Computational investigation of outflow graft variation impact on hemocompatibility profile in LVADs.

BACKGROUND: Hemocompatibility-related adverse events (HRAE) occur commonly in patients with left ventricular assist devices (LVADs) and add to morbidity and mortality. It is unclear whether the outflow graft orientation can impact flow conditions leading to HRAE. This study presents a simulation-based approach using exact patient anatomy from medical images to investigate the influence of outflow cannula orientation in modulating flow conditions leading to HRAEs. METHODS: A 3D model of a proximal aorta and outflow graft was reconstructed from a computed tomography (CT) scan of an LVAD patient and virtually modified to model multiple cannula orientations (n = 10) by varying polar (cranio-caudal) (n = 5) and off-set (anterior-posterior) (n = 2) angles. Time-dependent computational flow simulations were then performed for each anatomical orientation. Qualitative and quantitative hemodynamics metrics of thrombogenicity including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell platelet activation potential (ECAP), particle residence time (PRT), and platelet activation potential (PLAP) were analyzed. RESULTS: Within the simulations performed, endothelial cell activation potential (ECAP) and particle residence time (PRT) were found to be lowest with a polar angle of 85°, regardless of offset angle. However, polar angles that produced parameters at levels least associated with thrombosis varied when the offset angle was changed from 0° to 12°. For offset angles of 0° and 12° respectively, flow shear was lowest at 65° and 75°, time averaged wall shear stress (TAWSS) was highest at 85° and 35°, and platelet activation potential (PLAP) was lowest at 65° and 45°. CONCLUSION: This study suggests that computational fluid dynamic modeling based on patient-specific anatomy can be a powerful analytical tool when identifying optimal positioning of an LVAD. Contrary to previous work, our findings suggest that there may be an "ideal" outflow cannula for each individual patient based on a CFD-based hemocompatibility profile.

Deep Learning on Multiphysical Features and Hemodynamic Modeling for Abdominal Aortic Aneurysm Growth Prediction.

Prediction of abdominal aortic aneurysm (AAA) growth is of essential importance for the early treatment and surgical intervention of AAA. Capturing key features of vascular growth, such as blood flow and intraluminal thrombus (ILT) accumulation play a crucial role in uncovering the intricated mechanism of vascular adaptation, which can ultimately enhance AAA growth prediction capabilities. However, local correlations between hemodynamic metrics, biological and morphological characteristics, and AAA growth rates present high inter-patient variability that results in that the temporal-spatial biochemical and mechanical processes are still not fully understood. Hence, this study aims to integrate the physics-based knowledge with deep learning with a patch-based convolutional neural network (CNN) approach by incorporating important multiphysical features relating to its pathogenesis for validating its impact on AAA growth prediction. For this task, we observe that the unstructured multiphysical features cannot be directly employed in the kernel-based CNN. To tackle this issue, we propose a parameterization of features to leverage the spatio-temporal relations between multiphysical features. The proposed architecture was tested on different combinations of four features including radius, intraluminal thrombus thickness, time-average wall shear stress, and growth rate from 54 patients with 5-fold cross-validation with two metrics, a root mean squared error (RMSE) and relative error (RE). We conduct extensive experiments on AAA patients, the results show the effect of leveraging multiphysical features and demonstrate the superiority of the presented architecture to previous state-of-the-art methods in AAA growth prediction.

Association of vortical structures and hemodynamic parameters for regional thrombus accumulation in abdominal aortic aneurysms.

