Abstract
This study aims to evaluate the feasibility of turbulent kinetic energy (TKE) assessments using compressed sensing (CS)-accelerated three-dimensional time-resolved phase-contrast magnetic resonance imaging (4D flow MRI) in patients with aortic stenosis (AS). Conventional and CS 4D flow MRI (R = 2 with GRAPPA and R = 7.7 with CS, respectively) were sequentially acquired for voxel-wise comparison in healthy participants and patients. Total TKE was measured in both the ascending aorta (AAo) and the whole aortic region. The difference between GRAPPA and CS was expressed as the ratio of (CS 4D flow - Conventional 4D flow) to (Conventional 4D flow). A two-tailed paired t-test was used to assess statistical significance. In healthy participants, the maximum total TKE (TKEmax) measured by CS 4D flow MRI was substantially higher than that obtained with conventional 4D flow MRI, showing a 95.4% increase in the AAo region (0.74 ± 0.43 mJ by GRAPPA vs. 1.17 ± 0.72 mJ by CS; P = 0.053) and a 207.7% increase in the whole aortic region (1.13 ± 0.73 mJ by GRAPPA vs. 2.13 ± 0.95 mJ by CS; P = 0.006). In patients with AS, CS 4D flow MRI showed good agreement with conventional imaging, with only a 5.0% difference in TKEmax at the AAo (14.0 ± 4.6 mJ by GRAPPA vs. 14.8 ± 5.5 mJ by CS; P = 0.129) and a 7.4% difference in the whole region (16.3 ± 5.5 mJ by GRAPPA vs. 17.6 ± 6.5 mJ by CS; P = 0.050). CS 4D flow MRI demonstrated agreement, showing insignificant differences in total TKE measurements specifically within the AAo for AS patients. In healthy participants, CS-based TKE assessment showed larger relative differences compared with conventional 4D flow MRI, likely reflecting a low-TKE effect.
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-026-55843-9.
Keywords: Magnetic resonance imaging, 4D flow MRI, Aortic stenosis, Turbulent kinetic energy
Subject terms: Diseases, Engineering, Health care, Medical research
Introduction
Three-dimensional time-resolved phase-contrast magnetic resonance imaging (MRI), also known as 4D flow MRI, has emerged as a powerful tool for assessing complex 3D blood flow dynamics in vivo. While conventional modalities, such as 2D phase-contrast (PC) MRI and Doppler echocardiography, have been established for flow quantification1,2, 4D flow MRI offers a unique capability for the retrospective quantification of blood flow at any analysis plane within volumetric data3,4. This innovation extends beyond flow quantification, enabling the evaluation of advanced metrics, including flow energetics, wall shear stress (WSS), and turbulent kinetic energy (TKE)5–7. In particular, TKE estimation provides valuable insights into the energy dissipation of blood flow, offering crucial information for conditions such as bicuspid aortic valves and dilated ascending aortic geometries, which current echocardiography methods are likely unable to assess8.
However, conventional 4D flow MRI is associated with long scan times due to the acquisition of multidimensional data and the necessity for respiratory motion compensation, which is crucial for minimizing cardiothoracic motion artifacts. In addition, achieving accurate TKE estimation often requires a signal magnitude ratio,
(
and
represent the magnitude of MR signal at the flow-encoded and the reference scans, respectively), to approach ~0.6. Consequently, velocity-encoding (VENC) values are typically set below the maximum velocity to obtain
~0.69. This can potentially lead to velocity aliasing in MR phase images. Thus, additional MR scans are required to obtain appropriate velocity data from MR phase images without aliasing, using a VENC value comparable to the maximum velocity. These repeated MR scans pose practical challenges to test TKE assessments in patients with aortic valve diseases, and further hinder the clinical applicability of TKE estimation.
Recent advancements in 4D flow MRI have introduced compressed sensing (CS)-accelerated MRI imaging, leveraging the inherent compressibility of MR data10–14. Ma et al. have demonstrated substantial reductions in scan time, with CS 4D flow MRI scans taking only 2 minutes15. Moreover, key hemodynamic parameters such as Vmax and Qmax obtained from CS 4D flow MRI are in good agreement with those from conventional 4D flow MRI. As the clinical feasibility of CS 4D flow MRI with reduced scan times has been established, it was also observed that CS-accelerated image reconstruction can lead to the underestimation of hemodynamic parameters, such as flow rate and WSS, by approximately 10% in a parallel comparison with conventional 4D flow16.
Despite extensive research on CS 4D flow MRI and its impact on various hemodynamic parameters, including velocity and WSS, the effect of CS acceleration on TKE estimation remains largely unexplored. Therefore, this study aimed to evaluate the performance of TKE assessment using CS 4D flow MRI, specifically in patients with aortic stenosis (AS), through a parallel comparison with conventional 4D flow MRI commonly used in clinical settings.
