Multiyear Interval Changes in Aortic Wall Shear Stress in Patients with Bicuspid Aortic Valve Assessed by 4D Flow MRI.

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Fetal Echocardiographic Variables Associated with Pre-Surgical Mortality in Truncus Arteriosus: A Pilot Study.

Truncus arteriosus (TA) is a rare congenital heart defect that can be prenatally detected by fetal echocardiography. However, prognostication and prenatal counseling focus primarily on surgical outcomes due to limited fetal and neonatal pre-surgical mortality data. We aimed to describe the incidence and identify predictors of pre-surgical mortality in prenatally detected TA. This two-center, retrospective cohort study included fetuses diagnosed with TA between 01/2010 and 04/2020. The primary outcome was pre-surgical mortality, defined by fetal or neonatal pre-surgical death or primary listing for transplantation prior to discharge. Univariable regression modeling, Chi-square tests, and t tests assessed for associations between prenatal clinical, demographic, and fetal echocardiographic (fetal-echo) variables and pre-surgical mortality. Of 23 pregnancies with prenatal diagnosis of TA, 4 (17%) were terminated. Of the remaining 19, pre-surgical mortality occurred in 4 (26%), including 2 (11%) fetal deaths and 2 (11%) neonatal pre-surgical deaths. No transplantation listings. Of liveborn fetuses (n = 17), 15 (88%) underwent a neonatal surgery, and 1 (6%) required ECMO. As compared to the survivors, the pre-surgical mortality group had a higher likelihood of having left ventricular dysfunction (0% vs. 40%; p = 0.01), right ventricular dysfunction (0% vs. 60%; p = 0.002), cardiovascular profile score < 7 (0% vs. 40%; p = 0.01), skin edema (0% vs. 40%; p = 0.01), and abnormal umbilical venous (UV) Doppler (0% vs. 60%; p = 0.002). The presence of truncal valve regurgitation or stenosis neared significance. In this cohort with prenatally diagnosed TA, there is significant pre-surgical mortality, including fetal death and neonatal pre-surgical death. Termination rate is also high. Fetal-echo variables associated with pre-surgical mortality in this cohort include ventricular dysfunction, low CVP, skin edema, and abnormal UV Doppler. Knowledge about prenatal risk factors for pre-surgical mortality may guide parental counseling and postnatal planning in prenatally diagnosed TA.

Cardiac Magnetic Resonance Strain in Beta Thalassemia Major Correlates with Cardiac Iron Overload.

BACKGROUND: Beta thalassemia major (Beta-TM) is an inherited condition which presents at around two years of life. Patients with Beta-;TM may develop cardiac iron toxicity secondary to transfusion dependence. Cardiovascular magnetic resonance (CMR) T2*, a technique designed to quantify myocardial iron deposition, is a driving component of disease management. A decreased T2* value represents increasing cardiac iron overload. The clinical manifestation is a decline in ejection fraction (EF). However, there may be early subclinical changes in cardiac function that are not detected by changes in EF. CMR-derived strain assesses myocardial dysfunction prior to decline in EF. Our primary aim was to assess the correlation between CMR strain and T2* in the Beta-TM population. METHODS: Circumferential and longitudinal strain was analyzed. Pearson's correlation was calculated for T2* values and strain in the Beta-TM population. RESULTS: We identified 49 patients and 18 controls. Patients with severe disease (low T2*) were found to have decreased global circumferential strain (GCS) in comparison to other T2* groups. A correlation was identified between GCS and T2* (r = 0.5; p < 0.01). CONCLUSION: CMR-derived strain can be a clinically useful tool to predict early myocardial dysfunction in Beta-TM.

