A comparison of phase unwrapping methods in velocity-encoded MRI for aortic flows.

PURPOSE: The phase of a MRI signal is used to encode the velocity of blood flow. Phase unwrapping artifacts may appear when aiming to improve the velocity-to-noise ratio (VNR) of the measured velocity field. This study aims to compare various unwrapping algorithms on ground-truth synthetic data generated using computational fluid dynamics (CFD) simulations. METHODS: We compare four different phase unwrapping algorithms on two different synthetic datasets of four-dimensional flow MRI and 26 datasets of 2D PC-MRI acquisitions including the ascending and descending aorta. The synthetic datasets are constructed using CFD simulations of an aorta with a coarctation, with different levels of spatiotemporal resolutions and noise. The error of the unwrapped images was assessed by comparison against the ground truth velocity field in the synthetic data and dual-VENC reconstructions in the in vivo data. RESULTS: Using the unwrapping algorithms, we were able to remove aliased voxels in the data almost entirely, reducing the L2-error compared to the ground truth by 50%-80%. Results indicated that the best choice of algorithm depend on the spatiotemporal resolution and noise level of the dataset. Temporal unwrapping is most successful with a high temporal and low spatial resolution ( δ t = 30 $$ \delta t=30 $$ ms, h = 2 . 5 $$ h=2.5 $$ mm), reducing the L2-error by 70%-85%, while Laplacian unwrapping performs better with a lower temporal or better spatial resolution ( δ t = 60 $$ \delta t=60 $$ ms, h = 1 . 5 $$ h=1.5 $$ mm), especially for signal-to-noise ratio (SNR) 12 as opposed to SNR 15, with an error reduction of 55%-85% compared to the 50%-75% achieved by the Temporal method. The differences in performance between the methods are statistically significant. CONCLUSIONS: The temporal method and spatiotemporal Laplacian method provide the best results, with the spatiotemporal Laplacian being more robust. However, single- V enc $$ {V}_{\mathrm{enc}} $$ methods only situationally and not generally reach the performance of dual- V enc $$ {V}_{\mathrm{enc}} $$ unwrapping methods.

Comparison of Improved Unidirectional Dual Velocity-Encoding MRI Methods.

BACKGROUND: In phase-contrast (PC) MRI, several dual velocity encoding methods have been proposed to robustly increase velocity-to-noise ratio (VNR), including a standard dual-VENC (SDV), an optimal dual-VENC (ODV), and bi- and triconditional methods. PURPOSE: To develop a correction method for the ODV approach and to perform a comparison between methods. STUDY TYPE: Case-control study. POPULATION: Twenty-six volunteers. FIELD STRENGTH/SEQUENCE: 1.5 T phase-contrast MRI with VENCs of 50, 75, and 150 cm/second. ASSESSMENT: Since we acquired single-VENC protocols, we used the background phase from high-VENC (VENCH ) to reconstruct the low-VENC (VENCL ) phase. We implemented and compared the unwrapping methods for different noise levels and also developed a correction of the ODV method. STATISTICAL TESTS: Shapiro-Wilk's normality test, two-way analysis of variance with homogeneity of variances was performed using Levene's test, and the significance level was adjusted by Tukey's multiple post hoc analysis with Bonferroni (P < 0.05). RESULTS: Statistical analysis revealed no extreme outliers, normally distributed residuals, and homogeneous variances. We found statistically significant interaction between noise levels and the unwrapping methods. This implies that the number of non-unwrapped pixels increased with the noise level. We found that for ß = VENCL /VENCH  = 1/2, unwrapping methods were more robust to noise. The post hoc test showed a significant difference between the ODV corrected and the other methods, offering the best results regarding the number of unwrapped pixels. DATA CONCLUSIONS: All methods performed similarly without noise, but the ODV corrected method was more robust to noise at the price of a higher computational time. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

A parametric geometry model of the aortic valve for subject-specific blood flow simulations using a resistive approach.