Methods
Study cohort
Conventional and CS 4D flow MRI scans were prospectively acquired from thirteen healthy participants (mean age = 29 ± 5; range = 21 to 38; 7M/6F) and retrospectively from twenty-five patients with AS. Three patient datasets were further excluded: two due to poor signal-to-noise ratio caused by motion artifacts, and one due to partial coverage of the aorta (age = 78 ± 5; range = 66 to 85; 8M/14F; n = 2 with bicuspid aortic valve and n = 20 with tricuspid aortic valve). The demographics of healthy participants and AS patients are summarized in Table 1. All AS patients were diagnosed with moderate severity of AS by echocardiography (Table 2), and no valve replacement had been performed. Human studies were conducted after obtaining approval from the Institutional Review Board (IRB) of Daegu Gyeongbuk Medical Innovation Foundation (approval number: DGMIF-20210721-HR-001-01) for healthy participants and Eunpyeong St. Mary’s Hospital (IRB No. PC20OCSI0133) for AS patients, following the relevant guidelines and regulations. This study adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.
Table 1.
Demographics and MRI scan parameters for healthy participants and AS patients.
| Healthy participants | AS patients. | |||
|---|---|---|---|---|
| N (m/f) | 13 (7/6) | 22 (8/14) | ||
| BAV (%) | 0 (0) | 2 (9.1) | ||
| Age [y] | 29 ± 5 [21‒38] | 78 ± 5 [66‒85] | ||
| Weight [kg] | 69.4 ± 15.5 [46‒90] | 66.3 ± 10.9 [50‒90] | ||
| Height [cm] | 171.4 ± 10.6 [151‒190] | 159.3 ± 7.9 [150‒175] | ||
| BSA [m2] | 1.8 ± 0.2 [1.4‒2.2] | 1.7 ± 0.2 [1.4‒2.1] | ||
| Scan parameters | Conventional | CS | Conventional | CS |
| Scan time [s] | 420 ± 90 (336‒582) | 144 ± 36 (96‒210) | 390 ± 72 (270‒534) | 144 ± 30 (102‒198) |
| Acceleration Rate, R | 2 | 7.7 | 2 | 7.7 |
| Echo time [ms] | 2.58‒3.34 | 3.02‒3.31 | 2.25‒2.48 | |
| Repetition time [ms] | 4.9‒5.2 | 4.6‒4.7 | ||
| Field of view [mm3] | 271‒320 × 231‒256 × 54‒64 | 400 × 320 × 70 | ||
| Spatial resolution [mm3] | 1.7‒2.0 | 2.5 | ||
| Interpolated temporal resolution [ms] | 27.6‒45.6 | 28.2‒42.7 | 25.1‒49.6 | 25.0‒49.6 |
| Bandwidth [Hz/voxel] | 495 | 560 | 558 | |
| Flip angle [°] | 7‒15 | 8 | 7 (12 with contrast) | |
| VENC [cm/s] | 70‒90 | 188‒300 | ||
| Cardiac time frames | 25 | 25 | ||
Table 2.
Echocardiographic biomarkers for AS patients.
| Echocardiography | AS patients |
|---|---|
| Aortic valve area [cm2] | 1.2 ± 0.1 |
| Peak velocity [m/s] | 3.4 ± 0.2 |
| Mean pressure gradient [mmHg] | 26.6 ± 4.6 |
| Left-ventricular ejection fraction [%] | 61.9 ± 6.7 |
| Left-ventricular mass index [g/m2] | 91.6 ± 18.0 |
4D flow MRI image acquisitions
4D flow MRI scans for healthy participants and AS patients were conducted on two different 3T MRI systems: the MAGNETOM Skyra (Siemens Healthcare) at the Daegu Gyeongbuk Medical Innovation Foundation and the MAGNETOM Vida (Siemens Healthcare) at Eunpyeong St. Mary’s Hospital, respectively. 4D flow MRI scans were added to the clinical scans of AS patients to supplement the AS diagnosis process and were not part of their routine clinical assessments. Out of 22 AS patients, 16 received an infusion of the contrast agent gadoterate meglumine (0.2 mmol/kg) as part of their clinical procedure. The accuracy of TKE estimation can vary according to the magnitude signal attenuation ratio (
), which is optimized when approaching ~0.6 (analytically e-1/2)9. Thus, a VENC scout was first performed to determine the peak velocity. The acquisition order was fixed across all participants and not randomized. CS 4D flow (R = 7.7) was then acquired using a VENC set to approximately 75% of the peak velocity to optimize sensitivity for IVSD-based TKE estimation. Subsequently, conventional 4D flow (GRAPPA, R = 2) was acquired in the same imaging session using the same VENC setting (approximately 75% of the peak velocity) to ensure physiological consistency. All 4D flow scans were retrospectively ECG-gated during free breathing using navigator gating, whereby the scan time broadly varied depending on heart rate and respiratory navigator efficiency. For example, in AS patients, heart rate was 69.1 ± 13.4 bpm [range, 48.4–95.7] for GRAPPA and 69.4 ± 13.4 bpm [range, 48.4–96.0] for CS, while respiratory navigator efficiency was 64.0 ± 17.2% [range, 25.0–90.0] for GRAPPA and 63.2 ± 20.0% [range, 24.7–94.0] for CS. The sequence parameters between conventional and CS 4D flow scans are summarized in Table 1.
