Transition-Based Digital Twin Modelling for Alzheimer's Disease under Sparse Longitudinal Data

Alzheimer's disease (AD) progression is highly heterogeneous and is typically observed through sparse and irregular longitudinal data, posing challenges for prediction and personalised monitoring. Existing machine learning approaches have improved AD prediction using multimodal data, yet often focus on static classification or cohort-level risk estimation, providing limited support for subject-specific modelling and uncertainty-aware reasoning. To address these limitations, we present a personalised digital twin framework for AD prediction and scenario-based analysis using multimodal longitudinal data. The proposed approach integrates complementary modelling strategies to capture clinical transitions and temporal dependencies across visits. Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitive assessments, clinical variables, and MRI-derived phenotypes, the framework predicts cognitive status and diagnostic categories while quantifying predictive uncertainty and enabling patient-specific what-if trajectory analysis. Evaluation on leak-free subject-level splits demonstrates strong performance in score forecasting and diagnosis classification. In this sparse and irregular ADNI setting, transition-based modelling of adjacent visits achieved higher predictive accuracy than the sequence-based branch, suggesting that local transition modelling may be more data-efficient. While sequence models remain valuable for uncertainty-aware trajectory forecasting, local transition modelling offers a more data-efficient and robust predictive strategy. These findings highlight the importance of aligning temporal modelling strategies with clinical data structure and suggest that transition-based digital twin formulations may provide a practical and interpretable approach for personalised disease forecasting in neurodegenerative disorders.

From Baseline to Follow-Up: Counterfactual Spine DXA Image Synthesis in UK Biobank Using a Causal Hierarchical Variational Autoencoder

Dual-energy X-ray absorptiometry (DXA) is widely used for large-scale skeletal assessment, yet learning controllable and interpretable factor-specific anatomical variation remains challenging. We propose a metadata-conditioned causal hierarchical variational autoencoder (CHVAE) for causally consistent generation of anteroposterior (AP) spine DXA images from the UK Biobank (UKB). The model is trained on 3,743 raw AP spine scans from the first imaging visit and conditioned on basic participant attributes and lumbar morphometry. Causal consistency is evaluated in a baseline-to-follow-up setting using abduction--action--prediction (AAP): latent variables are abducted from baseline images, age is intervened to the repeat-imaging value, and the resulting counterfactual follow-up morphometry is compared with observed repeat-imaging measurements. Results show strong absolute-level agreement for key vertebral morphometry variables under age intervention, supporting intervention-aligned synthesis of anatomically plausible DXA images.

Understanding Imbalanced Forgetting in Rehearsal-Based Class-Incremental Learning

Neural networks suffer from catastrophic forgetting in class-incremental learning (CIL) settings. Rehearsal$\unicode{x2013}$replaying a subset of past samples$\unicode{x2013}$is a well-established mitigation strategy. However, recent results suggest that, despite balanced rehearsal allocation, some classes are forgotten substantially more than others. Despite its relevance, this imbalanced forgetting phenomenon remains underexplored. This work shows that imbalanced forgetting arises systematically and severely in rehearsal-based CIL and investigates it extensively. Specifically, we construct, from a principled analysis, three last-layer coefficients that capture different gradient-level sources of interference affecting each past class during an incremental step. We then demonstrate that, together, they reliably predict how past classes will rank in terms of forgetting at the end of that step. While predictive performance alone does not establish causality, these results support the interpretation of the coefficients as a plausible mechanistic account linking last-layer gradient-level interactions during training to class-level forgetting outcomes. Notably, one coefficient$\unicode{x2013}$capturing self-induced interference$\unicode{x2013}$emerges as the strongest predictor, with controlled experiments providing evidence consistent with this coefficient being influenced by the new-class interference coefficient. Overall, our findings provide valuable insights and suggest promising directions for mitigating imbalanced forgetting by reducing class-wise disparities in the identified sources of interference.

