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Abstract 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.

Abstract 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.

BackgroundIncreased 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).Methods4D 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.ResultsTortuosity and helicity were higher whereas TKE, velocity, and Reynolds number were lower in Old than in Young, for all aortic regions (p

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.

Abstract 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

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 equation-both 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; P

Abstract 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.

Abstract 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.

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.

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 >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.

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.

Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5×1.5×1.5 - 3×3×3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

BackgroundFlow 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.Methods43 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.ResultsGood correlation was found between 2D flow displacement and both maximum and average 3D values (r>0.8). Healthy controls had significantly lower flow displacement values with all approaches (p

PurposeTo 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 methodsVariable-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.ResultsUndersampling 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±2.56cm/s.ConclusionQualitative 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.

PurposeTo 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 methodsAn 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.ResultsThere 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).ConclusionArtifacts caused by the employed motion tasks deteriorated image quality in the nongated scans. These artifacts were alleviated with the proposed FID-navigator.

PurposeTo 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).Materials and methodsTwenty-five patients previously studied with four-dimensional (4D) Flow imaging who had at least two separate cross-sectional imaging studies to assess for aortic growth were included: tricuspid aortic valve (TAV) controls without valvular disease (n = 12) and patients with BAV (n = 13). Flow data from the ascending aorta was used for calculation of peak velocity, normalized flow displacement, maximum wall shear stress (WSS), mean WSS, and minimal WSS. Pearson's correlation was used to evaluate interobserver agreement, and linear regression to evaluate the correlation between the different hemodynamic markers and growth. Patient informed consent was waived by the institutional review board that approved the study.ResultsPeak velocity and flow displacement were very reproducible (r = 0.90-1.0 and r = 0.91-0.98, respectively). The range of WSS parameters was largely reproducible (0.47 < r < 0.96) with the greatest variability at the data extraction stage of analysis (0.47 < r < 0.85). Flow displacement best correlated with interval aortic growth (r = 0.65), peak velocity was moderately correlated (r = 0.35), but the WSS parameters did not correlate well with growth (r < 0.17).ConclusionFlow displacement is a simple and reproducible hemodynamic marker that shows good correlation with aortic growth in patients with bicuspid aortic valves.

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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.

ObjectivesThe authors sought to measure the turbulent kinetic energy (TKE) in the ascending aorta of patients with aortic stenosis and to assess its relationship to irreversible pressure loss.BackgroundIrreversible pressure loss caused by energy dissipation in post-stenotic flow is an important determinant of the hemodynamic significance of aortic stenosis. The simplified Bernoulli equation used to estimate pressure gradients often misclassifies the ventricular overload caused by aortic stenosis. The current gold standard for estimation of irreversible pressure loss is catheterization, but this method is rarely used due to its invasiveness. Post-stenotic pressure loss is largely caused by dissipation of turbulent kinetic energy into heat. Recent developments in magnetic resonance flow imaging permit noninvasive estimation of TKE.MethodsThe study was approved by the local ethics review board and all subjects gave written informed consent. Three-dimensional cine magnetic resonance flow imaging was used to measure TKE in 18 subjects (4 normal volunteers, 14 patients with aortic stenosis with and without dilation). For each subject, the peak total TKE in the ascending aorta was compared with a pressure loss index. The pressure loss index was based on a previously validated theory relating pressure loss to measures obtainable by echocardiography.ResultsThe total TKE did not appear to be related to global flow patterns visualized based on magnetic resonance-measured velocity fields. The TKE was significantly higher in patients with aortic stenosis than in normal volunteers (p < 0.001). The peak total TKE in the ascending aorta was strongly correlated to index pressure loss (R(2) = 0.91).ConclusionsPeak total TKE in the ascending aorta correlated strongly with irreversible pressure loss estimated by a well-established method. Direct measurement of TKE by magnetic resonance flow imaging may, with further validation, be used to estimate irreversible pressure loss in aortic stenosis.

Abstract Background Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements. Methods Forty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28–57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components’ volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components’ volume. Results The dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%–9.2% for the flow components’ volume ratio and between 13.5%–17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2–16.1% for the flow components’ volume ratio and 16.9–29.0% for the kinetic energy of the flow components. Conclusion LV flow components’ volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements.

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.

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 LV's compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling.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 P74 ml/m2 compared to patients with LVEDVI

Abstract Background The beating heart is the generator of blood flow through the cardiovascular system. Within the heart's own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data. Method In six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume. Results The volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 ± 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 ± 16) and Doppler ultrasound (58 ± 10), respectively. Calculated volumes of LV inflow (68 ± 11) and outflow (67 ± 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained. Conclusions This semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.