“Begin challenging your own assumptions. Your assumptions are your windows on the world. Scrub them off every once in a while, or the light will not come in.”—Alan Alda [1].The topic of the flow pattern inside the heart and vortex imaging has been a main stream of research in echocardiography during the past decade. Progress has been made to incorporate quantitative fluid dynamics into echocardiography using particle tracking algorithms [2, 3, 39] that are based mostly on the well-known optical imaging techniques of particle image velocimetry (PIV) [4, 5, 6] or color Doppler imaging [7, 8, 9, 10]. Recent advances in understanding left ventricular (LV) fluid dynamics based on experimental methods [11, 12, 13, 14] and numerical simulations [15, 16, 17] have shed light on many aspects of ventricular flow, such as the development of intraventricular vortices. These vortices are shown to significantly influence transmitral momentum transfer and help redirect the flow from the left atrium toward the left ventricular outflow tract (LVOT) [18, 19]. Alternatively, formation of unnatural vortices can be a sign of adverse blood flow, which may indicate progressive LV dysfunction [18, 19, 20, 21]. The knowledge gained about LV fluid dynamics, and in particular the associated vortical flow motion, has introduced novel clinical indicators for LV function based on vortex dynamics [18, 19, 21, 22, 23, 24, 25].PIV is an optical method for flow visualization used to obtain instantaneous velocity measurements and related properties in the fluids. In this technique, the fluid is seeded with tracer particles, which are assumed to faithfully follow the dynamics of flow. The motion of these seeding particles is used to compute the flow velocity. In its current form, 2D ultrasound-based PIV or 2D echocardiographic PIV (Echo-PIV) was introduced by Kim et al. [2], through capturing digital B-mode images of contrast agent particles, and further used for vortex imaging by Kheradvar et al. [21]. This technique computes the velocities of the ultrasound-imaged particles based on the PIV technique, with the ∆t being equal to scanning time. The number of beams and the samples along each beam define the number of pixels for each image after scan conversion. Particles used as the flow tracers are microbubbles filled with octafluoropropane encapsulated in either a lipid (DEFINITY®, Lantheus Medical Imaging, Inc.) or protein (Optison™, GE Healthcare) outer shell [3, 26], which are both FDA-approved for clinical use. This technique allows the velocity directions and streamlines, principal blood flow patterns, recirculation regions, and vortices to be drawn with reasonable confidence in a reproducible scheme [18, 21, 22, 27, 28, 29, 30, 31, 32].Alternatively, vector flow mapping (VFM) measures blood flow velocity by considering color Doppler imaging and ventricular wall velocity [7, 8, 9, 10]. This method works based on combining measured axial velocities with estimated radial velocities according to the physical principles [33]. VFM ignores the three-dimensional component of the flow by assuming the flow is two-dimensional, solves the 2D continuity equation, and use ventricular wall velocity acquired by tissue tracking to improve the results [34].In reality, any physical flow is three-dimensional. However, some flow regimens can be considered 2D if the out-of-plane velocity component does not (or at least minimally) exist. A good example for such a flow regime is laminar flow in an axisymmetric tube. In laminar flow, there is no lateral mixing, and the nearby layers pass each other in a totally parallel scheme. Laminar flow requires no cross-currents perpendicular to the flow direction or eddies/swirls in the fluid [35]. Non-uniform geometries, such as in the heart chambers, increase flow three-dimensionally. Furthermore, time-dependency and the rotational nature of the flow minimize the application and accuracy of the methods developed for potential flow. Principles of fluid dynamics should be properly considered and applied for each particular flow regimen to avoid fundamental oversights in solving cardiovascular problems [36].In prospect, intracardiac flow velocimetry is an emerging field in cardiac imaging. It should be considered that intracardiac flow is principally three-dimensional, time-dependent, and non-laminar. Modern echocardiography systems use ultrasound probes that can capture three-dimensional brightness fields associated with the blood flow. Generally, the ultrasound-based velocimetry methods are all bounded by the limitations and constraints of echocardiographic acquisitions, such as inter and intra-operator variabilities and acoustic shadowing. Furthermore, limited frame rate of echocardiographic acquisitions—particularly in 3D—is currently a major obstacle for accurate assessment of high-velocity values and advancement of 3D ultrasound-based velocimetry modalities for intracardiac flow [21, 33, 37]. More recent efforts may overcome these limitations and pave the way for routine clinical applications [33, 37, 38, 39].

