Abnormal Diastolic Hemodynamic Forces: A Link Between Right Ventricular Wall Motion, Intracardiac Flow, and Pulmonary Regurgitation in Repaired Tetralogy of Fallot.

Background and Objective: The effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dysfunction in repaired Tetralogy of Fallot (RTOF) patients is well recognized by cardiac magnetic resonance (CMR). However, the link between RV wall motion, intracardiac flow and PR has not been established. Hemodynamic force (HDF) represents the global force exchanged between intracardiac blood volume and endocardium, measurable by 4D flow or by a novel mathematical model of wall motion. In our study, we used this novel methodology to derive HDF in a cohort of RTOF patients, exclusively using routine CMR imaging. Methods: RTOF patients and controls with CMR imaging were retrospectively included. Three-dimensional (3D) models of RV were segmented, including RV outflow tract (RVOT). Feature-tracking software (QStrain 2.0, Medis Medical Imaging Systems, Leiden, Netherlands) captured endocardial contours from long/short-axis cine and used to reconstruct RV wall motion. A global HDF vector was computed from the moving surface, then decomposed into amplitude/impulse of three directional components based on reference (Apical-to-Basal, Septal-to-Free Wall and Diaphragm-to-RVOT direction). HDF were compared and correlated against CMR and exercise stress test parameters. A subset of RTOF patients had 4D flow that was used to derive vorticity (for correlation) and HDF (for comparison against cine method). Results: 68 RTOF patients and 20 controls were included. RTOF patients had increased diastolic HDF amplitude in all three directions (p<0.05). PR% correlated with Diaphragm-RVOT HDF amplitude/impulse (r = 0.578, p<0.0001, r = 0.508, p < 0.0001, respectively). RV ejection fraction modestly correlated with global HDF amplitude (r = 0.2916, p = 0.031). VO2-max correlated with Septal-to-Free Wall HDF impulse (r = 0.536, p = 0.007). Diaphragm-to-RVOT HDF correlated with RVOT vorticity (r = 0.4997, p = 0.001). There was no significant measurement bias between Cine-derived HDF and 4D flow-derived HDF by Bland-Altman analysis. Conclusion: RTOF patients have abnormal diastolic HDF that is correlated to PR, RV function, exercise capacity and vorticity. HDF can be derived from conventional cine, and is a potential link between RV wall motion and intracardiac flow from PR in RTOF patients.

Spatial correlations between MRI-derived wall shear stress and vessel wall thickness in the carotid bifurcation.

BACKGROUND: To explore the possibility of creating three-dimensional (3D) estimation models for patient-specific wall thickness (WT) maps using patient-specific and cohort-averaged WT, wall shear stress (WSS), and vessel diameter maps in asymptomatic atherosclerotic carotid bifurcations. METHODS: Twenty subjects (aged 75 ± 6 years [mean ± standard deviation], eight women) underwent a 1.5-T MRI examination. Non-gated 3D phase-contrast gradient-echo images and proton density-weighted echo-planar images were retrospectively assessed for WSS, diameter estimation, and WT measurements. Spearman's ρ and scatter plots were used to determine correlations between individual WT, WSS, and diameter maps. A bootstrapping technique was used to determine correlations between 3D cohort-averaged WT, WSS, and diameter maps. Linear regression between the cohort-averaged WT, WSS, and diameter maps was used to predict individual 3D WT. RESULTS: Spearman's ρ averaged over the subjects was - 0.24 ± 0.18 (p < 0.001) and 0.07 ± 0.28 (p = 0.413) for WT versus WSS and for WT versus diameter relations, respectively. Cohort-averaged ρ, averaged over 1000 bootstraps, was - 0.56 (95% confidence interval [- 0.74,- 0.38]) for WT versus WSS and 0.23 (95% confidence interval [- 0.06, 0.52]) for WT versus diameter. Scatter plots did not reveal relationships between individual WT and WSS or between WT and diameter data. Linear relationships between these parameters became apparent after averaging over the cohort. Spearman's ρ between the original and predicted WT maps was 0.21 ± 0.22 (p < 0.001). CONCLUSIONS: With a combination of bootstrapping and cohort-averaging methods, 3D WT maps can be predicted from the individual 3D WSS and diameter maps. The methodology may help to elucidate pathological processes involving WSS in carotid atherosclerosis.

