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.

Global Aortic Pulse Wave Velocity is Unchanged in Bicuspid Aortopathy With Normal Valve Function but Elevated in Patients With Aortic Valve Stenosis: Insights From a 4D Flow MRI Study of 597 Subjects.

BACKGROUND: Aortopathy is common with bicuspid aortic valve (BAV), and underlying intrinsic tissue abnormalities are believed causative. Valve-mediated hemodynamics are altered in BAV and may contribute to aortopathy and its progression. The contribution of intrinsic tissue defects versus altered hemodynamics to aortopathy progression is not known. PURPOSE: To investigate relative contributions of tissue-innate versus hemodynamics in progression of BAV aortopathy. STUDY TYPE: Retrospective. SUBJECTS: Four hundred seventy-three patients with aortic dilatation (diameter ≥40 mm; comprised of 281 BAV with varied AS severity, 192 tricuspid aortic valve [TAV] without AS) and 124 healthy controls. Subjects were 19-91 years (141/24% female). FIELD STRENGTH/SEQUENCE: 1.5T, 3T; time-resolved gradient-echo 3D phase-contrast (4D flow) MRI. ASSESSMENT: A surrogate measure for global aortic wall stiffness, pulse wave velocity (PWV), was quantified from MRI by standardized, automated technique based on through-plane flow cross-correlation maximization. Comparisons were made between BAV patients with aortic dilatation and varying aortic valve stenosis (AS) severity and healthy subjects and aortopathy patients with normal TAV. STATISTICAL TESTS: Multivariable regression, analysis of covariance (ANCOVA), Tukey's, student's (t), Mann-Whitney (U) tests, were used with significance levels P < 0.05 or P < 0.01 for post-hoc Bonferroni-corrected t/U tests. Bland-Altman and ICC calculations were performed. RESULTS: Multivariable regression showed age with the most significant association for increased PWV in all groups (increase 0.073-0.156 m/sec/year, R2  = 0.30-48). No significant differences in aortic PWV were observed between groups without AS (P = 0.20-0.99), nor were associations between PWV and regurgitation or Sievers type observed (P = 0.60, 0.31 respectively). In contrast, BAV AS patients demonstrated elevated PWV and a significant relationship for AS severity with increased PWV (covariate: age, R2  = 0.48). BAV and TAV patients showed no association between aortic diameter and PWV (P = 0.73). DATA CONCLUSION: No significant PWV differences were observed between BAV patients with normal valve function and control groups. However, AS severity and age in BAV patients were directly associated with PWV increases. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Systolic reverse flow derived from 4D flow cardiovascular magnetic resonance in bicuspid aortic valve is associated with aortic dilation and aortic valve stenosis: a cross sectional study in 655 subjects.

BACKGROUND: Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. METHODS: 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. RESULTS: BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = - 83.2 and c = - 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = - 253.1, p < 0.001) and diastolic (c = - 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). CONCLUSION: 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies.

Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan.

BACKGROUND: Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men. PURPOSE: To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults. STUDY TYPE: Retrospective. POPULATION: Ninety nine healthy participants (age: 46 ± 15 [19-79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45-65 years) (N = 37), and later life (>65 years) (N = 14) groups. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI. ASSESSMENT: Cardiac functional parameters of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant. RESULTS: PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = -0.29), ESV (r = -0.23), SV (r = -0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = -0.62). In the test-retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4-9.3] m/sec and ICC = 0.75. DATA CONCLUSION: 4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test-retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI-derived aortic PWV for studying aging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Investigation of Aortic Wall Thickness, Stiffness and Flow Reversal in Patients With Cryptogenic Stroke: A 4D Flow MRI Study.

