Haemodynamic significance of extrinsic outflow graft stenoses during HeartMate 3™ therapy.

Aims: The HeartMate 3 (HM3) implantable left ventricular assist device connects the left ventricle apex to the aorta via an outflow graft. Extrinsic obstruction of the graft (eOGO) is associated with serious morbidity and mortality and recently led to a Food and Drug Administration Class 1 device recall of HM3. This study aimed to provide a better understanding of the haemodynamic impact of extrinsic stenoses. Methods and results: Computed tomography (CT) images of two retrospectively identified patients with eOGO (29 and 36% decrease in cross-sectional area, respectively, by radiological evaluation) were acquired with a novel photon-counting CT system. Numerical evaluations of haemodynamics were conducted using a high-fidelity 3D computational fluid dynamics approach on both the patient-specific graft geometries and in two virtually augmented stenotic severities and three device flows. Visual analysis identified increased velocity, pressure, and turbulent flow in the outer anterior curvature of the outflow graft; however, changes in graft pressure gradients were slight (1-9 mmHg) across the range of stenosis severities and flow rates tested. Conclusion: Evidence of eOGO during HM3 support and the recent device recall can provoke clinical apprehension and interventions. The haemodynamic impact of a stenosis detected visually or by quantification of cross-sectional area reduction may be difficult to predict and easily overestimated. This numerical study suggests that, for clinically encountered flow rates and stenosis severities below 61% in cross-sectional area decrease, eOGO may have low haemodynamic impact. This suggests that patients without symptoms or signs consistent with haemodynamically significant obstruction might be managed expectantly.

Comprehensive left atrial flow component analysis reveals abnormal flow patterns in paroxysmal atrial fibrillation.

Left atrial (LA) blood flow plays an important role in diseases such as atrial fibrillation (AF) and atrial cardiomyopathy since alterations in the blood flow might lead to thrombus formation and stroke. Using traditional techniques, such as echocardiography, atrial flow velocities can be measured at the pulmonary veins and the mitral valve, but a comprehensive understanding of the three-dimensional atrial flow field is missing. Previously, ventricular flow has been analyzed using flow component analysis, revealing new insights into ventricular flow and function. Thus, the aim of this project was to develop a comprehensive flow component analysis method for the LA and explore its utility in 21 patients with paroxysmal atrial fibrillation compared with a control group of 8 participants. The flow field was derived from time-resolved CT acquired during sinus rhythm using computational fluid dynamics. Flow components were computed from particle tracking. We identified six atrial flow components: conduit, reservoir, delayed ejection, retained inflow, residual volume, and pulmonary vein backflow. It was shown that conduit flow, defined as blood entering and leaving the LA within the same diastolic phase, exists in most subjects. Although the volume of conduit and reservoir is similar in patients with paroxysmal AF in sinus rhythm and controls, the volume of the other components is increased in paroxysmal AF. Comprehensive quantification of LA flow using flow component analysis makes atrial blood flow quantifiable, thus facilitating investigation of mechanisms underlying atrial dysfunction and can increase understanding of atrial blood flow in disease progression and stroke risk.NEW & NOTEWORTHY We developed a new comprehensive approach to atrial blood component analysis that includes both conduit flow and residual volume and compared the flow components of atrial fibrillation (AF) patients in sinus rhythm with controls. Conduit and reservoir flow were similar between the groups, whereas components with longer residence time in the left atrium were increased in the AF group. This could add to the pathophysiological understanding of atrial diseases and possibly clinical management.

Corrigendum: Elevated atrial blood stasis in paroxysmal atrial fibrillation during sinus rhythm: a patient-specific computational fluid dynamics study.

[This corrects the article DOI: 10.3389/fcvm.2023.1219021.].

Elevated atrial blood stasis in paroxysmal atrial fibrillation during sinus rhythm: a patient-specific computational fluid dynamics study.

