Background Advances in four-dimensional fow cardiovascular magnetic resonance (4D fow CMR) have allowed quantifcation of left ventricular (LV) and right ventricular (RV) blood fow. We aimed to (1)... Show moreBackground Advances in four-dimensional fow cardiovascular magnetic resonance (4D fow CMR) have allowed quantifcation of left ventricular (LV) and right ventricular (RV) blood fow. We aimed to (1) investigate age and sex diferences of 4D fow CMR-derived LV and RV relative fow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the efects of age and sex on these parameters. Methods We performed 4D fow analysis in 163 healthy participants (42% female; mean age 43±13 years) of a pro‑ spective registry study (NCT03217240) who were free of cardiovascular diseases. Relative fow components (direct fow, retained infow, delayed ejection fow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. Results Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct fow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no diferences in fow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased signifcantly (r=0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r=− 0.355 for LV and − 0.318 for RV), and KEiEDV E/A ratio (r=− 0.475 for LV and − 0.504 for RV) decreased signifcantly, with age. Conclusion These data using state-of-the-art 4D fow CMR show that biventricular fow components and kinetic energy parameters vary signifcantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular fow. Show less
Wu, X.L.; Saaid, H.; Voorneveld, J.; Claessens, T.; Westenberg, J.J.M.; Jong, N. de; ... ; Kenjeres, S. 2023
PurposeIntraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure)... Show morePurposeIntraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice.MethodsIn this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed.ResultsAs a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction.ConclusionsThis work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis. Show less
Pulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the... Show morePulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the ability to quantify flow within an entire volume instead of a single plane. The aim of this study was to compare PA maximum velocities and stroke volumes between 4D flow CMR, two-dimensional phase-contrast (2D PCMR) and echocardiography. A prospective study including TGA patients after ASO was performed between December 2018 and October 2020. All patients underwent echocardiography and CMR, including 2D PCMR and 4D flow CMR. Maximum velocities and stroke volumes were measured in the main, right, and left PA (MPA, LPA, and RPA, respectively). A total of 39 patients aged 20 ± 8 years were included. Maximum velocities in the MPA, LPA, and RPA measured by 4D flow CMR were significantly higher compared to 2D PCMR (p < 0.001 for all). PA assessment by echocardiography was not possible in the majority of patients. 4D flow CMR maximum velocity measurements were consistently higher than those by 2D PCMR with a mean difference of 65 cm/s for the MPA, and 77 cm/s for both the RPA and LPA. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Maximum velocities in the PAs after ASO for TGA are consistently lower by 2D PCMR, while echocardiography only allows for PA assessment in a minority of cases. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Show less
Background: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve... Show moreBackground: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve during systole.Purpose: To assess multiphase segmentations and multiphase quantification of flow-related parameters in aortic 4D flow MRI.Study Type: Prospective.Population: 40 healthy volunteers (50% male, 28.9 +/- 5.0 years) and 10 patients with thoracic aortic aneurysm (80% male, 54 +/- 8 years).Field Strength/Sequence: 4D flow MRI with a velocity encoded turbo field echo sequence at 3 T.Assessment: Phase-specific segmentations were obtained for the aortic root and the ascending aorta. The whole aorta was segmented in peak systole. In all aortic segments, time to peak (TTP; for flow velocity, vorticity, helicity, kinetic energy, and viscous energy loss) and peak and time-averaged values (for velocity and vorticity) were calculated.Statistical Tests: Static vs. phase-specific models were assessed using Bland-Altman plots. Other analyses were performed using phase-specific segmentations for aortic root and ascending aorta. TTP for all parameters was compared to TTP of flow rate using paired t-tests. Time-averaged and peak values were assessed using Pearson correlation coefficient. P < 0.05 was considered statistically significant.Results: In the combined group, velocity in static vs. phase-specific segmentations differed by 0.8 cm/sec for the aortic root, and 0.1 cm/sec (P = 0.214) for the ascending aorta. Vorticity differed by 167 sec(-1) mL(-1) (P = 0.468) for the aortic root, and by 59 sec(-1) mL(-1) (P = 0.481) for the ascending aorta. Vorticity, helicity, and energy loss in the ascending aorta, aortic arch, and descending aorta peaked significantly later than flow rate. Time-averaged velocity and vorticity values correlated significantly in all segments.Data Conclusion: Static 4D flow MRI segmentation yields comparable results as multiphase segmentation for flow-related parameters, eliminating the need for time-consuming multiple segmentations. However, multiphase quantification is necessary for assessing peak values of aortic flow-related parameters. Show less
