Radiomics

Radiological artificial intelligence has advanced rapidly, yet most systems remain narrowly task-specific, data-intensive, and fragile under domain shift. Foundation models promise more transferable and data-efficient solutions, but existing approaches are limited in scale, evaluated narrowly, and often assume that a single pretrained model can support diverse downstream tasks. Here we present nnFoundation, complementary convolutional and transformer-based 3D radiological foundation models. Developed within the Human Radiome Project (THRP), nnFoundation is trained on 2.1 million CT, MRI, and PET image volumes from 125 institutional and public datasets. We evaluate them across 108 tasks spanning segmentation, detection, classification, report generation, and image retrieval, including evaluations under domain shift, by external partners and in low-data and low-compute regimes. Across all task types, our convolution- and transformer-based nnFoundation models consistently outperform both prior 3D foundation models and training from scratch, establishing state-of-the-art performance for radiological imaging. However, performance follows a consistent task-dependent structure: the convolutional nnFoundation model dominates spatially localized tasks, whereas the transformer-based nnFoundation model excels in tasks requiring global semantic reasoning and in frozen-feature settings. Dynamically aligning the foundation model topology with the dataset characteristics post-hoc further improves transfer across heterogeneous 3D settings. These results show that transferable 3D radiological performance is governed not by a single universal model, but by the interplay of scalable pretraining, complementary architectures, and dataset-aware adaptation. We release nnFoundation models integrated into nnU-Net and nnDetection, enabling immediate application across established radiology workflows.

Radiomics provides quantitative descriptions of tumour appearance that may complement disease-specific foundation models in small labelled cohorts. We investigate this complementarity for computed tomography-based classification of clear cell renal cell carcinoma. Our framework uses radiomics to modulate RenalCLIP features through feature-wise linear modulation (FiLM), while retaining a direct radiomics contribution. Internal testing and external validation compare it with conventional fusion strategies and reference classifiers. The FiLM model achieves an area under the receiver operating characteristic curve (AUC) of 0.804 internally and 0.854 externally, with the highest mean AUC among the evaluated RenalCLIP fusion strategies in both cohorts. Pathway ablations examine the contributions of conditional modulation and the direct radiomics residual, while feature permutation highlights the role of tumour texture. These findings support radiomics as a useful complement to RenalCLIP in a small labelled cohort and identify FiLM as an effective approach to integrating their representations for robust renal tumour classification.

Accurate preoperative subtype classification of renal cell carcinoma (RCC) from contrast-enhanced computed tomography remains clinically challenging. Radiomics provides structured tumour descriptors, whereas foundation representations offer transferable image features. However, it remains unclear whether radiomics still adds value beyond pretrained representations, and how 2D and 3D MedVAE encoders compare in this setting. We compared handcrafted radiomics, 2D MedVAE, 3D MedVAE, and their fusion for binary clear-cell RCC versus non-clear-cell RCC classification on KiTS23 under a unified preprocessing pipeline. Concatenation, cross-attention, and gated fusion were evaluated as representative integration strategies, and radiomics feature importance was analysed to support decision-centric interpretability. Fusion consistently improved discrimination over image-only MedVAE branches. The best overall performance was achieved by 3D gated fusion, with an AUC of 82.7%, outperforming the best 2D fusion model (79.6%), the radiomics baseline (74.4%), and the single-modality MedVAE branches. Ablation analysis further showed clear gains of the full fusion model over both image-only and radiomics-only variants, indicating complementary contributions from radiomics and image representations. These findings suggest that radiomics remains relevant for RCC CT classification in the presence of foundation representations, and that its integration with MedVAE is more effective in the 3D setting. More broadly, the study supports a complementary role for radiomics and foundation representations in clinically meaningful imaging decision support.

Pancreatic cancer is among the most lethal malignancies; risk stratification of intraductal papillary mucinous neoplasms (IPMNs) offers a crucial opportunity for early intervention but typically requires invasive tissue biopsy. Dominant vision-based approaches, including radiomics and deep learning, provide promising but initially separate discrimination opportunities. Similarly, multisequence MRI (T1W/T2W) and anatomically decomposed (head, body and tail) analysis of the pancreas provide additional and potentially complementary signals. Effective fusion of this information is crucial in ordinal IPMN dysplasia risk prediction and can be accomplished via a meticulously regularized and calibrated ensemble stacking combiner. We present cUPMI, a class-conditional Gaussian augmentation of a combiner's log-probability meta-features, and test it on various prediction paradigms. In our multi-center analysis, we find cUPMI adds limited value to properly regularized L2-logistic binary classification stacks, but consistently regularizes higher-capacity tree combiners in the binary and radiomics-only setting (RF +0.015 and XGBoost +0.024 binary AUC, positive in all seeds). Its cleanest ordinal benefit appears for XGBoost on an 8-stream radiomics task (3-class no < low < high, +0.022 QWK in all seeds). Separately, fold-locked fusion of radiomics and 2.5D CNN streams yields the strongest overall model, an RF stack reaching QWK 0.595 (95% CI [0.54, 0.64]) and binary AUC 0.839, surpassing radiomics, 2.5D ResNet, and 3D DenseNet-121 baselines.

