAV with dilatation but no AS, and TAV with both AS and dilatation, BAV without AS or dilatation, BAV without AS but with dilation. The protocol was approved by our institutional review board, and informed consent was obtained. Flow displacement was calculated for multiple planes along the ascending aorta, and 2D and 3D analyses were compared.Good correlation was found between 2D flow displacement and both maximum and average 3D values (r0.8). Healthy controls had significantly lower flow displacement values with all approaches (p0.05). The highest flow displacement was seen with stenotic TAV and aortic dilation (0.24±0.02 with maximum flow displacement). The 2D approach underestimated the maximum flow displacement by more than 20% in 13 out of 36 patients (36%).The extended 3D flow displacement analysis offers a more comprehensive quantitative evaluation of abnormal systolic flow in the ascending aorta than 2D analysis. Differences between patient subgroups are better demonstrated, and maximum flow displacement is more reliably assessed.

Purpose: To assess how 4D flow MRI-based pressure and energy loss estimates correspond to net transstenotic pressure gradients (TPG(net)) and their dependence on spatial resolution. Methods: Numeri ...

PurposeEvaluate spiral three-dimensional (3D) phase contrast MRI for the assessment of turbulence and velocity in stenotic flow. MethodsA-stack-of-spirals 3D phase contrast MRI sequence was evaluated in vitro against a conventional Cartesian sequence. Measurements were made in a flow phantom with a 75% stenosis. Both spiral and Cartesian imaging were performed using different scan orientations and flow rates. Volume flow rate, maximum velocity and turbulent kinetic energy (TKE) were computed for both methods. Moreover, the estimated TKE was compared with computational fluid dynamics (CFD) data. ResultsThere was good agreement between the turbulent kinetic energy from the spiral, Cartesian and CFD data. Flow rate and maximum velocity from the spiral data agreed well with Cartesian data. As expected, the short echo time of the spiral sequence resulted in less prominent displacement artifacts compared with the Cartesian sequence. However, both spiral and Cartesian flow rate estimates were sensitive to displacement when the flow was oblique to the encoding directions. ConclusionSpiral 3D phase contrast MRI appears favorable for the assessment of stenotic flow. The spiral sequence was more than three times faster and less sensitive to displacement artifacts when compared with a conventional Cartesian sequence. Funding Agencies|European Research Council [310612]; Swedish Research Council; Swedish e-Science Research Centre

The study of blood flow is essential in understanding the physiology and pathophysiology of the cardiovascular system. Small disturbances of the blood flow may over time evolve and contribute to cardiovascular pathology. While the blood flow in a healthy human appears to be predominately laminar, turbulent or transitional blood flow is thought to be involved in the pathogenesis of several cardiovascular diseases. Wall shear stress is the frictional force of blood on the vessel wall and has been linked to the pathogenesis of atherosclerosis and aneurysms. Despite the importance of hemodynamic factors, cardiovascular diagnostics largely relies on the indirect estimation of function based on morphological data.Time-resolved three-dimensional (3D) phase-contrast magnetic resonance imaging (MRI), often referred to as 4D flow MRI, is a versatile and non-invasive tool for cardiovascular blood flow assessment. The use of 4D flow MRI permits estimation of flow volumes, pressure losses, wall shear stress, turbulence intensity and many other unique hemodynamic parameters. However, 4D flow MRI suffers from long scan times, sometimes over 40 minutes. Furthermore, the accuracy of the many different 4D flow MRI-based applications and estimates have not been thoroughly examined.In this thesis, the accuracy of 4D flow MRI-based turbulence intensity mapping and wall shear stress estimation was investigated by using numerical simulations of MRI flow measurements. While the results from the turbulence intensity mapping agreed well with reference values from computational fluid dynamics data, the accuracy of the MRI-based wall shear stress estimates was found to be very sensitive to different parameters, especially to spatial resolution, and wall shear stress values over 5 N/m2 were not well resolved.To reduce the scan time, a 4D flow MRI sequence using spiral k-space trajectories was implemented and validated in-vivo and in-vitro. The scan time of 4D flow MRI was reduced by more than two-fold compared to a conventional Cartesian acquisition already accelerated using SENSE factor 2, and the data quality was maintained. For a 4D flow scan of the human heart, the use of spiral k-space trajectories resulted in a scan time of around 13 min, compared to 30 min for the Cartesian acquisition. By combining parallel imaging and spiral trajectories, the total scan time of a 4D flow measurement of the entire heart may be further reduced. This scan time reduction may also be traded for higher spatial resolution.Numerical simulation of 4D flow MRI may act as an important tool for future optimization and validation of the spiral 4D flow sequence. The scan-time reductions offered by the spiral k-space trajectories can help to cut costs, save time, reduce discomfort for the patient as well as to decrease the risk for motion artifacts. These benefits may facilitate an expanded clinical and investigative use of 4D flow MRI, including larger patient research studies.