Cardiac valves simulation is one of the most complex tasks in cardiovascular modeling. Fluid-structure interaction is not only highly computationally demanding but also requires knowledge of the mechanical properties of the tissue. Therefore, an alternative is to include valves as resistive flow obstacles, prescribing the geometry (and its possible changes) in a simple way, but, at the same time, with a geometry complex enough to reproduce both healthy and pathological configurations. In this work, we present a generalized parametric model of the aortic valve to obtain patient-specific geometries that can be included into blood flow simulations using a resistive immersed implicit surface (RIIS) approach. Numerical tests are presented for geometry generation and flow simulations in aortic stenosis patients whose parameters are extracted from ECG-gated CT images.

Inverse problems in blood flow modeling: A review.

Mathematical and computational modeling of the cardiovascular system is increasingly providing non-invasive alternatives to traditional invasive clinical procedures. Moreover, it has the potential for generating additional diagnostic markers. In blood flow computations, the personalization of spatially distributed (i.e., 3D) models is a key step which relies on the formulation and numerical solution of inverse problems using clinical data, typically medical images for measuring both anatomy and function of the vasculature. In the last years, the development and application of inverse methods has rapidly expanded most likely due to the increased availability of data in clinical centers and the growing interest of modelers and clinicians in collaborating. Therefore, this work aims to provide a wide and comparative overview of literature within the last decade. We review the current state of the art of inverse problems in blood flows, focusing on studies considering fully dimensional fluid and fluid-solid models. The relevant physical models and hemodynamic measurement techniques are introduced, followed by a survey of mathematical data assimilation approaches used to solve different kinds of inverse problems, namely state and parameter estimation. An exhaustive discussion of the literature of the last decade is presented, structured by types of problems, models and available data.

Assessment of 4D flow MRI's quality by verifying its Navier-Stokes compatibility.

4D Flow Magnetic Resonance Imaging (MRI) is the state-of-the-art technique to comprehensively measure the complex spatio-temporal and multidirectional patterns of blood flow. However, it is subject to artifacts such as noise and aliasing, which due to the 3D and dynamic structure is difficult to detect in clinical practice. In this work, a new mathematical and computational model to determine the quality of 4D Flow MRI is presented. The model is derived by assuming the true velocity satisfies the incompressible Navier-Stokes equations and that can be decomposed by the measurements u→meas plus an extra field w→ . Therefore, a non-linear problem with w→ as unknown arises, which serves as a measure of data quality. A stabilized finite element formulation tailored to this problem is proposed and analyzed. Then, extensive numerical examples-using synthetic 4D Flow MRI data as well as real measurements on experimental phantom and subjects-illustrate the ability to use w→ for assessing the quality of 4D Flow MRI measurements over space and time.

Multiple motion encoding in phase-contrast MRI: A general theory and application to elastography imaging.

While MRI allows to encode the motion of tissue in the magnetization's phase, it remains yet a challenge to obtain high fidelity motion images due to wraps in the phase for high encoding efficiencies. Therefore, we propose an optimal multiple motion encoding method (OMME) and exemplify it in Magnetic Resonance Elastography (MRE) data. OMME is formulated as a non-convex least-squares problem for the motion using an arbitrary number of phase-contrast measurements with different motion encoding gradients (MEGs). The mathematical properties of OMME are proved in terms of standard deviation and dynamic range of the motion's estimate for arbitrary MEGs combination which are confirmed using synthetically generated data. OMME's performance is assessed on MRE data from in vivo human brain experiments and compared to dual encoding strategies. The unwrapped images are further used to reconstruct stiffness maps and compared to the ones obtained using conventional unwrapping methods. OMME allowed to successfully combine several MRE phase images with different MEGs, outperforming dual encoding strategies in either motion-to-noise ratio (MNR) or number of successfully reconstructed voxels with good noise stability. This lead to stiffness maps with greater resolution of details than obtained with conventional unwrapping methods. The proposed OMME method allows for a flexible and noise robust increase in the dynamic range and thus provides wrap-free phase images with high MNR. In MRE, the method may be especially suitable when high resolution images with high MNR are needed.

Validation of 4D Flow based relative pressure maps in aortic flows.

