Stroke

Objectives: Quantitative assessment of infarct hypodensity on non-contrast computed tomography (NCCT), including net water uptake (NWU), requires manual or semi-manual lesion delineation, often guided by CT perfusion or diffusion-weighted MRI, limiting clinical applicability. Automated segmentation on NCCT could enable efficient biomarker extraction such as NWU but remains challenging across heterogeneous multicenter data. This study aimed to develop and externally test a domain-aware deep learning framework for ischemic stroke segmentation on NCCT and assess its suitability for NWU quantification. Materials & Methods: In this retrospective multicenter study of 801 patients from four datasets, an nnU-Net-based model was trained on NCCT scans from the University Medical Center Hamburg-Eppendorf and the Acute Ischemic Stroke Dataset. To adapt to new domains, the model was fine-tuned on target-domain subsets from Boston (n=11) and ISLES (n=75), with evaluation on held-out cases not used for fine-tuning. Automated segmentations and NWU values were compared with expert references. Results: For lesions $\geq$ 30 mL, median Dice was 0.68 (Boston) and 0.56 (ISLES). Including smaller lesions, which predominated in ISLES, median Dice was 0.54 (interquartile range [IQR] 0.30-0.70) for acute lesion segmentation (Boston dataset) and 0.20 (IQR 0.03-0.41) for NCCT lesion segmentations when compared to post-treatment infarct (primary target of the ISLES challenge). Automated NWU mean absolute error was 1.37 percentage points (SD 1.61, Boston). Conclusion: Target-domain adaptation supported NCCT-only infarct segmentation across heterogeneous external cohorts, although performance varied across domains. The approach enabled low-error NWU quantification from baseline NCCT without advanced imaging, supporting further prospective clinical evaluation.

Background: Large language models (LLMs) have achieved physician-comparable performance on multiple-choice medical knowledge examinations, but their capabilities in clinical history taking, urgency assessment, and safety remain insufficiently evaluated. We proposed Japanese Stroke LLM Evaluation, a multi-turn conversational benchmark for stroke care in Japanese, and evaluated LLM performance and safety under practice-oriented conditions. Methods: We created 10 stroke and related-condition cases and evaluated LLMs in multi-turn Japanese conversations. The LLM acted as physician, while a board-certified neurosurgeon acted as simulated patient and evaluator. Each case comprised history-taking and action phases scored using pre-specified criteria. Errors that could directly threaten life were defined as critical mistakes. The safety threshold was at least 80% overall with zero critical mistakes. Eighteen models were evaluated in October 2025 and June 2026. Results: Claude Fable 5 achieved the highest score (87.4%) with zero critical mistakes, followed by Claude Opus 4.7 (80.3%) and GLM-5.2 (75.6%). Two leaders met the safety threshold. Eleven models made 17 critical mistakes, including failure to confirm laboratory results or blood glucose before t-PA, surgery before airway stabilization, omission of cervical vascular evaluation, and t-PA outside its indication. History-taking question count correlated with history-taking score (r = 0.648, p = 0.007). Conclusions: Japanese Stroke LLM Evaluation provides a benchmark for LLM performance under practice-oriented conditions, including a cap on history-taking questions. Cases and evaluations were created by neurosurgical specialists rather than using an LLM-as-judge approach. Performance improved across cloud-based and on-premise models in 2026, with some exceeding the safety threshold. Further evaluation using real-world cases is required.

This study evaluated personalized gait phase estimation for stroke survivors using functional inertial measurement unit (IMU) alignment and two-stage sequential adaptation of models pre-trained on healthy gait. The estimator used signals from a thigh-mounted IMU. Heel force-sensitive resistor measurements provided reference phase labels for offline adaptation and evaluation. Stage 1 established a distillation-regularized participant-specific model, and Stage 2 performed conditional refinement using low-rank adaptation. Long Short-Term Memory (LSTM), Temporal Convolutional Network (TCN), and Transformer models were evaluated in five stroke survivors walking with a powered knee exoskeleton using leave-one-subject-out hyperparameter selection and sequential test-then-adapt Stage 2 replay. Relative to the non-adapted baselines, Stage 1+2 reduced the mean participant-wise phase root mean square error by 84.2%, 77.0%, and 60.7%, respectively. The Transformer achieved the lowest final error (2.90 +- 1.13$% of the gait cycle) and heel-strike timing error (23.7 +- 4.5ms). Policy-specific ablations showed that every-cycle updates generally produced the lowest or near-lowest error, whereas conditional updating reduced the update frequency with small accuracy differences. After personalization, alignment produced model-dependent changes in phase error while preserving or improving heel-strike detection and reducing heel-strike timing error for the LSTM and Transformer. Concurrent embedded tests showed that the TCN and Transformer maintained 100-Hz inference during Stage 2 updates without deadline misses, whereas the LSTM missed the 10-ms deadline in 6.6% of inferences. All updates completed within 0.8s. These results support the offline feasibility and embedded computational timing of the proposed framework for exoskeleton-assisted walking.

