Alison L. Marsden

Luca Pegolotti, Martin R. Pfaller, Natalia L. Rubio et al.

Reduced-order models based on physics are a popular choice in cardiovascular modeling due to their efficiency, but they may experience reduced accuracy when working with anatomies that contain numerous junctions or pathological conditions. We develop one-dimensional reduced-order models that simulate blood flow dynamics using a graph neural network trained on three-dimensional hemodynamic simulation data. Given the initial condition of the system, the network iteratively predicts the pressure and flow rate at the vessel centerline nodes. Our numerical results demonstrate the accuracy and generalizability of our method in physiological geometries comprising a variety of anatomies and boundary conditions. Our findings demonstrate that our approach can achieve errors below 2% and 3% for pressure and flow rate, respectively, provided there is adequate training data. As a result, our method exhibits superior performance compared to physics-based one-dimensional models, while maintaining high efficiency at inference time.

Matteo Salvador, Alison Lesley Marsden

We introduce Branched Latent Neural Maps (BLNMs) to learn finite dimensional input-output maps encoding complex physical processes. A BLNM is defined by a simple and compact feedforward partially-connected neural network that structurally disentangles inputs with different intrinsic roles, such as the time variable from model parameters of a differential equation, while transferring them into a generic field of interest. BLNMs leverage latent outputs to enhance the learned dynamics and break the curse of dimensionality by showing excellent generalization properties with small training datasets and short training times on a single processor. Indeed, their generalization error remains comparable regardless of the adopted discretization during the testing phase. Moreover, the partial connections significantly reduce the number of tunable parameters. We show the capabilities of BLNMs in a challenging test case involving electrophysiology simulations in a biventricular cardiac model of a pediatric patient with hypoplastic left heart syndrome. The model includes a 1D Purkinje network for fast conduction and a 3D heart-torso geometry. Specifically, we trained BLNMs on 150 in silico generated 12-lead electrocardiograms (ECGs) while spanning 7 model parameters, covering cell-scale and organ-level. Although the 12-lead ECGs manifest very fast dynamics with sharp gradients, after automatic hyperparameter tuning the optimal BLNM, trained in less than 3 hours on a single CPU, retains just 7 hidden layers and 19 neurons per layer. The resulting mean square error is on the order of $10^{-4}$ on a test dataset comprised of 50 electrophysiology simulations. In the online phase, the BLNM allows for 5000x faster real-time simulations of cardiac electrophysiology on a single core standard computer and can be used to solve inverse problems via global optimization in a few seconds of computational time.

Chloe H. Choi, Alison L. Marsden, Daniele E. Schiavazzi

Boundary condition tuning is a fundamental step in patient-specific cardiovascular modeling. Despite an increase in offline training cost, recent methods in data-driven variational inference can efficiently estimate the joint posterior distribution of boundary conditions, with amortization of training efforts over clinical targets. However, even the most modern approaches fall short in two important scenarios: open-loop models with known mean flow and assumed waveform shapes, and anatomies affected by vascular lesions where segmentation influences the reachability of pressure or flow split targets. In both cases, boundary conditions cannot be tuned in isolation. We introduce a general amortized inference framework based on probabilistic flow that treats clinical targets, inflow features, and point cloud embeddings of patient-specific anatomies as either conditioning variables or quantities to be jointly estimated. We demonstrate the approach on two patient-specific models: an aorto-iliac bifurcation with varying stenosis locations and severity, and a coronary arterial tree.

Natalia L. Rubio, Eric F. Darve, Alison L. Marsden · stanford

Physics-based 0D reduced-order models provide computationally lightweight predictions of cardiovascular flows, resolving bulk hemodynamics in fractions of a second that would take days to solve using traditional 3D finite-element techniques. However, the accuracy of 0D models is limited as a result of the dramatic simplifications made in their derivations. In this work, we use 0D parameters learned from high-fidelity 3D data to improve 0D model accuracy without sacrificing its low computational cost or interpretability. We use the resistor-quadratic resistor-inductor (RRI) model to predict pressure drops over 0D vessels and bifurcations, where the resistances and inductance (0D parameters) are predicted from the bifurcation or vessel geometry using neural networks trained on high-fidelity 3D simulations. We validate the hybrid physics-based data-driven framework in three types of patient-specific vasculature - aortic, aortofemoral, and pulmonary anatomies. Use of learned 0D parameters reduces error by at least 50% compared to baseline 0D parameters across all anatomical cohorts. The improvements are especially marked for the more complex pulmonary anatomies, where 0D models with learned parameters reduced error from 30% to 7%. Exclusion of the quadratic resistor in the RRI model improved convergence compared to using the full RRI model. The resulting hybrid model presents a means of real-time (personal laptop runtime of <2 seconds for the most complex pulmonary anatomies), interpretable, and accurate cardiovascular flow modeling, enabling digital twins that support clinical decision-making as well as cardiovascular science and engineering research.

