Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting 35% of extremely low birth weight infants. Defined by oxygen dependence at 36 weeks postmenstrual age, it causes lifelong respiratory complications. However, preventive interventions carry severe risks, including neurodevelopmental impairment, ventilator-induced lung injury, and systemic complications. Therefore, early BPD prognosis and prediction of BPD outcome is crucial to avoid unnecessary toxicity in low risk infants. Admission radiographs of extremely preterm infants are routinely acquired within 24h of life and could serve as a non-invasive prognostic tool. In this work, we developed and investigated a deep learning approach using chest X-rays from 163 extremely low-birth-weight infants ($\leq$32 weeks gestation, 401-999g) obtained within 24 hours of birth. We fine-tuned a ResNet-50 pretrained specifically on adult chest radiographs, employing progressive layer freezing with discriminative learning rates to prevent overfitting and evaluated a CutMix augmentation and linear probing. For moderate/severe BPD outcome prediction, our best performing model with progressive freezing, linear probing and CutMix achieved an AUROC of 0.78 $\pm$ 0.10, balanced accuracy of 0.69 $\pm$ 0.10, and an F1-score of 0.67 $\pm$ 0.11. In-domain pre-training significantly outperformed ImageNet initialization (p = 0.031) which confirms domain-specific pretraining to be important for BPD outcome prediction. Routine IRDS grades showed limited prognostic value (AUROC 0.57 $\pm$ 0.11), confirming the need of learned markers. Our approach demonstrates that domain-specific pretraining enables accurate BPD prediction from routine day-1 radiographs. Through progressive freezing and linear probing, the method remains computationally feasible for site-level implementation and future federated learning deployments.
Accurate gland segmentation in histopathology images is essential for cancer diagnosis and prognosis. However, significant variability in Hematoxylin and Eosin (H&E) staining and tissue morphology, combined with limited annotated data, poses major challenges for automated segmentation. To address this, we propose Color-Structure Dual-Student (CSDS), a novel semi-supervised segmentation framework designed to learn disentangled representations of stain appearance and tissue structure. CSDS comprises two specialized student networks: one trained on stain-augmented inputs to model chromatic variation, and the other on structure-augmented inputs to capture morphological cues. A shared teacher network, updated via Exponential Moving Average (EMA), supervises both students through pseudo-labels. To further improve label reliability, we introduce stain-aware and structure-aware uncertainty estimation modules that adaptively modulate the contribution of each student during training. Experiments on the GlaS and CRAG datasets show that CSDS achieves state-of-the-art performance in low-label settings, with Dice score improvements of up to 1.2% on GlaS and 0.7% on CRAG at 5% labeled data, and 0.7% and 1.4% at 10%. Our code and pre-trained models are available at https://github.com/hieuphamha19/CSDS.
Pathology image segmentation is crucial in computational pathology for analyzing histological features relevant to cancer diagnosis and prognosis. However, current methods face major challenges in clinical applications due to limited annotated data and restricted category definitions. To address these limitations, we propose PathSegmentor, the first text-prompted segmentation foundation model designed specifically for pathology images. We also introduce PathSeg , the largest and most comprehensive dataset for pathology segmentation, built from 17 public sources and containing 275k image-mask-label triples across 160 diverse categories. With PathSegmentor, users can perform semantic segmentation using natural language prompts, eliminating the need for laborious spatial inputs such as points or boxes. Extensive experiments demonstrate that PathSegmentor outperforms specialized models with higher accuracy and broader applicability, while maintaining a compact architecture. It significantly surpasses existing spatial- and text-prompted models by 0.145 and 0.429 in overall Dice scores, respectively, showing strong robustness in segmenting complex structures and generalizing to external datasets. Moreover, PathSegmentor's outputs enhance the interpretability of diagnostic models through feature importance estimation and imaging biomarker discovery, offering pathologists evidence-based support for clinical decision-making. This work advances the development of explainable AI in precision oncology.
