Federated Distillation for Whole Slide Image via Gaussian-Mixture Feature Alignment and Curriculum Integration
Authors: Luru Jing, Cong Cong, Yanyuan Chen, Yongzhi Cao
Organizations: School of Computer Science, Peking University, Beijing, China · Center for Health Informatics, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2113, Australia · School of Data Science, University of Virginia, Charlottesville, VA, USA.
Federated learning (FL) offers a promising framework for collaborative digital pathology by enabling model training across institutions. However, real-world deployments face heterogeneity arising from diverse multiple instance learning (MIL) architectures and heterogeneous feature extractors across institutions. We propose FedHD, a novel FL framework that performs local Gaussian-mixture feature alignment tailored for WSI analysis. Instead of exchanging model parameters, each client independently distills semantically rich synthetic feature representations aligned with the distribution of real WSIs. To preserve diagnostic diversity, FedHD adopts a one-to-one distillation strategy, generating a synthetic counterpart for each real slide to avoid over-compression. During federation, a curriculum-based integration strategy progressively incorporates cross-site synthetic features into local training once performance plateaus. Furthermore, an optional interpretation module reconstructs pseudo-patches from synthetic embeddings, enhancing transparency. FedHD is architecture-agnostic, privacy-preserving, and supports personalized yet collaborative training across diverse institutions. Experiments on TCGA-IDH, CAMELYON16, and CAMELYON17 show that FedHD consistently outperforms state-of-the-art federated and distillation baselines.
Robust whole-slide image (WSI) analysis under strict data-governance remains challenging due to substantial cross-institutional stain heterogeneity. Domain generalization (DG) mitigates these shifts but typically requires centralized data, conflicting with privacy regulations. Federated learning (FedL) provides a decentralized alternative; however, existing FedL and federated DG (FedDG) approaches rely almost exclusively on low-order statistics, assuming Gaussian-like stain distributions. In contrast, real-world staining processes often produce asymmetric, heavy-tailed color distributions due to biochemical diffusion and scanner nonlinearity. Consequently, current methods fail to model the higher-order, non-Gaussian characteristics dominating real-world stain variability. To address this, we propose FedStain, a stain-aware FedDG framework explicitly incorporating higher-order stain moments--skewness and kurtosis--as compact statistical descriptors exchanged during federated optimization. These descriptors require no pixel-level data transmission, preserving strict privacy and communication efficiency, while enabling the global model to capture stain variability missed by low-order statistics. FedStain also employs a contrastive, cross-site parameter aggregation strategy to promote stain-invariant representations without relaxing data constraints. Extensive experiments on Camelyon17 and our new MvMidog-Fed benchmark show FedStain yields consistent improvements, outperforming state-of-the-art FedL, DG, and FedDG baselines by up to +3.9% absolute accuracy. To our knowledge, FedStain is the first FedDG approach to explicitly model higher-order stain statistics, enabling robust cross-institutional deployment in computational pathology.
Histopathological whole slide images (WSIs) are central to cancer diagnosis, but their gigapixel scale, tissue heterogeneity, weak slide-level supervision, sparse diagnostic regions, and multi-scale evidence make robust automated analysis challenging. Multiple instance learning (MIL) is widely used to aggregate tile-level features into slide-level predictions, yet existing augmentation strategies often perturb tissue regions without preserving diagnostic relevance, slide context, or cross-scale structure. We propose SlideMix, a model-agnostic multimodal augmentation framework for MIL-based WSI analysis. SlideMix uses a retrieval-augmented vision-language model (VLM)-based Visual-Language Adaptive Region selector to identify diagnostically relevant regions and reduce weak-label noise. It then performs In-place Tile Shuffling within meaningful tissue regions to mix feature embeddings while preserving slide-level context. A VLM-based soft-labeling module supervises mixed samples, while a multi-factor, loss-driven online Curriculum-Learning Feedback scheme adaptively controls shuffle granularity, feature similarity, and shuffle ratio to promote cross-scale representation learning. Across 11 WSI datasets comprising 20,523 slides, 8 diagnostic tasks, and 10 WSI backbones, SlideMix improves accuracy and generalization in most settings and compares favorably with established augmentation baselines, providing a simple plug-and-play approach for more robust and scalable digital pathology models. Source code: https://github.com/Xia-Research-Lab/SlideMix
Federated Learning (FL) enables collaborative training of machine learning models across multiple institutions without sharing sensitive data, making it particularly suitable for medical imaging applications. However, heterogeneous data distributions across institutions and potential information leakage through model updates remain important challenges. In this work, we propose DP-SimAgg, a privacy-preserving federated learning framework that integrates similarity-weighted aggregation with a server-side differential privacy mechanism. The proposed method applies L2 clipping to bound collaborator updates, computes similarity-based aggregation weights to mitigate the effects of non-IID data distributions, and injects calibrated Gaussian noise at the central server, providing per-round privacy guarantees under the assumed sensitivity bound. The framework is implemented using Intel's OpenFL platform and evaluated on the FeTS 2022 dataset consisting of 1251 multi-modal MRI scans for brain tumor segmentation. Experimental results demonstrate that DP-SimAgg maintains competitive segmentation performance while providing privacy protection. Under a strict per-round privacy budget (epsilon = 1, cumulative epsilon_total = 20 over 20 rounds), the method achieves Dice scores of 0.6357, 0.5305, and 0.5274 for the enhancing tumor (ET), tumor core (TC), and whole tumor (WT) regions, respectively. With a more relaxed per-round budget (epsilon = 10, cumulative epsilon_total = 200), performance approaches that of the non-private baseline while incorporating a central Gaussian mechanism with per-round (epsilon, delta)-DP accounting under the assumed sensitivity bound. These results highlight the potential of DP-SimAgg for enabling privacy-preserving collaborative learning in medical imaging applications.
Muhammad Irfan Khan, Eero Lehtonen, Joni Obradovic +4