Explainable Medical Image Analysis

Medical imaging models often operate as black boxes, limiting interpretability and systematic debugging. We introduce an easy-to-use, plug-and-play framework for concept-based interpretation and model refinement. By aligning a single-modality encoder to BioMedCLIP, we construct a Concept Bottleneck Model (CBM) that enables concept-level interventions. These interventions allow us to isolate causal versus spuriously correlated concepts, validate insights with domain experts, and generate counterfactual samples for targeted fine-tuning. We evaluate our framework on a Mayo Clinic ultrasound dataset and the CheXpert 5x200 chest X-ray dataset. Results demonstrate that concept intervention enables reliable model diagnosis while maintaining, and occasionally improving predictive performance via guided fine-tuning. Our findings highlight the practical value of this framework for controlled, interpretable refinement of clinical deep learning models.

Background: Biomedical AI can generate plausible explanations without reliably verifying whether each statement is supported by patient-specific evidence. We developed a neuro-semantic verification framework that converts radiomic measurements into addressable evidence records and machine-checkable claims. Methods: UPenn-GBM radiomics were aligned with de novo CaPTk extraction from standardized MRI and expert-validated segmentations in an independent multicenter cohort. The shared space comprised 1,728 features from T1, T1GD, T2, and FLAIR MRI across three tumor regions. Reference-defined semantic states were derived from 611 UPenn cases. We evaluated cross-cohort transportability, model-linked provenance, deterministic verification, controlled predictive degradation, and an LLM claim-extraction pilot; MGMT prediction served only as a transport stress test. Results: Median semantic-state agreement was 0.786 (weighted kappa 0.709), ranging from 0.918 for morphologic to 0.252 for intensity features. The external evidence ledger contained 1,655 model-linked records for 331 patients. The verifier achieved 100% exact-set accuracy in a 6,620-claim corruption benchmark. In a 24-case pilot, GPT-5.6 Sol reproduced 72/72 prespecified atomic claims, and the frozen verifier recovered 24/24 expected conditions. During controlled degradation, ROC AUC declined from 0.899 to 0.500 while verification accuracy remained 1.000. External MGMT discrimination was weak (ROC AUC 0.543). Conclusions: Verifiability can be engineered and evaluated independently of predictive performance. LLMs may structure explanations, while final evidence-consistency checking remains deterministic.

Clinical diagnosis is inherently a structured reasoning process, yet existing deep learning models often bypass this structure by mapping image features directly to disease labels without explicitly interrogating the morphological and textural criteria that clinicians systematically evaluate. This limits diagnostic transparency and may compromise safe clinical deployment. We present MedCORE (Medical Criteria-Oriented Reasoning and Evidence), a structured diagnostic framework that operationalizes clinical reasoning within a vision-language architecture. For each input image, MedCORE decomposes the diagnostic process into clinically defined criteria, spatially localizes each criterion to diagnostically relevant image regions, encodes evidence through multi-scale representations that capture macro-structural and micro-textural pathological characteristics, and refines criterion representations using a Graph Attention Network that explicitly models inter-criteria dependencies. Criterion representations are further aligned with clinical text descriptors, reinforced through class-wise visual prototypes, and aggregated using uncertainty-calibrated weighting that proportionally discounts low-confidence diagnostic evidence. MedCORE is validated across three clinically heterogeneous imaging modalities, including dermoscopic lesion classification on ISIC 2018, breast ultrasound lesion characterization on BUSI, and diabetic retinopathy grading on IDRiD. Quantitatively, MedCORE achieves 89.2% accuracy, 85.7% macro-F1, and 96.4% AUC on ISIC 2018; 96.1% accuracy, 95.2% macro-F1, and 98.4% AUC on BUSI; and 84.3% accuracy, 80.2% macro-F1, and 92.8% AUC on IDRiD. These results demonstrate consistent improvements over strong CNN, transformer, biomedical vision-language, concept-based, and prototype-based baselines.

The clinical integration of AI systems in digital dermatology relies heavily on human trust. Clinically interpretable visual concepts can act as intermediate representations enhancing trust and reliability. However, research in this domain is currently limited by scattered, heterogeneous dataset annotations. In this work, we introduce SkinLex, a harmonized dataset of 48 clinical morphological attributes across four public datasets (SkinCon, DermaCon-IN, MM-Skin, and PASSION) for a total of 20,411 records. Supervised nine-partition classification of skin conditions shows that limiting features to specific visual groups, like shapes or colors alone, reduces diagnostic accuracy. Bootstrapped backward elimination reveals that the set of 48 visual concepts has some degree of redundancy for algorithmic nine-partition diagnosis on the examined dataset. This demonstrates that coarse diagnosis on the selected dataset requires a relatively small but varied combination of clinical concepts, and motivates further research to improve concept taxonomy. Results can be translated into clinical benefits by reducing inputs for concept-based models, improving efficiency for annotation and modeling, and further enhancing interpretability. Code and prompt templates are available at https://github.com/Digital-Dermatology/SkinLex.

Foundation models pretrained on large-scale datasets demonstrate strong transferability to medical imaging tasks. However, understanding how their latent representations encode clinically relevant information remains an open challenge in safety-critical domains. This study proposes a prototype-based fuzzy-rule framework that interprets the patch-level features produced by the inner layers of pretrained foundation models, without any fine-tuning. Class-specific prototypes are learned by clustering in the feature space, yielding compact visual patterns. Patch features are then expressed as prototype similarities and classified by fuzzy rules with linguistic IF-THEN conditions that are human readable. The framework is applied across the final two blocks of ViT-S/16 backbones pretrained on ImageNet-1K and GastroNet-5M, and benchmarked against k-nearest neighbours, kernel SVM, and linear probing under identical frozen features, on wireless capsule endoscopy classification, gastrointestinal endoscopy classification, and colonic polyp segmentation. The experimental analysis shows that the proposed method, without backbone fine-tuning, reaches accuracy comparable to these black-box classifiers, and that domain-specific pretraining yields features that are both discriminative and symbolically compressible. Because the resulting rules are extracted from real data and expressed in interpretable terms, they are further used as an instrument to investigate synthetic medical images, providing a human-readable account of which real prototypes and rules a generator reproduces or fails to reproduce, localising where a synthetic image departs from real tissue rather than summarising it with a single score. The framework thus offers a transparent, depth-resolved view of how foundation models organise clinically relevant structure, together with a practical downstream use of the extracted rules.

Deep learning classifiers for dermoscopic skin lesions often reach high in-distribution accuracy while quietly relying on spurious background cues such as skin tone, device vignetting, and embedded rulers, rather than on lesion morphology. This undermines robustness and fairness across skin tones. This work asks whether Explainable AI (XAI), typically used only to audit a finished model, can instead be repurposed as an active training signal that corrects this shortcut without sacrificing diagnostic accuracy. We introduce CAMEO (Class Activation Mapped Equitable Overlay), a framework that improves skin-lesion classification by selecting stable model explanations and using them to separate lesions from their backgrounds. It then replaces the background with realistic synthetic skin while keeping the lesion unchanged. On HAM10000 and dark-skin ISIC images, CAMEO maintained accuracy while reducing background-driven errors by nearly four times. It also made the model's attention more consistent when backgrounds changed. Results across multiple tests show that reducing reliance on background information improves robustness, with Fitzpatrick-based backgrounds providing a realistic and interpretable approach. Results show that XAI-guided augmentation can make dermoscopic classifiers measurably more robust and fair at no cost to accuracy. They also clarify that it is the mechanism and not the specific tone palette that matters, and that the lasting contribution of XAI here lies in stability-screened, annotation-free lesion localisation rather than in the robustness number itself.

Deep learning models for Alzheimer disease (AD) classification routinely report near-perfect discrimination, yet few are shown to rest on AD-relevant neurobiology rather than on dataset artifacts, subject-level leakage, or non-brain image content. We present a fusion network combining T1 MRI and FDG PET across axial, coronal, and sagittal planes, trained on ADNI consists of 554 paired subjects. The fusion model reaches AUC 0.962, accuracy 0.909, and F1 0.891, competitive with recent 3D CNN and multimodal transformer systems at substantially lower cost. We first quantify how much modality, plane and slice geometry matter. A validation-only search over slice centres and neighbour spacings moves AUC by 0.180 for MRI and 0.078 for PET, selecting narrow spacing for MRI and wide spacing for PET, with the chosen coronal centres falling on the hippocampal body and on the posterior cingulate respectively. The contribution, however, is the evidence layer built around that number. Shortcut controls collapse the model to AUC 0.622 (silhouette), 0.608 (exterior), and 0.500 (blank), and a label-permutation null yields 0.456. Forward region-of-interest (ROI) ablation shows that masking medial temporal cortex in MRI and the posterior default-mode network (DMN) in PET produces the largest shift in the AD logit, while area-matched controls remain indistinguishable from that null. Reverse ROI ablation shows that the medial temporal lobe alone retains 89.2% of above-chance discrimination in MRI and the posterior DMN alone retains 79.0% in PET. A quantitative comparison of attribution methods shows occlusion sensitivity reaching 3.5-5.0* enrichment inside a priori AD regions against 0.10-0.43* in controls. Ablation and attribution independently establish a biologically correct double dissociation: hippocampal evidence is carried by MRI, posterior cingulate evidence by PET.

