Getting the phase consistent: The importance of phase description in balanced steady-state free precession MRI of multi-compartment systems.

PURPOSE: Determine the correct mathematical phase description for balanced steady-state free precession (bSSFP) signals in multi-compartment systems. THEORY AND METHODS: Based on published bSSFP signal models, different phase descriptions can be formulated: one predicting the presence and the other predicting the absence of destructive interference effects in multi-compartment systems. Numerical simulations of bSSFP signals of water and acetone were performed to evaluate the predictions of these different phase descriptions. For experimental validation, bSSFP profiles were measured at 3T using phase-cycled bSSFP acquisitions performed in a phantom containing mixtures of water and acetone, which replicates a system with two signal components. Localized single voxel MRS was performed at 7T to determine the relative chemical shift of the acetone-water mixtures. RESULTS: Based on the choice of phase description, the simulated bSSFP profiles of water-acetone mixtures varied significantly, either displaying or lacking destructive interference effects, as predicted theoretically. In phantom experiments, destructive interference was consistently observed in the measured bSSFP profiles of water-acetone mixtures, supporting the theoretical description that predicts such interference effects. The connection between the choice of phase description and predicted observation enables unambiguous experimental identification of the correct phase description for multi-compartment bSSFP profiles, which is consistent with the Bloch equations. CONCLUSION: The study emphasizes that consistent phase descriptions are crucial for accurately describing multi-compartment bSSFP signals, as incorrect phase descriptions result in erroneous predictions.

Whole-Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo-Spiral Sampling and EPI Readout.

BACKGROUND: Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. HYPOTHESIS: Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. STUDY TYPE: Prospective. POPULATION: Twelve healthy subjects and eight patients with valvular regurgitation. FIELD STRENGTH/SEQUENCE: 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. ASSESSMENT: Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. STATISTICAL TESTS: We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. RESULTS: PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. CONCLUSION: PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Pseudo-spiral sampling and compressed sensing reconstruction provides flexibility of temporal resolution in accelerated aortic 4D flow MRI: A comparison with k-t principal component analysis.

INTRODUCTION: Time-resolved three-dimensional phase contrast MRI (4D flow) of aortic blood flow requires acceleration to reduce scan time. Two established techniques for highly accelerated 4D flow MRI are k-t principal component analysis (k-t PCA) and compressed sensing (CS), which employ either regular or random k-space undersampling. The goal of this study was to gain insights into the quantitative differences between k-t PCA- and CS-derived aortic blood flow, especially for high temporal resolution CS 4D flow MRI. METHODS: The scan protocol consisted of both k-t PCA and CS accelerated 4D flow MRI, as well as a 2D flow reference scan through the ascending aorta acquired in 15 subjects. 4D flow scans were accelerated with factor R = 8. For CS accelerated scans, we used a pseudo-spiral Cartesian sampling scheme, which could additionally be reconstructed at higher temporal resolution, resulting in R = 13. 4D flow data were compared with the 2D flow scan in terms of flow, peak flow and stroke volume. A 3D peak systolic voxel-wise velocity and wall shear stress (WSS) comparison between k-t PCA and CS 4D flow was also performed. RESULTS: The mean difference in flow/peak flow/stroke volume between the 2D flow scan and the 4D flow CS with R = 8 and R = 13 was 4.2%/9.1%/3.0% and 5.3%/7.1%/1.9%, respectively, whereas for k-t PCA with R = 8 the difference was 9.7%/25.8%/10.4%. In the voxel-by-voxel 4D flow comparison we found 13.6% and 3.5% lower velocity and WSS values of k-t PCA compared with CS with R = 8, and 15.9% and 5.5% lower velocity and WSS values of k-t PCA compared with CS with R = 13. CONCLUSION: Pseudo-spiral accelerated 4D flow acquisitions in combination with CS reconstruction provides a flexible choice of temporal resolution. We showed that our proposed strategy achieves better agreement in flow values with 2D reference scans compared with using k-t PCA accelerated acquisitions.

Highly accelerated 4D flow cardiovascular magnetic resonance using a pseudo-spiral Cartesian acquisition and compressed sensing reconstruction for carotid flow and wall shear stress.

