Matthew B. Schabath

Nikolas Koutsoubis, Asim Waqas, Yasin Yilmaz et al.

Artificial Intelligence (AI) has demonstrated significant potential in automating various medical imaging tasks, which could soon become routine in clinical practice for disease diagnosis, prognosis, treatment planning, and post-treatment surveillance. However, the privacy concerns surrounding patient data present a major barrier to the widespread adoption of AI in medical imaging, as large, diverse training datasets are essential for developing accurate, generalizable, and robust Artificial intelligence models. Federated Learning (FL) offers a solution that enables organizations to train AI models collaboratively without sharing sensitive data. federated learning exchanges model training information, such as gradients, between the participating sites. Despite its promise, federated learning is still in its developmental stages and faces several challenges. Notably, sensitive information can still be inferred from the gradients shared during model training. Quantifying AI models' uncertainty is vital due to potential data distribution shifts post-deployment, which can affect model performance. Uncertainty quantification (UQ) in FL is particularly challenging due to data heterogeneity across participating sites. This review provides a comprehensive examination of FL, privacy-preserving FL (PPFL), and UQ in FL. We identify key gaps in current FL methodologies and propose future research directions to enhance data privacy and trustworthiness in medical imaging applications.

Asim Waqas, Aakash Tripathi, Sabeen Ahmed et al.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling more effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through the integration of all available multi-omics data is still an under-study research direction. Here, we present SeNMo, a foundation model that has been trained on multi-omics data across 33 cancer types. SeNMo is particularly efficient in handling multi-omics data characterized by high-width and low-length attributes. We trained SeNMo for the task of overall survival of patients using pan-cancer multi-omics data involving 33 cancer sites from the GDC. The training multi-omics data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. SeNMo was validated on two independent cohorts: Moffitt Cancer Center and CPTAC lung squamous cell carcinoma. We evaluated the model's performance in predicting patient's overall survival using the C-Index. SeNMo performed consistently well in the training regime, reflected by the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo demonstrated robust performance on the classification task of predicting the primary cancer type of patients. SeNMo further demonstrated significant performance in predicting tertiary lymph structures from multi-omics data, showing generalizability across cancer types, molecular data types, and clinical endpoints.

Aakash Tripathi, Asim Waqas, Matthew B. Schabath et al.

Accurate cancer survival prediction requires integration of diverse data modalities that reflect the complex interplay between imaging, clinical parameters, and textual reports. However, existing multimodal approaches suffer from simplistic fusion strategies, massive computational requirements, and lack of interpretability-critical barriers to clinical adoption. We present EAGLE (Efficient Alignment of Generalized Latent Embeddings), a novel deep learning framework that addresses these limitations through attention-based multimodal fusion with comprehensive attribution analysis. EAGLE introduces four key innovations: (1) dynamic cross-modal attention mechanisms that learn hierarchical relationships between modalities, (2) massive dimensionality reduction (99.96%) while maintaining predictive performance, (3) three complementary attribution methods providing patient-level interpretability, and (4) a unified pipeline enabling seamless adaptation across cancer types. We evaluated EAGLE on 911 patients across three distinct malignancies: glioblastoma (GBM, n=160), intraductal papillary mucinous neoplasms (IPMN, n=171), and non-small cell lung cancer (NSCLC, n=580). Patient-level analysis showed high-risk individuals relied more heavily on adverse imaging features, while low-risk patients demonstrated balanced modality contributions. Risk stratification identified clinically meaningful groups with 4-fold (GBM) to 5-fold (NSCLC) differences in median survival, directly informing treatment intensity decisions. By combining state-of-the-art performance with clinical interpretability, EAGLE bridges the gap between advanced AI capabilities and practical healthcare deployment, offering a scalable solution for multimodal survival prediction that enhances both prognostic accuracy and physician trust in automated predictions.

Sabeen Ahmed, Nathan Parker, Margaret Park et al.

Cancer cachexia is a common metabolic disorder characterized by severe muscle atrophy which is associated with poor prognosis and quality of life. Monitoring skeletal muscle area (SMA) longitudinally through computed tomography (CT) scans, an imaging modality routinely acquired in cancer care, is an effective way to identify and track this condition. However, existing tools often lack full automation and exhibit inconsistent accuracy, limiting their potential for integration into clinical workflows. To address these challenges, we developed SMAART-AI (Skeletal Muscle Assessment-Automated and Reliable Tool-based on AI), an end-to-end automated pipeline powered by deep learning models (nnU-Net 2D) trained on mid-third lumbar level CT images with 5-fold cross-validation, ensuring generalizability and robustness. SMAART-AI incorporates an uncertainty-based mechanism to flag high-error SMA predictions for expert review, enhancing reliability. We combined the SMA, skeletal muscle index, BMI, and clinical data to train a multi-layer perceptron (MLP) model designed to predict cachexia at the time of cancer diagnosis. Tested on the gastroesophageal cancer dataset, SMAART-AI achieved a Dice score of 97.80% +/- 0.93%, with SMA estimated across all four datasets in this study at a median absolute error of 2.48% compared to manual annotations with SliceOmatic. Uncertainty metrics-variance, entropy, and coefficient of variation-strongly correlated with SMA prediction errors (0.83, 0.76, and 0.73 respectively). The MLP model predicts cachexia with 79% precision, providing clinicians with a reliable tool for early diagnosis and intervention. By combining automation, accuracy, and uncertainty awareness, SMAART-AI bridges the gap between research and clinical application, offering a transformative approach to managing cancer cachexia.

Nikolas Koutsoubis, Yasin Yilmaz, Ravi P. Ramachandran et al.

Machine learning (ML) and Artificial Intelligence (AI) have fueled remarkable advancements, particularly in healthcare. Within medical imaging, ML models hold the promise of improving disease diagnoses, treatment planning, and post-treatment monitoring. Various computer vision tasks like image classification, object detection, and image segmentation are poised to become routine in clinical analysis. However, privacy concerns surrounding patient data hinder the assembly of large training datasets needed for developing and training accurate, robust, and generalizable models. Federated Learning (FL) emerges as a compelling solution, enabling organizations to collaborate on ML model training by sharing model training information (gradients) rather than data (e.g., medical images). FL's distributed learning framework facilitates inter-institutional collaboration while preserving patient privacy. However, FL, while robust in privacy preservation, faces several challenges. Sensitive information can still be gleaned from shared gradients that are passed on between organizations during model training. Additionally, in medical imaging, quantifying model confidence\uncertainty accurately is crucial due to the noise and artifacts present in the data. Uncertainty estimation in FL encounters unique hurdles due to data heterogeneity across organizations. This paper offers a comprehensive review of FL, privacy preservation, and uncertainty estimation, with a focus on medical imaging. Alongside a survey of current research, we identify gaps in the field and suggest future directions for FL research to enhance privacy and address noisy medical imaging data challenges.