Creating hemodynamic atlases of cardiac 4D flow MRI.

PURPOSE: Hemodynamic atlases can add to the pathophysiological understanding of cardiac diseases. This study proposes a method to create hemodynamic atlases using 4D Flow magnetic resonance imaging (MRI). The method is demonstrated for kinetic energy (KE) and helicity density (Hd ). MATERIALS AND METHODS: Thirteen healthy subjects underwent 4D Flow MRI at 3T. Phase-contrast magnetic resonance cardioangiographies (PC-MRCAs) and an average heart were created and segmented. The PC-MRCAs, KE, and Hd were nonrigidly registered to the average heart to create atlases. The method was compared with 1) rigid, 2) affine registration of the PC-MRCAs, and 3) affine registration of segmentations. The peak and mean KE and Hd before and after registration were calculated to evaluate interpolation error due to nonrigid registration. RESULTS: The segmentations deformed using nonrigid registration overlapped (median: 92.3%) more than rigid (23.1%, P < 0.001), and affine registration of PC-MRCAs (38.5%, P < 0.001) and affine registration of segmentations (61.5%, P < 0.001). The peak KE was 4.9 mJ using the proposed method and affine registration of segmentations (P = 0.91), 3.5 mJ using rigid registration (P < 0.001), and 4.2 mJ using affine registration of the PC-MRCAs (P < 0.001). The mean KE was 1.1 mJ using the proposed method, 0.8 mJ using rigid registration (P < 0.001), 0.9 mJ using affine registration of the PC-MRCAs (P < 0.001), and 1.0 mJ using affine registration of segmentations (P = 0.028). The interpolation error was 5.2 ± 2.6% at mid-systole, 2.8 ± 3.8% at early diastole for peak KE; 9.6 ± 9.3% at mid-systole, 4.0 ± 4.6% at early diastole, and 4.9 ± 4.6% at late diastole for peak Hd . The mean KE and Hd were not affected by interpolation. CONCLUSION: Hemodynamic atlases can be obtained with minimal user interaction using nonrigid registration of 4D Flow MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1389-1399.

Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation.

Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored. Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2-3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed. Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009); The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002) and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 µg/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001) at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04) at Time-2. Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related atrial stunning.

The Effect of Spatial and Temporal Resolution of Cine Phase Contrast MRI on Wall Shear Stress and Oscillatory Shear Index Assessment.

INTRODUCTION: Wall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom. METHODS: A carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions. RESULTS: The mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI). CONCLUSION: We show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.

Relation between wall shear stress and carotid artery wall thickening MRI versus CFD.

Wall shear stress (WSS), a parameter associated with endothelial function, is calculated by computational fluid dynamics (CFD) or phase-contrast (PC) MRI measurements. Although CFD is common in WSS (WSSCFD) calculations, PC-MRI-based WSS (WSSMRI) is more favorable in population studies; since it is straightforward and less time consuming. However, it is not clear if WSSMRI and WSSCFD show similar associations with vascular pathology. Our aim was to test the associations between wall thickness (WT) of the carotid arteries and WSSMRI and WSSCFD. The subjects (n=14) with an asymptomatic carotid plaque who underwent MRI scans two times within 4 years of time were selected from the Rotterdam Study. We compared WSSCFD and WSSMRI at baseline and follow-up. Baseline WSSMRI and WSSCFD values were divided into 3 categories representing low, medium and high WSS tertiles. WT of each tertile was compared by a one-way ANOVA test. The WSSMRI and WSSCFD were 0.50±0.13Pa and 0.73±0.25Pa at baseline. Although WSSMRI was underestimated, a significant regression was found between WSSMRI and WSSCFD (r(2)=0.71). No significant difference was found between baseline and follow-up WSS by CFD and MRI-based calculations. The WT at baseline was 1.36±0.16mm and did not change over time. The WT was 1.55±0.21mm in low, 1.33±0.20mm in medium and 1.21±0.21mm in the high WSSMRI tertiles. Similarly, the WT was 1.49±0.21mm in low, 1.33±0.20mm in medium and 1.26±0.21mm in high WSSCFD tertiles. We found that WSSMRI and WSSCFD were inversely related with WT. WSSMRI and WSSCFD patterns were similar although MRI-based calculations underestimated WSS.