CS reconstruction
The CS reconstruction technique has been well described in the previous references15,16. In brief, the CS reconstruction involved solving the optimization problem represented by equation (1):
![]() |
1 |
where t denotes a time point;
represents the frames that need to be reconstructed for all t; and
and
are the system matrix and the measured data for each t, respectively. Spatial and temporal L1 regularization was conducted by employing a Haar wavelet transform where
and
are the spatial and temporal Wavelet transforms, respectively; and
and
are the spatial and temporal regularization parameters, respectively17. A FISTA optimization18 with 30 iterations resolved Equation (1) using
= 0.0015 and
= 5
, while considering a maximum image magnitude intensity of 1.
4D flow MRI data analysis
For velocity estimation, post-processing was performed to apply eddy-current correction, noise filtering, and anti-aliasing to MR images, acquired at lower VENC comparable to peak velocity19. As significant aliasing was observed throughout systole phases, anti-aliasing process was rigorously employed. This process was semi-automatically executed using our in-house MATLAB codes (Mathworks, Natick, MA)19. Subsequently, 3D phase-contrast magnetic resonance angiography (PC-MRA) images were generated from conventional 4D flow MRI to segment fluid and non-fluid regions, utilizing 3D Slicer (Version 5.4.0) software. The same segmentation of the fluid region was used for CS 4D flow MRI, enabling voxel-by-voxel comparison for velocity and TKE parameters without employing any co-registration methods. A noise filter, based on the method of the 99th percentile maximum value20, was applied to prevent capturing increased noise within a region of interest (ROI). Peak velocity was obtained within the ROI, which was selected to extend from just behind the coarctation to the end of the jet. Peak flow rate was also obtained behind the coarctation and averaged along the ROI to minimize the noise effect.
For TKE estimation, an intravoxel standard deviation of velocity (IVSD), which is associated with turbulence-induced signal attenuation in MR magnitude images9,21, was initially quantified using the following equation (2):
![]() |
2 |
where
represents the standard deviation at i-direction,
represents the net motion sensitivity, which equals π / VENC.
and
represent MR magnitude signal of reference and flow-encoded scans, respectively.
TKE per unit volume was subsequently estimated from
as follows:
![]() |
3 |
where ρ is the density of blood and
is the standard deviation at i-direction. It is important to note that the presence of both positive and negative noise contributions in the logarithm term,
, eliminates the need to take the square root when calculating total TKE [mJ]22,23. The obtained TKE values near the vessel edges, extracted by eroding one pixel, were further filtered using a 3×3 median filter to reduce border noise, in line with methods reported in previous studies24,25.
Total TKE was volumetrically calculated by summing TKE per unit volume within the ROI. The maximum of total TKE and the sum of total TKE values during the systole (total TKEmax and total TKEsys) were obtained. TKE parameters were regionally assessed at the AAo and whole aortic region. Velocity and TKE distributions at peak systole were visualized as MIPs, with representative images displayed as velocity streamlines, along with TKE and velocity colormaps. Voxel-by-voxel comparisons were employed based on the sequential acquisition of conventional and CS 4D flow MRI scans, and Bland-Altman analysis was also conducted to assess mean bias and limits of agreement (bias ± 1.96×SD) between conventional and CS 4D flow MRI. Change for CS [%] (% for CS) was defined as the ratio of (CS 4D flow – Conventional 4D flow) to (Conventional 4D flow). A two-tailed paired t-test was employed to evaluate statistical differences in peak velocity, peak flow rate, total TKEmax, and total TKEsys. A p-value < 0.05 was considered statistically significant. For each timeframe, a two-tailed paired t-test was performed, and P-values were adjusted using the Benjamini-Hochberg method to control the false discovery rate across all timeframes.
In vitro 4D flow MRI acquisitions
A coarctation phantom model was used to evaluate % for CS, as observed in healthy participants and AS patients, by assessing total TKE within regions with and without jet flow. The 4D flow scans were performed on a 3T MRI system (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany) at the Daegu Gyeongbuk Medical Innovation Foundation, with acceleration factors of R = 2 for conventional 4D flow MRI and R = 7.7 for CS 4D flow MRI. For a parallel comparison of CS and conventional 4D flow, images were sequentially acquired with a VENC of 375 cm/s, corresponding to approximately 75% of the peak velocity, and retrospectively gated using an external triggering signal from an in-house pulsatile pump26. Change for CS was evaluated using voxel sizes of 1.5 mm, 2.0 mm, and 2.5 mm.
