Explainable Medical Image Analysis
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12 papers in the last four weeks, up 33% on the four weeks before. 0.1% of all new papers.
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Deep learning models for medical imaging often exhibit overconfidence, creating safety risks in ambiguous diagnostic scenarios. While Conformal Prediction (CP) provides distribution-free statistical guarantees, standard methods such as Regularized Adaptive Prediction Sets (RAPS) optimize for average efficiency and can mask severe failures on difficult inputs. We propose an Adaptive Lambda Criterion for RAPS that minimizes the worst-case coverage violation across prediction set size strata. On OrganAMNIST (58,850 abdominal CT images, 11 classes), standard size-optimized RAPS converges to near-deterministic behavior with stratified undercoverage on uncertain samples, while our method achieves 95.72 percent global coverage with average set size 1.09 and at least 90 percent coverage across all strata. Cross-domain validation on PathMNIST (107,180 pathology images, 9 classes) confirms generalizability. Quantitative Grad-CAM analysis (rho = -0.30, p < 1e-22) shows that multi-label predictions correspond to focused attention on anatomically ambiguous regions. These results demonstrate that the proposed method improves reliability while maintaining efficiency, making it suitable for safety-critical medical AI applications.
Are Compact Rationales Free? Measuring Tile Selection Headroom in Frozen WSI-MIL
Whole-slide image (WSI) multiple instance learning (MIL) classifiers can achieve strong slide-level AUC while leaving the full-bag prediction opaque. Attention scores are widely reused as post-hoc explanations, but high attention can reflect aggregation preference rather than a compact, model-sufficient rationale. We study post-hoc rationale highlighting for frozen WSI-MIL: given a trained classifier, can its slide-level prediction be recovered from a compact, output-consistent tile subset without retraining the backbone? We instantiate this with Finding Optimal Contextual Instances (FOCI), a lightweight rationale-readout layer over a frozen MIL backbone. FOCI is trained with model-output sufficiency and exclusion objectives over keep/drop tile subsets, evaluated with an insertion-style Sequential Reveal Protocol (SRP) adapted to WSI-MIL, and summarized by the Selection Headroom Index (SHI). Across three WSI benchmarks and seven MIL backbones, FOCI reveals that compact rationales are selection-headroom dependent: transformer and multi-branch attention aggregators can admit compact rationales, near-minimal attention-pooling baselines enter a selection-saturation regime, and hard-selection backbones can conflict with an external readout. For TransMIL, relative to its documented CLS-proxy ranking, FOCI reduces the Minimum Sufficient K (MSK) tile count by 32-56% across benchmarks, while ACMIL+FOCI attains the highest mean SHI (+0.465). Deletion-based perturbation and selected-only downstream evaluation provide complementary checks. These results position FOCI as a model-level interpretability and audit layer: selected tiles are not claims of clinical or pathologist-level diagnostic sufficiency, but candidate rationales that offer a compact, reviewable view of when a frozen MIL prediction can be localized to a small output-consistent subset.
Explanation-Aware Learning for Enhanced Interpretability in Biomedical Imaging
Deep neural networks for medical image diagnosis often achieve high predictive accuracy while relying on spurious or clinically irrelevant visual cues, limiting their trustworthiness in practice. Post-hoc explanation methods are widely used to visualize model decisions in the form of saliency maps; however, these explanations do not influence how models learn during training, allowing non-causal or confounding features to persist. This motivates the incorporation of explanation supervision directly into the training objective to guide model attention toward clinically meaningful regions and promote clinically grounded decision-making. This paper presents a systematic approach to integrate explanation loss into model training and analyzes how different explanation loss designs and supervision strengths influence both predictive performance and spatial faithfulness of explanations. To quantitatively assess interpretability, two complementary explanation performance metrics-annotation coverage and saliency precision-are introduced, enabling rigorous evaluation beyond qualitative visualization. Our experimental results reveal a clear trade-off between explanation quality and explanation loss coefficients. Furthermore, quantitative statistical analysis yields consistently improved explanation alignment while maintaining comparable accuracy. Experiments were conducted on annotated chest X-ray datasets; however, the proposed framework is applicable to a broad range of annotated biomedical imaging modalities. Overall, these findings demonstrate that explanation supervision is not a monolithic design choice and provide practical guidance for incorporating explanation loss into training objectives under noisy clinical annotations.