BACKGROUND: Stroke etiology is undetermined in approximately one-sixth to one-third of patients. The presence of aortic flow reversal and plaques in the descending aorta (DAo) has been identified as a potential retrograde embolic mechanism. PURPOSE: To assess the relationships between aortic stiffness, wall thickness, and flow reversal in patients with cryptogenic stroke and healthy controls. STUDY TYPE: Prospective. POPULATION: Twenty one patients with cryptogenic stroke and proven DAo plaques (69 ± 9 years, 43% female), 18 age-matched controls (age: 65 ± 8 years, 61% female), and 14 younger controls (36 ± 9 years, 57% female). FIELD STRENGTH/SEQUENCE: 1.5T; 4D flow MRI and 3D dark blood T1 -weighted turbo spin echo MRI of the aorta. ASSESSMENT: Noncontrast aortic 4D flow MRI to measure 3D flow dynamics and 3D dark blood aortic wall MRI to assess wall thickness. 4D flow MRI analysis included automated quantification of aortic stiffness by pulse wave velocity (PWV) and voxelwise mapping of the flow reversal fraction (FRF). STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests, Student's unpaired t-tests or Wilcoxon rank-sum tests, regression analysis. RESULTS: Aortic PWV and FRF were statistically higher in patients (8.9 ± 1.7 m/s, 18.4 ± 7.7%) than younger controls (5.3 ± 0.8 m/s, P < 0.0167; 8.5 ± 2.9%, P < 0.0167), but not age-matched controls (8.2 ± 1.6 m/s, P = 0.22; 15.6 ± 5.8%, P = 0.22). Maximum aortic wall thickness was higher in patients (3.1 ± 0.7 mm) than younger controls (2.2 ± 0.2 mm, P < 0.0167) and age-matched controls (2.7 ± 0.5 mm) (P < 0.0167). For all subjects, positive relationships were found between PWV and age (R2 = 0.71, P < 0.05), aortic wall thickness (R2 = 0.20, P < 0.05), and FRF (R2 = 0.47, P < 0.05). Patients demonstrated relationships between PWV and FRF in the ascending aorta (R2 = 0.32, P < 0.05) and arch (R2 = 0.24, P < 0.05). DATA CONCLUSION: This study showed the utility of 4D flow MRI for evaluating aortic PWV and voxelwise flow reversal. Positive relationships between aortic PWV, wall thickness, and flow reversal support the hypothesis that aortic stiffness is involved in this retrograde embolic mechanism. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Renin Angiotensin System Inhibitors Reduce Aortic Stiffness and Flow Reversal After a Cryptogenic Stroke.

BACKGROUND: Blood flow reversal is a possible mechanism for retrograde embolism in the setting of high-risk atherosclerotic plaques in the descending aorta (DAo). Evidence suggests that pulse wave velocity (PWV) is a determinant of blood flow reversal and can be reduced by the destiffening effect of renin-angiotensin system inhibitors (RASI). PURPOSE: To evaluate the impact of antihypertensive therapy on in vivo changes in PWV and flow reversal in patients with cryptogenic stroke. STUDY TYPE: Prospective. POPULATION: Sixteen patients (69 ± 9 years; 10 males) included after cryptogenic stroke. FIELD STRENGTH/SEQUENCE: 3T. 4D flow sequence (temporal resolution = 19.6 msec) ASSESSMENT: Patients underwent aortic MRI at baseline and at 6-month follow-up. Patients received standard-of-care antihypertensive therapy that were classified as RASI vs. non-RASI medications (ie, destiffening vs. nondestiffening).We compared aortic PWV, flow reversal fraction (FRF), aortic measurements, cardiac function, and other aortic and cardiac measurements in the antihypertensive therapy groups. STATISTICAL TESTS: Two-tailed paired or unpaired Student's t-tests (normal distributions) or Wilcoxon tests (nonnormal distribution). Univariate correlations using Pearson correlation coefficients. RESULTS: There was a significant decrease in PWV in the RASI (n = 10) group (9.4 ± 1.6 m/s vs. 8.3 ± 1.9 m/s; P < 0.05), as well as FRF (18.6% ± 4.1% vs. 16.3% ± 4.0%; P < 0.05) between baseline and the 6-month MRI studies. There were no changes in PWV or FRF in the non-RASI (n = 6) group (P = 0.146 and P = 0.32). A decrease in FRF was significantly correlated with a decrease in PWV (r = 0.53; P < 0.05). DATA CONCLUSION: The findings of our study suggest that RASI therapy after cryptogenic stroke resulted in a decrease of blood flow reversal and aortic stiffness. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 4.

