A Monte Carlo Sensitivity Analysis for a Dimensionally Reduced-Order Model of the Aortic Dissection.

PURPOSE: Aortic dissection is associated with a high mortality rate. Although computational approaches have shed light on many aspects of the disease, a sensitivity analysis is required to determine the significance of different factors. Because of its complex geometry and high computational expense, the three-dimensional (3D) fluid-structure interaction (FSI) simulation is not a suitable approach for sensitivity analysis. METHODS: We performed a Monte Carlo simulation (MCS) to investigate the sensitivity of hemodynamic quantities to the lumped parameters of our zero-dimensional (0D) model with numerically calculated lumped parameters. We performed local and global analyses on the effect of the model parameters on important hemodynamic quantities. RESULTS: The MCS showed that a larger lumped resistance value for the false lumen and the tears result in a higher retrograde flow rate in the false lumen (the coefficient of variation, c v , i = 0.0183 , the sensitivity S X i σ = 0.54 , Spearman's coefficient, ρ s = 0.464 ). For the intraluminal pressure, our results show a significant role in the resistance and inertance of the true lumen (the coefficient of variation, c v , i = 0.0640 , the sensitivity S X i σ = 0.85 , and Spearman's coefficient, ρ s = 0.855 for the inertance of the true lumen). CONCLUSION: This study highlights the necessity of comparing the results of the local and global sensitivity analyses to understand the significance of multiple lumped parameters. Because of the efficiency of the method, our approach is potentially useful to investigate and analyze medical planning.

Using Gaussian process for velocity reconstruction after coronary stenosis applicable in positron emission particle tracking: An in-silico study.

Accurate velocity reconstruction is essential for assessing coronary artery disease. We propose a Gaussian process method to reconstruct the velocity profile using the sparse data of the positron emission particle tracking (PEPT) in a biological environment, which allows the measurement of tracer particle velocity to infer fluid velocity fields. We investigated the influence of tracer particle quantity and detection time interval on flow reconstruction accuracy. Three models were used to represent different levels of stenosis and anatomical complexity: a narrowed straight tube, an idealized coronary bifurcation with stenosis, and patient-specific coronary arteries with a stenotic left circumflex artery. Computational fluid dynamics (CFD), particle tracking, and the Gaussian process of kriging were employed to simulate and reconstruct the pulsatile flow field. The study examined the error and uncertainty in velocity profile reconstruction after stenosis by comparing particle-derived flow velocity with the CFD solution. Using 600 particles (15 batches of 40 particles) released in the main coronary artery, the time-averaged error in velocity reconstruction ranged from 13.4% (no occlusion) to 161% (70% occlusion) in patient-specific anatomy. The error in maximum cross-sectional velocity at peak flow was consistently below 10% in all cases. PEPT and kriging tended to overestimate area-averaged velocity in higher occlusion cases but accurately predicted maximum cross-sectional velocity, particularly at peak flow. Kriging was shown to be useful to estimate the maximum velocity after the stenosis in the absence of negative near-wall velocity.

A systematic review of cardiac in-silico clinical trials.

Computational models of the heart are now being used to assess the effectiveness and feasibility of interventions through in-silico clinical trials (ISCTs). As the adoption and acceptance of ISCTs increases, best practices for reporting the methodology and analysing the results will emerge. Focusing in the area of cardiology, we aim to evaluate the types of ISCTs, their analysis methods and their reporting standards. To this end, we conducted a systematic review of cardiac ISCTs over the period of 1 January 2012-1 January 2022, following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). We considered cardiac ISCTs of human patient cohorts, and excluded studies of single individuals and those in which models were used to guide a procedure without comparing against a control group. We identified 36 publications that described cardiac ISCTs, with most of the studies coming from the US and the UK. In 75% of the studies, a validation step was performed, although the specific type of validation varied between the studies. ANSYS FLUENT was the most commonly used software in 19% of ISCTs. The specific software used was not reported in 14% of the studies. Unlike clinical trials, we found a lack of consistent reporting of patient demographics, with 28% of the studies not reporting them. Uncertainty quantification was limited, with sensitivity analysis performed in only 19% of the studies. In 97% of the ISCTs, no link was provided to provide easy access to the data or models used in the study. There was no consistent naming of study types with a wide range of studies that could potentially be considered ISCTs. There is a clear need for community agreement on minimal reporting standards on patient demographics, accepted standards for ISCT cohort quality control, uncertainty quantification, and increased model and data sharing.

Using a reduced-order model to investigate the effect of the heart rate on the aortic dissection.