While the clinical gold standard for pressure difference measurements is invasive catheterization, 4D Flow MRI is a promising tool for enabling a non-invasive quantification, by linking highly spatially resolved velocity measurements with pressure differences via the incompressible Navier-Stokes equations. In this work we provide a validation and comparison with phantom and clinical patient data of pressure difference maps estimators. We compare the classical Pressure Poisson Estimator (PPE) and the new Stokes Estimator (STE) against catheter pressure measurements under a variety of stenosis severities and flow intensities. Specifically, we use several 4D Flow data sets of realistic aortic phantoms with different anatomic and hemodynamic severities and two patients with aortic coarctation. The phantom data sets are enriched by subsampling to lower resolutions, modification of the segmentation and addition of synthetic noise, in order to study the sensitivity of the pressure difference estimators to these factors. Overall, the STE method yields more accurate results than the PPE method compared to catheterization data. The superiority of the STE becomes more evident at increasing Reynolds numbers with a better capacity of capturing pressure gradients in strongly convective flow regimes. The results indicate an improved robustness of the STE method with respect to variation in lumen segmentation. However, with heuristic removal of the wall-voxels, the PPE can reach a comparable accuracy for lower Reynolds' numbers.

Reducing the impact of geometric errors in flow computations using velocity measurements.

Numerical blood flow simulations are typically set up from anatomical medical images and calibrated using velocity measurements. However, the accuracy of the computational geometry itself is limited by the resolution of the anatomical image. We first show that applying standard no-slip boundary conditions on inaccurately extracted boundaries can cause large errors in the results, in particular the pressure gradient. In this work, we therefore propose to augment the flow model calibration by slip/transpiration boundary conditions, whose parameters are then estimated using velocity measurements. Numerical experiments show that this methodology can considerably improve the accuracy of the estimated pressure gradients and 3D velocity fields when the vessel geometry is uncertain.

Optimal Dual-VENC Unwrapping in Phase-Contrast MRI.

Dual-VENC strategies have been proposed to improve the velocity-to-noise ratio in phase-contrast MRI. However, they are based on aliasing-free high-VENC data. The aim of this paper is to propose a dual-VENC velocity estimation method allowing high-VENC aliased data. For this purpose, we reformulate the phase-contrast velocity as a least squares estimator, providing a natural framework for including multiple encoding gradient measurements. By analyzing the mathematical properties of both single- and dual-VENC problems, we can justify theoretically high/low-VENC ratios such that the aliasing velocity can be minimized. The resulting reconstruction algorithm was assessed using three types of data: numerical, experimental, and volunteers. In clinical practice, this method would allow shorter examination times by avoiding tedious adaptation of VENC values by repeated scans.

Automatic mapping of atrial fiber orientations for patient-specific modeling of cardiac electromechanics using image registration.

Knowledge of appropriate local fiber architecture is necessary to simulate patient-specific electromechanics in the human heart. However, it is not yet possible to reliably measure in vivo fiber directions especially in human atria. Thus, we present a method that defines the fiber architecture in arbitrarily shaped atria using image registration and reorientation methods based on atlas atria with fibers predefined from detailed histological observations. Thereby, it is possible to generate detailed fiber families in every new patient-specific geometry in an automated, time-efficient process. We demonstrate the good performance of the image registration and fiber definition on 10 differently shaped human atria. Additionally, we show that characteristics of the electrophysiological activation pattern that appear in the atlas atria also appear in the patients' atria. We arrive to analogous conclusions for coupled electro-mechano-hemodynamical computations.

The importance of the pericardium for cardiac biomechanics: from physiology to computational modeling.

The human heart is enclosed in the pericardial cavity. The pericardium consists of a layered thin sac and is separated from the myocardium by a thin film of fluid. It provides a fixture in space and frictionless sliding of the myocardium. The influence of the pericardium is essential for predictive mechanical simulations of the heart. However, there is no consensus on physiologically correct and computationally tractable pericardial boundary conditions. Here, we propose to model the pericardial influence as a parallel spring and dashpot acting in normal direction to the epicardium. Using a four-chamber geometry, we compare a model with pericardial boundary conditions to a model with fixated apex. The influence of pericardial stiffness is demonstrated in a parametric study. Comparing simulation results to measurements from cine magnetic resonance imaging reveals that adding pericardial boundary conditions yields a better approximation with respect to atrioventricular plane displacement, atrial filling, and overall spatial approximation error. We demonstrate that this simple model of pericardial-myocardial interaction can correctly predict the pumping mechanisms of the heart as previously assessed in clinical studies. Utilizing a pericardial model not only can provide much more realistic cardiac mechanics simulations but also allows new insights into pericardial-myocardial interaction which cannot be assessed in clinical measurements yet.