4D flow MRI after aortic replacement with frozen elephant trunk using thoraflex hybrid graft.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) has not been used to describe flow through a Thoraflex Hybrid graft. We present the first 4D flow MRI depiction of Thoraflex Hybrid graft after use as a frozen elephant trunk to repair a DeBakey Type I aortic dissection.

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.

Parametric Hemodynamic 4D Flow MRI Maps for the Characterization of Chronic Thoracic Descending Aortic Dissection.

BACKGROUND: Systematic evaluation of complex flow in the true lumen and false lumen (TL, FL) is needed to better understand which patients with chronic descending aortic dissection (DAD) are predisposed to complications. PURPOSE: To develop quantitative hemodynamic maps from 4D flow MRI for evaluating TL and FL flow characteristics. STUDY TYPE: Retrospective. POPULATION: In all, 20 DAD patients (age = 60 ± 11 years; 12 male) (six medically managed type B AD [TBAD], 14 repaired type A AD [rTAAD] now with ascending aortic graft [AAo] or elephant trunk [ET1] repair) and 21 age-matched controls (age = 59 ± 10 years; 13 male) were included. FIELD STRENGTH/SEQUENCE: 1.5T, 3T, 4D flow MRI. ASSESSMENT: 4D flow MRI was acquired in all subjects. Data analysis included 3D segmentation of TL and FL and voxelwise calculation of forward flow, reverse flow, flow stasis, and kinetic energy as quantitative hemodynamics maps. STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests were performed for comparing subject groups. Correlation and Bland-Altman analysis was performed for the interobserver study. RESULTS: Patients with rTAAD presented with elevated TL reverse flow (AAo repair: P = 0.004, ET1: P = 0.018) and increased TL kinetic energy (AAo repair: P = 0.0002, ET1: P = 0.011) compared to controls. In addition, TL kinetic energy was increased vs. patients with TBAD (AAo repair: P = 0.021, ET1: P = 0.048). rTAAD was associated with higher FL kinetic energy and lower FL stasis compared to patients with TBAD (AAo repair: P = 0.002, ET1: P = 0.024 and AAo repair: P = 0.003, ET1: P = 0.048, respectively). DATA CONCLUSION: Quantitative maps from 4D flow MRI demonstrated global and regional hemodynamic differences between DAD patients and controls. Patients with rTAAD vs. TBAD had significantly altered regional TL and FL hemodynamics. These findings indicate the potential of 4D flow MRI-derived hemodynamic maps to help better evaluate patients with DAD. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1357-1368.

Caval to pulmonary 3D flow distribution in patients with Fontan circulation and impact of potential 4D flow MRI error sources.

PURPOSE: Uneven flow distribution in patients with Fontan circulation is suspected to lead to complications. 4D flow MRI offers evaluation using time-resolved pathlines; however, the potential error is not well understood. The aim of this study was to systematically assess variability in flow distribution caused by well-known sources of error. METHODS: 4D flow MRI was acquired in 14 patients with Fontan circulation. Flow distribution was quantified by the % of caval venous flow pathlines reaching the left and right pulmonary arteries. Impact of data acquisition and data processing uncertainties were investigated by (1) probabilistic 4D blood flow tracking at varying noise levels, (2) down-sampling to mimic acquisition at different spatial resolutions, (3) pathline calculation with and without eddy current correction, and (4) varied segmentation of the Fontan geometry to mimic analysis errors. RESULTS: Averaged among the cohort, uncertainties accounted for flow distribution errors from noise ≤3.2%, low spatial resolution ≤2.3% to 3.8%, eddy currents ≤6.4%, and inaccurate segmentation ≤3.9% to 9.1% (dilation and erosion, respectively). In a worst-case scenario (maximum additive errors for all 4 sources), flow distribution errors were as high as 22.5%. CONCLUSION: Inaccuracies related to postprocessing (segmentation, eddy currents) resulted in the largest potential error (≤15.5% combined) whereas errors related to data acquisition (noise, low spatial resolution) had a lower impact (≤5.5%-7.0% combined). Whereas it is unlikely that these errors will be additive or affect the identification of severe asymmetry, these results illustrate the importance of eddy current correction and accurate segmentation to minimize Fontan flow distribution errors.