The epidemiology of valvular heart disease has significantly changed in the past few decades with aging as one of the main contributing factors. The available options for replacement of diseased valves are currently limited to mechanical and bioprosthetic valves, while the tissue engineered ones that are under study are currently far from clinical approval. The main problem with the tissue engineered heart valves is their progressive deterioration that leads to regurgitation and/or leaflet thickening a few months after implantation. The use of bioresorbable scaffolds is speculated to be one factor affecting these valves’ failure. We have previously developed a non-degradable superelastic nitinol mesh scaffold concept that can be used for heart valve tissue engineering applications. It is hypothesized that the use of a non-degradable superelastic nitinol mesh may increase the durability of tissue engineered heart valves, avoid their shrinkage, and accordingly prevent regurgitation. The current work aims to study the effects of the design features on mechanical characteristics of this valve scaffold to attain proper function prior to in vivo implantation.

The engineering of technologies for heart valve replacement (i.e., heart valve engineering) is an exciting and evolving field. Since the first valve replacement, technology has progressed by leaps and bounds. Innovations emerge frequently and supply patients and physicians with new, increasingly efficacious and less invasive treatment options. As much as any other field in medicine the treatment of heart valve disease has experienced a renaissance in the last 10 years. Here we review the currently available technologies and future options in the surgical and transcatheter treatment of aortic valve disease. Different valves from major manufacturers are described in details with their applications.

In this portion of an extensive review of heart valve engineering, we focus on the current and emerging technologies and techniques to repair or replace the mitral valve. We begin with a discussion of the currently available mechanical and bioprosthetic mitral valves followed by the rationale and limitations of current surgical mitral annuloplasty methods; a discussion of the technique of neo-chordae fabrication and implantation; a review the procedures and clinical results for catheter-based mitral leaflet repair; a highlight of the motivation for and limitations of catheter-based annular reduction therapies; and introduce the early generation devices for catheter-based mitral valve replacement.

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed.

In this final portion of an extensive review of heart valve engineering, we focus on the computational methods and experimental studies related to heart valves. The discussion begins with a thorough review of computational modeling and the governing equations of fluid and structural interaction. We then move onto multiscale and disease specific modeling. Finally, advanced methods related to in vitro testing of the heart valves are reviewed. This section of the review series is intended to illustrate application of computational methods and experimental studies and their interrelation for studying heart valves.

The shape and formation of transmitral vortex ring are shown to be associated with diastolic function of the left ventricle (LV). Transmitral vortex ring is a flow feature that is observed to be non-axisymmetric in a healthy heart and its inherent asymmetry in the LV assists in efficient ejection of the blood during systole. This study is a first step towards understanding the effects of the mitral valve’s anterior leaflet on transmitral flow. We experimentally study a single-leaflet model of the mitral valve to investigate the effect of the anterior leaflet on the axisymmetry of the generated vortex ring based on the three-dimensional data acquired using defocusing digital particle image velocimetry. Vortex rings form downstream of a D-shaped orifice in presence or absence of the anterior leaflet in various physiological stroke ratios. The results of the statistical analysis indicate that the formed vortex ring downstream of a D-shaped orifice is markedly non-axisymmetric, and presence of the anterior leaflet improves the ring’s axisymmetry. This study suggests that the improvement of axisymmetry in presence of the anterior leaflet might be due to coupled dynamic interaction between rolling-up of the shear layer at the edges of the D-shaped orifice and the borders of the anterior leaflet. This interaction can reduce the non-uniformity in vorticity generation, which results in more axisymmetric behavior compared to the D-shaped orifice without the anterior leaflet.