Introduction: Atrial fibrillation (AF) is associated with an increased risk of stroke, often caused by thrombi that form in the left atrium (LA), and especially in the left atrial appendage (LAA). The underlying mechanism is not fully understood but is thought to be related to stagnant blood flow, which might be present despite sinus rhythm. However, measuring blood flow and stasis in the LAA is challenging due to its small size and low velocities. We aimed to compare the blood flow and stasis in the left atrium of paroxysmal AF patients with controls using computational fluid dynamics (CFD) simulations. Methods: The CFD simulations were based on time-resolved computed tomography including the patient-specific cardiac motion. The pipeline allowed for analysis of 21 patients with paroxysmal AF and 8 controls. Stasis was estimated by computing the blood residence time. Results and Discussion: Residence time was elevated in the AF group (p < 0.001). Linear regression analysis revealed that stasis was strongest associated with LA ejection ratio (p < 0.001, R2 = 0.68) and the ratio of LA volume and left ventricular stroke volume (p < 0.001, R2 = 0.81). Stroke risk due to LA thrombi could already be elevated in AF patients during sinus rhythm. In the future, patient specific CFD simulations may add to the assessment of this risk and support diagnosis and treatment.

Enhancing students' understanding of cardiac physiology by using 4D visualization.

Difficulties in achieving knowledge about physiology and anatomy of the beating heart highlight the challenges with more traditional pedagogical methods. Recent research regarding anatomy education has mainly focused on digital three-dimensional models. However, these pedagogical improvements may not be entirely applicable to cardiac anatomy and physiology due to the multidimensional complexity with moving anatomy and complex blood flow. The aim of this study was therefore to evaluate whether high quality time-resolved anatomical images combined with realistic blood flow simulations improve the understanding of cardiac structures and function. Three time-resolved datasets were acquired using time-resolved computed tomography and blood flow was computed using Computational Fluid Dynamics. The anatomical and blood flow information was combined and interactively visualized using volume rendering on an advanced stereo projection system. The setup was tested in interactive lectures for medical students. Ninety-seven students participated. Summative assessment of examinations showed significantly improved mean score (18.1 ± 4.5 vs 20.3 ± 4.9, p = 0.002). This improvement was driven by knowledge regarding myocardial hypertrophy and pressure-velocity differences over a stenotic valve. Additionally, a supplementary formative assessment showed significantly more agreeing answers than disagreeing answers (p < 0.001) when the participants subjectively evaluated the contribution of the visualizations to their education and knowledge. In conclusion, the use of simultaneous visualization of time-resolved anatomy data and simulated blood flow improved medical students' results, with a particular effect on understanding of cardiac physiology and these simulations may be useful educational tools for teaching complex anatomical and physiological concepts.

Cardiac Kinetic Energy and Viscous Dissipation Rate From Radial Flow Data.

Recent studies have correlated kinetic energy (KE) and viscous dissipation rate (VDR) in the left ventricle (LV) with heart health. These studies have relied on 4D-flow imaging or computational fluid dynamics modeling, which are able to measure, or compute, all 3 components (3C) of the blood flow velocity in 3 dimensional (3D) space. This richness of data is difficult to acquire clinically. Alternatively, color Doppler echocardiography (CDE) is more widespread clinically, but only measures a single radial component of velocity and typically only over a planar section. Because of this limitation, prior CDE-based studies have first reconstructed a second component of velocity in the measurement plane prior to evaluating VDR or KE. Herein, we propose 1C-based surrogates of KE and VDR that can be derived directly from the radial component of the flow velocity in the LV. Our results demonstrate that the proposed 1C-based surrogates of KE and VDR are generally as well-correlated with the true KE and VDR values as surrogates that use reconstructed 2C flow data. Moreover, the correlation of these 1C-based surrogates with the true values indicate that CDE (3D in particular) may be useful in evaluating these metrics in practice.

Impact of prosthetic mitral valve orientation on the ventricular flow field: Comparison using patient-specific computational fluid dynamics.

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in long- and short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning.

Publisher Correction: Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI.

PURPOSE: To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI. METHODS: Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization. RESULTS: VRT (R2 = 0.69) was more sensitive to noise than MVA (R2 = 0.98) and TDA (R2 = 0.99) at typical non-contrast signal-to-noise ratio levels (SNR = 20). VRT (R2 = 0.14) was more sensitive to background phase-offsets than MVA (R2 = 0.99) and TDA (R2 = 0.96) when considering a 95% effective background phase-offset correction. Qualitatively, TDA outperformed MVA (Wilcoxon p < 0.005, mean score improvement 1.6/5), and had good agreement (median score 4/5) with flow visualizations. CONCLUSION: Flow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.

Impact of Pulmonary Venous Inflow on Cardiac Flow Simulations: Comparison with In Vivo 4D Flow MRI.

