Papers

Computational head models are typically applied to isolated impacts, leaving repeated head loading largely unexplored. An Ogden-Roxburgh Mullins damage formulation was implemented in a high-fidelity finite element head model to represent loading-history-dependent softening during cyclic brain-tissue deformation. Repeated-loading histories derived from mixed martial arts head-impact data were applied and compared with damage-free hyperelastic (HE) and linear visco-hyperelastic (LVHE) model variants. Under five identical single-axis cycles, Mullins-type softening progressively increased strain and strain rate metrics relative to the HE model. Mullins-based injury probabilities progressively exceeded strain-based HE predictions and diverged from unchanged kinematics-based predictions, indicating that neglecting prior softening may underestimate injury risk. In a randomized twenty-cycle multiaxial sequence, cycles of similar kinematic intensity produced different deformation and injury-risk estimates depending on prior softening. HE and LVHE models predicted higher injury probabilities initially, whereas the Mullins-based model produced the largest later-cycle estimates and highest probability of at least one injury over the sequence. Regional amplification depended on loading direction and prior softening, with no direction-independent trend among brain substructures. Gyral elements exhibited higher cumulative maximum principal strain than sulcal elements, which showed greater amplification relative to initial responses. These findings demonstrate that short-term damage-mediated softening can substantially amplify tissue deformation and injury-risk estimates beyond damage-free head models under the same loading histories. Further experimental characterization of cyclic brain-tissue softening is needed to improve models of repeated head loading and traumatic brain injury.

Cardiac digital twin research is moving from subject-specific anatomical replicas toward virtual cohorts that represent clinically relevant population subgroups. Yet access to representative imaging-derived anatomy datasets remains limited by cohort size, subgroup sparsity, and data-sharing constraints. Conditional generative models could help address this gap, but virtual cohorts are useful only if they preserve realistic, metadata-dependent anatomical variability. Existing cardiac anatomy generators largely rely on conditional variational autoencoders (cVAEs), which couple representation learning and metadata conditioning through a shared regularized latent prior. We introduce CAN-FLOW, a two-step Conditional ANatomy generation framework based on normalizing FLOWs that first learns geometry-only latent representations of diffeomorphic cardiac shape momenta and then models their sex-, age-, and body-mass-index-dependent distribution with a conditional normalizing flow. We trained CAN-FLOW on 2,208 healthy UK Biobank subjects and compared it with cVAEs across regularization strengths. CAN-FLOW generated plausible stochastic biventricular anatomies that better reproduced clinical phenotype distributions, metadata-dependent trends, subgroup variability, point-cloud coverage, and high-dimensional shape variability. Together, these results establish CAN-FLOW as a shareable framework for generating realistic, stochastically varying, metadata-conditioned biventricular anatomies for virtual cohort construction and in silico clinical trial workflows.

We forecast clot growth from sparse early measurements with incomplete biochemical information. Using 1,000 simulated trajectories, we compare inverse search, which weights candidate inputs by their agreement with early observations, with a direct multilayer perceptron (MLP) predicting future clot size. Inverse search is more accurate when tissue factor alone, or tissue factor and fibrinogen, are unknown. When all five inputs are unknown, direct prediction achieves 2.16% pooled relative $L_2$ forecast error, outperforming search with 8,192 candidates using a forward MLP (3.25%) or latent neural ordinary differential equation model (3.36%). A conditional error bound separates candidate disagreement, weight on poor early fits, surrogate error, and candidate coverage. Increasing randomized quasi-Monte Carlo candidate budgets from 512 to 32,768 reduces numerical variation. A covariance score ranks additional assays by expected forecast value while accounting for measurement noise. At 10% range-scaled assay noise, incorporating assay uncertainty reduces forecast error from about 5% to below 3% for both surrogates. An independent reaction cascade verifies candidate integration against tensor quadrature, with mean normalized forecast-integration error below $10^{-5}$ at 32,768 candidates. These results demonstrate accurate clot-growth forecasting without full biochemical identification and support selecting prediction strategies and additional measurements according to accuracy, reliability, and computational cost.

Tree-like structures arise in numerous imaging applications, including vascular networks, neuronal arbors, airway trees, and cortical sulcal–gyral folding. We present a nonlinear registration framework based on screened Poisson flow and Wasserstein distance. The screened Poisson equation transforms geometric features into smooth multiscale probability distributions. Registration is formulated by minimizing the Wasserstein distance between these distributions, producing anatomically meaningful correspondences without explicit landmark or branch matching. The framework is demonstrated on the nonlinear registration of cortical sulcal–gyral folding patterns from structural MRI.