Discussion
The main aim of this study was to compare 4D flow MRI with 2DPC MRI for the clinical assessment of AR.
For years, 4D flow MRI good internal consistency and good interindividual reproducibility have been well known.22 Also, 4D flow MRI has been demonstrated to improve the right ventricular valve flow and diastolic function quantification,23 and it has even been used as a reference tool to compare the accuracy of 3D versus 2D echography for quantification of AR.24
Several authors have validated the use of 4D flow MRI in different clinical situations: to determine morphological and haemodynamic values such as velocity peak and flow displacement,25 26 to asses severity in hypertrophic myocardiopathy (measuring peak velocity),27 to asses dysfunction in bicuspid valves28 or to detect incipient haemodynamic changes in Marfan patients.29
Even, new automatic techniques for valve tracking have been validated, although not in AR.30
To our knowledge, despite the prevalence of AR, there is not a study comparing 4D flow MRI with 2DPC MRI for grading AR in routine clinical practice. Our aim was to determine if these two imaging modalities are equivalent with regard to AR quantification and if we can confidently change the habitual MRI protocol in this common clinical context.
Importantly, we found no statistically significant differences between the two techniques in the quantitative assessments (figures 1 and 2). For the comparison, 2DPC MRI was used as the reference technique because this sequence has been previously validated by comparison with echocardiography for AR quantification.7 9–11
Flow volume
Bollache et al found that net volumes measured with the patient in sustained breath-holding are lower than those acquired in, even when the same sequence is used.13 Another study showed that 4D flow MRI underestimates individual flow volume quantification compared with 2DPC MRI.31 In our study, we found no significant differences between 4D flow MRI and 2DPC MRI with regard to forward flow values.
RF and severity grading
Because RF depends on forward and regurgitant flow, small differences between 2DPC MRI and 4D flow MRI in these volume measurements explains why RF values measured by 2DPC MRI tend to be higher (figure 2).
Severity criteria for AR assessed by echocardiography, which include qualitative, semiquantitative and quantitative criteria, are well-established in clinical guidelines.1 By contrast, the reference values for MRI are less well-established and different authors have described different values. For example, some authors have used the same threshold values for MRI as for echocardiography,32 while other authors have established different cut-off points. For example, Myerson et al10 concluded that an RF>33% predicted the need for valve replacement.
Gelfand et al33 concluded that the cut-off points for RF that best correlate with echocardiography are as follows: mild AR (≤15%), moderate (16%–25%), moderate-severe (26%–48%) and severe (>48%).
If we apply these criteria—which provide narrower ranges that are useful in clinical practice—to our patient data, the severity grading obtained by 2DPC MRI and 4D flow MRI differ in 11 of the 34 patients in our cohort (table 3), with 4D flow MRI underestimating severity compared with 2DPC MRI in 10 of those 11 cases, probably because, as mentioned above, forward flow values tend to be lower when measured by 2DPC MRI (maybe because of the presence of non-laminar flow), whereas the 2DPC MRI regurgitant flow tend to be slightly higher.
Kappa agreement for classifying regurgitation can be calculated between both methods (kappa of 0.72), which means moderate agreement. Also, most of the cases with disagreement would be clinically classified as mild-moderate regurgitation with treatment depending on clinical predictors. Our hypothesis is that with 4D flow MRI, we would use other flow variables (turbulence, jet diameter and so on) that improve the AR grading. For this purpose, posterior studies are necessary.
Location of the ROI
In our study, we used a single double oblique planned acquisition plane orthogonal to the wall of the aorta for the 2DPC MRI acquisition.
However, the optimal location to most accurately measure AR is controversial19 20 because RF values vary depending on the plane that is used. Likewise, the stroke volume is also controversial. Chaturvedi et al34 found that the most accurate measures of cardiac output are obtained at the proximal ascending aorta; however, Bertelsen et al35 found a better correlation for stroke volume at the valve level. For this reason, we compared flow values obtained by placing an ROI in the same location for both MRI sequences (at the valve level or at the sinotubular junction), thus eliminating any possible influence of this variable on the comparative results. Although we found no statistically significant differences in any of the subgroups, the RF values obtained with the two techniques were more closely correlated when the ROI was located at the sinotubular junction (table 4), likely due to the decreased non-laminar flow in this area. This approach does not make use of the possible advantages of 4D flow MRI. We are aware that posterior studies are necessary to determine the best aortic plane for regurgitation quantification with 4D flow MRI for prognostic purposes.
Dilatation
In patients with dilated aortas and aortas with bicuspid valves, helical flow patterns differ from those observed in healthy patients, resulting in differences in flow measurements.36 37 In this regard, 4D flow MRI is believed to be more accurate than 2DPC MRI in measuring helical flow.38 Studies have shown that measurements of cardiac output present substantially more variability in the presence of complex flow patterns secondary to aortic stenosis.39 However, we found no significant differences in the values obtained by the two techniques in any of the subgroups analysed (dilated vs non-dilated aortas, tricuspid vs bicuspid/quadricuspid and stenotic vs non-stenotic). RF values were more closely correlated in smaller aortas (diameter 38 mm) (figure 3), probably due to non-laminar flow, but we were unable to assess correlations in the other subgroups due to the small number of patients in those groups.
The favourable findings of the present study suggest that the cardiac output values measured by 4D flow MRI and 2DPC MRI in routine clinical practice do not show statistically significant differences, and in the majority of the patients, the AR grading was concordant.
Also, we suggest that 4D flow MRI has several advantages over 2DPC MRI, particularly with regard to the assessment of complex flows in dilated aortas.
We believe that 4D flow MRI will, in the future, form part of standard MRI protocols replacing 2DPC MRI. However, additional clinical utility studies are needed to confirm these findings and to confirm the advantages of 4D flow MRI.
The advantages of 4D flow MRI we noticed in our initial practice can be summarised as follows: (1) 3D anatomical, functional and flow data; (2) acquisition during free breathing (2DPC MRI could be acquired with free breathing with navigator-based motion suppression); (3) capacity to retrospectively analyse any flow type (ie, laminar or non-laminar) included in the study, in any direction, compensating the longer duration of the sequence; (4) visualisation of complex or eccentric flows; (5) retrospective tracking of one or more jets to avoid underestimating the RF40; (6) allows assessment of internal validity (eg, by comparing values in the pulmonary artery with those obtained in the aorta); and (7) it can also be used to identify holodiastolic flow reversal in the descending aorta, an independent predictor of severe AR.41
Study limitations and strengths
One of the limitations of this study is the relatively small number of patients. For this reason, larger studies with longer follow-up will be necessary to strengthen the clinical evidence for 4D flow MRI. Another limitation inherent to the two sequences is that 2DPC MRI must be acquired with the patient in breath-hold, whereas 4D flow acquisition is made in free breathing. An important strength is that this study is the first study to compare 4D flow MRI for AR in routine clinical practice with the standard sequence (2DPC MRI).
Furthermore, we expected that 4D flow MRI would permit an accurate diagnosis and provide additional quantitative and qualitative data not obtainable with 2DPC MRI, thus providing a more precise analysis of blood flow, especially in cases with non-laminar or eccentric flow.