Deep learning models that synthesize PET from CT or MRI can reduce patient dose and scanner demand, but are typically optimized with global losses such as L1 or mean squared error (MSE) that treat all voxels similarly. In whole-body PSMA-PET, tumor voxels occupy only a small fraction of the volume, yet carry the clinically relevant activity signal; as a result, models can achieve high structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) while still underestimating lesion activity or failing to preserve tumor-specific structure. Radiomics provides biologically meaningful descriptors of tumor intensity and texture, but direct radiomics conditioning is time-consuming because it requires feature extraction from delineated lesion regions. We propose LAFNO, a Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA-PET synthesis that replaces high-dimensional radiomics conditioning with two efficient CT-derived proxy channels. Motivated by radiomics analysis of PSMA-avid tumor core and peritumoral regions, LAFNO uses a contrast proxy for local density variation and a disorder proxy for local texture heterogeneity, both injected into the model bottleneck. LAFNO combines whole-volume reconstruction with lesion-level total lesion activity (TLA), tumor-core contrast, and peritumoral supervision. We evaluated LAFNO against four baseline architectures on the TCIA PSMA-PET-CT-Lesions dataset. LAFNO remained competitive on whole-volume image quality, achieving SSIM of 0.960 and 0.938 for 18F- and 68Ga-PSMA, respectively, while reducing per-patient TLA error to 48.3% and 64.0% for 18F- and 68Ga-PSMA, respectively, and achieving the highest tumor-core radiomics reproducibility across all feature classes for both tracers. Peritumoral reproducibility remained tracer-dependent, indicating that biological fidelity in synthetic PSMA-PET remains challenging.

Virtual contrast enhancement (VCE) synthesizes enhanced breast MR images from pre-contrast acquisitions. Modern latent generators offer strong image priors, but their bounded natural-image autoencoders conflict with the non-canonical intensity scale of MRI. We show that the upper bound can alter radiomic fidelity before generation, while scaling source and target independently creates a coordinate inconsistency. We propose Predictive Enhancement Calibration (PEC), which represents each pair in a shared, case-adaptive coordinate during training and predicts its unavailable upper endpoint from the pre-contrast image at inference. We integrate PEC with a pretrained FLUX latent flow transformer via parameter-efficient reference conditioning. Target round trips first isolate representation loss before generation; near-matched conditional models then compare PEC with fixed-wide and separate coordinates under comparable training budgets and backbone settings. On the fixed internal MAMA100 development cohort, PEC improves all eight point estimates in this source-only VCE setting, with paired evidence strongest for MSE and LPIPS.\noindent\textbf{Code:} https://github.com/tanlei0/pec-breast-mri-vce

Lung cancer results in roughly 1.8 million fatalities annually worldwide, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite advancements in treatment, survival stratification remains challenging due to intratumoral heterogeneity inadequately captured by conventional descriptors. Standard radiomic and deep learning techniques regard imaging features as independent quantities, overlooking structured interactions between tumor characteristics. We evaluate whether structured proxy features can enhance multimodal NSCLC survival prediction by augmenting pretreatment computed tomography (CT) representations, radiomics, and clinical variables with six simulation-derived features designed to capture interactions between heterogeneity and morphology. A radiomic-parameterized cellular automaton generates growth-rate and necrosis-ratio proxy features from baseline CT by using entropy and sphericity to compute low-dimensional proxy parameters. The imaging backbone is a Transformer-based Masked Autoencoder (TMAE), which was chosen after a systematic evaluation with alternative encoders within the same pipeline and provides attention-based visualizations that highlight tumor regions receiving higher model attention. On the public Lung1 cohort (n = 390), the primary four-modality fusion attained a C-index of 0.641 (iAUC 0.731, log-rank p < 0.001). The primary result compares favorably with prior multimodal results on Lung1 (C-index 0.631; iAUC 0.592 [15]) under a comparable evaluation protocol, while a separate exploratory coefficient-optimization analysis achieved a best observed C-index of 0.662 (iAUC 0.748). These results indicate that, in addition to conventional radiomic, deep, and clinical representations within the Lung1 benchmark, simulation-derived proxy features may provide complementary predictive information within this fixed Lung1 benchmark.

Radiomics and imaging foundation models promise non-invasive biomarkers of tumour biology, yet predictive signatures may reflect tumour volume or acquisition artifacts rather than meaningful image structure. We introduce READII-2-ROQC, an open-source framework that uses volume-preserving negative controls to assess whether radiomic and deep imaging features capture independent spatial signals. READII-2-ROQC generates voxel-perturbed images across tumour, background and whole-image regions using configurable randomization strategies, then compares feature behaviour and model performance between original and control images. Applied to three public cancer imaging cohorts, the framework processed 3,552 tumour volumes and extracted PyRadiomics and foundation-model features from original images and nine matched controls. Reproducing published survival and HPV-status signatures, we show that multiple models retain performance after spatial structure is destroyed, revealing volume-driven or contextual confounding, whereas others show perturbation-sensitive signal. READII-2-ROQC provides a scalable quality-control strategy for developing interpretable, biologically grounded imaging biomarkers and reproducible radiomics workflows.