Large networks and ensembles often lead medical image segmentation challenges, but their storage and inference demands complicate deployment. We present LightMedSeg-ISLES, a 1.26-million-parameter pipeline for T1-weighted stroke lesion segmentation in ISLES'26. On a 146-case held-out cohort, flip test-time augmentation produces 0.618 mean Dice and 0.599 lesion-wise F1. A 102.35-million-parameter nnU-Net ResEnc-L produces 0.634 Dice and 0.544 lesion-wise F1 after size filtering. LightMedSeg therefore retains 97.5% of nnU-Net's Dice with 81.4$\times$ fewer parameters while improving lesion-wise F1 by 0.055. Its four-pass TTA operating point requires 4.7$\times$ fewer FLOPs per standardized patch than nnU-Net. It also slightly exceeds filtered UNETR++ and nnFormer. Longer training and stronger augmentation add 0.0358 Dice without increasing capacity, establishing a strong single-checkpoint alternative to much larger models.

Recent offline reinforcement learning (RL) studies report policies that outperform physician decisions on clinical outcomes. We conduct a systematic, partially crossed evaluation of five offline RL algorithm families and 14 reward designs in 44,894 post-2018 acute ischemic stroke patients from a nationwide registry (N = 129,033). Standard Fitted Q-Evaluation (FQE) yields an apparent policy-improvement estimate of +0.0069; adding an Early Neurological Deterioration penalty increases it to +0.0101. We identify reward-embedded confounding, in which a proxy terminal reward encodes baseline severity and prognosis as well as treatment efficacy. A 2 x 2 factorial analysis finds that terminal reward confounding accounts for 218.6% of the observed signal change, so its removal overshoots the null. After DML-inspired GBM reward residualization, the FQE estimate attenuates to +0.0033 (p = 0.132), and full deconfounding yields +0.0025 (p = 0.291). FQE-based diagnostics, T-learner analyses, and direct recurrence analyses converge away from a clinically meaningful aggregate improvement. A 1-year mRS factorial analysis replicates the attenuation. We provide an empirically motivated six-step evaluation checklist. NIHSS-stratified heterogeneity is hypothesis-generating for prospective trial design; hospital-level disagreement does not persist after full reward deconfounding.

Interpretability methods for large language models (LLMs) describe internal state but do not directly test whether that state is causally sufficient to produce the observed behavior. In earlier work, we lesioned LLMs to produce error profiles in picture naming, a central task for assessing aphasia, and found that specific lesions produced errors resembling those of individual stroke survivors. Here we ask the inverse question: given an error profile, can the lesion parameters that produced it be recovered, and what does this inverse problem reveal about transformer computation? Lesions in LLaVA-Vicuna 13B were parameterized by layer index, modification percentage, and noise sigma across 4,840 configurations, and error profiles were characterized by a seven-category clinical taxonomy (correct, semantic, unrelated, formal, mixed, neologism, no-response). We trained a multi-task neural network to map error profiles back to perturbation parameters. The problem admitted a partial solution: across 10 independently trained inverse models, modification percentage and noise sigma were recoverable, whereas layer index was recoverable only within a neighborhood. In counterfactual validation, a fresh model instance perturbed with the recovered parameters reproduced the target behavior in 81.4% of cases. This dissociation between low layer recovery and high counterfactual fidelity is consistent with functional redundancy across transformer layers, a property not captured by standard interpretability methods. As an out-of-distribution test, we applied the trained model to picture-naming error profiles from 278 stroke survivors; recovered parameters were syndrome-discriminative, most strongly for perturbation intensity, indicating generalization beyond the training distribution. Counterfactual validation provides a general framework for LLM interpretability claims beyond inverse mapping.

Machine learning models achieve strong predictive accuracy for 90-day outcome prediction in acute ischaemic stroke, yet clinical adoption is limited by the misalignment of model explanations with clinicians' reasoning. Motivated by a clinician user study calling for clinical guideline-aligned cut-offs, we ask whether continuous predictors can be replaced by clinically informed categorical encodings without sacrificing performance. On a multi-centre European registry stratified into three treatment cohorts, we compare standard and fully categorised gradient-boosted models, the latter using stroke guideline-aligned, treatment-specific thresholds. The fully categorised models are statistically indistinguishable from their continuous counterparts in two of the treatment cohorts, with a significant drop in predictive accuracy in one cohort. Global feature importance rankings remain consistent, suggesting that discretising continuous predictors into guideline-based categories preserves the core hierarchy of prognostic factors across all treatment groups. Guideline-based categorisation is thus a viable design choice for stroke-outcome models.