4-D flow magnetic-resonance-imaging-derived energetic biomarkers are abnormal in children with repaired tetralogy of Fallot and associated with disease severity.

BACKGROUND: Cardiac MRI plays a central role in monitoring children with repaired tetralogy of Fallot (TOF) for long-term complications. Current risk assessment is based on volumetric and functional parameters that measure late expression of underlying physiological changes. Emerging 4-D flow MRI techniques promise new insights. OBJECTIVE: To assess whether 4-D flow MRI-derived measures of blood kinetic energy (1) differentiate children and young adults with TOF from controls and (2) are associated with disease severity. MATERIALS AND METHODS: Pediatric patients post TOF repair (n=21) and controls (n=24) underwent 4-D flow MRI for assessment of time-resolved 3-D blood flow. Data analysis included 3-D segmentation of the right ventricle (RV) and pulmonary artery (PA), with calculation of peak systolic and diastolic kinetic energy (KE) maps. Total KERV and KEPA were determined from the sum of the KE of all voxels within the respective time-resolved segmentations. RESULTS: KEPA was increased in children post TOF vs. controls across the cardiac cycle, with median 12.5 (interquartile range [IQR] 10.3) mJ/m2 vs. 8.2 (4.3) mJ/m2, P<0.01 in systole; and 2.3 (2.7) mJ/m2 vs. 1.4 (0.9) mJ/m2, P<0.01 in diastole. Diastolic KEPA correlated with systolic KEPA (R2 0.41, P<0.01) and with pulmonary regurgitation fraction (R2 0.65, P<0.01). Diastolic KERV showed similar relationships, denoting increasing KE with higher cardiac outputs and increased right heart volume loading. Diastolic KERV and KEPA increased with RV end-diastolic volume in a non-linear relationship (R2 0.33, P<0.01 and R2 0.50, P<0.01 respectively), with an inflection point near 120 mL/m2. CONCLUSION: Four-dimensional flow-derived KE is abnormal in pediatric patients post TOF repair compared to controls and has a direct, non-linear relationship with traditional measures of disease progression. Future longitudinal studies are needed to evaluate utility for early outcome prediction in TOF.

4-D flow MRI aortic 3-D hemodynamics and wall shear stress remain stable over short-term follow-up in pediatric and young adult patients with bicuspid aortic valve.

BACKGROUND: Children with bicuspid aortic valve (BAV) are at risk for serious complications including aortic valve stenosis and aortic rupture. Most studies investigating biomarkers predictive of BAV complications are focused on adults. OBJECTIVE: To investigate whether hemodynamic parameters change over time in children and young adults with BAV by comparing baseline and follow-up four-dimensional (4-D) flow MRI examinations. MATERIALS AND METHODS: We retrospectively included 19 children and young adults with BAV who had serial 4-D flow MRI exams (mean difference in scan dates 1.8±1.0 [range, 0.6-3.4 years]). We compared aortic peak blood flow velocity, three-dimensional (3-D) wall shear stress, aortic root and ascending aortic (AAo) z-scores between baseline and follow-up exams. We generated systolic streamlines for all patients and visually compared their baseline and follow-up exams. RESULTS: The only significant difference between baseline and follow-up exams occurred in AAo z-scores (3.12±2.62 vs. 3.59±2.76, P<0.05) indicating growth of the AAo out of proportion to somatic growth. There were no significant changes in either peak velocity or 3-D wall shear stress between baseline and follow-up exams. Ascending aortic peak velocity at baseline correlated with annual change in AAo z-score (r=0.58, P=0.009). Visual assessment revealed abnormal blood flow patterns, which were unique to each patient and remained stable between baseline and follow-up exams. CONCLUSION: In our pediatric and young adult BAV cohort, hemodynamic markers and systolic blood flow patterns remained stable over short-term follow-up despite significant AAo growth, suggesting minimal acute disease progression. Baseline AAo peak velocity was a predictor of AAo dilation and might help in determining pediatric patients with BAV who are at risk of increased AAo growth.