CT-IDP: Segmentation-Derived Quantitative Phenotypes for Interpretable Abdominal CT Disease Classification
In this retrospective multi-institutional study, a quantitative phenotyping framework, CT-IDP (CT Image-Derived Phenotypes) was developed on the MERLIN abdominal CT benchmark (training, validation, and test sets- 15,175, 5,018, and 5,082 studies, respectively) and externally evaluated on two independent dataset: Duke-Abdomen (2,000) and AMOS (1,107). Multi-organ segmentations were generated with TotalSegmentator and used to derive over 900 organ and compartment-level descriptors spanning morphometry, attenuation, and contextual/burden findings. Sparse disease-specific logistic regression with elastic-net regularization was trained on MERLIN and externally validated under a frozen specification. Performance was compared against a DINOv3-based vision-transformer baseline using AUC and average precision (AP), supported by phenotype-stratified audits and coefficient-level inspection. Macro-AUC for CT-IDP versus the baseline was 0.897 versus 0.880 on MERLIN, 0.877 versus 0.857 on the Duke-Abdomen dataset, and 0.780 versus 0.756 on AMOS.
Radiologist-Guided Causal Concept Bottleneck Models for Chest X-Ray Interpretation
Concept Bottleneck Models (CBMs) in medical imaging aim to improve model interpretability by predicting intermediate clinical concepts before final diagnoses. However, most existing CBMs treat concepts as discriminative predictors of pathology labels, without explicitly modelling the underlying clinical generative process where diseases produce observable radiographic findings. We propose XpertCausal, a radiologist-guided causal CBM for chest X-ray interpretation which models pathology-to-concept relationships using a probabilistic noisy-OR framework. This generative model is then inverted via Bayesian inference to estimate pathology probabilities from predicted concepts. Radiologist-curated concept-pathology associations are used to constrain model structure to radiologist-defined clinically plausible reasoning pathways. We evaluate XpertCausal on MIMIC-CXR across pathology classification performance, calibration, explanation quality, and alignment with radiologist-defined reasoning pathways. Compared with both a non-causal CBM baseline and a causal ablation with unconstrained learned associations, XpertCausal achieves improved AUROC, calibration, and clinically relevant explanation quality, while learning concept-pathology relationships that more closely align with expert knowledge. These results demonstrate that incorporating clinically motivated causal structure and expert domain knowledge into CBMs can lead to more accurate, interpretable, and clinically aligned models for CXR interpretation.
Multimodal Stepwise Clinically-Guided Attention Learning for Pathological Complete Response Prediction in Breast Cancer
Pathological complete response (pCR) is a key prognostic factor in breast cancer patients undergoing neoadjuvant therapy, strongly associated with long-term survival and treatment personalization. However, accurate pre-treatment pCR prediction remains challenging due to severe class imbalance and limited generalizability across diverse clinical settings. In this work, we propose a multimodal stepwise clinically-guided attention learning framework for pCR prediction from breast magnetic resonance imaging (MRI), designed to address these limitations through medically grounded spatial guidance and multimodal integration. The approach follows a stepwise training strategy inspired by physician reasoning: the model first learns global discriminative imaging patterns, then attention mechanisms are introduced to constrain the network toward tumor regions, and finally clinical variables are integrated to refine decision-making. This guidance strategy encourages prioritization of task-relevant features, improving identification of responders despite their limited representation in the dataset. Moreover, grounding attention in anatomically consistent tumor regions reduces reliance on dataset-specific patterns, thereby enhancing cross-institutional generalization. The framework is evaluated through external validation across heterogeneous MRI cohorts. Compared to non-guided single-stage baselines, the proposed approach improves sensitivity while maintaining competitive specificity, and produces anatomically coherent attention maps that support interpretation of the model's predictions. These findings highlight the potential of clinically-guided multimodal attention learning for robust and generalizable pCR prediction in breast cancer.
Bridging visual saliency and large language models for explainable deep learning in medical imaging
The opaque nature of deep learning models remains a significant barrier to their clinical adoption in medical imaging. This paper presents a multimodal explainability framework that bridges the gap between convolutional neural network (CNN) predictions and clinically actionable insights for brain tumor classification, leveraging large language models (LLMs) to deliver human-interpretable diagnostic narratives. The proposed framework operates through three coupled stages. First, nine CNN architectures are extended with a dual-output hybrid formulation that simultaneously optimises a classification head and a segmentation head, enabling spatially richer feature learning. Second, visual saliency attribution methods, namely Grad-CAM, Grad-CAM++, and ScoreCAM, are applied to generate class-discriminative heatmaps, which are subsequently refined into binary tumor masks via an adaptive percentile thresholding pipeline. Third, the resulting masks are mapped onto the Harvard-Oxford cortical atlas to translate pixel-level evidence into named neuroanatomical structures, and the extracted findings are encoded into a structured JSON file that conditions three LLMs (Grok3, Mistral, and LLaMA) to generate coherent, radiological-style diagnostic reports. Evaluated on a dataset of 4,834 contrast-enhanced T1-weighted brain MRI images spanning three tumor classes, InceptionResNetV2 achieved the highest classification performance and Grad-CAM++ yielded the best segmentation overlap. Among the language models, Grok3 led in lexical diversity and coherence, while LLaMA achieved the highest readability score. By integrating visual, anatomical, and linguistic modalities into a unified pipeline, the framework produces explanations that are technically grounded and meaningfully interpretable, advancing the transparency and clinical accountability of artificial intelligence assisted brain tumor diagnosis.
Seeing What Shouldn't Be There: Counterfactual GANs for Medical Image Attribution
Ascription of an image gives insights into the objects that influence the classification of the whole image or its pixels towards a specific category. These insights help radiologists to visualize deformities in medical imaging. Most of the existing visualization techniques are based on discriminative models and highlight regions of the input image participating in the decision-making of a classifier. However, these approaches do not take all noticeable objects into account as their objective is to classify the input by using a minimal set of discriminative features. To overcome the issue, a counterfactual explanation (CX) based class-oriented feature attribution method is proposed. A counterfactual explanation (CX) explicates a causal reasoning process of the form: "if X had not happened, then Y would not have happened". The method is built on generative adversarial networks (GANs) with a cyclical-consistent loss function. We evaluate our method on three datasets: synthetic, tuberculosis and BraTS. All experiments confirm the efficacy of the proposed method. This study also highlighted the limitations of existing counterfactual explanation techniques in producing plausible counterfactual instances (CIs). Accompanying CXs with believable CIs thus provides self-explanatory analogy-based explanations. To this end, a CI generation method is proposed. Also, a novel technique is used to evaluate the quality of CI. The baseline results are produced on the BraTS dataset.
SAIL: Structure-Aware Interpretable Learning for Anatomy-Aligned Post-hoc Explanations in OCT
Optical coherence tomography (OCT), a commonly used retinal imaging modality, plays a central role in retinal disease diagnosis by providing high-resolution visualization of retinal layers. While deep learning (DL) has achieved expert-level accuracy in OCT-based retinal disease detection, its "black box" nature poses challenges for clinical adoption, where explainability is essential for clinical trust and regulatory approval. Existing post-hoc explainable AI (XAI) methods often struggle to delineate fine-grained lesion structures, respect anatomical boundaries, or suppress noise, limiting the trustworthiness of their explanations. To bridge these gaps, we propose a Structure-Aware Interpretable Learning (SAIL) framework that integrates retinal anatomical priors at the representation level and couples them with semantic features via a fusion design. Without modifying standard post-hoc explainability methods, this representation yields sharper and more anatomically aligned attribution maps. Comprehensive experiments on diverse OCT datasets demonstrate that our structure-aware method consistently enhances interpretability, producing clinically meaningful and anatomy-aware explanations. Ablation studies further show that strong interpretability requires both structural priors and semantic features, and that properly fusing the two is critical to achieve the best explanation quality. Together, these results highlight structure-aware representations as a key step toward reliable explainability in OCT.
TumorXAI: Self-Supervised Deep Learning Framework for Explainable Brain MRI Tumor Classification
Classifying brain tumors using magnetic resonance imaging (MRI) is crucial for early diagnosis and treatment; however, tumor heterogeneity and a dearth of annotated datasets restrict the use of supervised deep learning approaches. In this work, we use self-supervised learning (SSL) to study multi-class brain tumor classification. Using a ResNet-50 backbone, we evaluate four SSL frameworks including SimCLR, BYOL, DINO, and Moco v3 on a publicly available dataset of 4,448 MRIs with 17 distinct tumor types. On the dataset, SimCLR achieved 99.64% accuracy, 99.64% precision, 99.64% recall, and 99.64% F1-score. The workflow includes preprocessing, fine-tuning, linear evaluation, and SSL pretraining with data augmentations. Results show that, when labels are limited, SSL-pretrained models outperform supervised baselines in terms of F1-score, recall, accuracy, and precision. Additionally, by providing visual insights into model decisions, Explainable AI techniques (Grad-CAM, Grad-CAM++, EigenCAM) enhance interpretability. These results demonstrate SSL's scalability and dependability in diagnosing brain tumors from unlabeled medical data.
GeoSAE: Geometric Prior-Guided Layer-Wise Sparse Autoencoder Annotation of Brain MRI Foundation Models
Brain MRI foundation models learn rich representations of anatomy, but interpreting what clinical information they encode remains an open problem. Standard sparse autoencoders (SAEs) suffer from severe feature collapse in deep transformer layers, and in Alzheimer's disease (AD) research, aging confounds nearly every clinical variable, making naive annotation unreliable. We propose GeoSAE, a geometry-guided SAE framework that uses the foundation model's learned manifold structure to prevent feature collapse and annotates each surviving feature via age-deconfounded partial correlations. Applied to ~14k T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging biomarkers and Lifestyle (AIBL) datasets, GeoSAE identifies a compact, fully interpretable feature set that predicts mild cognitive impairment (MCI)-to-AD conversion (AUC 0.746) using only 2% of the embedding dimensions, while comorbidity-annotated features achieve only chance-level performance. The identified features replicate across cohorts without retraining (r=0.97) and localize to neuroanatomically distinct regions consistent with Braak staging. This shows that geometry-guided SAEs can extract interpretable, biomarkers from frozen brain MRI foundation models.
Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank
The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.
From ML Predictions to Informed Diagnostic Assistance Using the Toulmin Model of Argumentation
To provide a structured and interpretable assessment, we decompose the image-based diagnosis into components following the Toulmin model of argumentation. This model consists of a claim, grounds, warrant, qualifier, rebuttal, and backing. Consider a claim generated by a machine learning (ML) model for retinal diagnosis. Rather than accepting this claim at face value, one could either apply explainable AI (XAI) methods or adopt an argumentation-based approach. In our framework, a model specialized in biomarker extraction from images provides the grounds. The warrant-linking the grounds to the claim - is analyzed by an agent equipped with medical knowledge; in our architecture, this role is fulfilled by a MedGemma agent. The qualifier is determined based on the overall quantitative evaluation of both the warrant and grounds models. Finally, a rebuttal is constructed using image similarity measures computed with MedSigLip. All these components are presented to the human expert, enabling a more informed and critical assessment of the ML-generated diagnosis.
On the explainability of max-plus neural networks
We investigate the explanability properties of the recently proposed linear-min-max neural networks. At initialization, they can be interpreted as k-medoids with the infinity norm as a distance. Then, they are trained using subgradient descent to better fit the data. The model has been shown to be a universal approximator. Yet, we can trace the decision process because a single most activated neuron is responsible for the value of the output. Using this property, we designed a pixel fragility measure that determines whether changes to a single pixel may be responsible to a change in the classification output. Experiments on the PneumoniaMnist dataset show that this explanation for the output of the neural network compares favorably to SHAP and Integrated Gradient.
EXACT: an explainable anomaly-aware vision foundation model for analysis of 3D chest CT
Chest computed tomography (CT) is central to the detection and management of thoracic disease, yet the growing scale and complexity of volumetric imaging increasingly exceed what can be addressed by scan-level prediction alone. Clinically useful AI for CT must not only recognize disease across the whole volume, but also localize abnormalities and provide interpretable visual evidence. Existing vision-language foundation models typically compress scans and reports into global image-text representations, limiting their ability to preserve spatial evidence and support clinically meaningful interpretation. Here we developed EXACT, an explainable anomaly-aware foundation model for three-dimensional chest CT that learns spatially resolved representations from paired clinical scans and radiology reports. EXACT was pre-trained on 25,692 CT-reports pairs using anatomy-aware weak supervision, jointly learning organ segmentation and multi-instance anomaly localization without manual voxel-level annotations. The resulting organ-specific anomaly-aware maps assign each voxel a disease-specific anomaly score confined to its corresponding anatomy, jointly encoding lesion extent and organ-level context. In retrospective multinational and multi-center evaluations, EXACT showed broad and consistent improvements across clinically relevant CT tasks, spanning multi-disease diagnosis, zero-shot anomaly localization, downstream adaptation, and visually grounded report generation, outperforming existing three-dimensional medical foundation models. By transforming routine clinical CT scans and free-text reports into explainable voxel-level representations, EXACT establishes a scalable paradigm for trustworthy volumetric medical AI.
Knee-xRAI: An Explainable AI Framework for Automatic Kellgren-Lawrence Grading of Knee Osteoarthritis
Grading knee osteoarthritis (KOA) on plain radiographs is poorly reproducible across readers. A single-grade disagreement on the Kellgren-Lawrence (KL) scale can alter surgical management or redirect a patient from conservative therapy to intra-articular injection. Meanwhile, deep learning models that outperform human readers often offer no explanation for their decisions. We present Knee-xRAI, a pipeline that decomposes the grading process by mimicking clinical radiological workflows. It independently measures joint space narrowing (JSN), osteophytes, and subchondral sclerosis, then combines these findings into an explainable KL grade. Specifically, a U-Net++ architecture quantifies JSN via contour segmentation, an SE-ResNet-50 multi-task network grades osteophytes per anatomical site on the OARSI scale, and a hybrid texture-CNN detects binary sclerosis. This pipeline yields a 50-dimensional feature vector evaluated via an XGBoost-SHAP classifier (Path A, audit) and a ConvNeXt hybrid predictor (Path B, deployed). On 8,260 OAI-derived radiographs, the JSN module achieved a Dice score of 0.8909 and an mJSW ICC of 0.8674. Path A reached a QWK of 0.6294 and an AUC of 0.8046, confirming the structured feature vector carries substantial diagnostic signal. Path B achieved a QWK of 0.8436 and an AUC of 0.9017. SHAP analysis identifies JSN as the dominant feature, with osteophytes adding a consistent increment and sclerosis contributing marginally. Removing JSN evidence collapses KL3-KL4 recall while early grades remain intact, aligning with the KL diagnostic criteria. Knee-xRAI grounds every prediction in an auditable chain of measured radiographic findings, providing clinical transparency at the point of care.
