Simultaneous quantitative evaluation of both iliac arteries and veins via accelerated four-dimensional flow in healthy controls and patients with deep vein thrombosis: a pilot study
Introduction
Deep vein thrombosis (DVT) is a common multifactorial disease and a major cause of morbidity and mortality (1). The estimated annual incidence of DVT ranges from 50 to 160 cases per 100,000 person-years (2). Although risk factors of DVT including hypercoagulation, Virchow’s triad, and iliac vein compression syndrome (IVCS) (3) have been identified, the exact pathogenesis of DVT remains incompletely understood. Moreover, recent evidence suggests a potential bidirectional relationship between DVT and arterial diseases (4), underscoring the need for a greater understanding of DVT and the importance of accurate hemodynamic assessment in this field.
Four-dimensional (4D) flow magnetic resonance imaging (MRI) has been proven to be effective for the evaluation of various vascular disorders, although its current applications are primarily related to the assessment of cardiac, cerebral, and hepatic vasculature, including valvular diseases (5), aortopathies (6), congenital heart diseases (7), cerebrovascular stenosis (8), and hepatic diseases (9). However, its use in the pelvis remains limited due to its long acquisition time and a lack of population-based references. An abundance of research has demonstrated compressed sensing (CS), a widely used acceleration method, to be an effective 4D flow imaging approach. Garreau et al. reported that a CS factor of 7.6 yielded good agreement with the conventional generalized autocalibrating partially parallel acquisition (GRAPPA) method in a phantom aortic model (10). Aono et al. compared sensitivity encoding (SENSE), echo-planar imaging (EPI), and a CS factor of 12 for 4D flow acquisition, and their results showed that EPI and CS 12 could save 71–73% of time while obtaining accurate flow parameters (11). Ma et al. further tested a CS factor of 14.1 in a pulsatile phantom and found excellent agreement in net flow assessment (12). This evidence indicates the reliability of the 4D flow acceleration technique; however, no study has examined the application of accelerated 4D flow techniques for the evaluation of iliac vasculature.
Moreover, the majority of current 4D flow acquisition is performed with a single-velocity encoding (VENC) approach, which limits the simultaneous estimation of flow in vessels with different blood flow velocities. Therefore, dual- or multi-VENC 4D techniques have been developed to facilitate the evaluation of complex flow environments within a limited scan time. In their study, Kroeger et al. used multi-VENC 4D flow MRI acquisition to evaluate both the ascending aorta and main pulmonary artery, demonstrating the feasibility of multi-VENC 4D flow MRI for complex cardiac flow assessment within a clinically acceptable scan duration (13). Kroeger et al.’s subsequent study further confirmed that multi-VENC 4D flow MRI enhances image quality and improves interreader agreement for vortex evaluation in the pulmonary artery (14). Collectively, these findings highlight the clinical potential of 4D flow with multiple VENCs. The imaging of iliac vasculature, which includes both iliac arteries and veins and a comprehensive flow environment, will likely benefit from this technique, but further investigation is needed to clarify its value.
To our knowledge, no prior study has evaluated the application of CS 4D flow MRI in examining the iliac vasculature, nor has any multi-VENC 4D flow MRI sequence been tested for complex flow assessment in this region. Therefore, this study aimed to evaluate the performance of CS-accelerated dual-VENC 4D flow in assessing both iliac arteries and veins in healthy controls (HCs) and patients with DVT. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1886/rc).
Methods
The visual summary of this study is presented in Figure 1.
Study population
This prospective study enrolled HCs and patients with DVT who underwent 4D flow MRI of the iliac vasculature at Beijing Chaoyang Hospital between December 2024 and April 2025. The inclusion criteria for HCs were (I) age >18 years and (II) no known cardiovascular, cerebrovascular, systemic, or malignant diseases; the exclusion criterion for HCs was claustrophobia. Meanwhile, the inclusion criteria for patients with DVT were as follows: (I) age >18 years; (II) a confirmed DVT diagnosis via ultrasound, computed tomography (CT), or MRI within 1 week before the 4D flow MRI examination; and (III) no surgical thrombectomy before MRI. The exclusion criteria for patients were (I) accompanying malignancy, (II) pregnancy, and (III) contraindications to magnetic resonance (MR) scans.
This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of Beijing Chaoyang Hospital (No.: 2024-11-29-4). The registered clinical trial ID is ChiCTR2500099260. All participants provided written informed consent.
