Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

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.

Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D. METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was assessed using carotid-to-femoral applanation tonometry. Regional PWV was measured via 2D phase-contrast MRI and 4D flow MRI. RESULTS: Global arterial PWV did not differ between CWO and T2D. 2D PC-MRI PWV in the ascending aorta was higher in people with T2D compared with CWOs ( P  < 0.01). 4D flow PWV in the thoracic aorta was higher in CWO ( P  < 0.01), and T2D ( P  < 0.001) compared with RC. End-diastolic volume, end-systolic volume, stroke volume, and cardiac output were lower in CWO and T2D groups compared with reference control. CONCLUSION: Subclinical changes in arterial stiffening and cardiac remodeling in inactive CWO and T2D compared with reference control support obesity and/or physical inactivity as determinants of incipient CVD complications in uncomplicated T2D. Future studies should determine the mechanistic causes of the CVD complications in greater detail in order to create therapeutic targets. CLINICAL TRIAL REGISTRATION: Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex (NCT03419195).

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.

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.

Baseline 4D Flow-Derived in vivo Hemodynamic Parameters Stratify Descending Aortic Dissection Patients With Enlarging Aortas.

Purpose: The purpose of our study was to assess the value of true lumen and false lumen hemodynamics compared to aortic morphological measurements for predicting adverse-aorta related outcomes (AARO) and aortic growth in patients with type B aortic dissection (TBAD). Materials and Methods: Using an IRB approved protocol, we retrospectively identified patients with descending aorta (DAo) dissection at a large tertiary center. Inclusion criteria includes known TBAD with ≥ 6 months of clinical follow-up after initial presentation for TBAD or after ascending aorta intervention for patients with repaired type A dissection with residual type B aortic dissection (rTAAD). Patients with prior descending aorta intervention were excluded. The FL and TL of each patient were manually segmented from 4D flow MRI data, and 3D parametric maps of aortic hemodynamics were generated. Groups were divided based on (1) presence vs. absence of AARO and (2) growth rate ≥ vs. < 3 mm/year. True and false lumen kinetic energy (KE), stasis, peak velocity (PV), reverse/forward flow (RF/FF), FL to TL KE ratio, as well as index aortic diameter were compared between groups using the Mann-Whitney U or independent t-test. Results: A total of n = 51 patients (age: 58.4 ± 15.0 years, M/F: 31/20) were included for analysis of AARO. This group contained n = 26 patients with TBAD and n = 25 patients with rTAAD. In the overall cohort, AARO patients had larger baseline diameters, lower FL-RF, FL stasis, TL-KE, TL-FF and TL-PV. Among patients with de novo TBAD, those with AAROs had larger baseline diameter, lower FL stasis and TL-PV. In both the overall cohort and in the subgroup of de novo TBAD, subjects with aortic growth ≥ 3mm/year, patients had a higher KE ratio. Conclusion: Our study suggests that 4D flow MRI is a promising tool for TBAD evaluation that can provide information beyond traditional MRA or CTA. 4D flow has the potential to become an integral aspect of TBAD work-up, as hemodynamic assessment may allow earlier identification of at-risk patients who could benefit from earlier intervention.

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.

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.

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.

Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient's body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = -0.648, p < 0.001), RF (R = -0.441, p < 0.001), and stasis (R = -0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

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.

Aortic annular dimensions by non-contrast MRI using k-t accelerated 3D cine b-SSFP in pre-procedural assessment for transcatheter aortic valve implantation: a technical feasibility study.

To evaluate k-t accelerated 3D cine b-SSFP (balanced steady state free precession) as magnetic resonance imaging (MRI) technique for aortic annular area measurement in transcatheter aortic valve replacement (TAVR) planning compared to computed tomography angiography (CTA) and other non-contrast MRI sequences with reduced imaging time and without contrast administration. 6 volunteers and 7 TAVR candidates were prospectively enrolled. The volunteers underwent an MRI while TAVR candidates underwent an MRI and CTA. The following non-contrast MRI sequences were obtained at the level of the aortic root: 2D cine b-SSFP [GRAPPA (GeneRalized Autocalibrating Partially Parallel Acquisitions), R = 2], 3D cine b-SSFP [GRAPPA R = 2], navigator triggered 3D b-SSFP MRA [GRAPPA, R = 2] and k-t accelerated 3D cine b-SSFP [PEAK GRAPPA, R = 5]. Qualitative analysis and aortic annular area measurements in systole and diastole were obtained. k-t accelerated 3D cine b-SSFP provided image quality that is acceptable for confident diagnosis with very good interrater agreement. There was no statistically significant difference in aortic annular measurements between k-t accelerated 3D cine b-SSFP and CTA or other MRI sequences (p > 0.05). Bland-Altman analysis showed no systemic difference of annular area measurements between k-t accelerated 3D cine b-SSFP and each of the other techniques. There was excellent inter-rater agreement on aortic annular area measurements during systolic (ICC = 0.976, p < 0.001) and diastolic (ICC = 0.971, p < 0.001) phases using k-t accelerated 3D cine b-SSFP. K-t accelerated 3D cine b-SSFP is a promising alternative for the assessment of annular sizing in pre-TAVR evaluation while offering a reasonable combination of imaging parameters during one breath-hold.