Right Ventricular Remodeling Assessed by MRI in Duchenne Muscular Dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the right ventricle (RV) tends to be relatively well preserved, but characterization remains difficult due to its complex architecture. Tissue phase mapping (TPM) is a phase contrast cine MRI technique that allows for multidirectional assessment of myocardial velocities. PURPOSE: To use TPM to elucidate relationships between myocardial structure, function, and clinical variables in DMD. STUDY TYPE: Retrospective. SUBJECTS: A total of 20 patients with muscular dystrophy (median age: 16 years); 18 age-matched normal controls (median age: 15 years). FIELD STRENGTH/SEQUENCE: Three-directional velocity encoded cine gradient echo sequence (TPM) at 1.5 T, balanced steady-state free procession (bSSFP), T1 mapping with extracellular volume (ECV), and late gadolinium enhancement (LGE). ASSESSMENT: TPM in basal, mid, and apical short-axis planes was performed as part of a standard MRI study with collection of clinical data. Radial, circumferential, and longitudinal velocities (Vr, Vφ, and Vz, respectively) and corresponding time to peak (TTP) velocities were quantified from TPM and used to calculate RV twist as well as intraventricular and interventricular dyssynchrony. The correlations between TPM velocities, myocardial structure/function, and clinical variables were assessed. STATISTICAL TEST: Unpaired t-test, Wilcoxon rank-sum test, Bland-Altman analyses were used for comparisons between DMD patients and controls and between DMD subgroups. Pearson's test was used for correlations (r). Significance level: P < 0.05. RESULTS: Compared to controls, DMD patients had preserved RV ejection fraction (RVEF 53% ± 8%) but significantly increased interventricular dyssynchrony (Vφ: 0.49 ± 0.21 vs. 0.72 ± 0.17). Within the DMD cohort, RV dyssynchrony significantly increased with lower LV ejection fraction (intraventricular Vr and Vz: r = -0.49; interventricular Vz: r = 0.48). In addition, RV intraventricular dyssynchrony significantly increased with older age (Vz: r = 0.67). DATA CONCLUSION: RV remodeling in DMD occurs in the context of preserved RVEF. Within DMD, this abnormal RV deformation is associated with older age and decreased LVEF. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Accelerated dual-venc 4D flow MRI with variable high-venc spatial resolution for neurovascular applications.

PURPOSE: Dual-velocity encoded (dual-venc or DV) 4D flow MRI achieves wide velocity dynamic range and velocity-to-noise ratio (VNR), enabling accurate neurovascular flow characterization. To reduce scan time, we present interleaved dual-venc 4D Flow with independently prescribed, prospectively undersampled spatial resolution of the high-venc (HV) acquisition: Variable Spatial Resolution Dual Venc (VSRDV). METHODS: A prototype VSRDV sequence was developed based on a Cartesian acquisition with eight-point phase encoding, combining PEAK-GRAPPA acceleration with zero-filling in phase and partition directions for HV. The VSRDV approach was optimized by varying z, the zero-filling fraction of HV relative to low-venc, between 0%-80% in vitro (realistic neurovascular model with pulsatile flow) and in vivo (n = 10 volunteers). Antialiasing precision, mean and peak velocity quantification accuracy, and test-retest reproducibility were assessed relative to reference images with equal-resolution HV and low venc (z = 0%). RESULTS: In vitro results for all z demonstrated an antialiasing true positive rate at least 95% for RPEAK-GRAPPA$$ {R}_{\mathrm{PEAK}-\mathrm{GRAPPA}} $$  = 2 and 5, with no linear relationship to z (p = 0.62 and 0.13, respectively). Bland-Altman analysis for z = 20%, 40%, 60%, or 80% versus z = 0% in vitro and in vivo demonstrated no bias >1% of venc in mean or peak velocity values at any RZF$$ {R}_{\mathrm{ZF}} $$ . In vitro mean and peak velocity, and in vivo peak velocity, had limits of agreement within 15%. CONCLUSION: VSRDV allows up to 34.8% scan time reduction compared to PEAK-GRAPPA accelerated DV 4D Flow MRI, enabling large spatial coverage and dynamic range while maintaining VNR and velocity measurement accuracy.

4D flow MRI derived aortic hemodynamics multi-year follow-up in repaired coarctation with bicuspid aortic valve.

PURPOSE: The purpose of this study was to investigate the relationships between hemodynamic parameters and longitudinal changes in aortic dimensions on four-dimensional (4D) flow magnetic resonance imaging (MRI) in patients with bicuspid aortic valve (BAV) and repaired coarctation. MATERIALS AND METHODS: The study retrospectively included patients with BAV and childhood coarctation repair who had at least two cardiothoracic MRI examinations including 4D flow MRI at baseline and follow-up. Analysis included the calculation of aortic peak velocities, wall shear stress (WSS), pulse wave velocity (PWV), aortic dimensions and annual growth rates. Differences between examinations were assessed using paired t-test or Wilcoxon signed rank test. Relationships between growth rate and 4D flow metrics were assessed using Pearson or Spearman correlation tests. RESULTS: The cohort included 15 patients (mean age 35 ± 8 [SD] years, 9 men) with a median follow-up time of 3.98 years (Q1: 2.10; Q3: 4.96). There were no significant differences in aortic mean WSS, peak velocities, and PWV between baseline and follow-up values. Greater baseline peak velocities at the site of the coarctation were strongly associated with aortic narrowing (follow-up vs. baseline diameter) at coarctation zone (r = -0.64; P = 0.010) and moderately in descending aorta (r = -0.53; P = 0.042). In addition, increased baseline WSS in the aortic arch was strongly related with narrowing of the coarctation zone at follow-up (r = -0.64, P = 0.011). CONCLUSION: Measures of aortic hemodynamics and aortic WSS are stable over time in patients with BAV with coarctation repair. Increased peak velocity was associated with a progressive narrowing at the site of the coarctation repair.

Enhanced 4D Flow MRI-Based CFD with Adaptive Mesh Refinement for Flow Dynamics Assessment in Coarctation of the Aorta.

4D Flow MRI is a diagnostic tool that can visualize and quantify patient-specific hemodynamics and help interventionalists optimize treatment strategies for repairing coarctation of the aorta (COA). Despite recent developments in 4D Flow MRI, shortcomings include phase-offset errors, limited spatiotemporal resolution, aliasing, inaccuracies due to slow aneurysmal flows, and distortion of images due to metallic artifact from vascular stents. To address these limitations, we developed a framework utilizing Computational Fluid Dynamics (CFD) with Adaptive Mesh Refinement (AMR) that enhances 4D Flow MRI visualization/quantification. We applied this framework to five pediatric patients with COA, providing in-vivo and in-silico datasets, pre- and post-intervention. These two data sets were compared and showed that CFD flow rates were within 9.6% of 4D Flow MRI, which is within a clinically acceptable range. CFD simulated slow aneurysmal flow, which MRI failed to capture due to high relative velocity encoding (Venc). CFD successfully predicted in-stent blood flow, which was not visible in the in-vivo data due to susceptibility artifact. AMR improved spatial resolution by factors of 101 to 103 and temporal resolution four-fold. This computational framework has strong potential to optimize visualization/quantification of aneurysmal and in-stent flows, improve spatiotemporal resolution, and assess hemodynamic efficiency post-COA treatment.

Deep learning-based velocity antialiasing of 4D-flow MRI.

PURPOSE: To develop a convolutional neural network (CNN) for the robust and fast correction of velocity aliasing in 4D-flow MRI. METHODS: This study included 667 adult subjects with aortic 4D-flow MRI data with existing velocity aliasing (n = 362) and no velocity aliasing (n = 305). Additionally, 10 controls received back-to-back 4D-flow scans with systemically varied velocity-encoding sensitivity (vencs) at 60, 100, and 175 cm/s. The no-aliasing data sets were used to simulate velocity aliasing by reducing the venc to 40%-70% of the original, alongside a ground truth locating all aliased voxels (153 training, 152 testing). The 152 simulated and 362 existing aliasing data sets were used for testing and compared with a conventional velocity antialiasing algorithm. Dice scores were calculated to quantify CNN performance. For controls, the venc 175-cm/s scans were used as the ground truth and compared with the CNN-corrected venc 60 and 100 cm/s data sets RESULTS: The CNN required 176 ± 30 s to perform compared with 162 ± 14 s for the conventional algorithm. The CNN showed excellent performance for the simulated data compared with the conventional algorithm (median range of Dice scores CNN: [0.89-0.99], conventional algorithm: [0.84-0.94], p < 0.001, across all simulated vencs) and detected more aliased voxels in existing velocity aliasing data sets (median detected CNN: 159 voxels [31-605], conventional algorithm: 65 [7-417], p < 0.001). For controls, the CNN showed Dice scores of 0.98 [0.95-0.99] and 0.96 [0.87-0.99] for venc = 60 cm/s and 100 cm/s, respectively, while flow comparisons showed moderate-excellent agreement. CONCLUSION: Deep learning enabled fast and robust velocity anti-aliasing in 4D-flow MRI.