XAttn-BMD: Multimodal Deep Learning with Cross-Attention for Femoral Neck Bone Mineral Density Estimation

Poor bone health is a significant public health concern, and low bone mineral density (BMD) leads to an increased fracture risk, a key feature of osteoporosis. We present XAttn-BMD (Cross-Attention BMD), a multimodal deep learning framework that predicts femoral neck BMD from hip X-ray images and structured clinical metadata. It utilizes a novel bidirectional cross-attention mechanism to dynamically integrate image and metadata features for cross-modal mutual reinforcement. A Weighted Smooth L1 loss is tailored to address BMD imbalance and prioritize clinically significant cases. Extensive experiments on the data from the Hertfordshire Cohort Study show that our model outperforms the baseline models in regression generalization and robustness. Ablation studies confirm the effectiveness of both cross-attention fusion and the customized loss function. Experimental results show that the integration of multimodal data via cross-attention outperforms naive feature concatenation without cross-attention, reducing MSE by 16.7%, MAE by 6.03%, and increasing the R2 score by 16.4%, highlighting the effectiveness of the approach for femoral neck BMD estimation. Furthermore, screening performance was evaluated using binary classification at clinically relevant femoral neck BMD thresholds, demonstrating the model's potential in real-world scenarios.

3D Cardiac Shape Prediction with Deep Neural Networks: Simultaneous Use of Images and Patient Metadata

Large prospective epidemiological studies acquire cardiovascular magnetic resonance (CMR) images for pre-symptomatic populations and follow these over time. To support this approach, fully automatic large-scale 3D analysis is essential. In this work, we propose a novel deep neural network using both CMR images and patient metadata to directly predict cardiac shape parameters. The proposed method uses the promising ability of statistical shape models to simplify shape complexity and variability together with the advantages of convolutional neural networks for the extraction of solid visual features. To the best of our knowledge, this is the first work that uses such an approach for 3D cardiac shape prediction. We validated our proposed CMR analytics method against a reference cohort containing 500 3D shapes of the cardiac ventricles. Our results show broadly significant agreement with the reference shapes in terms of the estimated volume of the cardiac ventricles, myocardial mass, 3D Dice, and mean and Hausdorff distance.

High Throughput Computation of Reference Ranges of Biventricular Cardiac Function on the UK Biobank Population Cohort

The exploitation of large-scale population data has the potential to improve healthcare by discovering and understanding patterns and trends within this data. To enable high throughput analysis of cardiac imaging data automatically, a pipeline should comprise quality monitoring of the input images, segmentation of the cardiac structures, assessment of the segmentation quality, and parsing of cardiac functional indexes. We present a fully automatic, high throughput image parsing workflow for the analysis of cardiac MR images, and test its performance on the UK Biobank (UKB) cardiac dataset. The proposed pipeline is capable of performing end-to-end image processing including: data organisation, image quality assessment, shape model initialisation, segmentation, segmentation quality assessment, and functional parameter computation; all without any user interaction. To the best of our knowledge,this is the first paper tackling the fully automatic 3D analysis of the UKB population study, providing reference ranges for all key cardiovascular functional indexes, from both left and right ventricles of the heart. We tested our workflow on a reference cohort of 800 healthy subjects for which manual delineations, and reference functional indexes exist. Our results show statistically significant agreement between the manually obtained reference indexes, and those automatically computed using our framework.

2D Reconstruction of Small Intestine's Interior Wall

Examining and interpreting of a large number of wireless endoscopic images from the gastrointestinal tract is a tiresome task for physicians. A practical solution is to automatically construct a two dimensional representation of the gastrointestinal tract for easy inspection. However, little has been done on wireless endoscopic image stitching, let alone systematic investigation. The proposed new wireless endoscopic image stitching method consists of two main steps to improve the accuracy and efficiency of image registration. First, the keypoints are extracted by Principle Component Analysis and Scale Invariant Feature Transform (PCA-SIFT) algorithm and refined with Maximum Likelihood Estimation SAmple Consensus (MLESAC) outlier removal to find the most reliable keypoints. Second, the optimal transformation parameters obtained from first step are fed to the Normalised Mutual Information (NMI) algorithm as an initial solution. With modified Marquardt-Levenberg search strategy in a multiscale framework, the NMI can find the optimal transformation parameters in the shortest time. The proposed methodology has been tested on two different datasets - one with real wireless endoscopic images and another with images obtained from Micro-Ball (a new wireless cubic endoscopy system with six image sensors). The results have demonstrated the accuracy and robustness of the proposed methodology both visually and quantitatively.