Results
Comparisons between conventional and CS 4D flow in healthy participants
CS 4D flow with R = 7.7 had a large reduction in scan time compared to conventional 4D flow in healthy participants (420 ± 90 s for conventional vs. 144 ± 36 s for CS). Fig. 1IA depicts the representative differences in TKE patterns by CS-accelerated 4D flow, particularly in the proximal region of the aortic jet flow (indicated by arrows in the velocity stream with the TKE colormap in Fig. 1IB). However, the locations where TKE patterns were different varied when compared to the velocity colormap (Insets in the Fig. 1IB), where higher velocity intensity was observed at the sides of the jet flow and in the descending aorta.
Fig. 1.

Representative comparisons of velocity and TKE parameters between a healthy participant (I) and an AS patient (II). (A) MIPs of conventional 4D flow (R = 2) and CS 4D flow MRI (R = 7.7) are shown at peak systole. A black diamond indicates the location of maximum TKE. ROIs (I.A, top left) are used to quantify the total TKE in the ascending aorta (total TKEAAo) and the whole region (total TKEwhole). (B) The differences in TKE distributions between conventional and CS 4D flow are compared using velocity streamlines with a TKE colormap, shown alongside a velocity colormap (inset). Arrows indicate the locations of distinct differences in TKE and velocity patterns between conventional and CS 4D flow MRI. (C) Temporal variations of peak velocity, total TKEAAo, and total TKEwhole are compared. Voxel-by-voxel Bland-Altman (D) and orthogonal regression (E) analyses are conducted to compare TKE values across the whole region.
The total TKE curves at the AAo (TKEAAo) and the whole region (TKEwhole), plotted against cardiac time frames, showed increase in total TKE during systole (Fig. 1IC), while the velocity curve remained nearly identical, except during late diastole. Voxel-by-voxel Bland-Altman and orthogonal regression analyses further demonstrated a mean bias of 7.8 mJ, along with a low correlation (ICC = 0.42) throughout the whole region during systole (Fig. 1ID, 1IE). Orthogonal regression analysis for all healthy participants also showed a low correlation, with an ICC of 0.21 (Supplementary Fig S1).
Additionally, the total TKEAAo and the total TKEwhole for all healthy participants demonstrated significant increases, particularly during systole (Fig 2). Bland-Altman analysis also revealed that the mean biases were -0.00 m/s for peak velocity, 0.43 mJ for total TKEmax at the AAo, and 1.00 mJ for total TKEmax in the whole region. We also observed that total TKEmax and total TKEsys significantly increased, especially at the whole region, by 207.7 ± 286.4% (P = 0.006) and 720.8 ± 1008.6% (P = 0.004), respectively (Table 3). Our in vitro 4D flow MRI experiment also revealed substantial increases in % for CS within the non-jet flow region, ranging from 122.1% to 352.7% for total TKEmax and from 54.4% to 421.4% for total TKEsys (Supplementary Fig. S2 and Supplementary Table S1).
Fig. 2.

(A) Temporal variations of peak velocity, total TKEAAo, and total TKEwhole for all 13 healthy participants. Solid and dashed lines indicate mean and standard deviation for conventional 4D flow and CS 4D flow MRI, highlighted in blue and red colors, respectively. (B) Bland-Altman comparisons using the maximum of corresponding parameters. Mean biases and 95% limits of agreement (±1.96 SD) are shown by solid and dashed black lines, respectively. (*) denotes statistical differences (P < 0.05) between conventional 4D flow and CS 4D flow MRI after Benjamini-Hochberg correction for multiple comparisons across timeframes.
Table 3.
Comparisons of peak velocity, peak flow rate, total TKEmax, and total TKEsys between conventional 4D flow (R = 2) and CS 4D flow MRI (R = 7.7) in healthy participants and AS patients. TKE parameters were obtained at the ascending aorta (AAo) and the whole region. (*) denotes the significant difference between conventional 4D flow and CS 4D flow MRI with *p<0.05, **p<0.01.