MRI acquisition
All participants underwent MR scans with a 3T system (MAGNETOM Vida, Siemens Healthineers, Erlangen, Germany). Three sequential acquisitions, including two conventional single-VENC 4D flow MRI sequences with both high and low VENCs, together with a CS-accelerated dual-VENC research 4D flow MRI sequence, were performed without contrast injection, with random repeat acquisitions performed for the test-retest reliability assessment. Participants were scanned in the supine position with a 32-channel spine coil and an 18-channel body phased-array coil. All 4D flow MRI data were reconstructed to 25 cardiac frames via retrospective pulse oximeter gating. Initial VENC scout images were acquired at the abdominal aorta (AA) and inferior vena cava (IVC) levels with VENC settings of 50 and 120 cm/s. If aliasing was observed, the VENC was increased by 20 cm/s until a radiologist confirmed its absence. In one participant, all 4D flow MRI acquisitions maintained identical resolution, field of view (FOV), and oversampling parameters. The acquisition parameters were the following: acquisition resolution =1.50–1.76 × 1.50 × 1.50–1.76 mm3, FOV =112 (foot-head) × 144 (right-left) × 54–90 (anterior-posterior) mm3 (adjusted for vascular curvature), and phase oversampling = 25–50% (based on body size). For conventional 4D flow, the GRAPPA factor was 3, and for CS 4D flow MRI, the CS factor was 8.9 (Table S1).
Image processing
One experienced radiologist (Qiming Liu, with 5 years of experience in cardiac imaging) initially excluded images with significant artifacts and performed postprocessing using the freely available 4D-Flow-Matlab-Toolbox (MathWorks, Natick, MA, USA). This study also adhered to the recommendations of the most recent 4D flow consensus statement (15). The data processing included background phase offset correction (16), the semiautomatic segmentation of iliac arteries and veins, the tetrahedral finite element mesh generation (17), the velocity vector interpolation at each node of the mesh using linear interpolation, and the quantification of mean velocity and wall shear stress (WSS) (18,19). The quantification of hemodynamic parameters was carried out with a finite element approach, which was based on the least square stress projection method and Laplacian method (20).
For each participant, five arterial segments [including the AA, left common iliac artery (LCIA), right common iliac artery (RCIA), left external iliac artery (LEIA), and right external iliac artery (REIA)] and five venous segments [including the IVC, left common iliac vein (LCIV), right common iliac vein (RCIV), left external iliac vein (LEIV), and right external iliac vein (REIV)] were manually selected for calculation of the hemodynamic parameters.
For each participant, the mean values of each parameter were calculated as follows:
where is the weighted average (mean) of each parameter in a segment , and , and are the parameter and the Voronoi volume at node i in the segment , respectively.
To obtain the mean values of WSS, only the wall nodes were considered, and the relative mean error was calculated as follows:
where is the mean value of the parameter under the conventional single-VENC acquisition, and is the mean value of the parameter under the CS dual-VENC acquisition. Each segment corresponds to one of the vascular segments.
Phase synchronization
In this study, retrospective pulse oximeter gating was employed, resulting in various peak velocity phases due to participants’ pulse wave velocity, height, vessel curvature, heart rate, and other conditions. To standardize the analysis, the peak phase was defined as the phase with the highest mean velocity across three consecutive phases at the AA level and was designated as the new phase 10 (out of a total of 25 phases), which was defined as the “systole”, while phase 20 was defined as the “diastole” (21).
Quality control of quantitative 4D flow parameters
Random repeat acquisitions were performed 18, 19, and 16 times for single high-VENC, single low-VENC, and CS-accelerated dual-VENC acquisition, and these data were used for test-retest reliability examination. Moreover, to improve the reliability of this study, approximately 25% of HCs were randomly selected for interobserver and intra-observer correlation analyses (conducted by Qifan Lu, a cardiologist with 5 years of experience in cardiac imaging). The re-evaluation for intraobserver correlation analysis was performed after an interval of at least 30 days.
Clinical data
The left ventricular ejection fraction (LVEF) and pulmonary hypertension status were obtained from echocardiography data, and the information on pulmonary embolism was obtained through CT. For the description of DVT, the lower extremity deep veins on each side were divided into five segments: the common iliac, external iliac, femoral, popliteal, and calf veins. The IVC was assessed as a separate, non-laterality-specific segment. All images were independently reviewed by an experienced radiologist (X.W., with 7 years of experience) to identify thrombus in each segment. The location of the most proximal segment of each patient was recorded.