From Pixels to Explanations: Interpretable Diabetic Retinopathy Grading with CNN-Transformer Ensembles, Visual Explainability and Vision-Language Models
The quality of diabetic retinopathy (DR) screening relies on the ability to correctly grade severity; however, many deep-learning (DL) classifiers cannot be easily interpreted in the clinical context. This study presents a methodology that combines strong discriminative models with multimodal explanations, converting retinal pixels into clinically interpretable outputs. Using the APTOS 2019 benchmark, we evaluated six representative CNN- and transformer-based backbones under a controlled protocol with stratified five-fold cross-validation. We then compared ensembling strategies (hard voting, weighted soft voting, stacking) and investigated a hybrid class-level fusion variant to exploit grade-specific advantages. For interpretability, we produced Grad-CAM++ visual attribution maps and short textual rationales using vision-language models (VLMs) conditioned on the fundus image and classifier outputs under conservative prompting constraints. Modern CNN backbones (ResNet-50 and ConvNeXt-Tiny) provided the strongest single-model baselines, with cross-validated QWK up to 0.919 and 0.914, respectively. Ensembling improved ordinal agreement, and weighted soft voting was the most consistent across folds (QWK 0.934 +/- 0.017). Hybrid class-level fusion was competitive but did not yield a statistically reliable improvement over standard fusion in paired fold comparisons (Holm-adjusted p >= 1.000). For explanation quality, Grad-CAM++ offered plausible but coarse localization, and VLM rationales were generally grade-consistent. Quantitatively, VLM variants showed a trade-off between clinical completeness and template-level semantic similarity (coverage 0.700 vs. BERTScore 0.072), while image-text alignment was comparable (CLIPScore approximately 0.34).
an interpretable vision transformer framework for automated brain tumor classification
Brain tumors represent one of the most critical neurological conditions, where early and accurate diagnosis is directly correlated with patient survival rates. Manual interpretation of Magnetic Resonance Imaging (MRI) scans is time-intensive, subject to inter-observer variability, and demands significant specialist expertise. This paper proposes a deep learning framework for automated four-class brain tumor classification distinguishing glioma, meningioma, pituitary tumor, and healthy brain tissue from a dataset of 7,023 MRI scans. The proposed system employs a Vision Transformer (ViT-B/16) pretrained on ImageNet-21k as the backbone, augmented with a clinically motivated preprocessing and training pipeline. Contrast Limited Adaptive Histogram Equalization (CLAHE) is applied to enhance local contrast and accentuate tumor boundaries invisible to standard normalization. A two-stage fine-tuning strategy is adopted: the classification head is warmed up with the backbone frozen, followed by full fine-tuning with discriminative learning rates. MixUp and CutMix augmentation is applied per batch to improve generalization. Exponential Moving Average (EMA) of weights and Test-Time Augmentation (TTA) further stabilize and boost performance. Attention Rollout visualization provides clinically interpretable heatmaps of the brain regions driving each prediction. The proposed model achieves a test accuracy of 99.29%, macro F1-score of 99.25%, and perfect recall on both healthy and meningioma classes, outperforming all CNN-based baselines
Infection-Reasoner: A Compact Vision-Language Model for Wound Infection Classification with Evidence-Grounded Clinical Reasoning
Assessing chronic wound infection from photographs is challenging because visual appearance varies across wound etiologies, anatomical locations, and imaging conditions. Prior image-based deep learning methods have mainly focused on classification with limited interpretability, despite the need for evidence-grounded explanations to support point-of-care decision making. We present Infection-Reasoner, a compact 4B-parameter reasoning vision-language model for chronic wound infection classification and rationale generation. To address the scarcity of expert-labeled wound images with reasoning annotations, Infection-Reasoner is trained using a two-stage pipeline: (1) reasoning distillation, in which GPT-5.1 generates chain-of-thought rationales for unlabeled wound images to initialize wound-specific reasoning in a smaller student model (Qwen3-VL-4B-Thinking), and (2) reinforcement learning post-training with Group Relative Policy Optimization on a small labeled infection dataset to refine classification reasoning. On a held-out heterogeneous wound dataset, Infection-Reasoner achieved 86.8% accuracy, 86.4% sensitivity, and 87.1% specificity, outperforming several strong baselines, including GPT-5.1. Rationale quality was further evaluated using both multimodal large language model (MLLM) judges and wound expert review. Across four MLLM judges, visual-support agreement scores ranged from 0.722 to 0.903, while expert review rated 61.8% of rationales as Correct and 32.4% as Partially Correct.