Brain-machine interfaces (BMIs) can assist individuals with limited mobility, such as stroke survivors or amputees. One of the key challenges in developing BMIs is expanding their usability and control, which can be achieved by accurately decoding multiple kinematic and kinetic parameters. To address this, we propose three regression models: partial least squares regressor, multilayered perceptron, and attention based regressor, to decode multiple movement parameters from EEG signals. We evaluated these models on the WAY EEG GAL dataset, focusing on their performance under subject specific and subject independent conditions with two strategies: a single model for all parameters and a baseline with separate models for each parameter. Among all regressors, the attention based regressor achieved the best performance, with an $R^2$ of 0.8 and a latency of 29.2 milliseconds, demonstrating significant improvement in simultaneous multi parameter decoding. However, its performance dropped for single parameter decoding. The multi layered perceptron showed more consistent but lower accuracy across both decoding types ($R^2$ = 0.49). These findings highlight the potential of attention based models for real time multi command BMI systems and contribute to the development of more intuitive control devices.

Accurate segmentation of brain stroke lesions in non-contrast computed tomography (NCCT) scans is critical for rapid clinical decision-making, yet remains difficult due to the low contrast between lesion and normal brain tissue, heterogeneous lesion morphology across ischemic and hemorrhagic subtypes, and ambiguous boundaries caused by partial volume effects. Current deep learning approaches primarily optimize region-level overlap but lack explicit boundary modeling, leading to imprecise delineation that can affect volumetric assessment and treatment planning. We propose FSB-Net, a frequency-spatial boundary network that leverages frequency-domain analysis for boundary-aware stroke lesion segmentation. FSB-Net introduces three components: (i) a Wavelet Boundary Detection Head (WBDH) that applies the discrete wavelet transform to multi-scale encoder features, extracting high-frequency sub-bands as boundary representations; (ii) a Frequency-Spatial Cross-Attention Module (FSCAM) that performs bidirectional attention between wavelet boundary features and spatial decoder features for selective boundary enhancement; and (iii) a Spectral Boundary Loss that penalizes high-frequency discrepancies in the Fourier domain to optimize boundary sharpness. Built on a PVTv2-B2 encoder, FSB-Net is evaluated on a public Brain Stroke CT dataset containing both ischemic and hemorrhagic cases. Experimental results show that FSB-Net outperforms U-Net, UNet++, MANet, and DeepLabV3+ across all metrics, achieving state-of-the-art performance in mean Dice, mean IoU, and HD95.

Deep learning frameworks like nnU-Net achieve state-of-theart brain lesion segmentation performance but remain difficult to deploy in clinical research environments due to, among other reasons, software dependencies and computational requirements. We introduce StrokeSeg2, a lightweight, modular, cross-platform C++/Qt framework designed to adapt resource-intensive 3D stroke segmentation pipelines into portable and reproducible applications. To improve compatibility with standard clinical workstations, we investigate the combined effect of architectural compression through knowledge distillation and inference optimisation using ONNX Runtime with Float16 quantisation. Across heterogeneous hardware configurations (CPU, integrated GPU, and dedicated GPU) architectural distillation emerged as the primary contributor to efficiency gains, contributing to over 90% reduction in energy consumption and an average 84% reduction in inference time. Specifically, we identify a 0.84M-parameter student model as the most favourable trade-off, reducing the original 102.3M-parameter teacher architecture to a 2.1 MB disk footprint while preserving robust lesion localisation and competitive segmentation performance. This small footprint supports the development of a self-contained installer for clinical workstation targets. Finally, StrokeSeg2 packages these optimisations into standalone installers for Windows, macOS, and Linux. By providing both graphical and commandline interfaces without Docker or external environment dependencies, StrokeSeg2 facilitates deployment of high-performance segmentation workflows for routine clinical research pipelines.

Mechanical thrombectomy (MT) is a time-critical intervention for acute ischemic stroke; however, access remains limited due to a shortage of neuroradiologists and specialized centers. Reinforcement learning (RL) offers potential to automate endovascular navigation and improve accessibility, yet current models lack standardized frameworks to assess navigation difficulty for model training and evaluation. This study aims to identify vascular metrics associated with navigation difficulty and to develop an automated pipeline for quantitative vascular feature extraction, enabling future complexity grading. Vascular trees were segmented from computed tomography angiograms from 61 patients, and vascular metrics including aortic arch type, presence of bovine arch, vessel length, tortuosity, take-off angle, number of reverse curves, were measured using a custom pipeline. A Soft Actor-Critic RL algorithm was used for 120 s autonomous navigation. Outcomes were analyzed using both mixed effects linear and logistic regression. On the left side, the presence of a bovine arch and aortic arch type II/III increased navigation time by 30.19 s and 37.92 s, respectively, while greater tortuosity (\b{eta} = 118.20) further prolonged the procedure and reduced success probability. On the right side, type II/III arches extended procedure time by 45.94 s, while each additional reverse curve was associated with 3.96 s longer navigation time and lower probability of success. These findings demonstrate for the first time that MT agent navigation difficulty is strongly influenced by vascular geometry. The proposed automated pipeline enables objective and quantitative characterization of vascular features, providing a foundation for future development of standardized complexity grading and RL model evaluation, without aiming to demonstrate clinically generalizable autonomous navigation.