The rapid emergence of 3D CT foundation models has opened new avenues for predictive modeling from CT imaging, offering a compelling alternative to traditional radiomics which is known to suffer from reproducibility issues and sensitivity to acquisition protocol variations. Yet, as these models grow in availability, a critical need arises to evaluate how well their learned representations generalize across diverse clinical settings and whether adaptation to specific downstream tasks is necessary to unlock their full potential. To address these questions, we benchmarked several 3D CT foundation models for predicting recurrence-free survival in head and neck cancer across two public datasets totaling 3,644 patients, evaluating various adaptation strategies and modality fusion mechanisms. Our findings reveal persistent difficulty in identifying features that generalize consistently across different imaging distributions, as evidenced by significant performance drops on external validation cohorts. Ultimately, the integration of imaging features with clinical data remains the most accurate approach for prognostic prediction, though achieving universal generalization across varied clinical contexts continues to represent a substantial challenge for the current generation of models.

We present HERMES (Hybrid Ensemble for Radiotherapy-target segmentation, Malignancy staging, and Event-free Survival), a single containerized algorithm for the three HECKTOR 2026 subtasks: segmentation of the primary tumor (GTVp) and pathological lymph nodes (GTVn), radiological T/N staging, and recurrence-free survival (RFS), computed from a paired FDG-PET/CT scan and an electronic health record. A 10-fold ensemble of STU-Net Small networks produces the segmentation; the predicted mask then drives two downstream tasks. Rather than pass a generic radiomics vector to the staging models, we derive from the predicted masks a compact set of geometry features aligned with the size and number axes of AJCC/UICC 7th-edition radiological N/T staging. On internal cross-validation these features raise N-stage balanced accuracy from 0.691 to 0.720 (+0.030), our largest single design gain, at lower feature dimensionality. For prognosis we combine complementary deep and clinical risk experts in an equal-weight ensemble, and train one deep expert with a concordance-tracking survival loss of our own, whose value approximates the concordance index during training. Every component was selected on honest out-of-fold predictions under a regularization-oriented protocol, with no tuning on the public validation set, and deployed as two decorrelated submissions. On the HECKTOR 2026 validation leaderboard, HERMES achieved a weighted score of 0.6454 (Mean Dice 0.641, T balanced accuracy 0.580, N balanced accuracy 0.642, RFS C-index 0.679) and qualified for the testing phase. Team: AMC_HNC.

Background: Early prediction of distant metastasis (DM) risk in head and neck cancer (HNC) can enable timely interventions that may improve treatment outcomes. Many current machine learning methods rely on prior knowledge of the region of interest such as tumor segmentations, which require expert knowledge, is time-consuming and introduces user-dependent variability. Medical image-based foundation models have recently been developed for specific imaging modalities to streamline down-stream prediction tasks by extracting modality-relevant features. Purpose: In this study, we evaluate the effectiveness of using a foundation model as the feature extractor to predict DM risk in HNC patients and compare its performance with traditional approaches that require prior knowledge on the regions of interest. Methods: Preoperative CT images of 2327 patients from the RADCURE dataset were used. Three features-sets were created including radiomics, deep-learning based features, and CT Foundation derived features. The feature-sets were used individually in a multi-layer perceptron (MLP) to predict DM risk. Results: The model using CT Foundation embeddings outperformed the radiomics and deep learning-based models, achieving a Receiver Operating Characteristic Area Under the Curve (AUC) of 0.791, compared to AUC values of 0.772 and 0.753 for the radiomics and deep learning-based models, respectively. The CT Foundation based model had similar performance to a model that combined the use of radiomics and deep learning-based features that achieved an AUC of 0.794. Conclusions: Features based on foundation models offer a promising alternative to traditional radiomics while reducing the need for domain expertise and extensively annotated datasets. Their minimal preprocessing requirements also make them a more accessible and scalable option.

Radiomic biomarkers derived from magnetic resonance imaging (MRI) have been widely investigated as non-invasive tools for tumor characterization and prognostic modeling in glioblastoma (GBM). However, their clinical translation remains limited, in part due to sensitivity to tumor segmentation variability. In this study, we systematically investigate the relationship between feature robustness and predictive utility in GBM survival modeling using the University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics (UPENN-GBM) cohort. A total of 4,752 radiomic features were obtained from multiparametric MRI across three tumor subregions: enhancing tumor (ET), peritumoral edema (ED), and necrotic core (NC). Feature robustness was quantified using the intraclass correlation coefficient (ICC) based on the automatic and expert-refined segmentation versions. Among features with valid ICC estimates, 48.1% were classified as robust. Survival prediction was evaluated using cross-validation with Coxnet, Random Survival Forest, and Gradient Boosting Survival Analysis models. In this cohort, radiomic feature inclusion showed no consistent improvement over the clinical baseline, and robustness filtering produced no detectable performance gain. Model-selected features were less robust than the overall feature pool, indicating a lack of enrichment for robustness. These findings suggest that robustness alone is not a reliable criterion for feature selection in radiomics-based survival modelling.

The function of many genes is still unknown, and conventional driver-discovery methods, which rely on how frequently a gene is mutated, cannot assess genes that are only rarely affected. Here we pair Evo2-based genome analysis with routine clinical imaging to identify gene--phenotype associations at genome-wide scale. For every somatic mutation across three TCGA cohorts (cRCC=clear cell renal cell carcinoma, HCC=hepatocellular carcinoma, and BC=breast cancer; $n = 340$ total), Evo2 predicts a severity score, with no task-specific training. Per-gene severity summaries are then correlated with radiomic features extracted from paired tumor segmentations, controlling for total mutation burden. In TCGA-cRCC ($n = 162$), this sweep recovers established renal-cancer drivers and identifies 46 additional genes reaching false discovery rate (FDR) significance absent from curated cancer-gene panels, several of which are Mendelian ciliopathy and cytoskeletal-disease genes. These results demonstrate that pairing a genomic language model with widely available clinical imaging can serve as a hypothesis-free discovery tool for gene--imaging associations invisible to conventional approaches.

The Segment Anything Model (SAM) has demonstrated strong generalizability across a variety of segmentation tasks. However, SAM often struggles in situations where the target to be segmented is ambiguous. This poses a problem in medical imaging, where accurate delineation of targets such as tumors is vital, but even expert radiologists can disagree on the appropriate boundary for a target. Addressing this, we propose SARFA (Segment Anything with Radiomic Feature Alignment), a novel framework for improved medical image segmentation. Via probabilistic prompting, SARFA generates a diverse set of plausible masks for each input image and optimizes them with a radiomics-driven training objective based on Fréchet Radiomic Distance (FRD) and Direct Preference Optimization (DPO). By minimizing the FRD between masked predicted and ground truth regions within each image, SARFA encourages segmentation outputs whose anatomical and textural characteristics align with clinically meaningful ground truth representations, without relying solely on pixel-level overlap. Evaluated on computed tomography (CT) and magnetic resonance imaging (MRI) benchmarks, SARFA outperforms existing ambiguous segmentation methods, demonstrating the effectiveness of radiomic feature alignment and DPO-style candidate mask ranking as a training objective. Our code is available at https://github.com/tbwa233/SARFA.

Objective: Radiomic texture features are usually computed in voxel-index neighborhoods, implicitly assuming isotropic spatial relationships. In anisotropic images, this can confound voxel geometry with interpolation-induced signal changes. We developed a voxel-spacing-aware radiomic framework that incorporates physical geometry into texture computation without resampling. Approach: We modified PyRadiomics to account for voxel spacing while preserving the native image signal. Four configurations were compared: native non-resampled extraction (NR), isotropic resampling (RS), voxel-spacing-aware extraction (VS), and fake-isotropic preprocessing (FK), in which spacing metadata were overwritten without altering the image array. Experiments included 685 LIDC-IDRI pulmonary nodules and 209 I-SPY2 breast MRI cases, with 196 radiomic descriptors. Robustness was assessed using ICC, within-subject variability, Friedman testing, feature selection, machine learning, a multilayer perceptron, and external validation. Main results: VS showed near-native agreement with NR: median ICC(A,1) was 0.9976 in CT and 0.9984 in MRI. RS produced lower agreement and larger deviations, while FK showed intermediate behavior, confirming that spacing metadata alone can affect radiomic features. Gradient-derived and neighborhood-sensitive descriptors were most affected by preprocessing. VS preserved predictive performance comparable to NR in external CT validation, whereas MRI showed greater variability across preprocessing strategies and classifiers. Significance: Voxel-spacing-aware extraction separates geometric modeling from interpolation-induced signal modification while preserving the native image signal, offering a coherent alternative to isotropic resampling for radiomic analysis of anisotropic CT and MRI.

Diffusion-weighted imaging (DWI) is acquired as part of bi-parametric prostate MRI, but suffers from artifacts that degrade downstream quantitative and diagnostic performance. While DWI preprocessing is standard in brain imaging, its adoption in prostate imaging remains limited and lacks standardized pipelines. This study investigated the effect of different DWI preprocessing strategies on apparent diffusion coefficient (ADC) estimation and automatic Prostate Imaging Reporting and Data System (PI-RADS) classification. 268 cases were derived from the fastMRI prostate cohort by sequentially applying denoising, Gibbs-ringing correction, and diffeomorphic registration for susceptibility distortion correction. ADC maps were compared using linear least squares (LLS) and iteratively-weighted LLS (IWLLS). A 3-class DenseNet classifier was trained to predict PI-RADS scores from multi-channel MRI inputs. ADC analysis revealed statistically significant differences across preprocessing pipelines, with LLS and IWLLS producing numerically equivalent maps. Linear relationships between ADC values were preserved across most datasets (PCC ~0.99), while distortion correction realigned DWI to T2w anatomy and altered ADC values accordingly (PCC ~0.90). Classification showed the best AUROC and sensitivity for high-risk PI-RADS classes in the fully processed dataset. False-negative analysis revealed this dataset produced the least overconfident incorrect predictions on high-risk classes, which is a desirable property for clinical triage. DWI preprocessing, particularly distortion correction, enhances both ADC map quality and the predictive power of deep learning models for PI-RADS classification, supporting the need for optimized preprocessing pipelines in prostate MRI.

Radiomic features derived from medical images and segmentation masks are used to support decision making in clinical imaging pipelines. In practice, these features are often computed from predicted masks, but segmentation models can be overconfident or poorly calibrated, making derived measurements appear more reliable than they are. Conformal prediction (CP) provides distribution-free prediction intervals with finite-sample marginal coverage guarantees, but black-box intervals for segmentation-derived radiomics can be inefficient because they ignore test-time information about image appearance, mask geometry, and segmentation uncertainty. We propose ConRad, a conformal framework for scalar radiomic targets that uses covariates derived from the predicted mask, input image, predicted radiomics, and boundary uncertainty to construct adaptive intervals while maintaining coverage. Across five 2D medical imaging datasets and 171 retained radiomic targets, we show that ConRad improves feature-level efficiency compared to baselines while maintaining near-nominal empirical coverage. Ablation results further indicate that segmentation boundary uncertainty features are the largest contributors to interval efficiency.

Imaging signatures are quantitative features extracted from medical images that provide clinically meaningful information for tumor diagnosis, characterization, prognosis, and treatment planning. Although deep learning has shown great potential for imaging signature discovery, its limited interpretability remains a major barrier to clinical adoption. Existing approaches often achieve high predictive performance but provide little biological insight into the identified signatures. We propose a unified framework for interpretable imaging signature discovery by integrating deep learning based segmentation, explainable classification, and radiomic analysis. A robust segmentation model is first used to accurately delineate tumors, followed by a Grad-CAM guided pipeline that identifies diagnostically important regions as candidate imaging signatures. A mutual information based adaptive thresholding strategy enables patient-specific signature extraction. The resulting signatures are validated using a downstream deep learning classification model, while radiomic features extracted from the signature regions are evaluated with traditional machine learning models and interpreted using SHAP to identify the most discriminative biomarkers. The proposed framework is evaluated on the public BUSI breast ultrasound, KiTS renal CT, and BraTS brain tumor datasets, as well as a private UF Health renal CT cohort. Compared with conventional whole-tumor radiomics, the proposed signature-based approach achieves improved discriminative performance while providing greater biological interpretability. By converting deep learning attention into reproducible quantitative imaging biomarkers, this framework offers an interpretable and reproducible solution for non-invasive tumor characterization and imaging biomarker discovery.

Deep learning has achieved remarkable performance in medical image segmentation, yet it suffers from critical limitations: mathematical intractability, substantial parameter requirements, and lack of clinical interpretability. We propose RadiomicNet, a novel two-stream hybrid architecture that enhances standard deep learning by integrating handcrafted radiomics features directly into the segmentation learning process. The key contribution is the Radiomics Attention Gate (RAG), which leverages Gray-Level Co-occurrence Matrix (GLCM) and Local Binary Pattern (LBP) features to modulate skip-connection attention in a lightweight MobileNetV2-based encoder-decoder, providing ante-hoc interpretability without post-hoc approximations. A novel Radiomics Consistency Loss further enforces alignment between texture complexity and prediction uncertainty, reducing Expected Calibration Error (ECE) from 0.142 to 0.118. RadiomicNet achieves a Dice Similarity Coefficient (DSC) of 0.763 +/- 0.231 on the Breast Ultrasound Images (BUSI) dataset and 0.854 +/- 0.112 on Kvasir-SEG, outperforming U-KAN by 1.2% and 1.8%, respectively (p < 0.05, Wilcoxon signed-rank test), with only 3.27M parameters, 9.5x fewer than standard U-Net and 4.3x fewer than U-KAN. Gradient-based feature importance analysis reveals that GLCM dissimilarity (15.24%), GLCM energy (14.56%), and LBP entropy (11.49%) are the dominant radiomics cues, providing clinically meaningful explanations for segmentation decisions. The proposed approach demonstrates that compact, interpretable models grounded in domain knowledge can deliver state-of-the-art segmentation performance with substantially reduced computational overhead.

Radiomics is the established approach for CT-based lung cancer phenotyping, yet comparisons with foundation models rarely isolate contributions of feature extractor, classification head, and segmentation choice, or test cross-cohort robustness. We benchmark five feature extractors (Curia, Curia-2, DINOv3, Radiomics2D, Radiomics3D), seven classification heads (TabPFN, TabICL, XGBoost, CatBoost, Random Forest, logistic regression, Ridge), and three segmentation regimes on five tasks: tumor volume and stage classification, 2-year survival prediction, histology classification, and age prediction. Models are trained on LUNG1 (n=338) and evaluated on an internal test set (n=84) and the external LUNG2 cohort (n=211), with worst-case cross-cohort performance as the primary metric. The dominant design factor is task-dependent: segmentation drives volume and stage classification, while classifier choice drives survival, histology, and age prediction. Radiomics is competitive for tumor volume, tumor stage and survival (partly due to label-derivation effects for the former); Curia variants reach comparable peak scores for survival; DINOv3 falls slightly short across tasks. Patch and slice aggregation have negligible impact. We recommend Curia with tumor segmentation and a CatBoost head as a safe default, achieving the best mean rank across the three primary clinical tasks, though task-specific selection consistently outperforms any cross-task default. When tumor delineations are unavailable, Curia-2 with lung segmentation and logistic regression offers a competitive alternative. All pipelines use a two-stage design suited to small cohort sizes where end-to-end fine-tuning would risk overfitting.

Glioma grading and survival prediction require the integration of heterogeneous information collected at different spatial and biological scales. Histopathology describes tissue morphology, mRNA expression captures molecular activity, and magnetic resonance imaging provides a non-invasive view of tumor extent and radiological heterogeneity. Existing glioma prognosis models often combine only two of these sources, while their alignment objectives remain mostly pairwise. This paper introduces GLORIA, a novel trimodal framework for GLioma Omics - Radiology - hIstopathology Alignment. GLORIA processes whole-slide image regions, gene-expression profiles, and 3D MRI volumes through modality-specific encoders, projects them into a shared latent space, and aligns them with a Gramian contrastive loss that measures the volume spanned by the three modality embeddings. The aligned representations are fused through a cross-modal gating module and optimized jointly for three-class glioma grading and overall survival prediction. We evaluate GLORIA on a matched TCGA-GBM/LGG and BraTS21 cohort, comprising 132 patients with all three modalities. On the shared trimodal test set, GLORIA improves over the bimodal WSI-mRNA baseline in all the metrics considered.

Clinicians diagnose brain tumors by synthesizing patient symptoms, medical history, and quantitative imaging data from modalities such as MRI and CT scans into a unified clinical judgement. However, most deep learning models rely on MRI/CT images alone, failing to replicate the clinicians multimodal reasoning. We explore a two-branch multimodal network combining raw MRI scans with 91 extracted radiomic features (intensity, texture, shape, and boundary descriptors) to classify brain tumors into glioma, meningioma, pituitary, and no-tumor. A pre-trained CNN backbone encodes the image stream, whereas a dedicated MLP encodes the radiomic stream. Both streams are fused via concatenation, gated, or bidirectional cross-modal attention strategies. Across nine experimental runs on a balanced 7,200 image dataset, all multimodal configurations outperform unimodal baselines with gated fusion achieving the best accuracy of 96.13%.

Radiomics enables extraction of quantitative imaging biomarkers from medical images and has become an important tool for computer-aided cancer diagnosis. However, radiomics datasets are typically high-dimensional with limited samples, making feature selection a critical step for building reliable predictive models. This study proposes a Gradient-Loss Recursive Feature Elimination (GL-RFE) framework that integrates gradient sensitivity analysis from a deep neural network to identify the most influential radiomic features for lung cancer stage detection. A total of 106 radiomic features were extracted from chest Computed Tomography (CT) scans using the PyRadiomics extension of the 3D Slicer platform. The proposed method evaluates feature importance by computing gradients of the network loss with respect to input features and recursively eliminates features with minimal contribution. The resulting top-15 radiomic features are used to train a deep neural network classifier for distinguishing early-stage and advanced-stage lung cancer. The proposed framework achieves strong classification performance, with accuracy of 90.22%, precision of 90.10%, recall of 90.24%, and F1-score of 90.16% on the test dataset. Visualization analyses, including correlation heat maps and distribution plots, further confirm reduced feature redundancy and improved class separability. Compared to conventional feature selection techniques, GL-RFE effectively captures nonlinear feature interactions and enhances model generalization. The presented protocol provides a reproducible and interpretable methodology for radiomics-based cancer stage detection and is particularly suitable for high-dimensional, small-sample biomedical datasets, with potential applications in other domains such as genomics and multimodal clinical analysis.

Medical image computing software is essential for identifying imaging biomarkers that can support diagnosis, prognosis, treatment planning, and clinical research. However, the lack of standardized, user-friendly, and reproducible software environments has limited the broader adoption of advanced medical image analysis workflows. We present Radiuma, a freely available modular platform designed to support reliable and reproducible medical image analysis across multiple modalities and file formats. Radiuma integrates image reading, visualization, registration, fusion, processing, segmentation, radiomics feature extraction, and machine learning modules for classification, regression, and clustering. Its modular design allows users to execute each component independently or connect modules through a visual workflow system, where the output of one step can be graphically passed to the next. This enables the creation of custom, executable, and reproducible multi-step pipelines without requiring extensive programming expertise. Results from each module can be inspected directly in the visualization window, providing immediate feedback on processing quality and workflow accuracy. Radiuma also supports saving and sharing customized workflows, promoting transparency, reusability, and consistency across collaborative studies. By combining flexibility, usability, and standardized analysis tools, Radiuma provides a practical environment for radiomics and machine learning research in clinical and translational settings. The platform is designed to be accessible to users with diverse expertise, including radiologists, physicists, clinicians, and data scientists.

A main barrier for the deployment of AI radiomic systems in clinical routine is their drop in performance under heterogeneous multicentre acquisition protocols. This work presents a performance-oriented framework for quantifying scan parameter sensitivity of radiomic AI models, while identifying clinically significant parameter regions associated with improved cross-dataset robustness. We formulate a mixed-effects framework for quantifying the influence that clinically relevant acquisition parameters have on models performance, while accounting for subject-level random effects. We have applied our framework to lung cancer diagnosis in CT scans using two independent multicentre datasets (a public database and own-collected data) and several SoA architectures. To evaluate across-database reproducibility, CT parameters have been adjusted using the data collected and tested on the public set. The optimal configuration selected is the current of the X-ray tube >= 200 mA, spiral pitch <= 1.5, slice thickness <= 1.25 mm, which balances diagnostic quality with low radiation dose. These configuration push metrics from 0.79+-0.04 sensitivity, 0.47+-0.10 specificity in low quality scans to 0.90+-0.10 sensitivity, 0.79 +- 0.13 specificity in high quality ones.