Purpose: The objective of this study was to compare multiple methods for estimation of PWV from 4D flow MRI velocity data and to investigate if 4D flow MRI-based PWV estimation with piecewise linear regression modeling of travel-distance vs. travel time is sufficient to discern age-related regional differences in PWV. Methods: 4D flow MRI velocity data were acquired in 8 young and Solder (age: 23 +/- 2 vs. 58 +/- 2 years old) normal volunteers. Travel-time and travel-distance were measured throughout the aorta and piecewise linear regression was used to measure global PWV in the descending aorta and regional PWV in three equally sized segments between the top of the aortic arch and the renal arteries. Six different methods for extracting travel-time were compared. Results: Methods for estimation of travel-time that use information about the whole flow waveform systematically overestimate PWV when compared to methods restricted to the upslope-portion of the waveforms (p less than 0.05). In terms of regional PWV, a significant interaction was found between age and location (p less than 0.05). The age-related differences in regional PWV were greater in the proximal compared to distal descending aorta. Conclusion: Care must be taken as different classes of methods for the estimation of travel-time produce different results. 4D flow MRI-based PWV estimation with piecewise linear regression modeling of travel-distance vs. travel time can discern age-related differences in regional PWV well in line with previously reported data. Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Medical Research Council of Southeast Sweden (FORSS)

Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 ± 3.0 y.o.) and 20 old normal males (70.9 ± 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3–19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 ± 1.8 mJ, old = 6.4 ± 2.4 mJ, p < 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

The pressure drop across a stenotic vessel is an important parameter in medicine, providing a commonly used and intuitive metric for evaluating the severity of the stenosis. However, non-invasive estimation of the pressure drop under pathological conditions has remained difficult. This study demonstrates a novel method to quantify the irreversible pressure drop across a stenosis using 4D Flow MRI by calculating the total turbulence production of the flow. Simulation MRI acquisitions showed that the energy lost to turbulence production can be accurately quantified with 4D Flow MRI within a range of practical spatial resolutions (1-3 mm; regression slope = 0.91, R-2 = 0.96). The quantification of the turbulence production was not substantially influenced by the signal-to-noise ratio (SNR), resulting in less than 2% mean bias at SNR amp;gt; 10. Pressure drop estimation based on turbulence production robustly predicted the irreversible pressure drop, regardless of the stenosis severity and post-stenosis dilatation (regression slope = 0.956, R-2 = 0.96). In vitro validation of the technique in a 75% stenosis channel confirmed that pressure drop prediction based on the turbulence production agreed with the measured pressure drop (regression slope = 1.15, R-2 = 0.999, Bland-Altman agreement = 0.75 +/- 3.93 mmHg). Funding Agencies|European Research Council [310612]; Swedish Research Council [2013-6077, 2014-6191]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2016R1A6A3A03006337]

Purpose To investigate an effective time-resolved variable-density random undersampling scheme combined with an efficient parallel image reconstruction method for highly accelerated aortic 4D flow MR imaging with high reconstruction accuracy. Materials and Methods Variable-density Poisson-disk sampling (vPDS) was applied in both the phase-slice encoding plane and the temporal domain to accelerate the time-resolved 3D Cartesian acquisition of flow imaging. In order to generate an improved initial solution for the iterative self-consistent parallel imaging method (SPIRiT), a sample-selective view sharing reconstruction for time-resolved random undersampling (STIRRUP) was introduced. The performance of different undersampling and image reconstruction schemes were evaluated by retrospectively applying those to fully sampled data sets obtained from three healthy subjects and a flow phantom. Results Undersampling pattern based on the combination of time-resolved vPDS, the temporal sharing scheme STIRRUP, and parallel imaging SPIRiT, were able to achieve 6-fold accelerated 4D flow MRI with high accuracy using a small number of coils (N = 5). The normalized root mean square error between aorta flow waveforms obtained with the acceleration method and the fully sampled data in three healthy subjects was 0.04 ± 0.02, and the difference in peak-systolic mean velocity was − 0.29 ± 2.56 cm/s. Conclusion Qualitative and quantitative evaluation of our preliminary results demonstrate that time-resolved variable-density random sampling is efficient for highly accelerating 4D flow imaging while maintaining image reconstruction accuracy.

Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients w ...

Bicuspid aortic valve (BAV)-related aortopathy is characterized by histological abnormalities that result in aortic wall stiffening and aortic dilation. The study aim was to determine the range of ascending aortic stiffness seen in a clinical cohort of patients with BAV, and to identify the association of aortic stiffness with standard clinical and imaging parameters.Patients with BAV (n = 65) and normal subjects (n = 10) were studied using conventional phase-contrast magnetic resonance imaging through the ascending aorta. Local aortic stiffness was estimated by measuring pulse wave velocity (PWV) using the flow-area (QA) method. Correlations between PWV and other imaging and clinical variables were assessed, and multiple linear regression models were used to examine independent predictors of PWV.BAV patients demonstrated a significantly higher mean PWV compared to normal subjects (6.53 ± 5.88 versus 3.51 ± 0.92 m/s; p0.01) with a considerably wider range of values noted in the BAV group. Significant associations were found between PWV and age (r = 0.4, p0.001) and history of hypertension (r = 0.36, p = 0.005) in the overall BAV cohort. The correlation between age and PWV was significantly strengthened above 40 years of age. In a subgroup of BAV patients aged40 years (n = 37) there were no significant predictors of PWV identified by multiple linear regression models.BAV patients demonstrated an increased average ascending aortic stiffness and a dramatically higher range of stiffness values compared to normal subjects. Increased stiffness is not predicted by standard clinical or imaging parameters in patients aged40 years. Ascending aortic stiffness may be a unique marker of early aortic dysfunction in young BAV patients.

PURPOSE:To develop a framework for prospective free-induction decay (FID)-based navigator gating for suppression of motion artifacts in carotid magnetic resonance imaging (MRI) and to assess its capability in vivo.MATERIALS AND METHODS:An FID-navigator, comprising a spatially selective low flip-angle sinc-pulse followed by an analog-to-digital converter (ADC) readout, was added to a conventional turbo spin-echo (TSE) sequence. Real-time navigator processing delivered accept/reject-and-reacquire decisions to the sequence. In this Institutional Review Board (IRB)-approved study, seven volunteers were scanned with a 2D T2-weighted TSE sequence. A reference scan with volunteers instructed to minimize motion as well as nongated and gated scans with volunteers instructed to perform different motion tasks were performed in each subject. Multiple image quality measures were employed to quantify the effect of gating.RESULTS:There was no significant difference in lumen-to-wall sharpness (2.3 ± 0.3 vs. 2.3 ± 0.4), contrast-to-noise ratio (CNR) (9.0 ± 2.0 vs. 8.5 ± 2.0), or image quality score (3.1 ± 0.9 vs. 2.6 ± 1.2) between the reference and gated images. For images acquired during motion, all image quality measures were higher (P < 0.05) in the gated compared to nongated images (sharpness: 2.3 ± 0.4 vs. 1.8 ± 0.5, CNR: 8.5 ± 2.0 vs. 7.2 ± 2.0, score: 2.6 ± 1.2 vs. 1.8 ± 1.0).CONCLUSION:Artifacts caused by the employed motion tasks deteriorated image quality in the nongated scans. These artifacts were alleviated with the proposed FID-navigator.

Purpose To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV).

Quantitative aortic magnetic resonance (MR) blood flow imaging is a rapidly advancing technique that is likely to impact clinical medicine in the near future. The acquisition of comprehensive 4D velocity datasets is now possible in a clinically acceptable time frame. Unique and intuitive visualization methods are available. A number of important hemodynamic biomarkers can be derived from the data, and exploited to help understand how abnormal flow is inter-related with aortic pathology. Initial data suggest that some of the derived biomarkers can refine the clinical assessment of aortic disease and predict disease progression. We provide an overview of aortic imaging with emphasis on how flow imaging is currently used, discuss the fundamental technical aspects of multidimensional MR flow imaging, introduce key hemodynamic markers, and show how this type of imaging may soon be used for the early identification of patients at risk for the development of potentially devastating aortic complications.