Voxel-by-voxel 4D flow MRI-based assessment of regional reverse flow in the aorta.

BACKGROUND: Complex and reverse flow in the aorta has been implicated in aneurysm development and stroke via retrograde embolization. PURPOSE: To evaluate global and regional differences between standard 2D plane-based and volumetric voxel-based quantification of regional forward/reverse flow, and reverse flow fraction (RFF) in the aorta. STUDY TYPE: Retrospective. SUBJECTS: In all, 35 subjects: 10 healthy controls (age: 57 ± 7 years, nine male), nine patients without aortic valve regurgitation (AR) (age: 63 ± 10 years, seven male), six patients with mild AR (age: 66 ± 6 years, five male), and 10 with moderate or severe AR (age: 60 ± 16 years, eight male). FIELD STRENGTH/SEQUENCE: 4D flow MRI (3T and 1.5T) was employed to acquire 3D blood flow velocities with entire thoracic aorta in all subjects. ASSESSMENT: Data analysis included standard 2D plane-based quantification of forward/reverse flow, and RFF-plane. In addition, a new semiautomatic workflow based on 3D segmentation and extraction of an aorta centerline was developed for voxel-by-voxel visualization (forward/reverse flow and RFF-voxel maps) and quantification of regional voxel-by-voxel forward/reverse flow in the entire thoracic aorta. STATISTICAL TESTS: Kruskal-Wallis tests were performed to test for differences between groups. A two-sample t-test or Wilcoxon rank sum test was used to compare voxel-based and plane-based results. RESULTS: Semiautomatic plane-based analysis showed excellent agreement with standard manual plane-based analysis for net flow and RFF-plane (RFF-plane: y = 0.99x-0.0, net flow: y = 1.00x-0.21, R > 0.99, P < 0.0001). Voxel-by-voxel maps demonstrated marked regional flow reversal in the ascending aorta in all patients and RFF-voxel was significantly increased (P < 0.001) compared to RFF-plane for all four groups, with the most pronounced differences for mild AR (18.0 ± 15.2% vs. 4.7 ± 5.4%). Voxel-based flow and RFF-voxel along the aorta showed areas with marked regional flow reversal (eg, vortex flow) compared to plane-based analysis. DATA CONCLUSION: Voxel-based analysis demonstrated regional flow reversal that was not detected by plane-based analysis. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1276-1286.

Distribution of blood flow velocity in the normal aorta: Effect of age and gender.

PURPOSE: To apply flow distribution analysis in the entire aorta across a wide age range from pediatric to adult subjects. MATERIAL AND METHODS: In all, 98 healthy subjects (age 9-78 years, 41 women) underwent 4D flow MRI at 1.5T and 3T for the assessment of 3D blood flow in the thoracic aorta. Subjects were categorized into age groups: group 1 (n = 9, 5 women): 9-15 years; group 2 (n = 13, 8 women): 16-20 years; group 3 (n = 27, 14 women): 21-39 years; group 4 (n = 40, 11 women): 40-59 years; group 5 (n = 9, 3 women): >60 years. Data analysis included the 3D segmentation of the aorta, aortic valve peak velocity, mid-ascending aortic diameter, and calculation of flow velocity distribution descriptors (mean, median, standard deviation, incidence of velocities >1 m/s, skewness, and kurtosis of aortic velocity magnitude). Ascending aortic diameter was normalized by body surface area. RESULTS: Age was significantly associated with normalized aortic diameter (R = 0.73, P < 0.001), skewness (R = 0.76, P < 0.001), and kurtosis (R = 0.74, P < 0.001), all adjusted by heart rate. Aortic peak velocity and velocity distribution descriptors, adjusted by heart rate, were significantly different between age groups (P < 0.001, analysis of covariance). Skewness and kurtosis significantly increased (P < 0.001) during adulthood (>40 years) as compared with childhood (<21 years). Men and women revealed significant differences (P ≤ 0.05) for peak velocity, incidence, mean, median, standard deviation, and skewness, all adjusted by heart rate. CONCLUSION: Aortic hemodynamics significantly change with age and gender, indicating the importance of age- and gender-matched control cohorts for the assessment of the impact of cardiovascular disease on aortic blood flow. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:487-498.