Predicting molecular profiles from histopathology remains challenging because whole-slide images contain spatially organized, heterogeneous tissue patterns, while gene expression comprises thousands of correlated targets. We introduce MoSPR (Morpho-Spatial Program Regression), a linear framework that couples an adjacency-informed histology representation with a low-rank molecular basis. MoSPR clusters frozen patch embeddings into morphology microstates, aggregates their spatial adjacencies across the training cohort, and groups microstates with similar adjacency patterns into shared macrostates. Each slide is then represented by global morphology and macrostate-specific deviations, which are linearly mapped to coefficients of a training-derived low-rank gene-expression basis. Across three cancer cohorts from The Cancer Genome Atlas, MoSPR achieves the highest mean gene-expression prediction scores among all evaluated methods. Without pathway-level supervision, pathway scores derived from its predicted expression profiles rank first in eight of nine comparisons across three pathway collections. Ablation studies on the breast cancer cohort show complementary gains from adjacency-derived macrostate representation and low-rank molecular prediction. Moreover, with half of the training data on this cohort, MoSPR exceeds the full-data gene-prediction score of the strongest competing baseline. Finally, its linear formulation enables exact decomposition of each predicted expression profile into global and macrostate-specific molecular contributions, providing an interpretable link between spatially coherent macrostate regions and their associated molecular programs. Our code is available at https://github.com/Radisen-Panthera/MoSPR.

Purpose: To develop and evaluate an interpretable artificial intelligence (AI) framework for glaucoma screening from low-cost portable, handheld retinal fundus photographs in a West African population and to compare its performance with clinical tabletop fundus imaging. Methods: We used data from a community-based study of 681 participants (1,362 eyes) in Nigeria, comprising 414 glaucoma, 478 glaucoma suspect, and 470 non-glaucoma eyes. Fundus photographs were acquired using the low-cost handheld, portable Volk Viva retinal camera and the Canon CR-2-AF tabletop camera. We fine-tuned component models separately to each device to perform vessel segmentation, cup and disc boundary segmentation, and feature extraction to detect optic nerve head features. A final classification model combined these components to classify scans as glaucoma, glaucoma suspect or non-glaucoma. Feature-weight analysis and Gradient-weighted Class Activation Mapping were used for interpretation. Results: The models performed well on both Volk Viva and Canon CR-2-AF images: Vessel segmentation: 0.98 Dice Coefficient (DC) (Volk) and 0.94 DC (Canon); Cup and disc segmentation: 0.95 DC (Volk) and 0.96 DC (Canon); Optic nerve head feature detection: area under the receiver operating characteristic curve (AUCs) of 0.83$\pm$0.03 (Volk) and 0.87$\pm$0.04 (Canon); Classification model: AUCs of 0.85$\pm$0.01 (Volk) and 0.93$\pm$0.01 (Canon). Reports for each image, present model decision confidence scores and decision-rationale visualizations to support clinical interpretation. Conclusions: Volk Viva results were reasonably comparable to Canon CR-2-AF in the component models and not far behind in classification. This shows that interpretable AI combined with low-cost, portable imaging may enhance community-level glaucoma screening, especially in settings with limited specialist access and resources.

More than 80 countries have reported malaria cases with 610 thousand deaths and are projected to increase. Identifying malaria early and accurately helps save lives and effective way to diagnose malaria is through microscopic methods that are labor intensive and require experts with special equipment. Deep learning (DL) has shown promising results in medical diagnosis. Here, we explored various DL models: ResNet18, MobileNetV2, EfficientNet-B2, VGG19 and proposed model ResNet18+TTA (ResNet18 backbone with modified classification head and test time augmentation) for detecting malaria presence using blood smears taken from the NIH Malaria dataset. Our experiment shows MobileNetV2 achieved 96.85 % accuracy with smallest model size (8.49 MB) and fastest inference (1.35 ms). The ResNet18+TTA model achieved 97.96 % accuracy, 0.996 AUC with longest inference time (13.32 ms). Larger architecture outputs a larger model size with moderate accuracy. Upon further pruning, ResNet18+TTA model gained a slight improvement in accuracy and reduced inference time. GRAD-CAM, SHAP and LIME provide explainable AI (XAI) insights into model predictions, using explanation agreement and divergence to evaluate predictive reliability.

Deep networks trained on structural MRI for Alzheimer's disease (AD) staging often reach reasonable accuracy while attending to anatomically irrelevant regions, and multimodal models that add clinical tables frequently rely on variables that were used to assign the diagnostic label in the first place. We study both issues with a deliberately lightweight slice-based encoder (ResNet18 with a one-layer Transformer over slices) on 1,075 baseline T1-weighted scans from ADNI-1. First, we use FastSurfer segmentations as an anatomical reference: YOLOv8 models trained on segmentation-derived labels localize Alzheimer-relevant structures with mAP_50 above 0.96, and a Grad-CAM comparison shows that the image-only classifier frequently attends to the skull, orbits and background. Second, we adapt a CLIP-style image - tabular contrastive framework and organize ADNIMERGE variables along a label-leakage spectrum. Fusion with cognitive scores yields 87.3% three-way accuracy, which we treat as a leakage-driven upper bound rather than an imaging result; fusion with regional volumes yields 73.0%. We observe that the choice of contrastive target changes what the image encoder learns: on MCI vs. CN, the image-only head reaches 52.4% when the encoder is aligned to cognitive scores and 73.8% when aligned to volumes, although no tabular input is used at inference. Third, restricting the input to a per-subject crop of the medial temporal lobe raises image-only three-way accuracy from 58.7% to 65.1%. All results come from single runs on a small balanced test set, and we report confidence intervals and the protocol differences that prevent direct comparison with published numbers.

Medical counterfactual generation modifies images to change model predictions for interpretability. However, existing diffusion-based approaches are often prohibitively slow and memory-intensive, making them difficult to apply in high-resolution settings. Moreover, existing masking strategies are tightly coupled with pixel-space representations, making them incompatible with latent-space diffusion editing. To address these challenges, we propose MedDiME, a latent-space classifier-guided diffusion framework that reduces computational and memory overhead while introducing a latent-compatible, gradient-driven adaptive masking mechanism for spatially precise medical counterfactual generation. Extensive experiments demonstrate that MedDiME achieves high-quality counterfactual generation with significant efficiency gains compared to prior classifier-guided diffusion baselines, achieving up to 40 times faster inference and 13 times lower peak GPU memory usage.

Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI ($\rho=0.94$) and OASIS-3 ($\rho=0.96$); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.

Cancer segmentation models can fail silently, generating plausible but incorrect masks that risk missed findings or unnecessary biopsies. A critical question arises: Do AI models "know" when they are wrong, and if so, can we use the signal to predict their own failures? Humans do have a "Feeling of Error" (FOE): a spontaneous sense of unease that flags a potential error during thinking. We investigate whether cancer segmentation models exhibit an analogous internal signal. Unlike output-level cues (e.g., prediction confidence or uncertainty), which offer no insight into why a failure occurs and suffer from a sensitivity-quality tradeoff where high detection sensitivity could degrade overall segmentation quality. We instead propose to capture the model's FOE from its inner workings. Using mechanistic interpretability tools, specifically Sparse Autoencoders, we decompose internal neural activations into a dictionary of human-interpretable concepts and show that failure cases exhibit a distinct latent signature: fewer active concepts with lower activation magnitudes compared to successful segmentation. By training a classifier on these concept activations, we achieve accurate failure detection along with explanations for the model's mistakes. Experiments on prostate, pancreatic, and brain cancer segmentation demonstrate that our approach outperforms output-based methods in failure detection while preserving segmentation quality.

Multiple Instance Learning (MIL) is widely used for weakly supervised learning, particularly in digital pathology, where fine-grained annotations are costly. Most MIL methods aggregate instance features via attention mechanisms. However, attention weights do not always faithfully reflect instance importance and may focus on spuriously correlated regions. In this work, we propose CAR-MIL, a framework that explicitly guides attention learning through a counterfactual attention regularization objective inspired by counterfactual explanations. Built on a standard attention-based MIL architecture, our approach introduces a lightweight counterfactual attention branch trained to produce an alternative prediction while remaining close to the factual attention distribution. This encourages prediction changes to arise from minimal, structured redistributions of attention, leading to more informative evidence allocation. The resulting factual and counterfactual attention maps capture complementary evidence: the former highlights regions supporting the prediction, while the latter reveals regions whose reweighting would challenge it. We evaluate our method on synthetic MIL benchmarks with instance-level ground truth enabling controlled analysis of attention behavior and on five digital pathology datasets across four tasks. CAR-MIL maintains competitive classification performance, with the largest gains observed on more challenging tasks, while improving attention reliability, demonstrating the benefits of integrating counterfactual explainability reasoning into attention learning. Code is available at: https://github.com/ImaneCR/CAR-MIL/.

