Fourier Transform Multiple Instance Learning for Whole Slide Image Classification

Whole Slide Image (WSI) classification relies on Multiple Instance Learning (MIL) with spatial patch features, yet existing methods struggle to capture global dependencies due to the immense size of WSIs and the local nature of patch embeddings. This limitation hinders the modeling of coarse structures essential for robust diagnostic prediction. We propose Fourier Transform Multiple Instance Learning (FFT-MIL), a framework that augments MIL with a frequency-domain branch to provide compact global context. Low-frequency crops are extracted from WSIs via the Fast Fourier Transform and processed through a modular FFT-Block composed of convolutional layers and Min-Max normalization to mitigate the high variance of frequency data. The learned global frequency feature is fused with spatial patch features through lightweight integration strategies, enabling compatibility with diverse MIL architectures. FFT-MIL was evaluated across six state-of-the-art MIL methods on three public datasets (BRACS, LUAD, and IMP). Integration of the FFT-Block improved macro F1 scores by an average of 3.51% and AUC by 1.51%, demonstrating consistent gains across architectures and datasets. These results establish frequency-domain learning as an effective and efficient mechanism for capturing global dependencies in WSI classification, complementing spatial features and advancing the scalability and accuracy of MIL-based computational pathology.

Anthony Bilic, Guangyu Sun, Ming Li, Md Sanzid Bin Hossain, Yu Tian, Wei Zhang, Laura Brattain, Dexter Hadley, Chen Chen · 2025