LadderMIL: Multiple Instance Learning with Coarse-to-Fine Self-Distillation

Shuyang Wu; Yifu Qiu; Ines P. Nearchou; Sandrine Prost; Jonathan A. Fallowfield; Hideki Ueno; Hitoshi Tsuda; David J. Harrison; Hakan Bilen; Timothy J. Kendall

arXiv · 2502.02707

LadderMIL: Multiple Instance Learning with Coarse-to-Fine Self-Distillation

Shuyang Wu·Yifu Qiu·Ines P. Nearchou·Sandrine Prost·Jonathan A. Fallowfield·Hideki Ueno·Hitoshi Tsuda·David J. Harrison·Hakan Bilen·Timothy J. Kendall

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Abstract

Multiple Instance Learning (MIL) for whole slide image (WSI) analysis in computational pathology often neglects instance-level learning as supervision is typically provided only at the bag level, hindering the integrated consideration of instance and bag-level information during the analysis. In this work, we present LadderMIL, a framework designed to improve MIL through two perspectives: (1) employing instance-level supervision and (2) learning inter-instance contextual information at bag level. Firstly, we propose a novel Coarse-to-Fine Self-Distillation (CFSD) paradigm that probes and distils a network trained with bag-level information to adaptively obtain instance-level labels which could effectively provide the instance-level supervision for the same network in a self-improving way. Secondly, to capture inter-instance contextual information in WSI, we propose a Contextual Encoding Generator (CEG), which encodes the contextual appearance of instances within a bag. We also theoretically and empirically prove the instance-level learnability of CFSD. Our LadderMIL is evaluated on multiple clinically relevant benchmarking tasks including breast cancer receptor status classification, multi-class subtype classification, tumour classification, and prognosis prediction. Average improvements of 8.1%, 11% and 2.4% in AUC, F1-score, and C-index, respectively, are demonstrated across the five benchmarks, compared to the best baseline.

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Shuyang Wu, Yifu Qiu, Ines P. Nearchou, Sandrine Prost, Jonathan A. Fallowfield, Hideki Ueno, Hitoshi Tsuda, David J. Harrison, Hakan Bilen, Timothy J. Kendall. 2025-02-04. LadderMIL: Multiple Instance Learning with Coarse-to-Fine Self-Distillation. https://arxiv.org/abs/2502.02707

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