Multiple instance learning (MIL) has shown significant promise in histopathology whole slide image (WSI) analysis for cancer diagnosis and prognosis. However, the inherent spatial heterogeneity of WSIs presents critical challenges, as morphologically similar tissue types are often dispersed across distant anatomical regions. Conventional MIL methods struggle to model these scattered tissue distributions and capture cross-regional spatial interactions effectively. To address these limitations, we propose a novel Multiple instance learning framework with Context-Aware Clustering (MiCo), designed to enhance cross-regional intra-tissue correlations and strengthen inter-tissue semantic associations in WSIs. MiCo begins by clustering instances to distill discriminative morphological patterns, with cluster centroids serving as semantic anchors. To enhance cross-regional intra-tissue correlations, MiCo employs a Cluster Route module, which dynamically links instances of the same tissue type across distant regions via feature similarity. These semantic anchors act as contextual hubs, propagating semantic relationships to refine instance-level representations. To eliminate semantic fragmentation and strengthen inter-tissue semantic associations, MiCo integrates a Cluster Reducer module, which consolidates redundant anchors while enhancing information exchange between distinct semantic groups. Extensive experiments on two challenging tasks across nine large-scale public cancer datasets demonstrate the effectiveness of MiCo, showcasing its superiority over state-of-the-art methods. The code is available at https://github.com/junjianli106/MiCo.
The refractory period and conduction delay of the atrioventricular (AV) node play a crucial role in regulating the heart rate during atrial fibrillation (AF). Beat-to-beat variations in these properties are known to be induced by the autonomic nervous system (ANS) but have previously not been assessable during AF. Assessing these could provide novel information for improved diagnosis, prognosis, and treatment on an individual basis. To estimate AV nodal conduction properties with beat-to-beat resolution, we propose a methodology comprising a network model of the AV node, a particle filter, and a smoothing algorithm. The methodology was evaluated using simulated data and using synchronized electrogram (EGM) and ECG recordings from five patients in the intracardiac atrial fibrillation database. The methodology's ability to quantify ANS-induced changes in AV node conduction properties was evaluated by analyzing ECG data from 21 patients in AF undergoing a tilt test protocol. The estimated refractory period and conduction delay matched the simulated ground truth based on ECG recordings with a mean absolute error ($\pm$ std) of 169$\pm$14 ms for the refractory period in the fast pathway; 131$\pm$13 ms for the conduction delay in the fast pathway; 67$\pm$10 ms for the refractory period in the slow pathway; and 178$\pm$28 ms for the conduction delay in the slow pathway. These errors decreased when using simulated ground truth based on EGM recordings. Moreover, a decrease in conduction delay and refractory period in response to head-up tilt was seen during the tilt test protocol, as expected under sympathetic activation. These results suggest that beat-to-beat estimation of AV nodal conduction properties during AF from ECG is feasible, with different levels of uncertainty, and that the estimated properties agree with expected AV nodal modulation.
Clinical laboratory results are ubiquitous in any diagnosis making. Predicting abnormal values of not prescribed tests based on the results of performed tests looks intriguing, as it would be possible to make early diagnosis available to everyone. The special place is taken by the Common Blood Count (CBC) test, as it is the most widely used clinical procedure. Combining routine biochemical panels with CBC presents a set of test-value pairs that varies from patient to patient, or, in common settings, a table with missing values. Here we formulate a tabular modeling problem as a set translation problem where the source set comprises pairs of GPT-like label column embedding and its corresponding value while the target set consists of the same type embeddings only. The proposed approach can effectively deal with missing values without implicitly estimating them and bridges the world of LLM with the tabular domain. Applying this method to clinical laboratory data, we achieve an improvement up to 8% AUC for joint predictions of high uric acid, glucose, cholesterol, and low ferritin levels.
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Early and precise diagnosis of AD is crucial for timely intervention and treatment planning to alleviate the progressive neurodegeneration. However, most existing methods rely on single-modality data, which contrasts with the multifaceted approach used by medical experts. While some deep learning approaches process multi-modal data, they are limited to specific tasks with a small set of input modalities and cannot handle arbitrary combinations. This highlights the need for a system that can address diverse AD-related tasks, process multi-modal or missing input, and integrate multiple advanced methods for improved performance. In this paper, we propose ADAgent, the first specialized AI agent for AD analysis, built on a large language model (LLM) to address user queries and support decision-making. ADAgent integrates a reasoning engine, specialized medical tools, and a collaborative outcome coordinator to facilitate multi-modal diagnosis and prognosis tasks in AD. Extensive experiments demonstrate that ADAgent outperforms SOTA methods, achieving significant improvements in accuracy, including a 2.7% increase in multi-modal diagnosis, a 0.7% improvement in multi-modal prognosis, and enhancements in MRI and PET diagnosis tasks.
