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Two basic types of preparation are used to visualize specimens with a light microscope: wet mounts and fixed specimens.
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GHMS-CycleGAN: Graph-Based Hierarchical Multi-stain CycleGAN for Stain Normalization and Classification in Digital

Mohamed Elmanna1, Ahmed Elsafty2, Yomna Ahmed2

  • 1Department of Biomedical Engineering and Systems, Faculty of Engineering, Cairo University, Cairo University St, Giza, 12613, Egypt.

Journal of Imaging Informatics in Medicine
|March 27, 2026
PubMed
Summary
This summary is machine-generated.

Novel deep learning methods normalize digital pathology images, improving classification accuracy for histopathology, red blood cell (RBC), and white blood cell (WBC) images despite staining variations.

Keywords:
Blood cell classificationCycleGANDigital pathologyGraph-based cycle lossHierarchical cycle lossStain normalization

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Area of Science:

  • Digital pathology and medical imaging analysis
  • Artificial intelligence in healthcare
  • Computational pathology

Background:

  • Digital pathology (DP) offers computer-aided diagnosis (CAD) tools using deep learning (DL).
  • Staining variations and scanner distortions degrade DL-based CAD system performance.
  • Robust image normalization is crucial for reliable DL models in pathology.

Purpose of the Study:

  • To introduce novel stain and scan normalization methods for histopathology, RBC, and WBC image classification.
  • To develop a framework using hierarchical multi-stain CycleGAN (HMS-CycleGAN) and graph-based HMS-CycleGAN (GHMS-CycleGAN).
  • To evaluate the impact of normalization on downstream image classification tasks.

Main Methods:

  • Proposed HMS-CycleGAN and GHMS-CycleGAN for multi-stain and color normalization.
  • Exploited hierarchical and network structures in DP images for normalization mapping.
  • Validated on diverse histopathology, RBC, and WBC datasets from multiple scanners and institutions.

Main Results:

  • HMS-CycleGAN demonstrated superior robustness and consistency across staining variations compared to state-of-the-art methods.
  • Normalization methods consistently improved classification performance over unnormalized classifiers.
  • Achieved 84.05% accuracy on Wilds Camelyon and 51.06% F1-score for WBC classification.
  • HMS-CycleGAN and GHMS-CycleGAN reached 80-91% F1-scores for cross-scanner RBC classification.

Conclusions:

  • Image normalization is vital for building robust and generalizable DL models in digital pathology.
  • The proposed HMS-CycleGAN and GHMS-CycleGAN methods significantly enhance DL-based image classification performance.
  • These normalization techniques address key challenges in digital pathology, paving the way for improved diagnostic tools.