Four-Dimensional flow Magnetic Resonance Imaging for Assessment of Pediatric Coarctation of the Aorta.

BACKGROUND: Coarctation of the aorta (CoA) typically requires repair, but re-interventions and vascular complications occur, particularly with associated defects like bicuspid aortic valve (BAV). Magnetic resonance imaging (MRI) may identify anatomic and hemodynamic factors contributing to clinical complications. PURPOSE: To investigate 4D flow MRI characteristics in pediatric CoA to determine parameters for long-term clinical surveillance. STUDY TYPE: Retrospective. POPULATION: CoA (n = 21), CoA with BAV (n = 24), BAV alone (n = 29), and healthy control (n = 25). FIELD STRENGTH/SEQUENCE: A 1.5 T, 3D CE IR FLASH MRA, 4D flow MRI using 3D time resolved PC-MRI with velocity encoding. ASSESSMENT: Thoracic aorta diameters were measured from 3D CE-MRA. Peak systolic velocities and wall shear stress were calculated and flow patterns were visualized throughout the thoracic aorta using 4D flow. Repair characteristics, re-interventions, and need for anti-hypertensive medications were recorded. STATISTICS: Descriptive statistics, ANOVA with post hoc t-testing and Bonferroni correction, Kruskal-Wallis H, intraclass correlation coefficient, Fleiss' kappa. RESULTS: Patients with CoA with or without repair had smaller transverse arch diameters compared to BAV alone and control cohorts (P < 0.05), higher peak systolic flow velocities and wall shear stress compared to controls in the transverse arch and descending aorta (P < 0.05), and flow derangements in the descending aorta. The most common CoA repairs were extended end-to-end anastomosis (n = 22/45, 48.9%, age at repair 1 ± 2 years, seven re-interventions) and stent/interposition graft placement (n = 10/45, 22.2%, age at repair 12 ± 3 years, one re-intervention). Anti-hypertensive medications were prescribed to 33.3% (n = 15/45) of CoA and 34.4% of BAV alone patients (n = 10/29). DATA CONCLUSIONS: Despite repair, CoA alters hemodynamics and flow patterns in the transverse arch and descending aorta. These findings may contribute to vascular remodeling and secondary complications. 4D flow MRI may be valuable in risk stratification, treatment selection and postintervention assessment. Long-term, prospective studies are warranted to correlate patient and MRI factors with clinical outcomes. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy.

BACKGROUND: The progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV. METHODS: We performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters. RESULTS: Mean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p < 0.001) and ECV (26.5 ± 4.0% vs 24.0 ± 2.7%; p = 0.017) were higher in PHT compared to helathy controls. Significant relationships between changes in myocardial tissue structure and function were noted in PHT: increased T2 correlated with reduced LVEF (r = - 0.57, p = 0.005), reduced global circumferential strain (r = - 0.73, p < 0.001) and reduced global longitudinal strain (r = - 0.49, p = 0.03). In addition, significant relationships were noted between higher rejection score and global T1 (r = 0.38, p = 0.05), T2 (r = 0.39, p = 0.058) and ECV (r = 0.68, p < 0.001). The presence of even low-grade CAV was associated with higher global T1, global ECV and maximum segmental T2. No major side effects were noted with stress testing. MPRI was analyzed with good interobserver reliability and was lower in PHT compared to healthy controls (0.69 ± - 0.21 vs 0.94 ± 0.22; p < 0.001). CONCLUSION: In a PHT population with low incidence of rejection or high-grade CAV, CMR demonstrates important differences in myocardial structure, function and perfusion compared to age-matched healthy controls. Regadenoson stress perfusion CMR could be safely and reliably performed. Increasing T2 values were associated with worsening left ventricular function and increasing T1/ECV values were associated with rejection history and low-grade CAV. These findings warrant larger prospective studies to further define the role of CMR in PHT graft surveillance.

