skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Energetics of Cardiac Blood Flow in Hypertrophic Cardiomyopathy through Individualized Computational Modeling
Hypertrophic cardiomyopathy (HCM) is a congenital heart disease characterized by thickening of the heart’s left ventricle (LV) wall that can lead to cardiac dysfunction and heart failure. Ventricular wall thickening affects the motion of cardiac walls and blood flow within the heart. Because abnormal cardiac blood flow in turn could lead to detrimental remodeling of heart walls, aberrant ventricular flow patterns could exacerbate HCM progression. How blood flow patterns are affected by hypertrophy and inter-patient variability is not known. To address this gap in knowledge, we present here strategies to generate personalized computational fluid dynamics (CFD) models of the heart LV from patient cardiac magnetic resonance (cMR) images. We performed simulations of CFD LV models from three cases (one normal, two HCM). CFD computations solved for blood flow velocities, from which flow patterns and the energetics of flow within the LV were quantified. We found that, compared to a normal heart, HCM hearts exhibit anomalous flow patterns and a mismatch in the timing of energy transfer from the LV wall to blood flow, as well as changes in kinetic energy flow patterns. While our results are preliminary, our presented methodology holds promise for in-depth analysis of HCM patient hemodynamics in clinical practice.  more » « less
Award ID(s):
2109918
PAR ID:
10506086
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
MDPI
Date Published:
Journal Name:
Journal of Cardiovascular Development and Disease
Volume:
10
Issue:
10
ISSN:
2308-3425
Page Range / eLocation ID:
411
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Computational fluid dynamics (CFD) modeling of left ventricle (LV) flow combined with patient medical imaging data has shown great potential in obtaining patient-specific hemodynamics information for functional assessment of the heart. A typical model construction pipeline usually starts with segmentation of the LV by manual delineation followed by mesh generation and registration techniques using separate software tools. However, such approaches usually require significant time and human efforts in the model generation process, limiting large-scale analysis. In this study, we propose an approach toward fully automating the model generation process for CFD simulation of LV flow to significantly reduce LV CFD model generation time. Our modeling framework leverages a novel combination of techniques including deep-learning based segmentation, geometry processing, and image registration to reliably reconstruct CFD-suitable LV models with little-to-no user intervention.1 We utilized an ensemble of two-dimensional (2D) convolutional neural networks (CNNs) for automatic segmentation of cardiac structures from three-dimensional (3D) patient images and our segmentation approach outperformed recent state-of-the-art segmentation techniques when evaluated on benchmark data containing both magnetic resonance (MR) and computed tomography(CT) cardiac scans. We demonstrate that through a combination of segmentation and geometry processing, we were able to robustly create CFD-suitable LV meshes from segmentations for 78 out of 80 test cases. Although the focus on this study is on image-to-mesh generation, we demonstrate the feasibility of this framework in supporting LV hemodynamics modeling by performing CFD simulations from two representative time-resolved patient-specific image datasets. 
    more » « less
  2. Abstract BackgroundThe developing zebrafish ventricle generates higher intraventricular pressure (IVP) with increasing stroke volume and cardiac output at different developmental stages to meet the metabolic demands of the rapidly growing embryo (Salehin et al. Ann Biomed Eng, 2021;49(9): 2080‐2093). To understand the changing role of the developing embryonic heart, we studied its biomechanical characteristics during in vivo cardiac cycles. By combining changes in wall strains and IVP measurements, we assessed ventricular wall stiffness during diastolic filling and the ensuing systolic IVP‐generation capacity during 3‐, 4‐, and 5‐day post fertilization (dpf). We further examined the anisotropy of wall deformation, in different regions within the ventricle, throughout a complete cardiac cycle. ResultsWe found the ventricular walls grow increasingly stiff during diastolic filling with a corresponding increase in IVP‐generation capacity from 3‐ to 4‐ and 5‐dpf groups. In addition, we found the corresponding increasing level of anisotropic wall deformation through cardiac cycles that favor the latitudinal direction, with the most pronounced found in the equatorial region of the ventricle. ConclusionsFrom 3‐ to 4‐ and 5‐dpf groups, the ventricular wall myocardium undergoes increasing level of anisotropic deformation. This, in combination with the increasing wall stiffness and IVP‐generation capacity, allows the developing heart to effectively pump blood to meet the rapidly growing embryo's needs. 
    more » « less
  3. Introduction: Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. Methods: We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart. Results: While previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. Discussion: While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice. 
    more » « less
  4. Abstract The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell–cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair. 
    more » « less
  5. null (Ed.)
    Rotating miniature magnetic swimmers are de-vices that could navigate within the bloodstream to access remote locations of the body and perform minimally invasive procedures. The rotational movement could be used, for example, to abrade a pulmonary embolus. Some regions, such as the heart, are challenging to navigate. Cardiac and respiratory motions of the heart combined with a fast and variable blood flow necessitate a highly agile swimmer. This swimmer should minimize contact with the walls of the blood vessels and the cardiac structures to mitigate the risk of complications. This paper presents experimental tests of a millimeter-scale magnetic helical swimmer navigating in a blood-mimicking solution and describes its turning capabilities. The step-out frequency and the position error were measured for different values of turn radius. The paper also introduces rapid movements that increase the swimmer's agility and demonstrates these experimentally on a complex 3D trajectory. 
    more » « less