Class-Agnostic Weighted Normalization of Staining in Histopathology Images Using a Spatially Constrained Mixture Model

Sobhan Shafiei, Amir Safarpoor, Ahad Jamalizadeh, H. R. Tizhoosh

Research output: Contribution to journalArticlepeer-review


The colorless biopsied tissue samples are usually stained in order to visualize different microscopic structures for diagnostic purposes. But color variations associated with the process of sample preparation, usage of raw materials, diverse staining protocols, and using different slide scannersmay adversely influence both visual inspection and computer-aided image analysis. As a result, manymethods are proposed for histopathology image stain normalization in recent years. In this study, we introduce a novel approach for stain normalization based on learning a mixture of multivariate skew-normal distributions for stain clustering and parameter estimation alongside a stain transformation technique. The proposed method, labeled "Class-Agnostic Weighted Normalization"(short CLA Wnormalization), has the ability to normalize a source image by learning the color distribution of both source and target images within an expectation-maximization framework. The novelty of this approach is its flexibility to quantify the underlying both symmetric and nonsymmetric distributions of the different stain components while it is considering the spatial information. The performance of this new stain normalization scheme is tested on several publicly available digital pathology datasets to compare it against state-ofthe- art normalization algorithms in terms of ability to preserve the image structure and information. All in all, our proposed method performed superior more consistently in comparison with existing methods in terms of information preservation, visual quality enhancement, and boosting computer-aided diagnosis algorithm performance.

Original languageEnglish (US)
Pages (from-to)3355-3366
Number of pages12
JournalIEEE transactions on medical imaging
Issue number11
StatePublished - Nov 2020


  • H&E staining
  • histopathology
  • skewnormal distribution
  • spatial information
  • stain normalization

ASJC Scopus subject areas

  • Software
  • Radiological and Ultrasound Technology
  • Electrical and Electronic Engineering
  • Computer Science Applications


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