| Healthy participants (n = 13) | Patients (n = 22) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| GRAPPA | CS | % for CS | P-value | GRAPPA | CS | % for CS | P-value | ||
| Peak velocity [m/s] | 1.38 ± 0.25 | 1.38 ± 0.24 | 0.5 ± 9.7 | 0.981 | 3.65 ± 0.99 | 3.47 ± 0.85 | -3.6 ± 11.1* | 0.029 | |
| Peak flow rate [mL/s] | 269.3 ± 61.5 | 266.7 ± 61.4 | -0.7 ± 7.0 | 0.623 | 245.5 ± 69.7 | 240.6 ± 71.5 | -2.4 ± 9.2 | 0.263 | |
| Total TKEmax [mJ] | AAo | 0.74 ± 0.43 | 1.17 ± 0.72 | 95.4 ± 127.4 | 0.053 | 14.0 ± 4.6 | 14.8 ± 5.5 | 5.0 ± 19.3 | 0.129 |
| Whole | 1.13 ± 0.73 | 2.13 ± 0.95 | 207.7 ± 286.4** | 0.006 | 16.3 ± 5.5 | 17.6 ± 6.5 | 7.4 ± 19.3* | 0.050 | |
| Total TKEsys [mJ] | AAo | 2.10 ± 1.44 | 4.21 ± 2.60 | 212.0 ± 293.3* | 0.016 | 51.9 ± 19.3 | 56.5 ± 25.1 | 6.5 ± 20.7 | 0.056 |
| Whole | 3.46 ± 3.13 | 7.99 ± 3.53 | 720.8 ± 1008.6** | 0.004 | 61.4 ± 23.2 | 68.8 ± 29.6 | 10.9 ± 21.2* | 0.017 | |
Comparisons between conventional and CS 4D flow in patients with AS
The scan times of conventional and CS 4D flow in AS patients were 390 ± 72 s and 144 ± 30 s, respectively. Fig. 1IIA shows representative MIPs for conventional and CS 4D flow MRI, displaying a similar TKE distribution in contrast to the healthy participant shown in Fig. 1IA. However, CS 4D flow tended to provide a somewhat blunted TKE distribution at the AAo. Two distinct differences, indicated by arrows, are shown in the velocity stream with the TKE colormap in Fig 1IIB. The locations showing differences in TKE patterns appeared nearly identical to those showing differences in velocity patterns, as visualized in the streamlines with velocity colormaps (insets in Fig. 1IIB).
The total TKEmax curves demonstrated the distinct increases both in the AAo and the whole region (Fig. 1IIC). Voxel-by-voxel Bland-Altman analysis showed a mean bias of 16.5 mJ (Fig. 1IID). Orthogonal regression analyses exhibited good correlations of ICC = 0.81 for the representative AS patient (Fig. 1IIE) and 0.70 for all AS patients (Supplementary Fig. S1).
No statistically significant differences were observed across all timeframes in AS patients for velocity, total TKEAAo and total TKEwhole, except for a single diastolic phase in total TKEwhole (Fig. 3). In addition, Bland-Altman analysis for all AS patients revealed mean biases of -0.18 m/s for peak velocity, 0.84 mJ for total TKEmax at the AAo, and 1.31 mJ for total TKEmax in the whole region. We also observed small percentage changes for CS, with -3.6% for peak velocity (P = 0.029), 5.0% for total TKEmax at the AAo (P = 0.129), and 6.5% for total TKEsys at the AAo (P = 0.056) (Table 3), suggesting good agreement between conventional and CS 4D flow MRI. Our in vitro findings also showed that % for CS in the jet flow region was relatively small compared to that in the region without jet flow, ranging from -0.22% to 15.8% for total TKEmax and from 9.9% to 22.7% for total TKEsys (Supplementary Fig. S2 and Supplementary Table S1).
Fig. 3.

(A) Temporal variations of peak velocity, total TKEAAo, and total TKEwhole for all 22 AS patients. Solid and dashed lines indicate mean and standard deviation for conventional 4D flow and CS 4D flow MRI, highlighted in blue and red colors, respectively. (B) Bland-Altman comparisons using the maximum of corresponding parameters. Mean biases and 95% limits of agreement (±1.96 SD) are shown by solid and dashed black lines, respectively. (*) denotes statistical differences (P < 0.05) between conventional 4D flow and CS 4D flow MRI after Benjamini-Hochberg correction for multiple comparisons across timeframes.
Discussion
In this study, we demonstrated that CS 4D flow significantly increased total TKE parameters compared to conventional 4D flow in healthy participants, with differences ranging from 2 to 8 folds for CS. For AS patients, CS resulted in relatively small differences in total TKEmax at the AAo and whole region by 5.0% and 7.4%, respectively. These findings suggest that CS 4D flow may be useful for estimating TKE within AS patients, where elevated turbulent flow was observed. However, because healthy participants and AS patients were scanned on different MRI systems and differed in age and sequence parameters, the present findings should be interpreted primarily as within-group comparisons between conventional and CS 4D flow MRI rather than direct between-group comparisons. This approach may facilitate clinical assessment of turbulent energy dissipation in AS patients while significantly reducing scan time.
The CS-based approach has been associated with the underestimation of MRI-derived velocity parameters11,27. This underestimation is likely due to both spatial and temporal undersampling, as well as regularization15. However, our study demonstrates that peak velocity and peak flow rate were not significantly different between conventional and CS 4D flow for healthy participants. This may be attributed to the relatively low VENC setting used for TKE assessment in the present study compared with the VENC settings used in previous CS 4D flow MRI studies, which were generally selected to capture peak velocity. Since this study was aimed to test feasibility of CS 4D flow MRI for TKE assessment, a lower VENC than peak velocity is required (typically, 150 cm/s is used for healthy participants from the 4D flow MRI consensus28). It is well-known that a higher VENC can lead to a lower velocity-to-noise ratio, ultimately resulting in poor signal quality in low-flow regions29. In addition, a recent study also demonstrated that a low VENC could more accurately capture peak velocity than a higher VENC30. Thus, the low VENC setting in this study may improve the velocity-to-noise ratio, leading to better agreement in peak velocity between CS and conventional 4D flow.