The computational cost of a three-dimensional (3D) fluid-structure interaction (FSI) simulation of a dissected aorta has prevented researchers from investigating the effect of a wide range of the heart rate on the hemodynamic quantities in the disease. We have presented a systematic procedure to develop a zero-dimensional (0D) model for a dissected aorta. A series of numerical experiments were used to calculate the values for the resistance, inertance, and compliance of each lumen with irregular geometries. Having validated the results from the 0D model against those from the 3D model for one heart rate, we used the 0D model to investigate the effect of the heart rate of 50-150 bpm on the flow rates and the pressures in an idealized geometry of an aortic dissection. The 0D model showed acceptable accuracy when compared with the 3D FSI simulation. For instance, at peak systole, 7.18% relative error in the flow rate in the true lumen was observed for 0D and 3D simulations. The flow rate in the true lumen showed a stronger dependency on the heart rate, that is, 300% for the true lumen and 1.5% for the false lumen. The pressure difference between the lumina increased non-monotonically as the heart beats faster. Because of its efficiency, the reported procedure can be used for uncertainty and sensitivity analysis of the hemodynamic quantities in a diseased aorta with complex geometries such as that of the aortic dissection.

Multiscale modeling of a modified Blalock-Taussig surgery in a patient-specific tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a congenital heart anomaly that causes a drastic reduction in the oxygen level. In this study, we coupled a lumped-parameter model with a patient-specific three-dimensional (3D) model which included a modified Blalock-Taussig (MBT) shunt. By forming a closed loop, we investigated the effects of certain parameters on the flow rates and the pressures at different locations of the developed network. A local sensitivity analysis on an initial zero-dimensional (0D) closed-loop model was conducted. The 0D lumped parameter (LP) model was then refined based on the results of the multiscale 0D-3D model and the local sensitivity analysis was repeated for the refined 0D model. It was shown that the maximum pressure of the pulmonary bed had the highest sensitivity of 94% to the diameter of MBT shunt. We observed that the existence of the flow in the shunt during the diastole caused an elevated wall shear stress (WSS) in the pulmonary artery. In this work, we calculated the flow velocity and pressure field in a 3D patient-specific aorta with an MBT shunt, and then we used the results to increase the accuracy of our LP model to simulate numerous 0D simulations in a significantly shorter time, which is potentially applicable for medical decision-making.

Functional reservoir microcapsules generated via microfluidic fabrication for long-term cardiovascular therapeutics.

Cardiovascular disease is a chronic disease that leads to impaired cardiac function and requires long-term management to control its progression. Despite the importance of hydrogels for therapeutic applications, a contradiction between the size of a hydrogel and the amount of loaded drug has been encountered when using conventional fabrication methods. In this study, biocompatible reservoir microcapsules (diameter ∼100 µm) with a large liquid core and polymeric shell were fabricated via a one-step phase separation of poly(ethylene glycol)diacrylate (PEGDA) and dextran within pre-gel droplets through microfluidics. By controlling the process of phase separation, high drug-loading efficiency (∼80%) for long-term release (30 days) of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was achieved. Drug molecules were dispersed within the liquid core at a concentration above saturation solubility for sustained delivery via regulation of the shells. Effective therapeutic enhancement of human umbilical vein endothelial cell (HUVEC) and umbilical artery smooth muscle cell (SMC) proliferation and tube formation in vitro promoted rapid cell proliferation and increased the number of migrated cells by ∼1.7 times. Moreover, in vivo blood vessel regeneration for cardiovascular control induced by sustained dual-drug (VEGF and PDGF) delivery to the rat heart was achieved, showing the effectiveness of long-term protein delivery in improving cardiac function and significantly reducing ventricular wall thickness and fibrosis of the infarct region. The ratio of heart tissue scarring was reduced to 11.2% after microcapsule treatment compared with 21.4% after saline treatment in the rat model. By using these reservoir microcapsules, similar sustained delivery of proteins, mRNAs and biologic drugs could be developed for the treatment of a range of long-term chronic diseases and regenerative medicine.

The effect of the entry and re-entry size in the aortic dissection: a two-way fluid-structure interaction simulation.

Aortic dissection (AD) is one of the most catastrophic cardiovascular diseases. AD occurs when a layer inside the aorta is disrupted and gives rise to the formation of a true lumen and a false lumen. These lumens can be connected through tears in the intimal flap which are known as entries. Despite being known for about two centuries, the effects of many factors on the morbidity and mortality of this disease are still unknown. As the blood interaction with the aorta is crucial in the severity and the progression of the aortic dissection, a biomechanical approach is chosen to investigate the influence of different morphologies on the severity of this disease. Using the finite element method (FEM) and the fluid-structure interaction (FSI) approach, we have evaluated the blood flow characteristics along the diseased aorta, in conjunction with the deformation of the aortic wall. In this study, an idealized geometry of a dissected descending aorta (type B) with two entries has been studied. The values for the diameter of the entry tear were chosen to be 5 mm and 10 mm. Therefore, a total of four conditions were investigated. According to our results, the retrograde flow through the proximal tear is dependent on the size of the distal re-entry and vice versa. Our results revealed that when both entry and re-entry tears are 10 mm in diameter, the flow passes through the true and false lumens with smaller resistance, resulting in a smaller flutter of the intimal flap, and therefore more stable intimal flap. Major oscillation frequencies of 2.5 Hz and 7.4 Hz were observed for the oscillation of the intimal flap, and amplitudes of the waves with higher frequencies were negligible.