Measurement of the three-dimensional flow field inside the cardiac chambers has proven to be a challenging task. This is mainly due to the fact that generalized full-volume velocimetry techniques cannot be easily implemented to the heart chambers. In addition, the rapid pace of the events in the heart does not allow for accurate real-time flow measurements in 3D using imaging modalities such as magnetic resonance imaging, which neglects the transient variations of the flow due to averaging of the flow over multiple heartbeats. In order to overcome these current limitations, we introduce a multi-planar velocity reconstruction approach that can characterize 3D incompressible flows based on the reconstruction of 2D velocity fields. Here, two-dimensional, two-component velocity fields acquired on multiple perpendicular planes are reconstructed into a 3D velocity field through Kriging interpolation and by imposing the incompressibility constraint. Subsequently, the scattered experimental data are projected into a divergence-free vector field space using a fractional step approach. We validate the method in exemplary 3D flows, including the Hill’s spherical vortex and a numerically simulated flow downstream of a 3D orifice. During the process of validation, different signal-to-noise ratios are introduced to the flow field, and the method’s performance is assessed accordingly. The results show that as the signal-to-noise ratio decreases, the corrected velocity field significantly improves. The method is also applied to the experimental flow inside a mock model of the heart’s right ventricle. Taking advantage of the periodicity of the flow, multiple 2D velocity fields in multiple perpendicular planes at different locations of the mock model are measured while being phase-locked for the 3D reconstruction. The results suggest the metamorphosis of the original transvalvular vortex, which forms downstream of the inlet valve during the early filling phase of the right ventricular model, into a streamline single-leg vortex extending toward the outlet.

When implanted inside the body, bioprosthetic heart valve leaflets experience a variety of cyclic mechanical stresses such as shear stress due to blood flow when the valve is open, flexural stress due to cyclic opening and closure of the valve, and tensile stress when the valve is closed. These types of stress lead to a variety of failure modes. In either a natural valve leaflet or a processed pericardial tissue leaflet, collagen fibers reinforce the tissue and provide structural integrity such that the very thin leaflet can stand enormous loads related to cyclic pressure changes. The mechanical response of the leaflet tissue greatly depends on collagen fiber concentration, characteristics, and orientation. Thus, understating the microstructure of pericardial tissue and its response to dynamic loading is crucial for the development of more durable heart valve, and computational models to predict heart valves' behavior. In this work, we have characterized the 3D collagen fiber arrangement of bovine pericardial tissue leaflets in response to a variety of different loading conditions under Second-Harmonic Generation Microscopy. This real-time visualization method assists in better understanding of the effect of cyclic load on collagen fiber orientation in time and space.

Despite substantial research in the past few decades, only slight progress has been made toward developing biocompatible, tissue-engineered scaffolds for heart valve leaflets that can withstand the dynamic pressure inside the heart. Recent progress on the development of hybrid scaffolds, which are composed of a thin metal mesh enclosed by multi-layered tissue, appear to be promising for heart valve engineering. This approach retains all the advantages of biological scaffolds while developing a strong extracellular matrix backbone to withstand dynamic loading. This study aims to test the inflammatory response of hybrid tissue-engineered leaflets based on characterizing the activation of macrophage cells cultured on the surfaces of the tissue construct. The results indicate that integration of biological layers around a metal mesh core—regardless of its type—may reduce the evoked inflammatory responses by THP-1 monocyte-like cells. This observation implies that masking a metal implant within a tissue construct prior to implantation can hide it from the immune system and may improve the implant’s biocompatibility.

Abnormality in cardiac fluid dynamics is highly correlated with several heart conditions. This is particularly true in valvular heart diseases and congenital heart defects where changes in flow-field accompany significant variations in chambers’ pressure gradients. Particle Image Velocimetry (PIV) is a convenient technique in assessing cardiac fluid dynamics in vitro. With PIV, it is possible to quantitatively differentiate between normal and abnormal intracardiac flow fields in transparent models of cardiac chambers. Understanding the flow-field inside the heart chambers is challenging due to the fast pace of the flow, three dimensionality of the events, and complex deformability of the heart chambers that highly depends on compliance. Defining standard test-phantoms for particular performance studies ensure accuracy of the tests and reproducibility of the data for implantable devices, regardless of who performs the tests. In this work, we have described several different measures for assessment of cardiac fluid dynamics of heart valves using our novel experimental system that is particularly designed and developed for in vitro investigation of intracardiac flow.

