The K-Space Signature: Frequency-Domain Representation Learning for Medical Deepfake Detection

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.

While deep generative models offer new opportunities for medical image synthesis and data sharing, their ability to memorize and reproduce training samples raises serious concerns about patient confidentiality. Detecting such memorization at scale remains challenging: traditional pixel-based metrics are sensitive to generation artifacts, whereas generic embedding-based metrics often lack the anatomical sensitivity required for medical data. To address this challenge, we introduce DeepSSIM++, a self-supervised similarity metric for scalable memorization auditing in medical generative models. By leveraging multi-scale feature aggregation and anatomy-preserving augmentations, DeepSSIM++ learns an embedding space where cosine similarity approximates the Structural Similarity Index (SSIM), eliminating the need for exact pixel-level registration. Compared with state-of-the-art baselines, DeepSSIM++ achieves an average Macro F1 improvement of 33 percentage points under ideal alignment and 46 percentage points under realistic spatial and intensity perturbations. Furthermore, it accelerates large-scale similarity computation by several orders of magnitude compared with analytical SSIM. By combining anatomical sensitivity and computational efficiency, DeepSSIM++ provides an open-source tool for scalable memorization auditing in medical generative AI. Code and data are publicly available at: https://github.com/brAIn-science/DeepSSIM.

Deepfakes are artificially generated images, audio, or videos that threaten privacy, security, and information integrity. Detecting such content is crucial for countering disinformation, as the latest models generate highly realistic content. While spatial- or frequency-based approaches achieve good detection rates on Generative Adversarial Networks (GANs)-based generated deepfakes, they often struggle with recent diffusion model-generated images. In particular, existing approaches rarely exploit complementary multi-domain representations or systematically evaluate cross-generator robustness. To address these challenges, we propose a multi-domain deepfake detection framework called SGFF-Net (Spatial-Gradient-Frequency Fusion Network) that integrates spatial, gradient, and DWT (Discrete Wavelet Transform)-based frequency representations within a dual residual learning architecture. Experimental results show that the SGFF-Net achieves 98.95% accuracy in intra-dataset evaluation and improves performance in both cross-model (70.46%) and cross-paradigm (69.94%) settings. Incorporating multi-source training and data augmentation further enhances robustness, increasing accuracy from 70.46% to 79.80% in cross-model evaluation, from 69% to 78% in cross-paradigm evaluation, and from 61.50% to 75.80% on real-world data. Unlike single-domain detectors, the SGFF-Net learns complementary forensic cues across spatial, gradient, and wavelet-frequency domains, resulting in greater robustness under cross-generator and cross-paradigm evaluation. The results further show that combining multi-domain representations with data diversity and augmentation substantially improves generalization, providing practical insights for developing more reliable deepfake detection systems.