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.

This work describes a new approach to multipoint Dixon fatwater separation that is amenable to pulse sequences that require short echo time (TE) increments, such as steady-state free precession (SSFP) and fast spin-echo (FSE) imaging. Using an iterative linear least-squares method that decomposes water and fat images from source images acquired at short TE increments, images with a high signal-to-noise ratio (SNR) and uniform separation of water and fat are obtained. This algorithm extends to multicoil reconstruction with minimal additional complexity. Examples of single-and multicoil fat-water decompositions are shown from source images acquired at both 1.5T and 3.0T. Examples in the knee, ankle, pelvis, abdomen, and heart are shown, using FSE, SSFP, and spoiled gradient-echo (SPGR) pulse sequences. The algorithm was applied to systems with multiple chemical species, and an example of water-fatsilicone separation is shown. An analysis of the noise performance of this method is described, and methods to improve noise performance through multicoil acquisition and field map smoothing are discussed. Steady-state free precession (SSFP) is a rapid, short-TR imaging technique that offers specific advantages over short-TR gradient-echo techniques, including a high signal-to-noise ratio (SNR) and favorable contrast behavior. This is especially true for the visualization of fluid, because its contrast depends upon both T 1 and T 2 (1-3). However, the use of SSFP has been limited by the fact that fluid and fat both appear bright on SSFP images. This characteristic of SSFP may cause abnormalities to appear similar to normal fat and thus obscure underlying pathology.The application of a Dixon fat-water separation method to SSFP imaging could potentially provide homogeneous and reliable separation of fat and water from SSFP images (4,5). Current methods for SSFP fat suppression include fluctuating equilibrium magnetic resonance (FEMR), linear combination SSFP, and fat-suppressed SSFP. However, all of these techniques are sensitive to field heterogeneities (6 -8). The notion of combining Dixon methods with SSFP is challenging for several reasons. First, SSFP requires short repetition times (TRs) to prevent image degradation from field heterogeneities (1,2). This constraint limits TE increments to values that are smaller than those traditionally used in three-point Dixon methods (5). In addition, resonant frequency offsets from chemical shift and field heterogeneities produce additional phase shifts that are unique to SSFP and are problematic for Dixon fat-water decomposition techniques (2,6).The application of Dixon imaging in fast spin-echo (FSE) sequences has also been limited because the acquisition of echoes at different time shifts with respect to the SE increases the spacing between successive refocusing pulses (echo spacing) (9). Increasing the echo spacing reduces the number of echoes that can be collected in a time that maintains acceptable blurring from T 2 decay (10), offsetting the scan time benefits of FSE. A fat...

Quantification of CINE phase contrast (PC)-MRI data is a challenging task because of the limited spatiotemporal resolution and signal-to-noise ratio (SNR). The method presented in this work combines B-spline interpolation and Green's theorem to provide optimized quantification of blood flow and vessel wall parameters. The B-spline model provided optimal derivatives of the measured three-directional blood velocities onto the vessel contour, as required for vectorial wall shear stress (WSS) computation. Eight planes distributed along the entire thoracic aorta were evaluated in a 19-volunteer study using both high-spatiotemporal-resolution planar two-dimensional (2D)-CINE-PC ( approximately 1.4 x 1.4 mm(2)/24.4 ms) and lower-resolution 3D-CINE-PC ( approximately 2.8 x 1.6 x 3 mm(3)/48.6 ms) with three-directional velocity encoding. Synthetic data, error propagation, and interindividual, intermodality, and interobserver variability were used to evaluate the reliability and reproducibility of the method. While the impact of MR measurement noise was only minor, the limited resolution of PC-MRI introduced systematic WSS underestimations. In vivo data demonstrated close agreement for flow and WSS between 2D- and 3D-CINE-PC as well as observers, and confirmed the reliability of the method. WSS analysis along the aorta revealed the presence of a circumferential WSS component accounting for 10-20%. Initial results in a patient with atherosclerosis suggest the potential of the method for understanding the formation and progression of cardiovascular diseases.

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.

Traditionally, magnetic resonance imaging (MRI) of flow using phase contrast (PC) methods is accomplished using methods that resolve single-directional flow in two spatial dimensions (2D) of an individual slice. More recently, three-dimensional (3D) spatial encoding combined with three-directional velocity-encoded phase contrast MRI (here termed 4D flow MRI) has drawn increased attention. 4D flow MRI offers the ability to measure and to visualize the temporal evolution of complex blood flow patterns within an acquired 3D volume. Various methodological improvements permit the acquisition of 4D flow MRI data encompassing individual vascular structures and entire vascular territories such as the heart, the adjacent aorta, the carotid arteries, abdominal, or peripheral vessels within reasonable scan times. To subsequently analyze the flow data by quantitative means and visualization of complex, three-directional blood flow patterns, various tools have been proposed. This review intends to introduce currently used 4D flow MRI methods, including Cartesian and radial data acquisition, approaches for accelerated data acquisition, cardiac gating, and respiration control. Based on these developments, an overview is provided over the potential this new imaging technique has in different parts of the body from the head to the peripheral arteries.

BackgroundPhase contrast cardiovascular magnetic resonance (CMR) is able to measure all three directional components of the velocities of blood flow relative to the three spatial dimensions and the time course of the heart cycle. In this article, methods used for the acquisition, visualization, and quantification of such datasets are reviewed and illustrated.MethodsCurrently, the acquisition of 3D cine (4D) phase contrast velocity data, synchronized relative to both cardiac and respiratory movements takes about ten minutes or more, even when using parallel imaging and optimized pulse sequence design. The large resulting datasets need appropriate post processing for the visualization of multidirectional flow, for example as vector fields, pathlines or streamlines, or for retrospective volumetric quantification.ApplicationsMultidirectional velocity acquisitions have provided 3D visualization of large scale flow features of the healthy heart and great vessels, and have shown altered patterns of flow in abnormal chambers and vessels. Clinically relevant examples include retrograde streams in atheromatous descending aortas as potential thrombo-embolic pathways in patients with cryptogenic stroke and marked variations of flow visualized in common aortic pathologies. Compared to standard clinical tools, 4D velocity mapping offers the potential for retrospective quantification of flow and other hemodynamic parameters.ConclusionsMultidirectional, 3D cine velocity acquisitions are contributing to the understanding of normal and pathologically altered blood flow features. Although more rapid and user-friendly strategies for acquisition and analysis may be needed before 4D velocity acquisitions come to be adopted in routine clinical CMR, their capacity to measure multidirectional flows throughout a study volume has contributed novel insights into cardiovascular fluid dynamics in health and disease.