BACKGROUND: 4D flow cardiovascular magnetic resonance (CMR) enables visualization of complex blood flow and quantification of biomarkers for vessel wall disease, such as wall shear stress (WSS). Because of the inherently long acquisition times, many efforts have been made to accelerate 4D flow acquisitions, however, no detailed analysis has been made on the effect of Cartesian compressed sensing accelerated 4D flow CMR at different undersampling rates on quantitative flow parameters and WSS. METHODS: We implemented a retrospectively triggered 4D flow CMR acquisition with pseudo-spiral Cartesian k-space filling, which results in incoherent undersampling of k-t space. Additionally, this strategy leads to small jumps in k-space thereby minimizing eddy current related artifacts. The pseudo-spirals were rotated in a tiny golden-angle fashion, which provides optimal incoherence and a variable density sampling pattern with a fully sampled center. We evaluated this 4D flow protocol in a carotid flow phantom with accelerations of R = 2-20, as well as in carotids of 7 healthy subjects (27 ± 2 years, 4 male) for R = 10-30. Fully sampled 2D flow CMR served as a flow reference. Arteries were manually segmented and registered to enable voxel-wise comparisons of both velocity and WSS using a Bland-Altman analysis. RESULTS: Magnitude images, velocity images, and pathline reconstructions from phantom and in vivo scans were similar for all accelerations. For the phantom data, mean differences at peak systole for the entire vessel volume in comparison to R = 2 ranged from - 2.3 to - 5.3% (WSS) and - 2.4 to - 2.2% (velocity) for acceleration factors R = 4-20. For the in vivo data, mean differences for the entire vessel volume at peak systole in comparison to R = 10 were - 9.9, - 13.4, and - 16.9% (WSS) and - 8.4, - 10.8, and - 14.0% (velocity), for R = 20, 25, and 30, respectively. Compared to single slice 2D flow CMR acquisitions, peak systolic flow rates of the phantom showed no differences, whereas peak systolic flow rates in the carotid artery in vivo became increasingly underestimated with increasing acceleration. CONCLUSION: Acquisition of 4D flow CMR of the carotid arteries can be highly accelerated by pseudo-spiral k-space sampling and compressed sensing reconstruction, with consistent data quality facilitating velocity pathline reconstructions, as well as quantitative flow rate and WSS estimations. At an acceleration factor of R = 20 the underestimation of peak velocity and peak WSS was acceptable (< 10%) in comparison to an R = 10 accelerated 4D flow CMR reference scan. Peak flow rates were underestimated in comparison with 2D flow CMR and decreased systematically with higher acceleration factors.

Insufficient slow-flow suppression mimicking aneurysm wall enhancement in magnetic resonance vessel wall imaging: a phantom study.

OBJECTIVE: MR vessel wall imaging (VWI) is increasingly performed in clinical settings to support treatment decision-making regarding intracranial aneurysms. Aneurysm wall enhancement after contrast agent injection is expected to be related to aneurysm instability and rupture status. However, the authors hypothesize that slow-flow artifacts mimic aneurysm wall enhancement. Therefore, in this phantom study they assess the effect of slow flow on wall-like enhancement by using different MR VWI techniques. METHODS: The authors developed an MR-compatible aneurysm phantom model, which was connected to a pump to enable pulsatile inflow conditions. For VWI, 3D turbo spin echo sequences-both with and without motion-sensitized driven equilibrium (MSDE) and delay alternating with nutation for tailored excitation (DANTE) preparation pulses-were performed using a 3-T MR scanner. VWI was acquired both before and after Gd contrast agent administration by using two different pulsatile inflow conditions (2.5 ml/sec peak flow at 77 and 48 beats per minute). The intraluminal signal intensity along the aneurysm wall was analyzed to assess the performance of slow-flow suppression. RESULTS: The authors observed wall-like enhancement after contrast agent injection, especially in low pump rate settings. Preparation pulses, in particular the DANTE technique, improved the performance of slow-flow suppression. CONCLUSIONS: Near-wall slow flow mimics wall enhancement in VWI protocols. Therefore, VWI should be carefully interpreted. Preparation pulses improve slow-flow suppression, and therefore the authors encourage further development and clinical implementation of these techniques.

Accelerated 4D phase contrast MRI in skeletal muscle contraction.

