Advanced Analysis Techniques for Intra-cardiac Flow Evaluation from 4D Flow MRI
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Purpose of the Review
Time-resolved 3D velocity-encoded MR imaging with velocity encoding in three directions (4D Flow) has emerged as a novel MR acquisition technique providing detailed information on flow in the cardiovascular system. In contrast to other clinically available imaging techniques such as echo-Doppler, 4D Flow MRI provides the 3D Flow velocity field within a volumetric region of interest over the cardiac cycle. This work reviews the most recent advances in the development and application of dedicated image analysis techniques for the assessment of intra-cardiac flow features from 4D Flow MRI.
Novel image analysis techniques have been developed for extraction of relevant intra-cardiac flow features from 4D Flow MRI, which have been successfully applied in various patient cohorts and volunteer studies. Disturbed flow patterns have been linked with valvular abnormalities and ventricular dysfunction. Recent technical advances have resulted in reduced scan times and improvements in image quality, increasing the potential clinical applicability of 4D Flow MRI.
4D Flow MRI provides unique capabilities for 3D visualization and quantification of intra-cardiac blood flow. Contemporary knowledge on 4D Flow MRI shows promise for further exploration of the potential use of the technique in research and clinical applications.
Keywords4D Flow CMR Kinetic energy Vortex Image processing Streamlines Path lines Flow components
Two-dimensional (2D) phase-contrast MRI (PC-MRI) is an established acquisition method in clinical MR protocols for vascular flow quantification by acquiring time-resolved cross-sectional images with velocity encoding in the through-plane direction. Based on the area of the vessel cross-section and the average velocity within the defined region, the instantaneous flow rate and total forward and backward flow during a cardiac cycle can be derived. However, the moving geometry of the heart and the complexity of intra-cardiac flow patterns during systole and diastole make it very challenging to quantify flow using 2D phase-contrast PC-MRI. Time-resolved 3D imaging with velocity information in each of the three spatial dimensions has demonstrated reliability and accuracy in quantification of intra-cardiac flow. 4D Flow MRI provides 3D images with encoding of the velocity magnitude and direction of each voxel within the defined volume throughout the cardiac cycle by acquiring data over multiple cardiac cycles. The 3D velocity information obtained, therefore, describes an average cardiac cycle, and information related to beat-to-beat variations is not provided. More than 15 years ago, researchers have started investigating the feasibility of 4D Flow MRI for intra-cardiac flow analysis [1, 2, 3]. Until now, relatively few groups have been active in this area of research, potentially because of limitations in the availability of 4D Flow MRI and the long acquisition times limiting the applicability. However, advances in MR hardware and sequence design have resulted in a significant increase in the use of 4D Flow MRI for vascular and intra-cardiac applications . More recently, consensus statement guidelines on the use of 4D Flow MRI were formulated, which aim to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels [5•]. The focus of the current review is to summarize methods used and the applications for visual and quantitative analysis of intra-cardiac flow from 4D Flow MRI.
Imaging Protocol Considerations
The imaging protocol for whole-heart 4D Flow MRI should be tailored to the specific analysis for which it is being used. Parameters to be considered are the volumetric coverage of the acquisition, velocity encoding sensitivity (VENC) selection, temporal and spatial resolution, and the type of respiratory motion compensation. For the assessment of the complete cardiac cycle, including the phases of early and late diastolic filling, retrospective cardiac gating should be employed, such that velocity images are obtained equally spaced over the complete cardiac cycle. Evaluation of the large-scale flow patterns in the heart requires a spatial resolution equal to or <3 × 3 × 3 mm [5•]. Flow analysis using particle tracing requires sufficiently high temporal resolution. As is typical in MR sequence optimization, a proper trade-off needs to be made in order to find the right balance between the parameters to be optimized. Validation studies should be performed, ideally including phantom experiments, in order to gain insight into the accuracy and precision of the parameters to be derived from the employed 4D Flow sequence.
As the magnitude images which are obtained with the 4D Flow scan are typically of poor quality, additional cine MR imaging is often acquired in multiple views to provide an anatomical reference. This allows visualization and analysis of the velocity data from the 4D Flow acquisition in relation to the cardiac motion and anatomy. The number of frames reconstructed from the cine scans should ideally be equal to that of the 4D Flow scan. A disadvantage of such multi-sequence approach is that as a result of patient motion and heart rate variation between scans additional post-processing may be required to correct for image misalignment between sequences. Hsiao et al. have proposed the use of an accelerated post-contrast 4D Flow sequence generating velocity information in the three spatial dimensions along with diagnostic quality anatomical images . They could demonstrate that using this approach reliable assessment of ventricular dimensions in addition to valvular flow quantification can be performed in a single acquisition .