Fanwei Kong, Sascha Stocker, Perry S. Choi et al.

Congenital heart disease (CHD) encompasses a spectrum of cardiovascular structural abnormalities, often requiring customized treatment plans for individual patients. Computational modeling and analysis of these unique cardiac anatomies can improve diagnosis and treatment planning and may ultimately lead to improved outcomes. Deep learning (DL) methods have demonstrated the potential to enable efficient treatment planning by automating cardiac segmentation and mesh construction for patients with normal cardiac anatomies. However, CHDs are often rare, making it challenging to acquire sufficiently large patient cohorts for training such DL models. Generative modeling of cardiac anatomies has the potential to fill this gap via the generation of virtual cohorts; however, prior approaches were largely designed for normal anatomies and cannot readily capture the significant topological variations seen in CHD patients. Therefore, we propose a type- and shape-disentangled generative approach suitable to capture the wide spectrum of cardiac anatomies observed in different CHD types and synthesize differently shaped cardiac anatomies that preserve the unique topology for specific CHD types. Our DL approach represents generic whole heart anatomies with CHD type-specific abnormalities implicitly using signed distance fields (SDF) based on CHD type diagnosis, which conveniently captures divergent anatomical variations across different types and represents meaningful intermediate CHD states. To capture the shape-specific variations, we then learn invertible deformations to morph the learned CHD type-specific anatomies and reconstruct patient-specific shapes. Our approach has the potential to augment the image-segmentation pairs for rarer CHD types for cardiac segmentation and generate cohorts of CHD cardiac meshes for computational simulation.

Matteo Salvador, Alison L. Marsden

Scientific Machine Learning (ML) is gaining momentum as a cost-effective alternative to physics-based numerical solvers in many engineering applications. In fact, scientific ML is currently being used to build accurate and efficient surrogate models starting from high-fidelity numerical simulations, effectively encoding the parameterized temporal dynamics underlying Ordinary Differential Equations (ODEs), or even the spatio-temporal behavior underlying Partial Differential Equations (PDEs), in appropriately designed neural networks. We propose an extension of Latent Dynamics Networks (LDNets), namely Liquid Fourier LDNets (LFLDNets), to create parameterized space-time surrogate models for multiscale and multiphysics sets of highly nonlinear differential equations on complex geometries. LFLDNets employ a neurologically-inspired, sparse, liquid neural network for temporal dynamics, relaxing the requirement of a numerical solver for time advancement and leading to superior performance in terms of tunable parameters, accuracy, efficiency and learned trajectories with respect to neural ODEs based on feedforward fully-connected neural networks. Furthermore, in our implementation of LFLDNets, we use a Fourier embedding with a tunable kernel in the reconstruction network to learn high-frequency functions better and faster than using space coordinates directly as input. We challenge LFLDNets in the framework of computational cardiology and evaluate their capabilities on two 3-dimensional test cases arising from multiscale cardiac electrophysiology and cardiovascular hemodynamics. This paper illustrates the capability to run Artificial Intelligence-based numerical simulations on single or multiple GPUs in a matter of minutes and represents a significant step forward in the development of physics-informed digital twins.

Bozhi Sun, Seda Tierney, Jeffrey A. Feinstein et al.

Scheduling echocardiographic exams in a hospital presents significant challenges due to non-deterministic factors (e.g., patient no-shows, patient arrival times, diverse exam durations, etc.) and asymmetric resource constraints between fetal and non-fetal patient streams. To address these challenges, we first conducted extensive pre-processing on one week of operational data from the Echo Laboratory at Stanford University's Lucile Packard Children's Hospital, to estimate patient no-show probabilities and derive empirical distributions of arrival times and exam durations. Based on these inputs, we developed a discrete-event stochastic simulation model using SimPy, and integrate it with the open source Gymnasium Python library. As a baseline for policy optimization, we developed a comparative framework to evaluate on-the-fly versus reservation-based allocation strategies, in which different proportions of resources are reserved in advance. Considering a hospital configuration with a 1:6 ratio of fetal to non-fetal rooms and a 4:2 ratio of fetal to non-fetal sonographers, we show that on-the-fly allocation generally yields better performance, more effectively adapting to patient variability and resource constraints. Building on this foundation, we apply reinforcement learning (RL) to derive an approximated optimal dynamic allocation policy. This RL-based policy is benchmarked against the best-performing rule-based strategies, allowing us to quantify their differences and provide actionable insights for improving echo lab efficiency through intelligent, data-driven resource management.