PURPOSE: 3D time-resolved (4D) phase contrast MRI can be used to study muscle contraction. However, 3D coverage with sufficient spatiotemporal resolution can only be achieved by interleaved acquisitions during many repetitions of the motion task, resulting in long scan times. The aim of this study was to develop a compressed sensing accelerated 4D phase contrast MRI technique for quantification of velocities and strain rate of the muscles in the lower leg during active plantarflexion/dorsiflexion. METHODS: Nine healthy volunteers were scanned during active dorsiflexion/plantarflexion task. For each volunteer, we acquired a reference scan, as well as 4 different accelerated scans (k-space undersampling factors: 3.14X, 4.09X, 4.89X, and 6.41X) obtained using Cartesian Poisson disk undersampling schemes. The data was reconstructed using a compressed sensing pipeline. For each scan, velocity and strain rate values were quantified in the gastrocnemius lateralis, gastrocnemius medialis, tibialis anterior, and soleus. RESULTS: No significant differences in velocity values were observed as a function acceleration factor in the investigated muscles. The strain rate calculation resulted in one positive (s+ ) and one negative (s- ) eigenvalue, whereas the third eigenvalue (s3 ) was consistently 0 for all the acquisitions. No significant differences were observed for the strain rate eigenvalues as a function of acceleration factor. CONCLUSIONS: Data undersampling combined with compressed sensing reconstruction allowed obtainment of time-resolved phase contrast acquisitions with 3D coverage and quantitative information comparable to the reference scan. The 3D sensitivity of the method can help in understanding the connection between muscle architecture and muscle function in future studies.

Regional assessment of carotid artery pulse wave velocity using compressed sensing accelerated high temporal resolution 2D CINE phase contrast cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) allows for non-invasive assessment of arterial stiffness by means of measuring pulse wave velocity (PWV). PWV can be calculated from the time shift between two time-resolved flow curves acquired at two locations within an arterial segment. These flow curves can be derived from two-dimensional CINE phase contrast CMR (2D CINE PC CMR). While CMR-derived PWV measurements have proven to be accurate for the aorta, this is more challenging for smaller arteries such as the carotids due to the need for both high spatial and temporal resolution. In this work, we present a novel method that combines retrospectively gated 2D CINE PC CMR, high temporal binning of data and compressed sensing (CS) reconstruction to accomplish a temporal resolution of 4 ms. This enables accurate flow measurements and assessment of PWV in regional carotid artery segments. METHODS: Retrospectively gated 2D CINE PC CMR data acquired in the carotid artery was binned into cardiac frames of 4 ms length, resulting in an incoherently undersampled ky-t-space with a mean undersampling factor of 5. The images were reconstructed by a non-linear CS reconstruction using total variation over time as a sparsifying transform. PWV values were calculated from flow curves by using foot-to-foot and cross-correlation methods. Our method was validated against ultrasound measurements in a flow phantom setup representing the carotid artery. Additionally, PWV values of two groups of 23 young (30 ± 3 years, 12 [52%] women) and 10 elderly (62 ± 10 years, 5 [50%] women) healthy subjects were compared using the Wilcoxon rank-sum test. RESULTS: Our proposed method produced very similar flow curves as those measured using ultrasound at 1 ms temporal resolution. Reliable PWV estimation proved possible for transit times down to 7.5 ms. Furthermore, significant differences in PWV values between healthy young and elderly subjects were found (4.7 ± 1.0 m/s and 7.9 ± 2.4 m/s, respectively; p < 0.001) in accordance with literature. CONCLUSIONS: Retrospectively gated 2D CINE PC CMR with CS allows for high spatiotemporal resolution flow measurements and accurate regional carotid artery PWV calculations. We foresee this technique will be valuable in protocols investigating early development of carotid atherosclerosis.

Mitral valve regurgitation assessed by intraventricular CMR 4D-flow: a systematic review on the technological aspects and potential clinical applications.

Cardiac magnetic resonance (CMR) four-dimensional (4D) flow is a novel method for flow quantification potentially helpful in management of mitral valve regurgitation (MVR). In this systematic review, we aimed to depict the clinical role of intraventricular 4D-flow in MVR. The reproducibility, technical aspects, and comparison against conventional techniques were evaluated. Published studies on SCOPUS, MEDLINE, and EMBASE were included using search terms on 4D-flow CMR in MVR. Out of 420 screened articles, 18 studies fulfilled our inclusion criteria. All studies (n = 18, 100%) assessed MVR using 4D-flow intraventricular annular inflow (4D-flowAIM) method, which calculates the regurgitation by subtracting the aortic forward flow from the mitral forward flow. Thereof, 4D-flow jet quantification (4D-flowjet) was assessed in 5 (28%), standard 2D phase-contrast (2D-PC) flow imaging in 8 (44%) and the volumetric method (the deviation of left ventricle stroke volume and right ventricular stroke volume) in 2 (11%) studies. Inter-method correlations among the 4 MVR quantification methods were heterogeneous across studies, ranging from moderate to excellent correlations. Two studies compared 4D-flowAIM to echocardiography with moderate correlation. In 12 (63%) studies the reproducibility of 4D-flow techniques in quantifying MVR was studied. Thereof, 9 (75%) studies investigated the reproducibility of the 4D-flowAIM method and the majority (n = 7, 78%) reported good to excellent intra- and inter-reader reproducibility. Intraventricular 4D-flowAIM provides high reproducibility with heterogeneous correlations to conventional quantification methods. Due to the absence of a gold standard and unknown accuracies, future longitudinal outcome studies are needed to assess the clinical value of 4D-flow in the clinical setting of MVR.