Estimation of Cardiovascular Relative Pressure Using Virtual Work-Energy.

Many cardiovascular diseases lead to local increases in relative pressure, reflecting the higher costs of driving blood flow. The utility of this biomarker for stratifying the severity of disease has thus driven the development of methods to measure these relative pressures. While intravascular catheterisation remains the most direct measure, its invasiveness limits clinical application in many instances. Non-invasive Doppler ultrasound estimates have partially addressed this gap; however only provide relative pressure estimates for a range of constricted cardiovascular conditions. Here we introduce a non-invasive method that enables arbitrary interrogation of relative pressures throughout an imaged vascular structure, leveraging modern phase contrast magnetic resonance imaging, the virtual work-energy equations, and a virtual field to provide robust and accurate estimates. The versatility and accuracy of the method is verified in a set of complex patient-specific cardiovascular models, where relative pressures into previously inaccessible flow regions are assessed. The method is further validated within a cohort of congenital heart disease patients, providing a novel tool for probing relative pressures in-vivo.

Relative pressure estimation from velocity measurements in blood flows: State-of-the-art and new approaches.

The relative pressure difference across stenotic blood vessels serves as an important clinical index for the diagnosis of many cardiovascular diseases. While the clinical gold standard for relative pressure difference measurements is invasive catheterization, Phase-Contrast Magnetic Resonance Imaging has emerged as a promising tool for enabling a noninvasive quantification, by linking highly spatially resolved velocity measurements with relative pressures via the incompressible Navier-Stokes equations. In this work, we provide a review and analysis of current methods for relative pressure estimation and propose 3 additional techniques. Methods are compared using synthetic data from numerical examples, and sensitivity to subsampling and noise was explored. Through our analysis, we verify that the newly proposed approaches are more robust with respect to spatial subsampling and less sensitive to noise and therefore provide improved means for estimating relative pressure differences noninvasively.

An adaptive hybridizable discontinuous Galerkin approach for cardiac electrophysiology.

Cardiac electrophysiology simulations are numerically challenging because of the propagation of a steep electrochemical wave front and thus require discretizations with small mesh sizes to obtain accurate results. In this work, we present an approach based on the hybridizable discontinuous Galerkin method (HDG), which allows an efficient implementation of high-order discretizations into a computational framework. In particular, using the advantage of the discontinuous function space, we present an efficient p-adaptive strategy for accurately tracking the wave front. The HDG allows to reduce the overall degrees of freedom in the final linear system to those only on the element interfaces. Additionally, we propose a rule for a suitable integration accuracy for the ionic current term depending on the polynomial order and the cell model to handle high-order polynomials. Our results show that for the same number of degrees of freedom, coarse high-order elements provide more accurate results than fine low-order elements. Introducing p-adaptivity further reduces computational costs while maintaining accuracy by restricting the use of high-order elements to resolve the wave front. For a patient-specific simulation of a cardiac cycle, p-adaptivity reduces the average number of degrees of freedom by 95% compared to the nonadaptive model. In addition to reducing computational costs, using coarse meshes with our p-adaptive high-order HDG method also simplifies practical aspects of mesh generation and postprocessing.

Benchmark problems for numerical treatment of backflow at open boundaries.

In computational fluid dynamics, incoming velocity at open boundaries, or backflow, often yields unphysical instabilities already for moderate Reynolds numbers. Several treatments to overcome these backflow instabilities have been proposed in the literature. However, these approaches have not yet been compared in detail in terms of accuracy in different physiological regimes, in particular because of the difficulty to generate stable reference solutions apart from analytical forms. In this work, we present a set of benchmark problems in order to compare different methods in different backflow regimes (with a full reversal flow and with propagating vortices after a stenosis). The examples are implemented in FreeFem++, and the source code is openly available, making them a solid basis for future method developments.

Maximum likelihood estimation of cardiac fiber bundle orientation from arbitrarily spaced diffusion weighted images.

We propose an estimation scheme for local fiber bundle direction in the left ventricle directly from gray values of arbitrarily spaced cardiac diffusion weighted images (DWI). The approach is based on a parametric and space-dependent mathematical representation of the myocardial fiber bundle orientation and hence the diffusion tensor (DT) for the ventricular geometry. By solving a nonlinear inverse problem derived from a maximum likelihood estimator, the degrees of freedom of the fiber and DT model can be estimated from the measured gray values of the DWIs. The continuity of the DT model allows to relax the restriction to the individual DWIs to match spatially like for voxelwise DT calculation. Hence, the spatial misalignment between image slices with different diffusion encoding directions, that is encountered in-vivo cardiac imaging practice can be integrated into the estimation scheme. This feature results then in a negligible impact of the spatial misalignment on the reconstructed solution. We illustrate the methodology using synthetic data and compare it against a previously reported fiber bundle reconstruction technique. To show the potential for real data, we also present results for multi-slice data constructed from ex-vivo cardiac diffusion weighted measurements in both mono- and bi-ventricular configurations.

Multiphysics Modeling of the Atrial Systole under Standard Ablation Strategies.

The aim of this study was to develop a computational framework to compare the impact of standard ablation concepts on the mechanical performance of the atria, since different line combinations cannot be applied in practice to the same patient. For this purpuse, we coupled electro-mechano-hemodynamic mathematical models based on biophysical principles and simulate the contractile performance of the atria. We computed systolic pressures and volumes in two patient-specific atrial geometries (one of normal size and one hypertrophied) with various ablation concepts. We found that our computational model is able to detect the differences in the left atrial contractility and ejection fraction for various electrical activation sequences resulting from different ablation line combinations. We show that multiphysics modeling has the potential to quantify the hemodynamic performance of left atria for different ablation lines, which could be used as additional pre-operative clinical information for the choice of the ablation concept in the future.

Material modeling of cardiac valve tissue: Experiments, constitutive analysis and numerical investigation.

A key element of the cardiac cycle of the human heart is the opening and closing of the four valves. However, the material properties of the leaflet tissues, which fundamentally contribute to determine the mechanical response of the valves, are still an open field of research. The main contribution of the present study is to provide a complete experimental data set for porcine heart valve samples spanning all valve and leaflet types under tensile loading. The tests show a fair degree of reproducibility and are clearly indicative of a number of fundamental tissue properties, including a progressively stiffening response with increasing elongation. We then propose a simple anisotropic constitutive model, which is fitted to the experimental data set, showing a reasonable interspecimen variability. Furthermore, we present a dynamic finite element analysis of the aortic valve to show the direct usability of the obtained material parameters in computational simulations.

Identification of artery wall stiffness: in vitro validation and in vivo results of a data assimilation procedure applied to a 3D fluid-structure interaction model.

We consider the problem of estimating the stiffness of an artery wall using a data assimilation method applied to a 3D fluid-structure interaction (FSI) model. Recalling previous works, we briefly present the FSI model, the data assimilation procedure and the segmentation algorithm. We present then two examples of the procedure using real data. First, we estimate the stiffness distribution of a silicon rubber tube from image data. Second, we present the estimation of aortic wall stiffness from real clinical data.

Sequential parameter estimation for fluid-structure problems: application to hemodynamics.

We present a robust and computationally efficient parameter estimation strategy for fluid-structure interaction problems. The method is based on a filtering algorithm restricted to the parameter space, known as the reduced-order unscented Kalman filter. It does not require any adjoint or tangent problems. In addition, it can easily be run in parallel, which is of great interest in fluid-structure problems where the computational cost of the forward simulation is already a challenge in itself. We illustrate our methodology with the estimation of the artery wall stiffness from the wall displacement measurements - as they could be extracted from medical imaging - in a three-dimensional idealized abdominal aortic aneurysm. We also show preliminary results about the estimation of the proximal Windkessel resistance, which is an important parameter for setting appropriate fluid boundary conditions.