Statistical analysis
Statistical analysis was performed with SPSS 23.0 (IBM Corp., Armonk, NY, USA) and Python 3.7.10 (Python Software Foundation, Wilmington, DE, USA) and its associated packages (including pingouin, sklearn, and scipy). The Kolmogorov-Smirnov test was used to evaluate the normality of continuous data. Normally distributed continuous variables are expressed as the mean ± standard deviation (SD), while nonnormally distributed variables are presented as the median and interquartile range (IQR). Meanwhile, categorical variables are reported as frequencies (%). Flow parameters were compared via paired-samples t tests or Wilcoxon rank-sum tests, as appropriate. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability, interreader agreement, and intrareader agreement under the following scheme: 0.0–0.3, no agreement; 0.31–0.5, weak agreement; 0.51–0.7, moderate agreement; 0.71–0.9, strong agreement; and 0.91–1.00, very strong agreement. The Pearson correlation coefficient (R) was used to evaluate the correlations between measurements obtained with different techniques and the association between key flow parameters and age, with R≥0.7 indicating strong correlation, R>0.3 but <0.7 indicating moderate correlation, and R<0.3 indicating weak correlation. A P value <0.05 was considered statistically significant.
Results
Baseline characteristics
A total of 62 HCs and 20 patients with DVT were initially enrolled. After the exclusion criteria were applied, 47 HCs (median age 49 years; 66% male) and 15 patients with DVT (median age 67 years; 60% male) were included in the final analysis (Figure 2). The age of patients with DVT (median age 67.0 years, IQR 50.0–75.0 years) was significantly higher compared with the HCs (median age 49.0 years, IQR 28.5–57.0 years) (P<0.001), while other baseline characteristics were similar between the two groups. The LVEF results indicated that all patients with DVT had normal cardiac function (all >55.0%; median 68.0%, IQR 66.5–71.5%), with three patients with pulmonary hypertension and four patients with pulmonary embolism (Table 1).
Table 1
| Parameters | HC (n=47) | Patients with DVT (n=15) | P value |
|---|---|---|---|
| Age, years | 49.0 (28.5, 57.0) | 67.0 (50.0, 75.0) | <0.001 |
| Male | 31 (65.9) | 9 (60.0) | 0.677 |
| Weight, kg | 70.0 (60.0, 78.5) | 70.0 (65.0, 75.0) | 0.987 |
| Height, cm | 170.0 (163.5, 175.0) | 170.0 (162.5, 175.5) | 0.889 |
| BMI, kg/m2 | 24.9 (22.4, 27.2) | 23.7 (22.6, 25.9) | 0.616 |
| SBP, mmHg | 127 (116, 136) | 125 (121, 134) | 0.837 |
| DBP, mmHg | 77 (72, 82) | 78 (70, 80) | 0.570 |
| LVEF, % | 68.0 (66.5, 71.5) | ||
| Pulmonary embolism | 4 (26.7) | ||
| Pulmonary hypertension | 3 (20.0) | ||
| DVT location | |||
| IVC | 1 (6.7) | ||
| Left | 9 (60.0) | ||
| Right | 5 (33.3) | ||
| DVT extent | |||
| Common iliac vein | 3 (20.0) | ||
| External iliac vein | 0 (0.0) | ||
| Femoral vein | 6 (40.0) | ||
| Popliteal vein | 3 (20.0) | ||
| Calf vein | 2 (13.3) | ||
| DVT classification | |||
| Acute | 5 (33.3) | ||
| Subacute | 4 (26.7) | ||
| Chronic | 6 (40.0) |
Values are presented as n (%) or median (lower quartile, upper quartile). BMI, body mass index; DBP, diastolic blood pressure; DVT, deep vein thrombosis; HC, healthy control; IVC, inferior vena cava; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure.
The detailed analysis of DVT showed that 1, 9, and 6 thrombi were located at the IVC, the left side deep veins, and the right side deep veins, respectively. Most thrombi were present at the femoral vein (n=6, 40.0%), while 3, 3, 2, and 1 thrombi were present at the common iliac vein, popliteal vein, calf vein, and IVC, respectively (Table 1).
The average acquisition times for conventional high-VENC, conventional low-VENC, and CS dual-VENC 4D flow MRI were 10.6, 10.7, and 8.8 min, respectively, demonstrating a significant improvement in acquisition efficiency with an average reduction of 59%. Representative 4D flow visualization of the iliac arteries and veins with conventional and CS-accelerated techniques in an HC and a patient with DVT is shown in Figure 3, which also provides DVT visualized via the MR black-blood thrombus imaging technique.
