Patient-specific CFD simulation of intraventricular haemodynamics based on 3D ultrasound imaging

Background: The goal of this paper is to present a computational fluid dynamic (CFD) model with moving boundaries to study the intraventricular flows in a patient-specific framework. Starting from the segmentation of real-time transesophageal echocardiographic images, a CFD model including the complete left ventricle and the moving 3D mitral valve was realized. Their motion, known as a function of time from the segmented ultrasound images, was imposed as a boundary condition in an Arbitrary Lagrangian-Eulerian framework. Results: The model allowed for a realistic description of the displacement of the structures of interest and for an effective analysis of the intraventricular flows throughout the cardiac cycle. The model provides detailed intraventricular flow features, and highlights the importance of the 3D valve apparatus for the vortex dynamics and apical flow. Conclusions: The proposed method could describe the haemodynamics of the left ventricle during the cardiac cycle. The methodology might therefore be of particular importance in patient treatment planning to assess the impact of mitral valve treatment on intraventricular flow dynamics

Modelling and application of mitral valve dynamics for reproducing the flow in the left ventricle of the human heart

The fluid dynamics in the left ventricle of the human heart is considered an important player for the prediction of long term cardiovascular outcome. To this end, numerical simulations represent an important tool for integrating the existing medical imaging technology and uncover physical flow phenomena. This study presents a computational method for the fluid dynamics inside the left ventricle designed to be efficiently integrated in clinical scenarios. It includes an original model of the mitral valve dynamics, which describes an asymptotic behavior for tissues with no elastic stiffness other than the constrain of the geometry obtained from medical imaging; in particular, the model provides an asymptotic description without requiring details of tissue properties that may not be measurable in vivo. The advantages of this model with respect to a valveless orifice and its limitations with respect to a complete tissue modeling are verified. Its performances are then analyzed in details to ensure a correct interpretation of results. It represents a potential option when information about tissue mechanical properties is insufficient for the implementations of a full fluid-structure interaction approach. Geometries of left ventricle (LV) and mitral valve (MV) are extracted from 4D-transesophageal echocardiography. MV geometries are extracted in open and closed configurations and the intraventricular fluid dynamics is reproduced by a dedicated approach to direct numerical simulation (DNS) that includes flow-tissue interaction for the MV leaflet (Collia et al. 2019). This approach is applied to normal and pathological ventricles to investigate the dynamics of the MV during the cardiac cycle: how it interacts with the ventricular flow and how it affects clinical measurements. The dynamics of mitral opening at the onset of diastole, as well as the closure at the transition between diastole and systole, is governed by the high pressure gradients associated with the bulk cardiac flow. On the opposite, during the flow diastasis in the middle of the diastolic filling, valvular motion is primarily influenced by the intraventricular circulation that gives an increased tendency to close in enlarged ventricles. This observation provides a physical interpretation to echocardiographic measurements commonly employed in the clinical diagnostic process. Results demonstrated the properties of false regurgitation, blood that did not cross the open MV orifice and returns into the atrium during the backward motion of the MV leaflets, whose entity should be accounted when evaluating small regurgitation (Collia et al. 2019). The regurgitating volume is found to be proportional to the effective orifice area, with the limited dependence of the LV geometry and type of prolapse. These affect the percentage of old blood returning to the atrium which may be associated with thrombogenic risk. This non-invasive method is useful for the assessment of blood flow, to improve early detection of cardiac dysfunctions and for provide a concrete helpful in clinical routines

Material transport in the left ventricle with aortic valve regurgitation

This experimental in vitro work investigates material transport properties in a model left ventricle in the case of aortic regurgitation, a valvular disease characterized by a leaking aortic valve and consequently double-jet filling within the elastic left ventricular geometry. This study suggests that material transport phenomena are strongly determined by the motion of the counterrotating vortices driven by the regurgitant aortic and mitral jets. The overall particle residence time appears to be significantly longer with moderate aortic regurgitation, attributed to the dynamics resulting from the timing between the onset of the two jets. Increasing regurgitation severity is shown to be associated with higher frequencies in the time-frequency spectra of the velocity signals at various points in the flow, suggesting nonlaminar mixing past moderate regurgitation. Additionally, a large part of the regurgitant inflow is retained for at least one cardiac cycle. Such an increase in particle residence time accompanied by the occurrence and persistence of a number of attracting Lagrangian coherent structures presents favorable conditions and locations for activated platelets to agglomerate within the left ventricle, potentially posing an additional risk factor for patients with aortic regurgitation

DEVELOPMENT AND IMPLEMENTATION OF NOVEL STRATEGIES TO EXPLOIT 3D ULTRASOUND IMAGING IN CARDIOVASCULAR COMPUTATIONAL BIOMECHANICS