Nabeta, T.; Meucci, M.C.; Westenberg, J.J.M.; Reiber, J.H.C.; Knuuti, J.; Bijl, P. van der; ... ; Bax, J.J. 2023
Risk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV... Show moreRisk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV systolic function, derived from feature tracking cardiac magnetic resonance (CMR) imaging. We aimed to investigate the prognostic impact of InD in patients with IHD and prior myocardial infarction. A total of 111 patients (mean age 57 +/- 10, 86% male) with a history of myocardial infarction who underwent CMR were included. LV InD was quantified by measuring the displacement of endocardially tracked points towards the centreline of the LV during systole with feature tracking CMR. The endpoint was a composite of all-cause mortality, heart failure hospitalization and arrhythmic events. During a median follow-up of 142 (IQR 107-159) months, 31 (27.9%) combined events occurred. Kaplan-Meier analysis demonstrated that patients with LV InD below the study population median value (23.0%) had a significantly lower event-free survival (P < 0.001). LV InD remained independently associated with outcomes (HR 0.90, 95% CI 0.84-0.98, P = 0.010) on multivariate Cox regression analysis. InD also provided incremental prognostic value to LVEF, LV global radial strain and CMR scar burden. LV InD, measured with feature tracking CMR, was independently associated with outcomes in patients with IHD and prior myocardial infarction. LV InD also provided incremental prognostic value, in addition to LVEF and LV global radial strain. LV InD holds promise as a pragmatic imaging biomarker for post-infarct risk stratification. Show less
Background It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS).... Show moreBackground It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS). However, the effects of ageing on aortic hemodynamics have not yet been described. Case summary 4D-Flow MRI derived aorta hemodynamics were derived in the ascending aorta of a patient with ascending aortic aneurysm (mean +/- standard deviation: 46 +/- 1 mm) and a healthy volunteer (aortic diameter 30 +/- 1 mm) with long-term follow-up of ten and eight years, respectively. At all timepoints, compared to the healthy volunteer, the patient demonstrated higher magnitudes of FDN (7% +/- 1% vs. 3% +/- 1%) and WSS angle (36 degrees +/- 3 degrees vs. 24 degrees +/- 6 degrees), and lower WSS magnitude (565 +/- 100 mPa vs. 910 +/- 115 mPa), axial WSS (426 +/- 71 mPa vs. 800 +/- 108 mPa) and circumferential WSS (297 +/- 64 mPa vs. 340 +/- 85 mPa). The patient and healthy volunteer demonstrated different aortic dilatation rates (regression slope +/- standard error: 0.2 +/- 0.1 vs. 0.1 +/- 0.2 mm per year) and trends in FDN (0.1% +/- 0.1% vs. 0.1% +/- 0.2% per year), WSS magnitude (22 +/- 9 vs. 35 +/- 13 mPa per year), axial WSS (19 +/- 4 vs. 37 +/- 7 mPa per year), circumferential WSS (9 +/- 8 vs. 5 +/- 15 mPa per year), and WSS angle (-0.5 degrees +/- 0.4 degrees vs. -0.8 degrees +/- 1.0 degrees per year). Discussion Aortic hemodynamic parameters are marginally affected by ageing and the aortic diameter in this case series. Since aortic hemodynamic parameters have been associated with aortic dilation by previous studies, the outcomes of the two subjects suggest that the aortic dilatation rate will remain constant while individuals are ageing and dilating. Show less
Background: Particle tracing based on 4D Flow MRI has been applied as a quantitative and qualitative postprocessing technique to study temporally evolving blood flow patterns. Purpose: To... Show moreBackground: Particle tracing based on 4D Flow MRI has been applied as a quantitative and qualitative postprocessing technique to study temporally evolving blood flow patterns. Purpose: To systematically review the various methods to perform 4D Flow MRI-based particle tracing, as well as the clinical value, clinical applications, and current developments of the technique. Study type: The study type is systematic review. Subjects: Patients with cardiovascular disease (such as Marfan, Fontan, Tetralogy of Fallot), healthy controls, and cardiovascular phantoms that received 4D Flow MRI with particle tracing. Field Strength/Sequence: Three-dimensional three-directional cine phase-contrast MRI, at 1.5 T and 3 T. Assessment: Two systematic searches were performed on the PubMed database using Boolean operators and the relevant key terms covering 4D Flow MRI and particle tracing. One systematic search was focused on particle tracing methods, whereas the other on applications. Additional articles from other sources were sought out and included after a similar inspection. Particle tracing methods, clinical applications, clinical value, and current developments were extracted. Statistical Tests: The main results of the included studies are summarized, without additional statistical