Assessment of transmitral and left atrial appendage flow rate from cardiac 4D-CT.

BACKGROUND: Cardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however. METHODS: To measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients. RESULTS: For the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml). There are larger differences in the diastolic peak flow rates, with a larger bias for the early flow rate than the late flow rate. The peak LAA outflow rate measured with both modalities matches well (bias: -6 ml/s). CONCLUSIONS: Overall, the developed algorithm provides accurate tracking of dynamic cardiac geometries resulting in similar flow rates at the MV and LAA compared to 4D flow MRI.

Assessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart.

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.

Characterization of anisotropic turbulence behavior in pulsatile blood flow.

Turbulent-like hemodynamics with prominent cycle-to-cycle flow variations have received increased attention as a potential stimulus for cardiovascular diseases. These turbulent conditions are typically evaluated in a statistical sense from single scalars extracted from ensemble-averaged tensors (such as the Reynolds stress tensor), limiting the amount of information that can be used for physical interpretations and quality assessments of numerical models. In this study, barycentric anisotropy invariant mapping was used to demonstrate an efficient and comprehensive approach to characterize turbulence-related tensor fields in patient-specific cardiovascular flows, obtained from scale-resolving large eddy simulations. These techniques were also used to analyze some common modeling compromises as well as MRI turbulence measurements through an idealized constriction. The proposed method found explicit sites of elevated turbulence anisotropy, including a broad but time-varying spectrum of characteristics over the flow deceleration phase, which was different for both the steady inflow and Reynolds-averaged Navier-Stokes modeling assumptions. Qualitatively, the MRI results showed overall expected post-stenotic turbulence characteristics, however, also with apparent regions of unrealizable or conceivably physically unrealistic conditions, including the highest turbulence intensity ranges. These findings suggest that more detailed studies of MRI-measured turbulence fields are needed, which hopefully can be assisted by more comprehensive evaluation tools such as the once described herein.

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.

Characterization and estimation of turbulence-related wall shear stress in patient-specific pulsatile blood flow.

Disturbed, turbulent-like blood flow promotes chaotic wall shear stress (WSS) environments, impairing essential endothelial functions and increasing the susceptibility and progression of vascular diseases. These flow characteristics are today frequently detected at various anatomical, lesion and intervention-related sites, while their role as a pathological determinant is less understood. To present-day, numerous WSS-based descriptors have been proposed to characterize the spatiotemporal nature of the WSS disturbances, however, without differentiation between physiological laminar oscillations and turbulence-related WSS (tWSS) fluctuations. Also, much attention has been focused on magnetic resonance (MR) WSS estimations, so far with limited success; promoting the need of a near-wall surrogate marker. In this study, a new approach is explored to characterize the tWSS, by taking advantage of the tensor characteristics of the fluctuating WSS correlations, providing both a magnitude and an anisotropy measure of the disturbances. These parameters were studied in two patient-specific coarctation models (sever and mild), using large eddy simulations, and correlated against near-wall reciprocal Reynolds stress parameters. Collectively, results showed distinct regions of differing tWSS characteristics, features which were sensitive to changes in flow conditions. Generally, the post-stenotic tWSS was governed by near axisymmetric fluctuations, findings that where not consistent with conventional WSS disturbance predictors. At the 2-3 mm wall-offset range, a strong linear correlation was found between tWSS magnitude and near-wall turbulence kinetic energy (TKE), in contrast to the anisotropy indices, suggesting that MR-measured TKE can be used to assess elevated tWSS regions while tWSS anisotropy estimates request well-resolved simulation methods.

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.

Non-invasive Assessment of Systolic and Diastolic Cardiac Function During Rest and Stress Conditions Using an Integrated Image-Modeling Approach.

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 ± 0.3 to 2 ± 0.5 (p = 0.038)] and relaxation constant [from 37.2 ± 6.9 to 46.1 ± 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 ± 0.04 s to 0.3 ± 0.03 s (p = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics of pathophysiology that are otherwise difficult to obtain non-invasively in clinical practice.

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).

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.

Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models.

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

Quantitative Assessment of Turbulence and Flow Eccentricity in an Aortic Coarctation: Impact of Virtual Interventions.

Turbulence and flow eccentricity can be measured by magnetic resonance imaging (MRI) and may play an important role in the pathogenesis of numerous cardiovascular diseases. In the present study, we propose quantitative techniques to assess turbulent kinetic energy (TKE) and flow eccentricity that could assist in the evaluation and treatment of stenotic severities. These hemodynamic parameters were studied in a pre-treated aortic coarctation (CoA) and after several virtual interventions using computational fluid dynamics (CFD), to demonstrate the effect of different dilatation options on the flow field. Patient-specific geometry and flow conditions were derived from MRI data. The unsteady pulsatile flow was resolved by large eddy simulation including non-Newtonian blood rheology. Results showed an inverse asymptotic relationship between the total amount of TKE and degree of dilatation of the stenosis, where turbulent flow proximal the constriction limits the possible improvement by treating the CoA alone. Spatiotemporal maps of TKE and flow eccentricity could be linked to the characteristics of the jet, where improved flow conditions were favored by an eccentric dilatation of the CoA. By including these flow markers into a combined MRI-CFD intervention framework, CoA therapy has not only the possibility to produce predictions via simulation, but can also be validated pre- and immediate post treatment, as well as during follow-up studies.