Medical Image Classification

State Space Models (SSMs), particularly VMamba, have emerged as efficient alternatives for modeling long-range dependencies in medical image analysis. However, distinguishing subtle pathological features from visually similar anatomical backgrounds remains a significant challenge. Existing SSM architectures often learn entangled representations, lacking explicit mechanisms to separate disease-specific signals from normal anatomy. To address this limitation, we propose Spatial-Contextual Differential Mamba (SCDM), an asymmetric dual-branch architecture designed for selective representational disentanglement. SCDM introduces a Positive Branch for extracting discriminative features and a Negative Branch that actively models and suppresses normal anatomical context. This separation is achieved through a similarity-driven repulsion gate and a differential inference rule, which promote competitive feature learning without requiring additional branch labels or increasing model capacity. Evaluated on the RSNA Pneumonia dataset, SCDM achieves competitive classification performance (AUC of 0.858) while requiring significantly fewer parameters (29.4M) and FLOPs (1.44G) compared to standard VMamba and vision transformer baselines. Furthermore, activation analyses demonstrate that our differential mechanism yields highly precise localization, effectively isolating lesions by inhibiting irrelevant anatomical distractors.

Out-of-distribution (OOD) detection is crucial for safe deployment of medical AI systems, where domain shifts arise across institutions, acquisition protocols, and patient populations. VLMs enable zero-shot OOD detection by embedding images into a language-aligned latent space, where cross-modal similarity serves as a non-parametric confidence signal for identifying in-distribution samples. Yet existing methods rely almost exclusively on final-layer embeddings, implicitly assuming that the deepest representations are universally optimal. We first show that this assumption does not hold in medical imaging: intermediate layers provide complementary OOD signals, and the optimal representational depth depends on the respective image modality. While prior work selects layer combinations via entropy minimization of normalized histograms, we demonstrate that single-resolution entropy estimation is highly sensitive to binning choices, leading to performance variations of up to 19.3% AUROC. To address this instability, we propose a multi-resolution entropy estimation strategy that aggregates histogram statistics across multiple discretization scales, enabling robust and stable intermediate-layer selection. Across two medical OOD benchmarks, namely MIDOG and OASIS, covering distinct imaging modalities, diverse shift types, and different VLM backbones, our method consistently outperforms state-of-the-art approaches, offering a lightweight and stable solution for zero-shot OOD detection.

Thoracic pathologies rarely occur in isolation, yet standard multi-label classifiers rely on shared global descriptors, discarding \emph{where} findings lie and \emph{how} they co-occur. We propose \textbf{C$\mathbf{^2}$A} (Co-occurrence Aware Class Attention), a classification head that explicitly couples spatial evidence with clinical priors. First, C$^2$A casts pooling as an expectation over learned per-class spatial attention maps, yielding localized descriptors for each disease. Second, it couples these descriptors via a learnable graph warm-started from empirical label co-occurrence. A single residual message-passing step shares evidence among related findings, proving to be a bounded perturbation of the identity where co-occurrence enters each logit through an explicit bilinear interaction. On CheXpert, C$^2$A achieves a superior $0.895$ macro-mean AUROC, outperforming advanced context-gating baselines. Crucially, gains concentrate on highly co-occurrent classes with ambiguous spatial evidence (rescuing Atelectasis by $+1.5$ over GCG), demonstrating the prior's regularizing effect with a negligible overhead of one linear projection and a $C\!\times\!C$ edge matrix.

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.

Active learning (AL) promises to reduce the cost of medical imaging projects by lowering the number of clinical labels required. However, practical deployment requires committing to a sampling strategy before the full annotation budget is spent, and choosing the wrong strategy can increase rather than decrease costs. We propose Active-Learning Deployment Advisor (ALDA), a deployment-oriented framework for AL method selection under clinical performance constraints. Given a short pilot phase, ALDA fits a parametric learning-curve model to each candidate strategy, estimates whether that strategy is expected to reach a required clinical performance target, and predicts the number of expert annotations needed to do so. In addition to absolute annotation cost, ALDA introduces a deployment window that quantifies the sensitivity of this cost estimate to uncertainty in the clinical threshold. The final recommendation follows a risk-aware rule: among strategies with near-optimal predicted cost, ALDA prefers the strategy with the narrowest deployment window, the most robust to threshold revisions. Experiments on four medical imaging classification domains show that ALDA predicts the deployment-optimal method from a pilot of 15-30% of the intended budget and reduces annotation costs by up to 82% compared with a poor strategy choice. Rather than introducing a new sampling heuristic, ALDA provides a practical decision layer that answers a deployment-critical question: how many labels are enough?

Medical image classification often suffers from class imbalance due to the inherent disparities in disease incidence. Existing approaches, such as class resampling and loss reweighting, mainly improve learning within the observed feature distribution, but do not explicitly enlarge the latent support region of tail classes. As a result, tail-class representations remain overly compact and are easily encroached upon by head classes, leading to biased decision boundaries. In this work, we propose Recurrent Contrastive Learning (RCL) for imbalanced medical image classification. RCL progressively expands the support region of tail classes by recurrently reusing historical feature states across training phases. Specifically, we adopt DINOv3 with LoRA adapters as the backbone to provide robust feature embeddings. We then devise a Temporal Memory Queue (TMQ) to preserve corpus-level features across training phases and provide diversified global references for contrastive learning. Based on TMQ, we construct Temporal Anchors (TARs) to form an anchor field around tail classes. This field enlarges the support region of tail classes, suppresses head-class encroachment, and improves inter-class separation. Extensive experiments on three imbalanced medical datasets demonstrate that RCL achieves consistent improvements over strong baselines. The code is available at https://github.com/dndins/RCL.

Adapting deep learning models to profound clinical heterogeneity typically relies on parameter-efficient fine-tuning (PEFT) to avoid the severe overfitting associated with full end-to-end network updates. Although PEFT successfully navigates limited data scenarios, it inherently forces the training of a separate, isolated adapter for every specific diagnostic task. Consolidating these isolated adapters into a single generalist network risks negative transfer, as optimization gradients from conflicting visual domains interfere. To address this, we propose MoPET, a mixture-of-experts (MoE) method that uses a learned sparse router to direct each input through a small subset of low-rank PEFT experts injected into a frozen foundation model, sharing capacity across datasets while limiting cross-domain gradient conflict. Through selected evaluations on the MedMNIST benchmark, we first establish that PEFT outperforms full network updates, improving average accuracy from 86.50% to 88.97%. We then show that a single MoPET model consolidates four heterogeneous datasets into one network, improving average accuracy over the best isolated PEFT adapters (93.46% versus 92.83%). Finally, we show that co-training with auxiliary datasets improves accuracy on data-constrained clinical targets, raising average target accuracy over the strongest isolated adapter from 81.58% to 83.58%. Our source code is publicly available at https://github.com/sdoerrich97/mopet.

Classifying pathological scars from clinical photographs requires distinguishing keloids from hypertrophic scars despite limited expert-labeled data and substantial acquisition variation across hospitals. End-to-end image models remain data-dependent, whereas sending photographs to a hosted vision-language model (VLM) may conflict with local data-governance requirements and yields decisions that are difficult to reproduce and audit. We introduce ScaFE (Scar Feature Engineering), which transfers clinical knowledge from a large language model (LLM) into deterministic, executable feature programs instead of asking the model to diagnose images. A web-enabled LLM retrieves clinical evidence and synthesizes programs that measure visually assessable scar attributes. Candidate programs execute in a restricted local environment, and only aggregate validation statistics and feature-level SHAP summaries are returned for iterative repair and refinement; raw images and patient-level outputs remain local. A lightweight Random Forest then operates on the resulting structured representation. On 600 photographs from three hospitals under leave-one-site-out evaluation, ScaFE achieves 81.0% site-macro balanced accuracy, exceeding the strongest baseline, BiomedCLIP, by 10.0 percentage points. With only 10% of the development data, ScaFE retains 72.0% balanced accuracy and an 11.8-point lead. Iterative refinement also raises the executable-program rate from 66.7% to 95.0%, with verified evidence for 91.7% of the final features. These results show that LLM knowledge can support data-efficient, cross-site medical image classification through local and auditable feature programs rather than direct VLM decisions.