Pre-processing and Data Verification
The obtained image data may require data pre-processing before reliable analyses can be performed. Correction methods have been described for potential errors in the velocity data including velocity aliasing and phase offset errors due to Eddy currents, Maxwell terms, and gradient non-linearity [8, 9, 10]. Depending on the MR system used, the scanner software may apply these correction methods in the reconstruction software. Careful evaluation of the data is required as, depending on the analysis performed, small errors in the data may lead to large discrepancies. Visual inspection of the raw velocity images of the three velocity components may reveal velocity aliasing artifacts. Automated phase unwrapping algorithms have been developed to correct phase wrapping artifacts . In order to use the additionally acquired cine MR acquisitions which can be used as an anatomical reference for the velocity data from the 4D Flow scan, misalignment between the cine MR data and the 4D Flow data should be corrected for. Once corrected for misalignment, the cine MRI data facilitate defining anatomical regions and velocity information within defined regions of interest can be interrogated in conjunction with cardiac anatomy. In case cine MRI and 4D Flow acquisition are both obtained using the same breathing motion compensation technique, correction for image misalignment may not be needed. The absence of visually apparent data quality issues does not guarantee that the velocity data are reliable. Based on the conservation of mass principle, additional quantitative verification steps are recommended to further assess the reliability of the data. One such test is the verification of the consistency in net aortic and pulmonary artery outflow which should be equal in the absence of shunts. Another useful check is the comparison of aortic stroke volume as derived from the 4D Flow acquisition with flow assessment from a validated 2D phase-contrast scan. Comparing data from 4D Flow MRI with conventional 2D phase-contrast has also been proposed to evaluate the accuracy of peak velocity measurements .
Visual analysis is typically the first step in the evaluation of an intra-cardiac 4D Flow acquisition. However, the complexity and enormous size of a typical whole-heart 4D Flow dataset poses challenges for effective visual data interpretation. Conventional 3D workstations providing visualization techniques such as volume rendering are of limited value. Nevertheless, for various reasons, visualization of the data is of utmost importance as it can help provide quick clinically relevant insight into the presence of a particular pathology. Additionally, visualization is needed in the process of subsequent quantitative analysis.
2D-Velocity Vector Display
2D Streamline Display
Flow Quantification Using Retrospectively Defined Measurement Planes
Particle Tracing Quantification
Flow component classification. Flow component classification rules for labeling particles used in particle tracing flow analysis (derived from Eriksson et al. )
Blood that enters the LV during diastole and leaves the LV during systole in the analyzed heart beat; component of both inflow and ejected volume
Blood that enters the LV during diastole but does not leave during systole in the analyzed heart beat; component of inflow volume only
Delayed ejection flow
Blood that starts and resides inside the LV during diastole and leaves during systole in the analyzed heart beat; component of ejected volume only
Blood that resides within the LV for at least two cardiac cycles; not a component of inflow or ejected volume
Kinetic Energy Quantification
Analysis of Vortical Flow
For optimized cardiac pump function, it would be advantageous if the KE of inflowing blood flow is preserved until the end of diastole and would contribute to energy-efficient ejection of blood during systole. The development of vortical flow patterns in the heart during diastole is believed to play an important role in the process of flow redirection and contributes to cardiac pump efficiency [26, 27•]. Töger et al. proposed the use of Lagrangian Coherent Structures to derive the vortical flow volume within LV cavity during diastole . In their experiments, they found the volume of vortical flow in healthy individuals to encompass 52 % of the total LV volume. Elbaz et al. used the Lambda-2 method for the detection of the ring-like vortex core structures that develop distal to the mitral valve annulus during early and late diastolic filling . In healthy subjects, it was found that the vortex cores were more circular in shape during early filling compared to late filling and the shape of the vortex ring core was found to correlate with the shape of the mitral valve annulus. In a cohort of 32 patients with a corrected atrioventricular septal defect, which have abnormal mitral valve geometry, Calkoen et al. applied the same Lambda-2-based vortex core detection method and found a strong association between vortex core presence and shape and mitral valve shape and LV inflow direction .
Over the past 15 years, 4D Flow MRI has developed into a technique suitable for research use, but also with high potential for clinical application. The interaction between myocardial dynamics and intra-cardiac blood flow can now be studied with 4D Flow MRI in an individual subject. Moreover, this allows verification and refinements of concepts from the field of computational flow engineering to enhance our insight into normal and abnormal cardiac physiology. 4D Flow MRI has already been shown to be applicable for clinical application in the assessment of transvalvular flow and for a comprehensive evaluation of patients with heart disease. Further improvements in 4D Flow acquisition and data analysis are highly desirable to make the imaging and analysis more time efficient and easier to use. Additional research is also required to evaluate the added value of 4D Flow MRI in clinical patient management.