Synthesis of patient-specific multipoint 4D flow MRI data of turbulent aortic flow downstream of stenotic valves.

We propose to synthesize patient-specific 4D flow MRI datasets of turbulent flow paired with ground truth flow data to support training of inference methods. Turbulent blood flow is computed based on the Navier-Stokes equations with moving domains using realistic boundary conditions for aortic shapes, wall displacements and inlet velocities obtained from patient data. From the simulated flow, synthetic multipoint 4D flow MRI data is generated with user-defined spatiotemporal resolutions and reconstructed with a Bayesian approach to compute time-varying velocity and turbulence maps. For MRI data synthesis, a fixed hypothetical scan time budget is assumed and accordingly, changes to spatial resolution and time averaging result in corresponding scaling of signal-to-noise ratios (SNR). In this work, we focused on aortic stenotic flow and quantification of turbulent kinetic energy (TKE). Our results show that for spatial resolutions of 1.5 and 2.5 mm and time averaging of 5 ms as encountered in 4D flow MRI in practice, peak total turbulent kinetic energy downstream of a 50, 75 and 90% stenosis is overestimated by as much as 23, 15 and 14% (1.5 mm) and 38, 24 and 23% (2.5 mm), demonstrating the importance of paired ground truth and 4D flow MRI data for assessing accuracy and precision of turbulent flow inference using 4D flow MRI exams.

Advances in machine learning applications for cardiovascular 4D flow MRI.

Four-dimensional flow magnetic resonance imaging (MRI) has evolved as a non-invasive imaging technique to visualize and quantify blood flow in the heart and vessels. Hemodynamic parameters derived from 4D flow MRI, such as net flow and peak velocities, but also kinetic energy, turbulent kinetic energy, viscous energy loss, and wall shear stress have shown to be of diagnostic relevance for cardiovascular diseases. 4D flow MRI, however, has several limitations. Its long acquisition times and its limited spatio-temporal resolutions lead to inaccuracies in velocity measurements in small and low-flow vessels and near the vessel wall. Additionally, 4D flow MRI requires long post-processing times, since inaccuracies due to the measurement process need to be corrected for and parameter quantification requires 2D and 3D contour drawing. Several machine learning (ML) techniques have been proposed to overcome these limitations. Existing scan acceleration methods have been extended using ML for image reconstruction and ML based super-resolution methods have been used to assimilate high-resolution computational fluid dynamic simulations and 4D flow MRI, which leads to more realistic velocity results. ML efforts have also focused on the automation of other post-processing steps, by learning phase corrections and anti-aliasing. To automate contour drawing and 3D segmentation, networks such as the U-Net have been widely applied. This review summarizes the latest ML advances in 4D flow MRI with a focus on technical aspects and applications. It is divided into the current status of fast and accurate 4D flow MRI data generation, ML based post-processing tools for phase correction and vessel delineation and the statistical evaluation of blood flow.

Septaly Oriented Mild Aortic Regurgitant Jets Negatively Influence Left Ventricular Blood Flow-Insights From 4D Flow MRI Animal Study.

Objectives: Paravalvular leakage (PVL) and eccentric aortic regurgitation remain a major clinical concern in patients receiving transcatheter aortic valve replacement (TAVR), and regurgitant volume remains the main readout parameter in clinical assessment. In this work we investigate the effect of jet origin and trajectory of mild aortic regurgitation on left ventricular hemodynamics in a porcine model. Methods: A pig model of mild aortic regurgitation/PVL was established by transcatheter piercing and dilating the non-coronary (NCC) or right coronary cusp (RCC) of the aortic valve close to the valve annulus. The interaction between regurgitant blood and LV hemodynamics was assessed by 4D flow cardiovascular MRI. Results: Six RCC, six NCC, and two control animals were included in the study and with one dropout in the NCC group, the success rate of model creation was 93%. Regurgitant jets originating from NCC were directed along the ventricular side of the anterior mitral leaflet and integrated well into the diastolic vortex forming in the left ventricular outflow tract. However, jets from the RCC were orientated along the septum colliding with flow within the vortex, and progressing down to the apex. As a consequence, the presence as well as the area of the vortex was reduced at the site of impact compared to the NCC group. Impairment of vortex formation was localized to the area of impact and not the entire vortex ring. Blood from the NCC jet was largely ejected during the following systole, whereas ejection of large portion of RCC blood was protracted. Conclusions: Even for mild regurgitation, origin and trajectory of the regurgitant jet does cause a different effect on LV hemodynamics. Septaly oriented jets originating from RCC collide with the diastolic vortex, reduce its size, and reach the apical region of the left ventricle where blood resides extendedly. Hence, RCC jets display hemodynamic features which may have a potential negative impact on the long-term burden to the heart.