Personalizing exoskeleton assistance requires user-specific gait data across many locomotor tasks, yet collecting this data demands repeated motion capture sessions that are costly, time-intensive, and especially burdensome for clinical populations. This challenge is most acute across walking speeds, where gait changes substantially and deviates further in clinical gait. This work introduces a subject-conditioned residual diffusion framework that generates personalized lower-limb kinematics at unseen walking speeds from a subject's gait sequence at a single seen speed. Given sagittal-plane hip, knee, and ankle trajectories at a seen speed and a desired unseen speed, the model generates a residual that transforms the seen trajectory into the unseen one, using a transformer denoiser conditioned on the subject's gait and the two speeds through feature-wise linear modulation. Trained only on able-bodied data, the model achieved a mean absolute error (MAE) of 3.4° on held-out able-bodied subjects. Without any stroke-specific fine-tuning, it achieved a 6.0° MAE on out-of-training-distribution stroke subjects, retaining subject identity for clinical gait. The framework reduced the MAE by over 70% relative to supervised feed-forward baselines, and a single seen speed matched the accuracy of four speeds within 0.4°. These results demonstrate that subject-conditioned residual diffusion can synthesize personalized gait across speeds from minimal data, reducing the collection burden for downstream exoskeleton personalization.

Objective: Accurate identification of acute ischemic infarcts on diffusion-weighted magnetic resonance imaging (DWI) is a critical prerequisite for reliable lesion quantification and effective clinical decision support in the management of cerebrovascular events. Methods: This study presents EPRA U-Net (Efficient Pyramid Residual Attention U-Net), a task-specific integrated architecture for efficient and accurate infarct segmentation of DWI images. In the proposed architecture, an EfficientNet-based encoder was used as a hierarchical feature extractor with a minimized parameterization. In addition, a Residual-Recurrent (R2) block (recurrent unrolling step t = 2, following the original formulation) and Atrous Spatial Pyramid Pooling (ASPP) were integrated to enhance the performance of spatial dependency modeling. Additionally, a dual attention mechanism was incorporated to highlight lesion-related activations while concurrently enabling the suppression of extraneous background responses. To prioritize lesion detection consistent with clinical imperative, a Tversky loss function was adopted, emphasizing the sensitivity of detection over its specificity during the optimization process. Results: Experimental evaluations were conducted utilizing an in-house dataset comprising 167 patients with 4,895 DWI slices; subsequently, the performance of the proposed EPRA U-Net was assessed in comparison with state-of-the-art models, specifically UNet++, DeepLabV3+, and TransUNet. The experimental results suggest that EPRA U-Net attained superior performance, evidenced by a pixel-aggregated Dice of 0.8984, a per-sample Dice of 0.9469, an IoU of 0.8155, a Recall of 0.8887, a Lesion F1 of 0.9378, and an HD95 of 11.62 px. Furthermore, a clear reduction in the rate of missed lesions, specifically by 16%, 25%, and 29%, was observed when compared with UNet++, DeepLabV3+, and TransUNet, respectively.

Teaching machines to emulate natural handwriting styles remains an open challenge, as it requires synthesizing stroke sequences that dynamically vary in shape, texture, pressure and script - not only across individuals, but also within a single person's handwriting. Attempts at this challenge have largely explored deep learning methods in both online and offline settings. However, these approaches are often constrained by style-specific architectural choices, heavy reliance on large datasets, high compute costs, and a lack of flexible control over writing styles through natural language. To this end, we introduce HandwritingAgent, a language-driven agent that can synthesize natural handwriting sequences directly in Scalable Vector Graphics (SVG) format with no need for style-specific training. The agent leverages a large reasoning model to geometrically analyse and autoregressively generate target handwritten glyphs as stroke sequences in a discrete grid canvas environment. Generation is conditioned on texts provided in either conversational or non-conversational mode, along with a reference handwriting-style image. Experiments on diverse handwriting tasks spanning imitation, recognition, multi-lingual handwriting synthesis, and generation of complex handwritten maths and science expressions indicate substantial improvement in performance, with HandwritingAgent matching or surpassing state-of-the-art generative handwriting models, while providing a more efficient, controllable, and generalizable synthesis method.

We built a multi-task pipeline for tennis stroke biomechanics from plain RGB video. On top of pose-based stroke recognition, it adds two new tasks, predicting shot direction and grading posture quality, plus a rule-based feedback layer that suggests coaching tips. Strokes are found automatically using a weighted joint velocity score, s(t) = 0.5 v_wrist + 0.3 m_elbow + 0.2 m_shoulder, removing the need for manual annotation. Pose comes from MediaPipe Pose Landmarker (33 landmarks, metric world coordinates), with each stroke turned into a 30-frame by 39-feature sequence for TennisTransformerGPU, a compact 564,103-parameter transformer (4 layers, 4 heads, d=128) with three parallel output heads. Trained on 1,281 labeled strokes from 7 pros and 1 amateur across 11 videos, it hits 83.7% stroke-type accuracy, 61.9% on direction, and 62.6% on posture under a random 80/20 split. The interesting test is cross-player: train on pros, evaluate on the amateur. Stroke type barely budges, 82.9%, a 0.8% drop. Direction prediction does not transfer; it just falls back to the majority class. An ablation shows why world coordinates matter so much here: switching to image-space landmarks tanks cross-player stroke-type accuracy from 83% to 47% and direction from 68% to 21%. Everything runs on Kaggle's free T4 GPU tier and is fully reproducible.

Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a major determinant of acute triage and treatment decisions in neurosurgical care. However, most existing methods provide either a binary expansion risk or a single follow-up volume, limiting uncertainty-aware decisions. We introduce HemExp, a clinically-guided latent diffusion model that generates patient-specific follow-up non-contrast CT images, along with segmentations of intraparenchymal and intraventricular hemorrhage. Generation is conditioned on baseline imaging, clinical variables, and an explicit expansion indicator, enabling controllable simulation of realistic clinical scenarios. HemExp uses a hemorrhage-aware multi-head variational autoencoder and models progression as the difference between baseline and follow-up latent representations with a conditional diffusion model. The model is trained on paired scans from 450 patients across multiple centers and evaluated on 107 patients from a held-out institution. HemExp produces spatial HE probability maps by generating multiple synthetic follow-up images per patient to estimate distributions of plausible follow-up hematoma volumes. Perturbing clinical inputs such as symptom-onset-to-imaging time or anticoagulant status shifts the predicted follow-up volume distribution. HemExp extends binary predictors and demonstrates robust estimation of clinically relevant outcomes in the imaging space, such as hematoma volume, intraventricular involvement, and mass effects. Overall, our results support controllable latent diffusion as a promising direction for uncertainty-aware modeling of early ICH progression.

Leptomeningeal collaterals (LMCs) are an important prognostic factor in acute ischemic stroke. Existing automated methods rely on CT angiography (CTA), but individual LMCs are often too small to be resolved on CTA, limiting these methods to coarse collateral scoring. Digital subtraction angiography (DSA) visualizes individual collaterals at superior resolution, yet current assessment remains subjective, relying on manual grading scales that suffer from poor inter-rater agreement. We present a framework that formulates collateral detection as the classification of individual vessel segments on a graph derived from DSA. A hybrid graph-pixel architecture combines a topology-aware graph branch with a dense pixel branch, fused in a shared node-probability space. In a five-fold cross-validation setting, the fused model achieves a PR-AUC of 0.434, outperforming the graph-only (0.403) and pixel-only (0.362) baselines. To our knowledge, this is the first method to enable the individualization of LMCs in DSA, allowing for precise per-vessel quantitative assessment. This integration shifts DSA assessment toward objective evaluation, supporting future biomarker and pattern discovery for individual LMCs.

Personalized medicine in acute ischemic stroke requires moving beyond average treatment effects (ATE) to individualized treatment effect (ITE) estimates to support treatment decisions. In acute ischemic stroke, mechanical thrombectomy has been shown to be more effective on average than lysis in randomized controlled trials (RCTs), such as the MR CLEAN study. We aim to identify which individual patients benefit most from mechanical thrombectomy compared to lysis. The outcome of interest is the modified Rankin Scale (mRS) at three months, an ordinal measure of functional disability (0: no symptoms, 6: death). We demonstrate that causal transformation models on directed acyclic graphs (TRAM-DAG) can be used for ITE estimation after being fitted on observational MAGIC multi-center stroke patient data. To ensure comparability with the MR CLEAN population, which we use for validation, we train the TRAM-DAG on a MAGIC sub-population with NIHSS at admission >= 6, corresponding to one inclusion criterion of MR CLEAN. The fitted model is then used to estimate ITEs for stroke patients in the MR CLEAN population. While these ITE estimates cannot be confirmed experimentally, we show that their average is consistent with the trial's reported ATE. Furthermore, the ITE estimates correctly rank trial patients by their observed frequency of a good outcome (mRS at three months <= 2). These findings support the use of causal models like TRAM-DAG for personalized decision-making in stroke care and highlight their ability to bridge the gap between observational evidence and clinical trials.

Objective: Conformance checking in healthcare seeks to assess whether patient care pathways adhere to clinical guidelines. However, its practical application often depends on the availability of formal, machine-interpretable representations of guidelines, such as Computer-Interpretable Guidelines (CIGs), which are seldom available in real-world clinical settings. Methods: This work introduces a modular framework based on the orchestration of Large Language Models (LLMs) to support medical conformance checking directly from unstructured clinical and guideline texts, without requiring predefined CIGs. The proposed architecture integrates multiple LLMs and supporting components to extract patient traces from clinical discharge letters, identify normative rules from textual clinical guidelines, translate these rules into executable scripts, and compute a Trace Conformance Indicator to quantify compliance within the event log. Results: The framework was implemented and evaluated in the stroke care domain at the neurological ward of Alessandria Hospital. Hundreds of patient traces were automatically extracted from hospital data and assessed against 50 rules derived from the reference guideline. The analysis showed that more than 86% of the available traces were conformant. Conclusion: The results demonstrate the feasibility of using orchestrated LLMs for practical healthcare conformance analysis. At the same time, the study provides evidence of a high level of adherence to stroke care guidelines at Alessandria Hospital.