Elena Martinez, Beatrice Moscoloni, Matteo Salvador et al.

Combining physics-based modeling with data-driven methods is critical to enabling the translation of computational methods to clinical use in cardiology. The use of rigorous differential equations combined with machine learning tools allows for model personalization with uncertainty quantification in time frames compatible with clinical practice. However, accurate and efficient surrogate models of cardiac function, built from physics-based numerical simulation, are still mostly geometry-specific and require retraining for different patients and pathological conditions. We propose a novel computational pipeline to embed cardiac anatomies into full-field surrogate models. We generate a dataset of electrophysiology simulations using a complex multi-scale mathematical model coupling partial and ordinary differential equations. We adopt Branched Latent Neural Maps (BLNMs) as an effective scientific machine learning method to encode activation maps extracted from physics-based numerical simulations into a neural network. Leveraging large deformation diffeomorphic metric mappings, we build a biventricular anatomical atlas and parametrize the anatomical variability of a small and challenging cohort of 13 pediatric patients affected by Tetralogy of Fallot. We propose a novel statistical shape modeling based z-score sampling approach to generate a new synthetic cohort of 52 biventricular geometries that are compatible with the original geometrical variability. This synthetic cohort acts as the training set for BLNMs. Our surrogate model demonstrates robustness and great generalization across the complex original patient cohort, achieving an average adimensional mean squared error of 0.0034. The Python implementation of our BLNM model is publicly available under MIT License at https://github.com/StanfordCBCL/BLNM.

Chloe H. Choi, Andrea Zanoni, Daniele E. Schiavazzi et al.

Solving inverse problems in cardiovascular modeling is particularly challenging due to the high computational cost of running high-fidelity simulations. In this work, we focus on Bayesian parameter estimation and explore different methods to reduce the computational cost of sampling from the posterior distribution by leveraging low-fidelity approximations. A common approach is to construct a surrogate model for the high-fidelity simulation itself. Another is to build a surrogate for the discrepancy between high- and low-fidelity models. This discrepancy, which is often easier to approximate, is modeled with either a fully connected neural network or a nonlinear dimensionality reduction technique that enables surrogate construction in a lower-dimensional space. A third possible approach is to treat the discrepancy between the high-fidelity and surrogate models as random noise and estimate its distribution using normalizing flows. This allows us to incorporate the approximation error into the Bayesian inverse problem by modifying the likelihood function. We validate five different methods which are variations of the above on analytical test cases by comparing them to posterior distributions derived solely from high-fidelity models, assessing both accuracy and computational cost. Finally, we demonstrate our approaches on two cardiovascular examples of increasing complexity: a lumped-parameter Windkessel model and a patient-specific three-dimensional anatomy.

Natalia L. Rubio, Eric F. Darve, Alison L. Marsden

Three-dimensional (3D) finite-element simulations of cardiovascular flows provide high-fidelity predictions to support cardiovascular medicine, but their high computational cost limits clinical practicality. Reduced-order models (ROMs) offer computationally efficient alternatives but suffer reduced accuracy, particularly at vessel bifurcations where complex flow physics are inadequately captured by standard Poiseuille flow assumptions. We present an enhanced numerical framework that integrates machine learning-predicted bifurcation coefficients into zero-dimensional (0D) hemodynamic ROMs to improve accuracy while maintaining computational efficiency. We develop a resistor-resistor-inductor (RRI) model that uses neural networks to predict pressure-flow relationships from bifurcation geometry, incorporating linear and quadratic resistances along with inductive effects. The method employs non-dimensionalization to reduce training data requirements and apriori flow split prediction for improved bifurcation characterization. We incorporate the RRI model into a 0D model using an optimization-based solution strategy. We validate the approach in isolated bifurcations and vascular trees, across Reynolds numbers from 0 to 5,500, defining ROM accuracy by comparison to 3D finite element simulation. Results demonstrate substantial accuracy improvements: averaged across all trees and Reynolds numbers, the RRI method reduces inlet pressure errors from 54 mmHg (45%) for standard 0D models to 25 mmHg (17%), while a simplified resistor-inductor (RI) variant achieves 31 mmHg (26%) error. The enhanced 0D models show particular effectiveness at high Reynolds numbers and in extensive vascular networks. This hybrid numerical approach enables accurate, real-time hemodynamic modeling for clinical decision support, uncertainty quantification, and digital twins in cardiovascular biomedical engineering.

