Clinical 4D flow MRI assessment in aortopathy—what the clinician needs to know

Introduction

Interval cross-sectional imaging for aortopathy has become standard practice, with the recent American College of Cardiology (ACC)/American Heart Association (AHA) aortic disease guidelines detailing recommended measurement techniques and imaging planes (1).

Anatomical imaging

Three-dimensional (3D) imaging ensures the measurement is orthogonal to the dilated vessel and reduces overestimation of diameters, which can happen on echocardiography due to oblique imaging in the more difficult-to-image ascending aorta. The guideline suggests measuring aortic sinus to sinus on computed tomography (CT)/magnetic resonance imaging (MRI) (rather than commissure to sinus) as these measurements correlate better with surveillance echocardiographic measures (1).

In the adult population, measures are often indexed to body surface area (BSA), but the increased incidence of obesity has posed the question, whether indexing to height is more reliable (2). Most guidelines still recommend absolute measures as cut-off based on genetic diagnosis (3).

In pediatric populations, z-scores remain widely used. Outcome data based on z-scores is limited, in part due to the rarity of aortic dissection or the need for ascending aortic replacement during childhood. MRI reference data is sparse, with the largest dataset to date derived from magnetic resonance (MR) angiography (4). Nevertheless, respiratory-navigated 3D whole-heart acquisitions during end-diastole are now favored in most centers, as this technique eliminates the need for intravenous cannulation and contrast administration. As four-dimensional (4D) flow MRI becomes more widespread, comparative studies utilizing 4D flow MRI magnitude imaging for aortic size measurements are currently underway (5).

4D flow MRI

4D flow MRI is an advanced imaging technique that captures blood flow dynamics in three dimensions over time, providing detailed visualization of blood flow patterns, velocity, and direction. 4D flow MRI is now widely available, and an aortic acquisition can be completed in 1–5 min using advanced techniques (6,7). In genetic aortopathies, the role of 4D flow MRI is still under investigation. However, in bicuspid valve disease (BAV), abnormal hemodynamics have been shown to be a major contributor in the pathology of aortic dilation (7,8). Several advanced parameters can be calculated using research and commercially available software.

Visual assessment

Normal ascending aortic systolic flow can be laminar, though some flow disturbance has been seen even in healthy aortas (9), whereas abnormal aortic systolic flow is associated with increased eccentricity and its associated increase in helicity and vorticity. In healthy individuals, the left ventricular outflow typically produces flow patterns that are directed towards the inner curvature of the aorta, creating a mild right-handed helical flow in the ascending aorta and its arch (10). Research indicates that in conditions of aortopathy, these helical and vortical flow patterns can become significantly more pronounced (11).

Helical aortic flow is usually defined as the swirling motion of blood around the centerline of the ascending aorta. In contrast, vortex flow refers to the rotational movement of blood along the long axis of the aortic root (Figure 1).

Figure 1 4D flow MRI visualizations of aortic blood flow in different conditions: healthy adults, hypertensive with mild aortic dilatation, and patients with bioprosthetic valves post-TAVR and SAVR. In a healthy adult, flow is smooth and laminar with minimal helical and no vortical flow, indicating efficient blood circulation. Hypertensive patients show increased helical and some vortical flow, reflecting disturbed patterns that can elevate shear stress, contributing to further dilatation and reduced cardiovascular efficiency. Post-TAVR, flow is highly turbulent with significant helical and vortical patterns, potentially causing high shear stress, endothelial damage, and thrombus formation. SAVR shows reduced vortical flow compared to TAVR, but even higher helical flow. Excessive helical and vortical flows indicate maladaptive responses, increasing energy dissipation, highlighting the challenge of restoring physiological flow in these patients. 4D, four-dimensional; MRI, magnetic resonance imaging; SAVR, surgical aortic valve replacement; TAVR, transcutaneous aortic valve replacement.

The degree of helical or vortical flow can be visually graded (12) by the assessment of streamlines (13). While visual grading has not been linked to outcome measures, the rare and likely very pathological left-handed helical flow is associated with especially large aortas. Therefore, it is reasonable to monitor these patients more frequently.

Wall shear stress (WSS)

High WSS values in the vessel wall have been shown to correlate with areas of abnormal vessel wall structure with thinner fibers and reduced elastin content (8,14).

Overall, WSS remains constant with increasing aortic diameter in BAV (11), whereas it decreases with increasing diameter in healthy volunteers and in other aortopathies (11).

Areas of increased WSS can be found in BAV even without stenosis (15). But increasing stenosis increases WSS in BAV, tricuspid aortic valve (TAV) disease (15) and also in aortic stenosis (AS) due to rheumatic heart disease (16). Interestingly, TAV AS does not suffer from the same degree of dilation than BAV counterparts. This may in part be due to the length of time increased WSS has been present, which is much longer in BAV as the WSS is increased even prior to any significant stenosis. However, the directionality of WSS might be another important contributor, as endothelial cells are designed to withstand through plane but not circular in plane shear stress (17). Indeed, in longitudinal follow-up studies, in-plane WSS is correlated with increasing aortic diameters, but not overall WSS (18-23).