analysis. Results: Of 127 unique articles retrieved from the initial search, 56 were included (28 for methods and 54 for applications). Most articles that described particle tracing methods used an adaptive timestep, a fourth order Runge-Kutta integration method, and linear interpolation in the time dimension. Particle tracing was applied in heart chambers, aorta, venae cavae, Fontan circulation, pulmonary arteries, abdominal vasculature, peripheral arteries, carotid arteries, and cerebral vasculature. Applications were grouped as intravascular, intracardiac, flow stasis, and research. Data Conclusions: Particle tracing based on 4D Flow MRI gives unique insight into blood flow in several cardiovascular diseases, but the quality depends heavily on the MRI data quality. Further studies are required to evaluate the clinical value of the technique for different cardiovascular diseases. Evidence Level: 5. Technical Efficacy: Stage 1. Show less
OBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection ... Show moreOBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics. METHODS: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16-20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm(2)/l/min). Peak (predicted) oxygen uptake was assessed. RESULTS: The median age was 16.2 years (Q1-Q3 14.0-18.2). The normalized mean conduit CSA was 35-73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P < 0.001). The median TCPC pressure gradient was 0.7 mmHg (Q1-Q3 0.5-0.8) and 2.0 (Q1-Q3 1.4-2.6) during rest and simulated exercise, respectively. A moderate-strong inverse non-linear relationship was present between normalized mean conduit CSA and TCPC haemodynamics in rest and exercise. TCPC pressure gradients of >= 1.0 at rest and >= 3.0 mmHg during simulated exercise were observed in patients with a conduit CSA <= 45 mm(2)/l/min and favourable haemodynamics (< 1 mmHg during both rest and exercise) in conduits >= 125 mm(2)/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake. CONCLUSIONS: Extracardiac conduits of 16-20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics. Show less
Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that... Show moreBackground Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (beta=0.253), heart rate (beta=0.236), systolic blood pressure (beta=-0.264), and diastolic blood pressure (beta=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (beta=0.248) and fasting glucose (beta=0.242), next to aortic lumen area (beta=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease. Show less
Abstract OBJECTIVES Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by... Show moreAbstract OBJECTIVES Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by altered flow dynamics. Aortic wall shear stress (WSS) distribution at rest and under dobutamine stress (DS) conditions using 4D flow magnetic resonance imaging were investigated in relation to thoracic aorta geometry. METHODS 4D flow magnetic resonance imaging was performed in 16 adolescent TGA patients after ASO (rest and DS condition) and in 10 healthy controls (rest). The primary outcome measure was the WSS distribution along the aortic segments and the WSS change with DS in TGA patients. Based on the results, we secondary zoomed in on factors [aortic geometry and left ventricular (LV) function parameters] that might relate to these WSS distribution differences. Aortic diameters, arch angle, LV function parameters (stroke volume, LV ejection fraction, cardiac output) and peak systolic aortic WSS were obtained. RESULTS TGA patients had significantly larger neoaortic root and smaller mid-ascending aorta (AAo) dimensions and aortic arch angle. At rest, patients had significantly higher WSS in the entire thoracic aorta, except for the dilated root. High WSS levels beyond the proximal AAo were associated with the diameter decrease from the root to the mid-AAo (correlation coefficient r = 0.54–0.59, P = 0.022–0.031), not associated with the aortic arch angle. During DS, WSS increased in all aortic segments (P < 0.001), most pronounced in the AAo segments. The increase in LV ejection fraction, stroke volume and cardiac output as a result of DS showed a moderate linear relationship with the WSS increase in the distal AAo (correlation coefficient r = 0.54–0.57, P = 0.002–0.038). CONCLUSIONS Increased aortic WSS was observed in TGA patients after ASO, related to the ASO-specific geometry, which increased with DS. Stress-enhanced elevated WSS may play a role in neoaortic root dilatation and anterior aortic wall thinning of the distal AAo. Show less
Juffermans, J.F.; Assen, H.C. van; Kiefte, B.J.C. te; Ramaekers, M.J.F.G.; Palen, R.L.F. van der; Boogaard, P. van den; ... ; Westenberg, J.J.M. 2022
(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm ... Show more(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 +/- 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16-30% and ICC = 0.84-0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3-26% and ICC = 0.87-1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3-10% and ICC = 0.96-1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients. Show less