Model pruning is widely used to compress deep neural networks, reducing memory and computational requirements with minimal impact on aggregate performance. However, its effect on model behavior remains poorly understood, particularly for long-tailed medical datasets where rare but clinically important conditions are underrepresented. Furthermore, it remains unclear whether pruned models preserve reliable explanations of their predictions. To address this gap, we present a systematic study of long-tail forgetting and explanation reliability under model pruning. Across two long-tailed medical imaging datasets, two CNN architectures, four pruning methods, and sparsity levels up to 95%, we evaluate predictive performance, explanation stability, and explanation faithfulness. Our results show that predictive performance exhibits a strong frequency-dependent trend, with lower-frequency classes generally experiencing earlier and larger degradation than higher-frequency classes. In contrast, explanation stability and faithfulness are influenced primarily by the pruning strategy, with gradient-informed methods preserving explanation reliability more effectively under aggressive compression. Qualitative and mechanistic analyses further indicate that explanation degradation is primarily associated with the collapse of class-discriminative gradients rather than the disappearance of feature activations. These findings suggest that model compression should be evaluated beyond aggregate performance. Incorporating class-aware and explanation-aware evaluation reveals failure modes that would otherwise remain hidden, while moderate sparsity levels provide a practical balance between compression, predictive performance, and explanation reliability.

Smartphone skin photographs are indispensable to teledermatology, yet assessing the diagnostic suitability of submitted cases (gradability) remains a critical bottleneck in mobile care workflows. Dermatologists routinely review multiple photographic views (regional, angled, and close-up) to identify consistent textural detail rather than relying on a single image. We present the Semantic Tri-view Pipeline, an interpretable architecture for automated teledermatology gradability screening that formalizes epidermal micro-relief as a computable biomarker of image quality. Using an expert-annotated subset of the public SCIN dataset, we train a lightweight DeepLabV3+ model to segment micro-relief fidelity. These spatial masks are then aggregated across up to three case views with a logistic regression classifier, leveraging viewpoint redundancy to support robustness under uncontrolled smartphone acquisition. This approach learns context-aware, clinically intelligible heuristics, such as penalizing high-fidelity texture in regional distance views. Evaluated at a predefined 90% sensitivity operating point, the system's apparent errors largely reflect subjective clinical variance on borderline cases where clinicians rely on non-visual metadata. On SCIN, performance improves from an AUC of 0.81 (80.6% PPV) on variance-heavy majority-consensus cases to 0.96 (97.7% PPV) on optically unambiguous unanimous cases. Overall, this work delivers an interpretable, privacy-by-design, edge-ready system that can provide real-time feedback during case submission to filter ungradable photo sets before review.

Deep neural networks often exploit spurious associations, a failure known as shortcut learning. Before deployment, models should be audited for reliance on a set of concepts, such as acquisition artifacts or demographics. Current methods, such as linear probes and concept activation vectors, measure reliance by asking whether each concept, in isolation, is decodable from a layer. Their scores therefore reflect not only reliance but also correlations in the audit dataset. We introduce Independent Canonical cONcept (ICON) decomposition, which quantifies the share of a layer's variance each concept explains, conditional on all other concepts and the outcome. ICON scores are variance shares, comparable across layers and between continuous and categorical concepts. ICON also reports the share the set leaves unexplained. On simulated data, ICON recovers the true importance more accurately than seven baselines. On skin-cancer and neuroimaging models, ICON distinguishes learned shortcuts from correlated concepts, confirmed by retraining and out-of-distribution tests.

Breast ultrasound diagnosis relies on clinically meaningful semantic concepts, yet most deep learning methods adopt end-to-end image-to-label paradigms that lack interpretability and robustness. While concept-based approaches offer a promising alternative, they often assume complete annotations or require multimodal inputs at inference, which significantly limits their real-world applicability. To tackle these issues, we propose Training-time Report-guided and Clinically Ordered Concept Editing (TRACE), a training-time report-guided framework that leverages structured radiology reports as privileged concept supervision while enabling image-only diagnosis at test time. TRACE refines image-derived concepts through a teacher-guided editing mechanism within a malignancy-aware ordered concept space. To address incomplete annotations, we introduce Strategic Concept Missing Training (SCMT) and train an image-only self-editor via edit distillation for autonomous concept refinement. Besides, we introduce BUSC, a concept-enriched benchmark linking images, labels, and structured attributes. Experiments across multiple datasets demonstrate that TRACE achieves superior performance and improved cross-domain robustness compared to existing methods.

Visual Counterfactual Explanations (VCEs) aim to explain image classifiers by generating minimally edited and realistic versions of an input image that change the classifier's prediction. Existing VCE methods are inherently classifier-dependent and therefore susceptible to classifier biases and failure modes, such as sensitivity to shortcut features and calibration errors. In this paper, we propose a classifier-free approach for visual counterfactual generation based on Contrastive Analysis (CA). Given two datasets corresponding to different classes (e.g., healthy and patients), we disentangle the generative factors that are common across the two datasets from those that are salient to each dataset, and generate counterfactual images by swapping only the salient factors. By operating directly on data distributions rather than decision boundaries, our method provides model-agnostic VCEs that are less sensitive to classifier biases. Our approach leverages the high-quality synthesis and well-structured latent space of StyleGAN2. We use the feature space F, instead than the usual W-space, to improve detail preservation. Unlike conventional CA approaches, which typically assume salient factors in only one dataset, we introduce an adapted framework and loss functions for VCE that allow multiple salient factors in each dataset. We evaluate our method on three medical imaging datasets and demonstrate superior counterfactual generation quality compared to existing approaches.

Concept bottleneck models (CBMs) can improve the transparency of cancer image diagnostic prediction by expressing predictions through radiological concepts. However, their dependence on instance-level concept annotations limits practical applicability. We propose a prior-guided hybrid CBM that integrates limited concept annotations, class-conditional concept distribution matching on unannotated patients, and prior initialization of the concept-to-diagnosis head. We evaluate the method on CBIS-DDSM mammographic masses and calcifications and LIDC-IDRI pulmonary nodules across 0-100% concept annotation. In the clinically relevant 0-20% annotation regime, the hybrid CBM consistently improves mean concept AUC over a matched standard CBM, while maintaining diagnostic performance close to black-box models. At 10% annotation specifically, concept AUC increases from 0.619 to 0.741 for masses, from 0.650 to 0.787 for calcifications, and from 0.597 to 0.642 for pulmonary nodules. Ablation experiments identify prior initialization as the main component contributing to improved concept detection, likely by stabilizing the concept-to-diagnosis head. Zero-shot VLMs remain insufficient for reliable fine-grained tumor-level concept prediction. These findings suggest that structured priors can substantially reduce the annotation burden of interpretable cancer imaging models.

Explainability is essential for deploying deep learning models in high-stakes medical applications. Existing explainability methods for volumetric imaging predominantly operate in voxel space, overlooking the structured representations introduced by recent advances in 3D scene modeling. We present COGENT (Counterfactual Gaussian Explanations), a framework that generates counterfactual explanations directly in the parameter space of Gaussian-based volumetric representations. Built upon MedGS and the Sybil lung cancer risk prediction model, COGENT optimizes selected Gaussian primitives through a differentiable rendering pipeline, enabling gradients from the downstream predictor to identify representation components that most influence model decisions. Unlike conventional pixel- or voxel-level attribution methods, our approach formulates explainability as a counterfactual optimization problem over an explicit 3D scene representation, producing sparse and spatially localized explanations while preserving anatomical consistency. We evaluate COGENT on lung CT scans using quantitative comparisons with existing explainability methods together with qualitative analysis by medical experts. The results demonstrate that representation-space counterfactual optimization provides clinically meaningful explanations while offering a new perspective on interpreting volumetric deep learning models.