Several post-processing platforms now allow WSS assessment (though not always CE labelled). Accurate WSS is inherently difficult as it relies on a very accurate aortic wall definition. Most analysis platforms (research and commercial) do not track the aortic wall throughout the cardiac cycle, which would be even more labor-intensive. Computational fluid dynamics (CFD) calculations always quote much higher values than measured using in vivo 4D flow MRI, which is likely due to the increased resolution of CFD simulations. Even CFD simulations are affected by different spatial resolutions (24).

To date, no publication directly compares WSS values from different analysis methods (research or commercial). But differences in flow volume and peak velocities across vendors have been described (25) and will likely also include variations in WSS calculations.

Therefore, comparison of WSS across patient cohorts to use in-plane WSS cut-off values to predict increasing aortic growth remains a future aim rather than a tool ready for clinical implementation. However, within-patient comparison is much more reliable, and any patient undergoing ascending aortic replacement will benefit from a WSS map, as areas of increased WSS should be excised as part of the replacement, as these are likely showing abnormal wall histopathology (8).

Flow displacement

Systolic flow displacement (SFD) and systolic flow reversal ratio (sFRR) are two parameters used to quantify aortic flow abnormalities, particularly eccentricity and vorticity. SFD measures the displacement of the blood flow from the centerline of the aorta, indicating flow eccentricity. This is a significant marker for identifying patients at risk of ascending aortic dilatation, as greater SFD is associated with abnormal aortic flow and future aortic growth (26). As it uses the angle of flow jet indexed to aortic diameter (in diastole as per measurement standard) it is less sensitive to wall motion and spatial resolution of the 4D flow MRI acquisition and therefore a more robust clinical marker. A recent study also validated through-plane two-dimensional (2D) phase contrast methods of SFD compared to more complex flow visualization and assessment (13). These simplified 2D methods are comparable to the more complex 4D flow MRI, offering broader clinical applicability for analyzing flow displacement. However, larger follow-on studies are needed to further assess reproducibility across vendors and its predictive capabilities.

Retrograde flow—sFRR

Vortical flow can be assessed by the quantification of sFRR. sFRR quantifies the degree of retrograde flow, or backward blood flow during systole, reflecting poor aortic conduit function. An elevated sFRR suggests impaired aortic efficiency, commonly seen in conditions like aortic dilatation. Similar flow disturbances have also been observed in aortic flow in heart failure with preserved ejection fraction (HFpEF) with significantly higher SFD and sFRR (27). Reverse flow is also elevated in the true lumen of patients with chronic descending aortic dissection (28,29).

4D flow MRI in aortic valve replacement

In TAV, aortic flow abnormalities are linked to exercise efficiency measured by maximum oxygen uptake (VO₂max) (30). This emphasizes the physiological notion that aortic flow abnormalities result in higher viscous energy loss within the cardiovascular system, rendering it inefficient. Therefore, assessment of the degree of flow eccentricity and its hemodynamic impact on the ascending aortic root is possibly becoming a new therapeutic outcome target. Mechanical AVR can reduce the helical flow in BAV (31) compared to bioprosthetic AVR. Nevertheless, most clinical decision-making is driven by other factors such as the need for anticoagulation, but as less and less anticoagulation is needed in mechanical AVR, other factors are entering into the decision-making (32). TAVI is a widely accepted treatment for patients with severe AS. In more recent development, bioprosthetic valve manufacturers are using 4D flow MRI to help design valves with increased laminar flow, again enforcing the point that aortic flow is an independent outcome in AV disease (33).

Conclusions

The use of 4D flow MRI in aortic flow assessment has revolutionized our understanding of blood flow dynamics and their role in aortic disease. By providing comprehensive, 3D insights into flow patterns, velocity, and WSS, 4D flow MRI enables clinicians to identify abnormal flow patterns like helicity and vorticity, which are critical markers in conditions such as bicuspid aortic valve and aortic dilatation. Flow abnormalities are better at predicting aortic dilatation and novel aortic flow biomarkers are being embraced as therapeutic targets in aortic valve structural intervention planning and assessment. Further larger studies are needed to cement the incremental role of aortic flow assessment in aortopathies.

Limitations

As with all techniques, 4D flow MRI has limitations. Standard acquisition can be long >5–10 min. Accelerated sequences risk introducing error, and are prone to underestimating maximum peak velocities. Advanced hemodynamic parameters are sensitive to spatial resolution. In severe stenosis, high velocity settings are necessary to avoid aliasing. Image quality can be reduced at these high velocity settings.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Harald Kaemmerer) for the series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part VI” published in Cardiovascular Diagnosis and Therapy. The article has undergone external peer review.

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-478/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-478/coif). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part VI” was commissioned by the editorial office without any funding or sponsorship. P.G. is a clinical advisor for Neosoft, Pie Medical Imaging, and Medis Medical Imaging and consults for Anteris and Edward Life Sciences. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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