We observed that CS 4D flow increased total TKE at the AAo and whole aortic region during both systole and diastole in healthy participants. The prior CFD study demonstrated that TKE increases at a lower VENC of 0.5 m/s, where total TKEmax in the whole region increased to 5.4, 6.3, and 7.6 at R ≈ 1.9, 9.1, and 18.1, respectively, suggesting that undersampling itself may contribute to the observed increase in total TKE during systole in healthy participants30. However, when the underlying TKE level is low, as expected in relatively non-turbulent or non-jet flow regions, small absolute differences or noise contributions may produce large relative percentage differences. This interpretation is supported by our in vitro experiment, in which larger percentage changes with CS were observed in the non-jet flow region than in the jet-flow region (Supplementary Fig. S2 and Supplementary Table S1). Therefore, the larger relative differences observed in healthy participants should be interpreted primarily as a low-TKE effect.
In AS patients, CS 4D flow showed a generally similar TKE distribution compared with conventional 4D flow, although a blunted TKE region was observed in the AAo (Fig. 1IIA). This region was visually observed in a similar anatomical location to differences in the velocity-field appearance between conventional and CS 4D flow (Fig. 1IIB), but not to imply a direct relationship between the IVSD-based TKE distribution and velocity-field appearance.
In addition, AS patients exhibited increases of total TKEmax and total TKEsys with CS 4D flow, ranging from 5.0% to 10.9% (Table 3), with significant differences observed when analyzing the whole aortic region. This suggests that CS 4D flow allows consistent TKE assessments within AAo region, whereas inclusion of the arch and DAo further introduces additional bias. Previous work with conventional 4D flow demonstrated that TKE parameters across whole aortic region could discriminate between dilated AAo and bicuspid aortic valve from normal controls8. Our findings therefore highlight that whole-aorta TKE assessment using CS 4D flow should be interpreted with caution, as it may be subject to potential biases.
Our CS 4D flow detected relatively small differences in peak velocity and peak flow rate, both ranging from -4% to -2% across conventional and CS 4D flow, which was less pronounced than the ~10% underestimation reported in previous studies15,16. This discrepancy may be also related to the lower VENC setting used in our study, which, similar to the healthy cohort, allowed for more accurate peak velocity capture30. These findings suggest that CS 4D flow performance may be influenced by both acceleration rate and velocity-to-noise ratio across different VENC settings.
A recent study demonstrated that a multi-VENC approach provides reliable estimation of both velocity and TKE simultaneously, as low VENC optimizes sensitivity to IVSD while high VENC ensures peak velocity measurement without aliasing in the phase images of 4D flow data30. Although conventional multi-VENC increases scan time, CS acceleration may mitigate this limitation by enabling reliable acquisition of both velocity and TKE within practical scan durations. In addition, machine learning-based anti-aliasing strategies could be applied during post-processing to correct for velocity aliasing at lower VENC, further enhancing the feasibility of CS-based TKE assessment31.
The current study has several limitations: (1) A systematic investigation of TKE estimation across varying acceleration rates would be beneficial, as the acceleration rate affects both TKE and flow-derived parameters. (2) A recent study demonstrated that the parameter λ used in CS reconstruction governs the strength of CS regularization and contributes to the discrepancies observed between conventional and CS 4D flow MRI32. Therefore, further studies are warranted to delineate its impact on TKE estimation. (3) The differences between the Skyra scanner used for healthy participants and the Vida scanner used for AS patients may have contributed to systematic biases, as different scanners from the same vendor or from different vendors can serve as major confounders33. However, this study compares TKE values between conventional and CS 4D flow within each scanner, thereby not directly resulting from this issue. Future studies that might compare TKE values in AS patients acquired from Skyra and Vida both, then caution may be considered for systemic biases.
(4) CS-accelerated TKE distribution may be affected differently by the spatial and temporal evolution of flow patterns. However, the current study did not include a systematic analysis of the effects of blood flow structures. An in-depth investigation into the relationship between complex blood flow and the corresponding CS-accelerated signal changes in MR magnitude images may be necessary to better understand CS reconstruction. (5) Clinical parameters such as peak velocity, mean pressure gradient, and aortic valve area were not widely distributed among AS patients diagnosed with moderate AS. While the current study demonstrated the feasibility of using CS-accelerated TKE estimation, larger cohorts are needed to evaluate the % for CS across a wide range of pathophysiological conditions. (6) Inconsistencies in age and sequence parameters, including voxel size, between healthy participants and AS patients can affect TKE estimation. Therefore, future studies using comparable cohorts and standardized sequence parameters would be valuable for systematically comparing TKE parameters.