Skin cancer diagnosis from dermoscopic images remains challenging due to high intra-class variability, inter-class similarity, class imbalance, and the limited interpretability of deep learning models. This paper proposes an uncertainty-aware and explainable deep learning framework for multi-class skin lesion classification. The framework combines a vision transformer model (MaxViT-Tiny) with CNN-based models (ConvNeXt-Tiny and EfficientNetV2-B0) through deep ensemble learning. Monte Carlo (MC) Dropout estimates predictive uncertainty and identifies unreliable predictions, while Grad-CAM++, an explainable AI (XAI) technique, provides visual explanations by highlighting lesion regions that influence model decisions. Evaluated on the HAM10000 dataset, the framework achieves 96% accuracy and 99% ROC-AUC under uncertainty-aware filtering (entropy < 1.0, confidence >= 0.7), with macro-average precision, recall, and F1-score of 94%, 95%, and 95%, respectively, and 96% weighted-average scores across all three metrics. The results demonstrate accurate, interpretable, and uncertainty-aware skin lesion classification for trustworthy computer-aided diagnosis.

Vision foundation models are increasingly used as reusable encoders in medical image computing, yet their high-dimensional spatial embeddings are difficult to inspect beyond downstream task performance or global dimensionality reduction. We propose position-prompted PCA (P3CA), an encoder-agnostic method for local probing of channel-rich spatial tensors. Given a user-selected spatial prompt, P3CA estimates the feature normalization and dominant covariance directions within that region, then applies the resulting projection to the full tensor to visualize where locally informative directions are expressed. This produces a region-conditioned representation lens without modifying the encoder, retraining, or requiring task-specific labels. We implement P3CA in EmbedVision, an interactive 3D Slicer-based workflow, and evaluate it across natural images, colorectal pathology foundation-model embeddings, and spatial transcriptomic tensors. Across these settings, prompted projections reveal local structure suppressed by global PCA, improve prompt-matched pathology discrimination from frozen three-dimensional projections, and support comparison between learned and measured spatial representations.

Retinal fundus images frequently exhibit multiple co-occurring pathologies, yet standard deep learning classifiers apply static, identical computation to every image regardless of the underlying disease distribution. We propose a novel architecture that resolves this via sparse conditional computation, pairing a Guided Context Gating (GCG) spatial attention front-end with a sparsely-routed Mixture-of-Experts (MoE) block operating over feature tokens. Crucially, this routing yields an interpretable, data-driven decomposition. Expert allocation is significantly disease-dependent (p < 0.001), with the healthy Normal state and morphologically distinct pathologies (e.g., ERM, AMD) isolating to dedicated experts. On a five-class, patient-disjoint 5-fold cross-validation benchmark, our model achieves 0.912 +/- 0.008 macro AUC and 0.653 +/- 0.014 macro F1. Furthermore, Grad-CAM++ and post-MoE t-SNE visualizations confirm that expert routing aligns with localized lesions and geometrically maps co-occurring cases between their constituent clusters, positioning sparse MoE as an interpretable approach to multi-disease retinal screening.

Diabetic retinopathy (DR) remains a leading cause of vision loss among working-age adults worldwide, making reliable severity grading clinically important. Despite strong performance, most deep models formulate DR grading as image-level classification and do not explicitly model clinically grounded evidence, such as lesion types and spatial relations. In this paper, we propose PARAGraph, a Pathology-Anatomy-Aware Hierarchical Graph framework for DR grading. PARAGraph represents each image as a three-level hierarchical graph with lesion-level nodes, intermediate category and region nodes, and global anatomical and semantic nodes. To incorporate medical priors into nodes, we construct an optic disc-fovea-anchored coordinate frame that provides a scale- and rotation-normalized retinal reference system. Within this frame, lesion nodes are encoded with category, normalized area, and anatomical coordinates. To mitigate noisy lesion segmentation, PARAGraph uses a dual-fusion strategy that introduces global visual context into a graph semantic node and a decision-level prediction branch, improving robustness when lesion evidence is unreliable. Extensive experiments on Messidor-2, APTOS, and DDR show that PARAGraph achieves consistent DR grading performance over state-of-the-art methods. Interpretability and robustness analyses further demonstrate that its predictions are clinically grounded, closely associated with lesion evidence and robust to lesion segmentation noise.

