Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5×1.5×1.5 – 3×3×3 mm3, typical temporal resolution of 30–40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

Correspondence to Alex J. Barker, PhD, Department of Radiology, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL 60611. E-mail alex.barker@northwestern.edu Background-Hemodynamics may play a role contributing to the progression of bicuspid aortic valve (BAV) aortopathy.This study measured the impact of BAV on the distribution of regional aortic wall shear stress (WSS) compared with control cohorts. Methods and Results-Local WSS distribution was measured in the thoracic aorta of 60 subjects using 4-dimensional (4D) flow-sensitive magnetic resonance imaging. WSS analysis included 15 BAV patients: 12 with fusion of the right-left coronary cusp (6 stenotic) and 3 with fusion of the right and noncoronary cusp. The right-left BAV cohort was compared with healthy subjects (n=15), age-appropriate subjects (n=15), and age-/aorta size-controlled subjects (n=15). Compared with the age-appropriate and age-/aorta size-matched controls, WSS patterns in the right-left BAV ascending aorta were significantly elevated, independent of stenosis severity (peak WSS=0.9±0.3 N/m 2 compared with 0.4±0.3 N/m 2 in age-/aorta size-controlled subjects; P<0.001). Time-resolved (cine) 2D images of the bicuspid valves were coregistered with 4D flow data, directly linking cusp fusion pattern to a distinct ascending aortic flow jet pattern. The observation of right-anterior ascending aorta wall/jet impingement in right-left BAV patients corresponded to regions with statistically elevated WSS. Alternative jetting patterns were observed in the right and noncoronary cusp fusion patients. Conclusions-The results of this study demonstrate that bicuspid valves induced significantly altered ascending aorta hemodynamics compared with age-and size-matched controls with tricuspid valves. Specifically, the expression of increased and asymmetric WSS at the aorta wall was related to ascending aortic flow jet patterns, which were influenced by the BAV fusion pattern. (Circ Cardiovasc Imaging. 2012;5:457-466.)

Background: Aortic 3D blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy. Methods and Results: 4D flow MRI measured in vivo 3D blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4mm; n=15 RN-BAV, 39.6±7.2mm); aorta size controls with tricuspid aortic valves (n=30, 41.1±4.4mm); healthy volunteers (n=15, 24.9±3.0mm). Aortopathy type (0-3), systolic flow angle, flow displacement, and regional wall shear stress (WSS) were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional WSS (p<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV compared to aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV were associated with altered flow displacement in the proximal and mid AAo for type 1 (42-81% decrease versus type 2) and distal AAo for type 3 (33-39% increase versus type 2). Conclusions: The presence and type of BAV fusion was associated with changes in regional WSS distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiologic mechanism by which valve morphology phenotype can influence phenotypes of BAV aortopathy.

BACKGROUND Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) has influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients. OBJECTIVES We assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation. METHODS BAV patients (n = 20) undergoing ascending aortic resection underwent preoperative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression. RESULTS Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS. CONCLUSIONS Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted.

BackgroundThe purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers.MethodsThoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified.ResultsIncidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05).ConclusionsIncrease in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.

Background Ascending aortic dilation is important in bicuspid aortic valve disease (BAV), with increased risk of aortic dissection. We used cardiovascular magnetic resonance (CMR) to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function and aortic dilation. Methods and Results 142 subjects underwent CMR (mean age 40 years; 95 with BAV, 47 healthy volunteers [HV]). BAV patients had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3 ±3.3 vs. 15.2 ±2.2mm/m2, p<0.001), and higher rotational (helical) flow (31.7 ±15.8 vs. 2.9 ±3.9mm2/s, p<0.001), systolic flow angle (23.1 ±12.5 vs. 7.0 ±4.6°, p<0.001) and systolic wall shear stress (WSS) (0.85 ±0.28 vs. 0.59 ±0.17N/m2, p<0.001) compared to HV. BAV with right-handed flow and right-non coronary cusp fusion (n= 31) showed more severe flow abnormalities (rotational flow 38.5 ±16.5 vs. 27.8 ±12.4mm2/s, p<0.001; systolic flow angle 29.4 ±10.9 vs. 19.4 ±11.4°, p<0.001; in-plane WSS 0.64 ±0.23 vs. 0.47 ±0.22N/m2, p<0.001) and larger aortas (19.5 ±3.4 vs. 17.5 ±3.1mm/m2, p<0.05) than right-left cusp fusion (n=55). BAV patients with normal flow patterns had similar aortic dimensions and WSS to HV and younger BAV patients showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the etiology of aortic dilation. Aortic function measures (distensibility, aortic strain and pulse wave velocity) were similar across all groups. Conclusions Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities, and may allow better risk prediction and selection of patients for earlier surgical intervention.

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Bicuspid aortic valve (BAV) is often concomitant with aortic dilatation, aneurysm, and dissection. This valve lesion and its complications may affect positional and temporal wall shear stress (WSS), a parameter reported to regulate transcriptional events in vascular remodeling. Thus, this pilot study seeks to determine if the WSS in the ascending aorta (AAo) of BAV patients differs from control patients. Phase-contrast magnetic resonance imaging (PC-MRI) was used to perform flow analysis at the level of the AAo in 15 BAV and 15 control patients. Measurement of the aorta dimensions, flow rates, regurgitant fraction (RF), flow reversal ratio (FRR), temporal and spatial WSS, and shear range indices (SRI) were performed. The BAV and control group showed a significant difference between the circumferentially averaged WSS (p = 0.03) and positional WSS at systole (minimum p<0.001). Regressions found that SRI (r = 0.77, p<0.001), RF (r = 0.68, p<0.001), and WSS at systole (r = 0.66, p<0.001) were correlated to AAo size. The spatial distribution and magnitude of systolic WSS in BAV patients (−6.7 ± 4.3 dynes/cm2) differed significantly from control patients (−11.5 ± 6.6 dynes/cm2, p = 0.03). The SRI metric, a measure of shear symmetry along the lumen circumference, was also significantly different (p = 0.006) and indicated a heterogenic pattern of dilatation in the BAV patients.