Compliance with Ethics Guidelines
Conflict of Interest
Rob J. van der Geest and Pakaj Garg each declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent
All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Westenberg JJ, Roes SD, Ajmone Marsan N, Binnendijk NM, Doornbos J, Bax JJ, Reiber JH, de Roos A, van der Geest RJ. Mitral valve and tricuspid valve blood flow: accurate quantification with 3D velocity-encoded MR imaging with retrospective valve tracking. Radiology. 2008;249(3):792–800.CrossRefPubMedGoogle Scholar
- 4.Markl M, Kilner PJ, Ebbers T. Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2011;7:13.Google Scholar
- 5.• Dyverfeldt P, Bissell M, Barker AJ, Bolger AF, Carlhäll CJ, Ebbers T, Francios CJ, Frydrychowicz A, Geiger J, Giese D, Hope MD, Kilner PJ, Kozerke S, Myerson S, Neubauer S, Wieben O, Markl M. 4D flow cardiovascular magnetic resonance consensus statement. J Cardiovasc Magn Reson 2015;17:22. Consensus statement paper providing guidelines for 4D Flow MRI acquisition and analysis methods for evaluation of the heart and greater vessels. Google Scholar
- 12.Carlsson M, Töger J, Kanski M, Bloch KM, Ståhlberg F, Heiberg E, Arheden H. Quantification and visualization of cardiovascular 4D velocity mapping accelerated with parallel imaging or k-t BLAST: head to head comparison and validation at 1.5 T and 3 T. J Cardiovasc Magn Reson. 2011;13:55.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Roes SD, Hammer S, van der Geest RJ, Marsan NA, Bax JJ, Lamb HJ, Reiber JH, de Roos A, Westenberg JJ. Flow assessment through four heart valves simultaneously using 3-dimensional 3-directional velocity-encoded magnetic resonance imaging with retrospective valve tracking in healthy volunteers and patients with valvular regurgitation. Invest Radiol. 2009;44(10):669–75.CrossRefPubMedGoogle Scholar
- 14.Calkoen EE, Roest AA, Kroft LJ, van der Geest RJ, Jongbloed MR, van den Boogaard PJ, Blom NA, Hazekamp MG, de Roos A, Westenberg JJ. Characterization and improved quantification of left ventricular inflow using streamline visualization with 4DFlow MRI in healthy controls and patients after atrioventricular septal defect correction. J Magn Reson Imaging. 2015;41(6):1512–20.CrossRefPubMedGoogle Scholar
- 19.Fredriksson AG, Zajac J, Eriksson J, Dyverfeldt P, Bolger AF, Ebbers T, Carlhäll CJ. 4-D blood flow in the human right ventricle. Am J Physiol. 2011;301(6):H2344–50.Google Scholar
- 21.Carlsson M, Heiberg E, Töger J, Arheden H. Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements. Am J Physiol. 2012;302:H893–900.Google Scholar
- 24.• Wong J, Chabiniok R, de Vecchi A, Dedieu N, Sammut E, Schaeffter T, Razavi R. Age-related changes in intra-ventricular kinetic energy: a physiological or pathological adaptation? Am J Physiol Heart Circ Physiol. 2016; 310(6):H747–755. Kinetic energy calculation was performed in the left ventricle from 4D Flow MRI in healthy subjects of different age ranges and patients with left ventricular dysfunction. Age related changes in kinetic energy were observed in healthy subjects. Peak diastolic kinetic energy in the oldest subject was shown to be comparable to those in patient with LV dysfunction. Google Scholar
- 25.Eriksson J, Bolger AF, Ebbers T, Carlhäll CJ. Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy. Eur Heart J. 2013;14(5):417–24.Google Scholar
- 27.• Pedrizzetti G, La Canna G, Alfieri O, Tonti G. The vortex—an early predictor of cardiovascular outcome? Nat. Rev. Cardiol 2014;11(9):545–553. The role cardiac fluid dynamics and in particular vortex formation in the heart is described and proposed as a new potential marker that can be used for cardiac risk stratification. Google Scholar
- 29.Elbaz MS, Calkoen EE, Westenberg JJ, Lelieveldt BP, Roest AA, van der Geest RJ. Vortex flow during early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis. J Cardiovasc Magn Reson. 2014;16:78.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Calkoen EE, Elbaz MS, Westenberg JJ, Kroft LJ, Hazekamp MG, Roest AA, van der Geest RJ. Altered left ventricular vortex ring formation by 4-dimensional flow magnetic resonance imaging after repair of atrioventricular septal defects. J Thorac Cardiovasc Surg. 2015;150(5):1233.e1–1240.e1.CrossRefGoogle Scholar
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