Aim This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise... Show moreAim This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. Background The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). Methods Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. Results Sixty-two Fontan patients were included (53% male, 17.3 +/- 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 +/- 6.2 ml/kg/min, 56 +/- 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. Conclusions Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency. Show less
The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease ... Show moreThe prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from 'The Cognitive decline in Older Patients with End stage renal disease' (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology. Show less
Identification of flow patterns within the heart has long been recognized as a potential contribution to the understanding of physiological and pathophysiological processes of cardiovascular... Show moreIdentification of flow patterns within the heart has long been recognized as a potential contribution to the understanding of physiological and pathophysiological processes of cardiovascular diseases. Although the pulsatile flow itself is multi-dimensional and multi-directional, current available non-invasive imaging modalities in clinical practice provide calculation of flow in only 1-direction and lack 3-dimensional volumetric velocity information. Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) has emerged as a novel tool that enables comprehensive and critical assessment of flow through encoding velocity in all 3 directions in a volume of interest resolved over time. Following technical developments, 4D flow CMR is not only capable of visualization and quantification of conventional flow parameters such as mean/peak velocity and stroke volume but also provides new hemodynamic parameters such as kinetic energy. As a result, 4D flow CMR is being extensively exploited in clinical research aiming to improve understanding of the impact of cardiovascular disease on flow and vice versa. Of note, the analysis of 4D flow data is still complex and accurate analysis tools that deliver comparable quantification of 4D flow values are a necessity for a more widespread adoption in clinic. In this article, the acquisition and analysis processes are summarized and clinical applications of 4D flow CMR on the heart including conventional and novel hemodynamic parameters are discussed. Finally, clinical potential of other emerging intra-cardiac 4D flow imaging modalities is explored and a near-future perspective on 4D flow CMR is provided. Show less
Purpose To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). Methods Three 3T MRI experiments were... Show morePurpose To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). Methods Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume. Results In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were <= 5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 +/- 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow. Conclusions Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (<= 10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers. Show less
Rijnberg, F.M.; Woude, S.F.S. van der; Hazekamp, M.G.; Boogaard, P.J. van den; Lamb, H.J.; Monteros, C.T.E. de los; ... ; Roest, A.A.W. 2021
OBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit... Show moreOBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit velocity mismatch factor along the respiratory cycle.METHODS: Real-time 2D flow MRI was prospectively acquired in 50 extracardiac (16-20mm conduits) Fontan patients (mean age 16.9 +/- 4.5 years) at the subhepatic IVC, conduit and superior vena cava. Hepatic venous flow was determined by subtracting IVC flow from conduit flow. The cross-sectional area (CSA) was reported for each vessel. Mean flow and velocity was calculated during the average respiratory cycle, inspiration and expiration. The IVC-conduit velocity mismatch factor was determined as follows: V-conduit/V-IVC where V is the mean velocity.RESULTS: Median conduit CSA and IVC CSA were 221 mm(2) (Q1-Q3 201-255) and 244 mm(2) (Q1-Q3 203-265), respectively. From the IVC towards the conduit, flow rates increased significantly due to the entry of hepatic venous flow (IVC 1.9, Q1-Q3 1.5-2.2) versus conduit (3.3, Q1-Q3 2.5-4.0 1/min, P < 0.001). Consequently, mean velocity significantly increased (IVC 12 (Q1-Q3 11-14 cm/s) versus conduit 25 (Q1-Q3 17-31 cm/s), P < 0.001), resulting in a median IVC-conduit velocity mismatch of 1.8 (Q1-Q3 1.5-2.4), further augmenting during inspiration (median 2.3, Q1-Q3 1.8-3.0). IVC-conduit mismatch was inversely related to measured conduit size and positively correlated with conduit flow. The normalized IVC-conduit velocity mismatch factor during expiration and the entire respiratory cycle correlated with peak VO2 (r = -0.37, P = 0.014 and r = -0.31, P = 0.04, respectively).CONCLUSIONS: Important blood flow accelerations are observed from the IVC towards the conduit in adolescent Fontan patients, which is related to peak VO2. This study, therefore, raises concerns that implanted 16-20mm conduits have become undersized for older Fontan patients and future studies should clarify its effect on long-term outcome. Show less