This paper introduces Spectral Fault Receptive Fields (SFRFs), a biologically inspired technique for degradation state assessment in bearing fault diagnosis and remaining useful life (RUL) estimation. Drawing on the center-surround organization of retinal ganglion cell receptive fields, we propose a frequency-domain feature extraction algorithm that enhances the detection of fault signatures in vibration signals. SFRFs are designed as antagonistic spectral filters centered on characteristic fault frequencies, with inhibitory surrounds that enable robust characterization of incipient faults under variable operating conditions. A multi-objective evolutionary optimization strategy based on NSGA-II algorithm is employed to tune the receptive field parameters by simultaneously minimizing RUL prediction error, maximizing feature monotonicity, and promoting smooth degradation trajectories. The method is demonstrated on the XJTU-SY bearing run-to-failure dataset, confirming its suitability for constructing condition indicators in health monitoring applications. Key contributions include: (i) the introduction of SFRFs, inspired by the biology of vision in the primate retina; (ii) an evolutionary optimization framework guided by condition monitoring and prognosis criteria; and (iii) experimental evidence supporting the detection of early-stage faults and their precursors. Furthermore, we confirm that our diagnosis-informed spectral representation achieves accurate RUL prediction using a bagging regressor. The results highlight the interpretability and principled design of SFRFs, bridging signal processing, biological sensing principles, and data-driven prognostics in rotating machinery.
INTRODUCTION: Quantification of amyloid plaques (A), neurofibrillary tangles (T2), and neurodegeneration (N) using PET and MRI is critical for Alzheimer's disease (AD) diagnosis and prognosis. Existing pipelines face limitations regarding processing time, variability in tracer types, and challenges in multimodal integration. METHODS: We developed petBrain, a novel end-to-end processing pipeline for amyloid-PET, tau-PET, and structural MRI. It leverages deep learning-based segmentation, standardized biomarker quantification (Centiloid, CenTauR, HAVAs), and simultaneous estimation of A, T2, and N biomarkers. The pipeline is implemented as a web-based platform, requiring no local computational infrastructure or specialized software knowledge. RESULTS: petBrain provides reliable and rapid biomarker quantification, with results comparable to existing pipelines for A and T2. It shows strong concordance with data processed in ADNI databases. The staging and quantification of A/T2/N by petBrain demonstrated good agreement with CSF/plasma biomarkers, clinical status, and cognitive performance. DISCUSSION: petBrain represents a powerful and openly accessible platform for standardized AD biomarker analysis, facilitating applications in clinical research.
Oral cancer presents a formidable challenge in oncology, necessitating early diagnosis and accurate prognosis to enhance patient survival rates. Recent advancements in machine learning and data mining have revolutionized traditional diagnostic methodologies, providing sophisticated and automated tools for differentiating between benign and malignant oral lesions. This study presents a comprehensive review of cutting-edge data mining methodologies, including Neural Networks, K-Nearest Neighbors (KNN), Support Vector Machines (SVM), and ensemble learning techniques, specifically applied to the diagnosis and prognosis of oral cancer. Through a rigorous comparative analysis, our findings reveal that Neural Networks surpass other models, achieving an impressive classification accuracy of 93,6 % in predicting oral cancer. Furthermore, we underscore the potential benefits of integrating feature selection and dimensionality reduction techniques to enhance model performance. These insights underscore the significant promise of advanced data mining techniques in bolstering early detection, optimizing treatment strategies, and ultimately improving patient outcomes in the realm of oral oncology.
Lung cancer remains one of the most prevalent and fatal diseases worldwide, demanding accurate and timely diagnosis and treatment. Recent advancements in large AI models have significantly enhanced medical image understanding and clinical decision-making. This review systematically surveys the state-of-the-art in applying large AI models to lung cancer screening, diagnosis, prognosis, and treatment. We categorize existing models into modality-specific encoders, encoder-decoder frameworks, and joint encoder architectures, highlighting key examples such as CLIP, BLIP, Flamingo, BioViL-T, and GLoRIA. We further examine their performance in multimodal learning tasks using benchmark datasets like LIDC-IDRI, NLST, and MIMIC-CXR. Applications span pulmonary nodule detection, gene mutation prediction, multi-omics integration, and personalized treatment planning, with emerging evidence of clinical deployment and validation. Finally, we discuss current limitations in generalizability, interpretability, and regulatory compliance, proposing future directions for building scalable, explainable, and clinically integrated AI systems. Our review underscores the transformative potential of large AI models to personalize and optimize lung cancer care.
m5C modification is a type of RNA methylation modification, and its major methyltransferase, NSUN2, catalyzes m5C modification. NSUN2 is overexpressed in a variety of cancers, and it affects the metabolism of RNA from target genes by affecting the level of m5C modification in cancer cells, which in turn promotes the development of cancers and is associated with poor prognosis. This review summarizes the mechanisms by which NSUN2 and m5C play a pro-cancer role in various cancers, and the relationship between NSUN2 and the prognosis of various cancers, with the aim of identifying NSUN2 as a prognostic indicator and a target for future cancer therapy, and to provide a clearer therapeutic idea and direction for the future treatment of cancer.