Automated segmentation of biventricular contours in tissue phase mapping using deep learning.

Tissue phase mapping (TPM) is an MRI technique for quantification of regional biventricular myocardial velocities. Despite its potential, clinical use is limited due to the requisite labor-intensive manual segmentation of cardiac contours for all time frames. The purpose of this study was to develop a deep learning (DL) network for automated segmentation of TPM images, without significant loss in segmentation and myocardial velocity quantification accuracy compared with manual segmentation. We implemented a multi-channel 3D (three dimensional; 2D + time) dense U-Net that trained on magnitude and phase images and combined cross-entropy, Dice, and Hausdorff distance loss terms to improve the segmentation accuracy and suppress unnatural boundaries. The dense U-Net was trained and tested with 150 multi-slice, multi-phase TPM scans (114 scans for training, 36 for testing) from 99 heart transplant patients (44 females, 1-4 scans/patient), where the magnitude and velocity-encoded (Vx , Vy , Vz ) images were used as input and the corresponding manual segmentation masks were used as reference. The accuracy of DL segmentation was evaluated using quantitative metrics (Dice scores, Hausdorff distance) and linear regression and Bland-Altman analyses on the resulting peak radial and longitudinal velocities (Vr and Vz ). The mean segmentation time was about 2 h per patient for manual and 1.9 ± 0.3 s for DL. Our network produced good accuracy (median Dice = 0.85 for left ventricle (LV), 0.64 for right ventricle (RV), Hausdorff distance = 3.17 pixels) compared with manual segmentation. Peak Vr and Vz measured from manual and DL segmentations were strongly correlated (R ≥ 0.88) and in good agreement with manual analysis (mean difference and limits of agreement for Vz and Vr were -0.05 ± 0.98 cm/s and -0.06 ± 1.18 cm/s for LV, and -0.21 ± 2.33 cm/s and 0.46 ± 4.00 cm/s for RV, respectively). The proposed multi-channel 3D dense U-Net was capable of reducing the segmentation time by 3,600-fold, without significant loss in accuracy in tissue velocity measurements.

Divergence-Free Constrained Phase Unwrapping and Denoising for 4D Flow MRI Using Weighted Least-Squares.

A novel divergence-free constrained phase unwrapping method was proposed and evaluated for 4D flow MRI. The unwrapped phase field was obtained by integrating the phase variations estimated from the wrapped phase data using weighted least-squares. The divergence-free constraint for incompressible blood flow was incorporated to regulate and denoise the resulting phase field. The proposed method was tested on synthetic phase data of left ventricular flow and in vitro 4D flow measurement of Poiseuille flow. The method was additionally applied to in vivo 4D flow measurements in the thoracic aorta from 30 human subjects. The performance of the proposed method was compared to the state-of-the-art 4D single-step Laplacian algorithm. The synthetic phase data were completely unwrapped by the proposed method for all the cases with velocity encoding (venc) as low as 20% of the maximum velocity and signal-to-noise ratio as low as 5. The in vitro Poiseuille flow data were completely unwrapped with a 60% increase in the velocity-to-noise ratio. For the in-vivo aortic datasets with venc ratio less than 0.4, the proposed method significantly improved the success rate by as much as 40% and reduced the velocity error levels by a factor of 10 compared to the state-of-the-art method. The divergence-free constrained method exhibits reliability and robustness on phase unwrapping and shows improved accuracy of velocity and hemodynamic quantities by unwrapping the low-venc 4D flow MRI data.