Conclusion
This study demonstrated the feasibility of using CS 4D flow MRI for TKE estimation, particularly in AS patients. Given the predominance of turbulent flow in AS, CS 4D flow showed good voxel-by-voxel agreement in TKE estimation. Larger relative TKE differences were observed when the underlying TKE level was low, suggesting that CS-based TKE assessment should be interpreted with caution in low-TKE or non-jet flow regions. These findings provide valuable insights into assessing AS severity through the energy dissipation of blood flow, with the potential to substantially reduce scan times in routine clinical practice.
Supplementary Information
Acknowledgments
We would like to thank Flonics for providing access to the Streamliner, which enabled cross validation in this study.
Author contributions
S. Park, J.-E. Yi, A.J. Barker, and H. Huh participated in the study design. S. Park and J.-E. Yi analyzed the data. S. Park and J.-E. Yi drafted the manuscript. Others participated in editing and reviewing the manuscript. All authors read and approved the final version of the submitted manuscript.
Funding
This research was supported by NRF grant funded by the Korea government (MSIP) (RS-2021-NR061225, RS-2024-00451584), supported by Commercialization Promotion Agency for R&D Outcomes (COMPA) funded by the Ministry of Science and ICT (MSIT) Grant No. 2710086063 (RS-2025-02653196), supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (RS-2025-02263007), supported by the Korean Cardiac Research Foundation (202002-01), and supported by the Regional Innovation System & Education (RISE) program through the Gangwon RISE Center, funded by the Ministry of Education (MOE) and the Gangwon State (G.S.), Republic of Korea (2026-RISE-10-002).
Data availability
The datasets used and or analyzed during the current study are available from the corresponding author upon reasonable request.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Sungho Park, Jeong-Eun Yi have contributed equally to this work.
Contributor Information
Alex J Barker, Email: alex.barker@cuanschutz.edu.
Hyungkyu Huh, Email: hkhuh@kmedihub.re.kr.
References
- 1.Enzmann, D. R., Ross, M. R., Marks, M. P. & Pelc, N. J. Blood flow in major cerebral arteries measured by phase-contrast cine MR. AJNR Am. J. Neuroradiol.15, 123–129 (1994). [PMC free article] [PubMed] [Google Scholar]
- 2.Members, W. C. et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. J. Am. Coll. Cardiol.77, e25–e197 (2021). [DOI] [PubMed] [Google Scholar]
- 3.Dyverfeldt, P. et al. 4D flow cardiovascular magnetic resonance consensus statement. J. Cardiovasc. Magn. Reson.17, 1–19 (2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Markl, M., Frydrychowicz, A., Kozerke, S., Hope, M. & Wieben, O. 4D flow MRI. J. Magn. Reson. Imaging36, 1015–1036 (2012). [DOI] [PubMed] [Google Scholar]
- 5.Garcia, J., Barker, A. J. & Markl, M. The role of imaging of flow patterns by 4D flow MRI in aortic stenosis. JACC. Cardiovasc. Imaging.12, 252–266 (2019). [DOI] [PubMed] [Google Scholar]
- 6.Barker, A. J. et al. Bicuspid aortic valve is associated with altered wall shear stress in the ascending aorta. Circ. Cardiovasc. Imaging.5, 457–466 (2012). [DOI] [PubMed] [Google Scholar]
- 7.Ha, H. et al. The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta. Sci. Rep.6, 1–14 (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Binter, C. et al. Turbulent kinetic energy assessed by multipoint 4-dimensional flow magnetic resonance imaging provides additional information relative to echocardiography for the determination of aortic stenosis severity. Circ. Cardiovasc. Imaging.10, e005486 (2017). [DOI] [PubMed] [Google Scholar]
- 9.Dyverfeldt, P., Gårdhagen, R., Sigfridsson, A., Karlsson, M. & Ebbers, T. On MRI turbulence quantification. Magn. Reson. Imaging27, 913–922 (2009). [DOI] [PubMed] [Google Scholar]
- 10.Feng, L. et al. XD-GRASP: Golden-angle radial MRI with reconstruction of extra motion-state dimensions using compressed sensing. Magn. Reson. Med.75, 775–788 (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hsiao, A., Lustig, M., Alley, M. T., Murphy, M. J. & Vasanawala, S. S. Evaluation of valvular insufficiency and shunts with parallel-imaging compressed-sensing 4D phase-contrast MR imaging with stereoscopic 3D velocity-fusion volume-rendered visualization. Radiology265, 87–95 (2012). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Feng, L. et al. Golden-angle radial sparse parallel MRI: combination of compressed sensing, parallel imaging, and golden-angle radial sampling for fast and flexible dynamic volumetric MRI. Magn. Reson. Med.72, 707–717 (2014). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Neuhaus, E. et al. Accelerated aortic 4D flow cardiovascular magnetic resonance using compressed sensing: Applicability, validation and clinical integration. J. Cardiovasc. Magn. Reson.21, 1–11 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Lustig, M., Donoho, D. & Pauly, J. M. Sparse MRI: the application of compressed sensing for rapid MR imaging. Magn. Reson. Med.58, 1182–1195 (2007). [DOI] [PubMed] [Google Scholar]