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.

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.

Detection and Hemodynamic Evaluation of Flap Fenestrations in Type B Aortic Dissection with 4D Flow MRI: Comparison with Conventional MRI and CTA.

PURPOSE: The purpose of this study was to compare dissection flap fenestration visualization between 4D flow MRI, clinical MRI/MRA, and clinical CTA studies and describe the presence of hemodynamically active fenestration flow using 4D flow. MATERIALS AND METHODS: Nineteen patients with type B dissection (age: 57±5 years) who had undergone standard of-care MRI/MRA of the chest including 4D flow MRI were retrospectively identified. Fourteen of the 19 patients also had CTA performed within 2 years of the MRI/MRA study with no interval surgery. Image review was performed independently by two radiologists. The number of fenestrations (including entry and exit tears), location, and flow directionality were recorded. Differences in the rate of detection between techniques was assessed using a Wilcoxon signed rank test. RESULTS: 4D flow detected more fenestrations relative to MRI/MRA [rev 1: +3 (10%), rev 2: +5 (20%)]. There were similar numbers of fenestrations detected by 4D flow relative to CTA [rev 1: +1 (4%), rev 2: -3 (-12%)]. MRI/MRA detected fewer fenestration relative to CTA in this cohort [rev 1: -6 (-24%), rev 2: -5 (-19%)]. No differences were significant. Combining 4D flow and MRI/MRA resulted in additional fenestration detection. Most fenestrations demonstrated biphasic flow over the cardiac cycle (flow entering false lumen in systole and exiting during diastole, rev 1:18/33, rev 2: 16/30). CONCLUSIONS: 4D flow MRI can detect small flap fenestration in type B dissection patients while providing additional information about flow through fenestrations throughout the cardiac cycle relative to CTA and conventional MRI.

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.

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.

Two-Minute k-Space and Time-accelerated Aortic Four-dimensional Flow MRI: Dual-Center Study of Feasibility and Impact on Velocity and Wall Shear Stress Quantification.

PURPOSE: To investigate the two-center feasibility of highly k-space and time (k-t)-accelerated 2-minute aortic four-dimensional (4D) flow MRI and to evaluate its performance for the quantification of velocities and wall shear stress (WSS). MATERIALS AND METHODS: This cross-sectional study prospectively included 68 participants (center 1, 11 healthy volunteers [mean age ± standard deviation, 61 years ± 15] and 16 patients with aortic disease [mean age, 60 years ± 10]; center 2, 14 healthy volunteers [mean age, 38 years ± 13] and 27 patients with aortic or cardiac disease [mean age, 78 years ± 18]). Each participant underwent highly accelerated 4D flow MRI (k-t acceleration, acceleration factor of 5) of the thoracic aorta. For comparison, conventional 4D flow MRI (acceleration factor of 2) was acquired in the participants at center 1 (n = 27). Regional aortic peak systolic velocities and three-dimensional WSS were quantified. RESULTS: k-t-accelerated scan times (center 1, 2:03 minutes ± 0:29; center 2, 2:06 minutes ± 0:20) were significantly reduced compared with conventional 4D flow MRI (center 1, 12:38 minutes ± 2:25; P < .0001). Overall good agreement was found between the two techniques (absolute differences ≤15%), but proximal aortic WSS was significantly underestimated in patients by using k-t-accelerated 4D flow when compared with conventional 4D flow (P ≤ .03). k-t-accelerated 4D flow MRI was reproducible (intra- and interobserver intraclass correlation coefficient ≥0.98) and identified significantly increased peak velocities and WSS in patients with stenotic (P ≤ .003) or bicuspid (P ≤ .04) aortic valves compared with healthy volunteers. In addition, k-t-accelerated 4D flow MRI-derived velocities and WSS were inversely related to age (r ≥-0.53; P ≤ .03) over all healthy volunteers. CONCLUSION: k-t-accelerated aortic 4D flow MRI providing 2-minute scan times was feasible and reproducible at two centers. Although consistent healthy aging- and disease-related changes in aortic hemodynamics were observed, care should be taken when considering WSS, which can be underestimated in patients.© RSNA, 2019See also the commentary by François in this issue.