Highly accelerated aortic 4D flow MRI using compressed sensing: Performance at different acceleration factors in patients with aortic disease.

PURPOSE: To systematically assess the feasibility and performance of a highly accelerated compressed sensing (CS) 4D flow MRI framework at three different acceleration factors (R) for the quantification of aortic flow dynamics and wall shear stress (WSS) in patients with aortic disease. METHODS: Twenty patients with aortic disease (58 ± 15 y old; 19 M) underwent four 4D flow scans: one conventional (GRAPPA, R = 2) and three CS 4D flows with R = 5.7, 7.7, and 10.2. All scans were acquired with otherwise equivalent imaging parameters on a 1.5T scanner. Peak-systolic velocity (Vmax ), peak flow (Qmax ), and net flow (Qnet ) were quantified at the ascending aorta (AAo), arch, and descending aorta (DAo). WSS was calculated at six regions within the AAo and arch. RESULTS: Mean scan times for the conventional and CS 4D flows with R = 5.7, 7.7, and 10.2 were 9:58 ± 2:58 min, 3:40 ± 1:19 min, 2:50 ± 0:56 min, and 2:05 ± 0:42 min, respectively. Vmax , Qmax , and Qnet were significantly underestimated by all CS protocols (underestimation ≤ -7%, -9%, and -10% by CS, R = 5.7, 7.7, and 10.2, respectively). WSS measurements showed the highest underestimation by all CS protocols (underestimation ≤ -9%, -12%, and -14% by CS, R = 5.7, 7.7, and 10.2). CONCLUSIONS: Highly accelerated aortic CS 4D flow at R = 5.7, 7.7, and 10.2 showed moderate agreement with the conventional 4D flow, despite systematically underestimating various hemodynamic parameters. The shortened scan time may enable the clinical translation of CS 4D flow, although potential hemodynamic underestimation should be considered when interpreting the results.

Fully automated 3D aortic segmentation of 4D flow MRI for hemodynamic analysis using deep learning.

PURPOSE: To generate fully automated and fast 4D-flow MRI-based 3D segmentations of the aorta using deep learning for reproducible quantification of aortic flow, peak velocity, and dimensions. METHODS: A total of 1018 subjects with aortic 4D-flow MRI (528 with bicuspid aortic valve, 376 with tricuspid aortic valve and aortic dilation, 114 healthy controls) comprised the data set. A convolutional neural network was trained to generate 3D aortic segmentations from 4D-flow data. Manual segmentations served as the ground truth (N = 499 training, N = 101 validation, N = 418 testing). Dice scores, Hausdorff distance, and average symmetrical surface distance were calculated to assess performance. Aortic flow, peak velocity, and lumen dimensions were quantified at the ascending, arch, and descending aorta and compared using Bland-Altman analysis. Interobserver variability of manual analysis was assessed on a subset of 40. RESULTS: Convolutional neural network segmentation required 0.438 ± 0.355 seconds versus 630 ± 254 seconds for manual analysis and demonstrated excellent performance with a median Dice score of 0.951 (0.930-0.966), Hausdorff distance of 2.80 (2.13-4.35), and average symmetrical surface distance of 0.176 (0.119-0.290). Excellent agreement was found for flow, peak velocity, and dimensions with low bias and limits of agreement less than 10% difference versus manual analysis. For aortic volume, limits of agreement were moderate within 16.3%. Interobserver variability (median Dice score: 0.950; Hausdorff distance: 2.45; and average symmetrical surface distance: 0.145) and convolutional neural network-based analysis (median Dice score: 0.953-0.959; Hausdorff distance: 2.24-2.91; and average symmetrical surface distance: 0.145-1.98 to observers) demonstrated similar reproducibility. CONCLUSIONS: Deep learning enabled fast and automated 3D aortic segmentation from 4D-flow MRI, demonstrating its potential for efficient clinical workflows. Future studies should investigate its utility for other vasculature and multivendor applications.

Altered 4-D magnetic resonance imaging flow characteristics in complex congenital aortic arch repair.