Purpose The purpose of this work was to assess the impact of respiratory motion and to compare methods for suppression of respiratory motion artifacts in 4D Flow MRI. Methods A numerical 3D aorta phantom was designed based on an aorta velocity field obtained by computational fluid mechanics. Motion‐distorted 4D Flow MRI measurements were simulated and several different motion‐suppression techniques were evaluated: Gating with fixed acceptance window size, gating with different window sizes in inner and outer k‐space, and k‐space reordering. Additionally, different spatial resolutions were simulated. Results Respiratory motion reduced the image quality. All motion‐suppression techniques improved the data quality. Flow rate errors of up to 30% without gating could be reduced to less than 2.5% with the most successful motion suppression methods. Weighted gating and gating combined with k‐space reordering were advantageous compared with conventional fixed‐window gating. Spatial resolutions finer than the amount of accepted motion did not lead to improved results. Conclusion Respiratory motion affects 4D Flow MRI data. Several different motion suppression techniques exist that are capable of reducing the errors associated with respiratory motion. Spatial resolutions finer than the degree of accepted respiratory motion do not result in improved data quality. Magn Reson Med 78:1877–1882, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution Non‐Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques.Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60 × 0.60 × 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH.Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64 ± 0.2737% versus 9.294 ± 0.1762% (mean ± standard error of the mean [SEM]; P 0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 ± 1.276 sQuantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH. Magn Reson Med 78:285-296, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Aims: 4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LVs compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling. Methods and Results: We acquired 4D flow and morphological MRI data from 26 patients with chronic ischemic heart disease with New York Heart Association (NYHA) class I and II and with no to mild LV systolic dysfunction and remodeling, and from 10 healthy controls. A previously validated method was used to separate the LV end-diastolic volume (LVEDV) into functional components: direct flow, which passes directly to ejection, and non-ejecting flow, which remains in the LV for at least 1 cycle. The direct flow and non-ejecting flow proportions of end-diastolic volume and KE were assessed. The proportions of direct flow volume and KE fell with increasing LVEDV-index (LVEDVI) and LVESV-index (LVESVI) (direct flow volume r = -0.64 and r = -0.74, both Pamp;lt;0.001; direct flow KE r = -0.48, P = 0.013, and r = -0.56, P = 0.003). The proportions of non-ejecting flow volume and KE rose with increasing LVEDVI and LVESVI (non-ejecting flow volume: r = 0.67 and r = 0.76, both Pamp;lt;0.001; non-ejecting flow KE: r = 0.53, P = 0.005 and r = 0.52, P = 0.006). The proportion of direct flow volume correlated moderately to LVEF (r = 0.68, P amp;lt; 0.001) and was higher in a sub-group of patients with LVEDVI amp;gt; 74 ml/m(2) compared to patients with LVEDVI amp;lt; 74 ml/m(2) and controls (both Pamp;lt;0.05). Conclusion: Direct flow volume and KE proportions diminish with increased LV volumes, while non-ejecting flow proportions increase. A decrease in direct flow volume and KE at end-diastole proposes that alterations in these novel 4D flow-specific markers may detect LV dysfunction even in subtle or subclinical LV remodeling. Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Union FP7 [223615]; Medical Research Council of Southeast Sweden [FORSS-35141, FORSS-88731, FORSS-157921]; County Council of Ostergotland/Heart and Medicine Center [20090120]

Flow-induced blood damage plays an important role in determining the hemodynamic impact of abnormal blood flow, but quantifying of these effects, which are dominated by shear stresses in highly fluctuating turbulent flow, has not been feasible. This study evaluated the novel application of turbulence tensor measurements using simulated 4D Flow MRI data with six-directional velocity encoding for assessing hemodynamic stresses and corresponding blood damage index (BDI) in stenotic turbulent blood flow. The results showed that 4D Flow MRI underestimates the maximum principal shear stress of laminar viscous stress (PLVS), and overestimates the maximum principal shear stress of Reynolds stress (PRSS) with increasing voxel size. PLVS and PRSS were also overestimated by about 1.2 and 4.6 times at medium signal to noise ratio (SNR) = 20. In contrast, the square sum of the turbulent viscous shear stress (TVSS), which is used for blood damage index (BDI) estimation, was not severely affected by SNR and voxel size. The square sum of TVSS and the BDI at SNR amp;gt;20 were underestimated by less than 1% and 10%, respectively. In conclusion, this study demonstrated the feasibility of 4D Flow MRI based quantification of TVSS and BDI which are closely linked to blood damage. Funding Agencies|European Research Council [310612]; Swedish Research Council [2013-6077, 2014-6191]; National Research Foundation of Korea (NRF) - Ministry of Education [2016R1A6A3A03006337]