4.7 Article

Unpaired Stain Transfer Using Pathology-Consistent Constrained Generative Adversarial Networks

Journal

IEEE TRANSACTIONS ON MEDICAL IMAGING
Volume 40, Issue 8, Pages 1977-1989

Publisher

IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TMI.2021.3069874

Keywords

Cancer; Generative adversarial networks; Task analysis; Tumors; Image analysis; Histopathology; Annotations; Histopathology; stain transfer; pathology consistency constraint; Ki-67; hematoxylin-eosin (H&E)

Funding

  1. National Science Foundation of China (NSFC) [61875102, 81871395, 61675113]
  2. Science and Technology Research Program of Shenzhen City [JCYJ20170816161836562, JCYJ20170817111912585, JCYJ20160427183803458, JCYJ20170412171856582, JCY20180508152528735]
  3. Oversea Cooperation Foundation
  4. Graduate School at Shenzhen, Tsinghua University [HW2018007]

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Pathological examination is crucial for cancer diagnosis, with virtual IHC image generation playing an important role in areas where traditional IHC examination is challenging. A novel adversarial learning method is proposed to effectively generate Ki-67-stained images, showcasing superior performance and robustness.
Pathological examination is the gold standard for the diagnosis of cancer. Common pathological examinations include hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). In some cases, it is hard to make accurate diagnoses of cancer by referring only to H&E staining images. Whereas, the IHC examination can further provide enough evidence for the diagnosis process. Hence, the generation of virtual IHC images from H&E-stained images will be a good solution for current IHC examination hard accessibility issue, especially for some low-resource regions. However, existing approaches have limitations in microscopic structural preservation and the consistency of pathology properties. In addition, pixel-level paired data is hard available. In our work, we propose a novel adversarial learning method for effective Ki-67-stained image generation from corresponding H&E-stained image. Our method takes fully advantage of structural similarity constraint and skip connection to improve structural details preservation; and pathology consistency constraint and pathological representation network are first proposed to enforce the generated and source images hold the same pathological properties in different staining domains. We empirically demonstrate the effectiveness of our approach on two different unpaired histopathological datasets. Extensive experiments indicate the superior performance of our method that surpasses the state-of-the-art approaches by a significant margin. In addition, our approach also achieves a stable and good performance on unbalanced datasets, which shows our method has strong robustness. We believe that our method has significant potential in clinical virtual staining and advance the progress of computer-aided multi-staining histology image analysis.

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