Automated CT triage requires models that are simultaneously accurate across diverse pathologies and reliable under institutional shift. While Vision Transformers provide strong visual representations, many clinically significant findings are defined by quantitative imaging biomarkers rather than appearance alone. We introduce JANUS, a physiology-guided dual-stream architecture that conditions visual embeddings on macro-radiomic priors via Anatomically Guided Gating. On the MERLIN test set (N=5082), JANUS attains macro-AUROC 0.88 and AUPRC 0.74, outperforming all reproduced baselines. It generalizes to an external dataset N=2000; AUROC 0.87), with the largest gains on findings defined by size and attenuation as well as improved calibration on both datasets. We further quantify prediction suppression using the Physiological Veto Rate (PVR), showing that under domain shift JANUS reduces high-confidence false positives substantially more often than true positives. Together, these results are consistent with physically grounded conditioning that improves both discrimination and reliability in CT triage. Code is made publicly available at github repository https://github.com/lavsendahal/janus and model weights are at https://huggingface.co/lavsendahal/janus.

Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.

The rapid proliferation of open-source medical foundation models (FMs) raises a practical question: how well do their pre-trained representations transfer to clinically relevant but data-scarce classification tasks? Particularly in CT-based renal lesion classification, a push toward greater generalizability would be meaningful, as the field is constrained by inherently limited training data. We addressed this through a benchmark of three medical FMs on this specific task. This six-class problem spans common entities like cysts and clear cell renal cell carcinoma, alongside rare subtypes. Using a frozen feature-probing protocol, we compared FM embeddings against a handcrafted radiomics classifier and a 3D ResNet-50 trained from scratch. Models were trained on a composite dataset of 2,854 lesions and evaluated on an external test set of 234 lesions from The Cancer Imaging Archive. Our results reveal two key findings. First, FM performance (AUC 0.70-0.77) matched the from-scratch ResNet (AUC 0.72) while drastically reducing hardware demand, requiring only seconds on a CPU after feature extraction. However, the conventional radiomics baseline significantly outperformed all deep learning approaches, achieving an AUC of 0.88 (all p $\leq$ 0.002). This suggests that current generalist FM embeddings do not yet capture the fine-grained texture and shape heterogeneity driving histological subtype discrimination. Despite their potential in data-scarce settings, medical FMs did not surpass established models for renal lesion stratification, leaving radiomics as the current state-of-the-art.

Precise molecular subtyping of gliomas, including isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion, directly guides surgical and therapeutic decisions, yet currently relies on invasive tissue sampling. Deep learning on structural MRI has emerged as a non-invasive alternative, but anatomy-only approaches cannot capture the hemodynamic signatures that distinguish molecular subtypes. Radiogenomics based on dynamic susceptibility contrast (DSC) MRI holds immense potential for non-invasively characterizing glioma molecular subtypes, yet clinical deployment has been hindered by inter-site variability and the limitations of voxel-wise analysis. We introduce HiPerfGNN, a framework that first learns discrete hemodynamic representations from raw time-intensity curves using a vector-quantized variational autoencoder (VQ-VAE). These quantized perfusion codes define coarse-level graph nodes representing functional tumor habitats, each of which is hierarchically subdivided into fine-level subregions guided by structural MRI. A hierarchical graph neural network then propagates information across scales for molecular prediction. On an internal cohort (n=475), the model achieved AUCs of 0.96 (IDH), 0.89 (1p/19q), and 0.84 (WHO grade), and maintained robust IDH performance (AUC 0.89) on an independent external cohort (n=397) without recalibration. Gradient-based saliency analysis confirms biologically grounded attention patterns aligned with known glioma pathophysiology. Our results demonstrate the added value of integrating perfusion dynamics into radiogenomic pipelines for glioma molecular subtyping. Code is available at https://github.com/janghana/HiPerfGNN.

Rheumatoid arthritis (RA) assessment from hand radiographs requires multi-level analysis and modeling of anatomical structures and fine-grained local pathological changes. However, existing public resources do not support such unified multi-level analysis, often lacking full-hand coverage, fine-grained annotations, and consistent integration with clinical scoring systems. In particular, annotations that enable quantitative analysis of bone erosion (BE) remain scarce. RAM-H1200 contains 1,200 hand radiographs collected from six medical centers, with multi-level annotations including (i) whole-hand bone structure instance segmentation, (ii) pixel-level BE masks, (iii) SvdH-defined joint regions of interest, and (iv) joint-level SvdH scores for both BE and joint space narrowing (JSN). It is designed to evaluate whether models can jointly capture anatomical structure, localized erosive pathology, and clinically standardized RA severity from hand radiographs. The proposed BE masks enable, for the first time, quantitative BE analysis beyond coarse categorical grading by providing explicit spatial supervision for lesion extent and morphology. To our knowledge, RAM-H1200 is the first public large-scale benchmark that jointly supports whole-hand bone structure instance segmentation, pixel-level BE delineation, and clinically grounded joint-level SvdH scoring for both BE and JSN. Results across benchmark tasks show that anatomical modeling is substantially more mature than quantitative BE analysis: whole-hand bone segmentation achieves strong performance, whereas BE segmentation remains a major open challenge. By unifying anatomical structure modeling, quantitative lesion analysis, and clinically grounded SvdH scoring, RAM-H1200 provides a single benchmark for comprehensive RA analysis on hand radiographs.

