HexMIL: Hierarchical Attention MIL for Ante-Hoc Explainable Detection of AI-Manipulated CT Volumes

The emergence of medical deepfakes, i.e., medical images manipulated by deep generative models, poses a significant threat to clinical workflows. However, existing detectors suffer from two critical limitations: poor generalization to unseen generative architectures for manipulation detection and lack of interpretability. In this context, we present HexMIL (Hierarchical EXplainable Multiple Instance Learning), a mask-free medical deepfake detector that simultaneously addresses both limitations using only binary volume-level supervision. HexMIL decomposes each CT volume into a two-level hierarchy of patches and slices, aggregated via independent Gated Attention modules whose weights are directly combined into a full-resolution 3D attention volume that localizes the manipulated sub-region without any pixel-level annotation. Unlike post-hoc methods such as Grad-CAM, HexMIL's attention weights constitute the exact forward computation driving the classification decision, providing ante-hoc and structurally faithful spatial attribution. We evaluate HexMIL on M3DSynth and CT-GAN datasets under a rigorous cross-generator generalization protocol, training on a single generative architecture and testing on unseen ones. HexMIL outperforms all baselines by +9.1 AUC and +9.4 F1 in out-of-domain classification, and achieves the best average IoU and Pointing Game score in localization. Project page: opontorno.github.io/hexmil.