Long-Term Serial Follow-Up of Pulmonary Artery Size and Wall Shear Stress in Fontan Patients.

Pulmonary arterial (PA) flow is abnormal after the Fontan operation and is marked by a lack of pulsatility. We assessed the effects of this abnormal flow on the size and function of the PA's in Fontan patients in long-term serial follow-up. Twenty-three Fontan patients with serial follow-up were included. Median age was 11.1 (9.5-16.0) years at baseline and 15.5 (12.5-22.7) years at follow-up. Median follow-up duration was 4.4 (4.0-5.8) years. Flow and size of the left pulmonary artery were determined using phase-contrast MRI. From this wall shear stress (WSS), distensibility and pulsatility were determined. A group of healthy peers was included for reference. Flow and pulsatility were significantly lower in patients than in controls (p < 0.001). Mean area was comparable in patients and controls, but distensibility was significantly higher in controls (p < 0.001). Mean and peak WSS were significantly lower in Fontan patients (p < 0.001). Between baseline and follow-up, there was a significant increase in normalized flow (15.1 (14.3-19.1) to 18.7 (14.0-22.6) ml/s/m(2), p = 0.023). Area, pulsatility, distensibility and WSS did not change, but there was a trend toward a lower mean WSS (p = 0.068). Multivariable regression analysis showed that flow, area and age were important predictors for WSS. WSS in Fontan patients is decreased compared to healthy controls and tends to decrease further with age. Pulsatility and distensibility are significantly lower compared to healthy controls. Pulmonary artery size, however, is not significantly different from healthy controls and long-term growth after Fontan operation is proportionate to body size.

The effect of resolution on viscous dissipation measured with 4D flow MRI in patients with Fontan circulation: Evaluation using computational fluid dynamics.

Viscous dissipation inside Fontan circulation, a parameter associated with the exercise intolerance of Fontan patients, can be derived from computational fluid dynamics (CFD) or 4D flow MRI velocities. However, the impact of spatial resolution and measurement noise on the estimation of viscous dissipation is unclear. Our aim was to evaluate the influence of these parameters on viscous dissipation calculation. Six Fontan patients underwent whole heart 4D flow MRI. Subject-specific CFD simulations were performed. The CFD velocities were down-sampled to isotropic spatial resolutions of 0.5mm, 1mm, 2mm and to MRI resolution. Viscous dissipation was compared between (1) high resolution CFD velocities, (2) CFD velocities down-sampled to MRI resolution, (3) down-sampled CFD velocities with MRI mimicked noise levels, and (4) in-vivo 4D flow MRI velocities. Relative viscous dissipation between subjects was also calculated. 4D flow MRI velocities (15.6 ± 3.8 cm/s) were higher, although not significantly different than CFD velocities (13.8 ± 4.7 cm/s, p=0.16), down-sampled CFD velocities (12.3 ± 4.4 cm/s, p=0.06) and the down-sampled CFD velocities with noise (13.2 ± 4.2 cm/s, p=0.06). CFD-based viscous dissipation (0.81 ± 0.55 mW) was significantly higher than those based on down-sampled CFD (0.25 ± 0.19 mW, p=0.03), down-sampled CFD with noise (0.49 ± 0.26 mW, p=0.03) and 4D flow MRI (0.56 ± 0.28 mW, p=0.06). Nevertheless, relative viscous dissipation between different subjects was maintained irrespective of resolution and noise, suggesting that comparison of viscous dissipation between patients is still possible.

Wall shear stress calculations based on 3D cine phase contrast MRI and computational fluid dynamics: a comparison study in healthy carotid arteries.

Wall shear stress (WSS) is involved in many pathophysiological processes related to cardiovascular diseases, and knowledge of WSS may provide vital information on disease progression. WSS is generally quantified with computational fluid dynamics (CFD), but can also be calculated using phase contrast MRI (PC-MRI) measurements. In this study, our objectives were to calculate WSS on the entire luminal surface of human carotid arteries using PC-MRI velocities (WSSMRI ) and to compare it with WSS based on CFD (WSSCFD ). Six healthy volunteers were scanned with a 3 T MRI scanner. WSSCFD was calculated using a generalized flow waveform with a mean flow equal to the mean measured flow. WSSMRI was calculated by estimating the velocity gradient along the inward normal of each mesh node on the luminal surface. Furthermore, WSS was calculated for a down-sampled CFD velocity field mimicking the MRI resolution (WSSCFDlowres ). To ensure minimum temporal variation, WSS was analyzed only at diastole. The patterns of WSSCFD and WSSMRI were compared by quantifying the overlap between low, medium and high WSS tertiles. Finally, WSS directions were compared by calculating the angles between the WSSCFD and WSSMRI vectors. WSSMRI magnitude was found to be lower than WSSCFD (0.62 ± 0.18 Pa versus 0.88 ± 0.30 Pa, p < 0.01) but closer to WSSCFDlowres (0.56 ± 0.18 Pa, p < 0.01). WSSMRI patterns matched well with those of WSSCFD. The overlap area was 68.7 ± 4.4% in low and 69.0 ± 8.9% in high WSS tertiles. The angles between WSSMRI and WSSCFD vectors were small in the high WSS tertiles (20.3 ± 8.2°), but larger in the low WSS tertiles (65.6 ± 17.4°). In conclusion, although WSSMRI magnitude was lower than WSSCFD , the spatial WSS patterns at diastole, which are more relevant to the vascular biology, were similar. PC-MRI-based WSS has potential to be used in the clinic to indicate regions of low and high WSS and the direction of WSS, especially in regions of high WSS.

Computational fluid dynamics in Fontan patients to evaluate power loss during simulated exercise.

OBJECTIVE: Exercise intolerance is common in total cavopulmonary connection (TCPC) patients. It has been suggested that power loss (Ploss) inside the TCPC plays a role in reduced exercise performance. Our objective is to establish the role of Ploss inside the TCPC during increased flow, simulating exercise in a patient-specific way. METHODS: Cardiac MRI (CMR) was used to obtain flow rates from the caval veins during rest and increased flow, simulating exercise with dobutamine. A 3D reconstruction of the TCPC was created using CMR data. Computational fluid dynamics (CFD) simulations were performed to calculate Ploss inside the TCPC structure for rest and stress conditions. To reflect the flow distribution during exercise, a condition where inferior caval vein (IVC) flow was increased twofold compared with rest was added. 29 TCPC patients (15 intra-atrial lateral tunnel (ILT) and 14 extracardiac conduit (ECC)) were included. RESULTS: Mean Ploss at rest was 1.36 ± 0.94 (ILT) and 3.20 ± 1.26 (ECC) mW/m(2) (p<0.001), 2.84 ±1.95 (ILT) and 8.41 ± 3.77 (ECC) mW/m(2) (p<0.001) during dobutamine and 5.21 ± 3.50 (ILT) and 15.28 ± 8.30 (ECC) mW/m(2) (p=0.001) with twofold IVC flow. The correlation between cardiac index and Ploss was exponential (ILT: R(2)=0.811, p<0.001; ECC: R(2)=0.690, p<0.001). CONCLUSIONS: Ploss inside the TCPC structure is limited but increases with simulated exercise. This relates to the anatomy of TCPC and the surgical technique used. In all flow conditions, ILT patients have lower Ploss than ECC patients. We did not find a relationship between Ploss and exercise capacity.

Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge.

Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.