Image-based computational assessment of vascular wall mechanics and hemodynamics in pulmonary arterial hypertension patients

Abstract

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevated pulmonary arterial (PA) pressure. While several computational hemodynamic models of the pulmonary vasculature have been developed to understand PAH, they are lacking in some aspects, such as the vessel wall deformation and its lack of calibration against measurements in humans. Here, we describe a computational modeling framework that addresses these limitations. Specifically, computational models describing the coupling of hemodynamics and vessel wall mechanics in the pulmonary vasculature of a PAH patient and a normal subject were developed. Model parameters, consisting of linearized stiffness E of the large vessels and Windkessel parameters for each outflow branch, were calibrated against in vivo measurements of pressure, flow and vessel wall deformation obtained, respectively, from right-heart catheterization, phase-contrast and cine magnetic resonance images. Calibrated stiffness E of the proximal PA was 2.0 and 0.5 MPa for the PAH and normal models, respectively. Calibrated total compliance C and resistance R of the distal vessels were, respectively, 0.32 ml/mmHg and 11.3 mmHg∗min/l for the PAH model, and 2.93 ml/mmHg and 2.6 mmHg∗min/l for the normal model. These results were consistent with previous findings that the pulmonary vasculature is stiffer with more constricted distal vessels in PAH patients. Individual effects on PA pressure due to remodeling of the distal and proximal compartments of the pulmonary vasculature were also investigated in a sensitivity analysis. The analysis suggests that the remodeling of distal vasculature contributes more to the increase in PA pressure than the remodeling of proximal vasculature.

Blood Flow Dynamics at the Pulmonary Artery Bifurcation

“…The walls of the vessels are assumed to be rigid and a no-slip condition is applied. Fluid-structure interaction models for the pulmonary circulation are remarkably challenging, particularly as they require knowledge of the vessel wall properties [42,46]. We should note that in the simulations reported in this study, where the inflow and outflow boundary conditions are driven by in-vivo imaging data which account for the compliance and downstream impedance, the effects of vessel compliance may be secondary.…”

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

“…Image-based computational models of PAH, including both biventricular cardiac models as well as hemodynamic models of the pulmonary vasculature, hold promise to advance our understanding of cardiac and vascular remodeling under PAH, and there has been growing interest in developing such models [13][14][15][16]. As computational cardiac models have elucidated the marked effect of myofiber orientation in the load distribution in the myocardial wall [17][18][19][20], remodeling in fiber structure alone is expected to influence the overall contractile function of the ventricle.…”

Direct Effects of Cigarette Smoke in Pulmonary Arterial Cells alter Vascular Tone through Arterial Remodeling and Kv7.4 Channel Dysregulation

“…PASMC contractile properties are essential for the regulation of blood flow and vascular tone homeostasis throughout the pulmonary system, undergoing constriction under hypoxia in the alveolar compartment [49]. Previous studies highlight the importance of an abnormal mechanical behavior of the pulmonary artery in different pathologies, including COPD and PH [50,51]. Despite this, the connection between main COPD risk factors, such as cigarette smoke, and biophysical changes in the pulmonary artery cells remains unexplored.…”