Pre-trained encoders for offline feature extraction followed by multiple instance learning (MIL) aggregators have become the dominant paradigm in computational pathology (CPath), benefiting cancer diagnosis and prognosis. However, performance limitations arise from the absence of encoder fine-tuning for downstream tasks and disjoint optimization with MIL. While slide-level supervised end-to-end (E2E) learning is an intuitive solution to this issue, it faces challenges such as high computational demands and suboptimal results. These limitations motivate us to revisit E2E learning. We argue that prior work neglects inherent E2E optimization challenges, leading to performance disparities compared to traditional two-stage methods. In this paper, we pioneer the elucidation of optimization challenge caused by sparse-attention MIL and propose a novel MIL called ABMILX. It mitigates this problem through global correlation-based attention refinement and multi-head mechanisms. With the efficient multi-scale random patch sampling strategy, an E2E trained ResNet with ABMILX surpasses SOTA foundation models under the two-stage paradigm across multiple challenging benchmarks, while remaining computationally efficient (<10 RTX3090 hours). We show the potential of E2E learning in CPath and calls for greater research focus in this area. The code is https://github.com/DearCaat/E2E-WSI-ABMILX.
The importance of clinical variables in the prognosis of the disease is explained using statistical correlation or machine learning (ML). However, the predictive importance of these variables may not represent their causal relationships with diseases. This paper uses clinical variables from a heart failure (HF) patient cohort to investigate the causal explainability of important variables obtained in statistical and ML contexts. Due to inherent regression modeling, popular causal discovery methods strictly assume that the cause and effect variables are numerical and continuous. This paper proposes a new computational framework to enable causal structure discovery (CSD) and score the causal strength of mixed-type (categorical, numerical, binary) clinical variables for binary disease outcomes. In HF classification, we investigate the association between the importance rank order of three feature types: correlated features, features important for ML predictions, and causal features. Our results demonstrate that CSD modeling for nonlinear causal relationships is more meaningful than its linear counterparts. Feature importance obtained from nonlinear classifiers (e.g., gradient-boosting trees) strongly correlates with the causal strength of variables without differentiating cause and effect variables. Correlated variables can be causal for HF, but they are rarely identified as effect variables. These results can be used to add the causal explanation of variables important for ML-based prediction modeling.
Objective: Heart failure (HF) patients present with diverse phenotypes affecting treatment and prognosis. This study evaluates models for phenotyping HF patients based on left ventricular ejection fraction (LVEF) classes, using structured and unstructured data, assessing performance and interpretability. Materials and Methods: The study analyzes all HF hospitalizations at both Amsterdam UMC hospitals (AMC and VUmc) from 2015 to 2023 (33,105 hospitalizations, 16,334 patients). Data from AMC were used for model training, and from VUmc for external validation. The dataset was unlabelled and included tabular clinical measurements and discharge letters. Silver labels for LVEF classes were generated by combining diagnosis codes, echocardiography results, and textual mentions. Gold labels were manually annotated for 300 patients for testing. Multiple Transformer-based (black-box) and Aug-Linear (white-box) models were trained and compared with baselines on structured and unstructured data. To evaluate interpretability, two clinicians annotated 20 discharge letters by highlighting information they considered relevant for LVEF classification. These were compared to SHAP and LIME explanations from black-box models and the inherent explanations of Aug-Linear models. Results: BERT-based and Aug-Linear models, using discharge letters alone, achieved the highest classification results (AUC=0.84 for BERT, 0.81 for Aug-Linear on external validation), outperforming baselines. Aug-Linear explanations aligned more closely with clinicians' explanations than post-hoc explanations on black-box models. Conclusions: Discharge letters emerged as the most informative source for phenotyping HF patients. Aug-Linear models matched black-box performance while providing clinician-aligned interpretability, supporting their use in transparent clinical decision-making.