Quality control
In the test-retest reliability analysis, arterial velocity with conventional high-VENC and CS high-VENC imaging yielded ICCs ranging from 0.832 to 0.952 (all P values <0.001), while venous parameter quantification with low-VENC imaging yielded ICCs of 0.898 to 0.981 (all P values <0.001). Systolic WSS quantification produced similar results: except for RCIA WSS assessed with the conventional method (ICC =0.808; P=0.001), all WSS parameters exhibited ICCs >0.8 and P<0.001, indicating strong technical reproducibility for both conventional and CS methods. Intra- and inter-observer correlation analyses revealed comparable findings, with arterial and venous velocity and WSS measurements demonstrating ICCs >0.85 and P<0.001, confirming robust flow parameter assessment across experienced readers (Table S2).
The correlation between measurements obtained from interobserver, intraobserver, and test-retest experiments was strong. The R values all exceeded 0.9 for intra- and inter-observer velocity parameters and were greater than 0.85 for test-retest velocity parameters (all P values <0.001).
Comparison of flow parameters obtained with conventional and CS methods
The flow measurements of arterial segments at systole are presented in Figure 4A,4B and Figure S1A,S1B. Specifically, in HCs, the velocity at the AA measured with the conventional method (median 0.46 m/s, IQR 0.4–0.53 m/s) was higher than that with the CS method (median 0.44 m/s, IQR 0.39–0.51 m/s) (P<0.001). Similarly, measured WSS was also significantly higher under conventional methods (median 1.45, IQR 1.3–1.75) than with the CS method (median 1.44, IQR 1.19–1.64) (P<0.001) (Table 2). In patients with DVT, no significant differences were observed in velocity (conventional: median 0.41 m/s, IQR 0.39–0.46 m/s; CS: median 0.4 m/s, IQR 0.38–0.46 m/s; P=0.85) or WSS (conventional: median 1.31, IQR 1.17–1.49; CS: median 1.3, IQR 1.17–1.43; P=0.622) at the AA due to limited sample size, although the tendency to underestimation remained (2.1% for velocity and 5.1% for WSS).
Table 2
| Parameters | HC | DVT | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Conventional | CS | Percent error | P value | Conventional | CS | Percent error | P value | ||
| AA | |||||||||
| Velocity, m/s | 0.46 (0.40, 0.53) | 0.44 (0.39, 0.51) | 2.8 (0.4, 7.3) | 0.001 | 0.41 (0.39, 0.46) | 0.40 (0.38, 0.46) | 2.1 (−9.3, 8.3) | 0.850 | |
| WSS, N/m2 | 1.45 (1.30, 1.75) | 1.44 (1.19, 1.64) | 5.8 (0.3, 10.7) | <0.001 | 1.31 (1.17, 1.49) | 1.30 (1.17, 1.43) | 5.1 (−9.5, 12.9) | 0.622 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.093 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.317 | |
| Forward velocity, m/s | 0.46 (0.39, 0.53) | 0.44 (0.38, 0.51) | 3.8 (1.2, 9.0) | <0.001 | 0.41 (0.38, 0.45) | 0.40 (0.37, 0.45) | 2.2 (−6.2, 8.3) | 0.569 | |
| LCIA | |||||||||
| Velocity, m/s | 0.43 (0.38, 0.49) | 0.41 (0.35, 0.48) | 5.4 (0.6, 7.8) | 0.010 | 0.43 (0.40, 0.47) | 0.41 (0.37, 0.45) | 8.6 (−2.6, 16.7) | 0.204 | |
| WSS, N/m2 | 1.60 (1.36, 1.84) | 1.53 (1.26, 1.77) | 5.2 (0, 10.4) | 0.004 | 1.61 (1.49, 1.79) | 1.54 (1.33, 1.70) | 7.9 (−1.9, 17.8) | 0.151 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.612 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.317 | |