Efficient method for volumetric assessment of peak blood flow velocity using 4D flow MRI.

PURPOSE: To test the feasibility and effectiveness of using maximum intensity plots (MIPs) based on 4D flow magnetic resonance imaging (MRI) velocity data to assess systolic peak velocities in a cohort of bicuspid aortic valve (BAV) patients. MATERIALS AND METHODS: 4D flow MRI at 1.5T was performed on 51 BAV patients. MIPs were generated from the 4D flow MRI velocity data and used by two users to determine peak velocities in three regions of interest (ROIs): ascending aorta (AAo), aortic arch, and descending aorta. 4D flow MRI peak velocities in the AAo were compared to peak velocities recorded by 2D phase contrast MRI (2D PCMRI) in a subcohort of 36 patients and by Doppler echocardiography in a subcohort of 34 patients. 4D flow MRI peak velocities recorded by each observer were compared for all ROIs to test for interobserver variability. RESULTS: 4D flow MRI recorded significantly higher velocities compared to 2D PCMRI (2.04 ± 0.71 m/s vs. 1.69 ± 0.79 m/s, 17.2% difference, P < 0.001) and similar velocities compared to Doppler echocardiography. There was excellent agreement between the observers, with a mean difference of 0.005 m/s and an intraclass correlation coefficient of 0.98. CONCLUSION: 4D flow MRI velocity MIPs allow for efficient measurement of peak velocities in BAV patients with higher accuracy than 2D PCMRI and similar accuracy to Doppler echocardiography. J. Magn. Reson. Imaging 2016;44:1673-1682.

Hemodynamic evaluation in patients with transposition of the great arteries after the arterial switch operation: 4D flow and 2D phase contrast cardiovascular magnetic resonance compared with Doppler echocardiography.

BACKGROUND: Peak velocity measurements are used to evaluate the significance of stenosis in patients with transposition of the great arteries after the arterial switch operation (TGA after ASO). 4D flow cardiovascular magnetic resonance (CMR) provides 3-directional velocity encoding and full volumetric coverage of the great arteries and may thus improve the hemodynamic evaluation in these patients. The aim of this study was to compare peak velocities measured by 4D flow CMR with 2D phase contrast (PC) CMR and the gold standard Doppler echocardiography (echo) in patients with TGA after ASO. METHODS: Nineteen patients (mean age 13 ± 9 years, range 1-25 years) with TGA after ASO who underwent 2D PC CMR and 4D flow CMR were included in this study. Peak velocities were measured with 4D flow CMR in the aorta and pulmonary arteries and compared to peak velocities measured with 2D PC CMR and Doppler echo. 2D PC CMR data were available in the ascending aorta, main, right and left pulmonary arteries (AAO/MPA/RPA/LPA) for 19/18/17/17 scans, respectively, and Doppler echo data were available for 13/9/6/6 scans, respectively. Peak velocities were measured with: 1) a single cross section for 2D PC CMR, 2) velocity maximum intensity projections (MIPs) for 4D flow CMR and 3) Doppler echo. RESULTS: Significantly higher peak velocities were found with 4D flow CMR than 2D PC CMR in the AAO (p = 0.003), MPA (p = 0.002) and RPA (p = 0.005) but not in the LPA (p = 0.200). No difference in peak velocity was found between 4D flow CMR and Doppler echo (p > 0.46) or 2D PC CMR and echo (p > 0.11) for all analyzed vessel segments. CONCLUSIONS: 4D flow CMR evaluation of patients with TGA after ASO detected higher peak velocities than 2D PC CMR, indicating the potential of 4D flow CMR to provide improved stenosis assessment in these patients.

Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI.

BACKGROUND: Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. OBJECTIVE: We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. MATERIALS AND METHODS: Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). RESULTS: Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R(2)=0.50, P=0.02; SVC to LPA: R(2)=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. CONCLUSION: Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability.

Thoracic aorta 3D hemodynamics in pediatric and young adult patients with bicuspid aortic valve.