Foundation models provide transferable CT representations, but predictions based directly on these embeddings are difficult to interpret. We developed concept bottleneck models that map two frozen CT foundation-model representations to eight radiologist-defined pulmonary-nodule attributes and predict malignancy from the estimated concepts and nodule size. The models included CT-FM, a whole-CT self-supervised encoder using a 96^3-voxel nodule-centered patch, and FMCIB, a nodule-focused contrastive encoder using a 50-mm crop. Eight ridge-regression concept heads were trained on 2,610 LIDC-IDRI nodules. Malignancy models were trained on LUNA25 and evaluated on a held-out internal test set and the external DLCS cohort. Concept fidelity was assessed using five-fold cross-validated R^2, and malignancy discrimination was assessed using AUROC with 95% confidence intervals estimated by patient-grouped bootstrap resampling. Concept fidelity was modest but higher for FMCIB than CT-FM for subtlety (R2, 0.24 vs. 0.11), spiculation (0.17 vs. 0.08), texture (0.17 vs. 0.07), and lobulation (0.15 vs. 0.05). Internally, the CT-FM and FMCIB concept+size models achieved AUROCs of 0.86 (95% CI, 0.80-0.92) and 0.86 (0.79-0.92), respectively. Externally, AUROCs were 0.72 (0.68-0.75) and 0.73 (0.70-0.76), compared with 0.73 for nodule size alone and 0.60 and 0.67 for the corresponding embedding only probes. Additive predictions could be decomposed into feature-level contributions and modified through controlled concept interventions. Concept bottlenecks provided transparent malignancy predictions with discrimination similar to nodule size alone, while differences in concept fidelity suggest that concept recovery depends on the underlying foundation-model representation.

Radiology reporting is time-consuming and subject to inter-rater variability, making automated report generation an attractive clinical application for Vision-Language Models (VLMs). We benchmark state-of-the-art VLMs on lumbar spine MRI with a focus on diagnostic accuracy and demonstrate that standard lexical and semantic metrics poorly reflect clinical correctness: fluent, well-structured reports can score highly while containing clinically meaningful diagnostic errors. To address this failure mode, we propose an architecture-agnostic framework that augments VLM inputs with spatially localized, disc-level anomaly heatmaps generated by a semi-supervised U-Net++ model. These heatmaps both improve anatomical sensitivity through explicit visual grounding and provide an independent interpretability output for clinical oversight, moving us closer to diagnostically reliable, visually grounded VLMs for lumbar spine MRI interpretation.

Edge Artificial Intelligence (Edge AI) enables the deployment of AI models directly on local edge devices, while such deployments are subject to strict resource constraints, particularly in clinical applications requiring local and timely inference. In such contexts, explainable artificial intelligence (XAI) can serve as a human-AI interface intended to support healthcare professionals' and patients' understanding of model predictions and informed decision-making. To fulfill this role, XAI method selection for TinyML deployments can be formulated as a human-centered multi-objective design problem that jointly considers qualitative stakeholder preferences, explanation quality, and proxy-based deployment cost. We propose a framework that integrates a large language model (LLM)-guided design interface that maps qualitative stakeholder preferences to candidate XAI methods, followed by deterministic feasibility filtering and Pareto-based optimization. The framework exposes trade-offs among explanation fidelity, stability, and proxy-based deployment cost while characterizing their implications for explanation quality and estimated deployment feasibility. A proof-of-concept evaluation on a skin lesion classification task illustrates how the framework systematically compares candidate XAI methods and identifies Pareto-efficient trade-offs. The present evaluation covers the computational selection stages, while physical MCU deployment and empirical human-expert validation remain outside the scope of this study.

Medical visual grounding connects free-form clinical queries to spatial evidence in medical images and is an important component of interpretable medical artificial intelligence. However, general-purpose grounding models are predominantly trained on natural images, while existing medical localization resources remain fragmented across imaging modalities, datasets, and task formulations. To address this gap, we construct LocAnyMed-200K, a multimodal medical visual grounding dataset containing approximately 200K image-query-answer examples across computed tomography, optical medical imaging, ultrasound, and X-ray. We harmonize heterogeneous detection and localization resources into a unified free-form instruction format that supports one or multiple bounding boxes, point coordinates, and no-target outputs for negative queries. Full-parameter fine-tuning of LocateAnything-3B on LocAnyMed-200K improves F1@IoU 0.50 from 10.64 to 85.59 on a held-out evaluation split, demonstrating that large-scale domain-specific supervision can equip a general grounding model with effective medical localization capabilities. Beyond spatial coordinates, a clinically interpretable grounding system should also communicate the evidence supporting its prediction. We therefore derive LocAnyMed-CoT-20K, a rationale-augmented subset that connects anatomical context, visual observations, and spatial conclusions through structured reasoning and further improves cross-source generalization through fine-tuning. Together, these resources provide a unified foundation for studying both localization accuracy and rationale quality across heterogeneous medical imaging modalities. The code is publicly available at https://github.com/MiliLab/LocAnyMed.