Skull-base meningiomas are often characterized by favorable long-term prognosis, yet their anatomical complexity and proximity to critical neurovascular structures make treatment selection challenging. Stereotactic radiosurgery with CyberKnife represents an effective therapeutic option when surgical resection is not feasible; however, not all patients benefit equally from this treatment. Early identification of patients likely to respond to radiosurgery remains an open clinical problem. In this study, we propose a radiomics- and clinical feature-driven framework for predicting volumetric response in skull-base meningiomas treated with CyberKnife. Unlike most existing approaches that focus on progression-free survival or recurrence, our method targets volumetric response as an indicator of treatment efficacy. Pre-treatment MRI images from 104 patients were processed to extract radiomic features, which were combined with clinical variables and analyzed using six models. To ensure methodological rigor, the entire modeling process was implemented within a nested cross-validation scheme. Among the evaluated models, TabPFN achieved the best overall performance, with an AUC of 0.81 and consistently favorable classification metrics. These results suggest that advanced machine learning architectures, when combined with robust validation strategies, can effectively capture patterns associated with treatment response even in small-sample, high-dimensional settings.

Feature selection (FS) is essential for biomarker discovery and clinical predictive modeling. Over the past decades, methodological literature on FS has become rich and mature, offering a wide spectrum of algorithmic approaches. However, much of this methodological progress has not fully translated into applied biomedical research. Moreover, challenges inherent in biomedical data, such as high-dimensional feature space, low sample size, multicollinearity, and missing values, make FS non-trivial. To help bridge this gap between methodological development and practical application, we propose ROOFS (RObust biOmarker Feature Selection), a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. ROOFS benchmarks multiple FS methods on the user's data and generates reports summarizing a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, robustness of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of ROOFS on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. Of the 34 FS methods gathered in ROOFS, we evaluated 23 in combination with 11 classifiers (253 models) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including widely used LASSO. We conclude that comprehensive benchmarking with ROOFS has the potential to improve the reproducibility of FS discoveries and increase the translational value of clinical models.

Accurate delineation of tumors and surrounding organs-at-risk is essential for radiotherapy, surgery and treatment response assessment, yet remains time-consuming and expertise-intensive. Existing artificial intelligence systems often require manual spatial prompts or task-specific retraining, while generic class labels provide limited semantic grounding for heterogeneous disease targets. Here we present SyRe, a promptable segmentation foundation model based on Synergistic vision-language Reinforcement. SyRe strengthens bidirectional interaction between visual and linguistic representations to improve semantically grounded spatial understanding. To support large-scale training, we introduce the Color Region Description strategy and construct SyReData, comprising 20 million image-mask-description triplets across 9 modalities and 229 segmentation tasks. Training with diversified prompt forms further enables open-ended prompting, invalid-prompt rejection and flexible switching between single- and multi-target analysis. SyRe achieves accurate text-prompted segmentation across diverse clinical scenarios, with particularly strong performance on disease-related targets. Across 28 unseen external datasets, including 20 cancer types and multinational in-house cohorts, SyRe generalizes robustly under real-world distribution shifts. SyRe-generated masks also preserve clinically relevant quantitative information in pathology and yield radiomics features that stratify survival and improve prognostic modeling across five retrospective CT and MRI tumor cohorts. Finally, clinician-in-the-loop refinement enables efficient case-level correction when greater precision is required. These results establish SyRe as a generalizable foundation for scalable quantitative oncology and clinician-guided segmentation refinement.

Quantitative assessment of muscle MRI is crucial for monitoring neuromuscular disorders (NMD). This study introduces an automated radiomic phenotyping framework based on original features engineered across five main architectural domains: quantitative morphometry, spatial distribution, geometric shape, interactions between progressive fat replacement stages, and graph-based topology. Utilizing 1184 MRI scans from the CoMPaSS-NMD project, we map the complex 3D architecture of heterogeneous intramuscular lipodegeneration into objective, morphologically interpretable biomarkers. We introduce a graph-based skeletonization of fat infiltrates to quantify muscle architectural changes, establishing a multi-dimensional extension of traditional, spatially-agnostic volume metrics by mapping topological networks across the entire 3D muscle volume. Statistical screening via non-parametric Kruskal-Wallis analysis confirmed the discriminative power of these novel descriptors across the genetic hierarchy. Notably, topological network metrics (e.g., SF1_Skel_Nodes, $\epsilon^2$ = 0.2656) and interface dynamics metrics (e.g., SF2_To_SF1_Dist_Min, $\epsilon^2$ = 0.2092) demonstrated substantial effect sizes, providing deeper structural insights than classical volumetric assessments. Post-hoc pairwise evaluations and UMAP projections further indicated the capability of these topological and 3D geometric invariants to capture disease-specific macroscopic infiltration patterns. These results demonstrate that global architectural features represent a highly promising class of biomarkers for differential diagnosis, offering new avenues for tracking longitudinal disease dynamics in neuromuscular diagnostics. The developed automated feature extraction pipeline is integrated and available within the MUSCAT (MUSCle fAt Topology) library.