The intraluminal thrombus (ILT) has been shown to negatively impact the progression of the abdominal aortic aneurysms (AAAs). The formation of this thrombus layer has been connected to the local flow environment within AAAs, but the specific mechanisms leading to thrombus formation are still not fully understood. Our study investigated the association between vortical structures, near-wall hemodynamic metrics (e.g., time averaged wall shear stress (TAWSS) and oscillatory shear index (OSI)), and ILT accumulation in a longitudinal cohort of 14 AAAs (53 scans total). Vortices and hemodynamic parameters were estimated using hemodynamic simulations performed to each scan of each patient and compared to local 3D changes of ILT thickness between two consecutive scans (ΔILT). Results showed that vortices formed and remained strong and close to the lumen surface in AAAs without an ILT, while in AAAs with ILTs these detached from the lumen surface and dissipated nearby wall region where an increase in ILT thickness was observed. Although low TAWSS was observed in regions with and without ILT accumulation, an inverse correlation between ∆ILT and TAWSS was observed within the regions that experienced a thrombus growth. Our results support the idea that vortical structures might be playing a role modulating ILT accumulation into specific wall regions. Also, it submits the idea that the low TAWSS will be modulating the growth of thrombus within these preferred ILT accumulated regions.

A 3D Bioprinted In Vitro Model of Pulmonary Artery Atresia to Evaluate Endothelial Cell Response to Microenvironment.

Vascular atresia are often treated via transcatheter recanalization or surgical vascular anastomosis due to congenital malformations or coronary occlusions. The cellular response to vascular anastomosis or recanalization is, however, largely unknown and current techniques rely on restoration rather than optimization of flow into the atretic arteries. An improved understanding of cellular response post anastomosis may result in reduced restenosis. Here, an in vitro platform is used to model anastomosis in pulmonary arteries (PAs) and for procedural planning to reduce vascular restenosis. Bifurcated PAs are bioprinted within 3D hydrogel constructs to simulate a reestablished intervascular connection. The PA models are seeded with human endothelial cells and perfused at physiological flow rate to form endothelium. Particle image velocimetry and computational fluid dynamics modeling show close agreement in quantifying flow velocity and wall shear stress within the bioprinted arteries. These data are used to identify regions with greatest levels of shear stress alterations, prone to stenosis. Vascular geometry and flow hemodynamics significantly affect endothelial cell viability, proliferation, alignment, microcapillary formation, and metabolic bioprofiles. These integrated in vitro-in silico methods establish a unique platform to study complex cardiovascular diseases and can lead to direct clinical improvements in surgical planning for diseases of disturbed flow.

Defining a master curve of abdominal aortic aneurysm growth and its potential utility of clinical management.

OBJECTIVE: The maximum diameter measurement of an abdominal aortic aneurysm (AAA), which depends on orthogonal and axial cross-sections or maximally inscribed spheres within the AAA, plays a significant role in the clinical decision making process. This study aims to build a total of 21 morphological parameters from longitudinal CT scans and analyze their correlations. Furthermore, this work explores the existence of a "master curve" of AAA growth, and tests which parameters serve to enhance its predictability for clinical use. METHODS: 106 CT scan images from 25 Korean AAA patients were retrospectively obtained. We subsequently computed morphological parameters, growth rates, and pair-wise correlations, and attempted to enhance the predictability of the growth for high-risk aneurysms using non-linear curve fitting and least-square minimization. RESULTS: An exponential AAA growth model was fitted to the maximum spherical diameter, as the best representative of the growth among all parameters (r-square: 0.94) and correctly predicted to 15 of 16 validation scans based on a 95% confidence interval. AAA volume expansion rates were highly correlated (r=0.75) with thrombus accumulation rates. CONCLUSIONS: The exponential growth model using spherical diameter provides useful information about progression of aneurysm size and enables AAA growth rate extrapolation during a given surveillance period.

Intraluminal thrombus effect on the progression of abdominal aortic aneurysms by using a multistate continuous-time Markov chain model.

OBJECTIVE: To investigate the relationship between the characteristics of intraluminal thrombus (ILT) with abdominal aortic aneurysm (AAA) expansion. METHODS: This retrospective clinical study applied homogeneous multistate continuous-time Markov chain models to longitudinal computed tomography (CT) data from Korean patients with AAA. Four AAA states were considered (early, mild, severe, fatal) and the maximal thickness of the ILT (maxILT), the fraction of the wall area covered by the ILT (areafrac) and the fraction of ILT volume (volfrac) were used as covariates. RESULTS: The analysis reviewed longitudinal CT images from 26 patients. Based on likelihood-ratio statistics, the areafrac was the most significant biomarker and maxILT was the second most significant. In addition, within AAAs that developed an ILT layer, the analysis found that the AAA expands relatively quickly during the early stage but the rate of expansion reduces once the AAA has reached a larger size. CONCLUSION: The results recommend surgical intervention when a patient has an areafrac more than 60%. Although this recommendation should be considered with caution given the limited sample size, physicians can use the proposed model as a tool to find such recommendations with their own data.

