FMaMIL: Frequency-Driven Mamba Multi-Instance Learning for Weakly Supervised Lesion Segmentation in Medical Images

Abstract: Accurate lesion segmentation in histopathology images is essential for diagnostic interpretation and quantitative analysis, yet it remains challenging due to the limited availability of costly pixel-level annotations. To address this, we propose FMaMIL, a novel two-stage framework for weakly supervised lesion segmentation based solely on image-level labels. In the first stage, a lightweight Mamba-based encoder is introduced to capture long-range dependencies across image patches under the MIL paradigm. To enhance spatial sensitivity and structural awareness, we design a learnable frequency-domain encoding module that supplements spatial-domain features with spectrum-based information. CAMs generated in this stage are used to guide segmentation training. In the second stage, we refine the initial pseudo labels via a CAM-guided soft-label supervision and a self-correction mechanism, enabling robust training even under label noise. Extensive experiments on both public and private histopathology datasets demonstrate that FMaMIL outperforms state-of-the-art weakly supervised methods without relying on pixel-level annotations, validating its effectiveness and potential for digital pathology applications.