Introduction In the past two decades, major advances have been made in cardiovascular diseases assessment and treatment owing to the advent of sophisticated and more accurate imaging techniques, allowing for better understanding the complexity of 3D anatomical cardiovascular structures1. Volumetric acquisition enables the visualization of cardiac districts from virtually any perspective, better appreciating patient-specific anatomical complexity, as well as an accurate quantitative functional evaluation of chamber volumes and mass avoiding geometric assumptions2. Additionally, this scenario also allowed the evolution from generic to patient-specific 3D cardiac models that, based on in vivo imaging, faithfully represent the anatomy and different cardiac features of a given alive subject, being pivotal either in diagnosis and in planning guidance3. Precise morphological and functional knowledge about either the heart valves\u2019 apparatus and the surrounding structures is crucial when dealing with diagnosis as well as preprocedural planning4. To date, computed tomography (CT) and real-time 3D echocardiography (rt3DE) are typically exploited in this scenario since they allow for encoding comprehensive structural and dynamic information even in the fourth dimension (i.e., time)5,6. However, owing to its cost-effectiveness and very low invasiveness, 3D echocardiography has become the method of choice in most situations for performing the evaluation of cardiac function, developing geometrical models which can provide quantitative anatomical assessment7. Complementing this scenario, computational models have been introduced as numerical engineering tools aiming at adding qualitative and quantitative information on the biomechanical behavior in terms of stress-strain response and other multifactorial parameters8. In particular, over the two last decades, their applications have been ranging from elucidating the heart biomechanics underlying different patho-physiological conditions9 to predicting the effects of either surgical or percutaneous procedures, even comparing several implantation techniques and devices10. At the early stage, most of the studies focused on FE modeling in cardiac environment were based on paradigmatic models11\u201315, being mainly exploited to explore and investigate biomechanical alterations following a specific pathological scenario or again to better understand whether a surgical treatment is better or worse than another one. Differently, nowadays the current generation of computational models heavily exploits the detailed anatomical information yielded by medical imaging to provide patient-specific analyses, paving the way toward the development of virtual surgical-planning tools16\u201319. In this direction, cardiac magnetic resonance (CMR) and CT/micro-CT are the mostly accomplished imaging modality, since they can provide well-defined images thanks to their spatial and temporal resolutions20\u201325. Nonetheless, they cannot be applied routinely in clinical practice, as it can be differently done with rt3DE, progressively became the modality of choice26 since it has no harmful effects on the patient and no radiopaque contrast agent is needed. Despite these advantages, 3D volumetric ultrasound imaging shows intrinsic limitations beyond its limited resolution: i) the deficiency of morphological detail owing to either not so easy achievable detection (e.g., tricuspid valve) or not proper acoustic window, ii) the challenge of tailoring computational models to the patient-specific scenario mimicking the morphology as well as the functionality of the investigated cardiac district (e.g., tethering effect exerted by chordal apparatus in mitral valve insufficiency associated to left ventricular dilation), and iii) the needing to systematically analyse devices performances when dealing with real-life cases where ultrasound imaging is the only performable technique but lacking of standardized acquisition protocol. Main findings In the just described scenario, the main aim of this work was focused on the implementation, development and testing of numerical strategies in order to overcome issues when dealing with 3D ultrasound imaging exploitation towards predictive patient-specific modelling approaches focused on both morphological and biomechanical analyses. Specifically, the first specific objective was the development of a novel approach integrating in vitro imaging and finite element (FE) modeling to evaluate tricuspid valve (TV) biomechanics, facing with the lack of information on anatomical features owing to the clinically evident demanding detection of this anatomical district through in vivo imaging. \u2022 An innovative and semi-automated framework was implemented to generate 3D model of TV, to quantitively describe its 3D morphology and to assess its biomechanical behaviour. At this aim, an image-based in vitro experimental approach was integrated with numerical models based on FE strategy. Experimental measurements directly performed on the benchmark (mock circulation loop) were compared with geometrical features computed on the 3D reconstructed model, pinpointing a global good consistency. Furthermore, obtained realistic reconstructions were used as the input of the FE models, even accounting for proper description of TV leaflets\u2019 anisotropic mechanical response. As done experimentally, simulations reproduced both \u201cincompetent\u201d (FTR) and \u201ccompetent-induced\u201d (PMA), proving the efficiency of such a treatment and suggesting translational potential to the clinic. The second specific aim was the implementation of a computational framework able to reproduce a functionally equivalent model of the mitral valve (MV) sub-valvular apparatus through chordae tendineae topology optimization, aiming at chordae rest length arrangement to be able to include their pre-stress state associated to specific ventricular conformation. \u2022 We sought to establish a framework to build geometrically tractable, functionally equivalent models of the MV chordae tendineae, addressing one of the main topics of the computational scientific literature towards the development of faithful patient-specific models from in vivo imaging. Exploiting the mass spring model (MSM) approach, an iterative tool was proposed aiming to the topology optimization of a paradigmatic chordal apparatus of MVs affected by functional regurgitation, in order to be able to equivalently account for tethering effect exerted by the chordae themselves. The results have shown that the algorithm actually lowered the error between the simulated valve and ground truth data, although the intensity of this improvement is strongly valve-dependent.Finally, the last specific aim was the creation of a numerical strategy able to allow for patient-specific geometrical reconstruction both pre- and post- LVAD implantation, in a specific high-risk clinical scenario being rt3DE the only available imaging technique to be used but without any acquisition protocol. \u2022 We proposed a numerical approach which allowed for a systematic and selective analysis of the mechanism associated to intraventricular thrombus formation and thrombogenic complications in a LVAD-treated dilated left ventricle (LV). Ad-hoc geometry reconstruction workflow was implemented to overcome limitations associated to imaging acquisition in this specific scenario, thus being able to generate computational model of the LV assisted with LVAD. In details, results suggested that blood stasis is influenced either by LVAD flow rate and, to a greater extent, by LV residual contractility, being the positioning of the inflow cannula insertion mandatory to be considered when dealing with LVAD thrombogenic potential assessment

Simplified mitral valve modeling for prospective clinical application of left ventricular fluid dynamics

The fluid dynamics inside the left ventricle of the human heart is considered a potential indicator of long term cardiovascular outcome. In this respect, numerical simulations can play an important role for integrating existing technology to reproduce flow details and even conditions associated to virtual therapeutic solutions. Nevertheless, numerical models encounter serious practical difficulties in describing the interaction between flow and surrounding tissues due to the limited information inherently available in real clinical applications. This study presents a computational method for the fluid dynamics inside the left ventricle designed to be efficiently integrated in clinical scenarios. It includes an original model of the mitral valve dynamics, which describes an asymptotic behavior for tissues with no elastic stiffness other than the constrain of the geometry obtained from medical imaging; in particular, the model provides an asymptotic description without requiring details of tissue properties that may not be measurable in vivo. The advantages of this model with respect to a valveless orifice and its limitations with respect to a complete tissue modeling are verified. Its performances are then analyzed in details to ensure a correct interpretation of results. It represents a potential option when information about tissue mechanical properties is insufficient for the implementations of a full fluid-structure interaction approach

A coupled mitral valve -- left ventricle model with fluid-structure interaction

Understanding the interaction between the valves and walls of the heart is important in assessing and subsequently treating heart dysfunction. With advancements in cardiac imaging, nonlinear mechanics and computational techniques, it is now possible to explore the mechanics of valve-heart interactions using anatomically and physiologically realistic models. This study presents an integrated model of the mitral valve (MV) coupled to the left ventricle (LV), with the geometry derived from in vivo clinical magnetic resonance images. Numerical simulations using this coupled MV-LV model are developed using an immersed boundary/finite element method. The model incorporates detailed valvular features, left ventricular contraction, nonlinear soft tissue mechanics, and fluid-mediated interactions between the MV and LV wall. We use the model to simulate the cardiac function from diastole to systole, and investigate how myocardial active relaxation function affects the LV pump function. The results of the new model agree with in vivo measurements, and demonstrate that the diastolic filling pressure increases significantly with impaired myocardial active relaxation to maintain the normal cardiac output. The coupled model has the potential to advance fundamental knowledge of mechanisms underlying MV-LV interaction, and help in risk stratification and optimization of therapies for heart diseases.Comment: 25 pages, 6 figure

Three-dimensional structure of the flow inside the left ventricle of the human heart

The laboratory models of the human heart left ventricle developed in the last decades gave a valuable contribution to the comprehension of the role of the fluid dynamics in the cardiac function and to support the interpretation of the data obtained in vivo. Nevertheless, some questions are still open and new ones stem from the continuous improvements in the diagnostic imaging techniques. Many of these unresolved issues are related to the three-dimensional structure of the left-ventricular flow during the cardiac cycle. In this paper we investigated in detail this aspect using a laboratory model. The ventricle was simulated by a flexible sack varying its volume in time according to a physiologically shaped law. Velocities measured during several cycles on series of parallel planes, taken from two orthogonal points of view, were combined together in order to reconstruct the phase averaged, three-dimensional velocity field. During the diastole, three main steps are recognized in the evolution of the vortical structures: i) straight propagation in the direction of the long axis of a vortex-ring originated from the mitral orifice; ii) asymmetric development of the vortex-ring on an inclined plane; iii) single vortex formation. The analysis of three-dimensional data gives the experimental evidence of the reorganization of the flow in a single vortex persisting until the end of the diastole. This flow pattern seems to optimize the cardiac function since it directs velocity towards the aortic valve just before the systole and minimizes the fraction of blood residing within the ventricle for more cycles