Introduction
The aortic diameter is not a good predictor of complications of aortic dilatation [
1,
2]. The reason for using it is the law of Laplace, which links the expansion rate with the diameter of a vessel, but the biological genesis of aortic dilatation and dissection is more complex [
3]. Other sources underlined that aortic flow abnormalities can contribute to the progression of dilatation [
4,
5], e.g. in the setting of bicuspid aortic valve (BAV) [
6‐
8].
4D flow allows the visualization and measurements of flow parameters like helical flow or analysis of the flow jet and may provide deeper insights into cardiovascular pathologies [
9]. 4D flow might deliver new imaging biomarkers for surveillance of patients with aortic pathologies and may help to identify patients at risk for complication of aortic dilatation such as rupture and dissection, and finally to adapt patient management. This study is an extension of previous works, which have shown that absolute quantification of helical flow patterns, e.g. of helical volumes and helical duration, can help to differentiate between physiological and pathological flow patterns [
10].
However, those new techniques are still neither an established part of the evaluation of patients with aortic disease, nor part of the decision-making process. Nevertheless, before it comes to analysis of pathologies, it is necessary to identify the normal range of these parameters. Thus, the aim of this study was to utilize 4D flow in the aorta of healthy individuals to generate normal values and elucidate changes of helical flow and flow jet as well as wall shear stress (WSS).
Discussion
Numerous 4D flow parameters were already described [
19,
24‐
26]. These parameters were mostly assessed visually only, which might limit the use in the clinical routine. We are convinced that quantitative parameters, which can be assessed in a highly standardized manner, might be one way to overcome this limitation. We utilized 4D flow to establish normal values regarding helical flow, the flow jet and WSS in the ascA in a large cohort.
In line with other studies, we found that the ascA diameter increased with age [
3,
27]: Our calculations regarding the normal range of the ascending aortic diameter indicate an upper limit > 40 mm in volunteers > 51 years, which could be interpreted as an aortic ectasia [
1,
2]. Since we only included healthy subjects in this study, one possible conclusion—in line with other sources—could be that the aortic diameter alone is a poor parameter for the evaluation of aortic diseases [
1,
3,
28].
Furthermore, we were able to detect at least one helix in the ascA in all participants. Additionally, we found a second helix in the aortic arch in 16 (19%) participants. Interestingly, the aortic arch helices started right at the spot where the ascending aortic helices ended. We state that this sharp separation of the helices is most likely artificial due to the used technique of pressure-based helix extraction. However, it shows that there seems to be a “transition-zone” in between those two helices, right at the transition from the ascA to the aortic arch. In other words: There are differences regarding pressure and flow characteristics between the ascA and the aortic arch, which is in accordance with the literature: Frydrychowicz et al found significant differences in the distribution of WSS between the ascA and the aortic arch. The authors stated that this is helpful for explaining why atherosclerotic lesions predominantly develop and progress mainly at the origins of the supra-aortic vessels [
29]. Other sources underlined that the flow abnormalities in the setting of BAV might extend into the aortic arch (Fig.
1), which fits our observation [
6].
We found out that in the ascA, helices mainly occur during systole and vanish during diastole. This is in line with the literature: Kilner et al [
30] described “spiral” flow predominantly occurring during systole. Other studies investigated the evolution of helical flow by visual analyses and demonstrated that helical flow emerges mainly in peak systole [
31].
Additionally, helices in the early systole were usually small, while they reached their maximum volume and length around mid-systole. We assume that some small helices were missed due to the overlay of pathlines with laminar and helical flow, while (semi)automatic analyses might enable the detection of even small helices.
We found a
THEX of 25.7% to be normal; previously, it has been shown that
THEX in BAV patients can be more than 2-fold elevated [
10], indicating that
THEX can be helpful discriminating normal and abnormal flow.
This current study extends previous attempts to utilize the technique of pressure-based helix extraction to measure volumes and lengths of helices. We found a
HVacc of up to 39.6ml to be normal, whereas a recent study found a
HVacc of up to 236ml in BAV patients [
10].
The helical maximum flow velocities within a helix in healthy volunteers were generally lower than the general “2D peak flow velocities”. We found a reduction of helical
forward velocity (
Vfor) by 55.7% with age (18 to 63 years), while there was no link between age or gender and the
circumferential velocity (
Vcirc), and we found a general decrease of peak flow velocity by 29.8% in the ascA. One possible explanation for this finding could be the ascA diameter increases causing a slower laminar and non-laminar flow in general. This is partially in line with the results of van Ooij et al [
32]. They investigated the maximum velocity of bulk blood flow and demonstrated decreasing velocities with age. Although they did not investigate helical blood flow, their findings fit our findings, indicating decreasing forward velocities with age. Contrarily, we found no correlation between the helices’
circumferential velocity (
Vcirc) and age or gender. To the best of our knowledge, there is no study that has systematically evaluated the impact of circumferential helical flow velocities, yet.
In line with Lorenz et al, we found both right- and left-handed helical flows to be normal in healthy volunteers, suggesting that this parameter cannot distinguish between healthy and pathological flows [
33].
Dyverfeldt et al stated that the normalized
flow displacement (
FD) is a suitable parameter for identifying and risk-stratifying patients who are likely to develop clinically significant aortic dilation, but their study did not include healthy volunteers [
34]. Later, Sigovan et al compared patients with BAV and seven healthy volunteers and found the normalized
flow displacement (
FD) to be of importance for distinguishing between physiological and pathological flows [
35]. We found a normalized
FD of 0.02 to be normal; they found a mean normalized flow displacement of 0.12 in patients while Dux-Santoy et al found a normalized displacement of 0.05–0.08 in patients with BAV [
6]. This suggests that the parameter “normalized displacement” can distinguish between physiological and pathological flows. As expected, we found that
WSS was closely related to
forward velocity: Both parameters demonstrated a negative correlation with age. van Ooij et al investigated
WSS in healthy volunteers and found a decreasing
WSS with normal aging [
32,
36]. Additionally, they elucidated
WSS in patients with BAV and found a good correlation between abnormal velocities and
WSS. They found
WSS of 0.8 to be normal for healthy adults < 30 years; in our study, we found 0.88 Pa to be normal for this age group (the differences between those values occur due to slightly different scan parameters).
They found significantly elevated
WSS in BAV patients using matched WSS maps [
32,
36]; therefore,
WSS could potentially be an important marker for aortic dilatation. It is known that WSS measurements depend strongly on the used scan parameters [
26,
37]. This indicates that the here provided normal values only apply when using the same parameters as reported.
One limitation of our study is that we did not differentiate between helices and vortices. A visual, qualitative but also a quantitative differentiation between both is often not possible. There is a smooth transition between both phenomena and definite cutoffs do not exist. Nevertheless, this differentiation could be of interest because there is evidence that vortical flow is a relevant factor, e.g. in aortic dissection, and should be addressed in future research [
38].
In conclusion, we demonstrated in 86 healthy volunteers that strong correlations exist between age and the hemodynamic parameters helical forward velocity and WSS at peak systole. Interestingly, the “spatio-temporal helical parameters” like volume, length and temporal existence did not depend on gender and age. We elucidated that the parameters THEX, the helical volumes and normalized displacement enable to discriminate between physiological and pathological flows. We provided normal ranges for all these flow parameters, which might be an important presupposition for the assessment of patients with aortic disease.
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