Deep learning has shown promise for automated tongue diagnosis in traditional Chinese medicine (TCM), yet the design space remains underexplored. We conducted a systematic ablation study spanning 20+ model versions under rigorous 5-fold cross-validation on TongueDx2 (5,109 images, 976 expert-annotated) and a merged dataset of 11,101 samples. We compared six backbone architectures, four loss functions, five augmentation strategies, and six training strategies. The best 976-sample model achieved weighted-F1 of 0.6625 using ConvNeXt-Tiny with restrained augmentation and weak-group ensemble, while the best 11,101-sample model reached weighted-F1 of 0.7761. Six key design principles emerged: (1) ConvNeXt-Tiny offers optimal parameter efficiency; (2) BCE substantially outperforms Asymmetric Loss (+2.7%); (3) restrained color augmentation is critical; (4) weak-group ensemble replacement (+2.1%) outperforms probability averaging; (5) data scaling yielded +20.6% improvement; (6) expanding from 13 to 45 label dimensions caused catastrophic collapse (0.78 to 0.22). These principles are generalizable to multi-label medical image classification with class imbalance.

Deep learning has shown strong potential in medical image analysis, but most existing methods rely on large-scale annotations and a closed-world assumption that rarely holds in clinical practice. Although Generalized Category Discovery (GCD) has advanced rapidly on natural images, it remains underexplored in medical imaging. To address this issue, we propose MedXplore, a unified framework for reliable and unbiased medical GCD, optimizing from both perceptual and decision levels. Specifically, at the perceptual level, taking a frequency domain perspective, Frequency-SNR Adaptive Attention and Consistency (FAAC) performs learnable full-spectrum filtering and global-local energy contrast activation to not only highlight local abnormal signals relative to the global context, but also provide reliable semantic anchors for patch consistency learning. At the decision level, Adaptive Cosine-Angular Margin (ACAM) adjusts angular margins using semantic difficulty and feature confidence to balance intra-class compactness and inter-class separability. Together, the two modules improve lesion-sensitive representation learning and mitigate old-class bias. Experiments on multiple benchmarks show an average \textbf{8.5%} gain in \textit{All} accuracy over the strongest competing methods. On Kvasir, MedXplore reduces false-old errors from 14.50% to 0.80%, demonstrating strong robustness under severe old-new ambiguity.

Cross-modal knowledge distillation can transfer diagnostic knowledge from a strong but costly teacher modality to a cheaper and more deployable student modality. In medical image analysis, however, the two modalities are often unpaired: they are collected from different patient cohorts and occupy geometrically incompatible feature spaces. This makes instance-level distillation invalid and direct feature matching unreliable. To address these challenges, we propose Shared Semantic Codebook Distillation (SSCD), which compares teacher and student representations through a shared discrete codebook. Each image is represented as a distribution over a common, modality-agnostic vocabulary, and knowledge is transferred by aligning these distributions across modalities, both globally and class-conditionally, without requiring paired samples or directly comparable raw features. The codebook is evolved online by exponential moving average and kept diverse through entropy regularization and dead-code restart. At inference, all teacher-side and codebook modules are discarded, leaving only the student encoder and classifier. On two heterogeneous unpaired settings, OCT-to-fundus retinal disease classification and CT-to-chest-X-ray pneumonia classification, SSCD improves the student from 64.5 to 70.2 macro-F1 and from 73.8 to 76.3 macro-F1, respectively, outperforming all evaluated distillation baselines on both settings. Code and pretrained models are available at https://github.com/DillanImans/SSCD-unpaired-distillation

Background/Objectives: Dermoscopic skin-lesion classifiers lose accuracy when images arrive from a new clinic or a new device. We asked which data augmentations reduce that loss, and measured the effect under a protocol that keeps policy selection separate from policy evaluation. Methods: A ConvNeXt-Large binary malignant-versus-non-malignant classifier was trained on six dermoscopic sources (25,903 images); HAM10000 and ISIC 2016-2020 were held out of training entirely. Single augmentations, photometric combinations and eleven composite policies were ranked on a development split of 1511 held-out images. The winning policy was then evaluated on a confirmation set of 8073 held-out images that took no part in that ranking and from which we removed every image sharing a lesion identifier with the training data and every image contributed by an institution represented in training. Both policies were retrained with four random seeds each and compared with an exact permutation test. Results: The mix policy raised confirmation-set ROC-AUC from 0.787 to 0.826 (+0.039; per-seed ranges 0.772-0.797 and 0.815-0.840, non-overlapping; exact permutation p=0.029), with the same direction on each contributing source. At matched sensitivity the gain is larger in clinical terms: specificity rose from 0.612 to 0.713 at a sensitivity of 0.80, and from 0.284 to 0.397 at a sensitivity of 0.95. In-domain ROC-AUC was preserved (0.938 to 0.941). On an independent clinical cohort acquired with a different device at a different institution (472 images, 22 malignant), performance was maintained (0.934 versus 0.930). Conclusions: Augmentations that model the physical causes of domain shift improve cross-source transfer at no cost to in-domain accuracy, and the improvement survives a selection-disjoint, contamination-free evaluation.

Variational quantum algorithms often encounter barren plateaus, where cost gradients decay rapidly with increasing circuit depth, undermining the trainability of parameterized quantum circuits. This paper evaluates AdaInit (Adaptive Initialization), proposed by Zhuang and Cunningham, which uses large language models to propose initial parameters for quantum neural networks. We study a simplified single-query AdaInit variant paired with GPU-accelerated simulation in NVIDIA CUDA-Q and apply it to binary classification on the DMR-IR mammography dataset. AdaInit delivers 14.6 times higher gradient variance at initialization than random initialization (0.0095 vs. 0.0006), producing 160 times faster convergence (1.1s vs. 176 s) while maintaining the same classification accuracy of 61.4 percent. We provide theoretical analysis grounded in the geometry of parameterized circuit landscapes and show empirically that LLM-guided initialization places the optimizer in trainable regions of parameter space. Beyond performance, our results indicate that a single LLM query can yield informative parameters without iterative refinement, suggesting a low-overhead path to improved trainability. The findings validate AdaInit in a medical imaging setting and demonstrate its compatibility with GPU-accelerated quantum backends for practical speedups.

In this paper, we examine the difficulties of using standard techniques for medical image classification due to long-tailed distributions (wherein rarer conditions have very few samples) resulting in bias towards diagnosing common diseases and away from rarer diseases. We then discuss and implement deep learning models with techniques such as augmentation to minimize error, especially from rarer diseases. We evaluate various different models with AP, F1 score, AUROC, and loss (all on the validation set). We conclude with the promising results from our best model, and potential applications in the healthcare space.

Numerous studies have analyzed the use of hybrid quantum-classical convolutional neural networks as a promising alternative to classical deep learning. However, network components on quantum hardware impose fundamental limitations, while the scalability of quantum circuits leads to trainability issues. In this work, we investigate whether small, classically-emulated quantum circuit components can play a meaningful role within complex models, offering an alternative to purely classical convolutional architectures. To this end, we present a systematic study of the effectiveness of a Hybrid Quantum-inspired Convolutional Neural Network (HQiCNN) compared with a parameter-matched classical Convolutional Neural Network (CNN) that differs only in an intermediate dense neural layer. Both models are evaluated on two real-world medical datasets while systematically varying the different hyperparameters, ensuring a fair model comparison that is both dataset and hyperparameter independent. The results show that no architecture consistently dominates the other: the HQiCNN achieves its largest gains in intermediate-data regimes, whereas the CNN reaches the highest accuracies for the largest training sets in both datasets. Furthermore, removing entanglement produces comparable performance while enabling substantially better scalability of quantum simulations, and richer observable sets become beneficial only when sufficient training data are available. Finally, we propose two SHAP-based explainability tools for comparing the predictions between both models, $|SHAP|$IoU and $EMD_{pos}$ metric, to demonstrate that both architectures consistently attend to anatomically plausible regions. Thus, we provide a comprehensive benchmark showing that, under certain conditions, hybrid quantum-inspired models are an alternative that can offer benefits in practical tasks such as medical image classification.

Automated detection of vision impairing retina-based ocular conditions from fundus images is important for early screening, timely referral and reducing dependency on specialist-only assessment, for which neural network-based deep learning (DL) models have been widely utilized. However, explainability of the DL frameworks remains a major bottleneck for clinical adoption, particularly when model decisions are not linked to retinal regions that are clinically meaningful. To address this issue, this study presents CounterFundus, a novel CycleGAN-driven counterfactual explainability framework, integrating EfficientNet-B5-based retinal disease detection with visually interpretable disease-to-normal fundus image translation. For each pathological image, the counterfactual yielded by the CycleGAN generator represents an estimated healthy counterpart and the resultant difference map is utilized to localize disease-associated retinal changes. Unlike conventional post-hoc saliency methods, CounterFundus provides counterfactual explanations through visually plausible disease-to-normal retinal translation. Thereafter, to quantify the spatial agreement between counterfactual difference maps and classifier saliency, the Counterfactual-Classifier Alignment Score (CCAS) is introduced, embedding Spearman correlation, binary IoU and pointing accuracy into a single assessment protocol. To this end, EigenCAM-aligned evaluation demonstrates that the generated counterfactual explanations remain spatially consistent with classifier-relevant retinal evidence across all CCAS dimensions. Along with that, ablation studies further confirm that CCAS-filtered counterfactual augmentation improves the downstream classification performance in fundus images, establishing CounterFundus as a clinically-grounded, explainable artificially intelligence (XAI) framework for retinal disease detection.

Federated learning (FL) enables multiple clinical institutions to collaboratively train a shared disease classifier without centralizing patient data. In practice, however, each institution annotates only the pathologies within its area of expertise, so the federation operates under task heterogeneity: each client holds labels for a strict subset of the target disease categories while the remaining classes are entirely unobserved at that site. Existing gradient-based FL methods fail under this setting because they require hundreds of communication rounds to converge and because missing class labels introduce systematic false-negative bias that the model cannot correct without a principled mechanism. We propose an analytic federated learning framework for multi-label medical image classification under task heterogeneity. The proposed method replaces iterative gradient optimization with three closed-form operations: a balanced label projection that neutralizes class-imbalance bias by normalizing positive and negative contributions to equal total mass; a per-class absolute aggregation law that independently assembles the optimal ridge-regression classifier for each disease category from the sufficient statistics uploaded by its annotating clients; and an optional analytic pseudo-label refinement round that propagates missing-class knowledge from a confidence-filtered teacher classifier to non-annotating clients. The entire procedure requires at most two communication rounds, irrespective of the degree of task heterogeneity or the number of participating clients. Experiments on ChestXray14 under four progressively severe missing-class configurations demonstrate that the proposed method consistently outperforms the state-of-the-art federated multi-label method FedMLP by up to 18.44 BACC points and 13.24 AUC points, while reducing the communication.

Lung ultrasound (LUS) is a bedside tool for assessing pulmonary edema in patients at risk due to heart failure or impaired kidney function. However, automated LUS analysis remains challenging because of speckle noise, imaging artifacts, and operator-dependent acquisition variability. In this work, we present a deep learning framework for multi-class LUS video classification that explores two components: hierarchy-aware training, and anatomy-guided learning. Starting from a strong baseline, we introduce hierarchical training strategies and then introduce pleural line mask supervision to guide model attention toward anatomically relevant regions. We study four clinically relevant classes--healthy, B-lines, consolidations, and mixed B-lines with consolidations--using an open-access dataset of 1,886 videos from 219 patients, evaluated with patient-level five-fold cross-validation. Results show that hierarchy-aware training improves pathological separation relative to flat classification, while mask-guided attention supervision achieves the highest mean macro-F1 of 65.7% and produces more localized attention patterns. Transfer experiments on the external COVID-BLUeS dataset further show competitive and parameter-efficient adaptation while preserving pleural-focused attention behavior. These findings suggest that combining clinically structured objectives with anatomy-guided supervision is a practical approach to robust, interpretable LUS video analysis. Code and model implementations are available at https://github.com/Alya-Almsouti/LUS-video-classification.

Per-subgroup fairness audits of medical image classifiers face a sample-size problem: minority subgroups in held-out test sets have so few samples that the resulting confidence intervals on per-subgroup performance are wider than the bias the audit is meant to detect. We argue that a demographically-conditioned synthetic generator can do both: mitigate bias on the training side and detect bias on the evaluation side. Working on COVID-19 chest CT classification with an end-to-end fine-tuned Stable Diffusion 2.1 generator, we make two findings. For bias mitigation (training), a demographically-balanced synthetic cohort is most useful as a pretraining prior, not as joint augmentation: with the same fixed data, sequential pretraining followed by fine-tuning substantially outperforms joint augmentation, and the resulting classifier surpasses the full-real baseline at \sim$$100\times real-data efficiency. For bias detection (evaluation), across five synthetic minority cohorts and five classifier seeds, the synthetic estimator reproduces the subgroup ranking of a well-powered real oracle (Spearman $ρ= 1.00$ on MCC and Recall) and gives the more reliable per-cell estimate where the small real test set runs out of samples. The synthetic cohort is therefore most useful in exactly the cells that fairness audits care about, as both a fix for and a measure of subgroup bias.

Deploying medical visual question answering (MedVQA) systems in real-world clinical settings requires models that adapt to new clinical tasks without forgetting previously acquired knowledge. Continual learning (CL) provides a practical framework for this setting. Despite rapid progress in medical vision-language models, the behavior of CL methods when training these models across heterogeneous MedVQA tasks remains underexplored. This work presents a systematic evaluation of CL for MedVQA across diverse clinical objectives, including classification, multi-label classification, detection, cell counting, and report generation. Specifically, we explore (1) the ability of existing CL methods to mitigate catastrophic forgetting; (2) their sensitivity to task ordering, analyzing how different task sequences influence performance retention and forgetting; and (3) the evolution of low-rank adaptation parameters as new tasks are learned, revealing patterns of weight drift under different CL methods. Our findings suggest that existing CL methods struggle to maintain stability-plasticity balance when tasks with different objectives and supervision formats are interleaved. Code and full experimental setup will be publicly available.

Medical image classification models are ideally expected to identify diagnostically relevant regions while making predictions, yet standard classification losses rarely provide spatial supervision. Explicit supervision via anatomical shape information, such as segmentation masks of task-relevant anatomy, has been shown to guide the network toward regions relevant to the target prediction. However, obtaining such masks incurs substantial manual annotation effort and computational overhead. With the advent of segmentation foundation models that exhibit strong localization of anatomical structures across diverse imaging modalities, we leverage this capability to extract anatomical shape priors without the burden of training a dedicated segmentation model. In this paper, we propose a new framework, Locus, an anatomical attention regularization framework that leverages pretrained segmentation foundation models to guide a classifier's attention toward diagnostically meaningful anatomical structures across diverse imaging modalities. Instead of enforcing pixel-wise alignment with the foundation-model-derived mask, we introduce a regularization term that adaptively balances attention between anatomical (foreground) and background regions, penalizing the classifier when background attention dominates. We validate Locus on eight diverse medical imaging datasets spanning dermoscopy, X-ray, histopathology, and cardiac MRI, showing consistent gains in classification performance alongside improved anatomically grounded attention.

Medical image classifiers are often trained within one source population, yet clinical deployment requires robustness to patients whose appearance, acquisition style, and disease prevalence differ from the source cohort. Existing fairness and robustness methods often require group supervision or treat appearance variation as an undifferentiated nuisance, which is insufficient when population-correlated low-level cues and lesion evidence share edge and texture structure. We study a strict source-only cross-population setting, where external populations are unseen during optimization, validation, scheduling, hyperparameter and model selection. We propose RED-Sphere, a plug-and-play robustness framework for image classification under unseen population shifts. It estimates shortcut-sensitive nuisance responses with an edge and feature energy prior, attenuates dominant responses through residual soft gating, regularizes masked nuisance views with counterfactual-inspired consistency and separation losses, and predicts labels with normalized spherical prototypes. It favours angular semantic evidence over source-correlated activation magnitude while preserving lesion structure. Although demonstrated on 2D Scanning Laser Ophthalmoscopy (SLO) fundus classification for Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR), RED-Sphere is not tied to retinal anatomy: the same principle can be adapted with modality-specific nuisance priors wherever appearance shortcuts and semantic evidence are entangled. Under a strict White-only Harvard-FairVision protocol, RED-Sphere improves held-out macro-F1 across all 20 task and backbone comparisons, with average gains of 1.28 and 2.98 F1 points on AMD and DR. Gains in AUC and PR-AUC, visual diagnostics, ablations, and sensitivity analyses further support stronger external semantic alignment and more stable angular disease geometry.

Deep models for retinal optical coherence tomography (OCT) classification report high accuracy but rarely report whether their confidence can be trusted -- a gap that matters when a wrong-but-confident reading delays sight-saving treatment. We pair a hybrid convolutional-Transformer encoder with a gradient-boosting (XGBoost) classification head and a three-part clinical safety layer: confidence calibration, out-of-distribution (OOD) rejection, and per-prediction uncertainty flagging. On four-class OCT (84,495 scans) the model reaches 95.4% accuracy while cutting calibration error twelve-fold (expected calibration error, ECE = 0.0024), so the confidence it reports tracks its true accuracy. To our knowledge this is the first OCT classifier to validate all three safety mechanisms jointly, with public weights and reproducible multi-seed evaluation.

Cloud-based deep learning enables large-scale medical image analysis but raises significant privacy concerns when sensitive patient images are outsourced for model development. Image disguising has recently emerged as a promising privacy-enhancing technology (PET) that transforms images into visually unintelligible representations while preserving information for downstream learning. We established a unified framework to evaluate representative methods, DisguisedNets and NeuraCrypt, across four datasets involving classification and semantic segmentation tasks. Our analysis assessed predictive utility, efficiency, and robustness against reconstruction attacks. Results showed that image disguising performance varies significantly between tasks; while methods preserved utility for medical image classification, they caused substantial degradation in dense semantic segmentation. Specifically, Randomized Multidimensional Transformation (RMT) offered the optimal balance of performance and security, whereas AES-based disguising severely impacted utility. Furthermore, regression-based reconstruction attacks effective on natural images proved considerably less successful on realistic medical images. These findings provide a systematic assessment of PET suitability for confidential medical AI applications.

Existing deep learning methods perform well in medical image classification but struggle with multi-scale morphology and limited annotations due to fixed sampling and data-hungry training. Existing approaches address these challenges in isolation: DCN-based models provide adaptive sampling but lack explicit multi-scale attention fusion and label-efficient regularisation; multi-scale architectures typically rely on static fusion; and semi-supervised methods target label scarcity without jointly modelling adaptive cross-scale representations. We propose MSA-DCNN, a scale-consistent deformable attention learning framework that introduces adaptive multi-scale sampling, within-scale saliency refinement, learned cross-scale fusion, and auxiliary self-distillation within a unified optimisation scheme, with potential to generalise to structurally heterogeneous anatomy. We evaluate on three public benchmarks and an external hold-out set for leukaemia. MSA-DCNN demonstrates competitive and often better performance against ViT baselines, CNN baselines, and a MICCAI semi-supervised baseline under distribution shift and label scarcity in accuracy, F1, and AUC (binary), while using fewer parameters. Ablations confirm complementary component contributions, supporting MSA-DCNN as a practical foundation for data-efficient medical image classification.

Accurate and efficient classification of thoracic diseases in chest X-ray (CXR) images is crucial for timely diagnosis and treatment. However, the presence of multiple pathologies with overlapping visual characteristics poses significant challenges for automated classification systems. In this study, we propose two novel hierarchical multi-label classification techniques, namely the loss-based and logit-based methods, to address these challenges by leveraging the hierarchical relationships among different thoracic pathologies. The loss-based technique integrates hierarchical information directly into the optimization process, while the logit-based method adjusts the predicted probabilities of each class based on its parent class in the disease taxonomy. We evaluate the performance of both techniques using three large-scale CXR datasets: CheXpert (224,316 CXRs), PADCHEST (160,000 CXRs), and NIH (112,120 CXRs). The experimental results demonstrate significant improvements in accuracy, AUC, and F1 scores compared to the baseline method across various pathologies. The logit-based and loss-based methods improve accuracy by 12% and 11%, AUC by 13% and 10%, and F1 scores by 24% and 12%, respectively compared to the baseline. These results represent a substantial improvement over the baseline method. Furthermore, we conduct a comprehensive statistical analysis to validate the robustness and reliability of the proposed techniques. The integration of domain-specific hierarchical knowledge not only enhances the classification performance but also provides a more interpretable output for clinical decision support. Our findings highlight the potential of hierarchical multi-label classification in advancing computer-aided diagnosis systems for chest radiography.

Automated chest X-ray classification remains challenging due to severe class imbalance, co-occurring pathologies, and the loss of localized features in conventional architectures. To address these, we propose an explainable hierarchical multi-view ensemble framework for the robust classification of 14 thoracic pathologies. The framework employs view-specific training by independently modeling frontal and lateral radiographs using an ensemble of five complementary convolutional neural networks. Replacing global average pooling, a multi-scale feature fusion strategy augmented with Convolutional Block Attention Modules (CBAM) preserves fine-grained intermediate representations while emphasizing high-level pathology-specific semantic features. To mitigate positive-negative imbalance and varying inter-class difficulty, models are optimized using a novel hybrid objective combining Asymmetric Loss with Adaptive Focal Loss. Beyond simple probability averaging, the framework incorporates a hierarchical meta-learning strategy where test-time augmentation (TTA) predictions and cross-model uncertainty measures are integrated into Level-1 gradient-boosting meta-learners (XGBoost, LightGBM, and CatBoost), followed by Level-2 stacking with optimized alpha blending. Evaluated on a large-scale CheXpert-style dataset, the framework achieves state-of-the-art macro-average AUROC scores of 0.9319 for frontal and 0.9154 for lateral radiographs. Furthermore, comprehensive explainability analysis using seven post-hoc attribution techniques demonstrates strong anatomical consistency and clinically meaningful decision localization. By integrating architectural diversity, multi-scale attention, hierarchical meta-learning, and rigorous explainability, the proposed framework provides a transparent, highly accurate, and clinically practical computer-aided diagnosis system for thoracic disease classification.

Deep learning (DL) has shown strong performance in medical image classification, but its trustworthy deployment remains challenging in safety-critical clinical settings, where prediction errors under perturbations may lead to severe consequences. Existing studies mainly focus on adversarial robustness (AR) from a worst-case perspective; however, such settings may be less representative of real medical applications. In this work, we investigate probabilistic robustness (PR) as a more practical measure of model trustworthiness. To this end, we construct a set of natural corruption settings for medical image classification and systematically evaluate commonly used DL models on MedMNIST v2 dataset. Our study provides a statistically grounded perspective on assessing the trustworthiness of DL models, thereby supporting their more trustworthy deployment in medical imaging applications.

Medical imaging models often degrade when deployed at new clinical sites due to differences in imaging equipment, protocols, and patient populations. Test-time adaptation (TTA) addresses this by updating a pretrained model using only unlabeled target data, without access to source data. However, existing TTA methods were designed for single-label classification on natural image benchmarks, minimizing entropy uniformly across all samples without considering label dependencies. This overlooks a key property of multi-label medical imaging: pathologies do not occur independently but exhibit structured co-occurrence patterns. In this work, we propose Co-occurrence Weighted Adaptation (CoWA), which leverages disease co-occurrence patterns as a reliability signal for adaptation. CoWA estimates label co-occurrence structure from model predictions and downweights samples that deviate from expected patterns, enabling adaptation to rely more on consistent predictions while reducing the impact of noisy ones. We evaluate CoWA on chest X-ray benchmarks under domain shifts and demonstrate consistent improvements over established baselines.

Ultrasound image classification is essential for computer-aided diagnosis. However, current methods often neglect clinical priors, leading to poor generalization in challenging scenarios and a lack of interpretability that limits clinical adoption. To address these issues, we aim to develop a medical-prior module that can be seamlessly integrated into existing pipelines to enhance both diagnostic performance and interpretability. In this paper, we propose an attribute-guided dual-branch framework for ultrasound classification that introduces domain-agnostic medical attribute priors, improving generalization while offering interpretable evidence. Specifically, a baseline branch follows conventional architectures and predicts image categories via a fully connected classifier. An attribute-guided branch injects domain-agnostic attributes as priors and produces human-interpretable decision cues. Finally, an adaptive decision module fuses the two branches in a data-dependent manner to yield the final prediction. Experiments across diverse ultrasound classification tasks demonstrate that our approach can be integrated into multiple backbones and state-of-the-art methods with low overhead, consistently improving accuracy and interpretability. Code is available at: https://github.com/zhaobo253-crypto/AttrGuide.

High resolution medical images contain fine grained, spatially sparse cues that are critical for diagnosis, yet preserving full resolution incurs substantial computational and memory costs. Most deep models process images uniformly, leading to redundant computation or loss of diagnostic detail under downsampling. We propose Chained Perceptual Refinement, CPR, a coarse to fine framework that formulates medical image analysis as a sequential global to local decision process. Starting from a low resolution global view, CPR dynamically predicts the location and spatial extent of refinement regions, extracts high resolution evidence from the original image, and incrementally integrates it with global context. By keeping the backbone input size fixed while contracting the perceptual field, CPR preserves diagnostic fidelity with constant peak GPU memory. Extensive experiments on five medical imaging datasets and multiple backbone architectures demonstrate that CPR consistently outperforms both fixed resolution and multi scale state of the art baselines, achieving improvements of up to 2.27 percentage points over the second best method. It also achieves up to a 19.6 fold reduction in GFLOPs at matched accuracy, establishing a superior accuracy and efficiency trade off for high resolution medical image analysis. The code is available on GitHub.

Prototype-based medical image classifiers present three clinical limitations: they treat findings as independent, silently amplify unsafe physician feedback, and require full retraining whenever a new finding is needed. We present GRAPE (Graph-Augmented Prototype Explanations), a unified architecture that addresses all three challenges. First, a Graph Attention Task Head models anatomical concept co-occurrence, boosting macro-F1 by +13.8,pp over the prototype baseline on TBX11K. Second, a Concept-Mismatch Safety Check - the first such mechanism in prototype-based medical classifiers - warns when the model's dominant finding inside a doctor-drawn region conflicts with the claimed label, catching 85% of erroneous annotations versus 51% for MC-Dropout with no extra inference cost. Third, Open-Vocabulary Prototype Anchoring aligns visual prototypes to clinical text, allowing a new finding to be added from a single labeled image without modifying any other component. On NIH ChestX-ray14, one Effusion example recovers full-supervision localization accuracy; on TBX11K, prototype maps achieve 2.6x better lesion localization than end-to-end baselines. All three capabilities add only +1~ms latency at interactive batch size. The project page is https://github.com/KurbanIntelligenceLab/GRAPE.

Neurological disorders involve diverse pathologies of the brain and nervous system, making early and accurate detection essential. While many deep CNNs have been developed for MRI-based classification of neurological disorders, most are optimized for binary tasks and often fail to capture the multi-class features needed to distinguish subtle anatomical differences across conditions. This study proposes the Enhanced Neurological Disorder Detection Network (End-Net) for multi-class MRI classification of neurological disorders. End-Net includes 24 convolutional layers, beginning with convolutional blocks followed by 21 optimized inception modules. These modules extract multiscale features via parallel 1 x 1, 3 x 3, and factorized 5 x 5 convolutional branches, along with max pooling, enabling the model to capture complementary texture, edge, shape, and contextual information. A global average pooling head, compact fully connected classifier, and dropout reduce parameters, limit overfitting, and improve robustness. End-Net was evaluated on the Multi-Class Neurological Disorder dataset, comprising MRI scans from patients with Alzheimer's disease, brain tumors, multiple sclerosis, and healthy controls. Severe class imbalance was addressed by augmenting minority classes with WGAN-GP and randomly undersampling the majority class. The results show that End-Net outperforms existing architectures in both accuracy and generalization. The model is also integrated into an online system for real-time web-based inference and accessibility.

Jointly learning to segment and classify medical images demands cross-task synergy, yet encoder-sharing architectures limit decoder reconstruction to task-private representations, permanently discarding the boundary cues and semantic priors each branch could supply to the other. This work introduces BTI-Net, which establishes bidirectional communication at every decoder level through two parallel pathways via Task Interaction Modules (TIM). Spatial boundary context is gated into the classification branch, while global semantic priors multiplicatively modulate the decoder, with refined features propagating progressively from coarse semantics to fine boundary detail across all four decoder resolutions. Since cross-task interaction is not equally reliable for every input, Uncertainty Proxy Attention (UPA) gates each TIM output per instance and per level using three signals that capture cross-task alignment, scene complexity, and prediction confidence, without external annotations or additional inference passes. Experiments on three medical benchmarks spanning ultrasound, dermoscopy, and brain MRI demonstrate consistent improvements in segmentation IoU and classification accuracy over both encoder-sharing and decoder-interaction baselines. Ablation confirms adaptive gating contributes +2.36 IoU over fixed bidirectional interaction, and classification accuracy improves by up to +2.26 points over the strongest multi-task baseline. UPA's uncertainty proxies serve as reliable single-pass task-failure signals without the overhead of stochastic sampling. Code: https://github.com/C-loud-Nine/BTI-Net_MTL

Limited data availability, class imbalance, and domain variability remain major barriers to reliable medical image classification. Conventional augmentation can improve training diversity but may distort diagnostically informative structures, whereas unconstrained generative augmentation may introduce label-inconsistent content. This paper proposes MedDiffuseMix, a saliency-guided diffusion mixing framework for controlled medical image augmentation. The method uses classifier-derived saliency maps to separate high-saliency diagnostic regions from low-saliency background areas and applies diffusion-guided mixing mainly to regions with lower diagnostic importance. Adaptive mixing, Gaussian boundary blending, and a saliency-preservation constraint reduce semantic distortion and reject or attenuate samples that shift model attention away from clinically relevant evidence. The framework is evaluated on four public benchmarks: the Radiological Society of North America pneumonia chest radiography dataset, Musculoskeletal Radiographs, PatchCamelyon, and the Breast Cancer Histopathological Image Classification dataset. Experiments with convolutional and transformer-based classifiers show that MedDiffuseMix improves accuracy, F1-score, and area under the receiver operating characteristic curve compared with standard augmentation, Mixup, GenMix, SaliencyMix, and diffusion-based augmentation baselines. Ablation studies confirm the importance of saliency guidance, adaptive region mixing, and smooth boundary blending. Visual attribution analysis further indicates that MedDiffuseMix better preserves diagnostically salient regions. These results suggest that saliency-guided diffusion mixing is an effective augmentation strategy for limited-data medical image classification.

Training medical image classifiers on entire datasets is wasteful when annotation budgets are limited: not all samples contribute equally, yet acquiring expert labels is expensive. Active learning reduces annotation cost through iterative querying, but assumes repeated access to an oracle and requires multiple rounds of model training. One-shot geometry-based methods such as facility location avoid retraining but operate on pairwise distances that ignore the local structure of the data manifold. We propose a graph-based one-shot selection method that operates entirely on frozen foundation model embeddings. Given embeddings from a pretrained encoder, we construct a k-nearest neighbor graph over all training samples and derive a two-term coverage kernel from the heat diffusion kernel, capturing both direct and two-hop neighborhood relationships. Greedy facility location on this kernel selects class-balanced subsets that maximize coverage of the data manifold. The two-term kernel matches the full spectral heat kernel in selection behavior while reducing computation to sparse matrix operations with a single hyperparameter. We evaluate on five MedMNIST datasets spanning histopathology, radiology, and microscopy, comparing against both training-dynamics and geometry-based baselines. Our method achieves the highest balanced accuracy on nine of ten dataset-ratio conditions, with the largest gains on class-imbalanced datasets where global graph construction captures cross-class structure that per-class methods miss, all without any model training during selection. Code is available at https://github.com/zahiriddin-rustamov/graph-coverage-selection.

Multimodal medical imaging fuses complementary anatomical and functional information, yet modalities frequently disagree in pathologically heterogeneous regions. Current segmentation models handle this in one of two inadequate ways: deterministic fusion that averages away disagreement, or post-hoc uncertainty estimation decoupled from the fusion process that produces it. Both obscure the clinically critical question: why is this prediction unreliable? We present EnTrust, a framework that treats inter-modal conflict as the primary source of predictive uncertainty. Our EnFuse module decomposes multimodal features into three disentangled components: shared anatomical consensus (F_c), modality-specific cues (F_{u,m}), and spatially localized conflict signals (F_{cf}), with independence enforced via a cross-covariance objective. This structured decomposition conditions SegDiff, a diffusion-based generative segmentation model whose sampled hypotheses diverge specifically in regions of modal disagreement. TrustMap then translates this hypothesis divergence into calibrated, pixel-wise uncertainty using ensemble entropy, conflict-guided perturbation probing, and a learned calibration head, enabling clinicians to understand not only where predictions are uncertain, but why. Across four benchmarks spanning brain, cardiac, lesion, and oncology domains, EnTrust achieves state-of-the-art segmentation accuracy while reducing calibration error by 40% compared to the strongest baseline. Notably, it outperforms 5x deep ensembles using a single model at roughly half the memory footprint. Code and checkpoints are available at https://github.com/GenMI-Lab/EnTrust.git.

Inference-time engineering can alter model behavior without fine-tuning. However, its utility for improving diagnostic performance in medical vision-language models (VLMs) remains unclear. We aim to evaluate whether Contrastive Activation Addition (CAA) can improve pneumonia classification in chest radiograph VLMs without updating model weights. Three frozen chest radiograph VLMs (MedGemma-4B-IT, NV-Reason-CXR-3B, and CheXOne-3B) were evaluated on the public Kermany pneumonia test set. Classification was based on the logits of the tokens Yes and No under a binary prompt. Steering vectors included a 30-pair answer-bias control, a 30-pair pneumonia text contrast, and an image-conditioned contrast derived from 30 pneumonia and 30 normal development images. A deterministic 200-image development set was used for layer and scale selection (100 images) and threshold calibration (100 images). Performance was assessed using ROC-AUC, PR-AUC, F1 score, threshold analyses, reverse-vector controls, random-vector controls, and conditional bootstrap confidence intervals. Fixed-threshold F1 improvements were frequently observed but did not consistently indicate improved diagnostic performance. For MedGemma-4B-IT. NV-Reason-CXR-3B showed the strongest benefit: calibrated F1 improved from 0.7692 in the zero-shot setting to 0.8619 with pneumonia-text steering and to 0.8727 with image-conditioned steering. For CheXOne-3B, pneumonia-text steering increased calibrated F1 from 0.8528 to 0.8666, although the confidence interval crossed zero. On this public pneumonia benchmark, CAA substantially altered prediction score distributions and operating characteristics without fine-tuning. Meaningful performance gains were observed in one of three evaluated VLMs, suggesting that activation steering may serve as a lightweight approach for adapting medical VLM behavior.

Multi-view imaging, such as mammography and chest radiography, is a standard component of clinical practice. However, medical images are often unregistered and contain view-specific artifacts or irrelevant background cues that can obscure diagnostically relevant findings. Many existing methods directly fuse per-view representations, allowing such irrelevant content to contaminate the fused embedding and reducing robustness under varying view configurations. We propose OTCHA, a confidence-aware latent hub token alignment module based on optimal transport (OT) that refines patch tokens before fusion for multi-view classification. OTCHA introduces a set of learnable latent hub tokens shared across views. For each view, we compute an OT plan between patch tokens and hub tokens that jointly considers feature similarity and geometry, and augment the OT formulation with token-conditional dustbins to enable partial matching and discard irrelevant tokens. The resulting transport plan provides token-wise matching confidence, which gates hub-mediated message passing and weights a novel optimal-transport-based representation alignment loss to stabilize refinement. Experiments on three multi-view medical image datasets demonstrate consistent improvements over competing baselines across diverse anatomies and view configurations. Our code is available at https://github.com/labhai/OTCHA.

Medical image classification is often constrained by limited labeled data, motivating generative augmentation; recently, quantum generative models have been proposed for this purpose, frequently reporting accuracy gains. However, such claims are typically based on single training runs, do not match the parameter budgets of the quantum and classical generators, and do not characterize the data regime in which any benefit appears. We present a controlled benchmark that isolates the contribution of a quantum generator to brain-MRI augmentation. Images are encoded into a KL-regularized latent space in which a conditional Wasserstein GAN with gradient penalty is trained using either a variational quantum generator or a classical generator of near-identical parameter count (1648 vs. 1632). Synthetic samples are decoded and used to augment a pretrained classifier across labeled data fractions from 5% to 100%, evaluated over eight random seeds with paired significance testing (with multiple-comparison correction) and with intraset diversity and latent-distribution analyses. Across all fractions, no augmentation variant significantly outperforms real-data-only training, and the quantum and classical generators are statistically indistinguishable. Any low-data benefit behaves as regularization rather than faithful data expansion:synthetic samples are off distribution and severely mode collapsed precisely where data is scarce, and the quantum generator is no more diverse thanits classical counterpart. We release the protocol as a testbed for rigorous evaluation of quantum generative augmentation in medical imaging.

We introduce SMART, a framework for learning a flexible, interpretable, and scalable spatio-temporal brain atlas from longitudinal high-resolution 3D medical images. Existing approaches to spatio-temporal atlas construction rely on black-box generative models that lack flexibility, limit interpretability, and struggle to scale to high-dimensional data. SMART addresses these challenges by learning a continuous disease-time atlas that decouples global group-wise disease dynamics from their patient-specific anatomical manifestation. Guided by anatomically inspired priors, SMART models interpretable global trajectories of regional progression along a shared disease timeline through region-specific differential equations. Global trajectories are further personalized to individual anatomies via dense diffeomorphic displacements parameterized by a flexible and scalable multi-scale Neural Cellular Automata. Evaluated on five longitudinal MRI datasets in Alzheimer's disease (ADNI-1/GO/2, OASIS-3, AIBL; > 1,300 subjects), SMART produces anatomically meaningful predictions of disease progression and achieves state-of-the-art forecasting accuracy and improved temporal consistency over adversarial and diffusion baselines. Our approach establishes a new paradigm for flexible, interpretable, and scalable modeling of spatio-temporal change in high-dimensional medical image time-series.

Medical image classification faces a fundamental dilemma: while deep learning models achieve remarkable performance at scale, real-world clinical scenarios often suffer from severe data scarcity due to annotation costs, privacy constraints, and disease rarity. This challenge is particularly pronounced in pathological scar classification, where differentiating keloids from hypertrophic scars requires subtle expert knowledge and labeled images are extremely limited. We propose a novel paradigm that repositions large language models (LLMs) as knowledge-driven feature engineers rather than end-to-end classifiers. We call this framework ScaFE (Scar Feature Engineering). Our key insight is that LLMs encode rich medical knowledge that can be externalized as executable feature extraction code, enabling the transformation of high-dimensional images into low-dimensional, clinically interpretable representations. Specifically, we prompt an LLM with established scar assessment criteria to generate deterministic Python code that extracts features aligned with clinical scoring systems such as the Vancouver Scar Scale. Our approach offers three key advantages: (1) data efficiency, achieving robust performance with limited training samples by decoupling knowledge acquisition from statistical learning; (2) privacy preservation, as raw images are processed locally without exposure to external LLMs; and (3) interpretability, through explicit features grounded in clinical reasoning. Extensive experiments on scar classification demonstrate that our method consistently outperforms end-to-end deep learning baselines or using LLMs as black-box classifiers under limited data conditions, establishing a promising direction for integrating LLMs into data-efficient and clinically transparent medical AI systems.

This study proposes a domain-specific LLM-based Visual Explanation Evaluation Framework for assessing Grad-CAM explanations in facial skin disease diagnosis models. While previous studies have primarily focused on improving classification performance through data augmentation techniques, relatively few studies have systematically examined whether model explanations are grounded in clinically relevant lesion regions. In this study, geometric augmentation, color-based augmentation, and mixed augmentation strategies were applied to facial skin disease classification models based on EfficientNet-B0, MobileNetV3, and ResNet18. Grad-CAM was employed to generate visual explanations representing the models' decision-making processes. Furthermore, an LLM-as-a-Judge evaluation framework was designed using GPT-5.5, Gemini 3.5 Flash, and Claude Sonnet 4.6 to assess Grad-CAM explanations from the perspectives of lesion localization and explanation trustworthiness. To improve evaluation consistency and clinical grounding, a progressive prompt engineering strategy was introduced, incorporating evaluation rubrics, clinical knowledge, penalty rules, and structured output formats.

Deep neural networks have achieved strong performance in medical image classification, but often work like black-box. Commonly used post-hoc interpretation methods often provide heuristic visualizations whose relationship to the classifier's predictive distribution is indirect. This work introduces a local sensitivity analysis framework based on the input-dependent Fisher Information Matrix (iFIM) of a trained classifier. The iFIM characterizes how the classifier's predictive distribution changes under infinitesimal perturbations of the input image. By using a Gram-matrix formulation, the nonzero eigenspectrum of the iFIM can be recovered without explicitly forming the full image-dimensional Fisher matrix. The leading iFIM eigenspace is then used to project an input image into a high local-sensitivity component and its orthogonal component. These components provide a model-intrinsic description of local predictive sensitivity, rather than a conventional pixel-wise attribution heatmap or a causal segmentation of task-relevant anatomy. The framework is evaluated on controlled and clinical medical image classification tasks using multiple classifier architectures. Perturbation-based experiments show that high-sensitivity iFIM components are more strongly coupled to changes in predictive confidence and classification performance than lower-sensitivity complementary components. The results support the iFIM framework as a principled tool for analyzing local decision sensitivity and for complementing existing attribution-based interpretability methods in medical imaging.

Deep neural networks have achieved remarkable performance across medical imaging tasks, yet their tendency to overgeneralize under distributional shifts poses a major obstacle to safe clinical deployment. Out-of-Distribution (OOD) detection methods aim to mitigate this risk, but most existing approaches rely on opaque internal signals with poorly understood semantic meaning, limiting trust in safety-critical settings. In this work, we propose an interpretable OOD detection framework that probes the stability of model predictions under class-conditioned semantic perturbations. Leveraging sparse autoencoders (SAEs), we learn class-specific concept vectors from in-distribution data that disentangle dense intermediate representations into sparse, semantically meaningful components. At inference, we perturb deeper-layer representations using the concept vectors associated with the model's predicted class and measure the class logits stability. We hypothesize that in-distribution samples exhibit low sensitivity to such perturbations, as their representations align with class-specific semantic directions, whereas OOD samples show amplified deviations due to representational misalignment. By framing OOD detection as a concept conditioned stability analysis, our approach provides both a discriminative OOD signal and an interpretable lens into the internal mechanisms driving model uncertainty, making it particularly suitable for high stakes medical applications.

Deep learning has revolutionized medical image analysis, delivering exceptional diagnostic accuracy across diverse applications. Yet, the lack of interpretability in its decision-making hinders clinical adoption, particularly in high-stakes medical contexts where transparency is paramount for trustworthiness. For example, in Placenta Accreta Spectrum (PAS), subtle cues in ultrasound imaging challenge reliable diagnosis, rendering black-box models untrustworthy for accurate scoring. To address this, Concept Bottleneck Models (CBMs) offer a promising avenue by embedding clinically meaningful intermediate concepts into the diagnosis pipeline, enabling clinicians to scrutinize and refine model outputs. However, conventional CBMs falter in capturing complex inter-concept dependencies and demand costly, expert-driven concept annotations, limiting their scalability. This study introduces a novel semi-supervised CBM framework designed for medical imaging, which leverages dual-level hypergraph learning to model high-order concept dependencies and generate domain-adaptive pseudo-labels. Our approach achieves superior interpretability and performance by integrating a concept-level hypergraph for enhanced reasoning and an image-level hypergraph for robust pseudo-label generation. Experiments on a newly annotated PAS ultrasound dataset and a breast ultrasound public dataset demonstrate the effectiveness of the proposed concept label-efficient interpretable framework. Its universality is further validated on the dermoscopic image dataset SkinCon. The code is available at https://github.com/scott-yjyang/HyperCBM.

Medical image analysis models can exhibit performance disparities across patient subgroups, threatening clinical safety and fairness. Existing methods typically address this issue by optimizing accuracy and fairness metrics for visible demographic attributes (e.g., sex or age) considered in isolation. This strategy not only overlooks potentially more informative latent stratifications, which may reveal deeper sources of model error and inequity, but also fails to scale when multiple demographic attributes are considered simultaneously due to the resulting sparsity of training data within each subgroup. We deal with these issues by introducing the label-free hidden-cohort fairness (LHCF) training paradigm that instead of maximizing fairness over visible demographic attributes, it optimizes fairness across latent subpopulations discovered from image appearance. By clustering images into K appearance-based cohorts and applying fairness optimization over them, LHCF uncovers underlying sources of model error and avoids the combinatorial sparsity of multi-demographic attributes, reducing disparities across both single and multiple demographic attributes. We demonstrate on our proposed fairness benchmark, HIDFairBench, that LHCF provides state-of-the-art fairness results on single and multiple demographic attributes, despite never using demographic labels for training. Our results position hidden-cohort fairness as a practical, scalable, and robust alternative to demographic-based fairness optimization for trustworthy medical image analysis.

Self-Supervised Learning (SSL) has emerged as a powerful paradigm to mitigate the reliance on large, annotated datasets, a common bottleneck in medical image analysis. However, standard SSL methods, which rely on simple geometric and color augmentations, may fail to capture the fine-grained, complex textural details necessary for classifying subtle pathologies. This paper introduces Chaos-SSL, a novel two-stage framework for medical image classification. In the first stage, we propose a new self-supervised pre-training strategy that leverages 1D chaotic maps (Logistic, Tent, and Sine) as a complex, non-linear augmentation for contrastive learning. We hypothesize that these chaotic transformations create ``harder'' and more semantically-rich views, forcing a network to learn robust representations of fine-grained medical textures. In the second stage, we introduce an attention-based fusion model that dynamically combines the specialized features from our Chaos-SSL model with the general-purpose features of a larger, ImageNet-pre-trained model. We validate our method on two public datasets: ISIC 2018 (skin lesions) and APTOS 2019 (diabetic retinopathy). Our results demonstrate that the Chaos-SSL model pre-trained with a Tent map for 30 epochs, followed by attention fusion, achieves performance fully competitive with the state-of-the-art, yielding an accuracy of 0.9261 on ISIC 2018 and 0.8726 on APTOS 2019. This significantly outperforms existing SSL methods, including several recent approaches.

In biomedical and neurodegenerative disorders, accurate and early disease identification remains challenging due to the scarcity of labeled data and the complexity of imaging patterns. To address these challenges, we introduce ARMA-C3, a unified unsupervised and semi-supervised graph learning framework for node classification based on contrastive learning and graph-cut regularization to learn structurally meaningful and discriminative representations. By modeling samples or images as graph nodes and exploiting inter-sample relationships, the proposed framework captures subject-level dependencies that conventional machine learning methods typically overlook. We conduct extensive binary classification experiments across five clinically relevant datasets: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Neuroimaging in Frontotemporal Dementia (NIFD) dataset, and three medical imaging benchmarks (BreastMNIST, PneumoniaMNIST, and a liver ultrasound dataset). Experimental results demonstrate that ARMA-C3 achieves competitive and frequently superior performance compared to classical clustering techniques, state-of-the-art machine learning models, and existing graph-based deep learning approaches across multiple evaluation settings, particularly under limited supervision and severe class imbalance. The proposed framework further demonstrates robust representation learning and strong cross-modal generalization across diverse biomedical imaging modalities.

The emergence of machine learning and deep learning has revolutionized the efficiency of diagnostic, therapeutic, and administrative systems in healthcare. However, this rapid adoption has come at the cost of requiring significant computing power and energy consumption, as well as e-waste disposal and carbon emissions. One of the challenges of these models is choosing the right model for classification tasks. To this end, researchers attempt to identify the optimal model using their data through trial and error, which involves energy consumption and waste. The goal of this study is to develop a model-based recommender system for medical image classification. For this purpose, a data set was collected from 3,000 articles in the field of medical image classification. This dataset, publicly available under the name MedicalRec-Bench, contains over 5,000 records of models tested in various tasks, including Skin Cancer Classification, Tumour Classification, Wound Classification, Breast Cancer, and MRI classification. The dataset was evaluated in four different modes, depending on the number of features: MedicalRec I (5 features), MedicalRec II (9 features), MedicalRec III (11 features), and MedicalRec IV (18 features). Collecting all values for the features is challenging due to non-reporting by the authors; hence, the dataset contains significant amounts of missing values. The Medical Recommender System (MedicalRec) is a transformer-based model used for item recommendations in this study. This model achieved remarkable results in the evaluation on the dataset and in the evaluation with 12 base models. This model achieved a maximum HitRate@100 of 75.5%. The dataset and implementations are available through the GitHub link: https://github.com/Ramin1Mousa/MedicalRec

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

Deep learning has brought significant progress to medical image classification, yet most existing methods still rely on isolated visual evidence and cannot effectively leverage similar cases or external knowledge. In clinical practice, diagnosis is typically supported by similar historical cases and their associated symptoms. To explicitly model this evidence-based diagnostic process, we propose a case-aware reasoning framework driven by multimodal knowledge graphs for medical image classification. Specifically, we construct a case-aware multimodal knowledge graph as a structured diagnostic memory, where diseases, images, and symptoms are hierarchically organized. Given an input image, our method adaptively retrieves similar cases from this memory and extracts their corresponding case-centered subgraphs. We further introduce a knowledge propagation and injection mechanism, in which an image-centric Graph Attention Network aggregates heterogeneous semantics into case-based features, followed by a bidirectional cross-modal attention mechanism that injects these features into visual representations for cross-modal alignment. To mitigate noisy retrieval, we design a confidence-calibrated decision refinement scheme that estimates the reliability of each retrieved case by jointly considering prediction confidence and sample similarity, and reweights its contribution to the final prediction, providing interpretable case-level evidence. Extensive experiments on multiple medical imaging datasets demonstrate that our approach consistently outperforms strong baselines, while ablation and qualitative analyses validate its effectiveness and interpretability. The code is available at https://anonymous.4open.science/r/MKG-CARE-8B7B.

Accurate and robust medical image classification is paramount for early disease diagnosis and treatment planning. However, challenges such as limited annotated data, high intra-class variability, and subtle inter-class differences often hinder the performance of deep learning models. This paper introduces a synergistic deep learning framework that leverages the strengths of self-supervised learning and transfer learning for enhanced medical image classification. Our approach employs two distinct ConvNeXt-Tiny models: one pre-trained on a large-scale natural image dataset (ImageNet) and another pre-trained using an entropy-guided Masked Autoencoder (MAE) on the target medical dataset. Both models are then fine-tuned on specific medical image classification tasks. A final ensemble strategy, based on averaging predicted probabilities, is utilized to combine the complementary insights from these two models. Rigorous experimental validation across four diverse medical imaging datasets (Breast Ultrasound Images (BUSI), International Skin Imaging Collaboration (ISIC) 2018, Kvasir, and COVID) demonstrates the superior performance and robustness of our ensemble approach. The MAE pre-training significantly improves feature learning on domain-specific data, while the ImageNet pre-training provides strong generalizable features. The ensemble consistently achieves state-of-the-art results, outperforming individual models and existing methods, highlighting the efficacy of combining diverse pre-training strategies for challenging medical image analysis.

Deep learning models for medical image classification are susceptible to subgroup performance disparities across demographic attributes such as age, gender, and race. We identify a latent representational mechanism underlying these disparities: in transfer-learned models, the dominant penultimate-layer activation channel under positive predictions is co-activated by both disease-positive samples and privileged demographic groups (male, older patients), producing over-diagnosis; conversely, the dominant channel under negative predictions is co-activated by disadvantaged groups (female, younger patients), producing systematic under-diagnosis. To address this, we propose Neuron Incidence Redistribution (NIR), a lightweight regularization method that penalizes the variance of predicted-probability-weighted mean activations across penultimate-layer neurons, requiring no demographic labels at training time. On HAM10000, TPR disparity drops from 10.81% to 0.93% across age groups and from 12.04% to 0.74% across gender, with a marginal AUC improvement of 0.51 points. On Harvard OCT-RNFL, NIR reduces FPR disparity for race (from 15.68% to 10.66%) and age (from 12.69% to 1.80%), demonstrating that distributing latent disease evidence across the full penultimate layer is a principled and effective strategy for improving demographic fairness in medical AI.

Age dependent performance disparities in medical image classification often arise because age acts as a confounder, linking imaging morphology with disease prevalence. In practice, disparities can manifest as overdiagnosis at ages where disease prevalence is higher and underdiagnosis at ages where prevalence is lower, and can worsen under train test shifts in the age distribution. Conventional mitigation approaches that enforce strict age invariance may suppress diagnostically meaningful information encoded in age. We therefore propose a robust framework that mitigates the effects of age-dependent confounding by targeting spurious age linked trends rather than enforcing invariance. Following a warm-up phase, we characterize sample difficulty and model its age-dependent trends in a label-conditioned manner. We decorrelate age from dominant age difficulty trends using robust, Huber weighted affinity weights, attenuating confounding-driven shortcuts while preserving clinically meaningful, nonlinear age information. We further introduce an Age Coverage Score that scales the decorrelation penalty by minibatch age variance to ensure stable optimization under limited age diversity. Across two radiology datasets, our approach reduces age dependent true and false positive disparities with minimal AUC impact and remains robust to increasing train test age distribution shifts.

Diagnostic performance in medical AI varies systematically across demographic groups, yet subgroup AUC can mask clinically important disparities. At a fixed inference-time operating point, some groups may exhibit over-diagnostic behaviour, characterized by elevated true and false positive rates, while others show under-diagnostic patterns with reduced true and false positive rates. These opposing tendencies can cancel in aggregate AUCs while producing meaningful inequities in clinical decision-making. Motivated by the need to assess and mitigate such disparities at the operating point and across multiple demographic attributes simultaneously, we propose a worst-group equalized-odds margin regularizer. The proposed regularizer explicitly targets subgroup-level deviations on both the true positive and false positive sides at inference. At each update, the method identifies subgroups defined by explicit demographic attributes (e.g., age, sex, and race) that exhibit the most extreme margin deviations and applies a unified penalty, enabling fairness optimization across multiple demographic axes without requiring explicit intersectional constraints. Across two medical imaging datasets in realistic multi-label settings, our method consistently reduces disparities in Equalized Odds and Equalized Opportunity with minimal impact on AUC, preserving diagnostic performance while improving fairness.

Deep learning models have shown strong performance in medical image analysis, but deploying them in low-resource clinical environments remains difficult due to computational, memory, and power constraints. This paper presents a multi-strategy compression framework for brain tumor classification from MRI, encompassing quantization-aware training, knowledge distillation from a DenseNet-101 teacher to a compact DenseNet-32 student with low-bit post-training quantization, and Float16 post-training quantization on a lightweight MobileNetV2 backbone. Using a multi-class brain tumor MRI dataset containing glioma, meningioma, pituitary tumors, and healthy controls, we provide full experimental validation of the MobileNetV2-based pipeline, training the classifier through a three-stage transfer learning process and applying Float16 quantization via TensorFlow Lite. The DenseNet-based distillation and quantization-aware training strategies are described as complementary compression approaches within the framework, with their complete empirical evaluation reserved for future work. Experimental results on the MobileNetV2 pipeline show that the quantized model achieves 82.37 percent validation accuracy compared to the 82.20 percent full-precision baseline, reducing model size from 35.34 MB to 5.76 MB, a 6.14x compression ratio with no meaningful accuracy loss. Per-class evaluation confirms that quantization preserves diagnostic performance uniformly across all four tumor categories. These findings demonstrate that lightweight quantized models can deliver clinically viable brain tumor screening in resource-constrained healthcare settings.

Flexible continuous-time survival modeling is critical for capturing complex time-varying hazard dynamics in high-dimensional data; however, training such models remains challenging due to the intractable integral required for likelihood estimation. We introduce QSurv, a scalable deep learning framework that enables nonparametric continuous-time modeling without relying on time discretization or restrictive distributional assumptions. We propose a training objective based on Gauss-Legendre numerical quadrature, which approximates the cumulative hazard with high-order accuracy while facilitating efficient end-to-end training via standard backpropagation. Furthermore, to effectively capture non-stationary hazard dynamics in complex architectures, we introduce time-conditioned low-rank adaptation, a mechanism that conditions general neural backbones on time by dynamically modulating weights via low-rank updates. We provide theoretical analysis establishing approximation error bounds for cumulative-hazard evaluation. Comprehensive experiments across synthetic benchmarks, large-scale real-world tabular datasets, and high-dimensional medical imaging tasks demonstrate that QSurv achieves competitive predictive performance with advantages in instantaneous hazard function estimation, enabling more interpretable characterization of time-varying risk patterns.

Objective: The primary goal of this study was to systematically examine the impact of commonly used imbalance handling methods (IHMs) on predictive performance in biomedical binary classification, considering the interplay between model complexity and diverse data modalities. Material and Methods: We evaluated five representative IHMs: random undersampling (RUS), random oversampling (ROS), SMOTE, re-weighting (RW), and direct F1-score optimization (DMO), against a raw training (RAW) baseline. The evaluation encompassed three public biomedical datasets: MIMIC-III (tabular), ADE-Corpus-V2 (text), and MURA (image), spanning three common biomedical data modalities. To assess varying model complexity, we employed a range of architectures, from classical logistic regression and random forest to deep neural networks, including multilayer perceptron (MLP), BiLSTM, BERT, DenseNet, and DINOv2. Results: For simpler models such as logistic regression on tabular data, IHMs yielded no significant advantage over the RAW baseline, aligning with prior findings. However, clear benefits were observed for more complex models and unstructured data: (a) ROS and RW consistently enhanced the performance of powerful models; (b) direct F1-score optimization demonstrated utility primarily for unstructured text and image data; and (c) RUS and SMOTE consistently degraded performance and are therefore not recommended. Conclusion: The effectiveness of IHMs depends on both model complexity and data modality. Performance gains are most pronounced when leveraging appropriate IHMs, such as ROS, RW, and DMO, on high-complexity models.

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.