| Forward velocity, m/s | 0.42 (0.38, 0.48) | 0.39 (0.34, 0.46) | 6.4 (0.8, 10.5) | 0.002 | 0.43 (0.40, 0.46) | 0.40 (0.36, 0.43) | 8.8 (−1.4, 17.5) | 0.151 | |
| RCIA | |||||||||
| Velocity, m/s | 0.42 (0.36, 0.50) | 0.38 (0.30, 0.47) | 9.6 (2.4, 17.3) | <0.001 | 0.39 (0.37, 0.43) | 0.38 (0.34, 0.43) | 1.9 (−7.0, 7.9) | 1.000 | |
| WSS, N/m2 | 1.51 (1.36, 1.85) | 1.46 (1.14, 1.82) | 8.5 (3.8, 18.4) | <0.001 | 1.49 (1.34, 1.59) | 1.42 (1.26, 1.55) | 3.1 (−7.4, 9.5) | 0.850 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.128 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 1.000 | |
| Forward velocity, m/s | 0.42 (0.36, 0.50) | 0.37 (0.30, 0.46) | 10.3 (4.8, 18.4) | <0.001 | 0.38 (0.36, 0.43) | 0.37 (0.34, 0.41) | 1.9 (−6.5, 8.1) | 0.910 | |
| LEIA | |||||||||
| Velocity, m/s | 0.38 (0.35, 0.43) | 0.34 (0.31, 0.40) | 9.2 (3.2, 18.3) | <0.001 | 0.41 (0.38, 0.46) | 0.40 (0.38, 0.44) | 4.9 (−11.5, 14.5) | 0.622 | |
| WSS, N/m2 | 1.69 (1.46, 1.85) | 1.56 (1.39, 1.75) | 10 (2.8, 18.8) | <0.001 | 1.75 (1.57, 2.01) | 1.74 (1.53, 1.94) | 4.8 (−11.4, 13.9) | 0.622 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.285 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.317 | |
| Forward velocity, m/s | 0.37 (0.34, 0.42) | 0.34 (0.30, 0.39) | 0.0 (0.0, 0.0) | <0.001 | 0.41 (0.37, 0.46) | 0.39 (0.37, 0.43) | 5.1 (−8.2, 16.1) | 0.470 | |
| REIA | |||||||||
| Velocity, m/s | 0.41 (0.35, 0.47) | 0.36 (0.30, 0.42) | 11.6 (2.4, 17.2) | <0.001 | 0.41 (0.36, 0.45) | 0.36 (0.33, 0.39) | 13.3 (−8.0, 19.1) | 0.577 | |
| WSS, N/m2 | 1.72 (1.54, 2.01) | 1.51 (1.31, 1.72) | 11.8 (3.9, 18) | <0.001 | 1.82 (1.43, 2.00) | 1.54 (1.25, 1.78) | 14.8 (−6.2, 19.5) | 0.577 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.131 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.317 | |
| Forward velocity, m/s | 0.41 (0.35, 0.47) | 0.35 (0.29, 0.42) | 12.2 (5.8, 18.4) | <0.001 | 0.41 (0.34, 0.45) | 0.36 (0.32, 0.39) | 13.5 (−6.7, 19.3) | 0.638 | |
Values are presented as median (lower quartile, upper quartile). AA, abdominal aorta; CS, compressed sensing; DVT, deep vein thrombosis; HC, healthy control; LCIA, left common iliac artery; LEIA, left external iliac artery; RCIA, right common iliac artery; REIA, right external iliac artery; WSS, wall shear stress.
The flow measurements of veins at systole are presented in Figure 4C,4D and Figure S1C,S1D. Similar to arterial flow parameters, all parameters in the HCs exhibited underestimation under the CS method (0.0% to 13.2%). In the DVT group at the IVC level, conventional measurements yielded a significantly higher peak velocity (conventional: median 0.12 m/s, IQR 0.06–0.15 m/s; CS: median 0.09 m/s, IQR 0.07–0.14 m/s; P=0.009) and WSS (conventional: median 0.37, IQR 0.21–0.54; CS: median 0.31, IQR 0.23–0.51; P=0.016). For HCs, conventional measurements exhibited a higher peak velocity (median 0.1 m/s, IQR 0.07–0.13 m/s; CS: median 0.09 m/s, IQR 0.07–0.12 m/s; P=0.078) and WSS (median 0.3, IQR 0.24–0.43; CS: median 0.3, IQR 0.21–0.39; P=0.109) compared to CS methods, but not significantly so (Table 3).