Coronary Flow Assessment Using Accelerated 4D Flow MRI With Respiratory Motion Correction.

Magnetic resonance imaging (MRI) can potentially be used for non-invasive screening of patients with stable angina pectoris to identify probable obstructive coronary artery disease. MRI-based coronary blood flow quantification has to date only been performed in a 2D fashion, limiting its clinical applicability. In this study, we propose a framework for coronary blood flow quantification using accelerated 4D flow MRI with respiratory motion correction and compressed sensing image reconstruction. We investigate its feasibility and repeatability in healthy subjects at rest. Fourteen healthy subjects received 8 times-accelerated 4D flow MRI covering the left coronary artery (LCA) with an isotropic spatial resolution of 1.0 mm3. Respiratory motion correction was performed based on 1) lung-liver navigator signal, 2) real-time monitoring of foot-head motion of the liver and LCA by a separate acquisition, and 3) rigid image registration to correct for anterior-posterior motion. Time-averaged diastolic LCA flow was determined, as well as time-averaged diastolic maximal velocity (VMAX) and diastolic peak velocity (VPEAK). 2D flow MRI scans of the LCA were acquired for reference. Scan-rescan repeatability and agreement between 4D flow MRI and 2D flow MRI were assessed in terms of concordance correlation coefficient (CCC) and coefficient of variation (CV). The protocol resulted in good visibility of the LCA in 11 out of 14 subjects (six female, five male, aged 28 ± 4 years). The other 3 subjects were excluded from analysis. Time-averaged diastolic LCA flow measured by 4D flow MRI was 1.30 ± 0.39 ml/s and demonstrated good scan-rescan repeatability (CCC/CV = 0.79/20.4%). Time-averaged diastolic VMAX (17.2 ± 3.0 cm/s) and diastolic VPEAK (24.4 ± 6.5 cm/s) demonstrated moderate repeatability (CCC/CV = 0.52/19.0% and 0.68/23.0%, respectively). 4D flow- and 2D flow-based diastolic LCA flow agreed well (CCC/CV = 0.75/20.1%). Agreement between 4D flow MRI and 2D flow MRI was moderate for both diastolic VMAX and VPEAK (CCC/CV = 0.68/20.3% and 0.53/27.0%, respectively). In conclusion, the proposed framework of accelerated 4D flow MRI equipped with respiratory motion correction and compressed sensing image reconstruction enables repeatable diastolic LCA flow quantification that agrees well with 2D flow MRI.

An isolated beating pig heart platform for a comprehensive evaluation of intracardiac blood flow with 4D flow MRI: a feasibility study.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) in large animals is cumbersome for various reasons, including ethical considerations, costs of housing and maintenance, and need for anaesthesia. Our primary purpose was to show the feasibility of an isolated beating pig heart model for four-dimensional (4D) flow MRI for investigating intracardiac blood flow patterns and flow parameters using slaughterhouse side products. In addition, the feasibility of evaluating transcatheter aortic valve replacement (TAVR) in the model was investigated. METHODS: Seven slaughterhouse pig hearts were installed in the MRI-compatible isolated beating pig heart platform. First, Langendorff perfusion mode was established; then, the system switched to working mode, in which blood was actively pumped by the left ventricle. A pacemaker ensured a stable HR during 3-T MRI scanning. All hearts were submitted to human physiological conditions of cardiac output and stayed vital for several hours. Aortic flow was measured from which stroke volume, cardiac output, and regurgitation fraction were calculated. RESULTS: 4D flow MRI acquisitions were successfully conducted in all hearts. Stroke volume was 31 ± 6 mL (mean ± standard deviation), cardiac output 3.3 ± 0.9 L/min, and regurgitation fraction 16% ± 9%. With 4D flow, intracardiac and coronary flow patterns could be visualised in all hearts. In addition, we could study valve function and regurgitation in two hearts after TAVR. CONCLUSIONS: The feasibility of 4D flow MRI in an isolated beating pig heart loaded to physiological conditions was demonstrated. The platform is promising for preclinical assessment of cardiac blood flow and function.