Dual-Modal Lung Cancer AI: Interpretable Radiology and Microscopy with Clinical Risk Integration
Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Conventional computed tomography (CT) imaging, while essential for detection and staging, has limitations in distinguishing benign from malignant lesions and providing interpretable diagnostic insights. To address this challenge, this study proposes a dual-modal artificial intelligence framework that integrates CT radiology with hematoxylin and eosin (H&E) histopathology for lung cancer diagnosis and subtype classification. The system employs convolutional neural networks to extract radiologic and histopathologic features and incorporates clinical metadata to improve robustness. Predictions from both modalities are fused using a weighted decision-level integration mechanism to classify adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell lung cancer, and normal tissue. Explainable AI techniques including Grad-CAM, Grad-CAM++, Integrated Gradients, Occlusion, Saliency Maps, and SmoothGrad are applied to provide visual interpretability. Experimental results show strong performance with accuracy up to 0.87, AUROC above 0.97, and macro F1-score of 0.88. Grad-CAM++ achieved the highest faithfulness and localization accuracy, demonstrating strong correspondence with expert-annotated tumor regions. These results indicate that multimodal fusion of radiology and histopathology can improve diagnostic performance while maintaining model transparency, suggesting potential for future clinical decision support systems in precision oncology.
Ranking XAI Methods for Head and Neck Cancer Outcome Prediction
For head and neck cancer (HNC) patients, prognostic outcome prediction can support personalized treatment strategy selection. Improving prediction performance of HNC outcomes has been extensively explored by using advanced artificial intelligence (AI) techniques on PET/CT data. However, the interpretability of AI remains a critical obstacle for its clinical adoption. Unlike previous HNC studies that empirically selected explainable AI (XAI) techniques, we are the first to comprehensively evaluate and rank 13 XAI methods across 24 metrics, covering faithfulness, robustness, complexity and plausibility. Experimental results on the multi-center HECKTOR challenge dataset show large variations across evaluation aspects among different XAI methods, with Integrated Gradients (IG) and DeepLIFT (DL) consistently obtained high rankings for faithfulness, complexity and plausibility. This work highlights the importance of comprehensive XAI method evaluation and can be extended to other medical imaging tasks.
RadAgent: A tool-using AI agent for stepwise interpretation of chest computed tomography
Vision-language models (VLM) have markedly advanced AI-driven interpretation and reporting of complex medical imaging, such as computed tomography (CT). Yet, existing methods largely relegate clinicians to passive observers of final outputs, offering no interpretable reasoning trace for them to inspect, validate, or refine. To address this, we introduce RadAgent, a tool-using AI agent that generates CT reports through a stepwise and interpretable process. Each resulting report is accompanied by a fully inspectable trace of intermediate decisions and tool interactions, allowing clinicians to examine how the reported findings are derived. In our experiments, we observe that RadAgent improves chest CT report generation over its 3D VLM counterpart, CT-Chat, across three dimensions. Clinical accuracy improves by 5.8 points (35.4% relative) in macro-F1 and 5.1 points (18.6% relative) in micro-F1. Robustness under adversarial conditions improves by 24.7 points (41.9% relative). Furthermore, RadAgent achieves 37.0% in faithfulness, a new capability entirely absent in its 3D VLM counterpart. By structuring the interpretation of chest CT as an explicit, tool-augmented and iterative reasoning trace, RadAgent brings us closer toward transparent and reliable AI for radiology.
Expert-Annotated Embryo Image Dataset with Natural Language Descriptions for Evidence-Based Patient Communication in IVF
Embryo selection is one of multiple crucial steps in in-vitro fertilization, commonly based on morphological assessment by clinical embryologists. Although artificial intelligence methods have demonstrated their potential to support embryo selection by automated embryo ranking or grading methods, the overall impact of AI-based solutions is still limited. This is mainly due to the required adaptation of automated solutions to custom clinical data, reliance on time lapse incubators and a lack of interpretability to understand AI reasoning. The modern, informed patient is questioning expert decisions, particularly if the treatment is not successful. Thus, evidence-based decision justification in tasks like embryo selection would support transparent decision making and respectful patient communication. To support this aim, we hereby present an expert-annotated dataset consisting of embryo images and corresponding morphological description using natural language. The description contains relevant information on embryonic cell cycle, developmental stage and morphological features. This dataset enables the finetuning of modern foundational vision-language models to learn and improve over time with high accuracy. Predicted embryo descriptions can then be leveraged to automatically extract scientific evidence from literature, facilitating well-informed, evidence-based decision-making and transparent communication with patients. Our proposed dataset supports research in language-based, interpretable, and transparent automated embryo assessment and has the potential to enhance the decision-making process and improve patient outcomes significantly over time.
Towards Interpretable Foundation Models for Retinal Fundus Images
Foundation models are used to extract transferable representations from large amounts of unlabeled data, typically via self-supervised learning (SSL). However, many of these models rely on architectures that offer limited interpretability, a critical issue in high-stakes domains such as medical imaging. We propose \model, a foundation model that is interpretable-by-design via a BagNet backbone whose small receptive fields generate class evidence maps that are faithful to the model's decision-making process. Additionally, \model{} incorporates a projection layer during pretraining that enables direct visualization of the representation space, providing a dataset-level view of the learned structure including meaningful clinical clusters as well as potential spurious correlations. We trained \model{} on over 800,000 color fundus photographs from various sources to learn generalizable representations for different downstream tasks. Our model achieves performance comparable to RETFound, which has more parameters, while providing interpretable predictions on out-of-distribution data. These results suggest that large-scale SSL pretraining paired with inherent interpretability can lead to robust representations for retinal imaging. Code and pretrained models are available at www.anonymous.4open.science/dual-IFM.
SFL-Net: Source-Factorized Latent Representation Learning for Multi-Contrast MRI to Tau-PET Synthesis
Tau positron emission tomography supports Alzheimer's disease staging but is difficult to scale because of tracer, scanner, and radiation constraints. Synthesis from structural MRI is therefore attractive, but it is a particularly difficult setting. T1-weighted and FLAIR MRI provide anatomy and disease correlated morphology, but they do not directly measure Tau-PET relevant signal. We introduce SFL-Net, a multi-input synthesis framework that predicts Tau-PET from T1-weighted and FLAIR MRI. SFL-Net factorizes the latent representation into shared, T1-specific, FLAIR-specific, and complementary pathways and preserves anatomical detail through latent structural conditioning rather than direct encoder-decoder connections. We evaluated SFL-Net and baseline models using 605 training and 83 validation subjects from ADNI-3 and OASIS-3 datasets. Evaluation included raw image fidelity, standardized uptake value ratio agreement, high uptake overlap, regional Bland-Altman bias, braak derived stage agreement, non-inferiority sensitivity analysis, and latent component Shapley attribution. SFL-Net performed competitively on both clinically relevant and reconstruction metrics, while also delivering explicit source level auditability that conventional UNet derived models lack.
retinalysis-vascx: An explainable software toolbox for the extraction of retinal vascular biomarkers
Automatic extraction of retinal vascular biomarkers from color fundus images (CFI) is crucial for large-scale studies of the retinal vasculature. We present VascX, an open-source Python toolbox that extracts biomarkers from CFI artery-vein segmentations. VascX starts from vessel segmentation masks, extracts their skeletons, builds undirected and directed vessel graphs, and resolves vessel segments into longer vessels. A comprehensive set of biomarkers is derived, including vascular density, central retinal equivalents (CREs), and tortuosity. Spatially localized biomarkers may be calculated over grids placed relative to the fovea and optic disc. VascX is released via GitHub and PyPI with comprehensive documentation and examples. Our test-retest reproducibility analysis on repeat imaging of the same eye by different devices shows that most VascX biomarkers have moderate to excellent agreement (ICC > 0.5), with important differences in the level of robustness of different biomarkers. Our analyses of biomarker sensitivity to image perturbations and heuristic parameter values support these differences and further characterize VascX biomarkers. Ultimately, VascX provides an explainable and easily modifiable feature-extraction toolbox that complements segmentation to produce reliable retinal vascular biomarkers. Our graph-based biomarker computation stages support reproducible, region-aware measurements suited for large-scale clinical and epidemiological research. By enabling easy extraction of existing biomarkers and rapid experimentation with new ones, VascX supports oculomics research. Its robustness and computational efficiency facilitate scalable deployment in large databases, while open-source distribution lowers barriers to adoption for ophthalmic researchers and clinicians.
MedAD-R1: Consistency-Reinforced Policy Optimization for Interpretable Medical Anomaly Detection
Medical Anomaly Detection (MedAD) offers a promising direction for medical image analysis with Large Multimodal Models (LMMs). However, progress is limited by fragmented datasets and the tendency of Supervised Fine-Tuning (SFT) to learn superficial image-text correlations rather than verifiable diagnostic reasoning. Consequently, current models often generate fluent explanations that are either insufficiently grounded in the image or inconsistent with their final answers, limiting their reliability in high-stakes medical applications. To address these issues, we introduce MedAD-38K, a large-scale, multimodal, and multicenter benchmark containing structured Visual Question Answering pairs and quality-controlled diagnostic Chain-of-Thought annotations across five core MedAD tasks. Based on this benchmark, we propose a two-stage framework. Cognitive Injection first uses SFT to inject domain-specific medical knowledge and establish a structured think-then-answer format. Consistency Group Relative Policy Optimization (Con-GRPO) then employs an Evidence-Aware Consistency Reward to reinforce reasoning that remains grounded in the image and logically supports the final answer. The resulting MedAD-R1 achieves state-of-the-art performance on MedAD-38K and consistently outperforms all evaluated baselines across five source-disjoint external datasets spanning diverse imaging modalities. Beyond accuracy, it achieves higher reasoning-answer consistency and visual-grounding scores across multiple backbones. With only 0.8B parameters, MedAD-R1 offers practical potential for resource-constrained deployment. These results demonstrate the generality of evidence-aware consistency optimization for interpretable MedAD. Project resources are available at https://github.com/zhtstar/MedAD-R1.
A Tool Bottleneck Framework for Clinically-Informed and Interpretable Medical Image Understanding
Recent tool-use frameworks powered by vision-language models (VLMs) improve image understanding by grounding model predictions with specialized tools. Broadly, these frameworks leverage VLMs and a pre-specified toolbox to decompose the prediction task into multiple tool calls (often deep learning models) which are composed to make a prediction. The dominant approach to composing tools is using text, via function calls embedded in VLM-generated code or natural language. However, these methods often perform poorly on medical image understanding, where salient information is encoded as spatially-localized features that are difficult to compose or fuse via text alone. To address this, we propose a tool-use framework for medical image understanding called the Tool Bottleneck Framework (TBF), which composes VLM-selected tools using a learned Tool Bottleneck Model (TBM). For a given image and task, TBF leverages an off-the-shelf medical VLM to select tools from a toolbox that each extract clinically-relevant features. Instead of text-based composition, these tools are composed by the TBM, which computes and fuses the tool outputs using a neural network before outputting the final prediction. We propose a simple and effective strategy for TBMs to make predictions with any arbitrary VLM tool selection. Overall, our framework not only improves tool-use in medical imaging contexts, but also yields more interpretable, clinically-grounded predictors. We evaluate TBF on tasks in histopathology and dermatology and find that these advantages enable our framework to perform on par with or better than deep learning-based classifiers, VLMs, and state-of-the-art tool-use frameworks, with particular gains in data-limited regimes. The project details and the code are available at https://christinaliu2020.github.io/tbm/.
Towards Cellular-Scale Interpretability in Pathology Foundation Models for Biomarker Assessment
Molecular biomarker testing in pathology is often costly and tissue-consuming, limiting scalable clinical deployment. Artificial intelligence applied to hematoxylin and eosin (HE)-stained histology could enable rapid biomarker screening, but clinical translation requires models that are both accurate and interpretable. Here we introduce Hireca, a biomarker-focused pathology foundation model pretrained on more than 80,000 whole-slide images spanning 38 organ types from three medical centers, together with CytoMap, an interpretability module that localizes cellular-scale evidence underlying predictions. Across 10 biomarker tasks encompassing morphological, molecular, genetic, and spatial-transcriptomic-proxy readouts, Hireca ranked first in five tasks and outperformed comparable models overall. In evaluation by eight pathologists from two countries, CytoMap was consistently preferred over alternative visualization approaches and revealed error patterns in difficult cases. These results position Hireca and CytoMap as a transparent framework for clinically reviewable biomarker assessment directly from routine HE histology.
CXRAgent: Director-Orchestrated Multi-Stage Reasoning for Chest X-Ray Interpretation
Chest X-ray (CXR) plays a pivotal role in clinical diagnosis, and a variety of task-specific and foundation models have been developed for automatic CXR interpretation. However, these models often struggle to adapt to new diagnostic tasks and complex reasoning scenarios. Recently, LLM-based agent models have emerged as a promising paradigm for CXR analysis, enhancing model's capability through tool coordination, multi-step reasoning, and team collaboration, etc. However, existing agents often rely on a single diagnostic pipeline and lack mechanisms for assessing tools' reliability, limiting their adaptability and credibility. To this end, we propose CXRAgent, a director-orchestrated, multi-stage agent for CXR interpretation, where a central director coordinates the following stages: (1) Tool Invocation: The agent strategically orchestrates a set of CXR-analysis tools, with outputs normalized and verified by the Evidence-driven Validator (EDV), which grounds diagnostic outputs with visual evidence to support reliable downstream diagnosis; (2) Diagnostic Planning: Guided by task requirements and intermediate findings, the agent formulates a targeted diagnostic plan. It then assembles an expert team accordingly, defining member roles and coordinating their interactions to enable adaptive and collaborative reasoning; (3) Collaborative Decision-making: The agent integrates insights from the expert team with accumulated contextual memories, synthesizing them into an evidence-backed diagnostic conclusion. Experiments on various CXR interpretation tasks show that CXRAgent delivers strong performance, providing visual evidence and generalizes well to clinical tasks of different complexity. Code and data are valuable at this link.