Blood flow simulations are making their way into the clinic, and much attention is given to estimation of fractional flow reserve in coronary arteries. Intracardiac blood flow simulations also show promising results, and here the flow field is expected to depend on the pulmonary venous (PV) flow rates. In the absence of in vivo measurements, the distribution of the flow from the individual PVs is often unknown and typically assumed. Here, we performed intracardiac blood flow simulations based on time-resolved computed tomography on three patients, and investigated the effect of the distribution of PV flow rate on the flow field in the left atrium and ventricle. A design-of-experiment approach was used, where PV flow rates were varied in a systematic manner. In total 20 different simulations were performed per patient, and compared to in vivo 4D flow MRI measurements. Results were quantified by kinetic energy, mitral valve velocity profiles and root-mean-square errors of velocity. While large differences in atrial flow were found for varying PV inflow distributions, the effect on ventricular flow was negligible, due to a regularizing effect by mitral valve. Equal flow rate through all PVs most closely resembled in vivo measurements and is recommended in the absence of a priori knowledge.

Intracardiac Flow at 4D CT: Comparison with 4D Flow MRI.

Purpose To investigate four-dimensional (4D) flow CT for the assessment of intracardiac blood flow patterns as compared with 4D flow MRI. Materials and Methods This prospective study acquired coronary CT angiography and 4D flow MRI data between February and December 2016 in a cohort of 12 participants (age range, 36-74 years; mean age, 57 years; seven men [age range, 36-74 years; mean age, 57 years] and five women [age range, 52-73 years; mean age, 64 years]). Flow simulations based solely on CT-derived cardiac anatomy were assessed together with 4D flow MRI measurements. Flow patterns, flow rates, stroke volume, kinetic energy, and flow components were quantified for both techniques and were compared by using linear regression. Results Cardiac flow patterns obtained by using 4D flow CT were qualitatively similar to 4D flow MRI measurements, as graded by three independent observers. The Cohen κ score was used to assess intraobserver variability (0.83, 0.79, and 0.70) and a paired Wilcoxon rank-sum test showed no significant change (P > .05) between gradings. Peak flow rate and stroke volumes between 4D flow MRI measurements and 4D flow CT measurements had high correlation (r = 0.98 and r = 0.81, respectively; P < .05 for both). Integrated kinetic energy quantified at peak systole correlated well (r = 0.95, P < .05), while kinetic energy levels at early and late filling showed no correlation. Flow component analysis showed high correlation for the direct and residual components, respectively (r = 0.93, P < .05 and r = 0.87, P < .05), while the retained and delayed components showed no correlation. Conclusion Four-dimensional flow CT produced qualitatively and quantitatively similar intracardiac blood flow patterns compared with the current reference standard, four-dimensional flow MRI. © RSNA, 2018 Online supplemental material is available for this article.

Automated three-dimensional tracking of the left ventricular myocardium in time-resolved and dose-modulated cardiac CT images using deformable image registration.

BACKGROUND: Assessment of myocardial deformation from time-resolved cardiac computed tomography (4D CT) would augment the already available functional information from such an examination without incurring any additional costs. A deformable image registration (DIR) based approach is proposed to allow fast and automatic myocardial tracking in clinical 4D CT images. METHODS: Left ventricular myocardial tissue displacement through a cardiac cycle was tracked using a B-spline transformation based DIR. Gradient of such displacements allowed Lagrangian strain estimation with respect to end-diastole in clinical 4D CT data from ten subjects with suspected coronary artery disease. Dice similarity coefficient (DSC), point-to-curve error (PTC), and tracking error were used to assess the tracking accuracy. Wilcoxon signed rank test provided significance of tracking errors. Topology preservation was verified using Jacobian of the deformation. Reliability of estimated strains and torsion (normalized twist angle) was tested in subjects with normal function by comparing them with normal strain in the literature. RESULTS: Comparison with manual tracking showed high accuracy (DSC: 0.99±0.05; PTC: 0.56mm±0.47 mm) and resulted in determinant(Jacobian)>0 for all subjects, indicating preservation of topology. Average radial (0.13 mm), angular (0.64) and longitudinal (0.10 mm) tracking errors for the entire cohort were not significant (p > 0.9). For patients with normal function, average strain [circumferential, radial, longitudinal] and peak torsion estimates were: [-23.5%, 31.1%, -17.2%] and 7.22°, respectively. These estimates were in conformity with the reported normal ranges in the existing literature. CONCLUSIONS: Accurate wall deformation tracking and subsequent strain estimation are feasible with the proposed method using only routine time-resolved 3D cardiac CT.

