Comorbidities such as anemia or hypertension and physiological factors related to exertion can influence a patient’s hemodynamics and increase the severity of many cardiovascular diseases. Observing and quantifying associations between these factors and hemodynamics can be difficult due to the multitude of co-existing conditions and blood flow parameters in real patient data. Machine learning-driven, physics-based simulations provide a means to understand how potentially correlated conditions may affect a particular patient. Here, we use a combination of machine learning and massively parallel computing to predict the effects of physiological factors on hemodynamics in patients with coarctation of the aorta. We first validated blood flow simulations against in vitro measurements in 3D-printed phantoms representing the patient’s vasculature. We then investigated the effects of varying the degree of stenosis, blood flow rate, and viscosity on two diagnostic metrics – pressure gradient across the stenosis (ΔP) and wall shear stress (WSS) - by performing the largest simulation study to date of coarctation of the aorta (over 70 million compute hours). Using machine learning models trained on data from the simulations and validated on two independent datasets, we developed a framework to identify the minimal training set required to build a predictive model on a per-patient basis. We then used this model to accurately predict ΔP (mean absolute error within 1.18 mmHg) and WSS (mean absolute error within 0.99 Pa) for patients with this disease.

Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies, as well as for planning their surgical repair. In vitro experiments are required to validate the simulations against real world data, and the experiments require a pulsatile flow pump system that can provide physiologic flow conditions characteristic of the aorta. We designed a newly capable piston-based pulsatile flow pump system that can generate high volume flow rates (850 mL/s), replicate physiologic waveforms, and pump high viscosity fluids against large impedances. The system is also compatible with a broad range of fluid types, and is operable in magnetic resonance imaging environments. Performance of the system was validated using image processing-based analysis of piston motion as well as particle image velocimetry. The new system represents a more capable pumping solution for aortic flow experiments than other available designs, and can be manufactured at a relatively low cost.

The development of atherosclerosis in the aorta is associated with low and oscillatory wall shear stress for normal patients. Moreover, localized differences in wall shear stress heterogeneity have been correlated with the presence of complex plaques in the descending aorta. While it is known that coarctation of the aorta can influence indices of wall shear stress, it is unclear how the degree of narrowing influences resulting patterns. We hypothesized that the degree of coarctation would have a strong influence on focal heterogeneity of wall shear stress. To test this hypothesis, we modeled the fluid dynamics in a patient-specific aorta with varied degrees of coarctation. We first validated a massively parallel computational model against experimental results for the patient geometry and then evaluated local shear stress patterns for a range of degrees of coarctation. Wall shear stress patterns at two cross sectional slices prone to develop atherosclerotic plaques were evaluated. Levels at different focal regions were compared to the conventional measure of average circumferential shear stress to enable localized quantification of coarctation-induced shear stress alteration. We find that the coarctation degree causes highly heterogeneous changes in wall shear stress.

The lattice Boltzmann method (LBM) is a popular alternative to solving the Navier-Stokes equations for modeling blood flow. When simulating flow using the LBM, several choices for inlet and outlet boundary conditions exist. While boundary conditions in the LBM have been evaluated in idealized geometries, there have been no extensive comparisons in image-derived vasculature, where the geometries are highly complex. In this study, the Zou-He (ZH) and finite difference (FD) boundary conditions were evaluated in image-derived vascular geometries by comparing their stability, accuracy, and run times. The boundary conditions were compared in four arteries: a coarctation of the aorta, dissected aorta, femoral artery, and left coronary artery. The FD boundary condition was more stable than ZH in all four geometries. In general, simulations using the ZH and FD method showed similar convergence rates within each geometry. However, the ZH method proved to be slightly more accurate compared with experimental flow using three-dimensional printed vasculature. The total run times necessary for simulations using the ZH boundary condition were significantly higher as the ZH method required a larger relaxation time, grid resolution, and number of time steps for a simulation representing the same physiological time. Finally, a new inlet velocity profile algorithm is presented for complex inlet geometries. Overall, results indicated that the FD method should generally be used for large-scale blood flow simulations in image-derived vasculature geometries. This study can serve as a guide to researchers interested in using the LBM to simulate blood flow. KEYWORDS boundary conditions, finite difference, hemodynamics, image-derived vasculature, lattice Boltzmann method, Zou-He Int J Numer Meth Biomed Engng. 2019;35:e3198.wileyonlinelibrary.com/journal/cnm

The ankle-brachial index (ABI), a ratio of arterial blood pressure in the ankles and upper arms, is used to diagnose and monitor cirulatory conditions such as coarctation of the aorta and peripheral artery disease. Computational simulations of the ABI can potentially determine the parameters that produce an ABI indicative of ischemia or other abnormalities in blood flow. However, 0-and 1-D computational methods are limited in describing a 3-D patient-derived geometry. Thus, we present a massively parallel framework for computational fluid dynamics (CFD) simulations in the full arterial system. Using the lattice Boltzmann method to solve the Navier-Stokes equations, we employ highly parallelized and scalable methods to generate the simulation domain and efficiently distribute the computational load among processors. For the first time, we compute an ABI with 3-D CFD. In this proof-of-concept study, we investigate the dependence of ABI on the presence of stenoses, or narrowed regions of the arteries, by directly modifying the arterial geometry. As a result, our framework enables the computation a hemodynamic factor characterizing flow at the scale of the full arterial system, in a manner that is extensible to patient-specific imaging data and holds potential for treatment planning.

No abstract

The cover image is based on the Research Article ‐ Application Suitability of lattice Boltzmann inlet and outlet boundary conditions for simulating flow in image‐derived vasculature by Bradley Feiger et al., https://doi.org/10.1002/cnm.3198. Cover image © Liam Krauss/Lawrence Livermore National Laboratory.