Table 3
| Parameters | HC | DVT | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Conventional | CS-accelerated | Percent error | P value | Conventional | CS-accelerated | Percent error | P value | ||
| IVC | |||||||||
| Velocity, m/s | 0.10 (0.07, 0.13) | 0.09 (0.07, 0.12) | 6.8 (−6.9, 19.7) | 0.078 | 0.12 (0.06, 0.15) | 0.09 (0.07, 0.14) | 3.0 (0.9, 19.6) | 0.009 | |
| WSS, N/m2 | 0.30 (0.24, 0.43) | 0.30 (0.21, 0.39) | 6.3 (−8.9, 15.3) | 0.109 | 0.37 (0.21, 0.54) | 0.31 (0.23, 0.51) | 7.4 (2.6, 18.7) | 0.016 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.084 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 29.0 (0.0, 98.0) | 0.204 | |
| Forward velocity, m/s | 0.09 (0.07, 0.12) | 0.08 (0.06, 0.11) | 13.2 (−0.2, 30.0) | <0.001 | 0.11 (0.05, 0.15) | 0.08 (0.06, 0.13) | 12.9 (0.7, 28.9) | 0.519 | |
| LCIV | |||||||||
| Velocity, m/s | 0.08 (0.06, 0.09) | 0.07 (0.05, 0.08) | 10.7 (−3.5, 18.6) | <0.001 | 0.12 (0.09, 0.13) | 0.10 (0.09, 0.11) | 13.3 (9.3, 19.6) | 0.624 | |
| WSS, N/m2 | 0.30 (0.25, 0.36) | 0.25 (0.21, 0.32) | 12.0 (−1.1, 20.3) | <0.001 | 0.44 (0.37, 0.49) | 0.40 (0.33, 0.44) | 14.2 (9.8, 18.1) | 0.501 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.004 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.733 | |
| Forward velocity, m/s | 0.07 (0.06, 0.08) | 0.06 (0.04, 0.07) | 0.0 (0.0, 0.0) | <0.001 | 0.12 (0.09, 0.12) | 0.08 (0.07, 0.09) | 27.2 (12.0, 29.0) | 0.791 | |
| RCIV | |||||||||
| Velocity, m/s | 0.10 (0.07, 0.12) | 0.09 (0.07, 0.12) | 6.8 (−13.4, 16.6) | 0.262 | 0.10 (0.07, 0.12) | 0.10 (0.06, 0.12) | 1.3 (−4.0, 12.9) | 0.569 | |
| WSS, N/m2 | 0.34 (0.27, 0.48) | 0.33 (0.25, 0.43) | 5.0 (−8.0, 19.8) | 0.196 | 0.37 (0.27, 0.47) | 0.41 (0.23, 0.47) | 2.1 (−6.3, 14.5) | 0.380 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.034 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.677 | |
| Forward Velocity, m/s | 0.10 (0.07, 0.11) | 0.09 (0.06, 0.11) | 7.3 (−13.4, 19.2) | 0.174 | 0.09 (0.06, 0.12) | 0.10 (0.06, 0.12) | 2.8 (−4.9, 14.6) | 0.176 | |
| LEIV | |||||||||
| Velocity, m/s | 0.07 (0.05, 0.08) | 0.07 (0.05, 0.08) | 5.8 (−8.3, 10.0) | 0.152 | 0.09 (0.09, 0.10) | 0.08 (0.06, 0.09) | 6.4 (−2.7, 18.5) | 0.791 | |
| WSS, N/m2 | 0.26 (0.20, 0.30) | 0.25 (0.18, 0.30) | 7.4 (−5.1, 12.6) | 0.047 | 0.34 (0.31, 0.36) | 0.32 (0.24, 0.35) | 5.4 (−4.4, 16.7) | 0.233 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.208 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.013 | |
| Forward velocity, m/s | 0.06 (0.05, 0.08) | 0.07 (0.04, 0.08) | 8.1 (−3.8, 13.5) | 0.006 | 0.09 (0.09, 0.09) | 0.08 (0.06, 0.09) | 5.9 (−2.9, 19.5) | 0.721 | |
| REIV | |||||||||
| Velocity, m/s | 0.07 (0.05, 0.09) | 0.07 (0.04, 0.09) | 1.1 (−11.4, 21.2) | 0.477 | 0.07 (0.04, 0.08) | 0.07 (0.05, 0.09) | 4.5 (−14.2, 7.2) | 0.365 | |
| WSS, N/m2 | 0.26 (0.19, 0.34) | 0.26 (0.15, 0.34) | 5.3 (−10.2, 23.9) | 0.305 | 0.30 (0.17, 0.34) | 0.26 (0.20, 0.38) | 2.3 (−12.6, 5.9) | 0.365 | |
| Backward velocity, m/s | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.327 | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | 0.0 (0.0, 0.0) | 0.278 | |
| Forward velocity, m/s | 0.06 (0.04, 0.08) | 0.06 (0.04, 0.09) | 0.0 (0.0, 0.0) | 0.232 | 0.07 (0.04, 0.08) | 0.07 (0.04, 0.09) | −3.8 (−23.8, 4.5) | 0.646 | |
Values are presented as median (lower quartile, upper quartile). CS, compressed sensing; DVT, deep vein thrombosis; HC, healthy control; IVC, inferior vena cava; LCIV, left common iliac vein; LEIV, left external iliac vein; RCIV, right common iliac vein; REIV, right external iliac vein; WSS, wall shear stress.