- 15.Ma, L. E. et al. Aortic 4D flow MRI in 2 minutes using compressed sensing, respiratory controlled adaptive k-space reordering, and inline reconstruction. Magn. Reson. Med.81, 3675–3690 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Pathrose, A. et al. Highly accelerated aortic 4D flow MRI using compressed sensing: Performance at different acceleration factors in patients with aortic disease. Magn. Reson. Med.85, 2174–2187 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Wetzl, J. et al. High-resolution dynamic CE-MRA of the thorax enabled by iterative TWIST reconstruction. Magn. Reson. Med.77, 833–840 (2017). [DOI] [PubMed] [Google Scholar]
- 18.Beck, A. & Teboulle, M. A fast iterative shrinkage-thresholding algorithm for linear inverse problems. SIAM J. Imaging Sci.2, 183–202 (2009). [Google Scholar]
- 19.Bock, J., Kreher, B., Hennig, J. & Markl, M. In Proc. of the 15th Annual meeting of ISMRM. Berlin, Germany (2007).
- 20.Rose, M. J. et al. Efficient method for volumetric assessment of peak blood flow velocity using 4D flow MRI. J. Magn. Reson. Imaging.44, 1673–1682 (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Dyverfeldt, P., Sigfridsson, A., Kvitting, J. P. E. & Ebbers, T. Quantification of intravoxel velocity standard deviation and turbulence intensity by generalizing phase‐contrast MRI. Magn. Reson. Med.56, 850–858 (2006). [DOI] [PubMed] [Google Scholar]
- 22.Dyverfeldt, P. & Ebbers, T. Letter by Dyverfeldt and Ebbers regarding article" Estimation of turbulent kinetic energy using 4D phase-contrast MRI: effect of scan parameters and target vessel size". Magn. Reson. Imaging.34, 1226–1226 (2016). [DOI] [PubMed] [Google Scholar]
- 23.Ha, H. et al. Reply to letter by Dyverfeldt and Ebbers regarding the article" Estimation of turbulent kinetic energy using 4D phase-contrast MRI: effect of scan parameters and target vessel size". Magn. Reson. Imaging.34, 1338–1340 (2016). [DOI] [PubMed] [Google Scholar]
- 24.Ziegler, M., Lantz, J., Ebbers, T. & Dyverfeldt, P. Assessment of turbulent flow effects on the vessel wall using four‐dimensional flow MRI. Magn. Reson. Med.77, 2310–2319 (2017). [DOI] [PubMed] [Google Scholar]
- 25.Ha, H. et al. In-vitro and in-vivo assessment of 4D flow MRI Reynolds stress mapping for pulsatile blood flow. Front. Bioeng. Biotechnol.9, 774954 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Park, S., Kwon, M., Nam, H. & Huh, H. Interpolation time-optimized aortic pulse wave velocity estimation by 4D flow MRI. Sci. Rep.13, 16484 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Dyvorne, H. et al. Abdominal 4D flow MR imaging in a breath hold: combination of spiral sampling and dynamic compressed sensing for highly accelerated acquisition. Radiology275, 245–254 (2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Bissell, M. M. et al. 4D Flow cardiovascular magnetic resonance consensus statement: 2023 update. J Cardiovasc. Magn. Reson.25, 40 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Wang, Y., Riederer, S. J. & Ehman, R. L. Respiratory motion of the heart: Kinematics and the implications for the spatial resolution in coronary imaging. Magn. Reson. Med.33, 713–719 (1995). [DOI] [PubMed] [Google Scholar]
- 30.Dirix, P., Buoso, S. & Kozerke, S. Optimizing encoding strategies for 4D flow MRI of mean and turbulent flow. Sci. Rep.14, 19897 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Berhane, H. et al. Deep learning–based velocity antialiasing of 4D-flow MRI. Magn. Reson. Med.88, 449–463 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Sjöberg, P. et al. Image reconstruction impacts haemodynamic parameters derived from 4D flow magnetic resonance imaging with compressed sensing. Eur. Heart J.2, qyae137 (2024). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Oechtering, T. H. et al. Repeatability and reproducibility of various 4D flow MRI postprocessing software programs in a multi-software and multi-vendor cross-over comparison study. J. Cardiovasc. Magn. Reson.25, 22 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and or analyzed during the current study are available from the corresponding author upon reasonable request.



