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Using Variational Autoencoders for Out of Distribution Detection in Histological Multiple Instance Learning.

Francisco Javier Sáez-Maldonado1, Luz García2, Lee A D Cooper3,4,5

  • 1Department of Computer Science and Artificial Intelligence, Universidad de Granada, 18071 Granada, Spain.

IEEE Access : Practical Innovations, Open Solutions
|October 16, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces an out-of-distribution (OOD)-aware deep multiple instance learning (MIL) model for histological image classification. The model effectively detects unseen tissues and artifacts, enhancing computer-assisted diagnosis systems with high accuracy.

Keywords:
Out-of-distribution detectionmultiple instance learningvariational autoencoder

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Area of Science:

  • Computational pathology
  • Machine learning for medical imaging
  • Histopathology analysis

Background:

  • Multiple Instance Learning (MIL) methods simplify histological image classification by using Whole Slide Image (WSI) level labels, reducing annotation burden.
  • Real-world deployment requires MIL models to identify Out-of-Distribution (OOD) samples, such as novel tissues or artifacts, for quality control in Computer Assisted Diagnosis (CADx).

Purpose of the Study:

  • To develop an OOD-aware probabilistic deep MIL model for histological image classification.
  • To enable CADx systems to flag potentially problematic samples for further review.

Main Methods:

  • A novel OOD-aware probabilistic deep MIL model integrating a variational autoencoder's latent representation with an attention mechanism was proposed.
  • The model utilizes instance latent representations for both classification and OOD detection at test time.
  • A deterministic variant using reconstruction error as an OOD score was also developed.

Main Results:

  • The model achieved classification results competitive with state-of-the-art methods on Panda (prostate) and Camelyon16 (lymph node) datasets.
  • For OOD detection, the model achieved 100% AUC when distinguishing between prostate tissue and artifacts (artif dataset).
  • The model also demonstrated high AUCs (100% and 97%) for lymph node OOD detection using Panda and B-cell lymphoma (bcell) datasets.

Conclusions:

  • The developed models exhibit strong classification performance and effective OOD slide detection capabilities.
  • These findings highlight the clinical potential of the proposed OOD-aware MIL approach for enhancing diagnostic accuracy and reliability.