BACKGROUND: To evaluate the 3D hemodynamics in the thoracic aorta of pediatric and young adult bicuspid aortic valve (BAV) patients. METHODS: 4D flow MRI was performed in 30 pediatric and young adult BAV patients (age: 13.9 ± 4.4 (range: [3.4, 20.7]) years old, M:F = 17:13) as part of this Institutional Review Board-approved study. Nomogram-based aortic root Z-scores were calculated to assess aortic dilatation and degree of aortic stenosis (AS) severity was assessed on MRI. Data analysis included calculation of time-averaged systolic 3D wall shear stress (WSSsys ) along the entire aorta wall, and regional quantification of maximum and mean WSSsys and peak systolic velocity (velsys ) in the ascending aorta (AAo), arch, and descending aorta (DAo). The 4D flow MRI AAo velsys was also compared with echocardiography peak velocity measurements. RESULTS: There was a positive correlation with both mean and max AAo WSSsys and peak AAo velsys (mean: r = 0.84, P < 0.001, max: r = 0.94, P < 0.001) and AS (mean: rS = 0.43, P = 0.02, max: rS = 0.70, P < 0.001). AAo peak velocity was significantly higher when measured with echo compared with 4D flow MRI (2.1 ± 0.98 m/s versus 1.27 ± 0.49 m/s, P < 0.001). CONCLUSION: In pediatric and young adult patients with BAV, AS and peak ascending aorta velocity are associated with increased AAo WSS, while aortic dilation, age, and body surface area do not significantly impact AAo hemodynamics. Prospective studies are required to establish the role of WSS as a risk-stratification tool in these patients.

Neurofunctional effects of quetiapine in patients with bipolar mania.

OBJECTIVES: Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. METHODS: Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. RESULTS: At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003). CONCLUSIONS: These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change.

4-D flow magnetic resonance imaging: blood flow quantification compared to 2-D phase-contrast magnetic resonance imaging and Doppler echocardiography.

BACKGROUND: Doppler echocardiography (echo) is the reference standard for blood flow velocity analysis, and two-dimensional (2-D) phase-contrast magnetic resonance imaging (MRI) is considered the reference standard for quantitative blood flow assessment. However, both clinical standard-of-care techniques are limited by 2-D acquisitions and single-direction velocity encoding and may make them inadequate to assess the complex three-dimensional hemodynamics seen in congenital heart disease. Four-dimensional flow MRI (4-D flow) enables qualitative and quantitative analysis of complex blood flow in the heart and great arteries. OBJECTIVES: The objectives of this study are to compare 4-D flow with 2-D phase-contrast MRI for quantification of aortic and pulmonary flow and to evaluate the advantage of 4-D flow-based volumetric flow analysis compared to 2-D phase-contrast MRI and echo for peak velocity assessment in children and young adults. MATERIALS AND METHODS: Two-dimensional phase-contrast MRI of the aortic root, main pulmonary artery (MPA), and right and left pulmonary arteries (RPA, LPA) and 4-D flow with volumetric coverage of the aorta and pulmonary arteries were performed in 50 patients (mean age: 13.1 ± 6.4 years). Four-dimensional flow analyses included calculation of net flow and regurgitant fraction with 4-D flow analysis planes similarly positioned to 2-D planes. In addition, 4-D flow volumetric assessment of aortic root/ascending aorta and MPA peak velocities was performed and compared to 2-D phase-contrast MRI and echo. RESULTS: Excellent correlation and agreement were found between 2-D phase-contrast MRI and 4-D flow for net flow (r = 0.97, P < 0.001) and excellent correlation with good agreement was found for regurgitant fraction (r = 0.88, P < 0.001) in all vessels. Two-dimensional phase-contrast MRI significantly underestimated aortic (P = 0.032) and MPA (P < 0.001) peak velocities compared to echo, while volumetric 4-D flow analysis resulted in higher (aortic: P = 0.001) or similar (MPA: P = 0.98) peak velocities relative to echo. CONCLUSION: Excellent flow parameter agreement between 2-D phase-contrast MRI and 4-D flow and the improved volumetric 4-D flow velocity analysis relative to echo suggests that 4-D flow has the potential to become a clinical alternative to 2-D phase-contrast MRI.