Assessment of Reynolds stress components and turbulent pressure loss using 4D flow MRI with extended motion encoding.

PURPOSE: To measure the Reynolds stress tensor using 4D flow MRI, and to evaluate its contribution to computed pressure maps. METHODS: A method to assess both velocity and Reynolds stress using 4D flow MRI is presented and evaluated. The Reynolds stress is compared by cross-sectional integrals of the Reynolds stress invariants. Pressure maps are computed using the pressure Poisson equation-both including and neglecting the Reynolds stress. RESULT: Good agreement is seen for Reynolds stress between computational fluid dynamics, simulated MRI, and MRI experiment. The Reynolds stress can significantly influence the computed pressure loss for simulated (eg, -0.52% vs -15.34% error; P < 0.001) and experimental (eg, 306 ± 11 vs 203 ± 6 Pa; P < 0.001) data. A 54% greater pressure loss is seen at the highest experimental flow rate when accounting for Reynolds stress (P < 0.001). CONCLUSION: 4D flow MRI with extended motion-encoding enables quantification of both the velocity and the Reynolds stress tensor. The additional information provided by this method improves the assessment of pressure gradients across a stenosis in the presence of turbulence. Unlike conventional methods, which are only valid if the flow is laminar, the proposed method is valid for both laminar and disturbed flow, a common presentation in diseased vessels. Magn Reson Med 79:1962-1971, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.

Estimating the irreversible pressure drop across a stenosis by quantifying turbulence production using 4D Flow MRI.

The pressure drop across a stenotic vessel is an important parameter in medicine, providing a commonly used and intuitive metric for evaluating the severity of the stenosis. However, non-invasive estimation of the pressure drop under pathological conditions has remained difficult. This study demonstrates a novel method to quantify the irreversible pressure drop across a stenosis using 4D Flow MRI by calculating the total turbulence production of the flow. Simulation MRI acquisitions showed that the energy lost to turbulence production can be accurately quantified with 4D Flow MRI within a range of practical spatial resolutions (1-3 mm; regression slope = 0.91, R2 = 0.96). The quantification of the turbulence production was not substantially influenced by the signal-to-noise ratio (SNR), resulting in less than 2% mean bias at SNR > 10. Pressure drop estimation based on turbulence production robustly predicted the irreversible pressure drop, regardless of the stenosis severity and post-stenosis dilatation (regression slope = 0.956, R2 = 0.96). In vitro validation of the technique in a 75% stenosis channel confirmed that pressure drop prediction based on the turbulence production agreed with the measured pressure drop (regression slope = 1.15, R2 = 0.999, Bland-Altman agreement = 0.75 ± 3.93 mmHg).

Assessment of turbulent flow effects on the vessel wall using four-dimensional flow MRI.

PURPOSE: To explore the use of MR-estimated turbulence quantities for the assessment of turbulent flow effects on the vessel wall. METHODS: Numerical velocity data for two patient-derived models was obtained using computational fluid dynamics (CFD) for two physiological flow rates. The four-dimensional (4D) Flow MRI measurements were simulated at three different spatial resolutions and used to investigate the estimation of turbulent wall shear stress (tWSS) using the intravoxel standard deviation (IVSD) of velocity and turbulent kinetic energy (TKE) estimated near the vessel wall. RESULTS: Accurate estimation of tWSS using the IVSD is limited by the spatial resolution achievable with 4D Flow MRI. TKE, estimated near the wall, has a strong linear relationship to the tWSS (mean R2 = 0.84). Near-wall TKE estimates from MR simulations have good agreement to CFD-derived ground truth (mean R2 = 0.90). Maps of near-wall TKE have strong visual correspondence to tWSS. CONCLUSION: Near-wall estimation of TKE permits assessment of relative maps of tWSS, but direct estimation of tWSS is challenging due to limitations in spatial resolution. Assessment of tWSS and near-wall TKE may open new avenues for analysis of different pathologies. Magn Reson Med 77:2310-2319, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Multidirectional WSS disturbances in stenotic turbulent flows: A pre- and post-intervention study in an aortic coarctation.

