Normal Guidance is what Attention Needs

Despite being resource-intensive to train, 3D convolutional neural networks (CNNs) have been the standard approach to classify CT and MRI scans. Recent work suggests that deep multiple instance learning (MIL) may be a more efficient alternative for 3D brain scans, especially when the pre-trained image encoder used to embed each 2D slice is frozen and only the pooling operation and classifier are trained. In this paper, we provide a systematic comparison of simple MIL, attention-based MIL, 3D CNNs, and 3D ViTs across three CT and four MRI datasets, including two large datasets of at least 10,000 scans. Our goal is to help resource-constrained practitioners understand which neural networks work well for 3D neuroimages and why. We further compare design choices for attention-based MIL, including different encoders, pooling operations, and architectural orderings. We find that simple mean pooling MIL, without any learnable attention, matches or outperforms recent MIL or 3D CNN alternatives on 4 of 6 moderate-sized tasks. This baseline remains competitive on two large datasets while being 25x faster to train. To explain mean pooling's success, we examine per-slice attention quality and a semi-synthetic dataset where we can derive the best possible classifier via a Bayes estimator. This analysis reveals the limits of existing MIL approaches and suggests routes for future improvements.

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.

Attention-based Multiple Instance Learning aggregators in medical imaging are prone to attention concentration, producing overconfident and unstable predictions. We introduce QG-MIL, a gated transformer aggregator that addresses this through four synergistic architectural components: RMSNorm-based pre-normalization, per-head QK normalization, fine-grained attention output gating, and SwiGLU-style feed-forward modules. Together, these design choices stabilize training and distribute attention more uniformly across instances without auxiliary losses, masking, or multi-stage regularization. We evaluate QG-MIL across six benchmarks spanning whole-slide pathology and cell-level hematology, covering two fundamentally different MIL scales. The best-performing QG-MIL variants outperform leading baselines on all six benchmarks, with an average improvement of +6.1 mean macro F1 points. Attention overlays and attention mass analysis confirm more distributed instance weighting. Ablation studies show that while individual components can match the full model on specific datasets, the QG-MIL design provides the most consistent cross-domain performance and tightest variance when compared to selected baselines. We release a configurable implementation to support reproducibility at: https://github.com/unica-visual-intelligence-lab/QG-MIL