# AEM: Attention Entropy Maximization for Multiple Instance Learning based Whole Slide Image Classification

arXiv: https://arxiv.org/abs/2406.15303 · HTML: https://mlsanity.com/paper/2406.15303/

## Key facts

- Cited by 10 papers in the map (data through 14 Oct 2026).
- Builds on 42 of its 67 references that are in the map.
- First posted on arXiv 18 Jun 2024.

## Builds on (most cited first, 30 of 42)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Proximal Policy Optimization Algorithms](https://mlsanity.com/paper/1707.06347/) (2017)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [On Layer Normalization in the Transformer Architecture](https://mlsanity.com/paper/2002.04745/) (2020)
- [Virtual Adversarial Training: A Regularization Method for Supervised and Semi-Supervised Learning](https://mlsanity.com/paper/1704.03976/) (2017)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Scaling Vision Transformers to 22 Billion Parameters](https://mlsanity.com/paper/2302.05442/) (2023)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Semi-supervised Domain Adaptation via Minimax Entropy](https://mlsanity.com/paper/1904.06487/) (2019)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [LongNet: Scaling Transformers to 1,000,000,000 Tokens](https://mlsanity.com/paper/2307.02486/) (2023)
- [Quilt-1M: One Million Image-Text Pairs for Histopathology](https://mlsanity.com/paper/2306.11207/) (2023)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Stabilizing Transformer Training by Preventing Attention Entropy Collapse](https://mlsanity.com/paper/2303.06296/) (2023)
- [Benchmarking Self-Supervised Learning on Diverse Pathology Datasets](https://mlsanity.com/paper/2212.04690/) (2022)
- [Artificial Intelligence for Digital and Computational Pathology](https://mlsanity.com/paper/2401.06148/) (2023)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [Cluster-to-Conquer: A Framework for End-to-End Multi-Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2103.10626/) (2021)
- [Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2311.07125/) (2023)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Whole Slide Image Classification](https://mlsanity.com/paper/2307.15254/) (2023)
- [Task-specific Fine-tuning via Variational Information Bottleneck for Weakly-supervised Pathology Whole Slide Image Classification](https://mlsanity.com/paper/2303.08446/) (2023)
- [Histopathology Whole Slide Image Analysis with Heterogeneous Graph Representation Learning](https://mlsanity.com/paper/2307.04189/) (2023)
- [Self-Supervision Closes the Gap Between Weak and Strong Supervision in Histology](https://mlsanity.com/paper/2012.03583/) (2020)
- [Bi-directional Weakly Supervised Knowledge Distillation for Whole Slide Image Classification](https://mlsanity.com/paper/2210.03664/) (2022)
- [Accounting for Dependencies in Deep Learning Based Multiple Instance Learning for Whole Slide Imaging](https://mlsanity.com/paper/2111.01556/) (2021)
- [ReMix: A General and Efficient Framework for Multiple Instance Learning based Whole Slide Image Classification](https://mlsanity.com/paper/2207.01805/) (2022)

## Built on by (most cited first, 10 of 10)

- [From Correlation to Causation: Max-Pooling-Based Multi-Instance Learning Leads to More Robust Whole Slide Image Classification](https://mlsanity.com/paper/2408.09449/) (2024)
- [ASMIL: Attention-Stabilized Multiple Instance Learning for Whole Slide Imaging](https://mlsanity.com/paper/2603.06658/) (2026)
- [Normalized Conditional Mutual Information Surrogate Loss for Deep Neural Classifiers](https://mlsanity.com/paper/2601.02543/) (2026)
- [Cluster-Level Sparse Multi-Instance Learning for Whole-Slide Images](https://mlsanity.com/paper/2509.11034/) (2025)
- [Revisiting Data Challenges of Computational Pathology: A Pack-based Multiple Instance Learning Training Framework](https://mlsanity.com/paper/2509.20923/) (2025)
- [Spatial Blindness in Whole-Slide Multiple Instance Learning](https://mlsanity.com/paper/2605.17449/) (2026)
- [GCE-MIL: Faithful and Recoverable Evidence for Multiple Instance Learning in Whole-Slide Imaging](https://mlsanity.com/paper/2605.17456/) (2026)
- [Normal Guidance is what Attention Needs](https://mlsanity.com/paper/2605.27306/) (2026)
- [A Multi-Cohort Validation of Censoring-Aware Conformal Lower Predictive Bounds for Pathology Survival Models](https://mlsanity.com/paper/2608.04025/) (2026)
- [Weakly Supervised Spatial Grounding for Discriminative Attention-Based Ultrasound-Histopathology Alignment in Prostate Cancer Grading](https://mlsanity.com/paper/2609.15150/) (2026)

## Abstract (arXiv)

Multiple Instance Learning (MIL) effectively analyzes whole slide images but faces overfitting due to attention over-concentration. While existing solutions rely on complex architectural modifications or additional processing steps, we introduce Attention Entropy Maximization (AEM), a simple yet effective regularization technique. Our investigation reveals the positive correlation between attention entropy and model performance. Building on this insight, we integrate AEM regularization into the MIL framework to penalize excessive attention concentration. To address sensitivity to the AEM weight parameter, we implement Cosine Weight Annealing, reducing parameter dependency. Extensive evaluations demonstrate AEM's superior performance across diverse feature extractors, MIL frameworks, attention mechanisms, and augmentation techniques. Here is our anonymous code: https://github.com/dazhangyu123/AEM.