BACKGROUND: Interrupted aortic arch (IAA) is a rare but severe congenital abnormality often associated with bicuspid aortic valve (BAV). Complex re-interventions are often needed despite surgical advances, but the impact of aortic hemodynamics in repaired patients is unknown. OBJECTIVE: Investigate effect of IAA repairs on aortic hemodynamics, wall shear stress and flow derangements via 4-D flow MRI. MATERIALS AND METHODS: We retrospectively analyzed age- and gender-matched cohorts (IAA [n=6], BAV alone [n=6], controls [n=6]) undergoing cardiac MRI including 4-D flow. Aortic dimensions were measured from standard MR angiography. We quantified peak systolic velocities, regurgitant fractions and wall shear stress in the ascending aorta (AAo), transverse arch and descending aorta (DAo) from 4-D flow, and we graded helix/vortex flow patterns from 3-D blood flow visualization. RESULTS: Children and young adults with IAA had a wide range of arch dimensions, peak systolic velocities, regurgitant fractions and flow grades. Peak transverse arch systolic velocities were higher in patients with IAA versus controls (P=0.02). Flow derangements in the AAo were found in patients with IAA (median grade=2, 5/6 patients, P=0.04) and BAV (median grade=3, 5/6 patients, P=0.03) versus controls. Flow derangements in the DAo were only seen in patients with IAA (median grade=1, 5/6 patients, P=0.04), and 5/6 people with IAA had helical flow in head and neck vessels. Wall shear stress was increased in people with IAA along the superior transverse arch and proximal DAo versus controls (P=0.02). CONCLUSION: Complex congenital aortic arch repairs can change aortic hemodynamics. Associated cardiac defects can further alter findings. Studies are warranted to investigate clinical implications in larger cohorts.

Myocardial velocity, intra-, and interventricular dyssynchrony evaluated by tissue phase mapping in pediatric heart transplant recipients.

BACKGROUND: Endomyocardial biopsy (EMB) is the standard method for detecting allograft rejection in pediatric heart transplants (Htx). As EMB is invasive and carries a risk of complications, there is a need for a noninvasive alternative for allograft monitoring. PURPOSE: To quantify left and right ventricular (LV & RV) peak velocities, velocity twist, and intra-/interventricular dyssynchrony using tissue phase mapping (TPM) in pediatric Htx compared with controls, and to explore the relationship between global cardiac function parameters and the number of rejection episodes to these velocities and intra-/interventricular dyssynchrony. STUDY TYPE: Prospective. SUBJECTS: Twenty Htx patients (age: 16.0 ± 3.1 years, 11 males) and 18 age- and sex-matched controls (age: 15.5 ± 4.3 years, nine males). FIELD STRENGTH/SEQUENCE: 5T; 2D balanced cine steady-state free-precession (bSSFP), TPM (2D cine phase contrast with three-directional velocity encoding). ASSESSMENT: LV and RV circumferential, radial, and long-axis velocity-time curves, global and segmental peak velocities were measured using TPM. Short-axis bSSFP images were used to measure global LV and RV function parameters. STATISTICAL TESTS: A normality test (Lilliefors test) was performed on all data. For comparisons, a t-test was used for normally distributed data or a Wilcoxon rank-sum test otherwise. Correlations were determined by a Pearson correlation. RESULTS: Htx patients had significantly reduced LV (P < 0.05-0.001) and RV (P < 0.05-0.001) systolic and diastolic global and segmental long-axis velocities, reduced RV diastolic peak twist (P < 0.01), and presented with higher interventricular dyssynchrony for long-axis and circumferential motions (P < 0.05-0.001). LV diastolic long-axis dyssynchrony (r = 0.48, P = 0.03) and RV diastolic peak twist (r = -0.64, P = 0.004) significantly correlated with the total number of rejection episodes. DATA CONCLUSION: TPM detected differences in biventricular myocardial velocities in pediatric Htx patients compared with controls and indicated a relationship between Htx myocardial velocities and rejection history. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1212-1222.