Bland-Altman plots were also generated to compare the differences in flow parameters between HCs and patients with DVTs. The results indicated that for velocity, the mean difference for the AA and IVC were 0.02 m/s [95% confidence interval (CI): 0.00–0.03 m/s] and 0.01 m/s (95% CI: 0.00–0.01 m/s), respectively; for WSS, the mean differences for AA and IVC were 0.08 N/m2 (95% CI: 0.03–0.12 N/m2) and 0.02 N/m2 (95% CI: −0.01 to 0.04 N/m2), respectively (Figure S2).
Correlation between age and flow parameters
In the correlation analysis, there were significant negative correlations were observed between the age of HCs and velocity (R=−0.33; P=0.024) and WSS (R=−0.34; P=0.019) of the AA, while for patients with DVT, age demonstrated nonsignificant negative correlations with velocity (R=−0.25; P=0.366) and WSS (R=−0.23; P=0.408) (Figure 5A,5B).
Regarding the IVC in HCs, there was a significant negative correlation between velocity and age (R=−0.29; P=0.047); however, the correlation between WSS and age was not significant (R=−0.21; P=0.158). Meanwhile, in patients with DVT, although no statistical significance was observed, there were positive correlations between velocity/WSS and age (Figure 5C,5D).
Discussion
This study systematically evaluated and quantified flow parameters in iliac arteries and veins using conventional and dual-VENC 4D flow MRI techniques in both HCs and patients with DVT. The results demonstrated that both the conventional and CS techniques had robust performance when applied to the iliac vasculature; moreover, negative correlations between velocity/WSS and age were confirmed in HCs. In contrast, in patients with DVT, a nonsignificant positive correlation was found between venous velocity/WSS and age, a finding that needs to be scrutinized further.
High spatial and temporal resolution is key to accurate flow estimation, and according to the expert consensus on 4D flow MRI (15), the optimal spatial resolution for large vessels should be 2 mm3, and the temporal resolution should not exceed 50 ms. For iliac vasculature, an even higher spatial resolution is required due to the smaller vessel diameters. However, without acceleration, this strict acquisition protocol often results in prolonged scan times in clinical practice which limits its application. Ghibes et al. reported a median acquisition time of 12 min and 12 s for venous imaging with a spatial resolution of 1.5×1.5×1.6 mm3 and a temporal resolution (22) of 74.6 ms; meanwhile, You et al. used a coarser resolution of 1.7×2.1×3.0 mm3 for flow quantification in the LCIA and LCIV (23). In our study, we adopted a protocol with high temporal (~40 ms) and spatial (1.5 mm isotropic) resolution to evaluate the feasibility of 4D flow in the pelvis. We found that dual-VENC CS 4D flow MRI could reduce the acquisition time by 59% time and produce highly consistent results for visualization and velocity/WSS assessment. This parameter setting also improved region-of-interest segmentation accuracy. Moreover, in clinic, patients with DVT often experience limb pain, swelling, or reduced mobility. A shorter examination time could improve patient comfort, reduce motion artifacts, and enhance the feasibility of follow-up imaging acquisition in symptomatic or acute settings. Another practical challenge was the choice of triggering technique. Electrocardiogram gating was initially tested; however, low VENC increased signal interference, leading to corrupted triggering and low-quality data (22,24). Consequently, pulse oximeter gating was selected, and combining the phase synchronization processing proposed in this study, we developed a complete acquisition-processing-analysis pipeline for 4D flow imaging of the iliac vasculature. This study also found that the CS 4D technique flow underestimates velocity and WSS as compared to GRAPPA methods, with the percent error ranging from 1% to 14%, a finding consistent with previous studies. For instance, Ikoma et al. found that high-VENC 4D flow for pulmonary artery evaluation may result in underestimation of flow parameters (25), and Varga-Szemes et al. reported a 10% underestimation of flow measurements with a CS factor of 7.7 (26). These findings suggest that the comparison of 4D flow measurements acquired with different techniques should be treated with caution, especially in clinical scenarios. Moreover, we believe that the underestimation observed in the CS techniques should be carefully considered, especially in future multicenter studies in which data can be collected with different MR acquisition protocols. This underestimation also supports the development of a novel algorithm that can convert the CS-based results into GRAPPA-based ones, thus facilitating the comparison of CS values and GRAPPA values.
Vascular aging is also an important factor in the evaluation of flow parameters. Roberts et al. found that with aging, cerebral blood flow reduces while pulsatility increases (24). Ramaekers et al. reported similar findings in the aorta, with both velocity and WSS decreasing with age (27). We also analyzed the correlation of the flow parameters of the AA and IVC with age, and results in HCs were highly consistent with those of previous studies (24,27), confirming the presence of iliac vascular aging. Interestingly, a nonsignificant positive correlation of WSS at the IVC level with age was observed in patients with DVT, indicating that DVT formation may play an important role in vascular remodeling, especially the venous system; however, this remains speculative and further validation is required.
Functional change of vessels is a key factor in the development of DVT, and WSS is a sensitive parameter for the evaluation of vascular change (28). Wang et al. demonstrated that iliac veins with higher time-averaged WSS and lower relative residence time exhibit narrowed luminal areas, which could impede blood flow and promote the accumulation of blood components, thereby increasing DVT risk (29). Meanwhile, Lyu et al. found that positive WSS divergence may promote thrombus formation in patients with intracranial aneurysms (30). Although our study did not directly compare flow parameters between HCs and patients with DVT due to age differences and the limited sample size, the positive correlation between age and flow parameters observed in patients with DVT suggests that future research should focus more on patients with DVT. Furthermore, different thrombus locations and extent may alter venous hemodynamics, although we did not quantify the effect of thrombus location on hemodynamic change, our example case presented in Figure 3C,3D, suggests that hemodynamic alterations may also serve as valuable indicators for thrombus detection.
Besides MR, the evaluation of the iliac vasculature can also be performed using other imaging modalities. For instance, Assi et al. found that ultrasound and computational fluid dynamics (CFD) methods had excellent performance in assessing the iliac veins in patients with IVCS (31). Moreover, Guo et al. reported that a positive iliac vein ultrasound finding was associated with a higher risk of concurrent IVCS (32). Computed tomography venography (CTV) is another widely used modality for quantifying the iliac vasculature. Zhang et al. identified female and advanced age as risk factors for IVCS (33), while Jiang et al. found that hemodynamic changes derived from CTV and CFD could aid in predicting iliac vein stenosis (34). In contrast to CTV, 4D flow MR is contrast-free and can record dynamic flow information, and compared with ultrasound, it provides higher objectivity and a larger FOV for minimizing the operator dependence. Additionally, flow patterns can be directly calculated via 4D imaging, avoiding potential CFD simulation errors.
Certain limitations to this study should be acknowledged. First, only one CS factor and the conventional GRAPPA acceleration technique were examined in this study due to time constraints, and future studies should include and compare other acceleration methods. Second, we conducted a pilot study focused on technical validation; therefore, certain baseline characteristics were not measured. In future large-scale, prospective studies, cardiac function status and vascular indices (e.g., cardio-ankle vascular index, ankle-brachial index, and pulse wave velocity) should be obtained along with 4D flow MRI to better characterize the association between hemodynamic parameters and the underlying DVT mechanisms. Finally, the comparison of flow dynamics should be compared in a large, age- and sex-matched cohort, and the hemodynamic alteration under DVT conditions should be better quantified.
Conclusions
This study evaluated and quantified the flow parameters of iliac arteries and veins in HCs and patients with DVT using conventional and dual-VENC 4D flow techniques. Although underestimation was observed, dual-VENC 4D flow enabled comprehensive velocity and WSS assessment. However, the WSS measurement exhibited insufficient stability, indicating a need for further sequence optimization.
Acknowledgments
The authors would like to thank all volunteers for their participation in this study. J.S. thanks to Millennium Science Initiative Program—ICN2021_004 and Department of Medical Imaging and Radiation Sciences at Monash University.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1886/rc
Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1886/dss
Funding: This research received funding from
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1886/coif). C.Z. is from Siemens Healthineers and G.D. is from Siemens Healthineers AG. The other authors have no 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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Ethics Committee of Beijing Chaoyang Hospital (No.: 2024-11-29-4). All participants provided written informed consent.
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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