Patient-Specific Computational Analysis of Hemodynamics and Wall Mechanics and Their Interactions in Pulmonary Arterial Hypertension.

Vascular wall stiffness and hemodynamic parameters are potential biomechanical markers for detecting pulmonary arterial hypertension (PAH). Previous computational analyses, however, have not considered the interaction between blood flow and wall deformation. Here, we applied an established computational framework that utilizes patient-specific measurements of hemodynamics and wall deformation to analyze the coupled fluid-vessel wall interaction in the proximal pulmonary arteries (PA) of six PAH patients and five control subjects. Specifically, we quantified the linearized stiffness (E), relative area change (RAC), diastolic diameter (D), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance (R t ) and compliance (C t ) at the distal pulmonary vasculature. Results found that the average proximal PA was stiffer [median: 297 kPa, interquartile range (IQR): 202 kPa vs. median: 75 kPa, IQR: 5 kPa; P = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; P = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; P = 0.004) in PAH compared to our control group. Also, higher total resistance (R t ; median: 6.89 mmHg × min/l, IQR: 2.16 mmHg × min/l vs. median: 3.99 mmHg × min/l, IQR: 1.15 mmHg × min/l; P = 0.002) and lower total compliance (C t ; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; P = 0.041) were observed in the PAH group. Furthermore, lower TAWSS values were seen at the main PA arteries (MPAs) of PAH patients (median: 0.81 Pa, IQR: 0.47 Pa vs. median: 1.56 Pa, IQR: 0.89 Pa; P = 0.026) compared to controls. Correlation analysis within the PAH group found that E was directly correlated to the PA regurgitant flow (r = 0.84, P = 0.018) and inversely related to TAWSS (r = -0.72, P = 0.051). Results suggest that the estimated elastic modulus E may be closely related to PAH hemodynamic changes in pulmonary arteries.

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

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 CT and resistance RT 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.

Computational fluid dynamic simulation of human carotid artery bifurcation based on anatomy and volumetric blood flow rate measured with magnetic resonance imaging.

Blood flow patterns and local hemodynamic parameters have been widely associated with the onset and progression of atherosclerosis in the carotid artery. Assessment of these parameters can be performed noninvasively using cine phase-contrast (PC) magnetic resonance imaging (MRI). In addition, in the last two decades, computational fluid dynamics (CFD) simulation in three dimensional models derived from anatomic medical images has been employed to investigate the blood flow in the carotid artery. This study developed a workflow of a subject-specific CFD analysis using MRI to enhance estimating hemodynamics of the carotid artery. Time-of-flight (TOF) MRI scans were used to construct three-dimensional computational models. PC-MRI measurements were utilized to impose the boundary condition at the inlet and a 0-dimensional lumped parameter model was employed for the outflow boundary condition. The choice of different viscosity models of blood flow as a source of uncertainty was studied, by means of the axial velocity, wall shear stress, and oscillatory shear index. The sequence of workflow in CFD analysis was optimized for a healthy subject using PC-MRI. Then, a patient with carotid artery stenosis and its hemodynamic parameters were examined. The simulations indicated that the lumped parameter model used at the outlet gives physiologically reasonable values of hemodynamic parameters. Moreover, the dependence of hemodynamics parameters on the viscosity models was observed to vary for different geometries. Other factors, however, may be required for a more accurate CFD analysis, such as the segmentation and smoothness of the geometrical model, mechanical properties of the artery's wall, and the prescribed velocity profile at the inlet.

Association of Intraluminal Thrombus, Hemodynamic Forces, and Abdominal Aortic Aneurysm Expansion Using Longitudinal CT Images.

While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal computer tomography scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented.