Importance of localized dilatation and distensibility in identifying determinants of thoracic aortic aneurysm with neural operators

Thoracic aortic aneurysms (TAAs) arise from diverse mechanical and mechanobiological disruptions to the aortic wall that increase the risk of dissection or rupture. Evidence links TAA development to dysfunctions in the aortic mechanotransduction axis, including loss of elastic fiber integrity and cell-matrix connections. Because distinct insults create different mechanical vulnerabilities, there is a critical need to identify interacting factors that drive progression. Here, we use a finite element framework to generate synthetic TAAs from hundreds of heterogeneous insults spanning varying degrees of elastic fiber damage and impaired mechanosensing. From these simulations, we construct spatial maps of localized dilatation and distensibility to train neural networks that predict the initiating combined insult. We compare several architectures (Deep Operator Networks, UNets, and Laplace Neural Operators) and multiple input data formats to define a standard for future subject-specific modeling. We also quantify predictive performance when networks are trained using only geometric data (dilatation) versus both geometric and mechanical data (dilatation plus distensibility). Across all networks, prediction errors are significantly higher when trained on dilatation alone, underscoring the added value of distensibility information. Among the tested models, UNet consistently provides the highest accuracy across all data formats. These findings highlight the importance of acquiring full-field measurements of both dilatation and distensibility in TAA assessment to reveal the mechanobiological drivers of disease and support the development of personalized treatment strategies.

Neural operator learning of heterogeneous mechanobiological insults contributing to aortic aneurysms

Thoracic aortic aneurysm (TAA) is a localized dilatation of the aorta resulting from compromised wall composition, structure, and function, which can lead to life-threatening dissection or rupture. Several genetic mutations and predisposing factors that contribute to TAA have been studied in mouse models to characterize specific changes in aortic microstructure and material properties that result from a wide range of mechanobiological insults. Assessments of TAA progression in vivo is largely limited to measurements of aneurysm size and growth rate. It has been shown that aortic geometry alone is not sufficient to predict the patient-specific progression of TAA but computational modeling of the evolving biomechanics of the aorta could predict future geometry and properties from initiating insults. In this work, we present an integrated framework to train a deep operator network (DeepONet)-based surrogate model to identify contributing factors for TAA by using FE-based datasets of aortic growth and remodeling resulting from prescribed insults. For training data, we investigate multiple types of TAA risk factors and spatial distributions within a constrained mixture model to generate axial--azimuthal maps of aortic dilatation and distensibility. The trained network is then capable of predicting the initial distribution and extent of the insult from a given set of dilatation and distensibility information. Two DeepONet frameworks are proposed, one trained on sparse information and one on full-field grayscale images, to gain insight into a preferred neural operator-based approach. Performance of the surrogate models is evaluated through multiple simulations carried out on insult distributions varying from fusiform to complex. We show that the proposed approach can predict patient-specific mechanobiological insult profile with a high accuracy, particularly when based on full-field images.