Ischemic stroke is a major global disease. Treatment decisions are highly time-sensitive, as eligibility for reperfusion therapies relies on the interval between stroke onset and intervention. However, the true onset time is often uncertain in clinical practice, necessitating imaging-based assessment of tissue age as a surrogate marker. Early ischemic changes on routinely acquired non-contrast CT (NCCT) are often subtle, and real-world clinical datasets exhibit pronounced onset-time class imbalance and center-scanner-related heterogeneity. In this work, we propose StrokeTimer, a fully automated framework for onset-time estimation in acute ischemic stroke. StrokeTimer integrates self-supervised disentanglement learning with energy-guided contrastive learning to capture subtle ischemic patterns while addressing long-tailed data distributions under acquisition variability. Onset time is categorized into three clinically relevant windows: <4.5 h, 4.5-6 h, and >6 h. Experimental results on a large multi-center NCCT dataset from two national cohorts, MR CLEAN Registry and MR CLEAN LATE, show that StrokeTimer achieves a macro AUC of 0.69 and a macro F1-score of 0.57, improving the strongest baseline by nearly 50% (p < 0.005). In this realistic, challenging setting, representative baseline approaches exhibit near-chance macro performance. Model explanations further highlight subtle gray-white matter blurring and hypodense regions consistent with established radiological biomarkers. These findings demonstrate the potential of StrokeTimer to support treatment decision-making in acute ischemic stroke. Code is available at https://github.com/BrainVas/StrokeTimer.

The treatment of ischemic stroke using mechanical thrombectomy involves difficult decisions under intense time constraints. Numerical physics simulations can in theory inform operators to make better decisions regarding treatment approaches and device selection, but are too slow to do so in practice. In this thesis, we investigate if current machine learning based surrogates can accurately emulate these simulations in a step-by-step manner while making them significantly faster. To do this we train three surrogate models on two simulations that involve a simplified aspiration procedure, with varying levels of geometric complexity. Our results show that two of our models accurately predict singular simulation steps and provide substantial speedups, especially when combined with specific data augmentations. However, the models showed a lack of stability when emulating simulations with complex geometries over longer time periods. Overall, this work provides a foundation for future studies to develop stable methods that scale to realistic numerical physics simulations of mechanical thrombectomy.

This paper presents the HRVConformer, a novel deep learning architecture for the classification of hypoxic-ischemic encephalopathy (HIE) using the instantaneous heart rate (HR) signal. Unlike conventional approaches that rely on handcrafted features, HRVConformer directly processes raw HR signals in an end-to-end manner, capturing both local and long-range dependencies through a hybrid Convolution-Transformer framework. By integrating convolutional layers for local feature extraction and Transformer-based attention mechanisms for global context modelling, the architecture effectively enhances signal representation and classification performance. The model was trained using supervised learning on a large HR dataset consisting of 1,573 one-hour epochs, including 259 one-hour expert-annotated epochs and a substantial set of weakly labelled data. A 314-hour validation set provided a robust performance estimation, while an independent 215-hour dataset with expert annotations was reserved for final testing. HR signals were extracted from electrocardiogram (ECG) recordings using an improved Pan-Tompkins algorithm, which significantly enhanced both signal quality and data availability. Experimental results demonstrate that the HRVConformer achieves an AUC of 83.23% and accuracy of 74.56% on the test set. These results surpass the performance of the Transformer, ResNet50 and fully convolutional networks baselines, highlighting the advantages of integrating convolutional and Transformer-based components for HR-based HIE classification. The proposed method provides a promising step toward a more accurate and automated assessment of HIE using HR signals. The code is available at: https://github.com/syu-kylin/HRVConformer.

When the blood supply to the brain is obstructed by a clot, oxygen delivery to brain tissues becomes insufficient, leading to cellular necrosis. In healthcare settings, accurately identifying and delineating ischemic lesion boundaries is essential for treatment and surgical planning. However, ischemic stroke lesions vary widely in shape, size, and location, and in grayscale MRI modalities such as T1W they may resemble surrounding brain structures. This makes lesion detection and segmentation a challenging task for clinicians. This study introduces a novel VRU-Net architecture, derived from visual features, residual connections, and a U-shaped network, for detecting and segmenting ischemic stroke lesions in 3D magnetic resonance imaging scans. The proposed method first uses a modified VGG model to identify ischemic stroke in separate 2D slices. Then, a U-shaped segmentation model with residual blocks segments the lesion in each slice. This procedure is applied independently to the axial, sagittal, and coronal planes, and the final output is generated by aggregating the three segmentation results. To improve both performance and processing speed, a high-performance classifier is applied before the segmentation model in a sequential framework. This strategy reduces unnecessary segmentation of non-lesion slices and improves overall accuracy. In addition, decomposing 3D images into 2D slices reduces model complexity while allowing information from three anatomical planes to support more accurate lesion localization. The proposed model is trained on the Anatomical Tracings of Lesions After Stroke dataset and outperforms state-of-the-art models in terms of accuracy and Dice coefficient. Moreover, the segmentation output provides feedback that helps the classification model reduce false-positive predictions.

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.

Stroke patient cross-subject electroencephalography (EEG) decoding of motor imagery (MI) brain-computer interface (BCI) is essential for motor rehabilitation, yet lesion-related abnormal temporal dynamics and pronounced inter-patient heterogeneity often undermine generalization. Existing adaptation methods are easily misled by pathological slow-wave activity and unstable target-domain pseudo-labels. To address this challenge, we propose PA-TCNet, a pathology-aware temporal calibration framework with physiology-guided target refinement for stroke motor imagery decoding. PA-TCNet integrates two coordinated components. The Pathology-aware Rhythmic State Mamba (PRSM) module decomposes EEG spatiotemporal features into slowly varying rhythmic context and fast transient perturbations, injecting the fused pathological context into selective state propagation to more effectively capture abnormal temporal dynamics. The Physiology-Guided Target Calibration (PGTC) module constructs source-domain sensorimotor region-of-interest templates, imposing physiological consistency constraints and dynamically refining target-domain pseudo-labels, thereby improving adaptation reliability. Leave-one-subject-out experiments on two independent stroke EEG datasets, XW-Stroke and 2019-Stroke, yielded mean accuracies of 66.56% and 72.75%, respectively, outperforming state-of-the-art baselines. These results indicate that jointly modeling pathological temporal dynamics and physiology-constrained pseudo-supervision can provide more robust cross-subject initialization for personalized post-stroke MI-BCI rehabilitation. The implemented code is available at https://github.com/wxk1224/PA-TCNet.

Portable CT scanners may support earlier stroke assessment, but reduced photon counts introduce noise that affects image quality and may alter automated classification. We compared direct classification of simulated low-dose slices with residual U-Net denoising followed by the same fixed classifier. Poisson noise was generated at photon-count scaling factors of 1, 5, 10, 20, and 40 using three deterministic seeds. The held-out set contained 809 slices, including 242 positive and 567 negative slices. Direct classification reached its highest mean ROC-AUC at a scaling factor of 20 (0.937 +/- 0.002). Denoising followed by classification reached 0.842 +/- 0.005 at a scaling factor of 1 and declined to 0.655 +/- 0.002 at a scaling factor of 40. Meanwhile, reconstruction quality rose steadily from 21.92 to 40.91 dB PSNR and from 0.761 to 0.987 SSIM. Both pathways had poor sensitivity at a fixed 0.5 cutoff because their classification scores were concentrated near zero. Patient-level analysis was limited by the test-set composition: all 10 patients were positive under the mask-derived patient label, preventing estimation of patient-level AUC and specificity. Overall, higher reconstruction fidelity did not translate into better discrimination by the fixed classifier except at the lowest photon-count setting.

Physics-informed neural networks (PINNs) have shown promise in addressing the ill-posed deconvolution problem in computed tomography perfusion (CTP) imaging for acute ischemic stroke assessment. However, existing PINN-based approaches remain deterministic and do not quantify uncertainty associated with violations of physics constraints, limiting reliability assessment. We propose Evidential Perfusion Physics-Informed Neural Networks (EPPINN), a framework that integrates evidential deep learning with physics-informed modeling to enable uncertainty-aware perfusion parameter estimation. EPPINN models arterial input, tissue concentration, and perfusion parameters using coordinate-based networks, and places a Normal--Inverse--Gamma distribution over the physics residual to characterize voxel-wise aleatoric and epistemic uncertainty in physics consistency without requiring Bayesian sampling or ensemble inference. The framework further incorporates physiologically constrained parameterization and stabilization strategies to promote robust per-case optimization. We evaluate EPPINN on digital phantom data, the ISLES 2018 benchmark, and a clinical cohort. On the evaluated datasets, EPPINN achieves lower normalized mean absolute error than classical deconvolution and PINN baselines, particularly under sparse temporal sampling and low signal-to-noise conditions, while providing conservative uncertainty estimates with high empirical coverage. On clinical data, EPPINN attains the highest voxel-level and case-level infarct-core detection sensitivity. These results suggest that evidential physics-informed learning can improve both accuracy and reliability of CTP analysis for time-critical stroke assessment. Source code is available at https://github.com/jhlee0619/EPPINN.