Accurate lesion-level segmentation on MRI is critical for multiple sclerosis (MS) diagnosis, prognosis, and disease monitoring. However, current evaluation practices largely rely on semantic segmentation post-processed with connected components (CC), which cannot separate confluent lesions (aggregates of confluent lesion units, CLUs) due to reliance on spatial connectivity. To address this misalignment with clinical needs, we introduce formal definitions of CLUs and associated CLU-aware detection metrics, and include them in an exhaustive instance segmentation evaluation framework. Within this framework, we systematically evaluate CC and post-processing-based Automated Confluent Splitting (ACLS), the only existing methods for lesion instance segmentation in MS. Our analysis reveals that CC consistently underestimates CLU counts, while ACLS tends to oversplit lesions, leading to overestimated lesion counts and reduced precision. To overcome these limitations, we propose ConfLUNet, the first end-to-end instance segmentation framework for MS lesions. ConfLUNet jointly optimizes lesion detection and delineation from a single FLAIR image. Trained on 50 patients, ConfLUNet significantly outperforms CC and ACLS on the held-out test set (n=13) in instance segmentation (Panoptic Quality: 42.0% vs. 37.5%/36.8%; p = 0.017/0.005) and lesion detection (F1: 67.3% vs. 61.6%/59.9%; p = 0.028/0.013). For CLU detection, ConfLUNet achieves the highest F1[CLU] (81.5%), improving recall over CC (+12.5%, p = 0.015) and precision over ACLS (+31.2%, p = 0.003). By combining rigorous definitions, new CLU-aware metrics, a reproducible evaluation framework, and the first dedicated end-to-end model, this work lays the foundation for lesion instance segmentation in MS.
Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.
A cardiac digital twin is a virtual replica of a patient's heart for screening, diagnosis, prognosis, risk assessment, and treatment planning of cardiovascular diseases. This requires an anatomically accurate patient-specific 3D structural representation of the heart, suitable for electro-mechanical simulations or study of disease mechanisms. However, generation of cardiac digital twins at scale is demanding and there are no public repositories of models across demographic groups. We describe an automatic open-source pipeline for creating patient-specific left and right ventricular meshes from cardiovascular magnetic resonance images, its application to a large cohort of ~55000 participants from UK Biobank, and the construction of the most comprehensive cohort of adult heart models to date, comprising 1423 representative meshes across sex (male, female), body mass index (range: 16 - 42 kg/m$^2$) and age (range: 49 - 80 years). Our code is available at https://github.com/cdttk/biv-volumetric-meshing/tree/plos2025 , and pre-trained networks, representative volumetric meshes with fibers and UVCs will be made available soon.
The emergence of pathology foundation models has revolutionized computational histopathology, enabling highly accurate, generalized whole-slide image analysis for improved cancer diagnosis, and prognosis assessment. While these models show remarkable potential across cancer diagnostics and prognostics, their clinical translation faces critical challenges including variability in optimal model across cancer types, potential data leakage in evaluation, and lack of standardized benchmarks. Without rigorous, unbiased evaluation, even the most advanced PFMs risk remaining confined to research settings, delaying their life-saving applications. Existing benchmarking efforts remain limited by narrow cancer-type focus, potential pretraining data overlaps, or incomplete task coverage. We present PathBench, the first comprehensive benchmark addressing these gaps through: multi-center in-hourse datasets spanning common cancers with rigorous leakage prevention, evaluation across the full clinical spectrum from diagnosis to prognosis, and an automated leaderboard system for continuous model assessment. Our framework incorporates large-scale data, enabling objective comparison of PFMs while reflecting real-world clinical complexity. All evaluation data comes from private medical providers, with strict exclusion of any pretraining usage to avoid data leakage risks. We have collected 15,888 WSIs from 8,549 patients across 10 hospitals, encompassing over 64 diagnosis and prognosis tasks. Currently, our evaluation of 19 PFMs shows that Virchow2 and H-Optimus-1 are the most effective models overall. This work provides researchers with a robust platform for model development and offers clinicians actionable insights into PFM performance across diverse clinical scenarios, ultimately accelerating the translation of these transformative technologies into routine pathology practice.
Ratio-based biomarkers -- such as the proportion of necrotic tissue within a tumor -- are widely used in clinical practice to support diagnosis, prognosis and treatment planning. These biomarkers are typically estimated from soft segmentation outputs by computing region-wise ratios. Despite the high-stakes nature of clinical decision making, existing methods provide only point estimates, offering no measure of uncertainty. In this work, we propose a unified \textit{confidence-aware} framework for estimating ratio-based biomarkers. We conduct a systematic analysis of error propagation in the segmentation-to-biomarker pipeline and identify model miscalibration as the dominant source of uncertainty. To mitigate this, we incorporate a lightweight, post-hoc calibration module that can be applied using internal hospital data without retraining. We leverage a tunable parameter $Q$ to control the confidence level of the derived bounds, allowing adaptation towards clinical practice. Extensive experiments show that our method produces statistically sound confidence intervals, with tunable confidence levels, enabling more trustworthy application of predictive biomarkers in clinical workflows.