Interpretable Multimodal MRI-Clinical Fusion for Functional Outcome Prediction After Acute Ischemic Stroke

Multimodal prediction models based on imaging and clinical data are increasingly used for clinical decision support, yet their interpretability remains limited. We present multimodal Deep Transformation Models (DTMs) combining statistical approaches and neural networks to achieve strong predictive performance while preserving interpretability for tabular data. A key contribution of this work is the adaption of the xAI methods Grad-CAM and Occlusion to DTMs relying on 3D CNNs, enabling interpretation of the image branch through the generation of explanation maps. We developed DTMs to predict functional independence three months after stroke using diffusion-weighted imaging and clinical data from 407 patients. In a ten-fold cross-validation, the models achieved state-of-the-art predictive performance (AUC 0.81 [0.75, 0.87]) while maintaining interpretability for tabular features, with functional independence before stroke and stroke severity on admission emerging as the strongest predictors. Explanation maps from both xAI methods highlighted consistent regions, including frontal lobe areas which are known to be associated with age, a strong predictor of functional outcome. Notably, these regions disappeared once age was included as an explicit tabular predictor. Similarity analyses of explanation maps revealed distinct spatial patterns, providing meaningful insights into stroke pathophysiology, systematic error analysis and hypothesis generation.

Deep learning and multi-modal fusion have demonstrated transformative potential in medical diagnosis by integrating diverse data sources. However, accurate prognosis for ischemic stroke remains challenging due to limitations in existing multi-modal approaches. First, current methods are predominantly confined to dual-modal fusion, lacking a framework that effectively integrates the trifecta of medical images, structured clinical data, and unstructured text. Second, they often fail to establish deep bidirectional interactions between modalities; To address these critical gaps, this paper proposes a novel tri-modal fusion model for ischemic stroke prognosis. Our approach first enriches the data representation by employing a Large Language Model (LLM) to automatically generate semi-structured diagnostic text from brain MRIs. This process not only addresses the scarcity of expert annotations but also serves as a regularized semantic enhancement, improving multimodal fusion robustness. Furthermore, we design a core component termed the Vision-Conditioned Dual Alignment Fusion Module (VDAFM), which strategically uses visual features as a conditional prior to guide fine-grained interaction with the generated text. This module achieves a dynamic and profound fusion through a dual semantic alignment loss, effectively mitigating modal heterogeneity. Extensive experiments on a real-world clinical dataset demonstrate that our model achieves state-of-the-art performance.

$\textbf{Objective:}$ Brain-predicted age difference (BrainAGE) is a neuroimaging biomarker reflecting brain health. However, training robust BrainAGE models requires large datasets, often restricted by privacy concerns. This study evaluates the performance of federated learning (FL) for BrainAGE estimation in ischemic stroke patients treated with mechanical thrombectomy, and investigates its association with clinical phenotypes and functional outcomes. $\textbf{Methods:}$ We used FLAIR brain images from 1674 stroke patients across 16 hospital centers. We implemented standard machine learning and deep learning models for BrainAGE estimates under three data management strategies: centralized learning (pooled data), FL (local training at each site), and single-site learning. We reported prediction errors and examined associations between BrainAGE and vascular risk factors (e.g., diabetes mellitus, hypertension, smoking), as well as functional outcomes at three months post-stroke. Logistic regression evaluated BrainAGE's predictive value for these outcomes, adjusting for age, sex, vascular risk factors, stroke severity, time between MRI and arterial puncture, prior intravenous thrombolysis, and recanalisation outcome. $\textbf{Results:}$ While centralized learning yielded the most accurate predictions, FL consistently outperformed single-site models. BrainAGE was significantly higher in patients with diabetes mellitus across all models. Comparisons between patients with good and poor functional outcomes, and multivariate predictions of these outcomes showed the significance of the association between BrainAGE and post-stroke recovery. $\textbf{Conclusion:}$ FL enables accurate age predictions without data centralization. The strong association between BrainAGE, vascular risk factors, and post-stroke recovery highlights its potential for prognostic modeling in stroke care.