Cerebrovascular research heavily relies on quantitative analysis of intracranial arteries from time-of-flight magnetic resonance angiography, yet existing processing pipelines remain limited by inconsistent artery labeling and a high manual correction burden. We present ArteryX, a toolbox for extracting features that standardizes artery classification across proximal and distal vascular territories. It integrates segmentation handling, isotropic processing, vessel-fused graph construction, and constrained landmark-based classification within a unified artery-specific feature reporting and reproducible workflow. The toolbox extracts morphological, topological, and complexity features including total length, mean radius, volume, surface area, branch count, tortuosity, and fractal dimensionality for standardized artery-segments. Test-and-validation were performed using three complementary datasets: (1)TopBrain-Challenge benchmarking with annotated arteries, (2)synthetic known-reference validation, and (3)exploratory in-vivo cohort of cerebral small vessel disease. In TopBrain analyses, ArteryX with supervised nnUnet segmentation showed minimal bias, while iCafe showed the highest bias and a large limit-of-agreement. ArteryX consistently demonstrated robust downstream quantification performance across segmentation sources (unsupervised/supervised). Agreement analyses showed minimal bias for radius and good sensitivity of extent-dependent metrics throughout the noisier segmentations compared to the state-of-the-art iCafe-toolbox. Furthermore, a stage-wise human-in-the-loop protocol showed lower intervention time than iCafe. In an in-vivo-cohort (48CSVD+, 20CSVD-), ArteryX-derived distal and territory-level features showed group-level differences, not evident with iCafe. To facilitate adoption-and-reproducibility, ArteryX is designed with versioned builds, tutorials, and documentation.

$\textbf{Objective:}$ 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.

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.

Every year in the United States, 800,000 individuals suffer a stroke - one person every 40 seconds, with a death occurring every four minutes. While individual factors vary, certain predictors are more prevalent in determining stroke risk. As strokes are the second leading cause of death and disability worldwide, predicting stroke likelihood based on lifestyle factors is crucial. Showing individuals their stroke risk could motivate lifestyle changes, and machine learning offers solutions to this prediction challenge. Neural networks excel at predicting outcomes based on training features like lifestyle factors, however, they're not the only option. Logistic regression models can also effectively compute the likelihood of binary outcomes based on independent variables, making them well-suited for stroke prediction. This analysis will compare both neural networks (dense and convolutional) and logistic regression models for stroke prediction, examining their pros, cons, and differences to develop the most effective predictor that minimizes false negatives.

BrainAGE is a promising imaging-derived biomarker of neurobiological ageing and disease risk, yet current approaches rely predominantly on T1-weighted structural MRI, overlooking functional vascular changes that may precede tissue damage and cognitive decline. DeepCBV maps, synthesized from non-contrast MRI, offer a scalable alternative to contrast-enhanced perfusion imaging by capturing vascular information relevant to early neurodegeneration. We developed a multimodal BrainAGE framework that combines predictions from two separate three-dimensional convolutional neural networks: one trained only on structural MRI scans and another trained only on DeepCBV maps. Each model was trained and validated on 2851 scans from 13 open-source datasets and was evaluated for concordance with MCI and AD. The combined model achieved the most accurate brain age gap for CN controls, with a mean absolute error of 3.95 years, outperforming models trained on MRI or DeepCBV alone. Saliency maps revealed complementary modality contributions: MRI emphasized white matter and cortical atrophy, while DeepCBV highlighted vascular-rich and periventricular regions implicated in hypoperfusion and early cerebrovascular dysfunction, consistent with known patterns of normal ageing. Next, we observed that BrainAGE increased stepwise across diagnostic strata (CN < MCI < AD) and correlated with cognitive impairment. DeepCBV-based BrainAGE showed a particularly strong separation between stable versus progressive MCI, suggesting sensitivity to prodromal vascular changes that precede overt atrophy. Integrating structural MRI with deep learning-derived vascular measures substantially enhances BrainAGE estimation and improves sensitivity to MCI and AD progression, supporting its potential role in risk stratification, early detection and monitoring of therapeutic response.

The scarcity of temporally aligned pre-event physiological data limits the study of stroke risk states before documented clinical recognition. We focus on patients who experienced stroke during hospitalization while undergoing continuous monitoring, enabling retrospective analysis of pre-anchor photoplethysmography (PPG). Using MIMIC-III and MC-MED, an LLM-assisted pipeline generated candidate stroke anchors from unstructured notes. All retained anchors underwent physician adjudication, and a stratified 100-case double-review audit showed 95.0% candidate-to-adjudicated agreement within +/-15 min. We identified 176 MIMIC-III patients and 154 MC-MED patients with eligible synchronized pre-anchor PPG. A fixed 17-channel hemodynamic representation and ResNet-1D classifier were evaluated using patient-level five-fold internal validation and frozen external testing. At validation-selected operating points, F1-scores were 0.7956, 0.8759, and 0.9406 for 4-, 5-, and 6-hour horizons in MIMIC-III and 0.9256, 0.9595, and 0.9888 in MC-MED; the corresponding threshold-free AUCs ranged from 0.6124 to 0.7079. The PPG model achieved higher F1 than four non-waveform clinical and structured-EHR comparators in all six cohort-horizon settings. On high-risk non-stroke controls, window-level false-positive rates ranged from 0.1371 to 0.2938 and decreased to 0.0183-0.1739 after persistence aggregation. These retrospective findings support measurable pre-anchor PPG structure, but do not establish biological stroke onset, a calibrated bedside alarm, or a clinically validated prediction lead time.