Altered regional myocardial velocities by tissue phase mapping and feature tracking in pediatric patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with heart failure, atrial fibrillation and sudden death. Reduced myocardial function has been reported in HCM despite normal left ventricular (LV) ejection fraction. Additionally, LV fibrosis is associated with elevated T1 and might be an outcome predictor. OBJECTIVE: To systematically compare tissue phase mapping and feature tracking for assessing regional LV function in children and young adults with HCM and pediatric controls, and to evaluate structure-function relationships among myocardial velocities, LV wall thickness and myocardial T1. MATERIALS AND METHODS: Seventeen pediatric patients with HCM and 21 age-matched controls underwent cardiac MRI including standard cine imaging, tissue phase mapping (two-dimensional cine phase contrast with three-directional velocity encoding), and modified Look-Locker inversion recovery to calculate native global LV T1. Maximum LV wall thickness was measured on cine images. LV radial, circumferential and long-axis myocardial velocity time courses, as well as global and segmental systolic and diastolic peak velocities, were quantified from tissue phase mapping and feature tracking. RESULTS: Both tissue phase mapping and feature tracking detected significantly decreased global and segmental diastolic radial and long-axis peak velocities (by 12-51%, P<0.001-0.05) in pediatric patients with HCM vs. controls. Feature tracking peak velocities were lower than directly measured tissue phase mapping velocities (mean bias = 0.3-2.9 cm/s). Diastolic global peak velocities correlated moderately with global T1 (r = -0.57 to -0.72, P<0.01) and maximum wall thickness (r = -0.37 to -0.61, P<0.05). CONCLUSION: Both tissue phase mapping and feature tracking detected myocardial velocity changes in children and young adults with HCM vs. controls. Associations between impaired diastolic LV velocities and elevated T1 indicate structure-function relationships in HCM.

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity (P > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted r = 0.28-0.55; all P < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Choe in this issue.

Comprehensive MR Analysis of Cardiac Function, Aortic Hemodynamics and Left Ventricular Strain in Pediatric Cohort with Isolated Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) disease demonstrates a range of clinical presentations and complications. We aim to use cardiac MRI (CMR) to evaluate left ventricular (LV) parameters, myocardial strain and aortic hemodynamics in pediatric BAV patients with and without aortic stenosis (AS) or regurgitation (AR) compared to tricuspid aortic valve (TAV) controls. We identified 58 pediatric BAV patients without additional cardiovascular pathology and 25 healthy TAV controls (15.3 ± 2.2 years) who underwent CMR with 4D flow. BAV cohort included subgroups with no valvulopathy (n = 13, 14.3 ± 4.7 years), isolated AS (n = 19, 14.5 ± 4.0 years), mixed valve disease (AS + AR) (n = 13, 17.1 ± 3.2 years), and prior valvotomy/valvuloplasty (n = 13, 13.9 ± 3.2 years). CMR data included LV volumetric and mass indices, myocardial strain and aortic hemodynamics. BAV patients with no valvulopathy or isolated AS had similar LV parameters to controls excepting cardiac output (p < 0.05). AS + AR and post-surgical patients had abnormal LV volumetric and mass indices (p < 0.01). Post-surgical patients had decreased global longitudinal strain (p = 0.02); other subgroups had comparable strain to controls. Patients with valvulopathy demonstrated elevated velocity and wall shear stress (WSS) in the ascending aorta (AAo) and arch (p < 0.01), while those without valve dysfunction had only elevated AAo velocity (p = 0.03). Across the cohort, elevated AAo velocity and WSS correlated to higher LV mass (p < 0.01), and abnormal hemodynamics correlated to decreased strain rates (p < 0.045). Pediatric BAV patients demonstrate abnormalities in LV parameters as a function of valvular dysfunction, most significantly in children with AS + AR or prior valvotomy/valvuloplasty. Correlations between aortic hemodynamics, LV mass and strain suggest valvular dysfunction could drive LV remodeling. Multiparametric CMR assessment in pediatric BAV may help stratify risk for cardiac remodeling and dysfunction.