Wall shear stress (WSS) disturbances are commonly expressed at sites of abnormal flow obstructions and may play an essential role in the pathogenesis of various vascular diseases. In laminar flows these disturbances have recently been assessed by the transverse wall shear stress (transWSS), which accounts for the WSS multidirectionality. Site-specific estimations of WSS disturbances in pulsatile transitional and turbulent type of flows are more challenging due to continuous and unpredictable changes in WSS behavior. In these complex flow settings, the transWSS may serve as a more comprehensive descriptor for assessing WSS disturbances of general nature compared to commonly used parameters. In this study large eddy simulations (LES) were used to investigate the transWSS properties in flows subjected to different pathological turbulent flow conditions, governed by a patient-specific model of an aortic coarctation pre and post balloon angioplasty. Results showed that regions of strong near-wall turbulence were collocated with regions of elevated transWSS and turbulent WSS, while in more transitional-like near-wall flow regions a closer resemblance was found between transWSS and low, and oscillatory WSS. Within the frame of this study, the transWSS parameter demonstrated a more multi-featured picture of WSS disturbances when exposed to different types of flow regimes, characteristics which were not depicted by the other parameters alone.

Assessment of turbulent viscous stress using ICOSA 4D Flow MRI for prediction of hemodynamic blood damage.

Flow-induced blood damage plays an important role in determining the hemodynamic impact of abnormal blood flow, but quantifying of these effects, which are dominated by shear stresses in highly fluctuating turbulent flow, has not been feasible. This study evaluated the novel application of turbulence tensor measurements using simulated 4D Flow MRI data with six-directional velocity encoding for assessing hemodynamic stresses and corresponding blood damage index (BDI) in stenotic turbulent blood flow. The results showed that 4D Flow MRI underestimates the maximum principal shear stress of laminar viscous stress (PLVS), and overestimates the maximum principal shear stress of Reynolds stress (PRSS) with increasing voxel size. PLVS and PRSS were also overestimated by about 1.2 and 4.6 times at medium signal to noise ratio (SNR) = 20. In contrast, the square sum of the turbulent viscous shear stress (TVSS), which is used for blood damage index (BDI) estimation, was not severely affected by SNR and voxel size. The square sum of TVSS and the BDI at SNR >20 were underestimated by less than 1% and 10%, respectively. In conclusion, this study demonstrated the feasibility of 4D Flow MRI based quantification of TVSS and BDI which are closely linked to blood damage.

Patient-Specific Simulation of Cardiac Blood Flow From High-Resolution Computed Tomography.

Cardiac hemodynamics can be computed from medical imaging data, and results could potentially aid in cardiac diagnosis and treatment optimization. However, simulations are often based on simplified geometries, ignoring features such as papillary muscles and trabeculae due to their complex shape, limitations in image acquisitions, and challenges in computational modeling. This severely hampers the use of computational fluid dynamics in clinical practice. The overall aim of this study was to develop a novel numerical framework that incorporated these geometrical features. The model included the left atrium, ventricle, ascending aorta, and heart valves. The framework used image registration to obtain patient-specific wall motion, automatic remeshing to handle topological changes due to the complex trabeculae motion, and a fast interpolation routine to obtain intermediate meshes during the simulations. Velocity fields and residence time were evaluated, and they indicated that papillary muscles and trabeculae strongly interacted with the blood, which could not be observed in a simplified model. The framework resulted in a model with outstanding geometrical detail, demonstrating the feasibility as well as the importance of a framework that is capable of simulating blood flow in physiologically realistic hearts.

Quantification of turbulence and velocity in stenotic flow using spiral three-dimensional phase-contrast MRI.

PURPOSE: Evaluate spiral three-dimensional (3D) phase contrast MRI for the assessment of turbulence and velocity in stenotic flow. METHODS: A-stack-of-spirals 3D phase contrast MRI sequence was evaluated in vitro against a conventional Cartesian sequence. Measurements were made in a flow phantom with a 75% stenosis. Both spiral and Cartesian imaging were performed using different scan orientations and flow rates. Volume flow rate, maximum velocity and turbulent kinetic energy (TKE) were computed for both methods. Moreover, the estimated TKE was compared with computational fluid dynamics (CFD) data. RESULTS: There was good agreement between the turbulent kinetic energy from the spiral, Cartesian and CFD data. Flow rate and maximum velocity from the spiral data agreed well with Cartesian data. As expected, the short echo time of the spiral sequence resulted in less prominent displacement artifacts compared with the Cartesian sequence. However, both spiral and Cartesian flow rate estimates were sensitive to displacement when the flow was oblique to the encoding directions. CONCLUSION: Spiral 3D phase contrast MRI appears favorable for the assessment of stenotic flow. The spiral sequence was more than three times faster and less sensitive to displacement artifacts when compared with a conventional Cartesian sequence.