Background Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures.... Show moreBackground Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. Hypothesis Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. Study Type Prospective. Population Twelve healthy subjects and eight patients with valvular regurgitation. Field Strength/Sequence 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. Assessment Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. Statistical Tests We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. Results PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 +/- 0.8 [8.7 +/- 1.1] mL/beat for PROUD, 5.5 +/- 2.9 [13.7 +/- 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 +/- 1.2 [15.3 +/- 5.9] mL/beat for PROUD, 0.6 +/- 0.6 [19.3 +/- 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. Conclusion PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. Level of Evidence 1 Technical Efficacy Stage 2 Show less
Background Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures.... Show moreBackground Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. Hypothesis Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. Study Type Prospective. Population Twelve healthy subjects and eight patients with valvular regurgitation. Field Strength/Sequence 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. Assessment Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. Statistical Tests We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. Results PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 +/- 0.8 [8.7 +/- 1.1] mL/beat for PROUD, 5.5 +/- 2.9 [13.7 +/- 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 +/- 1.2 [15.3 +/- 5.9] mL/beat for PROUD, 0.6 +/- 0.6 [19.3 +/- 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. Conclusion PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. Level of Evidence 1 Technical Efficacy Stage 2 Show less
In this study, we analyzed turbulent flows through a phantom (a 180 degrees bend with narrowing) at peak systole and a patient-specific coarctation of the aorta (CoA), with a pulsating flow, using... Show moreIn this study, we analyzed turbulent flows through a phantom (a 180 degrees bend with narrowing) at peak systole and a patient-specific coarctation of the aorta (CoA), with a pulsating flow, using magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). For MRI, a 4D-flow MRI is performed using a 3T scanner. For CFD, the standard k - epsilon, shear stress transport k - omega, and Reynolds stress (RSM) models are applied. A good agreement between measured and simulated velocity is obtained for the phantom, especially for CFD with RSM. The wall shear stress (WSS) shows significant differences between CFD and MRI in absolute values, due to the limited near-wall resolution of MRI. However, normalized WSS shows qualitatively very similar distributions of the local values between MRI and CFD. Finally, a direct comparison between in vivo 4D-flow MRI and CFD with the RSM turbulence model is performed in the CoA. MRI can properly identify regions with locally elevated or suppressed WSS. If the exact values of the WSS are necessary, CFD is the preferred method. For future applications, we recommend the use of the combined MRI/CFD method for analysis and evaluation of the local flow patterns and WSS in the aorta. Show less
Congenital heart disease is the most common birth defect and functionally univentricular heart defects represent the most severe end of this spectrum. The Fontan circulation provides an unique... Show moreCongenital heart disease is the most common birth defect and functionally univentricular heart defects represent the most severe end of this spectrum. The Fontan circulation provides an unique solution for single ventricle patients, by connecting both caval veins directly to the pulmonary arteries. As a result, the pulmonary circulation in Fontan palliated patients is characterized by a passive, low-energy circulation that depends on increased systemic venous pressure to drive blood toward the lungs. The absence of a subpulmonary ventricle led to the widely believed concept that respiration, by sucking blood to the pulmonary circulation during inspiration, is of great importance as a driving force for antegrade blood flow in Fontan patients. However, recent studies show that respiration influences pulsatility, but has a limited effect on net forward flow in the Fontan circulation. Importantly, since MRI examination is recommended every 2 years in Fontan patients, clinicians should be aware that most conventional MRI flow sequences do not capture the pulsatility of the blood flow as a result of the respiration. In this review, the unique flow dynamics influenced by the cardiac and respiratory cycle at multiple locations within the Fontan circulation is discussed. The impact of (not) incorporating respiration in different MRI flow sequences on the interpretation of clinical flow parameters will be covered. Finally, the influence of incorporating respiration in advanced computational fluid dynamic modeling will be outlined. Show less