Riccardo Tenderini, Luca Pegolotti, Fanwei Kong et al.

This work introduces AD-SVFD, a deep learning model for the deformable registration of vascular shapes to a pre-defined reference and for the generation of synthetic anatomies. AD-SVFD operates by representing each geometry as a weighted point cloud and models ambient space deformations as solutions at unit time of ODEs, whose time-independent right-hand sides are expressed through artificial neural networks. The model parameters are optimized by minimizing the Chamfer Distance between the deformed and reference point clouds, while backward integration of the ODE defines the inverse transformation. A distinctive feature of AD-SVFD is its auto-decoder structure, that enables generalization across shape cohorts and favors efficient weight sharing. In particular, each anatomy is associated with a low-dimensional code that acts as a self-conditioning field and that is jointly optimized with the network parameters during training. At inference, only the latent codes are fine-tuned, substantially reducing computational overheads. Furthermore, the use of implicit shape representations enables generative applications: new anatomies can be synthesized by suitably sampling from the latent space and applying the corresponding inverse transformations to the reference geometry. Numerical experiments, conducted on healthy aortic anatomies, showcase the high-quality results of AD-SVFD, which yields extremely accurate approximations at competitive computational costs.

A. Kontogiannis, P. Nair, M. Loecher et al.

We solve a Bayesian inverse Reynolds-averaged Navier-Stokes (RANS) problem that assimilates mean flow data by jointly reconstructing the mean flow field and learning its unknown RANS parameters. We devise an algorithm that learns the most likely parameters of an algebraic effective viscosity model, and estimates their uncertainties, from mean flow data of a turbulent flow. We conduct a flow MRI experiment to obtain mean flow data of a confined turbulent jet in an idealized medical device known as the FDA (Food and Drug Administration) nozzle. The algorithm successfully reconstructs the mean flow field and learns the most likely turbulence model parameters without overfitting. The methodology accepts any turbulence model, be it algebraic (explicit) or multi-equation (implicit), as long as the model is differentiable, and naturally extends to unsteady turbulent flows.

Gabriel Maher, Casey Fleeter, Daniele Schiavazzi et al.

We propose a novel approach to generate samples from the conditional distribution of patient-specific cardiovascular models given a clinically aquired image volume. A convolutional neural network architecture with dropout layers is first trained for vessel lumen segmentation using a regression approach, to enable Bayesian estimation of vessel lumen surfaces. This network is then integrated into a path-planning patient-specific modeling pipeline to generate families of cardiovascular models. We demonstrate our approach by quantifying the effect of geometric uncertainty on the hemodynamics for three patient-specific anatomies, an aorto-iliac bifurcation, an abdominal aortic aneurysm and a sub-model of the left coronary arteries. A key innovation introduced in the proposed approach is the ability to learn geometric uncertainty directly from training data. The results show how geometric uncertainty produces coefficients of variation comparable to or larger than other sources of uncertainty for wall shear stress and velocity magnitude, but has limited impact on pressure. Specifically, this is true for anatomies characterized by small vessel sizes, and for local vessel lesions seen infrequently during network training.

Jameson Merkow, David Kriegman, Alison Marsden et al.

In this work, we present a novel 3D-Convolutional Neural Network (CNN) architecture called I2I-3D that predicts boundary location in volumetric data. Our fine-to-fine, deeply supervised framework addresses three critical issues to 3D boundary detection: (1) efficient, holistic, end-to-end volumetric label training and prediction (2) precise voxel-level prediction to capture fine scale structures prevalent in medical data and (3) directed multi-scale, multi-level feature learning. We evaluate our approach on a dataset consisting of 93 medical image volumes with a wide variety of anatomical regions and vascular structures. In the process, we also introduce HED-3D, a 3D extension of the state-of-the-art 2D edge detector (HED). We show that our deep learning approach out-performs, the current state-of-the-art in 3D vascular boundary detection (structured forests 3D), by a large margin, as well as HED applied to slices, and HED-3D while successfully localizing fine structures. With our approach, boundary detection takes about one minute on a typical 512x512x512 volume.