•Deep learning for segmentation.•Excellent agreement.•High correlation for indices.Segmentation of the left ventricle (LV) from cardiac magnetic resonance imaging (MRI) datasets is an essential step for calculation of clinical indices such as ventricular volume and ejection fraction. In this work, we employ deep learning algorithms combined with deformable models to develop and evaluate a fully automatic LV segmentation tool from short-axis cardiac MRI datasets. The method employs deep learning algorithms to learn the segmentation task from the ground true data. Convolutional networks are employed to automatically detect the LV chamber in MRI dataset. Stacked autoencoders are used to infer the LV shape. The inferred shape is incorporated into deformable models to improve the accuracy and robustness of the segmentation. We validated our method using 45 cardiac MR datasets from the MICCAI 2009 LV segmentation challenge and showed that it outperforms the state-of-the art methods. Excellent agreement with the ground truth was achieved. Validation metrics, percentage of good contours, Dice metric, average perpendicular distance and conformity, were computed as 96.69%, 0.94, 1.81 mm and 0.86, versus those of 79.2−95.62%, 0.87–0.9, 1.76–2.97 mm and 0.67–0.78, obtained by other methods, respectively.Download high-res image (114KB)Download full-size image

BackgroundPrevious experimental models have related transmitral vortex formation to the longitudinal recoil of left ventricle. However, little is known about the relationships among left ventricular (LV) longitudinal relaxation, transmitral filling patterns, and LV vortex formation in clinical settings. The aim of this study was to compare the vortex formation time index among a heterogeneous group of patients with diastolic dysfunction to understand the relationship between transmitral vortex formation and abnormal diastolic filling patterns.MethodsEchocardiographic data from 107 subjects were retrospectively evaluated. The study population was categorized into four groups on the basis of transmitral early and late diastolic Doppler filling patterns as normal (n = 45), impaired relaxation (n = 14), pseudonormal (n = 26), and restrictive (n = 22). Vortex formation time was computed from the governing equations based on transmitral flow and ejection fraction.ResultsDifferences in vortex formation time index were found to be significant among all the studied groups (P < .0001). The trend of vortex formation during a cardiac cycle was compared in normal hearts and those with diastolic dysfunction. Mitral annular velocity (e′) was found to decrease significantly (P < .0001) in subjects with abnormal transmitral filling patterns compared with normal subjects. The difference in e′ among all the affected groups was not found to be significant (P = .68).ConclusionsThe findings of this study suggest that patients with different patterns of transmitral diastolic filling show significant changes in LV vortex formation time despite the absence of significant differences in mitral annulus recoil during diastole.

The prevalence of aortic valve stenosis (AS) is increasing in the aging society. More recently, novel treatments and devices for AS, especially transcatheter aortic valve replacement (TAVR) have significantly changed the therapeutic approach to this disease. Research and development related to TAVR require testing these devices in the calcified heart valves that closely mimic a native calcific valve. However, no animal model of AS has yet been available. Alternatively, animals with normal aortic valve that are currently used for TAVR experiments do not closely replicate the aortic valve pathology required for proper testing of these devices. To solve this limitation, for the first time, we developed a novel polymeric valve whose leaflets possess calcium hydroxyapatite inclusions immersed in them. This study reports the characteristics and feasibility of these valves. Two types of the polymeric valve, i.e., moderate and severe calcified AS models were developed and tested by deploying a transcatheter valve in those and measuring the related hemodynamics. The valves were tested in a heart flow simulator, and were studied using echocardiography. Our results showed high echogenicity of the polymeric valve, that was correlated to the severity of the calcification. Aortic valve area of the polymeric valves was measured, and the severity of stenosis was defined according to the clinical guidelines. Accordingly, we showed that these novel polymeric valves closely mimic AS, and can be a desired cost-saving solution for testing the performance of the transcatheter aortic valve systems in vitro.