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.

Computational modelling of multi-temporal ventricular-vascular interactions during the progression of pulmonary arterial hypertension.

A computational framework is developed to consider the concurrent growth and remodelling (G&R) processes occurring in the large pulmonary artery (PA) and right ventricle (RV), as well as ventricular-vascular interactions during the progression of pulmonary arterial hypertension (PAH). This computational framework couples the RV and the proximal PA in a closed-loop circulatory system that operates in a short timescale of a cardiac cycle, and evolves over a long timescale due to G&R processes in the PA and RV. The framework predicts changes in haemodynamics (e.g. 68.2% increase in mean PA pressure), RV geometry (e.g. 38% increase in RV end-diastolic volume) and PA tissue microstructure (e.g. 90% increase in collagen mass) that are consistent with clinical and experimental measurements of PAH. The framework also predicts that a reduction in RV contractility is associated with long-term RV chamber dilation, a common biomarker observed in the late-stage PAH. Sensitivity analyses on the G&R rate constants show that large PA stiffening (both short and long term) is affected by RV remodelling more than the reverse. This framework can serve as a foundation for the future development of a more predictive and comprehensive cardiovascular G&R model with realistic heart and vascular geometries.

Machine learning approaches to surrogate multifidelity Growth and Remodeling models for efficient abdominal aortic aneurysmal applications.

Computational Growth and Remodeling (G&R) models have been widely used to capture the pathological development of arterial diseases and have shown promise for aiding clinical diagnosis, prognosis prediction, and staging classification. However, due to the high complexity of the arterial adaptation mechanism, high-fidelity arterial G&R simulation usually takes hours or even days, which hinders its application in clinical practice. To remedy this problem, we develop a computationally efficient arterial G&R simulation framework that comprehensively combines the physics-based G&R simulations and data-driven machine learning approaches. The proposed framework greatly enhances the computational efficiency of arterial G&R simulations, thereby enabling more time-consuming arterial applications, including personalized parameter estimation and arterial disease progression prediction. In particular, we achieve significant computational cost reduction mainly through two methods: (1) constructing a Multifidelity Surrogate (MFS) to approximate multifidelity G&R simulations by using a cokriging approach and (2) developing a novel iterative optimization algorithm for personalized parameter estimation. The proposed framework is demonstrated by estimating G&R model parameters and predicting individual aneurysm growth using follow-up CT images of Abdominal Aortic Aneurysms (AAAs) from 21 patients. Results show that the personalized parameters are satisfactorily estimated and the growth of AAAs is predicted within the clinically relevant time frame, i.e., less than 2 h, without a loss of accuracy.

Inverse modeling framework for characterizing patient-specific microstructural changes in the pulmonary arteries.

Microstructural changes in the pulmonary arteries associated with pulmonary arterial hypertension (PAH) is not well understood and characterized in humans. To address this issue, we developed and applied a patient-specific inverse finite element (FE) modeling framework to characterize mechanical and structural changes of the micro-constituents in the proximal pulmonary arteries using in-vivo pressure measurements and magnetic resonance images. The framework was applied using data acquired from a pediatric PAH patient and a heart transplant patient with normal pulmonary arterial pressure, which serves as control. Parameters of a constrained mixture model that are associated with the structure and mechanical properties of elastin, collagen fibers and smooth muscle cells were optimized to fit the patient-specific pressure-diameter responses of the main pulmonary artery. Based on the optimized parameters, individual stress and linearized stiffness resultants of the three tissue constituents, as well as their aggregated values, were estimated in the pulmonary artery. Aggregated stress resultant and stiffness are, respectively, 4.6 and 3.4 times higher in the PAH patient than the control subject. Stress and stiffness resultants of each tissue constituent are also higher in the PAH patient. Specifically, the mean stress resultant is highest in elastin (PAH: 69.96, control: 14.42 kPa-mm), followed by those in smooth muscle cell (PAH: 13.95, control: 4.016 kPa-mm) and collagen fibers (PAH: 13.19, control: 2.908 kPa-mm) in both the PAH patient and the control subject. This result implies that elastin may be the key load-bearing constituent in the pulmonary arteries of the PAH patient and the control subject.

Mitochondrial AOX Supports Redox Balance of Photosynthetic Electron Transport, Primary Metabolite Balance, and Growth in Arabidopsis thaliana under High Light.

When leaves receive excess light energy, excess reductants accumulate in chloroplasts. It is suggested that some of the reductants are oxidized by the mitochondrial respiratory chain. Alternative oxidase (AOX), a non-energy conserving terminal oxidase, was upregulated in the photosynthetic mutant of Arabidopsis thaliana, pgr5, which accumulated reductants in chloroplast stroma. AOX is suggested to have an important role in dissipating reductants under high light (HL) conditions, but its physiological importance and underlying mechanisms are not yet known. Here, we compared wild-type (WT), pgr5, and a double mutant of AOX1a-knockout plant (aox1a) and pgr5 (aox1a/pgr5) grown under high- and low-light conditions, and conducted physiological analyses. The net assimilation rate (NAR) was lower in aox1a/pgr5 than that in the other genotypes at the early growth stage, while the leaf area ratio was higher in aox1a/pgr5. We assessed detailed mechanisms in relation to NAR. In aox1a/pgr5, photosystem II parameters decreased under HL, whereas respiratory O2 uptake rates increased. Some intermediates in the tricarboxylic acid (TCA) cycle and Calvin cycle decreased in aox1a/pgr5, whereas γ-aminobutyric acid (GABA) and N-rich amino acids increased in aox1a/pgr5. Under HL, AOX may have an important role in dissipating excess reductants to prevent the reduction of photosynthetic electron transport and imbalance in primary metabolite levels.

Patient-Specific Prediction of Abdominal Aortic Aneurysm Expansion Using Bayesian Calibration.

Translating recent advances in abdominal aortic aneurysm (AAA) growth and remodeling (G&R) knowledge into a predictive, patient-specific clinical treatment tool requires a major paradigm shift in computational modeling. The objectives of this study are to develop a prediction framework that first calibrates the physical AAA G&R model using patient-specific serial computed tomography (CT) scan images, predicts the expansion of an AAA in the future, and quantifies the associated uncertainty in the prediction. We adopt a Bayesian calibration method to calibrate parameters in the G&R computational model and predict the magnitude of AAA expansion. The proposed Bayesian approach can take different sources of uncertainty; therefore, it is well suited to achieve our aims in predicting the AAA expansion process as well as in computing the propagated uncertainty. We demonstrate how to achieve the proposed aims by solving the formulated Bayesian calibration problems for cases with the synthetic G&R model output data and real medical patient-specific CT data. We compare and discuss the performance of predictions and computation time under different sampling cases of the model output data and patient data, both of which are simulated by the G&R computation. Furthermore, we apply our Bayesian calibration to real patient-specific serial CT data and validate our prediction. The accuracy and efficiency of the proposed method is promising, which appeals to computational and medical communities.

High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling.

While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular-arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure-volume loop, (2) aorta pressure-diameter relationship, (3) pressure-waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles.