Re-mixing Embeddings for Patient Augmentation in Data Scarce Multiple Instance Learning

Rare diseases dominate the diagnostic challenge in medical imaging yet are severely underrepresented in clinical datasets, causing classifiers to fail on exactly the conditions where reliable detection matters most. Generative augmentation can supply the missing tail-class coverage, but coarse disease labels aggregate diverse subtypes and acquisition settings into multi-modal conditionals that bias generators toward dominant submodes, while a shared Gaussian source forces rare subpopulations through disproportionately long transport paths. We propose an offline strategy that introduces informative priors at two levels: first, we partition each coarse label into coherent submodes via Gaussian mixture modeling in the generative model's latent space; second, we learn subclass-conditioned source distributions that re-center and re-scale the starting distribution per submode, shortening trajectories and reducing within-subclass dispersion. To prevent degenerate solutions we impose explicit geometric control, moderately concentrating normalized displacement directions around learnable prototypes while capping path-length outliers. On long-tailed chest X-ray (MIMIC-LT, NIH-LT) and CT slice (CT-RATE) benchmarks the proposed method consistently improves tail-class generation fidelity and diversity (FID, IRS) and is a promising augmentation strategy that reliably improves downstream balanced accuracy and macro-F1 over a non-augmented baseline across modalities.

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.

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/.